Cell adhesion and culture medium dependent changes in the high frequency mechanical vibration induced proliferation, osteogenesis, and intracellular organization of human adipose stem cells

High frequency (HF) mechanical vibration appears beneficial for in vitro osteogenesis of mesenchymal stem cells (MSCs). However, the current mechanobiological understanding of the method remains insufficient. We designed high-throughput stimulators to apply horizontal or vertical high magnitude HF (HMHF; 2.5 Gpeak, 100 Hz) vibration on human adipose stem cells (hASCs). We analyzed proliferation, alkaline phosphatase (ALP) activity, mineralization, and effects on the actin cytoskeleton and nuclei using immunocytochemical stainings. Proliferation was studied on a standard tissue culture plastic (sTCP) surface and on an adhesion supporting tissue culture plastic (asTCP) surface in basal (BM) and osteogenic (OM) culture medium conditions. We discovered that the improved cell adhesion was a prerequisite for vibration induced changes in the proliferation of hASCs. Similarly, the adhesion supporting surface enabled us to observe vibration initiated ALP activity and mineralization changes in OM condition. The horizontal vibration increased ALP activity, while vertical stimulation reduced ALP activity. However, mineralization was not enhanced by the HMHF vibration. We performed image-based analysis of actin and nuclei to obtain novel data of the intracellular-level responses to HF vibration in BM and OM conditions. Our quantitative results suggest that actin organizations were culture medium and stimulation direction dependent. Both stimulation directions decreased OM induced changes in nuclear size and elongation. Consequently, our findings of the nuclear deformations provide supportive evidence for the involvement of the nuclei in the mechanocoupling of HF vibration. Taken together, the results of this study enhanced the knowledge of the intracellular mechanisms of HF vibration induced osteogenesis of MSCs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech, Tampere University Hospital
Contributors: Halonen, H. T., Ihalainen, T. O., Hyväri, L., Miettinen, S., Hyttinen, J. A.
Publication date: 1 Jan 2020
Peer-reviewed: Yes

Publication information

Journal: Journal of the Mechanical Behavior of Biomedical Materials
Volume: 101
Article number: 103419
ISSN (Print): 1751-6161
Original language: English
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering, Mechanics of Materials
Keywords: Adipose stem cells, Bone tissue engineering, HMHF vibration, Horizontal stimulation, Mechanobiology, Vertical stimulation
Electronic versions: 
Source: Scopus
Source ID: 85072013214

Research output: Contribution to journalArticleScientificpeer-review

Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films

In vitro cell culture models representing the physiological and pathological features of the outer retina are urgently needed. Artificial tissue replacements for patients suffering from degenerative retinal diseases are similarly in great demand. Here, we developed a co-culture system based solely on the use of human induced pluripotent stem cell (hiPSC)-derived cells. For the first time, hiPSC-derived retinal pigment epithelium (RPE) and endothelial cells (EC) were cultured on opposite sides of porous polylactide substrates prepared by breath figures (BF), where both surfaces had been collagen-coated by Langmuir–Schaefer (LS) technology. Small modifications of casting conditions during material preparation allowed the production of free-standing materials with distinct porosity, wettability and ion diffusion capacity. Complete pore coverage was achieved by the collagen coating procedure, resulting in a detectable nanoscale topography. Primary retinal endothelial cells (ACBRI181) and umbilical cord vein endothelial cells (hUVEC) were utilised as EC references. Mono-cultures of all ECs were prepared for comparison. All tested materials supported cell attachment and growth. In mono-culture, properties of the materials had a major effect on the growth of all ECs. In co-culture, the presence of hiPSC-RPE affected the primary ECs more significantly than hiPSC-EC. In consistency, hiPSC-RPE were also less affected by hiPSC-EC than by the primary ECs. Finally, our results show that the modulation of the porosity of the materials can promote or prevent EC migration. In short, we showed that the behaviour of the cells is highly dependent on the three main variables of the study: the presence of a second cell type in co-culture, the source of endothelial cells and the biomaterial properties. The combination of BF and LS methodologies is a powerful strategy to develop thin but stable materials enabling cell growth and modulation of cell-cell contact. Statement of significance: Artificial blood-retinal barriers (BRB), mimicking the interface at the back of the eye, are urgently needed as physiological and disease models, and for tissue transplantation targeting patients suffering from degenerative retinal diseases. Here, we developed a new co-culture model based on thin, biodegradable porous films, coated on both sides with collagen, one of the main components of the natural BRB, and cultivated endothelial and retinal pigment epithelial cells on opposite sides of the films, forming a three-layer structure. Importantly, our hiPSC-EC and hiPSC-RPE co-culture model is the first to exclusively use human induced pluripotent stem cells as cell source, which have been widely regarded as an practical candidate for therapeutic applications in regenerative medicine.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Tampere University, Tampere University Hospital
Contributors: Calejo, M. T., Saari, J., Vuorenpää, H., Vuorimaa-Laukkanen, E., Kallio, P., Aalto-Setälä, K., Miettinen, S., Skottman, H., Kellomäki, M., Juuti-Uusitalo, K.
Number of pages: 17
Pages: 327-343
Publication date: 2020
Peer-reviewed: Yes
Early online date: 2019

Publication information

Journal: Acta Biomaterialia
Volume: 101
ISSN (Print): 1742-7061
Original language: English
ASJC Scopus subject areas: Biotechnology, Biomaterials, Biochemistry, Biomedical Engineering, Molecular Biology
Keywords: Breath figures, Co-culture, hiPSC-endothelial cells, hiPSC-RPE, Polylactide
Electronic versions: 
Source: Scopus
Source ID: 85075520020

Research output: Contribution to journalArticleScientificpeer-review

Ectopic Beat Detection from Wrist Optical Signals for Sinus Rhythm and Atrial Fibrillation Subjects

Ectopic beats are abnormal cardiac beats originating from a location different than the sino-atrial node and therefore not being controlled by the autonomous nervous system. Thus, correct heart rate variability analysis inevitably requires accurate ectopic beat detection. Furthermore, an accurate ectopic beat detection is crucial to differentiate irregular cardiac rhythm due to different types of pathological arrhythmias from those caused by isolated ectopic beats. In this paper, we present an algorithm for ectopic beat detection based on wrist plethysmographic (PPG) signals. The proposed algorithm relies on analyzing the inter-beat patterns while considering the heart-rhythm condition; whether sinus rhythm (SR) or atrial fibrillation (AF). We monitor 29 patients recovering from surgery in the post-anesthesia care unit. During the recordings, 15 patients had SR and 14 patients had AF. The proposed ectopic beat detection algorithm achieves a sensitivity of and a specificity of 2.12.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Sensor Technology and Biomeasurements (STB), PulseOn SA, Tampere University Hospital, Pulseon Oy, Tampere University
Contributors: Haddad, S., Harju, J., Tarniceriu, A., Halkola, T., Parak, J., Korhonen, I., Yli-Hankala, A., Vehkaoja, A.
Number of pages: 9
Pages: 150-158
Publication date: 2020

Host publication information

Title of host publication: 15th Mediterranean Conference on Medical and Biological Engineering and Computing – MEDICON 2019 - Proceedings of MEDICON 2019
Publisher: Springer
Editors: Henriques, J., de Carvalho, P., Neves, N.
ISBN (Print): 9783030316341

Publication series

Name: IFMBE Proceedings
Volume: 76
ISSN (Print): 1680-0737
ISSN (Electronic): 1433-9277
ASJC Scopus subject areas: Bioengineering, Biomedical Engineering
Keywords: Atrial fibrillation, Ectopic beat detection, Heart rate variability, Photoplethysmography

Bibliographical note

EXT="Parak, Jakub"

Source: Scopus
Source ID: 85075876200

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Tidal breathing flow profiles during sleep in wheezing children measured by impedance pneumography

For the first time, impedance pneumography (IP) enables a continuous analysis of the tidal breathing flow volume (TBFV), overnight. We studied how corticosteroid inhalation treatments, sleep stage, and time from sleep onset modify the nocturnal TBFV profiles of children. Seventy children, 1–5 years old and with recurrent wheezing, underwent three, full-night TBFVs recordings at home, using IP. The first recorded one week before ending a 3-months inhaled corticosteroids treatment, and remaining two, 2 and 4 weeks after treatment. TBFV profiles were grouped by hour from sleep onset and estimated sleep stage. Compared with on-medication, the off-medication profiles showed lower volume at exhalation peak flow, earlier interruption of expiration, and less convex middle expiration. The differences in the first two features were significant during non-rapid eye movement (NREM), and the differences in the third were more prominent during REM after 4 h of sleep. These combinations of TBFV features, sleep phase, and sleep time potentially indicate airflow limitation in young children.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Physiological Measurement Systems and Methods Group, BioMediTech, Revenio Research Ltd., Tampere University Hospital
Contributors: Gracia-Tabuenca, J., Seppä, V., Jauhiainen, M., Paassilta, M., Viik, J., Karjalainen, J.
Publication date: 2020
Peer-reviewed: Yes
Early online date: 1 Oct 2019

Publication information

Journal: Respiratory Physiology and Neurobiology
Volume: 271
Article number: 103312
ISSN (Print): 1569-9048
Original language: English
ASJC Scopus subject areas: Neuroscience(all), Physiology, Pulmonary and Respiratory Medicine
Keywords: Impedance pneumography, Lung function, Tidal breathing, Wheezing children

Bibliographical note

EXT="Seppä, Ville-Pekka"

Source: Scopus
Source ID: 85073034217

Research output: Contribution to journalArticleScientificpeer-review

Analysis of ATP-Induced Ca2+ Responses at Single Cell Level in Retinal Pigment Epithelium Monolayers.

Calcium is one of the most important second messengers in cells and thus involved in a variety of physiological processes. In retinal pigment epithelium (RPE), Ca2+ and its ATP-dependent signaling pathways play important roles in the retina maintenance functions. Changes in intracellular Ca2+ concentration can be measured from living cells by Ca2+ imaging. Combining these measurements with quantitative analysis of Ca2+ response properties enables studies of signaling pathways affecting RPE functions. However, robust tools for response analysis from large cell populations are lacking. We developed MATLAB-based analysis tools for single cell level Ca2+ response data recorded from large fields of intact RPE monolayers. The analysis revealed significant heterogeneity in ATP-induced Ca2+ responses inside cell populations regarding magnitude and response kinetics. Further analysis including response grouping and parameter correlations allowed us to characterize the populations at the level of single cells.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, BioMediTech, University of Tampere
Contributors: Sorvari, J., Viheriälä, T., Ilmarinen, T., Ihalainen, T., Nymark, S.
Number of pages: 6
Pages: 525-530
Publication date: 29 Dec 2019

Host publication information

Title of host publication: Retinal Degenerative Diseases : Mechanisms and Experimental Therapy
Publisher: Springer
ISBN (Print): 978-3-030-27377-4
ISBN (Electronic): 978-3-030-27378-1

Publication series

Name: Advances in Experimental Medicine and Biology
Volume: 1185
ISSN (Print): 0065-2598
ISSN (Electronic): 2214-8019
Keywords: ATP-induced Ca2+ response; Ca2+ imaging; Human embryonic stem cells; Image analysis; Retinal pigment epithelium

Bibliographical note

JUFOID=81217
DUPL=51243317

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Data-driven multiscale modeling reveals the role of metabolic coupling for the spatio-temporal growth dynamics of yeast colonies

Background: Multicellular entities like mammalian tissues or microbial biofilms typically exhibit complex spatial arrangements that are adapted to their specific functions or environments. These structures result from intercellular signaling as well as from the interaction with the environment that allow cells of the same genotype to differentiate into well-organized communities of diversified cells. Despite its importance, our understanding how this cell-cell and metabolic coupling lead to functionally optimized structures is still limited. Results: Here, we present a data-driven spatial framework to computationally investigate the development of yeast colonies as such a multicellular structure in dependence on metabolic capacity. For this purpose, we first developed and parameterized a dynamic cell state and growth model for yeast based on on experimental data from homogeneous liquid media conditions. The inferred model is subsequently used in a spatially coarse-grained model for colony development to investigate the effect of metabolic coupling by calibrating spatial parameters from experimental time-course data of colony growth using state-of-the-art statistical techniques for model uncertainty and parameter estimations. The model is finally validated by independent experimental data of an alternative yeast strain with distinct metabolic characteristics and illustrates the impact of metabolic coupling for structure formation. Conclusions: We introduce a novel model for yeast colony formation, present a statistical methodology for model calibration in a data-driven manner, and demonstrate how the established model can be used to generate predictions across scales by validation against independent measurements of genetically distinct yeast strains.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Systems Biology, Aalto University, University of Washington Seattle, Utah State University, Institute for Systems Biology, Seattle, Washington, USA, University of Luxembourg, University of California San Diego, Pacific Northwest Research Institute
Contributors: Intosalmi, J., Scott, A. C., Hays, M., Flann, N., Yli-Harja, O., Lähdesmäki, H., Dudley, A. M., Skupin, A.
Number of pages: 13
Publication date: 19 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: BMC Molecular and Cell Biology
Volume: 20
Issue number: 1
Article number: 59
ISSN (Print): 2661-8850
Original language: English
ASJC Scopus subject areas: Molecular Biology, Cell Biology
Keywords: Bayesian optimization, Diauxic shift, Markov chain Monte Carlo, Metabolic coupling, Multicellular systems, Multiscale modeling, Yeast colony
Electronic versions: 

Bibliographical note

EXT="Intosalmi, Jukka"
EXT="Lähdesmäki, Harri"

Source: Scopus
Source ID: 85076968105

Research output: Contribution to journalArticleScientificpeer-review

Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor with Multi-Dimensional Anti-Tumor Effect (Running Title: Cancer Cells Death Signalling Activation)

Glioblastoma (GB), a grade IV glioma, with high heterogeneity and chemoresistance, obligates a multidimensional antagonist to debilitate its competence. Considering the previous reports on thioesters as antitumor compounds, this paper investigates on use of this densely functionalized sulphur rich molecule as a potent anti-GB agent. Bio-evaluation of 12 novel compounds, containing α-thioether ketone and orthothioester functionalities, identified that five analogs exhibited better cytotoxic profile compared to standard drug cisplatin. Detailed toxicity studies of top compound were evaluated in two cell lines, using cell viability test, apoptotic activity, oxidative stress and caspase activation and RNA-sequencing analysis, to obtain a comprehensive molecular profile of drug activity. The most effective molecule presented half maximal inhibitory concentration (IC50) values of 27 μM and 23 μM against U87 and LN229 GB cells, respectively. Same compound effectively weakened various angiogenic pathways, mainly MAPK and JAK-STAT pathways, downregulating VEGF. Transcriptome analysis identified significant promotion of apoptotic genes, and genes involved in cell cycle arrest, with concurrent inhibition of various tyrosine kinase cascades and stress response genes. Docking and immunoblotting studies suggest EGFR as a strong target of the orthothioester identified. Therefore, orthothioesters can potentially serve as a multi-dimensional chemotherapeutic possessing strong cytotoxic, anti-angiogenic and chemo-sensitization activity, challenging glioblastoma pathogenesis.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Molecular Signaling Lab, Research group: Computational Systems Biology, BioMediTech, Research group: Predictive Society and Data Analytics (PSDA), Research group: Computational Medicine and Statistical Learning Laboratory (CMSL), Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Department of Biotechnology, Lady Doak College, Thallakulam, Madurai, 625002, India., Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal., Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China., Molecular Signaling Lab, Faculty of Medicine and Health Technology, Tampere University, BioMeditech and Tays Cancer Center, Tampere University Hospital, P.O. Box 553, 33101 Tampere, Finland.
Contributors: Viswanathan, A., Musa, A., Murugesan, A., Vale, J. R., Afonso, C. A. M., Konda Mani, S., Yli-Harja, O., Candeias, N. R., Kandhavelu, M.
Number of pages: 18
Publication date: 12 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Cells
Volume: 8
Issue number: 12
Article number: 1624
ISSN (Print): 2073-4409
Original language: English
Source: PubMed
Source ID: 31842391

Research output: Contribution to journalArticleScientificpeer-review

Synthesis and preclinical validation of novel P2Y1 receptor ligands as a potent anti-prostate cancer agent

Purinergic receptor is a potential drug target for neuropathic pain, Alzheimer disease, and prostate cancer. Focusing on the structure-based ligand discovery, docking analysis on the crystal structure of P2Y1 receptor (P2Y1R) with 923 derivatives of 1-indolinoalkyl 2-phenolic compound is performed to understand the molecular insights of the receptor. The structural model identified the top novel ligands, 426 (compound 1) and 636 (compound 2) having highest binding affinity with the docking score of -7.38 and -6.92. We have reported the interaction efficacy and the dynamics of P2Y1R protein with the ligands. The best hits synthesized were experimentally optimized as a potent P2Y1 agonists. These ligands exhibits anti-proliferative effect against the PC-3 and DU-145 cells (IC50 = 15 µM - 33 µM) with significant increase in the calcium level in dose- and time-dependent manner. Moreover, the activation of P2Y1R induced the apoptosis via Capase3/7 and ROS signaling pathway. Thus it is evidenced that the newly synthesized ligands, as a P2Y1R agonists could potentially act as a therapeutic drug for treating prostate cancer.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Molecular Signaling Lab, Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Department of Crystallography & Biophysics, University of Madras, Guindy Campus, Chennai, 600025, India., Department of Biotechnology, Lady Doak College, Thallakulam, Madurai, 625002, India., Computational Systems Biology Research Group, Faculty of Medicine and Health Technology and BioMediTech, Tampere University, P.O.Box 553, 33101, Tampere, Finland., Institute for Systems Biology, 1441 N 34th Street, Seattle, WA, 98103-8904, USA.
Contributors: Le, H. T. T., Rimpilainen, T., Konda Mani, S., Murugesan, A., Yli-Harja, O., Candeias, N. R., Kandhavelu, M.
Publication date: 12 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Scientific Reports
Volume: 9
Article number: 18938
ISSN (Print): 2045-2322
Original language: English
Source: PubMed
Source ID: 31831761

Research output: Contribution to journalArticleScientificpeer-review

Accelerated simulation of a neuronal population via mathematical model order reduction

Mathematical modeling of biological neuronal net-
works is important in order to increase understanding of the
brain and develop systems capable of brain-like learning. While
mathematical analysis of these comprehensive, stochastic, and
complex models is intractable, and their numerical simulation
is very resource intensive, mean-field modeling is an effective
tool in enabling the analysis of these models. The mean-field
approach allows the study of populations of biophysically detailed
neurons with some assumptions of the mean behaviour of the
population, but ultimately requires numerical solving of high-
dimensional differential equation systems. Mathematical model
order reduction methods can be employed to accelerate the anal-
ysis of high-dimensional nonlinear models with a purely software-
based approach. Here we compare state-of-the-art methods for
improving the simulation time of a neuronal mean-field model
and show that a nonlinear Fokker-Planck-McKean-Vlasov model
can be accurately approximated in low-dimensional subspaces
with these methods. Using Proper Orthogonal Decomposition
and different variations of the Discrete Empirical Interpolation
Method, we improved the simulation time by over three orders
of magnitude while achieving low approximation error.

General information

Publication status: Accepted/In press
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Computing Sciences, Research group: Computational Neuro Science-CNS
Contributors: Lehtimäki, M., Seppälä, I., Paunonen, L., Linne, M.
Publication date: 10 Dec 2019

Host publication information

Title of host publication: Proceedings of the IEEE International Conference on Artificial Intelligence Circuits and Systems
Publisher: IEEE Xplore

Bibliographical note

Ei ilm. 9.1.20 M. K.

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Textile-Based Batteryless Moisture Sensor

In this paper, we established a new type of passive Ultra-High-Frequency (UHF) Radio Frequency Identification (RFID) technology-based sensor with a referenced readout for moisture. We introduced the sensor system, which consisted of a sensor tag and a reference tag. In a highly moist environment, the sensor tag, which was fabricated by embroidery and 3D printing, permanently changed its shape from flat to curved, which then influenced its wireless performance. By recording the backscattered powers of the sensor tag and the unaffected reference tag, the presence of moisture could be detected. Based on our preliminary results, when the mean value of $Delta$P% was higher than 80%, the sensor system indicated exposure to high moisture environment. Our moisture sensing system can provide cost-effective zero-energy monitoring of moisture exposure for versatile application fields.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Wireless Identification and Sensing Systems Research Group
Contributors: Chen, X., He, H., Khan, Z., Sydanheimo, L., Ukkonen, L., Virkki, J.
Publication date: 6 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: IEEE Antennas and Wireless Propagation Letters
ISSN (Print): 1548-5757
Original language: English
Keywords: Antennas, Radiofrequency identification, Moisture, Antenna measurements, Wireless sensor networks, Wireless communication, passive UHF RFID technology, moisture sensor, wireless sensor, 3D printing, embroidery, zero-energy
Electronic versions: 
Source: Bibtex
Source ID: 8926377

Research output: Contribution to journalArticleScientificpeer-review

Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men

The increase in cardiovascular risk associated with metabolic syndrome (MS) seems higher in women than in men. We examined hemodynamics during head-up tilt in 252 men and 250 women without atherosclerosis, diabetes, or antihypertensive medication, mean age 48 years, using whole-body impedance cardiography and radial pulse wave analysis. MS was defined according to Alberti et al. 2009. Men and women with MS presented with corresponding elevations of systolic and diastolic blood pressure (10-14%, p ≤ 0.001) versus controls. Supine pulse wave velocity (16–17%, p < 0.001) and systemic vascular resistance (7–9%, p ≤ 0.026), and upright cardiac output (6–11%, p ≤ 0.008) were higher in both MS groups than controls. Elevation of supine aortic characteristic impedance was higher in women than in men with MS (16% vs. 8%, p = 0.026), and in contrast to men, no upright impedance reduction was observed in women. When upright, women but not men with MS showed faster return of reflected pressure wave (p = 0.036), and smaller decrease in left cardiac work (p = 0.035) versus controls. The faster upright return of reflected pressure, lower upright decrease in left cardiac work, and higher elevation of aortic characteristic impedance may contribute to the greater increase in MS-related cardiovascular risk in women than in men.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University, Tampere University Hospital
Contributors: Kangas, P., Tikkakoski, A., Kettunen, J., Eräranta, A., Huhtala, H., Kähönen, M., Sipilä, K., Mustonen, J., Pörsti, I.
Number of pages: 11
Publication date: 5 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Scientific Reports
Volume: 9
Issue number: 1
Article number: 18377
ISSN (Print): 2045-2322
Original language: English
ASJC Scopus subject areas: General
Electronic versions: 
Source: Scopus
Source ID: 85076028803

Research output: Contribution to journalArticleScientificpeer-review

Comparing biological information contained in mRNA and non-coding RNAs for classification of lung cancer patients

Background

Deciphering the meaning of the human DNA is an outstanding goal which would revolutionize medicine and our way for treating diseases. In recent years, non-coding RNAs have attracted much attention and shown to be functional in part. Yet the importance of these RNAs especially for higher biological functions remains under investigation.

Methods

In this paper, we analyze RNA-seq data, including non-coding and protein coding RNAs, from lung adenocarcinoma patients, a histologic subtype of non-small-cell lung cancer, with deep learning neural networks and other state-of-the-art classification methods. The purpose of our paper is three-fold. First, we compare the classification performance of different versions of deep belief networks with SVMs, decision trees and random forests. Second, we compare the classification capabilities of protein coding and non-coding RNAs. Third, we study the influence of feature selection on the classification performance.

Results

As a result, we find that deep belief networks perform at least competitively to other state-of-the-art classifiers. Second, data from non-coding RNAs perform better than coding RNAs across a number of different classification methods. This demonstrates the equivalence of predictive information as captured by non-coding RNAs compared to protein coding RNAs, conventionally used in computational diagnostics tasks. Third, we find that feature selection has in general a negative effect on the classification performance which means that unfiltered data with all features give the best classification results.

Conclusions

Our study is the first to use ncRNAs beyond miRNAs for the computational classification of cancer and for performing a direct comparison of the classification capabilities of protein coding RNAs and non-coding RNAs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA)
Contributors: Smolander, J., Stupnikov, A., Glazko, G., Dehmer, M., Emmert-Streib, F.
Publication date: 3 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: BMC Cancer
Volume: 19
Issue number: 1
Article number: 1176
ISSN (Print): 1471-2407
Original language: English

Bibliographical note

INT=COMP, "Smolander, Johannes"

Source: RIS
Source ID: urn:FE1C56A6CF0C79C12793BEB3682D35A9

Research output: Contribution to journalArticleScientificpeer-review

Automatic classification of IgA endomysial antibody test for celiac disease: a new method deploying machine learning

Widespread use of endomysial autoantibody (EmA) test in diagnostics of celiac disease is limited due to its subjectivity and its requirement of an expert evaluator. The study aimed to determine whether machine learning can be applied to create a new observer-independent method of automatic assessment and classification of the EmA test for celiac disease. The study material comprised of 2597 high-quality IgA-class EmA images collected in 2017–2018. According to standard procedure, highly-experienced professional classified samples into the following four classes: I - positive, II - negative, III - IgA deficient, and IV - equivocal. Machine learning was deployed to create a classification model. The sensitivity and specificity of the model were 82.84% and 99.40%, respectively. The accuracy was 96.80%. The classification error was 3.20%. The area under the curve was 99.67%, 99.61%, 100%, and 99.89%, for I, II, III, and IV class, respectively. The mean assessment time per image was 16.11 seconds. This is the first study deploying machine learning for the automatic classification of IgA-class EmA test for celiac disease. The results indicate that using machine learning enables quick and precise EmA test analysis that can be further developed to simplify EmA analysis.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group, Tampere University, Tampere University Hospital
Contributors: Caetano dos Santos, F. L., Michalek, I. M., Laurila, K., Kaukinen, K., Hyttinen, J., Lindfors, K.
Publication date: 1 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Scientific Reports
Volume: 9
Issue number: 1
Article number: 9217
ISSN (Print): 2045-2322
Original language: English
ASJC Scopus subject areas: General
Electronic versions: 
Source: Scopus
Source ID: 85068094140

Research output: Contribution to journalArticleScientificpeer-review

Transcription closed and open complex formation coordinate expression of genes with a shared promoter region

Many genes are spaced closely, allowing coordination without explicit control through shared regulatory elements and molecular interactions. We study the dynamics of a stochastic model of a gene-pair in a head-to-head configuration, sharing promoter elements, which accounts for the rate-limiting steps in transcription initiation. We find that only in specific regions of the parameter space of the rate-limiting steps is orderly coexpression exhibited, suggesting that successful cooperation between closely spaced genes requires the coevolution of compatible rate-limiting step configuration. The model predictions are validated using in vivo single-cell, single-RNA measurements of the dynamics of pairs of genes sharing promoter elements. Our results suggest that, in E. coli, the kinetics of the rate-limiting steps in active transcription can play a central role in shaping the dynamics of gene-pairs sharing promoter elements.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Laboratory of Biosystem Dynamics-LBD
Contributors: Häkkinen, A., Oliveira, S. M., Neeli-Venkata, R., Ribeiro, A. S.
Number of pages: 11
Publication date: 1 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of the Royal Society Interface
Volume: 16
Issue number: 161
Article number: 20190507
ISSN (Print): 1742-5689
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biomaterials, Biochemistry, Biomedical Engineering
Keywords: Bidirectional promoter, Gene expression noise, Transcription
Source: Scopus
Source ID: 85076351347

Research output: Contribution to journalArticleScientificpeer-review

Tissue adhesive hyaluronic acid hydrogels for sutureless stem cell delivery and regeneration of corneal epithelium and stroma

Regeneration of a severely damaged cornea necessitates the delivery of both epithelium-renewing limbal epithelial stem cells (LESCs) and stroma-repairing cells, such as human adipose-derived stem cells (hASCs). Currently, limited strategies exist for the delivery of these therapeutic cells with tissue-like cellular organization. With the added risks related to suturing of corneal implants, there is a pressing need to develop new tissue adhesive biomaterials for corneal regeneration. To address these issues, we grafted dopamine moieties into hydrazone-crosslinked hyaluronic acid (HA-DOPA) hydrogels to impart tissue adhesive properties and facilitate covalent surface modification of the gels with basement membrane proteins or peptides. We achieved tissue-like cellular compartmentalization in the implants by encapsulating hASCs inside the hydrogels, with subsequent conjugation of thiolated collagen IV or laminin peptides and LESC seeding on the hydrogel surface. The encapsulated hASCs in HA-DOPA gels exhibited good proliferation and cell elongation, while the LESCs expressed typical limbal epithelial progenitor markers. Importantly, the compartmentalized HA-DOPA implants displayed excellent tissue adhesion upon implantation in a porcine corneal organ culture model. These results encourage sutureless implantation of functional stem cells as the next generation of corneal regeneration.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, BioMediTech, Adult Stem Cell Research Group, Tampere University Hospital, Tampere University
Contributors: Koivusalo, L., Kauppila, M., Samanta, S., Parihar, V. S., Ilmarinen, T., Miettinen, S., P. Oommen, O., Skottman, H.
Publication date: Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Biomaterials
Volume: 225
Article number: 119516
ISSN (Print): 0142-9612
Original language: English

Bibliographical note

dupl=50470647

Source: ORCID
Source ID: /0000-0002-6044-2121/work/62617220

Research output: Contribution to journalArticleScientificpeer-review

Sources of variability in expiratory flow profiles during sleep in healthy young children

Standard lung function tests are not feasible in young children, but recent studies show that the variability of expiratory tidal breathing flow-volume (TBFV) curves during sleep is a potential indirect marker of lower airway obstruction. However, the neurophysiological sources of the TBFV variability in normal subjects has not been established. We investigated sleep stages and body position changes as potential sources for the TBFV curve variability. Simultaneous impedance pneumography (IP), polysomnography (PSG) and video recordings were done in 20 children aged 1-7 years without significant respiratory disorders during sleep. The early part of expiratory TBFV curves are less variable between cycles of REM than NREM sleep. However, within individual sleep cycles, TBFV curves during N3 are the least variable. The differences in TBFV curve shapes between sleep stages are the main source of overnight variability in TBFV curves and the changes in body position have a lesser impact.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Revenio Research Ltd.
Contributors: Hult, A., Juraški, R. G., Gracia-Tabuenca, J., Partinen, M., Plavec, D., Seppä, V.
Publication date: 30 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Respiratory Physiology and Neurobiology
ISSN (Print): 1569-9048
Original language: English
Keywords: Tidal breathing, Flow-volume curves, impedance pneumography, sleep stages, airway obstruction

Bibliographical note

EXT="Seppä, Ville-Pekka"

Source: RIS
Source ID: urn:3F7E0B8AED7341CDE240E2C9693B9C08

Research output: Contribution to journalArticleScientificpeer-review

A device for measuring sternal bone connectivity using vibration analysis techniques

Objectives: Stability of bone splitting sternotomy is essential for normal healing after open cardiac surgery. Mechanical vibration transmittance may offer a means for early detection of separation of bone (diastasis) in the sternotomy and prevent further complications. This article describes the technical implementation and validation of vibration analysis-based prototype device built for measuring sternal bone connectivity after sternotomy. Methods: An in-house built measurement system, sternal vibration device, consisting of actuator, sensor, and main controller and signal acquisition unit was designed and manufactured. The system was validated, and three different test settings were studied in mockups (polylactide rods in ballistic gel) and in two human sternums: intact, stable wire fixation, and unstable wire fixation with a gap mimicking bone diastasis. The transmittance of vibration stimulus across the median sternotomy was measured. Results: The validation showed that the force produced by the actuator was stable, and the sensor could be calibrated to precisely measure the acceleration values. The vibration transmittance response to material cut and sternotomy was evident and detectable in the 20 Hz to 2 kHz band. The transmittance decreased when the connectivity between the sternal halves became unstable. The trend was visible in all the settings. Conclusion: Technical solutions and description of validation process were given. The device was calibrated, and the vibration transmittance analysis differentiated intact and cut polylactide rod. In the sternum, intact bone, wire fixation with exact apposition, and with a gap were identified separately. Although further studies are needed to assess the accuracy of the method to detect different levels of diastases, the method appears to be feasible.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Physiological Measurement Systems and Methods Group, Research group: Computational Biophysics and Imaging Group, Sole Trader Esa Jaatinen
Contributors: Joutsen, A., Hautalahti, J., Jaatinen, E., Goebeler, S., Paldanius, A., Viik, J., Laurikka, J., Hyttinen, J.
Number of pages: 10
Publication date: 15 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine
Article number: 0954411919884802
ISSN (Print): 0954-4119
Original language: English
Keywords: Biomechanical testing, analysis, biomedical devices, bone biomechanics, frequency analysis, sensors, sensor applications, WOUND COMPLICATIONS, MEDIAN STERNOTOMY, CLOSURE, INSTABILITY, DEHISCENCE, ACCURACY
Source: WOS
Source ID: 000497089800001

Research output: Contribution to journalArticleScientificpeer-review

Development and Characterization of Gellan Gum Based Hydrogels for Soft Tissue Engineering Applications

The aim of tissue engineering (TE) is the production of live and functional tissues by combining a biomaterial scaffold, living cells, and a relevant bioactive stimulus. The engineering of soft tissues, such as brain and heart, requires a scaffold material that represents the natural tissue, meaning that it needs to be soft, elastic, flexible, and possibly strain hardening. Additionally, a scaffold material must allow the diffusion of nutrients and the penetration of migrating cells inside the microstructure. Furthermore, the scaffold must provide the encapsulated cells with enough attachment sites to ensure the cells can function in their natural way.

Hydrogels are promising scaffold candidates for soft tissue engineering applications. They are crosslinked, hydrophilic polymer networks with a high water content in the structure. Hydrogels can be produced from a large variety of natural or synthetic polymers by implementing a variety of physical and chemical crosslinking strategies. Here, hydrogels based on the polysaccharide gellan gum are studied in a conclusive manner from both the materials science and biological perspective. The gelation process and chemistry of modified hydrogel-forming biopolymers are characterized. The mechanical properties of the hydrogels as well as their microstructure and the effects of different functionalization strategies on these characteristics are studied in detail. Novel
imaging methods are applied for the analysis of hydrogel microstructure. Similarly, the mechanical properties of the hydrogels are studied using methods that have never before been applied to gels in hydrated form. Then, the newly developed hydrogel formulations are used with human cells for the soft tissue engineering of the two most vital and poorly regenerating organs of the human body – the central nervous system and the heart.

The developed gellan gum-based hydrogels have biomimicking mechanical properties with adjustable stiffness corresponding to either brain or heart muscle tissue, depending on the exact composition used. The elasticity of the hydrogel network enables the spontaneous beating of human induced pluripotent stem cell-derived cardiomyocytes in three-dimensional culture. The polymer network creating the hydrogels is loose enough so that the cells can grow inside and that nutrients and waste products of cell metabolism
can also be transported in and out of the hydrogel. The functionalization of gellan gum with extracellular matrix proteins, such as laminin and collagen-derived gelatin, enhances the cytocompatibility, growth, and elongation of cells cultured in the novel three-dimensional microenvironments

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: Research group: Biomaterials and Tissue Engineering Group, BioMediTech, Heart Group, BioMediTech Institute and Faculty of Medicine and Life Science, University of Tampere
Contributors: Koivisto, J.
Number of pages: 146
Publication date: 15 Nov 2019

Publication information

Place of publication: Tampere
Publisher: Tampere University
Volume: 162
ISBN (Print): 978-952-03-1326-5
ISBN (Electronic): 978-952-03-1327-2
Original language: English

Publication series

Name: Tampere University Dissertations
Volume: 162
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion

Background: Progression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved. Methods: We used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets. Results: Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens. Conclusions: Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Turun yliopisto, Tampere University, University of Eastern Finland, Helsinki University, Fimlab Laboratories
Contributors: Eerola, S. K., Santio, N. M., Rinne, S., Kouvonen, P., Corthals, G. L., Scaravilli, M., Scala, G., Serra, A., Greco, D., Ruusuvuori, P., Latonen, L., Rainio, E. M., Visakorpi, T., Koskinen, P. J.
Publication date: 15 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: CELL COMMUNICATION AND SIGNALING
Volume: 17
Issue number: 1
Article number: 148
ISSN (Print): 1478-811X
Original language: English
ASJC Scopus subject areas: Biochemistry, Molecular Biology, Cell Biology
Keywords: Cell motility, Metastatic carcinoma, NFATC1, PIM kinases, Prostate cancer
Electronic versions: 
Source: Scopus
Source ID: 85075057648

Research output: Contribution to journalArticleScientificpeer-review

Utilizing Social Media Data for Psychoanalysis to Study Human Personality

Social media data, for instance from Twitter or Facebook, provide a new type of data that consist of a mixture of text, image and video information. From a scientific point of view, the capabilities of this type of data from such microblogs are not well explored and to date it is largely unknown what principal knowledge can be extracted thereof. In this paper, we present a discussion of the capabilities of data from microblogs for performing a psychoanalysis. This could allow an analysis of the human personality of individual users. Such prospects raises serious concerns regarding the privacy of users of social media platforms.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA), BioMediTech, Research group: Computational Systems Biology, University of Applied Sciences Upper Austria, School of Management, Hall in Tyrol, Nankai University
Contributors: Emmert-Streib, F., Yli-Harja, O., Dehmer, M.
Publication date: 15 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Psychology
Volume: 10
Article number: 2596
ISSN (Print): 1664-1078
Original language: English
ASJC Scopus subject areas: Psychology(all)
Keywords: computational social science, data science, privacy, psychoanalysis, psychology
Source: Scopus
Source ID: 85075971230

Research output: Contribution to journalArticleScientificpeer-review

Model order reduction of multiscale models in neuroscience

The current trend in computational neuroscience is to incorporate multiple physical levels of the brain into mathematical models, which often results in large networks of interconnected neural cells. Comprehensive models with accurate system dynamics are necessary in order to increase understanding of different mechanisms in the whole brain, but these models are analytically intractable. Additionally, their numerical simulation is very resource intensive. Useful ways of mitigating the computational burden include using a mean-field approach, as well as mathematical model order reduction (MOR).

Using mean-field approximation, one can account for the random fluctuations of variables by replacing them by their mean averages. The cells are grouped together into populations based on their statistical similarities, in order to represent the dynamics of the system in terms of the averaged out ensemble behaviour. These populations can then be described by a probability density function expressing the distribution of neuronal states at a given time. This approach ensures that the essential system dynamics converge to a stationary attractor consistent with the steady-state dynamics of the original system.Here we use the Fokker-Planck formalism, which results in a nonlinear system of partial differential equations (PDEs).

PDE systems can be difficult to solve analytically, and thus discretisation for numerical analysis is necessary. This discretisation often leads to very high-dimensional numerical models that correspond to equally high computational demand. Discretised PDE systems can be reduced using mathematical model order reduction methods [1]. MOR methods are well established in engineering sciences, such as control theory, as they improve computational efficiency of simulations of large-scale nonlinear mathematical models. In computational neuroscience MOR is underutilised, although the potential benefits in enabling multilevel simulations are obvious [2].

In this study we use mathematical MOR methods to reduce the dimensions of a PDE model derived using the mean-field approach. The system can be reduced with minimal information loss, by deriving a subspace that approximates the entire system and its dynamics with a smaller number of dimensions compared to the original model. Here we use Proper Orthogonal Decomposition with Discrete Empirical Interpolation Method (POD+DEIM), a subspace projection method for reducing the dimensionality of general nonlinear systems [1]. By applying these methods, the simulation time of the model is radically shortened, albeit not without dimension-dependent approximation error. The tolerated amount of inaccuracy depends on the final application of the model.

Due to being well-suited for depicting mesoscopic behaviour, the mean-field approach in combination with the POD+DEIM method allows us to describe the behaviour of any large multiscale brain model with a relatively low computational burden. This can be particularly useful when attempting to model whole-brain connectivity, for which there is an immediate demand in clinical and robotic applications.

1.Chaturantabut, S. and Sorensen, D.C., Nonlinear model reduction via discrete empirical interpolation. SIAM Journal on Scientific Computing. 2010, 32(5),pp.2737-2764.
2. Lehtimäki, M. , Paunonen, L., Pohjolainen, S. and Linne, M.-L., Order reduction for a signaling pathway model of neuronal synaptic plasticity. IFAC Papers OnLine. 2017, 50-1:7687–7692.

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: BioMediTech, Computing Sciences
Contributors: Seppälä, I., Lehtimäki, M., Paunonen, L., Linne, M.
Publication date: 14 Nov 2019
Peer-reviewed: Unknown
Event: Paper presented at 28th Annual Computational Neuroscience Meeting (CNS*2019), Barcelona, Spain.
Keywords: Neuroscience, Control theory, model reduction

Bibliographical note

Best poster award

Research output: Other conference contributionPaper, poster or abstractScientific

Kinetic Energy Harvesting for Wearable Medical Sensors

The process of collecting low-level kinetic energy, which is present in all moving systems, by using energy harvesting principles, is of particular interest in wearable technology, especially in ultra-low power devices for medical applications. In fact, the replacement of batteries with innovative piezoelectric energy harvesting devices can result in mass and size reduction, favoring the miniaturization of wearable devices, as well as drastically increasing their autonomy. The aim of this work is to assess the power requirements of wearable sensors for medical applications, and address the intrinsic problem of piezoelectric kinetic energy harvesting devices that can be used to power them; namely, the narrow area of optimal operation around the eigenfrequencies of a specific device. This is achieved by using complex numerical models comprising modal, harmonic and transient analyses. In order to overcome the random nature of excitations generated by human motion, novel excitation modalities are investigated with the goal of increasing the specific power outputs. A solution embracing an optimized harvester geometry and relying on an excitation mechanism suitable for wearable medical sensors is hence proposed. The electrical circuitry required for efficient energy management is considered as well.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electrical Engineering, Research area: Power engineering
Contributors: Gljušćić, P., Zelenika, S., Blažević, D., Kamenar, E.
Publication date: 12 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 19
Issue number: 4922
ISSN (Print): 1424-8220
Original language: English
Source: ORCID
Source ID: /0000-0001-9287-6146/work/64569210

Research output: Contribution to journalArticleScientificpeer-review

General principles for the validation of proarrhythmia risk prediction models: an extension of the CiPA In Silico strategy

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group, University of Bologna, University of Oxford
Contributors: Li, Z., Mirams, G., Yoshinaga, T., Ridder, B., Han, X., Chen, J. E., Stockbridge, N. L., Wisialowski, T. A., Damiano, B., Severi, S., Morissette, P., Kowey, P. R., Holbrook, M., Smith, G., Rasmusson, R. L., Liu, M., Song, Z., Qu, Z., Leishman, D. J., Steidl‐Nichols, J., Rodriguez, B., Bueno-Orovio, A., Zhou, X., Passini, E., Edwards, A. G., Morotti, S., Ni, H., Grandi, E., Clancy, C. E., Vandenberg, J., Hill, A., Nakamura, M., Singer, T., Polonchuk, L., Greiter‐Wilke, A., Wang, K., Nave, S., Fullerton, A., Sobie, E. A., Paci, M., Tshinanu, F. M., Strauss, D. G.
Number of pages: 10
Publication date: 10 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: CLINICAL PHARMACOLOGY AND THERAPEUTICS
ISSN (Print): 0009-9236
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Alternative Electrode Materials for Prototyping Cell Model-Specific Microelectrode Arrays

A microelectrode array, MEA, is a tool used by biologists for measuring the electrical activity of cells in vitro. Instead of only studying random cell clusters and monolayers, an increasing number of biological research questions are aimed at studying welldefined cell networks or single cells. This places special demands on the location, size, and overall performance of the MEA electrodes, which the standard, commercially available layouts cannot usually meet. Therefore, custom-designed MEAs are needed for a wide range of applications from basic cell biology and disease model development to toxicity testing and drug screening. This thesis focuses on the fabrication of microelectrodes made of titanium, atomic layer deposited (ALD) iridium oxide (IrOx), and ion beam-assisted e-beam deposited (IBAD) titanium nitride (TiN). These MEAs are characterized, for example, in terms of their impedance, noise level, and surface morphology, and their biocompatibility and functionality are verified by simple experiments with human stem cell-derived neuronal cells and cardiomyocytes. The aim of these studies is to offer more alternatives for MEA fabrication, enabling researchers and practitioners to choose the electrode material that best fits their application from their available resources. Pure titanium is commonly disregarded as an electrode material because of its oxidation tendency, which destabilizes the electrical performance. However, when prototyping customised MEAs, the time and cost of fabricating the subsequent iterations of the prototype can be more decisive factors than the device’s ultimate electrical performance, which is typically evaluated by the impedance value at 1 kHz. As might be expected, although titanium electrodes underperformed in terms of impedance (>1700 kΩ), when used in the cell experiments, the field potentials from both neuronal cells and cardiomyocytes were still easily distinguishable from the noise. There are a number of benefits to using titanium as an electrode material. Besides the fact that it is about hundred times cheaper than other commonly-used materials, such as gold or platinum, it usually requires fewer and often simpler process steps than the most common alternatives. IrOx and TiN are common electrode coatings which, when applied on top of e.g. a titanium electrode, can lower the impedance and the noise level of the electrode. In this study, two alternative deposition methods, ALD and IBAD, were used for IrOx and TiN in MEA applications. Even if the impedance of these 30 μm electrodes (450 kΩ for ALD IrOx and ~90 kΩ for IBAD TiN) did not quite reach the impedance levels of the industry standards, i.e. sputtered TiN (30-50 kΩ) and Pt black (20-30 kΩ), in cell experiments the IBAD TiN electrodes in particular showed no tangible differences in peak amplitudes and noise levels compared with sputtered TiN electrodes. This makes IBAD TiN an attractive alternative material for those who prefer to use TiN electrodes, but do not have access to a sputter coater, for example. ALD IrOx, on the other hand, relies on the potential of the general properties of ALD and IrOx (yet unverified) to provide exceptional performance in designs requiring excellent step coverage or stimulation capability. Finally, as an application example of a custom-designed MEA, a version capable of measuring cardiomyocytes at the single-cell level was developed. The benefit of such an MEA is to offer a unique noninvasive method to study single cells without destroying them with the time-consuming patch clamp method, and without losing cell-specific information, which often occurs if the cell clusters studied with standard MEAs are too heterogenous. This was achieved with a number of innovations. For example, the electrodes were placed near the perimeter of the cell culturing area and had a larger diameter (80 μm) than the usual 30 μm electrodes. This simplified the plating of the cells to the electrodes and enabled the beating of the cells to be electrically recorded. It is also possible to combine that with image-based analysis of mechanical beating through transparent indium tin oxide (ITO) electrodes.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: BioMediTech
Contributors: Ryynänen, T.
Number of pages: 82
Publication date: 8 Nov 2019

Publication information

Publisher: Tampere University
Volume: 123
ISBN (Print): 978-952-03-1230-5
ISBN (Electronic): 978-952-03-1231-2
Original language: English

Publication series

Name: Tampere University Dissertations
Volume: 123
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks

New strategies for spatially controlled growth of human neurons may provide viable solutions to treat and recover peripheral or spinal cord injuries. While topography cues are known to promote attachment and direct proliferation of many cell types, guided outgrowth of human neurites has been found difficult to achieve so far. Here, three-dimensional (3D) micropatterned carbon nanotube (CNT) templates are used to effectively direct human neurite stem cell growth. By exploiting the mechanical flexibility, electrically conductivity and texture of the 3D CNT micropillars, a perfect environment is created to achieve specific guidance of human neurites, which may lead to enhanced therapeutic effects within the injured spinal cord or peripheral nerves. It is found that the 3D CNT micropillars grant excellent anchoring for adjacent neurites to form seamless neuronal networks that can be grown to any arbitrary shape and size. Apart from clear practical relevance in regenerative medicine, these results using the CNT based templates on Si chips also can pave the road for new types of microelectrode arrays to study cell network electrophysiology. [Figure not available: see fulltext.].

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Biomaterials and Tissue Engineering Group, BioMediTech, Univ of Oulu, NeuroGroup, Rice University, Tampere University, Tampere University
Contributors: Lorite, G. S., Ylä-Outinen, L., Janssen, L., Pitkänen, O., Joki, T., Koivisto, J. T., Kellomäki, M., Vajtai, R., Narkilahti, S., Kordas, K.
Number of pages: 6
Pages: 2894-2899
Publication date: 1 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Nano Research
Volume: 12
Issue number: 11
ISSN (Print): 1998-0124
Original language: English
ASJC Scopus subject areas: Materials Science(all), Electrical and Electronic Engineering
Keywords: carbon nanotubes, guided neurite outgrowth, human neural stem cells, multiple cues, neuronal networks
Source: Scopus
Source ID: 85074254867

Research output: Contribution to journalArticleScientificpeer-review

Hyaluronan derived nanoparticle for simvastatin delivery: evaluation of simvastatin induced myotoxicity in tissue engineered skeletal muscle

Statins are currently the most prescribed hypercholesterolemia-lowering drugs worldwide, with estimated usage approaching one-sixth of the population. However, statins are known to cause pleiotropic skeletal myopathies in 1.5% to 10% of patients and the mechanisms by which statins induce this response, are not fully understood. In this study, a 3D collagen-based tissue-engineered skeletal muscle construct is utilised as a screening platform to test the efficacy and toxicity of a new delivery system. A hyaluronic acid derived nanoparticle loaded with simvastatin (HA-SIM-NPs) is designed and the effect of free simvastatin and HA-SIM-NPs on cellular, molecular and tissue response is investigated. Morphological ablation of myo-tubes and lack of de novo myotube formation (regeneration) was evident at the highest concentrations (333.33 µM), independent of delivery vehicle (SIM or HA-SIM-NP). A dose-dependent disruption of the cytoskeleton, reductions in metabolic activity and tissue engineered (TE) construct tissue relaxation was evident in the free drug condition (SIM, 3.33 µM and 33.33 nM). However, most of these changes were ameliorated when SIM was delivered via HA-SIM-NPs. Significantly, homogeneous expressions of MMP2, MMP9, and myogenin in HA-SIM-NPs outlined enhanced regenerative responses compared to SIM. Together, these results outline statin delivery via HA-SIM-NP as an effective delivery mechanism to inhibit deleterious myotoxic side-effects.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group
Contributors: Jones, J. M., Player, D. J., Samanta, S., Rangasami, V. K., Hilborn, J., Lewis, M. P., P. Oommen, O., Mudera, V.
Publication date: 1 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Biomaterials Science
ISSN (Print): 2047-4830
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films

In vitro cell culture models representing the physiological and pathological features of the outer retina are urgently needed. Artificial tissue replacements for patients suffering from degenerative retinal diseases are similarly in great demand. Here, we developed a co-culture system based solely on the use of human induced pluripotent stem cell (hiPSC)-derived cells. For the first time, hiPSC-derived retinal pigment epithelium (RPE) and endothelial cells (EC) were cultured on opposite sides of porous polylactide substrates prepared by breath figures (BF), where both surfaces had been collagen-coated by Langmuir–Schaefer (LS) technology. Small modifications of casting conditions during material preparation allowed the production of free-standing materials with distinct porosity, wettability and ion diffusion capacity. Complete pore coverage was achieved by the collagen coating procedure, resulting in a detectable nanoscale topography. Primary retinal endothelial cells (ACBRI181) and umbilical cord vein endothelial cells (hUVEC) were utilised as EC references. Mono-cultures of all ECs were prepared for comparison. All tested materials supported cell attachment and growth. In mono-culture, properties of the materials had a major effect on the growth of all ECs. In co-culture, the presence of hiPSC-RPE affected the primary ECs more significantly than hiPSC-EC. In consistency, hiPSC-RPE were also less affected by hiPSC-EC than by the primary ECs. Finally, our results show that the modulation of the porosity of the materials can promote or prevent EC migration.

In short, we showed that the behaviour of the cells is highly dependent on the three main variables of the study: the presence of a second cell type in co-culture, the source of endothelial cells and the biomaterial properties. The combination of BF and LS methodologies is a powerful strategy to develop thin but stable materials enabling cell growth and modulation of cell-cell contact.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Research group: Micro and Nanosystems Research Group, Heart Group, BioMediTech Institute and Faculty of Medicine and Life Science, University of Tampere, The Heart Center, Tampere University Hospital , Univ Tampere, University of Tampere, BioMediTech, BMT FM5, BioMediTech, Tampere University, Tampere University Hospital, Tampere University, University of Tampere, Adult Stem Cell Research Group
Contributors: Rebelo Calejo, T., Vuorenpää, H., Vuorimaa-Laukkanen, E., Kallio, P., Aalto-Setälä, K., Miettinen, S., Skottman, H., Kellomäki, M., Juuti-Uusitalo, K.
Pages: 327-343
Publication date: Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Acta Biomaterialia
ISSN (Print): 1742-7061
Original language: English
Keywords: Polylactide, Breath figures, Co-culture, hiPSC-endothelial cells, hiPSC-RPE
Electronic versions: 

Bibliographical note

INT=BMTE,"Saari, Jaakko"
INT=BMTE,"Vuorenpää, Hanna"
INT=BMTE,"Aalto-Setälä, Katriina"
INT=BMTE,"Miettinen, Susanna"
INT=BMTE,"Skottman, Heli"
INT=BMTE,"Juuti-Uusitalo, Kati"

Research output: Contribution to journalArticleScientificpeer-review

A Smart Chair Physiotherapy Exergame for Fall Prevention – User Experience Study

Older adults form a large and increasing proportion of the world’s population, with falls representing one of the major causes of their mortality and morbidity. When considering the aging population, falls and fall-related injuries pose a major challenge, affecting continued ability to perform activities of daily living (ADLs), independence, and quality of life. With the emergence of smart furniture technologies, opportunities arise within the health and rehabilitation sector. Amalgamating technology with game orientated exercise (exergames) facilitates the delivery of entertaining, complimentary tools in the provision of preventative and rehabilitative intervention. The aim of this paper is to study the potential of an exergame for seniors’ physical activation. In this study, a prototype physiotherapeutic exergames based on a smart chair was developed in collaboration with physiotherapists and game developers. User experiences were then investigated through a demo event to investigate the motivation, interest, social interaction, and suitability of the game concept for self-initiated physical training. User experience data was gathered based on researchers’ observations and a questionnaire. This data was collected from users (older adults) and facilitators (social and health care professionals and students). The results indicate the game and the chair controller to be suitable and accepted by elderly as a mean of self-activation and physical training. The game concept also showed potential in enhancing social interaction in a group-setting. Although the responses from the participants show some variation, generally the results indicate feeling of usefulness and need for exergames. More research is required to investigate the long-term effects of the games on user experiences, physical/social effects, and potential decrease of fall risk.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Wireless Identification and Sensing Systems Research Group
Contributors: Merilampi, S., Mulholland, K., Ihanakangas, V., Ojala, J., Valo, P., Virkki, J.
Number of pages: 5
Publication date: 28 Oct 2019

Host publication information

Title of host publication: 2019 IEEE 7th International Conference on Serious Games and Applications for Health (SeGAH)
Publisher: IEEE
ISBN (Print): 978-1-7281-0301-3
ISBN (Electronic): 978-1-7281-0300-6

Publication series

Name: IEEE International Conference on Serious Games and Applications for Health
ISSN (Print): 2330-5649
ISSN (Electronic): 2573-3060
Keywords: Games, Prototypes, Training, Senior citizens, Medical services, Visualization, physical ability, fall-prevention, older adults, recreation, self-managed rehabilitation, serious games

Bibliographical note

EXT="Merilampi, Sari"

Source: Bibtex
Source ID: 8882482

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Noninvasive Cardiorespiratory Signals Analysis for Asthma Evolution Monitoring in Preschool Children

Objective: Despite its increasing prevalence, diagnosis of asthma in children remains problematic due to their difficulties in producing repeatable spirometric maneuvers. Moreover, low adherence to inhaled corticosteroids (ICS) treatment could result in permanent airway remodeling. The growing interest in a noninvasive and objective way for monitoring asthma, together with the apparent role of autonomic nervous system (ANS) in its pathogenesis, have attracted interest towards heart rate variability (HRV) and cardiorespiratory coupling (CRC) analyses. Methods: HRV and CRC were analyzed in 70 children who were prescribed ICS treatment due to recurrent obstructive bronchitis. They underwent three different electrocardiogram and respiratory signals recordings, during and after treatment period. After treatment completion, they were followed up during 6 months and classified attending to their current asthma status. Results: Vagal activity, as measured from HRV, and CRC, were reduced after treatment in those children at lower risk of asthma, whereas it kept unchanged in those with a worse prognosis. Conclusion: Results suggest that HRV analysis could be useful for the continuous monitoring of ANS anomalies present in asthma, thus contributing to evaluate the evolution of the disease, which is especially challenging in young children. Significance: Noninvasive ANS assessment using HRV analysis could be useful in the continuous monitoring of asthma in children.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Physiological Measurement Systems and Methods Group, BioMediTech
Contributors: Milagro, J., Gracia, J., Seppä, V., Karjalainen, J., Paassilta, M., Orini, M., Bailón, R., Gil, E., Viik, J.
Publication date: 28 Oct 2019
Peer-reviewed: Yes

Publication information

Journal: IEEE Transactions on Biomedical Engineering
ISSN (Print): 0018-9294
Original language: English
Keywords: Respiratory system, Heart rate variability, Integrated circuits, Monitoring, Pediatrics, IP networks, Signal to noise ratio, asthma, heart rate variability, children, inhaled corticosteroids, obstructive bronchitis

Bibliographical note

EXT="Seppä, Ville-Pekka"

Source: Bibtex
Source ID: 8884104

Research output: Contribution to journalArticleScientificpeer-review

Direct Measurement of Contraction Force in Human Cardiac Tissue Model Using Piezoelectric Cantilever Sensor Technique

A proof-of-concept method for measuring cardiac tissue contraction force using an in-house-developed piezoelectric cantilever sensor system is demonstrated. Contracting forces of 7.2 to 16.6 μN were measured from a human cardiac tissue construct. Beating cardiac tissue constructs were monitored in-situ under a microscope during the contraction force measurements. Development of the measurement method allows very low forces such as the ones that appear in biological small scale systems to be determined.

General information

Publication status: Accepted/In press
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Tampere University
Contributors: Virtanen, J., Toivanen, M., Toimela, T., Heinonen, T., Tuukkanen, S.
Number of pages: 6
Pages: 155-160
Publication date: 25 Oct 2019
Peer-reviewed: Yes

Publication information

Journal: Current Applied Physics
Volume: 20
Issue number: 1
ISSN (Print): 1567-1739
Original language: English
Keywords: cardiomyocyte, piezoelectric sensor, cantilever, contraction force
URLs: 

Research output: Contribution to journalArticleScientificpeer-review

Wireless Power Transfer to Intra-Abdominal Implants Using an Around-the-Body Loop Antenna

We study the wireless powering of intra-abdominal implants using a wearable around-the-body loop antenna. The study includes the wireless link characterization and modelling of the specific absorption rate (SAR) obtained by an anatomical human body model and a simplified homogenous elliptic cylinder model. We also assess the robustness of the system in terms of the power gain uniformity at the cross-sectional plane of the abdominal cavity. Overall, our system achieves the link power efficiency of −6.6 dB at 7.25 MHz to an implant (2.3-by-2.3 cm square loop) at the center of the abdominal cavity. According to SAR analysis, under the 1.6 W/kg limit, we can transmit 530 mW and the maximum power available at the implant is 149 mW with the voltage amplitude of 3.6 V. Moreover, the voltage at the implant remains above 1 V for transmission power levels down to 10% of the maximum.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Wireless Identification and Sensing Systems Research Group
Contributors: Ahmed, S., Sydänheimo, L., Ukkonen, L., Björninen, T.
Number of pages: 5
Pages: 0055-0059
Publication date: 24 Oct 2019

Host publication information

Title of host publication: 2019 International Conference on Electromagnetics in Advanced Applications (ICEAA)
Publisher: IEEE
ISBN (Print): 978-1-7281-0564-2
ISBN (Electronic): 978-1-7281-0563-5
Keywords: Implants, Biological system modeling, Wireless communication, Transmitting antennas, Mathematical model, Wireless sensor networks, Wireless power transfer, power transfer efficiency, implant antenna, intra-abdominal implants
Source: Bibtex
Source ID: 8879253

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Estimating RNA numbers in single cells by RNA fluorescent tagging and flow cytometry

Estimating the statistics of single-cell RNA numbers has become a key source of information on gene expression dynamics. One of the most informative methods of in vivo single-RNA detection is MS2d-GFP tagging. So far, it requires microscopy and laborious semi-manual image analysis, which hampers the amount of collectable data. To overcome this limitation, we present a new methodology for quantifying the mean, standard deviation, and skewness of single-cell distributions of RNA numbers, from flow cytometry data on cells expressing RNA tagged with MS2d-GFP. The quantification method, based on scaling flow-cytometry data from microscopy single-cell data on integer-valued RNA numbers, is shown to readily produce precise, big data on in vivo single-cell distributions of RNA numbers and, thus, can assist in studies of transcription dynamics.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, BioMediTech, Boston University
Contributors: Bahrudeen, M. N., Chauhan, V., Palma, C. S., Oliveira, S. M., Kandavalli, V. K., Ribeiro, A. S.
Publication date: 22 Oct 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Microbiological Methods
Volume: 166
Article number: 105745
ISSN (Print): 0167-7012
Original language: English
ASJC Scopus subject areas: Microbiology, Molecular Biology, Microbiology (medical)
Keywords: Flow cytometry, MS2d-GFP RNA tagging, Single-cell RNA numbers, Time-lapse microscopy
Electronic versions: 

Bibliographical note

DUPL=50893300

Source: Scopus
Source ID: 85073824125

Research output: Contribution to journalArticleScientificpeer-review

3D-Printed Whole Prostate Models with Tumor Hotspots Using Dual-Extruder Printer

3D printing has emerged as a popular technology in various biomedical applications. Physical models of anatomical structures concretize the digital representations and can be used for teaching and analysis. In this study we combine 3D histology with 3D printing, creating realistic physical models of tissues with hotspots of interest. As an example we use mouse prostates containing tumors. Surface meshes are created from binary masks of HE-stained serial sections of mouse prostates and manually annotated tumor areas. Sections are interpolated to expand sparse image stacks for smoother results. Fiji, Meshlab and Tinkercad are used for mesh creation and processing. Objects are printed with Prusa-based dual-extruder printer enabling different colors for tumors and the surrounding prostate tissue. Our 3D-printed mouse prostates appear realistic and tumors located at the edges of the organ are clearly visible. When transparent filament is used, the tumor hotspots are visible even when they are inside the prostate.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Computational Systems Biology, Research group: Data-analytics and Optimization
Contributors: Liimatainen, K., Latonen, L., Kartasalo, K., Ruusuvuori, P.
Number of pages: 5
Pages: 2867-2871
Publication date: 7 Oct 2019

Host publication information

Title of host publication: 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
Publisher: IEEE
ISBN (Print): 978-1-5386-1312-2
ISBN (Electronic): 978-1-5386-1311-5

Publication series

Name: Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
ISSN (Print): 1557-170X
ISSN (Electronic): 1558-4615
Keywords: Tumors, Solid modeling, Three-dimensional displays, Biological system modeling, Interpolation, Three-dimensional printing, Models of organ physiology, Organ modeling

Bibliographical note

51545730

Source: Bibtex
Source ID: 8857068

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Augmenting Soft Tissue Contrast Using Edge-Enhancing Phase-Imaging Techniques in X-Ray Microtomography

Conventional X-ray imaging is based on the attenuation of X-rays and the technique provides sufficient contrast when the difference between attenuation coefficients of neighboring structures is sufficient. A promising imaging possibility on a µCT is the use of phase information of an X-ray beam to generate an image of the sample. This is known as phase-contrast imaging. Propagation-based phase imaging sets the least amount of requirements on the imaging setup - lateral coherence for the X-ray source and a movable detector and source. The Zeiss Xradia MicroXCT-400 at our laboratory provides this possibility. Therefore, the phase-contrast imaging protocol, which provides an edge-enhancement effect, on the µCT device was optimized using thin polylactic acid fibers in order to enhance the visibility of low density samples. The optimization consisted of source and detector distance variation measurements. To demonstrate the contrast enhancement results, the optimization was applied to two types of collagen samples embedded in air, ethanol, and water.The results showed enhanced contrast for the edge-enhanced phase-contrast images compared to absorption images. Most importantly, the results indicated that the source does not need to placed at the negative limit to obtain useful phase information. Additionally, the visibility increases with increasing sample-to-detector distance. Finally, significantly enhanced contrast was obtained for the collagen sample embedded in water using phase-imaging techniques. The technique is limited due to the focal spot size and voltage of the X-ray source. The phase-imaging technique has the possibility to enhance contrast of low density samples and to reveal structures that cannot be seen using other imaging techniques.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group
Contributors: Reunamo, A., Hannula, M., Hyttinen, J.
Number of pages: 4
Pages: 4867-4870
Publication date: 7 Oct 2019

Host publication information

Title of host publication: 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
Publisher: IEEE
ISBN (Print): 978-1-5386-1312-2
ISBN (Electronic): 978-1-5386-1311-5

Publication series

Name: Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
ISSN (Print): 1557-170X
ISSN (Electronic): 1558-4615
Keywords: Detectors, Image edge detection, Absorption, X-ray imaging, Tomography, Programmable logic arrays

Bibliographical note

dupl=51545698

Source: Bibtex
Source ID: 8857017

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Effect of Different ECG Leads on Estimated R–R Intervals and Heart Rate Variability Parameters

Heart rate and heart rate variability parameters provide important information on sympathetic and parasympathetic branches of autonomous nervous system. These parameters are usually extracted from electrocardiograms often measured between two electrodes and called an ECG lead. Besides systems intended only for heart rate measurement, ECG measurement devices employ several well-known lead systems including the standard 12-lead system, EASI lead system and Mason-Likar systems. Therefore, the first step is to select the appropriate lead for heart rate variability analysis. The appropriate electrode locations for single-lead measurement systems or the preferred measurement lead in multi-lead measurement are choices that the user needs to make when the heart rate variability is of interest. However, it has not been addressed in the literature, if the lead selection has an effect on the obtained HRV parameters. In this work, we characterized the amount of deviation of heart rate and heart rate variability parameters extracted from nine ECG leads, six from EASI leads and three modified limb leads. The results showed a deviation of 2.04, 2.88, 2.06 and 3.45 ms in SDNN, rMSSD, SD1 and SD2, respectively. A relative difference up to 10% was observed in HRV parameters for single signal frames. Additionally, the discrimination of the R-peaks by amplitudes was evaluated. The A–S lead appeared to have the best performance in all the tests.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Research group: Sensor Technology and Biomeasurements (STB), BioMediTech, Electrical Engineering, Research group: Wireless Communications and Positioning
Contributors: Jeyhani, V., Mäntysalo, M., Noponen, K., Seppänen, T., Vehkaoja, A.
Number of pages: 5
Pages: 3786-3790
Publication date: 7 Oct 2019

Host publication information

Title of host publication: 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
Publisher: IEEE
ISBN (Print): 978-1-5386-1312-2
ISBN (Electronic): 978-1-5386-1311-5

Publication series

Name: Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
ISSN (Print): 1557-170X
ISSN (Electronic): 1558-4615
Keywords: Heart rate variability, Lead, Electrocardiography, Electrodes, Rail to rail inputs, Standards
Source: Bibtex
Source ID: 8857954

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Prediction of Self-Perceived Stress and Arousal Based on Electrodermal Activity

Electrodermal activity (EDA) reflects the functions of autonomic nervous system and is often used in evaluation of mental states, e.g. short- and long-term stress. In this study, test subjects were exposed to a 3-phase adapted MIST test (relaxation, arousal, stress) during which EDA was recorded, and the self-perceived stress and arousal were assessed. The objective of the study was to evaluate the feasibility of EDA features to predict the MIST test phases and self-perceived stress and arousal. With EDA features, the test phases were classified with accuracy of 94.1%, and the self-perceived stress and arousal were classified with accuracy of 60.5–72.2%. Results are promising for the use of EDA for long-term assessment of self-perceived stress and arousal during work.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Personal Health Informatics-PHI
Contributors: Pakarinen, T., Pietilä, J., Nieminen, H.
Number of pages: 5
Pages: 2191-2195
Publication date: 7 Oct 2019

Host publication information

Title of host publication: 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
Publisher: IEEE
ISBN (Print): 978-1-5386-1312-2
ISBN (Electronic): 978-1-5386-1311-5

Publication series

Name: Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
ISSN (Print): 1557-170X
ISSN (Electronic): 1558-4615
Keywords: Stress, Stress measurement, Physiology, Task analysis, Support vector machines, Mathematical model, Correlation
Source: Bibtex
Source ID: 8857621

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells in a three-dimensional environment

Cell therapy combined with biomaterial scaffolds is used to treat cartilage defects. We hypothesized that chondrogenic differentiation bone marrow-derived mesenchymal stem cells (BM-MSCs) in three-dimensional biomaterial scaffolds would initiate cartilaginous matrix deposition and prepare the construct for cartilage regeneration in situ. The chondrogenic capability of human BM-MSCs was first verified in a pellet culture. The BM-MSCs were then either seeded onto a composite scaffold rhCo-PLA combining polylactide and collagen type II (C2) or type III (C3), or commercial collagen type I/III membrane (CG). The BM-MSCs were either cultured in a proliferation medium or chondrogenic culture medium. Adult human chondrocytes (ACs) served as controls. After 3, 14, and 28 days, the constructs were analyzed with quantitative polymerase chain reaction and confocal microscopy and sulfated glycosaminoglycans (GAGs) were measured. The differentiated BM-MSCs entered a hypertrophic state by Day 14 of culture. The ACs showed dedifferentiation with no expression of chondrogenic genes and low amount of GAG. The CG membrane induced the highest expression levels of hypertrophic genes. The two different collagen types in composite scaffolds yielded similar results. Regardless of the biomaterial scaffold, culturing BM-MSCs in chondrogenic differentiation medium resulted in chondrocyte hypertrophy. Thus, caution for cell fate is required when designing cell-biomaterial constructs for cartilage regeneration.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electrical Engineering
Contributors: Salonius, E., Kontturi, L., Laitinen, A., Haaparanta, A., Korhonen, M., Nystedt, J., Kiviranta, I., Muhonen, V.
Number of pages: 11
Publication date: 25 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Cellular Physiology
ISSN (Print): 0021-9541
Original language: English
Keywords: biomaterial, cartilage, chondrogenesis, MSC, scaffold, ARTICULAR-CARTILAGE REPAIR, STEM-CELLS, GENE-EXPRESSION, COLLAGEN, DEFECTS, CHONDROCYTES, SCAFFOLDS, THERAPY, KNEE
Source: WOS
Source ID: 000487988600001

Research output: Contribution to journalArticleScientificpeer-review

Phosphate Glasses and Fibers as an Alternative to Silicate Bioactive Glasses

The field of bioactive glasses started with the discovery of the first bioactive glass composition 45S5 or Bioglass® in 1969. In the 1980s, the glass particulates of 45S5 depicted the ability to induce osteogenesis, as opposed to the then preva- lent bioinert metallic implants. Later, the dissolution products of 45S5, which was a silicate glass, were found to stimulate the genes in human osteoblasts and act as growth factors, providing signals to the cells. Over the years, other bioactive glass compositions such as 13-93 and BonAlive® (S53P4) were discovered, which were also silicate glasses. Even today, 45S5 remains the gold standard for bioactive glasses. However, in recent times, there has been a rise in the demand for more sophisticated implants, such as scaffolds made from polymer and glass, or only glass. Furthermore, bioactive glass fibers are also appealing to the re- searchers for mechanically reinforcing the scaffolds, owing to their better me- chanical properties than polymers. However, in this regard, the silicate glasses are known to pose serious challenges to the researchers, due to their incongruent dissolution mechanism and poor thermal processability. Moreover, for short term applications, ranging from a few weeks to a few months, the degradation rate of the commercially available silicate glasses is considered too slow.

In light of the above facts, the main aims of this thesis are: (i) to develop new glasses within the phosphate glass family, which possess good thermal pro- cessability, have additional functionalities such as antimicrobial properties and invoke favorable cell response for developing novel biomaterials in future, and (ii) to develop glass fibers based on these compositions for advanced applications such as biosensing, and possessing decent mechanical properties for reinforcing composites.

To accomplish these objectives, a new series of phosphate glasses doped with metallic ions such as Ag, Cu and Fe was developed based on a promising phos- phate glass composition studied earlier. These glasses were analyzed in terms of their structural, thermal and in-vitro dissolution properties. Furthermore, the
antimicrobial properties of Ag and Cu glasses were also tested, relative to com mercial silicate bioactive glass. Then, preliminary cell culture tests were con- ducted using glass discs, and glass extracts (glass dissolution products contain- ing cell culture medium). Moving forward, two approaches were taken simultane- ously to improve the cell response to these glasses. Firstly, the glasses were subjected to a series of surface treatments to improve protein adhesion at their surface, which in-turn should play a role in improving the cell attachment at their surface. In the second approach, a small addition of borate at the expense of phosphate was done to increase the glass’ resistance to aqueous dissolution. Cell culture tests were then performed using glass extracts obtained from the new borophosphate glasses, and cell viability and proliferation were assessed and cytotoxicity of the extracts obtained. Finally, newly developed single core and core-clad glass fibers were also studied in terms of their mechanical properties and their potential in biosensing.


The newly developed phosphate glasses depicted a high degree of thermal pro- cessability and promising in-vitro dissolution characteristics. The Ag and Cu glasses presented antimicrobial properties even superior to the commercially available S53P4 in eliminating Staphylococcus epidermis. The surface treat- ments performed on the glass discs revealed an improvement in the protein ad- hesion, which in-turn vastly improved the cell attachment at their surface. In the other approach to improve cell growth and proliferation in the glass extracts, a small addition of borate at the expense of phosphate resulted in an improved cell response to the glass extracts, barring that of the Cu-doped glass. Indeed, the undiluted Cu extract exhibited a much higher cytotoxicity than all the other glass extracts, and hence was toxic to cell survival. In the study on phosphate glass fibers, the core-clad fiber was found to be promising for biosensing, owing to its ability to guide light effectively and maintain decent mechanical properties in-vitro (up to 4 weeks, and ~6 weeks in TRIS buffer solution respectively).

In summary, phosphate glasses with favorable cell response were obtained by tailoring their composition and using suitable surface treatments. These glasses were found to possess favorable thermal properties for fiber drawing and scaffold sintering, and the fibers drawn from these glass compositions showed promise in biosensing. Furthermore, they possessed high mechanical strength, and in the
future, they can be considered for reinforcing scaffolds. These new glasses and
glass fibers should pave the way for a new family of bioresorbable implants for a
wide array of biomedical applications in future.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: BioMediTech
Contributors: Mishra, A.
Number of pages: 145
Publication date: 20 Sep 2019

Publication information

Publisher: Tampere University
Volume: 120
ISBN (Print): 978-952-03-1224-4
ISBN (Electronic): 978-952-03-1225-1
Original language: English

Publication series

Name: Tampere University Dissertations
Volume: 120
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

MATHEMATICAL MODEL ORDER REDUCTION OF A FOKKER-PLANCK MEAN-FIELD MODEL

Development of large-scale models of neuronal network dynamics is important in order to increase understanding of the whole brain. Although mathematical analysis of these models is intractable and their numerical simulation is very resource intensive, mean-field approximation has been shown to be an effective tool for studying populations of biophysically detailed neurons [1]. Here we compare state-of-the-art methods for improving the simulation time of mathematical models and show that a nonlinear Fokker-Planck-McKean-Vlasov-type neuronal mean-field model can be accurately approximated in low-dimensional subspaces with these methods.

Using mean-field approximation, cells are grouped together into populations
based on their statistical similarities, in order to represent the dynamics of
the system in terms of the ensemble behaviour. These populations can then be
described by a probability density function expressing the distribution of
neuronal states at a given time. In this study we focus on a mean-field model of
a network of FitzHugh-Nagumo neurons with chemical synapses using the
Fokker-Planck formalism, which results in a nonlinear McKean-Vlasov partial
differential equation (PDE) [1]. For numerical simulations the PDE is discretized in
space over three variables and a high-dimensional system, whose domain is a cube, is obtained.

The dimensionality, and hence simulation time, of discretized PDE systems can be reduced using mathematical model order reduction (MOR) methods. MOR methods are well established in engineering sciences, such as control theory. However, in computational neuroscience MOR is underutilised, although the potential benefits in enabling large-scale simulations are obvious [3].

Here we use recently developed advanced variants of the Discrete Empirical
Interpolation Method (DEIM) [2] to reduce a nonlinear mean-field model. The
system can be reduced with minimal information loss by deriving subspaces where the entire system is approximated with a small number of dimensions during the simulation phase, and after simulation the original model can be fully
reconstructed (see Fig. 1). By applying these methods, the simulation time of
the model is radically shortened, albeit not without dimension-dependent
approximation error. This can be particularly useful when attempting to model
whole-brain activity, for which there is an immediate demand in clinical and
robotic applications.

1. Baladron J, Fasoli D, Faugeras O, Touboul J. Mean-field description and
propagation of chaos in networks of Hodgkin-Huxley and FitzHugh-Nagumo
neurons. The Journal of Mathematical Neuroscience. 2012 Dec 1;2(1):10.
2. Chaturantabut, S. and Sorensen, D.C., Nonlinear model reduction via discrete
empirical interpolation. SIAM Journal on Scientific Computing. 2010, 32(5),
pp.2737-2764.
3. Lehtimäki, M. , Paunonen, L., Pohjolainen, S. and Linne, M.-L., Order
reduction for a signaling pathway model of neuronal synaptic plasticity.
IFAC Papers OnLine. 2017, 50-1:7687–7692.

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: BioMediTech, Computing Sciences, Mathematics
Contributors: Lehtimäki, M., Seppälä, I., Paunonen, L., Linne, M.
Publication date: 18 Sep 2019
Peer-reviewed: Unknown
Event: Paper presented at Bernstein Conference 2019, Berlin, Germany.
Keywords: Neuroscience, Control theory, Model reduction

Research output: Other conference contributionPaper, poster or abstractScientific

Unique Features of Network Bursts Emerge From the Complex Interplay of Excitatory and Inhibitory Receptors in Rat Neocortical Networks

Spontaneous network activity plays a fundamental role in the formation of functional networks during early development. The landmark of this activity is the recurrent emergence of intensive time-limited network bursts (NBs) rapidly spreading across the entire dissociated culture in vitro. The main excitatory mediators of NBs are glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-Methyl-D-aspartic-acid receptors (NMDARs) that express fast and slow ion channel kinetics, respectively. The fast inhibition of the activity is mediated through gamma-aminobutyric acid type A receptors (GABAARs). Although the AMPAR, NMDAR and GABAAR kinetics have been biophysically characterized in detail at the monosynaptic level in a variety of brain areas, the unique features of NBs emerging from the kinetics and the complex interplay of these receptors are not well understood. The goal of this study is to analyze the contribution of fast GABAARs on AMPAR- and NMDAR- mediated spontaneous NB activity in dissociated neonatal rat cortical cultures at 3 weeks in vitro. The networks were probed by both acute and gradual application of each excitatory receptor antagonist and combinations of acute excitatory and inhibitory receptor antagonists. At the same time, the extracellular network-wide activity was recorded with microelectrode arrays (MEAs). We analyzed the characteristic NB measures extracted from NB rate profiles and the distributions of interspike intervals, interburst intervals, and electrode recruitment time as well as the similarity of spatio-temporal patterns of network activity under different receptor antagonists. We show that NBs were rapidly initiated and recruited as well as diversely propagated by AMPARs and temporally and spatially maintained by NMDARs. GABAARs reduced the spiking frequency in AMPAR-mediated networks and dampened the termination of NBs in NMDAR-mediated networks as well as slowed down the recruitment of activity in all networks. Finally, we show characteristic super bursts composed of slow NBs with highly repetitive spatio-temporal patterns in gradually AMPAR blocked networks. To the best of our knowledge, this study is the first to unravel in detail how the three main mediators of synaptic transmission uniquely shape the NB characteristics, such as the initiation, maintenance, recruitment and termination of NBs in cortical cell cultures in vitro.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Neuro Science-CNS
Contributors: Teppola, H., Aćimović, J., Linne, M. L.
Publication date: 6 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: FRONTIERS IN CELLULAR NEUROSCIENCE
Volume: 13
Article number: 377
ISSN (Print): 1662-5102
Original language: English
ASJC Scopus subject areas: Cellular and Molecular Neuroscience
Keywords: AMPA receptor, cell culture, GABA receptor, microelectrode array, neocortical cells, neuronal network, NMDA receptor, spontaneous network burst activity
Electronic versions: 
Source: Scopus
Source ID: 85072963878

Research output: Contribution to journalArticleScientificpeer-review

Effect of melt-derived bioactive glass particles on the properties of chitosan scaffolds

This study reports on the processing of three-dimensional (3D) chitosan/bioactive glass composite scaffolds. On the one hand, chitosan, as a natural polymer, has suitable properties for tissue engineering applications but lacks bioactivity. On the other hand, bioactive glasses are known to be bioactive and to promote a higher level of bone formation than any other biomaterial type. However, bioactive glasses are hard, brittle, and cannot be shaped easily. Therefore, in the past years, researchers have focused on the processing of new composites. Difficulties in reaching composite materials made of polymer (synthetic or natural) and bioactive glass include: (i) The high glass density, often resulting in glass segregation, and (ii) the fast bioactive glass reaction when exposed to moisture, leading to changes in the glass reactivity and/or change in the polymeric matrix. Samples were prepared with 5, 15, and 30 wt% of bioactive glass S53P4 (BonAlive ®), as confirmed using thermogravimetric analysis. MicrO–Computed tomography and optical microscopy revealed a flaky structure with porosity over 80%. The pore size decreased when increasing the glass content up to 15 wt%, but increased back when the glass content was 30 wt%. Similarly, the mechanical properties (in compression) of the scaffolds increased for glass content up to 15%, but decreased at higher loading. Ions released from the scaffolds were found to lead to precipitation of a calcium phosphate reactive layer at the scaffold surface. This is a first indication of the potential bioactivity of these materials. Overall, chitosan/bioactive glass composite scaffolds were successfully produced with pore size, machinability, and ability to promote a calcium phosphate layer, showing promise for bone tissue engineering and the mechanical properties can justify their use in non-load bearing applications.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech, Tampere University
Contributors: Faqhiri, H., Hannula, M., Kellomäki, M., Calejo, M. T., Massera, J.
Publication date: 1 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: JOURNAL OF FUNCTIONAL BIOMATERIALS
Volume: 10
Issue number: 3
Article number: 38
ISSN (Print): 2079-4983
Original language: English
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering
Keywords: Bioactive glass, Bone tissue engineering, Chitosan, Composites
Electronic versions: 

Bibliographical note

INT=bmte,"Faqhiri, Hamasa"
dupl=50709653

Source: Scopus
Source ID: 85073050007

Research output: Contribution to journalArticleScientificpeer-review

Porous polybutylene succinate films enabling adhesion of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE)

In the last decade, several studies have shown that polybutylene succinate (PBSu)has a high potential as a biomaterial enabling cell adhesion and growth. In this study, porous PBSu films have been prepared by the breath figure method (BF)and by particulate leaching (PL), and characterized in terms of thickness, surface properties, diffusion capacity and in vitro stability. Because porous films are of high interest for tissue engineering of retinal pigment epithelium (RPE), the initial viability and adhesion of human embryonic stem cell-derived RPE onto the PBSu films was then evaluated. To the best of our knowledge, this is the first study on the adhesion behavior of hESC-RPE onto porous and biodegradable polymer surfaces. The results clearly demonstrated that the two manufacturing methods produced materials with very distinct properties. Films produced by BF expressively demonstrated the highest roughness and surface area, and the lowest water contact angle. These features likely contributed to increase the biocompatibility of the surface, particularly when coated with laminin and collagen IV, as observed by the improved cell viability, cell morphology, adhesion and production of extracellular matrix proteins. Altogether, our results showed not only that PBSu holds high potential in retinal tissue engineering, but also that the physical properties and biocompatibility of the material are highly dependent on the adopted casting method.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University, Tampere University Hospital
Contributors: Calejo, M. T., Haapala, A., Skottman, H., Kellomäki, M.
Number of pages: 10
Pages: 78-87
Publication date: 1 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: European Polymer Journal
Volume: 118
ISSN (Print): 0014-3057
Original language: English
ASJC Scopus subject areas: Physics and Astronomy(all), Polymers and Plastics, Organic Chemistry, Materials Chemistry
Keywords: Biodegradable films, Breath figures, Cell adhesion, Polybutylene succinate, Retinal pigment epithelium
Source: Scopus
Source ID: 85066269398

Research output: Contribution to journalArticleScientificpeer-review

User-driven development with scientific applied research - RFID-controlled physiogame case study

The role of technology in health care is growing. One major challenge caused by the rapid evolvement of technologies, is the implementation and application of the latest technology advances into actual care practises. In this paper, we present how combination of scientific research and multidisciplinary applied research activities can boost the development of need-based solutions to real-life challenges. The paper concentrates on the ideation phase of the development process. This paper presents a case study, in which a body movement-controlled physiotherapy game is developed in close collaboration of technology developers and physiotherapy professionals. Textile-integrated passive UHF RFID tags are used as game controllers to enable identification of certain movements. The results indicate the early stage prototype used in the study to enhance ideation and identification of application areas for the technology. In addition, the joint development process, in which the clients (rehabilitation professionals) are involved from the beginning, is also found to create commitment to continue collaboration, by helping the technology developers to meet the needs and to take user group-specific requirements into account in the development. This kind of process serves multidisciplinary projects well.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Wireless Identification and Sensing Systems Research Group
Contributors: Merilampi, S., Ihanakangas, V., Virkki, J.
Number of pages: 4
Pages: 167-170
Publication date: 1 Sep 2019

Host publication information

Title of host publication: 2019 IEEE International Conference on RFID Technology and Applications (RFID-TA)
Publisher: IEEE
ISBN (Print): 978-1-7281-0590-1
ISBN (Electronic): 978-1-7281-0589-5
Keywords: passive UHF RFID technology, research collaboration, self-managed rehabilitation, serious games, wearable electronics, women in RFID

Bibliographical note

EXT="Merilampi, Sari"

Source: Bibtex
Source ID: 8892150

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Processing methods for making porous bioactive glass-based scaffolds-A state-of-the-art review

Bioactive glasses exhibit the unique ability of bone bonding, thus creating a stable interface by stimulating bone cells toward mechanisms of regeneration and self-repair activated by ionic dissolution products. Therefore, 3D glass-derived scaffolds can be considered ideal porous templates to be used in bone tissue engineering strategies and regenerative medicine. This review provides a comprehensive overview of all technological aspects relevant to the fabrication of bioactive glass scaffolds, including the fundamentals of materials processing, a summary of the conventional porogen, and template-based methods and of recent additive manufacturing technologies, which are promising for large-scale production of highly reproducible and reliable implants suitable for a wide range of clinical applications.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group
Contributors: Baino, F., Fiume, E., Barberi, J., Kargozar, S., Marchi, J., Massera, J., Verne, E.
Number of pages: 35
Pages: 1762-1796
Publication date: Sep 2019
Peer-reviewed: Yes

Publication information

Journal: International Journal of Applied Ceramic Technology
Volume: 16
Issue number: 5
ISSN (Print): 1546-542X
Original language: English
Keywords: additive manufacturing, bioactive glasses, bioceramics, scaffolds, CALCIUM-PHOSPHATE SCAFFOLDS, IN-VITRO CHARACTERIZATION, CERAMIC FOAM SCAFFOLDS, SOL-GEL, MECHANICAL-PROPERTIES, COMPOSITE SCAFFOLDS, BONE SUBSTITUTES, TISSUE, FABRICATION, BIOGLASS(R)
Source: WOS
Source ID: 000478610900009

Research output: Contribution to journalReview ArticleScientificpeer-review

Bioactive glass ions for in vitro osteogenesis and microvascularization in gellan gum-collagen hydrogels

Lack of bone grafts appeals for bone augmentation solutions. We aimed at osteogenic differentiation of human adipose stem cells (hASCs) and microvascularization in coculture with human umbilical vein endothelial cells (HUVECs) embedded in three-dimensional (3D) gellan gum (GG) and collagen type I (COL) hydrogel mixture. We compared endothelial growth medium-2 (EGM-2) and bioactive glass extract-based endothelial and osteogenic medium (BaG EM-OM) for vascularized bone-like graft development in vitro. Cell viability, cell number, and osteogenic and endothelial gene expression were analyzed. Mineralized hydroxyapatite residues, immunocytochemical staining of endothelial marker CD31 production and late osteogenic marker osteocalcin were imaged. With both media, good cell viability was observed within 3D hydrogel. EGM-2 condition induced significantly higher cell number compared to BaG EM-OM condition at both 7 and 14 days. Interestingly, both media supported osteogenic as well as endothelial marker gene expression. Moreover, formation of reticulated cellular structures was observed in both EGM-2 and BaG EM-OM conditions. However, hydroxyapatite mineralization and strong osteocalcin staining were detected only in BaG EM-OM condition. Importantly, strong production of CD31 and elongated tube-like structures were apparent in EGM-2 culture alone. In conclusion, we demonstrated efficient hASC osteogenic differentiation and microvessel-like network formation in coculture with HUVECs.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Tampere University Hospital, Abo Akad Univ, Abo Akademi University, Dept Phys
Contributors: Vuornos, K., Huhtala, H., Kääriäinen, M., Kuismanen, K., Hupa, L., Kellomäki, M., Miettinen, S.
Publication date: 31 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Biomedical Materials Research - Part B Applied Biomaterials
ISSN (Print): 1552-4973
Original language: English
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering
Keywords: adipose stem cell, bioactive glass, collagen type I hydrogel, gellan gum hydrogel, human umbilical vein endothelial cell, osteogenic differentiation, vascularization
Source: Scopus
Source ID: 85071483860

Research output: Contribution to journalArticleScientificpeer-review

Design of modular gellan gum hydrogel functionalized with avidin and biotinylated adhesive ligands for cell culture applications

This article proposes the coupling of the recombinant protein avidin to the polysaccharide gellan gum to create a modular hydrogel substrate for 3D cell culture and tissue engineering. Avidin is capable of binding biotin, and thus biotinylated compounds can be tethered to the polymer network to improve cell response. The avidin is successfully conjugated to gellan gum and remains functional as shown with fluorescence titration and electrophoresis (SDS-PAGE). Self-standing hydrogels were formed using bioamines and calcium chloride, yielding long-term stability and adequate stiffness for 3D cell culture, as confirmed with compression testing. Human fibroblasts were successfully cultured within the hydrogel treated with biotinylated RGD or biotinylated fibronectin. Moreover, human bone marrow stromal cells were cultured with hydrogel treated with biotinylated RGD over 3 weeks. We demonstrate a modular and inexpensive hydrogel scaffold for cell encapsulation that can be equipped with any desired biotinylated cell ligand to accommodate a wide range of cell types.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, BioMediTech, Fimlab Laboratories Ltd, University of Tampere, Adult Stem Cell Research Group, Tampere University Hospital
Contributors: Gering, C., Koivisto, J. T., Parraga, J., Leppiniemi, J., Vuornos, K., Hytönen, V. P., Miettinen, S., Kellomäki, M.
Publication date: 30 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 14
Issue number: 8
Article number: e0221931
ISSN (Print): 1932-6203
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

IEC 62304 Ed. 2: Software Life Cycle Standard for Health Software

The quality of software is high in medical devices due to the strict regulatory requirements and their implementation in the software development processes through the use of the IEC 62304 standard. The goal of this standard revision project was to extend the scope of the standard to all health software and also to bring the requirements of the 12 year old standard back to the state-of-the-art including provisions for cybersecurity. The joint IEC/SC62A and ISO/TC215 project team revised the standard and adapted its risk management, usability, and security requirements to serve both the medical device industry and the overall health software industry. The resulting second version of the standard has gone through a multistage global voting process to achieve a consensus of the requirements to serve both these communities. The resulting standard has potential to have a major impact on the quality of software used in health care globally

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Medtronic, Silver Lake Group Inc.
Contributors: Värri, A., Kranz-Zuppan, P., de la Cruz, R.
Number of pages: 5
Pages: 868-872
Publication date: 23 Aug 2019

Host publication information

Title of host publication: Medinfo 2019 : Proceedings of the 17th World Congress on Medical and Health Informatics
Publisher: IOP Press
Editors: Ohno-Machado, L., Séroussi, B.
ISBN (Print): 978-1-64368-002-6
ISBN (Electronic): 978-1-64368-003-3

Publication series

Name: Studies in Health Technology and Informatics
Publisher: IOS Press
Volume: 264
ISSN (Print): 0926-9630
ISSN (Electronic): 1879-8365
ASJC Scopus subject areas: Computer Science(all)
Keywords: Standards, Software Engineering, Health Care Technology
Electronic versions: 

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Pneumatic unidirectional cell stretching device for mechanobiological studies of cardiomyocytes

In this paper, we present a transparent mechanical stimulation device capable of uniaxial stimulation, which is compatible with standard bioanalytical methods used in cellular mechanobiology. We validate the functionality of the uniaxial stimulation system using human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs). The pneumatically controlled device is fabricated from polydimethylsiloxane (PDMS) and provides uniaxial strain and superior optical performance compatible with standard inverted microscopy techniques used for bioanalytics (e.g., fluorescence microscopy and calcium imaging). Therefore, it allows for a continuous investigation of the cell state during stretching experiments. The paper introduces design and fabrication of the device, characterizes the mechanical performance of the device and demonstrates the compatibility with standard bioanalytical analysis tools. Imaging modalities, such as high-resolution live cell phase contrast imaging and video recordings, fluorescent imaging and calcium imaging are possible to perform in the device. Utilizing the different imaging modalities and proposed stretching device, we demonstrate the capability of the device for extensive further studies of hiPSC-CMs. We also demonstrate that sarcomere structures of hiPSC-CMs organize and orient perpendicular to uniaxial strain axis and thus express more maturated nature of cardiomyocytes.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Micro and Nanosystems Research Group, BioMediTech, Risø Campus, Tampere University of Applied Sciences, Eindhoven University of Technology, Tampere University Hospital
Contributors: Kreutzer, J., Viehrig, M., Pölönen, R. P., Zhao, F., Ojala, M., Aalto-Setälä, K., Kallio, P.
Publication date: 23 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
ISSN (Print): 1617-7959
Original language: English
ASJC Scopus subject areas: Biotechnology, Modelling and Simulation, Mechanical Engineering
Keywords: Cardiomyocytes, hiPSC, Mechanical stimulation, PDMS

Bibliographical note

EXT="Zhao, Feihu"

Source: Scopus
Source ID: 85070939275

Research output: Contribution to journalArticleScientificpeer-review

Health timeline: an insight-based study of a timeline visualization of clinical data

Background The increasing complexity and volume of clinical data poses a challenge in the decision-making process. Data visualizations can assist in this process by speeding up the time required to analyze and understand clinical data. Even though empirical experiments show that visualizations facilitate clinical data understanding, a consistent method to assess their effectiveness is still missing. Methods The insight-based methodology determines the quality of insights a user acquires from the visualization. Insights receive a value from one to five points based on a domain-specific criteria. Five professional psychiatrists took part in the study using real de-identified clinical data spanning 4 years of medical history. Results A total of 50 assessments were transcribed and analyzed. Comparing a total of 558 insights using Health Timeline and 576 without, the mean value using the Timeline (1.7) was higher than without (1.26; p<0.01), similarly the cumulative value with the Timeline (11.87) was higher than without (10.96: p<0.01). The average time required to formulate the first insight with the Timeline was higher (13.16 s) than without (7 s; p<0.01). Seven insights achieved the highest possible value using Health Timeline while none were obtained without it. Conclusions The Health Timeline effectively improved understanding of clinical data and helped participants recognize complex patterns from the data. By applying the insight-based methodology, the effectiveness of the Health Timeline was quantified, documented and demonstrated. As an outcome of this exercise, we propose the use of such methodologies to measure the effectiveness of visualizations that assist the clinical decision-making process.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Flinders University, University of Adelaide, VTT Tech Res Ctr Finland, VTT Technical Research Center Finland, VTT Technical Research Centre of Finland
Contributors: Ledesma, A., Bidargaddi, N., Strobel, J., Schrader, G., Nieminen, H., Korhonen, I., Ermes, M.
Publication date: 22 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: BMC Medical Informatics and Decision Making
Volume: 19
Issue number: 1
Article number: 170
ISSN (Print): 1472-6947
Original language: English
Keywords: Health informatics, data visualisation, decision making, electronic health records
Electronic versions: 

Research output: Contribution to journalArticleScientificpeer-review

Influence of ions to modulate hydrazone and oxime reaction kinetics to obtain dynamically cross-linked hyaluronic acid hydrogels

Dynamic covalent chemistry forming hydrazone and oxime linkages is attractive due to its simplicity, selectivity and compatibility under aqueous conditions. However, the low reaction rate at physiological pH hampers its use in biomedical applications. Herein, we present different monovalent and bivalent aqueous salt solutions as bio-friendly, non-toxic catalysts which can drive the hydrazone and oxime reactions with excellent efficacy at physiological pH. Direct comparison of hydrazone and oxime reactions using a small molecule model, without any salt catalysis, indicated that oxime formation is 6-times faster than hydrazone formation. Addition of different salts (NaCl, NaBr, KCl, LiCl, LiClO4, Na2SO4, MgCl2 and CaCl2) accelerated the pseudo-first-order reaction kinetics by ∼1.2-4.9-fold for acylhydrazone formation and by ∼1.5-6.9-fold for oxime formation, in a concentration-dependent manner. We further explored the potential of such catalysts to develop acylhydrazone and oxime cross-linked hyaluronic acid (HA) hydrogels with different physicochemical properties without changing the degree of chemical modification. Analogous to the small molecule model system, the addition of monovalent and divalent salts as catalysts significantly reduced the gelling time. The gelling time for the acylhydrazone cross-linked HA-hydrogel (1.6 wt%) could be reduced from 300 min to 1.2 min by adding 100 mM CaCl2, while that for the oxime cross-linked HA-hydrogel (1.2 wt%) could be reduced from 68 min to 1.1 min by adding 50 mM CaCl2. This difference in the gelling time also resulted in hydrogels with differential swelling properties as measured after 24 h. Our results are the first to demonstrate the use of salts, for catalyzing hydrogel formation under physiologically relevant conditions.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, University of Montreal, Uppsala University
Contributors: Wang, S., Nawale, G. N., Oommen, O. P., Hilborn, J., Varghese, O. P.
Number of pages: 6
Pages: 4322-4327
Publication date: 21 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: Polymer Chemistry
Volume: 10
Issue number: 31
ISSN (Print): 1759-9954
Original language: English
ASJC Scopus subject areas: Bioengineering, Biochemistry, Polymers and Plastics, Organic Chemistry
Electronic versions: 
Source: Scopus
Source ID: 85070404630

Research output: Contribution to journalArticleScientificpeer-review

Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium

Background: Voltage-gated sodium (Nav) channels have traditionally been considered a trademark of excitable cells. However, recent studies have shown the presence of Nav channels in several non-excitable cells, such as astrocytes and macrophages, demonstrating that the roles of these channels are more diverse than was previously thought. Despite the earlier discoveries, the presence of Nav channel-mediated currents in the cells of retinal pigment epithelium (RPE) has been dismissed as a cell culture artifact. We challenge this notion by investigating the presence and possible role of Nav channels in RPE both ex vivo and in vitro. Results: Our work demonstrates that several subtypes of Nav channels are found in human embryonic stem cell (hESC)-derived and mouse RPE, most prominently subtypes Nav1.4, Nav1.6, and Nav1.8. Whole cell patch clamp recordings from the hESC-derived RPE monolayers showed that the current was inhibited by TTX and QX-314 and was sensitive to the selective blockers of the main Nav subtypes. Importantly, we show that the Nav channels are involved in photoreceptor outer segment phagocytosis since blocking their activity significantly reduces the efficiency of particle internalization. Consistent with this role, our electron microscopy results and immunocytochemical analysis show that Nav1.4 and Nav1.8 accumulate on phagosomes and that pharmacological inhibition of Nav channels as well as silencing the expression of Nav1.4 with shRNA impairs the phagocytosis process. Conclusions: Taken together, our study shows that Nav channels are present in RPE, giving this tissue the capacity of fast electrical signaling. The channels are critical for the physiology of RPE with an important role in photoreceptor outer segment phagocytosis.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University, University of Jyvaskyla, Tampere University Hospital
Contributors: Johansson, J. K., Karema-Jokinen, V. I., Hakanen, S., Jylhä, A., Uusitalo, H., Vihinen-Ranta, M., Skottman, H., Ihalainen, T. O., Nymark, S.
Publication date: 15 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: BMC BIOLOGY
Volume: 17
Issue number: 1
Article number: 63
ISSN (Print): 1741-7007
Original language: English
ASJC Scopus subject areas: Biotechnology, Structural Biology, Ecology, Evolution, Behavior and Systematics, Physiology, Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all), Plant Science, Developmental Biology, Cell Biology
Keywords: Ion channels, Na, Patch clamp, Phagocytosis, Photoreceptors, Retina, RPE
Electronic versions: 
Source: Scopus
Source ID: 85071165212

Research output: Contribution to journalArticleScientificpeer-review

Characterisation and in vitro and in vivo evaluation of supercritical-CO2-foamed β-TCP/PLCL composites for bone applications

Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable β-tricalciumphosphate/poly(L-lactide-co-ε-caprolactone) (β-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 °C, tested samples returned to 95 % of their original height. Hydrolytic degradation of β-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, β-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the β-TCP/PLCL composite. The elastic and highly porous β-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech
Contributors: Pitkänen, S., Paakinaho, K., Pihlman, H., Ahola, N., Hannula, M., Asikainen, S., Manninen, M., Morelius, M., Keränen, P., Hyttinen, J., Kellomäki, M., Laitinen-Vapaavuori, O., Miettinen, S.
Number of pages: 16
Pages: 35-50
Publication date: 5 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: European cells & materials
Volume: 38
ISSN (Print): 1473-2262
Original language: English
ASJC Scopus subject areas: Bioengineering, Biochemistry, Biomaterials, Biomedical Engineering, Cell Biology
Electronic versions: 
Source: Scopus
Source ID: 85071152630

Research output: Contribution to journalArticleScientificpeer-review

Projection-based order reduction of a nonlinear biophysical neuronal network model

In this study mathematical model order reduction
is applied to a nonlinear model of a network of biophysically
realistic heterogeneous neurons. The neuron model describes a
pyramidal cell in the hippocampal CA3 area of the brain and
includes a state-triggered jump condition. The network displays
synchronized firing of action potentials (spikes), a fundamental
phenomenon of sensory information processing in the brain.
Simulation of the system is computationally expensive, which
limits network size and hence biological realism. We reduce the
network using advanced variations of Proper Orthogonal De-
composition and Discrete Empirical Interpolation Method. The
reduced models should recreate the original spiking activity. We
show that reduction methods with online adaptivity achieve the
most accurate reduction results. Some of the reduced models
consume less computational resources than the original, at the
cost of changes in population activity of the tested network
model.

General information

Publication status: Accepted/In press
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Computing Sciences
Contributors: Lehtimäki, M., Paunonen, L., Linne, M.
Publication date: 19 Jul 2019

Host publication information

Title of host publication: Proceedings of the IEEE Conference on Decision and Control
Publisher: IEEE Xplore
Keywords: Neuroscience, Control theory, Model reduction

Bibliographical note

Presented as a talk. Ei ilm. 9.1.20 M. K.

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

3D Scaffolds of Polycaprolactone/Copper-Doped Bioactive Glass: Architecture Engineering with Additive Manufacturing and Cellular Assessments in a Coculture of Bone Marrow Stem Cells and Endothelial Cells

The local delivery of Cu2+ from copper-doped bioactive glass (Cu-BaG) was combined with 3D printing of polycaprolactone (PCL) scaffolds for its potent angiogenic effect in bone tissue engineering. PCL and Cu-BaG were, respectively, dissolved and dispersed in acetone to formulate a moderately homogeneous ink. The PCL/Cu-BaG scaffolds were fabricated via direct ink writing into a cold ethanol bath. The architecture of the printed scaffolds, including strut diameter, strut spacing, and porosity, were investigated and characterized. The PCL/Cu-BaG scaffolds showed a Cu-BaG content-dependent mechanical property, as the compressive Young's modulus ranged from 7 to 13 MPa at an apparent porosity of 60%. The ion dissolution behavior in simulated body fluid was evaluated, and the hydroxyapatite-like precipitation on the strut surface was confirmed. Furthermore, the cytocompatibility of the PCL/Cu-BaG scaffolds was assessed in human bone marrow stem cell (hBMSC) culture, and a dose-dependent cytotoxicity of Cu2+ was observed. Here, the PCL/BaG scaffold induced the higher expression of late osteogenic genes OSTEOCALCIN and DLX5 in comparison to the PCL scaffold. The doping of Cu2+ in BaG elicited higher expression of the early osteogenic marker gene RUNX2a but decreased the expression of late osteogenic marker genes OSTEOCALCIN and DLX5 in comparison to the PCL/BaG scaffold, demonstrating the suppressing effect of Cu2+ on osteogenic differentiation of hBMSCs. In a coculture of hBMSCs and human umbilical vein endothelial cells, both the PCL/BaG and PCL/Cu-BaG scaffolds stimulated the formation of a denser tubule network, compared to the PCL scaffold. Meanwhile, only slightly higher gene expression of vWF was observed with the PCL/Cu-BaG scaffold than with the PCL/BaG scaffold, indicating the potent angiogenic effect of the released Cu2+.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group, Johan Gadolin Process Chemistry Centre, Abo Akademi University, University of Wollongong, Tampere University Hospital, Tampere University
Contributors: Wang, X., Molino, B. Z., Pitkänen, S., Ojansivu, M., Xu, C., Hannula, M., Hyttinen, J., Miettinen, S., Hupa, L., Wallace, G.
Pages: 4496-4510
Publication date: 18 Jul 2019
Peer-reviewed: Yes

Publication information

Journal: ACS Biomaterials Science and Engineering
Volume: 5
Issue number: 9
ISSN (Print): 2373-9878
Original language: English
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering
Keywords: 3D printing, angiogenesis, coculture of mesenchymal stem cells and endothelial cells, copper-doped bioactive glass, gradient porosity, polycaprolactone, tissue engineering scaffold
Electronic versions: 
Source: Scopus
Source ID: 85070677224

Research output: Contribution to journalArticleScientificpeer-review

In vitro anti-glioblastoma activity of L-valine derived boroxazolidones

In the present study, a series of L-valine derived boroxazolidones, previously synthesized and reported to have residual activity in a human epithelial cell line, have been evaluated in vitro for their anti-glioblastoma activity. A boroxazolidone derivative containing 2,4-difluorophenyl moieties (6) was found to have higher cytotoxicity than the standard drug, Temozolomide (TMZ). Compound 6 was found to exhibit dose-dependent growth inhibitory effects with an IC50 of 49 μM and 53 μM for LN229 and SNB19 cells, respectively. Additionally, 6 was assessed for its role in apoptosis, caspase 3/7 activation and oxidative stress in SNB19 and LN229 cells. SNB19 cells treated with 6 showed 45.3% apoptosis in the population, while TMZ had 24.7%. In LN229 cells, the percentage of apoptotic cells treated with compound 6 and TMZ were the same. Both 6 and TMZ induced apoptosis through the activation of caspase 3/7 in SNB19 and LN229 cells. Interestingly, 6 exhibited a higher effectivity in promoting reactive oxygen species production in LN229, while it was 6-fold less in SNB19. Boroxazolidone-treated GBM cell lines increased reactive oxygen species production, suggesting that such species may be interlinked with the observed programmed cell death. Additionally, the treatment of both GBM cell lines with 6 led to G2/M phase arrest. The magnitude of anti-GBM effect of 6 is significantly higher than the known chemotherapeutic agent TMZ. This work further demonstrates the anticancer properties of L-valine derived boroxazolidones, adding another potential derivative to the collection of promising chemotherapeutic agents for GBM treatment.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Systems Biology, Research group: Molecular Signaling Lab, Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Institute for Systems Biology
Contributors: Viswanathan, A., Sebastianelli, G., Brown, K., Raunio, J., Sipilä, V., Yli-Harja, O., Candeias, N. R., Kandhavelu, M.
Number of pages: 7
Pages: 194-200
Publication date: 5 Jul 2019
Peer-reviewed: Yes

Publication information

Journal: European Journal of Pharmacology
Volume: 854
ISSN (Print): 0014-2999
Original language: English
Keywords: Apoptosis, Boroxazolidone, Cell cycle arrest, Cytotoxicity, Glioblastoma

Bibliographical note

INT=bmte,"Sebastianelli, Giulia"
INT=bmte,"Brown, Kenna"
INT=msee,"Raunio, Jenna"
INT=bmte,"Sipilä, Vili"

Source: RIS
Source ID: urn:5D8BFA1B0ED702CD1DB6CC279168DDE5

Research output: Contribution to journalArticleScientificpeer-review

Carbon Nanotube-Based Matrices for Tissue Engineering

General information

Publication status: Published
MoE publication type: A3 Part of a book or another research book
Organisations: Research group: Biomaterials and Tissue Engineering Group, BioMediTech, University of Oulu, State University of Campinas, State University of Campinas
Contributors: Lorite , G. S., Pitkänen, O., Mohl, M., Kordas, K., Koivisto, J., Kellomäki, M., Culturato Padilha Mendonça, M., de Jesus, M. B.
Pages: 350-380
Publication date: 27 Jun 2019

Host publication information

Title of host publication: Materials for Biomedical Engineering : Bioactive Materials, Properties and Applications
Publisher: Elsevier
Editors: Grumezescu, A. M., Grumezescu, V.
Edition: 1st
ISBN (Print): 9780128184318

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Airway obstruction is associated with reduced variability in specific parts of the tidal breathing flow-volume curve in young children

Impedance pneumography recordings during sleep at night show reduced variability in specific parts of the expiratory flow-volume curve in children with recurrent wheeze http://bit.ly/2Wkfap0.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Physiological Measurement Systems and Methods Group, BioMediTech, Revenio Research Ltd, Vantaa, Finland., Allergy Centre, Tampere University Hospital, Tampere, Finland., Medical Faculty, University J.J. Strossmayer, Osijek, Croatia.
Contributors: Seppä, V., Hult, A., Gracia-Tabuenca, J., Paassilta, M., Viik, J., Plavec, D., Karjalainen, J.
Publication date: 17 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: BMJ Open
Volume: 5
Issue number: 2
ISSN (Print): 2312-0541
Original language: English

Bibliographical note

EXT="Seppä, Ville-Pekka"

Source: PubMed
Source ID: 31218218

Research output: Contribution to journalArticleScientificpeer-review

Mean-field methods for multiscale models in neuroscience

Multiscale modelling of the brain is necessary in order to understand how
interactions on the molecular and cellular levels can give rise to higher-level
brain functions. As microscale processes tie into mesoscopic populations that
facilitate whole-brain behaviour, being able to describe the full-scale
interconnectivity of the brain is clearly imperative. In order to interpret all
of the different mechanisms, we need comprehensive models with accurate system dynamics. However, incorporating multiple levels into mathematical models often results in large networks of interlinked neural cells that are analytically intractable. Additionally, their numerical simulation is resource intensive. Useful ways of mitigating the computational burden include using a mean-field approach, as well as mathematical model order reduction (MOR).

Using mean-field approximation, random fluctuations of variables can be
accounted for by replacing them by their averages. Cells are grouped together
into populations based on their statistical similarities, in order to represent
the dynamics of the system in terms of the mean ensemble behaviour. These
populations can then be described by a probability density function expressing
the distribution of neuronal states at a given time. We use the Fokker-Planck
formalism, which results in a nonlinear system of partial differential
equations (PDEs).

With mathematical MOR methods the dimensions of a PDE model can be reduced with minimal information loss. The simulation time of the model is radically
shortened, albeit not without dimension-dependent approximation error. The
tolerated amount of inaccuracy depends on the final application of the model.
Due to being well-suited for depicting mesoscopic behaviour, the mean-field
approach in combination with the MOR methods allows us to describe the
behaviour of any large multiscale brain model with a relatively low computational burden. This can be particularly useful when attempting to model whole-brain connectivity, for which there is an immediate demand in clinical and robotic applications.

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: BioMediTech, Computing Sciences
Contributors: Seppälä, I., Lehtimäki, M., Paunonen, L., Linne, M.
Publication date: 12 Jun 2019
Peer-reviewed: Unknown
Event: Paper presented at 3RD Nordic Neuroscience Meeting 2019, Helsinki, Finland.

Research output: Other conference contributionPaper, poster or abstractScientific

Assessment of Ca2+ Dynamics in Human Retinal Pigment Epithelial Cell Cultures

Retinal pigment epithelium is a monolayer of cells located beneath photoreceptors of the retina maintaining their functionality. Malfunction of RPE leads to retinal degenerative diseases, such as age-related macular degeneration and Stargardt disease. Ca2+ is a ubiquitous ion that takes part in regulation of vital cellular processes. The knowledge of Ca2+ dynamics is essential for understanding RPE physiology. This is especially important for functionality assessment of cells intended for transplantation and for drug testing.

The aim of this thesis was to study spontaneous and mechanically induced Ca2+ activity in human RPE and to assess the effect of cellular maturation and wounding on the [Ca2+]i dynamics. For this, various methods, such as fluorescent Ca2+ imaging, immunofluorescence staining, PCR, and mathematical modeling were applied. In addition, novel methods were developed to analyze large amounts of Ca2+ imaging data. ARPE-19 and human embryonic stem cell-derived RPE cells (hESC-RPE) were used as RPE cell models.

In this thesis, it was shown that both ARPE-19 and hESC-RPE exhibit intercellular Ca2+ waves upon mechanical stimulation. With live-cell Ca2+ imaging and mathematical modeling, it was demonstrated that in ARPE-19 cells, the mechanically induced Ca2+ waves propagate intracellularly through gap junctions and extracellularly involving diffusion of a paracrine factor. By applying in-house image analysis tools for the experimental fluorescence time-series, it was found that in hESC-RPE cells, spontaneous [Ca2+]i transients and the ability to propagate intercellular Ca2+ waves upon mechanical stimulation strongly depend on the maturation status of the cells. Finally, it was demonstrated that wounding affects spontaneous Ca2+ activity close to the wound edges, and cells within the healed areas resemble Ca2+ dynamics of immature hESC-RPE.

To conclude, this thesis has provided important insights into human RPE Ca2+ dynamics, as well as into the events of single cell mechanical stimulation and large scale monolayer wounding. In addition, it was demonstrated that maturation drastically affects RPE Ca2+ dynamics. This knowledge and the developed image analysis algorithms contribute to understanding RPE physiology and can facilitate establishment of novel tools for assessment of RPE functionality prior to transplantation and in drug testing assays.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: BioMediTech
Contributors: Abu Khamidakh, A.
Number of pages: 120
Publication date: 7 Jun 2019

Publication information

Publisher: Tampere University
Volume: 66
ISBN (Print): 978-952-03-1099-8
ISBN (Electronic): 978-952-03-1100-1
Original language: English

Publication series

Name: Tampere University Dissertations
Volume: 66
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

Synthetic Design of Asymmetric miRNA with an Engineered 3′ Overhang to Improve Strand Selection

We developed a novel miRNA design that significantly improves strand selection within the RISC complex by engineering the 3′ end by adding extra nucleotides. Addition of seven nucleotides at the 3′ ends of the miR or miR* strand resulted in a thermodynamic asymmetry at either of the two ends, which resulted in selective RISC recruitment, as demonstrated by a stem-loop PCR experiment. Such selective recruitment was also corroborated at the protein level by western blot analysis. To investigate the functional effect because of selective recruitment, we performed apoptosis and metastasis studies using human colon carcinoma cells (HCT116)and human osteosarcoma cells (MG63). These experiments indicated that recruitment of the miR strand is responsible for inducing apoptosis and inhibiting the invasiveness of cancer cells. Recruitment of the miR* strand, on the other hand, had the opposite effect. To the best of our knowledge, our strand engineering strategy is the first report of improved strand selection of a desired miRNA strand by RISC without using any chemical modifications or mismatches. We believe that such structural modifications of miR34a could mitigate some of the off-target effects of miRNA therapy and would also allow a better understanding of sequence-specific gene regulation. Such a design could also be adapted to other miRNAs to enhance their therapeutic potential.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Uppsala University
Contributors: Kadekar, S., Nawale, G. N., Karlsson, K., Ålander, C., Oommen, O. P., Varghese, O. P.
Number of pages: 8
Pages: 597-604
Publication date: 7 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Molecular Therapy - Nucleic Acids
Volume: 16
ISSN (Print): 2162-2531
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Drug Discovery
Keywords: anticancer therapy, miR34a, miRNA, RNAi, strand selection
Electronic versions: 
Source: Scopus
Source ID: 85065418583

Research output: Contribution to journalArticleScientificpeer-review

Analytical Expressions for Spring Constants of Capillary Bridges and Snap-in Forces of Hydrophobic Surfaces

When a force probe with a small liquid drop adhered to its tip makes contact with a substrate of interest, the normal force right after contact is called the snap-in force. This snap-in force is related to the advancing contact angle or the contact radius at the substrate. Measuring snap-in forces has been proposed as an alternative to measure the advancing contact angles of surfaces. The snap-in occurs when the distance between the probe surface and the substrate is hS, which is amenable to geometry, assuming the drop was a spherical cap before snap-in. Equilibrium is reached at a distance hE < hS. At equilibrium, the normal force F = 0, and the capillary bridge is a spherical segment, amenable again to geometry. For a small normal displacement Δh = h - hE, the normal force can be approximated with F ≈ -k1Δh or F ≈ -k1Δh - k2Δh2, where k1 = -∂F/∂h and k2 = -1/2·∂2F/∂h2 are the effective linear and quadratic spring constants of the bridge, respectively. Analytical expressions for k1,2 are found using Kenmotsu's parameterization. Fixed contact angle and fixed contact radius conditions give different forms of k1,2. The expressions for k1 found here are simpler, yet equivalent to the earlier derivation by Kusumaatmaja and Lipowsky (2010). Approximate snap-in forces are obtained by setting Δh = hS - hE. These approximate analytical snap-in forces agree with the experimental data from Liimatainen et al. (2017) and a numerical method based on solving the shape of the interface. In particular, the approximations are most accurate for super liquid-repellent surfaces. For such surfaces, readers may find this new analytical method more convenient than solving the shape of the interface numerically.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech
Contributors: Sariola, V.
Number of pages: 7
Pages: 7129-7135
Publication date: 4 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Langmuir
Volume: 35
Issue number: 22
ISSN (Print): 0743-7463
Original language: English
ASJC Scopus subject areas: Materials Science(all), Condensed Matter Physics, Surfaces and Interfaces, Spectroscopy, Electrochemistry
Electronic versions: 
Source: Scopus
Source ID: 85066806357

Research output: Contribution to journalArticleScientificpeer-review

Correlation of Surface Morphology and Interfacial Adhesive Behavior between Cellulose Surfaces: Quantitative Measurements in Peak-Force Mode with the Colloidal Probe Technique

A better understanding of cellulose-cellulose interactions is needed in applications such as paper making and all-cellulose composites. To date, cellulose-cellulose studies have been chemistry-oriented. In these studies, the sample surfaces have been modified with different chemicals and then tested under an atomic force microscope (AFM) using a colloidal probe (CP). Studies of cellulose-cellulose interaction based on sample morphology and mechanical properties have been rare as a result of the complex surface structure and the soft texture of the cellulose. The current surface interaction models, such as the Johnson-Kendall-Roberts (JKR) model in which the studied bodies are assumed to have smooth surfaces, can no longer fully reveal the interfacial behavior between two cellulose surfaces. Therefore, we propose a new type of contact model for rough-rough interaction by dividing the surface contacts into primary and secondary levels. The main idea of the new model is to take into account local individual contact details between rough surfaces. The model considers the effect of the surface topography by including the asperities and valleys on a cellulose sphere used as the colloidal probe in imaging the topography of a cellulose membrane (CM). In addition, the correlation between the surface morphology and adhesion is studied. To verify the importance of including the effect of the surface roughness in contact analysis and validate our hypothesis on the correlation between the surface morphology and adhesion, an extensive set of experiments was performed. In the experiments, a combination of the AFM peak-force mode (PFM) and the CP technique was employed to acquire a massive amount of information on cellulose-cellulose interactions by measuring the adhesion among six CSs of different sizes and a CM.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Micro and Nanosystems Research Group, BioMediTech, Harbin Institute of Technology, Tokyo University of Science
Contributors: Lai, Y., Zhang, H., Sugano, Y., Xie, H., Kallio, P.
Number of pages: 10
Pages: 7312-7321
Publication date: 4 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Langmuir
Volume: 35
Issue number: 22
ISSN (Print): 0743-7463
Original language: English
ASJC Scopus subject areas: Materials Science(all), Condensed Matter Physics, Surfaces and Interfaces, Spectroscopy, Electrochemistry
Electronic versions: 
Source: Scopus
Source ID: 85066731882

Research output: Contribution to journalArticleScientificpeer-review

Polyethylene Terephthalate Textiles Enhance the Structural Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have the potential to serve as a model for human cardiomyocytes. However, hiPSC-CMs are still considered immature. CMs differentiated from hiPSCs more resemble fetal than adult cardiomyocytes. Putative factors enhancing maturation include in vitro culture duration, culture surface topography, and mechanical, chemical, and electrical stimulation. Stem cell-derived cardiomyocytes are traditionally cultured on glass surfaces coated with extracellular matrix derivatives such as gelatin. hiPSC-CMs are flat and round and their sarcomeres are randomly distributed and unorganized. Morphology can be enhanced by culturing cells on surfaces providing topographical cues to the cells. In this study, a textile based-culturing method used to enhance the maturation status of hiPSC-CMs is presented. Gelatin-coated polyethylene terephthalate (PET)-based textiles were used as the culturing surface for hiPSC-CMs and the effects of the textiles on the maturation status of the hiPSC-CMs were assessed. The hiPSC-CMs were characterized by analyzing their morphology, sarcomere organization, expression of cardiac specific genes, and calcium handling. We show that the topographical cues improve the structure of the hiPSC-CMs in vitro. Human iPSC-CMs grown on PET textiles demonstrated improved structural properties such as rod-shape structure and increased sarcomere orientation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Tampere University, BioMediTech, University of Tampere
Contributors: Pekkanen-Mattila, M., Häkli, M., Pölönen, R., Mansikkala, T., Junnila, A., Talvitie, E., Koivisto, J. T., Kellomäki, M., Aalto-Setälä, K.
Number of pages: 16
Publication date: 3 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Materials
Volume: 12
Issue number: 11
Article number: 1805
ISSN (Print): 1996-1944
Original language: English
Source: ORCID
Source ID: /0000-0002-7904-4780/work/58124591

Research output: Contribution to journalArticleScientificpeer-review

Bioactive glass ions induce efficient osteogenic differentiation of human adipose stem cells encapsulated in gellan gum and collagen type I hydrogels

Background: Due to unmet need for bone augmentation, our aim was to promote osteogenic differentiation of human adipose stem cells (hASCs) encapsulated in gellan gum (GG) or collagen type I (COL) hydrogels with bioactive glass (experimental glass 2-06 of composition [wt-%]: Na 2 O 12.1, K 2 O 14.0, CaO 19.8, P 2 O5 2.5, B 2 O 3 1.6, SiO 2 50.0) extract based osteogenic medium (BaG OM) for bone construct development. GG hydrogels were crosslinked with spermidine (GG-SPD) or BaG extract (GG-BaG). Methods: Mechanical properties of cell-free GG-SPD, GG-BaG, and COL hydrogels were tested in osteogenic medium (OM) or BaG OM at 0, 14, and 21 d. Hydrogel embedded hASCs were cultured in OM or BaG OM for 3, 14, and 21 d, and analyzed for viability, cell number, osteogenic gene expression, osteocalcin production, and mineralization. Hydroxyapatite-stained GG-SPD samples were imaged with Optical Projection Tomography (OPT) and Selective Plane Illumination Microscopy (SPIM) in OM and BaG OM at 21 d. Furthermore, Raman spectroscopy was used to study the calcium phosphate (CaP) content of hASC-secreted ECM in GG-SPD, GG-BaG, and COL at 21 d in BaG OM. Results: The results showed viable rounded cells in GG whereas hASCs were elongated in COL. Importantly, BaG OM induced significantly higher cell number and higher osteogenic gene expression in COL. In both hydrogels, BaG OM induced strong mineralization confirmed as CaP by Raman spectroscopy and significantly improved mechanical properties. GG-BaG hydrogels rescued hASC mineralization in OM. OPT and SPIM showed homogeneous 3D cell distribution with strong mineralization in BaG OM. Also, strong osteocalcin production was visible in COL. Conclusions: Overall, we showed efficacious osteogenesis of hASCs in 3D hydrogels with BaG OM with potential for bone-like grafts.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Biomaterials and Tissue Engineering Group, BioMediTech, Research group: Computational Biophysics and Imaging Group, Tampere University Hospital, Research, University of Jyvaskyla, Abo Akad Univ, Abo Akademi University, Dept Phys, Tampere University of Applied Sciences
Contributors: Vuornos, K., Ojansivu, M., Koivisto, J. T., Häkkänen, H., Belay, B., Montonen, T., Huhtala, H., Kääriäinen, M., Hupa, L., Kellomäki, M., Hyttinen, J., Ihalainen, J. A., Miettinen, S.
Number of pages: 14
Pages: 905-918
Publication date: 1 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Materials Science and Engineering C
Volume: 99
ISSN (Print): 0928-4931
Original language: English
ASJC Scopus subject areas: Materials Science(all), Condensed Matter Physics, Mechanics of Materials, Mechanical Engineering
Keywords: Adipose stem cell, Bioactive glass, Collagen type I hydrogel, Gellan gum hydrogel, Osteogenic differentiation
URLs: 

Bibliographical note

DUPL=47148426

Source: Scopus
Source ID: 85061661719

Research output: Contribution to journalArticleScientificpeer-review

VASIM: an automated tool for the quantification of carotid atherosclerosis by computed tomography angiography

The diagnostic imaging techniques currently used to evaluate the arterial atherosclerosis hinge on the manual marking and calculation of the stenosis degree. However, the manual assessment is highly dependent on the operator and characterized by low replicability. The study aimed to develop a fully-automated tool for the segmentation and analysis of atherosclerosis in the extracranial carotid arteries. The dataset consisted of 59 randomly-chosen individuals who had undergone head-and-neck computed tomography angiography (CTA), at the Tampere University Hospital, Tampere, Finland. The analysis algorithm was mainly based on the detection of carotid arteries, delineation of the vascular wall, and extraction of the atherosclerotic plaque. To improve the vascular detection rate, the model-based and volume-wide analytical approaches were deployed. A new fully-automated vascular imaging (VASIM) software tool was developed. For stenosis over 50%, the success rate was 83% for the detection and segmentation. Specificity and sensitivity of the algorithm were 25% and 83%, respectively. The overall accuracy was 71%. The VASIM tool is the first published approach for the fully-automated analysis of atherosclerosis in extracranial carotid arteries. The tool provides new outputs, which may help with the quantitative and qualitative, clinical evaluation of the atherosclerosis burden and evolution. The findings from this study provide a basis for the further development of automated atherosclerosis diagnosis and plaque analysis with CTA.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Quantitative medical imaging, Research group: Computational Biophysics and Imaging Group
Contributors: Caetano Dos Santos, F. L., Kolasa, M., Terada, M., Salenius, J., Eskola, H., Paci, M.
Number of pages: 10
Pages: 1149-1159
Publication date: Jun 2019
Peer-reviewed: Yes

Publication information

Journal: International Journal of Cardiovascular Imaging
Volume: 35
Issue number: 6
ISSN (Print): 1569-5794
Original language: English

Bibliographical note

EXT="Caetano Dos Santos, Florentino Luciano"

Research output: Contribution to journalArticleScientificpeer-review

Bioimpedance Sensor Array for Long-Term Monitoring of Wound Healing from Beneath the Primary Dressings and Controlled Formation of H2O2 Using Low-Intensity Direct Current

Chronic wounds impose a significant financial burden for the healthcare system. Currently, assessment and monitoring of hard-to-heal wounds are often based on visual means and measuring the size of the wound. The primary wound dressings must be removed before assessment can be done. We have developed a quasi-monopolar bioimpedance-measurement-based method and a measurement system to determine the status of wound healing. The objective of this study was to demonstrate that with an appropriate setup, long-term monitoring of wound healing from beneath the primary dressings is feasible. The developed multielectrode sensor array was applied on the wound area and left under the primary dressings for 142 h. The impedance of the wounds and the surrounding intact skin area was measured regularly during the study at 150 Hz, 300 Hz, 1 kHz, and 5 kHz frequencies. At the end of the follow-up period, the wound impedance had reached the impedance of the intact skin at the higher frequencies and increased significantly at the lowest frequencies. The measurement frequency affected the measurement sensitivity in wound monitoring. The skin impedance remained stable over the measurement period. The sensor array also enabled the administration of periodical low-intensity direct current (LIDC) stimulation in order to create an antimicrobial environment across the wound area via the controlled formation of hydrogen peroxide (H2O2).

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Turku University Hospital, Kaarinantie 700, Åbo Akademi University
Contributors: Kekonen, A., Bergelin, M., Johansson, M., Kumar Joon, N., Bobacka, J., Viik, J.
Publication date: 31 May 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 19
Issue number: 11
ISSN (Print): 1424-8220
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: beneath the dressings, bioimpedance, hydrogen peroxide, long-term monitoring, low-intensity direct current, multielectrode, quasi-monopolar, sensor array, wound dressing, wound monitoring, wound stimulation
Electronic versions: 
Source: Scopus
Source ID: 85067176313

Research output: Contribution to journalArticleScientificpeer-review

Systems Pharmacogenomic Landscape of Drug Similarities from LINCS data: Drug Association Networks

Modern research in the biomedical sciences is data-driven utilizing high-throughput technologies to generate big genomic data. The Library of Integrated Network-based Cellular Signatures (LINCS) is an example for a large-scale genomic data repository providing hundred thousands of high-dimensional gene expression measurements for thousands of drugs and dozens of cell lines. However, the remaining challenge is how to use these data effectively for pharmacogenomics. In this paper, we use LINCS data to construct drug association networks (DANs) representing the relationships between drugs. By using the Anatomical Therapeutic Chemical (ATC) classification of drugs we demonstrate that the DANs represent a systems pharmacogenomic landscape of drugs summarizing the entire LINCS repository on a genomic scale meaningfully. Here we identify the modules of the DANs as therapeutic attractors of the ATC drug classes.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, BioMediTech, Research group: Predictive Society and Data Analytics (PSDA), Institute for Intelligent Production, University of Applied Sciences Upper Austria, School of Management, UMIT-The Health and Life Sciences University, Nankai University, Institute for Systems Biology, Seattle, Washington, USA
Contributors: Musa, A., Tripathi, S., Dehmer, M., Yli-Harja, O., Kauffman, S. A., Emmert-Streib, F.
Publication date: 24 May 2019
Peer-reviewed: Yes

Publication information

Journal: Scientific Reports
Volume: 9
Issue number: 1
Article number: 7849
ISSN (Print): 2045-2322
Original language: English

Bibliographical note

EXT="Kauffman, Stuart A."
EXT="Tripathi, Shailesh"

Source: Scopus
Source ID: 85066962993

Research output: Contribution to journalArticleScientificpeer-review

Miniaturized stimulator for imaging of live cell responses to high frequency mechanical vibration

Cellular mechanobiology is highly important for tissue development and disease formation. However, lack of proper tools limit investigation of the cellular responses to different mechanical cues. High frequency (HF) vibration has already been applied in different cellular applications, but the knowledge of the stimulation effect on cells is limited. To meet this challenge, we designed a HF vibration stimulator for combined mechanical manipulation of live cells and high-resolution light-microscopy. Our system utilizes a commercial miniaturized speaker to vibrate a 3D printed sample vehicle horizontally. Technical tests demonstrated excellent performance at lower frequencies (30–60 Hz), enabling even high magnitude (HMHF, G peak ≥ 1 G peak ) method. Real-time acceleration measurement and light-microscopy both revealed accurately and precisely produced low magnitude (LMHF, G peak < 1 G peak ) vibrations. With our system, we could observe cellular responses to the LMHF (0.2 G peak , 30 Hz) vibration. In this paper, we introduce an inexpensive stimulation platform for the mechanobiology research of different cell applications.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech
Contributors: Halonen, H. T., Hyttinen, J. A., Ihalainen, T. O.
Number of pages: 7
Pages: 21-27
Publication date: 11 May 2019

Host publication information

Title of host publication: CMBEBIH 2019 - Proceedings of the International Conference on Medical and Biological Engineering
Publisher: Springer Verlag
Editors: Badnjevic, A., Gurbeta Pokvić, L., Škrbić, R., Badnjevic, A., Gurbeta Pokvić, L.
ISBN (Print): 9783030179700

Publication series

Name: IFMBE Proceedings
Volume: 73
ISSN (Print): 1680-0737
ASJC Scopus subject areas: Bioengineering, Biomedical Engineering
Keywords: High frequency vibration, Live cell imaging, Mechanotransduction

Bibliographical note

jufoid=58152

Source: Scopus
Source ID: 85066029834

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

The national SotePeda 24/7 project develops future professional competencies for the digital health and social care sector in Finland

The SotePeda 24/7 project, financed by the Finnish Ministry of Education and Culture, aims at increasing competencies in developing digital services in the health and social care sector, and to create digital pedagogical solutions to support multidisciplinary learning. The national project, encompassing practically all the relevant universities of applied sciences educating health and social care workers, and two universities in Finland, defines the required eHealth skills and develops educational material, pedagogy and learning environments for the participating organizations. The project covers also eHealth service design skills, management skills, co-developing and the ethical aspects in the new digitally supported health and social care environments.

General information

Publication status: Published
MoE publication type: D1 Article in a trade journal
Organisations: BioMediTech, Laurea-ammattikorkeakoulu
Contributors: Värri, A., Kinnunen, U., Pöyry-Lassila, P., Ahonen, O.
Number of pages: 4
Pages: 232-235
Publication date: 6 May 2019
Peer-reviewed: Unknown

Publication information

Journal: Finnish Journal of eHealth and eWelfare
Volume: 11
Issue number: 3
ISSN (Print): 1798-0798
Original language: English

Research output: Contribution to journalConference articleProfessional

Tidal breathing flow volume profiles during sleep in wheezing infants measured by impedance pneumography

Overnight analysis of tidal breathing flow volume (TBFV) loops, recorded by impedance pneumography (IP), has been successfully applied in the home monitoring of children with wheezing disorders. However, little is known on how sleep physiology modifies the relationship between TBFV profiles and wheeze. We studied such interactions in wheezing infants. Forty-three infants recruited because of recurrent lower airway symptoms were divided into three groups based on their risk of asthma: high (HR), intermediate (IR), or low (LR). Sedated patients underwent infant lung function testing including assessment of airway responsiveness to methacholine at the hospital and a full-night recording of TBFV profiles at home with IP during natural sleep. Overnight TBFV indexes were estimated from periods of higher and lower respiration variability, presumably belonging to active [rapid eye movement (REM)] and quiet [non-REM (NREM)] sleep, respectively. From 35 valid recordings, absolute time indexes showed intrasubject sleep phase differences. Peak flow relative to time and volume was lower in HR compared with LR only during REM, suggesting altered expiratory control. Indexes estimating the concavity/convexity of flow decrease during exhalation suggested limited flow during passive exhale in HR compared with IR and LR, similarly during NREM and REM. Moreover, during REM convexity was negatively correlated with maximal flow at functional residual capacity and methacholine responsiveness. We conclude that TBFV profiles determined from overnight IP recordings vary because of sleep phase and asthma risk. Physiological changes during REM, most likely decrease in respiratory muscle tone, accentuate the changes in TBFV profiles caused by airway obstruction. NEW & NOTEWORTHY Impedance pneumography was used to investigate overnight tidal breathing flow volume (TBFV) indexes and their interactions with sleep phase [rapid eye movement (REM) vs. non-REM] at home in wheezing infants. The study shows that TBFV indexes vary significantly because of sleep phase and asthma risk of the infant and that during REM the changes in TBFV indexes caused by airway obstruction are accentuated and better associated with lung function of the infant.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Physiological Measurement Systems and Methods Group, BioMediTech, Research group: Personal Health Informatics-PHI, Department of Allergology, University Central Hospital , Helsinki , Finland.
Contributors: Gracia-Tabuenca, J., Seppä, V., Jauhiainen, M., Kotaniemi-Syrjänen, A., Malmström, K., Pelkonen, A., Mäkelä, M., Viik, J., Malmberg, L. P.
Number of pages: 10
Pages: 1409-1418
Publication date: 1 May 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Applied Physiology
Volume: 126
Issue number: 5
ISSN (Print): 8750-7587
Original language: English
Source: PubMed
Source ID: 30763165

Research output: Contribution to journalArticleScientificpeer-review

Viability of Mouse Retinal Explant Cultures Assessed by Preservation of Functionality and Morphology

Purpose: Retinal explant cultures provide simplified systems where the functions of the retina and the effects of ocular therapies can be studied in an isolated environment. The purpose of this study was to provide insight into long-term preservation of retinal tissue in culture conditions, enable a deeper understanding of the interdependence of retinal morphology and function, and ensure the reliability of the explant technique for prolonged experiments. Methods: Retinal explants from adult mice were cultured as organotypic culture at the air-medium interface for 14 days in vitro (DIV). Retinal functionality was assessed by multielectrode array technique and morphology by immunohistochemical methods at several time points during culture. Results: Retinal explants retained viability for 14 DIV, although with diminishing neuronal activity, progressing neuronal loss, and increasing reactive gliosis. We recorded spontaneous retinal ganglion cell (RGC) activity up to 14 DIV with temporally changing distribution of RGC firing rates. Light responsiveness was measurable from RGCs for 7 DIV and from photoreceptors for 2 DIV. Apoptotic cells were detected beginning at 3 DIV with their density peaking at 7 DIV. The number of RGCs gradually decreased by 70% during 14 DIV. The change was accompanied by the loss of RGC functionality, resulting in 84% loss of electrically active RGCs. Conclusions: Retinal explants provide a valuable tool for studies of retinal functions and development of ocular therapies. However, critical for long-term use, retinal functionality was lost before structural loss, emphasizing a need for both functional and morphologic readouts to determine the overall state of the cultured retina.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech, Tampere University, Tampere University Hospital
Contributors: Alarautalahti, V., Ragauskas, S., Hakkarainen, J. J., Uusitalo-Järvinen, H., Uusitalo, H., Hyttinen, J., Kalesnykas, G., Nymark, S.
Number of pages: 14
Pages: 1914-1927
Publication date: 1 May 2019
Peer-reviewed: Yes

Publication information

Journal: Investigative ophthalmology & visual science
Volume: 60
Issue number: 6
ISSN (Print): 0146-0404
Original language: English
ASJC Scopus subject areas: Ophthalmology, Sensory Systems, Cellular and Molecular Neuroscience
Electronic versions: 

Bibliographical note

DUPL=47898722

Source: Scopus
Source ID: 85065551723

Research output: Contribution to journalArticleScientificpeer-review

Effects of percutaneous transluminal angioplasty of superficial femoral artery on photoplethysmographic pulse transit times

We analyze the changes in upper and lower limb pulse transit times (PTT) caused by peripheral artery disease (PAD) and its treatment with percutaneous transluminal angioplasty (PTA) of the superficial femoral artery. PTTs were extracted from the photoplethysmograms (PPG) recorded from an index finger and 2nd toes. PTTs were defined between the R-peaks of the ECG and different reference points of the (PPG): foot and peak points, maxima of 1st and 2nd derivative, and by means of intersecting tangents method. Also the PTTs between the toe and finger pulses were analyzed. Our sample consists of 24 subjects examined before and after the PTA and in 1-month follow-up visit. Also 28 older than 65 years controls having normal ankle-to-brachial pressure index (ABI) and no history in cardiovascular diseases as well as 21 younger subjects were examined. The differences between the groups and pre- and post-treatment phases were analyzed by means of non-parametric statistical tests. The changes in the PTTs of upper limb and non-treated lower limb were negligible. The agreement with the reference values, ABI and toe pressures, was studied by kappa-analysis, resulting in kappa-values of 0.33<formula><tex>$\times$</tex></formula>0.91. Differences in PTTs were found between pre-treatment state of the treated limb, post-treatment state and the follow-up visit, as well as between the pre-treatment state and controls. If patients' age and systolic blood pressure were taken into consideration, the method of lower limb PTT calculation from the peak point turns out feasible in finding the markers of PAD and monitoring post- treatment vascular remodellation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Division of Vascular Surgery, Division of Interventional Radiology, Oulu University Hospital, Tampere University Hospital
Contributors: Peltokangas, M., Suominen, V., Vakhitov, D., Korhonen, J., Verho, J., Mattila, V. M., Romsi, P., Lekkala, J., Vehkaoja, A., Oksala, N.
Pages: 1058-1065
Publication date: May 2019
Peer-reviewed: Yes
Early online date: 27 Jun 2018

Publication information

Journal: IEEE Journal of Biomedical and Health Informatics
Volume: 23
Issue number: 3
ISSN (Print): 2168-2194
Original language: English
ASJC Scopus subject areas: Biotechnology, Computer Science Applications, Electrical and Electronic Engineering, Health Information Management
Keywords: Atherosclerosis, Peripheral artery disease, Photoplethysmography, Pulse wave measurements
Additional files: 
Source: Scopus
Source ID: 85049142393

Research output: Contribution to journalArticleScientificpeer-review

Structural dynamics of tight junctions modulate the properties of the epithelial barrier

Tight junctions are dynamic structures that are crucial in establishing the diffusion and electrical barrier of epithelial monolayers. Dysfunctions in the tight junctions can impede this barrier function and lead to many pathological conditions. Unfortunately, detailed understanding of the non-specific permeation pathway through the tight junctions, the so-called leak pathway, is lacking. We created computational models of the leak pathway to describe the two main barrier measures, molecular permeability and transepithelial electric resistance while using common structural dynamics. Our results showed that the proposed alternatives for the leak pathway, the bicellular strand opening dynamics and the tricellular pores, contribute together with distinct degrees, depending on the epithelium. The models can also capture changes in the tight junction barrier caused by changes in tight junction protein composition. In addition, we observed that the molecular permeability was markedly more sensitive to changes in the tight junction structure and strand dynamics compared with transepithelial electric resistance. The results highlight that our model creates a good methodological framework to integrate knowledge on the tight junction structure as well as to provide insights and tools to advance tight junction research.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group, Research group: Biophysics of the eye
Contributors: Tervonen, A., Ihalainen, T. O., Nymark, S., Hyttinen, J.
Publication date: 9 Apr 2019
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 14
Issue number: 4
Article number: e0214876
ISSN (Print): 1932-6203
Original language: English

Bibliographical note

INT=BMTE,"Ihalainen, Teemu O."
DUPL=47149187

Research output: Contribution to journalArticleScientificpeer-review

Facial muscle reanimation by transcutaneous electrical stimulation for peripheral facial nerve palsy

Reanimation of paralysed facial muscles by electrical stimulation has been studied extensively in animal models, but human studies in this field are largely lacking. Twenty-four subjects with a peripheral facial nerve palsy with a median duration of three years were enrolled. We studied activations of four facial muscles with electrical stimulation using surface electrodes. In subjects whose voluntary movement was severely impaired or completely absent, the electrical stimulation produced a movement that was greater in amplitude compared with the voluntary effort in 10 out of 18 subjects in the frontalis muscle, in 5 out of 14 subjects in the zygomaticus major muscle, and in 3 out of 8 subjects in the orbicularis oris muscle. The electrical stimulation produced a stronger blink in 8 subjects out of 22 compared with their spontaneous blinks. The stimulation could produce a better movement even in cases where the muscles were clinically completely paretic, sometimes also in palsies that were several years old, provided that the muscle was not totally denervated. Restoring the function of paralysed facial muscles by electrical stimulation has potential as a therapeutic option in cases where the muscle is clinically paretic but has reinnervation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Sensor Technology and Biomeasurements (STB), BioMediTech, Pirkanmaan sairaanhoitopiiri, Tampere University, Helsinki University Central Hospital, Tampere University Hospital
Contributors: Mäkelä, E., Venesvirta, H., Ilves, M., Lylykangas, J., Rantanen, V., Ylä-Kotola, T., Suominen, S., Vehkaoja, A., Verho, J., Lekkala, J., Surakka, V., Rautiainen, M.
Number of pages: 10
Pages: 155-164
Publication date: 3 Apr 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Medical Engineering and Technology
Volume: 43
Issue number: 3
ISSN (Print): 0309-1902
Original language: English
ASJC Scopus subject areas: Biomedical Engineering
Keywords: Facial paralysis, functional electrical stimulation, prosthetics, rehabilitation

Bibliographical note

INT=comp,"Venesvirta, Hanna"
INT=comp,"Ilves, Mirja"
INT=comp,"Lylykangas, Jani"
INT=comp,"Surakka, Veikko"
INT=bmte,"Rautiainen, Markus"

Source: Scopus
Source ID: 85069057565

Research output: Contribution to journalArticleScientificpeer-review

Exploring associations between the self-reported values, well-being, and health behaviors of finnish citizens: Cross-sectional analysis of more than 100,000 web-survey responses

Background: Understanding the relationship between personal values, well-being, and health-related behavior could facilitate the development of engaging, effective digital interventions for promoting well-being and the healthy lifestyles of citizens. Although the associations between well-being and values have been quite extensively studied, the knowledge about the relationship between health behaviors and values is less comprehensive. Objective: The aim of this study was to assess retrospectively the associations between self-reported values and commitment to values combined with self-reported well-being and health behaviors from a large cross-sectional dataset. Methods: We analyzed 101,130 anonymous responses (mean age 44.78 years [SD 13.82]; 78.88%, 79,770/101,130 women) to a Finnish Web survey, which were collected as part of a national health promotion campaign. The data regarding personal values were unstructured, and the self-reported value items were classified into value types based on the Schwartz value theory and by applying principal component analysis. Logistic and multiple linear regression were used to explore the associations of value types and commitment to values with well-being factors (happiness, communal social activity, work, and family-related distress) and health behaviors (exercise, eating, smoking, alcohol consumption, and sleep). Results: Commitment to personal values was positively related to happiness (part r2=0.28), communal social activity (part r2=0.09), and regular exercise (part r2=0.06; P<.001 for all). Health, Power (social status and dominance), and Mental balance (self-acceptance) values had the most extensive associations with health behaviors. Regular exercise, healthy eating, and nonsmoking increased the odds of valuing Health by 71.7%, 26.8%, and 40.0%, respectively (P<.001 for all). Smoking, unhealthy eating, irregular exercise, and increased alcohol consumption increased the odds of reporting Power values by 27.80%, 27.78%, 24.66%, and 17.35%, respectively (P<.001 for all). Smoking, unhealthy eating, and irregular exercise increased the odds of reporting Mental balance values by 20.79%, 16.67%, and 15.37%, respectively (P<.001 for all). In addition, lower happiness levels increased the odds of reporting Mental balance and Power values by 24.12% and 20.69%, respectively (P<.001 for all). Conclusions: The findings suggest that commitment to values is positively associated with happiness and highlight various, also previously unexplored, associations between values and health behaviors.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, VTT Technical Research Centre of Finland, Northeastern University, College of Computer & Information Science, Bouvé College of Health Sciences, Duodecim Medical Publications Ltd.
Contributors: Honka, A. M., Helander, E., Pavel, M., Jimison, H., Mustonen, P., Korhonen, I., Ermes, M.
Publication date: 1 Apr 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Medical Internet Research
Volume: 21
Issue number: 4
Article number: e12170
ISSN (Print): 1439-4456
Original language: English
ASJC Scopus subject areas: Health Informatics
Keywords: Cross-sectional survey, Happiness, Health behavior, Healthy lifestyle, Value orientation

Bibliographical note

EXT="Jimison, Holly"
EXT="Honka, Anita Marianne"

Source: Scopus
Source ID: 85067296712

Research output: Contribution to journalArticleScientificpeer-review

Hydrolysis and drug release from poly(ethylene glycol)-modified lactone polymers with open porosity

The ability to release active agents from a porous scaffold structure in situ enables the simultaneous structural support for the cells proliferating and differentiating towards tissue as well as the stimulation of tissue regeneration. Due to the great potentiality of such approach, drug-releasing scaffolds were fabricated from hydrolytically degradable polymers. Three copolymers of poly(ethylene glycol), ɛ-caprolactone, L- and D,L-lactide were synthesized and blended with bone-growth inducing active agents, dexamethasone (DM) and 2-phospho-L-ascorbic acid trisodium salt (AS). Porous scaffolds were prepared by means of super-critical carbon dioxide foaming. In the final scaffold structures, the particle size, location and the water solubility of the drug affected the release kinetics. As the large and water soluble AS particles were more exposed to the buffer solution compared to small DM particles, the AS release was burst-like whereas DM showed a long-term release. The material structure had a significant effect on the release kinetics as the porous scaffolds released active agents faster compared to the solid cylinders. Furthermore, this study showed the strong effect of polymer degradation and wettability on the release, which were more determinative than the pore architecture.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Aalto University, Orton Orthopaedic Hospital
Contributors: Asikainen, S., Paakinaho, K., Kyhkynen, A. K., Hannula, M., Malin, M., Ahola, N., Kellomäki, M., Seppälä, J.
Number of pages: 11
Pages: 165-175
Publication date: 1 Apr 2019
Peer-reviewed: Yes

Publication information

Journal: European Polymer Journal
Volume: 113
ISSN (Print): 0014-3057
Original language: English
ASJC Scopus subject areas: Physics and Astronomy(all), Organic Chemistry, Polymers and Plastics, Materials Chemistry
Keywords: 2-Phospho-L-ascorbic acid trisodium salt, Bulk degradation, Dexamethasone, Drug release, Hydrolytic degradation, Supercritical carbon dioxide foaming
Source: Scopus
Source ID: 85060767586

Research output: Contribution to journalArticleScientificpeer-review

Quantification of Stem Cell Derived Cardiomyocyte Beating Mechanics using Video Microscopy Image Analysis

Until recently, the studying of human cardiac cells had been a difficult and to some extent dangerous task due to the risks involved in cardiac biopsies. Induced pluripotent stem cell technology enables the conversion of human adult cells to stem cells, which can be further differentiated to cardiac cells. These cells have the same genotype as the patient from whom they were derived, allowing the studying of genetic cardiac diseases, as well as the cardiac safety and efficacy screening of pharmaceutical agents using human cardiac cells instead of animal cell models. Using the stem cell derived cardiac cells in these studies, however, requires novel and specialized measurement methods for understanding the functioning of these cells.

Long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) are genetic cardiac diseases, which can induce deadly arrhythmias. The induced pluripotent stem cell derived cardiac cells allow the studying of these diseases in laboratory conditions. A greater understanding of these diseases is important for prevention of sudden cardiac death, more accurate diagnosis, and development of possible treatment options. In order to understand the functioning of these cells, new methods are sought after. Traditionally, the electrical function of these cells are measured. However, the primary function of the cardiac cells is to beat in order to pump blood for circulation. The methods to quantify this mechanical function, the contraction and relaxation movement of cells, has been in lesser focus.

The main objective of this work is to develop a measurement method, which allows the in vitro quantification of biomechanics of single human cardiac cells using video microscopy. The method uses digital image correlation to determine movement occurring in cardiac cells during contractile movement. The method is implemented in a software tool, which enables the characterization and parametrization of the cardiomyocyte beating function. The beating function itself can be affected by environmental factors, pharmacological agents and cardiac disease.

Here, the quantification of mechanical function is performed using digital image correlation to estimate displacement between subsequent video frames. Velocity vector fields can then be used to calculate signals that characterize the contraction and relaxation movement. We estimate its accuracy in cardiac cell studies using artificial data sets and its feasibility with concurrent electrical measurements. Cardiac diseases are studied by quantifying beating mechanics from Long QT and CPVT specific cell lines. Traditional electrophysiological measurements are used for validation and comparison. The interaction between calcium and contraction is studied with a simultaneous measurement of biomechanics and calcium imaging.

This thesis resulted a new and accessible analysis method capable of measuring cardiomyocyte biomechanics. This method was determined to be non-toxic and minimally invasive, and found capable to be automated for high-throughput analysis. Due to not harming the cells, repeated measurements are enabled. Using the method, we observed for the first time abnormal beating phenotypes in two long QT associated mutations in single cardiomyocytes. Further, we demonstrated a concurrent calcium and motion measurement without background corrections. This provided also evidence that this combined analysis could be particularly useful in some cardiac disease cases. The methods and results shown in the thesis represent key early advances in the field.

The method was implemented in a software tool, which enabled cell biologists to use it different stages of cardiomyocyte studies. Overall, the results of the thesis represent an accessible method of studying cardiomyocyte biomechanics, which improves the understanding of contraction-calcium coupling and paves way for high-throughput analysis of cardiomyocytes in genetic cardiac disease and pharmacological research.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: BioMediTech
Contributors: Ahola, A.
Number of pages: 114
Publication date: 29 Mar 2019

Publication information

Publisher: Tampere University
Volume: 34
ISBN (Print): 978-952-03-1006-6
ISBN (Electronic): 978-952-03-1007-3
Original language: English

Publication series

Name: Tampere University Dissertations
No.: 34
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

Quantitative Diffusion Tensor Image Analysis: A Clinical Approach to Central Nervous System Injuries

Since the introduction of magnetic resonance imaging (MRI), the full extent of its possibilities has been extensively studied. Diffusion weighted imaging is a specific MRI protocol that enables the quantitative study of water diffusion in tissue. More recently, diffusion imaging has been extended to diffusion tensor imaging (DTI), which can extract detailed information of tissue microstructure. Overall, the most popular clinical application of DTI is the assessment of human brain white matter (WM). DTI can reveal changes in the brain WM microstructure that are not visible by other means of medical imaging. This microstructural resolution allows DTI to be used for the detection of several neuropathologies affecting the brain’s neural network, such as traumatic brain injuries and various types of neurodegenerative disorders.

Mild traumatic brain injury (mTBI) can be defined as a traumatically induced brain function disruption which, in most cases, is not detectable by conventional medical imaging. mTBIs are grievous ailments due to high occurrence and a lack of distinct quantitative diagnostic tools and biomarkers. This signifies that the diagnosis of mTBI is based on subjective clinical measures. Extensive research has been carried out in order to find a clear correlation between DTI derived quantitative metrics and the post-mTBI brain WM. No uniform evidence of absolute conditions of pathology or association with post-injury prognosis has yet been found. However, many previous studies report different correlations between DTI metrics and postinjury brain WM. Unfortunately, the observed changes vary between studies, and final conclusions on the effects of mTBI on brain WM have yet to be made. One source of variation is the incoherency of the analysis methods used in the assessment of mTBI patients. Additionally, the heterogeneity of the studied patient cohorts hinders the chances of drawing a generalisable clinical conclusion.

Our work aims to overcome the issues in quantitative mTBI analysis methods by introducing a simple yet robust automated analysis method for human brain WM analysis. Our research began by applying a novel third-party group level analysis method, tract-based spatial statistics (TBSS), to an mTBI patient sample. We tested the whole sample and several subgroups for abnormal WM, but the results were negative. It was also noted during the study that TBSS would not be a suitable tool for clinical mTBI diagnostic purposes as the method is not fully modifiable for the assessment of individual patients and involves an excessive amount of complex image data manipulation. An additional study of traumatic spinal cord injury (SCI) patients was successfully performed applying TBSS. We found widespread neurodegenerative changes in the post-SCI cerebral WM, but also signs of possible neuroplasticity. The results further confirmed the method’s applicability to neuropathologic conditions with homogeneous effects on the brain WM microstructure.

Based on our findings, we began to create an automated analysis method using a region of interest (ROI) approach. We utilised human brain atlas-based ROIs in the analysis, which were automatically registered to the analysed subjects. The procedure ensures that the subjects’ images are not heavily processed. This in turn minimises the bias caused by image manipulation. The patients were compared against a normal population DTI reference value model created from our control subjects. The preliminary normal population DTI model created for the purpose was a successful quantitative model of DTI reference values. The normal population model could be used in a variety of clinical applications if a large enough number of control subjects were introduced to the model. The normal model would be especially useful in support of mTBI diagnosis methods.

In summary, this thesis has three conclusions. First, we found no DTI measurable associations between WM integrity and acute mTBI when applying TBSS. Second, we found extensive WM changes in the post-SCI brain, which imply an ongoing neuroplastic process in addition to the initial SCI-induced changes. These cerebral WM changes were far more extensive than previously reported. Third, an automated quantitative DTI brain analysis method with prospective clinical applications was introduced. The sensitivity and specificity of the automated method is at an acceptable level when used in conjunction with our preliminary control population set. For clinical applicability, the method requires minor refinements to its usability. More importantly, the normal population model needs to be updated to clinical standards by increasing its statistical power. A large enough normal population data pool could be achieved through an MRI data collection scheme resembling that of a biobank data collection method. In addition, machine learning could be applied in future to create better statistical models for the analysis with more accurate model predicted DTI scalar values.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: BioMediTech
Contributors: Ilvesmäki, T.
Number of pages: 80
Publication date: 29 Mar 2019

Publication information

Publisher: Tampere University
Volume: 39
ISBN (Print): 978-952-03-1014-1
ISBN (Electronic): 978-952-03-1015-8
Original language: English

Publication series

Name: Tampere University Dissertations
Volume: 39
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

Microelectrode Array With Transparent ALD TiN Electrodes

Low noise platinum black or sputtered titanium nitride (TiN) microelectrodes are typically used for recording electrical activity of neuronal or cardiac cell cultures. Opaque electrodes and tracks, however, hinder the visibility of the cells when imaged with inverted microscope, which is the standard method of imaging cells plated on microelectrode array (MEA). Even though transparent indium tin oxide (ITO) electrodes exist, they cannot compete in impedance and noise performance with above-mentioned opaque counterparts. In this work, we propose atomic layer deposition (ALD) as the method to deposit TiN electrodes and tracks which are thin enough (25–65 nm) to be transparent (transmission ∼18–45%), but still benefit from the columnar structure of TiN, which is the key element to decrease noise and impedance of the electrodes. For ALD TiN electrodes (diameter 30 μm) impedances from 510 to 590 kΩ were measured at 1 kHz, which is less than the impedance of bare ITO electrodes. Human induced pluripotent stem cell (hiPSC)-derived cortical neurons were cultured on the ALD TiN MEAs for 14 days without observing any biocompatibility issues, and spontaneous electrical activity of the neurons was recorded successfully. The results show that transparent ALD TiN film is a suitable electrode material for producing functional MEAs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Sensor Technology and Biomeasurements (STB)
Contributors: Ryynänen, T., Pelkonen, A., Grigoras, K., Ylivaara, O. M. E., Hyvärinen, T., Ahopelto, J., Prunnila, M., Narkilahti, S., Lekkala, J.
Number of pages: 7
Publication date: 22 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Neuroscience
Volume: 13
Article number: 226
ISSN (Print): 1662-453X
Original language: English
Keywords: MEA, ALD, TiN, neurons, transparent, microelectrode
Source: ORCID
Source ID: /0000-0001-7424-1841/work/64393492

Research output: Contribution to journalArticleScientificpeer-review

2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile as novel inhibitor of receptor tyrosine kinase and PI3K/AKT/mTOR signaling pathway in glioblastoma

Nerve growth factor receptor (NGFR), a member of kinase protein, is emerging as an important target for Glioblastoma (GBM) treatment. Overexpression of NGFR is observed in many metastatic cancers including GBM, promoting tumor migration and invasion. Hydrazones have been reported to effectively interact with receptor tyrosine kinases (RTKs). We report herein the synthesis of 23 arylhydrazones of active methylene compounds (AHAMCs) compounds and their anti-proliferative activity against GBM cell lines, LN229 and U87. Compound R234, 2-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)benzonitrile, was identified as the most active anti-neoplastic compound, with the IC50 value ranging 87 μM - 107 μM. Molecular docking simulations of the synthesized compounds into the active site of tyrosine receptor kinase A (TrkA), demonstrated a strong binding affinity with R234 and concurs well with the obtained biological results. R234 was found to be a negative regulator of PI3K/Akt/mTOR pathway and an enhancer of p53 expression. In addition, R234 treated GBM cells exhibited the downregulation of cyclins, cyclin-dependent kinases and other key molecules involved in cell cycle such as CCNE, E2F, CCND, CDK6, indicating that R234 induces cell cycle arrest at G1/S. R234 also exerted its apoptotic effects independent of caspase3/7 activity, in both cell lines. In U87 cells, R234 induced oxidative effects whereas LN229 cells annulled oxidative stress. The study thus concludes that R234, being a negative modulator of RTKs and cell cycle inhibitor, may represent a novel class of anti-GBM drugs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Molecular Signaling Lab, Research group: Computational Systems Biology, BioMediTech, Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA)
Contributors: Viswanathan, A., Kute, D., Musa, A., Mani, S. K., Sipilä, V., Emmert-Streib, F., Zubkov, F. I., Gurbanov, A. V., Yli-Harja, O., Kandhavelu, M.
Pages: 291 - 303
Publication date: 15 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: European Journal of Medicinal Chemistry
Volume: 166
ISSN (Print): 0223-5234
Original language: English

Bibliographical note

INT=BMTE, "Kute, Dinesh"
INT=BMTE, "Sipilä, Vili"

Source: Bibtex
Source ID: VISWANATHAN2019291

Research output: Contribution to journalArticleScientificpeer-review

The Resistivity of Human Brain Tumours In Vivo

The histological structure of tumour tissues differs from healthy brain tissues. It can therefore be assumed that there are differences also in the electrical characteristics of these tissues. The electrical characteristics of the tissues define how electric current is distributed within volume conductors, such as the human body or head. Incorrect values affect, for example, the accuracy of impedance tomography or EEG source localisation. However, no controlled experimental data for human in vivo brain tumour resistivity values have been reported thus far. We have developed a controlled method for detecting the electrical resistivities of living brain tissue and investigated different types of brain tumours. The measurements were taken during brain surgeries conducted to remove the tumours. For analysis purposes, the tumours were divided into the following categories: meningiomas, low-grade gliomas, high-grade gliomas (glioblastomas) and other tumours or lesions. The averages of the measured resistivity values were 530 Ω-cm for meningiomas, 160 Ω-cm for low-grade gliomas, and 498 Ω-cm for high-grade gliomas. The differences in high- and low-grade glioma values and meningioma and low-grade glioma values were statistically highly significant. The tumour values were also compared to surrounding healthy brain tissues, and the difference ranged from 40 to 330%. The results suggest that certain tumour types have different electronic properties and that the resistivity values could be used to distinguish tumour tissue from surrounding healthy tissue and to identify and classify certain brain tumour types.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Quantitative medical imaging
Contributors: Latikka, J., Eskola, H.
Number of pages: 8
Pages: 706-713
Publication date: 15 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: Annals of Biomedical Engineering
Volume: 47
Issue number: 3
ISSN (Print): 0090-6964
Original language: English
ASJC Scopus subject areas: Biomedical Engineering
Keywords: Conductivity, Modelling, Tissue electrical properties
Source: Scopus
Source ID: 85059561987

Research output: Contribution to journalArticleScientificpeer-review

Chromosome and plasmid-borne PLacO3O1 promoters differ in sensitivity to critically low temperatures

Temperature shifts trigger genome-wide changes in Escherichia coli's gene expression. We studied if chromosome integration impacts on a gene's sensitivity to these shifts, by comparing the single-RNA production kinetics of a PLacO3O1 promoter, when chromosomally-integrated and when single-copy plasmid-borne. At suboptimal temperatures their induction range, fold change, and response to decreasing temperatures are similar. At critically low temperatures, the chromosome-integrated promoter becomes weaker and noisier. Dissection of its initiation kinetics reveals longer lasting states preceding open complex formation, suggesting enhanced supercoiling buildup. Measurements with Gyrase and Topoisomerase I inhibitors suggest hindrance to escape supercoiling buildup at low temperatures. Consistently, similar phenomena occur in energy-depleted cells by DNP at 30 °C. Transient, critically-low temperatures have no long-term consequences, as raising temperature quickly restores transcription rates. We conclude that the chromosomally-integrated PLacO3O1 has higher sensitivity to low temperatures, due to longer-lasting super-coiled states. A lesser active, chromosome-integrated native lac is shown to be insensitive to Gyrase overexpression, even at critically low temperatures, indicating that the rate of escaping positive supercoiling buildup is temperature and transcription rate dependent. A genome-wide analysis supports this, since cold-shock genes exhibit atypical supercoiling-sensitivities. This phenomenon might partially explain the temperature-sensitivity of some transcriptional programs of E. coli.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Laboratory of Biosystem Dynamics-LBD, CA3 CTS/UNINOVA. Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal., Gene Bridges, Im Neuenheimer Feld 584, 69120, Heidelberg, Germany., Biostatistics Department, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA., Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA, 02142, USA., CA3 CTS/UNINOVA. Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal. andre.sanchesribeiro@tuni.fi.
Contributors: Oliveira, S. M., Goncalves, N. S., Kandavalli, V. K., Martins, L., Neeli-Venkata, R., Reyelt, J., Fonseca, J. M., Lloyd-Price, J., Kranz, H., Ribeiro, A. S.
Publication date: 14 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: Scientific Reports
Volume: 9
Article number: 4486
ISSN (Print): 2045-2322
Original language: English
Source: PubMed
Source ID: 30872616

Research output: Contribution to journalArticleScientificpeer-review

Identification of motor symptoms related to Parkinson disease using motion-tracking sensors at home (KÄVELI): Protocol for an observational case-control study

Background: Clinical characterization of motion in patients with Parkinson disease (PD) is challenging: Symptom progression, suitability of medication, and level of independence in the home environment can vary across time and patients. Appointments at the neurological outpatient clinic provide a limited understanding of the overall situation. In order to follow up these variations, longer-term measurements performed outside of the clinic setting could help optimize and personalize therapies. Several wearable sensors have been used to estimate the severity of symptoms in PD; however, longitudinal recordings, even for a short duration of a few days, are rare. Home recordings have the potential benefit of providing a more thorough and objective follow-up of the disease while providing more information about the possible need to change medications or consider invasive treatments. Objective: The primary objective of this study is to collect a dataset for developing methods to detect PD-related symptoms that are visible in walking patterns at home. The movement data are collected continuously and remotely at home during the normal lives of patients with PD as well as controls. The secondary objective is to use the dataset to study whether the registered medication intakes can be identified from the collected movement data by looking for and analyzing short-term changes in walking patterns. Methods: This paper described the protocol for an observational case-control study that measures activity using three different devices: (1) a smartphone with a built-in accelerometer, gyroscope, and phone orientation sensor, (2) a Movesense smart sensor to measure movement data from the wrist, and (3) a Forciot smart insole to measure the forces applied on the feet. The measurements are first collected during the appointment at the clinic conducted by a trained clinical physiotherapist. Subsequently, the subjects wear the smartphone at home for 3 consecutive days. Wrist and insole sensors are not used in the home recordings. Results: Data collection began in March 2018. Subject recruitment and data collection will continue in spring 2019. The intended sample size was 150 subjects. In 2018, we collected a sample of 103 subjects, 66 of whom were diagnosed with PD. Conclusions: This study aims to produce an extensive movement-sensor dataset recorded from patients with PD in various phases of the disease as well as from a group of control subjects for effective and impactful comparison studies. The study also aims to develop data analysis methods to monitor PD symptoms and the effects of medication intake during normal life andoutside of the clinic setting. Further applications of these methods may include using them as tools for health care professionals to monitor PD remotely and applying them to other movement disorders.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Industrial Engineering and Management, Satakunta Central Hospital, University of Helsinki, Hospital Services, Turku University of Applied Science, Satakunta University of Applied Sciences
Contributors: Jauhiainen, M., Puustinen, J., Mehrang, S., Ruokolainen, J., Holm, A., Vehkaoja, A., Nieminen, H.
Publication date: 1 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Medical Internet Research
Volume: 21
Issue number: 3
Article number: e12808
ISSN (Print): 1439-4456
Original language: English
ASJC Scopus subject areas: Health Informatics
Keywords: Gait, Home monitoring, Mobile phone, Movement analysis, Parkinson disease, Smartphone, Wearable sensors
Source: Scopus
Source ID: 85067441033

Research output: Contribution to journalArticleScientificpeer-review

Core-clad phosphate glass fibers for biosensing

Recently, a phosphate glass with composition 20 CaO-20 SrO-10 Na2O-50 P2O5 (mol%) was found to have good potential as a biomaterial and to possess thermal properties suitable for fiber drawing. This study opened the path towards the development of fully bioresorbable fibers promising for biosensing. In the past, this phosphate glass with CeO2 was found to increase the refractive index and the glass stability. Therefore, a new SrO-containing glass was prepared with 1 mol% of CeO2 and core fibers were drawn from it. A core-clad fiber was also processed, where the core was a Ce-doped glass and the clad undoped, to allow for total internal reflection. The mechanical properties of the core and core-clad fibers are discussed as a function of immersion time in TRIS-buffer solution. Finally, a sensing region was created, in the core-clad fiber, by etching the cladding using phosphoric acid. Then, the change in light transmission, upon immersion in TRIS-buffer solution, was quantified to assess the potential use of the novel core-clad fiber as a biosensor. Upon immersion in TRIS, the core-clad fiber was found to guide light effectively and to maintain a tensile strength of ~150–200 MPa up to 6 weeks in TRIS, clearly showing that this fiber has potential as a biosensing device.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Physics, Research group: Photonics Glasses
Contributors: Mishra, A., Désévédavy, F., Petit, L., Smektala, F., Massera, J.
Pages: 458 - 465
Publication date: Mar 2019
Peer-reviewed: Yes

Publication information

Journal: Materials Science and Engineering C: Materials for Biological Applications
Volume: 96
ISSN (Print): 0928-4931
Original language: English
Source: Bibtex
Source ID: MISHRA2019458

Research output: Contribution to journalArticleScientificpeer-review

Real-Time Bioimpedance-Based Biopsy Needle Can Identify Tissue Type with High Spatial Accuracy

Histological analysis is meaningful in diagnosis only if the targeted tissue is obtained in the biopsy. Often, physicians have to take a tissue sample without accurate information about the location of the instrument tip. A novel biopsy needle with bioimpedance-based tissue identification has been developed to provide data for the automatic classification of the tissue type at the tip of the needle. The aim of this study was to examine the resolution of this identification method and to assess how tissue heterogeneities affect the measurement and tissue classification. Finite element method simulations of bioimpedance measurements were performed using a 3D model. In vivo data of a porcine model were gathered with a moving needle from fat, muscle, blood, liver, and spleen, and a tissue classifier was created and tested based on the gathered data. Simulations showed that very small targets were detectable, and targets of 2 texttimes 2 texttimes 2 mm3 and larger were correctly measurable. Based on the in vivo data, the performance of the tissue classifier was high. The total accuracy of classifying different tissues was approximately 94%. Our results indicate that local bioimpedance-based tissue classification is feasible in vivo, and thus the method provides high potential to improve clinical biopsy procedures.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Injeq Ltd., BioMediTech
Contributors: Halonen, S., Kari, J., Ahonen, P., Kronström, K., Hyttinen, J.
Pages: 836-851
Publication date: Mar 2019
Peer-reviewed: Yes
Early online date: 18 Dec 2018

Publication information

Journal: Annals of Biomedical Engineering
Volume: 47
Issue number: 3
ISSN (Print): 1573-9686
Original language: English

Bibliographical note

EXT="Halonen, Sanna"

Source: Bibtex
Source ID: urn:2f48743c1e57d7a84777bcc0f5a5f267

Research output: Contribution to journalArticleScientificpeer-review

Unexpected role of hyaluronic acid in trafficking siRNA across cellular barrier: First biomimetic, anionic, non-viral transfection method

Circulating nucleic acids, such as short interfering RNA (siRNA), regulate many biological processes; however, the mechanism by which these molecules enter the cell is poorly understood. The role of extracellular‐matrix‐derived polymers in binding siRNAs and trafficking them across the plasma membrane is reported. Thermal melting, dynamic light scattering, scanning electron microscopy, and computational analysis indicate that hyaluronic acid can stabilize siRNA via hydrogen bonding and Van der Waals interactions. This stabilization facilitated HA size‐ and concentration‐dependent gene silencing in a CD44‐positive human osteosarcoma cell line (MG‐63) and in human mesenchymal stromal cells (hMSCs). This native HA‐based siRNA transfection represents the first report on an anionic, non‐viral delivery method that resulted in approximately 60 % gene knockdown in both cell types tested, which correlated with a reduction in translation levels.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Materials Science and Environmental Engineering, Research group: Materials Characterization, Research group: Nanophotonics, Physics
Contributors: Podiyan Oommen, O., Rangasami, V., Mohanty, G., Salminen, T.
Pages: 2815-2819
Publication date: 25 Feb 2019
Peer-reviewed: Yes

Publication information

Journal: Angewandte Chemie (International Edition)
Volume: 58
Issue number: 9
ISSN (Print): 1433-7851
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

A mathematical model and iterative inversion for fluorescent optical projection tomography

Solving the fluorophore distribution in a tomographic setting has been difficult because of the lack of physically meaningful and computationally applicable propagation models. This study concentrates on the direct modelling of fluorescence signals in optical projection tomography (OPT), and on the corresponding inverse problem. The reconstruction problem is solved using emission projections corresponding to a series of rotational imaging positions of the sample. Similarly to the bright field OPT bearing resemblance with the transmission x-ray computed tomography, the fluorescent mode OPT is analogous to x-ray fluorescence tomography (XFCT). As an improved direct model for the fluorescent OPT, we derive a weighted Radon transform based on the XFCT literature. Moreover, we propose a simple and fast iteration scheme for the slice-wise reconstruction of the sample. The developed methods are applied in both numerical experiments and inversion of fluorescent OPT data from a zebrafish embryo. The results demonstrate the importance of propagation modelling and our analysis provides a flexible modelling framework for fluorescent OPT that can easily be modified to adapt to different imaging setups.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, BioMediTech, Research group: Computational Biophysics and Imaging Group, Champalimaud Foundation
Contributors: Koljonen, V., Koskela, O., Montonen, T., Rezaei, A., Belay, B., Figueiras, E., Hyttinen, J., Pursiainen, S.
Publication date: 18 Feb 2019
Peer-reviewed: Yes

Publication information

Journal: Physics in Medicine and Biology
Volume: 64
Issue number: 4
Article number: 045017
ISSN (Print): 0031-9155
Original language: English
ASJC Scopus subject areas: Radiological and Ultrasound Technology, Radiology Nuclear Medicine and imaging
Keywords: beam modelling, fluorescence tomography, iterative reconstruction, optical projection tomography, weighted Radon transform

Bibliographical note

DUPL=48034291

Source: Scopus
Source ID: 85062084216

Research output: Contribution to journalArticleScientificpeer-review

Iterative unsupervised domain adaptation for generalized cell detection from brightfield z-stacks

Background: Cell counting from cell cultures is required in multiple biological and biomedical research applications. Especially, accurate brightfield-based cell counting methods are needed for cell growth analysis. With deep learning, cells can be detected with high accuracy, but manually annotated training data is required. We propose a method for cell detection that requires annotated training data for one cell line only, and generalizes to other, unseen cell lines. Results: Training a deep learning model with one cell line only can provide accurate detections for similar unseen cell lines (domains). However, if the new domain is very dissimilar from training domain, high precision but lower recall is achieved. Generalization capabilities of the model can be improved with training data transformations, but only to a certain degree. To further improve the detection accuracy of unseen domains, we propose iterative unsupervised domain adaptation method. Predictions of unseen cell lines with high precision enable automatic generation of training data, which is used to train the model together with parts of the previously used annotated training data. We used U-Net-based model, and three consecutive focal planes from brightfield image z-stacks. We trained the model initially with PC-3 cell line, and used LNCaP, BT-474 and 22Rv1 cell lines as target domains for domain adaptation. Highest improvement in accuracy was achieved for 22Rv1 cells. F 1 -score after supervised training was only 0.65, but after unsupervised domain adaptation we achieved a score of 0.84. Mean accuracy for target domains was 0.87, with mean improvement of 16 percent. Conclusions: With our method for generalized cell detection, we can train a model that accurately detects different cell lines from brightfield images. A new cell line can be introduced to the model without a single manual annotation, and after iterative domain adaptation the model is ready to detect these cells with high accuracy.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University of Applied Sciences, University of Eastern Finland
Contributors: Liimatainen, K., Kananen, L., Latonen, L., Ruusuvuori, P.
Publication date: 15 Feb 2019
Peer-reviewed: Yes

Publication information

Journal: BMC Bioinformatics
Volume: 20
Issue number: 1
Article number: 80
ISSN (Print): 1471-2105
Original language: English
ASJC Scopus subject areas: Structural Biology, Biochemistry, Molecular Biology, Computer Science Applications, Applied Mathematics
Keywords: Brightfield, Cell detection, Deep learning, Semi-supervised learning, Unsupervised domain adaptation
Electronic versions: 

Bibliographical note

DUPL=47150514

Source: Scopus
Source ID: 85061610929

Research output: Contribution to journalArticleScientificpeer-review

Facial muscle activations by functional electrical stimulation

The present aim was to investigate transcutaneous facial muscle stimulation in order to take further steps in developing facial pacing technology, which can offer a new treatment option for patients with unilateral facial paralysis. This technology ultimately measures muscle activations from one side of the face and simultaneously activates the corresponding muscles of the other side with electrical stimulation. Four facial muscle locations—frontalis, orbicularis oculi, zygomaticus major, and orbicularis oris—of the healthy participants (N = 24) were stimulated to produce an eyebrow raise, eye blink, smile, and lip pucker, respectively. The results showed that a visually observable movement of the forehead and the lower lip was achieved in all participants. On average, the stimulations at the movement threshold were rated as tolerable in terms of pain ratings and neutral in terms of pleasantness ratings. Complete eye blink was achieved in 22 participants, and most did not experience painful sensations. The stimulation of the cheek evoked observable movement in 23 participants, but the stimulation also often resulted in concurrent activation of the eye, mouth, and nose area. The results suggest that transcutaneous stimulation seems to be a promising method for developing further facial pacing technology.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), University of Tampere, Tampere University Hospital, University of Tampere (UTA)
Contributors: Ilves, M., Lylykangas, J., Rantanen, V., Mäkelä, E., Vehkaoja, A., Verho, J., Lekkala, J., Rautiainen, M., Surakka, V.
Number of pages: 7
Pages: 248-254
Publication date: Feb 2019
Peer-reviewed: Yes
Early online date: 5 Nov 2018

Publication information

Journal: Biomedical Signal Processing and Control
Volume: 48
ISSN (Print): 1746-8094
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Functional Voltage-Gated Calcium Channels Are Present in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium

Retinal pigment epithelium (RPE) performs important functions for the maintenance of photoreceptors and vision. Malfunctions within the RPE are implicated in several retinal diseases for which transplantations of stem cell‐derived RPE are promising treatment options. Their success, however, is largely dependent on the functionality of the transplanted cells. This requires correct cellular physiology, which is highly influenced by the various ion channels of RPE, including voltage‐gated Ca2+ (CaV) channels. This study investigated the localization and functionality of CaV channels in human embryonic stem cell (hESC)‐derived RPE. Whole‐cell patch‐clamp recordings from these cells revealed slowly inactivating L‐type currents comparable to freshly isolated mouse RPE. Some hESC‐RPE cells also carried fast transient T‐type resembling currents. These findings were confirmed by immunostainings from both hESC‐ and mouse RPE that showed the presence of the L‐type Ca2+ channels CaV1.2 and CaV1.3 as well as the T‐type Ca2+ channels CaV3.1 and CaV3.2. The localization of the major subtype, CaV1.3, changed during hESC‐RPE maturation co‐localizing with pericentrin to the base of the primary cilium before reaching more homogeneous membrane localization comparable to mouse RPE. Based on functional assessment, the L‐type Ca2+ channels participated in the regulation of vascular endothelial growth factor secretion as well as in the phagocytosis of photoreceptor outer segments in hESC‐RPE. Overall, this study demonstrates that a functional machinery of voltage‐gated Ca2+ channels is present in mature hESC‐RPE, which is promising for the success of transplantation therapies.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Research group: Biophysics of the eye, University of Tampere, Univ Tampere, University of Tampere, BioMediTech, BMT FM5, BioMediTech
Contributors: Korkka, I., Viheriälä, T., Juuti-Uusitalo, K., Uusitalo-Järvinen, H., Skottman, H., Hyttinen, J., Nymark, S.
Pages: 179-193
Publication date: Feb 2019
Peer-reviewed: Yes
Early online date: 4 Nov 2018

Publication information

Journal: Stem Cells Translational Medicine
Volume: 8
Issue number: 2
ISSN (Print): 2157-6564
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Lower limb pulse rise time as a marker of peripheral arterial disease

Objective: The aim of the study was to show if pulse rise times (PRTs) extracted from photoplethysmographic (PPG) pulse waves (PWs) have an association with peripheral arterial disease (PAD) or its endovascular treatment, percutanoeus transluminal angioplasty (PTA) of the superficial femoral artery. Methods: Lower and upper limb PPG PWs were recorded and analyzed from 24 patients who suffered from PAD. The measurements were conducted before and after the treatment, and one month later by using transmission-mode PPG-probes placed in the index finger and second toe. Ankle-to-brachial pressure index and toe pressures were used as references in clinical patient measurements. PRTs, i.e., the time from the foot point to the peak point of the PW, were extracted from the PWs and compared bilaterally. The results from the PAD patients were also compared with 31 same-aged and 34 younger control subjects. Results: Statistically significant differences were found between the pretreatment PRTs of the treated limb of the PAD patients and the same-aged control subjects ( $p< 10^{-9}$ , Mann–Whitney U-test). The changes in the PRT of the treated lower limb were observed immediately after the PTA ( $p< 0.001$ , Student's t -test), and after one month ( $p< 0.0005$ ), whereas the PRTs of the non-treated lower limb and upper limb did not indicate changes between different examinations. Conclusion: Results show that a PRT greater than 240 ms indicates PAD-lesions in the lower limb. Significance: This proof-of-concept study suggests that the PRT could be an effective and easy-to-use indicator for PAD and monitoring the effectiveness of its treatment.

General information

Publication status: Accepted/In press
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Sensor Technology and Biomeasurements (STB), Tampere University Hospital, Division of Vascular Surgery, Division of Interventional Radiology, Oulu University Hospital, Department of Surgery, Faculty of Medicine and Life Sci- ences, University of Tampere, Finnish Cardiovascular Research Center
Contributors: Peltokangas, M., Vakhitov, D., Suominen, V., Korhonen, J., Huotari, M., Verho, J., Röning, J., Mattila, V. M., Romsi, P., Oksala, N., Vehkaoja, A.
Pages: 2596-2603
Publication date: 31 Jan 2019
Peer-reviewed: Yes

Publication information

Journal: IEEE Transactions on Biomedical Engineering
Volume: 66
Issue number: 9
ISSN (Print): 0018-9294
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Versatile Application of Nanocellulose: From Industry to Skin Tissue Engineering and Wound Healing

Nanocellulose is cellulose in the form of nanostructures, i.e., features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, found in bacterial cellulose; nanofibers, present particularly in electrospun matrices; and nanowhiskers, nanocrystals, nanorods, and nanoballs. These structures can be further assembled into bigger two-dimensional (2D) and three-dimensional (3D) nano-, micro-, and macro-structures, such as nanoplatelets, membranes, films, microparticles, and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluconacetobacter), plants (trees, shrubs, herbs), algae (Cladophora), and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology, and biomedical applications, namely for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: BioMediTech, Research group: Micro and Nanosystems Research Group
Contributors: Bacakova, L., Pajorova, J., Bacakova, M., Skogberg, A., Kallio, P., Kolarova, K., Svorcik, V.
Number of pages: 39
Publication date: 29 Jan 2019
Peer-reviewed: Yes

Publication information

Journal: Nanomaterials
Volume: 9
Issue number: 2
ISSN (Print): 2079-4991
Original language: English
Keywords: bacterial nanocellulose, nanofibrillated cellulose, animal nanocellulose, algal nanocellulose, tissue engineering, tissue repair, wound dressing, cell delivery, drug delivery, antimicrobial properties
Electronic versions: 

Research output: Contribution to journalReview ArticleScientificpeer-review

Vibration transmittance measures sternotomy stability - a preliminary study in human cadavers

Background: Stability is essential for the normal healing of a sternotomy. Mechanical vibration transmittance may provide a new means of early detection of diastasis in the sternotomy and thus enable the prevention of further complications. We sought to confirm that vibration transmittance detects sternal diastasis in human tissue. Methods: Ten adult human cadavers (8 males and 2 females) were used for sternal assessments with a device constructed in-house to measure the transmittance of a vibration stimulus across the median sternotomy at the second, third, and fourth costal cartilage. Intact bone was compared to two fixed bone junctions, namely a stable wire fixation and an unstable wire fixation with a 10 mm wide diastasis mimicking a widely rupturing sternotomy. A generalized Linear Mixed Model with the lme function was used to determine the ability of the vibration transmittance device to differentiate mechanical settings in the sternotomy. Results: The transmitted vibration power was statistically significantly different between the intact chest and stable sternotomy closure, stable and unstable closure, as well as intact and unstable closure (t-values and p-values respectively: t = 6.87, p < 0.001; t = 7.41, p < 0.001; t = 14.3, p < 0.001). The decrease of vibration transmittance from intact to stable at all tested costal levels was 78%, from stable to unstable 58%, and from intact to unstable 91%. The vibration transmittance power was not statistically significantly different between the three tested costal levels (level 3 vs. level 2; level 4 vs. level 2; level 4 vs. level 3; t-values and p-values respectively t = - 0.36, p = 0.723; t = 0.35, p = 0.728; t = 0.71, p = 0.484). Conclusions: Vibration transmittance analysis differentiates the intact sternum, wire fixation with exact apposition, and wire fixation with a gap. The gap detection capability is not dependent on the tested costal level. The method may prove useful in the early detection of sternal instability and warrants further exploration.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere Heart Hospital Co., Tampere University of Applied Sciences, Department of Cardiothoracic Surgery, National Public Health Institute, Tampere University Hospital
Contributors: Hautalahti, J., Joutsen, A., Goebeler, S., Luukkaala, T., Khan, J., Hyttinen, J., Laurikka, J.
Publication date: 7 Jan 2019
Peer-reviewed: Yes

Publication information

Journal: JOURNAL OF CARDIOTHORACIC SURGERY
Volume: 14
Issue number: 1
Article number: 2
ISSN (Print): 1749-8090
Original language: English
ASJC Scopus subject areas: Surgery, Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine
Keywords: Electronics, Integrity, Postoperative complications, Sternotomy, Sternum, Vibration transmittance, Wound healing
Electronic versions: 

Bibliographical note

DUPL=47151387

Source: Scopus
Source ID: 85059574086

Research output: Contribution to journalArticleScientificpeer-review

Functionality of Genetic Circuits at Fluctuating Temperatures

Temperature affects virtually all biophysical processes inside cells. Relevantly, it shifts over time, periodically and stochastically, sometimes in minutes. For these reasons, organisms have evolved complex mechanisms to cope with both temperature shifts as well as with temperature cycles.

Endothermic organisms have evolved cellular processes to generate and dissipate heat so as to regulate their body temperature. Failure in these processes can lead to death. Meanwhile, ectothermic organisms, such as Escherichia coli, do not have this ability. Instead, they evolved mechanisms to minimize potential harms. These are activated if temperature deviates from optimal ranges and are controlled by genes and genetic circuits. The robustness and sensitivity of genetic circuits to temperature shifts and what determines them remain largely uncharacterized.

In this thesis, we have studied the effects of temperature shifts on the dynamics of genes and small genetic circuits in Escherichia coli using in vivo single-cell, single-RNA detection techniques, microscopy and microfluidics devices, and image and signal analysis tools. Relevantly, two synthetic constructs were built specifically for these studies: i) an RNA sequence with multiple binding sequences for fluorescent probes was integrated into E. coli’s chromosome and, ii) the Elowitz-Leibler ‘repressilator’ circuit was inserted into a single-copy F-plasmid.

First, we focused on the effects of temperature shifts on the dynamics of a synthetic genetic clock, the above mentioned Elowitz-Leibler low-copy repressilator (LCR). By studying its fluorescence over time, we observed a loss of functionality (fraction of cells exhibiting oscillations) and robustness (fraction of expected oscillations that do occur) for higher-than-optimal temperatures. We hypothesized that this is due to a loss of functionality of the CI repressor, which is one of the proteins composing the structure of this circuit. To test this, we made use of a genetic switch (CICro, where CI is also a component of the circuit’s structure), which we subjected to the same temperature shifts. We found a behavioral change at the same temperature. Namely, as temperature is increased, at a given value, the kinetics of RNA production of the PRM promoter changes from sub-Poissonian to super-Poissonian, consistent with the emergence of tangible repression by the opposing protein, Cro. These behavioral changes in the two circuits, at the same temperature ranges, are best explained by the loss of functionality of CI, which is the only component present in both circuits.

Second, we investigated how coupling within a cell between the copies of the Elowitz-Leibler synthetic genetic clock affects its efficiency in time tracking. For that, we compared the functionality and robustness of the LCR and the newly engineered single-copy repressilator (SCR) to temperature shifts and to external perturbations by introducing Isopropyl β-D-1-thiogalactopyranoside (IPTG), an inducer of the PL-LacO promoter. By analyzing the mean and variability of the periods of oscillation of these two constructs we found that, surprisingly, contrary to when at optimal conditions, the SCR is more robust in regimes of low-temperatures and low-concentrations of IPTG.

Third, we focused on how intrinsic factors to single gene expression dynamics are affected by temperature shifts. Namely, we studied the effects of temperature fluctuations on the kinetics of transcription initiation of the promoters Plac-ara-1 and PtetA. For that, time intervals between consecutive transcription events were extracted using time-lapse, single-RNA microscopy measurements in live cells. To identify which rate-limiting steps of transcription initiation were responsible for the observed differences in varying temperature conditions, detailed stochastic models were fitted to the empirical data using statistical methods. The results suggest that different genes have different rate-limiting steps patterns, i.e. in number and duration of rate-limiting steps, which may allow them to adapt their sensitivity and RNA production kinetics (mean rate and variability) to environmental fluctuations.

Next, we studied the differences in the dynamics of RNA production of a gene when integrated into the chromosome and when integrated into a single-copy plasmid, for various temperature conditions. The results showed that when chromosome-integrated, long-lasting super-coiled states affect the temperature-dependence of the kinetics of transcription initiation. This was not observed in the plasmid-borne promoter, explaining why it is less noisy at low temperatures. We expect this to occur in other genes and to depend on the location in the chromosome. If true, and assuming that the location of genes in the chromosome is subject to natural selection, it implies that cells may make use of supercoiling as a means to regulate noise in gene expression.

Finally, we focused on the effects of temperature shifts on extrinsic factors to gene expression. In particular, we focused on the temperature-dependence of the cytoplasm viscosity. For that, the spatial distribution and mobility of large synthetic and natural protein aggregates in cells were assessed. Previous studies reported that their spatial distribution, at optimal temperatures, is heavily affected by the phenomenon of nucleoid exclusion. However, when cells were subject to critically low temperatures or osmotic stress, we found that both the natural and synthetic protein aggregates became more homogeneously distributed (consistent with weaker effects from nucleoid exclusion). We showed also that this is a result of increased cytoplasm viscosity, which reduced the effects of nucleoid exclusion. Interestingly, in agreement, we observed a reduction in the degree of asymmetries in aggregate numbers between sister cells across generations, which may affect the ability of rejuvenation of cell lineages.

Overall, the results above contribute to a better understanding of the complex consequences of temperature shifts on cellular processes. By affecting intrinsic and extrinsic factors, these shifts can alter significantly the dynamics of gene networks in bacteria. This knowledge is particularly important to understand the high degree of plasticity of natural genetic circuits, which will assist the engineering of robust synthetic genetic circuits.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: BioMediTech
Contributors: Matos Da Costa, S.
Number of pages: 93
Publication date: 4 Jan 2019

Publication information

Publisher: Tampere University
Volume: 1
ISBN (Print): 978-952-03-0969-5
ISBN (Electronic): 978-952-03-0970-1
Original language: English

Publication series

Name: Tampere University Dissertations
Volume: 1
ISSN (Print): 2489-9860
ISSN (Electronic): 2490-0028

Research output: Book/ReportDoctoral thesisCollection of Articles

Tango™ wellness motivator for supporting permanent lifestyle change

We present a system designed for assisting people in obtaining healthier lifestyle. The system includes a monitoring device worn on the chest and a web portal that visualizes the measured parameters and provides the user motivating tips for healthier lifestyles. The monitored parameters include heart rate, step count, calorie consumption, activity level, heart rate variability and sleep quality. A unique feature of the system is that the communication from the wearable unit to the backend server is arranged via direct mobile network connection, thus avoiding the need for a separate gateway device. The measured data can be viewed with a web browser user interface. We evaluated the beat-to-beat heart rate estimation performance with ten subjects in a controlled exercise protocol and with three subjects in 24-h free-living conditions. The average mean absolute error of the R-R interval estimation was 8.0 ms and 6.4 ms in the two test scenarios, respectively and the corresponding coverages of the obtained R-R intervals 76% and 94%.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Health Care Success Ltd
Contributors: Vehkaoja, A., Verho, J., Peltokangas, M., Rantaniva, T., Jeyhani, V., Råglund, J.
Number of pages: 5
Pages: 183-187
Publication date: 1 Jan 2019

Host publication information

Title of host publication: World Congress on Medical Physics and Biomedical Engineering 2018 : June 3-8, 2018, Prague, Czech Republic
Publisher: Springer
ISBN (Print): 978-981-10-9022-6
ISBN (Electronic): 978-981-10-9023-3

Publication series

Name: IFMBE Proceedings
Volume: 68
No.: 3
ISSN (Print): 1680-0737
ASJC Scopus subject areas: Biomedical Engineering
Keywords: Lifestyle coaching, Wearable monitoring
URLs: 

Bibliographical note

jufoid=58152

Source: Scopus
Source ID: 85048261148

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

The Duke treadmill score with bicycle ergometer: Exercise capacity is the most important predictor of cardiovascular mortality

Background: The Duke treadmill score, a widely used treadmill testing tool, is a weighted index combining exercise time or capacity, maximum ST-segment deviation and exercise-induced angina. No previous studies have investigated whether the Duke treadmill score and its individual components based on bicycle exercise testing predict cardiovascular death. Design: Two populations with a standard bicycle testing were used: 3936 patients referred for exercise testing (2371 men, age 56 ± 13 years) from the Finnish Cardiovascular Study (FINCAVAS) and a population-based sample of 2683 men (age 53 ± 5.1 years) from the Kuopio Ischaemic Heart Disease study (KIHD). Methods: Cox regression was applied for risk prediction with cardiovascular mortality as the primary endpoint. Results: In FINCAVAS, during a median 6.3-year (interquartile range (IQR) 4.5–8.2) follow-up period, 180 patients (4.6%) experienced cardiovascular mortality. In KIHD, 562 patients (21.0%) died from cardiovascular causes during the median follow-up of 24.1 (IQR 18.0–26.2) years. The Duke treadmill score was associated with cardiovascular mortality in both populations (FINCAVAS, adjusted hazard ratio (HR) 3.15 for highest vs. lowest Duke treadmill score tertile, 95% confidence interval (CI) 1.83–5.42, P < 0.001; KIHD, adjusted HR 1.71, 95% CI 1.34–2.18, P < 0.001). However, after progressive adjustment for the Duke treadmill score components, the score was not associated with cardiovascular mortality in either study population, as exercise capacity in metabolic equivalents of task was the dominant harbinger of poor prognosis. Conclusions: The Duke treadmill score is associated with cardiovascular mortality among patients who have undergone bicycle exercise testing, but metabolic equivalents of task, a component of the Duke treadmill score, proved to be a superior predictor.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, University of Helsinki, University of Eastern Finland, Central Finland Health Care District, University of Jyvaskyla, University of Bristol, Leicester General Hospital, Tampere Uni. of Applied Sci., Tampere University of Applied Sciences, Pirkanmaan sairaanhoitopiiri, Department of Internal Medicine, South Karelia Central Hospital
Contributors: Salokari, E., Laukkanen, J. A., Lehtimaki, T., Kurl, S., Kunutsor, S., Zaccardi, F., Viik, J., Lehtinen, R., Nikus, K., Kööbi, T., Turjanmaa, V., Kähönen, M., Nieminen, T.
Number of pages: 9
Pages: 199-207
Publication date: 1 Jan 2019
Peer-reviewed: Yes
Early online date: 24 Oct 2018

Publication information

Journal: European Journal of Preventive Cardiology
Volume: 26
Issue number: 2
ISSN (Print): 2047-4873
Original language: English
ASJC Scopus subject areas: Epidemiology, Cardiology and Cardiovascular Medicine
Keywords: Cardiovascular mortality, prognostic factors, stress test
Electronic versions: 
Source: Scopus
Source ID: 85060105677

Research output: Contribution to journalArticleScientificpeer-review

Capacity Analysis of a Peripheral Nerve using Modulated Compound Action Potential Pulses

Artificial neural stimulation of a peripheral nerve can create an in-body data communications channel. We propose the stimulation of a peripheral nerve using energy-harvesting arrays of nanodevices, embedded in biocompatible tissue patches. The resulting extracellular compound action potential (CAP) pulse can provide a data bit-stream for communicating with an embedded receiver. Our objective is to determine the maximum achievable transmission range of a CAP along a nerve and the maximum sustainable bit rate.We model the generation of a CAP and then compute the reduction in amplitude and the spreading of the pulse with propagation distance. The channel capacity is calculated for on-off keying (OOK) and digital pulse interval modulation (DPIM). We show that the transmission range depends on the number and diameters of the activated neurons contributing to the CAP amplitude and width. Our modulation analysis demonstrates the effects of attenuation, background noise, the neural refractory period and pulse broadening on the achievable bit-rate. We show how a maximum OOK bit rate of 200 bit/s can be sustained over transmission distances greater than 100 mm. The proposed approach provides a low bit-rate, unidirectional asynchronous transmission system that could, for example, deliver simple instructions to an embedded drug-delivery system.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electronics and Communications Engineering, Research group: Emerging Technologies for Nano-Bio-Info-Cogno, Waterford Institute of Technology
Contributors: Donohoe, M., Jennings, B., Balasubramaniam, S.
Number of pages: 12
Pages: 154-164
Publication date: Jan 2019
Peer-reviewed: Yes
Early online date: 19 Sep 2018

Publication information

Journal: IEEE Transactions on Communications
Volume: 67
Issue number: 1
ISSN (Print): 0090-6778
Original language: English
ASJC Scopus subject areas: Electrical and Electronic Engineering
Keywords: Action Potentials, Asynchronous Communication, Channel Capacity, Nanobiotechnology, Neurostimulation
Source: Scopus
Source ID: 85053596211

Research output: Contribution to journalArticleScientificpeer-review

Detection of Pancreatic Cancer by Urine Volatile Organic Compound Analysis

BACKGROUND/AIM: Most pancreatic cancer patients are diagnosed at an advanced stage, since the diagnosis is demanding. Field asymmetric waveform ion mobility spectrometry (FAIMS) is a sensitive technique used for the detection of volatile organic compounds (VOC). We evaluated the ability of FAIMS to discriminate between pancreatic cancer and healthy controls from a urine sample. PATIENTS AND METHODS: For a proof-of-concept study in three Finnish hospitals, 68 patients with pancreatic cancer, 36 with acute pancreatitis, 18 with chronic pancreatitis, 8 with pancreatic pre-malign lesions and 52 healthy controls were prospectively recruited. Urine samples were collected at the time of diagnosis and stored at -70°C. The samples were subsequently measured with FAIMS. The data were processed with linear discriminant analysis and cross-validated with leave-one-out cross-validation. RESULTS: FAIMS distinguished pancreatic cancer from controls with a sensitivity of 79% and specificity of 79%. CONCLUSION: As a non-invasive and rapid urine test, FAIMS can discriminate patients with pancreatic cancer from healthy controls.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, University of Eastern Finland, University Central Hospital Kuopio, Hatanpää Hospital, Central Hospital of Seinäjoki, Tampere University Hospital, Fimlab Laboratories Ltd, Finnish Cardiovascular Research Center
Contributors: Nissinen, S. I., Roine, A., Hokkinen, L., Karjalainen, M., Venäläinen, M., Helminen, H., Niemi, R., Lehtimäki, T., Rantanen, T., Oksala, N.
Number of pages: 7
Pages: 73-79
Publication date: Jan 2019
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Anticancer Research
Volume: 39
Issue number: 1
ISSN (Print): 0250-7005
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: FAIMS, linear discriminant analysis, Pancreatic cancer, pre-malignant lesion, urine test, volatile organic compound
Source: Scopus
Source ID: 85059243029

Research output: Contribution to journalArticleScientificpeer-review

Diffusion tensor imaging and disability progression in multiple sclerosis: A 4-year follow-up study

Objectives: Diffusion tensor imaging (DTI) is sensitive technique to detect widespread changes in water diffusivity in the normal-appearing white matter (NAWM) that appears unaffected in conventional magnetic resonance imaging. We aimed to investigate the prognostic value and stability of DTI indices in the NAWM of the brain in an assessment of disability progression in patients with a relapsing-onset multiple sclerosis (MS). Methods: Forty-six MS patients were studied for DTI indices (fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity) in the NAWM of the corpus callosum (CC) and the internal capsule at baseline and at 1 year after. DTI analysis for 10 healthy controls was also performed at baseline. Simultaneously, focal brain lesion volume and atrophy measurements were done at baseline for MS patients. Associations between DTI indices, volumetric measurements, and disability progression over 4 years were studied by multivariate logistic regression analysis. Results: At baseline, most DTI metrics differed significantly between MS patients and healthy controls. There was tendency for associations between baseline DTI indices in the CC and disability progression (p < 0.05). Changes in DTI indices over 1 year were observed only in the CC (p < 0.008), and those changes were not found to predict clinical worsening over 4 years. Clear-cut association with disability progression was not detected for baseline volumetric measurements. Conclusion: Aberrant diffusivity measures in the NAWM of the CC may provide additional information for individual disability progression over 4 years in MS with the relapsing-onset disease. CC may be a good target for DTI measurements in monitoring disease activity in MS, and more studies are needed to assess the related prognostic potential.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Tampere University Hospital, Department of Radiology, Department of Medical Physics
Contributors: Kolasa, M., Hakulinen, U., Brander, A., Hagman, S., Dastidar, P., Elovaara, I., Sumelahti, M.
Publication date: Jan 2019
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Brain and Behavior
Volume: 9
Issue number: 1
Article number: e01194
ISSN (Print): 2162-3279
Original language: English
ASJC Scopus subject areas: Behavioral Neuroscience
Keywords: diffusion tensor imaging, longitudinal study, multiple sclerosis

Bibliographical note

EXT="Dastidar, Prasun"

Source: Scopus
Source ID: 85059078902

Research output: Contribution to journalArticleScientificpeer-review

Treatment of telangiectasia on the cheeks with a compact yellow (585 nm) semiconductor laser and a green (532 nm) KTP laser: a randomized double-blinded split-face trial

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: ORC, Epilaser Oy, Helsinki University Central Hospital, University of Helsinki, Kuopio University Hospital, INSERM, Institut National de la Sante et de la Recherche Medicale (Inserm), French Inst Hlth & Med Res, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Tampere University Hospital
Contributors: Karppinen, T., Kantola, E., Karppinen, A., Rantamäki, A., Kautiainen, H., Mordon, S., Guina, M.
Number of pages: 7
Pages: 223-229
Publication date: Jan 2019
Peer-reviewed: Yes

Publication information

Journal: Lasers in Surgery and Medicine
Volume: 51
Issue number: 3
ISSN (Print): 0196-8092
Original language: English

Bibliographical note

EXT="Mordon, Serge"
DUPL=47150080

Research output: Contribution to journalArticleScientificpeer-review

Action and power efficiency in self-organization: The case for growth efficiency as a cellular objective in escherichia coli

Complex systems of different nature self-organize using common mechanisms. One of those is increase of their efficiency. The level of organization of complex systems of different nature can be measured as increased efficiency of the product of time and energy for an event, which is the amount of physical action consumed by it. Here we apply a method developed in physics to study the efficiency of biological systems. The identification of cellular objectives is one of the central topics in the research of microbial metabolic networks. In particular, the information about a cellular objective is needed in flux balance analysis which is a commonly used constrained-based metabolic network analysis method for the prediction of cellular phenotypes. The cellular objective may vary depending on the organism and its growth conditions. It is probable that nutritionally scarce conditions are very common in the nature, and, in order to survive in those conditions, cells exhibit various highly efficient nutrient-processing systems like enzymes. In this study, we explore the efficiency of a metabolic network in transformation of substrates to new biomass, and we introduce a new objective function simulating growth efficiency. We are searching for general principles of self-organization across systems of different nature. The objective of increasing efficiency of physical action has been identified previously as driving systems toward higher levels of self-organization. The flow agents in those networks are driven toward their natural state of motion, which is governed by the principle of least action in physics. We connect this to a power efficiency principle. Systems structure themselves in a way to decrease the average amount of action or power per one event in the system. In this particular example, action efficiency is examined in the case of growth efficiency of E. coli. We derive the expression for growth efficiency as a special case of action (power) efficiency to justify it through first principles in physics. Growth efficiency as a cellular objective of E. coli coincides with previous research on complex systems and is justified by first principles in physics. It is expected and confirmed outcome of this work. We examined the properties of growth efficiency using a metabolic model for Escherichia coli. We found that the maximal growth efficiency is obtained at a finite nutrient uptake rate. The rate is substrate dependent and it typically does not exceed 20 mmol/h/gDW. We further examined whether the maximal growth efficiency could serve as a cellular objective function in metabolic network analysis and found that cellular growth in batch cultivation can be predicted reasonably well under this assumption. The fit to experimental data was found slightly better than with the commonly used objective function of maximal growth rate. Based on our results, we suggest that the maximal growth efficiency can be considered a plausible optimization criterion in metabolic modeling for E. coli. In the future, it would be interesting to study growth efficiency as an objective also in other cellular systems and under different cultivation conditions.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Wireless Innovation Laboratory at Worcester Polytechnic Institute, Assumption College, Tufts University, Complex Systems Center, University of Vermont
Contributors: Georgiev, G. Y., Aho, T., Kesseli, J., Yli-Harja, O., Kauffman, S. A.
Number of pages: 16
Pages: 229-244
Publication date: 2019

Host publication information

Title of host publication: Evolution, Development and Complexity - Multiscale Evolutionary Models of Complex Adaptive Systems
Publisher: Springer
Editors: Flores Martinez, C. L., Georgiev, G. Y., Smart, J. M., Price, M. E.
ISBN (Print): 9783030000745

Publication series

Name: Springer Proceedings in Complexity
ISSN (Print): 2213-8684
ISSN (Electronic): 2213-8692
ASJC Scopus subject areas: Applied Mathematics, Modelling and Simulation, Computer Science Applications
Keywords: Action efficiency, Constraint-based modeling, Metabolism, Microorganism, Principle of least action

Bibliographical note

jufoid=84878

Source: Scopus
Source ID: 85071889407

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Activity Level and Body Mass Index as Predictors of Physical Workload During Working Career

The increasing prevalence of inactivity and obesity, along with aging, has implications on work capacity of labor force. This study reports the relationships between activity level and BMI by age with objectively measured physical workload. Data were examined from a sample of 19 481 Finnish employees using an estimate of minute-to-minute oxygen consumption based on R-R interval recordings. The mean estimated %VO2max during the working day was 12.1 (±3.6) and 15.1 (±4.5)% for men and women, respectively. Based on a linear model, the mean %VO2max increased by 1.5%-unit per 10-year increase in age, by 2.1%-unit per 5 kg/m2 increase in BMI, and decreased by 1.6%-unit if improving physical activity class by two (p < 0.001 for all). Overweight and obesity, together with inactivity, notably increases workload throughout the career, even though at young adulthood, the daily workload is almost the same for each person regardless of the BMI, activity level, or gender. This study highlights the importance of regular physical activity and normal weight in protecting the worker from excessive physical (cardiovascular) workload during the whole working career.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Personal Health Informatics-PHI, Tyoterveyslaitos
Contributors: Mänttäri, S. K., Oksa, J. A., Virkkala, J., Pietilä, J. A.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Safety and Health at Work
ISSN (Print): 2093-7911
Original language: English
ASJC Scopus subject areas: Safety, Risk, Reliability and Quality, Safety Research, Public Health, Environmental and Occupational Health, Chemical Health and Safety
Keywords: Aging worker, Big data, Functional capacity, Physical activity, Work ability
Electronic versions: 
Source: Scopus
Source ID: 85072749291

Research output: Contribution to journalArticleScientificpeer-review

Advances in Human Stem Cell-Derived Neuronal Cell Culturing and Analysis

This chapter provides an overview of the current stage of human in vitro functional neuronal cultures, their biological application areas, and modalities to analyze their behavior. During the last 10 years, this research area has changed from being practically non-existent to one that is facing high expectations. Here, we present a case study as a comprehensive short history of this process based on extensive studies conducted at NeuroGroup (University of Tampere) and Computational Biophysics and Imaging Group (Tampere University of Technology), ranging from the differentiation and culturing of human pluripotent stem cell (hPSC)-derived neuronal networks to their electrophysiological analysis. After an introduction to neuronal differentiation in hPSCs, we review our work on their functionality and approaches for extending cultures from 2D to 3D systems. Thereafter, we discuss our target applications in neuronal developmental modeling, toxicology, drug screening, and disease modeling. The development of signal analysis methods was required due to the unique functional and developmental properties of hPSC-derived neuronal cells and networks, which separate them from their much-used rodent counterparts. Accordingly, a line of microelectrode array (MEA) signal analysis methods was developed. This work included the development of action potential spike detection methods, entropy-based methods and additional methods for burst detection and quantification, joint analysis of spikes and bursts to analyze the spike waveform compositions of bursts, assessment methods for network synchronization, and computational simulations of synapses and neuronal networks.

General information

Publication status: Published
MoE publication type: A3 Part of a book or another research book
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech, NeuroGroup, Danish Research Institute of Translational Neuroscience - DANDRITE, Aarhus Universitet, Department of Biomedicine, Tampere University
Contributors: Ylä-Outinen, L., Tanskanen, J. M., Kapucu, F. E., Hyysalo, A., Hyttinen, J. A., Narkilahti, S.
Number of pages: 31
Pages: 299-329
Publication date: 2019

Host publication information

Title of host publication: In Vitro Neuronal Networks : From Culturing Methods to Neuro-Technological Applications
Publisher: Springer New York LLC
ISBN (Print): 978-3-030-11134-2
ISBN (Electronic): 978-3-030-11135-9

Publication series

Name: Advances in Neurobiology
Volume: 22
ISSN (Print): 2190-5215
ASJC Scopus subject areas: Biochemistry, Neurology, Developmental Neuroscience, Cellular and Molecular Neuroscience
Keywords: Human neurons, Human pluripotent stem cells, Microelectrode arrays, Signal analysis

Bibliographical note

EXT="Ylä-Outinen, Laura"
EXT="Kapucu, Fikret E."

Source: Scopus
Source ID: 85065845190

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Alkylaminophenol induces G1/S phase cell cycle arrest in glioblastoma cells through p53 and cyclin-dependent kinase signaling pathway

Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. We show here that small molecule 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), a potential anticancer agent, increases the human glioblastoma cell death. Its mechanism of action and the interaction of selective signaling pathways remain elusive. Three structurally related phenolic compounds were tested in multiple glioma cell lines in which the potential activity of the compound, THTMP, was further validated and characterized. Upon prolonged exposer to THTMP, all glioma cell lines undergo p53 and cyclin-dependent kinase mediated cell death with the IC50 concentration of 26.5 and 75.4 μM in LN229 and Snb19, respectively. We found that THTMP strongly inhibited cell growth in a dose and in time dependent manner. THTMP treatment led to G1/S cell cycle arrest and apoptosis induction of glioma cell lines. Furthermore, we identified 3,714 genes with significant changes at the transcriptional level in response to THTMP. Further, a transcriptional analysis (RNA-seq) revealed that THTMP targeted the p53 signaling pathway specific genes causing DNA damage and cell cycle arrest at G1/S phase explained by the decrease of cyclin-dependent kinase 1, cyclin A2, cyclin E1 and E2 in glioma cells. Consistently, THTMP induced the apoptosis by regulating the expression of Bcl-2 family genes and reactive oxygen species while it also changed the expression of several anti-apoptotic genes. These observations suggest that THTMP exerts proliferation activity inhibition and pro-apoptosis effects in glioma through affecting cell cycle arrest and intrinsic apoptosis signaling. Importantly, THTMP has more potential at inhibiting GBM cell proliferation compared to TMZ, the current chemotherapy treatment administered to GBM patients; thus, we propose that THTMP may be an alternative therapeutic option for glioblastoma.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Molecular Signaling Lab, BioMediTech, Computing Sciences, Materials Science and Environmental Engineering, Research group: Computational Systems Biology, Research group: Predictive Society and Data Analytics (PSDA)
Contributors: Doan, P., Musa, A., Candeias, N. R., Emmert-Streib, F., Yli-Harja, O., Kandhavelu, M.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: FRONTIERS IN PHARMACOLOGY
Volume: 10
Issue number: APR
Article number: 330
ISSN (Print): 1663-9812
Original language: English
ASJC Scopus subject areas: Pharmacology, Pharmacology (medical)
Keywords: Anticancer, Apoptosis induction, Cell cycle, Cytotoxicity, Gene expression, Phenol
Electronic versions: 
Source: Scopus
Source ID: 85068363943

Research output: Contribution to journalArticleScientificpeer-review

Astrocyte lineage cells are essential for functional neuronal differentiation and synapse maturation in human iPSC-derived neural networks

Human astrocytes differ dramatically in cell morphology and gene expression from murine astrocytes. The latter are well known to be of major importance in the formation of neuronal networks by promoting synapse maturation. However, whether human astrocyte lineage cells have a similar role in network formation has not been firmly established. Here, we investigated the impact of human astrocyte lineage cells on the functional maturation of neural networks that were derived from human induced pluripotent stem cells (hiPSCs). Initial in vitro differentiation of hiPSC-derived neural progenitor cells and immature neurons (glia+ cultures) resulted in spontaneously active neural networks as indicated by synchronous neuronal Ca2+ transients. Depleting proliferating neural progenitors from these cultures by short-term antimitotic treatment resulted in strongly astrocyte lineage cell-depleted neuronal networks (glia− cultures). Strikingly, in contrast to glia+ cultures, glia− cultures did not exhibit spontaneous network activity. Detailed analysis of the morphological and electrophysiological properties of neurons by patch clamp recordings revealed reduced dendritic arborization in glia− cultures. In addition, a reduced action potential frequency upon current injection in pyramidal-like neurons was observed, whereas the electrical excitability of multipolar neurons was unaltered. Furthermore, we found a reduced dendritic density of PSD95-positive excitatory synapses, and more immature properties of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) miniature excitatory postsynaptic currents (mEPSCs) in glia− cultures, suggesting that the maturation of glutamatergic synapses depends on the presence of hiPSC-derived astrocyte lineage cells. Intriguingly, addition of the astrocyte-derived synapse maturation inducer cholesterol increased the dendritic density of PSD95-positive excitatory synapses in glia− cultures.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Heinrich Heine University Düsseldorf, Philipps University
Contributors: Klapper, S. D., Garg, P., Dagar, S., Lenk, K., Gottmann, K., Nieweg, K.
Number of pages: 17
Pages: 1893-1909
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Glia
Volume: 67
Issue number: 10
ISSN (Print): 0894-1491
Original language: English
ASJC Scopus subject areas: Neurology, Cellular and Molecular Neuroscience
Keywords: human iPSCs, iPSC-derived astrocyte lineage cells, network function, neuronal differentiation, synapse maturation
Source: Scopus
Source ID: 85068131634

Research output: Contribution to journalArticleScientificpeer-review

Automaticity in cardiomyocytes derived from human induced pluripotent stem cells as result of different mechanisms

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group, University of Bologna
Contributors: Paci, M., Severi, S., Hyttinen, J.
Publication date: 2019

Host publication information

Title of host publication: The International Conference in Computing in Cardiology CINC 2019 : September 8-11, 2019, Singapore.
Publisher: IEEE

Bibliographical note

jufoid=72942

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Biophysical Psychiatry—How Computational Neuroscience Can Help to Understand the Complex Mechanisms of Mental Disorders

The brain is the most complex of human organs, and the pathophysiology underlying abnormal brain function in psychiatric disorders is largely unknown. Despite the rapid development of diagnostic tools and treatments in most areas of medicine, our understanding of mental disorders and their treatment has made limited progress during the last decades. While recent advances in genetics and neuroscience have a large potential, the complexity and multidimensionality of the brain processes hinder the discovery of disease mechanisms that would link genetic findings to clinical symptoms and behavior. This applies also to schizophrenia, for which genome-wide association studies have identified a large number of genetic risk loci, spanning hundreds of genes with diverse functionalities. Importantly, the multitude of the associated variants and their prevalence in the healthy population limit the potential of a reductionist functional genetics approach as a stand-alone solution to discover the disease pathology. In this review, we outline the key concepts of a “biophysical psychiatry,” an approach that employs large-scale mechanistic, biophysics-founded computational modelling to increase transdisciplinary understanding of the pathophysiology and strive toward robust predictions. We discuss recent scientific advances that allow a synthesis of previously disparate fields of psychiatry, neurophysiology, functional genomics, and computational modelling to tackle open questions regarding the pathophysiology of heritable mental disorders. We argue that the complexity of the increasing amount of genetic data exceeds the capabilities of classical experimental assays and requires computational approaches. Biophysical psychiatry, based on modelling diseased brain networks using existing and future knowledge of basic genetic, biochemical, and functional properties on a single neuron to a microcircuit level, may allow a leap forward in deriving interpretable biomarkers and move the field toward novel treatment options.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Neuro Science-CNS, Simula Research Laboratory, University of Oslo, Oslo University Hospital, University of California, Massachusetts General Hospital, Harvard Medical School, University of Bergen, University of Heidelberg, Radboud University Medical Center, University of Basel, Prof. Dr. Alex. Obregia Clinical Hospital of Psychiatry, Titu Maiorescu University, Victor Babes National Institute of Pathology, Norwegian University of Life Sciences, Norwegian University of Life Sciences, University of Hertfordshire, Technische Universität Berlin, University of California, Norwegian University of Life Science
Contributors: Mäki-Marttunen, T., Kaufmann, T., Elvsåshagen, T., Devor, A., Djurovic, S., Westlye, L. T., Linne, M., Rietschel, M., Schubert, D., Borgwardt, S., Efrim-Budisteanu, M., Bettella, F., Halnes, G., Hagen, E., Næss, S., Ness, T. V., Moberget, T., Metzner, C., Edwards, A. G., Fyhn, M., Dale, A. M., Einevoll, G. T., Andreassen, O. A.
Number of pages: 14
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Psychiatry
Volume: 10
Article number: 534
ISSN (Print): 1664-0640
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

µCT based characterization of biomaterial scaffold microstructure under compression

Scaffolds are often designed with progressive degradation to make way for cell proliferation of seeded cells for native tissue. The viability of the scaffold has been shown to depend on, among other things, the microstructure. Common parameters, that are used to describe microstructure, are porosity, material thickness, pore size and surface area. These properties quantify the suitability of the scaffold as a substrate for cell adhesion, fluid exchange and nutrient transfer. Bone and cartilage scaffolds are often placed or operated under loads (predominantly compression). This can alter the structural parameters depending on the stiffness of the scaffold and applied deformation. It is important to know, how scaffolds’ parameters change under deformation. In this study, two scaffolds (PLCL-TCP and collagen-PLA) intended for use in bone and cartilage applications, were studied through micro computed tomography based imaging and in situ mechanical testing. The scaffolds were subjected to uniaxial compressive deformation up to 50% of the original size. The corresponding changes in the individual scaffold bulk characteristics were analyzed. Our results show an expected decrease in porosity with increasing deformation (with PLCL-TCP scaffold 52% deformation resulted in 56% decrease in porosity). Especially in the sandwich constructs of collagen-PLA, but also in PLCL-TCP composites, it was evident that different materials are affected differently which may be of significance in applications with mechanical loading. Our results are a step towards understanding the changes in the structure of these scaffolds under loading.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Division of Biomedical Engineering, University of Cape Town, Faculty of Health Sciences
Contributors: Hannula, M., Narra, N., Paakinaho, K., Haaparanta, A., Kellomäki, M., Hyttinen, J.
Number of pages: 5
Pages: 165-169
Publication date: 2019

Host publication information

Title of host publication: World Congress on Medical Physics and Biomedical Engineering 2018
Publisher: Springer
ISBN (Electronic): 978-981-10-9023-3

Publication series

Name: IFMBE Proceedings
Volume: 68
No.: 3
ISSN (Print): 1680-0737
ASJC Scopus subject areas: Bioengineering, Biomedical Engineering
Keywords: Biomaterials, Compression, In situ imaging, Porosity, X-ray microtomography
Source: Scopus
Source ID: 85048307904

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Disease modeling of a mutation in α-actinin 2 guides clinical therapy in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease accompanied by structural and contractile alterations. We identified a rare c.740C>T (p.T247M) mutation in ACTN2, encoding α-actinin 2 in a HCM patient, who presented with left ventricular hypertrophy, outflow tract obstruction, and atrial fibrillation. We generated patient-derived human-induced pluripotent stem cells (hiPSCs) and show that hiPSC-derived cardiomyocytes and engineered heart tissues recapitulated several hallmarks of HCM, such as hypertrophy, myofibrillar disarray, hypercontractility, impaired relaxation, and higher myofilament Ca2+ sensitivity, and also prolonged action potential duration and enhanced L-type Ca2+ current. The L-type Ca2+ channel blocker diltiazem reduced force amplitude, relaxation, and action potential duration to a greater extent in HCM than in isogenic control. We translated our findings to patient care and showed that diltiazem application ameliorated the prolonged QTc interval in HCM-affected son and sister of the index patient. These data provide evidence for this ACTN2 mutation to be disease-causing in cardiomyocytes, guiding clinical therapy in this HCM family. This study may serve as a proof-of-principle for the use of hiPSC for personalized treatment of cardiomyopathies.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Hamburg-Eppendorf, National Research Council, Humanitas Clinical and Research Center, University of Oxford, partner site Hamburg/Kiel/Lübeck
Contributors: Prondzynski, M., Lemoine, M. D., Zech, A. T., Horváth, A., Di Mauro, V., Koivumäki, J. T., Kresin, N., Busch, J., Krause, T., Krämer, E., Schlossarek, S., Spohn, M., Friedrich, F. W., Münch, J., Laufer, S. D., Redwood, C., Volk, A. E., Hansen, A., Mearini, G., Catalucci, D., Meyer, C., Christ, T., Patten, M., Eschenhagen, T., Carrier, L.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: EMBO Molecular Medicine
Article number: e11115
ISSN (Print): 1757-4676
Original language: English
ASJC Scopus subject areas: Molecular Medicine
Keywords: disease modeling, human-induced pluripotent stem cells, hypertrophic cardiomyopathy, long QT syndrome, precision medicine
Electronic versions: 
Source: Scopus
Source ID: 85074749509

Research output: Contribution to journalArticleScientificpeer-review

Dissolution, bioactivity and osteogenic properties of composites based on polymer and silicate or borosilicate bioactive glass

Bioactive glass (BAG)/Poly (Lactic Acid) (PLA) composites have great potential for bone tissue engineering. The interest in these materials is to obtain a scaffold with tailorable properties bringing together the advantages of the composites’ constituents such as the biodegradability, bioactivity and osteoinduction. The materials studied are PLA/13–93 and PLA/13-93B20 (20% of SiO2 is replaced with B2O3 in the 13–93 composition). To characterize them, they were dissolved in TRIS buffer and Simulated Body Fluid (SBF) in vitro. Over the 10 weeks of immersion in TRIS, the ion release from the composites was constant. Following immersion in SBF for 2 weeks, the hydroxyapatite (HA) layer was found to precipitate at the composites surface. By adding Boron, both these reactions were accelerated, as the borosilicate glass dissolves faster than pure silicate glass alone. Polymer degradation was studied and showed that during immersion, the pure PLA rods maintained their molecular weight whereby the composites decreased with time, but despite this the mechanical properties remained stable for at least 10 weeks. Their ability to induce osteogenic differentiation of myoblastic cells was also demonstrated with cell experiments showing that C2C12 cells were able to proliferate and spread on the composites. The Myosin Heavy Chain and Osteopontin were tracked by immunostaining the cells and showed a suppression of the myosin signal and the presence of osteopontin, when seeded onto the composites. This proves osteoinduction occurred. In studying the mineralization of the cells, it was found that BAG presence conditions the synthesizing of mineral matter in the cells. The results show that these composites have a potential for bone tissue engineering.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Biomaterials and Tissue Engineering Group, BioMediTech, Tampere University of Technology, Maison Internationale de la Recherche (MIR)
Contributors: Houaoui, A., Lyyra, I., Agniel, R., Pauthe, E., Massera, J., Boissière, M.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Materials Science and Engineering C
Volume: 107
Article number: 110340
ISSN (Print): 0928-4931
Original language: English
ASJC Scopus subject areas: Materials Science(all), Condensed Matter Physics, Mechanics of Materials, Mechanical Engineering
Keywords: Bioactive glass, Composite material, Osteogenic differentiation
Source: Scopus
Source ID: 85074174905

Research output: Contribution to journalArticleScientificpeer-review

Do bone geometric properties of the proximal femoral diaphysis reflect loading history, muscle properties, or body dimensions?

Objectives: The aim of this study was to investigate activity-induced effects from bone geometric properties of the proximal femur in athletic vs nonathletic healthy females by statistically controlling for variation in body size, lower limb isometric, and dynamic muscle strength, and cross-sectional area of Musculus gluteus maximus. Methods: The material consists of hip and proximal thigh magnetic resonance images of Finnish female athletes (N = 91) engaged in either high jump, triple jump, soccer, squash, powerlifting, endurance running or swimming, and a group of physically active nonathletic women (N = 20). Cross-sectional bone geometric properties were calculated for the lesser trochanter, sub-trochanter, and mid-shaft of the femur regions. Bone geometric properties were analyzed using a general linear model that included body size, muscle size, and muscle strength as covariates. Results: Body size and isometric muscle strength were positively associated with bone geometric properties at all three cross-sectional levels of the femur, while muscle size was positively associated with bone properties only at the femur mid-shaft. When athletes were compared to nonathletic females, triple jump, soccer, and squash resulted in greater values in all studied cross-sections; high jump and endurance running resulted in greater values at the femoral mid-shaft cross-section; and swimming resulted in lower values at sub-trochanter and femur mid-shaft cross-sections. Conclusions: Activity effects from ground impact loading were associated with higher bone geometric values, especially at the femur mid-shaft, but also at lesser and sub-trochanter cross-sections. Bone geometric properties along the femur can be used to assess the mechanical stimuli experienced, where ground impact loading seems to be more important than muscle loading.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Civil Engineering, BioMediTech, Univ of Oulu, Natural Resources Institute Finland (Luke), Jyväskylän yliopisto, GeroCenter Foundation, Jyvaskyla Central Hospital, CNRS, Université de Bordeaux, ICMCB, UKK Institute Finland
Contributors: Niinimäki, S., Narra, N., Härkönen, L., Abe, S., Nikander, R., Hyttinen, J., Knüsel, C. J., Sievänen, H.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: American Journal of Human Biology
Article number: e23246
ISSN (Print): 1042-0533
Original language: English
ASJC Scopus subject areas: Anatomy, Ecology, Evolution, Behavior and Systematics, Anthropology, Genetics
Source: Scopus
Source ID: 85064702174

Research output: Contribution to journalArticleScientificpeer-review

Electrical stimulation of eye blink in individuals with dry eye symptoms caused by chronic unilateral facial palsy

The aim was to validate the functionality and subjective experiences of timer-triggered electrical blink stimulation with participants (N = 6) suffering from dry eye symptoms caused by chronic unilateral facial palsy. In a stimulation condition, the muscles responsible for eye blinking were stimulated at fixed intervals while watching a video for about 120 min. In a control condition, the participants watched a video without stimulation. The participants rated their dry eye symptoms with a questionnaire before and after the both conditions. They also rated the levels of felt pain, discomfort and naturalness of the stimulated movement. Additionally, the magnitude of the stimulated eye blinks over time was evaluated. The results showed that the magnitude of the stimulated eye blink did not decrease significantly during the watching task. The stimulation was rated as painless, slightly uncomfortable, and fairly natural. The experienced eye dryness decreased significantly in the stimulation condition. Most participants got used to the stimulation, or even forgot it during the task. The findings are promising in respect to the use of timer-triggered blink stimulation.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Faculty of Medicine and Health Technology (Otorhinolaryngology), Department of Clinical Neurophysiology, Pirkanmaan sairaanhoitopiiri
Contributors: Lylykangas, J., Ilves, M., Venesvirta, H., Rantanen, V., Mäkelä, E., Vehkaoja, A., Verho, J., Lekkala, J., Rautiainen, M., Surakka, V.
Number of pages: 5
Pages: 7-11
Publication date: 2019

Host publication information

Title of host publication: CMBEBIH 2019 - Proceedings of the International Conference on Medical and Biological Engineering
Publisher: Springer Verlag
Editors: Badnjevic, A., Gurbeta Pokvić, L., Škrbić, R., Badnjevic, A., Gurbeta Pokvić, L.
ISBN (Print): 9783030179700

Publication series

Name: IFMBE Proceedings
Volume: 73
ISSN (Print): 1680-0737
ASJC Scopus subject areas: Bioengineering, Biomedical Engineering
Keywords: Dry eye disease, Dry eye symptoms, Electrical stimulation, Eye blink, Facial palsy

Bibliographical note

jufoid=58152

Source: Scopus
Source ID: 85066049117

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

High Efficiency Lattice Matched Four-Junction Solar Cells on GaAs (Oral)

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: Physics, Faculty of Engineering and Natural Sciences, Research group: ORC
Contributors: Aho, A., Isoaho, R., Raappana, M., Aho, T., Polojärvi, V., Tukiainen, A., Guina, M.
Publication date: 2019
Peer-reviewed: Unknown
Event: Paper presented at Euro MBE 2019, Lenggries, Germany.

Research output: Other conference contributionPaper, poster or abstractScientific

Human Neural Tissues from Neural Stem Cells Using Conductive Biogel and Printed Polymer Microelectrode Arrays for 3D Electrical Stimulation

Electricity is important in the physiology and development of human tissues such as embryonic and fetal development, and tissue regeneration for wound healing. Accordingly, electrical stimulation (ES) is increasingly being applied to influence cell behavior and function for a biomimetic approach to in vitro cell culture and tissue engineering. Here, the application of conductive polymer (CP) poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) pillars is described, direct-write printed in an array format, for 3D ES of maturing neural tissues that are derived from human neural stem cells (NSCs). NSCs are initially encapsulated within a conductive polysaccharide-based biogel interfaced with the CP pillar microelectrode arrays (MEAs), followed by differentiation in situ to neurons and supporting neuroglia during stimulation. Electrochemical properties of the pillar electrodes and the biogel support their electrical performance. Remarkably, stimulated constructs are characterized by widespread tracts of high-density mature neurons and enhanced maturation of functional neural networks. Formation of tissues using the 3D MEAs substantiates the platform for advanced clinically relevant neural tissue induction, with the system likely amendable to diverse cell types to create other neural and non-neural tissues. The platform may be useful for both research and translation, including modeling tissue development, function and dysfunction, electroceuticals, drug screening, and regenerative medicine.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech, University of Wollongong, The University of Auckland, Department of Chemistry and Bioengineering, MacDiarmid Institute for Advanced Materials and Nanotechnology, University of Melbourne
Contributors: Tomaskovic-Crook, E., Zhang, P., Ahtiainen, A., Kaisvuo, H., Lee, C. Y., Beirne, S., Aqrawe, Z., Svirskis, D., Hyttinen, J., Wallace, G. G., Travas-Sejdic, J., Crook, J. M.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: ADVANCED HEALTHCARE MATERIALS
Article number: 1900425
ISSN (Print): 2192-2640
Original language: English
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering, Pharmaceutical Science
Keywords: 3D electrical stimulation, conductive biogels, human neural tissue, printed conducting polymer electrodes, stem cells
Source: Scopus
Source ID: 85067695878

Research output: Contribution to journalArticleScientificpeer-review

Identifying brain tumors by differential mobility spectrometry analysis of diathermy smoke

OBJECTIVE

There is a need for real-time, intraoperative tissue identification technology in neurosurgery. Several solutions are under development for that purpose, but their adaptability for standard clinical use has been hindered by high cost and impracticality issues. The authors tested and preliminarily validated a method for brain tumor identification that is based on the analysis of diathermy smoke using differential mobility spectrometry (DMS).
METHODS

A DMS connected to a special smoke sampling system was used to discriminate brain tumors and control samples ex vivo in samples from 28 patients who had undergone neurosurgical operations. They included meningiomas (WHO grade I), pilocytic astrocytomas (grade I), other low-grade gliomas (grade II), glioblastomas (grade IV), CNS metastases, and hemorrhagic or traumatically damaged brain tissue as control samples. Original samples were cut into 694 smaller specimens in total.
RESULTS

An overall classification accuracy (CA) of 50% (vs 14% by chance) was achieved in 7-class classification. The CA improved significantly (up to 83%) when the samples originally preserved in Tissue-Tek conservation medium were excluded from the analysis. The CA further improved when fewer classes were used. The highest binary classification accuracy, 94%, was obtained in low-grade glioma (grade II) versus control.
CONCLUSIONS

The authors’ results show that surgical smoke from various brain tumors has distinct DMS profiles and the DMS analyzer connected to a special sampling system can differentiate between tumorous and nontumorous tissue and also between different tumor types ex vivo.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Sensor Technology and Biomeasurements (STB), BioMediTech, Tampere University Hospital, Fimlab Laboratories, Tampere University, Tampere University
Contributors: Haapala, I., Karjalainen, M., Kontunen, A., Vehkaoja, A., Nordfors, K., Haapasalo, H., Haapasalo, J., Oksala, N., Roine, A.
Number of pages: 7
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Neurosurgery
ISSN (Print): 0022-3085
Original language: English
Source: RIS
Source ID: urn:211D8C3BA4EB59961A9A3676132F2620

Research output: Contribution to journalArticleScientificpeer-review

Influence of astrocytic gap junction coupling on in silico neuronal network activity

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group
Contributors: Genocchi, B., Lenk, K., Hyttinen, J.
Publication date: 2019

Host publication information

Title of host publication: XV Mediterranean Conference on Medical and Biological Engineering and Computing – MEDICON 2019, IFMBE Proceedings : September 26-28, 2019, Coimbra, Portugal
Volume: 76
Publisher: Springer International Publishing
Editors: Henriques, J., Neves, N., de Carvalho, P.
ISBN (Print): 978-3-030-31634-1
ISBN (Electronic): 978-3-030-31635-8

Publication series

Name: IFMBE Proceedings
ISSN (Print): 1680-0737
ISSN (Electronic): 1433-9277

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Mean and variability in RNA polymerase numbers are correlated to the mean but not the variability in size and composition of Escherichia coli cells

Cell morphology differs with cell physiology in general and with gene expression in particular. We investigate the degree to which these relationships differ with medium richness. Using Escherichia coli cells with fluorescently tagged β' subunits, flow cytometry, and statistical analysis, we study at the single-cell level the correlation between parameters associated to cell morphology and composition (FSC, SSC, and Width channels) and GFP tagged RNA polymerase (RNAp) levels (FITC channel). From measurements in three media differing in richness (M63, LB, and TB) and, thus, cell growth rates, we find that the mean and cell-to-cell variability in RNAp levels are correlated to the mean values of FSC, SSC, and/or Width. Further, in all growth conditions considered, RNAp levels are positively correlated to FSC, SSC, and Width at the single-cell level, with the correlation decreasing for increasing medium richness. Overall, the results suggest that the mean and cell-to-cell variability in levels of RNAp, a master regulator of gene expression, are correlated to the mean values of the parameters assessing the cellular morphology and composition, as measured by flow cytometry, but they do not correlate to the degree of variability of these parameter values.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, BioMediTech, Department of Chemistry and Bioengineering
Contributors: Almeida, B., Chauhan, V., Kandavalli, V., Ribeiro, A.
Number of pages: 8
Pages: 226-233
Publication date: 2019

Host publication information

Title of host publication: BIOINFORMATICS 2019 - 10th International Conference on Bioinformatics Models, Methods and Algorithms, Proceedings; Part of 12th International Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2019
Publisher: SCITEPRESS
Editors: De Maria, E., Gamboa, H., Fred, A.
ISBN (Electronic): 9789897583537
ASJC Scopus subject areas: Biomedical Engineering, Electrical and Electronic Engineering
Keywords: Cell-to-cell Variability, Flow Cytometry, RNA Polymerase, Single-cell Biology, Statistical Analysis
Source: Scopus
Source ID: 85064697521

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Mechanical characterization of pore-graded bioactive glass scaffolds produced by robocasting

Since the discovery of 45S5 Bioglass® by Larry Hench, bioactive glasses have been widely studied as bone substitute materials and, in more recent years, have also shown great promise for producing three-dimensional scaffolds. The development of additive manufacturing techniques and their application in bone tissue engineering allows the design and fabrication of complex structures with controlled porosity. However, achieving strong and mechanically-reliable bioactive glass scaffolds is still a great challenge. Furthermore, there is a relative paucity of studies reporting an exhaustive assessment of other mechanical properties than compressive strength of glass-derived scaffolds. This research work aimed at determining key mechanical properties of silicate SiO2-Na2O-K2OMgO-CaO-P2O5 glass scaffolds fabricated by robocasting and exhibiting a porosity gradient. When tested in compression, these scaffolds had a strength of 6 MPa, a Young's modulus around 340 MPa, a fracture energy of 93 kJ/m3 and a Weibull modulus of 3, which provides a quantification of the scaffold reliability and reproducibility. Robocasting was a suitable manufacturing method to obtain structures with favorable porosity and mechanical properties comparable to those of the human cancellous bone, which is fundamental regarding osteointegration of bone implants.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Politecnico di Torino, McGill University
Contributors: Barberi, J., Nommeots-Nomm, A., Fiume, E., Verné, E., Massera, J., Baino, F.
Number of pages: 8
Pages: 140-147
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Biomedical Glasses
Volume: 5
Issue number: 1
ISSN (Print): 2299-3932
Original language: English
ASJC Scopus subject areas: Electronic, Optical and Magnetic Materials, Ceramics and Composites, Surfaces, Coatings and Films, Materials Chemistry
Keywords: Bioactive glass, Mechanical properties, Robocasting, Scaffold

Bibliographical note

EXT="Nommeots-Nomm, Amy"

Source: Scopus
Source ID: 85078096149

Research output: Contribution to journalArticleScientificpeer-review

Mechanical impact stimulation platform tailored for high-resolution light microscopy

High frequency (HF) mechanical vibration has been used in vitro to study the cellular response to mechanical stimulation and induce stem cell differentiation. However, detailed understanding of the effect of the mechanical cues on cellular physiology is lacking. To meet this limitation, we have designed a system, which enables monitoring of living cells by high-resolution light microscopy during mechanical stimulation by HF vibration or mechanical impacts. The system consists of a commercial speaker, and a 3D printed sample vehicle and frame. The speaker moves the sample in the horizontal plane, allowing simultaneous microscopy. The HF vibration (30–200 Hz) performances of two vehicles made of polymer and aluminum were characterized with accelerometer. The mechanical impacts were characterized by measuring the acceleration of the aluminum vehicle and by time lapse imaging. The lighter polymer vehicle produced higher HF vibration magnitudes at 30–50 Hz frequencies than the aluminum vehicle. However, the aluminum vehicle performed better at higher frequencies (60–70 Hz, 90–100 Hz, 150 Hz). Compatibility of the system in live cell experiments was investigated with epithelial cells (MDCKII, expressing Emerald-Occludin) and HF (0.56 Gpeak, 30 Hz and 60 Hz) vibration. Our findings indicated that our system is compatible with high-resolution live cell microscopy. Furthermore, the epithelial cells were remarkable stable under mechanical vibration stimulation. To conclude, we have designed an inexpensive tool for the studies of cellular biophysics, which combines versatile in vivo like mechanical stimuli with live cell imaging, showing a great potential for several cellular applications.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group
Contributors: Halonen, H. T., Hyttinen, J. A., Ihalainen, T. O.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: HEALTH AND TECHNOLOGY
ISSN (Print): 2190-7188
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Applied Microbiology and Biotechnology, Biomedical Engineering
Keywords: HF vibration, In vitro mechanical stimulation, Live cell imaging, Mechanical impacts, Mechanobiology, Real-time imaging
Source: Scopus
Source ID: 85074696220

Research output: Contribution to journalArticleScientificpeer-review

Non-Linear Heart Rate Variability Measures in Sleep Stage Analysis with Photoplethysmography

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Physics, BioMediTech, Tampere University Hospital, PulseOn SA, Department of Clinical Neurophysiology, Medical Imaging Centre and Hospital Pharmacy, University of Texas, School of Medicine, Department of Epidemiology and Biostatistics, San Antonio, USA, University of Tampere
Contributors: Molkkari, M., Tenhunen, M., Tarniceriu, A., Vehkaoja, A., Himanen, S., Räsänen, E.
Publication date: 2019

Host publication information

Title of host publication: The International Conference in Computing in Cardiology CINC 2019 : September 8-11, 2019, Singapore.

Bibliographical note

jufoid=72942
EXT="Tenhunen, Mirja"

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Possible strategy to use differential mobility spectrometry in real time applications

Differential Mobility Spectrometry (DMS), also called as FAIMS is a variation of atmospheric pressure ion mobility measurement techniques and is capable of providing information about the electric field - mobility dependence of ions. In this method, a combined electric field is used. This field consists of asymmetric oscillating electric field of high intensity and low static field component. Analytical information in DMS is 2-dimensional dependence of ionic current on oscillating field amplitude and the value of static field intensity. The measurement of DMS signal for whole ranges of both variables is time consuming and also generates lot of data. It is a disadvantage of DMS method, which limits the use of this otherwise powerful technology in real time applications that require a response time of few seconds. This paper presents a way to limit measurement time by heuristic knowledge of the properties of the data space and another method based on the concept of Shannon Entropy to find operating parameters satisfying both separation and signal to noise ratio requirements.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University Hospital, Military University of Technology, Department of Surgery, Tampere University of Applied Sciences, LappeenrantaLahti University of Technology LUT
Contributors: Anttalainen, O., Puton, J., Kontunen, A., Karjalainen, M., Kumpulainen, P., Oksala, N., Safaei, Z., Roine, A.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: International Journal for Ion Mobility Spectrometry
ISSN (Print): 1435-6163
Original language: English
ASJC Scopus subject areas: Spectroscopy
Keywords: Differential mobility spectrometry, DMS, FAIMS, Shannon entropy
Source: Scopus
Source ID: 85067989586

Research output: Contribution to journalArticleScientificpeer-review

Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients

Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer (BC/OC) with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3,156 cases and 2,089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish BC patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of BC in the unselected patient group (OR = 5.40 [95% CI 1.58–18.45], p = 0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2,487 BC patients, 556 OC patients and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1,141 BRCA1/2-negative familial BC patients, 7.5% in 1,727 unselected BC patients and 7.2% in 556 unselected OC patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR = 2.63 [1.15–5.48], p = 0.011). These results support gene panel testing of even multiple members of BC families where several mutations may segregate in different individuals.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Helsinki University Central Hospital, Turku University Hospital, University of Helsinki
Contributors: Nurmi, A., Muranen, T. A., Pelttari, L. M., Kiiski, J. I., Heikkinen, T., Lehto, S., Kallioniemi, A., Schleutker, J., Bützow, R., Blomqvist, C., Aittomäki, K., Nevanlinna, H.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: International Journal of Cancer
ISSN (Print): 0020-7136
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: breast cancer, CHEK2, double heterozygote, moderate-risk gene, ovarian cancer
Source: Scopus
Source ID: 85064913446

Research output: Contribution to journalArticleScientificpeer-review

Robocasting of Bioactive SiO2-P2O5-CaO-MgO-Na2O-K2O Glass Scaffolds

Bioactive silicate glass scaffolds were fabricated by a robocasting process in which all the movements of the printing head were programmed by compiling a script (text file). A printable ink made of glass powder and Pluronic F-127, acting as a binder, was extruded to obtain macroporous scaffolds with a grid-like three-dimensional structure. The scaffold architecture was investigated by scanning electron microscopy and microtomographic analysis, which allowed quantifying the microstructural parameters (pore size 150-180 μm and strut diameter 300 μm). In vitro tests in simulated body fluid (SBF) confirmed the apatite-forming ability (i.e., bioactivity) of the scaffolds. The compressive strength (around 10 MPa for as-produced scaffolds) progressively decreased during immersion in SBF (3.3 MPa after 4 weeks) but remains acceptable for bone repair applications. Taken together, these results (adequate porosity and mechanical strength as well as bioactivity) support the potential suitability of the prepared scaffolds for bone substitution.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Politecnico di Torino, Innovation Center Iceland (ICI)
Contributors: Baino, F., Barberi, J., Fiume, E., Orlygsson, G., Massera, J., Verné, E.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Healthcare Engineering
Volume: 2019
Article number: 5153136
ISSN (Print): 2040-2295
Original language: English
ASJC Scopus subject areas: Biotechnology, Surgery, Biomedical Engineering, Health Informatics
Electronic versions: 
Source: Scopus
Source ID: 85065603850

Research output: Contribution to journalArticleScientificpeer-review

Scent Classification by K Nearest Neighbors using Ion-Mobility Spectrometry Measurements

Various classifiers for scent classification based on measurements using an electronic nose (eNose) have been studied recently. In general, classifiers rely on a static database containing reference eNose measurements for known scents. However, most of these approaches require retraining of the classifier every time a new scent needs to be added to the training database. In this paper, the potential of a K nearest neighbors (KNN) classifier is investigated to avoid the time-consuming retraining when updating the database. To speed up classification, a k-dimensional tree search in the KNN classifier and principal component analysis (PCA) are studied. The tests with scents presented to an eNose based on ion-mobility spectrometry (IMS) show that the KNN method classifies scents with high accuracy. Using a k-dimensional tree search instead of an exhaustive search has no significant influence on the misclassification rate but reduces the classification time considerably. The use of PCA-transformed data results in a higher misclassification rate than the use of IMS data when only the first principal components explaining 95% of the total variance are used but in a similar misclassification rate when the first principal components explaining 99% of the total variance are used. In conclusion, the proposed method can be recommended for classifying scents measured with IMS-based eNoses.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Micro and Nanosystems Research Group, Research group: Sensor Technology and Biomeasurements (STB), University of Tampere
Contributors: Müller, P., Salminen, K., Nieminen, V., Kontunen, A., Karjalainen, M., Isokoski, P., Rantala, J., Savia, M., Väliaho, J., Kallio, P., Lekkala, J., Surakka, V.
Pages: 593-606
Publication date: 2019
Peer-reviewed: Yes
Early online date: 28 Aug 2018

Publication information

Journal: Expert Systems with Applications
Volume: 115
ISSN (Print): 0957-4174
Original language: English

Bibliographical note

INT=tut-bmt,"Nieminen, Ville"

Research output: Contribution to journalArticleScientificpeer-review

The electrical conductivity of human cerebrospinal fluid in vivo

Cerebrospinal fluid (CSF) is a clear, highly conductive liquid. Due to its much higher electric conductivity compared to other intracranial tissues, its influence is significant, for example, on volume conductor models, current distribution and heat generation in RF surgery. It has already been shown previously that it is important to include CSF in models to achieve more accurate results. Conductivity values measured in vitro are commonly used in modelling because in vivo values are not available. We have developed a method for taking calibrated in vivo human CSF conductivity measurements with a needle electrode. We used this method to take CSF conductivity measurements from four patients during brain surgeries that were conducted to remove tumours. The patients were selected so that the surgical path went through a ventricle to make sure that there was enough CSF volume to take the measurements. Two of the patients had meningiomas and the other two had gliomas. Measurements taken from clear CSF with our method resulted in conductivity values of 1.79–1.81 S/m. Impurities such as blood or the presence of cystic brain tumour decreased the measured electrical conductivity of CSF. Our results support the findings that the previously suggested conductivity value of 1.79 S/m for human CSF at 37 °C taken from in vitro measurements is applicable for modelling purposes.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Research group: Quantitative medical imaging, Faculty of Biomedical Sciences and Engineering
Contributors: Latikka, J., Eskola, H.
Number of pages: 4
Pages: 773-776
Publication date: 2019

Host publication information

Title of host publication: World Congress on Medical Physics and Biomedical Engineering 2018
Publisher: Springer
ISBN (Electronic): 978-981-10-9035-6

Publication series

Name: IFMBE Proceedings
Volume: 68
No.: 1
ISSN (Print): 1680-0737
ASJC Scopus subject areas: Bioengineering, Biomedical Engineering
Keywords: Brain tissue, Electrical properties, Measurements, Modelling

Bibliographical note

INT=tut-bmt,"Latikka, Juha"
jufoid=58152

Source: Scopus
Source ID: 85048302965

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Defining Data Science by a Data-Driven Quantification of the Community

Data science is a new academic field that has received much attention in recent years. One reason for this is that our increasingly digitalized society generates more and more data in all areas of our lives and science and we are desperately seeking for solutions to deal with this problem. In this paper, we investigate the academic roots of data science. We are using data of scientists and their citations from Google Scholar, who have an interest in data science, to perform a quantitative analysis of the data science community. Furthermore, for decomposing the data science community into its major defining factors corresponding to the most important research fields, we introduce a statistical regression model that is fully automatic and robust with respect to a subsampling of the data. This statistical model allows us to define the ‘importance’ of a field as its predictive abilities. Overall, our method provides an objective answer to the question ‘What is data science?’.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Predictive Society and Data Analytics (PSDA), Research group: Computational Medicine and Statistical Learning Laboratory (CMSL), BioMediTech, University of Applied Sciences Upper Austria, Steyr, Austria., UMIT, Nankai University
Contributors: Emmert-Streib, F., Dehmer, M.
Pages: 235-251
Publication date: 19 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Machine Learning and Knowledge Extraction
ISSN (Print): 2504-4990
Original language: English
Source: ORCID
Source ID: /0000-0003-0745-5641/work/51829234

Research output: Contribution to journalArticleScientificpeer-review

Psoas muscle area and quality are independent predictors of survival in patients treated for abdominal aortic aneurysms

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Department of Surgery, Faculty of Medicine and Life Sci- ences, University of Tampere
Contributors: Lindström, I., Khan, N., Vänttinen, T., Peltokangas, M., Sillanpää, N., Oksala, N.
Publication date: 10 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: ANNALS OF VASCULAR SURGERY
ISSN (Print): 0890-5096
Ratings: 
  • Scopus rating (2018): CiteScore 1.14 SJR 0.595 SNIP 0.721
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Ion Beam Assisted E-Beam Deposited TiN Microelectrodes-Applied to Neuronal Cell Culture Medium Evaluation

Microelectrode material and cell culture medium have significant roles in the signal-to-noise ratio and cell well-being in in vitro electrophysiological studies. Here, we report an ion beam assisted e-beam deposition (IBAD) based process as an alternative titanium nitride (TiN) deposition method for sputtering in the fabrication of state-of-the-art TiN microelectrode arrays (MEAs). The effects of evaporation and nitrogen flow rates were evaluated while developing the IBAD TiN deposition process. Moreover, the produced IBAD TiN microelectrodes were characterized by impedance, charge transfer capacity (CTC) and noise measurements for electrical properties, AFM and SEM for topological imaging, and EDS for material composition. The impedance (at 1 kHz) of brand new 30 mu m IBAD TiN microelectrodes was found to be double but still below 100 k Omega compared with commercial reference MEAs with sputtered TiN microelectrodes of the same size. On the contrary, the noise level of IBAD TiN MEAs was lower compared with that of commercial sputtered TiN MEAs in equal conditions. In CTC IBAD TiN electrodes (3.3 mC/cm(2)) also outperformed the sputtered counterparts (2.0 mC/cm(2)). To verify the suitability of IBAD TiN microelectrodes for cell measurements, human pluripotent stem cell (hPSC)-derived neuronal networks were cultured on IBAD TiN MEAs and commercial sputtered TiN MEAs in two different media: neural differentiation medium (NDM) and Brain Phys (BPH). The effect of cell culture media to hPSC derived neuronal networks was evaluated to gain more stable and more active networks. Higher spontaneous activity levels were measured from the neuronal networks cultured in BPH compared with those in NDM in both MEA types. However, BPH caused more problems in cell survival in long-term cultures by inducing neuronal network retraction and clump formation after 1-2 weeks. In addition, BPH was found to corrode the Si(3)N(4 )insulator layer more than NDM medium. The developed IBAD TiN process gives MEA manufacturers more choices to choose which method to use to deposit TiN electrodes and the medium evaluation results remind that not only electrode material but also insulator layer and cell culturing medium have crucial role in successful long term MEA measurements.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Research group: Nanophotonics, Photonics, Univ Tampere, University of Tampere, Fac Med & Life Sci
Contributors: Ryynanen, T., Toivanen, M., Salminen, T., Yla-Outinen, L., Narkilahti, S., Lekkala, J.
Number of pages: 13
Publication date: 4 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Neuroscience
Volume: 12
Article number: 882
ISSN (Print): 1662-453X
Ratings: 
  • Scopus rating (2018): CiteScore 3.99
Original language: English
Keywords: titanium nitride, microelectrode array, MEA, IBAD, cell culture medium, THIN-FILMS, ELECTRICAL-PROPERTIES, TITANIUM, ARRAYS, STIMULATION, TEMPERATURE, PARAMETERS, COLOR
Electronic versions: 
Source: WOS
Source ID: 000452088800001

Research output: Contribution to journalArticleScientificpeer-review

A Portable Microscale Cell Culture System with Indirect Temperature Control

A physiologically relevant environment is essential for successful long-term cell culturing in vitro. Precise control of temperature, one of the most crucial environmental parameters in cell cultures, increases the fidelity and repeatability of the experiments. Unfortunately, direct temperature measurement can interfere with the cultures or prevent imaging of the cells. Furthermore, the assessment of dynamic temperature variations in the cell culture area is challenging with the methods traditionally used for measuring temperature in cell culture systems. To overcome these challenges, we integrated a microscale cell culture environment together with live-cell imaging and a precise local temperature control that is based on an indirect measurement. The control method uses a remote temperature measurement and a mathematical model for estimating temperature at the desired area. The system maintained the temperature at 37±0.3 °C for more than 4 days. We also showed that the system precisely controls the culture temperature during temperature transients and compensates for the disturbance when changing the cell cultivation medium, and presented the portability of the heating system. Finally, we demonstrated a successful long-term culturing of human induced stem cell–derived beating cardiomyocytes, and analyzed their beating rates at different temperatures.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Research group: Sensor Technology and Biomeasurements (STB), Research group: Micro and Nanosystems Research Group, Tampere University Hospital
Contributors: Mäki, A. J., Verho, J., Kreutzer, J., Ryynänen, T., Rajan, D., Pekkanen-Mattila, M., Ahola, A., Hyttinen, J., Aalto-Setälä, K., Lekkala, J., Kallio, P.
Pages: 566-579
Publication date: 1 Dec 2018
Peer-reviewed: Yes
Early online date: 1 Apr 2018

Publication information

Journal: SLAS Technology
Volume: 23
Issue number: 6
ISSN (Print): 2472-6303
Ratings: 
  • Scopus rating (2018): CiteScore 1.96 SJR 0.511 SNIP 0.508
Original language: English
ASJC Scopus subject areas: Computer Science Applications, Medical Laboratory Technology
Keywords: cell culture, feedback control, microfluidics, modeling, temperature
Source: Scopus
Source ID: 85046801632

Research output: Contribution to journalArticleScientificpeer-review

Normalization of force to muscle cross-sectional area: A helpful attempt to reduce data scattering in contractility studies?

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Hamburg-Eppendorf, University of Murcia, University of Freiburg
Contributors: Pecha, S., Koivumäki, J., Geelhoed, B., Kempe, R., Berk, E., Engel, A., Reichenspurner, H., Eschenhagen, T., Ravens, U., Kaumann, A., Christ, T.
Number of pages: 4
Publication date: 1 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Acta Physiologica
Volume: 224
Issue number: 4
Article number: e13202
ISSN (Print): 1748-1708
Ratings: 
  • Scopus rating (2018): CiteScore 3.4 SJR 1.751 SNIP 1.264
Original language: English
ASJC Scopus subject areas: Physiology
Source: Scopus
Source ID: 85056564696

Research output: Contribution to journalEditorialScientificpeer-review

Happy dogs and happy owners - using dog activity monitoring technology in everyday life



Today, the markets are populated with dozens of devices for dog activity tracking and monitoring. Our aim was to get detailed insights on how dog owners use these devices in their everyday life. Two studies, an interview study with Finnish dog owners (N=7) and an international online questionnaire (N=35) were done to capture the motivations for using dog activity trackers, their utility, user experience, gained insights, and impacts of use. The results showed that the use of the devices was motivated by monitoring health, behavior, learning related issues, and by balancing the amount of activity and rest to an appropriate level. The tracker inspired the owners to spend more time with the dog and to be more observant to his/her behavior. In return, this had the potential to improve their relationship. The owners wanted to keep their dog happy, and in turn, perceiving the dog as happy made the owners happy. Based on the results, we also briefly discuss development needs for dog activity monitoring solutions.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Sensor Technology and Biomeasurements (STB), Computing Sciences, Research area: User experience, University of Helsinki, Stockholm University
Contributors: Väätäjä, H., Majaranta, P., Isokoski, P., Gizatdinova, Y., Kujala, M., Somppi, S., Vehkaoja, A., Vainio, O., Juhlin, O., Ruohonen, M., Surakka, V.
Publication date: Dec 2018

Host publication information

Title of host publication: Proceeding ACI '18 Proceedings of the Fifth International Conference on Animal-Computer Interaction : December 4-6, 2018, Atlanta, Georgia, USA
Publisher: ACM Digital Library
ISBN (Electronic): 978-1-4503-6219-1

Bibliographical note

INT=COMP,"Isokoski, Poika"
INT=COMP,"Gizatdinova, Yulia"
INT=COMP,"Ruohonen, Mikko"
INT=COMP,"Surakka, Veikko"

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Simulation of the Readout Methods for Inductively Coupled High-Frequency Resonance Sensors

The readout methods for inductively coupled resonance sensors were simulated using a lumped element model. The purpose of the study was to analyze the readout methods at high frequencies where the self-resonance of the reader coil is likely to interfere with the measurements. Furthermore, the changes in the reading distance cause measurement errors. This phenomenon was studied using simulation. In addition, an algorithm that compensates these errors was tested. The simulation results were in agreement with the test measurements. In addition, the tested error compensation improved the resonance frequency estimates calculated using the simulated and measured data.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Research group: Biomaterials and Tissue Engineering Group, BioMediTech
Contributors: Salpavaara, T., Hänninen, A., Lekkala, J., Kellomäki, M.
Publication date: 27 Nov 2018

Host publication information

Title of host publication: Eurosensors 2018
Article number: 13: 923

Publication series

Name: Proceedings
Volume: 2
ISSN (Electronic): 2504-3900

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

An Inductively Coupled Biodegradable Capacitive Pressure Sensor

A biodegradable inductively coupled pressure sensor is presented. Three sensors were fabricated using melt processed biodegradable polymers and electron-beam evaporated magnesium. All the sensors showed similar pressure responses from 0 to 0.2 bar. In addition, the responses of the sensors to temperature changes and static pressure are reported. Due to the limited quality factor of the resonance sensors, single measurements were noisy. For this reason, averaging of multiple measurements was needed to achieve consistent results.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, Research group: Sensor Technology and Biomeasurements (STB)
Contributors: Hänninen, A., Salpavaara, T., Lekkala, J., Kellomäki, M.
Publication date: 26 Nov 2018

Host publication information

Title of host publication: Proceedings : Eurosensors 2018
Volume: 2

Publication series

Name: Proceedings
Volume: 2
ISSN (Electronic): 2504-3900

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Cell response to round and star-shaped polylactide fibers

The surface topography of tissue engineering biomaterials is known to affect cell behavior. Polymer fibers can be processed into a variety of diameters and shapes, which both affect the orientation and organization of cells. The fibers can be used to manufacture tissue engineering scaffolds. The aim of this work was to study cell response to microfibers with round and star-shaped cross-sections. In addition, the retention of fiber properties during hydrolytic degradation was evaluated.

Melt spinning method was used to process poly-L/D-lactide 96/4 (PLDLA 96/4) fibers. Knitted scaffolds were manufactured from the fibers for the cell culture experiment. A hydrolytic degradation experiment was conducted for the fibers to evaluate retention of mechanical properties and changes in crystallinity and thermal properties. Human urothelial cells (hUCs) and human foreskin fibroblasts (hFFs) were used in the cell culture experiment. Cell response was assessed using live/dead analysis and crystal violet staining.

Both fibers had suitable mechanical properties to be processed into knitted scaffolds. The hydrolytic degradation experiment demonstrated good retention of properties for the fibers. The number of cells attached to the fibers increased throughout the experiment. The hFFs oriented to the fiber direction on both fibers. The cell culture experiment demonstrated good biocompatibility and no observable difference in cell response was seen between the fiber types.

General information

Publication status: Published
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, University of Tampere, Faculty of Medicine and Life Sciences, Lääkärinkatu 1, 33520 Tampere, Finland, Adult Stem Cell Research Group
Contributors: Kroon, M., Talvitie, E., Miettinen, S., Kellomäki, M.
Publication date: 23 Nov 2018
Peer-reviewed: Unknown
Event: Paper presented at BioMediTech Research Day 2018, Tampere, Finland.
ASJC Scopus subject areas: Biomaterials
Keywords: Polylactide, Tissue Engineering, Cell Culture, Scaffolds, Biotextiles

Research output: Other conference contributionPaper, poster or abstractScientific

Transportable system enabling multiple irradiation studies under simultaneous hypoxia in vitro

Background
Cells in solid tumours are variably hypoxic and hence resistant to radiotherapy - the essential role of oxygen in the efficiency of irradiation has been acknowledged for decades. However, the currently available methods for performing hypoxic experiments in vitro have several limitations, such as a limited amount of parallel experiments, incapability of keeping stable growth conditions and dependence on CO2 incubator or a hypoxia workstation. The purpose of this study was to evaluate the usability of a novel portable system (Minihypoxy) in performing in vitro irradiation studies under hypoxia, and present supporting biological data.

Materials and methods
This study was conducted on cancer cell cultures in vitro. The cells were cultured in normoxic (~ 21% O2) or in hypoxic (1% O2) conditions either in conventional hypoxia workstation or in the Minihypoxy system and irradiated at dose rate 1.28 Gy/min ± 2.9%. The control samples were sham irradiated. To study the effects of hypoxia and irradiation on cell viability and DNA damage, western blotting, immunostainings and clonogenic assay were used. The oxygen level, pH, evaporation rate and osmolarity of the culturing media on cell cultures in different conditions were followed.

Results
The oxygen concentration in interest (5, 1 or 0% O2) was maintained inside the individual culturing chambers of the Minihypoxy system also during the irradiation. The radiosensitivity of the cells cultured in Minihypoxy chambers was declined measured as lower phosphorylation rate of H2A.X and increased clonogenic capacity compared to controls (OER~ 3).

Conclusions
The Minihypoxy system allows continuous control of hypoxic environment in multiple wells and is transportable. Furthermore, the system maintains the low oxygen environment inside the individual culturing chambers during the transportation and irradiation in experiments which are typically conducted in separate facilities.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Micro and Nanosystems Research Group, University of Turku, Faculty of Medicine, Åbo Akademi University, University of Turku, University of Helsinki
Contributors: Kreutzer, J., Metsälä, O., Högel, H., Miikkulainen, P., Kallio, P., Jaakkola, P.
Number of pages: 11
Publication date: 13 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: RADIATION ONCOLOGY
Volume: 13
Issue number: 220
ISSN (Print): 1748-717X
Ratings: 
  • Scopus rating (2018): CiteScore 3.12 SJR 1.139 SNIP 1.127
Original language: English
ASJC Scopus subject areas: Biomedical Engineering
Keywords: Hypoxia, Cancer, Radiotherapy, In vitro, Minihypoxy
Electronic versions: 

Research output: Contribution to journalArticleScientificpeer-review

Evaluation of Wearable Optical Heart Rate Monitoring Sensors

Heart rate monitoring provides valuable information about an individual’s physiological condition. The information obtained from heart rate monitoring can be used for a wide range of purposes such as clinical diagnostics, assessment of the efficiency of training for sports and fitness, or of sleep quality and stress levels in wellbeing applications. Other useful parameters for describing a person’s fitness, such as maximal oxygen uptake and energy expenditure, can also be estimated using heart rate measurement. The traditional ‘gold standard’ for heart rate monitoring is the electrocardiograph, but nowadays there are a number of alternative methods too. Of these, optical sensors provide a relatively simple, lowcost and unobtrusive technology for monitoring heart rate and they are widely accepted by users. There are many factors affecting the measurement of optical signals that have an effect on the accuracy of heart rate estimation. However, there is a lack of standardized and unified methodology for comparing the accuracy of optical heart rate sensors to the ‘gold standard’ methods of measuring heart rate. The widespread use of optical sensors for different purposes has led to a pressing need for a common objective methodology for the evaluation of how accurate these sensors are. This thesis presents a methodology for the objective evaluation of optical heart-rate sensors. The methodology is applied in evaluation studies of four commercially available optical sensors. These evaluations were carried out during both controlled and non-controlled sporting and daily life activities. In addition, evaluation of beat detection accuracy was carried out in non-controlled sleep conditions. The accuracy of wrist-worn optical heart-rate sensors in estimating of maximal oxygen uptake during submaximal exercise and energy expenditure during maximal exercise using heart rate as input parameter were also evaluated. The accuracy of a semi-continuous heart rate estimation algorithm designed to reduce power consumption for long-term monitoring was also evaluated in various conditions. The main findings show that optical heart-rate sensors may be highly accurate during rhythmic sports activities, such as jogging, running, and cycling, including ramp-up running during maximal exercise testing. During non-rhythmic activities, such as intermittent hand movements, the sensors’ accuracy depends on where they are worn. During sleep and motionless conditions, the optical heart-rate sensors’ estimates for beat detection and inter-beat interval showed less than one percent inaccuracy against the values obtained using standard measurement techniques. The sensors were also sufficiently accurate at measuring the interbeat intervals to be used for calculating the heart rate variability parameters. The estimation accuracy of the fitness parameters derived from measured heart rate can be described as follows. An assessment of the maximal oxygen uptake estimation during a sub-maximal outdoor exercise had a precision close to a sport laboratory measurement. The energy expenditure estimation during a maximal exercise was more accurate during higher intensity of exercise above aerobic threshold but the accuracy decreased at lower intensity of exercise below the aerobic threshold, in comparison with the standardized reference measurement. The semi-continuous algorithm was nearly as accurate as continuous heart-rate detection, and there was a significant reduction in the power consumption of the optical chain components up to eighty percent. The results obtained from these studies show that, under certain conditions, optical sensors may be similarly accurate in measuring heart rate as the ‘gold standard’ methods and they can be relied on to monitor heart rate for various purposes during sport, everyday activities, or sleep.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: Faculty of Biomedical Sciences and Engineering
Contributors: Parak, J.
Number of pages: 113
Publication date: 8 Nov 2018

Publication information

Publisher: Tampere University of Technology
ISBN (Print): 978-952-15-4210-7
ISBN (Electronic): 978-952-15-4246-6
Original language: English

Publication series

Name: Tampere University of Technology. Publication
Volume: 1580
ISSN (Print): 1459-2045

Research output: Book/ReportDoctoral thesisCollection of Articles

Kvantitatiivinen menetelmä ja mittalaitteisto laskimoperäisen haavan paranemisen seurantaan

General information

Publication status: Published
MoE publication type: A3 Part of a book or another research book
Organisations: Faculty of Biomedical Sciences and Engineering, Turku Univ Hosp, University of Turku, Åbo Akademi
Contributors: Kekonen, A., Bergelin, M., Viik, J.
Number of pages: 7
Pages: 95-101
Publication date: 5 Nov 2018

Host publication information

Title of host publication: Haavanhoidon kaksi vuosikymmentä
Publisher: Suomen Haavanhoitoyhdistys ry
Editors: Iivanainen, A., Kallio, H.
ISBN (Print): 978-951-98633-4-4
ASJC Scopus subject areas: Biomedical Engineering, Dermatology

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Added value of autoregulation and multi-step kinetics of transcription initiation

Bacterial gene expression regulation occurs mostly during transcription, which has two main rate-limiting steps: the close complex formation, when the RNA polymerase binds to an active promoter, and the subsequent open complex formation, after which it follows elongation. Tuning these steps’ kinetics by the action of e.g. transcription factors, allows for a wide diversity of dynamics. For example, adding autoregulation generates single-gene circuits able to perform more complex tasks. Using stochastic models of transcription kinetics with empirically validated parameter values, we investigate how autoregulation and the multi-step transcription initiation kinetics of single-gene autoregulated circuits can be combined to fine-tune steady state mean and cell-to-cell variability in protein expression levels, as well as response times. Next, we investigate how they can be jointly tuned to control complex behaviours, namely, time counting, switching dynamics and memory storage. Overall, our finding suggests that, in bacteria, jointly regulating a single-gene circuit’s topology and the transcription initiation multi-step dynamics allows enhancing complex task performance.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Laboratory of Biosystem Dynamics-LBD
Contributors: Prajapat, M. K., Ribeiro, A. S.
Publication date: 1 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Royal Society Open Science
Volume: 5
Issue number: 11
Article number: 181170
ISSN (Print): 2054-5703
Ratings: 
  • Scopus rating (2018): CiteScore 2.71 SJR 1.131 SNIP 1.058
Original language: English
ASJC Scopus subject areas: General
Keywords: Autoregulation mechanisms, Cell-to-cell variability, Rate-limiting steps, Transcription initiation
Electronic versions: 
Source: Scopus
Source ID: 85058415001

Research output: Contribution to journalArticleScientificpeer-review

Health and Social Care Needs Multidisciplinary Competences

The SotePeda 24/7 project (2018–2020) aims to improve the future digital and co-creation skills and competences of multidisciplinary developers of health and social care services. The project develops digital competences for health and social care, information communication and technology (ICT), and business professionals. It offers digital studies, pedagogical solutions, competence frameworks, ethical principles, and a new open-study environment. The purpose of this article is to describe the aims of SotePeda 24/7 and explain what kinds of digital solutions and pedagogical tools it will offer to meet health and social care sector reforms for educators, students, and working life representatives. Future health and social care requires multidisciplinary, boundary-crossing competence to utilise digitalisation as part of health and social care services.

General information

Publication status: Published
MoE publication type: D1 Article in a trade journal
Organisations: Research group: Personal Health Informatics-PHI, Research group: Sleep and Sensory Signal Analysis Group-SSSAG, Faculty of Biomedical Sciences and Engineering, Laurea-ammattikorkeakoulu, Lahden ammattikorkeakoulu
Contributors: Ahonen, O., Id-Korhonen, A., Juvonen, S., Kinnunen, U., Koivisto, J., Koski, A., Koskinen, R., Laakkonen, T., Paldanius, M., Poikela, P., Pöyry-Lassila, P., Rajalahti, E., Romppanen, T., Sanerma, P., Sirviö, T., Säätelä, S., Vesterinen, O., Värri, A.
Publication date: 29 Oct 2018
Peer-reviewed: Unknown

Publication information

Journal: Laurea Journal
Volume: 2018
Issue number: 29.10.2018
ISSN (Print): 2489-9690
Original language: English

Research output: Contribution to journalArticleProfessional

Automatic Evaluation of Carotid Stenosis Based on Computed Tomography Angiography

Atherosclerosis is a systemic disease, affecting individuals of all ages. It is characterized by the deposition of foreign elements in the arterial intima-media layer, leading to a gradual narrowing of the vascular lumen, impeding the blood flow. One of the possible consequences of atherosclerosis is transient ischemia or infarction of internal organs, including heart and brain.

In the clinical practice, the diagnosis and evaluation of the progression of carotid atherosclerosis are usually performed by ultrasound imaging or computed tomography angiography. In both techniques, a large dependence on hand-operated assessment is present. To evaluate the stage of stenosis, a clinician has to take two measurements manually - the average lumen diameter, and the narrowest lumen diameter, i.e., where the plaque is located. The manual assessment of the carotid diameters does not guarantee reproducibility and repeatability of the results. It is also far from optimal due to the large chance of human error. An alternative approach is necessary.

The thesis focuses on the development of a tool capable of reducing or even eliminating human dependency and possible errors that can occur during the manual assessment. A fully automatic tool - VASIM (Vascular Imaging) was developed. It uses reliable, fast, and simple methods, such as morphological operators both in 2D and in 3D, to segment the lumen volume and areas for stenosis calculation but also for the examination of vascular walls, plaque, and vessel-surrounding tissues. The section analyzed by VASIM encompasses the carotid arteries, one of the most common locations of atherosclerotic plaques in the arterial system. VASIM presents to the user not only the routinely used metrics but also new parameters. They are based on different tissues’ volumes, areas and progression throughout the arterial tree. Furthermore, VASIM creates 3D models, which could be used for surgery planning, plaque morphology and composition evaluation, and 2D linearization of all the components of the plaque.

To validate VASIM, a clinical material of fifty-nine individuals, both healthy and suffering from atherosclerosis of the carotid arteries, was tested and analyzed. For cases with stenosis over 50%, VASIM had a clinical accuracy of 71%. The software prototype results suggest that this approach has potential in areas such as analysis of the atherosclerosis of carotid arteries and it could be applied in a clinical environment.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: Faculty of Biomedical Sciences and Engineering
Contributors: Caetano Dos Santos, F.
Number of pages: 52
Publication date: 26 Oct 2018

Publication information

Publisher: Tampere University of Technology
ISBN (Print): 978-952-15-4196-4
ISBN (Electronic): 978-952-15-4238-1
Original language: English

Publication series

Name: Tampere University of Technology. Publication
Volume: 1573
ISSN (Print): 1459-2045

Research output: Book/ReportDoctoral thesisCollection of Articles

Optimizing elastomeric mechanical cell stretching device

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: BioMediTech, Research group: Micro and Nanosystems Research Group
Contributors: Mäki, A., Kreutzer, J., Kallio, P.
Number of pages: 1
Publication date: 22 Oct 2018
Peer-reviewed: Unknown
Event: 

Research output: Other conference contributionPaper, poster or abstractProfessional

Tutkimuskatsaus: Uusia menetelmiä haavan paranemisen arviointiin ja seurantaan

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Turku Univ Hosp, University of Turku, Åbo Akademi
Contributors: Kekonen, A., Bergelin, M., Viik, J.
Number of pages: 3
Pages: 30-32
Publication date: 20 Oct 2018
Peer-reviewed: Yes

Publication information

Journal: HAAVA
Volume: 20
Issue number: 3
ISSN (Print): 1456-3037
Original language: Finnish
ASJC Scopus subject areas: Biomedical Engineering, Dermatology

Research output: Contribution to journalArticleScientificpeer-review

Application of air bladders for medical compression hosieries

The research work presents a new design of compression hosiery where compression around a human limb is generated using special air bladders. The pressure inside the air bladders is adjustable. The objective of the research was to study graduated compression and its control on the limb using the prototype with air bladders and two commercial compression products. The compression forces were measured around the limb under a knee in three sectors: a foot, a middle part and an upper part of the leg. Measurements were mainly done in vivo using the limb of a test person – although some pre-trials were done in vitro. During the tests it was concluded that the exact control of the compression was very difficult to achieve due to, for example, the shape and the composition of the limb. Based on the results, the compression values were unstable under the sectors and the graduated compression was nonlinear in the vertical direction for every tested hosiery. There is some analogy concerning the pressure distribution reported about standard mechanical compression hosiery. The results prove that our prototype enables one to achieve very high compression values in seconds, and to manage and to adjust instantly the compression rate in each sector. Efficient controllability and comfort are important matters in the medical treatment, where a patient wears the hosieries for prolonged times.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science, Research group: Plastics and Elastomer Technology, Electronics and Communications Engineering, Research group: Personal Electronics Group, Silvergreen Corp., Icraft Corp.
Contributors: Hakala, T., Puolakka, A., Nousiainen, P., Vuorela, T., Vanhala, J.
Pages: 2169-2181
Publication date: 1 Oct 2018
Peer-reviewed: Yes
Early online date: 4 Jul 2017

Publication information

Journal: Textile Research Journal
Volume: 88
Issue number: 19
ISSN (Print): 0040-5175
Ratings: 
  • Scopus rating (2018): CiteScore 1.87 SJR 0.527 SNIP 1.329
Original language: English

Bibliographical note

EXT="Nousiainen, Pertti"
EXT="Vuorela, Timo"

Research output: Contribution to journalArticleScientificpeer-review

Novel osteoconductive β-tricalcium phosphate/poly(L-lactide-co-e-caprolactone) scaffold for bone regeneration: a study in a rabbit calvarial defect

The advantages of synthetic bone graft substitutes over autogenous bone grafts include abundant graft volume, lack of complications related to the graft harvesting, and shorter operation and recovery times for the patient. We studied a new synthetic supercritical CO2 –processed porous composite scaffold of β-tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone graft substitute in a rabbit calvarial defect. Bilateral 12 mm diameter critical size calvarial defects were successfully created in 18 rabbits. The right defect was filled with a scaffold moistened with bone marrow aspirate, and the other was an empty control. The material was assessed for applicability during surgery. The follow-up times were 4, 12, and 24 weeks. Radiographic and micro-CT studies and histopathological analysis were used to evaluate new bone formation, tissue ingrowth, and biocompatibility. The scaffold was easy to shape and handle during the surgery, and the bone-scaffold contact was tight when visually evaluated after the implantation. The material showed good biocompatibility and its porosity enabled rapid invasion of vasculature and full thickness mesenchymal tissue ingrowth already at four weeks. By 24 weeks, full thickness bone ingrowth within the scaffold and along the dura was generally seen. In contrast, the empty defect had only a thin layer of new bone at 24 weeks. The radiodensity of the material was similar to the density of the intact bone. In conclusion, the new porous scaffold material, composed of microgranular β-TCP bound into the polymer matrix, proved to be a promising osteoconductive bone graft substitute with excellent handling properties. [Figure not available: see fulltext.].

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electronics and Communications Engineering, Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Faculty of Veterinary Medicine, University of Helsinki, Orton Orthopaedic Hospital, Muonio Health Center
Contributors: Pihlman, H., Keränen, P., Paakinaho, K., Linden, J., Hannula, M., Manninen, I. K., Hyttinen, J., Manninen, M., Laitinen-Vapaavuori, O.
Publication date: 1 Oct 2018
Peer-reviewed: Yes

Publication information

Journal: Journal of Materials Science: Materials in Medicine
Volume: 29
Issue number: 10
Article number: 156
ISSN (Print): 0957-4530
Ratings: 
  • Scopus rating (2018): CiteScore 2.51 SJR 0.612 SNIP 0.824
Original language: English
ASJC Scopus subject areas: Biophysics, Bioengineering, Biomaterials, Biomedical Engineering
Source: Scopus
Source ID: 85054473480

Research output: Contribution to journalArticleScientificpeer-review

Characteristics and determinants of recurrent occupational accidents

Recurrent occupational accidents provide valuable information for prevention purposes. Characteristics of recurrent occupational accidents were studied using a dataset of a Finnish insurance company including 21,580 subjects having at least two compensated workplace accidents with the same working process. For more than two thirds (70%) of the subjects, the circumstances and causes of the first accident did not reoccur in the second accident but their recurrence was substantial, typically around 30%. Working process and characteristics of the first accident affected the reoccurrence. In services, the violence-related accidents reoccurred for every second subject but losing control of machine only for every eighth subject. Moreover, the latter accidents were more severe than the former accidents. On average, two times more days were lost in the second than in the first accident.
The determinants of recurrent occupational accidents were examined for a small subset of 41 victims who had answered to a health-related questionnaire. Compared to age-matched controls with only one occupational accident, the subjects with at least two accidents were 3.2 times more likely to exercise less frequently, 3.2 times more likely to have relatives with diabetes and 2.6 times more likely to have symptoms of health problems.
The substantial reoccurrence of occupational accidents emphasizes the importance of assessing the prevention policies after each accident. Occupational accidents are related to work conditions and organizational practices but analysis of more in-depth data e.g. questionnaires may promote the means to improve the prevention policies of occupational accidents (e.g. violence-related) currently being difficult to prevent.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Personal Health Informatics-PHI, Finnish Institute of Occupational Health, University of Oulu
Contributors: Pietilä, J., Räsänen, T., Reiman, A., Ratilainen, H., Helander, E.
Pages: 269-277
Publication date: Oct 2018
Peer-reviewed: Yes
Early online date: 20 Dec 2017

Publication information

Journal: Safety Science
Volume: 108
ISSN (Print): 0925-7535
Ratings: 
  • Scopus rating (2018): CiteScore 4.49 SJR 1.29 SNIP 2.251
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Long-term monitoring of acute wound healing from beneath the primary wound dressings

Our group has developed a quasimonopolar bioimpedance measurement-based method and a measurement system to determine the status of wound healing. So far, we have shown that the bioimpedance method is a prospective tool for assessment of wound healing by monitoring the healing of both acute wounds and venous ulcers at discrete time points. The objective of this study was to demonstrate that the method is capable for monitoring wound healing also long-term while the wound is covered by the primary dressings. For this purpose we arranged a follow-up study of a single acute wound. The purpose-built multi-electrode dressing was applied on the wound and left under the primary dressings until the complete re-epithelization was achieved. The bioimpedance of the wound and surrounding skin area was measured regularly during a 120 hours study. Based on the results, we can confirm that the method applies for long-term monitoring of acute wound healing without necessity to remove the primary dressings.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Physiological Measurement Systems and Methods Group, BioMediTech, CutoSense Ltd.
Contributors: Kekonen, A., Bergelin, M., Eriksson, J., Vesa, M., Johansson, M., Viik, J.
Number of pages: 4
Publication date: Oct 2018

Host publication information

Title of host publication: 2018 16th Biennial Baltic Electronics Conference (BEC)
Publisher: IEEE
ISBN (Print): 978-1-5386-7313-3
ISBN (Electronic): 978-1-5386-7312-6
Keywords: Electrodes, Wounds, Impedance, Skin, Biomedical measurement, Monitoring, Bioimpedance, bioimpedance beneath dressing, healing, longterm wound monitoring, multi-electrode
Source: Bibtex
Source ID: urn:054660b869151d1efd2f9613e80b4431

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Molecular Communications Pulse-based Jamming Model for Bacterial Biofilm Suppression

Studies have recently shown that the bacteria survivability within biofilms is responsible for the emergence of superbugs. The combat of bacterial infections, without enhancing its resistance to antibiotics, includes the use of nanoparticles to quench the quorum sensing of these biofilm-forming bacteria. Several sequential and parallel multi-stage communication processes are involved in the formation of biofilms. In this paper, we use proteomic data from a wet lab experiment to identify the communication channels that are vital to these processes.We also identified the main proteins from each channel and propose the use of jamming signals from synthetically engineered bacteria to suppress the production of those proteins. This biocompatible technique is based on synthetic biology and enables the inhibition of biofilm formation. We analyse the communications performance of the jamming process, by evaluating the path loss for a number of conditions that include different engineered bacterial population sizes, distances between the populations and molecular signal power. Our results show that sufficient molecular pulsebased jamming signals are able to prevent the biofilm formation by creating lossy communications channels (almost -3 dB for certain scenarios). From these results, we define the main design parameters to develop a fully operational bacteria-based jamming system.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electronics and Communications Engineering, Research group: Emerging Technologies for Nano-Bio-Info-Cogno, Waterford Institute of Technology, Kasetsart University
Contributors: Martins, D. P., Leetanasaksakul, K., Barros, M. T., Thamchaipenet, A., Donnelly, W., Balasubramaniam, S.
Number of pages: 12
Pages: 533-542
Publication date: Oct 2018
Peer-reviewed: Yes
Early online date: 19 Sep 2018

Publication information

Journal: IEEE Transactions on Nanobioscience
Volume: 17
Issue number: 4
ISSN (Print): 1536-1241
Ratings: 
  • Scopus rating (2018): CiteScore 2.23 SJR 0.541 SNIP 0.741
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Medicine (miscellaneous), Biomedical Engineering, Pharmaceutical Science, Computer Science Applications, Electrical and Electronic Engineering
Keywords: Biofilm suppression, Communications systems, Jamming, Synthetic logic circuits
Source: Scopus
Source ID: 85053611196

Research output: Contribution to journalArticleScientificpeer-review

Temperature Dependence of the Transcription Dynamics of Synthetic Genes in Escherichia coli

One of the major current goals in synthetic biology is the design of genetic components with more predictable functions. This predictability, however, does not depend solely on these components, but also on the environment where they will be inserted in.

Escherichia coli is one of the most studied microorganisms in Microbiology, and it is commonly used in Synthetic Biology as a host strain to test the functioning of the components of genetic systems. These components are typically well characterized under controlled laboratory conditions. However, it is unclear how unfavorable environmental conditions, such as temperature fluctuations, can affect their functionality and robustness.

In this thesis, we investigated how temperature affects the kinetics of transcription activation and subsequent dynamics of RNA production of synthetic genes in E. coli. For this, we made use of state-of-the-art in vivo single RNA-detection techniques and image analysis tools, to dissect, at the single-cell and single-RNA level, the kinetics of the rate-limiting steps in transcription, as well as the intake kinetics of inducer molecules. In addition, we analyzed how the temperature dependency is affected by the promoter structure.

Specifically, first, we characterized the intake kinetics of inducer molecules, from the media to the cell periplasm and then cytoplasm, at optimal and suboptimal temperatures. We found that, for a wide range of extracellular inducer concentrations, and in the absence of a transporter protein, the intake process is diffusive-like. The results also show that, the mean intake time increases nonlinearly with decreasing temperature, likely due to the emergence of additional rate-limiting steps at low temperatures. Finally, our results indicate that the dynamics of this intake process affects significantly the expected RNA numbers in individual cells for a significant amount of time following induction and, thus, the overall distribution of RNA numbers of the cell population.

Next, we studied the temperature dependence of the dynamics of transcription initiation of a synthetic gene, engineered from a viral promoter. This dependency is shown to occur at the level of the underlying kinetics of the rate limiting steps in initiation. From the analysis of the empirical data, we found that, first, similarly to E. coli promoters, the T7 phage Phi 10 promoter exhibits more than one rate-limiting step during initiation. Also, the mean time-length of these steps is temperature dependent. However, contrary to E. coli promoters, the noise in RNA production increases with increasing temperature within the range of temperatures tested.

Finally, we investigated a key mechanism of transcription, namely, the robustness of a transcription repression mechanism by analyzing the rate of ‘leaky’ transcription events, i.e., RNA production events when under full repression. Using the LacO3O1 as a model promoter, from the analysis of the empirical data on single RNA production kinetics, we found that this promoter exhibits a leakiness rate that is higher at low temperatures, suggesting that its repression mechanism is less efficient under these conditions.

We believe that the studies presented here contribute to a better understanding of how temperature affects the transcription dynamics of synthetic genes in environments where temperature fluctuations occur. Since the acquired knowledge is of use to better understand the behavior of synthetic promoters, we expect our main contribution to be in the area of Synthetic Biology, namely, to be of value in predicting the robustness of future synthetic genetic circuits to temperature shifts. In particular, our results show that, in the genes studied, the repression mechanism is the most affected by temperature. This strong temperature dependence translates into the hindering of the promoter responsiveness to induction at sub-optimal temperature conditions. Additionally, our results suggest that this temperature-dependence of the robustness and responsiveness can be tuned, which indicates that it is possible to engineer synthetic promoters of higher response accuracy for a wider range of environmental conditions than those studied here. This knowledge can be used in the construction of synthetic genetic circuits with a more predictable, robust behavior.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Laboratory of Biosystem Dynamics-LBD
Contributors: Moreira Goncalves, N.
Number of pages: 78
Publication date: 21 Sep 2018

Publication information

Publisher: Tampere University of Technology
ISBN (Print): 978-952-15-4186-5
ISBN (Electronic): 978-952-15-4191-9
Original language: English

Publication series

Name: Tampere University of Technology. Publication
Volume: 1567
ISSN (Print): 1459-2045

Research output: Book/ReportDoctoral thesisCollection of Articles

A COMPARATIVE IN VITRO STUDY OF CELL GROWTH ON TEXTILE SCAFFOLDS FOR TISSUE ENGINEERING APPLICATIONS

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, Tampere University of Technology, BioMediTech, University of Tampere, BioMediTech, Adult Stem Cell Research Group
Contributors: Kroon, M., Talvitie, E., Miettinen, S., Kellomäki, M.
Publication date: 12 Sep 2018
Peer-reviewed: Unknown
Event: Paper presented at ESB2018 - 29th Annual Meeting of European Society for Biomaterials, Maastricht, Netherlands.
ASJC Scopus subject areas: Biomaterials, Biomedical Engineering

Research output: Other conference contributionPaper, poster or abstractScientific

Focal Adhesion Kinase and ROCK Signaling Are Switch-Like Regulators of Human Adipose Stem Cell Differentiation towards Osteogenic and Adipogenic Lineages

Adipose tissue is an attractive stem cell source for soft and bone tissue engineering applications and stem cell therapies. The adipose-derived stromal/stem cells (ASCs) have a multilineage differentiation capacity that is regulated through extracellular signals. The cellular events related to cell adhesion and cytoskeleton have been suggested as central regulators of differentiation fate decision. However, the detailed knowledge of these molecular mechanisms in human ASCs remains limited. This study examined the significance of focal adhesion kinase (FAK), Rho-Rho-associated protein kinase (Rho-ROCK), and their downstream target extracellular signal-regulated kinase 1/2 (ERK1/2) on hASCs differentiation towards osteoblasts and adipocytes. Analyses of osteogenic markers RUNX2A, alkaline phosphatase, and matrix mineralization revealed an essential role of active FAK, ROCK, and ERK1/2 signaling for the osteogenesis of hASCs. Inhibition of these kinases with specific small molecule inhibitors diminished osteogenesis, while inhibition of FAK and ROCK activity led to elevation of adipogenic marker genes AP2 and LEP and lipid accumulation implicating adipogenesis. This denotes to a switch-like function of FAK and ROCK signaling in the osteogenic and adipogenic fates of hASCs. On the contrary, inhibition of ERK1/2 kinase activity deceased adipogenic differentiation, indicating that activation of ERK signaling is required for both adipogenic and osteogenic potential. Our findings highlight the reciprocal role of cell adhesion mechanisms and actin dynamics in regulation of hASC lineage commitment. This study enhances the knowledge of molecular mechanisms dictating hASC differentiation and thus opens possibilities for more efficient control of hASC differentiation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Systems Biology
Contributors: Hyväri, L., Ojansivu, M., Juntunen, M., Kartasalo, K., Miettinen, S., Vanhatupa, S.
Pages: 2190657
Publication date: 12 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: Stem Cells International
ISSN (Print): 1687-966X
Original language: English

Bibliographical note

EXT="Ojansivu, Miina"
EXT="Vanhatupa, Sari"

Source: PubMed
Source ID: 30275837

Research output: Contribution to journalArticleScientificpeer-review

Evaluation of Median Root Prior for Robust In-Beam PET Reconstruction

Dose delivery verification in proton beam radiotherapy is used to ensure the delivery of the dose to the correct location. A positron emission tomography (PET) scanner can be used to detect the secondary radiation during the treatment, so-called in-beam PET. This is a challenging application for PET due to the low counts and limited angular coverage. We propose a maximum a posteriori (MAP) reconstruction with median root prior (MRP) for the reconstruction of in-beam PET data. The proposed method was compared against MAP with total variation (TV) prior and maximum likelihood expectation maximization (MLEM), which have previously been used for this application. The effects of different ring configurations and time-of-flight information were tested with simulations of a geometrical phantom and a realistic patient treatment plan. The results indicate that both MAP methods produced sharper edges than MLEM, allowing more accurate edge localization in the reconstructed images. Even for the partial ring configurations, no elongation was observed with MAP methods. MAP-MRP successfully reduced the noise, whereas MAP-TV resulted in checkerboard artifacts. MAP-MRP was also more stable against the selection of the reconstruction parameters. In conclusion, MAP-MRP offers a simple and robust alternative for the reconstruction of in-beam PET data.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, Signal Processing, Research group: M2oBSI, University of Groningen
Contributors: Us, D., Brzezinski, K., Buitenhuis, T., Dendooven, P., Ruotsalainen, U.
Number of pages: 8
Pages: 490-498
Publication date: 5 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: IEEE Transactions on Radiation and Plasma Medical Sciences
Volume: 2
Issue number: 5
ISSN (Print): 2469-7303
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation: Recent advances and future challenges

The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Faculty of Biomedical Sciences and Engineering, Simula Research Laboratory, Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, University of Oslo, Center for Cardiological Innovation, University of Eastern Finland
Contributors: Vagos, M. R., van Herck, I. G., Sundnes, J., Arevalo, H. J., Edwards, A. G., Koivumäki, J. T.
Publication date: 4 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Physiology
Volume: 9
Issue number: SEP
Article number: 1221
ISSN (Print): 1664-042X
Ratings: 
  • Scopus rating (2018): CiteScore 3.22 SJR 1.153 SNIP 0.986
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: Atrial fibrillation, Computational modeling, Drug therapies, In silico drug screening, Pathophysiology, Pharmacodynamics, Pharmacology
Electronic versions: 
Source: Scopus
Source ID: 85053074392

Research output: Contribution to journalReview ArticleScientificpeer-review

A compact olfactometer for IMS measurements and testing human perception

Production of easily controllable and measurable odor stimuli is needed when studying human olfaction, olfaction-related physiology and psychological reactions to odors. Controlled odor producing instruments are called olfactometers. For testing and calibrating new olfactometers or sensor arrays, a reliable input signal has to be produced to verify their accurate functionality. A common input signal in various olfactometers has been the use of volatile organic compounds (VOCs) in gaseous form. We present a compact olfactometer able to produce controlled continuous odor stimuli from three individual channels. For measuring the output gas flow, we used a ChemPro 100i (Environics, Finland) device that is based on aspiration ion mobility spectrometry (aIMS). IMS is a robust and sensitive method for measuring VOCs and is used especially in detecting toxic industrial chemicals and chemical warfare agents, but the technology is also suitable for other olfactory-related applications. The olfactometer was used to produce synthetic jasmine scent using three main odor components from jasmine oil and all the components were diluted using propylene glycol. The dilutions were supplied to the system using programmable syringe pumps, which guided the dilutions to individual evaporation units. We conducted experiments to verify the functionality of our olfactometer. Analysis of the ChemPro100i data showed that olfactometer can use different odor components to produce continuous, stable output flows with controlled concentrations.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Micro and Nanosystems Research Group, Research group: Sensor Technology and Biomeasurements (STB)
Contributors: Nieminen, V., Karjalainen, M., Salminen, K., Rantala, J., Kontunen, A., Isokoski, P., Müller, P., Kallio, P., Surakka, V., Lekkala, J.
Number of pages: 10
Pages: 71-80
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 21 Jun 2018

Publication information

Journal: International Journal for Ion Mobility Spectrometry
Volume: 21
Issue number: 3
ISSN (Print): 1435-6163
Ratings: 
  • Scopus rating (2018): CiteScore 1.74 SJR 0.712 SNIP 0.756
Original language: English
ASJC Scopus subject areas: Spectroscopy
Keywords: Human perception, Ion mobility spectrometry, Odor, Olfactometer

Bibliographical note

INT=tut-bmt,"Nieminen, Ville"

Source: Scopus
Source ID: 85048753843

Research output: Contribution to journalArticleScientificpeer-review

In vitro detection of common rhinosinusitis bacteria by the eNose utilising differential mobility spectrometry

Acute rhinosinusitis (ARS) is a sudden, symptomatic inflammation of the nasal and paranasal mucosa. It is usually caused by respiratory virus infection, but bacteria complicate for a small number of ARS patients. The differential diagnostics between viral and bacterial pathogens is difficult and currently no rapid methodology exists, so antibiotics are overprescribed. The electronic nose (eNose) has shown the ability to detect diseases from gas mixtures. Differential mobility spectrometry (DMS) is a next-generation device that can separate ions based on their different mobility in high and low electric fields. Five common rhinosinusitis bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pseudomonas aeruginosa) were analysed in vitro with DMS. Classification was done using linear discriminant analysis (LDA) and k-nearest neighbour (KNN). The results were validated using leave-one-out cross-validation and separate train and test sets. With the latter, 77% of the bacteria were classified correctly with LDA. The comparative figure with KNN was 79%. In one train-test set, P. aeruginosa was excluded and the four most common ARS bacteria were analysed with LDA and KNN; the correct classification rate was 83 and 85%, respectively. DMS has shown its potential in detecting rhinosinusitis bacteria in vitro. The applicability of DMS needs to be studied with rhinosinusitis patients.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Tampere University of Applied Sciences, Fimlab Laboratories Ltd
Contributors: Virtanen, J., Hokkinen, L., Karjalainen, M., Kontunen, A., Vuento, R., Numminen, J., Rautiainen, M., Oksala, N., Roine, A., Kivekäs, I.
Pages: 2273-2279
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: European Archives of Oto-Rhino-Laryngology
Volume: 275
Issue number: 9
ISSN (Print): 0937-4477
Ratings: 
  • Scopus rating (2018): CiteScore 1.65 SJR 0.787 SNIP 0.938
Original language: English
ASJC Scopus subject areas: Otorhinolaryngology
Keywords: Acute rhinosinusitis, Differential mobility spectrometry, Electronic nose, eNose
Source: Scopus
Source ID: 85050626169

Research output: Contribution to journalArticleScientificpeer-review

Neuroinformatics and Computational Modelling as Complementary Tools for Neurotoxicology Studies

Neuroinformatics is an area of science that aims to integrate neuroscience data and develop modern computational tools to increase our understanding of the functions of the nervous system in health and disease. Neuroinformatics tools include, among others, databases for storing and sharing data, repositories for managing documents and source code, and software tools for analysing, modelling and simulating signals and images. This MiniReview aims to present the state of the art in neuroinformatics and computational in silico modelling of neurobiological processes and neuroscientific phenomena as well as to discuss the use of in silico models in neurotoxicology research. In silico modelling can be considered a new, complementary tool in chemical design to predict potential neurotoxicity and in neurotoxicity testing to help clarify initial hypothesis obtained in in vitro and in vivo. Validated in silico models can be used to identify pharmacological targets, to help bridge in vitro and in vivo studies and, ultimately, to develop safer chemicals and efficient therapeutic strategies.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Faculty of Biomedical Sciences and Engineering
Contributors: Linne, M.
Pages: 56-61
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Basic and Clinical Pharmacology and Toxicology
Volume: 123
Issue number: S5
ISSN (Print): 1742-7835
Ratings: 
  • Scopus rating (2018): CiteScore 2.23 SJR 0.728 SNIP 0.832
Original language: English
ASJC Scopus subject areas: Toxicology, Pharmacology
Source: Scopus
Source ID: 85052786993

Research output: Contribution to journalReview ArticleScientificpeer-review

Nocturnal Heart Rate Variability Spectrum Characterization in Preschool Children with Asthmatic Symptoms

Asthma is a chronic lung disease that usually develops during chilhood. Despite that symptoms can almost be controlled with medication, early diagnosis is desirable in order to reduce permanent airway obstruction risk. It has been suggested that abnormal parasympathetic nervous system (PSNS) activity might be closely related with the pathogenesis of asthma, and that this PSNS activity could be reflected in cardiac vagal control. In this work, an index to measure the spectral regularity of the high frequency (HF) component of heart rate variability (HRV) spectrum, named peakness (P), is proposed. Three different implementations of P, based on electrocardiogram (ECG) recordings, impedance pneumography (IP) recordings and a combination of both, were employed in the characterization of a group of pre-school children classified attending to their risk of developing asthma. Peakier componentswere observed in the HF band of those children classified as high-risk (p &lt; 0.005), who also presented reduced sympathvoagal balance. Results suggest that high-risk of developing asthma might be related with a lack of adaptability of PSNS.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Physiological Measurement Systems and Methods Group, University of Zaragoza, KU Leuven, University of Helsinki
Contributors: Milagro, J., Gil, E., Lazaro, J., Seppae, V. P., Malmberg, L. P., Pelkonen, A. S., Kotaniemi-Syrjanen, A., Makela, M., Viik, J., Bailon, R.
Pages: 1332-1340
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 16 Nov 2017

Publication information

Journal: IEEE Journal of Biomedical and Health Informatics
Volume: 22
Issue number: 5
ISSN (Print): 2168-2194
Ratings: 
  • Scopus rating (2018): CiteScore 5.67 SJR 1.122 SNIP 2.4
Original language: English
ASJC Scopus subject areas: Biotechnology, Computer Science Applications, Electrical and Electronic Engineering, Health Information Management
Keywords: asthma, children, Electrocardiography, Heart rate variability, heart rate variability, Informatics, parasympathetic nervous system, peakness, Pediatrics, Pregnancy, Respiratory system, Signal to noise ratio
Source: Scopus
Source ID: 85035749268

Research output: Contribution to journalArticleScientificpeer-review

Quantitative characterization of pore structure of several biochars with 3D imaging

Pore space characteristics of biochars may vary depending on the used raw material and processing technology. Pore structure has significant effects on the water retention properties of biochar amended soils. In this work, several biochars were characterized with three-dimensional imaging and image analysis. X-ray computed microtomography was used to image biochars at resolution of 1.14 μm and the obtained images were analysed for porosity, pore size distribution, specific surface area and structural anisotropy. In addition, random walk simulations were used to relate structural anisotropy to diffusive transport. Image analysis showed that considerable part of the biochar volume consist of pores in size range relevant to hydrological processes and storage of plant available water. Porosity and pore size distribution were found to depend on the biochar type and the structural anisotopy analysis showed that used raw material considerably affects the pore characteristics at micrometre scale. Therefore, attention should be paid to raw material selection and quality in applications requiring optimized pore structure.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, Research group: Computational Biophysics and Imaging Group, BioMediTech, Natural Resources Institute Finland (Luke), VTT Technical Research Centre of Finland
Contributors: Hyväluoma, J., Kulju, S., Hannula, M., Wikberg, H., Källi, A., Rasa, K.
Number of pages: 11
Pages: 1-11
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 24 Mar 2017

Publication information

Journal: Environmental Science and Pollution Research
Volume: 25
Issue number: 26
ISSN (Print): 0944-1344
Ratings: 
  • Scopus rating (2018): CiteScore 3.14 SJR 0.828 SNIP 1.032
Original language: English
ASJC Scopus subject areas: Environmental Chemistry, Pollution, Health, Toxicology and Mutagenesis
Keywords: Biochar, Image analysis, Pore structure, Soil amendment, Water retention, X-ray tomography

Bibliographical note

EXT="Kulju, Sampo"

Source: Scopus
Source ID: 85015999251

Research output: Contribution to journalArticleScientificpeer-review

3D bioprinting of the kidney—hype or hope?

Three-dimensional (3D) bioprinting is an evolving technique that is expected to revolutionize the field of regenerative medicine. Since the organ donation does not meet the demands for transplantable organs, it is important to think of another solution, which may and most likely will be provided by the technology of 3D bioprinting. However, even smaller parts of the printed renal tissue may be of help, e.g. in developing better drugs. Some simple tissues such as cartilage have been printed with success, but a lot of work is still required to successfully 3D bioprint complex organs such as the kidneys. However, few obstacles still persist such as the vascularization and the size of the printed organ. Nevertheless, many pieces of the puzzle are already available and it is just a matter of time to connect them together and 3D bioprint the kidneys. The 3D bioprinting technology provides the precision and fast speed required for generating organs. In this review, we describe the recent developments in the field of developmental biology concerning the kidneys; characterize the bioinks available for printing and suitable for kidney printing; present the existing printers and possible printing strategies. Moreover, we identify the most difficult challenges in printing of the kidneys and propose a solution, which may lead to successful bioprinting of the kidney.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, 3DTech Oy, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 3D Bioprinting Solutions, Institute for Regenerative Medicine, Sechenov Medical University
Contributors: Turunen, S., Kaisto, S., Skovorodkin, I., Mironov, V., Kalpio, T., Vainio, S., Rak-Raszewska, A.
Number of pages: 44
Pages: 119-162
Publication date: 28 Aug 2018
Peer-reviewed: Yes

Publication information

Journal: AIMS Cell and Tissue Engineering
Volume: 2
Issue number: 3
ISSN (Print): 2574-0105
Original language: English
Keywords: organ biofabrication, bioprinting of kidneys, organoids, bioink, 3D bioprinters, printing strategy
Electronic versions: 

Research output: Contribution to journalReview ArticleScientificpeer-review

Comparison of food frequency questionnaire data and shopping records for the assessment of food intake

Questionnaires are typically used for collecting information
describing health behavior in areas such as diet, physical activity and sleep.
Utilization of the digital footprint, formed from an individual’s unique digital
activities, forms a potential new opportunity for describing lifestyle and
health-related behavior. We studied if passively collected shopping data
describes food intake when compared to food frequency questionnaire (FFQ)
data providing information on food and beverage consumption. For 4 out of 21
food groups the results were comparable. Shopping information from only one
department store chain gives only a partial picture of the food consumption and
differing family sizes add noise to the estimate. If the whole digital footprint
would be available, including detailed product-level shopping information from
all stores and restaurants, the food intake could probably be estimated more
accurately and applied e.g. in personalized coaching.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Faculty of Biomedical Sciences and Engineering, Tampere University of Technology, Institute for Molecular Medicine, FIMM, HiLIFE, University of Helsinki
Contributors: Kallonen, A., Nieminen, H., Das, S., Sallinen, R.
Pages: 25-30
Publication date: 27 Aug 2018

Host publication information

Title of host publication: Proceedings of Seventh International Conference on Well-Being in the Information Society: Fighting Inequalities (WIS 2018)
ISBN (Electronic): 978-952-12-3727-0

Publication series

Name: TUCS Lecture Notes
Volume: 28
ISSN (Electronic): 1797-8831
ASJC Scopus subject areas: Molecular Medicine
Keywords: Food intake assessment, shopping data, food frequency questionnaire, digital footprint

Bibliographical note

INT=TUT-BMT,"Das, Soumya"

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Modeling and Control of Microscale Cell Culture Environments

Culturing cells in vitro is one of the core techniques used in a wide range of biomedical engineering areas. Special care is required to successfully grow cells in an artificial environment. It is essential to ensure that the culture environment is cell-friendly and sterile, supplies important products such as nutrients and growth factors, and provides a proper physiological microenvironment. To optimize long-term cell culturing, parameters such as pH, oxygen concentration, and temperature, should be precisely maintained at the desired levels. Furthermore, it is sometimes desirable to change environmental parameter(s) in a controlled way to study the cell response.

Bioreactors are typically used for cell culture in vitro. However, precise control of each cell culture’s microenvironment is difficult, leading to uneven culture conditions that can affect cell behavior. Furthermore, studying how certain environmental parameter affect the cultures is challenging, as it is difficult, or even impossible, to vary certain parameters in a controlled manner between each culture.

Microscale cell culture systems, known as microbioreactors, have recently been extensively studied to enhance control and improve long-term cell culturing by better mimicking cells’ microenvironments. Microbioreactors provide better environment control, thereby enhancing long-term cell cultivation. Unfortunately, integrating microbioreactors with the required sensors, actuators, electronics and other required devices can be challenging. Implementing sensors near the cell culture can also disturb them or prevent other measurements, such as optical microscopy. Certain measurements, such as direct longterm pH measurement, can be impossible, as there are no suitable microscale sensors available.

For these reasons, there is a huge demand for methods that can be used to study and develop proper microbioreactors. This thesis includes several studies in which modeling was used as design tools to improve and control culture environments. First, an analytical model to study gravity-driven flows in microfluidic devices is developed. Next, developed finite element method (FEM) computer models are used to study fluid flow profiles, drug distributions, shear stress levels on cells, and sensitivity of a calorimetric flow measurement system. A FEM model of carbon dioxide transport and liquid pH is also created. Additionally, the thesis proposes a novel method to indirectly control the cell culture temperature. Using system identification techniques, a developed estimation model can precisely control temperature with a sensor that does not disturb cells or other measurements. Although this thesis only demonstrates temperature control in the cell culture, the method can potentially be used to control other environment parameters as well. Lastly, this thesis considers the limitations of the presented models and control methods, and provides recommendations for future studies.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: Faculty of Biomedical Sciences and Engineering
Contributors: Mäki, A.
Number of pages: 59
Publication date: 16 Aug 2018

Publication information

Publisher: Tampere University of Technology
ISBN (Print): 978-952-15-4168-1
ISBN (Electronic): 978-952-15-4174-2
Original language: English

Publication series

Name: Tampere University of Technology. Publication
Volume: 1557
ISSN (Print): 1459-2045

Research output: Book/ReportDoctoral thesisCollection of Articles

Fabrication and Performance Evaluation of Carbon-based Stretchable RFID Tags on Textile Substrates

We fabricate carbon-based stretchable antennas for passive UHF RFID tags. The tag antennas are created on a stretchable elastic band by brush-painting. In addition to wireless evaluation of the fabricated RFID tags before and after cyclic stretching, the properties of the novel carbon-based antenna material are studied. The wireless performance of the established RFID tags is compared to similar stretchable silver-based RFID tags. Based on the achieved results, the established carbon-based tag antennas do not perform in the same high level as the silver-based tag antennas but their read ranges of around 2 to 2.4 meters are suitable for versatile textile-integrated RFID applications. Stretching causes permanent decrease to the tag read range but they remain functional even after 100 stretching cycles. These preliminary results are very promising, considering the current trend towards more environmentally friendly and cost-effective materials in electronics.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Wireless Identification and Sensing Systems Research Group, BioMediTech
Contributors: He, H., Chen, X., Mokhtari, O., Nishikawa, H., Ukkonen, L., Virkki, J.
Number of pages: 5
Publication date: Aug 2018

Host publication information

Title of host publication: 2018 International Flexible Electronics Technology Conference (IFETC)
Publisher: IEEE
ISBN (Print): 978-1-5386-3358-8
ISBN (Electronic): 978-1-5386-3357-1
Keywords: Antennas, Conductors, Substrates, Passive RFID tags, Wireless communication, Textiles, antennas, carbon-based materials, passive UHF RFID, stretchable electronics, textile substrates, wearable electronics
Source: Bibtex
Source ID: urn:0cabdb4dc2d6a9e652c7809c77a8ae0b

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Tissue Identification in a Porcine Model by Differential Ion Mobility Spectrometry Analysis of Surgical Smoke

Electrosurgery is widely used in various surgical operations. When tissue is cut with high-frequency current, the cell contents at the incision area evaporate and together with water and possible soot particles, form surgical smoke. The smoke contains cell metabolites, and therefore, possible biomarkers for cancer or bacterial infection. Thus, the analysis of surgical smoke could be used in intraoperative medical diagnostics. We present a method that can be used to detect the characteristics of various tissue types by means of differential ion mobility spectrometry (DMS) analysis of surgical smoke. We used our method to test tissue identification with ten different porcine tissues. We classified the DMS responses with cross-validated linear discriminant analysis models. The classification accuracy in a measurement set with ten tissue types was 95%. The presented tissue identification by DMS analysis of surgical smoke is a proof-of-concept, which opens the possibility to research the method in diagnosing human tissues and diseases in the future.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Hatanpää Hospital, Tampere University Hospital, Finnish Cardiovascular Research Center
Contributors: Kontunen, A., Karjalainen, M., Lekkala, J., Roine, A., Oksala, N.
Number of pages: 10
Pages: 1091-1100
Publication date: Aug 2018
Peer-reviewed: Yes
Early online date: 24 Apr 2018

Publication information

Journal: Annals of Biomedical Engineering
Volume: 46
Issue number: 8
ISSN (Print): 0090-6964
Ratings: 
  • Scopus rating (2018): CiteScore 3.52 SJR 1.065 SNIP 1.227
Original language: English
ASJC Scopus subject areas: Biomedical Engineering
Keywords: Electrosurgery, FAIMS, LDA, VOC
Source: Scopus
Source ID: 85045876072

Research output: Contribution to journalArticleScientificpeer-review

Wound healing of human embryonic stem cell-derived retinal pigment epithelial cells is affected by maturation stage

Background: Wound healing of retinal pigment epithelium (RPE) is a complex process that may take place in common age-related macular degeneration eye disease. The purpose of this study was to evaluate whether wounding and wound healing has an effect on Ca2+ dynamics in human embryonic stem cell (hESC)-RPEs cultured different periods of time. Methods: The 9-day-cultured or 28-day-cultured hESC-RPEs from two different cell lines were wounded and the dynamics of spontaneous and mechanically induced intracellular Ca2+ activity was measured with live-cell Ca2+ imaging either immediately or 7days after wounding. The healing time and speed were analyzed with time-lapse bright field microscopy. The Ca2+ activity and healing speed were analysed with image analysis. In addition the extracellular matrix deposition was assessed with confocal microscopy. Results: The Ca2+ dynamics in hESC-RPE monolayers differed depending on the culture time: 9-day-cultured cells had higher number of cells with spontaneous Ca2+ activity close to freshly wounded edge compared to control areas, whereas in 28-day-cultured cells there was no difference in wounded and control areas. The 28-day-cultured, wounded and 7-day-healed hESC-RPEs produced wide-spreading intercellular Ca2+ waves upon mechanical stimulation, while in controls propagation was restricted. Most importantly, both wave spreading and spontaneous Ca2+ activity of cells within the healed area, as well as the cell morphology of 28-day-cultured, wounded and thereafter 7-day-healed areas resembled the 9-day-cultured hESC-RPEs. Conclusions: This acquired knowledge about Ca2+ dynamics of wounded hESC-RPE monolayers is important for understanding the dynamics of RPE wound healing, and could offer a reliable functionality test for RPE cells. The data presented in here suggests that assessment of Ca2+ dynamics analysed with image analysis could be used as a reliable non-invasive functionality test for RPE cells.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, University of Eastern Finland, University Central Hospital Kuopio
Contributors: Abu Khamidakh, A. E., Rodriguez-Martinez, A., Kaarniranta, K., Kallioniemi, A., Skottman, H., Hyttinen, J., Juuti-Uusitalo, K.
Publication date: 31 Jul 2018
Peer-reviewed: Yes

Publication information

Journal: BioMedical Engineering Online
Volume: 17
Issue number: 1
Article number: 102
ISSN (Print): 1475-925X
Ratings: 
  • Scopus rating (2018): CiteScore 2.44 SJR 0.595 SNIP 1.047
Original language: English
ASJC Scopus subject areas: Radiological and Ultrasound Technology, Biomaterials, Biomedical Engineering, Radiology Nuclear Medicine and imaging
Keywords: Ca waves, Cell maturation, HESC-RPE, Image analysis, Mechanical stimulation, Mechanically induced intercellular Ca waves, RPE, Spontaneous [Ca] increases, Wound healing
Electronic versions: 
Source: Scopus
Source ID: 85050745629

Research output: Contribution to journalArticleScientificpeer-review

Impact loading history modulates hip fracture load and location: A finite element simulation study of the proximal femur in female athletes

Sideways falls impose high stress on the thin superolateral cortical bone of the femoral neck, the region regarded as a fracture-prone region of the hip. Exercise training is a natural mode of mechanical loading to make bone more robust. Exercise-induced adaptation of cortical bone along the femoral neck has been previously demonstrated. However, it is unknown whether this adaption modulates hip fracture behavior. The purpose of this study was to investigate the influence of specific exercise loading history on fall-induced hip fracture behavior by estimating fracture load and location with proximal femur finite element (FE) models created from magnetic resonance images (MRI) of 111 women with distinct exercise histories: 91 athletes (aged 24.7 ± 6.1 years, >8 years competitive career) and 20 women as controls (aged 23.7 ± 3.8 years). The athletes were divided into five groups based on typical loading patterns of their sports: high-impact (H-I: 9 triple-jumpers and 10 high jumpers), odd-impact (O-I: 9 soccer and 10 squash players), high-magnitude (H-M: 17 power-lifters), repetitive-impact (R-I: 18 endurance runners), and repetitive non-impact (R-NI: 18 swimmers). Compared to the controls, the H-I, O-I, and R-I groups had significantly higher (11–26%, p < 0.05) fracture loads. Also, the fracture location in the H-I and O-I groups was significantly more proximal (7–10%) compared to the controls. These results suggest that an exercise loading history of high impacts, impacts from unusual directions, or repetitive impacts increases the fracture load and may lower the risk of fall-induced hip fracture.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Civil Engineering, Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, UKK Institute for Health Promotion Research, Jyväskylän yliopisto, Jyvaskyla Central Hospital, GeroCenter Foundation, GeroCenter Foundation for Aging Research and Development
Contributors: Abe, S., Narra Girish, N., Nikander, R., Hyttinen, J., Kouhia, R., Sievänen, H.
Number of pages: 8
Pages: 136-143
Publication date: 25 Jul 2018
Peer-reviewed: Yes

Publication information

Journal: Journal of Biomechanics
Volume: 76
ISSN (Print): 0021-9290
Ratings: 
  • Scopus rating (2018): CiteScore 2.83 SJR 1.149 SNIP 1.387
Original language: English
ASJC Scopus subject areas: Public Health, Environmental and Occupational Health, Biomedical Engineering
Keywords: Bone strength, finite element modeling, Exercise, falling, femoral neck

Bibliographical note

EXT="Sievänen, Harri"

Research output: Contribution to journalArticleScientificpeer-review

Activity level and body mass index as predictors of physical workload during working career

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: BioMediTech, Research group: Personal Health Informatics-PHI, Finnish Institute of Occupational Health
Contributors: Pietilä, J., Mänttäri, S., Helander, E., Virkkala, J., Oksa, J.
Publication date: 23 Jul 2018

Host publication information

Title of host publication: 9th International Conference on Applied Human Factors and Ergonomics (AHFE 2018) : 22-26 July 2018, Orlando, Florida, USA
Publisher: Springer
Editors: Ahram, T., Karwowski, W.
ISBN (Print): 978-3-319-98302-8

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Activation game for older adults - Development and initial user experiences

The purpose of this study is to introduce a new type of activation game and evaluate the attitudes and user experiences of Chinese elderly people. The game controlling is done with a specific 3D-printed handle and is based on an acceleration sensor. The developed activation game, which requires both cognitive and motor skills was tested with test groups in three Chinese eldercare homes. The game was played by the residents and user feedback was collected by researchers' observations and players' comments in the gaming event. The most significant finding was the positive user experience of the elderly and the experience of the game being both cognitively stimulating and supportive for player activation. The game controller handle was found to be convenient for elderly people as it supports active use of hands, which was seen important by the players. Based on the observations, the developed game also seemed to provide great potential for social interaction. However, also some challenges were noticed, related to the game controller handle and game implementation. These positive finding as well as the discovered challenges are reported in this study. As a conclusion, the results are a strong encouragement for continuing activation game development for older adults.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Wireless Identification and Sensing Systems Research Group, Satakunta University of Applied Sciences
Contributors: Merilampi, S., Koivisto, A., Virkki, J.
Number of pages: 5
Pages: 1-5
Publication date: 29 Jun 2018

Host publication information

Title of host publication: 2018 IEEE 6th International Conference on Serious Games and Applications for Health, SeGAH 2018
Publisher: IEEE
ISBN (Electronic): 9781538662984
ASJC Scopus subject areas: Health(social science), Computer Science Applications, Human-Computer Interaction
Keywords: Activation, cognitive impairment, mobile game, motor impairment, older adults, recreation, self-managed rehabilitation, serious games

Bibliographical note

EXT="Merilampi, Sari"

Source: Scopus
Source ID: 85050242350

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities

The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca2+ handling. We used (i) the hiPSC-CM Paci2013 model as starting point, (ii) a new dataset of Ca2+ transient measurements to tune the parameters of the inward and outward Ca2+ fluxes of sarcoplasmic reticulum, and (iii) an automatic parameter optimization to fit action potentials and Ca2+ transients. The Paci2018 model simulates, together with the typical hiPSC-CM spontaneous action potentials, more refined Ca2+ transients and delayed afterdepolarizations-like abnormalities, which the old Paci2013 was not able to predict due to its mathematical formulation. The Paci2018 model was validated against (i) the same current blocking experiments used to validate the Paci2013 model, and (ii) recently published data about effects of different extracellular ionic concentrations. In conclusion, we present a new and more versatile in silico model, which will provide a platform for modeling the effects of drugs or mutations that affect Ca2+ handling in hiPSC-CMs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, University of Bologna, Faculty of Medicine and Life Sciences, Tampere University Hospital
Contributors: Paci, M., Pölönen, R., Cori, D., Penttinen, K., Aalto-Setälä, K., Severi, S., Hyttinen, J.
Publication date: 26 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Physiology
Volume: 9
Issue number: JUN
Article number: 709
ISSN (Print): 1664-042X
Ratings: 
  • Scopus rating (2018): CiteScore 3.22 SJR 1.153 SNIP 0.986
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: Action potential, Calcium transient, Computer simulation, Human induced pluripotent stem cell-derived cardiomyocyte, In silico modeling
Electronic versions: 

Bibliographical note

EXT="Penttinen, Kirsi"

Source: Scopus
Source ID: 85049116471

Research output: Contribution to journalArticleScientificpeer-review

Monitoring of heart rate and inter-beat intervals with wrist plethysmography in patients with atrial fibrillation

Objective: Atrial fibrillation (AF) causes marked risk for patients, while silent fibrillation may remain unnoticed if not suspected and screened. Development of comfortable yet accurate beat-to-beat heart rate (HR) monitoring with good AF detection sensitivity would facilitate screening and improve treatment. The purpose of this study was to evaluate whether a wrist-worn photoplethysmography (PPG) device can be used to monitor beat-to-beat HR accurately during post-operative treatment in patients suffering from AF and whether wrist-PPG can be used to distinguish AF from sinus rhythm (SR). Approach: Twenty-nine patients (14 with AF, 15 with SR, mean age 71.5 years) with multiple comorbidities were monitored during routine post-operative treatment. The monitoring included standard ECG, finger PPG monitoring and a wrist-worn PPG monitor with green and infrared light sources. The HR from PPG sensors was compared against ECG-derived HR. Main results: The wrist PPG technology had very good HR and beat detection accuracy when using green light. For the SR group, the mean absolute error (MAE) for HR was 1.50 bpm, and for the inter-beat intervals (IBI), the MAE was 7.64 ms. For the AF group, the MAE for HR was 4.28 bpm and for IBI, the MAE was 14.67 ms. Accuracy for the infrared (IR) channel was worse. Finger PPG provided similar accuracy for HR and better accuracy for the IBI. AF detection sensitivity using green light was 99.0% and the specificity was 93.0%. Performance can be improved by discarding unreliable IBI periods. Significance: Results suggest that wrist PPG measurement allows accurate HR and beat-to-beat HR monitoring also in AF patients, and could be used for differentiating between SR and AF with very good sensitivity.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Tampere University Hospital, PulseOn SA, Pulseon Oy, University of Tampere, Medical School
Contributors: Harju, J., Tarniceriu, A., Parak, J., Vehkaoja, A., Yli-Hankala, A., Korhonen, I.
Publication date: 26 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Physiological Measurement
Volume: 39
Issue number: 6
Article number: 065007
ISSN (Print): 0967-3334
Ratings: 
  • Scopus rating (2018): CiteScore 2.44 SJR 0.609 SNIP 1.179
Original language: English
ASJC Scopus subject areas: Biophysics, Physiology, Biomedical Engineering, Physiology (medical)
Keywords: atrial fibrillation, heart rate, perioperative monitoring, photoplethysmography, pulse rate
URLs: 
Source: Scopus
Source ID: 85049779555

Research output: Contribution to journalArticleScientificpeer-review

Human Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue as a Sensitive Test System for QT Prolongation and Arrhythmic Triggers

BACKGROUND: Cardiac repolarization abnormalities in drug-induced and genetic long-QT syndrome may lead to afterdepolarizations and life-threatening ventricular arrhythmias. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) should help to overcome the limitations of animal models based on species differences in repolarization reserve. Here, we compared head-to-head the contribution of IKs (long QT1) and IKr (long QT2) on action potentials (APs) in human left ventricular (LV) tissue and hiPSC-CM-derived engineered heart tissue (EHT).

METHODS: APs were measured with sharp microelectrodes in EHT from 3 different control hiPSC-CM lines and in tissue preparations from failing LV.

RESULTS: EHT from hiPSC-CMs showed spontaneous diastolic depolarization and AP generation that were sensitive to low concentrations of ivabradine. IKr block by E-4031 prolonged AP duration at 90% repolarization with similar half-effective concentration in EHT and LV but larger effect size in EHT (+281 versus +110 ms in LV). Although IKr block alone evoked early afterdepolarizations and triggered activity in 50% of EHTs, slow pacing, reduced extracellular K+, and blocking of IKr, IKs, and IK1 were necessary to induce early afterdepolarizations in LV. In accordance with their clinical safety, moxifloxacin and verapamil did not induce early afterdepolarizations in EHT. In both EHT and LV, IKs block by HMR-1556 prolonged AP duration at 90% repolarization slightly in the combined presence of E-4031 and isoprenaline.

CONCLUSIONS: EHT from hiPSC-CMs shows a lower repolarization reserve than human LV working myocardium and could thereby serve as a sensitive and specific human-based model for repolarization studies and arrhythmia, similar to Purkinje fibers. In both human LV and EHT, IKs only contributed to repolarization under adrenergic stimulation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Germany (M.D.L., T.K., M.P., M.L.S., S.W., A.H., T.E., T.C.)., A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio (J.T.K.)., BioMediTech Institute and Faculty of Biomedical Sciences and Engineering, Tampere University of Technology, Finland (J.T.K.)., Department of Cardiovascular Surgery (E.G.), University Heart Center, Hamburg-Eppendorf, Germany.
Contributors: Lemoine, M. D., Krause, T., Koivumäki, J. T., Prondzynski, M., Schulze, M. L., Girdauskas, E., Willems, S., Hansen, A., Eschenhagen, T., Christ, T.
Pages: e006035
Publication date: 20 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: CIRCULATION: ARRHYTHMIA AND ELECTROPHYSIOLOGY
Volume: 11
Issue number: 7
ISSN (Print): 1941-3149
Ratings: 
  • Scopus rating (2018): CiteScore 3.68
Original language: English
Keywords: action potential, E-4031, Induced pluripotent stem cells (iPSC), ivabradine, long-QT syndrome, moxifloxacin

Bibliographical note

© 2018 American Heart Association, Inc.

Source: PubMed
Source ID: 29925535

Research output: Contribution to journalArticleScientificpeer-review

Medical Device Regulation (MDR) and its relation with standardization activities: Presentation in the CEN/TC251 June 2018 meeting in Brussels, Belgium

The European Union has converted it Medical Device Directive into Medical Device Regulation. This video presents the consequences of the new regulation to the standardization in Health Informatics.

General information

Publication status: Published
MoE publication type: I1 Audiovisual material
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sleep and Sensory Signal Analysis Group-SSSAG, Research group: Personal Health Informatics-PHI
Contributors: Värri, A.
Publication date: 12 Jun 2018
Media of output: Online
Size: 338 MBytes

Event information

Event: CEN/TC251 Plenary meeting
Location: CEN-CENELEC meeting Centre, Brussels, Belgium
ASJC Scopus subject areas: Health Information Management, Computer Science(all)
Keywords: medical device regulation, health software, European Union, medical device directive

Research output: Artistic and non-textual formDigital or Visual ProductsProfessional

Exploring membrane permeability of Tomatidine to enhance lipid mediated nucleic acid transfections

Intracellular delivery of nucleic acids is one of the critical steps in the transfections. Prior findings demonstrated various strategies including membrane fusion, endosomal escape for the efficient cytoplasmic delivery. In our continuing efforts to improve the nucleic acids transfections, we harnessed cell permeable properties of Tomatidine (T), a steroidal alkaloid abundantly found in green tomatoes for maximizing intracellular delivery of lipoplexes. We doped Tomatidine into liposomes of cationic lipid with amide linker (A) from our lipid library. Six liposomal formulations (AT) of Lipid A (1 mM) with varying concentrations of Tomatidine (0-1 mM) were prepared and evaluated for their transfection efficacies. Owing to its signature characteristic of cell membrane permeability, Tomatidine modulated endocytosis process, enhanced the intracellular delivery of the lipoplexes, and in turn increased the transfection efficacy of cationic liposomes. Our findings provide 'proof of concept' for enhancing transfections in gene delivery applications with Tomatidine in cationic liposomal formulations. These findings can be further applied in lipid mediated gene therapy and drug delivery applications.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group
Contributors: Rangasami, V. K., Lohchania, B., Voshavar, C., Rachamalla, H. R., Banerjee, R., Dhayani, A., Thangavel, S., Vemula, P. K., Marepally, S.
Publication date: 11 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Biochimica et Biophysica Acta: Biomembranes
Volume: 1861
Issue number: 1
ISSN (Print): 0005-2736
Ratings: 
  • Scopus rating (2018): CiteScore 3.64 SJR 1.427 SNIP 1.08
Original language: English

Research output: Contribution to journalArticleScientificpeer-review

Inductively Powered Implantable System with Far-field Data Transmitter for an Intracranial Pressure Monitoring Application: Design and Performance Validation

Monitoring of the intracranial pressure (ICP) is an essential activity for many brain diseases and injuries. For an adult, ICP value is between 7 mmHg to 15 mmHg . However, for a critically ill patient, the ICP should be maintained below 20 mmHg. Therefore, continuous monitoring of ICP is a life-saving activity. Several invasive and non-invasive methods have been proposed for monitoring of the ICP. However, invasive methods cannot be used for continuous monitoring of the ICP due to the risk of infection. Moreover, non-invasive methods lack in accuracy.

Therefore, many researchers reported battery-powered or fully passive implantable systems. However, a battery-powered implant has limited life and large size. On the other hand, in a fully passive implant the readout distance is relatively small in comparison with a battery-powered implant due to its zero-power operation.

In contrast, this work presents the development of an inductively powered implantable system equipped with a data transmission unit for an ICP monitoring application. The developed system has three main parts: an implant or in-body unit, an on-body unit and an off-body unit. The on-body unit powers the implant through inductive near-field link. After the activation, the implant, consists of a piezoresistive pressure sensor and a data transmission unit, transmits the pressure signal at the industrial, scientific, and medical radio (ISM) band of 2.45 GHz. The off-body unit receives the transmitted signal from the implant and estimates the pressure value.

The simulation and the measurement results of both near-filed and far-field links are presented. After the development of the system, the pressue readout measurement results have been presented in the air, water and in a setting mimicking the human head dielectric properties. For biocompatibility, the implant is coated with biocompatible adhesive silicone. The effect of coating on both wireless links has also been studied.

Finally, this work also presents the effect of misalignment between the inductively coupled antennas on the pressure readout accuracy of the developed ICP monitoring system and discusses the solution to overcome this impact. The thesis also presents the response of the developed ICP monitoring system with the change in the temperature.

General information

Publication status: Published
MoE publication type: G5 Doctoral dissertation (article)
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Wireless Identification and Sensing Systems Research Group
Contributors: Khan, M. W. A.
Number of pages: 47
Publication date: 7 Jun 2018

Publication information

Publisher: Tampere University of Technology
ISBN (Print): 978-952-15-4152-0
ISBN (Electronic): 978-952-15-4155-1
Original language: English

Publication series

Name: Tampere University of Technology. Publication
Volume: 1552
ISSN (Print): 1459-2045

Research output: Book/ReportDoctoral thesisCollection of Articles

Acquiring respiration rate from photoplethysmographic signal by recursive bayesian tracking of intrinsic modes in time-frequency spectra

Respiration rate (RR) provides useful information for assessing the status of a patient. We propose RR estimation based on photoplethysmography (PPG) because the blood perfusion dynamics are known to carry information on breathing, as respiration-induced modulations in the PPG signal. We studied the use of amplitude variability of transmittance mode finger PPG signal in RR estimation by comparing four time-frequency (TF) representation methods of the signal cascaded with a particle filter. The TF methods compared were short-time Fourier transform (STFT) and three types of synchrosqueezing methods. The public VORTAL database was used in this study. The results indicate that the advanced frequency reallocation methods based on synchrosqueezing approach may present improvement over linear methods, such as STFT. The best results were achieved using wavelet synchrosqueezing transform, having a mean absolute error and median error of 2.33 and 1.15 breaths per minute, respectively. Synchrosqueezing methods were generally more accurate than STFT on most of the subjects when particle filtering was applied. While TF analysis combined with particle filtering is a promising alternative for real-time estimation of RR, artefacts and non-respiration-related frequency components remain problematic and impose requirements for further studies in the areas of signal processing algorithms an PPG instrumentation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB)
Contributors: Pirhonen, M., Peltokangas, M., Vehkaoja, A.
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 18
Issue number: 6
Article number: 1693
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2018): CiteScore 3.72 SJR 0.592 SNIP 1.576
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Particle filters, Photoplethysmography, Respiration, Synchrosqueezing, Time-frequency analysis
Electronic versions: 

Bibliographical note

int=TUT-BMT,"Pirhonen, Mikko"

Source: Scopus
Source ID: 85047608517

Research output: Contribution to journalArticleScientificpeer-review

Altered polyamine profiles in colorectal cancer

Background: The declining mortality rate of patients with colorectal cancer (CRC) can be explained, at least partially, with early diagnosis. Simple diagnostic methods are needed to achieve a maximal patient participation rate in screening. Materials and Methods: Liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) was used to determine urinary polyamine (PA) profiles. In a prospective setting, 116 patients were included in the study: 57 with CRC, 13 with inflammatory bowel disease (IBD), 12 with adenoma, and 34 controls. Results: N1,N12-diacetylspermine (DiAcSPM) level was significantly higher in patients with CRC than controls (sensitivity=78.0%, specificity=70.6%; p=0.00049). The level of diacetylated cadaverine (p=0.0068) was lower and that of diacetylated putrescine (p=0.0078) was higher in patients with CRC than in those with IBD. Cadaverine (p=0.00010) and spermine (p=0.042) levels were lower and that of DiAcSPM (p=0.018) higher in patients with CRC than in those with adenoma. Conclusion: The simultaneous determination of urinary PAs by means of LC-MS/MS can be used to discriminate CRC from controls and patients with benign colorectal diseases.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Ita-Suomen yliopisto, University Central Hospital Kuopio, Hatanpää Hospital, Fimlab Laboratories Ltd, Tampere University Hospital, Central Hospital of Seinäjoki
Contributors: Venäläinen, M. K., Roine, A. N., Häkkinen, M. R., Vepsäläinen, J. J., Kumpulainen, P. S., Kiviniemi, M. S., Lehtimäki, T., Oksala, N. K., Rantanen, T. K.
Number of pages: 7
Pages: 3601-3607
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Anticancer Research
Volume: 38
Issue number: 6
ISSN (Print): 0250-7005
Ratings: 
  • Scopus rating (2018): CiteScore 1.9 SJR 0.722 SNIP 0.637
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: Colorectal cancer, Diagnostic methods, Inflammatory bowel disease, Polyamines
Source: Scopus
Source ID: 85048248512

Research output: Contribution to journalArticleScientificpeer-review

Gain characteristics of 1.3µm GaInNAs/GaAs quantum wells monolithically integrated on Ge

General information

Publication status: Published
Organisations: Faculty of Natural Sciences, Photonics
Contributors: Viheriälä, J., Aho, A., Isoaho, R., Aho, A., Tukiainen, A., Guina, M.
Publication date: 30 May 2018
Peer-reviewed: Unknown
Event: Paper presented at The European Conference on Integrated Optics 2018, Valencia, Spain.

Research output: Other conference contributionPaper, poster or abstractScientific

Platform for controlling cellular environment

General information

Publication status: Published
MoE publication type: Not Eligible
Organisations: BioMediTech, Research group: Micro and Nanosystems Research Group, Research group: Sensor Technology and Biomeasurements (STB), Research area: Measurement Technology and Process Control, BioMediTech, Research group: Computational Biophysics and Imaging Group, Heart Group, BioMediTech Institute and Faculty of Medicine and Life Science, University of Tampere, The Heart Center, Tampere University Hospital
Contributors: Mäki, A., Kattipparambil Rajan, D., Kreutzer, J., Skogberg, A., Pekkanen-Mattila, M., Verho, J. A., Ryynänen, T., Välimäki, H., Ahola, A., Hyttinen, J., Aalto-Setälä, K., Lekkala, J., Kallio, P.
Number of pages: 1
Publication date: 24 May 2018
Peer-reviewed: Unknown
Event: 

Research output: Other conference contributionPaper, poster or abstractScientific

The precision of the symmetry in Z-ring placement in Escherichia coli is hampered at critical temperatures

Cell division in Escherichia coli is morphologically symmetric due to, among other things, the ability of these cells to place the Z-ring at midcell. Studies have reported that, at sub-optimal temperatures, this symmetry decreases at the single-cell level, but the causes remain unclear. Using fluorescence microscopy, we observe FtsZ-GFP and DAPI-stained nucleoids to assess the robustness of the symmetry of Z-ring formation and positioning in individual cells under sub-optimal and critical temperatures. We find the Z-ring formation and positioning to be robust at sub-optimal temperatures, as the Z-ring's mean width, density and displacement from midcell maintain similar levels of correlation to one another as at optimal temperatures. However, at critical temperatures, the Z-ring displacement from midcell is greatly increased. We present evidence showing that this is due to enhanced distance between the replicated nucleoids and, thus, reduced Z-ring density, which explains the weaker precision in setting a morphologically symmetric division site. This also occurs in rich media and is cumulative, i.e. combining richer media and critically high temperatures enhances the asymmetries in division, which is evidence that the causes are biophysical. To further support this, we show that the effects are reversible, i.e. shifting cells from optimal to critical, and then to optimal again, reduces and then enhances the symmetry in Z-ring positioning, respectively, as the width and density of the Z-ring return to normal values. Overall, our findings show that the Z-ring positioning in E. coli is a robust biophysical process under sub-optimal temperatures, and that critical temperatures cause significant asymmetries in division.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, Faculty of Biomedical Sciences and Engineering, Faculdade de Ciencias e Tecnologia, New University of Lisbon
Contributors: Neeli-Venkata, R., Oliveira, S. M., Martins, L., Startceva, S., Bahrudeen, M., Fonseca, J. M., Minoia, M., Ribeiro, A. S.
Publication date: 18 May 2018
Peer-reviewed: Yes

Publication information

Journal: Physical Biology
Volume: 15
Issue number: 5
Article number: 056002
ISSN (Print): 1478-3967
Ratings: 
  • Scopus rating (2018): CiteScore 1.93 SJR 1.066 SNIP 0.632
Original language: English
ASJC Scopus subject areas: Biophysics, Structural Biology, Molecular Biology, Cell Biology
Keywords: asymmetry in cell division, critical temperatures, Escherichia coli, single-cell microscopy, Z-ring formation and positioning
Electronic versions: 
Source: Scopus
Source ID: 85049839706

Research output: Contribution to journalArticleScientificpeer-review

Anticancer activity study of A adenosine receptor agonists

AIMS: A3 adenosine receptor (A3AR) signalling activation seems to mediate anticancer effect, and it has been targeted for drug development. The identification of potent and selective A3AR agonists could be crucial for cancer drug development.

MATERIALS AND METHODS: In the present study was determined the in vitro activity of known 1-3 and newly 4-6 synthesized compounds with high A3AR affinity and selectivity (Ki in the low nanomolar range) in binding studies. Effect of known and novel A3AR agonists on human prostate cancer (PC3), hepatocellular carcinoma (Hep G2), and epithelial colorectal carcinoma (Caco-2) cells were analysed by cytotoxicity assay, dose and time dependent inhibitor assay, migration, apoptosis, autophagy and reactive oxygen species (ROS) assays.

KEY FINDINGS: Results show that the anticancer effect is not due to A3AR activation alone. In fact, the more active and selective agonist versus A3AR, compound 1, results inactive on cancer cells such as compounds 2-4. Moreover, results show that the novel compound 5, at micromolar concentration range (IC50 = 28.0 μM), inhibits the growth of PC3, Hep G2, and Caco-2 cells and their migration in time- and dose- dependent manner. The mechanism involved in cell death is attributable to apoptosis. At the same time compound 5 promo