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At least 487 records · Page 27Linked to original sources

Muscle Fatigue Analysis Using OpenSim

In this research, attempts are made to conduct concrete muscle fatigue analysis of arbitrary motions on OpenSim, a digital human modeling platform. A plug-in is written on the base of a muscle fatigue model, which makes it possible to calculate the decline of force-output capability of each muscle along time. The plug-in is tested on a three-dimensional, 29 degree-of-freedom human model. Motion data is obtained by motion capturing during an arbitrary running at a speed of 3.96 m/s. Ten muscles are selected for concrete analysis. As a result, the force-output capability of these muscles reduced to 60%-70% after 10 minutes' running, on a general basis. Erector spinae, which loses 39.2% of its maximal capability, is found to be more fatigue-exposed than the others. The influence of subject attributes (fatigability) is evaluated and discussed.

q-bio.TO↗

Computational simulation of bone remodelling post reverse total shoulder arthroplasty

Bone is a living material. It adapts, in an optimal sense, to loading by changing its density and trabeculae architecture - a process termed remodelling. Implanted orthopaedic devices can significantly alter the loading on the surrounding bone, which can have a detrimental impact on bone ingrowth that is critical to ensure secure implant fixation. In this contribution, a computational model that accounts for bone remodelling is developed to elucidate the response of bone following a reverse shoulder procedure for rotator cuff deficient patients. The physical process of remodelling is modelled using continuum scale, open system thermodynamics whereby the density of bone evolves isotropically in response to the loading it experiences. The fully-nonlinear continuum theory is solved approximately using the finite element method. The code developed to model the reverse shoulder procedure is validated using a series of benchmark problems.

q-bio.TO↗

Modelling the order of driver mutations and metabolic mutations as structures in cancer dynamics

Recent works have stressed the important role that random mutations have in the development of cancer phenotype. We challenge this current view by means of bioinformatic data analysis and computational modelling approaches. Not all the mutations are equally important for the development of metastasis. The survival of cancer cells from the primary tumour site to the secondary seeding sites depends on the occurrence of very few driver mutations promoting oncogenic cell behaviours and on the order with which these mutations occur. We introduce a model in the framework of Cellular Automata to investigate the effects of metabolic mutations and mutation order on cancer stemness and tumour cell migration in bone metastasised breast cancers. The metabolism of the cancer cell is a key factor in its proliferation rate. Bioinformatics analysis on a cancer mutation database shows that metabolism-modifying alterations constitute an important class of key cancer mutations. Our approach models three types of mutations: drivers, the order of which is relevant for the dynamics, metabolic which support cancer growth and are estimated from existing databases, and non--driver mutations. Our results provide a quantitative basis of how the order of driver mutations and the metabolic mutations in different cancer clones could impact proliferation of therapy-resistant clonal populations and patient survival. Further mathematical modelling of the order of mutations is presented in terms of operators. We believe our work is novel because it quantifies two important factors in cancer spreading models: the order of driver mutations and the effects of metabolic mutations.

q-bio.CB↗

Muscle-Cell-Based "Living Diodes"

A new type of diode that is made entirely of electrically excitable muscle cells and nonexcitable fibroblast cells is designed, fabricated, and characterized. These two cell types in a rectangular pattern allow the signal initiated on the excitable side to pass to the nonexcitable side, and not in the opposite direction.

q-bio.TO↗

White matter hyperintensity and stroke lesion segmentation and differentiation using convolutional neural networks

The accurate assessment of White matter hyperintensities (WMH) burden is of crucial importance for epidemiological studies to determine association between WMHs, cognitive and clinical data. The manual delineation of WMHs is tedious, costly and time consuming. This is further complicated by the fact that other pathological features (i.e. stroke lesions) often also appear as hyperintense. Several automated methods aiming to tackle the challenges of WMH segmentation have been proposed, however cannot differentiate between WMH and strokes. Other methods, capable of distinguishing between different pathologies in brain MRI, are not designed with simultaneous WMH and stroke segmentation in mind. In this work we propose to use a convolutional neural network (CNN) that is able to segment hyperintensities and differentiate between WMHs and stroke lesions. Specifically, we aim to distinguish between WMH pathologies from those caused by stroke lesions due to either cortical, large or small subcortical infarcts. As far as we know, this is the first time such differentiation task has explicitly been proposed. The proposed fully convolutional CNN architecture, is comprised of an analysis path, that gradually learns low and high level features, followed by a synthesis path, that gradually combines and up-samples the low and high level features into a class likelihood semantic segmentation. Quantitatively, the proposed CNN architecture is shown to outperform other well established and state-of-the-art algorithms in terms of overlap with manual expert annotations. Clinically, the extracted WMH volumes were found to correlate better with the Fazekas visual rating score. Additionally, a comparison of the associations found between clinical risk-factors and the WMH volumes generated by the proposed method, were found to be in line with the associations found with the expert-annotated volumes.

q-bio.TO↗

Unlocking datasets by calibrating populations of models to data density: a study in atrial electrophysiology

The understanding of complex physical or biological systems nearly always requires a characterisation of the variability that underpins these processes. In addition, the data used to calibrate such models may also often exhibit considerable variability. A recent approach to deal with these issues has been to calibrate populations of models (POMs), that is multiple copies of a single mathematical model but with different parameter values. To date this calibration has been limited to selecting models that produce outputs that fall within the ranges of the dataset, ignoring any trends that might be present in the data. We present here a novel and general methodology for calibrating POMs to the distributions of a set of measured values in a dataset. We demonstrate the benefits of our technique using a dataset from a cardiac atrial electrophysiology study based on the differences in atrial action potential readings between patients exhibiting sinus rhythm (SR) or chronic atrial fibrillation (cAF) and the Courtemanche--Ramirez--Nattel model for human atrial action potentials. Our approach accurately captures the variability inherent in the experimental population, and allows us to identify the differences underlying stratified data as well as the effects of drug block.

q-bio.TO↗

Continuum mechanics at nanoscale. A tool to study trees' watering and recovery

The cohesion-tension theory expounds the crude sap ascent thanks to the negative pressure generated by evaporation of water from leaves. Nevertheless, trees pose multiple challenges and seem to live in unphysical conditions: the negative pressure increases cavitation; it is possible to obtain a water equilibrium between connected parts where one is at a positive pressure and the other one is at negative pressure; no theory is able to satisfactorily account for the refilling of vessels after embolism events. A theoretical form of our paper in the Journal of Theoretical Biology is proposed together with new results: a continuum mechanics model of the disjoining pressure concept refers to the Derjaguin School of physical chemistry. A comparison between liquid behaviour both in tight-filled microtubes and in liquid thin-films is offered when the pressure is negative in liquid bulks and is positive in liquid thin-films and vapour bulks. In embolized xylem microtubes, when the air-vapour pocket pressure is greater than the air-vapour bulk pressure, a refilling flow occurs between the air-vapour domains to empty the air-vapour pockets although the liquid-bulk pressure remains negative. The model has a limit of validity taking the maximal size of trees into account. These results drop inkling that the disjoining pressure is an efficient tool to study biological liquids in contact with substrates at a nanoscale range.

cond-mat.soft↗

Correlates of severity of disease in Macaca mulatta infected with Plasmodium cynomolgi

Characterization of host responses associated with severe malaria through an integrative approach is necessary to understand the dynamics of a \textit{Plasmodium cynomolgi} infection. In this study, we conducted temporal immune profiling, cytokine profiling and transcriptomic analysis of five \textit{Macaca mulatta} infected with \textit{P. cynomolgi}. This experiment resulted in two severe infections, and two mild infections. Our analysis reveals that differential transcriptional up-regulation of genes linked with response to pathogen-associated molecular pattern (PAMP) and pro-inflammatory cytokines is characteristic of hosts experiencing severe malaria. Furthermore, our analysis discovered associations of transcriptional differential regulation unique to severe hosts with specific cellular and cytokine responses. The combined data provide a molecular and cellular basis for the development of severe malaria during \textit{P. cynomolgi} infection.

q-bio.TO↗

The Strong Cell-based Hydrogen Peroxide Generation Triggered by Cold Atmospheric Plasma

Hydrogen peroxide (H2O2) is an important signaling molecule in cancer cells. However, the significant secretion of H2O2 by cancer cells have been rarely observed. Cold atmospheric plasma (CAP) is a near room temperature ionized gas composed of neutral particles, charged particles, reactive species, and electrons. Here, we first demonstrated that breast cancer cells and pancreatic adenocarcinoma cells generated micromolar level H2O2 during just 1 min of direct CAP treatment on these cells. The cell-based H2O2 generation is affected by the medium volume, the cell confluence, as well as the discharge voltage. The application of cold atmospheric plasma (CAP) in the cancer treatment has been intensively investigated over the past decade. Several cellular responses to the CAP treatment have been observed including the consumption of the CAP-originated reactive species, the rise of intracellular reactive oxygen species, the damage on DNA and mitochondria, as well as the activation of apoptotic events. This is a new previously unknown cellular response to CAP, which provides a new prospective to understand the interaction between CAP and cells.

q-bio.CB↗

Predicting therapeutic and aggravating drugs for hepatocellular carcinoma based on tissue-specific pathways

Motivation: Hepatocellular carcinoma (HCC) is a significant health problem worldwide and annual number of cases are nearly more than 700,000. However,there are few safe and effective thera-peutic options for HCC patients.Here, we propose a new approach for predicting therapeutic and aggravating drugs for HCCbased ontissue-specificpathways, which considersnot onlyliver tis-sueand functional informationof pathways, but also the changes of single gene in pathways. Results: Firstly, we map genes related to HCC to the liver-specific protein interaction network and get anextended tissue-specific gene set of HCC. Then, based on the extended gene set, 12 en-riched KEGGfunctional pathways are extracted.Using Kolmogorov-Smirnov statistic, we calculate the therapeutic scores of drugs based on the 12 tissue-specific pathways. Finally, after filtering by Comparative Toxicogenomics Database (CTD) benchmark,we get 3 therapeutic drugs and 3 ag-gravating drugs for HCC. Furthermore, we validate the6potentially related drugs of HCC by analyz-ingtheiroverlaps with drug indications reported in PubMed literatures, and also making CMapprofile similarity analysis and KEGG enrichment analysis based on their targets. All analysis results sug-gest thatour approach is effective and accurate for discovering novel therapeutic options for HCC and it can be easily extended to other diseases.More importantly, our method can clearly distin-guish therapeutic and aggravating drugsforHCC, which also can be used to indicateunmarked drug-disease associations in CTD as positive or negative.

q-bio.TO↗

A Tissue Engineered Model of Aging: Interdependence and Cooperative Effects in Failing Tissues

Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues. We found that while microscopic mechanisms drive aging, the interdependency between cells plays a major role in tissue death, providing evidence on how cellular aging is connected to its higher systemic consequences.

q-bio.TO↗

A New Conceptual Framework for the Therapy by Optimized Multidimensional Pulses of Therapeutic Activity. The case of Multiple Myeloma Model

We developed simulation methodology to assess eventual therapeutic efficiency of exogenous multiparametric changes in a four-component cellular system described by the system of ordinary differential equations. The method is numerically implemented to simulate the temporal behavior of a cellular system of multiple myeloma cells. The problem is conceived as an inverse optimization task where the alternative temporal changes of selected parameters of the ordinary differential equations represent candidate solutions and the objective function quantifies the goals of the therapy. The system under study consists of two main cellular components, tumor cells and their cellular environment, respectively. The subset of model parameters closely related to the environment is substituted by exogenous time dependencies - therapeutic pulses combining continuous functions and discrete parameters subordinated thereafter to the optimization. Synergistic interaction of temporal parametric changes has been observed and quantified whereby two or more dynamic parameters show effects that absent if either parameter is stimulated alone. We expect that the theoretical insight into unstable tumor growth provided by the sensitivity and optimization studies could, eventually, help in designing combination therapies.

q-bio.TO↗

Reaction-Diffusion Models for Glioma Tumor Growth

Mathematical modelling of tumor growth is one of the most useful and inexpensive approaches to determine and predict the stage, size and progression of tumors in realistic geometries. Moreover, these models has been used to get an insight into cancer growth and invasion and in the analysis of tumor size and geometry for applications in cancer treatment and surgical planning. The present revision attempts to present a general perspective of the use of models based on reaction-diffusion equations not only for the description of tumor growth in gliomas, addressing for processes such as tumor heterogeneity, hypoxia, dormancy and necrosis, but also its potential use as a tool in designing optimized and patient specific therapies.

physics.med-ph↗

Glia

Essential introduction to glial cells with emphasis on astrocytes, microglia and their interplay in reactive astrogliosis.

q-bio.NC↗

Constraint on the stem cell numbers and division rates posed by the risk of cancer

Compiled data for the stem cell numbers, Ns, and division rates, ms, is reanalized in order to show that we can distinguish two groups of human tissues. In the first one, there is a relatively high fraction of maintenance (stem and transit) cells in the tissue, but the division rates are low. The second group, on the other hand, is characterized by very high transit cell division rates, of around one division per day. These groups do not have an embrionary origin. We argue that their properties arise from a combination of the needs of tissue homeostasis (in particular turnover rate) and a bound on cancer risk, which is roughly a linear function of the product Ns ms. The bound on cancer risk leads to a threshold at ms = 8/year, where the fraction of stem cells falls down two orders of magnitude.

q-bio.TO↗

Locating Order-Disorder Phase Transition in a Cardiac System

To prevent sudden cardiac death, predicting where in the cardiac system an order-disorder phase transition into ventricular fibrillation begins is as important as when it begins. We present a computationally efficient, information-theoretic approach to predicting the locations of wavebreaks that initiate fibrillation in a cardiac system where the order-disorder behavior is controlled by a single driving component, mimicking electrical misfiring from the pulmonary veins or the Purkinje fibers. Communication analysis between the driving component and each component of the system reveals that channel capacity, mutual information and transfer entropy can locate the wavebreaks. This approach is applicable to interventional therapies to prevent sudden death, as well as to a wide range of systems to mitigate or prevent imminent phase transitions.

q-bio.QM↗

A two dimensional model of curvilinear blood vessels with layered elastic walls

We present a two dimensional model describing the elastic behaviour of the wall of a curved blood vessel. The wall has a laminate structure consisting of several anisotropic layers of varying thickness and is assumed to be much smaller in thickness than the radius of the vessel which itself is allowed to vary. Our two-dimensional model takes the interaction of the wall with the surrounding tissue and the blood flow into account and is obtained via a dimension reduction procedure. The curvature and twist of the vessel axis as well as the anisotropy of the laminate wall present the main challenges in applying the dimension reduction procedure so plenty of examples of canonical shapes of vessels and their walls are supplied with explicit systems of differential equations at the end.

q-bio.TO↗