A mathematical model quantifies proliferation and motility effects of TGF--β\beta on cancer cells

Transforming growth factor (TGF) $\beta$ is known to have properties of both a tumor suppressor and a tumor promoter. While it inhibits cell proliferation, it also increases cell motility and decreases cell--cell adhesion. Coupling mathematical modeling and experiments, we investigate the growth and motility of oncogene--expressing human mammary epithelial cells under exposure to TGF--$\beta$. We use a version of the well--known Fisher--Kolmogorov equation, and prescribe a procedure for its parametrization. We quantify the simultaneous effects of TGF--$\beta$ to increase the tendency of individual cells and cell clusters to move randomly and to decrease overall population growth. We demonstrate that in experiments with TGF--$\beta$ treated cells \textit{in vitro}, TGF--$\beta$ increases cell motility by a factor of 2 and decreases cell proliferation by a factor of 1/2 in comparison with untreated cells.Comment: 15 pages, 4 figures; to appear in Computational and Mathematical Methods in Medicin

Finite element surface registration incorporating curvature, volume preservation, and statistical model information

We present a novel method for nonrigid registration of 3D surfaces and images. The method can be used to register surfaces by means of their distance images, or to register medical images directly. It is formulated as a minimization problem of a sum of several terms representing the desired properties of a registration result: smoothness, volume preservation, matching of the surface, its curvature, and possible other feature images, as well as consistency with previous registration results of similar objects, represented by a statistical deformation model. While most of these concepts are already known, we present a coherent continuous formulation of these constraints, including the statistical deformation model. This continuous formulation renders the registration method independent of its discretization. The finite element discretization we present is, while independent of the registration functional, the second main contribution of this paper. The local discontinuous Galerkin method has not previously been used in image registration, and it provides an efficient and general framework to discretize each of the terms of our functional. Computational efficiency and modest memory consumption are achieved thanks to parallelization and locally adaptive mesh refinement. This allows for the first time the use of otherwise prohibitively large 3D statistical deformation models

Products of Compartmental Models in Epidemiology.

We show that many structured epidemic models may be described using a straightforward product structure in this paper. Such products, derived from products of directed graphs, may represent useful refinements including geographic and demographic structure, age structure, gender, risk groups, or immunity status. Extension to multistrain dynamics, that is, pathogen heterogeneity, is also shown to be feasible in this framework. Systematic use of such products may aid in model development and exploration, can yield insight, and could form the basis of a systematic approach to numerical structural sensitivity analysis

Investigating properties of the cardiovascular system using innovative analysis algorithms based on ensemble empirical mode decomposition

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright @ 2012 Jia-Rong Yeh et al.Cardiovascular system is known to be nonlinear and nonstationary. Traditional linear assessments algorithms of arterial stiffness and systemic resistance of cardiac system accompany the problem of nonstationary or inconvenience in practical applications. In this pilot study, two new assessment methods were developed: the first is ensemble empirical mode decomposition based reflection index (EEMD-RI) while the second is based on the phase shift between ECG and BP on cardiac oscillation. Both methods utilise the EEMD algorithm which is suitable for nonlinear and nonstationary systems. These methods were used to investigate the properties of arterial stiffness and systemic resistance for a pig's cardiovascular system via ECG and blood pressure (BP). This experiment simulated a sequence of continuous changes of blood pressure arising from steady condition to high blood pressure by clamping the artery and an inverse by relaxing the artery. As a hypothesis, the arterial stiffness and systemic resistance should vary with the blood pressure due to clamping and relaxing the artery. The results show statistically significant correlations between BP, EEMD-based RI, and the phase shift between ECG and BP on cardiac oscillation. The two assessments results demonstrate the merits of the EEMD for signal analysis.This work is supported by the National Science Council (NSC) of Taiwan (Grant number NSC 99-2221-E-155-046-MY3), Centre for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan which is sponsored by National Science Council (Grant number: NSC 100–2911-I-008-001) and the Chung-Shan Institute of Science & Technology in Taiwan (Grant numbers: CSIST-095-V101 and CSIST-095-V102)

A semiparametric bivariate probit model for joint modeling of outcomes in STEMI patients

In this work we analyse the relationship among in-hospital mortality and a treatment effectiveness outcome in patients affected by ST-Elevation myocardial infarction. The main idea is to carry out a joint modeling of the two outcomes applying a Semiparametric Bivariate Probit Model to data arising from a clinical registry called STEMI Archive. A realistic quantification of the relationship between outcomes can be problematic for several reasons. First, latent factors associated with hospitals organization can affect the treatment efficacy and/or interact with patient’s condition at admission time. Moreover, they can also directly influence the mortality outcome. Such factors can be hardly measurable. Thus, the use of classical estimation methods will clearly result in inconsistent or biased parameter estimates. Secondly, covariate-outcomes relationships can exhibit nonlinear patterns. Provided that proper statistical methods for model fitting in such framework are available, it is possible to employ a simultaneous estimation approach to account for unobservable confounders. Such a framework can also provide flexible covariate structures and model the whole conditional distribution of the response

RNA packaging motor: From structure to quantum mechanical modelling and sequential-stochastic mechanism

The bacteriophages of the Cystoviridae family package their single stranded RNA genomic precursors into empty capsid (procapsids) using a hexameric packaging ATPase motor (P4). This molecular motor shares sequence and structural similarity with RecA-like hexameric helicases. A concerted structural, mutational and kinetic analysis helped to define the mechanical reaction coordinate, i.e. the conformational changes associated with RNA translocation. The results also allowed us to propose a possible scheme of coupling between ATP hydrolysis and translocation which requires the cooperative action of three consecutive subunits. Here, we first test this model by preparing hexamers with defined proportions of wild type and mutant subunits and measuring their activity. Then, we develop a stochastic kinetic model which accounts for the catalytic cooperativity of the P4 hexamer. Finally, we use the available structural information to construct a quantum-chemical model of the chemical reaction coordinate and obtain a detailed description of the electron density changes during ATP hydrolysis. The model explains the results of the mutational analyses and yields new insights into the role of several conserved residues within the ATP binding pocket. These hypotheses will guide future experimental work

Comparing Strategies to Prevent Stroke and Ischemic Heart Disease in the Tunisian Population: Markov Modeling Approach Using a Comprehensive Sensitivity Analysis Algorithm.

Background. Mathematical models offer the potential to analyze and compare the effectiveness of very different interventions to prevent future cardiovascular disease. We developed a comprehensive Markov model to assess the impact of three interventions to reduce ischemic heart diseases (IHD) and stroke deaths: (i) improved medical treatments in acute phase, (ii) secondary prevention by increasing the uptake of statins, (iii) primary prevention using health promotion to reduce dietary salt consumption. Methods. We developed and validated a Markov model for the Tunisian population aged 35–94 years old over a 20-year time horizon. We compared the impact of specific treatments for stroke, lifestyle, and primary prevention on both IHD and stroke deaths. We then undertook extensive sensitivity analyses using both a probabilistic multivariate approach and simple linear regression (metamodeling). Results. The model forecast a dramatic mortality rise, with 111,134 IHD and stroke deaths (95% CI 106567 to 115048) predicted in 2025 in Tunisia. The salt reduction offered the potentially most powerful preventive intervention that might reduce IHD and stroke deaths by 27% (−30240 [−30580 to −29900]) compared with 1% for medical strategies and 3% for secondary prevention. The metamodeling highlighted that the initial development of a minor stroke substantially increased the subsequent probability of a fatal stroke or IHD death. Conclusions. The primary prevention of cardiovascular disease via a reduction in dietary salt consumption appeared much more effective than secondary or tertiary prevention approaches. Our simple but comprehensive model offers a potentially attractive methodological approach that might now be extended and replicated in other contexts and populations

Two-dimensional matrix algorithm using detrended fluctuation analysis to distinguish Burkitt and diffuse large B-cell lymphoma

Copyright © 2012 Rong-Guan Yeh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A detrended fluctuation analysis (DFA) method is applied to image analysis. The 2-dimensional (2D) DFA algorithms is proposed for recharacterizing images of lymph sections. Due to Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), there is a significant different 5-year survival rates after multiagent chemotherapy. Therefore, distinguishing the difference between BL and DLBCL is very important. In this study, eighteen BL images were classified as group A, which have one to five cytogenetic changes. Ten BL images were classified as group B, which have more than five cytogenetic changes. Both groups A and B BLs are aggressive lymphomas, which grow very fast and require more intensive chemotherapy. Finally, ten DLBCL images were classified as group C. The short-term correlation exponent α1 values of DFA of groups A, B, and C were 0.370 ± 0.033, 0.382 ± 0.022, and 0.435 ± 0.053, respectively. It was found that α1 value of BL image was significantly lower (P < 0.05) than DLBCL. However, there is no difference between the groups A and B BLs. Hence, it can be concluded that α1 value based on DFA statistics concept can clearly distinguish BL and DLBCL image.National Science Council (NSC) of Taiwan the Center for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan (also sponsored by National Science Council)