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21 projects in result set. Displaying 20 per page. Projects sorted by alphabetical order.
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Whole-Cell Computational Model of Mycoplasma genitalium
- The goal of this project was to develop the first detailed, "whole-cell" computational model of the entire life cycle of living organism, <i>Mycoplasma genitalium</i>. The model describes the dynamics of every molecule over the entire life cycle and accounts for the specific function of every annotated gene product.
We anticipate that whole-cell models will be critical for synthetic biology and personalized medicine. Please see the project website <a href="http://wholecell.org">wholecell.org</a> and the Downloads page to explore the whole-cell knowledge base and simulations and obtain the model code. | |
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Registered: 2012-01-24 03:21 |
Predicting Cell Deformation from Body Level Mechanical Loads
- This project is a NIBIB/NIH funded study (1R01EB009643-01) to establish models and computational platforms to predict cellular deformations from joint level mechanical loading.
Collaborators:
Ahmet Erdemir (PI), Amit Vasanji, Jason Halloran (Cleveland Clinic)
Cees Oomens, Frank Baaijens (Eindhoven University of Technology)
Jeff Weiss (University of Utah)
Farshid Guilak (Duke University)
Summary (from grant proposal):
Cells of the musculoskeletal system are known to have a biological response to deformation. Deformations, when abnormal in magnitude, duration, and/or frequency content, can lead to cell damage and possible disruption in homeostasis of the extracellular matrix. These mechanisms can be studied in an isolated fashion but connecting mechanical cellular response to organ level mechanics and human movement requires a multiscale approach. At the organ level, physicians perform surgical procedures, investigators try to understand risk of injury, and clinicians prescribe preventive and therapeutic interventions. Many of these operations are aimed at management and prevention of cell damage, and to associate joint level mechanical markers of failure to cell level failure mechanisms. Through human movement, one explores neuromuscular control mechanisms and the influence of physical activity on musculoskeletal tissue properties. At a lower level, mechanical sensation of cell deformations regulate movement control. Physical rehabilitation and exercise regimens are prescribed to promote tissue healing and/or strengthening through cellular regeneration. The knowledge of the mechanical pathway, through which the body level loads are distributed between organs, then within the tissues and further along the extracellular matrix and the cells, is critical for the success of various interventions. However, this information is not established. The goal of this research proposal is to portray that prediction of cell deformations from loads acting on the human body, therefore a clear depiction of the mechanical pathway, is possible, if a multiscale simulation approach is used. Multiresolution models of the knee joint, representative of joint, tissue and cell structure and mechanics, will be developed for this purpose. The knee endures high rates of traumatic injury to its soft tissue structures and it is predominantly affected by osteoarthritis, chronically induced by abnormalities in mechanical loading or how it is transferred to the cartilage. Through multiscale mechanical coupling of these models, a map of cellular deformation in cartilage, ligaments and menisci under a variety of tibiofemoral joint loads will be obtained. Comprehensive mechanical testing at joint, tissue and cell levels will be conducted for parameter estimation and validation, including in vitro loading of the knee joint representative of lifelike loading scenarios. In addition, imaging modalities will capture joint and tissue anatomy, and spatial and deformation related information from cell and extracellular matrix. Advanced computational approaches will be used to obtain model properties and to facilitate multiscale simulations. The approach will combine the expertise of many investigators experienced in biomechanical modeling and experimentation at various biological scales, some with clinical expertise. In future, the research team will utilize this platform to establish the relationship between the structural and loading state of the knee and chondrocyte stresses to explore potential mechanisms of cartilage degeneration. Through documented dissemination of data and models, simulations of other pathologies and translation of the methodology to other organs can be carried out by any interested investigator. | |
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Registered: 2009-07-23 17:33 |
Integrated Flux Balance Analysis Model of Escherichia coli
- This project includes several MATLAB scripts that simulate E. coli central metabolism and the effects of single gene deletions on metabolism using 3 approaches -- iFBA, rFBA, and ODE. The project also includes several MATLAB scripts that simulate biochemical networks using 1) integrated flux balance analysis (iFBA) -- a combined FBA, boolean regulatory, and ODE approach; 2) regulatory flux balance analysis (rFBA); and 3) ordinary differential equations (ODE). Additionally, the project includes several MATLAB and php scripts for visualizing metabolic simulations. | |
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Registered: 2008-06-11 23:27 |
Agent-based (AB) pharmacokinetic, AB pathology, and AB PK/PD tutorial models
- The tutorials in this publication outline the development and simulation results of three agent-based (AB) models: a pharmacokinetic (PK), pathology, and pharmacokinetic/pharmacodynamic (PKPD) models. 1) The AB PK model uses a two-compartment system, including five agents that transfer, store, and record simulation information. 2) The AB pathology model includes a Morbidity agent and Symptom information. 3) The AB PK/PD model integrates the two earlier models and allows the user to delivery an intervention Dose that diminishes Symptom until Dose is cleared. | |
Activity Percentile: 0.00 Registered: 2015-08-10 18:01 |
Bionet biological cell network pathway simulation
- The methodology in bionet is distinguished from previous qualitative modeling approaches in several ways. The goal was to develop a model that would allow experimental biologists to use the kind of qualitative data found in typical journal articles to describe the interaction of genes, proteins, and other cellular components to create computer models of large numbers of interacting parts. This arose from a practical need in our research to keep track of myriad components in pathway models that were built from data extracted from dozens of journal articles. Biologists already do this kind of mental modeling every time they make a new hypothesis; a tool was needed to aid in this reasoning. Secondly, with new sources of data becoming available, it was important to design a methodology that could be expanded in the future to integrate new data sources to refine models.
Finally, biological processes span many scales. A kind of heuristic modeling is common in the literature, where molecular interactions are analyzed and used to create new hypotheses about cellular events, tissue processes or disease progression. For example, specific gene mutations accelerate tumor growth in specific tissues. This is a semi-quantitative relationship between two very different scales. Fuzzy network modeling can be used as a tool for aiding human reasoning when many interacting variables participate in complex interaction networks on several scales. Though the interactions can sometimes only be described approximately, the logic of the interactions is rigorous.
Pathway models can be constructed manually by biologists and manipulated to study the dynamics of alternative pathways. However, the power of this method is that it provides a framework for using various soft computing technologies to integrate diverse data sources to improve and refine models. Rule-based or fuzzy logic models are appropriate for manipulation by genetic or other evolutionary algorithms, which may be useful for drug target discovery. This process will be discussed in future papers that expand the basic model presented here. Details about methods for integration of high-throughput data with expert knowledge will also be reserved for future publications. Because the soft computing paradigm has been widely adopted for many engineering tasks, it is hoped that the framework presented here can be adopted and rapidly expanded by many researchers with expertise in these methods. Input files and code for all examples presented are available at the Bionet website.
Continued development of Bionet is funded in part by the Stowers Institute for Medical Research (http://www.stowers-institute.org). | |
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Activity Percentile: 0.00 Registered: 2009-08-12 20:28 |
C++ and Python code, distributed computing and OpenMM interfaces for simulations
- please cite: "Interplay of Protein and DNA Structure Revealed in Simulations of the lac Operon" (PLOS One 2013)
for any code related to protein-DNA modeling and
"Free Energy Monte Carlo Simulations on a Distributed Network" (Lecture Notes in Computer Science Journal for PARA 2010)
http://link.springer.com/chapter/10.1007%2F978-3-642-28145-7_1
for parallel client-server code, users of additional code should cite this web site. Code is provided as-is with no warranty and examples are provided to illustrate the usage of these modeling techniques with some sample systems. Code is the intellectual property of Luke Czapla, developer and biophysicist. Examples are provided in C/C++ and Python. | |
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Activity Percentile: 0.00 Registered: 2014-02-01 22:32 |
CompuCell3D
- For more information please visit: http://www.compucell3d.org/
Modeling the behavior of multi-cell biological systems using multi-scale approach is one of the goals behind CompuCel3D project.
CompuCell3D was originally written to model morphogenesis, the process in embryonic development where cells cluster into patterns which eventually differentiate into organs, muscle or bone. Through integration of multiple mathematical models into a software implementation with easy to use XML based syntax scientists were able to build models within few hours as opposed to weeks when writing source code from scratch. compuCell3D is based on Glazier-graner-Hogeweg model (GGH) also known as the Cellular Potts Model (CPM).The model is capable of capturing key cellular behaviors: cell clustering as well as growth, division, death, intracellular adhesion, and volume and surface area constraints;
In addition researchers may include partial differential equation models for external chemical fields which can model reaction-diffusion, and cell type automata to provide a method for categorizing cells by behavior into types and algorithms for changing cell type.
These models can communicate to establish for example cellular reactions to external chemical fields such as secretion or resorption, and cellular responses such as chemotaxis and haptotaxis. Using scripting language (Python) users may build sophisticated intra-cellular models e.g. reaction-kinetics models, gene pathways etc that determine macroscopic properties of cells. Thus using CompuCell3D one can build truly multi-scale, multi-cell models.
The Graphical User Interface CompuCellPlayer, built upon Qt, interactively visualizes these simulations in three dimensions and also provides the ability to switch to 2D cross sections in each dimension, and also the ability to alternate between chemical fields being visualized. Through this player you can easily pause a simulation to view results and restart again, and also use camera techniques such as zooming, rotating, translating and projecting to more easily view results. The Player uses Qt Threads to enable parallel execution with the CompuCell3D back end. Through the player you can save screenshots of a simulation and for long simulations the Player can be run in silent mode to improve performance, generating images every certain number of steps.
We provide all these features in a single package - CompuCell3D. Both source code and binaries are available for Windows, Linux and Mac OS X. For complete download selection please visit
http://www.compucell3d.org
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Registered: 2006-02-05 19:55 |
Flexible (flexFBA) and time-linked (tFBA) Flux Balance Analysis methods
- (provided for computational biologists to reproduce publication results, and a small utility written for example use with the Cobra toolbox) The associated publication describes two complimentary methods that remove the inherent long-time assumptions of the biomass reaction used in FBA. Implementing a flexible objective flexFBA, enables a metabolic network to produce biological process reactants independently from one another. This flexibility is in contrast to the rigid proportion held by the traditional biomass reaction of FBA. Also, time-linked simulation (tFBA) can represent transitions between metabolic steady states by returning cell process byproducts at subsequent time-steps. | |
Activity Percentile: 0.00 Registered: 2013-08-19 17:12 |
Agent-based model of skeletal muscle disuse-induced atrophy
- This project is a tissue level prediction of muscle atrophy. The model aims to incorporate cellular interactions to establish the extent of muscle atrophy observed during disuse. Current predictions are focused on muscle fiber CSA, but methods are being developed to analyze ECM content and turnover as well | |
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Activity Percentile: 0.00 Registered: 2015-01-19 17:07 |
Acetaminophen Induced Liver Injury
- The AILI project is a type of In-Silico Liver (ISL) project, which consists of a body of Java code used and reused for exploring hypothetical liver mechanisms. For AILI, the liver mechanisms are those that cause cellular damage, specifically necrosis, because of exposure to acetaminophen. Moreover, the model, a mouse analog, is used for virtual experimentation to explore and explain AILI phenomena, analogous to wet-lab experimentation. A recent addition to this project is studying the disconnect between in vitro and in vivo wet-lab experiments by comparing and contrasting virtual Mouse and Culture Analogs. | |
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Activity Percentile: 0.00 Registered: 2015-05-07 23:25 |
Proteolytic and non-proteolytic regulation of collective cell invasion
- Cancer cells manoeuvre through extracellular matrices (ECMs) using different invasion modes, including single cell and collective cell invasion. These modes rely on MMP-driven ECM proteolysis to make space for cells to move. How cancer-associated alterations in ECM influence the mode of invasion remains unclear. Further, the sensitivity of the two invasion modes to MMP dynamics remains unexplored. In this paper, we address these open questions using a multiscale hybrid computational model combining ECM density-dependent MMP secretion, MMP diffusion, ECM degradation by MMP and active cell motility. Our results demonstrate that in randomly aligned matrices, collective cell invasion is more efficient than single cell invasion. Although increase in MMP secretion rate enhances invasiveness independent of cell–cell adhesion, sustenance of collective invasion in dense matrices requires high MMP secretion rates. However, matrix alignment can sustain both single cell and collective cell invasion even without ECM proteolysis. Similar to our in-silico observations, increase in ECM density and MMP inhibition reduced migration of MCF-7 cells embedded in sandwich gels. Together, our results indicate that apart from cell intrinsic factors (i.e., high cell–cell adhesion and MMP secretion rates), ECM density and organization represent two important extrinsic parameters that govern collective cell invasion and invasion plasticity. | |
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Activity Percentile: 0.00 Registered: 2016-03-07 06:05 |
Toward virtual biomedical experiments
- Envision a biomedical R&D landscape in which researchers plan detailed wet-lab experiments and execute them in a virtual laboratory—all before putting on their lab coat. They choose virtual reagents, lab equipment, and specimens; they implement virtual protocols and take virtual measurements using virtual instrumentation. They use the results of virtual experiments to design new or refocused wet-lab experiments, which they then conduct in a physical laboratory.
This is the virtual biomedical experiment (VBE) vision. A virtual biomedical experiment is a simulation of a wet-lab or clinical experiment. When developing a VBE, the modeler aspires to mimic particular relevant aspects of the referent experiment—from hypothesis formation to data analysis, and key concepts in between—not just features of the underlying biological processes. | |
Activity Percentile: 0.00 Registered: 2016-04-27 19:44 |
T cell calcium dynamics regulated by age-induced oxidation
- T cells reach a state of replicative senescence characterized by a decreased ability to proliferate and respond to foreign antigens. Calcium release associated with TCR engagement is widely used as a surrogate measure of T cell response. Using an ex vivo culture model that partially replicates features of organismal aging, we observe that while the amplitude of Ca2+ signaling does not change with time in culture, older T cells exhibit faster Ca2+ rise and a faster decay. Gene expression analysis of Ca2+ channels and pumps expressed in T cells by RT-qPCR identified overexpression of the plasma membrane CRAC channel subunit ORAI1 and PMCA in older T cells. To test whether overexpression of the plasma membrane Ca2+ channel is sufficient to explain the kinetic information, we adapted a previously published computational model by Maurya and Subramaniam to include additional details on the store-operated calcium entry (SOCE) process to recapitulate Ca2+ dynamics after T cell receptor stimulation. Simulations demonstrated that upregulation of ORAI1 and PMCA channels is not sufficient to explain the observed alterations in Ca2+ signaling. Instead, modeling analysis identified kinetic parameters associated with the IP3R and STIM1 channels as potential causes for alterations in Ca2+ dynamics associated with the long term ex vivo culturing protocol. Due to these proteins having known cysteine residues susceptible to oxidation, we subsequently investigated and observed transcriptional remodeling of metabolic enzymes, a shift to more oxidized redox couples, and post-translational thiol oxidation of STIM1. The model-directed findings from this study highlight changes in the cellular redox environment that may ultimately lead to altered T cell calcium dynamics during immunosenescence or organismal aging. | |
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Registered: 2016-07-01 17:00 |
Agent-Based Model of Skeletal Muscle Injury, Inflammation, and Regeneration
- This model simulates the sterile inflammation process that follows a muscle injury (contusion, laceration, etc). The simulation tracks key inflammatory cells (neutrophils and macrophages), as well as their secretions and interactions with native muscle cells (muscle fibers, satellite cells, fibroblasts). | |
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Activity Percentile: 0.00 Registered: 2015-06-25 19:33 |
Anatomicaly-based 3D models of the middle ear and the inner ear
- The OtoBiomechanics Group at Stanford is developing three-dimensional and multiscale bio-computational models of the middle ear and the inner ear and their applications to understanding disease processes and interventions.
This project is a collection of code that simulates the biomechanics of the cochlea and the middle ear. At the core is FAST4. This is a program for calculating axisymmetric shells of revolution. FAST4 uses asymptotic methods for calculations, which are orders of magnitude faster than other methods including the finite element approach. The interface to FAST4 is built using MATLAB or Mathematica. | |
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Activity Percentile: 0.00 Registered: 2006-06-05 05:53 |
Osmotic pressure, bacterial growth, and bacterial division.
- This project aims to test the hypothesis that bacteria exploit osmotic pressure as a physical driving force for growth and division. | |
Activity Percentile: 0.00 Registered: 2013-03-04 20:25 |
FEBio: Finite Elements for Biomechanics
- FEBio is a nonlinear finite element solver that is specifically designed for biomechanical applications. It offers modeling scenarios, constitutive models, and boundary conditions that are relevant to many research areas in biomechanics and biophysics. All features can be used together seamlessly, giving the user a powerful tool for solving 3D problems in computational biomechanics. The software is open-source, and pre-compiled executables for Windows, Mac OS X and Linux platforms are available.
Current modeling capabilities include:
* Large deformation quasi-static and dynamic structural mechanics analysis.
* Modeling of complex structures that contain a combination of deformable and rigid parts.
* Multiphasic modeling, where the solvent can contain any number of solutes that may undergo chemical reactions.
* Fluid mechanics analysis, both steady-state and transient
* Fluid-solid interaction (FSI), which combines the powerful solid and fluid solvers.
FEBio also supports a plugin framework that can be used to easily develop new features for FEBio, including new constitutive models, boundary conditions, and even entire new physics solvers.
For more information check out the FEBio website at http://www.febio.org | |
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Registered: 2007-09-14 16:08 |
Simple Immune System Response Agent Based Model
- This is a simple Agent Based Model of the immune response to a hypothetical wound. The model accompanies a Science News for Students article as a supplement to allow readers the opportunity to directly experiment with biological simulation. Adjust the strength of the immune response, the number of bacteria in the wound, the bacterial colony growth rate, and other parameters to view the time course of healing. | |
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Activity Percentile: 0.00 Registered: 2015-07-29 00:16 |
Dynamic Redox Regulation of IL-4 Signaling
- Incomplete reduction of oxygen during respiration results in the formation of highly reactive molecules known as reactive oxygen species (ROS) that react indiscriminately with cellular components and adversely affect cellular function. For a long time ROS were thought solely to be undesirable byproducts of respiration. Indeed, high levels of ROS are associated with a number of diseases. Despite these facts, antioxidants, agents that neutralize ROS, have not shown any clinical benefits when used as oral supplements. This paradox is partially explained by discoveries over the last two decades demonstrating that ROS are not always detrimental and may be essential for controlling physiological processes like cell signaling. However, the mechanisms by which ROS react with biomolecules are not well understood. In this work we combined biological experiments with novel computational methods to identify the most important mechanisms of ROS-mediated regulation in the IL-4 signaling pathway of the immune system. We developed a detailed computer model of the IL-4 pathway and its regulation by ROS dependent and independent methods. Our work enhances the understanding of principles underlying regulation of cell signaling by ROS and has potential implications in advancing therapeutic methods targeting ROS and their adverse effects. | |
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Activity Percentile: 0.00 Registered: 2015-10-16 21:42 |
Cell Movement Simulation
- simulation of cell movements | |
Activity Percentile: 0.00 Registered: 2013-11-13 18:02 |
21 projects in result set. Displaying 20 per page. Projects sorted by alphabetical order.
<1> <2>