1,287 research outputs found
Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Logic Integer Programming Models for Signaling Networks
We propose a static and a dynamic approach to model biological signaling
networks, and show how each can be used to answer relevant biological
questions. For this we use the two different mathematical tools of
Propositional Logic and Integer Programming. The power of discrete mathematics
for handling qualitative as well as quantitative data has so far not been
exploited in Molecular Biology, which is mostly driven by experimental
research, relying on first-order or statistical models. The arising logic
statements and integer programs are analyzed and can be solved with standard
software. For a restricted class of problems the logic models reduce to a
polynomial-time solvable satisfiability algorithm. Additionally, a more dynamic
model enables enumeration of possible time resolutions in poly-logarithmic
time. Computational experiments are included
A constitutive model for analyzing martensite formation in austenitic steels deforming at high strain rates
This study presents a constitutive model for steels exhibiting SIMT, based on previous seminal works, and the corresponding methodology to estimate their parameters. The model includes temperature effects in the phase transformation kinetics, and in the softening of each solid phase through the use of a homogenization technique. The model was validated with experimental results of dynamic tensile tests on AISI 304 sheet steel specimens, and their predictions correlate well with the experimental evidence in terms of macroscopic stressâstrain curves and martensite volume fraction formed at high strain rates. The work shows the value of considering temperature effects in the modeling of metastable austenitic steels submitted to impact conditions. Regarding most of the works reported in the literature on SIMT, modeling of the martensitic transformation at high strain rates is the distinctive feature of the present paper.The researchers of the University Carlos III of Madrid are indebted to the Comunidad AutĂłnoma de Madrid (Project CCG10-UC3M/DPI-5596)) and to the Ministerio de Ciencia e InnovaciĂłn de España (Project DPI/2008-06408) for the financial support received which allowed conducting part of this work. The authors express their thanks to Mr. Philippe and Mr. Tobisch from the company Zwick for the facilities provided to perform the tensile tests at high strain rates
A constitutive model for analyzing martensite formation in austenitic steels deforming at high strain rates
This study presents a constitutive model for steels exhibiting SIMT, based on previous seminal works, and the corresponding methodology to estimate their parameters. The model includes temperature effects in the phase transformation kinetics, and in the softening of each solid phase through the use of a homogenization technique. The model was validated with experimental results of dynamic tensile tests on AISI 304 sheet steel specimens, and their predictions correlate well with the experimental evidence in terms of macroscopic stressâstrain curves and martensite volume fraction formed at high strain rates. The work shows the value of considering temperature effects in the modeling of metastable austenitic steels submitted to impact conditions. Regarding most of the works reported in the literature on SIMT, modeling of the martensitic transformation at high strain rates is the distinctive feature of the present paper.The researchers of the University Carlos III of Madrid are indebted to the Comunidad AutĂłnoma de Madrid (Project CCG10-UC3M/DPI-5596)) and to the Ministerio de Ciencia e InnovaciĂłn de España (Project DPI/2008-06408) for the financial support received which allowed conducting part of this work. The authors express their thanks to Mr. Philippe and Mr. Tobisch from the company Zwick for the facilities provided to perform the tensile tests at high strain rates
A methodology for the structural and functional analysis of signaling and regulatory networks
BACKGROUND: Structural analysis of cellular interaction networks contributes to a deeper understanding of network-wide interdependencies, causal relationships, and basic functional capabilities. While the structural analysis of metabolic networks is a well-established field, similar methodologies have been scarcely developed and applied to signaling and regulatory networks. RESULTS: We propose formalisms and methods, relying on adapted and partially newly introduced approaches, which facilitate a structural analysis of signaling and regulatory networks with focus on functional aspects. We use two different formalisms to represent and analyze interaction networks: interaction graphs and (logical) interaction hypergraphs. We show that, in interaction graphs, the determination of feedback cycles and of all the signaling paths between any pair of species is equivalent to the computation of elementary modes known from metabolic networks. Knowledge on the set of signaling paths and feedback loops facilitates the computation of intervention strategies and the classification of compounds into activators, inhibitors, ambivalent factors, and non-affecting factors with respect to a certain species. In some cases, qualitative effects induced by perturbations can be unambiguously predicted from the network scheme. Interaction graphs however, are not able to capture AND relationships which do frequently occur in interaction networks. The consequent logical concatenation of all the arcs pointing into a species leads to Boolean networks. For a Boolean representation of cellular interaction networks we propose a formalism based on logical (or signed) interaction hypergraphs, which facilitates in particular a logical steady state analysis (LSSA). LSSA enables studies on the logical processing of signals and the identification of optimal intervention points (targets) in cellular networks. LSSA also reveals network regions whose parametrization and initial states are crucial for the dynamic behavior. We have implemented these methods in our software tool CellNetAnalyzer (successor of FluxAnalyzer) and illustrate their applicability using a logical model of T-Cell receptor signaling providing non-intuitive results regarding feedback loops, essential elements, and (logical) signal processing upon different stimuli. CONCLUSION: The methods and formalisms we propose herein are another step towards the comprehensive functional analysis of cellular interaction networks. Their potential, shown on a realistic T-cell signaling model, makes them a promising tool
A cost-effective chemical approach to retaining and regenerating the strength of thermally recycled glass fibre
The purpose of this research study was to investigate the efficacy of alkaline treatments on restoring mechanical strength of thermally damaged glass fibres for potential reuse as reinforcement material. Here, E-glass fibres were heat treated in a furnace at 450 °C for 25 minutes in order to simulate the harsh thermal conditions required for the recycling of glass fibre thermosetting composites. Following heat conditioning, fibres were treated with three different alkaline solutions: sodium hydroxide (NaOH), potassium hydroxide (KOH) and lithium hydroxide (LiOH). Results showed little effect of LiOH solution, however both NaOH and KOH were proved to be successful in regenerating strength of fibres heat treated at 450 °C. It is believed these alkaline treatments might improve fibre strength by etching away surface defects. Factors such as concentration of alkali and treatment time were investigated in order to find optimum conditions for strength regeneration
Revisiting the Training of Logic Models of Protein Signaling Networks with a Formal Approach based on Answer Set Programming
A fundamental question in systems biology is the construction and training to
data of mathematical models. Logic formalisms have become very popular to model
signaling networks because their simplicity allows us to model large systems
encompassing hundreds of proteins. An approach to train (Boolean) logic models
to high-throughput phospho-proteomics data was recently introduced and solved
using optimization heuristics based on stochastic methods. Here we demonstrate
how this problem can be solved using Answer Set Programming (ASP), a
declarative problem solving paradigm, in which a problem is encoded as a
logical program such that its answer sets represent solutions to the problem.
ASP has significant improvements over heuristic methods in terms of efficiency
and scalability, it guarantees global optimality of solutions as well as
provides a complete set of solutions. We illustrate the application of ASP with
in silico cases based on realistic networks and data
Big science and big data in nephrology
There have been tremendous advances during the last
decade in methods for large-scale, high-throughput data
generation and in novel computational approaches to
analyze these datasets. These advances have had a
profound impact on biomedical research and clinical
medicine. The field of genomics is rapidly developing
toward single-cell analysis, and major advances in
proteomics and metabolomics have been made in recent
years. The developments on wearables and electronic
health records are poised to change clinical trial design.
This rise of âbig dataâ holds the promise to transform not
only research progress, but also clinical decision making
towards precision medicine. To have a true impact, it
requires integrative and multi-disciplinary approaches that
blend experimental, clinical and computational expertise
across multiple institutions. Cancer research has been at
the forefront of the progress in such large-scale initiatives,
so-called âbig science,â with an emphasis on precision
medicine, and various other areas are quickly catching up.
Nephrology is arguably lagging behind, and hence these
are exciting times to start (or redirect) a research career to
leverage these developments in nephrology. In this review,
we summarize advances in big data generation,
computational analysis, and big science initiatives, with a
special focus on applications to nephrology
Acelerated partial breast irradiation (APBI) with high dose rate brachytherapy: Feasibility, clinical results in terms of survival, relapse and toxicity
Machine Learning Prediction of Cancer Cell Sensitivity to Drugs Based on Genomic and Chemical Properties
Predicting the response of a specific cancer to a therapy is a major goal in modern oncology that should ultimately lead to a personalised treatment. High-throughput screenings of potentially active compounds against a panel of genomically heterogeneous cancer cell lines have unveiled multiple relationships between genomic alterations and drug responses. Various computational approaches have been proposed to predict sensitivity based on genomic features, while others have used the chemical properties of the drugs to ascertain their effect. In an effort to integrate these complementary approaches, we developed machine learning models to predict the response of cancer cell lines to drug treatment, quantified through IC50 values, based on both the genomic features of the cell lines and the chemical properties of the considered drugs. Models predicted IC50 values in a 8-fold cross-validation and an independent blind test with coefficient of determination R2 of 0.72 and 0.64 respectively. Furthermore, models were able to predict with comparable accuracy (R2 of 0.61) IC50s of cell lines from a tissue not used in the training stage. Our in silico models can be used to optimise the experimental design of drug-cell screenings by estimating a large proportion of missing IC50 values rather than experimentally measuring them. The implications of our results go beyond virtual drug screening design: potentially thousands of drugs could be probed in silico to systematically test their potential efficacy as anti-tumour agents based on their structure, thus providing a computational framework to identify new drug repositioning opportunities as well as ultimately be useful for personalized medicine by linking the genomic traits of patients to drug sensitivity
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