Search results for "Computer Science Applications"
showing 10 items of 3993 documents
Selective Inhibition of STAT3 with Respect to STAT1: Insights from Molecular Dynamics and Ensemble Docking Simulations
2016
STAT3 protein, which is known to be involved in cancer development, is a promising target for anticancer therapy. Successful inhibitors of STAT3 should not affect an activity of closely related protein STAT1, which makes their development challenging. The mechanisms of selectivity of several existing STAT3 inhibitors are not clear. In this work, we studied molecular mechanisms of selectivity of 13 experimentally tested STAT3 inhibitors by means of extensive molecular dynamics and ensemble docking simulations. It is shown that all studied inhibitors bind to the large part of the protein surface in an unspecific statistical manner. The binding to the dimerization interface of the SH2 domain, …
Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4…
2021
Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), a…
Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells
2021
Triple-negative breast cancer (TNBC) is a highly aggressive disease with invasive and metastasizing properties associated with a poor prognosis. The STAT3 signaling pathway has shown a pivotal role in cancer cell migration, invasion, metastasis and drug resistance of TNBC cells. IL-6 is a main upstream activator of the JAK2/STAT3 pathway. In the present study we examined the impact of the NO-donor glyceryl trinitrate (GTN) on the activation of the JAK2/STAT3 signaling pathway and subsequent migration, invasion and metastasis ability of TNBC cells through in vitro and in vivo experiments. We used a subtoxic dose of carboplatin and/or recombinant IL-6 to activate the JAK2/STAT3 signaling path…
A modal approach for the evaluation of the response sensitivity of structural systems subjected to non-stationary random processes
2005
A method for the evaluation of the response sensitivity of both classically and non-classically damped discrete linear structural systems under stochastic actions is presented. The proposed approach requires the following items: (a) a suitable modal expansion of the response; (b) the derivation in analytical form of the equations governing the evolution of the derivatives of the response (the so-called sensitivity equations) with respect to the parameters that define the structural model; (c) an extensive use of the Kronecker algebra for determining the analytical expressions of the sensitivity of the structural response statistics to non-stationary random input processes. Moreover, a step-…
A Multivariate Analysis of HIV-1 Protease Inhibitors and Resistance Induced by Mutation
2005
This paper describes the use of the multivariate statistical procedure principal component analysis as a tool to explore the inhibitory activity of classes of protease inhibitors (PIs) against HIV-1 viruses (wild type and more-frequent single mutants, V82A, V82F, and I84V) and against protease enzymes. The analysis of correlations between biological activity and molecular descriptors or similarity indexes allowed a reliable classification of the 51 derivatives considered in this study. The best results were obtained in the case of the I84V mutant for which a high number of predictions was achieved. On this basis, this statistical approach is proposed as a reliable method for the prediction …
A general strategy to determine the congruence between a hierarchical and a non-hierarchical classification
2007
This article is available from: http://www.biomedcentral.com/1471-2105/8/442
Poly-sarcosine and poly(ethylene-glycol) interactions with proteins investigated using molecular dynamics simulations
2018
Nanoparticles coated with hydrophilic polymers often show a reduction in unspecific interactions with the biological environment, which improves their biocompatibility. The molecular determinants of this reduction are not very well understood yet, and their knowledge may help improving nanoparticle design. Here we address, using molecular dynamics simulations, the interactions of human serum albumin, the most abundant serum protein, with two promising hydrophilic polymers used for the coating of therapeutic nanoparticles, poly(ethylene-glycol) and poly-sarcosine. By simulating the protein immersed in a polymer-water mixture, we show that the two polymers have a very similar affinity for the…
Dissipative scaling of step-pool features
2021
Abstract This paper focuses on the dissipative similarity of step-pool units at rill, flume and stream scale. This investigation is carried out using recent advances in open channel flow resistance, applications of close-range photogrammetry to rill erosion, available published data on step-pool features in flumes and streams and a new dataset of measurements in fixed bed step-pool rills. A theoretically-based equation for calculating the Darcy-Weisbach friction factor obtained by integration of a power velocity profile is presented. The scale factor Γ of this power velocity profile, which is included in the flow resistance equation, was previously calibrated (Eq. 10) for mobile bed rills w…
THE OPTIMAL SCALING OF A LINEAR RELUCTANCE MOTOR BY FIELD COMPUTATION
1995
The work aims at investigating the law of miniaturization of a linear reluctance motor by expressing the ratio of force to mass as a function of bar position in per unit, for different scale factors. Corresponding to the same factors, inductance is also computed. Finally the ratio of the bar length to external diameter is changed and the analysis is accordingly repeated.
SCALING LAWS FOR THE LIFETIMES OF GOVERNMENTS IN THE SZNAJD DEMOCRACY
2005
We investigate the lifetimes of governments in the original and a randomized one-dimensional Sznajd model. We find various scaling laws for the lifetime of the democracy and for the reigning time of governments in this model, depending on the system size N.