Search results for "Computer simulation"
showing 10 items of 1054 documents
Search of Chemical Scaffolds for Novel Antituberculosis Agents
2005
3 A method to identify chemical scaffolds potentially active against Mycobacterium tuberculosis is presented. The molecular features of a set of structurally heterogeneous antituberculosis drugs were coded by means of structural invariants. Three tech- niques were used to obtain equations able to model the antituberculosis activity: linear discriminant analysis, multilinear re- gression, and shrinkage estimation-ridge regression. The model obtained was statistically validated through leave-n-out test, and an external set and was applied to a database for the search of new active agents. The selected compounds were assayed in vitro, and among those identified as active stand reserpine, N,N,N…
In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment
2016
Abstract: An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expre…
Repurposing old drugs to fight multidrug resistant cancers.
2020
Overcoming multidrug resistance represents a major challenge for cancer treatment. In the search for new chemotherapeutics to treat malignant diseases, drug repurposing gained a tremendous interest during the past years. Repositioning candidates have often emerged through several stages of clinical drug development, and may even be marketed, thus attracting the attention and interest of pharmaceutical companies as well as regulatory agencies. Typically, drug repositioning has been serendipitous, using undesired side effects of small molecule drugs to exploit new disease indications. As bioinformatics gain increasing popularity as an integral component of drug discovery, more rational approa…
Computational Fluid Dynamics Suggests Ecological Diversification among Stem-Gnathostomes.
2020
Summary The evolutionary assembly of the vertebrate bodyplan has been characterized as a long-term ecological trend toward increasingly active and predatory lifestyles, culminating in jawed vertebrates that dominate modern vertebrate biodiversity [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. This contrast is no more stark than between the earliest jawed vertebrates and their immediate relatives, the extinct jawless, dermal armor-encased osteostracans, which have conventionally been interpreted as benthic mud-grubbers with poor swimming capabilities and low maneuverability [ 9 , 10 , 11 , 12 ]. Using computational fluid dynamics, we show that osteostracan headshield morphology is compatible with a dive…
Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors
2021
The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirabl…
Metabolic detoxification: implications for thresholds.
2000
The fact that chemical carcinogenesis involves single, isolated, essentially irreversible molecular events as discrete steps, several of which must occur in a row to finally culminate in the development of a malignancy, rather suggests that an absolute threshold for chemical carcinogens may not exist. However, practical thresholds may exist due to saturable pathways involved in the metabolic processing, especially in the metabolic inactivation, of such compounds. An important example for such a pathway is the enzymatic hydrolysis of epoxides via epoxide hydrolases, a group of enzymes for which the catalytic mechanism has recently been established. These enzymes convert their substrates via…
What represents a face? A computational approach for the integration of physiological and psychological data.
1997
Empirical studies of face recognition suggest that faces might be stored in memory by means of a few canonical representations. The nature of these canonical representations is, however, unclear. Although psychological data show a three-quarter-view advantage, physiological studies suggest profile and frontal views are stored in memory. A computational approach to reconcile these findings is proposed. The pattern of results obtained when different views, or combinations of views, are used as the internal representation of a two-stage identification network consisting of an autoassociative memory followed by a radial-basis-function network are compared. Results show that (i) a frontal and a…
Stability of Asymmetric Lipid Bilayers Assessed by Molecular Dynamics Simulations
2009
The asymmetric insertion of amphiphiles into biological membranes compromises the balance between the inner and outer monolayers. As a result, area expansion of the receiving leaflet and curvature strain may lead to membrane permeation, shape changes, or membrane fusion events. We have conducted both atomistic and coarse-grained molecular dynamics simulations of dipalmitoyl-phosphatidylcholine (DPPC) bilayers to study the effect of an asymmetric distribution of lipids between the two monolayers on membrane stability. Highly asymmetric lipid bilayers were found to be surprisingly stable within the submicrosecond time span of the simulations. Even the limiting case of a monolayer immersed in …
Real-time simulation of tissue deformation for the nasal endoscopy simulator (NES).
1999
Endonasal sinus surgery requires a great amount of training before it can be adequately performed. The complicated anatomy involved, the proximity of relevant structures, and the variability of the anatomy due to inborn or iatrogenic variations make several complications possible. Today, cadaver dissections are the "gold standard" for surgical training. To overcome the drawbacks of traditional training methods, the Fraunhofer Institute for Computer Graphics is currently developing a highly interactive medical simulation system for nasal endoscopy and endonasal sinus surgery, in cooperation with the Mainz University Hospital. For the simulation of a rhinoscopic procedure, not only are the re…
Uncertainty quantification on a spatial Markov-chain model for the progression of skin cancer
2019
AbstractA spatial Markov-chain model is formulated for the progression of skin cancer. The model is based on the division of the computational domain into nodal points, that can be in a binary state: either in ‘cancer state’ or in ‘non-cancer state’. The model assigns probabilities for the non-reversible transition from ‘non-cancer’ state to the ‘cancer state’ that depend on the states of the neighbouring nodes. The likelihood of transition further depends on the life burden intensity of the UV-rays that the skin is exposed to. The probabilistic nature of the process and the uncertainty in the input data is assessed by the use of Monte Carlo simulations. A good fit between experiments on mi…