Search results for " Screening"
showing 10 items of 898 documents
Discovery of novel trichomonacidals using LDA-driven QSAR models and bond-based bilinear indices as molecular descriptors
2008
Few years ago, the World Health Organization estimated the number of adults with trichomoniasis at 170 million worldwide, more than the combined numbers for gonorrhea, syphilis, and chlamydia. To combat this sexually transmitted disease, Metronidazole (MTZ) has emerged, since 1959, as a powerful drug for the systematic treatment of infected patients. However, increasing resistance to MTZ, adverse effects associated to high-dose MTZ therapies and very expensive conventional technologies related to the development of new trichomonacidals necessitate novel computational methods that shorten the drug discovery pipeline. Therefore, bond-based bilinear indices, new 2-D bond-based TOMOCOMD-CARDD M…
Pyrocoll, an Antibiotic, Antiparasitic and Antitumor Compound Produced by a Novel Alkaliphilic Streptomyces Strain
2003
A new secondary metabolite was detected in the culture extract of Streptomyces sp. AK 409 by HPLC-diode-array screening. The metabolite was identified as pyrocoll, which is known to be a constituent of cigarette smoke. Pyrocoll is known as a synthetic compound, but until now had not been isolated as a natural product from a microorganism. The compound showed biological activity against various Arthrobacter strains, filamentous fungi, several pathogenic protozoa, and some human tumor cell lines.
Discovery and structure-activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A tr…
2014
Gram-positive bacteria, in general, and staphylococci, in particular, are the widespread cause of nosocomial and community-acquired infections. The rapid evolvement of strains resistant to antibiotics currently in use is a serious challenge. Novel antimicrobial compounds have to be developed to fight these resistant bacteria, and sortase A, a bacterial cell wall enzyme, is a promising target for novel therapies. As a transpeptidase that covalently attaches various virulence factors to the cell surface, this enzyme plays a crucial role in the ability of bacteria to invade the host's tissues and to escape the immune response. In this study we have screened a small molecule library against rec…
Pathway analysis of high-throughput biological data within a Bayesian network framework
2011
Abstract Motivation: Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network. Results: Proposed method takes into account the connectivity and relatedness between nodes of the p…
Bayesian assessment of times to diagnosis in breast cancer screening
2008
Breast cancer is one of the diseases with the most profound impact on health in developed countries and mammography is the most popular method for detecting breast cancer at a very early stage. This paper focuses on the waiting period from a positive mammogram until a confirmatory diagnosis is carried out in hospital. Generalized linear mixed models are used to perform the statistical analysis, always within the Bayesian reasoning. Markov chain Monte Carlo algorithms are applied for estimation by simulating the posterior distribution of the parameters and hyperparameters of the model through the free software WinBUGS.
Frequentist and Bayesian approaches for a joint model for prostate cancer risk and longitudinal prostate-specific antigen data
2015
The paper describes the use of frequentist and Bayesian shared-parameter joint models of longitudinal measurements of prostate-specific antigen (PSA) and the risk of prostate cancer (PCa). The motivating dataset corresponds to the screening arm of the Spanish branch of the European Randomized Screening for Prostate Cancer study. The results show that PSA is highly associated with the risk of being diagnosed with PCa and that there is an age-varying effect of PSA on PCa risk. Both the frequentist and Bayesian paradigms produced very close parameter estimates and subsequent 95% confidence and credibility intervals. Dynamic estimations of disease-free probabilities obtained using Bayesian infe…
Comparative Study of Human and Automated Screening for Antinuclear Antibodies by Immunofluorescence on HEp-2 Cells
2015
Background : Several automated systems had been developed in order to reduce inter-observer variability in indirect immunofluorescence (IIF) interpretation. We aimed to evaluate the performance of a processing system in antinuclear antibodies (ANA) screening on HEp-2 cells. Patients and Methods : This study included 64 ANA-positive sera and 107 ANA-negative sera that underwent IIF on two commercial kits of HEp-2 cells (BioSystems® and Euroimmun®). IIF results were compared with a novel automated interpretation system, the “ Cyclopus CADImmuno®” (CAD). Results : All ANA-positive sera images were recognized as positive by CAD (sensitivity = 100%), while 17 (15.9%) of the ANA-negative sera ima…
Lead-time and overdiagnosis estimation in neuroblastoma screening.
2003
In Germany, neuroblastoma is the most frequent extracranial solid childhood tumour. Its properties made it seem an ideal candidate for screening. A German trial assessed the effect of screening at one year of age from 1995-2001 in a nationwide project. We present here the methods developed for the estimation of lead-time and overdiagnosis in this project. Follow up on 1.5 million screened children and 2.1 million control children is currently available until June 2002. Ascertainment of control cohort cases and false negative cases is complete up to this date. A method for determining an empirical lead-time distribution and overdiagnosis estimate from comparing the age specific incidences in…
Synthesis and biological evaluation of cyclic derivatives of combretastatin A-4 containing group 14 elements
2018
Several tricyclic compounds inspired by the structure of combretastatin A-4 and bearing group 14 elements have been synthesized by homocoupling lithiated aryl fragments followed by ring-closing metathesis. These tricyclic compounds and their diolefin precursors were evaluated for their antiproliferative action on the tumor cell lines HT-29, MCF-7, HeLa and A-549 and on the non-tumor cell line HEK-293. In addition, their effects on the cell cycle were also measured. The tricyclic compounds show antiproliferative activity similar to that of combretastatin A-4, even though they are not so active in arresting the cell cycle. However, some diolefin precursors are able to cause accumulation of ce…
Acylated oleanane-type saponins from Ganophyllum giganteum
2014
Abstract Five oleanane-type saponins , 3- O -β- D -glucuronopyranosylzanhic acid 28- O -β- D -xylopyranosyl-(1→3)-[α- L -rhamnopyranosyl-(1→2)]-(4- O -acetyl)-β- D -fucopyranosyl ester ( 1 ), 3- O -β- D -glucopyranosylzanhic acid 28- O -β- D -xylopyranosyl-(1→3)-[α- L -rhamnopyranosyl-(1→2)]-(4- O -acetyl)-β- D -fucopyranosyl ester ( 2 ), zanhic acid 28- O -β- D -xylopyranosyl-(1→3)-[α- L -rhamnopyranosyl-(1→2)]-(4- O -acetyl)-β- D -fucopyranosyl ester ( 3 ), zanhic acid 28- O -α- L -rhamnopyranosyl-(1→2)-4- O -[(3′-hydroxy-2′-methyl-butyroyloxy)-3-hydroxy-2-methyl-butyroyloxy]-β- D -fucopyranosyl ester ( 4 ), medicagenic acid 28- O -α- L -rhamnopyranosyl-(1→2)-4- O -[(3′-hydroxy-2′-methyl-…