Результаты поиска

Development of Predictive QSAR Models of 4-Thiazolidinones Antitrypanosomal Activity Using Modern Machine Learning Algorithms.

This paper presents novel QSAR models for the prediction of antitrypanosomal activity among thiazolidines and related heterocycles. The performance of four machine learning algorithms: Random Forest regression, Stochastic gradient boosting, Multivariate adaptive regression splines and Gaussian processes regression have been studied in order to reach better levels of predictivity. The results for Random Forest and Gaussian processes regression are comparable and outperform other studied methods. The preliminary descriptor selection with Boruta method improved the outcome of machine learning met

The effect of anger expression style on cardiovascular responses to lateralized cognitive stressors.

To determine the effects of self-reported anger expression style on cerebrally lateralized physiological responses to neuropsychological stressors, changes in systolic blood pressure and heart rate were examined in response to a verbal fluency task and a figural fluency task among individuals reporting either "anger in" or "anger out" expression styles. Significant group by trial interaction effects was found for systolic blood pressure following administration of verbal fluency [F(1,54) = 5.86, p < 0.05] and nonverbal fluency stressors [F(1,54) = 13.68, p < .001]. Similar interactions were se

A Variant in RUNX3 Is Associated with the Risk of Ankylosing Spondylitis in Koreans.

Ankylosing spondylitis (AS) is a chronic autoinflammatory disease that affects the spine and sacroiliac joints. Regarding its etiology, although HLA-B27 is known to be the strongest genetic factor of AS, much evidence suggests the potential contribution of non-MHC genes to the susceptibility to AS. Most of these non-MHC genes have been discovered in non-Asian populations; however, just some of them have been validated in Koreans. In this study, we aimed to identify additional AS-associated single-nucleotide polymorphism (SNP) candidates by replicating the candidate SNPs in Korean AS patients a

Interleukin-10 Polymorphisms in Association with Prognosis in Patients with B-Cell Lymphoma Treated by R-CHOP.

Interleukin-10 (IL10) plays an important role in initiating and maintaining an appropriate immune response to non-Hodgkin lymphoma (NHL). Previous studies have revealed that the transcription of IL10 mRNA and its protein expression may be infl uenced by several single-nucleotide polymorphisms in the promoter and intron regions, including rs1800896, rs1800871, and rs1800872. However, the impact of polymorphisms of the IL10 gene on NHL prognosis has not been fully elucidated. Here, we investigated the association between IL10 polymorphisms and NHL prognosis. This study involved 112 NHL patients

Multilevel Precision-Based Rational Design of Chemical Inhibitors Targeting the Hydrophobic Cleft of Toxoplasma gondii Apical Membrane Antigen 1 (AMA1).

Toxoplasma gondii is an intracellular Apicomplexan parasite and a causative agent of toxoplasmosis in human. It causes encephalitis, uveitis, chorioretinitis, and congenital infection. T. gondii invades the host cell by forming a moving junction (MJ) complex. This complex formation is initiated by intermolecular interactions between the two secretory parasitic proteins-namely, apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) and is critically essential for the host invasion process. By this study, we propose two potential leads, NSC95522 and NSC179676 that can efficiently tar

Identification of a Copy Number Variation on Chromosome 20q13.12 Associated with Osteoporotic Fractures in the Korean Population.

Osteoporotic fractures (OFs) are critical hard outcomes of osteoporosis and are characterized by decreased bone strength induced by low bone density and microarchitectural deterioration in bone tissue. Most OFs cause acute pain, hospitalization, immobilization, and slow recovery in patients and are associated with increased mortality. A variety of genetic studies have suggested associations of genetic variants with the risk of OF. Genome-wide association studies have reported various single-nucleotide polymorphisms and copy number variations (CNVs) in European and Asian populations. To identif

Frontal lobe regulation of blood glucose levels: support for the limited capacity model in hostile violence-prone men.

Hostile men have reliably displayed an exaggerated sympathetic stress response across multiple experimental settings, with cardiovascular reactivity for blood pressure and heart rate concurrent with lateralized right frontal lobe stress (Trajanoski et al., in Diabetes Care 19(12):1412-1415, 1996; see Heilman et al., in J Neurol Neurosurg Psychiatry 38(1):69-72, 1975). The current experiment examined frontal lobe regulatory control of glucose in high and low hostile men with concurrent left frontal lobe (Control Oral Word Association Test [verbal]) or right frontal lobe (Ruff Figural Fluency Te

Joint L2,1 Norm and Fisher Discrimination Constrained Feature Selection for Rational Synthesis of Microporous Aluminophosphates.

Feature selection has been regarded as an effective tool to help researchers understand the generating process of data. For mining the synthesis mechanism of microporous AlPOs, this paper proposes a novel feature selection method by joint l2,1 norm and Fisher discrimination constraints (JNFDC). In order to obtain more effective feature subset, the proposed method can be achieved in two steps. The first step is to rank the features according to sparse and discriminative constraints. The second step is to establish predictive model with the ranked features, and select the most significant featur

The Comparison of the Combined Toxicity between Gram-negative and Gram-positive Bacteria: a Case Study of Antibiotics and Quorum-sensing Inhibitors.

Quorum-sensing inhibitors (QSIs) are being used increasingly in diverse fields, and are likely to end up in the environment, where they may encounter the antibiotics and consequently cause joint effects on biological systems. However, the potential joint effects of QSIs and antibiotics have received little attention. In this study, the joint effects of antibiotics, represented by sulfonamides (SAs) and penicillin, as well as three potential QSIs, were investigated using both Gram-negative (Escherichia coli, E. coli) and Gram-positive bacteria (Bacillus subtilis, B. subtilis). It was found that

Exploiting Literature-derived Knowledge and Semantics to Identify Potential Prostate Cancer Drugs.

In this study, we report on the performance of an automated approach to discovery of potential prostate cancer drugs from the biomedical literature. We used the semantic relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations using SemRep, to extract potential relationships using knowledge of cancer drugs pathways. Two cancer drugs pathway schemas were constructed using these relationships extracted from SemMedDB. Through both pathway schemas, we found drugs already used for prostate cancer therapy and drugs not currently listed as the prostate cancer

Совпадение в полном тексте источника
… Thus, the development of an efficient and accurate informatics system for drug repurposing, which can leverage the literature without significant manual effort, is needed. …

Global Model for Octanol-Water Partition Coefficients from Proton Nuclear Magnetic Resonance Spectra.

The ability to estimate chemical and physical properties from experimental spectra is highly desirable, as it eliminates the need for a priori knowledge of exact chemical structure and allows the property estimation of mixtures. Here we report the proof of principle that a predictive method for octanol-water partition coefficient (logP) based on (1) H-NMR spectra in d(3) -chloroform is feasible and can yield accuracy comparable to in silico logP models. The Spectrometric Data-Activity Relationship (QSDAR) reported predicts logP of neutral organic chemicals using descriptors derived only from (

Interaction of Flaviviruses with Reproduction Inhibitors Binding in β-OG Pocket: Insights from Molecular Dynamics Simulations.

Flaviviral diseases, including dengue fever, West Nile fever, yellow fever, tick-borne encephalitis, Omsk haemorrhagic fever, and Powassan encephalitis, threaten human health all over the world. Lack of effective antivirals targeting replication cycle of flaviviruses makes the search of such compounds a challenging task. Recently we have identified a reproduction inhibitor effective against tick-borne encephalitis virus and Powassan virus (POWV) (ACS Med. Chem. Lett., 2013, 4, 869-874). To enable using this inhibitor as a template for 3D pharmacophore search, a biologically active conformation

Genome-wide association study of orthostatic hypotension and supine-standing blood pressure changes in two korean populations.

Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing from a supine position. To understand the underlying genetic factors for OH traits (OH, dtSBP, and dtDBP), genome-wide association studies (GWASs) using 333,651 single nucleotide polymorphisms (SNPs) were conducted separately for two population-based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255).

Allelic frequencies of 20 visible phenotype variants in the korean population.

The prediction of externally visible characteristics from DNA has been studied for forensic genetics over the last few years. Externally visible characteristics include hair, skin, and eye color, height, and facial morphology, which have high heritability. Recent studies using genome-wide association analysis have identified genes and variations that correlate with human visible phenotypes and developed phenotype prediction programs. However, most prediction models were constructed and validated based on genotype and phenotype information on Europeans. Therefore, we need to validate prediction

Quality Issues with Public Domain Chemogenomics Data.

The key concept in chemogenomics is the similarity principle that states that similar ligands should bind similar targets. Chemogenomic analysis requires large amounts of data and both powerful computational algorithms and computers. Data used for chemogenomics analysis can either be compiled from open sources, or they can be produced in-house as is often done in the pharmaceutical industry. The chemogenomic modeller often has to resort to mixing activity values from different laboratories and even assay types to facilitate chemogenomic analysis. The amount of chemogenomics data available in t

QSPR Study of Valproic Acid and Its Functionalized Derivatives.

This work establishes a Quantitative Structure-Property Relationships (QSPR) based analysis with the aim of interpreting both the structural and electronic properties of the polar region of valproic acid and its derivatives, in terms of stabilizing intramolecular interactions related to the involved substituents. We consider ten different calculated properties as dependent variables for the QSPR models: the bond lengths C8 O9 , C8 X10 , and the percentage of s-character of the natural hybrids forming the bonding σ orbitals of the O9 C8 X10 region. The representative descriptors are the cha

Evaluation of Adamantane Derivatives as Inhibitors of Dengue Virus mRNA Cap Methyltransferase by Docking and Molecular Dynamics Simulations.

Binding of the Dengue virus S-adenosyl-L-methionine (AdoMet)-dependent mRNA cap methyltransferase (NS5MTaseDV ) with adamantane derivatives was explored using molecular modeling methods and (nucleoside-2'O)-methyltransferase bioassay. The studied compounds include urea derivatives of adamantane and the antiviral drugs amantadine and rimantadine. The urea derivatives of adamantanes had previously been identified as inhibitors of NS5MTaseDV . The docking simulations using GOLD, Glide, and Dock give consistent binding modes and binding affinities of adamantanes in the AdoMet-binding site of NS5MT

Growth Response of Trichoderma Species to Organic Solvents.

The growth response of 25 Trichoderma strains to 26 alkanols and 7 other organic solvents was examined in vitro. The sensitivity of strains considerably varied depending on their taxonomic position, thus the strains of Longibrachiatum section proved to be more tolerant than those of Pachybasium and Trichoderma sections. Significant relationship was revealed between structure of C1 -C24 alkanols and their growth inhibitory effect to Trichodermas, both efficacy and selectivity of C1 -C3 and C14 -C24 alkanols failed off the C9 -C11 alkanols. The non-alkanol solvents tested were non-toxic. The C8

Development of query strategies to identify a histologic lymphoma subtype in a large linked database system.

BACKGROUND: Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specificity of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specific cancer pa

The reference shapes the signal: chrX genotype summaries and classifier sex disparity between GRCh38 and T2T-CHM13 callsets.

Laboratories that move from GRCh38 to T2T-CHM13 take on a new callset as well as a new assembly. I asked whether the move changes sex-chromosome genotype summaries, and whether it changes how well classifiers trained on those summaries serve males and females. I compared the published 1000 Genomes GRCh38 and T2T-CHM13 callsets for 3,202 people. The two callsets come from different alignment, calling, phasing and filtering workflows, so every difference below belongs to the reference and its pipeline together. In women, the fraction of non-reference chrX genotypes that were heterozygous was 0.6