Search results for "QM"
showing 10 items of 284 documents
Inhibition Mechanism of SARS‐CoV‐2 Main Protease with Ketone‐Based Inhibitors Unveiled by Multiscale Simulations: Insights for Improved Designs**
2021
Abstract We present the results of classical and QM/MM simulations for the inhibition of SARS‐CoV‐2 3CL protease by a hydroxymethylketone inhibitor, PF‐00835231. In the noncovalent complex the carbonyl oxygen atom of the warhead is placed in the oxyanion hole formed by residues 143 to 145, while P1–P3 groups are accommodated in the active site with interactions similar to those observed for the peptide substrate. According to alchemical free energy calculations, the P1′ hydroxymethyl group also contributes to the binding free energy. Covalent inhibition of the enzyme is triggered by the proton transfer from Cys145 to His41. This step is followed by the nucleophilic attack of the Sγ atom on …
Programmatūras kvalitātes uzlabošana projektā „A”
2015
Maģistra darba temats ir „Programmatūras kvalitātes uzlabošana projektā „A””. Darba mērķis ir izpētīt programmatūras kvalitāti projektā „A” un ieviest programmatūras kvalitātes uzlabojumus darba procesā. Maģistra darbā bija izpētīta literatūra par programmatūras kvalitāti un tās uzlabošanas iespējām, aprakstīts projekta „A” programmatūras izstrādes process, noteiktas projekta programmatūras izstrādes procesa problēmas. Maģistra darbā bija izstrādāti priekšlikumi programmatūras kvalitātes uzlabošanai projektā „A” un ieviesti darba procesā. Pētījuma rezultātā bija novērtētas un aprakstītas programmatūras kvalitātes izmaiņas pēc autora priekšlikumu ieviešanas darba procesā.
Selectivity in Probabilistic Causality: Where Psychology Runs Into Quantum Physics
2011
Given a set of several inputs into a system (e.g., independent variables characterizing stimuli) and a set of several stochastically non-independent outputs (e.g., random variables describing different aspects of responses), how can one determine, for each of the outputs, which of the inputs it is influenced by? The problem has applications ranging from modeling pairwise comparisons to reconstructing mental processing architectures to conjoint testing. A necessary and sufficient condition for a given pattern of selective influences is provided by the Joint Distribution Criterion, according to which the problem of "what influences what" is equivalent to that of the existence of a joint distr…
Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic ir…
2014
Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighte…
PED in 2021: a major update of the protein ensemble database for intrinsically disordered proteins
2020
Abstract The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptor…
Muscle‐tendon morphology and function following long‐term exposure to repeated and strenuous mechanical loading
2019
We mapped structural and functional characteristics of muscle‐tendon units in a population exposed to very long‐term routine overloading. Twenty‐eight military academy cadets (age = 21.00 ± 1.1 years; height = 176.1 ± 4.8 cm; mass = 73.8 ± 7.0 kg) exposed for over 24 months to repetitive overloading were profiled via ultrasonography with a senior subgroup of them (n = 11; age = 21.4 ± 1.0 years; height = 176.5 ± 4.8 cm; mass = 71.4 ± 6.6 kg) also tested while walking and marching on a treadmill. A group of eleven ethnicity‐ and age‐matched civilians (age = 21.6 ± 0.7 years; height = 176.8 ± 4.3 cm; mass = 74.6 ± 5.6 kg) was also profiled and tested. Cadets and civilians exhibited similar mo…
Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells.
1999
Abstract Circulating plasma cells in 10 cases of reactive plasmacytosis had a shared phenotype with early plasma cell (CD19+CD38+ CD138+ CD40+CD45+ CD11a+ CD49e−CD56−). In most cases, a minor subpopulation of CD28+ plasma cells was also detected. Reactive plasma cells were highly proliferative, suggesting the presence of circulating progenitors (plasmablasts). After CD138+ plasma cell removal, highly proliferative CD138− plasmablasts differentiated into CD138+ plasma cells within a few days. This differentiation, which was associated with increased CD38 and decreased HLA-DR expression, was further confirmed by a large increase in intracellular Ig content (associated with Ig secretion) and w…
A data mining approach for grouping and analyzing trajectories of care using claim data: the example of breast cancer
2013
International audience; BACKGROUND: With the increasing burden of chronic diseases, analyzing and understanding trajectories of care is essential for efficient planning and fair allocation of resources. We propose an approach based on mining claim data to support the exploration of trajectories of care. METHODS: A clustering of trajectories of care for breast cancer was performed with Formal Concept Analysis. We exported Data from the French national casemix system, covering all inpatient admissions in the country. Patients admitted for breast cancer surgery in 2009 were selected and their trajectory of care was recomposed with all hospitalizations occuring within one year after surgery. Th…
An ancestral recombination graph for diploid populations with skewed offspring distribution
2013
A large offspring number diploid biparental multilocus population model of Moran type is our object of study. At each timestep, a pair of diploid individuals drawn uniformly at random contribute offspring to the population. The number of offspring can be large relative to the total population size. Similar `heavily skewed' reproduction mechanisms have been considered by various authors recently. Each diploid parental individual contributes exactly one chromosome to each diploid offspring, and hence ancestral lineages can only coalesce when in distinct individuals. A separation of timescales phenomenon is thus observed. A result of M\"{o}hle (1998) is extended to obtain convergence of the an…
Concordance of assays designed for the quantification of JAK2V617F: a multicenter study
2008
Background Many different techniques have been designed for the quantification of JAK2 V617F allelic burden, sometimes producing discrepant results. Design and Methods JAK2 V617F quantification techniques were compared among 16 centers using 11 assays based on quantitative polymerase chain reaction (with mutation-specific primers or probes, or fluorescent resonance energy transfer/melting curve analysis), allele-specific polymerase chain reaction, conventional sequencing or pyrosequencing. Results A first series of blinded samples (granulocyte DNA, n=29) was analyzed. Seven assays (12 centers) reported values inside the mean±2SD; the mean coefficient of variation was 31%. Sequencing techniq…