Assortative mixing in Protein Contact Networks and protein folding kinetics

Starting from linear chains of amino acids, the spontaneous folding of proteins into their elaborate three-dimensional structures is one of the remarkable examples of biological self-organization. We investigated native state structures of 30 single-domain, two-state proteins, from complex networks perspective, to understand the role of topological parameters in proteins' folding kinetics, at two length scales-- as ``Protein Contact Networks (PCNs)'' and their corresponding ``Long-range Interaction Networks (LINs)'' constructed by ignoring the short-range interactions. Our results show that, both PCNs and LINs exhibit the exceptional topological property of ``assortative mixing'' that is absent in all other biological and technological networks studied so far. We show that the degree distribution of these contact networks is partly responsible for the observed assortativity. The coefficient of assortativity also shows a positive correlation with the rate of protein folding at both short and long contact scale, whereas, the clustering coefficients of only the LINs exhibit a negative correlation. The results indicate that the general topological parameters of these naturally-evolved protein networks can effectively represent the structural and functional properties required for fast information transfer among the residues facilitating biochemical/kinetic functions, such as, allostery, stability, and the rate of folding.Comment: Published in Bioinformatic

Excessive Islet NO Generation in Type 2 Diabetic GK Rats Coincides with Abnormal Hormone Secretion and Is Counteracted by GLP-1

BACKGROUND: A distinctive feature of type 2 diabetes is inability of insulin-secreting beta-cells to properly respond to elevated glucose eventually leading to beta-cell failure. We have hypothesized that an abnormally increased NO production in the pancreatic islets might be an important factor in the pathogenesis of beta-cell dysfunction. PRINCIPAL FINDINGS: We show now that islets of type 2 spontaneous diabetes in GK rats display excessive NO generation associated with abnormal iNOS expression in insulin and glucagon cells, increased ncNOS activity, impaired glucose-stimulated insulin release, glucagon hypersecretion, and impaired glucose-induced glucagon suppression. Pharmacological blockade of islet NO production by the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) greatly improved hormone secretion from GK islets suggesting islet NOS activity being an important target to inactivate for amelioration of islet cell function. The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release. GLP-1 suppression of iNOS expression was reversed by PKA inhibition but unaffected by the proteasome inhibitor MG132. Injection of glucose plus GLP-1 in the diabetic rats showed that GLP-1 amplified the insulin response but induced a transient increase and then a poor depression of glucagon. CONCLUSION: The results suggest that abnormally increased NO production within islet cells is a significant player in the pathogenesis of type 2 diabetes being counteracted by GLP-1 through PKA-dependent, nonproteasomal mechanisms

Measurements of Higgs bosons decaying to bottom quarks from vector boson fusion production with the ATLAS experiment at √=13TeV

The paper presents a measurement of the Standard Model Higgs Boson decaying to b-quark pairs in the vector boson fusion (VBF) production mode. A sample corresponding to 126 fb−1 of s√=13TeV proton–proton collision data, collected with the ATLAS experiment at the Large Hadron Collider, is analyzed utilizing an adversarial neural network for event classification. The signal strength, defined as the ratio of the measured signal yield to that predicted by the Standard Model for VBF Higgs production, is measured to be 0.95+0.38−0.36 , corresponding to an observed (expected) significance of 2.6 (2.8) standard deviations from the background only hypothesis. The results are additionally combined with an analysis of Higgs bosons decaying to b-quarks, produced via VBF in association with a photon

Muon reconstruction and identification efficiency in ATLAS using the full Run 2 pp collision data set at \sqrt{s}=13 TeV

This article documents the muon reconstruction and identification efficiency obtained by the ATLAS experiment for 139 \hbox {fb}^{-1} of pp collision data at \sqrt{s}=13 TeV collected between 2015 and 2018 during Run 2 of the LHC. The increased instantaneous luminosity delivered by the LHC over this period required a reoptimisation of the criteria for the identification of prompt muons. Improved and newly developed algorithms were deployed to preserve high muon identification efficiency with a low misidentification rate and good momentum resolution. The availability of large samples of Z\rightarrow \mu \mu and J/\psi \rightarrow \mu \mu decays, and the minimisation of systematic uncertainties, allows the efficiencies of criteria for muon identification, primary vertex association, and isolation to be measured with an accuracy at the per-mille level in the bulk of the phase space, and up to the percent level in complex kinematic configurations. Excellent performance is achieved over a range of transverse momenta from 3 GeV to several hundred GeV, and across the full muon detector acceptance of |\eta |<2.7

Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]

Search for dark matter in events with missing transverse momentum and a Higgs boson decaying into two photons in pp collisions at root s=13 TeV with the ATLAS detector

A search for dark-matter particles in events with large missing transverse momentum and a Higgs boson candidate decaying into two photons is reported. The search uses 139 fb−1 of proton-proton collision data collected at s√ = 13 TeV with the ATLAS detector at the CERN LHC between 2015 and 2018. No significant excess of events over the Standard Model predictions is observed. The results are interpreted by extracting limits on three simplified models that include either vector or pseudoscalar mediators and predict a final state with a pair of dark-matter candidates and a Higgs boson decaying into two photons

Medium-Induced Modification of Z-Tagged Charged Particle Yields in Pb+Pb Collisions at 5.02 TeV with the ATLAS Detector

The yield of charged particles opposite to a Z boson with large transverse momentum ( p T ) is measured in 260     pb − 1 of p p and 1.7     nb − 1 of Pb + Pb collision data at 5.02 TeV per nucleon pair recorded with the ATLAS detector at the Large Hadron Collider. The Z boson tag is used to select hard-scattered partons with specific kinematics, and to observe how their showers are modified as they propagate through the quark-gluon plasma created in Pb + Pb collisions. Compared with p p collisions, charged-particle yields in Pb + Pb collisions show significant modifications as a function of charged-particle p T in a way that depends on event centrality and Z boson p T . The data are compared with a variety of theoretical calculations and provide new information about the medium-induced energy loss of partons in a p T regime difficult to measure through other channels

Search for pair production of third-generation scalar leptoquarks decaying into a top quark and a τ-lepton in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for pair production of third-generation scalar leptoquarks decaying into a top quark and a τ-lepton is presented. The search is based on a dataset of pp collisions at s√ = 13 TeV recorded with the ATLAS detector during Run 2 of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Events are selected if they have one light lepton (electron or muon) and at least one hadronically decaying τ -lepton, or at least two light leptons. In addition, two or more jets, at least one of which must be identified as containing b-hadrons, are required. Six final states, defined by the multiplicity and flavour of lepton candidates, are considered in the analysis. Each of them is split into multiple event categories to simultaneously search for the signal and constrain several leading backgrounds. The signal-rich event categories require at least one hadronically decaying τ-lepton candidate and exploit the presence of energetic final-state objects, which is characteristic of signal events. No significant excess above the Standard Model expectation is observed in any of the considered event categories, and 95% CL upper limits are set on the production cross section as a function of the leptoquark mass, for different assumptions about the branching fractions into tτ and bν. Scalar leptoquarks decaying exclusively into tτ are excluded up to masses of 1.43 TeV while, for a branching fraction of 50% into tτ, the lower mass limit is 1.22 TeV