Myricetin protects pancreatic β-cells from human islet amyloid polypeptide (hIAPP) induced cytotoxicity and restores islet function

The aberrant misfolding and self-assembly of human islet amyloid polypeptide (hIAPP)–a hormone that is co-secreted with insulin from pancreatic β-cells–into toxic oligomers, protofibrils and fibrils has been observed in type 2 diabetes mellitus (T2DM). The formation of these insoluble aggregates has been linked with the death and dysfunction of β-cells. Therefore, hIAPP aggregation has been identified as a therapeutic target for T2DM management. Several natural products are now being investigated for their potential to inhibit hIAPP aggregation and/or disaggregate preformed aggregates. In this study, we attempt to identify the anti-amyloidogenic potential of Myricetin (MYR)- a polyphenolic flavanoid, commonly found in fruits (like Syzygium cumini). Our results from biophysical studies indicated that MYR supplementation inhibits hIAPP aggregation and disaggregates preformed fibrils into non-toxic species. This protection was accompanied by inhibition of oxidative stress, reduction in lipid peroxidation and the associated membrane damage and restoration of mitochondrial membrane potential in INS-1E cells. MYR supplementation also reversed the loss of functionality in hIAPP exposed pancreatic islets via restoration of glucose-stimulated insulin secretion. Molecular dynamics simulation studies suggested that MYR molecules interact with the hIAPP pentameric fibril model at the amyloidogenic core region and thus prevents aggregation and distort the fibrils.Council of Scientific and industrial research, Government of India (RD/0111-CSIR000-016) and Indian Institute of Technology, Bombay (11IRCCSG003); Wadhwani Research Center of Bioengineering (RD/018/- DONWR04-001/); Ramalingaswami fellowship (BT/RLF/Re-entry/11/2012; Department of Biotechnology-DBT, Government of India); and University Grants Commission (UGC, Government of India F.4-5(18-FRP) (IV-Cycle)/2017(BSR)

Overlap-based undersampling method for classification of imbalanced medical datasets.

Early diagnosis of some life-threatening diseases such as cancers and heart is crucial for effective treatments. Supervised machine learning has proved to be a very useful tool to serve this purpose. Historical data of patients including clinical and demographic information is used for training learning algorithms. This builds predictive models that provide initial diagnoses. However, in the medical domain, it is common to have the positive class under-represented in a dataset. In such a scenario, a typical learning algorithm tends to be biased towards the negative class, which is the majority class, and misclassify positive cases. This is known as the class imbalance problem. In this paper, a framework for predictive diagnostics of diseases with imbalanced records is presented. To reduce the classification bias, we propose the usage of an overlap-based undersampling method to improve the visibility of minority class samples in the region where the two classes overlap. This is achieved by detecting and removing negative class instances from the overlapping region. This will improve class separability in the data space. Experimental results show achievement of high accuracy in the positive class, which is highly preferable in the medical domain, while good trade-offs between sensitivity and specificity were obtained. Results also show that the method often outperformed other state-of-the-art and well-established techniques

Z boson production in Pb+Pb collisions at √Snn = 5.02 TeV measured by the ATLAS experiment

The production yield of Z bosons is measured in the electron and muon decay channels in Pb+Pb collisions at √S = 5.02 TeV with the ATLAS detector. Data from the 2015 LHC run corresponding to an integrated luminosity of 0.49 nb are used for the analysis. The Z boson yield, normalised by the total number of minimum-bias events and the mean nuclear thickness function, is measured as a function of dilepton rapidity and event centrality. The measurements in Pb+Pb collisions are compared with similar measurements made in proton-proton collisions at the same centre-of-mass energy. The nuclear modification factor is found to be consistent with unity for all centrality intervals. The results are compared with theoretical predictions obtained at next-to-leading order using nucleon and nuclear parton distribution functions. The normalised Z boson yields in Pb+Pb collisions lie 1-3σ above the predictions. The nuclear modification factor measured as a function of rapidity agrees with unity and is consistent with a next-to-leading-order QCD calculation including the isospin effect. nn -

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb−1 of pp collisions at s=13TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5)

Measurement of J/ψ production in association with a W ± boson with pp data at 8 TeV

A measurement of the production of a prompt J/ψ meson in association with a W± boson with W± → μν and J/ψ → μ+μ− is presented for J/ψ transverse momenta in the range 8.5–150 GeV and rapidity |yJ/ψ| < 2.1 using ATLAS data recorded in 2012 at the LHC. The data were taken at a proton-proton centre-of-mass energy of s = 8 TeV and correspond to an integrated luminosity of 20.3 fb−1. The ratio of the prompt J/ψ plus W± cross-section to the inclusive W± cross-section is presented as a differential measurement as a function of J/ψ transverse momenta and compared with theoretical predictions using different double-parton-scattering cross-sections. [Figure not available: see fulltext.]

Measurement of Azimuthal Anisotropy of Muons from Charm and Bottom Hadrons in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

The elliptic flow of muons from the decay of charm and bottom hadrons is measured in pp collisions at sqrt[s]=13  TeV using a data sample with an integrated luminosity of 150  pb^{-1} recorded by the ATLAS detector at the LHC. The muons from heavy-flavor decay are separated from light-hadron decay muons using momentum imbalance between the tracking and muon spectrometers. The heavy-flavor decay muons are further separated into those from charm decay and those from bottom decay using the distance-of-closest-approach to the collision vertex. The measurement is performed for muons in the transverse momentum range 4-7 GeV and pseudorapidity range |η|<2.4. A significant nonzero elliptic anisotropy coefficient v_{2} is observed for muons from charm decays, while the v_{2} value for muons from bottom decays is consistent with zero within uncertainties

Measurement of W± boson production in Pb+Pb collisions at √sNN=5.02Te with the ATLAS detector

A measurement of W± boson production in Pb+Pb collisions at sNN=5.02Te is reported using data recorded by the ATLAS experiment at the LHC in 2015, corresponding to a total integrated luminosity of 0.49nb-1. The W± bosons are reconstructed in the electron or muon leptonic decay channels. Production yields of leptonically decaying W± bosons, normalised by the total number of minimum-bias events and the nuclear thickness function, are measured within a fiducial region defined by the detector acceptance and the main kinematic requirements. These normalised yields are measured separately for W+ and W- bosons, and are presented as a function of the absolute value of pseudorapidity of the charged lepton and of the collision centrality. The lepton charge asymmetry is also measured as a function of the absolute value of lepton pseudorapidity. In addition, nuclear modification factors are calculated using the W± boson production cross-sections measured in pp collisions. The results are compared with predictions based on next-to-leading-order calculations with CT14 parton distribution functions as well as with predictions obtained with the EPPS16 and nCTEQ15 nuclear parton distribution functions. No dependence of normalised production yields on centrality and a good agreement with predictions are observed for mid-central and central collisions. For peripheral collisions, the data agree with predictions within 1.7 (0.9) standard deviations for W- (W+) bosons

Combination of searches for Higgs boson pairs in pp collisions at s=13TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb−1 of proton–proton collision data at a centre-of-mass energy s=13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the bb¯bb¯, bb¯W+W−, bb¯τ+τ−, W+W−W+W−, bb¯γγ and W+W−γγ final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (κλ) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to −5.0<κλ<12.0 (−5.8<κλ<12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza–Klein Randall–Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model