Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment

The community-wide GPCR Dock assessment is conducted to evaluate the status of molecular modeling and ligand docking for human G protein-coupled receptors. The present round of the assessment was based on the recent structures of dopamine D3 and CXCR4 chemokine receptors bound to small molecule antagonists and CXCR4 with a synthetic cyclopeptide. Thirty-five groups submitted their receptor-ligand complex structure predictions prior to the release of the crystallographic coordinates. With closely related homology modeling templates, as for dopamine D3 receptor, and with incorporation of biochemical and QSAR data, modern computational techniques predicted complex details with accuracy approaching experimental. In contrast, CXCR4 complexes that had less-characterized interactions and only distant homology to the known GPCR structures still remained very challenging. The assessment results provide guidance for modeling and crystallographic communities in method development and target selection for further expansion of the structural coverage of the GPCR universe. © 2011 Elsevier Ltd. All rights reserved

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure

Placebo-controlled study of lisinopril in congestive heart failure: A multicentre study

A double-blind randomised, parallel, placebo-controlled study was performed in patients with congestive heart failure, at 13 centres in 10 countries, to assess the efficacy and safety of lisinopril, a new antiotensin-converting enzyme inhibitor. After a 2-week run-in period, 130 patients receiving digoxin and/or diuretics were randomised to 12 weeks of treatment with lisinopril 5 mg daily (87 patients) or with placebo (43 patients), with an option to increase lisinopril dosage to 10 or 20 mg. Patients treated with lisinopril improved significantly more than placebo-treated patients (p < 0.05) for all clinical parameters except oedema and paroxysmal nocturnal dyspnoea. Left ventricular ejection fraction rose by 8% in lisinopril patients compared to 2% in the placebo group, while the cardiothoracic ratio and echocardiographic end systolic diameter fell in the lisinopril group (p < 0.01) but not in the placebo group. Exercise duration was greater in the lisinopril group at all timepoints, and the increase in exercise duration at 12 weeks was greater by more than 2 min in the lisinopril group as compared to the placebo group (p < 0.01). Changes in clinical and noninvasive parameters such as the New York Heart Association status, were well correlated with changes in exercise duration. Four patients in the lisinopril group and three in the placebo group died in this study, and there were 31 adverse clinical experiences in the 87 lisinopril-treated patients compared to 13 in the 43 placebo-treated patients. We conclude that lisinopril in doses of 2.5-20 mg/ day is well tolerated and effective in patients with heart failure who are receiving digitalis and diuretics. © 1987 Raven Press, New York.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Search for R-parity violating decays of supersymmetric particles in e+ e- collisions at center-of-mass energies from 189-GeV to 202-GeV

Searches for the production of supersymmetric particles under the assumption that R-parity is violated via a single dominant LLE, LQD or UDD coupling were performed. These use the data collected by the ALEPH detector at LEP at centre-of-mass energies from 188.6 to 201.6 GeV. The numbers of candidate events observed in the data are consistent with Standard Model expectations. Upper limits on the production cross sections and lower limits on the masses of charginos, sleptons, squarks and sneutrinos are derived.Comment: 29 pages, 15 figure