77 research outputs found
First measurement of the forward-backward asymmetry in bottom-quark pair production at high mass
This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A. P. Sloan Foundation; the Bundesministerium für Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, United Kingdom; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; the Australian Research Council; and the EU community Marie Curie Fellowship Contract No. 302103
Molecular dynamics simulation of aqueous solutions of 26-unit segments of p(NIPAAm) and of p(NIPAAm) "doped" with amino acid based comonomers
We have performed 75-ns molecular dynamics (MD) simulations of aqueous solutions of a 26-unit NIPAAm
oligomer at two temperatures, 302 and 315 K, below and above the experimentally determined lower critical
solution temperature (LCST) of p(NIPAAm). We have been able to show that at 315 K the oligomer assumes
a compact form, while it keeps a more extended form at 302 K. A similar behavior has been demonstrated
for a similar NIPAAm oligomer, where two units had been substituted by methacryloyl-l-valine (MAVA)
comonomers, one of them being charged and one neutral. For another analogous oligomer, where the same
units had been substituted by methacryloyl-l-leucine (MALEU) comonomers, no transition from the extended
to the more compact conformation has been found within the same simulation time. Statistical analysis of the
trajectories indicates that this transition is related to the dynamics of the oligomer backbone, and to the formation
of intramolecular hydrogen bonds and water-bridges between distant units of the solute. In the MAVA case,
we have also evidenced an important role of the neutral MAVA comonomer in stabilizing the compact coiled
structure. In the MALEU case, the corresponding comonomer is not equally efficacious and, possibly, is
even hindering the readjustment of the oligomer backbone. Finally the self-diffusion coefficient of water
molecules surrounding the oligomers at the two temperatures for selected relevant times is observed to
characteristically depend on the distance from the solute molecules
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EFFECTS OF THE BET-INHIBITOR APABETALONE ON CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ACUTE CORONARY SYNDROME, ACCORDING TO PRESENCE OR ABSENCE OF CHRONIC KIDNEY DISEASE. A BETONMACE TRIAL REPORT
Abstract
Background and Aims
Patients with type 2 diabetes (T2D) and acute coronary syndrome (ACS) are at high risk for recurrent cardiovascular (CV) events, particularly in the presence of chronic kidney disease (CKD). Apabetalone (APB) is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Its cardiovascular efficacy and safety were evaluated in a phase 3 trial, BETonMACE.
Method
BETonMACE was a randomized, double-blind, comparison of effects of ABP or placebo (PBO) on major adverse CV events (MACE) defined as CV-death, non-fatal myocardial infarct or stroke, in 2425 pts with T2D and recent ACS. Here we report MACE plus CHF hospitalization in subjects with or without CKD Stage 3.
Results
Baseline characteristics: median age 62 years, 25.6% female, 87.6% white, 90% high intensity statin use, mean LDL-C 70.3 and HDL-C 33.3 mg/dl, median HbA1c 7.3%, and 11% with CKD Stage 3. Overall in the trial, MACE plus CHF hospitalization occurred in 139 (11.5%) patients with ABP and 173 (14.3%) with PBO (HR 0.78, 95% CI 0.63-0.98). In the subgroup with CKD, MACE plus CHF hospitalization occurred in 16 (12.9%) on APB and 41 (25%) on PBO (HR 0.48, 95% CI 0.26-0.89). In the subgroup without CKD, MACE plus CHF hospitalization occurred in 123 (11.3%) and 132 (12.7%) with APB or PBO, respectively (HR 0.89, 95% CI 0.70-1.
Conclusion
Patients with T2D, ACS, and Stage 3 CKD have a very high risk of subsequent MACE plus CHF hospitalization. The BET protein inhibitor ABP may reduce this risk
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Apabetalone Reduces Cardiovascular Events in Patients with Chronic Kidney Disease, Type 2 Diabetes, and Recent Acute Coronary Syndrome: A Betonmace Trial Report.:
Involvement of corticosteroids in acoustic induction of audiogenic seizure susceptibility in mice
The Truth About Torts: Defensive Medicine and the Unsupported Case for Medical Malpractice 'Reform'
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