Bound excitons in time-dependent density-functional-theory: optical and energy-loss spectra

A robust and efficient frequency dependent and non-local exchange-correlation $f_{xc}(r,r';\omega)$ is derived by imposing time-dependent density-functional theory (TDDFT) to reproduce the many-body diagrammatic expansion of the Bethe-Salpeter polarization function. As an illustration, we compute the optical spectra of LiF, \sio and diamond and the finite momentum transfer energy-loss spectrum of LiF. The TDDFT results reproduce extremely well the excitonic effects embodied in the Bethe-Salpeter approach, both for strongly bound and resonant excitons. We provide a working expression for $f_{xc}$ that is fast to evaluate and easy to implement.Comment: 4 pages, 2 figures. To appear in Phys. Rev. Let

First-Principle Description of Correlation Effects in Layered Materials

We present a first-principles description of anisotropic materials characterized by having both weak (dispersion-like) and strong covalent bonds, based on the Adiabatic--Connection Fluctuation--Dissipation Theorem within Density Functional Theory. For hexagonal boron nitride the in-plane and out of plane bonding as well as vibrational dynamics are well described both at equilibrium and when the layers are pulled apart. Also bonding in covalent and ionic solids is described. The formalism allows to ping-down the deficiencies of common exchange-correlation functionals and provides insight towards the inclusion of dispersion interactions into the correlation functional.Comment: Accepted for publication in Physical Review Letter

Stability of Dirac cone in artificial graphene

Trabajo presentado al 18th ETSF Workshop celebrado en Luxemburgo del 1 al 4 de Octubre de 2013.ETSF - European Theoretical Spectroscopy Facility I3 (211956).Peer Reviewe

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

13 p.-5 fig.-2 tab.-1 graph.abst.A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin–dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure–activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economía y Competitividad, grant S2010/BMD-2457 BIPEDD2 from Comunidad Autónoma de Madrid (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by nature—from natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra

HST/NICMOS detection of a partially embedded, intermediate-mass pre-main-sequence population in the 30 Doradus Nebula

We present the detection of an intermediate-mass pre-main-sequence population embedded in the nebular filaments surrounding the 30 Doradus region in the Large Magellanic Cloud (LMC) using HST/NICMOS. In addition to four previously known luminous Class I infrared ``protostars,'' the NICMOS data reveal 20 new sources with intrinsic infrared excess similar to Galactic pre-main sequence stars. Based on their infrared brightness, these objects can be identified as the LMC equivalent of Galactic pre-main sequence stars. The faintest LMC Young Stellar Objects in the sample have colors similar to T Tauri and have about the same brightness as T Tauri if placed at the distance of the LMC. We find no evidence for a lower-mass cut-off in the initial mass function. Instead, the whole spectrum of stellar masses from pre-main sequence stars with ~1.5Mo to massive O stars still embedded in dense knots appears to be present in the nebular filaments. The majority of the young stellar objects can be found to the north of the central starburst cluster R136. This region is very likely evolving into an OB association.Comment: 9 pages, 4 figures, uses emulateapj.sty and psfig.sty. accepted for publication in the Astronomical Journal (August 2001 issue

Shape study of the N = Z nucleus Kr-72 via beta decay

10 pags.; 11 figs.; 2 tabs.; PACS number(s): 23.40.Hc, 29.30.Kv, 27.50.+e, 21.10.Pc; Open Access funded by Creative Commons Atribution Licence 3.0The beta decay of the N = Z nucleus Kr-72 has been studied with the total absorption spectroscopy technique at ISOLDE (CERN). A total B(GT) = 0.79(4)g(A)(2)/4 pi has been found up to an excitation energy of 2.7 MeV. The B(GT) distribution obtained is compared with predictions from state-of-the-art theoretical calculations to learn about the ground state deformation of Kr-72. Although a dominant oblate deformation is suggested by direct comparison with quasiparticle random phase approximation (QRPA) calculations, beyond-mean-field and shell-model calculations favor a large oblate-prolate mixing in the ground state. Published by the American Physical SocietyJ.A.B. acknowledges the predoctoral grant BES-2008-009412 associated with the research project FPA2007-62170 funded by Ministerio de Ciencia e Innovacion (Spain). This work has ´ been partly supported by the Spanish Ministerio de Economía y Competitividad (MINECO) through projects FPA2012- 32443, FPA2011-24553, FPA2011-29854-C04-01, FPA2013- 41267-P, FPA2014-52823-C2-1-P and FIS2011-23565, by STFC-UK (Grant No. ST/F012012/1) and by the European Union by means of the European Commission within its Seventh Framework Programme (FP7) via ENSAR (Contract No. 262010)Peer Reviewe

Five microRNAs in Serum Are Able to Differentiate Breast Cancer Patients From Healthy Individuals

Breast cancer is the cancer with the most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients vs. 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based on the expression levels of five microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the overexpression and downregulation of proteins differently expressed in the serum of breast cancer patients vs. that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue, and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a, miR-497, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of miR-125b, miR-29c, miR-16, miR-1260, and miR-451 was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of miR-16 with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and the potential use of the predictor here described are discussed

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Hypoxic microenvironment shapes HIV-1 replication and latency

Abstract: Viral replication is defined by the cellular microenvironment and one key factor is local oxygen tension, where hypoxia inducible factors (HIFs) regulate the cellular response to oxygen. Human immunodeficiency virus (HIV) infected cells within secondary lymphoid tissues exist in a low-oxygen or hypoxic environment in vivo. However, the majority of studies on HIV replication and latency are performed under laboratory conditions where HIFs are inactive. We show a role for HIF-2α in restricting HIV transcription via direct binding to the viral promoter. Hypoxia reduced tumor necrosis factor or histone deacetylase inhibitor, Romidepsin, mediated reactivation of HIV and inhibiting HIF signaling-pathways reversed this phenotype. Our data support a model where the low-oxygen environment of the lymph node may suppress HIV replication and promote latency. We identify a mechanism that may contribute to the limited efficacy of latency reversing agents in reactivating HIV and suggest new strategies to control latent HIV-1