277 research outputs found

    Novel properties of the Kohn-Sham exchange potential for open systems: application to the two-dimensional electron gas

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    The properties of the Kohn-Sham (KS) exchange potential for open systems in thermodynamical equilibrium, where the number of particles is non-conserved, are analyzed with the Optimized Effective Potential (OEP) method of Density Functional Theory (DFT) at zero temperature. The quasi two-dimensional electron gas (2DEG) is used as an illustrative example. The main findings are that the KS exchange potential builds a significant barrier-like structure under slight population of the second subband, and that both the asymptotic value of the KS exchange potential and the inter-subband energy jump discontinuously at the one-subband (1S) -> two-subband (2S) transition. The results obtained in this system offer new insights on open problems of semiconductors, such as the band-gap underestimation and the band-gap renormalization by photo-excited carriers.Comment: 7 pages, 3 figures, uses epl.cls(included), accepted for publication in Europhysics Letter

    Simple Impurity Embedded in a Spherical Jellium: Approximations of Density Functional Theory compared to Quantum Monte Carlo Benchmarks

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    We study the electronic structure of a spherical jellium in the presence of a central Gaussian impurity. We test how well the resulting inhomogeneity effects beyond spherical jellium are reproduced by several approximations of density functional theory (DFT). Four rungs of Perdew's ladder of DFT functionals, namely local density approximation (LDA), generalized gradient approximation (GGA), meta-GGA and orbital-dependent hybrid functionals are compared against our quantum Monte Carlo (QMC) benchmarks. We identify several distinct transitions in the ground state of the system as the electronic occupation changes between delocalized and localized states. We examine the parameter space of realistic densities (1≀rs≀51 \le r_s\le 5) and moderate depths of the Gaussian impurity (Z<7Z<7). The selected 18 electron system (with closed-shell ground state) presents 1d→2s1d \to 2s transitions while the 30 electron system (with open-shell ground state) exhibits 1f→2p1f \to 2p transitions. For the former system, the accuracy for the transitions is clearly improving with increasing sophistication of functionals with meta-GGA and hybrid functionals having only small deviations from QMC. However, for the latter system, we find much larger differences for the underlying transitions between our pool of DFT functionals and QMC. We attribute this failure to treatment of the exact exchange within these functionals. Additionally, we amplify the inhomogeneity effects by creating the system with spherical shell which leads to even larger errors in DFT approximations.Comment: 8 pages, 4 figures, submitted to PRB as a regular article revisited version after revie

    Transcriptomic effects of Tet-on and mifepristone-inducible systems in mouse liver

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    Control of transgene expression from long-term expression vectors can be achieved with inducible and regulated promoters. The two most commonly used inducible systems employ doxycycline or mifepristone as the drug activating a silent trans-activator, which is expressed from a constitutive promoter. We evaluated the alterations provoked by constitutive expression in the liver of rtTA2(S)-M2 (rtTA2; second-generation reverse tetracycline-controlled trans-activator) and GLp65, which are the trans-activators of the doxycyline- and mifepristone-inducible systems, respectively. To this end we performed transcriptomic analysis of mice expressing these trans-activators in the liver over 1 month. rtTA2 expression induced alterations in a few genes (69 gene probesets; false discovery rate [FDR], approximately 0.05), whereas GLp65 caused more numerous changes (1059 gene probe-sets, an FDR of approximately 0.05). However, only 20 and 53 of the genes from the rtTA2 and GLp65 groups, respectively, showed changes (R-fold >or= 3). Functional assignments indicate that alterations were mild and of little general significance. Few additional transcriptomic changes were observed when expressing trans-activators in the presence of inducer drugs; most were due to the drugs themselves. These results and the absence of toxicity observed in treated animals indicate that the two inducible systems are well tolerated and have little impact on the liver transcriptome profile. The milder alterations found with the use of rtTA2 suggest that this system is possibly safer for gene therapy application

    Transcriptomic effects of Tet-on and mifepristone-inducible systems in mouse liver

    Get PDF
    Control of transgene expression from long-term expression vectors can be achieved with inducible and regulated promoters. The two most commonly used inducible systems employ doxycycline or mifepristone as the drug activating a silent trans-activator, which is expressed from a constitutive promoter. We evaluated the alterations provoked by constitutive expression in the liver of rtTA2(S)-M2 (rtTA2; second-generation reverse tetracycline-controlled trans-activator) and GLp65, which are the trans-activators of the doxycyline- and mifepristone-inducible systems, respectively. To this end we performed transcriptomic analysis of mice expressing these trans-activators in the liver over 1 month. rtTA2 expression induced alterations in a few genes (69 gene probesets; false discovery rate [FDR], approximately 0.05), whereas GLp65 caused more numerous changes (1059 gene probe-sets, an FDR of approximately 0.05). However, only 20 and 53 of the genes from the rtTA2 and GLp65 groups, respectively, showed changes (R-fold >or= 3). Functional assignments indicate that alterations were mild and of little general significance. Few additional transcriptomic changes were observed when expressing trans-activators in the presence of inducer drugs; most were due to the drugs themselves. These results and the absence of toxicity observed in treated animals indicate that the two inducible systems are well tolerated and have little impact on the liver transcriptome profile. The milder alterations found with the use of rtTA2 suggest that this system is possibly safer for gene therapy application

    ImportĂąncia prognĂłstica do alelo CYP2C19*2 apĂłs uma sĂ­ndrome coronĂĄria aguda: dados de um centro nacional

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    BACKGROUND: Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. OBJECTIVE: To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. METHODS: We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days. RESULTS: The median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group. CONCLUSION: In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker

    Clinical Performance of Two Methods for Detecting Anti SARS-CoV-2 Antibodies

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    Evaluating the clinical performance of available methods to detect antibodies against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has become a primordial issue in clinical laboratories. The aim of this study was to evaluate the clinical performance of two methods for SARS-CoV-2 antibodies detection, an automated Chemiluminescent Immunoassay (CLIA) and an immunochromatographic Lateral-Flow Assay (LFA) in patients with positive reverse transcription polymerase chain reaction (RT-PCR). Performance for CLIA method was Positive Agreement (PA) 56.6% and Negative Agreement (NA) 96,6% for IgM and PA 85.8%/NA 90,2% for IgG. Performance for LFA method was PA 56.2% and NA 100% for IgM and PA 95.5% and NA 100 % for IgG. LFA general agreement IgG was better than CLIA. In both methods, significant differences in Kappa index are observed when IgG and IgM are compared. When evaluating the data from a clinical perspective, we found that both method performance for IgM detection may not meet the expected requirements for their clinical utility and could lead to an inappropriate medical decision. The findings of this study show that both immunoassay methods might be reliable for assessing immunological response in COVID-19 patients. Our results also confirm that IgG measurement could be helpful, especially for epidemiological studies in our population. These results provide evidence to justify epidemiological studies in our population.Fil: Jacobsen, Dario Gustavo. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; ArgentinaFil: Gonzalez, D.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Instituto de FisiopatologĂ­a y BioquĂ­mica ClĂ­nica; ArgentinaFil: Jamardo, J.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; ArgentinaFil: Ibar, C.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; ArgentinaFil: Pugliese, L.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; ArgentinaFil: Fortuna, F.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; ArgentinaFil: Carrizo, E.. Coordinadora de Salud Misionar; ArgentinaFil: Caro, E. M.. Laboratorio Biogenar; ArgentinaFil: Perazzi, Beatriz Elizabeth. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Instituto de FisiopatologĂ­a y BioquĂ­mica ClĂ­nica; ArgentinaFil: Repetto, Esteban MartĂ­n. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; Argentina. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas; ArgentinaFil: Reboredo, G.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de ClĂ­nicas General San MartĂ­n; ArgentinaFil: Fabre, B.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Departamento de BioquĂ­mica ClĂ­nica; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂ­mica. Instituto de FisiopatologĂ­a y BioquĂ­mica ClĂ­nica; Argentin

    Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

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    The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGÎłC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNÎł in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

    Superimposed impacts of enhanced [CO2] and high temperature on the photosynthetic metabolism of C. arabica and C. canephora genotypes.

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    Summary: Coffee crop has been predicted to become threatened by future climate changes and global warming conditions. Yet, the long-term effects of elevated [CO2] on this plant remain to be fully elucidated. In this context, this work aims at linking coffee biochemical responses to environmental changes of [CO2] and temperature on genotypes from the two major producing species, using the photosynthetic metabolism as probe to evaluate the plant acclimation ability. Potted plants from C. arabica cv. IPR 108 and of C. canephora cv. Conilon Clone 153 were grown under environmental controlled conditions, either at 380 or 700 ?L CO2 L-1 air, for 1 year, without water, nutrient or root development restrictions. After that the temperature was gradually increased from 25/20 ÂșC (day/night) up to 42/34 ÂșC. The effects of elevated [CO2] and enhanced temperature on the photosynthetic structures were assessed through the characterization of the lipid components of chloroplast membranes, whereas the leaf metabolic performance was evaluated through the thylakoid electron transport rates (involving both photosystem (PS) I and II), and the activities of enzymes (ribulose 1,5-biphosphate carboxylase/oxygenase and ribulose 5-phosphate kinase), as well as through stable isotopes of C and N. The activities of respiratory enzymes (NADH-dependent malate dehydrogenase and pyruvate kinase) were also analyzed. The results pointed for a higher functional status along the experiment in the plants grown under elevated [CO2], with special relevance at 37 and 42ÂșC in IPR108. These results could be related to the qualitative changes of the membrane lipid matrix that might have helped to preserve suitable membrane fluidity for the membrane bound events (e.g., thylakoid electron transport). The PSs and enzyme data reflect an enhancement of the energetic metabolism (both photosynthesis and respiration), mostly, until 31 ÂșC for IPR108 and 37 ÂșC for CL153 at normal [CO2]. Yet, under enhanced [CO2] it was found an increase in the temperature (to 37 ÂșC) at which maximal values of some parameters in IPR108 (MDH, PSs activities, RuBisCO) were observed, concomitantly with the maintenance of high performance in other parameters when compared to the 380 plants. Under the highest temperature (42 ÂșC) the enzymes were the most sensitive point, displaying the strongest reductions, irrespective of genotype and [CO2] treatments. The temperature promoted changes in leaf ?13C, irrespective of genotype and [CO2], reflecting a decrease in WUE with heat. The changes in ?15N values may indicate different limitation steps of N assimilation, requiring further investigation. It was concluded that the coffee plants grown under elevated [CO2] apparently showed a better endurance to high temperatures, what is quite relevant in a context of predicted climate changes and global warming scenarios
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