170 research outputs found

    Flux-cutting and flux-transport effects in type-II superconductor slabs in a parallel rotating magnetic field

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    The magnetic response of irreversible type-II superconductor slabs subjected to in-plane rotating magnetic field is investigated by applying the circular, elliptic, extended-elliptic, and rectangular flux-line-cutting critical-state models. Specifically, the models have been applied to explain experiments on a PbBi rotating disk in a fixed magnetic field Ha{\bm H}_a, parallel to the flat surfaces. Here, we have exploited the equivalency of the experimental situation with that of a fixed disk under the action of a parallel magnetic field, rotating in the opposite sense. The effect of both the magnitude HaH_a of the applied magnetic field and its angle of rotation αs\alpha_s upon the magnetization of the superconductor sample is analyzed. When HaH_a is smaller than the penetration field HPH_P, the magnetization components, parallel and perpendicular to Ha{\bm H_a}, oscillate with increasing the rotation angle. On the other hand, if the magnitude of the applied field, HaH_a, is larger than HPH_P, both magnetization components become constant functions of αs\alpha_s at large rotation angles. The evolution of the magnetic induction profiles inside the superconductor is also studied.Comment: 12 pages, 29 figure

    Joint profiling of DNA methylation and chromatin architecture in single cells.

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    We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues

    Syndemic factors associated with adult sexual HIV risk behaviors in a sample of Latino men who have sex with men in New York City

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    Objective: Syndemic theory has been proposed as a framework for understanding the role of multiple riskfactors driving the HIV epidemic among sexual and gender minority individuals. As yet, the frameworkhas been relatively absent in research on Latinos/as.Methods: We used logistic regression to assess relationships among cumulative syndemic conditions –including clinically significant depression, high-risk alcohol consumption, discrimination, and childhoodsexual abuse – engagement with multiple partners and condomless anal intercourse (CAI) in a sample of176 Latino men who have sex with men (MSM) in New York City.Results: In bivariate analyses, an increase in the number of syndemic factors experienced was associatedwith an increased likelihood of reporting multiple partners and CAI. In multivariable analyses, participantswith 2, 3, and 4 factors were significantly more likely to report multiple partners than those with 0(aOR = 4.66, 95% CI [1.29, 16.85); aOR = 7.28, 95% CI [1.94, 27.28] and aOR = 8.25, 95% CI [1.74, 39.24]respectively; p \u3c 0.05. Regarding CAI, only participants with 3 and 4 factors differed from those with 0aOR = 7.35, 95% CI [1.64, 32.83] and OR = 8.06, 95% CI [1.39, 46.73] respectively.Conclusions: Comprehensive approaches that address syndemic factors, and capitalize on resiliency, areneeded to address the sexual health needs of Latino MSM

    Syndemic factors associated with adult sexual HIV risk behaviors in a sample of Latino men who have sex with men in New York City

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    Objective: Syndemic theory has been proposed as a framework for understanding the role of multiple riskfactors driving the HIV epidemic among sexual and gender minority individuals. As yet, the frameworkhas been relatively absent in research on Latinos/as.Methods: We used logistic regression to assess relationships among cumulative syndemic conditions –including clinically significant depression, high-risk alcohol consumption, discrimination, and childhoodsexual abuse – engagement with multiple partners and condomless anal intercourse (CAI) in a sample of176 Latino men who have sex with men (MSM) in New York City.Results: In bivariate analyses, an increase in the number of syndemic factors experienced was associatedwith an increased likelihood of reporting multiple partners and CAI. In multivariable analyses, participantswith 2, 3, and 4 factors were significantly more likely to report multiple partners than those with 0(aOR = 4.66, 95% CI [1.29, 16.85); aOR = 7.28, 95% CI [1.94, 27.28] and aOR = 8.25, 95% CI [1.74, 39.24]respectively; p \u3c 0.05. Regarding CAI, only participants with 3 and 4 factors differed from those with 0aOR = 7.35, 95% CI [1.64, 32.83] and OR = 8.06, 95% CI [1.39, 46.73] respectively.Conclusions: Comprehensive approaches that address syndemic factors, and capitalize on resiliency, areneeded to address the sexual health needs of Latino MSM

    Transcriptomic changes linked to age-dependent neuromelanin accumulation in a new Parkinson's disease mouse model

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    Resumen del trabajo presentado en el 50th Annual Meeting Society for Neuroscience, celebrado de forma virtual del 8 al 11 de noviembre de 2021In Parkinson's disease (PD) there is a preferential degeneration of neuromelanin (NM)-containing neurons, especially neurons from the Substantia Nigra (SN) but also from the Ventral Tegmental Area (VTA) and Locus Coeruleus (LC). We generated a new NM-producing mouse model, based on the tissue-specific constitutive expression of human tyrosinase (hTyr) under the tyrosine hydroxylase (TH) promoter (tgNM), that mimics the distribution and age-dependent accumulation of NM in the human brain (i.e. catecholaminergic groups A1-A14). TgNM mice exhibited major PD features, including both motor and non-motor behavioral alterations, inclusion body formation, neuronal degeneration in lower brainstem areas (LC) together with neuronal dysfunction in higher brainstem areas (SN and VTA). In order to understand the mechanisms by which NM accumulation in specific brain areas ultimately interferes with the normal functioning of cells, we characterized genome-wide transcriptomic changes linked to the intracellular presence and progressive accumulation of NM in two NM-accumulating neuronal subpopulations (SN and VTA) that are known to be differentially susceptible to PD pathology. We selectively isolated single dopaminergic NM-containing neurons by laser capture microdissection from male and female wild-type and tgNM animals at 3 months, 12 months and 20 months of age (n=4-6 mice per group). We performed differential expression analysis, resulting in statistically significant differentially expressed genes at all ages (p-value<0.5). Gene-set enrichment analysis (GSEA) with Reactome Pathway Database led to the identification of altered biological pathways in tgNM related to neuroinflammation, vesicle-mediated transport and lipid metabolism, transcription and translation, mitochondrial function and cell cycle (senescence) (False Discovery Rate<0.05). Targeted-based validation of candidate RNA species was performed in microdissected samples by quantitative real-time PCR and candidate biological pathways were validated at the protein level by western blot in dissected ventral midbrain tissues from biological replicates. The transcriptomic profiles identified in this project contribute to our understanding of selective vulnerability in PD and brain aging, and points to key biological pathways and molecular targets in prodromal and early PD

    Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study

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    Objective: To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. Methods: Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH <6 days (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units. Results: We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4–11): 2934 (34.3%) had a LOH 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0–64.9) when LOH was 11–15 days, and by 72.0% (95%CI = 42.6–107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4–36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk. Conclusions: Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments

    Prioritization of genes driving congenital phenotypes of patients with de novo genomic structural variants

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    Background:Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving the phenotypes of patients carrying de novo SVs are frequently unknown. Methods:We applied a combination of systematic experimental and bioinformatic methods to improve the molecular diagnosis of 39 patients with multiple congenital abnormalities and/or intellectual disability harboring apparent de novo SVs, most with an inconclusive diagnosis after regular genetic testing. Results: In 7 of these cases (18%), whole-genome sequencing analysis revealed disease-relevant complexities of the SVs missed in routine microarray-based analyses. We developed a computational tool to predict the effects on genes directly affected by SVs and on genes indirectly affected likely due to the changes in chromatin organization and impact on regulatory mechanisms. By combining these functional predictions with extensive phenotype information, candidate driver genes were identified in 16/39 (41%) patients. In 8 cases, evidence was found for the involvement of multiple candidate drivers contributing to different parts of the phenotypes. Subsequently, we applied this computational method to two cohorts containing a total of 379 patients with previously detected and classified de novo SVs and identified candidate driver genes in 189 cases (50%), including 40 cases whose SVs were previously not classified as pathogenic. Pathogenic position effects were predicted in 28% of all studied cases with balanced SVs and in 11% of the cases with copy number variants. Conclusions:These results demonstrate an integrated computational and experimental approach to predict driver genes based on analyses of WGS data with phenotype association and chromatin organization datasets. These analyses nominate new pathogenic loci and have strong potential to improve the molecular diagnosis of patients with de novo SVs

    Measurement of electrons from beauty-hadron decays in pp and Pb-Pb collisions at sNN=5.02 TeV

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    The production of electrons from beauty-hadron decays was measured at midrapidity in proton-proton (pp) and central Pb-Pb collisions at center-of-mass energy per nucleon-nucleon pair √s NN = 5.02 TeV, using the ALICE detector at the LHC. The cross section measured in pp collisions in the transverse momentum interval 2 < pT < 8 GeV/c was compared with models based on perturbative quantum chromodynamics calculations. The yield in the 10% most central Pb-Pb collisions, measured in the interval 2 < pT < 26 GeV/c, was used to compute the nuclear modification factor RAA, extrapolating the pp reference cross section to pT larger than 8 GeV/c. The measured R AA shows significant suppression of the yield of electrons from beauty-hadron decays at high pT and does not show a significant dependence above 8 GeV/c within uncertainties. The results are de- scribed by several theoretical models based on different implementations of the interaction of heavy quarks with a quark-gluon plasma, which predict a smaller energy loss for beauty quarks compared to light and charm quark

    Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H

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    The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process). The measured values τ=[253±11(stat)±6(syst)]  ps and B_{Λ}=[102±63(stat)±67(syst)]  keV are compatible with predictions from effective field theories and confirm that the _{Λ}^{3}H structure is consistent with a weakly bound system
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