266 research outputs found

    The momentum analyticity of two-point correlators from perturbation theory and AdS/CFT

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    The momentum plane analyticity of two point function of a relativistic thermal field theory at zero chemical potential is explored. A general principle regarding the location of the singularities is extracted. In the case of the N=4 supersymmetric Yang-Mills theory at large NcN_c, a qualitative change in the nature of the singularity (branch points versus simple poles) from the weak coupling regime to the strong coupling regime is observed with the aid of the AdS/CFT correspondence.Comment: 18 pages, 3 figures, typos fixed, 1 figure update

    Uncontrolled Donation after Circulatory Death: European practices and recommendations for the development and optimization of an effective programme.

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    Shortage of organs has made a global interest for donation after circulatory death (DCD) to re-emerge. While controlled DCD (cDCD) has been progressively increasing, uncontrolled DCD (uDCD) has only been developed in a few settings.1 This activity is quantitatively important in France and Spain, although it has also been reported in other European countries, as Austria, Belgium, Italy, the Netherlands, and recently in Russia.2,3 uDCD protocols have allowed the transplantation of a significant number of kidneys, livers and lungs at these countries.3 Excellent graft survival has been reported in kidney transplantation from uDCD, in spite of an increased incidence of delayed graft function (DGF).4,5,6,7,8,9,10,11,12,13,14,1516 Albeit promising, results with liver transplants obtained in uDCD protocols do not consistently provide similar outcomes compared with livers from donors after brain death (DBD), mainly due to a higher incidence of primary graft dysfunction and non-function and biliary complications.17,18,19,20,21,22 Lung transplantation is still facing limited experience, but preliminary results are encouraging.pre-print938 K

    Hippo pathway effectors YAP1/TAZ induce an EWS–FLI1‐opposing gene signature and associate with disease progression in Ewing sarcoma

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    YAP1 and TAZ (WWTR1) oncoproteins are the final transducers of the Hippo tumor suppressor pathway. Deregulation of the pathway leads to YAP1/TAZ activation fostering tumorigenesis in multiple malignant tumor types, including sarcoma. However, oncogenic mutations within the core components of the Hippo pathway are uncommon. Ewing sarcoma (EwS), a pediatric cancer with low mutation rate, is characterized by a canonical fusion involving the gene EWSR1 and FLI1 as the most common partner. The fusion protein is a potent driver of oncogenesis, but secondary alterations are scarce, and little is known about other biological factors that determine the risk of relapse or progression. We have observed YAP1/TAZ expression and transcriptional activity in EwS cell lines. Analyses of 55 primary human EwS samples revealed that high YAP1/TAZ expression was associated with progression of the disease and predicted poorer outcome. We did not observe recurrent SNV or copy number gains/losses in Hippo pathway‐related loci. However, differential CpG methylation of the RASSF1 locus (a regulator of the Hippo pathway) was observed in EwS cell lines compared with mesenchymal stem cells, the putative cell of origin of EwS. Hypermethylation of RASSF1 correlated with the transcriptional silencing of the tumor suppressor isoform RASFF1A, and transcriptional activation of the pro‐tumorigenic isoform RASSF1C, which promotes YAP1/TAZ activation. Knockdown of YAP1/TAZ decreased proliferation and invasion abilities of EwS cells and revealed that YAP1/TAZ transcription activity is inversely correlated with the EWS–FLI1 transcriptional signature. This transcriptional antagonism could be explained partly by EWS–FLI1‐mediated transcriptional repression of TAZ. Thus, YAP1/TAZ may override the transcriptional program induced by the fusion protein, contributing to the phenotypic plasticity determined by dynamic fluctuation of the fusion protein, a recently proposed model for disease dissemination in EwS

    Differential analysis of genome-wide methylation and gene expression in mesenchymal stemcells of patients with fractures and osteoarthritis

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    Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation

    Open clusters towards the Galactic center: chemistry and dynamics. A VLT spectroscopic study of NGC6192, NGC6404, NGC6583

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    In the framework of the study of the Galactic metallicity gradient and its time evolution, we present new high-resolution spectroscopic observations obtained with FLAMES and the fiber link to UVES at VLT of three open clusters (OCs) located within \sim7~kpc from the Galactic Center (GC): NGC~6192, NGC~6404, NGC~6583. We also present new orbit determination for all OCs with Galactocentric distances (RGC)_{\rm{GC}}) \leq8~kpc and metallicity from high-resolution spectroscopy. We aim to investigate the slope of the inner disk metallicity gradient as traced by OCs and at discussing its implication on the chemical evolution of our Galaxy. We have derived memberships of a group of evolved stars for each clusters, obtaining a sample of 4, 4, and 2 member stars in NGC~6192, NGC~6404, and NGC~6583, respectively. Using standard LTE analysis we derived stellar parameters and abundance ratios for the iron-peak elements Fe, Ni, Cr, and for the α\alpha-elements Al, Mg, Si, Ti, Ca. We calculated the orbits of the OCs currently located within 8~kpc from the GC, and discuss their implication on the present-time radial location. {The average metallicities of the three clusters are all oversolar: [Fe/H]= +0.12±0.04+0.12\pm0.04 (NGC~6192), +0.11±0.04+0.11\pm0.04 (NGC 6404), +0.37±0.03+0.37\pm0.03 (NGC 6583). They are in qualitative agreement with their Galactocentric distances, being all internal OCs, and thus expected to be metal richer than the solar neighborhood. The abundance ratios of the other elements over iron [X/Fe] are consistent with solar values. The clusters we have analysed, together with other OC and Cepheid data, confirm a steep gradient in the inner disk, a signature of an evolutionary rate different than in the outer disk.Comment: 17 pages, 13 figures, A&A accepted for publicatio

    Implication of type 4 NADPH oxidase (NOX4) in tauopathy.

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    Aggregates of the microtubule-associated protein tau are a common marker of neurodegenerative diseases collectively termed as tauopathies, such as Alzheimer’s disease (AD) and frontotemporal dementia. Therapeutic strategies based on tau have failed in late stage clinical trials, suggesting that tauopathy may be the consequence of upstream causal mechanisms. As increasing levels of reactive oxygen species (ROS) may trigger protein aggregation or modulate protein degradation and, we had previously shown that the ROS producing enzyme NADPH oxidase 4 (NOX4) is a major contributor to cellular autotoxicity, this study was designed to evaluate if NOX4 is implicated in tauopathy. Our results show that NOX4 is upregulated in patients with frontotemporal lobar degeneration and AD patients and, in a humanized mouse model of tauopathy induced by AVV-TauP301L brain delivery. Both, global knockout and neuronal knockdown of the Nox4 gene in mice, diminished the accumulation of pathological tau and positively modified established tauopathy by a mechanism that implicates modulation of the autophagy-lysosomal pathway (ALP) and, consequently, improving the macroautophagy flux. Moreover, neuronal-targeted NOX4 knockdown was sufficient to reduce neurotoxicity and prevent cognitive decline, even after induction of tauopathy, suggesting a direct and causal role for neuronal NOX4 in tauopathy. Thus, NOX4 is a previously unrecognized causative, mechanism-based target in tauopathies and blood-brain barrier permeable specific NOX4 inhibitors could have therapeutic potential even in established disease.post-print5895 K

    The effectiveness of a health promotion with group intervention by clinical trial. Study protocol

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    <p>Abstract</p> <p>Background</p> <p>The promotion of health and the interventions in community health continue to be one of the pending subjects of our health system. The most prevalent health problems (cardiovascular diseases, cancer, diabetes...) are for the most part related to life habits. We propose a holistic and integral approach as the best option for tackling behavior and its determinants. The research team has elaborated the necessary educational material to realize group teaching, which we call "Health Workshops". The goal of the present study is to evaluate the effectiveness of these Health Workshops in the following terms: Health Related Quality of Life (HRQOL), incorporate and maintain a balanced diet, do physical activity regularly, maintain risk factors such as tension, weight, cholesterol within normal limits and diminish cardiovascular risk.</p> <p>Methods/Design</p> <p>Controlled and random clinical testing, comparing a group of persons who have participated in the Health Workshops with a control group of similar characteristics who have not participated in the Health Workshops.</p> <p>Field of study: the research is being done in Health Centers of the city of Barcelona, Spain.</p> <p>Population studied: The group is composed of 108 persons that are actually doing the Health Workshops, and 108 that are not and form the control group. They are assigned at random to one group or the other.</p> <p>Data Analysis: With Student's t-distribution test to compare the differences between numerical variables or their non parametric equivalent if the variable does not comply with the criteria of normality. (Kolmogorov-Smirnof test). Chi-square test to compare the differences between categorical variables and the Logistic Regression Model to analyze different meaningful variables by dichotomous analysis related to the intervention.</p> <p>Discussion</p> <p>The Health Workshop proposed in the present study constitutes an innovative approach in health promotion, placing the emphasis on the person's self responsibility for his/her own health.</p> <p>The rhythm of a weekly session during 8 weeks with recommended activities to put into practice, as well as the support of the group is an opportunity to incorporate healthy habits and make a commitment to self-care. The sheets handed out are a Health Manual that can always be consulted after the workshop ends.</p> <p>Trial registration</p> <p>Clinical Trials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01440738">NCT01440738</a></p

    Magnetization dynamics of weakly interacting sub-100 nm square artificial spin ices

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    Artificial Spin Ice (ASI), consisting of a two dimensional array of nanoscale magnetic elements, provides a fascinating opportunity to observe the physics of out-of-equilibrium systems. Initial studies concentrated on the static, frozen state, whilst more recent studies have accessed the out-of-equilibrium dynamic, fluctuating state. This opens up exciting possibilities such as the observation of systems exploring their energy landscape through monopole quasiparticle creation, potentially leading to ASI magnetricity, and to directly observe unconventional phase transitions. In this work we have measured and analysed the magnetic relaxation of thermally active ASI systems by means of SQUID magnetometry. We have investigated the effect of the interaction strength on the magnetization dynamics at different temperatures in the range where the nanomagnets are thermally active. We have observed that they follow an Arrhenius-type Néel-Brown behaviour. An unexpected negative correlation of the average blocking temperature with the interaction strength is also observed, which is supported by Monte Carlo simulations. The magnetization relaxation measurements show faster relaxation for more strongly coupled nanoelements with similar dimensions. The analysis of the stretching exponents obtained from the measurements suggest 1-D chain-like magnetization dynamics. This indicates that the nature of the interactions between nanoelements lowers the dimensionality of the ASI from 2-D to 1-D. Finally, we present a way to quantify the effective interaction energy of a square ASI system, and compare it to the interaction energy computed with micromagnetic simulations

    Medios de comunicación y derecho a la información en Jalisco, 2016

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    Se rescata el acontecer mediático y las trasformaciones más relevantes en materia de derecho a la información entre 2015 y 2016. Este periodo arroja interesantes análisis con respecto a temas como los cambios del sistema de medios en Jalisco; la trasparencia y el acceso a la información, así como la configuración de quienes integran las instituciones que vigilan su aplicación; la transición a la televisión digital terrestre; los desaparecidos y la falta de acceso a la información, y el rostro de la prensa local a partir de sus capacidades financieras desde la perspectiva de su independencia editorial. Asimismo, se registraron hechos importantes que están marcando un parteaguas en el estado, como la alerta de violencia contra las mujeres en Jalisco, la iniciativa ciudadana #Ley3de3, las modificaciones al Premio Jalisco de Periodismo y las implicaciones del nuevo sistema penal para los medios y los periodistas. Cierra con un espacio para mantener viva la memoria de los profesionales de la comunicación que han participado en la construcción del acontecer informativo, cultural y de entretenimiento local
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