538 research outputs found

    Foreigner’s Pre-removal Detention: What Can We Learn from Data? Analysis of Pre-Removal Files Processed in the Province of Barcelona in 2015

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    This paper contains the most important findings of an empirical research on the detention files of undocumented migrants for the purpose of removal processed in the province of Barcelona in 2015. The analysis of 575 files with an innovative methodology offers relevant information about the profiles of deportable migrants and the way in which all involved actors (police, state prosecutors, lawyers and judges) behave. The study gives also information about the detention that precedes all files, as well as about the deportation order that should be executed thanks to pre-removal detention. All these figures show which is the way in which pre-removal detention works and which are the criteria that are used in the implementation of the legal rules that govern preremoval detention of undocumented migrants

    El internamiento de extranjeros: ¿Qué nos dicen los datos? Análisis de los expedientos de internamiento tramitados en la provincia de Barcelona en 2015

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    El trabajo presenta las principales conclusiones de una investigación empírica sobre los expedientes de internamiento tramitados en la provincia de Barcelona en el año 2015. A partir del análisis de 575 expedientes y del uso de una metodología innovadora, se arroja luz sobre el perfil de las personas extranjeras afectadas por el internamiento, así como sobre los criterios que emplean los diversos agentes que intervienen en esta decisión: policías, fiscales, abogados y jueces de instrucción. También se ofrece información sobre la detención que precede a la solicitud de internamiento y sobre las órdenes de salida obligatoria que se pretende garantizar mediante esta forma de privación de libertad. Todos estos datos permiten poner de relieve cuál es el funcionamiento real del internamiento y los criterios que se emplean en la aplicación de la normativa vigent

    OTX2 Duplication Is Implicated in Hemifacial Microsomia

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    Hemifacial microsomia (HFM) is the second most common facial anomaly after cleft lip and palate. The phenotype is highly variable and most cases are sporadic. We investigated the disorder in a large pedigree with five affected individuals spanning eight meioses. Whole-exome sequencing results indicated the absence of a pathogenic coding point mutation. A genome-wide survey of segmental variations identified a 1.3 Mb duplication of chromosome 14q22.3 in all affected individuals that was absent in more than 1000 chromosomes of ethnically matched controls. The duplication was absent in seven additional sporadic HFM cases, which is consistent with the known heterogeneity of the disorder. To find the critical gene in the duplicated region, we analyzed signatures of human craniofacial disease networks, mouse expression data, and predictions of dosage sensitivity. All of these approaches implicated OTX2 as the most likely causal gene. Moreover, OTX2 is a known oncogenic driver in medulloblastoma, a condition that was diagnosed in the proband during the course of the study. Our findings suggest a role for OTX2 dosage sensitivity in human craniofacial development and raise the possibility of a shared etiology between a subtype of hemifacial microsomia and medulloblastoma

    DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

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    Background: Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for lung cancer risk assessment of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we examined the relationship between the level of DNA repair and global gene expression. Methods: We conducted a blinded case-control study with 150 non-small cell lung cancer case patients and 143 control individuals. DNA Repair activity was measured in peripheral blood mononuclear cells, and the transcriptome of nasal and bronchial cells was determined by RNA sequencing. A combined DNA Repair score was formed using logistic regression, and its correlation with disease was assessed using cross-validation; correlation of expression to DNA Repair was analyzed using Gene Ontology enrichment. Results: DNA Repair score was lower in case patients than in control individuals, regardless of the case's disease stage. Individuals at the lowest tertile of DNA Repair score had an increased risk of lung cancer compared to individuals at the highest tertile, with an odds ratio (OR) of 7.2 (95% confidence interval [CI] = 3.0 to 17.5; P < .001), and independent of smoking. Receiver operating characteristic analysis yielded an area under the curve  of 0.89 (95% CI = 0.82 to 0.93). Remarkably, low DNA Repair score correlated with a broad upregulation of gene expression of immune pathways in patients but not in control individuals. Conclusions: The DNA Repair score, previously shown to be a lung cancer risk factor in the Israeli population, was validated in this independent study as a mechanism-based cancer risk biomarker and can substantially improve current lung cancer risk prediction, assisting prevention and early detection by computed tomography scanning.This work was funded by grants from NIH/NCI/EDRN (#1 U01 CA111219), the Flight Attendant Medical Research Institute, Florida, the Mike Rosenbloom Foundation and Weizmann Institute of Science to ZL and TPE; and by grants from Cancer Research UK to BP and to the Cancer Research UK Cambridge Centre; and by a UK National Institute for Health Research Senior Fellowship to BP; and by the Cambridge Biomedical Research Centre and the Cancer Research UK Cambridge Centre to RCR. Volunteer participant recruitment through the Cambridge Bioresource was funded by the Cambridge Biomedical Research Centre

    The C-terminal domain of eukaryotic initiation factor 5 promotes start codon recognition by its dynamic interplay with eIF1 and eIF2 beta

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    Recognition of the proper start codon on mRNAs is essential for protein synthesis, which requires scanning and involves eukaryotic initiation factors (eIFs) eIF1, eIF1A, eIF2, and eIF5. The carboxyl terminal domain (CTD) of eIF5 stimulates 43S preinitiation complex (PIC) assembly; however, its precise role in scanning and start codon selection has remained unknown. Using nuclear magnetic resonance (NMR) spectroscopy, we identified the binding sites of eIF1 and eIF2β on eIF5-CTD and found that they partially overlapped. Mutating select eIF5 residues in the common interface specifically disrupts interaction with both factors. Genetic and biochemical evidence indicates that these eIF5-CTD mutations impair start codon recognition and impede eIF1 release from the PIC by abrogating eIF5-CTD binding to eIF2β. This study provides mechanistic insight into the role of eIF5-CTD's dynamic interplay with eIF1 and eIF2β in switching PICs from an open to a closed state at start codons.publishedVersio

    S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse

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    Treatment of chronic hepatitis C (CHC) with pegylated interferon (pegIFN ) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFN signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFN signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFN on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFN /ribavirin

    The Ambivalent State: Determining Guilt in the Post-World War II Soviet Union

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    In the aftermath of the Second World War, the search for alleged traitors took place in each country that had been under foreign occupation. The most active country in this regard was the Soviet Union. This article analyzes how the Soviet authorities dealt with people who had lived in German-occupied territory during the war. It discusses divergent understandings of guilt, and examines means of punishment, retribution and justice. I argue that inconsistencies in Moscow’s politics of retribution, apart from reflecting tensions between ideology and pragmatism, resulted from contradictions within ideology, namely the belief that the war had uncovered mass enemies in hiding, and the belief that it had been won with the mass support of the Soviet population. The state that emerged from the war, then, was both powerful and insecure, able to quickly reassert its authority in formerly German-occupied areas, but also deeply ambivalent about its politics of retribution

    Reversible and Noisy Progression towards a Commitment Point Enables Adaptable and Reliable Cellular Decision-Making

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    Cells must make reliable decisions under fluctuating extracellular conditions, but also be flexible enough to adapt to such changes. How cells reconcile these seemingly contradictory requirements through the dynamics of cellular decision-making is poorly understood. To study this issue we quantitatively measured gene expression and protein localization in single cells of the model organism Bacillus subtilis during the progression to spore formation. We found that sporulation proceeded through noisy and reversible steps towards an irreversible, all-or-none commitment point. Specifically, we observed cell-autonomous and spontaneous bursts of gene expression and transient protein localization events during sporulation. Based on these measurements we developed mathematical population models to investigate how the degree of reversibility affects cellular decision-making. In particular, we evaluated the effect of reversibility on the 1) reliability in the progression to sporulation, and 2) adaptability under changing extracellular stress conditions. Results show that reversible progression allows cells to remain responsive to long-term environmental fluctuations. In contrast, the irreversible commitment point supports reliable execution of cell fate choice that is robust against short-term reductions in stress. This combination of opposite dynamic behaviors (reversible and irreversible) thus maximizes both adaptable and reliable decision-making over a broad range of changes in environmental conditions. These results suggest that decision-making systems might employ a general hybrid strategy to cope with unpredictably fluctuating environmental conditions

    Study of ordered hadron chains with the ATLAS detector

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