81 research outputs found

    Regresar de Irán

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    Entender los factores que repercuten en la decisión de los refugiados sobre su retorno y en la capacidad de las personas para reintegrarse tras ello resulta de vital importancia a la hora de planificar programas previos y posteriores al retorno para los refugiados afganos en Irán

    PCV15 ATRIAL VERSUS DUAL CHAMBER PACING IN SINUS NODE DISEASE

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    PDB4 THE DIABETES TYPE-2 COST PREDICTORS

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    Optimal Blends of History and Intelligence for Robust Antiterrorism Policy

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    Abstract Antiterrorism analysis requires that security agencies blend evidence on historical patterns of terrorist behavior with incomplete intelligence on terrorist adversaries to predict possible terrorist operations and devise appropriate countermeasures. We model interactions between reactive, adaptive and intelligent adversaries embedded in minimally sufficient organizational settings to study the optimal analytic mixture, expressed as historical memory reach-back and the number of anticipatory scenarios, that should be used to design antiterrorism policy. We show that history is a valuable source of information when the terrorist organization evolves and acquires new capabilities at such a rapid pace that makes optimal strategies advocated by game-theoretic reasoning unlikely to succeed

    Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton

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    AbstractThe mammalian TOR (mTOR) pathway integrates nutrient- and growth factor-derived signals to regulate growth, the process whereby cells accumulate mass and increase in size. mTOR is a large protein kinase and the target of rapamycin, an immunosuppressant that also blocks vessel restenosis and has potential anticancer applications. mTOR interacts with the raptor and GβL proteins [1–3] to form a complex that is the target of rapamycin. Here, we demonstrate that mTOR is also part of a distinct complex defined by the novel protein rictor (rapamycin-insensitive companion of mTOR). Rictor shares homology with the previously described pianissimo from D. discoidieum[4], STE20p from S. pombe[5], and AVO3p from S. cerevisiae[6, 7]. Interestingly, AVO3p is part of a rapamycin-insensitive TOR complex that does not contain the yeast homolog of raptor and signals to the actin cytoskeleton through PKC1 [6]. Consistent with this finding, the rictor-containing mTOR complex contains GβL but not raptor and it neither regulates the mTOR effector S6K1 nor is it bound by FKBP12-rapamycin. We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C α (PKCα) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals

    Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103

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    Orexins are neuropeptides that regulate the sleep-wake cycle and feeding behaviour. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity, thus playing an important role in energy homeostasis and regulation of appetite. The exact expression and signalling characteristics and physiological actions of QRFP and its receptor GPR103 are poorly understood. Alzheimerâ €™ s disease (AD) patients experience increased nocturnal activity, excessive daytime sleepiness, and weight loss. We hypothesised therefore that orexins and QRFP might be implicated in the pathophysiology of AD. We report that the down-regulation of hippocampal orexin receptors (OXRs) and GPR103 particularly in the cornu ammonis (CA) subfield from AD patients suffering from early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in vitro model we demonstrate that this downregulation is due to to Aβ-plaque formation and tau hyper-phosphorylation. Transcriptomics revealed a neuroprotective role for both orexins and QRFP. Finally we provide conclusive evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers to exert their effects involving activation of ERK 1/2. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways

    Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice

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    OBJECTIVE—Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a β-cell antigen epitope and T-cell autoreactivity in a model of autoimmune diabetes

    Development aid and international migration to Italy: Does aid reduce irregular flows?

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    In recent years, donors have claimed to tackle the root causes of migration from low‐income countries using aid. While others have studied the effects of aid on regular migration, we test whether aid deters irregular migration to Italy using two innovative dependent variables: asylum applications and apprehensions at border. For asylum applications, the largest significant effect size implies we should expect one extra application for an additional 162,000inbilateralaid.Forbordercrossings,theonlysignificanteffectimpliesthemarginalcostinbilateralaidis162,000 in bilateral aid. For border crossings, the only significant effect implies the marginal cost in bilateral aid is 1.8 million per deterred migrant. The conclusion that effect sizes are small is robust to different types of aid, measures of migration and various controls. We find robust evidence that irregular migration flows are significantly affected by conflict, poverty, and the pre‐existing stocks from that country. Comparing our results to the existing aid‐migration literature, we find similar effect sizes. The cost per deterred (regular) migrant is in the range $4‐7 million. Statistically significant estimates for the effect of aid on regular migration are only found for sub‐samples or specific specifications. In short, aid does not deter regular or irregular migration, so should be used for other purposes
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