54 research outputs found

    Aid, growth and peace: A comparative analysis.

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    yesThe paper examines patterns of post-conflict aid in a sample of 14 countries, with in-depth, qualitative analysis of seven cases (Bosnia, Cambodia, El Salvador, Nicaragua, Guatemala, Mozambique and Rwanda). The study takes previous work by Paul Collier and associates in this area as a starting point, but disaggregates the data by type of aid, time intervals, and historical period. The findings significantly qualify the Collier conclusion to the effect that donors respond to a CNN-effect in a dysfunctional manner by rushing in aid soon after a peace agreement is concluded and scaling back too soon. Rather, disaggregated analysis shows that post-war aid follows several patterns and can best be understood as strategic behavior designed to promote a range of economic and political objectives. This paper also questions the related policy recommendation of the Collier research on post-conflict aid, namely that post-conflict aid should be phased in so as to maximize economic growth on the grounds that this is important to sustain peace during the first post-conflict decade. Instead, this paper finds, aid strategies that demonstrate early and firm donor commitment to the new order are more likely to stabilize peace in the short run, and aid strategies that address the underlying sources of conflict are important to sustain peace in the longer run

    Single-cell transcriptomic analysis of mouse neocortical development

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    The development of the mammalian cerebral cortex depends on careful orchestration of proliferation, maturation, and migration events, ultimately giving rise to a wide variety of neuronal and non-neuronal cell types. To better understand cellular and molecular processes that unfold during late corticogenesis, we perform single-cell RNA-seq on the mouse cerebral cortex at a progenitor driven phase (embryonic day 14.5) and at birth—after neurons from all six cortical layers are born. We identify numerous classes of neurons, progenitors, and glia, their proliferative, migratory, and activation states, and their relatedness within and across age. Using the cell-type-specific expression patterns of genes mutated in neurological and psychiatric diseases, we identify putative disease subtypes that associate with clinical phenotypes. Our study reveals the cellular template of a complex neurodevelopmental process, and provides a window into the cellular origins of brain diseases

    Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1

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    Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin’s role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1). Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated protein degradation (ERAD). Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation. Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells. Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy

    Obituario. Clareance J. McCoy Jr

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