54 research outputs found
Aid, growth and peace: A comparative analysis.
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
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
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
Recommended from our members
Fuel and cladding oxidation under expected repository conditions
Although its containment is imperfect, fuel cladding provides a redundant barrier that can help control release of radionuclides. However, if the disposal container fails while the fuel assemblies are still hot, both cladding and fuel could oxidize. Such oxidation could have a significant effect on long-term safety and doses to the public because oxidation increases the surface area of the fuel, exposure of the fuel to groundwater, and dissolution rate. This paper uses fuel temperatures and oxidation rates to determine the period during which oxidation is a concern
Recommended from our members
SECOND WASTE PACKAGE PROBABILISTIC CRITICALITY ANALYSIS: GENERATION AND EVALUATION OF INTERNAL CRITICIALITY CONFIGURATIONS
This analysis is prepared by the Mined Geologic Disposal System (MGDS) Waste Package Development (WPD) department to provide an evaluation of the criticality potential within a waste package having sonic or all of its contents degraded by corrosion and removal of neutron absorbers. This analysis is also intended to provide an estimate of the consequences of any internal criticality, particularly in terms of any increase in radionuclide inventory. These consequence estimates will be used as part of the WPD input to the Total System Performance Assessment. The ultimate objective of this analysis is to augment the information gained from the Initial Waste Package Probabilistic Criticality Analyses (Ref. 5.8 and 5.9, hereafter referred to as IPA) to a degree which will support preliminary waste package design recommendations intended to reduce the risk of waste package criticality and the risk to total repository system performance posed by the consequences of any criticality. The IPA evaluated the criticality potential under the assumption that the waste package basket retained its structural integrity, so that the assemblies retained their initial separation, even when the neutron absorbers had been leached from the basket. This analysis is based on the more realistic condition that removal of the neutron absorbers is a consequence of the corrosion of the steel in which they are contained, which has the additional consequence of reducing the structural support between assemblies. The result is a set of more reactive configurations having a smaller spacing between assemblies, or no inter-assembly spacing at all. Another difference from the IPA is the minimal attention to probabilistic evaluation given in this study. Although the IPA covered a time horizon to 100,000 years, the lack of consideration of basket degradation modes made it primarily applicable to the first 10,000 years. In contrast, this study, by focusing on the degraded modes of the basket, is primarily applicable to the post 10,000 year time horizon. The principal probability related objective of this analysis is to estimate the earliest time at which a criticality can possibly occur, as a function of several environmental and material performance parameters, the specific values of which are subject to great uncertainty. It should be noted that the longer the possibility of criticality is delayed, the less will be the probability of any criticality at all, because of the increased probability that the waste package bottom will be penetrated by corrosion so that the waste package can no longer hold enough water to provide the necessary moderation to support the criticality
- …