143 research outputs found
Social Service Delivery in Violent Contexts: Achieving Results Against the Odds. A report from Afghanistan, Pakistan, and Nepal
This report provides the foundation for a new approach to service delivery in violence-affected contexts that is sensitive to the actual forms of violence, politics, and bargaining encountered in many conflict-affected states. The findings unearth issues about how development organizations should approach service delivery in contested settings. As many countries today are riven by conflict and internal division, some familiar rules of the game may be inadequate to deal with the mounting humanitarian and development challenges posed by complex conflict situations, particularly where affected people need access to social services. This raises dilemmas about the ethical and political judgments and trade-offs that development actors frequently have to make. A key challenge is whether development actors can adapt their procedures and ways of working to the fluidity, uncertainties, and risk taking that the new, conflict-riven landscape demands while preserving financial accountability, doing no harm, and ensuring aid effectiveness. Based on research in Afghanistan, Pakistan and Nepal, the report probes how social service delivery is affected by violent conflict and what are the critical factors that make or break successful delivery
Inclusive Scholarship: Developing Black Studies in the United States
Brings together four reports commissioned between 1982 and 2000 that examine the history of African American Studies, its impact, and its institutionalization. Reviews Ford's grantmaking to African American Studies programs from 1982 to 2007
Definition of Naturally Processed Peptides Reveals Convergent Presentation of Autoantigenic Topoisomerase I Epitopes in Scleroderma.
ObjectiveAutoimmune responses to DNA topoisomerase I (topo I) are found in a subset of scleroderma patients who are at high risk for interstitial lung disease (ILD) and mortality. Anti-topo I antibodies (ATAs) are associated with specific HLA-DRB1 alleles, and the frequency of HLA-DR-restricted topo I-specific CD4+ T cells is associated with the presence, severity, and progression of ILD. Although this strongly implicates the presentation of topo I peptides by HLA-DR in scleroderma pathogenesis, the processing and presentation of topo I has not been studied.MethodsWe developed a natural antigen processing assay (NAPA) to identify putative CD4+ T cell epitopes of topo I presented by monocyte-derived dendritic cells (mo-DCs) from 6 ATA-positive patients with scleroderma. Mo-DCs were pulsed with topo I protein, HLA-DR-peptide complexes were isolated, and eluted peptides were analyzed by mass spectrometry. We then examined the ability of these naturally presented peptides to induce CD4+ T cell activation in 11 ATA-positive and 11 ATA-negative scleroderma patients.ResultsWe found that a common set of 10 topo I epitopes was presented by Mo-DCs from scleroderma patients with diverse HLA-DR variants. Sequence analysis revealed shared peptide-binding motifs within the HLA-DRβ chains of ATA-positive patients and a subset of topo I epitopes with distinct sets of anchor residues capable of binding to multiple different HLA-DR variants. The NAPA-derived epitopes elicited robust CD4+ T cell responses in 73% of ATA-positive patients (8 of 11), and the number of epitopes recognized correlated with ILD severity (P = 0.025).ConclusionThese findings mechanistically implicate the presentation of a convergent set of topo I epitopes in the development of scleroderma
Dmrt1 polymorphism covaries with sex-determination patterns in Rana temporaria.
Patterns of sex-chromosome differentiation and gonadal development have been shown to vary among populations of Rana temporaria along a latitudinal transect in Sweden. Frogs from the northern-boreal population of Ammarnäs displayed well-differentiated X and Y haplotypes, early gonadal differentiation, and a perfect match between phenotypic and genotypic sex. In contrast, no differentiated Y haplotypes could be detected in the southern population of Tvedöra, where juveniles furthermore showed delayed gonadal differentiation. Here, we show that Dmrt1, a gene that plays a key role in sex determination and sexual development across all metazoans, displays significant sex differentiation in Tvedöra, with a Y-specific haplotype distinct from Ammarnäs. The differential segment is not only much shorter in Tvedöra than in Ammarnäs, it is also less differentiated and associates with both delayed gonadal differentiation and imperfect match between phenotypic and genotypic sex. Whereas Tvedöra juveniles with a local Y haplotype tend to ultimately develop as males, those without it may nevertheless become functional XX males, but with strongly female-biased progeny. Our findings suggest that the variance in patterns of sex determination documented in common frogs might result from a genetic polymorphism within a small genomic region that contains Dmrt1. They also substantiate the view that recurrent convergences of sex determination toward a limited set of chromosome pairs may result from the co-option of small genomic regions that harbor key genes from the sex-determination pathway
Laser Absorption Measurements of CO and H2O from Dimethyl Carbonate Combustion Behind Reflected Shock Waves for Safer Li-Ion Battery Applications
Dimethyl Carbonate (DMC) is a carbonate ester that can be produced in environment-friendly ways, from sources such as biomass or methanol and CO2. DMC can be used as a diesel fuel additive and is also one of the main components of the flammable electrolyte used in Li-ion batteries. Studying the combustion chemistry of DMC can therefore improve the use of biofuels and help in developing safer Li-ion batteries. The combustion chemistry of DMC has been investigated in a limited number of studies, and a few detailed kinetics models have been proposed in literature. The aim of this study was to complement the scarce data available for DMC combustion in the literature and to improve a detailed kinetic model.
Shock tubes were used to measure time histories of CO and H2O using tunable laser absorption techniques for the first time for DMC. Characteristic reaction times were also measured through OH* emission. Shock-tube spectroscopic measurements were performed under dilute conditions, at three equivalence ratios (fuel-lean, stoichiometric, and fuel-rich) between 1260 and 1660 K near 1.3±0.2 atm, and under pyrolysis conditions (98%+) ranging from 1230 to 2500 K near 1.3±0.2 atm. The model comparison and validation were further broadened using new laminar flame speed data collected in CNRS ICARE, France. Flame speeds at 318 K, 363 K and 464 K measured for equivalence ratios of 0.7-1.5 in a spherical vessel around atmospheric pressure were used to further extend the range of conditions investigated. Detailed kinetics models from the literature were compared to the data, and it was found that none can accurately predict the new data over the entire range of conditions investigated. A numerical analysis was performed, and updates to the most accurate model allowed for a significant improvement of the predictions for DMC combustion
Waking the sleeping dragon:Gene expression profiling reveals adaptive strategies of the hibernating reptile Pogona vitticeps
Koala cathelicidin PhciCath5 has antimicrobial activity, including against Chlamydia pecorum.
Devastating fires in Australia over 2019-20 decimated native fauna and flora, including koalas. The resulting population bottleneck, combined with significant loss of habitat, increases the vulnerability of remaining koala populations to threats which include disease. Chlamydia is one disease which causes significant morbidity and mortality in koalas. The predominant pathogenic species, Chlamydia pecorum, causes severe ocular, urogenital and reproductive tract disease. In marsupials, including the koala, gene expansions of an antimicrobial peptide family known as cathelicidins have enabled protection of immunologically naïve pouch young during early development. We propose that koala cathelicidins are active against Chlamydia and other bacteria and fungi. Here we describe ten koala cathelicidins, five of which contained full length coding sequences that were widely expressed in tissues throughout the body. Focusing on these five, we investigate their antimicrobial activity against two koala C. pecorum isolates from distinct serovars; MarsBar and IPTaLE, as well as other bacteria and fungi. One cathelicidin, PhciCath5, inactivated C. pecorum IPTaLE and MarsBar elementary bodies and significantly reduced the number of inclusions compared to the control (p<0.0001). Despite evidence of cathelicidin expression within tissues known to be infected by Chlamydia, natural PhciCath5 concentrations may be inadequate in vivo to prevent or control C. pecorum infections in koalas. PhciCath5 also displayed antimicrobial activity against fungi and Gram negative and positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Electrostatic interactions likely drive PhciCath5 adherence to the pathogen cell membrane, followed by membrane permeabilisation leading to cell death. Activity against E. coli was reduced in the presence of 10% serum and 20% whole blood. Future modification of the PhciCath5 peptide to enhance activity, including in the presence of serum/blood, may provide a novel solution to Chlamydia infection in koalas and other species
Sequence and gene content of a large fragment of a lizard sex chromosome and evaluation of candidate sex differentiating gene R-spondin 1
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