Secession Diplomacy: A Study of Thomas Butler King, Commissioner of Georgia to Europe, 1861

The objective of this thesis is to determine the function and effectiveness of state diplomats in the Confederate cause abroad by examining the mission of Thomas Butler King to the courts of Europe for the state of Georgia within the context of the international dimensions of the first year of the Civil War. The work will address the various Confederate arguments for recognition through the examination of propaganda documents published by King and their effect on French and British policies. The work will further investigate the direct trade movement of the 1850s and its effect on the southern diplomatic effort

Why do officers support community policing? A cross-departmental and cross-temporal comparison

Community policing is often seen as a way to repair fractured relationships between law enforcement and the public. Despite its relationship-building promise and widespread department-level adoption, individual officers show varying levels of support for community policing which can harm policy implementation. Why are some officers more supportive of community policing than others? Prior research suggests that demographic factors such as the officer\u27s gender, race, age, and education can explain this variance. Across these studies, however, there are several contradicting or non-replicating findings. Conflicting findings may result from differences by department or differences in methodology or temporal variance – but most policing studies focus on a single department. We begin to adjudicate between the possible explanations for conflicting findings using roll-call survey data from 741 officers across three neighboring police departments in 2016 and then a replication with 452 officers from one of the original departments in 2019. We find that experience with community policing consistently influences support for the practice while officer gender, age, and education consistently do not. Other results do not replicate across department or time, although we do find non-replicating significant factors associated with officer support for community policing. Our findings also suggest that departmental and temporal aspects help to explain why policing studies often do not replicate or generalize to other places or contexts

Understanding the prevalence and drivers of food bank use: evidence from deprived communities in Glasgow

This article provides quantitative analysis of a self-reported measure of food bank use in the UK, adding to a sparse evidence base. Evidence from fifteen deprived communities in Glasgow is used to examine the scale of food bank use and to consider its relationship with socio-demographic, health, and financial variables. Being affected by welfare reforms was found to increase the likelihood of food bank use. Young men and those with mental health problems were found to be more likely than others to have used a food bank. Food banks appear to be used by groups who are being under-served by the welfare state and suffering the most acute impacts of austerity. The very low prevalence of food bank use among those who struggle to afford food points to their inadequacy as a response to food insecurity

Intragraft gene expression profile associated with the induction of tolerance

<p>Abstract</p> <p>Background</p> <p>Xenotransplantation holds the promise of providing an unlimited supply of donor organs for terminal patients with organ failure. Pre-existing natural antibodies to the Galα1,3Galβ1,4GlcNac-R (αGal) carbohydrate xenoantigen, however, bind rapidly to the graft endothelium and initiate hyperacute rejection of wild type pig grafts in humans. Experimental procedures designed to prevent xenoantibody-mediated rejection have been tested in gal knockout mice. These mice produce anti-gal xenoantibodies and are widely used as small animal models for xenotransplantation research. In this model, chimerism for cells expressing the gal carbohydrate can be achieved by transplantation of mixed cells or by transduction of bone marrow cells with viral vectors expressing a functional α1,3 galactosyltransferase gene. Chimerism induces tolerance to heart grafts expressing αGal. The mechanisms by which tolerance is achieved include systemic changes such as clonal deletion and/or anergy. Intragraft changes that occur during the early stages of tolerance induction have not been characterized.</p> <p>Results</p> <p>Cytoprotective genes heme oxygenase-1 (HO-1), Bcl2, and A20 that have been reported to contribute to long-term graft survival in various models of accommodation were not expressed at high levels in tolerant heart grafts. Intragraft gene expression at both early (Day 10) and late (>2 month) time points after heart transplant were examined by real-time PCR and microarray analysis was used to identify changes associated with the induction of tolerance. Intragraft gene expression profiling using microarray analysis demonstrated that genes identified in the functional categories of stress and immunity and signal transduction were significantly up-regulated in early tolerant grafts compared with syngeneic control grafts. Biological process classification showed lower binomial p-values in the categories of "response to biotic stimulus, defense response, and immune response" suggesting that up-regulated genes identified in these grafts promote survival in the presence of an immune response. The expression of the incompatible carbohydrate antigen (αGal) was reduced by 2 months post-transplant when compared with the expression of this gene at Day 10 post-transplant. These results suggest that the gal carbohydrate antigen is downmodulated over time in grafts that demonstrate tolerance.</p> <p>Conclusion</p> <p>Our study suggests that tolerance is associated with intragraft gene expression changes that render the heart resistant to immune-mediated rejection. Genes associated with stress and immunity are up-regulated, however cytoprotective genes HO-1, Bcl2 and A20 were not up-regulated. The expression of the gal carbohydrate, the key target initiating an immune response in this model, is down-regulated in the post-transplant period.</p

Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens

BACKGROUND: Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgV(H )genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the V(H)3 family. We have previously identified the immunoglobulin heavy chain genes encoding V(H)3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgV(H )genes encoding the small proportion of V(H)4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling. RESULTS: The VH4-59 gene encodes antibodies in the V(H)4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for V(H)3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgV(H )gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding. CONCLUSION: Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the V(H)3 family, with a small proportion encoded by V(H)4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs

Debunked: How to Tell Fact from Fiction

editorial reviewe

Recent Trends in Local-Scale Marine Biodiversity Reflect Community Structure and Human Impacts

The modern biodiversity crisis reflects global extinctions and local introductions. Human activities have dramatically altered rates and scales of processes that regulate biodiversity at local scales [1-7]. Reconciling the threat of global biodiversity loss [2, 4, 6-9] with recent evidence of stability at fine spatial scales [10,11] is a major challenge and requires a nuanced approach to biodiversity change that integrates ecological understanding. With a new dataset of 471 diversity time series spanning from 1962 to 2015 from marine coastal ecosystems, we tested (1) whether biodiversity changed at local scales in recent decades, and (2) whether we can ignore ecological context (e.g., proximate human impacts, trophic level, spatial scale) and still make informative inferences regarding local change. We detected a predominant signal of increasing species richness in coastal systems since 1962 in our dataset, though net species loss was associated with localized effects of anthropogenic impacts. Our geographically extensive dataset is unlikely to be a random sample of marine coastal habitats; impacted sites (3% of our time series) were underrepresented relative to their global presence. These local-scale patterns do not contradict the prospect of accelerating global extinctions [2,4,6-9] but are consistent with local species loss in areas with direct human impacts and increases in diversity due to invasions and range expansions in lower impact areas. Attempts to detect and understand local biodiversity trends are incomplete without information on local human activities and ecological context

Similarities in the immunoglobulin response and V(H )gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

BACKGROUND: The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3) galactose (αGal) present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s) with bioartficial liver devices (BALs), composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (V(H)) immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgV(H )genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta) were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. RESULTS: Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the V(H)3 family, with a minor contribution from the V(H)4 family. Immunoglobulin heavy-chain gene (V(H)) cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, V(H)3-11(cyno), has not been previously identified, and encodes xenoantibodies at later time points post-transplant. Sequencing of IgG clones revealed increased usage of the monkey germline progenitor most similar to human IGHV3-11 and the onset of mutations. CONCLUSION: The small number of IGV(H )genes encoding xenoantibodies to porcine hepatocytes in non-human primates and humans is highly conserved. Rhesus monkeys are an appropriate preclinical model for testing novel reagents such as those developed using structure-based drug design to target and deplete antibodies to porcine xenografts