Much of the confusion about a central event in United States history begins with the name: the Civil War. In reality, the Civil War was not merely civil--meaning national--and not merely a war, but ...instead an international conflict of ideas as well as armies. Its implications transformed the U.S. Constitution and reshaped a world order, as political and economic systems grounded in slavery and empire clashed with the democratic process of republican forms of government. And it spilled over national boundaries, tying the United States together with Cuba, Spain, Mexico, Britain, and France in a struggle over the future of slavery and of republics. Here Gregory P. Downs argues that we can see the Civil War anew by understanding it as a revolution. More than a fight to preserve the Union and end slavery, the conflict refashioned a nation, in part by remaking its Constitution. More than a struggle of brother against brother, it entailed remaking an Atlantic world that centered in surprising ways on Cuba and Spain. Downs introduces a range of actors not often considered as central to the conflict but clearly engaged in broader questions and acts they regarded as revolutionary. This expansive canvas allows Downs to describe a broad and world-shaking war with implications far greater than often recognized.
In this highly original study, Gregory Downs argues that the most American of wars, the Civil War, created a seemingly un-American popular politics, rooted not in independence but in voluntary claims ...of dependence. Through an examination of the pleas and petitions of ordinary North Carolinians,Declarations of Dependencecontends that the Civil War redirected, not destroyed, claims of dependence by exposing North Carolinians to the expansive but unsystematic power of Union and Confederate governments, and by loosening the legal ties that bound them to husbands, fathers, and masters.Faced with anarchy during the long reconstruction of government authority, people turned fervently to the government for protection and sustenance, pleading in fantastic, intimate ways for attention. This personalistic, or what Downs calls patronal, politics allowed for appeals from subordinate groups like freed blacks and poor whites, and also bound people emotionally to newly expanding postwar states. Downs's argument rewrites the history of the relationship between Americans and their governments, showing the deep roots of dependence, the complex impact of the Civil War upon popular politics, and the powerful role of Progressivism and segregation in submerging a politics of dependence that--in new form--rose again in the New Deal and persists today.
At the close of the Civil War, it was clear that the military conflict that began in South Carolina and was fought largely east of the Mississippi River had changed the politics, policy, and daily ...life of the entire nation. In an expansive reimagining of post-Civil War America, the essays in this volume explore these profound changes not only in the South but also in the Southwest, in the Great Plains, and abroad. Resisting the tendency to use Reconstruction as a catchall, the contributors instead present diverse histories of a postwar nation that stubbornly refused to adopt a unified ideology and remained violently in flux. Portraying the social and political landscape of postbellum America writ large, this volume demonstrates that by breaking the boundaries of region and race and moving past existing critical frameworks, we can appreciate more fully the competing and often contradictory ideas about freedom and equality that continued to define the United States and its place in the nineteenth-century world.Contributors include Amanda Claybaugh, Laura F. Edwards, Crystal N. Feimster, C. Joseph Genetin-Pilawa, Steven Hahn, Luke E. Harlow, Stephen Kantrowitz, Barbara Krauthamer, K. Stephen Prince, Stacey L. Smith, Amy Dru Stanley, Kidada E. Williams, and Andrew Zimmerman.
Here, we present a genome-wide overview of transcriptional circuits in the agriculturally significant crop species maize (Zea mays). We examined transcript abundance data at 50 developmental stages, ...from embryogenesis to senescence, for 34,876 gene models and classified genes into 24 robust coexpression modules. Modules were strongly associated with tissue types and related biological processes. Sixteen of the 24 modules (67%) have preferential transcript abundance within specific tissues. Onethird of modules had an absence of gene expression in specific tissues. Genes within a number of modules also correlated with the developmental age of tissues. Coexpression of genes is likely due to transcriptional control. For a number of modules, key genes involved in transcriptional control have expression profiles that mimic the expression profiles of module genes, although the expression of transcriptional control genes is not unusually representative of module gene expression. Known regulatory motifs are enriched in several modules. Finally, of the 13 network modules with more than 200 genes, three contain genes that are notably clustered (P < 0.05) within the genome. This work, based on a carefully selected set of major tissues representing diverse stages of maize development, demonstrates the remarkable power of transcript-level coexpression networks to identify underlying biological processes and their molecular components.
Downs treats post-bellum history not as a time of reconciliation and stability but rather as a period haunted by fears that the end of the Civil War might lead only to more civil conflict. This ...concern was expressed in a now-forgotten but then-common discourse evoking the historical example of Mexico as a harbinger of permanent instability as the result of civil war. Recasting the contested 1876 US presidential election as a process of stabilization, Downs recovers the prevalence of the Mexican example, which served both to give voice to popular anxiety and to coax politicians toward a peaceful resolution of the crisis. By evoking contemporary fears of the possibility of state collapse, he provides an image of a strangely vulnerable nineteenth-century US.
The multifactorial risk prediction model BOADICEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects ...of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component - the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA.
The mean, SD, and proportion of the overall polygenic component explained by the PRS (α2) need to be estimated. $\alpha $ was estimated using logistic regression, where the age-specific log-OR is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA; and using a retrospective likelihood (RL) approach that models, in addition, the unmeasured polygenic component.
Parameters were computed for 11 PRS, including 6 variations of the 313 SNP PRS used in clinical trials and implementation studies. The logistic regression approach underestimates $\alpha $, as compared with the RL estimates. The RL $\alpha $ estimates were very close to those obtained by assuming proportionality to the OR per 1 SD, with the constant of proportionality estimated using the 313 SNP PRS. Small variations in the SNPs included in the PRS can lead to large differences in the mean.
BOADICEA can be readily adapted to different PRS in a manner that maintains consistency of the model.
: The methods described facilitate comprehensive breast cancer risk assessment.
This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent ...serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16-53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.
Development of crop varieties with high nitrogen use efficiency (NUE) is crucial for minimizing N loss, reducing environmental pollution and decreasing input cost. Maize is one of the most important ...crops cultivated worldwide and its productivity is closely linked to the amount of fertilizer used. A survey of the transcriptomes of shoot and root tissues of a maize hybrid line and its two parental inbred lines grown under sufficient and limiting N conditions by mRNA-Seq has been conducted to have a better understanding of how different maize genotypes respond to N limitation.
A different set of genes were found to be N-responsive in the three genotypes. Many biological processes important for N metabolism such as the cellular nitrogen compound metabolic process and the cellular amino acid metabolic process were enriched in the N-responsive gene list from the hybrid shoots but not from the parental lines' shoots. Coupled to this, sugar, carbohydrate, monosaccharide, glucose, and sorbitol transport pathways were all up-regulated in the hybrid, but not in the parents under N limitation. Expression patterns also differed between shoots and roots, such as the up-regulation of the cytokinin degradation pathway in the shoots of the hybrid and down-regulation of that pathway in the roots. The change of gene expression under N limitation in the hybrid resembled the parent with the higher NUE trait. The transcript abundances of alleles derived from each parent were estimated using polymorphic sites in mapped reads in the hybrid. While there were allele abundance differences, there was no correlation between these and the expression differences seen between the hybrid and the two parents.
Gene expression in two parental inbreds and the corresponding hybrid line in response to N limitation was surveyed using the mRNA-Seq technology. The data showed that the three genotypes respond very differently to N-limiting conditions, and the hybrid clearly has a unique expression pattern compared to its parents. Our results expand our current understanding of N responses and will help move us forward towards effective strategies to improve NUE and enhance crop production.
Von Hippel-Lindau disease (VHL) is an autosomal dominant, inherited syndrome with variants in the VHL gene causing predisposition to multi-organ benign and malignant neoplasms. A germline VHL variant ...is identified in 95-100% of individuals with a clinical diagnosis of VHL. Here, we present the case of an individual with a clinical diagnosis of VHL disease where peripheral blood DNA analysis did not detect a VHL variant. Sequencing of four tumor tissues (ccRCC, pheochromocytoma, lung via sputum, liver) revealed a VHL c.593 T > C (p.Leu198Pro) variant at varying allele fractions (range: 10-55%) in all tissues. Re-examination of the peripheral blood sequencing data identified this variant at 6% allele fraction. Tumor analysis revealed characteristic cytomorphological, immunohistochemical reactivity for alpha-inhibin, and CAIX, and reduced pVHL reactivity supported VHL-related pseudohypoxia. This report of a rare case of VHL mosaicism highlights the value of tissue testing in VHL variant negative cases.
After Appomattox Downs, Gregory P
2015, 2015-04-09, 2015-04-17
eBook
The Civil War did not end with Confederate capitulation in 1865. A second phase commenced which lasted until 1871--not Reconstruction but genuine belligerency whose mission was to crush slavery and ...create civil and political rights for freed people. But as Gregory Downs shows, military occupation posed its own dilemmas, including near-anarchy.
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