167 research outputs found

    A Woman\u27s Voice: Female Autobiography in the Nineteenth Century

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    Senior Project submitted to The Division of Social Studies of Bard College

    Walking the Talk: Toward a Values-Aligned Academy

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    Walking the Talk: Toward a Values-Aligned Academy is the culmination of 18 months of research interviews across the Big Ten Academic Alliance (BTAA). Conducted by the HuMetricsHSS Initiative as an extension of their previous work on values-enacted scholarly practice, the interviews focused on current systems of evaluation within BTAA institutions, the potential problems and inequalities of those processes, the kinds of scholarly work that could be better recognized and rewarded, and the contexts and pressures evaluators are under, including, as the process progressed, the onset and ongoing conditions of COVID-19. The interviews focused primarily on the reappointment, promotion, and tenure (RPT) process. Interviewees outlined a number of issues to be addressed, including toxicity in evaluation, scholars’ increased alienation from the work they are passionate about, and a high-level virtue-signaling of values by institutions without the infrastructure or resources to support the enactment of those values. Based on these conversations, this white paper offers a set of recommendations for making wide-scale change to address systematic injustice, erasure, and devaluation of academic labor in order to strengthen the positive public impact of scholarship

    Journey to the east: Diverse routes and variable flowering times for wheat and barley en route to prehistoric China.

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    Today, farmers in many regions of eastern Asia sow their barley grains in the spring and harvest them in the autumn of the same year (spring barley). However, when it was first domesticated in southwest Asia, barley was grown between the autumn and subsequent spring (winter barley), to complete their life cycles before the summer drought. The question of when the eastern barley shifted from the original winter habit to flexible growing schedules is of significance in terms of understanding its spread. This article investigates when barley cultivation dispersed from southwest Asia to regions of eastern Asia and how the eastern spring barley evolved in this context. We report 70 new radiocarbon measurements obtained directly from barley grains recovered from archaeological sites in eastern Eurasia. Our results indicate that the eastern dispersals of wheat and barley were distinct in both space and time. We infer that barley had been cultivated in a range of markedly contrasting environments by the second millennium BC. In this context, we consider the distribution of known haplotypes of a flowering-time gene in barley, Ppd-H1, and infer that the distributions of those haplotypes may reflect the early dispersal of barley. These patterns of dispersal resonate with the second and first millennia BC textual records documenting sowing and harvesting times for barley in central/eastern China

    Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

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    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

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    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4 × 10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10−10 for risk variants (P<10−4) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC
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