244 research outputs found

    Spesutia Hundred, 1681-1799: A Study of a Colonial Maryland Parish

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    My study of some aspects of the lives of the people of Spesutia Parish in Harford County, Maryland, was made possible by the discovery of three surviving documents from this area. There is a parish record listing births, marriages, and deaths from 1680 to 1790. Information about households and wealth, as well as slavery, can be learned from a census taken in 1776 and a tax list from 1783. From the parish record and census, I found data on births, and was able to estimate the birth rate. The total population grew rapidly, so there must have been significant in-migration. The number of children per family was about four. I was able to estimate the age at marriage from the parish record and census. Second marriages seemed common. There did not appear to be many single adults except for servants, and bachelors had to pay a special tax. There was little evidence of extended families in one house but many had servants. Deaths were the least frequent entry in the parish record, and, if the death entries were accurate, Spesutia had a low death rate. In 1776 there were significant numbers of blacks and whites over age fifty. Maternal and infant deaths from childbirth were not especially high. Spesutia's population of 1440 in 1776 was almost half free and half slave. Over half the households did not have any slaves. Slave owning contributed to taxable wealth, but wealth did not correlate with social and political leadership. Lastly, I compared my data with other studies of colonial Maryland, and studies of New England and the South. More demographic studies are necessary, however, before we can speak definitively about birth, death and marriage in colonial Maryland or other parts of the colonies

    Improving ionospheric predictability requires accurate simulation of the mesospheric polar vortex

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    The mesospheric polar vortex (MPV) plays a critical role in coupling the atmosphere-ionosphere system, so its accurate simulation is imperative for robust predictions of the thermosphere and ionosphere. While the stratospheric polar vortex is widely understood and characterized, the mesospheric polar vortex is much less well-known and observed, a short-coming that must be addressed to improve predictability of the ionosphere. The winter MPV facilitates top-down coupling via the communication of high energy particle precipitation effects from the thermosphere down to the stratosphere, though the details of this mechanism are poorly understood. Coupling from the bottom-up involves gravity waves (GWs), planetary waves (PWs), and tidal interactions that are distinctly different and important during weak vs. strong vortex states, and yet remain poorly understood as well. Moreover, generation and modulation of GWs by the large wind shears at the vortex edge contribute to the generation of traveling atmospheric disturbances (TADs) and traveling ionospheric disturbances (TIDs). Unfortunately, representation of the MPV is generally not accurate in state-of-the-art general circulation models (GCMs), even when compared to the limited observational data available. Models substantially underestimate eastward momentum at the top of the MPV, which limits the ability to predict upward effects in the thermosphere. The zonal wind bias responsible for this missing momentum in models has been attributed to deficiencies in the treatment of GWs and to an inaccurate representation of the high-latitude dynamics. Such deficiencies limit the use of these models to study the role of the MPV in the transport of constituents and in wave-mean flow interactions, and to elucidate the mechanisms by which the atmosphere-ionosphere system is interconnected. In the coming decade, simulations of the MPV must be improved. This can be accomplished by constraining the model temperature and wind fields in the mesosphere and lower thermosphere (MLT) with a more extensive suite of satellite and ground-based observations. In addition, improvements to current model GW parameterizations are required to more accurately simulate the processes that govern the generation, propagation, and dissipation of GWs

    In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma.

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    Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype. Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort. Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration. Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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