168 research outputs found

    Town development in the colonial backcountry: Virginia and North Carolina

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    The backcountry of colonial Virginia and North Carolina saw a process of urbanization during the third quarter of the eighteenth century uniquely shaped by a large-scale migration from colonies to the north, aided by the westward extension of local government. This rapid development did not lead to the creation of a hierarchical economic system of central places, but rather linear networks shaped by the geography of the region. Ironically, this phenomenon occurred in an area of two American colonies usually considered to be devoid of towns.;This dissertation is a study of twenty-eight towns established from 1744 to 1776 in the Piedmont Southside and Great Valley of Virginia and in Piedmont North Carolina. The towns are categorized by their primary function (administrative, migrant, or trade), and then analyzed individually, taking into account the circumstances of their establishment, their intended purpose, their design, and actual development.;The goal of this work is not only to provide a regional town study, but also to identify commonalities in town development, including methods of establishment, economic activities on local and regional levels, the roles of public institutions, and what factors helped determine success or failure. The interaction between towns is also explored to determine trade and communication links, any network systems, and areas of urban influence. The study is an attempt to identify and describe the growth of a significant colonial urban movement

    Bank Competition: Measurement, Decision-Making, and Risk Profiles

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    This paper investigates how competition impacts the future operating decisions and risk profile of banks. We construct a comprehensive, time-varying, bank-specific measure of a bank’s competitive environment (BCE) using textual analysis of banks’ 10-K filings. Using U.S. branch banking deregulation to capture exogenous changes in threats of entry, we provide evidence that BCE is a timely measure of real competitive pressures by showing that it significantly increases following decreases in barriers to entry. Measuring competition with BCE, we find that higher competition is associated with lower underwriting standards, less timely loan loss recognition and a shift towards non-interest revenue. Further, we find that higher competition is associated with higher stand-alone risk of individual banks, greater sensitivity of a bank’s downside equity risk to system-wide distress, and a greater contribution by individual banks to downside risk of the banking sector. We then show that these results using BCE are largely robust to replacing BCE with branch bank deregulation. Finally, we show that our BCE results hold in a post-deregulation analysis restricted to time periods following the final deregulation event in each state. These results combine to suggest that competition increases the risk profile of banks and that BCE can be of value to researchers and analysts for measuring competitive pressure at any point in time, regardless of the existence of a regulatory event.http://deepblue.lib.umich.edu/bitstream/2027.42/107866/1/1243_Williams.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107866/4/1243_Williams_Jan2015.pdfDescription of 1243_Williams_Jan2015.pdf : January 2015 revision (new title

    Isolating the photovoltaic junction: atomic layer deposited TiO2-RuO2 alloy Schottky contacts for silicon photoanodes

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    We synthesized nanoscale TiO2-RuO2 alloys by atomic layer deposition (ALD) that possess a high work function and are highly conductive. As such, they function as good Schottky contacts to extract photogenerated holes from n-type silicon while simultaneously interfacing with water oxidation catalysts. The ratio of TiO2 to RuO2 can be precisely controlled by the number of ALD cycles for each precursor. Increasing the composition above 16% Ru sets the electronic conductivity and the metal work function. No significant Ohmic loss for hole transport is measured as film thickness increases from 3 to 45 nm for alloy compositions >= 16% Ru. Silicon photoanodes with a 2 nm SiO2 layer that are coated by these alloy Schottky contacts having compositions in the range of 13-46% Ru exhibit average photovoltages of 525 mV, with a maximum photovoltage of 570 mV achieved. Depositing TiO2-RuO2 alloys on nSi sets a high effective work function for the Schottky junction with the semiconductor substrate, thus generating a large photovoltage that is isolated from the properties of an overlying oxygen evolution catalyst or protection layer

    Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials.

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    Background Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. Methodology A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Conclusions Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (\u3c1 \u3eweek). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development

    Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.

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    Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases. In cells, we found that nuclear PHIP (pleckstrin homology domain interacting protein) directly enhances transcription of pro-opiomelanocortin (POMC), a neuropeptide that suppresses appetite. Obesity-associated PHIP variants repressed POMC transcription. Our demonstration that PHIP is involved in human energy homeostasis through transcriptional regulation of central melanocortin signaling has potential diagnostic and therapeutic implications for patients with obesity and developmental delay. Additionally, we found an excess burden of predicted deleterious variants involving genes nearest to loci from obesity genome-wide association studies. Genes and gene sets influencing obesity with variable penetrance provide compelling evidence for a continuum of causality in the genetic architecture of obesity, and explain some of its missing heritability

    The state of the Martian climate

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    60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

    Designing high-quality implementation research: development, application, feasibility and preliminary evaluation of the implementation science research development (ImpRes) tool and guide

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    Background:  Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. Methods:  A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process of reviewing the literature and expert input informed the development and content of the tool. Once consensus had been reached, specialist expert input was sought on involving and engaging patients/service users; and economic evaluation. ImpRes was then applied to 15 implementation and improvement science projects across the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, a research organisation in London, UK. Researchers who applied the ImpRes tool completed an 11-item questionnaire evaluating its structure, content and usefulness. Results:  Consensus was reached on ten implementation science domains to be considered when designing implementation research. These include implementation theories, frameworks and models, determinants of implementation, implementation strategies, implementation outcomes and unintended consequences. Researchers who used the ImpRes tool found it useful for identifying project areas where implementation science is lacking (median 5/5, IQR 4–5) and for improving the quality of implementation research (median 4/5, IQR 4–5) and agreed that it contained the key components that should be considered when designing implementation research (median 4/5, IQR 4–4). Qualitative feedback from researchers who applied the ImpRes tool indicated that a supplementary guide was needed to facilitate use of the tool. Conclusions:  We have developed a feasible and acceptable tool, and supplementary guide, to facilitate consideration and incorporation of core principles and concepts of implementation science in applied health implementation research. Future research is needed to establish whether application of the tool and guide has an effect on the quality of implementation research
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