Genotype Imputation with Thousands of Genomes

Genotype imputation is a statistical technique that is often used to increase the power and resolution of genetic association studies. Imputation methods work by using haplotype patterns in a reference panel to predict unobserved genotypes in a study dataset, and a number of approaches have been proposed for choosing subsets of reference haplotypes that will maximize accuracy in a given study population. These panel selection strategies become harder to apply and interpret as sequencing efforts like the 1000 Genomes Project produce larger and more diverse reference sets, which led us to develop an alternative framework. Our approach is built around a new approximation that uses local sequence similarity to choose a custom reference panel for each study haplotype in each region of the genome. This approximation makes it computationally efficient to use all available reference haplotypes, which allows us to bypass the panel selection step and to improve accuracy at low-frequency variants by capturing unexpected allele sharing among populations. Using data from HapMap 3, we show that our framework produces accurate results in a wide range of human populations. We also use data from the Malaria Genetic Epidemiology Network (MalariaGEN) to provide recommendations for imputation-based studies in Africa. We demonstrate that our approximation improves efficiency in large, sequence-based reference panels, and we discuss general computational strategies for modern reference datasets. Genome-wide association studies will soon be able to harness the power of thousands of reference genomes, and our work provides a practical way for investigators to use this rich information. New methodology from this study is implemented in the IMPUTE2 software package

The Value of Government Tort Liability: Washington State\u27s Journey From Immunity to Accountability

Part I of this Article traces Washington\u27s history with the common law doctrine of government immunity from tort liability. It also identifies other distinct common law immunities protecting executive, legislative, and judicial functions-immunities that lay dormant during the reign of sovereign immunity. Part II discusses the legislature\u27s broad waiver of sovereign immunity in 1961 and the legislature\u27s subsequent reaffirmation of the waiver. It also notes isolated instances in which the legislature has partially restored immunity or otherwise limited tort liability. Part III addresses the development of case law interpreting the scope of government tort liability in light of the legislative waiver of sovereign immunity and examines the impact of the remaining related common law immunities for executive, legislative, and judicial functions. Part III also examines the role of the public duty doctrine, which has evolved as a conceptual framework for assessing whether a predicate duty supports government tort liability in any given circumstance. Finally, Part IV exalts the continuing value of holding government accountable for its tortious conduct, treating such accountability as a legitimate means to encourage responsible government and achieve individual justice. Part IV also urges that any marked retreat from the broad waiver of sovereign immunity is unnecessary and unjustified, whether viewed from a fiscal or ideological standpoint

Entrepreneur career paths, location choice, and ecosystems : an empirical analysis

This dissertation consists of three research articles investigating three related research questions about entrepreneurial ecosystems and the career and location transitions of technology entrepreneurs. Altogether, the analyses improve our understanding of how particular work experiences and skills can shape the career paths of entrepreneurs and executives and how certain locations are consistently better at retaining/attracting entrepreneurial talent. The first article explores the common career paths of entrepreneurs, executives, and senior managers in the high-tech industry. I build career trajectories (as network graphs) that provide insights on career paths of entrepreneurs, executives, and senior managers based on a large dataset of work histories. Focusing on the high-tech industry, I find that individuals with certain transferable skills—notably technical, management, mixed, and boundary-spanning experience—are more likely to be in position to capitalize on job opportunities across industries. Furthermore, I test these insights by developing and refining a supervised learning model for predicting individual career transitions. In the second article, I investigate why certain U.S. metropolitan areas are better able to retain and attract technology entrepreneurs. Placing the entrepreneur at the center of the analysis, I examine the role of regional economic factors, regional funding opportunities, and personal social networks on entrepreneur decisions to start a high-tech firm in a specific location. The third article investigates the entrepreneurial ecosystems of Silicon Valley, Austin, Boston, and New York, which are well-established innovation-centered business clusters and entrepreneurial “talent magnets”. Following a brief overview and history of the entrepreneurial ecosystems of each region, I specify models (for each region) testing the importance of social network ties, funding, education, and cumulative work experience in driving the entrepreneurs’ location choice decisions. I supplement the empirical findings by analyzing interview data collected from technology entrepreneurs to explain how particular structures within entrepreneurial ecosystems facilitate interaction and networking among entrepreneurs—offering potential explanations for some of the observed variation between regions.Sociolog

Trimodal cloudiness and tropical stable layers in simulations of radiative convective equilibrium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95176/1/grl24304.pd

Results from the NASA Spacecraft Fault Management Workshop: Cost Drivers for Deep Space Missions

Fault Management, the detection of and response to in-flight anomalies, is a critical aspect of deep-space missions. Fault management capabilities are commonly distributed across flight and ground subsystems, impacting hardware, software, and mission operations designs. The National Aeronautics and Space Administration (NASA) Discovery & New Frontiers (D&NF) Program Office at Marshall Space Flight Center (MSFC) recently studied cost overruns and schedule delays for five missions. The goal was to identify the underlying causes for the overruns and delays, and to develop practical mitigations to assist the D&NF projects in identifying potential risks and controlling the associated impacts to proposed mission costs and schedules. The study found that four out of the five missions studied had significant overruns due to underestimating the complexity and support requirements for fault management. As a result of this and other recent experiences, the NASA Science Mission Directorate (SMD) Planetary Science Division (PSD) commissioned a workshop to bring together invited participants across government, industry, and academia to assess the state of the art in fault management practice and research, identify current and potential issues, and make recommendations for addressing these issues. The workshop was held in New Orleans in April of 2008. The workshop concluded that fault management is not being limited by technology, but rather by a lack of emphasis and discipline in both the engineering and programmatic dimensions. Some of the areas cited in the findings include different, conflicting, and changing institutional goals and risk postures; unclear ownership of end-to-end fault management engineering; inadequate understanding of the impact of mission-level requirements on fault management complexity; and practices, processes, and tools that have not kept pace with the increasing complexity of mission requirements and spacecraft systems. This paper summarizes the findings and recommendations from that workshop, particularly as fault management development issues affect operations and the development of operations capabilities

The moderating and mediating role of local government in the community engagement strategy of a renewable energy company in South Africa

Adopting a qualitative case study approach of a renewable energy company in South Africa, the research investigated community engagement within the tripartite relationship of a wind farm, the communities, and the local government. It was found that local government played a moderating role in the community engagement efforts of the wind farm which had to comply with certain engagement protocols determined by local government. Local government also played a mediating role in corporate community engagement, as the wind farm developed their engagement strategy in alignment with local government’s policies and acted as a ‘dot-connector’ between local government and communities. The wind farm played a reciprocal mediating role on local government’s own engagement with their communities in the face of local government’s inefficiencies and complemented service delivery outcomes. The wind farm’s engagement strategy thus enabled local development which was appreciated by communities and local government

MOLES3: implementing an ISO standards driven data catalogue

ISO19156 Observations and Measurements (O&M) provides a standardised framework for organising information about the collection of information about the environment. Here we describe the implementation of a specialisation of O&M for environmental data, the Metadata Objects for Linking Environmental Sciences (MOLES3). MOLES3 provides support for organising information about data, and for user navigation around data holdings. The implementation described here, “CEDA-MOLES”, also supports data management functions for the Centre for Environmental Data Archival, CEDA. The previous iteration of MOLES (MOLES2) saw active use over five years, being replaced by CEDA-MOLES in late 2014. During that period important lessons were learnt both about the information needed, as well as how to design and maintain the necessary information systems. In this paper we review the problems encountered in MOLES2; how and why CEDA-MOLES was developed and engineered; the migration of information holdings from MOLES2 to CEDA-MOLES; and, finally, provide an early assessment of MOLES3 (as implemented in CEDA-MOLES) and its limitations. Key drivers for the MOLES3 development included the necessity for improved data provenance, for further structured information to support ISO19115 discovery metadata export (for EU INSPIRE compliance), and to provide appropriate fixed landing pages for Digital Object Identifiers (DOIs) in the presence of evolving datasets. Key lessons learned included the importance of minimising information structure in free text fields, and the necessity to support as much agility in the information infrastructure as possible without compromising on maintainability both by those using the systems internally and externally (e.g. citing in to the information infrastructure), and those responsible for the systems themselves. The migration itself needed to ensure continuity of service and traceability of archived assets