Functional annotation signatures of disease susceptibility loci improve SNP association analysis.

BACKGROUND: Genetic association studies are conducted to discover genetic loci that contribute to an inherited trait, identify the variants behind these associations and ascertain their functional role in determining the phenotype. To date, functional annotations of the genetic variants have rarely played more than an indirect role in assessing evidence for association. Here, we demonstrate how these data can be systematically integrated into an association study's analysis plan. RESULTS: We developed a Bayesian statistical model for the prior probability of phenotype-genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs in the GWAS Catalog (GC). The functional predictors examined included measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super-track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants in the Database of Genomic Variants and known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotations would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non-informative predictors and evaluated the model's ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP's presence in the GC. Further, using data from a genome-wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome-wide scale and improves power to detect associations. CONCLUSIONS: We show how diverse functional annotations can be efficiently combined to create 'functional signatures' that predict the a priori odds of a variant's association to a trait and how these signatures can be integrated into a standard genome-wide-scale association analysis, resulting in improved power to detect truly associated variants.

AMERICAN WOMEN COMPOSERS: SELECTED PUBLISHED WORKS FOR FLUTE AND PIANO AND FOR UNACCOMPANIED FLUTE COMPOSED BETWEEN 1930 AND 2008

The music of women composers often comprises only a small percentage of flutists‘ repertoire, yet there are actually many active women composers, many of whom have written for the flute. The aim of this dissertation is to chronicle a selection of works by several American women composers that have contributed to accessible flute repertoire. For the purpose of this dissertation, accessibility is described by the following parameters: works that limit the use of extended techniques, works that are suitable for performers from high school through a reasonably advanced level, works that are likely to elicit emotionally musical communication from the performer to the listener, and works that are reasonably available through music stores or outlets on the Internet that have a fairly comprehensive reach to the general public. My subjective judgment also played a role in the final selection of the 25 works included as part of this dissertation, and performed on three musically well-balanced recitals. A variety of resources were consulted for the repertoire, including Boenke‘s Flute Music by Women Composers: An Annotated Catalog, and the catalogs of publishers such as Arsis Press and Hildegard Publishing, both of which specialize in the music of women composers. The works performed and discussed are the following: Adrienne Albert – Sunswept; Marion Bauer – Prelude and Fugue, Op. 43.; Marilyn Bliss – Lament; Ann Callaway – Updraft; Ruth Crawford – Diaphonic Suite; Emma Lou Diemer – Sonata; Vivian Fine – Emily’s Images; Cynthia Folio – Arca Sacra; Nancy Galbraith – Atacama; Lita Grier – Sonata; Jennifer Higdon – The Jeffrey Mode; Edie Hill – This Floating World; Katherine Hoover – Masks; Mary Howe – Interlude between Two Pieces; Laura Kaminsky – Duo; Libby Larsen – Aubade; Alex Shapiro – Shiny Kiss; Judith Shatin – Coursing Through the Still Green; Faye-Ellen Silverman – Taming the Furies; Augusta Read Thomas – Euterpe’s Caprice; Joan Tower – Valentine Trills; Ludmila Ulehla – Capriccio; Elizabeth Vercoe – Kleemation; Gwyneth Walker – Sonata; and Judith Lang Zaimont – ‘Bubble-Up’ Rag. All of these works are worthy alternatives to the more frequently played flute repertoire, and they serve as a good starting point for anyone interested i n exploring the works of women composers.

A run-time configurable software architecture for self-managing systems

This paper describes a highly flexible component architecture, primarily designed for automotive control systems, that supports distributed dynamically- configurable context-aware behaviour. The architecture enforces a separation of design-time and run-time concerns, enabling almost all decisions concerning runtime composition and adaptation to be deferred beyond deployment. Dynamic context management contributes to flexibility. The architecture is extensible, and can embed potentially many different self-management decision technologies simultaneously. The mechanism that implements the run-time configuration has been designed to be very robust, automatically and silently handling problems arising from the evaluation of self- management logic and ensuring that in the worst case the dynamic aspects of the system collapse down to static behavior in totally predictable ways.

Investigation into a modular rule-based testing method for testing business rules in scheduling applications

Rule testing in transport scheduling is a complex and potentially costly business problem. This paper proposes an automated method for the rule-based testing of business rules using the extensible Markup Language for rule representation and transportation. A compiled approach to rule execution is also proposed for performance-critical scheduling systems.

WPS orchestration using the Taverna workbench: The eScience approach

eScience is an umbrella concept which covers internet technologies, such as web service orchestration that involves manipulation and processing of high volumes of data, using simple and efficient methodologies. This concept is normally associated with bioinformatics, but nothing prevents the use of an identical approach for geoinfomatics and OGC (Open Geospatial Consortium) web services like WPS (Web Processing Service). In this paper we present an extended WPS implementation based on the PyWPS framework using an automatically generated WSDL (Web Service Description Language) XML document that replicates the WPS input/output document structure used during an Execute request to a server. Services are accessed using a modified SOAP (Simple Object Access Protocol) interface provided by PyWPS, that uses service and input/outputs identifiers as element names. The WSDL XML document is dynamically generated by applying XSLT (Extensible Stylesheet Language Transformation) to the getCapabilities XML document that is generated by PyWPS. The availability of the SOAP interface and WSDL description allows WPS instances to be accessible to workflow development software like Taverna, enabling users to build complex workflows using web services represented by interconnecting graphics. Taverna will transform the visual representation of the workflow into a SCUFL (Simple Conceptual Unified Flow Language) based XML document that can be run internally or sent to a Taverna orchestration server. SCUFL uses a dataflow-centric orchestration model as opposed to the more commonly used orchestration language BPEL (Business Process Execution Language) which is process-centric.

Molecular Computational Elements Encode Large Populations of Small Objects

Since the introduction of molecular computation1, 2, experimental molecular computational elements have grown3, 4, 5 to encompass small-scale integration6, arithmetic7 and games8, among others. However, the need for a practical application has been pressing. Here we present molecular computational identification (MCID), a demonstration that molecular logic and computation can be applied to a widely relevant issue. Examples of populations that need encoding in the microscopic world are cells in diagnostics or beads in combinatorial chemistry (tags). Taking advantage of the small size9 (about 1 nm) and large 'on/off' output ratios of molecular logic gates and using the great variety of logic types, input chemical combinations, switching thresholds and even gate arrays in addition to colours, we produce unique identifiers for members of populations of small polymer beads (about 100 m) used for synthesis of combinatorial libraries10, 11. Many millions of distinguishable tags become available. This method should be extensible to far smaller objects, with the only requirement being a 'wash and watch' protocol12. Our focus on converting molecular science into technology concerning analog sensors13, 14, turns to digital logic devices in the present work.

Special issue on design and programming of signal processors for multimedia communication:Special issue on design and programming of signal processors for multimedia communication

The technical challenges in the design and programming of signal processors for multimedia communication are discussed. The development of terminal equipment to meet such demand presents a significant technical challenge, considering that it is highly desirable that the equipment be cost effective, power efficient, versatile, and extensible for future upgrades. The main challenges in the design and programming of signal processors for multimedia communication are, general-purpose signal processor design, application-specific signal processor design, operating systems and programming support and application programming. The size of FFT is programmable so that it can be used for various OFDM-based communication systems, such as digital audio broadcasting (DAB), digital video broadcasting-terrestrial (DVB-T) and digital video broadcasting-handheld (DVB-H). The clustered architecture design and distributed ping-pong register files in the PAC DSP raise new challenges of code generation.

Troubled Geographies: A Spatial History of Religion and Society in Ireland

Ireland’s landscape is marked by fault lines of religious, ethnic, and political identity that have shaped its troubled history. Troubled Geographies maps this history by detailing the patterns of change in Ireland from 16th century attempts to “plant” areas of Ireland with loyal English Protestants to defend against threats posed by indigenous Catholics, through the violence of the latter part of the 20th century and the rise of the “Celtic Tiger.” The book is concerned with how a geography laid down in the 16th and 17th centuries led to an amalgam based on religious belief, ethnic/national identity, and political conviction that continues to shape the geographies of modern Ireland. Troubled Geographies shows how changes in religious affiliation, identity, and territoriality have impacted Irish society during this period. It explores the response of society in general and religion in particular to major cultural shocks such as the Famine and to long term processes such as urbanization.

The biology and functional anatomy of Modiolarca tumida (Musculus marmoratus) Bivalvia: Mytilidae

Modiolarca tumida (Hanley, 1843) is a member of the sub-family Crenellinae (Mytilidae). The preferred habitat of the species is the test of certain ascidians. The shell is dorsally flattened, which prevents it from cutting into the test during dorso-ventral contraction of the byssal retractors. The use of the byssus enables it to surround itself completely with host tissue. Adoption of the feeding posture involves the anterior-posterior contraction of the byssal retractors, which elevates the posterior margin above the host's surface using the anterior margin as the fulcrum against the host. Modiolarca tumida are attracted by the tunicin of the host, a process probably facilitated by the host's feeding currents. The smallest individuals are found round the oral aperture. Colonization of other parts of the host may result from surface migration as M. tumida can be highly mobile, crawling by means of the very extensible foot. It is during this process that individuals may be swept away in local currents and be forced to adopt a free-living existence.

Absolute Magnitudes of Pan-STARRS 1 Asteroids

It is well known that the absolute magnitudes (H) in the MPCORB and ASTORB orbital element catalogs suffer from a systematic offset. Juric at al. (2002) found 0.4 mag offset in the SDSS data and detailed light curve studies of WISE asteroids by Pravec et al. (2012) revealed size-dependent offsets of up to 0.5 mag. The offsets are thought to be caused by systematic errors introduced by earlier surveys using different photometric catalogs and filters. The next generation asteroid surveys provide an order of magnitude more asteroids and well-defined and calibrated magnitudes. The Pan-STARRS 1 telescope (PS1) has observed hundreds of thousands asteroids, submitted more than 2 million detections to the Minor Planet Center (MPC) and discovered almost 300 NEOs since the beginning of operations in late 2010. We transformed the observed apparent magnitudes of PS1-detected asteroids from the gP1,rP1,iP1,yP1,zP1 and wP1-bands into Johnson photometric system by assuming the mean S and C-type asteroid color (Fitzsimmons 2011 - personal communication, Schlafly et al. 2012, Magnier et al. 2012 - in preparation) and calculated the absolute magnitude (H) in the V-band and its uncertainty (Bowell et al., 1989) for more than 200,000 known asteroids having on average 6.7 detections per object. The H error with respect to the MPCORB catalog revealed a mean offset of -0.49+0.30 mag in good agreement with published values. We will also discuss the statistical and systematical errors in H and slope parameter G.

English Language Education at University: Trends and Challenges in Teaching and Learning Academic Discourse in the UK

This chapter discusses English Language Education at university and highlights a number of trends and their associated challenges in teaching and learning academic discourse. Academic discourse refers to the ways in which language is used by participants in academia. It encompasses written discourse, from article and book publishing, PhD theses to course assignments; spoken discourse, from study groups, tutorials, conference presentations to inaugural lectures; and more recently, computer-mediated discourse, from asynchronous text-based conferencing to academic blogs. The role of English language educators in preparing students and academics for successful participation in these academic events, or the academy, in English is not to be underestimated. Academic communication is not only vital to an individual’s success at university, but to the maintenance and creation of academic communities and to scientific progress itself (Hyland, 2009). This chapter presents an overview of academic discourse and discusses recent issues which have an impact on teaching and learning English at university and discusses their associated challenges: first, the increasing internationalisation of universities. Second, the emergence of a mobile academe in its broadest sense, in which students and academics move across traditional geopolitical, institutional and disciplinary boundaries, is discussed. Third, the growth of UK transnational higher education is examined as a trend which sees academics and students vicariously or otherwise involved in English language teaching and learning. Fourth, the chapter delves into the rapid and ongoing development in technology assisted and online learning. While responding to trends can be difficult, they can also inspire ingenuity. Furthermore, such trends and challenges will not emerge in the same manner in different contexts. The discussion in this chapter is illustrated with examples from a UK context but the implications of the trends and challenges are such that they reach beyond borders.

Selection of burst-like transients and stochastic variables using multi-brand image differencing in the Pan-STARRS1 Medium Deep Survey

We present a novel method for the light-curve characterization of Pan-STARRS1 Medium Deep Survey (PS1 MDS) extragalactic sources into stochastic variables (SVs) and burst-like (BL) transients, using multi-band image-differencing time-series data. We select detections in difference images associated with galaxy hosts using a star/galaxy catalog extracted from the deep PS1 MDS stacked images, and adopt a maximum a posteriori formulation to model their difference-flux time-series in four Pan-STARRS1 photometric bands gP1, rP1, iP1, and zP1. We use three deterministic light-curve models to fit BL transients; a Gaussian, a Gamma distribution, and an analytic supernova (SN) model, and one stochastic light-curve model, the Ornstein-Uhlenbeck process, in order to fit variability that is characteristic of active galactic nuclei (AGNs). We assess the quality of fit of the models band-wise and source-wise, using their estimated leave-out-one cross-validation likelihoods and corrected Akaike information criteria. We then apply a K-means clustering algorithm on these statistics, to determine the source classification in each band. The final source classification is derived as a combination of the individual filter classifications, resulting in two measures of classification quality, from the averages across the photometric filters of (1) the classifications determined from the closest K-means cluster centers, and (2) the square distances from the clustering centers in the K-means clustering spaces. For a verification set of AGNs and SNe, we show that SV and BL occupy distinct regions in the plane constituted by these measures. We use our clustering method to characterize 4361 extragalactic image difference detected sources, in the first 2.5 yr of the PS1 MDS, into 1529 BL, and 2262 SV, with a purity of 95.00% for AGNs, and 90.97% for SN based on our verification sets. We combine our light-curve classifications with their nuclear or off-nuclear host galaxy offsets, to define a robust photometric sample of 1233 AGNs and 812 SNe. With these two samples, we characterize their variability and host galaxy properties, and identify simple photometric priors that would enable their real-time identification in future wide-field synoptic surveys.

An Evaluation of Complex Adaptive Evolvable System Simulation

Thesis (Master's)--University of Washington, 2016-03