Identification and validation of copy number variants using SNP genotyping arrays from a large clinical cohort.

BACKGROUND: Genotypes obtained with commercial SNP arrays have been extensively used in many large case-control or population-based cohorts for SNP-based genome-wide association studies for a multitude of traits. Yet, these genotypes capture only a small fraction of the variance of the studied traits. Genomic structural variants (GSV) such as Copy Number Variation (CNV) may account for part of the missing heritability, but their comprehensive detection requires either next-generation arrays or sequencing. Sophisticated algorithms that infer CNVs by combining the intensities from SNP-probes for the two alleles can already be used to extract a partial view of such GSV from existing data sets. RESULTS: Here we present several advances to facilitate the latter approach. First, we introduce a novel CNV detection method based on a Gaussian Mixture Model. Second, we propose a new algorithm, PCA merge, for combining copy-number profiles from many individuals into consensus regions. We applied both our new methods as well as existing ones to data from 5612 individuals from the CoLaus study who were genotyped on Affymetrix 500K arrays. We developed a number of procedures in order to evaluate the performance of the different methods. This includes comparison with previously published CNVs as well as using a replication sample of 239 individuals, genotyped with Illumina 550K arrays. We also established a new evaluation procedure that employs the fact that related individuals are expected to share their CNVs more frequently than randomly selected individuals. The ability to detect both rare and common CNVs provides a valuable resource that will facilitate association studies exploring potential phenotypic associations with CNVs. CONCLUSION: Our new methodologies for CNV detection and their evaluation will help in extracting additional information from the large amount of SNP-genotyping data on various cohorts and use this to explore structural variants and their impact on complex traits.

Iowa DOT GeoMedia Training Manual,1998.

The varying title of this manual is : Coordinated Transportation Analysis and Management System. It gives instructions on how to use GeoMedia in order to integrate data from multiple sources and formats into one environment, perform sophisticated queries and spatial analyses, and quickly produce complex maps.

MEPDG Work Plan Task No. 5: Characterization of Unbound Materials (Soils/Aggregates) for Mechanistic-Empirical Pavement Design Guide, 2009

The resilient modulus (MR) input parameters in the Mechanistic-Empirical Pavement Design Guide (MEPDG) program have a significant effect on the projected pavement performance. The MEPDG program uses three different levels of inputs depending on the desired level of accuracy. The primary objective of this research was to develop a laboratory testing program utilizing the Iowa DOT servo-hydraulic machine system for evaluating typical Iowa unbound materials and to establish a database of input values for MEPDG analysis. This was achieved by carrying out a detailed laboratory testing program designed in accordance with the AASHTO T307 resilient modulus test protocol using common Iowa unbound materials. The program included laboratory tests to characterize basic physical properties of the unbound materials, specimen preparation and repeated load triaxial tests to determine the resilient modulus. The MEPDG resilient modulus input parameter library for Iowa typical unbound pavement materials was established from the repeated load triaxial MR test results. This library includes the non-linear, stress-dependent resilient modulus model coefficients values for level 1 analysis, the unbound material properties values correlated to resilient modulus for level 2 analysis, and the typical resilient modulus values for level 3 analysis. The resilient modulus input parameters library can be utilized when designing low volume roads in the absence of any basic soil testing. Based on the results of this study, the use of level 2 analysis for MEPDG resilient modulus input is recommended since the repeated load triaxial test for level 1 analysis is complicated, time consuming, expensive, and requires sophisticated equipment and skilled operators.

The Half-Life of Election Pledges : What makes MPs change their positions?

"Thou shalt not bear false witness," as we all know. Yet changing one's mind in case of respectable reasons seems to be allowed. Which is good news for politicians, but reduces the effectiveness of prospective voting, i.e. the focus on "the commitments of candidates to take actions that citizens desire to be taken" (Powell 2000: 9). This may be bad news for voters. By comparing pre-election commitments of Swiss members of parliament (MPs) with actual voting behaviour in the lower house of parliament, the following article explores the question how much confidence voters can have in prospective voting and what factors explain (non-)fulfilment of election pledges.

Elections Laws of Iowa, 2013

This publication is produced by the Legislative Services Agency. This publication contains all election laws to be included in the 2014 Iowa Code. Changes in Code language to be included in the 2014 Iowa Code are marked by highlighting in yellow. Code sections with changes are also highlighted in yellow in the Table of Contents.

EADock: docking of small molecules into protein active sites with a multiobjective evolutionary optimization.

In recent years, protein-ligand docking has become a powerful tool for drug development. Although several approaches suitable for high throughput screening are available, there is a need for methods able to identify binding modes with high accuracy. This accuracy is essential to reliably compute the binding free energy of the ligand. Such methods are needed when the binding mode of lead compounds is not determined experimentally but is needed for structure-based lead optimization. We present here a new docking software, called EADock, that aims at this goal. It uses an hybrid evolutionary algorithm with two fitness functions, in combination with a sophisticated management of the diversity. EADock is interfaced with the CHARMM package for energy calculations and coordinate handling. A validation was carried out on 37 crystallized protein-ligand complexes featuring 11 different proteins. The search space was defined as a sphere of 15 A around the center of mass of the ligand position in the crystal structure, and on the contrary to other benchmarks, our algorithm was fed with optimized ligand positions up to 10 A root mean square deviation (RMSD) from the crystal structure, excluding the latter. This validation illustrates the efficiency of our sampling strategy, as correct binding modes, defined by a RMSD to the crystal structure lower than 2 A, were identified and ranked first for 68% of the complexes. The success rate increases to 78% when considering the five best ranked clusters, and 92% when all clusters present in the last generation are taken into account. Most failures could be explained by the presence of crystal contacts in the experimental structure. Finally, the ability of EADock to accurately predict binding modes on a real application was illustrated by the successful docking of the RGD cyclic pentapeptide on the alphaVbeta3 integrin, starting far away from the binding pocket.

The relationship between Lamb weather types and long-term changes in flood frequency, River Eden, UK

Research has found that both flood magnitude and frequency in the UK may have increased over the last five decades. However, evaluating whether or not this is a systematic trend is difficult because of the lack of longer records. Here we compile and consider an extreme flood record that extends back to 1770. Since 1770, there have been 137 recorded extreme floods. However, over this period, there is not a unidirectional trend of rising extreme flood risk over time. Instead, there are clear flood-rich and flood-poor periods. Three main flood-rich periods were identified: 18731904, 19231933, and 1994 onwards. To provide a first analysis of what is driving these periods, and given the paucity of more sophisticated datasets that extend back to the 18th century, objective Lamb weather types were used. Of the 27 objective Lamb weather types, only 11 could be associated with the extreme floods during the gauged period, and only 5 of these accounted for > 80% of recorded extreme floods The importance of these five weather types over a longer timescale for flood risk in Carlisle was assessed, through calculating the proportion of each hydrological year classified as being associated with these flood-generating weather types. Two periods clearly had more than the average proportions of the year classified as one of the flood causing weather types; 19001940 and 19832007; and these two periods both contained flood-rich hydrological records. Thus, the analysis suggests that systematic organisation of the North Atlantic climate system may be manifest as periods of elevated and reduced flood risk, an observation that has major implications for analyses that assume that climatic drivers of flood risk can be either statistically stationary or are following a simple trend. Copyright (c) 2011 Royal Meteorological Society

Characterization of Fly Ash for Use in Concrete, HR-225, 1983

Recent construction of new generation power plants burning western coal within Iowa has resulted in fly Ash production on the order of 760,000 tons annually. Although fly ash has long been accepted as a valuable replacement for portland cement in concrete, most experience has been with fly ash generated from eastern bituminous coals. A few years ago, fly ash in Iowa was not a significant factor because production was small and economics dictated disposal as the better alternative than construction use. Today, the economic climate, coupled with abundance of the material, makes constructive use in concrete feasible. The problem is, however, fly ash produced from new power plants is different than that for which information was available. It seems fly ash types have outgrown existing standards. The objective of this study was to develop fundamental information about fly ashes available to construction in Iowa such that its advantages and limitations as replacement to portland cement can be defined. Evaluative techniques used in this work involve sophisticated laboratory equipment, not readily available to potential fly ash users, so a second goal was preliminary development of rapid diagnostic tests founded on fundamental information. Lastly, Iowa Department of Transportation research indicated an interesting interdependency among coarse aggregate type, fly ash and concrete's resistance to freeze-thaw action. Thus a third charge of this research project was to verify and determine the cause for the phenomena. One objective of this project was to determine properties of Iowa fly ashes and evaluate their relevance to use of the material as an admixture of PCC. This phase of the research involved two approaches. The first involved the development of a rapid method for determining quantitative elemental composition while the second was aimed at both qualitative and quantitative determination of compounds. X-ray fluorescence techniques were adapted for rapid determination of elemental composition of fly ash. The analysis was performed using a Siemens SR-200 sequential x-ray spectrometer controlled by a PDP-11-03 microcomputer. The spectrometer was equipped with a ten sample specimen chamber and four interchangeable analyzing crystals. Unfiltered excitation radiation was generated using a chromium tube at 50 KV and 48 ma. Programs for the spectrometer were developed by the Siemens Corporation.

DCI Voter Fraud Investigations Report, May 8, 2014.

In March of 2012, the Iowa Secretary of State’s office compared Iowa’s voter registration records with the driver’s license record s of individuals that identified themselves as non-citizens with the Iowa Department of Transportation. After comparing those records, the Iowa Secretary of State’s office found that more than 3,000 individuals registered to vote that had previously identified themselves as non-citizens. More than 1,000 of these individuals had also cast a ballot. The Iowa Secretary of State’s office was not given timely access to the federal Systematic Alien Verification for Entitlements (SAVE)database, and therefore was unable to determine if any of these individuals had become citizens before they registered to vote or cast a ballot. On June 21, 2012, the Iowa Secretary of State’s office entered into an agreement with the Iowa Department of Public Safety’s Division of Criminal Investigation (DCI) to review potential election misconduct crimes and improve the administration of federal elections. Over the last two years,DCI agents have reviewed thousands of instances of possible election misconduct. DCI’s review included cases referred by the Iowa Secretary of State’s office as well as by other state and local government agencies.

Iowa Flood Mitigation Board Annual Report, 2013

The Iowa Flood Mitigation Program is created within Code of Iowa, Chapter 418. The Program seeks to provide funds for flood mitigation projects that otherwise would not be funded. The Flood Mitigation Board is responsible for the implementation Code of Iowa Chapter 418. The membership of the Board is comprised of four voting public members appointed by the Governor, five voting members representing state agencies, and four non-voting ex-officio members of the legislature.

A simple gas chromatography method for the analysis of monoethanolamine in air

A simple method determining airborne monoethanolamine has been developed. Monoethanolamine determination has traditionally been difficult due to analytical separation problems. Even in recent sophisticated methods, this difficulty remains as the major issue often resulting in time-consuming sample preparations. Impregnated glass fiber filters were used for sampling. Desorption of monoethanolamine was followed by capillary GC analysis and nitrogen phosphorous selective detection. Separation was achieved using a specific column for monoethanolamines (35% diphenyl and 65% dimethyl polysiloxane). The internal standard was quinoline. Derivatization steps were not needed. The calibration range was 0.5-80 μg/mL with a good correlation (R(2) = 0.996). Averaged overall precisions and accuracies were 4.8% and -7.8% for intraday (n = 30), and 10.5% and -5.9% for interday (n = 72). Mean recovery from spiked filters was 92.8% for the intraday variation, and 94.1% for the interday variation. Monoethanolamine on stored spiked filters was stable for at least 4 weeks at 5°C. This newly developed method was used among professional cleaners and air concentrations (n = 4) were 0.42 and 0.17 mg/m(3) for personal and 0.23 and 0.43 mg/m(3) for stationary measurements. The monoethanolamine air concentration method described here was simple, sensitive, and convenient both in terms of sampling and analytical analysis.

Elections Laws of Iowa, 2014

This publication is produced by the Legislative Services Agency. This publication contains all election laws to be included in the 2014 Iowa Code. Changes in Code language to be included in the 2014 Iowa Code are marked by highlighting in yellow. Code sections with changes are also highlighted in yellow in the Table of Contents.

A Carrot and Stick Approach to Agenda-Setting

This paper models a legislature in which the same agenda setter serves for two periods, showing how he can exploit a legislature (completely) in the first period by promising future benefits to legislators who support him. In equilibrium, a large majority of legislators vote for the first-period proposal because they thereby maintain the chance of belonging to the minimum winning coalition in the future. Legislators may therefore approve policies by large majorities, or even unanimously, that benefit few, or even none, of them. The results are robust; but institutional arrangements (such as entitlements) can reduce the agenda setter's power by reducing his discretion to reward and punish legislators, and rules (such as sequential voting) can increase a legislator's ability to resist exploitation. Keywords: Legislative bargaining, distributive politics, agenda-setting, proposal power. JEL C72, D72, D78.

Bases Teóricas y Herramientas para el Análisis y Comparación de Sistemas de Votación de Código Abierto

Dentro del proceso de definición de las vías de participación en el PLAN DIRECTOR DE PARTICIPACIÓN CIUDADANA 2010-2015 del Ayuntamiento de Barcelona, se plantea la necesidad de fomentar mecanismos de participación directa y a, partir de esta necesidad, se plantea el desarrollo de una aplicación de Consultas Populares.Dentro de los procesos participativos, las consultas a realizar pueden ser vinculantes y por tanto resulta de la mayor importancia fundamentar su desarrollo garantizando la corrección formal de todo el proceso.Entre los requerimientos, especificados por en Instituto Municipal de Informática, el sistema de votación a plantear debe estar cubierto por alguna de las licencias consideradas libres o de código abierto. Una de las principales características de este tipo de aplicaciones es que resulta posible la utilización y modificación del código.Como primer paso se definen los conceptos básicos implicados comenzando con la del propio concepto de e-Voting. A partir de las experiencias previas realizadas en nuestro entorno geográfico, es posible establecer que los estándares más utilizados son los generados por el Consejo de Europa, qué utilizaremos para concretar las diferentes fases de un Proceso de Consulta, los actores implicados así como las diferentes funciones a de cada uno de ellos para cada una de las fases.Sobre esta base se analizan las diferentes alternativas existentes entre lo que se denominan Esquemas de Votación. Centrándonos en el escogido como más conveniente, el Esquema de Voto Oculto, se describen las características de seguridad que permiten dar validez a un proceso de consulta realizado por este medio. Así mismo se describen los principales conceptos teóricos implicados mediante una aproximación que permita su comprensión de forma intuitiva, especialmente en lo que se refiere a las técnicas criptográficas implicadas.En tercer lugar se ha realizado una búsqueda de posibles aplicaciones que sirvan de punto de partida y se han hecho pruebas comparativas para las cuales se han adaptado las herramientas correspondientes a QSOS, relacionando los estándares especificados por el Consejo Europeo y las características de seguridad que deben cumplirse.

Learning about Bayesian networks for forensic interpretation : An example based on the "the problem of multiple propositions"

Both, Bayesian networks and probabilistic evaluation are gaining more and more widespread use within many professional branches, including forensic science. Notwithstanding, they constitute subtle topics with definitional details that require careful study. While many sophisticated developments of probabilistic approaches to evaluation of forensic findings may readily be found in published literature, there remains a gap with respect to writings that focus on foundational aspects and on how these may be acquired by interested scientists new to these topics. This paper takes this as a starting point to report on the learning about Bayesian networks for likelihood ratio based, probabilistic inference procedures in a class of master students in forensic science. The presentation uses an example that relies on a casework scenario drawn from published literature, involving a questioned signature. A complicating aspect of that case study - proposed to students in a teaching scenario - is due to the need of considering multiple competing propositions, which is an outset that may not readily be approached within a likelihood ratio based framework without drawing attention to some additional technical details. Using generic Bayesian networks fragments from existing literature on the topic, course participants were able to track the probabilistic underpinnings of the proposed scenario correctly both in terms of likelihood ratios and of posterior probabilities. In addition, further study of the example by students allowed them to derive an alternative Bayesian network structure with a computational output that is equivalent to existing probabilistic solutions. This practical experience underlines the potential of Bayesian networks to support and clarify foundational principles of probabilistic procedures for forensic evaluation.