<p>In this work, I present four studies across the range of 'omics data types - a Genome- Wide Association Study for gene-by-sex interaction of obesity traits, computational models for transcription start site classification, an assessment of reference-based mapping methods for RNA-Seq data from non-model organisms, and a statistical model for open-platform proteomics data alignment.</p><p>Obesity is an increasingly prevalent and severe health concern with a substantial heritable component, and marked sex differences. We sought to determine if the effect of genetic variants also differed by sex by performing a genome-wide association study modeling the effect of genotype-by-sex interaction on obesity phenotypes. Genotype data from individuals in the Framingham Heart Study Offspring cohort were analyzed across five exams. Although no variants showed genome-wide significant gene-by-sex interaction in any individual exam, four polymorphisms displayed a consistent BMI association (P-values .00186 to .00010) across all five exams. These variants were clustered downstream of LYPLAL1, which encodes a lipase/esterase expressed in adipose tissue, a locus previously identified as having sex-specific effects on central obesity. Primary effects in males were in the opposite direction as females and were replicated in Framingham Generation 3. Our data support a sex-influenced association between genetic variation at the LYPLAL1 locus and obesity-related traits.</p><p>The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: focused promot- ers with transcription start sites (TSSs) that occur in a narrowly defined genomic span and dispersed promoters with TSSs that are spread over a larger window. Pre- vious studies have explored the presence of genomic features, such as CpG islands and sequence motifs, in these promoter classes, and our collaborators recently inves- tigated the relationship with chromatin features. It was found that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Here, we present computational models supporting the stronger contribution of chro- matin features to the definition of dispersed promoters compared to focused start sites. Specifically, dispersed promoters display enrichment for well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II. These differences extend to histone vari- ants (H2A.Z) and marks (H3K4 methylation), as well as insulator binding (such as CTCF), independent of the expression levels of affected genes.</p><p>The application of next-generation sequencing technology to gene expression quantification analysis, namely, RNA-Sequencing, has transformed the way in which gene expression studies are conducted and analyzed. These advances are of partic- ular interest to researchers studying non-model organisms, as the need for knowl- edge of sequence information is overcome. De novo assembly methods have gained widespread acceptance in the RNA-Seq community for non-model organisms with no true reference genome or transcriptome. While such methods have tremendous utility, computational complexity is still a significant challenge for organisms with large and complex genomes. Here we present a comparison of four reference-based mapping methods for non-human primate data. We explore mapping efficacy, correlation between computed expression values, and utility for differential expression analyses. We show that reference-based mapping methods indeed have utility in RNA-Seq analysis of mammalian data with no true reference, and that the details of mapping methods should be carefully considered when doing so. We find that shorter seed sequences, allowance of mismatches, and allowance of gapped alignments, in addition to splice junction gaps result in more sensitive alignments of non-human primate RNA-Seq data.</p><p>Open-platform proteomics experiments seek to quantify and identify the proteins present in biological samples. Much like differential gene expression analyses, it is often of interest to determine how protein abundance differs in various physiological conditions. Label free LC-MS/MS enables the rapid measurement of thousands of proteins, providing a wealth of peptide intensity information for differential analysis. However, the processing of raw proteomics data poses significant challenges that must be overcome prior to analysis. We specifically address the matching of peptide measurements across samples - an essential pre-processing step in every proteomics experiment. Presented here is a novel method for open-platform proteomics data alignment with the ability to incorporate previously unused aspects of the data, particularly ion mobility drift times and product ion data. Our results suggest that the inclusion of additional data results in higher numbers of more confident matches, without increasing the number of mismatches. We also show that the incorporation of product ion data can improve results dramatically. Based on these results, we argue that the incorporation of ion mobility drift times and product ion information are worthy pursuits. In addition, alignment methods should be flexible enough to utilize all available data, particularly with recent advancements in experimental separation methods. The addition of drift times and/or high energy to alignment methods and accurate mass and time (AMT) tag databases can greatly improve experimenters ability to identify measured peptides, reducing analysis costs and potentially the need to run additional experiments.</p> / Dissertation

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Durch die wachsende Bedeutung der DNS-Sequenzierung wurden die Geräte zur Sequenzierung weiterentwickelt und ihr Durchsatz so erhöht, dass sie Millionen kurzer Nukleotidsequenzen innerhalb weniger Tage liefern. Moderne Algorithmen und Programme, welche die dadurch entstehenden großen Datenmengen in akzeptabler Zeit verarbeiten können, ermitteln jedoch nur einen Bruchteil der Positionen der Sequenzen in bekannten Datenbanken. Eine derartige Suche ist eine der wichtigsten Aufgaben in der modernen Molekularbiologie. Diese Arbeit untersucht mögliche Übertragungen moderner Genom-Alignment Programme auf hochparallele Plattformen wie FPGA und GPU. Die derzeitig an das Problem angepassten Programme und Algorithmen werden untersucht und hinsichtlich ihrer Parallelisierbarkeit auf den beiden Plattformen FPGA und GPU analysiert. Nach einer Bewertung der Alternativen erfolgt die Auswahl eines Algorithmus. Anschließend wird dessen Übertragung auf die beiden Plattformen entworfen und implementiert. Dabei stehen die Geschwindigkeit der Suche, die Anzahl der ermittelten Positionen sowie die Nutzbarkeit im Vordergrund. Der auf der GPU implementierte reduzierte Smith & Waterman-Algorithmus ist effizient an die Problemstellung angepasst und erreicht für kurze Sequenzen höhere Geschwindigkeiten als bisherige Realisierungen auf Grafikkarten. Eine vergleichbare Umsetzung auf dem FPGA benötigt eine deutlich geringere Laufzeit, findet ebenfalls jede Position in der Datenbank und erreicht dabei ähnliche Geschwindigkeiten wie moderne leistungsfähige Programme, die aber heuristisch arbeiten. Die Anzahl der gefundenen Positionen ist bei FPGA und GPU damit mehr als doppelt so hoch wie bei sämtlichen vergleichbaren Programmen. / Further developments of DNA sequencing devices produce millions of short nucleotide sequences. Finding the positions of these sequences in databases of known sequences is an important problem in modern molecular biology. Current heuristic algorithms and programs only find a small fraction of these positions. In this thesis genome alignment algorithms are implemented on massively parallel platforms as FPGA and GPU. The next generation sequencing technologies that are currently in use are reviewed regarding their possible parallelization on FPGA and GPU. After evaluation one algorithm is chosen for parallelization. Its implementation on both platforms is designed and realized. Runtime, accuracy as well as usability are important features of the implementation. The reduced Smith & Waterman algorithm which is realized on the GPU outperforms similar GPU programs in speed and efficiency for short sequences. The runtime of the FPGA approach is similar to those of widely used heuristic software mappers and much lower than on the GPU. Furthermore the FPGA guarantees to find all alignment positions of a sequence in the database, which is more than twice the number that is found by comparable software algorithms.

The research field argues for the importance of aligning business and IT, since organizations that has conducted a high degree of alignment in general perform better than other organizations. This is not easy to achieve, aligning business and IT is still one of the top challenges for organizations. This study aims to examine previous research to identify and describe scientifically validated ways of achieving and keeping business and IT aligned. To do this a systematic literature review is conducted. The result from the systematic literature review is processed to identify similarities between the different ways of achieving and keeping business and IT aligned. The study contributes with a theoretical ground for future research and for interested students and practitioners who want to gain insights in the field.

Multiple sequence alignment is an important bioinformatics problem, with applications in diverse types of biological analysis, such as structure prediction, phylogenetic analysis and critical sites identification. In recent years, the quality of multiple sequence alignment was improved a lot by newly developed methods, although it remains a difficult task for constructing accurate alignments, especially for divergent sequences. In this dissertation, we propose three new methods (PSAlign, ISPAlign, and NRAlign) for further improving the quality of multiple sequences alignment. In PSAlign, we propose an alternative formulation of multiple sequence alignment based on the idea of finding a multiple alignment which preserves all the pairwise alignments specified by edges of a given tree. In contrast with traditional NP-hard formulations, our preserving alignment formulation can be solved in polynomial time without using a heuristic, while still retaining very good performance when compared to traditional heuristics. In ISPAlign, by using additional hits from database search of the input sequences, a few strategies have been proposed to significantly improve alignment accuracy, including the construction of profiles from the hits while performing profile alignment, the inclusion of high scoring hits into the input sequences, the use of intermediate sequence search to link distant homologs, and the use of secondary structure information. In NRAlign, we observe that it is possible to further improve alignment accuracy by taking into account alignment of neighboring residues when aligning two residues, thus making better use of horizontal information. By modifying existing multiple alignment algorithms to make use of horizontal information, we show that this strategy is able to consistently improve over existing algorithms on all the benchmarks that are commonly used to measure alignment accuracy.

The liquid crystal display on the liquid crystal alignment is known to be influenced by the rubbing strength. In the thesis, in order to figure out the best condition for homeotropic alignment, we add the number of rubbing, which causes the increase of the rubbing strength. In the experiment, we discuss two parts. The first part discusses the relation between polarity and liquid crystal. The instrument used mainly is contact angle measurement system, which measures the contact angle between liquid and sample and calculates the polarity, the dispersion and the surface free energy. In the second part, we change the rubbing strength to analyze the influence of liquid crystal cell. Also, we use the electro-optical measurement to analyze the cell which is fabricated by different rubbing strength. It is at this part that we focus on analyzing the optical texture, transmittance, contract ratio, and sharpness. The sample¡¦s polarity rises as the rubbing strength increases. It is the influence of the liquid crystal pretitle angles that the polarity as well as the liquid crystal cell¡¦s optical property changes. Such changes could be seen in transmittance, contract ratio and sharpness

Growth and sustainability seem to be the goals for all corporations. However, in the reality, only small number of corporations can sustain and keep growing; most corporations belong to one-shoot success or just stay stagnantly. Therefore, this study tried to figure out what is the main factor to make some corporations grow and the others decay. This study is based on an assumption that the main factor of corporation success depends on the alignment of corporate policies. If managers neglect the interactions of policies, it is possible to cause crises within the corporation and even make the corporation fall into decay. Only well-aligned policies can make corporations grow prosperously. Hence, policy design plays an important role to achieve the alignment. While going through the literatures on this subject, the domestic literatures are quit few. Therefore, this study has not only reviewed the relevant literatures, but also taken a domestic corporation as a studying case. This study used ¡§Systems Thinking¡¨ as a research tool to testify to the importance of dynamically aligned principles of the corporate policy design, and found the following conclusions: 1.Good intentions of the founder will lead to good corporation design, and the well-designed structure raises the intended behavior of employees. 2.Corporations have to design the policy base on long-term perspectives, and also develop the endurance to tolerate time delay. 3.Corporations should view the dynamically alignment of all policies as a whole and look for global optimization. 4.Well-designed policies will bring out the best operation performance.

This paper attempts to develop a dynamic alignment approach to leverage design of system dynamics models. The approach developed in this research is a flow-based design, different from traditional macro designs of aggregated system structures or loop analysis. It is grounded on some major concepts in Synchronous management at plants and uses the Drum-Buffer-Rope (DBR) system to align the various operations of rate decisions. This paper takes two famous system dynamics models as examples to examine the performance of the proposed leverage design method. One is the customer-producer-employment model, and the other is the market growth model. Both of the models are developed by Forrester(1961; 1968). By applying the dynamic alignment approach, the redesigned customer-producer-employment system shows that the original oscillation behavior can be fully eliminated, and the redesigned market growth model can sustain its growth pattern instead of stagnation or collapse. By comparison with previous high leverage design methods, the dynamic alignment approach developed in this paper is proved to be more efficient and robust for system redesign in different scenario.

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Thesis (Ph.D.)--University of Nebraska-Lincoln, 2009. / Title from title screen (site viewed October 13, 2009). PDF text: xv, 233 p. : ill. ; 4 Mb. UMI publication number: AAT 3360173. Includes bibliographical references. Also available in microfilm and microfiche formats.