M.S. / Computer Science and Engineering / Genome-wide studies are sensitive to the quality of annotation data included for analyses and they often involve overlaying both computationally derived and experimentally generated data onto a genomic scaffold. A framework for successful integration of data from diverse sources needs to address, at a minimum, the conceptualization of the biological identity in the data sources, the relationship between the sources in terms of the data present, the independence of the sources and, any discrepancies in the data. The outcome of the process should either resolve or incorporate these discrepancies into downstream analyses. In this thesis we identify factors that are important in detecting errors within and between sources and present a generalized framework to detect discrepancies. An implementation of our workflow is used to demonstrate the utility of the approach in the construction of a genome-wide mouse transcription factor binding map and in the classification of Single nucleotide polymorphisms. We also present the impact of these discrepancies on downstream analyses. The framework is extensible and we discuss future directions including summarization of the discrepancies in a biological relevant manner.

The first part of this research focused on wide-cross whole-genome radiation hybrid (WWRH) mapping of the cotton (Gossypium) genome. Radiation hybrid mapping has been used extensively to map the genomes of human and certain animal species, but not plant species. In lieu of in vitro hybrid cell line technologies for plants, we developed a novel approach for radiation hybrid mapping based on wide-cross in vivo hybridization. Flowers from one species of cotton, either G. hirsutum or G. barbadense, were -irradiated and then used to pollinate the other species. The resulting hybrid plants were assessed as a mapping tool. Two WWRH mapping panels were constructed from 5- and 8-krad -irradiation treatments. Both panels demonstrated that the WWRH mapping method can be used to map the cotton genome, and that this method complements traditional linkage mapping approaches. The second part of this research focused on the identification of cold-responsive genes using spotted oligo-gene microarray analysis. Increased cold-tolerance in cotton would promote early and uniform seedling establishment, expand the growing season, decrease susceptibility to fungal infections and certain diseases, and increase fiber yield and quality. BLAST searches of the cotton database using amino acid sequences of 93 drought/cold-related genes from Arabidopsis and several other plant species led to 806 cotton orthologous cDNAs and expressed sequence tags (ESTs). Eight hundred and six cotton 70-mer oligos were designed and included in an oligo-gene microarray containing 1,536 70-mer oligos, each representing a cDNA or EST from cotton, or one of 121 chloroplast genes or 66 mitochondrial genes from Arabidopsis. Thirty-eight cotton cDNAs and ESTs were identified as cold-responsive genes based on experimental treatment and oligo-gene microarray analysis. Expression was up-regulated for 36 genes and down-regulated for two genes by cold treatment. Results from microarray analysis were tested and confirmed by northern blot analysis for 16 genes. Our data suggest that Arabidopsis orthologous genes can be used to identify homologous cotton genes. The oligo-gene microarray is a valid approach to study transcriptional changes in cotton.

When students write research papers they use a variety of sources in their paper. These sources range from web pages to research articles. The purpose of this study was to decide whether or not undergraduate students would choose to use scholarly or non-scholarly sources when presented with both types of sources in a set of search results. Twenty Duke University students were recruited for the study. They were given a research topic and asked to perform a search. Both the search results and interface were fabricated by the researcher in order to control the experimental environment. The students were asked to rate the sources found in the results, choose four sources to use for their research scenario, and finally, were asked to explain reasoning behind their choices. The findings concluded that the students in this study were more likely to choose scholarly sources over non-scholarly sources and give these scholarly sources higher ratings.

Les données extraites du Web sont chargées d'incertitude: elles peuvent contenir des contradictions ou résulter de processus par nature incertains comme l'intégration de données ou l'extraction automatique d'informations. Dans cette thèse d'habilitation, je présente les modèles de données XML probabilistes, la manière dont ils peuvent être utilisés pour représenter les données du Web, et la complexité de différentes opérations de gestion de données sur ces modèles. Je donne un état de l'art exhaustif du domaine, en insistant sur mes propres contributions. Je termine par un résumé de mes futurs projets de recherche.

We propose a definition of aboutness topicality that not only encompasses individual denoting DPs, but also indefinites. We concentrate on the interpretative effects of marking indefinites as topics: they either receive widest scope in their clause, or they are interpreted in the restrictor of an overt or covert Q-adverb. We show that in the first case they are direct aboutness topics insofar as they are the subject of a predication expressed by the comment, while in the second case they are indirect aboutness topics: they define the subject of a higher-order predication – namely the set of situations that the respective Q-adverb quantifies over.

SiC MESFETs and GaN HEMTs have an enormous potential in high-power amplifiers at microwave frequencies due to their wide bandgap features of high electric breakdown field strength, high electron saturation velocity and high operating temperature. The high power density combined with the comparably high impedance attainable by these devices also offers new possibilities for wideband power microwave systems. In this thesis, Class C switching response of SiC MESFET in TCAD and two different generations of broadband power amplifiers have been designed, fabricated and characterized. Input and output matching networks and shunt feedback topology based on microstrip and lumped components have been designed, to increase the bandwidth and to improve the stability. The first amplifier is a single stage 26-watt using a SiC MESFET covering the frequency from 200-500 MHz is designed and fabricated. Typical results at 50 V drain bias for the whole band are, 22 dB power gain, 43 dBm output power, minimum power added efficiency at P 1dB is 47 % at 200 MHz and maximum 60 % at 500 MHz and the IMD3 level at 10 dB back-off from P 1dB is below ‑45 dBc. The results at 60 V drain bias at 500 MHz are, 24.9 dB power gain, 44.15 dBm output power (26 W) and 66 % PAE. In the second phase, two power amplifiers at 0.7-1.8 GHz without feed back for SiC MESFET and with feedback for GaN HEMT are designed and fabricated (both these transistors were of 10 W). The measured maximum output power for the SiC amplifier at Vd = 48 V was 41.3 dBm (~13.7 W), with a PAE of 32 % and a power gain above 10 dB. At a drain bias of Vd= 66 V at 700 MHz the Pmax was 42.2 dBm (~16.6 W) with a PAE of 34.4 %. The measured results for GaN amplifier are; maximum output power at Vd = 48 V is 40 dBm (~10 W), with a PAE of 34 % and a power gain above 10 dB. The SiC amplifier gives better results than for GaN amplifier for the same 10 W transistor. A comparison between the physical simulations and measured device characteristics has also been carried out. A novel and efficient way to extend the physical simulations to large signal high frequency domain was developed in our group, is further extended to study the class-C switching response of the devices. By the extended technique the switching losses, power density and PAE in the dynamics of the SiC MESFET transistor at four different frequencies of 500 MHz, 1, 2 and 3 GHz during large signal operation and the source of switching losses in the device structure was investigated. The results obtained at 500 MHz are, PAE of 78.3%, a power density of 2.5 W/mm with a switching loss of 0.69 W/mm. Typical results at 3 GHz are, PAE of 53.4 %, a power density of 1.7 W/mm with a switching loss of 1.52 W/mm. / Report code: LIU-TEK-LIC-2008:32

Denna studie avser att undersöka och analysera fyra verksamma lärares uppfattningar om det vidgade textbegrepp som uttrycks i kursplanen i svenska 2000 och vilken betydelse deras uppfattning om det begreppet får för elevers undervisning i svenskämnet. Studien ska dessutom undersöka och analysera deras uppfattningar om hur ett vidgat textbegrepp kan förstås och relateras gentemot styrdokumenten i svenskämnet. För att fånga fyra lärares uppfattningar om ett vidgat textbegrepp och vilken betydelse deras uppfattning får för deras elevers svenskundervisning, har intervjuer genomförts i grundskolan med fyra lärare i år 6-9. Förhoppningen var att dessa intervjuer skulle ge en bild av verksamma lärares uppfattning om ett vidgat textbegrepp och hur det gestaltas i deras undervisning. Resultatdelen i uppsatsen upplyser om de fyra lärarnas olika uppfattningar om ett vidgat textbegrepp och vilken betydelse det får för elevers undervisning i svenskämnet. The purpose of this study is to examine and analyze the understanding, of four teachers, about the wide text concept as it is put in the Swedish curriculum of 2000, and what meaning their opinion has for their teaching in Swedish arts. Furthermore it will look into and analyze their comprehension about how a wide text concept can be understood and be related to the governing documents in Swedish arts. In order to catch the opinion about the wide text concept of four teachers and to see what significance their comprehension about it shows in their teaching, we have interviewed four teachers of Swedish arts in the years 6-9. The expectation was that these interviews should picture active teachers understanding about a wide text concept and how it is shown in their teaching. The result part in this essay informs about these four teachers different comprehension about a wide text concept and what significance it gets for the teaching of their students in Swedish arts.

Systemic Lupus Erythematosus (SLE) is a chronic multi-organ autoimmune disease considered a prototype for autoantibody and immune complex-mediated tissue injury. Although autoantibodies against a wide diversity of self-antigens are characteristically found in this disease, an important hallmark is the presence of autoantibodies to nuclear antigens. Despite this common clinical feature, individual patients vary widely in the organ systems afflicted, disease severity, disease course, and response to treatment. These characteristics make clinical management of SLE challenging and highlight the need for effective and less toxic therapeutic interventions. Susceptibility to lupus has been shown in both human studies and mouse models to be dependent on genetic predisposition. Therefore, it is likely that knowledge of the genetic basis of SLE will be required before full understanding of SLE pathogenesis can be achieved. In this thesis, studies to define the genetic basis of lupus in an induced and two spontaneous models of the disease are presented. These studies encompass mapping, characterization of interval congenic mice, and cloning of the Lmb3 locus gene. In the first study, a genomewide mapping study was performed to define the genetic basis for resistance of the DBA/2 mice to mercury-induced autoimmunity. On chromosome 1, a single quantitative trait was linked with resistance to HgIA. These results linked the locus Hmr1 to a late stage of lupus with GN. Interval congenic mice are important tools to define and characterize the roles of different loci in lupus-like diseases. The second paper identifies the effect of NZB and NZW Lbw2 alleles on lupus susceptibility by using BWF1 mice with none, one or two copies of the lupus-predisposing NZB.Lbw2 locus. The lack of the NZB locus significantly reduced mortality, GN and B cell activation. IgM anti-chromatin levels in genome-wide mapping was linked only to Lmb2 and none of the known B cell hyperactivity-promoting genes were present in this location, which might indicate a novel B cell activation gene. The third study used reciprocal single locus interval-specific congenic mice to characterize the contribution of Lmb1-4 on the MRL-Faslpr and B6-Faslpr backgrounds. The Lmb3 locus on chromosome 7 was found to have the most prominent phenotype with clear effects on lymphoproliferation, GN and mortality. In the fourth paper the Lmb3 was cloned and shown to be a spontaneous nonsense mutation in the Coro1a gene that encodes an actin-binding and -regulatory protein. Upon further characterization, this genetic alteration was discovered to be a new lupus suppressing mutation that reduced T cell migration, activation, and survival. Our findings highlight the complexity of the genetics of lupus, and further suggest that genes involved in controlling the actin cytoskeleton might be potential targets for autoimmune therapeutics.

The purpose of this qualitative study was to examine a problem of practice present in an actual school district. The study examined School-Wide Positive Behavior Support Implementation as it relates to the recidivism rates of students of color in the in-school suspension setting. Over the course of one school year, the perceptions of seven middle school teachers, three parents, and two administrators were explored in a suburban middle school in Southeast Texas. Although In-school suspension programs exist in every American public school to some degree, little research has been done in regards to the academic outcomes associated with those who are frequently placed in this campus based disciplinary alternative educational placement. In many of these "placement" many of the students assigned are not afforded access to instructional materials, supplies, or a certified teacher. Since the enactment of the federal No Child Left Behind Act (2001), the achievement gap has been discussed and studied. However, few studies have been done to understand how the current practices in in-school suspension contribute to the achievement gap specifically among students of color. This study examined key stakeholder's perceptions of School-Wide Positive Behavior Supports, and In-school suspension as a vehicle for referral reduction and removal of middle school students from their academic setting. The participants were "key-stakeholder" parents, teachers, and administrators who educate students at Caden Middle School. Findings from this problem of practice indicated that not only was the campus not imploring consistent practices and interventions related to and promoted by the SWPBS system in the in-school suspension setting, many of the staff members teachers and administrators alike did not adhere to the philosophical tenants of the SWPBS within the general classroom setting. The research presented in the record of study, identified gaps in both perceptions and understanding among key stakeholders in regards both in-school suspension and the school-wide positive behavior support systems at Caden Middle School. Results of this from this problem of practice found a severe disconnect in understanding the purpose and rationale of SWPBS among the administrators, teachers, and parents that participated in this study. Furthermore, the variance in the "self-sense making" done by each of the stakeholder groups after campus leadership failed to communicate, support, and sustain district expectations for program implementation with fidelity. Initiatives implemented through the investigation of the questions related to this problem of practice assisted in providing relevant professional development to re-solicit teacher and staff buy-in, prioritization of organization goals, and engaging teacher leadership to re-implement SWPBS to countermand system practices that were contrary to the district's original expectations.

Stroke is a common multi factorial cerebrovascular disorder with a large impact on global health. It is a disorder primarily associated with old age but environmental factors, lifestyle choices and medical history are all important for the risk of developing the disorder. It is also known that heritability is important for predisposition to the disorder. The aim of this work has been to identify genetic variations that increase the risk of being affected by stroke in the population of northern Sweden, a population well apt for genetic studies due to well kept church and medical records together with limited genetic diversity. In the first paper we used linkage analysis in families with early onset of stroke. By this approach we identified a region on chromosome 5q to be linked to an increased risk of developing stroke, a region previously identified as a susceptibility locus for stroke in the Icelandic population. In the second study we used genealogy to identify common ancestry and thereby identify common susceptibility to stroke. The seven families we connected showed significant linkage to the chromosome 9q31-33 region and four of the families shared a common haplotype over 2.1 megabases. In the third manuscript we investigated sequence variation of two candidate genes, TNFSF15 and TLR4. Sequencing of the TLR4 gene revealed previously identified variations in affected individuals from two of the families. Further SNP analysis showed five separate haplotypes among the investigated families and four haplotypes for TNFSF15. However none of these co-segregated with stroke among the investigated families. In the final paper we used a case-control stroke cohort to ascertain association for genetic variation in five genes and genetic regions previously suggested to be linked with stroke. Initial analyses showed association for the 9p21 chromosomal region and a variant in Factor 5 that showed protection against stroke, but after adjustments for common risk factors for stroke, the findings were no longer significant. In conclusion, by studying selected families we have been able to show linkage to two chromosomal regions, 5q and 9q31-33, that indicate genetic predisposition for developing stroke. Further we have shown that family based studies are still an important tool in deciphering the underlying mechanisms for complex disease.