Identification of the mechanisms by which genes are regulated in eukaryotes is one of the principal challenges of modern biology. The emergence of genome sequencing has facilitated the marked expansion of experimental and computational approaches designed to address this challenge. Integrating and assessing this information remains a major scientific endeavor that requires new and innovative application of technology. Furthermore, our limited understanding of the mechanisms of gene regulation in eukaryotes has undermined our ability to understand the role of genetics in gene regulation. Regulatory variants are thought to be responsible for a considerable amount of the heterogeneity within our population and to be fundamental determinants of health. New experimental approaches offer the opportunity to effectively identify markers of disease susceptibility in gene regulatory regions but the discovery of the molecular mechanism of dysregulation remains difficult and time-consuming. It is here where computational approaches are required to prioritize candidate regulatory variants. To do so requires the development of an extensive control set from which characteristic signals can be identified. This thesis introduces novel approaches for discovering, utilizing, comparing and visualizing regulatory element predictions in completed genomes. This thesis also introduces novel bioinformatics infrastructure for curating regulatory element and variant datasets, and introduces the largest-available, open-access dataset of functional regulatory variants hand-curated from literature. This dataset is used to identify signals which discriminate functional variants from other variants in the promoter regions of human genes using regulatory and population genetics-based computational approaches.

Versican, a chondroitin sulfate proteoglycan, is one of the main components of the extracellular matrix and hence plays a central role in tissue morphogenesis and a number of pathologic processes. My main goal has been to investigate the mechanisms of versican gene regulation, focusing on the signal transduction pathways, promoter regions, cis-acting elements,and trans- factors. This thesis puts forth new knowledge regarding transcriptional regulation of the human versican gene. In chapter III, I present the cloning of a 752-bp fragment of the human versican promoter (- 634/+118 bp) and nine stepwise 5' deletion fragments in the PGL3-luciferase reporter plasmid. Furthermore, I identify three potential enhancer and two repressor regions in this promoter. I also demonstrate that both cAMP and C/EBPf3 enhanced and repressed versican transcription in HeLa cells and rat aortic smooth muscle cells (SMC),respectively, suggesting that versican transcription is differentially regulated by the respective mediator and transcription factor in epithelial cells and SMC. In chapter IV, I reveal the role ofPI3K/PKB/GSK-30 signaling pathway in regulating versican promoter activity and transcription. Furthermore, I identify that the 0-catenin/TCF-4 transcription factor complex, one of the downstream targets of GSK-3[3, mediates versican promoter activity and transcription. In chapter V, I identify that variations in C-terminal regions of TCF family members determine the irrepressor or enhancer properties on Wnt target genes. Furthermore, I show that curcumin is a strong inhibitor of the P-catenin/TCF-p300 mediated gene expression. In chapter VI, I demonstrate that the androgen receptor trans-activates versican transcription in prostate cancer cells. Furthermore, I show cross-talk between the androgen receptor and 13-catenin in regulating versican transcription in prostate stromal fibroblasts. Overall, this study charts previously uncharacterized promoter elements, transcription factors, and signal transduction pathways involved in regulation of the versican gene.

Identification of the mechanisms by which genes are regulated in eukaryotes is one of the principal challenges of modern biology. The emergence of genome sequencing has facilitated the marked expansion of experimental and computational approaches designed to address this challenge. Integrating and assessing this information remains a major scientific endeavor that requires new and innovative application of technology. Furthermore, our limited understanding of the mechanisms of gene regulation in eukaryotes has undermined our ability to understand the role of genetics in gene regulation. Regulatory variants are thought to be responsible for a considerable amount of the heterogeneity within our population and to be fundamental determinants of health. New experimental approaches offer the opportunity to effectively identify markers of disease susceptibility in gene regulatory regions but the discovery of the molecular mechanism of dysregulation remains difficult and time-consuming. It is here where computational approaches are required to prioritize candidate regulatory variants. To do so requires the development of an extensive control set from which characteristic signals can be identified. This thesis introduces novel approaches for discovering, utilizing, comparing and visualizing regulatory element predictions in completed genomes. This thesis also introduces novel bioinformatics infrastructure for curating regulatory element and variant datasets, and introduces the largest-available, open-access dataset of functional regulatory variants hand-curated from literature. This dataset is used to identify signals which discriminate functional variants from other variants in the promoter regions of human genes using regulatory and population genetics-based computational approaches.

The concept of emotion and how to regulate it is a central aspect of modern psychology. Within the process model of emotion regulation (Gross, 1998), one issue is how attentional deployment affects emotion regulation and how this can be measured. In task 1, pictures of positive or negative valence were showed in two conditions, either attend or decrease emotional reaction, while participants’ eye movements were followed with an eye tracker. Ratings of arousal and valence were significantly affected by instruction, but dwell times were only significant for positive pictures. In task 2, participants were directed either to emotional or non-emotional parts of emotional pictures while skin conductance was recorded. Arousal and valence ratings decreased significantly in non-emotional areas, but no effect could be found for skin conductance data. Results were generally weak in regards to the effectiveness of measuring gaze to indicate emotion regulation in the form of attentional deployment. For future studies, research of individual differences in habitual usage of attentional deployment for emotion regulation was suggested.

In his 1757 essay “Of Tragedy”, Hume reflected on a curious puzzle about emotions. Sometimes people seek out emotions or experiences that are typically negative and associated with displeasure or pain. People often desire to watch horror films that will make them scared or listen to music that will make them sad. Some people even engage in the pursuit of negative emotions on a regular basis such as in the case of thrill-seeking. In this paper my goal is to update Hume’s puzzle with empirical evidence from the affective sciences and argue for two conclusions. First I will argue that Hume’s puzzle still runs deep. Though some recent scientific and philosophical accounts of emotions have tried to solve it, they have thus far failed. Second I attempt to construct a psychological account that solves the puzzle. Instead of focusing on how emotions are generated as previous theories have done, I argue that what is important is how emotions are regulated.

In todays GSM network more and more interfaces are run over IP instead of classic synchronized networks. This rises new issues to be solved, for example handling of jitter that use of IP networks introduces. The jitter can be handled by a jitter buffer which ensures that the packets are forwarded in evenly spaced intervals. In GSM, data is requested a certain time in advance before delivery to a cellphone. This "time in advance" needs to be adjusted according to the delay of the channel. For an IP network this delay varies (jitter), which means that it would be beneficial to have an algorithm which continuously adjusts how long in advance the packets should be requested. The adjustment is made according to current channel delay and jitter size. In this thesis work a model of a general IP network has been developed and isthen used for development of two algorithms for jitter buffer handling. Once the algorithms have been developed they are evaluated and compared to each other and previous solutions to the problem. One of the algorithms is new and the other is an already existing algorithm that has been extended. The simplified conclusion is that the behaviors of both algorithms are very similar. They mainly have small packet loss but sometimes the packets are requested earlier than needed and therefore are kept in the buffer a bit longer than necessary. When comparing the two developed algorithms with previous solutions it is visible that they improve the buffer handling a great deal.

People with high (HSEs) and low self-esteem (LSEs) often react differently to interpersonal risk. When concerns about their relationship are salient, HSEs seek connection with their partners to quell feelings of vulnerability whereas LSEs distance themselves from their partners to minimize the impact of potential rejection. In the present research, I investigate the extent to which these regulatory dynamics reflect executive-based processes that govern broader regulatory responses. In Studies 1 and 2, HSEs exhibited stronger approach goals (i.e., a greater tendency to pursue rewards and ignore risks) in non-social domains when faced with interpersonal risk whereas LSEs inhibited approach goals and made more conservative decisions. In Studies 3 and 4, I demonstrated that HSEs’ and LSEs’ divergent regulatory responses to risk were contingent on executive control. When participants were cognitively busy, HSEs were less likely to bolster relationship evaluations in the face of interpersonal risk whereas LSEs were more likely to do so. Finally, Study 5 demonstrated that these global regulatory strategies govern HSEs’ and LSEs’ responses to non-interpersonal risk as well. HSEs were more willing to engage in risky social comparison following failure than they were when they received neutral feedback about their performance, whereas LSEs were less willing to compare themselves with others after failure. These effects did not emerge when cognitive resources were depleted. Taken together, the results suggest that HSEs’ and LSEs’ self-regulatory responses to risk are broader and more controlled than previously theorized.

Sexual differentiation is a fundamental characteristic of all eukaryotes, dictating sex-specific morphology, physiology and behavior. Diploid organisms with heteromorphic sex chromosomes (XX or XY) require regulatory compensation of the X chromosome to maintain correct levels of genetic expression between the sexes, a process termed sex-specific dosage compensation (SSDC). The fruit fly, <i>Drosophila melanogaster</i> dosage compensates by upregulating transcription of most X-linked genes two-fold. Associated with this two-fold up regulation is the male-specific lethal (MSL) complex, a RNA-protein complex comprised of at least five known proteins; MSL1, MSL2, MSL3, males absent on the first (MOF), and maleless (MLE) and two non-translated RNA molecules; roX1 (RNA on the X chromosome) and roX2. The complex modulates the chromatin structure of the male X chromosome via acetylation of H4K16. MOF and MSL3 both exhibit an N-terminal chromodomain, whose function is unclear. The MSL3 chromodomain has been suggested to bind H3K36Me3. Chromodomains are a paradigm of how a single structural fold has evolved in diverse proteins to bind distinct targets. Chromodomains are common to nuclear regulators, and bind diverse targets including histones, DNA, and RNA. They function as recognition motifs of histone post-translational modifications and facilitate the translation of the histone code into a distinct local chromatin structure via recruiting the appropriate chromatin modulating machinery.<p> The goal of this research is to determine the structure of the <i>D. melanogaster</i> MOF and MSL3 chromodomains by X-ray crystallographic and/or nuclear magnetic resonance techniques, to advance our understanding of the structural characteristics of these diverse domains. Here we report the cloning and reproducible expression and purification of the <i>D. melanogaster</i> MOF and MSL3 chromodomains and their Homo sapiens orthologues. The <i>D. melanogaster</i> MOF chromodomain, whose NMR structure was published during this research, has been crystallized. Attempts to solve the crystal structure by molecular replacement, multiple-wavelength anomalous dispersion, and single-wavelength isomorphous replacement are reported.

Tvångsmässig shopping, compulsive buying, är en störning som innebär att individen har svårigheter att motstå shoppingimpulser. I huvudsak är det kvinnor som uppvisar tvångsmässig shopping och genomsnittsåldern är 30-31 år. Det finns dock forskningsresultat som tyder på att genus- och åldersskillnaderna minskar (Dittmar, 2005). Tvångsmässiga shoppare har också framträdande materialistiska värderingar och/eller svårigheter att reglera känslor visar separata studier. Syftet med denna studie var att undersöka relationen mellan tvångsmässig shopping, materialistiska värderingar och emotionsregleringsförmåga i en och samma studie. Tre etablerade mätinstrument användes i studien. Deltagarna, 136 varav 94 kvinnor,var huvudsakligen studenter vid Mälardalens högskola. Resultatet visade dessutom att kvinnor tvångsshoppar mer. Det fanns inget signifikant samband mellan tvångsmässig shopping och ålder. Studien visade att tvångsmässig shopping var signifikant relaterat till både materialistiska värderingar och bristande emotionsregleringsförmåga oberoende av varandra. Framtida forskning bör testa ytterligare hur emotionsreglering och materialistiska värderingar tillsammans eller var för sig producerar tvångsshopping.

This thesis experimentally investigates the effects of buffer regulation on the delivery of randomly spaced objects through a multi-conveyor system according to a demanded throughput and spacing. A regulator is developed and tested in conjunction with on ongoing research project at Georgia Tech investigating the automated transfer of live birds. In this thesis, an algorithm is proposed to identify and compensate for the spacing deviations of objects entering a system comprised of three serially connected conveyors. The regulator acts to delay the time each object spends on the middle conveyor, eliminating spacing variations by the time objects exit the system. The system is experimentally tested to determine how effectively the algorithm can locate and deliver objects onto specific moving points. The limits of the regulator and the considerations for practical implementation are investigated. The proposed buffering regulator has immediate applications in the poultry processing industry, wherein live birds must be sorted and hung on a uniform shackle line moving at a constant speed.