Universiẗat, Diss., 2004--München.

To study the interplay between spatial nuclear architecture and transcriptional activity during viral infections, I employed a genome-wide chromosome conformation capture approach (Hi-C) on infected murine and human cells and further enriched those libraries for genomic loci of interest and the viral genomes with biotinylated RNA baits. In parallel, I profiled newly transcribed RNA throughout the entire kinetic of murine cytomegalovirus (mCMV) infection in mice. Host genome rearrangement is a well-known phenomenon of mCMV infection but the underlying mechanisms are largely unknown. Furthermore, HPV infection can lead to cervical cancers in humans, with genomic instability and re-arrangements, leading to dysregulation of gene expression. Thus studying changes in genome architecture at early stages of HPV induced carcinogenesis can further our understanding on how certain integration events can provide a growth advantage. In this study, I identified clusters of genes characterized by distinct kinetic profiles upon CMV infection in the mouse, which were associated with distinct functional terms. ATAC-Seq uncovered proximal promoter regions (PPR) that showed an over-representation of specific transcription factor binding sites in each of the clusters. These correlated well with the annotated functions of the associated clusters. Further, I found that lytic mCMV infection is accompanied by local and global changes of chromosomal interactions in the host cell genome. Notably, chromatin properties, such as gene density, GC content and the association with the nuclear lamina, predict the structural dynamics upon infection and correlate well with transcriptional activity and changes thereof. High-resolution interaction profiles for TSSs of highly induced or repressed genes, suggest that in general, enhancer-promoter interactions already form in untreated cells; and these pre- existing DNA-structures are not significantly altered but function through transient activation or repression of enhancers. Finally, the viral genome showed a distinct pattern of open and closed chromatin late in infection. We found that the 7.2 kb viral intron displays the most open chromatin, and is highly enriched for chromosomal contacts with the host genome. Hi-C and capture Hi-C revealed that both short- (~50 kb) and long-range (~1 Mb) interactions occur during the early stages of HPV induced carcinogenesis between the host and the integrated HPV16 genomes. Integration and direct interactions between the viral genome and the host DNA were shown to be associated with changes in host gene expression. In addition, insertion of the virus can disrupt normal host architecture. In summary, this project pioneers the study of changes in nuclear architecture upon viral infection in man and mice. I uncover numerous structural features and changes of both the viral genomes and the infected host cellular genomes, and I demonstrate that these changes correlate with transcriptional activity.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

The project to design a CD transport (CD player) in conjunction with Perreaux Industries came about from the need for a source component in their Silhouette series of products. This project describes the design a high quality CD player, at a low price, to compliment Perreaux's Silhouette series. A CD drive is selected over a proprietary optical pickup due to the former's low cost and the standardisation of the interface. The control circuitry includes a micro controller and discrete logic to provide the correct data and clock signals to the SPDIF transmitter and DAC circuits. These two circuits provided a high quality analogue output, and facilitate an upgrade path by connecting the SPDIF output to an external DAC. After three board iterations, a final production ready revision was achieved. The design includes a high quality toroidal transformer, low jitter crystal oscillator, and a very high quality SPDIF pulse transformer output. The design also allows a remote input to control the player, and an optional digital cable via an RJ45 connector to provide synchronisation with a future design of the SXD2 DAC module, or to transmit SPDIF to a remote location. The specifications of the final design were higher than expectations. The digital output boasts equal or superior performance to competitive products in the same price range, with the analogue output attaining exceptionally high performance.

The aim of the research was to produce hollow yarn knitted fabrics with improved thermal comfort properties. Thermal comfort properties and utility properties determine the wearing comfort of textiles and the suitability of a new textile product for a particular application. Both, Thermal comfort properties such as thermal absorptiveness, thermal conductivity, air permeability and utility properties like percent stretch, spirality, bursting strength of core yarn knitted fabrics and hollow yarn knitted fabrics were assessed. A new method was proposed and discussed for producing hollow yarns at fabric stage (in this case knitted fabric) which involved the following steps: - a) Production of ring spun yarns, comprising nylon as a core and cotton as a sheath, using Ring Spinning System. b) Production of knitted fabrics of different knit structures viz., single jersey, rib and interlock using above mentioned yarn. c) Dissolution of core element i.e. Nylon into formic acid to obtain hollow yarn knitted fabrics and this hollow yarn knitted fabrics can be tailored for specific end use. The study covers comparative analysis of thermal insulation properties like thermal absorptiveness, thermal conductivity and others for core yarn knitted fabrics and hollow yarn knitted fabrics and the influence of the count of core nylon filament and the type of knit structures on the thermal properties of the fabrics. Based on the results obtained from the work, it can be stated that hollow yarn knitted fabrics offer numerous possibilities for creating fabric properties which influence their comfort of use.

In the current era of knowledge economy, the core of the competitions between corporations has evolved from production to management, and now focuses on the acquirement of adequate human resources and the amelioration of innovation. To corporations, the most vital task is often not how to obtain capable human resources, but rather how to ensure the existing ones continuously contribute to the progression of the firm. This involves the internal culture of the firm and its organizational layout; moreover, the most direct effect comes from the ¡§push-and-pull¡¨ interaction between the employer and employee, which is the fundamental quality of employee relations. This research first intends to explore and clarify the meaning of employee relation through a comprehensive study of the aggregated works on related applications of labor relations by previous scholars, including labor union, collective bargaining, negotiation, and labor involvement and participation. Bearing the attributes of high-tech industries in mind, the actual practice of employee relations can then be categorized under six major groups through an understanding of renowned models on labor relations: direct financial rewards and benefits, indirect financial rewards and benefits, non-financial rewards and benefits, employee participation and involvment, organizational communication and management on labor relations. Based on these six categories, an analysis of the actual practice on employee relations leads to the following conclusions: A.Direct financial rewards and benefits In respect to the base-salary system, position-oriented system is more widely adopted than the ability-oriented and the seniority-oriented ones. The ability-oriented system, though, imposes the maximal impacts on employee relations. In respect to the motivation system, the year-end profit-sharing system is the most common one, and it is also considered to be having the best effect on stimulating employee relations. In most firms, the department of human resources is the key unit in charge of the motivation system. B.Indirect financial rewards and benefits Regarding economical benefits, most companies follow the traditional model and engage in pension plan, the subsidy for marriage and funeral. Injury compensation is often acclaimed to be the most essential program in enhancing employee relations. These programs are often done through the Human Resource Department and the Employee Welfare Committee. Regarding benefits on leisure activities, the most common activity is domestic and international travel coordinated through the Employee Welfare Committee. Regarding facility benefits, high percentages of firms have contracts with stores or other corporations for discounts and pre-arranged special rates. However, labor co-ops are preferred as the facility that improves employee relations the most. In general, facility benefits are coordinated through the General Administrative Department, the Human Resource Department and the Employee Welfare Committee. Regarding services benefits, most firms respect foremost the smoothness of complain and appeal channel of lower-ranked employees, and they also achieve improvements on employee relation through family goodwill policy. Most of the services benefits are managed by the department of human resources. C.Non-financial rewards and benefits In respective to non-financial compensations, the leadership style of the high-tech industry often focus on the involvement and participation from the employees, and this is often done through inquiry and commentary. Regarding the working environment, the business sectors widely adopt regulation and policy on assessment, opportunities and fairness for advancement. Flexible working hours have also been known to have positive effect on employee relations. Benefits in this category are usually overseen by the Human Resource Department. D.Employee participation and involvement Most corporations implement labor participations through employee suggestion program, which also improves employee relations the most. Regarding the rights of employee participation, the participation level on financial management is the lowest, but the participation level on company¡¦s policy, marketing, production and human resource management are normal. E.Organizational communication Regarding organizational communication, parallel communication is more efficient based on survey results. The efficiency of downward communication and upward communication is normal. Besides, bulletin board, telephone, interview, meeting, and e-mail are commonly adopted, especially the last three improves employee relations most. F.Management in labor relations Regarding management on labor relations, there were only few unions in hi-tech companies. Conciliation is most widely adopted on labor dispute. Collective bargaining and collective agreement improves employee relations greatly. Since most companies do not organize unions, conciliation is more preferred, compared with arbitration and lawsuit.

Introduction: The Canadian Standards Association (CSA) Z94.3-07 ballistic impact test for industrial lenses, tests the ability of a lens material to withstand the impact of a 6.4 mm diameter steel ball travelling at a speed of 46.5 ± 0.5 m/s. The specific testing is waived if the lens made of various materials meets a minimum centre thickness requirement. New lens materials, like Hi-Vex, are not included in this list. The first study compared the breakage speed of Hi-Vex lenses to CR39 lenses at different conditioned temperatures. In the process of carrying out the literature review, it became apparent that the definition of lens failure varied. This led to the question as to how naïve individuals may interpret a National Standard definition of lens failure after being impacted by a missile. Naïve subjects were asked to classify impacted lenses as either pass or fail based on the written CSA Z94.3-07 failure criterion. Purpose:   Study 1: To investigate the impact resistance of a mid-index plastic lens material Hi-Vex (n=1.56) at different temperatures. Study 2: To investigate if people actually understood what the CSA classifies as a failed lens. Methods:  Study 1: Two groups of plano hard coated lenses were tested: CR39 and Hi-Vex. Lenses were ordered with 3mm centre thickness, cut to 50mm diameter and edged to achieve the Hide-a-Bevel® which was in agreement with the CSA requirement for prescription industrial safety lenses and frames. A pneumatic gun was used to propel a 6.35mm steel ball at the centre of each lens. Impact speed was varied using the Zippy Estimation by Sequential Testing (ZEST) protocol to determine the threshold breakage speed. Combined uncertainties as defined in the International organization for standardization (ISO) Guide to the expression of uncertainty in measurement were used to determine the statistical significance of all comparisons of the data sets. Study 2: Ten graduate students from the School of Optometry and ten patients from the general public were given 25 spectacle lenses that had been subjected to the ballistic impact test. They were asked to classify the lenses as either a pass or fail after reading the definition of a failure under the ballistic impact test in CSA Z94.3-07 clause 6.1.3.1. Lenses were presented to the participants in the same order. The responses of both groups of participants were compared to the classification of two experienced researchers who agreed on 100% of the lens outcomes. Results:  Study 1: The threshold breakage speeds of the industrial thickness Hi-Vex and CR39 lenses at 24°C were 50.88m/s and 50.64 m/s and at -29°C, 52.57m/s and 52.56 m/s respectively. Both comparisons were not statistically significant. The corresponding threshold breakage speeds for Hi-Vex and CR39 lenses at -49°C were 66.38m/s and 49.66m/s and at 50°C were 57.01m/s and 53.54m/s respectively. Both comparisons were statistically significant. Study 2: There were only two lenses in which all participants agreed with the outcome. These lenses were failed lenses. The naïve subjects were more likely to classify a lens that passed as a failure than a failed lens as a pass. This trend was more obvious in the general public results although the results across the various lenses for the graduate students and general public were not statistically different. Conclusions:  Study 1: We found that the mean breakage speeds of the Hi-Vex and CR39 lenses were greater than the level required of eye protector lenses by the Standards American National Standards institute (ANSI) Z87.1-2010 and CSA Z94.3-07. Hi-Vex was also superior to CR39 at more extreme temperatures with a threshold breakage speed of 57.01±3.51m/s at 50°C and 66.38±4.00m/s at -49°C. Although its impact resistance was less than that of both Trivex and Polycarbonate lenses, Hi-Vex may provide an acceptable level of impact protection in industrial settings. This is the first study to concomitantly assess impact resistance of a new lens material as well as compare the impact resistance at various temperatures. Study 2: Simply reading the definition of a lens failure is insufficient. Some type of training with actual lenses may be necessary. Whether revising the text of the Standard or repeating the instructions several times would reduce this problem is uncertain. Both the graduate students and general public tended to be more conservative in their classification of failure. If there were any visible damage to the lens as a result of the impact, at least one person would classify the lens as a failure regardless of whether the damage met the CSA definition. This result suggests that the vision care community and CSA may need to educate the public on the meaning of impact resistance of eye protectors.

Two-dimensional information on the kinematics and spatial distribution of gas in spiral galaxies is encoded in radio observations of their one-dimensional 21-cm neutral hydrogen (HI) line profiles. More than ten thousand HI profiles have been published and are publicly available. In order to explore the parameter space mapped out by the 21-cm neutral hydrogen line pro file, we have modified and run a FORTRAN-based computer simulation code. We have identified 7 control parameters that define the morphology of the modelled galaxy: they describe the neutral hydrogen gas distribution (density and spatial location of the gas), characteristics of its rotation curve, warps, asymmetries, and finally, the viewing angle. All except the last of these parameters tell us significant physical information about the galaxy but a determination of them is not immediately apparent from the two-dimensional 21-cm line profile. Hence, the goal of this exploration is to find meaningful correlations between the observed 21-cm line profile features and the underlying physical parameters.

Rheumatoid arthritis (RA) is a complex autoimmune disease affecting approximately 1% of the population. Multiple factors contribute to the development of RA, with genetic factors accounting for around 60% of the disease risk. Over the last few years, genome-wide association studies (GWAS) have successfully been used to identify regions of the genome predisposing to complex disease. There are now 101 confirmed RA risk loci, but for the vast majority of these loci the causal gene and causal variant remain unidentified and therefore, their function in disease is unexplored. The majority of genetic variants, or single nucleotide polymorphisms (SNPs), associated with disease map to non-coding enhancer regions, which may regulate transcription through long-range interactions with their target genes. The aims of this project were to identify the causal genes within an RA locus, pinpoint the causal variants and elucidate the mechanisms by which the variants modify gene function. Capture Hi-C (CHi-C) was carried out with the aim of identifying long range interactions between disease-associated SNPs and genes in four related autoimmune diseases. Many long-range interactions were identified which implicated novel candidate genes, interactions involving multiple genetic loci which had a common target, and interactions with loci which had previously been implicated in disease. Complex interaction patterns were observed in many of the disease associated loci, particularly in the 6q23 locus which is associated with a number of autoimmune diseases and is the focus of the present thesis. Within the 6q23 locus, associated SNPs lie a large distance from any gene (>180kb) making it difficult to pinpoint the exact causal gene. Results from CHi-C and chromosome conformation capture (3C-qPCR) experiments indicated that restriction fragments containing disease associated intergenic SNPs could display genotype-specific interactions with genes associated with autoimmunity (IL20RA and IFNGR1). Interactions could also be detected with long non-coding RNAs (lncRNAs), The lead SNP in the 6q23 region is in tight LD with eight other SNPs which are equally likely to be causal. Bioinformatics analysis suggested that the most plausible causal SNP in the 6q23 intergenic region was rs6927172, as it maps to an enhancer in both B-cells and T-cells, is in a DNaseI hypersensitivity cluster, shows transcription factor binding and is in a conserved region. Chromatin immunoprecipitation (ChIP) demonstrated binding of chromatin marks of active enhancers (H3K4me1 and H3K27ac) and the transcription factors BCL3 and NF-κB to the rs6927172 SNP target site in Jurkat T-cells and GM12878 B-cells, suggesting the risk allele could be associated with increased regulatory activity. In conclusion, these results show that CHi-C can help identify novel GWAS causal genes with the potential to suggest novel therapeutic targets. For example IL20RA is already a target for a monoclonal antibody which has been shown to be effective in treating RA in clinical trials. This project has also provided compelling evidence that the autoimmune risk variant in the 6q23 locus, rs6927172, is within a complex gene regulatory region, involving multiple immune genes and regulatory elements, such as lncRNAs.

Indiana University-Purdue University Indianapolis (IUPUI) / About 50 million years ago, an Hsmar1 transposon invaded an early primate genome and inserted itself downstream of a SET methyltransferase gene, leading to the birth of a new chimeric protein now called SETMAR. While all other Hsmar1 sequences in the human genome have suffered inactivating mutational damage, the transposase domain of SETMAR has remained remarkably intact, suggesting that it has gained a novel, evolutionarily advantageous function. While SETMAR can no longer transpose itself throughout the genome, it has retained its ancestral sequence-specific DNA binding activity, the importance of which is currently unknown. To investigate this, we performed ChIP-seq to examine SETMAR binding in the human genome. We also utilized RNA-sequencing to assess SETMAR overexpression as well as SETMAR deletion on the human transcriptome. Additionally, we explored SETMAR’s transposase-derived chromatin-looping ability using chromosome-conformation-capture-on-ChIP (4C) in the presence of SETMAR overexpression and performed genome-wide Hi-C to assess the impact of complete SETMAR silencing on global chromatin interactions. ChIP-seq revealed that SETMAR amassed 7,332 unique binding sites, 69% of which included a TIR motif. RNA-sequencing in cells overexpressing SETMAR indicated 177 differentially regulated transcripts, including repression of 17 histone transcripts, suggesting a possible role in chromatin dynamics. RNA-sequencing of parental and SETMAR knockout clones highlighted an average of 5,000 altered transcripts in each cell line, with 343 transcripts significantly differentially expressed in all three knockout clones, many of which participate in embryonic development pathways. 4C analysis in the presence of SETMAR overexpression discovered multiple intrachromosomal looping interactions, and Hi-C analysis of SETMAR knockout cell lines uncovered genome-wide loss of chromatin interactions and disruption of TAD boundaries. The prevalence of SETMAR binding in the human genome combined with its chromatin looping capability and its dramatic effects on the transcriptome suggest a previously undiscovered role for SETMAR as a novel chromatin organizing factor. / 2022-08-17