How Blue Can You Get? Urban Mythmaking and the Blues in Edmonton, Alberta

The blues is a genre of music that is rich in storytelling. Growing out of an oral tradition that has spanned generations, its influence on popular music today is undeniable. Many will have some vague recollection of some of these stories—whether related to blues figures, cities, regions, or to moments in time these are stories shared by the entire blues community, and through them, people have become familiar with the mythical importance of places such as Chicago or the Mississippi Delta to blues music. But how does a system of myth-making work in regions that do not have the luxury of being at a blues crossroads? Using the Edmonton blues scene as a case study, this thesis examines some of the stories told by people who have long called Edmonton their home and who have contributed to the mythologization of the local blues scene and turned it into an unlikely home for the blues. By employing qualitative research methodologies, such as participant observation and in-depth interviews, this study aims to understand the role that mythmaking has played in strengthening the Edmonton blues scene. To demonstrate this, the thesis first introduces the history of the Edmonton blues scene and, more generally, the city itself. It then looks at how myth has been written about by other anthropologists and popular music researchers. Finally, it shares some of the stories of important venues in Edmonton and important legends of the Edmonton scene before attempting to understand how these myths and stories have helped to carve out a space for Edmonton in the larger blues world

A case of cryocrystalglobulinemia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133638/1/trf13528_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133638/2/trf13528.pd

Comparative Analysis of DNA Replication Timing Reveals Conserved Large-Scale Chromosomal Architecture

Recent evidence suggests that the timing of DNA replication is coordinated across megabase-scale domains in metazoan genomes, yet the importance of this aspect of genome organization is unclear. Here we show that replication timing is remarkably conserved between human and mouse, uncovering large regions that may have been governed by similar replication dynamics since these species have diverged. This conservation is both tissue-specific and independent of the genomic G+C content conservation. Moreover, we show that time of replication is globally conserved despite numerous large-scale genome rearrangements. We systematically identify rearrangement fusion points and demonstrate that replication time can be locally diverged at these loci. Conversely, rearrangements are shown to be correlated with early replication and physical chromosomal proximity. These results suggest that large chromosomal domains of coordinated replication are shuffled by evolution while conserving the large-scale nuclear architecture of the genome

A standard based approach for biomedical knowledge representation

The new generation of health information standards, where the syntax and semantics of the content is explicitly formalized, allows for interoperability in healthcare scenarios and analysis in clinical research settings. Studies involving clinical and genomic data include accumulating knowledge as relationships between genotypic and phenotypic information as well as associations within the genomic and clinical worlds. Some involve analysis results targeted at a specific disease; others are of a predictive nature specific to a patient and may be used by decision support applications. Representing knowledge is as important as representing data since data is more useful when coupled with relevant knowledge. Any further analysis and cross-research collaboration would benefit from persisting knowledge and data in a unified way. This paper describes a methodology used in Hypergenes, an EC FP7 project targeting Essential Hypertension, which captures data and knowledge using standards such as HL7 CDA and Clinical Genomics, aligned with the CEN EHR 13606 specification. We demonstrate the benefits of such an approach for clinical research as well as in healthcare oriented scenarios

The effects of brain death and ischemia on tolerance induction are organ‐specific

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143776/1/ajt14674_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143776/2/ajt14674.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143776/3/ajt14674-sup-0001-FigS1-S2.pd

Decreased replication origin activity in temporal transition regions

Experimental attempts to activate replication origins within the temporal transition region in the IgH locus in mouse embryonic stem cells were not successful, and thus, why and how they become activated in B cells remains unclear

Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics

Replication Timing: A Fingerprint for Cell Identity and Pluripotency

Many types of epigenetic profiling have been used to classify stem cells, stages of cellular differentiation, and cancer subtypes. Existing methods focus on local chromatin features such as DNA methylation and histone modifications that require extensive analysis for genome-wide coverage. Replication timing has emerged as a highly stable cell type-specific epigenetic feature that is regulated at the megabase-level and is easily and comprehensively analyzed genome-wide. Here, we describe a cell classification method using 67 individual replication profiles from 34 mouse and human cell lines and stem cell-derived tissues, including new data for mesendoderm, definitive endoderm, mesoderm and smooth muscle. Using a Monte-Carlo approach for selecting features of replication profiles conserved in each cell type, we identify “replication timing fingerprints” unique to each cell type and apply a k nearest neighbor approach to predict known and unknown cell types. Our method correctly classifies 67/67 independent replication-timing profiles, including those derived from closely related intermediate stages. We also apply this method to derive fingerprints for pluripotency in human and mouse cells. Interestingly, the mouse pluripotency fingerprint overlaps almost completely with previously identified genomic segments that switch from early to late replication as pluripotency is lost. Thereafter, replication timing and transcription within these regions become difficult to reprogram back to pluripotency, suggesting these regions highlight an epigenetic barrier to reprogramming. In addition, the major histone cluster Hist1 consistently becomes later replicating in committed cell types, and several histone H1 genes in this cluster are downregulated during differentiation, suggesting a possible instrument for the chromatin compaction observed during differentiation. Finally, we demonstrate that unknown samples can be classified independently using site-specific PCR against fingerprint regions. In sum, replication fingerprints provide a comprehensive means for cell characterization and are a promising tool for identifying regions with cell type-specific organization

Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome