Detecting fiction

Thesis (M.A.)--University of Kansas, English, 2007.This thesis is an essayistic exploration of detective fiction, looking into why I like certain writers (or not) and trying to detect whether there is more artistic merit in their writing than simply proficient plotting and energetic action. The first essay is a general inquiry, looking at various authors and why I either like or dislike them; the second considers three classical noir-type mystery writers (Dashiell Hammett, Raymond Chandler, and Ross Macdonald); and the third examines a characteristic that many hard-boiled detectives display, namely, that each has been damaged in some way, either socially or psychologically. The thrust of these essays is not simply to display my taste but to discern as well whether and what kinds of literary merit is to be found in the detective writers I consider

Lower-Limb Muscular Strategies for Increasing Running Speed

SYNOPSIS: This clinical commentary discusses the mechanisms used by the lower-limb musculature to achieve faster running speeds. A variety of methodological approaches have been taken to evaluate lower-limb muscle function during running, including direct recordings of muscle electromyographic signal, inverse dynamics-based analyses, and computational musculoskeletal modeling. Progressing running speed from jogging to sprinting is mostly dependent on ankle and hip muscle performance. For speeds up to approximately 7.0 m/s, the dominant strategy is to push on the ground forcefully to increase stride length, and the major ankle plantar flexors (soleus and gastrocnemius) have a particularly important role in this regard. At speeds beyond approximately 7.0 m/s, the force-generating capacity of these muscles becomes less effective. Therefore, as running speed is progressed toward sprinting, the dominant strategy shifts toward the goal of increasing stride frequency and pushing on the ground more frequently. This strategy is achieved by generating substantially more power at the hip joint, thereby increasing the biomechanical demand on proximal lower-limb muscles such as the iliopsoas, gluteus maximus, rectus femoris, and hamstrings. Basic science knowledge regarding lower-limb muscle function during running has implications for understanding why sprinting performance declines with age. It is also of great value to the clinician for designing rehabilitation programs to restore running ability in young, previously active adults who have sustained a traumatic brain injury and have severe impairments of muscle function (eg, weakness, spasticity, poor motor control) that limit their capacity to run at any speed.</p

DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements

The precise splicing of genes confers an enormous transcriptional complexity to the human genome. The majority of gene splicing occurs cotranscriptionally, permitting epigenetic modifications to affect splicing outcomes. Here we show that select exonic regions are demarcated within the three-dimensional structure of the human genome. We identify a subset of exons that exhibit DNase I hypersensitivity and are accompanied by 'phantom' signals in chromatin immunoprecipitation and sequencing (ChIP-seq) that result from cross-linking with proximal promoter- or enhancer-bound factors. The capture of structural features by ChIP-seq is confirmed by chromatin interaction analysis that resolves local intragenic loops that fold exons close to cognate promoters while excluding intervening intronic sequences. These interactions of exons with promoters and enhancers are enriched for alternative splicing events, an effect reflected in cell type-specific periexonic DNase I hypersensitivity patterns. Collectively, our results connect local genome topography, chromatin structure and cis-regulatory landscapes with the generation of human transcriptional complexity by cotranscriptional splicing

Integrative analysis of 111 reference human epigenomes

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease