Lower Body Strength and Power Characteristics Influencing Change of Direction and Straight-Line Sprinting Performance in Division I Soccer Players: An Exploratory Study

The purpose of this dissertation was to investigate the influence of lower body strength characteristics on change of direction (COD) performance in NCAA Division I soccer athletes. Specifically, this dissertation served to examine: 1) whether the lower body strength and power were related to COD performance, 2) whether stronger athletes had superior COD performance than weaker athletes, 3) whether the force production asymmetry and strength dominant (SD) associated with COD performance, and 4) weather sex differences existed in kinetic variables during the stand phase of cutting. The major findings of this dissertation include: 1) strength and power characteristics were moderately to strongly related to COD performance. Furthermore, soccer athletes’ straight-line sprinting times were significantly related to COD performance outcomes. 2) Stronger athletes demonstrated the tendency to perform superiorly in modified 505 COD test when compared to weaker athletes. 3) Athletes who had more lower body force production asymmetry were more likely to perform asymmetrically during a COD test. However, the SD and the magnitude of asymmetry were not limiting factors for athletes’ COD performance.4) Male athletes demonstrated statistically significantly less COD total time, longer ground contact time (GCT), and better ability to apply forces and impulses while performing cutting. Based on the results, vertical forces and impulses during both the braking and propulsive phases of cutting ranged from 2.51 to 3.14 times larger than horizontal direction. In summary, stronger and more powerful soccer athletes were able to perform in a superior manner for both the COD tasks and straight-line sprinting. This may be due to the ability to produce high force and power during the critical time periods. Although force production asymmetry during related to the asymmetrical performance during COD tasks, the SD and the magnitude of asymmetry did not limit the COD performance. Finally, statistical differences existed between sexes in kinetic variables during cutting may be due to the different approaches to apply force in this task. Moreover, the ability to generate higher force and impulse in the vertical direction could affect COD performance

Dosage Compensation of Trisomy 21 and Its Implications for Hematopoietic Pathogenesis in Down Syndrome

Down Syndrome (DS), the most common aneuploidy seen in live-borns, is caused by trisomy for chromosome 21. DS imposes high risks for multiple health issues involving various systems of the body. The genetic complexity of trisomy 21 and natural variation between all individuals has impeded understanding of the specific cell pathologies and pathways involved. In addition, chromosomal disorders have been considered outside the hopeful progress in gene therapies for single-gene disorders. Here we test the feasibility of correcting imbalanced expression of genes across an extra chromosome by expression of a single gene, XIST, the key player in X chromosome inactivation. We targeted a large XIST transgene into one chromosome 21 in DS iPS cells, and demonstrated XIST RNA spreads and induces heterochromatin and gene silencing across that autosome in cis. By making XIST inducible, this allows direct comparison of effects of trisomy 21 expression on cell function and phenotypes. Importantly, XIST-induction during in vitro hematopoiesis normalized excess production of differentiated blood cell types (megakaryocytes and erythrocytes), known to confer high risk for myeloproliferative disorder and leukemia. In contrast, trisomy silencing enhances production of iPS and neural stem cells, consistent with DS clinical features. Further analysis revealed that trisomy 21 initially impacts the endothelial hematopoietic transition (EHT) to generate excess CD43+ progenitors, and also increases their colony forming potential. Furthermore, results provide evidence for a key role for enhanced IGF signaling, involving over-expression of non-chromosome 21 genes controlled by trisomy 21. Finally, experiments to examine trisomy effects on angiogenesis showed no effect on production of endothelial cells, but it remains unclear whether trisomic cells may differ in ability to form vessels. Collectively, this thesis demonstrates proof-of-principle for XIST-mediated “trisomy silencing”. Phenotypic improvement of hematopoietic and neural stem cells demonstrates the value for research into DS pathogenesis, but also provides a foundation of potential for future development of “chromosome therapy” for DS patients

A Novel Mechanism of Spermatogonia Death in Drosophila that Contributes to Tissue Homeostatis During Starvation.

Tissues are maintained in a homeostatic state by balancing the constant loss of old cells with the continued production of new cells. Importantly, dysfunction of tissue homeostasis can lead to tumors or aging. Tissue homeostasis is constantly shifting process as it has to cope with environmental stress while maintaining the integrity of the tissue. For example, tissues often slow down their turnover and scale down tissue size to conserve energy when nutrient availability is limited. The role and behavior of resident stem cells in response to changes in the external environment have been heavily studied. In most of the tissue, stem cell division only constitutes a small fraction of total cell proliferation. Instead, the transit-amplifying cells account for the majority of proliferation. However, the contribution of these cells to shifting tissue homeostasis is less studied. The Drosophila melanogaster testis serves as an ideal model system to study the behavior of stem cells and transit-amplifying cells, as a result of its well-defined anatomy and the genetic tools. Recently, we demonstrated that elimination of transit-amplifying cells (i.e. spermatogonia) plays a critical role in maintaining the stem cell population during protein starvation. Inhibition of starvation-induced spermatogonial death leads to a loss of stem cells, impairment of tissue homeostasis, and failure to recover from starvation when nutrients are reintroduced. Regulation of transit-amplifying cells in the face of an environmental challenge is thus an essential process; however, it remains unclear how the death of spermatogonia leads to stem cell survival during protein starvation. In this dissertation, we identified a gene, spict, which is specifically expressed in differentiating somatic cells, and the corresponding Spict protein, which is stabilized in cyst cells surrounding the dying germ cells. We found that starvation-induced spermatogonial death was decreased in the spict mutant, resulting in a failure to maintain germline stem cells during prolonged protein starvation. We further demonstrated that dying spermatogonia are phagocytosed by neighboring somatic cyst cells, in which Spict protein is stabilized. Taken together, we propose that phagocytosis of dead spermatogonia, which is promoted by Spict, contributes to nutrient recycling and subsequent stem cell maintenance during protein starvation.PHDCell and Developmental BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135898/1/cchia_1.pd

ATM deficiency results in accumulation of DNA-Topoisomerase I covalent intermediates in neural cells

Accumulation of peptide-linked DNA breaks contributes to neurodegeration in humans. This is typified by defects in tyrosyl DNA phosphodiesterase 1 (TDP1) and human hereditary ataxia. TDP1 primarily operates at single-strand breaks (SSBs) created by oxidative stress or by collision of transcription machinery with topoisomerase I intermediates (Top1-CCs). Cellular and cell-free studies have shown that Top1 at stalled Top1-CCs is first degraded to a small peptide resulting in Top1-SSBs, which are the primary substrates for TDP1. Here we established an assay to directly compare Top1-SSBs and Top1-CCs. We subsequently employed this assay to reveal an increased steady state level of Top1-CCs in neural cells lacking Atm; the protein mutated in ataxia telangiectasia. Our data suggest that the accumulation of endogenous Top1-CCs in Atm-/- neural cells is primarily due to elevated levels of reactive oxygen species. Biochemical purification of Top1-CCs from neural cell extract and the use of Top1 poisons further confirmed a role for Atm during the formation/resolution of Top1-CCs. Finally, we report that global transcription is reduced in Atm-/- neural cells and fails to recover to normal levels following Top1-mediated DNA damage. Together, these data identify a distinct role for ATM during the formation/resolution of neural Top1-CCs and suggest that their accumulation contributes to the neuropathology of ataxia telangiectasia

Area-Construction Algorithms Using Tangent Circles

Computer aided geometric design employs mathematical and computational methods for describing geometric objects, such as curves, areas in two dimensions (2D) and surfaces, and solids in 3D. An area can be represented using its boundary curves, and a solid can be represented using its boundary surfaces with intersection curves among these boundary surfaces. In addition, other methods, such as the medial-axis transform, can also be used to represent an area. Although most researchers have presented algorithms that find the medial-axis transform from an area, a algorithm using the contrasting approach is proposed; i.e., it finds an area using a medial-axis transform. The medial-axis transform is constructed using discrete points on a curve and referred to as the skeleton of the area. Subsequently, using the aforementioned discrete points, medial-axis circles are generated and referred to as the muscles of the area. Finally, these medial-axis circles are blended and referred to as the blended boundary curves skin of the area; consequently, the boundary of the area generated is smooth

Learning Deep Latent Spaces for Multi-Label Classification

Multi-label classification is a practical yet challenging task in machine learning related fields, since it requires the prediction of more than one label category for each input instance. We propose a novel deep neural networks (DNN) based model, Canonical Correlated AutoEncoder (C2AE), for solving this task. Aiming at better relating feature and label domain data for improved classification, we uniquely perform joint feature and label embedding by deriving a deep latent space, followed by the introduction of label-correlation sensitive loss function for recovering the predicted label outputs. Our C2AE is achieved by integrating the DNN architectures of canonical correlation analysis and autoencoder, which allows end-to-end learning and prediction with the ability to exploit label dependency. Moreover, our C2AE can be easily extended to address the learning problem with missing labels. Our experiments on multiple datasets with different scales confirm the effectiveness and robustness of our proposed method, which is shown to perform favorably against state-of-the-art methods for multi-label classification.Comment: published in AAAI-201

Exact Recursive Probabilistic Programming

Recursive calls over recursive data are widely useful for generating probability distributions, and probabilistic programming allows computations over these distributions to be expressed in a modular and intuitive way. Exact inference is also useful, but unfortunately, existing probabilistic programming languages do not perform exact inference on recursive calls over recursive data, forcing programmers to code many applications manually. We introduce a probabilistic language in which a wide variety of recursion can be expressed naturally, and inference carried out exactly. For instance, probabilistic pushdown automata and their generalizations are easy to express, and polynomial-time parsing algorithms for them are derived automatically. We eliminate recursive data types using program transformations related to defunctionalization and refunctionalization. These transformations are assured correct by a linear type system, and a successful choice of transformations, if there is one, is guaranteed to be found by a greedy algorithm