Hopf algebras and Markov chains: Two examples and a theory

The operation of squaring (coproduct followed by product) in a combinatorial Hopf algebra is shown to induce a Markov chain in natural bases. Chains constructed in this way include widely studied methods of card shuffling, a natural "rock-breaking" process, and Markov chains on simplicial complexes. Many of these chains can be explictly diagonalized using the primitive elements of the algebra and the combinatorics of the free Lie algebra. For card shuffling, this gives an explicit description of the eigenvectors. For rock-breaking, an explicit description of the quasi-stationary distribution and sharp rates to absorption follow.Comment: 51 pages, 17 figures. (Typographical errors corrected. Further fixes will only appear on the version on Amy Pang's website, the arXiv version will not be updated.

Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

Cross-cutting principles for planetary health education

Since the 2015 launch of the Rockefeller Foundation Lancet Commission on planetary health,1 an enormous groundswell of interest in planetary health education has emerged across many disciplines, institutions, and geographical regions. Advancing these global efforts in planetary health education will equip the next generation of scholars to address crucial questions in this emerging field and support the development of a community of practice. To provide a foundation for the growing interest and efforts in this field, the Planetary Health Alliance has facilitated the first attempt to create a set of principles for planetary health education that intersect education at all levels, across all scales, and in all regions of the world—ie, a set of cross-cutting principles

Bayesian Model-Based Clustering Methods Procedures for Data with Unknown Numbers of Clusters

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Biostatistics & Computational Biology, 2017.Uniformly across academia, industry, and government, extracting valuable information from data at hand is a primary goal directly linked to the success of an endeavor. Starting with the simplest models appropriate for a given situation, much can be learned about the available data. The advantage of simple models is the interpretability of findings to those not well-versed in statistical methodology. Aiming to increase the information that can be captured, it is often useful to identify subgroups within the data to learn more about the associations between the observations. For these purposes, model-based clustering is an incredibly powerful and flexible tool that can easily nest within such simple model frameworks to explore several different questions. Bayesian model-based clustering provides a platform on which to implement clustering procedures within the overall model-fitting that estimates the remaining model parameters of interest, allowing for improved estimation. Furthermore, the Bayesian paradigm allows for sampling from the posterior distribution of the grouping parameters, allowing for inference to be made on the groups and their defining characteristics. As with all clustering procedures, a priori identification of the appropriate number of groups is difficult and highly subjective, yet it has far-reaching impact on the analysis. This work focuses specifically on expanding two types of regression models commonly used in biostatistical applications: multiple outcomes models, and linear mixed models. Committing to a fully Bayesian approach, we incorporate the Dirichlet process prior or reversible jump methodology to allow the data to inform the selection of the appropriate number of groups. Applying the methodology separately to a study on childhood neurodevelopment, a study of physical activity in female adolescents, and a data set on hospital charges, we demonstrate the value in grouping the tests of child development, the female adolescents, and the hospitals, respectively

The Effects of Caffeine on Anaerobic Power DIII Female Ice Hockey Players

Caffeine is used widely by athletes as an ergogenic aid. Caffeine improves performance by enhancing anaerobic exercise capacity and power output. PURPOSE: The purpose of this study was to examine the effects of caffeine on anaerobic power in Division III female ice hockey players. METHODS: Ten collegiate Division III female ice hockey players were recruited to participate (age: 20 ± 1 yr, height: 166 ± 6 cm, weight: 71 ± 10 kg, and body composition: 30 ± 5-%). Subjects completed two Wingate test protocols in a randomized order. The subjects consumed either the CAF (120 mg) or the PLA (3 mg) 1 h prior to each test. The Wingate test protocol consisted of three 30 s bouts of maximal sprint pedaling with a 2 min rest interval between each sprint. The resistance was equivalent to 7.5% of body weight. Peak anaerobic power (PP), mean anaerobic power (MP), and fatigue index (FI) were calculated and recorded. RESULTS: There were no significant differences in PP, MP, or FI following the consumption of CAF or PLA (PP: CAF = 510.25 ± 27.03W vs PLA = 498.76 ± 24.54W; MP: CAF = 365.83 ± 13.29 vs PLA 368.67 ± 14.05W; FI: CAF = 47.46 ± 1.79 vs PLA = 47.43 ± 3.55%, p \u3e 0.05). CONCLUSION: The consumption of CAF one hour prior to exercise showed no significant improvements in anaerobic performance. A higher dosage of CAF may have resulted in enhanced anaerobic exercise capacity and power output

A Process and Outcomes Evaluation of the International AIDS Conference: Who Attends? Who Benefits Most?

The objective of the study was to conduct a process and outcomes evaluation of the International AIDS Conference (IAC). Reaction evaluation data are presented from a delegate survey distributed at the 2004 IAC held in Thailand. Input and output data from the Thailand IAC are compared to data from previous IACs to ascertain attendance and reaction trends, which delegates benefit most, and host country effects. Outcomes effectiveness data were collected via a survey and intercept interviews. Data suggest that the host country may significantly affect the number and quality of basic science IAC presentations, who attends, and who benefits most. Intended and executed HIV work-related behavior change was assessed under 9 classifications. Delegates who attended 1 previous IAC were more likely to report behavior changes than attendees who attended more than 1 previous IAC. The conference needs to be continually evaluated to elicit the required data to plan effective future IACs

New Avenues for the Treatment of Huntington’s Disease

Huntington’s disease (HD) is a neurodegenerative disorder caused by a CAG expansion in the HD gene. The disease is characterized by neurodegeneration, particularly in the striatum and cortex. The first symptoms usually appear in mid-life and include cognitive deficits and motor disturbances that progress over time. Despite being a genetic disorder with a known cause, several mechanisms are thought to contribute to neurodegeneration in HD, and numerous pre-clinical and clinical studies have been conducted and are currently underway to test the efficacy of therapeutic approaches targeting some of these mechanisms with varying degrees of success. Although current clinical trials may lead to the identification or refinement of treatments that are likely to improve the quality of life of those living with HD, major efforts continue to be invested at the pre-clinical level, with numerous studies testing novel approaches that show promise as disease-modifying strategies. This review offers a detailed overview of the currently approved treatment options for HD and the clinical trials for this neurodegenerative disorder that are underway and concludes by discussing potential disease-modifying treatments that have shown promise in pre-clinical studies, including increasing neurotropic support, modulating autophagy, epigenetic and genetic manipulations, and the use of nanocarriers and stem cells.Medicine, Faculty ofOther UBCReviewedOthe

Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies

The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry

Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies

The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry