Laplace Approximated EM Microarray Analysis: An Empirical Bayes Approach for Comparative Microarray Experiments

A two-groups mixed-effects model for the comparison of (normalized) microarray data from two treatment groups is considered. Most competing parametric methods that have appeared in the literature are obtained as special cases or by minor modification of the proposed model. Approximate maximum likelihood fitting is accomplished via a fast and scalable algorithm, which we call LEMMA (Laplace approximated EM Microarray Analysis). The posterior odds of treatment $\times$ gene interactions, derived from the model, involve shrinkage estimates of both the interactions and of the gene specific error variances. Genes are classified as being associated with treatment based on the posterior odds and the local false discovery rate (f.d.r.) with a fixed cutoff. Our model-based approach also allows one to declare the non-null status of a gene by controlling the false discovery rate (FDR). It is shown in a detailed simulation study that the approach outperforms well-known competitors. We also apply the proposed methodology to two previously analyzed microarray examples. Extensions of the proposed method to paired treatments and multiple treatments are also discussed.Comment: Published in at http://dx.doi.org/10.1214/10-STS339 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

MM Algorithms for Minimizing Nonsmoothly Penalized Objective Functions

In this paper, we propose a general class of algorithms for optimizing an extensive variety of nonsmoothly penalized objective functions that satisfy certain regularity conditions. The proposed framework utilizes the majorization-minimization (MM) algorithm as its core optimization engine. The resulting algorithms rely on iterated soft-thresholding, implemented componentwise, allowing for fast, stable updating that avoids the need for any high-dimensional matrix inversion. We establish a local convergence theory for this class of algorithms under weaker assumptions than previously considered in the statistical literature. We also demonstrate the exceptional effectiveness of new acceleration methods, originally proposed for the EM algorithm, in this class of problems. Simulation results and a microarray data example are provided to demonstrate the algorithm's capabilities and versatility.Comment: A revised version of this paper has been published in the Electronic Journal of Statistic

Injunctive Relief for Constitutional Violations: Does the Civil Service Reform Act Preclude Equitable Remedies?

This Note argues that the federal courts retain power to furnish equitable relief for constitutional violations to ensure adequate protection of federal employees\u27 rights. Statutory procedures and remedies available under the Civil Service Reform Act of 1978 (CSRA) and related legislation should preempt judicially created equitable relief only where the government or federal agency affirmatively demonstrates that these procedures are constitutionally sufficient. Part I canvasses the current lower court response to the question of preclusion and notes the various routes taken by the courts in inferring congressional intent to preempt. This Part discusses varying interpretations of the Civil Service Reform Act, the comprehensive legislation which some courts have recently held evinces Congress\u27 intent to preclude judicially created remedies. Part II charts the organization and procedural scheme of the civil service under the Act, calling attention to weaknesses in the statute which have hindered achievement of its objectives. Finally, Part III focuses on the judiciary\u27s role in safeguarding constitutional guarantees. The discussion highlights the traditional role injunctive relief has played in implementing constitutional protections. This Note concludes that judicially created equitable relief for constitutional deprivations promotes efficient operation of the civil service and, more importantly, ensures adequate protection of federal employees\u27 constitutional rights

Supporting Student Connectedness and Social Satisfaction During Recess

This project examines the effects of how recess preparation and reflection can be focused on providing students an opportunity to connect socially and strengthen overall happiness. By investigating the role social satisfaction plays in a child’s life during recess, educators may gain knowledge about how to foster social connectedness for every child. While most studies about recess focus on a child’s level of physical activity or negative behaviors, researchers have yet to investigate recess as a place to improve a child’s well-being and social satisfaction. This study was conducted at a public elementary school through qualitative interviews and observations. Teachers, administrators, and yard duty monitors were interviewed, and ninety-five children shared their perspectives by writing in journals during class time. When a teacher is more aware of what is going on with her students at recess, she is able to fully teach the whole child and better prepare them for the social skills needed to have a successful recess experience. Often teachers are not regularly on the playground to observe recess, so they are unaware of what students are doing or any social conflicts that may arise. Although teachers need the recess break for their own time, there can be classroom time built in daily or weekly for teachers to connect with their student’s recess experiences. If a teacher is able to prepare and reflect on recess by utilizing transitions, it will legitimize student feelings that recess is an important time in school

Recess Preparation and Reflection For Supporting Social Connectedness

This project examines the effects of how recess preparation and reflection can be focused on providing students an opportunity to connect socially and strengthen overall happiness. By investigating the role social satisfaction plays in a child’s life during recess, educators may gain knowledge about how to foster social connectedness for every child. While most studies about recess focus on a child’s level of physical activity or negative behaviors, researchers have yet to investigate recess as a place to improve a child’s well-being and social satisfaction. This study was conducted at an elementary school through qualitative interviews and observations. Teachers, administrators, and yard duty monitors were interviewed and ninety-five children shared their perspectives by writing in journals during class time. When a teacher is more aware of what is going on with her students at recess, she is able to fully teach the whole child and better prepare them for the social skills needed to have a successful recess experience. Often teachers are not regularly on the playground to observe recess, so they are unaware of what students are doing or any social conflicts that may arise. Although teachers need the recess break for their own time, there can be classroom time built in daily or weekly for teachers to connect with their student’s recess experiences. If a teacher is able to prepare and reflect on recess by utilizing transitions, it will legitimize student feelings that recess is an important time in school

Discovering the Impact of Diet, Genetic, and Sex Effects on Adipose, Skeletal Muscle, and Liver Metabolomes in Mice Using Untargeted Liquid-Chromatography Mass-Spectrometry

The metabolome is the end product of all biochemical reactions in the body and is sensitive to external perturbations, such as diet, genetics, sex, disease, and environment. Understanding the dynamic relationship between metabolites and external inputs is key to delineating the metabolic underpinnings of disease. Mass-spectrometry based metabolomics provides a means through which the metabolome can be systemically and systematically profiled to discern alterations across thousands of metabolites at a time. The research in this dissertation characterized the effects of diet, genetics, and sex on the tissue metabolome. Adipose, skeletal muscle, and liver tissue were chosen due to their role in energy metabolism. In the first study, we characterized the effects of five diets (Japanese, ketogenic, Mediterranean, American, and standard chow) on the tissue metabolome, across both sexes. This study described the metabolic response to diets that altered in macronutrient ratio and composition, independent of genetic differences. Our results revealed that liver tissue was most sensitive to metabolic changes but responded similarly for diet, sex, and sex-by-diet interaction while adipose and muscle remained largely stable. In the second study, we characterized the effects of four strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ) on the tissue metabolome, across both sexes. This study assessed the metabolic response to differing genetic backgrounds represented by various predispositions to metabolic disease, independent of diet. Our results showed that strain exerted the largest effect on metabolites across all three tissues. In contrast, sex and sex-by-strain interaction had little effect on adipose, muscle, and liver. The third study characterized the effects of diet, genetics, and sex on the tissue metabolome. We assessed the metabolic response to diet, genetics, sex, and their interactions to determine which factor/s were potentially driving metabolic differences. Strain exerted the largest effect across all tissues. Liver was most sensitive to metabolite changes when all factors and interactions were collectively assessed. Overall, the results in this dissertation aid in the understanding of complex relationships between diet, genetics, and sex at the systems-level. Furthermore, it was shown that tissues responded differentially to the same stimuli highlighting the need to consider sample type when performing metabolomics

Choices and compromises: the abortion movement in Canada 1969-1988

This dissertation explores pro-choice activism in Canada following the 1969 omnibus bill that decriminalized abortion. The 1969 legal amendments permitted abortions performed in accredited hospitals and approved by the hospital's therapeutic abortion committee, yet Canadian women continued to face barriers to access that were exacerbated by a range of social markers, particularly region and class. Activists identified these barriers and developed strategies to address these issues. The pro-choice movement worked to attain an uneasy balance between helping individual women to access services while simultaneously challenging the government to revise abortion laws. This dissertation explores the contradictions of a mass movement with a shared objective but divergent views as to how to achieve this desired end. The study also examines activists' compromises as they focused either on the immediate, time-sensitive needs of women seeking abortions, or on the long-term goals of effecting legal change. This study highlights four different activist strategies: hospital board challenges, referral and shuttle services, demonstrations and protests, and the establishment of free-standing abortion clinics. Drawing on an extensive range of archival sources from across the country, as well as oral interviews with individuals active in the pro-choice movement, this dissertation highlights regional particularities as well as the shared pro-choice objectives across the country. Activist organizations' archival holdings illuminate both the specific tactics employed by different groups and the ways that the pro-choice movement maintained a connection to the women's movement. Abortion access emerged as a unifying marker for second wave feminisms in Canada, as a framework that facilitated a critique of patriarchal, capitalist structures while simultaneously appealing to a wide support base

Molecular Analysis of N6-Methyladenine Patterns in \u3cem\u3eTetrahymena thermophila\u3c/em\u3e Nuclear DNA

We have cloned two DNA fragments containing 5\u27-GATC-3\u27 sites at which the adenine is methylated in the macronucleus of the ciliate Tetrahymena thermophila. Using these cloned fragments as molecular probes, we analyzed the maintenance of methylation patterns at two partially and two uniformly methylated sites. Our results suggest that a semiconservative copying model for maintenance of methylation is not sufficient to account for the methylation patterns we found during somatic growth of Tetrahymena. Although we detected hemimethylated molecules in macronuclear DNA, they were present in both replicating and nonreplicating DNA. In addition, we observed that a complex methylation pattern including partially methylated sites was maintained during vegetative growth. This required the activity of a methylase capable of recognizing and modifying sites specified by something other than hemimethylation. We suggest that a eucaryotic maintenance methylase may be capable of discriminating between potential methylation sites to ensure the inheritance of methylation patterns