Genomic integrative analysis to improve fusion transcript detection, liquid association and biclustering

More data provide more possibilities. Growing number of genomic data provide new perspectives to understand some complex biological problems. Many algorithms for single-study have been developed, however, their results are not stable for small sample size or overwhelmed by study-specific signals. Taking the advantage of high throughput genomic data from multiple cohorts, in this dissertation, we are able to detect novel fusion transcripts, explore complex gene regulations and discovery disease subtypes within an integrative analysis framework. In the first project, we evaluated 15 fusion transcript detection tools for paired-end RNA-seq data. Though no single method had distinguished performance over the others, several top tools were selected according to their F-measures. We further developed a fusion meta-caller algorithm by combining top methods to re-prioritize candidate fusion transcripts. The results showed that our meta-caller can successfully balance precision and recall compared to any single fusion detection tool. In the second project, we extended liquid association to two meta-analytic frameworks (MetaLA and MetaMLA). Liquid association is the dynamic gene-gene correlation depending on the expression level of a third gene. Our MetaLA and MetaMLA provided stronger detection signals and more consistent and stable results compared to single-study analysis. When applied our method to five Yeast datasets related to environmental changes, genes in the top triplets were highly enriched in fundamental biological processes corresponding to environmental changes. In the third project, we extended the plaid model from single-study analysis to multiple cohorts for bicluster detection. Our meta-biclustering algorithm can successfully discovery biclusters with higher Jaccard accuracy toward large noise and small sample size. We also introduced the concept of gap statistic for pruning parameter estimation. In addition, biclusters detected from five breast cancer mRNA expression cohorts can successfully select genes highly associated with many breast cancer related pathways and split samples with significantly different survival behaviors. In conclusion, we improved the fusion transcripts detection, liquid association analysis and bicluster discovery through integrative-analysis frameworks. These results provided strong evidence of gene fusion structure variation, three-way gene regulation and disease subtype detection, and thus contribute to better understanding of complex disease mechanism ultimately

p-Wave stabilization of three-dimensional Bose-Fermi solitons

We explore bright soliton solutions of ultracold Bose-Fermi gases, showing that the presence of p-wave interactions can remove the usual collapse instability and support stable soliton solutions that are global energy minima. A variational model that incorporates the relevant s- and p-wave interactions in the system is established analytically and solved numerically to probe the dependencies of the solitons on key experimental parameters. Under attractive s-wave interactions, bright solitons exist only as meta-stable states susceptible to collapse. Remarkably, the presence of repulsive p-wave interactions alleviates this collapse instability. This dramatically widens the range of experimentally-achievable soliton solutions and indicates greatly enhanced robustness. While we focus specifically on the boson-fermion pairing of 87Rb and 40K, the stabilization inferred by repulsive p-wave interactions should apply to the wider remit of ultracold Bose-Fermi mixtures.Comment: 9 pages, 6 figure

A Pilot Study of Value of Information Analysis to Support Research Recommendations for the National Institute for Health and Clinical Excellence

Background - This project developed as a result of the activities of the Research Teams at the Centre for Health Economics, University of York, and ScHARR at the University of Sheffield in the methods and application of decision analysis and value of information analysis as a means of informing the research recommendations made by NICE, as part of its Guidance to the NHS in England and Wales, and informing the deliberations of the NICE Research and Development Committee. Objectives - The specific objectives of the pilot study were to: • Demonstrate the benefits of using appropriate decision analytic methods and value of information analysis to inform research recommendations. • Establish the feasibility and resource implications of applying these methods in a timely way, to inform NICE. • Identify critical issues and methodological challenges to the use of value of information methods for research recommendations (with particular regard to the new reference case as a suitable basis for this type of analysis).

Environmental contaminants exposure and preterm birth: a systematic review

Preterm birth is an obstetric condition associated with a high risk of infant mortality and morbidities in both the neonatal period and later in life, which has also a significant public health impact because it carries an important societal economic burden. As in many cases the etiology is unknown, it is important to identify environmental factors that may be involved in the occurrence of this condition. In this review, we report all the studies published in PubMed and Scopus databases from January 1992 to January 2019, accessible as full-text articles, written in English, including clinical studies, original studies, and reviews. We excluded articles not written in English, duplicates, considering inappropriate populations and/or exposures or irrelevant outcomes and patients with known risk factors for preterm birth (PTB). The aim of this article is to identify and summarize the studies that examine environmental toxicants exposure associated with preterm birth. This knowledge will strengthen the possibility to develop strategies to reduce the exposure to these toxicants and apply clinical measures for preterm birth prevention

LOGICAL AND PSYCHOLOGICAL PARTITIONING OF MIND: DEPICTING THE SAME MAP?

The aim of this paper is to demonstrate that empirically delimited structures of mind are also differentiable by means of systematic logical analysis. In the sake of this aim, the paper first summarizes Demetriou's theory of cognitive organization and growth. This theory assumes that the mind is a multistructural entity that develops across three fronts: the processing system that constrains processing potentials, a set of specialized structural systems (SSSs) that guide processing within different reality and knowledge domains, and a hypecognitive system that monitors and controls the functioning of all other systems. In the second part the paper focuses on the SSSs, which are the target of our logical analysis, and it summarizes a series of empirical studies demonstrating their autonomous operation. The third part develops the logical proof showing that each SSS involves a kernel element that cannot be reduced to standard logic or to any other SSS. The implications of this analysis for the general theory of knowledge and cognitive development are discussed in the concluding part of the paper

A core eating network and its modulations underlie diverse eating phenomena

We propose that a core eating network and its modulations account for much of what is currently known about the neural activity underlying a wide range of eating phenomena in humans (excluding homeostasis and related phenomena). The core eating network is closely adapted from a network that Kaye, Fudge, and Paulus (2009) proposed to explain the neurocircuitry of eating, including a ventral reward pathway and a dorsal control pathway. In a review across multiple literatures that focuses on experiments using functional Magnetic Resonance Imaging (fMRI), we first show that neural responses to food cues, such as food pictures, utilize the same core eating network as eating. Consistent with the theoretical perspective of grounded cognition, food cues activate eating simulations that produce reward predictions about a perceived food and potentially motivate its consumption. Reviewing additional literatures, we then illustrate how various factors modulate the core eating network, increasing and/or decreasing activity in subsets of its neural areas. These modulating factors include food significance (palatability, hunger), body mass index (BMI, overweight/obesity), eating disorders (anorexia nervosa, bulimia nervosa, binge eating), and various eating goals (losing weight, hedonic pleasure, healthy living). By viewing all these phenomena as modulating a core eating network, it becomes possible to understand how they are related to one another within this common theoretical framework. Finally, we discuss future directions for better establishing the core eating network, its modulations, and their implications for behavior

Theoretical petrology

The central issues in petrology have remained remarkably unchanged in the last 50 years. In igneous petrology, the focus is on understanding the nature and cause of diversity in igneous rocks: on identifying primary magma types and constraints on the compositional and mineralogical characteristics, the physical conditions, and the evolutions of their source regions and on establishing the processes by which derivative magmas evolve from primary magmas. In metamorphic petrology, the major concern is with understanding the conditions and processes experienced by a rock in reaching its present state. In both igneous and metamorphic petrology, the ultimate goal is the integration of petrological constraints with those from other branches of earth science into regional and global theories of earth history. What has changed over the years, however, is the framework within which these issues are addressed: the backdrop provided by plate tectonics and geophysical constraints, the growing sophistication of chemical and physical models of rock systems, the ever increasing inputs from trace element and isotopic geochemistry, the sophistication and complexity of experimental approaches to petrological problems, and the growing body of detailed petrological studies of specific rock suites and associations from all over the world. What I will attempt in this report is to pinpoint and briefly review those areas of growing interest and emphasis in American efforts in petrology during the 1975–1978 quadrennium and the ways in which they were shaped by this framework