17,192 research outputs found

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    Structure and adsorption properties of gas-ionic liquid interfaces

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    Supported ionic liquids are a diverse class of materials that have been considered as a promising approach to design new surface properties within solids for gas adsorption and separation applications. In these materials, the surface morphology and composition of a porous solid are modified by depositing ionic liquid. The resulting materials exhibit a unique combination of structural and gas adsorption properties arising from both components, the support, and the liquid. Naturally, theoretical and experimental studies devoted to understanding the underlying principles of exhibited interfacial properties have been an intense area of research. However, a complete understanding of the interplay between interfacial gas-liquid and liquid-solid interactions as well as molecular details of these processes remains elusive. The proposed problem is challenging and in this thesis, it is approached from two different perspectives applying computational and experimental techniques. In particular, molecular dynamics simulations are used to model gas adsorption in films of ionic liquids on a molecular level. A detailed description of the modeled systems is possible if the interfacial and bulk properties of ionic liquid films are separated. In this study, we use a unique method that recognizes the interfacial and bulk structures of ionic liquids and distinguishes gas adsorption from gas solubility. By combining classical nitrogen sorption experiments with a mean-field theory, we study how liquid-solid interactions influence the adsorption of ionic liquids on the surface of the porous support. The developed approach was applied to a range of ionic liquids that feature different interaction behavior with gas and porous support. Using molecular simulations with interfacial analysis, it was discovered that gas adsorption capacity can be directly related to gas solubility data, allowing the development of a predictive model for the gas adsorption performance of ionic liquid films. Furthermore, it was found that this CO2 adsorption on the surface of ionic liquid films is determined by the specific arrangement of cations and anions on the surface. A particularly important result is that, for the first time, a quantitative relation between these structural and adsorption properties of different ionic liquid films has been established. This link between two types of properties determines design principles for supported ionic liquids. However, the proposed predictive model and design principles rely on the assumption that the ionic liquid is uniformly distributed on the surface of the porous support. To test how ionic liquids behave under confinement, nitrogen physisorption experiments were conducted for micro‐ and mesopore analysis of supported ionic liquid materials. In conjunction with mean-field density functional theory applied to the lattice gas and pore models, we revealed different scenarios for the pore-filling mechanism depending on the strength of the liquid-solid interactions. In this thesis, a combination of computational and experimental studies provides a framework for the characterization of complex interfacial gas-liquid and liquid-solid processes. It is shown that interfacial analysis is a powerful tool for studying molecular-level interactions between different phases. Finally, nitrogen sorption experiments were effectively used to obtain information on the structure of supported ionic liquids

    The Idiosyncrasy of Involuntary Musical Imagery Repetition (IMIR) Experiences: The Role of Tempo and Lyrics

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    Involuntary musical imagery repetition (IMIR), colloquially known as “earworms,” is a form of musical imagery that arises involuntarily and repeatedly in the mind. A growing number of studies, based on retrospective reports, suggest that IMIR experiences are associated with certain musical features, such as fast tempo and the presence of lyrics, and with individual differences in music training and engagement. However, research to date has not directly assessed the effect of such musical features on IMIR and findings about individual differences in music training and engagement are mixed. Using a cross-sectional design (Study 1, n = 263), we examined IMIR content in terms of tempo (fast, slow) and presence of lyrics (instrumental, vocal), and IMIR characteristics (frequency, duration of episode and section) in relation to 1) the musical content (tempo and lyrics) individuals most commonly expose themselves to (music-listening habits), and 2) music training and engagement. We also used an experimental design (Study 2, n = 80) to test the effects of tempo (fast or slow) and the presence of lyrics (instrumental or vocal) on IMIR retrieval and duration. Results from Study 1 showed that the content of music that individuals are typically exposed to with regard to tempo and lyrics predicted and resembled their IMIR content, and that music engagement, but not music training, predicted IMIR frequency. Music training was, however, shown to predict the duration of IMIR episodes. In the experiment (Study 2), tempo did not predict IMIR retrieval, but the presence of lyrics influenced IMIR duration. Taken together, our findings suggest that IMIR is an idiosyncratic experience primed by the music-listening habits and music engagement of the individual

    Studies of strategic performance management for classical organizations theory & practice

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    Nowadays, the activities of "Performance Management" have spread very broadly in actually every part of business and management. There are numerous practitioners and researchers from very different disciplines, who are involved in exploring the different contents of performance management. In this thesis, some relevant historic developments in performance management are first reviewed. This includes various theories and frameworks of performance management. Then several management science techniques are developed for assessing performance management, including new methods in Data Envelopment Analysis (DEA) and Soft System Methodology (SSM). A theoretical framework for performance management and its practical procedures (five phases) are developed for "classic" organizations using soft system thinking, and the relationship with the existing theories are explored. Eventually these results are applied in three case studies to verify our theoretical development. One of the main contributions of this work is to point out, and to systematically explore the basic idea that the effective forms and structures of performance management for an organization are likely to depend greatly on the organizational configuration, in order to coordinate well with other management activities in the organization, which has seemingly been neglected in the existing literature of performance management research in the sense that there exists little known research that associated particular forms of performance management with the explicit assumptions of organizational configuration. By applying SSM, this thesis logically derives some main functional blocks of performance management in 'classic' organizations and clarifies the relationships between performance management and other management activities. Furthermore, it develops some new tools and procedures, which can hierarchically decompose organizational strategies and produce a practical model of specific implementation steps for "classic" organizations. Our approach integrates popular types of performance management models. Last but not least, this thesis presents findings from three major cases, which are quite different organizations in terms of management styles, ownership, and operating environment, to illustrate the fliexbility of the developed theoretical framework

    In search of 'The people of La Manche': A comparative study of funerary practices in the Transmanche region during the late Neolithic and Early Bronze Age (250BC-1500BC)

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    This research project sets out to discover whether archaeological evidence dating between 2500 BC - 1500 BC from supposed funerary contexts in Kent, flanders and north-eastern Transmanche France is sufficient to make valid comparisons between social and cultural structures on either side of the short-sea Channel region. Evidence from the beginning of the period primarily comes in the form of the widespread Beaker phenomenon. Chapter 5 shows that this class of data is abundant in Kent but quite sparse in the Continental zones - most probably because it has not survived well. This problem also affects the human depositional evidence catalogued in Chapter 6, particularly in Fanders but also in north-eastern Transmanche France. This constricts comparative analysis, however, the abundant data from Kent means that general trends are still discernible. The quality and volume of data relating to the distribution, location, morphology and use of circular monuments in all three zones is far better - as demonstrated in Chapter 7 -mostly due to extensive aerial surveying over several decades. When the datasets are taken as a whole, it becomes possible to successfully apply various forms of comparative analyses. Most remarkably, this has revealed that some monuments apparently have encoded within them a sophisticated and potentially symbolically charged geometric shape. This, along with other less contentious evidence, demonstrates a level of conformity that strongly suggests a stratum of cultural homogeneity existed throughout the Transmanche region during the period 2500 BC - 1500 BC. The fact that such changes as are apparent seem to have developed simultaneously in each of the zones adds additional weight to the theory that contact throughout the Transmanche region was endemic. Even so, it may not have been continuous; there may actually have been times of relative isolation - the data is simply too course to eliminate such a possibility

    Anytime algorithms for ROBDD symmetry detection and approximation

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    Reduced Ordered Binary Decision Diagrams (ROBDDs) provide a dense and memory efficient representation of Boolean functions. When ROBDDs are applied in logic synthesis, the problem arises of detecting both classical and generalised symmetries. State-of-the-art in symmetry detection is represented by Mishchenko's algorithm. Mishchenko showed how to detect symmetries in ROBDDs without the need for checking equivalence of all co-factor pairs. This work resulted in a practical algorithm for detecting all classical symmetries in an ROBDD in O(|G|³) set operations where |G| is the number of nodes in the ROBDD. Mishchenko and his colleagues subsequently extended the algorithm to find generalised symmetries. The extended algorithm retains the same asymptotic complexity for each type of generalised symmetry. Both the classical and generalised symmetry detection algorithms are monolithic in the sense that they only return a meaningful answer when they are left to run to completion. In this thesis we present efficient anytime algorithms for detecting both classical and generalised symmetries, that output pairs of symmetric variables until a prescribed time bound is exceeded. These anytime algorithms are complete in that given sufficient time they are guaranteed to find all symmetric pairs. Theoretically these algorithms reside in O(n³+n|G|+|G|³) and O(n³+n²|G|+|G|³) respectively, where n is the number of variables, so that in practice the advantage of anytime generality is not gained at the expense of efficiency. In fact, the anytime approach requires only very modest data structure support and offers unique opportunities for optimisation so the resulting algorithms are very efficient. The thesis continues by considering another class of anytime algorithms for ROBDDs that is motivated by the dearth of work on approximating ROBDDs. The need for approximation arises because many ROBDD operations result in an ROBDD whose size is quadratic in the size of the inputs. Furthermore, if ROBDDs are used in abstract interpretation, the running time of the analysis is related not only to the complexity of the individual ROBDD operations but also the number of operations applied. The number of operations is, in turn, constrained by the number of times a Boolean function can be weakened before stability is achieved. This thesis proposes a widening that can be used to both constrain the size of an ROBDD and also ensure that the number of times that it is weakened is bounded by some given constant. The widening can be used to either systematically approximate an ROBDD from above (i.e. derive a weaker function) or below (i.e. infer a stronger function). The thesis also considers how randomised techniques may be deployed to improve the speed of computing an approximation by avoiding potentially expensive ROBDD manipulation
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