41,596 research outputs found

    The applied psychology of addictive orientations : studies in a 12-step treatment context.

    Get PDF
    The clinical data for the studies was collected at The PROMIS Recovery Centre, a Minnesota Model treatmentc entre for addictions,w hich encouragesth e membership and use of the 12 step Anonymous Fellowships, and is abstinence based. The area of addiction is contextualised in a review chapter which focuses on research relating to the phenomenon of cross addiction. A study examining the concept of "addictive orientations" in male and female addicts is described, which develops a study conductedb y StephensonM, aggi, Lefever, & Morojele (1995). This presents study found a four factor solution which appeared to be subdivisions of the previously found Hedonism and Nurturance factors. Self orientated nurturance (both food dimensions, shopping and caffeine), Other orientated nurturance (both compulsive helping dimensions and work), Sensation seeking hedonism (Drugs, prescription drugs, nicotine and marginally alcohol), and Power related hedonism (Both relationship dimensions, sex and gambling. This concept of "addictive orientations" is further explored in a non-clinical population, where again a four factor solution was found, very similar to that in the clinical population. This was thought to indicate that in terms of addictive orientation a pattern already exists in this non-clinical population and that consideration should be given to why this is the case. These orientations are examined in terms of gender differences. It is suggested that the differences between genders reflect power-related role relationships between the sexes. In order to further elaborate the significance and meaning behind these orientations, the next two chapters look at the contribution of personality variables and how addictive orientations relate to psychiatric symptomatology. Personality variables were differentially, and to a considerable extent predictably involved with the four factors for both males and females.Conscientiousness as positively associated with "Other orientated Nurturance" and negatively associated with "Sensation seeking hedonism" (particularly for men). Neuroticism had a particularly strong association with the "Self orientated Nurturance" factor in the female population. More than twice the symptomatology variance was explained by the factor scores for females than it was for males. The most important factorial predictors for psychiatric symptomatology were the "Power related hedonism" factor for males, and "Self oriented nurturance" for females. The results are discussed from theoretical and treatment perspectives

    Anytime algorithms for ROBDD symmetry detection and approximation

    Get PDF
    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

    Patterns of subspecies diversity in the giraffe, Giraffa camelopardalis (L. 1758): comparison of systematic methods and their implications for conservation policy

    Get PDF
    This thesis examines the subspecific taxonomic status of the giraffe and considers the role of formal taxonomy in the formulation of conservation policy. Where species show consistent. geographically structured phenotypic variation such geographic patterns may indicate selective forces (or other population-level effects) acting. upon local populations. These consistent geographic patterns may be recognised formally as subspecies and may be of interest in single or multi-species biodiversity or biogeography studies for delimiting areas of conservation priority. Subspecies may also be used in the formulation of management policies and legislation. Subspecies are, by definition, allopatric. This thesis explicitly uses methodology of systematic biology and phylogenetic reconstruction to investigate patterns of variation between geographic groups. The taxonomic status of the giraffe is apposite for review. The species provides three independent data sets that may be analysed quantitatively for geographic structure; pelage patterns, morphology and genetics. Museum specimens. grouped according to geographic origin, were favoured for study as more than one type of data was often available for an individual. Population aggregation analysis of forty pelage pattern characters maintained six separate subspecies, while agglomerating some neighbouring populations into a subspecies. A 'traditional' morphometric approach, using multivariate statistical analysis of adult skull measurements, was complemented by a geometric morphometric approach; landmarkrestricted eigenshape analysis. Four morphologically distinct groups were recognised by both morphological analyses. Phylogenetic analysis of mitochondrial DNA control region sequences indicates five major cIades. Nested cIade analysis identifies population fragmentation, range expansion and genetic isolation by distance as contributing to the genetic structure of the giraffe. The results of the analyses show remarkable congruence. These results are discussed in terms of the formulation of conservation policy and the differing requirements of'blological and legal classification systems. The value of a formal taxonomic framework to the recognition, and subsequent conservation, of biodiversity is emphasised

    Magnetized accretion disks around compact objects

    Get PDF
    Los recientes avances observacionales logrados por la colaboración LIGO-Virgo- KAGRA – con las primeras detecciones históricas de ondas gravitacionales de fusiones de sistemas binarios de objetos compactos – junto con la colaboración Event Horizon Telescope - con la imagen del agujero negro supermasivo que reside en el centro de la galaxia M87 - han brindado una oportunidad sin precedentes para investigar la física de la gravedad en el regimen de campo intenso e incluso analizar la Teoría General de la Relatividad de Einstein en esta situación tan extrema. En esta tesis se discute un caso particular de sistema astrofísico relativista que suele considerarse como el ejemplo paradigmático de sistema en el régimen de campo intenso – un agujero negro rodeado de un disco grueso de acreción (o toro). Se presentan nuevas prescripciones para construir datos iniciales de discos de acreción magnetizados alrededor de objetos compactos, extendiendo el estado actual del tema en varias direcciones, a saber, acomodando diferentes configuraciones de campo magnético, distribuciones de momento angular, y tipos de espacio-tiempo (incluyendo agujeros negros de Kerr, agujeros negros con pelo escalar y agujeros negros de Yukawa) sobre los que evoluciona el fluido. Los resultados obtenidos en esta tesis nos proporcionan valiosa información sobre los efectos que tiene añadir diferentes fenómenos físicos en las propiedades morfológicas y físicas del sistema. Además, los resultados de esta investigación también proporcionan una amplia muestra de datos iniciales de dominio público para que puedan ser usados en simulaciones evolutivas del sistema toro de acreción-agujero negro, gobernado por las ecuaciones de la magnetohidrodinámica relativista .The recent observational breakthroughs accomplished by the LIGO-Virgo-KAGRA Collaboration – with the historical first detections of gravitational waves from mergers of compact binaries – and by the Event Horizon Telescope Collaboration – with the image of the supermassive black hole lurking in the centre of the M87 galaxy – have provided an unprecedented opportunity to investigate the physics of strong gravity and to even test Einstein’s General Theory of Relativity in such a extreme situation. This thesis discusses one particular relativistic astrophysical system which is often invoked as a paradigmatic example of such strong-gravity realm – a black hole surrounded by a geometrically thick accretion disk (or torus). New prescriptions to build initial data of magnetized accretion disks around compact objects are presented, extending the current state-of-the-art in several directions, namely accommodating diverse magnetic field configurations, angular momentum distributions, and types of spacetimes (including Kerr black holes, black holes with scalar hair, and Yukawa black holes) where the fluid evolves. The results reported in this thesis provide insight on the eff ects that adding diff erent physics has in the system’s morphological and physical properties. In addition, this research o ers large new samples of open-source initial data to conduct time-dependent general-relativistic, magneto-hydrodynamical simulations of black hole-torus systems

    Affective Polarization: Over Time, Through the Generations, and During the Lifespan

    Get PDF
    The continual rise of affective polarization in the United States harms trust in democratic institutions. Scholars cite processes of ideological and social sorting of the partisan coalitions in the electorate as contributing to the rise of affective polarization, but how do these processes relate to one another? Most scholarship implicitly assumes period effects – that people change their feelings toward the parties uniformly and contemporaneously as they sort. However, it is also possible that sorting and affective polarization link with one another as a function of age or cohort effects. In this paper, I estimate age, period and cohort effects on affective polarization, partisan strength, and ideological sorting. I find that affective polarization increases over time, but also as people age. Age-related increases in affective polarization occur as a function of increases in partisan strength, and for Republicans, social sorting. Meanwhile, sorting only partially explains period effects. These effects combine such that each cohort enters the electorate more affectively polarized than the last

    The application of Evidence-Based Medicine methodologies in sports science: problems and solutions

    Get PDF
    This thesis analyses the use of 'Evidence-Based' methodologies of evidence assessment and intervention and policy design from medicine, and their use in sport and exercise science. It argues that problems exist with the application of Evidence-Based methodologies in sports science, meaning that the quality of evidence used to inform decision-making is lower than is often assumed. This thesis also offers realistic solutions to these problems, broadly arguing for the importance of taking evidence from mechanistic studies seriously, in addition to evidence from RCTs

    Estudio del mecanismo de reacción e inhibición de cisteína proteasas mediante métodos multiescala

    Get PDF
    En esta tesis doctoral se realizaron estudios computacionales para las enzimas caspasa-1 y la 3CLpro del SARS-CoV-2. Estas enzimas pertenecen a la familia de las cisteína proteasas, las cuales hidrolizan sus respectivos sustratos rompiendo un enlace peptídico en particular. En esta reacción interviene una diada catalítica conformada por un par Cis-His. La caspasa-1 fue seleccionada debido a su importancia farmacológica en la enfermedad de Alzheimer, y la enzima 3CLpro del SARS-CoV-2 por estar involucrada en el proceso de replicación del virus responsable de la enfermedad del COVID-19. Para ambas se realizaron estudios que ayudaron a racionalizar el mecanismo de reacción con su sustrato natural utilizando m todos QM/MM. También se realizaron estudios de una serie de inhibidores enzimáticos covalentes identificando las interacciones clave enzima-sustrato que ayudar n a mejorar el desempeño de los inhibidores frente a sus respectivas enzimas. El mecanismo de reacción encontrado para la enzima caspasa-1 ocurre por una ruta alternativa al mecanismo estándar de este tipo de enzimas. En el mecanismo encontrado en nuestras simulaciones la cisteína catalítica se activa directamente por el grupo amino de su sustrato natural, lo que facilita el posterior ataque nucleofílico del azufre al carbonilo y la ruptura del enlace peptídico. En este estudio se determinó que el estado de protonación de la dada catalítica que mejor correlaciona con los resultados experimentales es aquel en el que ambos residuos están neutros, encontrándose el protón de la histidina sobre el nitrógeno delta. También se determina que los inhibidores más potentes para la caspasa-1 son aquellos que, presentan mejores interacciones con los residuos His342, Pro343 and Arg383, adicionalmente a las interacciones ya bien caracterizadas para la estabilización del oxianión formado durante la reacción. En el caso de la 3CLpro del SARSCoV-2, los resultados apuntan a que la dada catalítica en el complejo de Michaelis se encuentra en estado neutro, siendo necesaria la activación de la cisteína por parte de la histidina catalítica para que la reacción proceda. Posteriormente el grupo amino del sustrato abstrae el protón de la histidina mientras se da el ataque nucleofílico del azufre de la cisteína sobre el carbono del carbonilo del enlace peptídico. Para la etapa de de-acilación se describió un mecanismo de reacción alternativo, en donde el grupo amino del grupo saliente desprotona la molécula de agua que posteriormente va a hidrolizar el complejo acil-enzima. En cuanto a la inhibición enzimática, se encontró un mecanismo de intercambio de protones mediado por una molécula de agua, o un grupo hidroxilo. Los hallazgos de esta tesis doctoral abren la puerta para el desarrollo de potentes inhibidores para las dos enzimas involucradas en este estudio, esperando así contribuir al desarrollo de medicamentos que ayuden a tratar las enfermedades en las que se encuentran involucradas.In this doctoral thesis, computational studies were carried out for the enzymes caspase-1 and 3CLpro of SARS-CoV-2. These enzymes belong to the cysteine ​​protease family, which hydrolyze their respective substrates by breaking a particular peptide bond. This reaction involves a catalytic dyad made up of a Cis-His pair. The enzymes Caspase-1 and the SARS-CoV-2 enzyme 3CLpro were selected due to its pharmacological importance in Alzheimer's disease and in the COVID-19 disease respectively. For both, studies were carried out that helped to rationalize the reaction mechanism with its natural substrate using QM/MM methods. Also, studies on a series of covalent inhibitors were conducted in order to identify the key enzyme-substrate interactions that will help improve the performance of the inhibitors against their respective enzymes. The reaction mechanism found for the caspase-1 enzyme occurs through an alternative route to the standard mechanism of this type of enzyme. In the mechanism found in our simulations, the catalytic cysteine ​​is activated directly by the amino group of its natural substrate, which facilitates the subsequent nucleophilic attack of sulfur on the carbonyl and the breaking of the peptide bond. In this study it was determined that the protonation state of the catalytic dyad that best correlates with the experimental results is the one in which both residues are neutral, with the histidine protonated on the delta nitrogen. It was also determined that the most potent inhibitors for caspase-1 are those that present better interactions with residues His342, Pro343 and Arg383, in addition to the interactions already well characterized for the stabilization of the oxyanion formed during the reaction. In the case of the 3CLpro of SARSCoV-2, the results indicate that the catalytic dyad in the Michaelis complex exist in a neutral state, requiring the cysteine be activated ​​by the catalytic histidine for the reaction to proceed. Subsequently, the amino group of the substrate abstracts the proton from the histidine while the nucleophilic attack of the cysteine ​​sulfur on the carbonyl carbon of the peptide bond takes place. An alternative reaction mechanism was described for the deacylation step, where the amino group of the leaving group deprotonates the water molecule that subsequently hydrolyzes the acyl-enzyme complex. Regarding enzyme inhibition, a proton exchange mechanism mediated by a water molecule or a hydroxyl group was found. The findings of this doctoral thesis open the door for the development of powerful inhibitors for the two enzymes involved in this study, thus hoping to contribute to the development of drugs that help treat the diseases in which they are involved

    Generation and Characterization of an In Vitro Organotypic Foreskin Model for Future Study of the Penile Microbiome

    Get PDF
    The foreskin is a site of HIV-1 acquisition in heterosexual males. The lack of relevant in vitro models that mimic the foreskin microenvironment, including innate immune and barrier functions, has limited our understanding of susceptibility at this site. We hypothesize that we can establish organotypic in vitro foreskin that mimics in vivo tissue. Organotypic foreskin models were generated and are composed of stratified cell layers that express E-cadherin suprabasally, filaggrin apically, and expressed TLR1, TLR2, and β-defensin-1 mRNA similar to in vivo foreskin. Preliminary results suggest organotypic foreskin tissues retain the ability to respond to LPS. Lastly, organotypic foreskin permeability appears high when subject to mechanical agitation. This work has established culture techniques to generate multi-layer epithelia and the methods necessary to characterize innate immune and barrier functions. This sets the foundation for future work to fully develop the model, including integrating immune cells, the microbiota, or HIV-1
    corecore