La recherche internationale en génétique et l’utilisation secondaire des données : entre dissociation et harmonisation

L’étude des polymorphismes et des aspects multifactoriels des déterminants de la santé suscite un engouement majeur envers la recherche populationnelle en génétique et génomique. Cette méthode de recherche requiert cependant la collecte et l’analyse d’un nombre élevé d’échantillons biologiques et de données associées, ce qui stimule le développement des biobanques. Ces biobanques, composées des données personnelles et de santé de milliers de participants, constituent désormais une ressource essentielle permettant l’étude de l’étiologie des maladies complexes et multifactorielles, tout en augmentant la rapidité et la fiabilité des résultats de recherche. Afin d’optimiser l’utilisation de ces ressources, les chercheurs combinent maintenant les informations contenues dans différentes biobanques de manière à créer virtuellement des mégacohortes de sujets. Cependant, tout partage de données à des fins de recherche internationale est dépendant de la possibilité, à la fois légale et éthique, d’utiliser ces données aux fins pressenties. Le droit d’utiliser les données personnelles, médicales et génétiques de participants dans le cadre de recherches internationales est soumis à un ensemble complexe et exhaustif d’exigences légales et éthiques. Cette complexité est exacerbée lorsque les participants sont décédés. Fondée sur une révision de l’interprétation individualiste du concept de consentement éclairé, ainsi qu’une perspective constructiviste des concepts de confiance et d’autonomie, cette thèse se situe au carrefour de la recherche, du droit et de l’éthique, et a pour objectif de proposer un modèle promouvant l’harmonisation éthique et juridique des données aux fins de recherches internationales en génétique.

DEVELOPMENT OF A CONDENSED PHASE VELOCITY MAP IMAGING APPARATUS: DISSOCIATION PHOTODYNAMICS OF NITROGEN DIOXIDE AT 355 NM

The photochemistry of the polar regions of Earth, as well as the interstellar medium, is driven by the effect of ultraviolet radiation on ice surfaces and on the materials trapped within them. While the area of ice photochemistry is vast and much research has been completed, it has only recently been possible to study the dynamics of these processes on a microscopic level. One of the leading techniques for studying photoreaction dynamics is Velocity Map Imaging (VMI). This technique has been used extensively to study several types of reaction dynamics processes. Although the majority of these studies have utilized molecular beams as the main medium for reactants, new studies showed the versatility of the technique when applied to molecular dynamics of molecules adsorbed on metal surfaces. Herein the development of a velocity map imaging apparatus capable of studying the photochemistry of condensed phase materials is described. The apparatus is used to study of the photo-reactivity of NO2 condensed within argon matrices to illustrate its capabilities. A doped ice surface is formed by condensing Ar and NO2 gas onto a sapphire rod which is cooled using a helium compressor to 20 K. The matrix is irradiated using an Nd:YAG laser at 355 nm, and the resulting NO fragment is state-selectively ionized using an excimer-pumped dye laser. In all, we are able to detect transient photochemically generated species and can collect information on their quantum state and kinetic energy distribution. It is found that the REMPI spectra changes as different sections of the dissociating cloud are probed. The rotational and translational energy populations are found to be bimodal with a low temperature component roughly at the temperature of the matrix, and a second component with much higher temperature, the rotational temperature showing a possible population inversion, and the translational temperature of 100-200 K. The low temperature translational component is found to dominate at long delay times between dissociation and ionization, while at short time delays the high temperature component plays a larger role. The velocity map imaging technique allows for the detection of both the axial and radial components of the translational energy. The distribution of excess energy over the rotational, electronic and translational states of the NO photofragments provides evidence for collisional quenching of the fragments in the Ar-matrix prior to their desorption.

Shame, Dissociation, and Complex PTSD Symptoms in Traumatized Psychiatric and Control Groups: Direct and Indirect Associations With Relationship Distress

Objectives: Elevated shame and dissociation are common in dissociative identity disorder (DID) and chronic posttraumatic stress disorder (PTSD) and are part of the constellation of symptoms defined as complex PTSD. Previous work examined the relationship between shame, dissociation, and complex PTSD and whether they are associated with intimate relationship anxiety, relationship depression, and fear of relationships. This study investigated these variables in traumatized clinical samples and a nonclinical community group.

Method: Participants were drawn from the DID (n = 20), conflict-related chronic PTSD (n = 65), and nonclinical (n = 125) populations and completed questionnaires assessing the variables of interest. A model examining the direct impact of shame and dissociation on relationship functioning, and their indirect effect via complex PTSD symptoms, was tested through path analysis.

Results: The DID sample reported significantly higher dissociation, shame, complex PTSD symptom severity, relationship anxiety, relationship depression, and fear of relationships than the other two samples. Support was found for the proposed model, with shame directly affecting relationship anxiety and fear of relationships, and pathological dissociation directly affecting relationship anxiety and relationship depression. The indirect effect of shame and dissociation via complex PTSD symptom severity was evident on all relationship variables.

Conclusion: Shame and pathological dissociation are important for not only the effect they have on the development of other complex PTSD symptoms, but also their direct and indirect effects on distress associated with relationships.

Spectroscopic constants and term values for the X2πi state of OH (v = 0-10)

info:eu-repo/semantics/published

La recherche internationale en génétique et l’utilisation secondaire des données : entre dissociation et harmonisation

L’étude des polymorphismes et des aspects multifactoriels des déterminants de la santé suscite un engouement majeur envers la recherche populationnelle en génétique et génomique. Cette méthode de recherche requiert cependant la collecte et l’analyse d’un nombre élevé d’échantillons biologiques et de données associées, ce qui stimule le développement des biobanques. Ces biobanques, composées des données personnelles et de santé de milliers de participants, constituent désormais une ressource essentielle permettant l’étude de l’étiologie des maladies complexes et multifactorielles, tout en augmentant la rapidité et la fiabilité des résultats de recherche. Afin d’optimiser l’utilisation de ces ressources, les chercheurs combinent maintenant les informations contenues dans différentes biobanques de manière à créer virtuellement des mégacohortes de sujets. Cependant, tout partage de données à des fins de recherche internationale est dépendant de la possibilité, à la fois légale et éthique, d’utiliser ces données aux fins pressenties. Le droit d’utiliser les données personnelles, médicales et génétiques de participants dans le cadre de recherches internationales est soumis à un ensemble complexe et exhaustif d’exigences légales et éthiques. Cette complexité est exacerbée lorsque les participants sont décédés. Fondée sur une révision de l’interprétation individualiste du concept de consentement éclairé, ainsi qu’une perspective constructiviste des concepts de confiance et d’autonomie, cette thèse se situe au carrefour de la recherche, du droit et de l’éthique, et a pour objectif de proposer un modèle promouvant l’harmonisation éthique et juridique des données aux fins de recherches internationales en génétique.

Mechanistic Dissection of the Cop9 Signalosome’s Deneddylation Activity on Cullin-RING Ligases

We set out to understand the precise mechanisms that regulate the activation and deactivation of Cullin-RING Ligases (CRLs). While a great deal of work has already gone into identifying the players involved in these pathways and the cellular consequences associated with the loss of each, the biochemical mechanisms regulating these steps have remained elusive. In this work we sought to gain a better understanding of the mechanisms behind these steps by teasing apart specific their biochemical reactions. By measuring the individual microscopic rate constants of the reactions we have shed light on both the proper sequence of events in the regulation of CRLs as well as how they are in fact controlled.

Prior to this work, it was believed that CSN deactivated CRLs by binding them and enzymatically removing the activating post-translation modification Nedd8. It was believed that CSN could not bind to CRLs while they were active due to the steric hindrance by the CRL substrates, and that they would remain bound to deneddylated CRLs as a sequestering agent until a new substrate could displace it. We now have some insight that substrates themselves cannot inhibit CSN very well, but that the active ubiquitination by an E2 enzyme precludes CSN binding and activity. When the substrate for a CRL becomes depleted, CSN then binds to the CRL in a low affinity, low activity conformation. This triggers a conformational change that pulls the autoinhibitory Ins-1 loop away from the active site in the catalytic subunit Csn5, resulting in a large increase in affinity and cleavage of the isopeptide bond between CRLs and Nedd8. Upon dissociation of Nedd8, CSN rapidly returns to the low affinity state and dissociates from the CRL, allowing it reenter its activation cycle.

Dissociation

Dissociation is an abstract materialist film that has migrated from 16mm film to the digital. It is made up of scratches, half-baked images and flicker. The film explores the tension between the image, the written text and the spoken word and the consequent struggle for meaning. A report on the anti-social nature of corporate space inspired by the first non-sense poem “The Great Lalula” by Christian Morgenstern.

Quantitative electroencephalographic comodulation : an investigation of patterns in chronic fatigue syndrome

Introduction. This is a pilot study of quantitative electro-encephalographic (QEEG) comodulation analysis, which is used to assist in identifying regional brain differences in those people suffering from chronic fatigue syndrome (CFS) compared to a normative database. The QEEG comodulation analysis examines spatial-temporal cross-correlation of spectral estimates in the resting dominant frequency band. A pattern shown by Sterman and Kaiser (2001) and referred to as the anterior posterior dissociation (APD) discloses a significant reduction in shared functional modulation between frontal and centro-parietal areas of the cortex. This research attempts to examine whether this pattern is evident in CFS. Method. Eleven adult participants, diagnosed by a physician as having CFS, were involved in QEEG data collection. Nineteen-channel cap recordings were made in five conditions: eyes-closed baseline, eyes-open, reading task one, math computations task two, and a second eyes-closed baseline. Results. Four of the 11 participants showed an anterior posterior dissociation pattern for the eyes-closed resting dominant frequency. However, seven of the 11 participants did not show this pattern. Examination of the mean 8-12 Hz amplitudes across three cortical regions (frontal, central and parietal) indicated a trend of higher overall alpha levels in the parietal region in CFS patients who showed the APD pattern compared to those who did not have this pattern. All patients showing the pattern were free of medication, while 71% of those absent of the pattern were using antidepressant medications. Conclusions. Although the sample is small, it is suggested that this method of evaluating the disorder holds promise. The fact that this pattern was not consistently represented in the CFS sample could be explained by the possibility of subtypes of CFS, or perhaps co-morbid conditions. Further, the use of antidepressant medications may mask the pattern by altering the temporal characteristics of the EEG. The results of this pilot study indicate that further research is warranted to verify that the pattern holds across the wider population of CFS sufferers.

Twisted Edwards curves revisited

This paper introduces fast algorithms for performing group operations on twisted Edwards curves, pushing the recent speed limits of Elliptic Curve Cryptography (ECC) forward in a wide range of applications. Notably, the new addition algorithm uses for suitably selected curve constants. In comparison, the fastest point addition algorithms for (twisted) Edwards curves stated in the literature use . It is also shown that the new addition algorithm can be implemented with four processors dropping the effective cost to . This implies an effective speed increase by the full factor of 4 over the sequential case. Our results allow faster implementation of elliptic curve scalar multiplication. In addition, the new point addition algorithm can be used to provide a natural protection from side channel attacks based on simple power analysis (SPA).

Jacobi quartic curves revisited

This paper provides new results about efficient arithmetic on Jacobi quartic form elliptic curves, y 2 = d x 4 + 2 a x 2 + 1. With recent bandwidth-efficient proposals, the arithmetic on Jacobi quartic curves became solidly faster than that of Weierstrass curves. These proposals use up to 7 coordinates to represent a single point. However, fast scalar multiplication algorithms based on windowing techniques, precompute and store several points which require more space than what it takes with 3 coordinates. Also note that some of these proposals require d = 1 for full speed. Unfortunately, elliptic curves having 2-times-a-prime number of points, cannot be written in Jacobi quartic form if d = 1. Even worse the contemporary formulae may fail to output correct coordinates for some inputs. This paper provides improved speeds using fewer coordinates without causing the above mentioned problems. For instance, our proposed point doubling algorithm takes only 2 multiplications, 5 squarings, and no multiplication with curve constants when d is arbitrary and a = ±1/2.

The distribution of the sample minimum-variance frontier

In this paper, we present a finite sample analysis of the sample minimum-variance frontier under the assumption that the returns are independent and multivariate normally distributed. We show that the sample minimum-variance frontier is a highly biased estimator of the population frontier, and we propose an improved estimator of the population frontier. In addition, we provide the exact distribution of the out-of-sample mean and variance of sample minimum-variance portfolios. This allows us to understand the impact of estimation error on the performance of in-sample optimal portfolios. Key Words: minimum-variance frontier; efficiency set constants; finite sample distribution

Biomechanical aspects of bone microstructure in vertebrates : potential approach to paleontological investigations

The biomechanical or biophysical principles can be applied to study biological structures in their modern or fossil form. Bone is an important tissue in paleontological studies as it is a commonly preserved element in most fossil vertebrates, and can often allow its microstructures such as lacuna and canaliculi to be studied in detail. In this context, the principles of Fluid Mechanics and Scaling Laws have been previously applied to enhance the understanding of bone microarchitecture and their implications for the evolution of hydraulic structures to transport fluid. It has been shown that the microstructure of bone has evolved to maintain efficient transport between the nutrient supply and cells, the living components of the tissue. Application of the principle of minimal expenditure of energy to this analysis shows that the path distance comprising five or six lamellar regions represents an effective limit for fluid and solute transport between the nutrient supply and cells; beyond this threshold, hydraulic resistance in the network increases and additional energy expenditure is necessary for further transportation. This suggests an optimization of the size of bone’s building blocks (such as osteon or trabecular thickness) to meet the metabolic demand concomitant to minimal expenditure of energy. This biomechanical aspect of bone microstructure is corroborated from the ratio of osteon to Haversian canal diameters and scaling constants of several mammals considered in this study. This aspect of vertebrate bone microstructure and physiology may provide a basis of understanding of the form and function relationship in both extinct and extant taxa.

Composite load model decomposition : induction motor contribution

In this thesis, a new technique has been developed for determining the composition of a collection of loads including induction motors. The application would be to provide a representation of the dynamic electrical load of Brisbane so that the ability of the power system to survive a given fault can be predicted. Most of the work on load modelling to date has been on post disturbance analysis, not on continuous on-line models for loads. The post disturbance methods are unsuitable for load modelling where the aim is to determine the control action or a safety margin for a specific disturbance. This thesis is based on on-line load models. Dr. Tania Parveen considers 10 induction motors with different power ratings, inertia and torque damping constants to validate the approach, and their composite models are developed with different percentage contributions for each motor. This thesis also shows how measurements of a composite load respond to normal power system variations and this information can be used to continuously decompose the load continuously and to characterize regarding the load into different sizes and amounts of motor loads.

Selection and optimization of piezoelectric polyvinylidene fluoride polymers for adaptive optics in space environments

Various piezoelectric polymers based on polyvinylidene fluoride (PVDF) are of interest for large aperture space-based telescopes. Dimensional adjustments of adaptive polymer films depend on charge deposition and require a detailed understanding of the piezoelectric material responses which are expected to deteriorate owing to strong vacuum UV, � -, X-ray, energetic particles and atomic oxygen exposure. We have investigated the degradation of PVDF and its copolymers under various stress environments detrimental to reliable operation in space. Initial radiation aging studies have shown complex material changes with lowered Curie temperatures, complex material changes with lowered melting points, morphological transformations and significant crosslinking, but little influence on piezoelectric d33 constants. Complex aging processes have also been observed in accelerated temperature environments inducing annealing phenomena and cyclic stresses. The results suggest that poling and chain orientation are negatively affected by radiation and temperature exposure. A framework for dealing with these complex material qualification issues and overall system survivability predictions in low earth orbit conditions has been established. It allows for improved material selection, feedback for manufacturing and processing, material optimization/stabilization strategies and provides guidance on any alternative materials.