The log K, ΔH° and ΔS° values for the interaction of several metal ions with the two isomers of the cyclic polyether, 2,5,8,15,-18,21 hexaoxatricyclo[20.4.0.0^9,14]hexacosane are reported. The stability order found for alkali metal ion interaction with either isomer is identical to the order of ion permeability through reconstituted biological membranes for structurally related antibiotics. The size of the metal ion is critical in determining the extent of interaction. A calorimetric titration study of proton ionization from several monosaccharides and derivatives, pyrimidine bases and their nucleosides, adenosine and its derivatives, and cycloheptaamylose is described. The heats of reaction obtained in this study show the acidity of adenosine to be associated with the ribose portion of the molecule and that the presence of both the 2' and 3'-hydroxyl groups results in a marked acidity increase compared to similar compounds lacking vicinal OH groups. The acidity in the sugars is associated with the 1 position.

Interstellar chemistry has been a growing field over the last several decades. There is particular interest on the nature and reactivity of interstellar molecules; most notably that of polycyclic aromatic hydrocarbons (PAHs). My thesis focused on the kinetics of unimolecular dissociation of small PAH and PAH-like molecules under interstellar conditions. PAHs (naphthalene (NAP), anthracene (ANT) and pyrene (PYR)), some dihydro- equivalents (1,2-dihydronapthalene (DHN) and 9,10-dihydrophenanthrene (DHP)) and a few other small aromatic organic molecules (indene (IND), ethynylbenzene (EB), propynylbenzene (PB) and benzocyclobutene (BCB)) were studied using imaging photo-electron photo-ion coincidence spectroscopy (iPEPICO) and electron impact mass spectrometry (MS); both mass analyzed ion kinetic energy spectrometry (MIKES) and collision induced dissociation (CID). Experiments were performed at different ionization energies to produce breakdown diagrams for the various fragments. These diagrams are then fit using RRKM theory to determine the zero Kelvin activation energy (E0) and the entropy of activation (Δ‡S); these results are then compared and discussed. All these molecules were compared in order to try and find any overlying trends which could be applied to their role in the interstellar medium (ISM). It was determined that H loss was the dominant fragmentation channel, as it was the only dissociation channel common to the majority of molecules studied. It was also seen that organic fragment loss (C2H2, CH3 and C4H2) was only observed in smaller molecules which indicates that PAHs are not likely a source of these molecules. The small fragment molecules gave insight into the stability of closed ring structures, such as PAHs, through the comparison of the dissociation of closed and open structures. The dihydro-PAHs, selected as a probe to investigate the proposed catalytic role of PAHs in the formation of molecular hydrogen, yielded very interesting results. It was seen that these molecules would readily undergo isomerisation prior to dissociation. This added an unexpected level of difficulty to the calculations but quickly demonstrated how the presence of additional hydrogen atoms could greatly disrupt the dissociations, as it was not the simple process of removing them as it was originally believed. The overall trend observed was that it is the structure, not the size, which has the dominating effect on the dissociation. Ions of similar structure behaved similarly, regardless of a change in mass; isomers, however, had radically different behaviours which can only be attributed to their differing molecular conformations. This observation could aid in the understanding of larger PAHs, those which are believed to exist in the ISM, and what role they may play in the chemistry of the universe.

Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are chronic, debilitating illnesses. Impairments in cognitive processes such as social cognition, episodic simulation, and neuropsychological performance have been documented separately in both disorders. Despite our increasing knowledge of these impairments, the potential underlying transdiagnostic mechanisms remain relatively unexplored. This thesis examines correlates of these processes in persons with a primary diagnosis of MDD with a history of trauma exposure, and in persons with PTSD. The first study examined the association between the social cognitive domain of empathy and parental bonding in women with PTSD associated with childhood abuse. Participants with PTSD reported altered levels of cognitive and affective empathy, compared to controls. Paternal care during childhood was the only predictor of cognitive empathy (i.e., perspective taking). The second study investigated the specificity of episodic simulation of future positive, negative, and neutral events in relation to parental bonding and neuropsychological functioning among participants with MDD. Optimal parental bonding and higher scores on measures of neuropsychological functioning were associated with increased specificity of episodic simulation. In the third study, we examined the relation between dissociative symptoms and neuropsychological functioning in participants with MDD. Patients with MDD report significantly higher levels of dissociation as compared to controls, and more severe dissociation was related to poorer neuropsychological performance among this patient group. Lastly, using independent component analysis of resting-state fMRI data, the fourth study examined the association between intrinsic connectivity networks and neuropsychological performance among participants with MDD. Connectivity within the default mode, salience, and central executive networks was associated with neuropsychological and clinical (i.e., depression, dissociation, PTSD) variables. Overall, this thesis demonstrates that variables such as parental attachment, dissociation, and intrinsic connectivity networks may underlie some of the alterations in cognitive processes seen in MDD and trauma-related disorders. / Dissertation / Doctor of Philosophy (PhD) / Major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) negatively affect quality of life and day-to-day functioning. These populations show difficulties in domains related to cognitive processing, such as empathy, imagining future events, and neuropsychological functioning (e.g., memory and attention). This thesis focuses on examining variables that may be related to these difficulties. In particular, we study developmental variables, such as parental bonding, clinical symptoms, such as dissociation, and neuroimaging data. Our findings suggest that these variables are all related to impairments in different areas of cognitive processing. By understanding what may be contributing to these cognitive difficulties, we may be able to design treatment strategies that target the underlying causes of these difficulties.

<p> This thesis is concerned with 2,21 -dimercaptodiethyl sulfide. In particular, the work reported herein deals with the stability of the reagent in both its pure form and in its solutions; the determination of its acid dissociation constants; its reactivity towards metal ions; the nature of its metal complexes with Co(II), Co(III), Ni(II) and Pd(II); and its application as a potentially useful analytical reagent for the spectrophotometric determination of Ni(II) and Pd(II). </p> / Thesis / Master of Science (MSc)

Bulimia is often viewed as an extreme expression of eating concerns and body image disturbances that afflicts many adolescent and adult women. The cognitive strategies employed by individuals to inhibit eating and facilitate bingeing and purging are thought to include disattending internal sensations of hunger and satiety while sustaining attention on food, distorted beliefs, and interoceptive experiences (e.g., Heatherton & Baumeister, 1991). To the extent that these attentional and perceptual shifts mediate bulimic symptomatology, individuals with bulimic tendencies should exhibit certain cognitive attributes. Because hypnotizability, dissociation, and absorption have each been invoked (either directly or indirectly) as explanatory constructs for clinical and subclinical bulimia, the present study evaluated the absolute and relative effects of these factors on bulimic symptomatology in a large sample of undergraduate women (N = 309) using structural equation modeling. Following 2 assessments of hypnotic susceptibility (Harvard Group Scale of Hypnotic Susceptibility, Form A [Shor & Orne, 1962] & Group Stanford Hypnotic Susceptibility Scale, Form C [Crawford & Allen, 1982]), participants completed measures of eating disorder symptomatology (Eating Disorders Inventory-2 [Garner, 1991]; Three Factor Eating Questionnaire [Stunkard & Messick, 1985]), dissociation (Dissociative Experiences Scale [Carlson & Putnam, 1986]; Dissociation Questionnaire [Vanderlinden et al., 1993]), and absorption (Tellegen Absorption Scale [Tellegen & Atkinson, 1974]; Differential Attentional Processes Inventory [Crawford, Brown, & Moon, 1993; Grumbles & Crawford, 1981]). A final model including the latent constructs Hypnotizability, Dissociation, Absorption, and Bulimic Symptomatology provided a very good fit to the data (X 2 (58, N = 309) = 31.09, NFI = .932, CFI = .967, & RMSEA = .053). As hypothesized, dissociation was found to a have moderate effect (Standardized coefficient = .32, p < .01) on Bulimic Symptomatology when controlling for Hypnotizability and Absorption. Moreover, contrary to past research, the path between Hypnotizability and Bulimic Symptomatology and the path between Absorption and Bulimic Symptomatology were not significant. Based on these finding, we can now speak with increased confidence of a meaningful link between dissociation and the continuum of bulimic symptomatology. A pathological dissociative style appears to contribute to the development of bulimia. / Ph. D.

Calcium sulphate was found to have a dissociation temperature some 60°-90°C. lower than the values reported by other workers. / Master of Science

Un grand nombre de maladies cardiaques apparaissent à la suite de problèmes développementaux dus à des mutations dans des gènes très conservés durant l'évolution. Il est donc crucial d'identifier les acteurs intervenants dans la cardiogenèse. Durant ma thèse, j'ai étudié la différenciation cardiaque, en utilisant la Drosophile comme modèle, avec comme objectifs d'identifier des nouveaux intervenants grâce à l'acquisition de données globales par une approche génomique tissue spécifique. J'ai tout d'abord mis au point un protocole permettant d'acquérir des données génomique spécifiquement dans le tube cardiaque de la Drosophile lors de la différenciation des cardiomyocytes. Ce fut une étape primordiale pour le reste de ma thèse. Ce protocole me permet d'isoler spécifiquement les cellules du système cardiaque.A partir de là, j'ai réalisé une cinétique transcriptomique qui a permis de mettre en évidence environ 1000 gènes différenciellement exprimés au cours de la différenciation cardiaque. Ensuite, En collaboration avec Delphine Potier, une thésarde bio-informaticienne de l'équipe, des modules Cis-régulateur (CRM) pouvant conduire à l'expression dans le tube cardiaque ont été prédits, ainsi que des facteurs de transcription putatifs régulant ces CRM. Ces nouveaux acteurs du réseau de régulation génique cardiaque sont en cours de validation.Dans un second temps, je me suis intéressé à un facteur de transcription à homéoboîte clé de la cardiogenèse : Abdominal-A (AbdA). AbdA est essentiel pour la différenciation de la partie postérieure du tube cardiaque, le cœur proprement dit, et à l'acquisition de sa fonction. Cependant, ses cibles ainsi que son action tissue spécifique sont encore inconnu à ce jourAfin d'apporter un élément de réponse, j'ai analysé le transcriptome consécutif à un Gain de Fonction de AbdA spécifiquement dans le système cardiaque ce qui m'a permis de mettre en évidence plus de 1000 gènes dérégulés par AbdA lors de la différenciation cardiaque. / Cardiac diseases generally arise from developmental disorders caused by mutations in genes that are highly conserved during evolution. It is therefore of prime interest to identify actors which participate to cardiogenesis. During my thesis, I have analyzed cardiac differentiation, using Drosophila as a model. My objective was to identify news actors of the cardiac Gene Regulatory Network (GRN) using a genomic approach and starting from tissue specific whole data acquisition.First, I have set a protocol to allow tissue specific genomic data acquisition during cardiac differentiation. It was a critical step for my thesis. This protocol allowed me to isolate specifically cardiac system cells.Using this protocol, I analyzed the transcriptome dynamics and determined that 1000 genes are dynamically expressed during cardiac differentiation.Next, in collaboration with Delphine Potier, a PhD student in bio-informatic in the team, cis-regulatory modules (CRM), which can drive expression in the cardiac tube, have been predicted, and also putative transcription factors regulating these CRM. These new cardiac GRN actors are currently tested in vivo.In a second time, I have analyzed the function of Abdominal-A (AbdA) a homeobox transcription factor which plays a key role during cardiogenesis. :. AbdA is crucial for the differentiation of the posterior part of the organ, called heart My aim was to identify cardiac specific AbdA targets.

Dans cette thèse, les caractéristiques de l’adsorption de dithiols sur des métaux sont étudiées en utilisant principalement l’XPS à haute résolution sur synchrotron, TOF DRS at LEED. L’objectif est de caractérisé les couches auto-assemblées de dithiols formées par évaporation sous vide, comprendre la transition de dithiols d’une phase couchée vers une phase debout, et des processus de réarrangement et de dissociation. Nous avons constaté que sur Au (111) une phase couchée de butanedithiol (C4DT) pouvait être remplacé par un octanethiol pour former une phase debout mixte, et aussi que la phase C4DT debout pouvait être formée lors d’exposition rapide à des grandes doses de vapeurs de C4DT.Cela montre que la phase couchée ne doit pas empêcher la formation d'une phase debout. L'adsorption de 1,4-benzenedimethanethiol (BDMT) sur Au (111), Ag (111), Au (110), Cu (111), Cu (100) et de Pd (111) ont été étudiés dans cette thèse. La phase debout peut être formée dans certains cas, lorsque la surface n'est pas très réactive. Dans le cas de Cu et Pd, la dissociation de BDMT a été observée et un sulfure de surface a été formé sur Pd. On a étudié également l'interaction entre les atomes de chalcogène (S et Se) et certains métaux en rapport avec le travail de l'auto assemblage. Les informations détaillées sur leurs caractéristiques d'adsorption devraient aider à résoudre des ambiguïtés dans la caractérisation des assemblages de thiols et sulfures. Lors de l’adsorption de Se atomes sur Au surface on observe la chemisorption de Se et la formation de structures de Se₈, tandis que pour l'Ag le séléniure d'argent est formé. L’adsorption de soufre sur des (111), Cu (100) et de Pd (111) résulte en la sulfuration et des structures ordonnées intéressantes ont été observées. / In this thesis, the characteristics of SAMs of dithiol molecules adsorption on metals are investigated mainly by HRXPS based on synchrotron radiation, TOF-DRS and LEED. The aim is to characterize self-assembled dithiol monolayers formed by evaporative assembly, to understand the transition of dithiols from a lying down phase to standing up phase, and eventually existence of rearrangement and dissociation processes. We found that on Au(111) a lying down phase of butanedithiol (C4DT) could be substituted by octanethiols to form a mixed standing up phase, and also that standing-up C4DT phase could be formed upon rapid very large exposure to C4DT vapors. This shows that the lying down phase should not impede formation of the standing up one. The adsorption of 1,4-benzenedimethanethiol (BDMT) on Au(111), Ag(111), Au(110), Cu(111), Cu(100) and Pd(111) were investigated in this thesis. The standing up phase could be formed in some cases, when the surface is not very reactive. In case of Cu and Pd dissociation of BDMT was observed and surface sulphide was formed on Pd. Also the interaction between chalcogen atoms (S and Se) and some metals was investigated in relation to the self assembly work. The detailed information about their adsorption characteristics should help in resolving ambiguities in characterization of thiol and sulphide assemblies. The result of Se atoms adsorption on Au surface shows chemisorbed Se and Se₈ features, while for Ag the silver selenide is formed. S atoms adsorption on Cu(111), Cu(100) and Pd(111) surfaces result in metal sulfidation and some interesting structures were observed.

This dissertation presents an investigation into the structure of macromolecular protein assemblies by mass spectrometry. The experiments described within are designed to systematically assess the analytical utility of surface-induced dissociation (SID) tandem mass spectrometry in the characterization of multi-subunit protein complexes. This is accomplished by studying the effects of ion-surface collision on the fragmentation products of protein assemblies that vary by mass, number of subunits, and protein structural features. The dissociation energetics and mechanisms of protein complexes are considered by examining the influence of ion internal energy and sub-oligomeric protein structure on the dissociation process. Conditions are first established for the preservation of “native” protein quaternary structure and applied to previously characterized systems for proof-ofconcept. These conditions are subsequently extended to determine the molecular weight and subunit stoichiometry of several small heat shock proteins. Native mass spectrometry is then combined with limited proteolysis experiments to characterize the subunit interface of a unique small heat shock protein, Hsp18.5 from Arabidopsis thaliana, identifying regions of the protein essential for preservation of the native dimer. The dissociation of non-covalent protein assemblies is then explored on a quadrupole time-of-flight (Q-TOF) mass spectrometer, modified for the study of ion-surface collisions. This instrument allows ions to be dissociated through collisions with a surface or more conventional collisions with gas atoms. The dissociation of protein complexes is explored by both activation methods beginning with specific and non-specific dimers with masses less than 40 kDa. These studies are extended to larger assemblies with as many as 14 subunits weighing over 800 kDa, and are applied to both homo- and hetero-oligomeric protein complexes. Activation of a protein complex with “n” subunits through multiple collisions with inert gas atoms results in asymmetric dissociation into a highly charged monomer and complementary (n-1)-mer regardless of protein size or subunit architecture. This process is known to occur through an unfolding of the ejected subunit, and limits the amount of structural insight that can be gleaned from such studies. Collision at a surface however, results in more charge and mass symmetric fragmentation, and in some instances reflects the substructure of the protein assembly under investigation. The differences observed between the CID and SID of protein complexes is attributed to the rapid deposition of large amounts of internal energy deposited upon collision at a more massive target such as a surface. The ion activation time-frame and energy transfer efficiency are proposed to induce dissociation on a time-scale that precedes subunit unfolding providing access to dissociation pathways that are inaccessible by traditional means of activation. The systems studied here represent the largest ions fragmented via surface collisions within a mass spectrometer, and the fragmentation products observed by SID demonstrate its promise for expanding the role of mass spectrometry in the field of structural biology.

This study tested a dissociative model of aggression measurement. Aggression is construed as having two components, each of which is associated more strongly with either implicit or explicit measures of aggression. A videogame based frustration manipulation was used to elicit hostile aggressive responses in the form of hard force applied to buttons. Instrumental aggression criteria were also assessed in the form of honesty in reporting game outcomes, willingness to pause games while believing that pausing could damage the study results, and willingness to use unfair strategies that are also described as damaging to study results. Differential prediction of these behaviors by implicit and explicit measures of aggression supported a dissociative model of aggression measurement.