O aminoácido selenocisteína (Sec) representa a principal forma biológica de selênio sendo requerida uma complexa maquinaria molecular para sua síntese e incorporação co-traducional em selenoproteínas. A Seril-tRNA sintetase (SerRS) inicia essa via, aminoacilando o Ser-tRNASec (SelC) com uma serina e também aminoacila os tRNAsSer. Sendo assim, um dos focos deste trabalho foi estudar a interação da SerRS de Trypanosoma brucei (T. brucei) com os tRNAsSer e o SelC utilizando a técnica de anisotropia de fluorescência para determinar suas constantes de dissociação. Em Kinetoplastidae, além da via de síntese de selenocisteína, há três selenoproteínas: SelT, SelK e SelTryp. No entanto, pouco se sabe a respeito das mesmas, sendo o estudo destas selenoproteínas o outro foco deste trabalho. Os fragmentos de DNA que codificam estas selenoproteínas foram subclonados em vetor de expressão pET 28a e 29a para posterior uso em células de Escherichia coli (E. coli). Para as proteínas SelK e SelTryp os ensaios de expressão apresentaram resultados insuficientes para dar continuidade aos experimentos planejados, pois o rendimento foi baixo e a purificação não foi possível. Já com a proteína SelT, devido à grande dificuldade encontrada para tornà-la solúvel, descobriu-se, no decorrer do trabalho, que tratava-se de uma proteína de membrana, ocasionando mudanças de alguns objetivos previamente propostos e consequentemente busca por novas estratégias. Conseguiu-se expressá-la na de forma solúvel e purificá-la por cromatografias. Ensaios realizados no SEC-MALLS mostraram uma estabilidade do complexo proteína-detergente. Com a TbSerRS é possível concluir que a organização de especificidade de ligação da enzima com seus ligantes se dá crescentemente: SelC>tRNASer7>tRNASer3a>tRNASer3b. E com as selenoproteínas do T. brucei faz-se necessários novas contruções para SelK e SelTryp e dar continuidade aos experimentos com a SelT tentando cristalizá-la, já que prototolo para a obtenção do complexo proteína-detergente está montado e estabilizado. / Selenocysteine (Sec) amino acid is the major biological form of selenium and requires a complex molecular machinery for its synthesis and co-translational incorporation into selenoproteins. The Seryl-tRNA synthetase (SerRS) starts this biosynthesis and matches the tRNASec (SELC) with a serine and the tRNAsSer, therefore the focus of this study is on SerRS of Trypanosoma brucei (T. brucei) and tRNAsSer and SELC interactions, with fluorescence anisotropy techinic to determinat dissociation constants. Three selenoproteins, namely SelT, SelK and SelTryp, besides the route of selenocysteine synthesis there be in Kinetoplastidae. DNA fragments that coding for these selenoproteins were subcloned in 28a and 29a to use into Escherichia coli (E. coli) cells. For Selk and SelTryp proteins, the expression protocol did not show an unsatisfactory result to continue the experiments. Many difficulties were encountered in studies with Selt protein, mainly in attempts to make it soluble. Our analyses revealed SelT was a membrane protein, therefore it could cause changes in some objectives and search for new strategies. It could be expressed and purified in cromatographis. SEC-MALLS assays showed a stability of the protein detergent complex. With TbSerRS is possible to conclude that the organization of binding specificity of the enzyme with its ligands occurs increasingly: SelC>tRNASer7>tRNASer3a>tRNASer3b. And selenoproteins in T. brucei, it is necessary for new constructions to SelK and SelTryp to continue the experiments trying to crystallizes SelT, since prototolo for obtaining the protein-detergent complex is assembled and stabilized.

Duan Lifang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 83-87). / Abstracts in English and Chinese. / Title Page --- p.i / Abstract (English) --- p.ii / Abstract (Chinese) --- p.iii / Acknowledgements --- p.iv / Table of Contents --- p.v / List of Tables --- p.vii / List of Figures --- p.viii / Symbols and Abbreviations --- p.x / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- Mass spectrometry in biochemistry --- p.1 / Chapter 1.2 --- Electrospray ionization (ESI) --- p.2 / Chapter 1.3 --- Fourier transforms ion cyclotron resonance mass spectrometry (FTICR-MS) --- p.4 / Chapter 1.3.1 --- Ion motions --- p.5 / Chapter 1.3.2 --- Mass calibration --- p.7 / Chapter 1.3.3 --- Tandem mass spectrometry --- p.11 / Chapter 1.4 --- Sustained off-resonance irradiation collision-induced dissociation (SORI-CID) of peptide ions --- p.13 / Chapter 1.5 --- Outline of present work --- p.18 / Chapter CHAPTER 2 --- INSTRUMENTATION AND EXPERIMENTAL / Chapter 2.1 --- Fourier-trans form ion cyclotron resonance mass spectrometer --- p.19 / Chapter 2.1.1 --- Vacuum system --- p.19 / Chapter 2.1.2 --- Nanospray source --- p.23 / Chapter 2.1.3 --- Ion transfer system --- p.26 / Chapter 2.1.4 --- Infinity cell --- p.28 / Chapter 2.1.5 --- Data acquisition system --- p.29 / Chapter 2.2 --- Experimental --- p.29 / Chapter 2.2.1 --- Simple acquisition pulse program --- p.30 / Chapter 2.2.2 --- Tandem mass spectrometry (SORI-CID MS/MS) --- p.32 / Chapter CHAPTER 3 --- DISSOCIATION OF MODEL PEPTIDE IONS UNDER SORI-CID CONDITIONS / Chapter 3.1 --- Introduction --- p.35 / Chapter 3.2 --- Experimental --- p.37 / Chapter 3.3 --- Results and discussion --- p.41 / Chapter 3.3.1 --- "SORI-CID of XG3WG3X (where X 二 R, K and N)" --- p.41 / Chapter 3.3.2 --- SORI-CID of RGnWGnR (where n=l -5) --- p.46 / Chapter 3.3.3 --- SORI-CID of RG3XG3R (where X = D and E) --- p.48 / Chapter 3.4.4 --- SORI-CID of sequence isomers of RG5WG5R --- p.51 / Chapter 3.4 --- Conclusions --- p.56 / Chapter CHAPTER 4 --- EXACT MASS MEASUREMENTS OF THE PRODUCT IONS DERIVED FROM SORI-CID FTICR-MS / Chapter 4.1 --- Introduction --- p.57 / Chapter 4.2 --- Experimental --- p.60 / Chapter 4.3 --- Results and discussion --- p.61 / Chapter 4.3.1 --- Origin(s) of the mass measurement error --- p.63 / Chapter 4.3.2 --- Pressure effect on the cyclotron frequencies of trapped ions --- p.67 / Chapter 4.3.3 --- Modified internal lock-mass calibration method --- p.70 / Chapter 4.4 --- Conclusions --- p.79 / Chapter CHAPTER 5 --- CONCLUSIONS --- p.81 / REFERENCES --- p.83 / APPENDIX I The Proton affinity (PA) and the structural formulae of 20 α-amino acids --- p.88 / APPENDIX II Schematics of the proposed mechanisms of peptide dissociation under low-energy CID conditions --- p.89 / APPENDIX III Pulse programs for simple MS and MS/MS experiments --- p.92 / APPENDIX IV Schematics of the proposed mechanisms for the formation of y8+ ions from the singly protonated arginine- and lysine-containing peptides --- p.99

超臨界水中的溶解和化學反應受到一系列因素的影響，如溶解能，熵以及溶液密度等，是決定化學平衡的基本熱力學量，同時這些又受到溫度和壓強的控制。爲了解釋這些因素的影響，有必要把量子化學的靜態優化與分子動力學模擬相結合和比較。通過量子化學可以得到0K下的優化結構，而分子動力學模擬可以提高實際時間的勢能面。本論文的研究，主要圍繞在氣態下甲醛分子HCHO和甲酸分子HCOOH跟不同數目水分子H2O結合的水合簇結構，以及在常溫水溶液和超臨界水溶液中，甲醛HCHO和甲酸HCOOH的溶解結構和溫度所帶來的熱效應，最後研究甲酸HCOOH在水催化下的離解反應機理。 / 使用化學計算軟件Gaussian03和密度泛函理論方法，用6-311++G(d,p)基組來計算和研究氣態下甲醛分子和甲酸分子的水簇合物。通過不同數目的水分子所得到的最穩定簇合物的結構和能量，來研究甲醛分子HCHO，甲酸根離子HCOO⁻以及甲酸分子HCOOH與水分子相互結合時的氫鍵作用力強弱和簇合物的穩定性。同時，也考慮了甲酸酸解后的水簇合物結構，通過與沒有酸解的水簇合物的比較，為進一步瞭解水溶解中甲酸的酸解離情況提供寶貴的信息。 / 使用基於贗勢和平面波基組，以及密度泛函理論的從頭計算分子動力學軟件VASP，來模擬和研究甲醛分子HCHO和甲酸分子在水溶液中的溶解情況。根據對半徑關聯函數PRDF的統計結果，可以觀察出溶質的溶解結構，以及溶劑分子之間，或者溶質與溶劑分子之間的氫鍵作用。通過水合數目可以看出氫鍵作用力隨著溫度的提升而減弱。水溶液的溫度在臨界點之上時，其結果證實了甲酸的酸解反應受到嚴重的抑制，與常溫水的結果相反。 / 使用從頭計算分子動力學軟件CPMD中基於Car-Parrinello分子動力學方法的Metadynamics方法對甲酸的反應機理進行系統的研究，包含脫水反應和脫氫反應。解離反應分別包含不同數目的分子，通過對比來研究反應中水分子所起的潛在的催化作用。除此之外，通過300K和700K這兩種不同溫度下的結果對比，來解釋超臨界水溶解中甲酸快速解離的原因。自由能曲面和自由能壘揭示了在不同環境下甲酸的主要解離途徑。 / Solvation and chemical reactions in supercritical water are affected by a number of factors. Solvation energy, entropy, and densities are the basic thermodynamic quantities that determine the chemical equilibriums, which can be controlled by temperature and pressure. To account for these factors, static optimization leading to zero-temperature structures should be combined and compared with molecular dynamics simulation in real time. In my thesis, the solvation structures are studied in gas phase and aqueous phase, to understand the properties of solvent water and the thermal effect on the reactions. / The hydrated clusters of formaldehyde and formic acid in gas phase are explored computationally by density functional theory (DFT) with a basis set 6-311++G(d,p). Investigation on the structures and energies of hydrated HCHO, HCOO⁻ and HCOOH solvated by a number of water molecules is important for understanding the hydrogen bond interactions as the number of water molecules increases. Comparisons between non-dissociated and dissociated clusters of hydrated formic acid provide valuable information on the acidic dissociation of formic acid in aqueous solution. / The solvations of formaldehyde and formic acid in aqueous solution are simulated by density functional theory based ab initio molecular dynamics (AIMD) method with pseudopotentials and a plane wave basis set using Vienna Ab-initio Simulation Package (VASP). The pair radial distribution function is obtained to elucidate the solvation structure and the hydrogen bond interaction among solvent molecules, and between solute and solvent. The hydration number indicates the weakening of the hydrogen bond with increasing temperature. The results at the temperatures above the critical point of water show that the acid dissociation of formic acid is greatly depressed which is different from the results in ambient water. / The mechanisms for the dissociations of formic acid in the gas phase and in aqueous solution are studied by Car-Parrinello (CP)-based metadynamics (MTD) method, implemented in the Car-Parrinello Molecular Dynamics (CPMD) program. The two main dissociations channels of dehydration and dehydrogenation, including zero, one, two and bulk water molecules, respectively, are simulated with a biased external potential to examine the potential catalytic role of water. In addition, the thermal effects at two different temperatures are included to account for the rapid dissociation of formic acid in supercritical water. The free energy surfaces are reconstructed and the barriers are calculated to show the main dissociation pathway of formic acid in different environments. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chen, Qiubo. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 185-194). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / TITLE PAGE --- p.i / ABSTRCACT (ENGLISH) --- p.ii / (CHINESE) --- p.v / AKNOWLEDGEMENTS --- p.vii / TABLE OF CONTENTS --- p.viii / LIST OF FIGURES --- p.xiv / LIST OF TABLES --- p.xxiv / Chapter Chapter ONE --- Background / Chapter 1.1 --- Introduction of green chemistry --- p.1 / Chapter 1.1.1 --- Green chemistry --- p.1 / Chapter 1.1.2 --- Supercritical fluid (SCF) and supercritical water (SCW) --- p.2 / Chapter 1.2 --- Formaldehyde and formic acid in supercritical water --- p.8 / Chapter 1.2.1 --- Formaldehyde --- p.8 / Chapter 1.2.2 --- Formic acid --- p.12 / Chapter 1.3 --- Scope of this thesis --- p.17 / Chapter Chapter TWO --- Theories and Calculation Methods / Chapter 2.1 --- General background --- p.19 / Chapter 2.1.1 --- Schrödinger equation --- p.19 / Chapter 2.1.2 --- Born-Oppenheimer approximation --- p.20 / Chapter 2.2 --- Hartree-Fock (HF) approximation and post-Hartree-Fock (post-HF) approximation --- p.22 / Chapter 2.3 --- Density functional theory (DFT) --- p.28 / Chapter 2.3.1 --- Kohn-Sham (KS) scheme --- p.29 / Chapter 2.3.2 --- Local density approximation (LDA) --- p.31 / Chapter 2.3.3 --- Generalized gradient approximation (GGA) --- p.33 / Chapter 2.3.4 --- Hybrid functionals --- p.34 / Chapter 2.4 --- Ab initio molecular dynamics (AIMD) --- p.35 / Chapter 2.4.1 --- Molecular dynamics --- p.35 / Chapter 2.4.2 --- Ab initio molecular dynamics --- p.36 / Chapter 2.4.3 --- Plane waves --- p.42 / Chapter 2.4.4 --- Pseudopotentials (PP) --- p.44 / Chapter 2.4.5 --- Periodic boundary condition (PBC) --- p.48 / Chapter 2.5 --- Metadynamics (MTD) method --- p.48 / Chapter 2.5.1 --- The Algorithm --- p.49 / Chapter 2.5.2 --- Lagrangian metadynamics and the choice of V(t,s) --- p.52 / Chapter 2.5.3 --- The choice of CVs --- p.53 / Chapter Chapter THREE --- Structures of the Hydrated Clusters of Formaldehyde and Formic Acid / Chapter 3.1 --- Introduction --- p.55 / Chapter 3.2 --- Computational details --- p.56 / Chapter 3.3 --- Results and discussions --- p.58 / Chapter 3.3.1 --- Studies of HCHO(H₂O)[subscript n] clusters, n = 0~4 --- p.58 / Chapter 3.3.1.1 --- The structures of HCHO(H₂O)[subscript n] clusters, n = 0~4 --- p.58 / Chapter 3.3.1.2 --- The energies of HCHO(H₂O)[subscript n] clusters, n = 0~4 --- p.63 / Chapter 3.3.2 --- Studies of HCHO⁻(H₂O)[subscript n] clusters, n = 0~6 --- p.65 / Chapter 3.3.2.1 --- The structures of HCHO⁻(H₂O)[subscript n] clusters, n = 0~4 --- p.66 / Chapter 3.3.2.2 --- The energies of HCHO⁻(H₂O)[subscript n] clusters, n = 0~4 --- p.71 / Chapter 3.3.2.3 --- Studies of HCOO⁻(H2O)[subscript n] clusters, n = 5 and 6 --- p.73 / Chapter 3.3.3 --- Studies of HCOOH⁻(H2O)[subscript n] and HCOO⁻(H₃O)⁺(H₂O)[subscript n-1] clusters --- p.76 / Chapter 3.3.3.1 --- Results of cis-HCOOH(H₂O)[subscript n] clusters and trans-HCOOH(H₂O)[subscript n] clusters, n = 0 ~ 4 --- p.76 / Chapter 3.3.3.2 --- Results of trans-HCOOH(H₂O)[subscript n] clusters, n > 4 --- p.82 / Chapter 3.3.3.3 --- Comparisons of non-dissociated trans-HCOOH(H₂O)[subscript n] clusters with dissociated ion pair HCOO⁻(H₃O)⁺(H₂O)[subscript n-1] clusters --- p.84 / Chapter 3.4 --- Summary --- p.87 / Chapter CHAPTER FOUR --- Ab initio Molecular Dynamics Studies on the Solvations of Formaldehyde HCHO and Formic Acid HCOOH in Water Solution at Different Temperatures / Chapter 4.1 --- Introduction --- p.90 / Chapter 4.2 --- Computational details --- p.93 / Chapter 4.3 --- Results and discussions --- p.94 / Chapter 4.3.1 --- The solvation of water solution --- p.94 / Chapter 4.3.1.1 --- The solvation of pure water solution at T = 300 K, 600 K, 700 K and 2000 K --- p.95 / Chapter 4.3.1.2 --- The solvation of proton H⁺ in water solution at T = 300 K and 700 K --- p.101 / Chapter 4.3.2 --- The solvation of formaldehyde HCHO in water solution at T = 300 K, 500 K, 700 K and 900 K --- p.104 / Chapter 4.3.3 --- The solvation of formate ion HCOO⁻ in water solution at T = 300 K, 500 K, 700 K and 900 K --- p.109 / Chapter 4.3.4 --- The solvation of formic acid HCOOH in water solution at T = 300 K, 500 K, 700 K and 900 K --- p.117 / Chapter 4.4 --- Summary --- p.125 / Chapter CHAPTER FIVE --- The Reactions of Formic Acid HCOOH: Insights from Car-Parrinello Based Metadynamics (MTD) Method / Chapter 5.1 --- Introduction --- p.128 / Chapter 5.2 --- Computational details --- p.130 / Chapter 5.3 --- Results and Discussions --- p.132 / Chapter 5.3.1 --- The intrinsic rotation of a single formic acid molecule HCOOH in gas phase at T = 300 K and T = 700 K --- p.132 / Chapter 5.3.2 --- The dehydration of formic acid in gas phase at T = 300 K and T = 700 K --- p.140 / Chapter 5.3.2.1 --- The dehydration of a single formic acid molecule trans-HCOOH --- p.140 / Chapter 5.3.2.2 --- The dehydration of formic acid molecule trans-HCOOH with one water molecule --- p.147 / Chapter 5.3.2.3 --- The dehydration of formic acid molecule trans-HCOOH with two water molecules --- p.152 / Chapter 5.3.3 --- The dehydrogenation of formic acid in gas phase at T = 300 K and T = 700 K --- p.158 / Chapter 5.3.3.1 --- The dehydrogenation of a single formic acid molecule cis-HCOOH --- p.158 / Chapter 5.3.3.2 --- The dehydrogenation of formic acid molecule cis-HCOOH with one water molecule --- p.163 / Chapter 5.3.3.3 --- The dehydrogenation of formic acid molecule cis-HCOOH with two water molecule --- p.167 / Chapter 5.3.4 --- The dissociations of formic acid in water solution at T = 300 K and T = 700 K --- p.171 / Chapter 5.3.4.1 --- The acid dissociation of formic acid in water solution --- p.173 / Chapter 5.3.4.2 --- The dehydration of formic acid in water solution --- p.175 / Chapter 5.3.4.3 --- The dehydrogenation of formic acid in water solution --- p.178 / Chapter 5.4 --- Summary --- p.181 / References --- p.185

The objective of this study is to investigate cocrystal solubility and dissolution behavior to elucidate the factors affecting these processes in various media. Six cocrystals with xanthines (theophylline (THP), caffeine (CAF) and theobromine (THB)) were prepared and characterized by powder X-ray diffraction and thermal methods. Two cocrystals (CAFCA I and THBSA) are new solids and their crystal structures were determined by single crystal X-ray diffraction. Cocrystal solubility behavior depended on the dissolving complex solubility and its dissociation behavior in solution. Two THP cocrystals - one with acetaminophen (ACE) and one with citric acid (CA) created different degrees of free THP supersaturation in solubility and dissolution studies. High transient THP supersaturation caused almost immediate THP hydrate crystallization from THPCAH and led to non-congruent solubility behavior. Such behavior was not observed with the ACETHP because free THP supersaturation was not sufficient to induce rapid crystallization but did so over longer equilibration times. Three salicylic acid (SA) cocrystals with xanthines (THP, CAF, and THB) were prepared; two (THPSA and CAFSA) had low aqueous solubility compared to their pure components and one (THBSA) had higher solubility. Both cocrystal components in these cocrystals produced higher solubility/dissolution rates in alkaline media due to ionization. Also, at higher pH, THB precipitated from THBSA solutions because of higher THB supersaturation under alkaline conditions. Caffeine (CAF) and theophylline (THP) both form cocrystals with citric acid (CA) which is a highly water-soluble cocrystal former. Both CAFCA Form I and II solubility and dissolution behavior were studied. THPCAH exhibited non-congruent dissolution because of rapid precipitation of THP hydrate on the dissolving cocrystal surface. CAFCA exhibited congruent dissolution because it did not produce sufficient supersaturation to precipitate CAF hydrate during dissolution. CA cocrystals also have the unusual behavior of high viscosities produced in the dissolution boundary layer due to CA’s high solubility. These viscosities alter diffusion coefficients which reduce dissolution rates from that expected based purely on solubility. To further understand cocrystal dissolution, a diffusion-convection-reaction (DCR) model was developed to predict cocrystal dissolution rates in various media. This model predicted concentration profiles of all species (complex, free components and reactive species) in the diffusion layer of a rotating disk intrinsic dissolution system. Predicted dissolution rates had varying degrees of agreement with experimental data depending on the cocrystal model and the medium into which the cocrystal dissolved.

Cholera is an epidemic infectious diarrhoeal disease that for centuries has proven its frightening ability to cause rapid and widespread loss of human life. All symptoms associated with cholera are a result of rapid dehydration due to infection by pathogenic strains of the bacterium Vibrio cholerae. The damaging effects associated with cholera are mainly attributed to the toxin, which is secreted by the bacterium and infects cells lining the gastrointestinal tract. A sialidase, also secreted by the bacterium, is believed to facilitate toxin uptake by the gastrointestinal epithelium. V. cholerae sialidase is therefore a potential target for therapeutic intervention. A survey of the literature reveals that sialidases from different species share common features with respect to their structure, substrate specificity and catalytic mechanism. The unsaturated sialic acid, Neu5Ac2en, inhibits most exosialidases with a dissociation constant of inhibitor of -10-4 to-10-6 M and has frequently been used as a template in the design of more potent sialidase inhibitors. In the case of V. cholerae sialidase, there have been no inhibitors reported to date that are significantly more potent than Neu5Ac2en itself The present research aimed to develop a range of mimics of Neu5Ac2en, which contain various substituents to replace the C-6 glycerol side chain, as potential inhibitors of V cholerae sialidase. The x-ray crystal structure of V cholerae sialidase was used to explore potential interactions between active site residues and C-6 modified Neu5Ac2en mimetics of known inhibitory potency. Opportunities for interactions within the glycerol side chain pocket in the active site of V cholerae sialidase are discussed. A novel synthetic strategy was developed for the synthesis of a series of glucuronidebased Neu5Ac2en mimetics starting from readily available GIcNAc. This approach was employed for the preparation of Neu5Ac2en mimetics that contained an ether or thioether substituent as replacement of the glycerol side chain of Neu5Ac2en. Progress was also made towards the synthesis of a series of C-6 acylamino Neu5Ac2en mimetics. Analysis by 1H NMR spectroscopy showed that the acylamino derivatives adopted a half-chair conformation that was similar to the conformation of Neu5Ac2en but different to the conformation adopted by the ether and thioether derivatives prepared. The inhibitory activity of the C-6 ether and thioether Neu5Ac2en mimetics prepared was evaluated in vitro using an enzyme assay. It was found that most of the derivatives inhibited V. cholerae sialidase with a K1 of approximately 1O-4 M. The derivatives containing a hydrophobic side chain were found to be slightly more potent compared to derivatives with more hydrophilic side chains. A more detailed study of binding interactions between the C-6 thioether Neu5Ac2en mimetics and V cholerae sialdiase was carried out using STD 1H NMR spectroscopy and computational molecular modelling.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 73-80).

<p>Självskadande är ett växande fenomen i vårt samhälle och dissociation erkänns allt mer. Aktuell forskning visar på en stark koppling mellan fenomenen. I syfte att få ökad kunskap om dissocierande självskadepatienter samt behandling av denna patientgrupp utifrån psykodynamisk teori intervjuades sex erfarna och verksamma terapeuter. Data från de sex intervjuerna strukturerades och bearbetades genom en kombinerad deduktiv och induktiv tematisk analys. Resultatet visar att huvudproblematiken ansågs vara dissociationen. Självskadandet sågs som ett sätt att handskas med underliggande problem, varför fokus främst låg på beteendets funktion. Karakteristiskt för det terapeutiska arbetet var att fokus i behandlingen inledningsvis låg på att bygga en förtroendefull terapeutisk relation, därefter att integrera patientens dissocierade delar, samt att bearbeta tidigare traumatiska upplevelser. Undersökningen visar att teori och forskning kring dissociation och självskadebeteende har klinisk och empirisk etablering.</p>

Självskadande är ett växande fenomen i vårt samhälle och dissociation erkänns allt mer. Aktuell forskning visar på en stark koppling mellan fenomenen. I syfte att få ökad kunskap om dissocierande självskadepatienter samt behandling av denna patientgrupp utifrån psykodynamisk teori intervjuades sex erfarna och verksamma terapeuter. Data från de sex intervjuerna strukturerades och bearbetades genom en kombinerad deduktiv och induktiv tematisk analys. Resultatet visar att huvudproblematiken ansågs vara dissociationen. Självskadandet sågs som ett sätt att handskas med underliggande problem, varför fokus främst låg på beteendets funktion. Karakteristiskt för det terapeutiska arbetet var att fokus i behandlingen inledningsvis låg på att bygga en förtroendefull terapeutisk relation, därefter att integrera patientens dissocierade delar, samt att bearbeta tidigare traumatiska upplevelser. Undersökningen visar att teori och forskning kring dissociation och självskadebeteende har klinisk och empirisk etablering.

Ce mémoire est composé de deux parties. Une partie théorique et une partie création. La partie création consiste en l'écriture d'une pièce de théâtre intitulée La gueule du loup où s'inscrivent certains éléments du désordre de la dissociation de l'identité à travers la structure du texte. Cette pièce raconte l'histoire de Marie, une insulaire qui subit la prise de contrôle de son corps par les diverses personnalités qui habitent son phare intérieur. Ses personnalités ressurgissent alors qu'un corps portant un vieil uniforme des phares et balises est découvert dans la faille d'un rocher. À travers la tempête des souvenirs qui ressurgissent, Marie tente de survivre au raz-de-marée qui l'attire vers le fond, dans le courant de ce désordre dévastateur. La partie théorique quant à elle se divise en trois chapitres. Le premier chapitre vise à lever le voile sur les différentes composantes de ce désordre rare et complexe à la lumière des travaux de Colin A. Ross et de Frank N. Putnam, spécialistes américains du DDI. Quant au deuxième chapitre, il s'attarde sur le phénomène de l'inceste au féminin à partir des théories de Michele Elliott et Anne Poiret. Il dresse un portrait de la mère incestueuse et analyse les répercussions de ce type d'agression, ultime tabou, sur la vie de l'enfant abusé. Cette inscription de la maladie « dans » et « entre » les mots vise à donner au lecteur/spectateur, la possibilité de ressentir plus qu'il ne constate les ravages que provoque le DDI chez l'être qui en est atteint. Le troisième chapitre de notre réflexion théorique traite spécifiquement de la façon dont l'auteure a choisi d'intégrer des éléments du désordre de la dissociation de l'identité comme fondations et murs portants de son œuvre. Il vise à rendre compte de l'inscription de certains aspects de la maladie et de son traitement à l'intérieur de l'architecture d'un texte dramatique. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Dissociation, inceste au féminin, personnalités multiples, inscription, structure dramatique.

This study applied the Process Dissociation Procedure (Bornstein, 2002) to test independence between personality processes represented by different implicit measurement techniques. In contrast to the commonly adopted literal view of dual processes in personality theory, the study predicted that two implicit measures (CRT-A and IAT-A) and one explicit measure (NEO-AH) of aggressive disposition would dissociate with each other in their 1) intercorrelations, 2) predictions of behavioral criteria of aggressiveness, and 3) potential moderation by situational cues. These hypotheses were generally, though not completely, supported. Most importantly, the two implicit measures dissociated in their lack of correlation and differential prediction of behavioral criteria, unaffected by changes in situational cues. As predicted, the CRT-A and the NEO-AH dissociated in their intercorrelations, predictions, and moderation by incentives. The IAT-A and the NEO-AH dissociated in their lack of intercorrelation and their differential moderation by changes in incentive conditions. As predicted, only the explicit measure was moderated by changes in incentive conditions. Unexpectedly, IAT-A and the NEO-AH were statistically indistinguishable in their prediction of behavioral criteria of aggression. The findings provided strong support for the hypotheses predicting multiple independent implicit personality processes.