Mass spectrometry (MS) has proven itself to be indispensable for the analysis of biomolecules and molecular systems. This research has three goals: (1) expand on prior work toward the discovery of novel diagnostic targets for Valley Fever, (2) evaluate current mass spectrometry based proteomics for the discovery of non-host protein in complex host biological samples, and (3) investigate the potential for two gas phase techniques, surface induced dissociation, and ion mobility for the analysis of carbohydrate based molecules. Mass spectrometry has allowed for great advances in the identification of proteins in biological samples through implementing liquid chromatography tandem mass spectrometry and bioinformatics techniques known as proteomics. Proteomics techniques were used to elucidate a portion of the biosignature of Valley Fever (VF), a disease of great importance in the arid regions of the western United States. Current diagnostics for this fungal lung disease are remarkably unreliable which creates a need for an unfailing diagnostic method. Using a new generation of instrumentation along with directed methods, four previously discovered VF marker proteins were evaluated for their presence in mouse plasma, lung homogenate and bronchoalveolar lavage fluid samples. Due to inconclusive data, discovery proteomics approaches were then used to identify possible diagnostic targets in both human and mouse bronchoalveolar lavage fluid. In human bronchoalveolar lavage fluid, one potential target was discovered in five out of eight VF positive samples, and two further identifications of VF in negative samples. Mouse bronchoalveolar lavage fluid also showed the presence of this protein. Multiple-reaction monitoring based validation, using two-dimensional online separations for the presence of either the newly discovered protein or the four previously discovered proteins, was inconclusive. Emerging from the difficulties observed by the author and colleagues in identifying infectious agent proteins in complex host biological samples, an investigation of the feasibility of undertaking such endeavors was performed. One of the main complications thwarting the discovery of infectious agent proteins is the dynamic range of protein concentration in the host biological sample. This issue was resolved by using commercially available mass spectrometry and a two-dimensional liquid chromatographic separations platform. This enhanced separation combined with cost-effective protein normalization techniques, identified non-host proteins with good sequence coverage and spectral counts. Combining antibody-based depletion of highly abundant plasma proteins in bronchoalveolar lavage fluid, with at least a three fraction sample analysis enabled detection of a low abundant non-host protein (2pmol in 50μg host protein) with high sequence coverage. Glycosylation, an abundant post-translational modification of protein composed of carbohydrate oligomers may hold within its structure more biologically relevant information than the DNA that encoded the protein on which the glycan resides. The analysis of glycosylation plays a critical role in understanding biology. Carbohydrate based moieties pose many distinct challenges to their analysis; two of which are isobaric fundamental units and complex branching chemistry. Mass spectrometry provides a way of overcoming some of these challenges. To examine the complex biomolecules, a gas phase ion separation technique, known as ion mobility, and a non-traditional ion activation technique, surface-induced dissociation, were used. Surface-induced dissociation provides analogous fragmentation patterns to those generated via collision-induced dissociation (CID); however, much more extensive fragmentation can be achieved in a single tandem MS experiment. Using the gas-phase separations power of ion mobility showed that multiple conformations were adopted by relatively simple oligosaccharides. Ion mobility was also successfully used to determine fragment ion lineage of isobaric fragment ions, through inline separation between two differential fragmentation experiments.

Dissociation may be broadly described as a subjective experience in which information from the individual's internal or external environment is not appropriately integrated into conscious awareness, memory or identity. A number of studies have found an association between dissociative experience and anxious arousal, and in particular, between dissociation and trauma. Recent reviews suggest the existence of an unspecified mediating variable that accounts for these associations. The present study compared dissociative experiences reported by a community sample (N = 74) and a sample of individuals with a range of anxiety disorders (N = 20). The potential influence of anxiety sensitivity was a particular focus. Participants completed a battery of measures assessing dissociative experience, anxious arousal, social anxiety, generalised anxiety, panic and agoraphobia, traumatic experience and posttraumatic stress in addition to measures of anxiety sensitivity and substance use. Participants in the anxiety group reported a greater variety and frequency of dissociative experiences, particularly of experiences considered to be pathological in nature. Elevated dissociation scores were associated with somatic symptoms of anxiety, social anxiety, generalised anxiety, agoraphobia and posttraumatic stress. No association between trauma exposure and dissociation was evident; however, trauma intensity was associated with dissociation in the anxiety group. Symptoms of depersonalisation / derealisation and absorption were most strongly associated with increased anxiety. Anxiety Sensitivity accounted for more of the variance in dissociation scores than did measures of expressed anxiety. These results suggest that anxiety sensitivity may account for the relationship between trauma anxiety and dissociation. Therapeutic intervention directed at anxiety sensitivity, particularly fear of cognitive discontrol, may prove helpful in treating dissociative detachment.

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Background: High levels of dissociation have been found in recent studies involving psychiatric inpatients. Proponents of the ‘dissociative psychoses’ have found that trauma-focused intervention strategies can improve outcomes of patients with major mental illness. Despite this, levels of dissociation have not been measured in forensic inpatients in Scotland. This study investigates levels of dissociative symptoms (DES-II) within a sample of male patients in secure forensic psychiatry settings in Scotland. It explores levels of psychosis (PANSS) and self-reported childhood trauma (CTQ), current PTSD symptoms (IES-R), levels of depression (BDI-II) and broad attachment style (RQ). Four groups were arbitrarily defined based on presence or absence of psychosis and childhood trauma. It was hypothesised that levels of dissociation would be predicted by presence of childhood trauma. Methods: A quantitative cross-sectional design was used in which 56 mentally disordered offenders were interviewed across three different secure hospitals in Scotland: The State Hospital – a maximum security psychiatric hospital, and two medium secure facilities. Attempts are made to clarify the relationship of dissociation with different types of childhood trauma and psychosis symptom clusters. By splitting the data into groups the study seeks to discern whether the groups differ significantly on dissociation scores in relation to the childhood experiences they reported and presence of psychosis they are experiencing. Results: Childhood traumatic experiences were frequent where median CTQ total score = 47.0 (IQR: 42-70.5). Physical neglect was reported by 58.9% of the sample closely followed by emotional neglect (55.4%). 46.4% of the sample reported physical abuse of significant levels, 44.6% reported being emotionally abused and almost a third reported being sexually abused (28.6%). DES-II (dissociation) scores were significantly associated with delusions and hallucinatory behaviour from PANSS. Emotional abuse and sexual abuse were significantly associated with dissociation scores. Mann Whitney tests revealed that dissociation was significantly higher in the groups which reported childhood trauma. Kruskal-Wallis results indicated no significant differences between groups within the data and dissociation scores. Conclusion: Patients with clinically significant levels of dissociative symptoms were identified. This indicates that dissociation is a key characteristic, warranting further consideration in this sample. Levels and severity of reported childhood trauma were higher than expected. The findings add weight and support to the importance of dissociation and trauma in formulations of male, mentally disordered offenders. Clinical implications of these findings are considered and further directions are discussed.

As an additional study, effect of tyrosine nitration on the BCD of protonated and metalated peptides was investigated. Some fragment ions that were inhibited in the ECD of protonated peptides were liberated in the ECD of metalated peptides. By theoretical calculation of the cation-pi and cation-nitro group coordination using the metal ions nitrated phenol complex as a model, it is found that the metal ions might favor coordinating with the nitro group of the nitrated tyrosine residue in the peptides. / In order to improve the performance of the electron capture dissociation (BCD) mass spectrometry for structural analysis of peptides/proteins, BCD of peptides cationized with various transition metal ions was investigated. It was found that peptides adducted with different divalent transition metal ions generated different BCD tandem mass spectra. For Mn2+and Zn2+, the incoming low-energy electron would not favor being trapped by the metal ions and instead trigger the usual BCD dissociation channel(s) via "hot-hydrogen" or "superbase" intermediates to form a series of c-/z·- fragments. For other first row transition metal ions, including Fe2+, Co2+, Ni 2+and Cu2+, reduction of the metal ions occurs preferentially during the electron capture event and lead to the formation of usual "slow-heating" type of fragment ions, i.e. metalated a-/y-fragments & metalated b-/y- fragments. / To further compare the behavior of metal ions with the same electronic configuration, BCD of Group IIB metal ions adducted peptides were investigated. In contrast to the ECD behavior of Zn2+ adducted peptides, peptide radical cations (M+· ) and fragment ions corresponding to losses of neutral side chain from M+· were observed in the ECD spectra of Hg2+ and Cd2+ adducted peptides. The experimental observations appeared to depend on the balance of the ionization energy of peptide and the solvation modulated ionization energies of the metal atom. The reduction of divalent metal ions by the electron capture event could induce spontaneous electron transfer from the peptide moiety to the monovalent metal centre and generate hydrogen-deficient M +· species. / Chen, Xiangfeng. / Adviser: T.-W. Dominic Chan. / Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 131-139). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Hon Wan Chee Nicole Wendy. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 85-87). / Abstracts in English and Chinese. / THESIS COMMITTEE --- p.ii / ABSTRACT (English version) --- p.iii / ABSTRACT (Chinese version) --- p.v / ACKNOWLEDGEMENTS --- p.vii / TABLE OF CONTENTS --- p.viii / LIST OF FIGURES --- p.x / LIST OF TABLES --- p.xiii / Chapter CHAPTER 1. --- General Introduction / Chapter Section 1.1 --- Introduction --- p.1 / Chapter Section 1.2 --- Electronic Structure Calculation --- p.2 / Chapter Section 1.3 --- Molecular Dynamics --- p.10 / Chapter CHAPTER 2. --- Ab Initio Molecular Dynamics Study on Thermal Dissociation of Azomethane / Chapter Section 2.1 --- Introduction / Chapter Section 2.2 --- Computational Method --- p.17 / Chapter Section 2.3 --- Results and Discussion --- p.21 / Chapter Section 2.4 --- Conclusion --- p.47 / Chapter CHAPTER 3. --- "Ab Initio Molecular Dynamics Study on Fluxionality of IF7, TeF7- and iof6-" / Chapter Section 3.1 --- Introduction --- p.49 / Chapter Section 3.2 --- Computational Method --- p.52 / Chapter Section 3.3 --- Analysis --- p.55 / Chapter Section 3.4 --- Results and Discussion --- p.56 / Chapter Section 3.5 --- Conclusion --- p.83 / REFERENCES --- p.85

Chen, Fan. / "October 2010." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 85-91). / Abstracts in English and Chinese. / ABSTRACT --- p.III / 摘要 --- p.IV / ACKNOWLEDGENTS --- p.V / TABLE OF CONTENTS --- p.VI / LIST OF FIGURES --- p.VIII / LIST OF TABLES --- p.X / SYMBOLS AND ABBREVIATIONS --- p.XI / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Mass spectrometry in proteomics --- p.1 / Chapter 1.2 --- Fourier-transform ion cyclotron resonance mass spectrometry --- p.2 / Chapter 1.2.1 --- Introduction --- p.2 / Chapter 1.2.2 --- Ionization --- p.3 / Chapter 1.2.3 --- Ions in ICR --- p.4 / Chapter 1.2.4 --- Ions excitation and detection --- p.7 / Chapter 1.3 --- Tandem mass spectrometry --- p.8 / Chapter 1.4 --- Electron capture dissociation --- p.12 / Chapter 1.4.1 --- Features ofECD --- p.13 / Chapter 1.4.2 --- Two popular mechanisms for ECD --- p.14 / Chapter 1.4.2.1 --- The Cornell mechanism --- p.15 / Chapter 1.4.2.2 --- The Utah-Washington mechanism --- p.17 / Chapter 1.4.3 --- Recombination energy --- p.19 / Chapter 1.5 --- Outline of the present work --- p.21 / Chapter CHAPTER 2 --- INSTRUMENTATION AND EXPERIMENTAL --- p.22 / Chapter 2.1 --- Fourier-transform ion cyclotron resonance mass spectrometer --- p.22 / Chapter 2.1.1 --- Vacuum system --- p.24 / Chapter 2.1.2 --- Nanospray system --- p.26 / Chapter 2.1.3 --- Ion transfer system --- p.29 / Chapter 2.1.4 --- Infinity´ёØ cell --- p.29 / Chapter 2.1.5 --- Electron emission source --- p.31 / Chapter 2.1.6 --- Data acquisition system --- p.32 / Chapter 2.2 --- Experimental --- p.32 / Chapter 2.2.1 --- Simple ESI acquisition pulse program --- p.32 / Chapter 2.2.2 --- ESI-ECD acquisition pulse program --- p.35 / Chapter CHAPTER 3 --- FRAGMENTATION OF MODEL PEPTIDE IONS IN DIFFERENT CHARGE STATES UNDER ECD CONDITIONS --- p.38 / Chapter 3.1 --- Introduction --- p.38 / Chapter 3.2. --- Experimental --- p.41 / Chapter 3.2.1 --- Sequence design and sample preparation --- p.41 / Chapter 3.2.2 --- ECD under fourier-transform ion cyclotron mass spectrometer --- p.43 / Chapter 3.3 --- Results and discussion --- p.43 / Chapter 3.3.1 --- General features of ECD spectra --- p.43 / Chapter 3.3.1.1 --- ECD of RRRR --- p.43 / Chapter 3.3.1.2 --- ECD of KKKK --- p.47 / Chapter 3.3.2 --- Effect of charge state of precursor ions --- p.49 / Chapter 3.3.3 --- Effect of proton carriers --- p.52 / Chapter 3.3.4 --- Effect of proton carrier location --- p.54 / Chapter 3.4 --- Conclusions --- p.60 / Chapter CHAPTER 4 --- EFFECT OF PRECURSOR ION HETEROGENEITY ON ECD FRAGMENTATION --- p.62 / Chapter 4.1 --- Introduction --- p.62 / Chapter 4.2 --- Method --- p.63 / Chapter 4.2.1 --- Preferential dissociation index --- p.64 / Chapter 4.2.2 --- Precursor ion heterogeneity --- p.65 / Chapter 4.3 --- Results and discussion --- p.67 / Chapter 4.3.1 --- PDI in model peptides --- p.67 / Chapter 4.3.2 --- PIH and PDI in RRRR and KKKK --- p.71 / Chapter 4.3.3 --- PDI and PIH in two-lysine containing peptides --- p.73 / Chapter 4.3.4 --- PDI and PIH in other peptides --- p.80 / Chapter 4.4 --- Conclusions --- p.82 / Chapter CHAPTER 5 --- CONCLUSIONS --- p.83 / References --- p.85 / Chapter Appendix I: --- Pulse program for simple MS and MS/MS experiment --- p.92 / Chapter (A) --- Simple ESI FT-ICR MS experiment --- p.92 / Chapter (B) --- ESI ECD FT-ICR MS experiment --- p.95 / Chapter Appendix II: --- ECD spectra of AC-XAAAXAAAXAAAX-NH2 peptide series in different charge states --- p.99 / Chapter Appendix III: --- The PDI of the hypothetic peptide --- p.110 / Chapter Appendix IV: --- The PIH among the investigated system --- p.111

The cognitive strategies of association and dissociation have been identified and studied in runners and other athletes. Association is said to involve thoughts that are task-oriented and may include a focus on pace, strategy, or physiological sensations. Conversely, dissociation involves task-irrelevant thoughts and may include thinking about such things as relationships, work, spiritual matters, or scenery. To date, studies have been largely descriptive, methodologically flawed, failed to use manipulation checks, and/or present unclear or differing conclusions. The emphasis with previous association and dissociation research has also been with elite and/or endurance athletes, such as marathon runners. Additionally, only a few studies have included more than one exercise setting, and these investigations seemed to indirectly suggest that the exercise environment may influence the use of cognitive strategies, performance, and perceived exertion. In an effort to clarify the effects of cognitive strategies and exercise setting on several dependent variables, the current study investigated a sample of experienced recreational runners in a 3 x 2 mixed experimental design. Exercise setting had three levels (treadmill, indoor track, and outdoor route) and was a within-groups independent variable and cognitive strategy had two levels (association vs. dissociation) as a between-groups factor. The dependent variables were the ratings of perceived exertion, course satisfaction, and performance time for a 5 km run. The results indicated strong effects for the influence of exercise setting. The treadmill setting was rated as least satisfying, while resulting in the highest perceived exertion and slowest performance time. Alternately, the outdoor route resulted in the highest level of course satisfaction, while also yielding the lowest level of perceived exertion. For the dissociation strategy, the outdoor setting garnered the lowest perceived exertion, followed by the indoor track and treadmill, respectively, while with the associative strategy perceived exertion did not significantly differ among the settings. There were no overall differences in perceived exertion or course satisfaction between the cognitive strategies; however, there was a medium effect size and trend for the association group to run faster. The implications and limitations of these data are discussed and suggestions for future research are provided.

A large body of research has demonstrated general relations of sleep complaints with psychological disorders, including anxiety, depression, and dissociation/schizotypy. In contrast, very few studies have focused on the specificity of sleep complaints to daytime symptoms. Identifying sleep disturbances that show evidence of specificity is important for differential diagnosis and assessment. This study used the structure of self-reported sleep complaints as a framework for examining specificity. Comprehensive questionnaire and interview measures of sleep disturbance were submitted to factor analyses in students and psychiatric patients. These analyses revealed the presence of three well defined higher order factors: Lassitude, Insomnia, and Unusual Sleep Experiences. These factors were then correlated with interview and questionnaire measures of daytime symptoms. Lassitude was specific to dysphoria, whereas Insomnia had weaker, nonspecific relations with daytime symptoms. Fatigue, a component of Lassitude, showed the strongest evidence of specificity. Unusual Sleep Experiences was specific to symptoms of posttraumatic stress disorder (PTSD) and dissociation. In particular, the Nightmares component of Unusual Sleep Experiences was strongly related to PTSD and the Sleep Hallucinations component of Unusual Sleep Experiences was strongly related to dissociation.