*LITERATURE REVIEW* Abstract Background: Insomnia is an increasing public health epidemic, affecting healthy, sub-clinical and clinical populations. Cognitive Behaviour Therapy for insomnia (CBT-I) is the most evidence-based treatment endorsed by the National Institute of Clinical Excellence (NICE) which provides guidance to health and social services in England. Research has demonstrated, however, that CBT-I has low or uncertain efficacy within various populations including those with coexisting health problems and clinical diagnoses. Furthermore, CBT-I is not accessible to most people due to poor prioritisation within services and a paucity of clinicians skilled in insomnia treatment. There is an urgent need to develop alternative interventions for this persistent and highly debilitating complaint. Acceptance based approaches to insomnia including mindfulness-based stress reduction (MBSR) provide an alternative model for holistic treatment of sleep distress. Objectives: This review summarises and synthesises the available literature investigating the effectiveness of MBSR as a treatment for insomnia in community and clinical populations (with some specific populations excluded). Method: Systematic review of all relevant quantitative and qualitative literature to date using PsycINFO, PsycARTICLES and Web of Knowledge databases. Results: 13 relevant articles were included (3 abstracts): randomised control trials (RCTs), experimental, quasi-experimental and qualitative studies. Conclusions: Overall, the limited research in this area was assessed to be of moderate quality and to provide preliminary evidence that MBSR offers an effective intervention for insomnia symptoms and disorder in various populations. The review highlighted the paucity of research specifically MBSR AND INSOMNIA SYMPTOMS 10 investigating the acceptability of MBSR as an insomnia treatment, particularly for more complex presentations. It is possible that MBSR provides holistic and bi-directional benefits for sleep and emotional well-being, however, further research is required to determine how participants experience the course process in relation to their sleep. Keywords: Insomnia, CBT-I, MBSR. *EMPIRICAL PAPER* Abstract: There is an urgent need to improve the availability and acceptability of interventions for insomnia. Low-levels of help-seeking and high levels of functional impairment are often characteristic of individuals with unremitting complaints. Ambivalence about the significance of insomnia and/or a helpless resignation can be further compounded by lack of available treatments and socio-cultural attitudes towards sleep. Insomnia is often complicated with coexisting mental and physical health problems, a syndromal presentation. Theoretical and empirical evidence suggests that eight-week, mindfulness-based stress reduction (MBSR) programmes may offer a holistic intervention to relieve emotional disturbance that may underlie the complaint. This research sought to understand the experience of MBSR for individuals in the community with persistent insomnia, to gain insight into its acceptability. Methods: Holloway and Jefferson’s psychosocial method was used which posits the ‘defended subject’ as key to data construction and analysis (2013). Defences, free associations, researcher-interviewee dynamic, textual information, cultural and sociological knowledge all contributed to an understanding of the ‘whole’ of the experience of interviewees as communicated within Free Association Narrative Interviewing. Results: Results indicate that for highly defended individuals with insomnia, MBSR can be a challenging intervention to engage with and to embody. Barriers to acceptability included: limited insight into emotional distress, (unconscious) relational secondary gains to insomnia, limited understanding of sleep as a physiological process, restricted understanding or misconceptions about mindfulness prior to participation, resistance to acknowledging insomnia MBSR AND INSOMNIA SYMPTOMS 66 as a mental health complaint and practical issues of delivery. Researcher-interviewee dynamics suggested significant unmet relational needs of many interviewees. An exceptional case was discussed where relational distress was not understood to underlie insomnia and where significant benefits to sleep were reported from MBSR. Conclusion: The methodology enabled novel insights into the challenges for highly defended individuals with complex insomnia for accessing MBSR. By contrast, it is possible that for less complex but acute and recurrent insomnia, MBSR is more readily acceptable. Study limitations, future research needs and recommendations for improving the acceptability of MBSR for complex cases of insomnia are discussed.

氧自由基曾被認為是有氧代謝过程的無用副產物。然而，在正常條件下，氧自由基也可以修飾蛋白質的結構與功能，同時能在多種細胞代謝過程中作為重要的信號分子。半胱氨酸的巰基極易被氧自由基、氮自由基以及其它的親電子分子所氧化，且其可逆的氧化反應對於與氧化還原相關的調控與信號傳遞是極其重要的。雖然僅有特定的一小部分半胱氨酸可以被氧化修飾，我們至今對於影響半胱氨酸對氧化還原敏感性的决定因素所知甚少。對於蛋白质半胱氨酸氧化修饰的比較分析及預測，不仅可以提高我們對半胱氨酸氧化還原敏感性的决定因素的認識，同時也能對後續关于重要的氧化還原敏感蛋白的實驗驗證起指導作用。 / 本研究中，本人主要做了如下三部分的工作：第一部分， RedoxDB數據庫的構建。这也是首個針對已被实验验证的蛋白氧化還原修飾的數據庫。第二部分，氧化還原敏感的半胱氨酸位點的特征分析及預測。本人分析了基於序列的各種可能與半胱氨酸氧化還原敏感性相關的特征，並發現其中三個特征可用於預測氧化還原敏感的半胱氨酸位點。基於這三個特征，我開發了RSCysPred 一个基於支持向量機且只依赖蛋白序列的預測氧化還原敏感的半胱氨酸位點的新方法。第三部分，可逆二硫鍵的分析。可逆二硫鍵的形成是蛋白質可逆氧化還原修飾的最主要的類型之一。我从RedoxDB中获取相关数据，然后針對功能位點標簽以及靜電特征等方面的特征，對可逆二硫鍵與結構二硫鍵進行了詳盡的比較分析。結果表明相比結構二硫鍵，可逆二硫鍵具有一些显著不同的特征。进一步的分析显示這些特征可用於可逆二硫鍵的預測。 / Reactive oxygen species (ROS) has been regarded as unwanted by-product of aerobic metabolism. However, under normal conditions, ROS can modify the structure and function of proteins and may also act as important signaling molecules in various cellular processes. Cysteine thiol groups of proteins are particularly susceptible to oxidation by ROS/RNS and other electrophilic molecules, and their reversible oxidation is of critical roles for redox regulation and signaling. Despite the fact that only a small fraction of cysteine residues undergone oxidative modification, the determinants of cysteine redox-sensitivity is poorly understood to date. Comparative analyses and computational prediction of protein cysteine oxidative modification will not only enhance our understanding about the determinants of cysteine redox-sensitivity, it may also facilitate further experimental investigation of important redox proteins. / This thesis includes the following three parts of work. Part I: Construction of RedoxDB - a curated database of protein oxidative modification. It is the first database for experimentally verified protein oxidative modification events. Part II: Feature analysis and computational prediction of redox-sensitive cysteines. I analyzed various sequence-based features potentially related to cysteine redox-sensitivity, and identified three features for efficient computational prediction of redox-sensitive cysteine. Based on these features, I developed RSCysPred, a SVM-based tool for predicting redox-sensitive cysteine using primary protein sequence only. Part III: Study on reversible disulfide formation, which is the major type of protein oxidative modification. By using data retrieved from RedoxDB, I performed extensive comparison between reversible disulfide-bonded cysteines and structural disulfide-bonded cysteines with regard to the functional site signatures and electrostatic properties. The results support that reversible disulfides show several remarkable differences compared with structural disulfides. Further analyses indicated that these features could be used for efficient prediction of reversible disulfide. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Sun, Mingan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 77-89). / Abstract also in Chinese. / Thesis/Assessment Committee --- p.I / Statement: --- p.I / Abstract of thesis entitled --- p.II / 摘要 --- p.IV / Acknowledgements --- p.V / Table of contents --- p.VI / List of Tables --- p.IX / List of Figures --- p.X / List of Abbreviations --- p.XI / CHAPTER 1 --- p.1 / General Introduction --- p.1 / Chapter 1.1 --- Generation of ROS and oxidative stress --- p.2 / Chapter 1.2 --- Protein cysteine oxidative modification --- p.3 / Chapter 1.2.1 --- Protein oxidative modification --- p.3 / Chapter 1.2.2 --- Special properties of cysteine --- p.3 / Chapter 1.2.3 --- Reversible cysteine oxidation and its function --- p.4 / Chapter 1.2.4 --- Specificity of cysteine oxidative modification --- p.5 / Chapter 1.3 --- Experimental approaches for detecting protein oxidative modification --- p.6 / Chapter 1.4 --- Computational prediction of protein oxidative modification --- p.7 / Chapter 1.5 --- Project Objectives --- p.8 / CHAPTER 2 --- p.11 / RedoxDB: a Curated Database of Experimentally Verified Protein Oxidative Modification --- p.11 / Chapter 2.1 --- Introduction --- p.12 / Chapter 2.2 --- Database concept --- p.13 / Chapter 2.3 --- Database interface and tools --- p.15 / Chapter 2.4 --- Discussion --- p.16 / CHAPTER 3 --- p.23 / Computational Prediction of Redox-Sensitive Cysteines Using Sequential Distance and Other Sequence-based Features --- p.23 / Chapter 3.1 --- Introduction --- p.24 / Chapter 3.2 --- Methods and Materials --- p.26 / Chapter 3.2.1 --- Datasets --- p.26 / Chapter 3.2.2 --- Feature extraction --- p.28 / Chapter 3.2.3 --- Support vector machines (SVMs) implementation and parameter optimization --- p.29 / Chapter 3.2.4 --- Performance assessment --- p.30 / Chapter 3.2.5 --- Statistical analyses --- p.30 / Chapter 3.3.6 --- Webserver implementation --- p.30 / Chapter 3.3 --- Results --- p.31 / Chapter 3.3.1 --- Performance evaluation by 10-fold cross-validation --- p.31 / Chapter 3.3.2 --- Evaluation of the most efficient features --- p.33 / Chapter 3.3.3 --- Comparison with current structure-based method --- p.34 / Chapter 3.3.4 --- Performance evaluation using OSCTdb --- p.36 / Chapter 3.4 --- Discussion --- p.37 / CHAPTER 4 --- p.49 / Comparative Analysis of Reversible and Structural Disulfides to Reveal Their Distinct Characteristics --- p.49 / Chapter 4.1 --- Introduction --- p.50 / Chapter 4.2 --- Materials and methods --- p.52 / Chapter 4.2.1 --- Datasets --- p.52 / Chapter 4.2.2 --- Functional site signatures --- p.53 / Chapter 4.2.3 --- Electrostatic properties --- p.55 / Chapter 4.2.4 --- Support vector machines (SVMs) implementation and parameter optimization --- p.56 / Chapter 4.2.5 --- Performance assessment --- p.56 / Chapter 4.2.6 --- Statistical analyses --- p.56 / Chapter 4.3 --- Results --- p.56 / Chapter 4.3.1 --- General features of the functional site signatures for reversible-SS Cys and structural-SS Cys --- p.56 / Chapter 4.3.2 --- Differences in amino acid composition are related to several physical-chemical properties --- p.58 / Chapter 4.3.3 --- Electrostatic characteristics of disulfide-bonded Cys --- p.60 / Chapter 4.3.4 --- Comparison of S-S distance --- p.61 / Chapter 4.3.5 --- Predictive power of newly identified features --- p.62 / Chapter 4.4 --- Discussion --- p.63 / Chapter 4.4.1 --- Reversible disulfides show distinct characteristics compared with structural disulfides --- p.63 / Chapter 4.4.2 --- Chances and challenges for computational prediction of reversible disulfides --- p.64 / CHAPTER 5 --- p.79 / Conclusions and Perspectives --- p.79 / Chapter 5.1 --- Contributions and conclusions from this thesis research --- p.80 / Chapter 5.2 --- Future perspectives --- p.81 / Reference --- p.82 / List of Publications --- p.95

On perçoit souvent la parole en présence de bien d’autres sons. Parfois les interférences sonores atteignent des niveaux tellement élevés que la parole devient inintelligible. Les méthodes de renforcement de la parole tentent de réduire les bruits ambiants, mais on en sait très peu sur l’effet qu’elles produisent sur l’intelligibilité de la parole. Cette thèse explore les effets des méthodes de renforcement de la parole, aussi appelées algorithmes de suppression du bruit, sur la l’intelligibilité.Après une brève introduction sur les notions de renforcement de la parole et d’intelligibilité, on présente trois études qui abordent les effets de ces méthodes d’un point de vue empirique. On démontre que le résultat de la suppression du bruit tend à réduire l’intelligibilité et que cet effet est constant pour une grande variété de niveaux sonores. Quand on fait appel à des experts pour mettre en place un système commercial de suppression du bruit dans le but d’améliorer l’intelligibilité, ils proposent des réglages qui dégradent l’intelligibilité. Les profanes perçoivent bien une amélioration de l’intelligibilité qui résulte des méthodes de renforcement de la parole.Trois autres études subséquentes tentent de préciser les propriétés du signal, qui ont des effets sur l’intelligibilité et qui sont généré par les méthodes de renforcement de la parole. Des métriques physiques basées sur différentes propriétés du signal ont été utilisées pour estimer l’intelligibilité de la parole renforcée. La plupart de ces mesures fournissent des estimations peu fiables ou biaisées de l’intelligibilité absolue. / Speech is often perceived in the presence of other sounds. At times the interfering sounds can reach such high levels that the speech becomes unintelligible. Speech enhancement methods attempt to reduce the audibility of noisy sounds, but little is known about how their influence on intelligibility. This thesis explores the effects of speech enhancement, also known as noise suppression algorithms, on speech intelligibility. After a short introduction to speech enhancement and intelligibility, three studies consider the effects from an empirical perspective. It is shown that noise suppression tends to reduce intelligibility and that its effect is mostly constant across a broad range of noise levels. When experts were asked to apply a commercial noise suppressor to optimise intelligibility, they proposed settings that degraded intelligibility. Laypeople successfully identified an increase in intelligibility resulting from speech enhancement. Three subsequent studies attempt to identify the signal properties responsible for the intelligibility effects and generated by speech enhancement.Physical metrics based on various signal properties were used to estimate the intelligibility of the speech-enhanced noisy signal. Most metrics provided unreliable or biased estimates of absolute intelligibility. Some could nevertheless be used to adjust speech enhancers such that intelligibility is optimal.

Disasters triggered by hazards, such as floods, earthquakes, droughts, and cyclones, pose significant impediments to sustainable development efforts in the most vulnerable and exposed countries. Mainstreaming disaster risk is hence seen as an important global agenda as reflected in the Sustainable Development Goals (SDGs) and the Sendai Framework for Disaster Risk Reduction (SFDRR) 2015-2030. Yet, conventional development indicators remain largely negligent of the potential setbacks that may be posed by disaster risk. This article discusses the need to reflect disaster risk in development indicators and proposes a concept disaster risk-adjusted human development index (RHDI) as an example. Globally available national-level datasets of disaster risk to public and private assets (including health, educational facilities, and private housing) is combined with an estimate of expenditure on health, education, and capital formation to construct an RHDI. The RHDI is then analyzed across various regions and HDI groups, and contrasted with other HDI variants including inequality-adjusted HDI (IHDI) and the gender-specific female HDI (FHDI) to identify groups of countries where transformational disaster risk reduction (DRR) approaches may be necessary.

Libby Larsen's Concerto for Trumpet and Orchestra was commissioned by Daniel Culver and the Quad City Youth Orchestra, in celebration of its 30th anniversary. It was written in 1987 and premiered on May 8, 1988. Daniel Culver conducted the Quad City Youth Orchestra and David Greenhoe was the trumpet soloist. Despite Libby Larsen's ongoing success as a composer, the premiere performance is the only time the concerto has been performed and it has since remained virtually-unknown to the public. This project serves as a way in which to reintroduce Libby Larsen's Trumpet Concerto to the trumpet, orchestral and academic communities by way of providing an historical account of the commission project; showing insight into the composer's inspiration for the work; and providing a reduction of the orchestral score for trumpet and piano.

Tetraphenylporphyrins can be used to absorb visible light and pass on their excitation energy to electron transfer agents. The purpose of this research has been to investigate our ability to understand and control the energetics of porphyrin derivatives in order to use their electron transfer ability to harness the energy of sunlight. Shifts in the redox (reduction and oxidation) potentials of tetraphenylporphyrins result from variations in the substituents attached at the para- position of the phenyl rings of tetraphenylporphyrins, as well as variations in the state of ionization of those substituents, and the solvent in which the reactions are carried out. To measure the effect these variations, results from cyclic voltammetric experiments were plotted versus literature values of Hammett substituent constants to confirm the validity of linear free energy relationships as a model of substituent effects. Solvent effects on reduction potentials were correlated using experimentally determined values of the empirical solvent parameter ET. Some specific conclusions are summarized. 1. The usefulness of linear free energy relationships in correlating variations in redox potentials with changes in substituent was confirmed with two exceptions. Two of the porphyrins were shown to undergo a different electrochemical oxidation mechanism than the remaining porphyrins, and another porphyrin was shown to be more difficult to reduce than predicted on the basis of its substituent constant. 2. Solvent effects, here investigated as the effect of added water on the reduction potential of tetraaminophenylporphyrin in DMSO, were demonstrated to correlate with the Dimroth-Reichardt solvent parameter, ET , determined experimentally for each water-DMSO mix. 3. Variations in the state of ionization of ionizable substituents such as carboxylic acid, amine, and hydroxyl substituents were shown to affect porphyrin electrochemistry mostly through the protonation of bulk, solution-phase porphyrin by added proton donor. An additional effect of added proton donor was noted in an alteration in the mechanism of reduction to include some of a different mechanism wherein reduced porphyrin is protonated in a chemical equilibrium and then further reduced electrochemically.

The use of physical restraints in residential treatment centers for children has been shown to be detrimental to both staff and the children. Although there have been nationwide initiatives to reduce or eliminate the use of physical restraints on children, to date, researchers have not yet identified the organizational factors that predict the likelihood of using physical restraints on children. Based on the two-factor theory, in which two different types of predictors of motivation and behavior in the workplace were identified, the purpose of this quantitative non-experimental study was to examine whether satisfaction with pay, a hygiene factor, and satisfaction with supervision and perceived organizational support, motivating factors, predict the frequency of the use of physical restraints. Satisfaction with pay and supervision were measured using the Job Satisfaction Survey and perceived organizational support was measured using the Perceived Organizational Support Survey. Data were collected from 245 direct care staff members employed at residential treatment centers for children. Pearson product moment correlations and multiple regression analysis were conducted. The results indicated that satisfaction with supervision was negatively and statistically significantly related to the use of physical restraints on children in residential care and satisfaction with pay approached significance. Organizational changes that address training, development, pay, and best practices for supervision may aid in the reduction of physical restraints used on children. The reduction in physical restraints would thereby reduce the undesirable impact they have on children and result in positive social change.

As a key constituent of proteins, nucleic acids, and other biomolecules, nitrogen is essential to all living organisms including human beings. Dinitrogen represents the largest pool of nitrogen, about 79% of the Earth’s atmosphere, yet it is unusable by most living organisms due to its inertness. There are two ways to fix this inert dinitrogen to usable ammonia. One is the industrial Haber-Bosch process, which needs to be conducted at high temperature and pressure. This process uses a lot of the non-renewable fossil fuel as the energy source. The other major pathway is the biological nitrogen fixation carried out by some microorganisms called diazotrophs. The usable nitrogen output from this biological pathway ultimately supports an estimated 60% of the human population’s demand for nitrogen.The catalyst responsible for the biological nitrogen fixation is called nitrogenase, the most studied form of which contains molybdenum and iron in its active center, so called molybdenum nitrogenase. The work in this dissertation attempts to understand howthis biological catalyst breaks down dinitrogen to ammonia by application of different modern techniques. Firstly, an approach was developed to understand the stepwise reduction mechanism of dinitrogen to ammonia by molybdenum nitrogenase.The second goal of my research is to understand the roles of iron and molybdenum centers in nitrogenase function. My results using carbon monoxide as a probe for genetically modified molybdenum nitrogenase indicate that iron should be the metal sites functioning for nitrogen fixation. This is further supported by another study aimed at understanding the role of molybdenum during nitrogenase functioning.Moreover, an approach was developed to understand the mechanism for the obligatory production of hydrogen gas when nitrogenase activates dinitrogen for reduction. The same study also suggests possible pathways for the addition of hydrogenous species to nitrogen to produce ammonia.As part of this work, we also found that remodeled nitrogenases can use poisonous carbon monoxide and greenhouse-gas carbon dioxide to produce useful hydrocarbons by coupling one or more small molecules, which is hard to be achieved by other catalysts. Further study of these new reactions might give us deep insights on nitrogenase mechanism and inspire scientists to design better catalysts for relevant industrial processes.

In situ reduction of hydrido-tris-(3,5-dimethylpyrazolyl)borato(trioxo) rhenium(V) with triphenylphosphine or triethylphosphite leads to a reactive rhenium(V) species that catalytically deoxygenates epoxides at 75-105��C. The reaction is stereospecific, except for trans- and cis-butene oxide which formed minor amounts of the opposite isomer. A variety of different functional groups were tolerated and even epoxides that reacted slowly could be pushed to greater than 95% conversion given extended time and/or higher temperature. The absence of clustering processes shows how the choice of ligand can have a major influence on the design of the catalytic cycle. The rhenium(V) species formed from reduction of Tp'ReO��� was identified as Tp'Re(O)(OH)���. Tp'Re(O)(OH)��� reacted with ethanol and HCl to form ethoxide and hydroxo chloride complexes, respectively. In addition, Tp'Re(O)(OH)��� was an excellent catalytic and stoichiometric reagent for the deoxygenation of epoxides and sulfoxides. Loss of water from Tp'Re(O)(OH)��� to form the catalytically active species Tp'Re02 was shown to be a necessary preequilibrium process. The kinetic behavior of the catalytic system is complex. First-order behavior in [Re][subscript T], zero-order dependence in [PPh���] and saturation behavior for epoxide were observed. The reversible formation of a coordinated epoxide complex was proposed to explain the saturation behavior. The epoxide complex was shown experimentally and computationally to engage in two separate reactions: ring expansion to form a syn-diolate complex, and direct fragmentation to alkene and trioxide. A steady-state concentration of diolate is eventually reached explaining a "burst" of alkene production prior to generation of a pseudo-zero-order catalytic system. The diolate formed is the syn-isomer, which is the kinetically formed product. Direct epoxide fragmentation is the primary source of alkene. This process was determined to be four times faster than ring expansion for cis-stilbene oxide. The synthesis and characterization of a tethered-epoxide Cp* rhenium trioxide complex has been achieved. Reduction of this complex leads to an unsaturated rhenium(V) species that is immediately complexed by the tethered epoxide. Experimental data and molecular mechanics modeling support intramolecular coordination of the epoxide to the rhenium center. These results confirm that the coordinate epoxide is a viable intermediate in rhenium-catalyzed epoxide deoxygenations. / Graduation date: 2003

Graduation date: 1995