Chan, Ho Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 92-94). / Abstracts in English and Chinese. / ABSTRACT --- p.i / 摘要 --- p.iii / ACKNOWLEDGEMENTS --- p.iv / PUBLISHED PAPERS --- p.vi / TABLE OF CONTENTS --- p.vii / LIST OF FIGURES --- p.ix / LIST OF TABLES --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Traditional methods of cell manipulation --- p.1 / Chapter 1.2 --- New methods of cell manipulation using MEMS technology --- p.2 / Chapter 1.2.1 --- Electrostatic actuation --- p.2 / Chapter 1 2.2 --- Shape memory effect --- p.4 / Chapter 1.2.3 --- Pneumatic --- p.5 / Chapter 1.2.4 --- Electromagnetic --- p.5 / Chapter 1.2.5 --- Thermal --- p.6 / Chapter 1.3 --- Objective of this project --- p.1 / Chapter Chapter 2 --- Literature review --- p.11 / Chapter Chapter 3 --- "Design, modeling and heat transfer analysis" --- p.14 / Chapter 3.1 --- Design and the temperature-radius relationship of thermal actuators --- p.14 / Chapter 3.2 --- Heat transfer analysis --- p.17 / Chapter 3.2.1 --- Heat dissipation from the actuator --- p.18 / Chapter 3.2.2 --- Thermal transient response in liquid environment --- p.23 / Chapter 3.3 --- "Temperature, radius of curvature and tip deflection and actuation voltage relationship" --- p.24 / Chapter Chapter 4 --- Fabrication process of the thermal actuators --- p.28 / Chapter 4.1 --- Basic processes involved in fabricating the thermal actuators --- p.28 / Chapter 4.1.1 --- Photolithography --- p.28 / Chapter 4.1.1.1 --- Spin on and pattern photoresist --- p.29 / Chapter 4.1.1.2 --- Methods for alignment --- p.31 / Chapter 4.1.2 --- Lift off and etching processes --- p.33 / Chapter 4.1.3 --- Sacrificial release process --- p.35 / Chapter 4.1.4 --- Deposition --- p.38 / Chapter 4.1.4.1 --- Sputtering --- p.39 / Chapter 4.1.4.2 --- Thermal evaporation --- p.39 / Chapter 4.1.4.3 --- Thermal oxidation --- p.40 / Chapter 4.1.4.4 --- Parylene deposition --- p.41 / Chapter 4.2 --- Fabrication process of thermal actuators/grippers --- p.45 / Chapter 4.2.1 --- Fabrication of thermal actuators --- p.45 / Chapter 4.2.1.1 --- Mask design and making --- p.45 / Chapter 4.2.1.2 --- Process flow --- p.49 / Chapter 4.2.1.3 --- Fabricated samples --- p.53 / Chapter 4.2.1.4 --- Problems encountered during fabrication process --- p.54 / Chapter 4.2.2 --- Fabrication of multi-finger gripper --- p.55 / Chapter 4.2.2.1 --- Mask design --- p.55 / Chapter 4.2.2.2 --- Process flow --- p.57 / Chapter 4.2.2.3 --- Fabricated samples --- p.57 / Chapter Chapter 5 --- Testing thermal actuators --- p.58 / Chapter 5.1 --- Actuation by applying voltage (underwater) --- p.58 / Chapter 5.1.1 --- Experimental setup --- p.58 / Chapter 5.1.2 --- Experimental results --- p.59 / Chapter 5.1.3 --- Discussion --- p.63 / Chapter 5.2 --- Actuation by water bath heating --- p.66 / Chapter 5.2.1 --- Experimental setup --- p.66 / Chapter 5.2.2 --- Experimental results --- p.66 / Chapter 5.2.3 --- Discussion --- p.68 / Chapter 5.3 --- Frequency response and force analysis --- p.69 / Chapter 5.3.1 --- Frequency response --- p.69 / Chapter 5.3.2 --- Force analysis --- p.70 / Chapter Chapter 6 --- Cell grasping system --- p.73 / Chapter 6.1 --- Demonstration of cell grasping using single arm gripper --- p.73 / Chapter 6.2 --- MEMS chip with multi-finger grippers --- p.75 / Chapter 6.2.1 --- Mask design for MEMS chip --- p.76 / Chapter 6.2.2 --- Actuation of thermal gripper in air --- p.78 / Chapter 6.2.3 --- Demonstration of actuation and cell grasping --- p.79 / Chapter 6.2.4 --- A flexible cell grasping motion --- p.80 / Chapter 6.3 --- Proposed cell grasping system --- p.82 / Chapter Chapter 7 --- Summary and future work --- p.83 / Chapter 7.1 --- Summary --- p.83 / Chapter 7.2 --- Future work --- p.84 / APPENDIX --- p.87 / BIBLIOGRAPHY --- p.92

Ko, Pui Hang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 86-90). / Abstracts in English and Chinese. / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Micro bearing in precision engineering --- p.1 / Chapter 1.2 --- Micro spiral spring --- p.5 / Chapter 1.3 --- Outline of the thesis --- p.9 / Chapter 2. --- Mainspring Segment with Carbon Nanotube Coating --- p.10 / Chapter 2.1 --- Introduction --- p.10 / Chapter 2.2 --- Coating on the mainspring --- p.12 / Chapter 2.2.1 --- Experimental Setup for Finding the Young's Modulus --- p.12 / Chapter 2.2.2 --- Elastic Modulus of the mainspring without coating --- p.15 / Chapter 2.2.3 --- Elastic Modulus of the mainspring with coating --- p.18 / Chapter 2.2.4 --- Thickness of the coating --- p.19 / Chapter 2.3 --- Elastic deformation of mainspring --- p.22 / Chapter 2.3.1 --- Mathematical Model Derivation --- p.24 / Chapter 2.3.2 --- Data Analysis --- p.35 / Chapter 2.4 --- Summary --- p.38 / Chapter 3. --- FEA of the Spiral Spring Structure --- p.53 / Chapter 3.1 --- Introduction --- p.53 / Chapter 3.2 --- Model Formation --- p.55 / Chapter 3.2.1 --- Preprocess --- p.56 / Chapter 3.2.2 --- Solver --- p.60 / Chapter 3.2.3 --- Post-process --- p.71 / Chapter 3.3 --- A Comparison between Simulation and Experiment Results --- p.74 / Chapter 3.3.1 --- Experimental setup --- p.74 / Chapter 3.3.2 --- Results Analysis --- p.77 / Chapter 3.4 --- Summary --- p.78 / Chapter 4. --- Conclusions and Future Work --- p.81 / Chapter 4.1 --- Summary of micro spiral spring --- p.81 / Chapter 4.2 --- Contributions --- p.83 / Chapter 4.3 --- Future work --- p.84 / Bibliography --- p.86 / Appendix --- p.91 / Chapter A1 --- "Specification of CSM Instrument, Swiss, Variocouple" --- p.91 / Chapter A2 --- Matlab® program of the spiral spring segment FEA --- p.91 / Chapter A3 --- "The paper: ""Nano-Bearing: A New Type of Air Bearing with Flexure Structure""" --- p.99

Reactions of the free radical nitrogen monoxide (NO) with metal–oxygen species of metalloproteins are relevant to NO metabolism and detoxification. For example, oxyhemoglobin and oxymyoglobin react with NO to form nitrate. The ferryl state of these globins also reacts with NO to reduce them to the FeIII state, forming nitrite. This has led to the suggestion that the role of NO could be that of an antioxidant of oxoiron(IV) and oxoiron(IV) protein radicals to inhibit oxidative damage. In turn, the ferrylglobin-mediated oxidation of NO to nitrite may play a role in NO scavenging and detoxification. In the case of peroxidase enzymes, NO has been shown to increase the activity of some enzymes by accelerating reduction of compound II to the FeIII state. While synthetic examples do exist for the chemistry of superoxometal complexes and NO, knowledge of the fundamental reactivity between oxometal complexes and NO is limited. To gain insight into the reactivity of synthetic oxoiron(IV) complexes toward NO, the reaction of [FeIVO(tmc)(OAc)]+ with NO, where the Fe center is coordinated by the macrocyclic nitrogen-donor ligand 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (tmc), has been investigated. This reaction caused reduction of the FeIV center to FeII and produced nitrite, which was identified in the form of [FeII(tmc)(ONO)]+. Mechanistic studies have been conducted to distinguish between two possible pathways involving either oxygen atom or oxide(·–) ion transfer from the FeIVO group to NO. As a result of studying the reactivity of a different oxoiron(IV) complex, [FeIVO(N4Py)]2+, toward NO, the formation of FeII and nitrate was observed. Mechanistic studies have revealed a 2:1 stoichiometry between FeIV and NO. From these results, a mechanism can be proposed that includes an initial oxide(·#8211;) ion transfer from FeIVO group to NO to form nitrite, followed by an oxygen atom transfer from a second equivalent of [FeIVO(N4Py)]2+ to the nitrite intermediate to form nitrate. This second step chemistry was confirmed by independently studying the reaction of [FeIVO(N4Py)]2+ with nitrite to form nitrate. There is also a biological inorganic chemistry in which metal nitrosyl species are oxidized to form innocuous nitrite or nitrate. In this context, the oxidation of the synthetic nitrosyl complex [Fe(tmc)(NO)]2+ has been studied, which also produced [FeII(tmc)(ONO)]+. The molecular structure of [FeII(tmc)(ONO)]+ determined by X-ray crystallography indicates a bidentate binding mode of the nitrito ligand via both oxygen atoms. The oxidation results are consistent with a net oxide(·–) ion transfer mechanism forming [FeII(tmc)(NO2)]+, followed by a subsequent linkage isomerization. For comparison purposes, several related, independently synthesized [FeII(tmc)X]+ complexes (X = NO2–, NO3–, AcO–) have been characterized by spectroscopic techniques, X-ray crystallography and differential pulse and cyclic voltammetry. A final investigation involved studying the reactivity of a series of [FeIVO(tmc)X]+ (X = CF3SO3–, CF3CO2–, AcO–) complexes toward organic substrates by oxygen atom transfer and hydrogen atom abstraction to construct a reactivity trend depending on the strength of the axial ligand X.

The Kizler North Field is near the western flank of the Forest City Basin in Lyon Co., Kansas, USA and produces oil from the Hunton Formation, Viola Formation and Simpson Group reservoirs. The structure strikes NW through the field that is part of a larger wrench fault system. This modern prospect analysis of the Kizler North Field, aids in understanding the reservoir properties of the Hunton Formation, Viola Formation and Simpson Group rocks, the play mechanism of the field, and provides recommendations for additional drilling locations.

Mechanisms of change in psychotherapy must be empirically investigated to shed light on how particular therapies work, as well as common mechanisms that may be at work across modalities. The current study investigated a proposed mechanism of change in a mindfulness intervention; this proposed mechanism, experiential avoidance (EA), may function more broadly as a mediator of change across multiple therapies. The primary hypothesis was that gains in mindfulness over the course of Mindfulness-Based Stress Reduction (MBSR) would be associated with reductions in negative affect, and that changes in EA would mediate the relation between changes in mindfulness and negative affect. The role of EA in mediating the effect of mindfulness on positive affect, disability, and life satisfaction was also investigated. Participants (N = 106) completed questionnaires before and after an 8-week MBSR program. A subset of participants (n = 74) completed questionnaires at the mid-point of treatment, and recorded time spent on mindfulness practice and level of relaxation after homework completion. Mediation analyses were conducted in which relations between change in predictor (mindfulness), mediator (EA), and outcome measures over the course of the intervention were assessed using regression steps, followed by PRODCLIN. Participants reported significant improvements in mindfulness, reductions in EA and disability, and improved affect and life satisfaction from pre- to post-MBSR. The relation between increased mindfulness and reduced negative affect over the course of the intervention was partially mediated by reduced EA. No evidence was found for relaxation as an additional mediator of the relation between mindfulness and negative affect. The relation between increased mindfulness and positive affect over the course of the intervention was fully mediated by decreased behavioral avoidance. Reductions in behavioral avoidance also fully mediated the relation between increased mindfulness and reduced disability. The relation between increased mindfulness and increased life satisfaction was mediated by EA. More mindfulness practice was linked with greater positive affect; the relation between practice and positive affect was mediated by EA. This study offers support for EA as a mediator of the effect of mindfulness on multiple outcomes, while highlighting a mechanism of change that may pertain across psychotherapeutic modalities.

In humans and most eukaryotes, thymidylate synthase (TSase) serves as a key enzyme that catalyzes the reductive methylation of deoxyuridine monophosphate (dUMP) to synthesize deoxythymidine monophosphate (dTMP), a key component of DNA. The N5, N10- methylene-5,6,7,8-tetrahydrofolate (MTHF) serves as both the methylene donor and the hydride donor while generating dihydrofolate (H2folate) as the byproduct. However, in 2002, Myllykallio reported the discovery of flavin-dependent thymidylate synthase (FDTS) that also functions to maintain the dTMP pool, although the mechanism is different. Since then, considerable progress was made in characterizing this enzyme. It was found that structurally FDTS is substantially different from TSase both with respect to structure and with respect to the mechanistic pathway of catalysis. In the FDTS-catalyzed methylation of dUMP, MTHF serves only as the methylene donor, generating tetrahydrofolate (H4folate), unlike TSase, and FDTS utilizes NADPH as a reductant. Activity of the enzyme depends on the presence of the noncovalently bound prosthetic group, flavin adenine dinucleotide (FAD). Interestingly, the enzyme FDTS is present in several human pathogens that cause diseases including syphilis, tuberculosis, anthrax poisoning, typhus, botulism, peptic ulcers and more, but is absent in humans; thus, it poses an attractive target for antibiotics. In the modern world, antibiotic resistance is a menace; consequently, new targets for new antibiotics are being sought. Hence, elucidating the chemical mechanism of FDTS is of paramount interest, as we and others believe this could allow for rational design of drugs that selectively target these pathogens with minimal human toxicity. Although several chemical mechanisms for FDTS catalysis have been put forward, complete understanding has still not been achieved. One of the primary concerns was the role of FAD in catalysis, and we found – as described in Chapter II and III – that FAD is a methylene carrier rather than just a hydride donor, as previously postulated. Secondly, all mechanisms proposed so far predict the presence of a noncovalently bound putative exocyclic methylene intermediate (an isomer of dTMP) occurring in the catalytic pathway of FDTS. However, direct evidence to prove its existence was lacking. Recently, we have been able to synthesize this intermediate, as described in Chapter IV. As shown in Chapter V and VI, we used steady-state kinetics, isotopic substitution and NMR studies to test this intermediate with FDTS. We believe our findings will greatly improve the understanding of this enzyme and will impact drug design by government agencies, pharmaceutical companies, and academic laboratories.

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.

Lacosamide (LCM) is a new antiepileptic drug with a previously unknown mode of action. Using electrophysiological recording techniques in a range of in vitro preparations I have determined a mechanism of action of the new drug. In a 4-aminopyridine model of tonic-clonic seizures in rat visual cortex in vitro, LCM stereoselectively reduced maximal frequency and duration of tonic activity with EC[50�s] of 71 and 41 [mu]M respectively. LCM (100 [mu]M) significantly reduced excitability in whole cell patch clamped neurons producing non-selective reduction in the incidence of excitatory/inhibitory postsynaptic currents (EPSCs; LCM: 46.1 � 15.5 %, P <0.01, n = 4, IPSCs; LCM: 24.9 � 9.6 %, P <0.01, n = 4) and block of spontaneous action potentials (EC₅₀ 61 [mu]M). The inhibitory effects of LCM did not result from changes in passive membrane properties (including resting membrane potential or input resistance) as assessed by application of voltage ramps between -70 to +20 mV. LCM did not mimic the effects of diazepam as an allosteric modulator of GABA[A] receptor currents, nor did it inhibit evoked excitatory currents mediated by AMPA or NMDA receptors. Unlike phenytoin (DPH), carbamazepine (CBZ) or lamotrigine (LTG) that blocked sustained action potential firing evoked by brief depolarising steps (750 ms) or ramps (-70 to 20 mV, 90 mV.sec⁻�), LCM could weakly reduce the frequency of action potentials evoked by brief depolarisation suggesting a potential interaction with VGSCs. In accordance with this, the effect of LCM upon neurotransmission was negated in the presence of tetrodotoxin (200 nM, TTX). The frequency of miniature EPSCs was not altered by the drug (100 [mu]M). These results discounted some crucial potential anticonvulsant targets for LCM but implied a potential interaction with electrogenic VGSCs. When SRF duration was prolonged (10 s) LCM produced significant (P <0.01, n = 4-10, EC₅₀: 48 [mu]M) inhibition, but not within the first second of the burst EC₅₀: 640 [mu]M). Evoked TTX sensitive sodium currents in N1E-115 neuroblastoma cells were significantly reduced by LCM, CBZ, LTG and DPH when V[h]: -60 mV. Hyperpolarizing pulses (500 ms) to -100 mV could reverse block by CBZ, LTG and DPH but not LCM. The V₅₀ for steady state fast inactivation was more hyperpolarized by CBZ (-79.45 � 2.64 mV, n = 5, P < 0.001), LTG (-72.30 � 1.70 mV, n = 6, P <0.05) and DPH (-77.17 � 2.32 mV, n = 6, P <0.05) but not by LCM (-65.02 � 1.75 mV, n = 6, CONTROL: -65.84 � 0.86 mV). In contrast to CBZ, LCM did not slow recovery from fast inactivation or produce frequency dependent facilitation of block of a 3 s, 10 Hz pulse train. LCM (100 [mu]M) did produce a (V₅₀: CONTROL ~64 mV, LCM -57.47 � 4.53 mV, P <0.001, n = 4-8) hyperpolarizing shift in the voltage dependence of slow sodium channel inactivation and promoted channel entry into the slow inactivated state (P <0.001, n = 6) but did not alter the rate of recovery. I therefore conclude that LCM produces inhibition of epileptiform cellular activity, at least in part, via enhancement of voltage gated sodium channel slow inactivation and represents a molecule possessing a unique anticonvulsant mechanism of action.

Doctor of Philosophy(PhD) / Particle formation in RAFT-mediated emulsion polymerization has been studied using reaction calorimetry. By measuring the heat flow during controlled feed ab-initio emulsion polymerization in the presence of amphipathic RAFT agents, particle formation by self-assembly of these species could be observed. Two different monomer systems, i.e. styrene and n-butyl acrylate, and various degrees of hydrophobicity of the initial macro-RAFT agents have been studied and compared. The different macro-RAFT agents were synthesized by first forming a hydrophilic block of poly(acrylic acid) that would later on act as the electrosteric stabilizing group for the particles. Subsequently, different lengths of hydrophobic blocks were grown at the reactive end of the poly(acrylic acid) hydrophilic block via the RAFT-mediated controlled radical polymerization, either comprised of n-butyl acrylate or styrene. Two processes govern particle formation: adsorption of macro-RAFT agents onto growing particles and formation of new particles by initiation of micellar aggregates or by homogeneous nucleation. Competition between these processes could be observed when monomers with a relatively high (n-butyl acrylate) or low (styrene) propagation rate coefficient were used. A model describing particle formation has been developed and the results of model calculations are compared with experimental observations. Preliminary modeling results based on a set of reasonable physico-chemical parameters already showed good agreement with the experimental results. Most parameters used have been verified experimentally. The development of the molecular weight distribution of the macro-RAFT agents has been analyzed by different techniques. Quantification of the particle formation process by analytical techniques was difficult, but qualitative insights into the fundamental steps governing the nucleation process have been obtained. The amount of macro-RAFT agents initially involved in particle formation could be determined from the increase of molecular weight. The particle size distribution has been measured by capillary hydrodynamic fractionation, transmission electron microscopy and dynamic light scattering. From the data obtained from these particle-sizing techniques, the number of particles during the reaction could be monitored, leading to an accurate estimate for the particle formation time. Upon implementation of the experimental data obtained for the surface active macro-RAFT systems, the model demonstrated to be very sensitive towards the “headgroup” area of the macro-RAFT species. Three nucleation cases based on the initial surface activity of the macro-RAFT species in the aqueous phase are proposed to explain the deviations from the assumptions of the nucleation model. Even though the macro-RAFT species have a narrow molecular weight distribution, they are nevertheless made up of a distribution of block lengths of polystyrene upon a distribution of block lengths of poly(acrylic acid). The resulting differences in initial surface activity are the most probable reason for the observed differences between model calculations and experimental results for the nucleation time and particle size distribution of the final latex product. With the procedure described above, latexes have been synthesized without using conventional surfactants and the mechanisms involved in the particle formation for these systems have been elucidated. The results of this work enable production of latex systems with well defined molecular mass distributions and narrow particle size distributions. Furthermore, the technique based on the application of amphipathic RAFT agents is promising for the production of complex polymeric materials in emulsion polymerization on a technical scale.

The thesis contributes to the study of the relationship between competition and incentives, when asymmetric information is taken into account. Our main focus is the analysis of loan relationships. The first two chapters analyze the relationship between borrowers' financial constraints and endogenous fluctuations. We try to provide a potential departure from the traditional corporate finance theories by showing that the characteristics of firms' capital structure (i.e. their debt-to-equity ratio) can be affected by macroeconomic conditions. We construct a dynamic economy with asymmetric information in the credit market. The features of optimal securities issued at equilibrium are influenced by macroeconomic conditions. As a by-product, the debt-to-equity ratio in the overall economy will evolve according to the dynamics of aggregate variables. The remaining of the thesis develops a theoretical analysis of credit relationships where multiple financiers compete over the loan contracts they are offering to entrepreneurs-borrowers. To this extent, Chapter 3 proposes a unified framework to analyze the so-called literature on competing mechanisms and provides new results in terms of characterizing the equilibria of multi-principal multi-agent games. In the specific context of common agency games, we show that the introduction of a separability requirement on agent's preferences with respect to the contract offers she receives from principals is a sufficient condition to retrieve the Revelation Principle. Importantly, no restriction on principals' preferences is introduced. Chapter 4 investigates credit market relationships when competing lenders are explicitly considered. A reformulation of the traditional credit channel of Monetary Policy is then suggested. When lenders are strategically competing on their credit contract offers, positive-profit equilibria typically arise. Our analysis considers both the exclusive case and the non-exclusive one and it argues that monetary factors may affect the real sector mainly by modifying the structure of markets. The last chapter discusses the welfare implications of contractual externalities that arise in the presence of multiple financiers. We consider a scenario where a Social Planner is subject to the same informational constraints faced by principals in a simple model of the credit market. We identify conditions that sustain constrained-efficiency of market equilibria.