Patients on dialysis are subject to a hugely elevated risk of cardiovascular mortality. Incidence and prevalence of, and mortality and morbidity from heart failure is significantly higher in the haemodialysis population than the general population as a whole. This thesis describes research work focusing on the large scale haemodynamic changes that occur during haemodialysis and how they may negatively impact on the cardiovascular system. Our results show that the haemodynamic disturbances which occur during haemodialysis are capable of causing a reduction in myocardial blood flow sufficient in magnitude to induce myocardial ischaemia. This is associated with a matched reduction in regional left ventricular (LV) function and is entirely in keeping with other published work describing haemodialysis induced myocardial stunning reflecting subclinical myocardial ischaemia (myocardial stunning). In addition, we now know that this phenomenon of haemodialysis induced myocardial ischaemia and stunning is common and associated with both short and long term complications including ventricular arrhythmias, left ventricular dysfunction, an increased hazard of death and time to first cardiovascular event. This is pertinent as in non-dialysis patients repeated episodes of myocardial stunning lead to chronic heart failure, and in dialysis patients the presence of LV dysfunction dramatically increases the risk of death. We also identified a number of factors associated with the presence of myocardial stunning including age, raised biochemical markers of cardiac damage (troponin-T), higher ultrafiltration volumes and lower intradialytic blood pressure. This is of crucial importance as ultrafiltration volumes and intradialytic haemodynamics are potentially modifiable risk factors that could provide targets for dialysis based interventions aimed at improving cardiovascular outcomes in the haemodialysis population.

氯胺酮是一種麻醉劑，也是一種濫用藥物。近年來，氯胺酮濫用增長迅速，在香港已經成爲第二大濫用藥物。氯胺酮的短期效果主要導致精神狀態改變，但對其長期效果還了解甚少。研究目的：本研究旨在探討長期使用氯胺酮對中樞神經系統，腎上腺，胰腺和膀胱的影響。研究方法：我們在氯胺酮濫用的動物模型中進行的行爲學，神經化學，組織學和分子生物學研究。在水迷宮中，對這些小鼠學習和記憶能力進行了評估。應用基因芯片評估中樞神經系統的基因表達變化。用聚合酶鏈式反應陣列研究神經遞質及其調控基因表達變化。通過實時定量聚合酶鏈式反應和免疫印迹法檢測-氨基丁酸受體和多巴胺相關基因的基因表達的變化。用酶聯免疫法測定多巴胺含量。用原位末端轉移酶標記技術染色（細胞凋亡），天狼星紅染色（纖維化），免疫組織化學（乳酸脫氫酶，酪氨酸羟化酶，多巴胺β羟化酶）研究腎上腺，胰腺，膀胱癌的組織學變化。研究結果：與對照組相比，氯胺酮組小鼠學習記憶能力下降。基因芯片結果顯示，110個基因表達上調和136個基因表達下調。基因本體分析表明，氯胺酮明顯影響神經遞質和受體的活性。特別地，4-氨基丁酸A受體5型亞基的mRNA和蛋白水平在前額皮層的顯著上調。聚合酶鏈式反應陣列結果表明，氯胺酮顯著改變-氨基丁酸受體，神經肽，多巴胺和膽鹼能系統基因表達。對多巴胺系統的研究結果顯示，中腦多巴胺含量上調，酪氨酸羟化酶的顯著增加。在腎上腺和胰腺，氯胺酮和氯胺酮加酒精組都未觀察到細胞凋亡增加，但是觀察到乳酸脫氫酶的陽性染色。此外，在腎上腺中發現酪氨酸羟化酶和多巴胺β羟化酶下調。在膀胱中，在肌肉層觀察到細胞凋亡和纖維化。結論：本研究的結果研究指出，長期使用氯胺酮能引起中樞神經系統異常的基因表達，還能導致腎上腺，胰腺，膀胱癌的病理性改變。這些結果爲氯胺酮濫用相關的健康風險評估提供了重要的信息。 / Ketamine is an anesthetic agent and a drug of abuse. In recent years, ketamine abuse has been increasing rapidly and it has become the second-most popular abusive drug in Hong Kong. While the acute effects of ketamine are mainly linked to altered mental status, the long-term effects of ketamine are poorly understood. Objectives: The present study was designed to investigate the long-term effects of ketamine on the CNS, adrenal, pancreas and urinary bladder. Methods: Behavioral, neurochemical, histological and molecular studies were performed in a ketamine abuse animal model. Learning and memory ability in these mice were assessed in a morris water maze. An Affymetrix Genechip study was performed to assess the global gene expression changes in the CNS and a PCR-array study focused on the neurotransmitters and regulators was also performed. Gene expression changes for gamma-aminobutyric acid (GABA) receptors and dopamine related genes were assay by real-time PCR and western blot. Dopamine contents were measured by ELISA. Histological changes in adrenal, pancreas and urinary bladder were examined by TUNEL staining (apoptosis), Sirius red staining (fibrosis), and immunohistochemistry. Results: Compared with saline controls, there was a decline in learning and memory performance in the ketamine-treated mice. Genechip results showed that 110 genes were up-regulated and 136 genes were down-regulated in ketamine group. An ontology analysis revealed the most significant effects of ketamine were on neurotransmitter and receptor activities. In particular, there was a significant up-regulation of both mRNA and protein levels of the alpha 5 subunit (Gabra5) of the GABAA receptors in the prefrontal cortex. Results from the PCR-array study revealed significant gene expression changes in the GABA receptors, neuropeptides, dopaminergic and cholinergic system following ketamine treatment. Studies on the DA system revealed significant increase of DA content and up-regulation of Tyrosine Hydroxylase (TH) in the midbrain. In the adrenal and pancreas, no obvious apoptosis was found while lactate dehydrogenase (LDH) positive staining was observed in both ketamine and ketamine plus alcohol treated groups. On top of these, downregulation of TH and DBH were observed. In the urinary bladder, apoptosis and fibrosis were observed in the muscular layer. Conclusion: The present study pointed out that long-term of ketamine use caused aberrant gene expression in the CNS and led to pathological changes in adrenal, pancreas and urinary bladder. These results have provided novel and important insights in evaluating the health risks in ketamine abusers. / Detailed summary in vernacular field only. / Tan, Sijie. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 138-154). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract --- p.I / 摘 要 --- p.III / List of abbreviations --- p.IV / Acknowledgements --- p.VI / Contents --- p.VII / Chapter Chapter 1 --- General introduction --- p.1 / Chapter 1.1 --- Ketamine and abuse --- p.1 / Chapter 1.2 --- Pharmacological effects of ketamine --- p.4 / Chapter 1.3 --- Effects of ketamine on the CNS --- p.6 / Chapter 1.4 --- GABA receptors --- p.9 / Chapter 1.5 --- Dopamine system in the CNS --- p.10 / Chapter 1.6 --- The modulation of dopaminergic neurons --- p.12 / Chapter 1.7 --- Toxic effects of ketamine on other organs --- p.14 / Chapter 1.8 --- Thesis outline --- p.17 / Chapter Chapter 2 --- Cognition and GABA receptor expression following long-term ketamine administration --- p.20 / Chapter 2.1 --- Introduction --- p.20 / Chapter 2.2 --- Materials and methods --- p.22 / Chapter 2.2.1 --- Animals and drug administrations --- p.22 / Chapter 2.2.3 --- Dosage Determination --- p.23 / Chapter 2.2.4 --- Morris water maze --- p.24 / Chapter 2.2.5 --- Brain tissue collection and RNA extraction --- p.25 / Chapter 2.2.6 --- Microarray analysis --- p.26 / Chapter 2.2.7 --- Quantitative real-time PCR --- p.27 / Chapter 2.2.8 --- Western blotting --- p.28 / Chapter 2.2.9 --- Statistical analysis --- p.29 / Chapter 2.3 --- Results --- p.29 / Chapter 2.3.1 --- Morris water maze --- p.29 / Chapter 2.3.2 --- Microarray analysis --- p.30 / Chapter 2.3.3 --- Quantitative real-time PCR --- p.30 / Chapter 2.3.4 --- Western blotting --- p.31 / Chapter 2.4 --- Discussion --- p.44 / Chapter Chapter 3 --- PCR-array gene expression profiling on the neurotransmitters following chronic ketamine administration --- p.49 / Chapter 3.1 --- Introduction --- p.49 / Chapter 3.2 --- Materials and methods --- p.50 / Chapter 3.3 --- Results --- p.51 / Chapter 3.4 --- Discussion --- p.63 / Chapter Chapter --- 4 Chronic ketamine administration modulates midbrain dopamine system in mice --- p.67 / Chapter 4.1 --- Introduction --- p.67 / Chapter 4.2 --- Materials and methods --- p.69 / Chapter 4.2.1 --- Cell culture and ketamine treatment --- p.69 / Chapter 4.2.2 --- MTT assay --- p.70 / Chapter 4.2.3 --- Animals and ketamine administration --- p.70 / Chapter 4.2.4 --- Dopamine determination --- p.71 / Chapter 4.2.5 --- Real-time PCR --- p.72 / Chapter 4.2.6 --- Western blotting --- p.73 / Chapter 4.2.7 --- Immunohistchemistry --- p.74 / Chapter 4.2.8 --- Statistical analysis --- p.74 / Chapter 4.3 --- Results --- p.75 / Chapter 4.3.1 --- Effects of ketamine on dopamine concentrations in PC12 cells --- p.75 / Chapter 4.3.2 --- Long-term effects of ketamine on dopamine in mouse brain --- p.76 / Chapter 4.3.3 --- Effects of ketamine on mRNA levels of dopamine related genes --- p.76 / Chapter 4.3.4 --- Long-term effects of ketamine on BDNF protein levels in mouse brain --- p.77 / Chapter 4.3.5 --- Increased TH inmmureactive neurons in midbrain following 3 months ketamine treatment --- p.78 / Chapter 4.4 --- Discussion --- p.90 / Chapter Chapter 5 --- Chronic treatment of ketamine affects adrenal gland and pancreas --- p.95 / Chapter 5.1 --- Introduction --- p.95 / Chapter 5.2 --- Materials and methods --- p.95 / Chapter 5.2.1 --- Grouping of experimental animals and treatments --- p.95 / Chapter 5.2.2 --- Histological studies on pancreas and adrenal --- p.96 / Chapter 5.2.3 --- Immunohistochemistry on pancreas and adrenal --- p.97 / Chapter 5.2.4 --- TUNEL evaluation --- p.99 / Chapter 5.3 --- Results --- p.100 / Chapter 5.4 --- Discussion --- p.114 / Chapter Chapter 6 --- Ketamine Effects on the Urogenital System-Changes in the Urinary Bladder and Sperm Motility --- p.117 / Chapter 6.1 --- Introduction --- p.117 / Chapter 6.2 --- Materials and methods --- p.117 / Chapter 6.2.1 --- Studies of the Bladder --- p.117 / Chapter 6.2.2 --- Studies on Sperm Motility --- p.120 / Chapter 6.3 --- Results --- p.121 / Chapter 6.4 --- Discussion --- p.131 / Chapter Chapter 7 --- Conclusion --- p.134 / Chapter 7.1 --- Conclusion --- p.134 / Chapter 7.2 --- Future studies --- p.137 / Bibliography --- p.138

In this thesis, the influence of an environment on molecules and, in particular, on the quantum control of such systems is investigated. Different approaches to describe system-bath dynamics are implemented and applied. The inclusion of a dissipation term in the system Hamiltonian leads to energy loss and relaxation to the ground state. As a first application, the isomerisation reaction in an aromatic complex is treated. It is shown that this simple model is able to reproduce results of time-resolved spectroscopic measurements. Next, the influence of noise is investigated. The incorporation of fluctuations reveals that energy is not conserved and coherences are destroyed. As an example, the quantum control of a population transfer in Na2 is examined. The efficiency of control processes is studied in dependence on the strength of the noise and different system-bath couplings. Starting with the unperturbed system, Local Control Theory is applied to construct a field which selectively transfers population into a single excited electronic state. The coupling to the bath is then switched on to monitor the dependence of the coupling strength on the transfer efficiency. The perturbation of the bath effects the Na2 molecule in such a way that potential energy curves and transition dipole moments are distorted. An important result is that already elastic collisions lead to a substantial loss of control efficiency. The most promising approach used in this thesis is the stochastic Schrödinger equation. It is equivalent to the commonly employed descriptions of system-bath dynamics within the reduced density matrix formalism. It includes decoherences and dissipation caused by elastic and inelastic collisions. Our contribution is the incorporation of laser excitation into the kinetic Monte-Carlo scheme. Thus we are able to apply this stochastic approach to the quantum control of population transfer in the sodium dimer. Because within our description it is possible to separate pure dephasing, inelastic transitions, and coherent time-evolution, we can identify the relative influence of these processes on the control efficiency. This leads to a far more physical picture of the basic processes underlying the perturbations of an environment then what a reduced density matrix description can provide. In utilising the stochastic wave function approach instead of the density matrix formalism, the computations are quite efficient. The stochastic Schrödinger equation is realised by N independent runs, where, in our case, an ensemble size of N = 1000 gives converged results. The efficiency of the laser control process is studied as a function of temperature and collision rates. A rise in temperature (or collision rate) reeffects a stronger fluctuation and thus results in a less efficient transfer by the control field. Though the Gaussian fluctuations used here do not strictly represent 'white'- noise, since a deterministic machine is not able to produce uncorrelated random numbers, an acceptable distribution is achieved by simple procedures. An improvement of the here applied algorithms would, for instance, include a more sophisticated sampling of the dephasing rates. Only one example of a control process is studied here and an application of the developed approach to other problems of quantum control is to be performed. This thesis established a systematic approach to understand quantum control in the presence of an environment. / In der vorliegenden Arbeit wird der Einfluss der Umgebung auf Moleküle und insbesondere der Quantenkontrolle solcher Systeme untersucht. Unterschiedliche Herangehensweisen, System-Bad-Kopplungen zu beschreiben, werden implementiert und angewendet. Die Berücksichtigung eines Dissipationstermes im System-Hamiltonoperator führt zu Energieabgabe und Relaxation in den Grundzustand. Als eine erste Anwendung wird die Isomerisation eines aromatischen Komplexes behandelt. Anhand dieses einfachen Modells ist es möglich, Resultate zeitaufgelöster, spektroskopischer Messungen zu reproduzieren. Weiterhin wird der Einfluss des Rauschens untersucht. Die Einführung von Fluktuationen führt dazu, dass Energie nicht erhalten bleibt und Kohärenz verloren geht. Als ein Beispiel dient hier die Quantenkontrolle eines Populationstransferprozesses im Na2 Molekül. Die Effizienz eines Kontrollprozesses wird in Abhängigkeit der Rauschstärke und verschiedener System-Bad-Kopplungen untersucht. Ausgehend vom ungestörten System wird die Lokale Kontrolltheorie benutzt, um ein Feld, welches selektiv Population in einen einzigen, angeregten Zustand transferiert, zu konstruieren. Die Kopplung an das Bad wird daraufhin eingeschaltet, um die Abhängigkeit der Kopplungsstärke auf die Transfereffizienz zu charakterisieren. Die Störung des Bades beeinflusst das Na2-Molekül dahingehend, dass Potentialkurven und Übergangsdipolmomente verzerrt werden. Eine wichtige Erkenntnis ist, dass bereits elastische Stöße zu einem substantiellen Verlust der Kontrolleffizienz führen. Die am meisten versprechende Methode, welche in dieser Arbeit Verwendung findet, ist die der stochastischen Schrödingergleichung. Sie ist der weitläufig gebräuchlichen Beschreibung von System-Bad-Wechselwirkungen innerhalb des Formalismus der reduzierten Dichtematrix gleichwertig. Dekohärenzen und Dissipationseffekte ausgelöst durch elastische und inelastische Stöße werden innerhalb der stochastischen Gleichungen separat berücksichtigt. Unser Beitrag ist die Einbindung der Laseranregung in das kinetische Monte-Carlo-Schema. Dies ermöglicht die Anwendung des stochastischen Ansatzes auf die Quantenkontrolle des Populationstransfers eines Natriumdimers. Da es innerhalb unserer Beschreibung möglich ist, reine Dephasierungen, inelastische Übergänge und kohärente Entwicklung in der Zeit zu beschreiben, können wir den relativen Einfluss jener Prozesse auf die Kontrolleffizienz identifizieren. Dies führt zu einer physikalischeren Beschreibung der zugrunde liegenden Prozesse, welche die Störungen der Umgebung bewirken, als sich aus einer reduzierten Dichtematrizendarstellung ergibt. Durch Benutzung des stochastischen Wellenfunktionsansatzes anstelle des Dichtematrizenformalismus ergeben sich effiziente Berechnungen. Die stochastische Schrödingergleichung wird für N unabhängige Programmdurchläufe gelöst, wobei in unserem Fall eine Ensemblegröße von N = 1000 konvergente Resultate liefert. Die Wirksamkeit des Laserkontrollprozesses wird anhand von Temperatur und Stoßrate untersucht. Ein Anstieg der Temperatur (oder der Stoßrate) spiegelt höhere Fluktuationen wider und resultiert daher in einem weniger effizienten, von einem Kontrollfeld hervorgerufenen Transfer. Obwohl die gaußverteilten Fluktuationen, welche hier benutzt werden, strenggenommen kein 'Weisses Rauschen' repräsentieren, da eine deterministische Rechenmaschine keine unkorrellierten Zufallszahlen generieren kann, wird dennoch eine akzeptable Verteilung aus einfachen Prozeduren erhalten. Eine Verbesserung der hier angewendeten Algorithmen würde zum Beispiel aus einer verfeinerten Implementierung der Dephasierungsraten bestehen. Lediglich ein Beispiel eines Kontrollprozesses wird hier untersucht und die Anwendung der erarbeiteten Methodik auf andere Fragestellungen der Quantenkontrolle ist noch offen. Diese Dissertation stellt somit eine systematische Annäherung dar, um die Quantenkontrolle in Anwesenheit von Umgebungseinflüssen zu verstehen.

The clonal selection/defence paradigm appears unable to reconcile immune function with homeostatic activity whereas organismic homeostasis is central to immune function in the network/autopoiesis paradigm. The aim of this investigation, therefore, was to test the proposition that immune function, that is not clonally driven (central immune system activity), contributes to organismic homeostasis in collaboration with psychoneural responses. In one experiment sheep were confined, either in groups or individually, and the time course of changes in cortisol levels, behaviour and T lymphocyte numbers were monitored. In another study, soldiers were monitored during the stressful experience of recruit training. The combined results suggest that, at least when the immune response is not clonally driven, the psychoneural system and the central immune system may not be operating independently of each other but rather as sub-networks of the organismic network. Consequently, homeostasis is properly characterised as a property of the whole organism. In autopoietic terms, then, homeostasis could be defined as the maintenance of network stability. / Doctor of Philosophy (PhD)

No description available.

This dissertation aims to address two optimization problems involving power system reliabilty analysis, namely multi-area power system adequacy planning and transformer maintenance optimization. A new simulation method for power system reliability evaluation is proposed. The proposed method provides reliability indexes and distributions which can be used for risk assessment. Several solution methods for the planning problem are also proposed. The first method employs sensitivity analysis with Monte Carlo simulation. The procedure is simple yet effective and can be used as a guideline to quantify effectiveness of additional capacity. The second method applies scenario analysis with a state-space decomposition approach called global decomposition. The algorithm requires less memory usage and converges with fewer stages of decomposition. A system reliability equation is derived that leads to the development of the third method using dynamic programming. The main contribution of the third method is the approximation of reliability equation. The fourth method is the stochastic programming framework. This method offers modeling flexibility. The implementation of the solution techniques is presented and discussed. Finally, a probabilistic maintenance model of the transformer is proposed where mathematical equations relating maintenance practice and equipment lifetime and cost are derived. The closed-form expressions insightfully explain how the transformer parameters relate to reliability. This mathematical model facilitates an optimum, cost-effective maintenance scheme for the transformer.

This thesis is an effort to develop closed-loop control strategies on computer networks and study their stability in the presence of network delays and packet losses. An algorithm using predictors was designed to ensure the system stability in presence of network delays and packet losses. A single actuator magnetic ball levitation system was used as a test bed to validate the proposed algorithm. A brief study of real-time requirements of the networked control system is presented and a client-server architecture is developed using real-time operating environment to implement the proposed algorithm. Real-time performance of the communication on Ethernet based on user datagram protocol (UDP) was explored and UDP is presented as a suitable protocol for networked control systems. Predictors were designed based on parametric estimation models. Autoregressive (AR) and autoregressive moving average (ARMA) models of various orders were designed using MATLAB and an eighth order AR model was adopted based on the best-fit criterion. The system output was predicted several steps ahead using these predictors and control output was calculated using the predictions. This control output output was used in the events of excessive network delays to maintain system stability. Experiments employing simulations of consecutive packet losses and network delays were performed to validate the satisfactory performance of the predictor based algorithm. The current system compensates for up to 20 percent data losses in the network without loosing stability.

In this paper, we present a automatic item classification system,called AICS. This system is according the content structure that are provided from the teacher for create a content tree. This content tree can correlate the item with content. The main works of AICS classify the item and find the most similar content. After than the system compute the relationship between the item and content, AICS can automatic compute the difficulty of item and examination. The work of this research has two categories: 1. The system can show the content that are related to the item and help the teacher understand the difficulty of the examination paper quickly. 2. When after the examination, the system provide the content for student understand the irrelevant items.

Real-time wave forecasts are critical to a variety of coastal and offshore opera- tions. NOAA’s global wave forecasts, at present, do not extend into many coastal regions of interest. Even after more than two decades of the historical Exxon Valdez disaster, Cook Inlet (CI) and Prince William Sound (PWS) are regions that suffer from a lack of accurate wave forecast information. This dissertation develops high- resolution integrated wave forecasting schemes for these regions in order to meet the critical requirements associated with shipping, commercial and sport fishing vessel safety, and oil spill response. This dissertation also performs a detailed qualitative and quantitative assessment of the impact of various forcing functions on wave pre- dictions, and develops maps showing extreme variations in significant wave heights (SWHs). For instance, it is found that the SWH could vary by as much as 1 m in the northern CI region in the presence of currents (hence justifying the need for integration of the wave model with a circulation model). Such maps can be useful for several engineering operations, and could also serve as guidance tool as to what can be expected in certain regions. Aside from the system development, the issue of forecast reliability is also addressed for PWS region in the context of the associated uncertainty which confronts the manager of engineering operations or other planners. For this purpose, high-resolution 36-h daily forecasts of SWHs are compared with measurements from buoys and satellites for about a year. The results show that 70% of the peak SWHs in the range 5-8 m were predicted with an accuracy of 15% or less for a forecast lead time of 9 h. On average, results indicate 70% or greater likelihood of the prediction falling within a tolerance of ±(1*RMSE) for all lead times. This analysis could not be performed for CI due to lack of data sources.

The report is focused on the implementation of a data acquisition system that will be used for measuring different parameters which are needed in solar panel behavior analysis. To accomplish the DAQ system a DAQ board has been designed and implemented. This DAQ board acquires measured climatic parameters that affect the PV module behavior and voltage and current of a PV module. The DAQ board may take measurements of multiple analog and digital signals that come from various sensors including solar radiation, temperature, wind sensors and other measurement devices. The DAQ board may also output analog signals for controlling other devices. The DAQ board is the basic part of the DAQ system and several of them can be connected via a single communication bus (RS485). A unique slave ID can be assigned to each DAQ board on the communication bus, which allows the control of all boards via a GUI application installed on a master computer. Therefore, the DAQ system can be used for monitoring a PV module installation as well as logging the measured data in a data storage server. This report outlines the details of the DAQ system design which are helpful in utilizing or upgrading this system. These details also include programming of DAQ board and implementation of MODBUS communication protocol within the DAQ system.