by Kam-Ming Au. / Thesis (M.Sc.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 87-101. / LIST OF TABLES / LIST OF FIGURES / ACKNOWLEDGEMENTS / ABSTRACT / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- Normal calcium homeostasis --- p.1 / Chapter 1.2 --- The incidence and common causes of hypercalcemia in hospital population --- p.6 / Chapter 1.3 --- Hypercalcemia in primary hyperparathyroidism --- p.10 / Chapter 1.4 --- Hypercalcemia of malignancy --- p.13 / Chapter 1.5 --- Pathophysiology of humoral hypercalcemia of malignancy --- p.16 / Chapter 1.6 --- Pathogenesis of humoral hypercalcemia of malignancy-evidence for a parathyroid hormone-related peptide --- p.20 / Chapter 1.7 --- Hypercalcemia in primary hepatocellular carcinoma --- p.27 / Chapter 1.8 --- Physiological role of cyclic adenosine monophosphate --- p.28 / Chapter 1.9 --- Aim of the present study --- p.29 / Chapter CHAPTER 2. --- MATERIALS AND METHODS --- p.30 / Chapter 2.1 --- Patients --- p.30 / Chapter 2.1.1 --- Hepatocellular carcinoma patients --- p.30 / Chapter 2.1.2 --- Cirrhotic patients --- p.30 / Chapter 2.2 --- Healthy control subjects --- p.30 / Chapter 2.3 --- Collection of blood and urine specimens --- p.32 / Chapter 2.4 --- Methods --- p.32 / Chapter 2.4.1 --- Routine chemistries --- p.32 / Chapter 2.4.2 --- Plasma and urine cyclic adenosine monophosphate --- p.33 / Chapter - --- commercial urine controls --- p.34 / Chapter - --- scintillation cocktail --- p.34 / Chapter - --- imprecision study --- p.34 / Chapter - --- accuracy study --- p.34 / Chapter 2.4.3 --- Nephrogenous cyclic adenosine monophosphate and total urinary cyclic adenosine monophosphate / 100 ml glomerular filtrate --- p.35 / Chapter 2.4.4 --- Total urinary cyclic adenosine monophosphate : creatinine ratio --- p.36 / Chapter 2.4.5 --- Components of hypercalcemia --- p.36 / Chapter 2.4.6 --- Urinary hydroxyproline : creatinine ratio --- p.37 / Chapter 2.4.7 --- Renal phosphate threshold --- p.37 / Chapter 2.4.8 --- Serum parathyroid hormone --- p.38 / Chapter 2.4.9 --- Serum parathyroid hormone-related peptide --- p.38 / Chapter 2.5 --- Statistical analysis --- p.39 / Chapter CHAPTER 3. --- RESULTS --- p.40 / Chapter 3.1 --- Method validation for cyclic adenosine monophosphate assay --- p.40 / Chapter 3.1.1 --- Standard curve of the cyclic adenosine monophosphate assay --- p.40 / Chapter 3.1.2 --- Results of imprecision study --- p.43 / Chapter 3.1.3 --- Results of accuracy study --- p.43 / Chapter 3.2 --- "Results of hypercalcemic and normocalcemic hepatocellular carcinoma patients, cirrhotic patients, and healthy control subjects" --- p.47 / Chapter 3.2.1 --- "Results of serum calcium, albumin adjusted calcium, serum albumin and serum alkaline phosphatase" --- p.47 / Chapter 3.2.2 --- "Results of serum phosphate, renal phosphate threshold and serum parathyroid hormone" --- p.51 / Chapter 3.2.3 --- Results of plasma cyclic adenosine monophosphate --- p.55 / Chapter 3.2.4 --- "Results of nephrogenous cyclic adenosine monophosphate , total urinary cyclic adenosine monophosphate / 100 ml glomerular filtrate and total urinary cyclic adenosine monophosphate : creatinine ratio 59" / Chapter 3.2.5 --- Results of urinary calcium : creatinine ratio and urinary hydroxyproline : creatinine ratio --- p.66 / Chapter 3.2.6 --- Factors contributing to hypercalcemia in hepatocellular carcinoma patients 71 / Chapter 3.2.7 --- Results of serum parathyroid hormone-related peptide --- p.75 / Chapter CHAPTER 4. --- DISCUSSION --- p.77 / REFERENCES --- p.87

by Hing Kee Wong. / Title also in Chinese. / Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 67-74.

"Mechanical loads play a pivotal role in the growth, maintenance, remodeling, and disease onset in connective tissues. Harnessing the relationship between mechanical signals and how cells remodel their surrounding extracellular matrix would provide new insights into the fundamental processes of wound healing and fibrosis and also assist in the creation of custom-tailored tissue equivalents for use in regenerative medicine. In 3D tissue models, uniaxial cyclic stretch has been shown to stimulate the synthesis and crosslinking of collagen while increasing the matrix density, fiber alignment, stiffness, and tensile strength in the direction of principal stretch. Unfortunately, the profound fiber realignment in these systems render it difficult to differentiate between passive effects and cell-mediated remodeling. Further, these previous studies generally focus on a single level of stretch magnitude and duration, and they also investigate matrix remodeling under a homogeneous strain conditions. Therefore, these studies are not sufficient to establish key information regarding stretch-dependent remodeling for use in tissue engineering and also do not simulate the complex mechanical environment of connective tissue. We first developed a novel in vitro model system using equibiaxial stretch on fibrin gels (early models of wound healing) that enabled the isolation of mechanical effects on cell-mediated matrix remodeling. Using this system we demonstrated that in the absence of in-plane alignment, stretch stimulates fibroblasts to produce a stronger tissue by synthesizing collagen and condensing their surrounding matrix. We then developed dose-response curves for multiple aspects of tissue remodeling as a function of stretch magnitude and duration (intermittent versus continuous stretch). Our results indicate that both the magnitude and the duration per day of stretch are important factors in mechanically induced cell activity, as evidenced by dose-dependent responses of several remodeling metrics in response to these two parameters (UTS, matrix stiffness, collagen content, cell number). In addition, we found that cellularity, collagen content, and resistance to tension increased when the tissues were mechanically loaded intermittently as opposed to continuously. Finally, we developed a novel model system that produces non-homogeneous strain distribution, allowing for the simultaneous study of strain gradients, strain anisotropy, and strain magnitude in 2D and 3D. Establishing a system that produces complex strain distributions provides a more accurate model of the mechanical conditions found in connective tissue, and also allows for the investigation of cellular adaptations to a changing mechanical environment. "

"Previous implementations of digital background calibration for cyclic ADCs have required linear amplifier behavior in the gain stage for accurate correction. Correction is digital decoding of ADC outputs to determine the original ADC input. Permitting nonlinearity in the gain stage of the ADC allows for less demanding amplifier design requirements, reducing power and size. However this requires a method of determining the value of this variable gain during digital correction. Look up tables (LUTs,) are an effective and efficient method of compensating for analog circuit imperfections. The LUT correction and calibration method discussed in this work has been simulated using Cadence integrated circuit simulation ADC specifications and MATLAB."

Aluminum-nickel (Al-Ni) alloys and Al/Ni bilayers were successfully electrodeposited from AlCl3-EMIM-NiCl2 electrolyte at room temperature. Dissolution of NiCl2 was shown to be favorable in Lewis basic (with molar ratio of AlCl3 < 0.5) AlCl3-EMIM solution. The use of electrochemically active Cu working electrode as opposed to inert W induced additional Cu oxidation and dissolution in the cyclic voltammetry scan. The reduction potentials of Al and Ni were found to be ~ – 0.3 and 0.15 V vs. Al/Al3+ respectively. Increasing [NiCl2] in the electrolyte leads to an increase of Ni concentration in the deposited structures. Dense and well-adherent Al-Ni alloys with Ni concentration up to 17.7 at.% were deposited by potential control. XRD analysis revealed that the deposited Al-Ni exhibit a supersaturated fcc crystalline structure. The visual appearance of the deposits ranged from bright silver, dull silver, grey, to black, where the darker shade typically indicated higher Ni content. SEM analysis revealed that the surface morphology of the deposits ranged from nodular to flake-like structures. Al-Ni alloy typically showed nodular morphology with cauliflower structure. Flake structures, which were independent of substrate roughness, were found to develop under pulsed potential deposition with 1:1 duty ratio. The concentration of Ni in electrodeposited Al-Ni alloys increases nonlinearly with the increase in molarity of NiCl2. Al and Ni contents increase with increasing the time of positive and negative cycle of the pulse respectively. Decreasing the frequency by half resulted in almost double the amount of Ni in the deposited alloy. A smoother substrate increased Ni concentration from 6 to 17.7 at.%. Al/Ni bilayer was successfully deposited in 1.5:1 AlCl3-EMIM containing 0.026 M NiCl2. Deposition of Al on Ni was achieved using constant potential and pulse potential control. The deposition of Ni on Al is complicated since the deposition potential of Ni lies in the vicinity of Al stripping potential thus inducing competition between Ni deposition and Al stripping.

No description available.

Essential hypertension is defined as a chronic elevation of blood pressure of unknown cause. Though a definitive trigger for this change in blood pressure has not been established, there is a strong association with an upregulation of sympathetic output from the central nervous system. There are a number of central autonomic nuclei involved in the maintenance of blood pressure, including the brainstem regions of the nucleus tractus solitarii (NTS), caudal ventrolateral medulla (CVLM), rostral ventrolateral medulla (RVLM), the sympathetic preganglionic neurons (SPNs) within the intermediolateral cell column (IML) of the spinal cord, as well as forebrain regions such as the paraventricular nucleus (PVN) of the hypothalamus. Within these centers, a vast number of neurotransmitters have been identified that contribute to the control of blood pressure, including glutamate, angiotensin II, serotonin, neurotensin, neuropeptide Y, opioids and catecholamines. Recognition of the role of nitric oxide (NO) and its multiple influences over the neural control of blood pressure is gaining increasing significance. Nitric oxide is a unique modulatory molecule that acts as a non-conventional neurotransmitter. As NO is a gas with a short half-life of 4 – 6 seconds, its’ synthesising enzyme, nitric oxide synthase (NOS) is often used as a marker of location of production. Once activated, the best-known “receptor” for NO is soluble guanylate cyclase (sGC), which drives the production of cyclic guanosine monophosphate (cGMP). Identifying the presence of cGMP can therefore be used to determine sites receptive to NO. Previous studies examining the role of NO in the central autonomic control of blood pressure have focused predominantly upon application of either excitatory or inhibitory drugs into the key central autonomic regions and assessing pressor or depressor effects. This thesis aims instead to study the neuroanatomical relationship and functional significance of NO and cGMP expression in the brain and spinal cord of a hypertensive and normotensive rat model. In the first experimental chapter (Chapter 3), a comparative neuroanatomical analysis of neuronal NOS expression and its relationship with cGMP in the SPN of mature Spontaneously Hypertensive Rats (SHR) and their controls, Wistar Kyoto (WKY) was undertaken. Fluorescence immunohistochemistry confirmed the expression of nNOS in the majority of SPN located within the IML region of both strains. However, a strain specific anatomical arrangement of SPN cell clusters was evident and while there was no significant difference between the total number of SPN in each strain, there were significantly fewer nNOS positive SPN in the SHR animals. All nNOS positive SPN were found to express cGMP, and a novel subpopulation of nNOS negative, cGMP-positive SPN was identified. These cells were located in the medial edge of the IML SPN cell group. These results suggest that cGMP is a key signalling molecule in SPN, and that a reduced number of nNOS positive SPN in the SHR may be associated with the increase in sympathetic tone seen in essential hypertension. The second experimental chapter (Chapter 4) aimed to determine if reduced numbers of nNOS containing SPN translated into reduced detectable cGMP. The functional significance of cGMP signalling in the two strains was then examined. Based on previous work by our group, it was predicted that reduced nNOS in the SHR would translate into reduced cGMP and that intrathecal administration of exogenous cGMP in the spinal cord would drive a differential pressor response in the two animal strains. Immunohistochemical techniques confirmed that within each SPN, the relative level of cGMP expression was significantly reduced in the SHR when compared to the WKY. Intrathecal application of 8-bromo-cGMP, a drug analogous to cGMP, increased blood pressure in both strains and had a differential and dose dependent effect, causing only a small increase in blood pressure in anaesthetised WKY animals, while driving a significant pressor response in the SHR. This finding raised the novel hypothesis that in the SHR, reduced nNOS expression is not a driver of hypertension, but is instead a protective mechanism limiting the potent pressor effects of cGMP within SPN. The third experimental chapter (Chapter 5) examines the expression of neuronal and inducible isoforms of NOS (nNOS, iNOS) within the RVLM of SHR and WKY rats. Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyse the level of mRNA expression and immunohistochemistry was then used to further analyse protein levels of nNOS. Total RNA was extracted and reverse transcribed from the RVLM of mature male WKY and SHR. Quantitative real-time PCR indicated that relative to WKY, mRNA levels for nNOS was significantly higher in RVLM of the SHR. This was confirmed immunohistochemically. When compared to iNOS, nNOS was expressed at significantly higher levels overall, however there was no difference in iNOS mRNA expression between the two strains. This demonstration of differential expression levels of nNOS and iNOS in the RVLM raises the possibilities that (i) NO production is up-regulated in the RVLM in SHR in response to increased sympathetic activity in order to re-establish homeostatic balance or alternatively that (ii) an alteration in the balance between nNOS and iNOS activity may underlie the genesis of augmented sympathetic vasomotor tone during hypertension. The fourth experimental chapter (Chapter 6) extends the observations in Chapter 5 through examination of the expression of cGMP and sGC within the RVLM. There is strong functional evidence to suggest that NO signalling in the RVLM relies on cGMP as an intracellular signalling molecule and that this pathway is impaired in hypertension. Immunohistochemistry was used to assess cGMP expression as a marker of active NO signalling in the C1 region of the RVLM, again comparing SHR and WKY animals. Fluorescence immunohistochemistry on sections of the RVLM, double labelled for cGMP and either nNOS or phenylethylamine methyl-transferase (PNMT) failed to reveal cGMP positive neurons in the RVLM from aged animals of either strain, despite consistent detection of cGMP immunoreactivity neurons in the nucleus ambiguus from the same or adjacent sections. This was demonstrated both in the presence and absence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) and in young vs. aged animals. In-vitro incubation of RVLM slices in the NO donor DETA-NO or NMDA did not reveal any additional cGMP neuronal staining within the RVLM. In all studies, cGMP was prominent within the vasculature. Soluble guanylate cyclase immunoreactivity was found throughout the RVLM, although it did not co-localise with the PNMT or nNOS neuronal populations. Overall, results suggest that within the RVLM, cGMP is not detectable in the resting state and cannot be elicited by phosphodiesterase inhibition, NMDA receptor stimulation or NO donor application. A short time course of cGMP signalling or degradation not inhibited by the phosphodiesterase inhibitor utilised (IBMX) in the RVLM cannot be excluded. The final experimental chapter (Chapter 7) examines cGMP expression in magnocellular and preautonomic parvocellular neurons of the PVN. Retrograde tracing techniques and immunohistochemistry were used to visualise cGMP immunoreactivity within functionally, neurochemically and topographically defined PVN neuronal populations in Wistar rats. Basal cGMP immunoreactivity was readily observed in the PVN, both in neuronal and vascular profiles. Cyclic GMP immunoreactivity was significantly higher in magnocellular compared to preautonomic neuronal populations. In preautonomic neurons, the level of cGMP expression was independent on their subnuclei location, innervated target or neurochemical phenotype. The data presented in this chapter indicates a highly heterogeneous distribution of basal cGMP levels within the PVN, and supports work by others indicating that constitutive NO inhibitory actions on preautonomic PVN neurons are likely mediated indirectly through activation of interneurons. Summary Together, these studies comprise a detailed analysis of the neuroanatomical expression of NO and its signalling molecule cGMP in key central autonomic regions involved in the regulation of blood pressure. Under resting or basal conditions, the studies demonstrate notable differences in the expression of NO synthesising enzymes between normotensive and hypertensive animals, and correlating changes in the downstream signalling molecule cGMP. In the spinal cord, novel functional differences in cGMP activity were also demonstrated. In the RVLM, although differences in nNOS were demonstrated, cGMP expression could not be readily detected in either the WKY or SHR, while in contrast within the PVN, cGMP was detected in both magnocellular and parvocellular neuronal populations. Conclusion This thesis gives insight into the physiological role of NO and cGMP as mediators of central blood pressure control. The results presented indicate that the NO-cGMP dependent signalling pathway may not be the dominant driver responsible for maintaining high blood pressure in the SHR model of essential hypertension, and that there is no globally consistent pattern of expression, and indeed the role of NO as a mediator of pressor and depressor function may vary between the autonomic regions examined. Further, it is possible that this pathway is only recruited during activation of reflex homeostatic pathways or during times of marked physiological stress, and that the differences we see in basal expression between the normotensive and SHR animals are instead a result of compensatory mechanisms.

Digital wireless communications have considerably changed not only the way people communicate, but also the way research is conducted in the field of telecommunications. In fact, the nature of the wireless medium has created a number of new challenging and fascinating research topics. In particular, a prerequisite for achieving higher and higher transmission rates in wireless systems is to develop strategies for efficiently dealing with the frequency selectivity of the wireless channel. A good candidate is the so-called cyclic prefixed block transmission, and in particular its two most popular variants which are the cyclic prefixed single-carrier (CPSC) and orthogonal frequency division multiplexing (OFDM) modulations. In this context, this thesis aims at analyzing and optimizing the use of cyclic prefixed block transmission for wireless communications. Firstly, this thesis contributes to the current state-of-the-art on the performance comparison between CPSC and OFDM, focusing on the derivation of analytical results when possible. If the channel state information is not available at the transmitter side, CPSC with minimum mean square error linear receiver is shown to achieve the best trade-off between performance and complexity, as it exploits the multipath diversity under some realistic hypotheses. Secondly, this thesis aims at using a system-based or cross-layer criterion, called goodput, for allocating resource in a coded OFDM system. Interestingly, the well-known waterfilling solution, when adequately parametrized, is proved to be near-optimal from a goodput point of view. Finally, this thesis discusses the possibility of improving the performance of a CPSC system by exploiting the cyclic prefix for equalization purposes.

tert-butyl 1-methoxycarbonyl-1-ferrocenecarbamate, Boc-NH-Fc-COOMe, (1) was synthesized according to the literature procedure and modified to 1-amino-n′-ferrocenemethylcarboxylate, 1,n′-H2N-Fc-COOCH3 (2) by removing the Boc-group with TFA/Et3N mixture in dichloromethane. Compound 2 reacted with alkylating agents like MeI, EtI, EtSCH2CH2Cl (MA) and (CN)(EtO)2P(O) (NA) to form MeNH-Fc-COOMe (3), EtNH-Fc-COOMe (4), EtSCH2CH2NH-Fc-COOMe (5), (EtO)2P(O)NH-Fc-COOMe (6), respectively. Cyclic voltammetry (CV) of these compounds showed different half-wave potential characteristics compared to aminoferrocene and was dependent on the nature of the substituents, which was rationalized by molecular orbital calculations. Electron donating groups (Me, Et and 2-chloroethyl ethylsulfide, MA) shifted the half-wave potential towards the cathodic direction while electron withdrawing group like diethyl cyanophosphonate, NA, shifted it toward anodic direction. Anodic to cathodic peak separation were found to be within 62-88 mV indicating a quasi-reversible system. <p>Hydrolysis of compound 1 resulted in the formation of tert-butyl 1-methoxycarbonyl-1-ferrocenecarboxylic acid, Boc-NH-Fc-COOH, (11) which was coupled with cystamine using the EDC/HOBt protocol to synthesize the cystamine conjugate [BocHN-Fc-CO-CSA]2 (12). This molecule is equipped with an amino group that directly linked to the redox receptor. Compound 12 was fully characterized by spectroscopic methods and by single crystal x-ray diffraction. The cystamine conjugate 12 formed films on gold substrates, which upon deprotection of the amino group, reacted with chemical warfare agents (CWAs) mimics, such as EtSCH2CH2Cl (MA), a simulant for the sulfur mustard HD, and (CN)(EtO)2P(O) (NA), a simulant for the nerve agent Tabun. Their reaction with the surface-bound ferrocene derivative results in the formation of N-substituted products. <p>CV measurements showed anodic shifts of the Fc redox potentials by 50 (±5) mV after exposure to MA, and NA. Measurements by quartz crystal microbalance (QCM) showed an increase in mass upon exposure to MA and NA. Ellipsometry measured a film thickness increase from 6 (±1) Å for the deprotected film to 10 (±4) Å for the film modified with MA and to 7 (±2) Å for the film modified with NA. The surfaces were analyzed by x-ray photoelectron spectroscopy (XPS) and clearly showed the attachment of the cystamine conjugate on the surface and its reaction with CWAs mimics.

Metal hydrides are used as anode material in nickel metal hydride batteries and are of particular interest because of the potential to be a part of energy systems completely involving renewable sources (e.g. solar power, wind power etc.). Preparation and electrochemical characterization of metal hydride electrodes have not previously been performed at the Department of Chemistry – Ångström Laboratory. Two basic techniques that are desired to be used in the characterization are cyclic voltammetry and chronopotentiometry. This thesis work is aimed at preparation and electrochemical characterization of a metal hydride electrode and, as a complement, study the electrode with X-ray diffraction. LaNi3.55Co0.75Mn0.4Al0.3, a standard material for metal hydride electrodes previously studied by Khaldi et al. was chosen, to ensure that electrochemical absorption of hydrogen was possible, and to be able to compare electrochemical results [1-3]. LaNi3.55Co0.75Mn0.4Al0.3 was synthesized with arc melting, with additional annealing at 900˚C for five days, ground in a cemented carbide ball mill and sieved to less than 56 µm. Electrodes were prepared containing 90 wt.-% of LaNi3.55Co0.75Mn0.4Al0.3 powder, 5 wt.-% of polytetrafluoroethylene and 5 wt.-% of carbon black. The hydrogen absorption and desorption capabilities of the electrode were studied electrochemically with cyclic voltammetry and chronopotentiometry, and the structural changes associated with absorption of hydrogen was studied with X-ray diffraction. The capacity increased, probably from activation of the material, during initial cycling up to the maximum capacity of 294 mAh/g, obtained after 9 cycles, followed by a small decrease, probably caused by corrosion and passivation of the material, in capacity of the remaining 11 cycles. Activation of the material causes the charge and the discharge potential to shift to a more positive and a more negative value, respectively. The final values for the charge potential and the discharge potential were -841mV and -945 mV vs. Hg/HgO, respectively, after 16 cycles. Khalid et al. [1-3]reported a maximum capacity of 300 mAh/g, a charge potential of about -960 mV and a discharge potential of about -840 mV after 16 cycles the results obtained in this study are considered to be in good agreement with those reported. X-ray diffraction of the electrodes revealed, as expected, a cell volume change of the charged electrode compared to the discharged electrode. The change in cell volume corresponds to an estimated capacity of 303 mAh/g, which is very close to the, above mentioned, electrochemically obtained maximum capacity of 294 mAh/g.