No description available.

Tie2 is a receptor tyrosine kinase (RTK) involved in numerous aspects of both normal and pathological angiogenesis. Proper functioning of this receptor is essential for normal development of the vasculature in the embryo as well as vessel maintenance and at sites of active angiogenesis in the adult. A growing list of pathological states has been attributed to a disruption of the angiogenic ‘balance’ including psoriasis, arthritis, atherosclerosis and diabetic retinopathy. Elucidating the molecular mechanisms behind this important biological process will provide insight into the various molecules involved as well as provide potential targets for novel angiogenic therapies. In an attempt to better understand the signaling pathways downstream of the Tie2 receptor we have studied tyrosine residues on the receptor believed to play an important role in Tie2 function. Of these, we have identified Y1111 as a negative regulatory site on Tie2. Mutation of this site affects receptor phosphorylation and kinase activity. Furthermore, protease digestion studies indicate that mutation of Y1111 may alter receptor conformation and potentially relieve negative inhibition imparted by the C-tail of Tie2. As well, we examined potential Tie2 downstream binding partners, specifically the novel Grb7 family of proteins. This work describes for the first time tyrosine phosphorylation of Grb14, an adaptor molecule previously shown to bind Tie2 in vitro. Moreover, our data suggests a role for this adaptor in Tie2 signal transduction involving two tyrosine residues in the receptor C-terminal tail; Y1100 and Y1106. These studies provide important insight into both signal transduction downstream of Tie2 as well as help us understand some of the molecular mechanisms behind the intrinsic ability of this RTK to regulate its own activity.

The observed physiological dynamics of an infant receiving intensive care contain a great deal of information about factors which cannot be examined directly, including the state of health of the infant and the operation of the monitoring equipment. This type of data tends to contain both common, recognisable patterns (e.g. as caused by certain clinical operations or artifacts) and some which are rare and harder to interpret. The problem of identifying the presence of these patterns using prior knowledge is clinically significant, and one which is naturally described in terms of statistical machine learning. In this thesis I develop probabilistic dynamical models which are capable of making useful inferences from neonatal intensive care unit monitoring data. The Factorial Switching Kalman Filter (FSKF) in particular is adopted as a suitable framework for monitoring the condition of an infant. The main contributions are as follows: (1) the application of the FSKF for inferring common factors in physiological monitoring data, which includes finding parameterisations of linear dynamical models to represent common physiological and artifactual conditions, and adapting parameter estimation and inference techniques for the purpose; (2) the formulation of a model for novel physiological dynamics, used to infer the times in which something is happening which is not described by any of the known patterns. EM updates are derived for the latter model in order to estimate parameters. Experimental results are given which show the developed methods to be effective on genuine monitoring data.

No description available.

To exit a non-proliferative state and enter cell division, metazoan cells require external signals to facilitate activation and metabolic reprogramming. As cell growth is required before cell division, cells redirect their metabolism for de novo synthesis of cell building blocks, including phospholipids for cell membrane construction. How cells coordinate initial signaling events with metabolism is unknown. Lineage-specific factors transmit activating signals via cell surface receptor-ligand interactions. Among these are PI3K/AKT, MAPK/ERK, and JAK/STAT, all of which have been described to contribute to metabolic regulation. In particular, the signal transducer and activator of transcription (STAT) is a transcription factor with broad roles in cell cycle progression and glucose metabolism. Previous data from our laboratory found that one STAT family member, STAT3, was one of the primary signaling pathways activated when transitioning out of a resting state. Inhibition of STAT3 was found to suppress the initiation of cell growth and citrate levels, a main intermediate for fatty acid synthesis, suggesting a connection to cell metabolism. This thesis investigates the role of STAT3 in the regulation of metabolism in cells transitioning from a resting state to a cell growth state. The first chapter of this thesis provides relevant background information on the metabolic and signaling pathways involved in a resting and cell growth state. It also provides data that supports an important role for STAT3 during initial cell growth. The second chapter demonstrates the importance of STAT3 in multiple cell types using a small molecule inhibitor of STAT3, STAT3 knockdown, and knockout experiments. I also establish a potential link between STAT3 and the metabolic enzyme citrate synthase (CS) for the synthesis of citrate. In the third chapter I show that STAT3 transcriptionally regulates CS through two binding sites, CS1 and CS2. Finally, I determine that CS is essential for initial cell growth and that exogenous citrate can rescue the loss in cell growth and proliferation observed in the CS and STAT3 knockdown cells. Together, these findings describe a novel mechanism for initial cell growth whereby signaling and metabolic events are tightly linked to regulate the transition from a resting state to a state of initial cell growth. These results may uncover new strategies to block the initiation of proliferation in human pathological conditions including tumor recurrence and autoimmunity. / Graduate

A research report submitted to the Faculty of Engineering and the Built Environment, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science in Engineering. Johannesburg, 2016 / Multiple-Input Multiple-Output (MIMO) radar is a more general form of phased array radar, where each antenna in the array transmits linearly independent or mutually orthogonal signals. Sustained growth in computational power as well as the decline in the cost of integrated radio frequency (RF) components has made MIMO more viable than in the past. The potential emergence of practical MIMO radar has prompted an investigation into the detectability of MIMO radar signals using existing conventional Electronic warfare Support (ES) receivers such as the Crystal Video Receiver (CVR) and a specific type of superheterodyne receiver (superhet) known as the Zero IF Receiver (ZIFR). Literature on the detectability of MIMO radar signals is extremely scarce and this investigation aims to offer insights into the detectability of MIMO radar signals by means of computer simulations. The fundamental theory necessary for this research includes phased array radar theory, MIMO array radar theory and ES receiver signal detection theory. The detection of MIMO radar signals is compared to a reference phased array case to provide relative context. This investigation focusses on co-located Uniform Linear Arrays (ULA) based radar systems. The result of interest is the relative Signal-to-Noise Ratio (SNR) at which each type of radar can be detected by the ES receiver. Therefore, a lossless transmission, without loss of generality, is assumed. Constraints such as the equal transmit power over all antenna elements in the arrays, are used for a fair comparison. Many different array simulation setups are simulated. These setups are achieved by varying the number of elements in the array and the inter-element spacing. The phased array radar transmitted complex linear chirp signals, and the MIMO radar transmitted Hadamard sequences, interpolated using a Constant Envelope Linear-Route-of-Unity (CE-LRU) technique. The CVR and ZIFR detection thresholds were determined for a Probability of False Alarm (PFA) of 10-4. For all of the setups, the phased array radar was found to be more detectable than the MIMO radar at values of Probability of Detection (PD) below 0.6. The in phase coherent combination of phased array radar signals in its main beam resulted in a signal gain caused by the constructive addition of the signals. This gain thus increases with the number of antenna elements. In contrast, the MIMO signals also add coherently, but the instantaneous phase for each signal is a function of the transmitted signal as well as the direction of propagation relative to the array face. The set of orthogonal signals thus add constructively and destructively, resulting in the average signal power remaining approximately constant despite the number of antenna elements increasing. The difference in detectability of the phased array radar over MIMO radar therefore increases as the number of antenna elements is increased, due to the fact that each element is constrained to transmit a fixed power. Comparing the performance of the ZIFR and CVR, the ZIFR outperforms the CVR. This is due to the fact that the ZIFR implements a quadrature ES receiver, and was able to detect both types of radar signals at a lower SNR than the CVR. However, both ES receivers struggle to detect MIMO radar signals in comparison to detecting phased array radar signals and this performance margin widens as the number of transmitting elements is increased. This result suggests that research into dedicated techniques for the detection of MIMO radar signals using ES receivers may be necessary should the need arise to detect MIMO radar signals in future. This is the first quantitative analysis of the detectability of MIMO radar signals using conventional ES receivers that the author is aware of. / MT2017

No description available.

This thesis describes and discusses design and implementation of digital filters inembedded systems. Digital filters provide great flexibility where an interchangeablefilter is needed and real valued components are limited. Common sampling problemssuch as aliasing and reconstruction are discussed and solved using analog filters.A circuitry is constructed to interact with the embedded system according to itsspecifications. Digital filter theory is reviewed and applied in both IIR (Infinite ImpulseResponse) and FIR (Finite Impulse Response) filters. Design methods used arewindow method for the FIR filter and zero-pole placement for the IIR filter. Thefilters are implemented in c code on an embedded system named UC3-A3 AVR-boardfrom Atmel. The complete system is effectively used to filter a music piece fromunwanted interference and noise with real-time computing.

by Leung Pak Ming. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1980. / Bibliography: leaves 199-206.

by Suen Yick-keung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Bibliography: leaves 163-170. / Abstract --- p.i / Acknowledgements --- p.v / Abbreviations --- p.vi / Objective of the study --- p.vii / Contents --- p.viii / Chapter Section 1 --- Introduction / Chapter 1. --- Roles of macrophges in immune system --- p.3 / Chapter 2. --- Special features of macrophages --- p.6 / Chapter 3. --- Transmembrane signalling in mammalian cells --- p.9 / Chapter 4. --- Transmembrane signalling in macrophages --- p.32 / Chapter 5. --- Choice of the macrophages for the study --- p.40 / Chapter Section 2 --- Materials and Methods / Materials / Chapter 1. --- Animals --- p.44 / Chapter 2. --- Chemicals --- p.44 / Chapter 3. --- Reagents --- p.45 / Methods / Chapter 1. --- pell culture --- p.47 / Chapter 2. --- 3H-thymidine incorporation --- p.48 / Chapter 3. --- Cytosolic free calcium determination --- p.48 / Chapter 4. --- Intracellular pH mesurement --- p.50 / Chapter 5. --- Determination of membrane potential --- p.50 / Chapter 6. --- Determination of phagocytic activity --- p.51 / Chapter 7. --- Cell adhesion assay --- p.52 / Chapter 8. --- Statistical analysis --- p.52 / Chapter Section 3 --- Results / Chapter 1. --- Effect of membrane potential on cell proliferation in PU5-1.8 cells and bone marrow-derived macrophages / Evidence for induction of cell proliferation mediated by membrane depolarization in PU5-1.8 cells --- p.53 / Evidence of an array of agonists on cell proliferation and membrane potential in PU5-1.8 cells --- p.57 / Interrelationship between membrane potential and FCS-mediated proliferation in PU5-1.8 cells --- p.61 / Cytosolic alkalinization induces membrane depolarization in PU5-1.8 cells --- p.64 / Suppression of membrane depolarization and cell proliferation by protein kinase C activation --- p.66 / Effect of membrane potentials on cell proliferation in bone marrow-derived macrophages --- p.68 / Chapter 2. --- Intracellular signals for the regulation of phagocytosis in PU5-1.8 cells / Phagocytosis of unopsonized yeast in PU5-1.8 cells --- p.71 / Effect of membrane potential on phagocytosis in PU5-1.8 cells --- p.73 / Changes in phagocytic activities in PU5-1.8 cells by activation of protein kinase C --- p.82 / Effects of protein kinase C on membrane potential- induced enhancement of phagocytosis in PU5-1.8 cells --- p.84 / Phagocytosis in PU5-1.8 cells requires assembly of microtubule --- p.90 / Effects of intracellular calcium and cAMP on phagocytosis in PU5-1.8 cells --- p.93 / Acidic intracellular pH enhances phagocytosis in PU5-1.8 cells --- p.98 / Chapter 3. --- Effects of various agonists on phagocytosis of yeast in PU5-1.8 cells / Effect of chemotactic peptide N-formyl- methionyl-leucyl-phenylalanine (FMLP) on phagocytosis in PU5-1.8 cells --- p.100 / Effects of lipopolysaccharide (LPS) on phagocytosis in PU5-1.8 cells --- p.105 / Effects of concanavalin A (Con A) on phagocytosis in PU5-1.8 cells --- p.109 / Effect of complement components on phagocytosis in PU5-1.8 cells --- p.113 / Chapter 4. --- Signal pathways for the regulation of cell adhesion on plastic surface in PU5-1.8 cells / Adhesion of PU5-1.8 cells on plastic surface --- p.119 / Effects of membrane potential on cell adhesion on plastic surface in PU5-1.8 cells --- p.121 / Effects of activation of protein kinase C on cell adhesion on plastic surface in PU5-1.8 cells --- p.125 / Effects of intracellular calcium and cAMP on adhesion on plastic surface in PU5-1.8 cells --- p.129 / In vivo cell adhesion of PU5-1.8 cells in Balb/c mice --- p.133 / Chapter 5. --- Effects of various agonists on the cell adhesion on plastic surface in PU5-1.8 cells / Dose dependent of various agonists against the cell adhesion ability of PU5-1.8 cells --- p.141 / Chapter 6. --- Cell adhesion to plastic surface in bone marrow-derived macrophages / Membrane potentials control the adhesiveness of bone marrow-derived macrophages (BMDM0) to plastic surface --- p.143 / Effects of phorbol ester PMA on cell adhesion to plastic surface in bone marrow-derived macrophages --- p.143 / "Effects of cAMP, [Ca2+ ]i and microtubule assembly on cell adhesion to plastic surfacein bone marrow-derived macrophages" --- p.146 / Chapter Section 4 --- Discussion / Chapter 1. --- Effects of membrane potential on cell proliferation in PU5-1.8 cells and bone marrow-derived macrophages --- p.148 / Chapter 2. --- Intracellular signals for the regulation of phagocytosis in PU5-1.8 cells --- p.151 / Chapter 3. --- Signal pathways for the regulation of cell adhesion on plastic surface in PU5-1.8 cells and bone marrow-derived macrophages --- p.158 / Chapter 4. --- General discussion --- p.161 / Chapter Section 5. --- Bibliography / References --- p.163