Thesis (M. Phil.)--University of Hong Kong, 1989.

Thesis (M. Phil.)--University of Hong Kong, 1989.

Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 167-170). Also available in electronic version. Access restricted to campus users.

The introduction of M-Code to the GPS signal structure can redefine the accuracy of the broadcast ephemeris. Existing ephemeris generation systems use dual frequency observations, obtained through the tracking of existing precise codes on the L1 and L2 frequencies. These codes are modulated using Binary Phase Shift Key (BPSK) modulation. The modernization signal M-Code is modulated using Binary Offset Carrier (BOC) modulation. In this study pseudorange observables derived from the tracking of M-Code are proven to have greater accuracy than those from existing precise codes, given equivalent receiver designs and operating conditions. In addition, the error due to specular multipath is derived. These general models of noise and multipath can be applied to any BOC modulated signals, including Galileo and QZSS. When applied to M-Code, the models predict that the maximum multipath error in the pseudorange is reduced in magnitude by 50% compared to the existing precise codes. However the range of multipath delays for which M-Code observables exhibit multipath is approximately twice that associated with existing precise BPSK codes. Existing ephemeris generation processes use the ionosphere free combination and carrier phase smoothing of the pseudorange to form smoothed pseudoranges. The smoothed pseudoranges are then input as measurements to an ephemeris filter. The analytic models of multipath error in the pseudorange and carrier phase observables are applied to predict errors in the smoothed pseudorange. Multipath error, amplified by ionosphere free combination, causes a bias in the smoothed pseudorange when parameterized as a function of multipath delay. There are conditions under which the bias is zero mean, and in those conditions multipath is suppressed. The mechanism for those conditions is solved and discussed, for both BOC and BPSK signal tracking. The solution of carrier phase multipath for BOC modulated signals also admits solutions with a special quality not seen in the BPSK solution. There are multipath delays for which the carrier phase multipath is identically zero regardless of the multipath phase. The zero carrier phase multipath condition may be the most promising feature associated with observables derived from BOC modulated codes. / text

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Sensor arrays have been successfully applied to many engineering fields and the theoretical as well as applied aspects of senor array processing have received intensive research interest. Practically, sensor array systems usually suffer from uncertainties such as unknown gains and phases, mutual coupling, and look direction mismatch. In this thesis, problems of direction finding and beamforming in the presence of array uncertainties are addressed, and new algorithms to tackle these problems are developed. In certain applications, senor arrays are only partly calibrated. Hence, the exact responses of some sensors are unknown, which degrades the performance of traditional direction finding techniques. To tackle this problem, a new method for direction finding with partly calibrated uniform linear arrays (ULAs) is proposed. It generalizes the estimation of signal parameters via rotational invariance techniques (ESPRIT) by modeling the imperfection of the ULA as gain and phase uncertainties. For a fully calibrated array, it reduces to the standard ESPRIT algorithm. In this method, the direction-of-arrivals (DOAs), unknown gains and phases of the uncalibrated sensors can be estimated in closed-form without performing spectral grid search. Moreover, it can be further improved by a refining scheme proposed. Its superiority over existing methods is demonstrated by simulation results. Apart from unknown gains and phases, the mutual coupling caused by interactions among sensors also seriously deteriorate the performance of array processing techniques. In ULAs, the mutual coupling matrix (MCM) can be approximated as a banded symmetric Toeplitz matrix. Using this specific property, a new parameterization of the steering vector is proposed and the corresponding method for joint estimation of DOAs and MCM is derived. Compared with the conventional subarray-based method, the proposed one makes use of the whole array and achieves better performance especially for weak signals. On the other hand, the specific property is further employed to develop a new approach to calibrate the steering vector. By incorporating the calibrated steering vector with a diagonally loaded robust beamformer, a new adaptive beamformer for ULAs with mutual coupling is obtained. It is found that the resultant steering vector estimate considerably improves the robustness of the beamformer against mutual coupling. Another common uncertainty in sensor array systems is the look direction mismatch. Though numerous robust beamformers have been developed accordingly, most of them cannot offer sufficient robustness against large look direction errors. To this end, a new robust beamforming method which can flexibly control the magnitude response in the look direction is proposed. By linearizing the nonconvex constraints in the original problem, the resultant problem is convex and can be solved using second-order cone programming (SOCP). Moreover, to further improve the robustness against array covariance uncertainties, this method is extended by optimizing its worst-case performance. Unlike some conventional methods restricted to specific arrays, the proposed method is applicable to arbitrary array geometries. Simulation results show that the proposed method offers comparable performance to the optimal solution for uniform linear arrays, and also achieves good results under different array specifications and geometries. / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Ca2+ signaling is essential for a wide variety of cellular activities, ranging from short term activities, such as synaptic and muscle contraction, to long term processes, such as proliferation and differentiation. Store-operated Ca2+ entry (SOCE), an important Ca2+ influx pathway in non-excitable cells, well coordinates Ca2+ release from ER and Ca2+ influx through plasma membrane. STIM1 and Orai1, serving as ER Ca2+ sensor and pore forming subunit, respectively, are the two essential components of SOCE machinery. In addition to activate Orai1 channel, studies have shown that STIM1 regulates other plasma membrane Ca2+ channels and senses a variety of cellular stresses to regulate SOCE. Therefore, it is of great interests to investigate the mechanisms and physiological functions of STIM1 and Orai1 mediated SOCE. Here, we performed tandem affinity purification to identify STIM1 associated proteins in Hela cells stably expressing STIM1-His6-3×Flag. Four candidate proteins, including GRP78, HSP70, IQGAP1, and Actin, were identified by mass spectrometry analyses. Surprisingly, IQGAP1 failed to affect the activity of SOCE. Interestingly, GRP78 knockdown only affected the inactivation phase while exerted no effect on the activation phase of SOCE. In addition, GRP78 knockdown markedly induced cell apoptosis and dramatically increased the ER Ca2+ concentration. Moreover, GRP78 was involved in the regulation of SOCE by the ER stress. These data indicate that GRP78 is an important regulator of SOCE to prevent Ca2+ overload in cells. HSP70, however, significantly reduced the activity of SOCE by inhibiting STIM1 translocation to ER-PM junctions. Future studies will explore the mechanism of GRP78 and HSP70 in regulating SOCE by confocal and TIRF imaging. Embryonic stem (ES) cells proliferate unlimitedly and can differentiate into all fetal and adult cell types. This property endows ES cells to be the promising candidates in the therapy of neurodegenerative diseases. Thus, it is important to identify novel signaling molecules or events that could play a role in the neural commitment of ES cells. Accumulated evidences have documented the role of STIM1 and Orai1 mediated SOCE in neuronal activities. Yet, the role of SOCE in early neural development remains to be determined. Here we examined the role of STIM1 and Orai1 during neural differentiation of mouse ES cells. Both of STIM1 and Orai1 were expressed and functionally active in ES cells, and expressions of STIM1 and Orai1 were dynamically regulated during neural differentiation of mouse ES cells. STIM1 knockdown inhibited the differentiation of mouse ES cells into neural progenitors, neurons, and astrocytes. In addition, STIM1 knockdown caused severe cell death and markedly suppressed the proliferation of neural progenitors. Surprisingly, Orai1 knockdown had little effect on neural differentiation of mouse ES cells, but the neurons derived from Orai1 knockdown ES cells, like those from STIM1 knockdown cells, had defective SOCE. Taken together, our data indicate that STIM1 is required for neural differentiation of mouse ES cells independent of Orai1-mediated SOCE. / published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

APPL BAR-PH heterodimer and APPL2 BAR-PH homodimer The APPL (Adaptor protein containing PH domain, PTB domain and Leucine zipper) family are adaptor proteins with only two isoforms, APPL1 and APPL2. They bind to early endosomes with a small GTPase, Rab5, and mediate the interactions between various receptors and downstream signaling components, thus functioning in many signaling pathways evoked by adiponectin, insulin, FSH, EGF, and so on. However, evidences have shown APPL1 and APPL2 should perform some opposite functions, which cannot be simply explained by the functional differences attributed to their PTB domains. We hypothesize that the heterodimerization of APPL1 and APPL2’s BAR domains may account for their opposing functions. The crystal structure of APPL BAR-PH heterodimer was solved to resolution 2.8 Å. Its overall structure exhibits crescent shape with a larger curvature radius of 76 Å, compared to 55 Å of the APPL1 BAR-PH homodimer. And the crystal structure APPL2 BAR-PH homodimer was solve to resolution 3.3 Å. The overall structure of APPL2 BAR-PH homodimer is very similar to that of APPL BAR-PH heterodimer, but shows greater difference in curvature to the APPL1 BAR-PH homodimer structure. The concave side of APPL BAR-PH heterodimer and APPL2 BAR-PH homodimer all possess less positive charge than the APPL1 BAR-PH homodimer. Structural analysis reveals that leucine patches at the dimer interface may account for the formation of dimeric curve with certain curvature. Consequently, APPL2 BAR is able to enforce the curvature reduction to APPL1 BAR upon heterodimerization. In conclusion, the alterations of curvature and electrostasis are responsible for the modulation of endosome binding specificity and can elucidate the opposite roles of APPL1 and APPL2. LanCL2 LanCL2 is a member of Lanthionine synthetase component C-like family. In human, LanCL2 binds to lanthionine derivatives and glutathione, participating in keeping intracellular reducing state. By binding to absiscic acid (ABA), LanCL2 is indispensible for the ABA-stimulated adipogenesis, insulin release, glucose homeostasis, and inflammatory response. It is also implicated in anticancer drug resistance. All these functions underscore the importance of LanCL2 in the diseases like diabetes, inflammation, and cancer. The crystal structure of LanCL2 was solved to resolution 1.8 Å. The overall structure displays canonical double-layer α-barrel. The major differences from LanCL1 lay in the loops on the barrel top, which are implicated in various substrate bindings. A zinc-coordinating pocket was found among the loops, with conserved amino acid residues of distinct conformation. The electrostatic surface shows remarkable differences compared to that of LanCL1, suggesting that it may contribute to distinct substrate binding profile. Future implications APPL proteins and LanCL proteins are all involved in the regulation of metabolism, such as glucose uptake, fatty acid oxidation, and insulin secretion, and play roles in diseases like obesity and type 2 diabete. Structural and functional studies of these proteins can provide insights into the molecular mechanisms and clues for related therapeutic approaches. / published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Not available / text