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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Comparison of the mechanism of transmembrane signaling in bacterial chemoreceptors and sensor kinases

Ward, Scott Michael 30 October 2006 (has links)
Membrane-bound receptors transmit information from the cell exterior to the cell interior. Bacterial receptors capable of transmitting this information include sensor kinases, which control gene expression via response regulators, and methyl-accepting chemotaxis proteins (MCPs), which control rotation of the flagellar motor. These receptors, which have a similar general architecture and function, are predicted to share similar mechanisms of transmembrane signaling. The majority of such work has been conducted on MCPs. Our goal is to extend this work to the closely related sensor kinases by creating functional hybrid transducers. I show that a chimeric protein (Nart) that joins the periplasmic, ligandbinding domain of the sensor kinase NarX (nitrate/nitrite sensor) to the cytoplasmic signaling domain of the chemoreceptor Tar is capable of modulating flagellar rotation in response to both nitrate and nitrite. Consistent with the properties of NarX, our Nart elicits a stronger response to nitrate than to nitrite. Introduction of mutations into a highly conserved periplasmic region affects Nart signaling in a fashion that is consistent with the effects seen in NarX. I also present the first example of a substitution in a presumed ligand-binding domain that confers a reverse-signal phenotype for both nitrate and nitrite in Nart. These results support the hypothesis that the key aspects of transmembrane signaling are closely similar in homodimeric bacterial chemoreceptors and sensor kinases.
2

Signaling Control and Timetable Planning for MRT Systems

Sun, Kuo-Hua 10 July 2006 (has links)
Automatic Train Control(ATC) of Signaling System for a Metro Systems comprise Automatic Train Supervision(ATS), Automatic Train Protection(ATP) and Automatic Train Operation(ATO). Based on theAutomatic Train Control(ATC) of Signaling System for a Metro Systems comprise Automatic Train Supervision(ATS), Automatic Train Protection(ATP) and Automatic Train Operation(ATO). Based on the Signaling Control System of Kaohsiung Mass Rapid Transit System(KMRT),the relationship of ATO propulsion power consumption and the run time between stations of train sets under the constraint of Automatic Train Protection(ATP) is investigated. By integrating the ATC function for the planning of timetable, the optimal timetable can be established. ATO solves the speed command for train sets operation by considering the propulsion system, track alignment and the operating timetable to achieve the efficiency of energy consumption by applying the operation modes of Cruising and Coasting to derive the speed profiles of train sets. Because of the correlationship of ATP, ATO and Operation Timetable of train sets, the ATP system is investigated first to ensure the safety of system operation. Based on the constraint of ATP, the energy conservation of train sets with ATO system is simulated. The optimal timetable is then derived by minimizing the objective function, which consists of the costs of train sets, driver¡¦s manpower and the simulated energy consumption. The Genetic Algorithm (GA) is applied to solve the optimal timetable by representing the Run Time Reserve and Loading Factor of train sets as the chromosomes. With the mutation of GA method, the global optimal solution can be obtained without falling into the local optimum. It is concluded that the optimal operation timetable solved by the proposed GA method can enhance the system performance of KMRT systems by reducing the operation cost of train sets.
3

A reproduceable noise generator

Watts, Donald George January 1958 (has links)
This thesis describes the design of a device for generating a reproduceable noise signals. The noise signal is generated by adding three periodic waveforms having non-multiple periods. Pulse techniques are used in the generation of the member functions so that the output may be reproduced exactly. Theoretical and experimental determinations of the amplitude probability distribution and of the autocorrelation function of the signal were made. On the basis of tests and observations made, it is concluded that the signal generated may be considered a noise signal having a near-Gaussian amplitude probability distribution, very little correlation for time-shifts greater than 30 seconds, and a bandwidth of about 60 cps. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate
4

Is open book testing viable within a military occupational producing school 25 uniform, Signal Support Systems Specialist, at Fort Gordon, GA.

Cierpial, Edwin C. January 2009 (has links) (PDF)
Thesis PlanB (M.S.)--University of Wisconsin--Stout, 2009. / Includes bibliographical references.
5

The Role of Norrie Disease Pseudoglioma (Ndp) in Cerebellar Development/Tumorigenesis and Its Relationship with the Sonic Hedgehog Pathway

Tokarew, Nicholas January 2017 (has links)
Medulloblastoma (MB), a cancer of the cerebellum, is the most common solid tumor affecting children. In the cerebellum, Sonic Hedgehog (Shh) drives the proliferative expansion of granule neuron progenitors (GNP). These cells are located in the external granule layer (EGL) and are the cells of origin of Shh-MB. We recently identified Norrie Disease Pseudoglioma (Ndp) as a novel downstream target of Hh signaling in the developing retina. Ndp encodes an X-linked cysteine-rich secreted protein called Norrin, which is best known for its role in angiogenesis and blood brain barrier (BBB) maintenance in the developing retina and cerebellum, respectively. Norrin mediates this effect by binding to its receptor Frizzled4 (Fzd4) and co-receptors LRP5/6 and Tpsan12 to activate the canonical, β-catenin-dependent Wnt signaling pathway in endothelial cells (ECs). We detected the expression of Ndp and all required receptors in mouse GNPs and MB samples. To investigate a potential role for Ndp in Hh-driven MB, we genetically and pharmacologically inactivated Ndp/Fzd4 signaling in Ptch+/- mice (a mouse model for human Gorlin syndrome), which dramatically increased the incidence and reduced the latency of MB. This accelerated rate of tumorigenesis was caused by an increase in the number of preneoplastic lesions (PNLs), the precursor lesions to MB, and a faster conversion of these lesions to MB. We showed that Ndp mediates this increase in tumorigenesis by signaling through endothelial cell receptor Fzd4 to alter the GNP stroma, which is characterised by 5 major alterations: 1) activated angiogenic program, 2) open BBB, 3) aberrant deposition of extracellular matrix, 4) aberrant lymphocyte recruitment and 5) reduction in meningeal lymphatic vasculature. We propose that these stromal alterations are associated with a pro-tumor microenvironment that promotes DNA damage in GNPs and leads to enhanced lesion formation and progression towards MB. This research highlights 1) an unanticipated role for Ndp/Fzd4 signaling in Shh-MB initiation and progression, 2) a role for stromal signaling in the regulation of MB development and 3) a previously undescribed role for Ndp signaling in maintaining meningeal cerebellum lymphatic vessels.
6

Perlecan regulation of sonic hedgehog signaling: from drosophila to humans

Hernandez, Ana Maria 15 May 2009 (has links)
Prostate cancer is the second leading cause of death from cancer in men in the United States. Most men will die of the advanced, metastatic form of the disease. Thus, treatment strategies targeting the metastatic form of the disease are especially needed. Emerging research on metastatic cancer highlights the importance of the microenvironment in cancer progression and metastasis, with an emphasis on deregulated developmental signaling in cancer progression. Research in model organisms has shown that developmental signaling pathways are regulated by various components of the extracellular matrix, including heparan sulfate proteoglycans. In the model system Drosophila, the heparan sulfate proteoglycan Trol is needed for Hhdependent proliferation in quiescent neural stem cells. In collaboration with others, I have shown that the human homolog of Trol, PERLECAN, regulates SONIC HEDGEHOG-dependent proliferation in advanced prostate cancer by two different mechanisms. This makes PERLECAN a potential drug target and biomarker for prostate cancer screening and treatment. My results also validate the discoveries made in Drosophila in the context of human disease. With this validation, I propose and describe the Drosophila Ejaculatory Bulb (EjB) as model for prostate cancer and prostate aging.
7

none

Lee, Meng-Pin 24 May 2002 (has links)
none
8

Role of the adaptor protein, beta-arrestin1, in the Notch signaling pathway

Witty, Marie-France 05 1900 (has links)
The Notch receptor is part of a highly conserved signaling pathway shared in Drosophila, C. elegans and mammals. Extensive studies of Notch signaling have revealed its participation in the development of diverse organ systems including brain, blood cells, blood vessels, gut, and skin. Many genetic modifiers of the Notch signaling pathway have been identified, including some which act at the membrane and others in the nucleus. One such member is Deltex, an E3 ubiquitin ligase, which was originally identified as a modifier of Notch in a Drosophila genetic screen. In early lymphoid development, Deltex has been demonstrated functionally to antagonize Notch signaling but the precise molecular mechanism for this functional antagonism between Notch and Deltex is not understood. However, in Drosophila, recent data supports the formation of a trimeric complex between Deltex, Kurtz and Notch that promotes Notch ubiquitin-mediated proteosomal degradation. Beta-arrestin1 is one of the closest mammalian homologues of Kurtz and functions as an adaptor protein in a variety of cellular processes such as endocytosis, ubiquitination and nuclear shuttling. We hypothesize that a similar interaction occurs in mammalian cells between Notch, beta-arrestin1 and Deltex to negatively modulate the Notch signaling pathway. Our data reveal a physical interaction between beta-arrestin1 and the Notch receptor. We could not, however, detect an interaction between Deltex and beta-arrestin1 by co-immunoprecipitation. We also demonstrate that Notch and beta-arrestin1 physically associate with both a membrane-bound form of activated Notch, as well as the intracellular form of Notch after membrane cleavage. Using RNA interference, as well as overexpression of beta-arrestin1, we demonstrate that beta-arrestin1 negatively regulates a Notch/CSL dependant reporter assay. We also show that the presence of Deltex enhances the negative modulation of the Notch signaling pathway mediated by beta-arrestin1. Therefore, we reveal a new Notch interacting protein and a novel role for beta-arrestin1 in the Notch signaling pathway.
9

Investigation of the phosphatidylinositol 3-kinase pathway in B cells

Ma, Kewei 05 1900 (has links)
There is hardly a cellular process that is not regulated in some way by phosphoinositides, which makes biochemical and physiological studies of these lipids extremely important. PI 3-kinases are key regulators of phosphoinositide metabolism and have been shown to affect a large variety of cellular responses. The key products of PI 3-kinases that have functional activity in higher eukaryotic cells are PI(3,4,5)P₃ and PI(3,4)P₂. PI(3,4,5)P₃ is universally accepted as one of the most important second messengers in signal transduction. However, our knowledge of the functions of PI(3,4)P₂ as a lipid second messenger is much less precise. In this dissertation, work was undertaken to elucidate the regulation of PI(3,4,5)P₃ and PI(3,4)P₂ production and downstream signaling in B cells. Cells with membrane targeted exogenous SHIP were utilized to manipulate phosphoinositide levels. The relationship of PI(3,4,5)P₃ and PI(3,4)P₂ levels to downstream PKB phosphorylation and activation was studied. PI(3,4,5)P₃ and PI(3,4)P₂ levels were found to closely correlate with PKB phosphorylation levels at Thr308 and Ser473, respectively. In addition, PI(3,4)P₂ levels determine the PKB activity in the cytosol; while PI(3,4,5)P₃ levels determine PKB activity at the plasma membrane. Different doses and different forms of B cell receptor (BCR) agonists were used for stimulation. PI 3-kinase activation was studied carefully following stimulation with low doses of anti-BCR antibody and F(ab')₂ fragments. Low concentrations of F(ab')₂ fragments produced higher levels of PI(3,4,5)P₃ than did a high concentration of F(ab')₂ fragments. Downstream PKB signaling was studied in these models. Similar conclusions were drawn from both SHIP over-expressing BJAB cells and dose-dependent BCR stimulations. We speculated that phosphoinositides’ regulation of the kinetics of PKB phosphorylation at Ser473 and Thr308 might be mediated by additional proteins. Investigation of plasma membrane-associated PKB showed that it formed a protein complex of around 400KD, which we attempted to characterize further with respect to PKB phosphorylation and association with lipids. In conclusion, phosphoinositide production is intricately regulated in vivo to control downstream signaling. The levels of PI(3,4)P₂ and PI(3,4,5)P₃ have precise and profound effects on PKB and other molecules such as TAPP and Bam32. This study has contributed new insight into the PI 3-kinase signaling pathway from the aspect of phosphoinositide lipid function.
10

On interaction and efficiency : prematch investments with hidden characteristics

Bidner, Christopher 05 1900 (has links)
I develop three models that are designed to aid in the analysis of environments in which agents i) benefit from interacting with others, and ii) optimally choose their characteristics mindful of the fact that such choices will influence the quality of interaction that they can expect. Of central interest is the ways in which a concern for interaction affects the efficiency with which agents choose their characteristics. The first two models contrast with previous work in that each agents' relevant characteristics are both unobserved and endogenously determined. The first model provides an explanation for credentialism in the labour market, and demonstrates how a concern for interaction can lead to over-investment in the relevant characteristic. The second model is motivated by human capital development in the presence of peer effects, and demonstrates how a concern for interaction can exacerbate an inherent under-investment problem. The third model retains the feature of unobserved characteristics, and contrasts with previous work by embedding frictions in the process by which agents compete for partners. The model is set in a labour market and demonstrates that outcomes of interest (equilibrium matching patterns, income, inequality and welfare) are generally not monotonic in the level of frictions.

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