Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

The choice of an efficient and effective production control mechanism (PCM)along with the appropriate buffer allocation pattern is very important for anyproduction engineer/decision maker when designing a production line in order toattain the required system performance. This project work aims to give an insightwith different PCMs, different buffer allocation patterns and arrangement ofworkers of different capability to help the production engineers/decision makersto select the right mechanism and pattern. This study has been performed withmulti-objective simulation optimisation (MOSO) tool. The result from manyexperiments have shown that the ascending buffer allocation pattern stands outas the prominent choice when the goal was to attain maximum throughput (TP)and simultaneously keeping minimum cycle time (CT) and work in process (WIP).The PCMs and workers imbalance patterns performance is different in differentregions of the Pareto-optimal CT-TP data plots obtained from MOSO so theirselection is depending on the interest of the desired level of throughput togetherwith the limit of cycle time.

As projects play a key role in implementing strategy, organizations of all kinds implement projects. Further, as the importance of the projects grow, management of the same also becomes crucial in terms of monitoring and controlling. However, as non-project based organizations lack distinctive project management approach, their project are controlled and monitored by the inherent management control system. While, several studies have highlighted that different organization control mechanisms are exercised at varying degree, there is a dearth of study done in project context. However, one recent study done by Nieminen and Lehtonen (2008) in a program context focusing only in organizational change revealed three organizational control mechanisms and 23 control tools being exercised as varying degree in four case programs. As several studies in the project management context highlight the need to tailor the approach according to the project types, this study focuses on understanding how the control mechanisms vary across different types of projects executed by non-project based organizations employing the project classification developed by Turner and Cochrane (1993). A qualitative study employing semi-structured interview was conducted with eight project managers of respective projects implemented by seven companies from China and Nepal. Based on the feedback given by the concerned project managers, the study revealed distinct organizational control mechanisms dominated distinct project types in rolling out a successful project, even though there was presence of all types of organizational control mechanisms in the sampled projects. Further, the application of the control tools within the control mechanism varied even across projects of similar type.

Sphingolipids are a complex family of molecules that participate in many aspects of cell structure and function, including an essential cellular process known as autophagy. Autophagy is a degradation and recycling pathway whereby intracellular components are sequestered into double-membrane vesicles, known as autophagosomes, for subsequent fusion with lysosomes and degradation. Autophagy takes part in cell survival, host immune defense against pathogens, and other biological processes, but is also sometimes lethal. Ceramide, sphingosine 1-phosphate, and more recently dihydroceramide have been shown to induce autophagy, which opens an interesting new field of cell regulation by sphingolipids. This dissertation describes two new cases in which sphingolipids participate in the induction of autophagy: a) RAW264.7 cells treated with Kdo2-Lipid A, a lipopolysaccharide sub-structure with endotoxin activity equal to LPS; and b) MCF7 cells treated with fenretinde, a chemotherapeutic agent which has shown success in clinical trials. It also analyzes the structural properties of fenretinide that contribute to its ability to modulate sphingolipid metabolism through inhibition of dihydroceramide desaturase, thereby elevating dihydroceramide and induction of autophagy. Autophagy was monitored by following the redistribution of GFP-LC3 into discrete punctate vesicles in response to the agents and by Western blotting; in parallel, the sphingolipid composition of the cells was monitored by liquid chromatography, electrospray ionization tandem mass spectrometry. These analyses revealed that Kdo2-Lipid A and fenretinide induce profound changes in sphingolipid metabolism in RAW264.7 and MCF7 cells, respectively, and that one of the purposes for increased de novo biosynthesis is to enable the production of autophagosomes, as the autophagic response was inhibited by myriocin. These studies have uncovered a direct link between sphingolipid metabolism and autophagy, which could pave the way for new therapeutic interventions for the treatment of pathogenic infection and be clinically useful in enhancing the efficacy of current cancer treatment strategies.

<p>The choice of an efficient and effective production control mechanism (PCM)along with the appropriate buffer allocation pattern is very important for anyproduction engineer/decision maker when designing a production line in order toattain the required system performance. This project work aims to give an insightwith different PCMs, different buffer allocation patterns and arrangement ofworkers of different capability to help the production engineers/decision makersto select the right mechanism and pattern. This study has been performed withmulti-objective simulation optimisation (MOSO) tool. The result from manyexperiments have shown that the ascending buffer allocation pattern stands outas the prominent choice when the goal was to attain maximum throughput (TP)and simultaneously keeping minimum cycle time (CT) and work in process (WIP).The PCMs and workers imbalance patterns performance is different in differentregions of the Pareto-optimal CT-TP data plots obtained from MOSO so theirselection is depending on the interest of the desired level of throughput togetherwith the limit of cycle time.</p>

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Medical Sciences - Medical Genetics. Title from pdf file main screen (viewed on March 19, 2010). Includes bibliographical references.

Not available / text

The goal of the current research was to examine the expression, signaling and function of the membrane progestin receptors (mPRs) in the ovarian follicular cells of the Atlantic croaker (Micropogonias undulatus) and in human breast cancer cells. Multiple studies have examined the role of mPRs in the germ cells of several vertebrate classes, yet few studies have examined the role of the mPRs in the somatic cells of reproductive tissues. Therefore this research examines the mechanism of mPR action and its function in somatic cells of female reproductive tissues. Results from studies on the expression, localization and signaling of the mPR[alpha] in co-cultures of granulosa and theca cells from the croaker suggest that the mPR[alpha] is localized to the plasma membrane of both cell types and that the mPR[alpha] is associated with and signals via pertussis toxin-sensitive inhibitory G proteins to decrease intracellular cAMP and activate ERK. In addition, exposure of follicular co-cultures to progestins that activate the mPR[alpha] results in a decrease in serum starvation-induced cell death which is not replicated by progestins which activate the nuclear progestin receptor (nPR), indicating mPR mediation. Similar studies in two immortalized human breast cancer cell lines, MDA-MB-468 and SKBR3, suggest that the mPR[alpha] is also present in the membranes of these cells and signals in human breast cancer cell lines via activation of a pertussis toxin-sensitive G protein to significantly decrease in intracellular cAMP and activate ERK. Progesterone exposure also decreased serum starvation-induced cell death in SKBR3 cells which are nPR positive and in MDA-MB-468 cells which are nPR negative. Synthetic progestins which activate the nPR but not the mPR were ineffective in inhibiting death in either cell type suggesting that the mPR is the mediator of this progestin action. mPR[alpha], mPR[beta] and mPR[gamma] expression analysis of paired normal and malignant breast tissue biopsies from thirteen women revealed that at least one mPR isoform was upregulated in the malignant tissue of 70% of the women. In addition the expression of mPR[gamma] was positively correlated with the expression of the nPR and CK19, a breast epithelial cell marker. / text

This thesis reports that checkpoint adaptation occurs in human brain cancer cells. M059K cells, after treatment with camptothecin (CPT), recruited γ-histone H2AX, phosphorylated Chk1 and arrested in the G2 phase. Strikingly, cells escaped the checkpoint, became rounded and entered mitosis as measured by phospho-histone H3 signals. Lamin A/C immunofluorescence microscopy revealed that 48% of the cells that survived checkpoint adaptation contained micronuclei. These data suggest that brain cancer cells undergo checkpoint adaptation and may have an altered genome. This thesis also explored if phosphatases participate in checkpoint adaptation. Human colon cancer cells were treated with CPT and the PP2A inhibitor cantharidin. Following treatment the cells became rounded and 65% were positive for phospho-histone H3 signals indicating that cantharidin caused cells to be in mitosis following CPT treatment. These data suggest that PP2A might have a role in checkpoint adaptation, or participate in a pathway that bypasses checkpoint adaptation. / xi, 114 leaves : ill. (some col.) ; 29 cm

Bibliography: p. 69-81. / 81, [52] p., [16] leaves of plates : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis demonstrates that string (a homologue of the mitotic initiator cdc 25 from Schizosaccharomyces pombe) is a downstream target of the patterning genes, making a direct connection between patterning information and morphogenesis, which suggests that mitotic timing forms an independent and important part of morphogenesis. / Thesis (Ph.D.)--University of Adelaide, Depts. of Biochemistry and Genetics, 1997