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Extension of the ADjoint Approach to a Laminar Navier-Stokes SolverPaige, Cody 16 July 2013 (has links)
The use of adjoint methods is common in computational fluid dynamics to reduce the cost of the sensitivity analysis in an optimization cycle. The forward mode ADjoint is a combination of an adjoint sensitivity analysis method with a forward mode automatic differentiation (AD) and is a modification of the reverse mode ADjoint method proposed by \citet{Mader:2008:B}. A colouring acceleration technique is presented to reduce the computational cost increase associated with forward mode AD. The forward mode AD facilitates the implementation of the laminar Navier--Stokes (NS) equations. The forward mode ADjoint method is applied to a three-dimensional computational fluid dynamics solver. The resulting Euler and viscous ADjoint sensitivities are compared to the reverse mode Euler ADjoint derivatives and a complex-step method to demonstrate the reduced computational cost and accuracy. Both comparisons demonstrate the benefits of the colouring method and the practicality of using a forward mode AD.
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Extension of the ADjoint Approach to a Laminar Navier-Stokes SolverPaige, Cody 16 July 2013 (has links)
The use of adjoint methods is common in computational fluid dynamics to reduce the cost of the sensitivity analysis in an optimization cycle. The forward mode ADjoint is a combination of an adjoint sensitivity analysis method with a forward mode automatic differentiation (AD) and is a modification of the reverse mode ADjoint method proposed by \citet{Mader:2008:B}. A colouring acceleration technique is presented to reduce the computational cost increase associated with forward mode AD. The forward mode AD facilitates the implementation of the laminar Navier--Stokes (NS) equations. The forward mode ADjoint method is applied to a three-dimensional computational fluid dynamics solver. The resulting Euler and viscous ADjoint sensitivities are compared to the reverse mode Euler ADjoint derivatives and a complex-step method to demonstrate the reduced computational cost and accuracy. Both comparisons demonstrate the benefits of the colouring method and the practicality of using a forward mode AD.
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Molecular and cellular analysis of skeletal muscle and neuronal development in a necdin-null mouse model of Prader-Willi syndromeBush, Jason Russell 11 1900 (has links)
Prader-Willi syndrome (PWS) is a recurrent microdeletion syndrome characterized by severe obesity, hyperphagia, hypotonia, and developmental delay, and is caused by the loss of expression of four protein-coding genes and set of small nucleolar RNAs on chromosome 15. NDN, encoding the protein necdin, is one of these genes, and a large body of literature supports the theory that necdin is important for the differentiation and survival of neurons. Given that necdin is also abundant in developing muscle and that hypotonia is a cardinal feature of PWS, I hypothesize that necdin promotes normal skeletal muscle development. I provide two lines of evidence demonstrating that loss of necdin impairs muscle development in mice. First, necdin interacts with the inhibitor of muscle differentiation EID-1 to relieve inhibition of MyoD-dependent transcription by sequestering this protein in the cytoplasm in over-expression assays. Unexpectedly, the presence of necdin increases EID-1 protein abundance in transfected cells and endogenous EID-1 is less abundant in Ndn-null embryonic mouse tissue compared to controls. Finally, conversion from MyoD+ to Myosin Heavy Chain+ cells is impaired in limb bud cultures from Ndn-null embryos, consistent with the hypothesis that loss of necdin impairs muscle differentiation by failing to relieve EID-1-dependent transcriptional inhibition. Second, loss of necdin impairs polarization of muscle progenitors in vitro and in vivo due to failed activation of the actin-myosin cytoskeleton, and reduces the proportional area of forelimb extensor muscles in Ndn-null mice at birth. This conclusion is supported by defective centrosome re-orientation due to impaired nuclear rearward movement and failed Cdc42 activation in Ndn-null mouse embryonic fibroblasts (MEFs), impaired myosin activation in Ndn-null MEFs and cortical neurons, and excessive branching and failure of hippocampal neurons to polarize with respect to a growth factor. Additionally, PWS patient fibroblasts display centrosome re-orientation defects and impaired myosin activation identical to Ndn-null MEFs, indicating that loss of necdin produces a similar phenotype in both mice and humans. These results provide strong evidence that necdin is critical for both the migration and primary differentiation of skeletal muscle, and validates the Ndn-null mouse as a model for hypotonia in PWS.
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Dehydroepiandrosterone and 17beta-Estradiol in plasma and brain of developing and adult zebra finchesShah, Amit Harendra 11 1900 (has links)
The classical model of sexual differentiation states that genes influence gonadal differentiation, and gonadal hormones then drive sexual differentiation throughout development. This model has been called into question by research, especially in songbirds, providing evidence for alternative mechanisms like direct effect of genes and local production of steroids via de novo synthesis or local metabolism of steroid precursors like DHEA, which can be metabolized to testosterone and E₂. In order to assess the role of local steroid production on sexual differentiation in songbirds, levels of DHEA and E₂ were measured in brachial and jugular plasma, as well as brain and peripheral tissues in zebra finches at critical ages during development and in adulthood. DHEA levels in brachial and jugular plasma peaked at P30 and higher DHEA levels in jugular plasma were found in males relative to females at P30. Also, at P30, higher DHEA levels were found in rostral telencephalon in females relative to males. The findings of this study indicate that DHEA may play a role in sexual differentiation of songbirds. Surprisingly, E₂ was non-detectable in many plasma and tissue samples. Higher E₂ was found in the diencephalon in females relative to males at P3/P4 and higher E₂ was found in gonads in adult females relative to males. There was little evidence to suggest that E₂ is synthesized de novo in the brain, although perhaps E₂ is being rapidly metabolized into another estrogen or E₂ synthesis is more localized in the synapse. The findings of this study support the role of alternative mechanisms like de novo steroid synthesis and local metabolism of steroid precursors and challenge the role of classical mechanisms of sexual differentiation in songbirds. Also, these findings may have important implications for sex differences, which develop independently of gonadal hormones, in other animal species.
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In Vitro Regulation of Growth, Differentiation and Survival of Leukemic CD5+ B CellsJanuary 1995 (has links)
B cell chronic lymphocytic leukemia (B-CLL) is a hematologic neoplasm characterised by the proliferation and accumulation of sIgM+/D+ B cells that fail to progress to the final stages of B cell development. The malignant cells in B-CLL also express the pan-T cell antigen CD5, suggesting that CLL is a malignancy of the CD5+ subset of B cells. Additional characteristics of the malignant clone include a low proliferative index, enhanced in vivo survival and constitutive expression of the anti-apoptosis oncoprotein bcl-2. The behaviour of leukemic CD5 B cells in vitro contrasts their arrested in vivo state. That is, despite the majority of cells being arrested in the G0 phase of the cell cycle, the leukemic B cells are not irreversibly frozen as they can be induced to differentiate to Ig-secreting cells under appropriate in vitro conditions. Furthermore, leukemic CD5 B cells rapidly undergo death by apoptosis following in vitro culture. This thesis describes the requirements for in vitro activation of leukemic CD5+ B cells, the characterisation of the events involved in apoptosis of these cells as well as the identification of various growth factors capable of modulating these events. Stimulation of unfractionated peripheral blood lymphocytes (PBLs) from three patients with B-CLL with the phorbol ester PMA and the mitogens PHA and PWM resulted in significant increases in cell proliferation, RNA synthesis and 1gM secretion when compared to unstimulated cell populations. PMA was the most potent inducer of 1gM secretion and this occurred irrespective of the presence of residual T cells. PMA-induced proliferation and RNA synthesis were also independent of T cells. However, in the presence of T cells, these parameters of cellular activation were enhanced during in vitro culture. Thus, the inductive ability of PMA on leukemic CD5 B cells was independent of T cells. In contrast, activation and differentiation of the leukemic CD5 B cells into 1gM-secreting cells following culture with mitogens did not occur in the absence of T cells. Interestingly, co-stimulation of leukemic CD5+ B cells with PMA and anti-Ig induced cellular responses that exceeded those induced by either activator alone. Thus, leukemic CD5+ B cells from patients with B-CLL can be activated in vitro and differentiate in response to stimulation via both T cell-dependent and T cell-independent mechanisms. Apoptotic cell death was characterised in purified leukemic CD5 B cells obtained from six B-CLL patients. All leukemic CD5 B cell populations entered an apoptotic pathway in vitro as evidenced by a reduction in cell size, loss of cell viability and fragmentation of DNA into multimers of -180 base pairs. Following 24 hours of in vitro culture 24.0±16% of DNA was fragmented. After 8 days, the majority of DNA was fragmented, and fewer than 10% of cultured cells were viable. Examination of bcl-2 expression in the malignant B cells by flow cytometry revealed a unimodal pattern of expression in greater than 85% of cells from each B-CLL patient prior to culture. During in vitro culture, bcl-2 expression became bimodal such that the B cells displayed a bcl-2hjgh and bcl-2iow phenotype. The level of expression by the bCl2hjgh cells was similar to that observed prior to in vitro culture, indicating that bcl-2 is down-regulated in apoptosing cells. Interestingly, despite this downregulation, the overall number of cells positive for bcl-2 remained constant. This suggests that the enhanced survival of leukemic CD5+ B cells in vivo is mediated by the sustained expression of bcl-2 and that additional mechanisms exist capable of overriding the protective effect of bcl-2 when bcl-2 is present at reduced levels. Leukemic B cell apoptosis has previously been reported to be delayed or prevented by IL-4, IFN-y and IFN-a. These results were confirmed in this study where it was found that culture of leukemic CD5 B cells with IL-4 or IFN-y enhanced cell viability and delayed apoptosis in 6/6 and 5/6 populations of leukemic B cells, respectively. This function was also found to be shared by IL-2, IL-6, IL-13 and TNF-a as these cytokines enhanced cell viability and delayed apoptosis in some of the cell populations examined at a level similar to that observed for IL-4 and IFN-y. These cytokines may mediate their effect via the expression of bcl2 as culture in the presence of IL-2, IL-4, IL-6, IL-13, IFN-y or TNF-a resulted in a higher percentage of cells displaying the bcl-2high phenotype, compared to unstimulated cells. Taken together, these results suggest that autocrine and/or paracrine growth loops may play a role in the pathogenesis of B-CLL and that cytokines that prevent apoptosis in vitro may be targets for treatment of this B cell malignancy.
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Chicken globin mRNA and its precursor / by Robert John CrawfordCrawford, Robert John January 1977 (has links)
Typescript (photocopy) / vii, 98 leaves : ill. ; 28 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Biochemistry, 1977
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Application of Magnetic Resonance Spectroscopy in Tumor PathologyRekas, Agata January 1999 (has links)
No description available.
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Notch ligand functionalized microheads for T cell differentiation of stem cellsTaqvi, Sabia Zehra, January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.
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Tissue engineered anterior cruciate ligaments /Altman, Gregory H. January 1900 (has links)
Thesis (Ph.D.)--Tufts University, 2002. / Adviser: David L. Kaplan. Submitted to the Dept. of Biotechnology Engineering. Includes bibliographical references (leaves 207-221). Access restricted to members of the Tufts University community. Also available via the World Wide Web;
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Beyond definition and differentiation : reconceptualizing the role of intelligence measures in reading disability classification research /O'Rourke, Alyssa Goldberg. January 1900 (has links)
Thesis (Ph.D.)--Tufts University, 2002. / Adviser: Maryanne Wolf. Submitted to the Dept. of Child Development. Includes bibliographical references (leaves 89-106). Access restricted to members of the Tufts University community. Also available via the World Wide Web;
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