Some Thermal Plate Deflections Determined by the Complex Variable Method

The first application of complex variables to elasticity dates with the beginning of this century. In 1902, L. N. G. Filon published a paper in which he developed the rudiments of the problem of plane theory of elasticity in complex variables. In 1909 G. V. Kolosov derived the equations of plane theory of elasticity in complex form and effected solutions to some boundary value problems. The major work relating complex variables and the theory of elasticity was given by N. R. Muskhelishvili whose published works began in 1919. Muskhelishvili’s [11] outstanding contribution is his brilliant monograph Some Basic Problems in the Mathematical Theory of Elasticity\u27\u27, published in 1933. This outstanding work as the catalyst necessary to initiate further research in the theory of elasticity and other related fields; however, it was not until 1953 that it was translated into English by J. R. M. Radok. In 1940, A. C. Stevenson independently developed that technique given by Muskhelishvili but his work was not published until 1945. (see more in text

Borrowing Hydrogen in the Synthesis of Alcohols and Amines

This thesis is concerned with the transformation of carbonyl compounds and allylic alcohols (and some amines) into alcohols via the process of transfer hydrogenation. The main work develops the idea of a new hydrogen donor for transfer hydrogenation and then applies it to an impressive one pot reaction. The transformation of amines shows an unexpected reaction and investigation into this reveals a possible mechanism for the reaction. Chapter 2: 1,4-Butanediol is introduced as a new hydrogen donor. It is used to convert a wide range of carbonyl substrates successfully into their alcohol counterparts after optimisation of conditions. A comparison with other straight chain alkanediols proves that 1,4-butanediol is the most suitable diol to use. The asymmetric aspect of the chemistry is investigated, but the results obtained do not compare to those already published in the literature. Chapter 3: A one pot reaction of isomerisation and reduction of allylic alcohols is proposed and proven. This is achieved by using 1,4-butanediol as the solvent and hydrogen donor. A wide range of allylic alcohols are converted to their corresponding saturated alcohols. The conditions were not applicable to asymmetric results. Chapter 4: The reaction of straight chain alkanediols with themselves is discovered and investigated to find they produce cyclic acetals. Results vary depending on the length of the alkyl chain. A series of experiments improved initial results to complete conversion. However isolation of these compounds remains a problem and requires more work. Chapter 5: During the synthesis of Diphenhydramine, an unexpected rearrangement reaction was discovered. This reaction was found to be specific to a certain structural arrangement on the compound. Investigations using 13C labelling found a plausible mechanism to explain the reaction.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Guest Artist Recital: BlueSHIFT Percussion

Kemp Recital Hall March 19, 2018 Monday Evening 8:00p.m

Gender-Based Violence and HIV Risk among Female Sex Workers in Iringa, Tanzania: Implications for a Community Empowerment Response

Globally, female sex workers (FSWs) bear a disproportionate burden of GBV and HIV. Prior work has demonstrated how substance use overlaps with GBV and HIV to further increase FSWs’ risk for negative health outcomes. This dissertation explored how aspects of the sex work environment, including physical, social, economic, and political factors, facilitate alcohol consumption and influence FSWs’ risk for GBV and HIV in Iringa, Tanzania. The ways in which sex workers collectively mobilize to address these factors and access their health and human rights was also explored. Additionally, this dissertation examined FSWs’ experiences accessing justice for violence perpetrated against them. This study was nested within a community-randomized controlled trial of a combination HIV prevention intervention among FSWs in Iringa, Tanzania. Utilizing baseline data from the parent study, this dissertation first conducted logistic regressions to assess the relationship between substance use, GBV, and consistent condom use with clients among a cohort of 496 FSWs. Additionally, 24 FSWs were purposively sampled to participate in in-depth interviews (IDIs) which aimed to gain a nuanced understanding of the role alcohol plays in both HIV and GBV related risk in the context of venue-based female sex work, as well as women’s experiences accessing justice for violence perpetrated against them. Qualitative data analysis was facilitated through the framework approach, in which the researcher begins analysis with a list of a priori codes, informed by the literature, while allowing for other domains to emerge from the data. Quantitative results suggest that intoxication during sex work is associated with significantly increased odds of GBV (aOR: 1.67, 95% CI: 1.08, 2.59) and reduced odds of consistent condom use with clients (aOR: 0.59, 95% CI: 0.37, 0.95). Qualitative analysis suggests that routine interactions between FSWs and their clients at specific moments in time and space during the sex exchange process facilitate alcohol consumption and increase FSWs’ risk for GBV and HIV. Furthermore, participants revealed how they mobilize their collective agency to address these environmental factors to limit alcohol consumption, prevent GBV, and promote condom use among their colleagues. Finally, qualitative results suggest that FSWs are routinely denied access to justice for violence perpetrated against them due to their occupation, and face human rights abuses at the hands of the police when they report violence to the authorities. Findings from this dissertation highlight the need for community empowerment approaches for HIV prevention among FSWs to address the intersection between alcohol consumption, GBV, and unprotected sex. Such models should provide FSWs with the opportunity to mobilize their collective agency to disrupt aspects of the sex work environment that facilitate alcohol use and increase FSWs’ risk for GBV and HIV. Finally, this study suggests that future community empowerment interventions should also provide FSWs with the skills and knowledge to join together in solidarity, in tandem with key stakeholders, to demand access to justice for violence perpetrated against them. It is possible that such an approach could reduce violence and HIV among FSWs in Tanzania and in similar settings

Using genome-wide data to model signalling-responsive gene regulatory mechanisms in blood development

The control of gene expression driving developmental haematopoiesis crucially depends on distal cis-regulatory elements such as enhancers which directly interact with promoters in the nucleus. However, no global experiments have been conducted which identify the cell type and cell stage-specific activity of enhancers in a chromatin context. It is through these elements that lineage specific transcription factors orchestrate cell fate decisions and direct haematopoietic lineage development emerging from the mesoderm. The roles of transcriptional regulators are beginning to be understood, however, it is still unclear how the myriad of extracellular signals modulate their activity. In this work, we report a global method which enables the identification of thousands tissue-specifically active cisregulatory elements able to stimulate a minimal promoter in cells representing five stages of haematopoietic specification derived from embryonic stem cells. Using serum-free differentiation culture, we demonstrate that our method can identify signalling-responsive enhancer elements and we highlight that it can be adapted to any embryonic stem cell differentiation system generating different cell types. We demonstrate that thousands of cell stage-specific sets of cis-elements are responsive to cytokine signals terminating at signalling-responsive transcription factors. Integrating these data with chromatin accessibility and single cell RNA-Seq data provided important new insights into the regulatory dynamics of the gene regulatory network transitions driving haematopoiesis. Our work identified the cytokine signalling-responsive transcription factors mediating responsiveness of enhancers at each developmental stage. We validated enhancers for Sparc, Pxn, Hspg2, Cdh5, Dlk1 and Mrpl15 as being signalling responsive to VEGF. We found that the cytokine VEGF is a crucial factor that regulates the balance between endothelial and haematopoietic development and our scRNA-seq analysis revealed that in the presence of VEGF Sox17 fails to be downregulated and Runx1 fails to be upregulated in the haemogenic endothelium and progenitor cells. For two Runx1 enhancers (the +23kb and +3.7kb) we studied the transcription factors motifs mediating the responsiveness of the enhancers to VEGF by mutation of these sites. Taken together, our work generated an important novel resource for future studies of haematopoietic differentiation and provides insights into how and where in the genome extrinsic signals program the cell type-specific chromatin landscape driving this process

Tropomyosin isoforms show unexpected differential effects on actin polymerization

Tropomyosin is a rod-like coiled-coil protein that forms a continuous filament that is weakly associated, but firmly-attached to the surface of the actin filaments in all eukaryotic cells. Simple eukaryotes such as yeasts have only one or two different tropomyosin isoforms which are known to be essential and perform roles in regulating the actin cytoskeleton. However higher eukaryotes have larger numbers of tropomyosins, the number of which appear linked to organismal complexity. Mammals have 4 genes producing over 40 different isoforms by alternative splicing. In higher organisms tropomyosin is best known and characterized in the regulation of striated muscle contraction. The role of tropomyosin outside of muscle is less well understood. It is generally thought to have a regulatory role in controlling interactions of actin-binding proteins and in providing additional stability to actin-filaments. In the latter case has been considered that tropomyosin binds to actin-filaments some time after their formation, both making them mechanically stiffer and protecting them from breakdown. We have produced a range of recombinant tropomyosins from all four mammalian genes and characterized their actin-binding affinities in a cosedimentation assay. We have then used them to systematically study the effects of different isoforms of tropomyosin on actin polymerization for the first time. We have monitored actin polymerization by the well-characterised change in fluorescence of a pyrene-label attached to actin. Actin polymerisation is monitored by measuring the significant fluorescence enhancement on polymerization. Our results characterize the actin-affinities of some of the TPM3 and TPM4 isoforms for the first time, These are in the same general range as mammalian isoforms previously characterized by our group and others. We demonstrate differential effects of the different isoforms on actin-polymerisation for the first time. The data unexpectedly show the most significant effects of the different isoforms appears to be in the early initiation / elongation stages of polymerizations. This is unexpected as tropomyosin is only considered to have significant affinity for actin filaments through itself forming a polymer along the surface of an actin filament. Different isoforms appear capable of both enhancing and inhibiting the early stages of polymerization, with examples of the shorter 6-actin spanning TPM1 gene isoforms showing a significant reduction in the lag-phase of early polymerization. These differential effects on different isoforms provides a new role for tropomyosin in not only stabilizing filaments, but also in helping catalyze their formation