The role of the NFAT signalling pathway on diffuse large B-cell lymphoma

PhD ThesisDiffuse Large B-Cell Lymphomas (DLBCL) are common, aggressive malignancies of mature B-lymphocytes that represent ~40% of lymphomas. Despite the widespread use of combined immunochemotherapy, approximately 50% of patients with DLBCL die from their disease. The two main DLBCL subgroups resemble activated B cells (ABC) or germinal centre B cells (GCB), where patients with ABC-DLBCL have significantly worse outcome. There is urgent need for novel therapeutic strategies in the treatment of DLBCL, which requires a better understanding of the molecular pathways upon which tumours depend. Accumulating evidence suggests that the signalling networks promoting and sustaining DLBCL derive from dysregulation of the normal pathways controlling B-lymphocyte activation and differentiation. There is increasing evidence indicating important roles for the NFAT family of transcription factors in DLBCL. Constitutively-active nuclear NFAT2 has been demonstrated in approximately 40% of primary DLBCL samples and NFAT has been shown to regulate a small number of genes associated with DLBCL growth/survival. This project investigated the role of NFAT in DLBCL. Nuclear localisation and activation of NFAT family members were characterised in a panel of DLBCL cell lines and chemical inhibition of calcineurin/NFAT, using Cyclosporin A (CsA), indicated dependency on the calcineurin/NFAT pathway for survival. Gene expression microarray analysis performed in DLBCL cell lines treated with CsA revealed potential NFAT target genes involved in the tumour microenvironment and anergy. These data revealed that the cytokine TNFα was downregulated by CsA in ABC, but not GCB cell lines. TNFα expression has recently been reported a significant prognostic factor for OS and PFS in DLBCL and evidence suggests dependency of some DLBCL on autocrine TNFα signalling for survival. Biologically active TNFα was produced by DLBCL cell lines, however inhibition of TNFα signalling using Infliximab and Etanercept had no effect on cell viability, suggesting that TNFα may be functionally important in DLBCL by other mechanisms.Cancer Research U

Drug-related activity in the United Kingdom of Great Britain and Ireland between 1900 and 1922: what evidence can be found through systematic searches of the Times digital achive.

Much has been written about drug-taking during the nineteenth century, particularly in relation to opium. However, the early twentieth century has received considerably less attention, despite being a crucial period in the history of drug-taking within Britain. During 1916, the Defence of the Realm Act Regulation 40b made it an offence to supply or to possess particular drugs without authorisation. This was a fundamental shift in government thinking that presaged the modern era in which the legal status of particular drugs continues to be an issue of public debate. Previous research focused on changes in the law and analysed the relationships between key individuals and influential groups with an interest in drug control. In part, this reflects the significance of the decision to alter the law but also the lack of available evidence concerning drug-takers of the era. This study seeks to address this gap in understanding and develops a new perspective on drug-taking, that of the participants. The study developed an innovative and, at times, speculative approach to tracing drug-takers of that era. This led to the use of articles from The Times identified from systematic searches of The Times Digital Archive. These articles by their nature were mediated accounts of drug-related activity but no other source could offer such a range of drug-takers over the selected time period (1900-1922). Furthermore, the large number of articles identified meant that it was easier to detect press influences and take these into account when analysing their content. The wealth of information that emerged from the articles was beyond initial expectations and led to an additional piece of analysis concerning the geographical spread of drug-taking activity within the period. Although the evidence did not allow the development of many in-depth accounts as had been the intention at the outset, it did provide insight to particular aspects of drug-taking activity. For example, the collated information regarding female participants suggested specific behavioural traits that possibly made female consumers harder to detect compared to their male counterparts. Drug-taking among military personnel and the operation of supply networks were other aspects illuminated by the articles. An association emerged between military conflicts and increased drug-taking by military personnel. It indicated, too, that periods of conflict could have implications for domestic prevalence from the cessation of hostilities. Geographical analysis illuminated the supply networks both in terms of drug procurement and relationships between drug-takers within their areas of settlement. Furthermore, some of the areas associated with drug-taking during the early twentieth century remain linked to drugs in the present day raising questions about how and why specific areas might become drug hot-spots. Further research arising from this thesis would involve the replication of the method during the later period, 1923 to 1950. This period would allow the female narrative of drug-related activity begun by this thesis to be developed further and to establish whether the First World War was a unique period for female participation or whether their participation evolved. Similarly, considering the articles from this later period could help illuminate further the subsequent spread and operation of supply networks. Replicating the method would also test whether it is transferable to other periods or whether changes to reporting style made the method era specific

The Desire for Utopia in the Critical Study of Religion

This dissertation argues that the critical methods developed by and used within the field of religious studies can be reimagined as an expression of the modern desire for Utopia. It investigates how applications of critical social theory occlude the category of experience either deliberately or through methodological slight. Utopia addresses this problematic of representing the existential dimension of social life through its particular formulation of social contradiction. Analyzing Utopia\u27s own representational situation within modernity affords scholars in religion a means to consider their investments in and desires for representing society as a totality that creates the conditions for and anticipates resolutions to these contradictions

Thinking “Outside the Box”: Unconstrained Creative Generation in Adults with Attention Deficit Hyperactivity Disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155985/1/jocb382.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155985/2/jocb382_am.pd

Review: Application of Tick Control Technologies for Blacklegged, Lone Star, and American Dog Ticks

Tick population control technologies have been studied for several decades but no method is successful in all situations. The success of each technology depends on tick species identity and abundance, host species identity and abundance, phenology of both ticks and hosts, geographic region, and a multitude of other factors. Here we review current technologies, presenting an overview of each and its effect on three common tick species in the eastern United States: blacklegged ticks (Ixodes scapularis (Say; Ixodida: Ixodidae)), lone star ticks (Amblyomma americanum (Linnaeus; Ixodida: Ixodidae)), and American dog ticks (Dermacentor variabilis (Say; Ixodida: Ixodidae)). Moreover, we assess the relative success among methods within the same season, as well as over successive years, in reducing tick populations by life stage. For each tick species and life stage, we present published findings, and in the absence of published studies, we hypothesize the most likely outcome based on tick life history. Integrated tick management over a specific time scale, using a variety of tick control technologies, will have the greatest effect on reducing tick abundance

For a Zemiology of Politics

Davis, H., & White, H., For a zemiology of politics, Journal of White Collar and Corporate Crime (Journal Volume Number and Issue Number) pp. xx-xx. Copyright © [2022] (Copyright Holder). Reprinted by permission of SAGE Publications.A zemiology of politics is required in the face of disastrous historic, contemporary and future social harms. Focusing on state-led politics, the article charts some politically generated or mediated social harms: military; ecological and economic. These can generate justificatory narratives of zemiogenic deceit and ignorance. In a contemporary political moment of authoritarian populism, nativism and racism, each feature as part of wider processes towards the corruption and destruction of politics. The article then suggests some of the potentials of healthy politics and fundamental principles for a zemiology of politics including: subordination of crime-centric criminology to a historically grounded international zemiology, the incorporation of agnotological perspectives, and an orientation that is public, inclusive, reflexive and non-fundamentalist

Men’s and women’s migration in coastal Ghana

This article uses life history calendar (LHC) data from coastal Ghana and event history statistical methods to examine inter-regional migration for men and women, focusing on four specific migration types: rural-urban, rural-rural, urban-urban, and urban-rural. Our analysis is unique because it examines how key determinants of migration—including education, employment, marital status, and childbearing—differ by sex for these four types of migration. We find that women are significantly less mobile than men overall, but that more educated women are more likely to move (particularly to urban areas) than their male counterparts. Moreover, employment in the prior year is less of a deterrent to migration among women. While childbearing has a negative effect on migration, this impact is surprisingly stronger for men than for women, perhaps because women’s search for assistance in childcare promotes migration. Meanwhile, being married or in union appears to have little effect on migration probabilities for either men or women. These results demonstrate the benefits of a LHC approach and suggest that migration research should further examine men’s and women’s mobility as it relates to both human capital and household and family dynamics, particularly in developing settings.event history analysis, Ghana, life history, migration, Sub-Saharan Africa, urbanization