Molecular mechanisms of interleukin-2 gene inducibility: developmental control and combinatorial action of transcription factors

Interleukin-2 is one of the lymphokines secreted by T helper type 1 cells upon activation mediated by T-cell receptor (TCR) and accessory molecules. The ability to express IL-2 is correlated with T-lineage commitment and is regulated during T cell development and differentiation. Understanding the molecular mechanism of how IL-2 gene inducibility is controlled at each transition and each differentiation process of T-cell development is to understand one aspect of T-cell development. In the present study, we first attempted to elucidate the molecular basis for the developmental changes of IL-2 gene inducibility. We showed that IL-2 gene inducibility is acquired early in immature CD4- CD8-TCR- thymocytes prior to TCR gene rearrangement. Similar to mature T cells, a complete set of transcription factors can be induced at this early stage to activate IL-2 gene expression. The progression of these cells to cortical CD4^+CD8^+TCR^(1o) cells is accompanied by the loss of IL-2 gene inducibility. We demonstrated that DNA binding activities of two transcription factors AP-1 and NF-AT are reduced in cells at this stage. Further, the loss of factor binding, especially AP-1, is attributable to the reduced ability to activate expression of three potential components of AP-1 and NF-AT, including c-Fos, FosB, and Fra-2. We next examined the interaction of transcription factors and the IL-2 promoter in vivo by using the EL4 T cell line and two non-T cell lines. We showed an all-or-none phenomenon regarding the factor-DNA interaction, i.e., in activated T cells, the IL-2 promoter is occupied by sequence-specific transcription factors when all the transcription factors are available; in resting T cells or non-T cells, no specific protein-DNA interaction is observed when only a subset of factors are present in the nuclei. Purposefully reducing a particular set of factor binding activities in stimulated T cells using pharmacological agents cyclosporin A or forskolin also abolished all interactions. The results suggest that a combinatorial and coordinated protein-DNA interaction is required for IL-2 gene activation. The thymocyte experiments clearly illustrated that multiple transcription factors are regulated during intrathymic T-cell development, and this regulation in tum controls the inducibility of the lineage-specific IL-2 gene. The in vivo study of protein-DNA interaction stressed the combinatorial action of transcription factors to stably occupy the IL-2 promoter and to initiate its transcription, and provided a molecular mechanism for changes in IL-2 gene inducibility in T cells undergoing integration of multiple environmental signals.

Dirac spectra, summation formulae, and the spectral action

Noncommutative geometry is a source of particle physics models with matter Lagrangians coupled to gravity. One may associate to any noncommutative space (A, H, D) its spectral action, which is defined in terms of the Dirac spectrum of its Dirac operator D. When viewing a spin manifold as a noncommutative space, D is the usual Dirac operator. In this paper, we give nonperturbative computations of the spectral action for quotients of SU(2), Bieberbach manifolds, and SU(3) equipped with a variety of geometries. Along the way we will compute several Dirac spectra and refer to applications of this computation.

Concerted action for successful coastal communities in Tanzania: Lessons from the Tanzania Coastal Management Partnership (TCMP) 2006-2009

The Tanzania Coastal Management Partnership (TCMP) works to implement the National Integrated Coastal Environmental Management Strategy (ICEMS) in Tanzania’s coastal landscapes and seascapes, funded in large measure by the U.S. Agency for International Development. The overarching goal of the Sustainable Coastal Communities and Ecosystems in Tanzania (SUCCESS Tanzania) initiative is to conserve coastal and marine biodiversity while improving the well being of coastal residents through implementation of the Tanzania ICEMS and related ICM policies and strategies. It does this by focusing on three key results: -Policies and Laws that Integrate Conservation and Development Applied -Participatory Landscape Scale Conservation Practiced -Conservation Enterprises Generate Increased and Equitable Benefits from Sustainable Use An additional result sought in the program is gender equity and HIV/AIDS preventive behaviors promoted through communicating HIV/AIDS, environment, and equity messages. (PDF contains 3 pages)

Geometric quantization and foliation reduction

A standard question in the study of geometric quantization is whether symplectic reduction interacts nicely with the quantized theory, and in particular whether “quantization commutes with reduction.” Guillemin and Sternberg first proposed this question, and answered it in the affirmative for the case of a free action of a compact Lie group on a compact Kähler manifold. Subsequent work has focused mainly on extending their proof to non-free actions and non-Kähler manifolds. For realistic physical examples, however, it is desirable to have a proof which also applies to non-compact symplectic manifolds.

In this thesis we give a proof of the quantization-reduction problem for general symplectic manifolds. This is accomplished by working in a particular wavefunction representation, associated with a polarization that is in some sense compatible with reduction. While the polarized sections described by Guillemin and Sternberg are nonzero on a dense subset of the Kähler manifold, the ones considered here are distributional, having support only on regions of the phase space associated with certain quantized, or “admissible”, values of momentum.

We first propose a reduction procedure for the prequantum geometric structures that “covers” symplectic reduction, and demonstrate how both symplectic and prequantum reduction can be viewed as examples of foliation reduction. Consistency of prequantum reduction imposes the above-mentioned admissibility conditions on the quantized momenta, which can be seen as analogues of the Bohr-Wilson-Sommerfeld conditions for completely integrable systems.

We then describe our reduction-compatible polarization, and demonstrate a one-to-one correspondence between polarized sections on the unreduced and reduced spaces.

Finally, we describe a factorization of the reduced prequantum bundle, suggested by the structure of the underlying reduced symplectic manifold. This in turn induces a factorization of the space of polarized sections that agrees with its usual decomposition by irreducible representations, and so proves that quantization and reduction do indeed commute in this context.

A significant omission from the proof is the construction of an inner product on the space of polarized sections, and a discussion of its behavior under reduction. In the concluding chapter of the thesis, we suggest some ideas for future work in this direction.

Implications of governance structures on urban climate action: evidence from Italy and Spain

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Pond action: Promoting the conservation of ponds in Britain

Pond Action is an independent freshwater conservation project which was started in 1987. It is based in the School of Biological and Molecular Sciences in Oxford Polytechnic and has five full-time staff with two senior advisors. The main aim of Pond Action's work has been to promote the conservation of ponds by creating a sound, scientific basis for pond conservation. An essential aspect of this work is the need to make the results of scientific work available and understandable to everybody concerned with pond conservation.

Action of ecdysterone on the moulting of amphipod females: Gammarus pulex (L.) and G.fossarum Koch. Early results. [Translation from: Crustaceana 28, 86-88, 1975.]

In studying sexual attraction in gammarids of the group pulex, it has seemed necessary to dissociate the processes of moulting and ovogenesis in order to recognize their respective effects on this phenomenon. For this purpose a synthetic hormone, ecdysterone, was utilized. In the first instance the author followed the action of the hormone on isolated females in vitellogenesis. It was proved that the behaviour of Gammarus pulex and Gammarus fossarum vis-a-vis the ecdysterone used proves to be very close to that of isopods that was observed in Orchestia gammarellus in earlier research. Although they were in vitellogenesis, the females saw their intermoult cycle shortened.

Decomposition in lake sediments: bacterial action and interaction

This review discusses the processes involved in the decomposition of organic carbon derived initially from structural components of algae and other primary producers. It describes how groups of bacteria interact in time and space in a eutrophic lake. The relative importance of anaerobic and aerobic processes are discussed. The bulk of decomposition occurs within the sediment. The role of bacteria in the nitrogen cycle and the iron cycle, and in sulphate reduction and methanogenesis as the terminal metabolism of organic carbon are described.

Análise das práticas de recrutamento e de seleção de pessoas com deficiência para o trabalho em empresas privadas: cumprimento à Lei n 8.213/1991

A proposta da presente pesquisa teve como objetivo analisar criticamente as melhores práticas de recrutamento e de seleção, direcionadas a pessoas com deficiência, candidatas a emprego em cinco empresas privadas, na cidade do Rio de Janeiro, que possuem em seu quadro de funcionários mais de 100 empregados, sendo assim, obrigadas ao cumprimento da Lei n 8.213/1991, a Lei de Cotas. Analisou-se também o modo como profissionais de Recursos Humanos adquiriram conhecimentos técnicos acerca destas práticas. Parte dos objetivos desta proposta de pesquisa foi identificar as bases desta determinação legal, no que se refere ao amparo técnico aos profissionais de RH no processo seletivo. Neste aspecto, o foco da investigação foi verificar a existência de programas de qualificação para estes profissionais, tendo em vista que a exigência de capacitação está sempre centrada na pessoa com deficiência, quando, na verdade, a carência está presente também nos responsáveis que lidam com este público, por ocasião do seu ingresso nas organizações corporativas. A abordagem metodológica incluiu uma pesquisa de campo com base em dados de entrevistas semi-estruturadas, sendo complementada pela técnica de análise de relato verbal. Seis foram os profissionais de RH escolhidos como participantes da pesquisa e que atuam diretamente na área de recrutamento e de seleção de pessoas com deficiência. Inevitavelmente, estes profissionais de RH se utilizam de instrumentos psicométricos dentre outros, cotidianamente empregados no processo seletivo, inclusive na avaliação de pessoas com deficiência. Os resultados da presente pesquisa apontam que as melhores práticas de recrutamento e de seleção, atualmente em uso, direcionadas a pessoas com deficiência, são discriminatórias, pois os profissionais envolvidos neste processo, por demonstrarem falta de conhecimento acerca de práticas apropriadas, se utilizam dos mesmos procedimentos adotados no atendimento de vagas para o público de pessoas ditas normais. Complementarmente, a revisão da literatura aponta a inexistência de amparo técnico e científico, no sentido de qualificar profissionais responsáveis pelo ingresso e permanência de pessoas com deficiência no mercado de trabalho, confirmando-se, assim, a limitação da ação de política pública em vigor. Por conta desse fato, propõe-se a adoção de ações afirmativas, neste caso de órgãos privados, no sentido de mobilizar esforços em prol da contratação de grupos socialmente excluídos no mercado de trabalho, como é o caso das pessoas com deficiência.