CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation

The clonal expansion of antigen-specific CD8+ T cells in response to microbial infections is essential for adaptive immunity. Although IL-2 has been considered to be primarily responsible for this process, quantitatively normal expansion occurs in the absence of IL-2 receptor signaling. Here, we show that ligating CD27 on CD8+ T cells that have been stimulated through the T cell receptor causes their expansion in the absence of IL-2 by mediating two distinct cellular processes: enhancing cell cycling and promoting cell survival by maintaining the expression of IL-7 receptor alpha. This pathway for clonal expansion of the CD8+ T cell is not associated with the development of a capacity either for production of IFN-gamma or for cytotoxic T lymphocyte function and, therefore, is uncoupled from differentiation. Furthermore, ligating CD27 increases the threshold concentration at which IL-2 induces IFN-gamma-producing capability by the CD8+ T cell, suggesting that CD27 signaling may suppress effector differentiation. Finally, CD8+ T cells that have been stimulated by the TCR/CD27 pathway maintain their capacity for subsequent expansion and effector differentiation in response to a viral challenge in vivo. Thus, the TCR/CD27 pathway enables the CD8+ T cell to replicate by a process of self-renewal, which may contribute to the continuous generation of new effector CD8+ T cells in persistent viral infections.

A policy critique of Stansted Airport's expansion to 25 million passengers per annum (MPPA)

In this paper we undertake a preliminary assessment of the regional planning and development implications of BAA Stansted Airport’s planning permission to grow to 25 million passengers per annum (mppa) by 2010. Our concern is not simply to consider the overall growth of the airport on the airport site itself but the nature and type of growth both on- and off-site. In this document we focus on the submitted planning permission documents and test them. The methodology we employed was to draw on published and unpublished numerical estimates of the airport’s growth – particularly including estimates produced by the airport owner, BAA, and their economic and planning consultants DTZ Pieda - and critically, and systematically analyse their figures. We adopted this approach because unless the figures which were employed in the initial calculations were correct then all of the subsequent projections which flow from them - and the polices which could then be based on them – could be flawed. The analysis is divided into two parts – firstly, are the growth forecasts correct?; and secondly, what do these forecasts actually mean in developmental terms? In effect, what we have done is to produce a critique of the existing body of evidence by questioning underpinning assumptions and then draw some preliminary conclusions for the region based on this analysis. A major focus of this report has been analyse the figures involved in the planning application to expand Stansted to 25mppa. Ironically, one of our key findings, that the local impact of Stansted’s proposed expansion in employment terms might well be less than was originally thought, might make it easier to gain the acceptance of the relevant local authorities involved to allow the development to take place. Our main overall findings are that the BAA projections over-estimate the local employment impact of the airport’s proposed growth and under-estimate its potential regional ‘transportation’ employment effect. These two findings are, of course, related to each other in important ways, and we also feel that they have potentially significant medium and long-term economic, competitiveness and planning policy implications for the East of England region

Multi-level planning for semi-autonomous vehicles in traffic scenarios based on separation maximization

The planning of semi-autonomous vehicles in traffic scenarios is a relatively new problem that contributes towards the goal of making road travel by vehicles free of human drivers. An algorithm needs to ensure optimal real time planning of multiple vehicles (moving in either direction along a road), in the presence of a complex obstacle network. Unlike other approaches, here we assume that speed lanes are not present and that different lanes do not need to be maintained for inbound and outbound traffic. Our basic hypothesis is to carry forward the planning task to ensure that a sufficient distance is maintained by each vehicle from all other vehicles, obstacles and road boundaries. We present here a 4-layer planning algorithm that consists of road selection (for selecting the individual roads of traversal to reach the goal), pathway selection (a strategy to avoid and/or overtake obstacles, road diversions and other blockages), pathway distribution (to select the position of a vehicle at every instance of time in a pathway), and trajectory generation (for generating a curve, smooth enough, to allow for the maximum possible speed). Cooperation between vehicles is handled separately at the different levels, the aim being to maximize the separation between vehicles. Simulated results exhibit behaviours of smooth, efficient and safe driving of vehicles in multiple scenarios; along with typical vehicle behaviours including following and overtaking.

Planning autonomous vehicles in the absence of speed lanes using an elastic strip

Planning of autonomous vehicles in the absence of speed lanes is a less-researched problem. However, it is an important step toward extending the possibility of autonomous vehicles to countries where speed lanes are not followed. The advantages of having nonlane-oriented traffic include larger traffic bandwidth and more overtaking, which are features that are highlighted when vehicles vary in terms of speed and size. In the most general case, the road would be filled with a complex grid of static obstacles and vehicles of varying speeds. The optimal travel plan consists of a set of maneuvers that enables a vehicle to avoid obstacles and to overtake vehicles in an optimal manner and, in turn, enable other vehicles to overtake. The desired characteristics of this planning scenario include near completeness and near optimality in real time with an unstructured environment, with vehicles essentially displaying a high degree of cooperation and enabling every possible(safe) overtaking procedure to be completed as soon as possible. Challenges addressed in this paper include a (fast) method for initial path generation using an elastic strip, (re-)defining the notion of completeness specific to the problem, and inducing the notion of cooperation in the elastic strip. Using this approach, vehicular behaviors of overtaking, cooperation, vehicle following,obstacle avoidance, etc., are demonstrated.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

A decision framework for considering climate change adaptation in biodiversity conservation planning

General principles of climate change adaptation for biodiversity have been formulated, but do not help prioritize actions. This is inhibiting their integration into conservation planning. We address this need with a decision framework that identifies and prioritizes actions to increase the adaptive capacity of species. The framework classifies species according to their current distribution and projected future climate space, as a basis for selecting appropriate decision trees. Decisions rely primarily on expert opinion, with additional information from quantitative models, where data are available. The framework considers in-situ management, followed by interventions at the landscape scale and finally translocation or ex-situ conservation. Synthesis and applications: From eight case studies, the key interventions identified for integrating climate change adaptation into conservation planning were local management and expansion of sites. We anticipate that, in combination with consideration of socio-economic and local factors, the decision framework will be a useful tool for conservation and natural resource managers to integrate adaptation measures into conservation plans.

A linear optimization approach to the combined production planning model

Two fundamental processes usually arise in the production planning of many industries. The first one consists of deciding how many final products of each type have to be produced in each period of a planning horizon, the well-known lot sizing problem. The other process consists of cutting raw materials in stock in order to produce smaller parts used in the assembly of final products, the well-studied cutting stock problem. In this paper the decision variables of these two problems are dependent of each other in order to obtain a global optimum solution. Setups that are typically present in lot sizing problems are relaxed together with integer frequencies of cutting patterns in the cutting problem. Therefore, a large scale linear optimizations problem arises, which is exactly solved by a column generated technique. It is worth noting that this new combined problem still takes the trade-off between storage costs (for final products and the parts) and trim losses (in the cutting process). We present some sets of computational tests, analyzed over three different scenarios. These results show that, by combining the problems and using an exact method, it is possible to obtain significant gains when compared to the usual industrial practice, which solve them in sequence. (C) 2010 The Franklin Institute. Published by Elsevier Ltd. All rights reserved.

The potential for first-generation ethanol production from sugarcane

Ethanol production from sugarcane, mainly in Brazil, on the basis of first-generation technology (22.5 billion liters, in 2007/2008 season, in 3.4 million hectares) replaces 1% of the gasoline used in the world today and is highly competitive in economic terms with ethanol produced from other crops in the USA and Europe. In this paper we discuss the potential for sugarcane ethanol expansion from two angles: (1) productivity gains which would allow greater production in the same area and (2) geographical expansion to larger areas. The potential of first-generation technology for the production of ethanol from sugarcane is far from being exhausted. There are gains in productivity of approximately a factor of two from genetically modified varieties and a geographical expansion by a factor of ten of the present level of production in many sugar-producing countries. The replacement of 10% of the gasoline used in the world by ethanol from sugarcane seems possible before second-generation technology reaches technological maturity and possibly economic competitiveness. (C) 2009 Society of Chemical Industry and John Wiley & Sons, Ltd

Generation of Vortices and Observation of Quantum Turbulence in an Oscillating Bose-Einstein Condensate

We report on the experimental observation of vortex formation and production of tangled vortex distribution in an atomic BEC of (87)Rb atoms submitted to an external oscillatory perturbation. The oscillatory perturbations start by exciting quadrupolar and scissors modes of the condensate. Then regular vortices are observed finally evolving to a vortex tangle configuration. The vortex tangle is a signature of the presence of a turbulent regime in the cloud. We also show that this turbulent cloud has suppression of the aspect ratio inversion typically observed in quantum degenerate bosonic gases during free expansion.

Acquisitions: The Next Generation

This article reviews a broad range of trends and concerns regarding the recruitment, training, and retention of acquisitions librarians. The survey of trends benefits library educators and students, members of search commillees seeking to fill acquisitions vacancies, and working acquisitions librarians.

Reuse-based test planning for core-based systems-on-chip

Electronic applications are currently developed under the reuse-based paradigm. This design methodology presents several advantages for the reduction of the design complexity, but brings new challenges for the test of the final circuit. The access to embedded cores, the integration of several test methods, and the optimization of the several cost factors are just a few of the several problems that need to be tackled during test planning. Within this context, this thesis proposes two test planning approaches that aim at reducing the test costs of a core-based system by means of hardware reuse and integration of the test planning into the design flow. The first approach considers systems whose cores are connected directly or through a functional bus. The test planning method consists of a comprehensive model that includes the definition of a multi-mode access mechanism inside the chip and a search algorithm for the exploration of the design space. The access mechanism model considers the reuse of functional connections as well as partial test buses, cores transparency, and other bypass modes. The test schedule is defined in conjunction with the access mechanism so that good trade-offs among the costs of pins, area, and test time can be sought. Furthermore, system power constraints are also considered. This expansion of concerns makes it possible an efficient, yet fine-grained search, in the huge design space of a reuse-based environment. Experimental results clearly show the variety of trade-offs that can be explored using the proposed model, and its effectiveness on optimizing the system test plan. Networks-on-chip are likely to become the main communication platform of systemson- chip. Thus, the second approach presented in this work proposes the reuse of the on-chip network for the test of the cores embedded into the systems that use this communication platform. A power-aware test scheduling algorithm aiming at exploiting the network characteristics to minimize the system test time is presented. The reuse strategy is evaluated considering a number of system configurations, such as different positions of the cores in the network, power consumption constraints and number of interfaces with the tester. Experimental results show that the parallelization capability of the network can be exploited to reduce the system test time, whereas area and pin overhead are strongly minimized. In this manuscript, the main problems of the test of core-based systems are firstly identified and the current solutions are discussed. The problems being tackled by this thesis are then listed and the test planning approaches are detailed. Both test planning techniques are validated for the recently released ITC’02 SoC Test Benchmarks, and further compared to other test planning methods of the literature. This comparison confirms the efficiency of the proposed methods.

Efeitos da regulação no custo de aquisição de energia elétrica no Brasil

Nos últimos vinte anos, o Setor Elétrico Brasileiro (SEB) vem passando por profundas transformações incluindo duas reestruturações. A primeira, em 1995, faz a transição de um modelo centralizado com empresas estatais operando no regime de monopólio para um modelo de livre mercado com ênfase na privatização do setor. A segunda, em 2004, retoma o papel do Estado no planejamento da expansão do setor, estabelece a convivência entre empresas estatais e privadas e busca promover a modicidade tarifária. A principal razão para as mudanças é a necessidade de investimento para expansão da oferta de energia elétrica. Este trabalho tem como objetivo apresentar estas reformas, descrever o funcionamento atual do setor elétrico e analisar a questão do término das concessões de geração a partir de 2015. A indefinição do governo federal entre prorrogar ou licitar estas concessões cria incertezas, adiando investimentos e provocando perdas ao país.

A intervenção do estado na economia: um estudo de caso do setor elétrico

Estuda-se a intervenção do Estado na economia através da regulação, tendo como objeto de análise o setor elétrico brasileiro. O presente estudo tem como objetivo verificar de que forma o Estado, desde a promulgação da Constituição de 1988, buscou cumprir os princípios estabelecidos na Ordem Econômica constitucional e exercer a sua função de ente regulador, fiscalizador, planejador e indutor do crescimento econômico, no setor elétrico. Analisa-se a reforma do Estado pensada pelo ex-Ministro Bresser Pereira e a inclusão de empresas do setor elétrico no Plano Nacional de Desestatização. Observa-se que o processo de privatização permanece inacabado nos segmentos da geração e da transmissão. Investiga-se a instituição do MAE e a criação do produtor independente de energia elétrica, no contexto de uma reforma que pretendia encaminhar o setor elétrico para o livre mercado. Estuda-se a crise de racionamento e a mudança de estratégia do Governo, cuja prioridade passou a ser um maior planejamento central que garantisse a segurança energética e a expansão da geração e transmissão. Analisa-se as diferenças entre o ACL e o ACR, bem como a formação do preço da energia elétrica em cada um e conclui-se, por meio da leitura de precedentes do CADE, que trata-se do mesmo mercado relevante na dimensão produto. Investiga-se as mudanças trazidas pela MP-579 e de que forma a intervenção do Estado no setor elétrico aumentou, e os impactos que isso trouxe. Conclui-se que, a partir da edição da MP-579, a intervenção do Estado no setor elétrico aumentou com o objetivo de controlar os preços e garantir a segurança energética, mas que as mudanças regulatórias não foram bem sucedidas em manter e a tarifa da energia paga pelo consumidor final em patamares baixos, tampouco em garantir a oferta de energia elétrica suficiente para cobrir a demanda das distribuidoras.

Interior point method for long-term generation scheduling of large-scale hydrothermal systems

This paper presents an interior point method for the long-term generation scheduling of large-scale hydrothermal systems. The problem is formulated as a nonlinear programming one due to the nonlinear representation of hydropower production and thermal fuel cost functions. Sparsity exploitation techniques and an heuristic procedure for computing the interior point method search directions have been developed. Numerical tests in case studies with systems of different dimensions and inflow scenarios have been carried out in order to evaluate the proposed method. Three systems were tested, with the largest being the Brazilian hydropower system with 74 hydro plants distributed in several cascades. Results show that the proposed method is an efficient and robust tool for solving the long-term generation scheduling problem.

Reactive power dispatch and planning using a non-linear branch-and-bound algorithm

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