25 resultados para Broad concept
em Consorci de Serveis Universitaris de Catalunya (CSUC), Spain
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Peer-reviewed
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Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.
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vegeu resum en el fitxer adjunt a l'inici del treball de recerca
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In the literature on risk, one generally assume that uncertainty is uniformly distributed over the entire working horizon, when the absolute risk-aversion index is negative and constant. From this perspective, the risk is totally exogenous, and thus independent of endogenous risks. The classic procedure is "myopic" with regard to potential changes in the future behavior of the agent due to inherent random fluctuations of the system. The agent's attitude to risk is rigid. Although often criticized, the most widely used hypothesis for the analysis of economic behavior is risk-neutrality. This borderline case must be envisaged with prudence in a dynamic stochastic context. The traditional measures of risk-aversion are generally too weak for making comparisons between risky situations, given the dynamic �complexity of the environment. This can be highlighted in concrete problems in finance and insurance, context for which the Arrow-Pratt measures (in the small) give ambiguous.
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The objective of this paper is to re-evaluate the attitude to effort of a risk-averse decision-maker in an evolving environment. In the classic analysis, the space of efforts is generally discretized. More realistic, this new approach emploies a continuum of effort levels. The presence of multiple possible efforts and performance levels provides a better basis for explaining real economic phenomena. The traditional approach (see, Laffont, J. J. & Tirole, J., 1993, Salanie, B., 1997, Laffont, J.J. and Martimort, D, 2002, among others) does not take into account the potential effect of the system dynamics on the agent's behavior to effort over time. In the context of a Principal-agent relationship, not only the incentives of the Principal can determine the private agent to allocate a good effort, but also the evolution of the dynamic system. The incentives can be ineffective when the environment does not incite the agent to invest a good effort. This explains why, some effici
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The aim of this paper is to measure the returns to human capital. We use a unique data set consisting of matched employer-employee information. Data on individuals' human capital include a set of 26 competences that capture the utilization of workers' skills in a very detailed way. Thus, we can expand the concept of human capital and discuss the type of skills that are more productive in the workplace and, hence, generate a higher payoff for the workers. The rich information on firm's and workplace characteristics allows us to introduce a broad range of controls and to improve previous research in this field. This paper gives evidence that the returns to generic competences differ depending on the position of the worker in the firm. Only numeracy skills are reward independent of the occupational status of the worker. The level of technology used by the firm in the production process does not directly increase workers’ pay, but it influences the pay-off to some of the competences. JEL Classification: J24, J31
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Gim & Kim (1998) proposed a generalization of Jeong (1982, 1984) reinterpretation of the Hawkins-Simon condition for macroeconomic stability to off-diagonal matrix elements. This generalization is conceptually relevant for it offers a complementary view of interindustry linkages beyond final or net output influence. The extension is completely similar to the 'total flow' idea introduced by Szyrmer (1992) or the 'output-to-output' multiplier of Miller & Blair (2009). However the practical implementation of Gim & Kim is actually faulty since it confuses the appropriate order of output normalization. We provide a new and elementary solution for the correct formalization using standard interindustry accounting concepts.
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This paper shows the impact of the atomic capabilities concept to include control-oriented knowledge of linear control systems in the decisions making structure of physical agents. These agents operate in a real environment managing physical objects (e.g. their physical bodies) in coordinated tasks. This approach is presented using an introspective reasoning approach and control theory based on the specific tasks of passing a ball and executing the offside manoeuvre between physical agents in the robotic soccer testbed. Experimental results and conclusions are presented, emphasising the advantages of our approach that improve the multi-agent performance in cooperative systems
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Innovation is a research topic with a broad tradition. However, learning processes,from which innovations emerge, and the dynamics of change and development havetraditionally been studied in relation with the manufacturing sector. Moreover, theobjects of study have been usually process and tangible product innovations. Althoughrecently researchers have focused their attention in other sectors, more research onservice innovation should be carried out. Furthermore, regarding innovation intourism, there is a need to adapt generic theories to the tourism sector and tocontribute with new ideas.In order to find out, which are the origins of innovation processes, it is necessary tolook into two fundamental subjects that are inherent to innovation, which are learningand interaction. Both are closely related. The first appears to be an intrinsic conditionof individuals. Moreover, it can also be identified in organizations. Thus, learning allowsindividuals as well as organizations to develop. However, learning and development isnot possible without taking the environment into account. Hence, it is necessary thatinteractions take place between individuals, groups of individuals, organizations, etc.Furthermore, the concept of interaction implies the transfer of knowledge, which isthe basis for innovations.The purposes of this master thesis are to study in detail several of these topics and to develop a conceptual framework for the research on innovation in tourism
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This research explores critical environmental concepts from the standpoint of political ecology. It contrasts the Ecuadorian Kichua indigenous concept of Sumak Kawsay (i.e., living well), with discourses about natural, urban and rural areas. Sumak Kawsay was included in Ecuador’s 2008 constitution as an alternative to the neoclassical idea of development. This work reveals interesting insights from a variety of social and political viewpoints from both rural and urban areas. The research is based on the medium sized city of Cuenca, which is located in the southern Ecuadorian Andes. We used an adaptation of the Q Method to investigate stakeholders’ perceptions. Four remarkably well-defined viewpoints were revealed. Although these views contrast strongly with Sumak Kawsay, it is possible to transform this paradigm in the foundation of Cuenca’s public policies and institutional structure.
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This book is concerned with the diversity debate in the context of Europe.It is about diversity both as a concept and as a policy. Indeed, the epicentreof the analysis is the link between the spheres of diversity-concepts anddiversity-policies. The book explores how the concept of diversity orientatespolicies and management, and also how public/private managementfacilitates new policy orientations. As such, the book enhances conceptualthinking on diversity, but also facilitates policy thinking on the conceptinvolved in novel policy orientations towards diversity.
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Adopting a simplistic view of Coase (1960), most economic analyses of property rightsdisregard both the key advantage that legal property rights (that is, in rem rights) provide torightholders in terms of enhanced enforcement, and the difficulties they pose to acquirers interms of information asymmetry about legal title. Consequently, these analyses tend to overstatethe role of "private ordering" and disregard the two key elements of property law: first, theessential conflict between property (that is, in rem) enforcement and transaction costs; and,second, the institutional solutions created to overcome it, mainly contractual registries capable ofmaking truly impersonal (that is, asset-based) trade viable when previous relevant transactionson the same assets are not verifiable by judges. This paper fills this gap by reinterpreting bothelements within the Coasean framework and thus redrawing the institutional foundations of bothproperty and corporate contracting.
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The approximants to regular continued fractions constitute `best approximations' to the numbers they converge to in two ways known as of the first and the second kind.This property of continued fractions provides a solution to Gosper's problem of the batting average: if the batting average of a baseball player is 0.334, what is the minimum number of times he has been at bat? In this paper, we tackle somehow the inverse question: given a rational number P/Q, what is the set of all numbers for which P/Q is a `best approximation' of one or the other kind? We prove that inboth cases these `Optimality Sets' are intervals and we give aprecise description of their endpoints.
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The aim of this brief is to present an original design methodology that permits implementing latch-up-free smart power circuits on a very simple, cost-effective technology. The basic concept used for this purpose is letting float the wells of the MOS transistors most susceptible to initiate latch-up.
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Colleagues, Ladies and Gentlemen. My presence here is due to accidental circumstances and I must confess that I feel a little embarassed by the fact Both your scientific quality and the worlwide acceptance of the results achieved by you in your research fields make me prudent and, to a certain extent, cautious.