246,881 research outputs found

    The influence of knowledge in the replication of routines

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    From a resource-based pespective, one of the most important levers of firm strategy are resources that are difficult to imitate. a crucial challenge for managers then is to replicate these resources wihin the firm, while at the same time protecting them from imitation by competitors. Organizational routines are often named as candidates for such resources. A good understanding of the replication of organizational routines is therefore of great strategic interest. This article focuses on one aspect that seems to play an important role in the replication of routines: knowledge. The objective of this article is to identify knowledge-related aspects that have an influence in the replication of routines. In this and by defining routines in their social and cognitive dimensions, it contributes to a better understanding of their duplication process.

    Fault Tolerance as an aspect using JReplica

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    Reliability and availability are very important trends in the development process of distributed systems. In order to improve these features, object replication mechanisms have been introduced. Programming replication policies for a given application is not an easy task, and this is the reason why transparency for the programmer has been one of the most important properties offered by all replication models. However, this transparency for the programmer is not always desirable. In this paper we present a replication model, JReplica, based on Aspect Oriented Programming (AOP). JReplica allows the separated specification of the replication code from the functional behaviour of objects, providing not only a high degree of transparency, as done by previous models, but also the possibility for programmers to introduce new behaviour to specify different fault tolerance requirements. Moreover, the replication aspect has been introduced at design time, and in this way, UML has been extended in order to consider replication issues separately when designing fault tolerance systems.Comisión Interministerial de Ciencia y Tecnología TIC99-1083-C02-0

    Treating HIV/AIDS patients in India with antiretroviral therapy: a management challenge

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    India stands at a critical junction of HIV pandemic. Controlling spread of HIV is critical. Ignoring this will lead millions of Indians in grip of this pandemic. Ever since HIV/AIDS was acknowledged as a problem, the strategies to address the issue have focused on prevention, treatment and research. This paper discusses the treatment aspect. With currently available antiretroviral agents, eradication of HIV infection is not likely. The aim of treatment is thus to prolong and improve the quality of life by maintaining maximal suppression of virus replication for as long as possible. Brazil has shown how to implement antiretroviral therapy programme. India has embarked upon an ambitious programme to introduce antiretroviral therapy in six high prevalent states and the national capital. The paper discusses the technical, management and financing challenge in implementing this intervention.

    The "enemies within":regions of the genome that are inherently difficult to replicate

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    An unusual feature of many eukaryotic genomes is the presence of regions that appear intrinsically difficult to copy during the process of DNA replication. Curiously, the location of these difficult-to-replicate regions is often conserved between species, implying a valuable role in some aspect of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis. This fragility is particularly apparent following perturbation of DNA replication—a phenomenon often referred to as “replication stress”. Here, we review recent data on the molecular basis for chromosome fragility and the role of fragile sites in the etiology of cancer. In particular, we highlight how studies on fragile sites have provided unexpected insights into how the DNA repair machinery assists in the completion of DNA replication

    The fixation probability of rare mutators in finite asexual populations

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    A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100 fold have been observed to spontaneously emerge and achieve high frequencies in natural populations and in long-term laboratory evolution experiments with \textit{E. coli}. In principle, the fixation of mutator alleles is limited by (i) competition with mutations in wild-type backgrounds, (ii) additional deleterious mutational load, and (iii) random genetic drift. Using a multiple locus model and employing both simulation and analytic methods, we investigate the effects of these three factors on the fixation probability PfixP_{fix} of an initially rare mutator as a function of population size NN, beneficial and deleterious mutation rates, and the strength of mutations ss. Our diffusion based approximation for PfixP_{fix} successfully captures effects (ii) and (iii) when selection is fast compared to mutation (μ/s1\mu/s \ll 1). This enables us to predict the conditions under which mutators will be evolutionarily favored. Surprisingly, our simulations show that effect (i) is typically small for strong-effect mutators. Our results agree semi-quantitatively with existing laboratory evolution experiments and suggest future experimental directions.Comment: 46 pages, 8 figure

    The origins and physical roots of life’s dual – metabolic and genetic – nature

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    This review paper aims at a better understanding of the origin and physical foundation of life’s dual – metabolic and genetic – nature. First, I give a concise ‘top-down’ survey of the origin of life, i.e., backwards in time from extant DNA/RNA/protein-based life over the RNA world to the earliest, pre-RNA stages of life’s origin, with special emphasis on the metabolism-first versus gene/replicator-first controversy. Secondly, I critically assess the role of minerals in the earliest origins of bothmetabolism and genetics. And thirdly, relying on the work of Erwin Schrödinger, Carl Woese and Stuart Kauffman, I sketch and reframe the origin of metabolism and genetics from a physics, i.e., thermodynamics, perspective. I conclude that life’s dual nature runs all the way back to the very dawn and physical constitution of life on Earth. Relying on the current state of research, I argue that life’s origin stems from the congregation of two kinds of sources of negentropy – thermodynamic and statistical negentropy. While thermodynamic negentropy (which could have been provided by solar radiation and/or geochemical and thermochemical sources), led to life’s combustive and/or metabolic aspect, the abundant presence of mineral surfaces on the prebiotic Earth – with their selectively adsorbing and catalysing (thus ‘organizing’) micro-crystalline structure or order – arguably provided for statistical negentropy for life to originate, eventually leading to life’s crystalline and/or genetic aspect. However, the transition from a prebiotic world of relatively simple chemical compounds including periodically structured mineral surfaces towards the complex aperiodic and/or informational structure, specificity and organization of biopolymers and biochemical reaction sequences remains a ‘hard problem’ to solve

    Sub-μ\mu structured Lotus Surfaces Manufacturing

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    Sub-micro structured surfaces allow modifying the behavior of polymer films or components. Especially in micro fluidics a lotus-like characteristic is requested for many applications. Structure details with a high aspect ratio are necessary to decouple the bottom and the top of the functional layer. Unlike to stochastic methods, patterning with a LIGA-mold insert it is possible to structure surfaces very uniformly or even with controlled variations (e.g. with gradients). In this paper we present the process chain to realize polymer sub-micro structures with minimum lateral feature size of 400 nm and up to 4 micrometers high.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

    Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the Late Asymptomatic Phase.

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    Feline immunodeficiency virus (FIV) infection results in viral persistence, a prolonged asymptomatic phase, and progressive immunopathology. During the asymptomatic phase, a cohort of experimentally FIV-infected cats exhibits features of viral latency in blood suggestive of inactive viral replication. We sought to investigate viral replication activity and genomic stability of the FIV proviral long terminal repeat (LTR) and the 5' aspect of gag over time. FIV-infected cats during the asymptomatic phase demonstrated undetectable plasma FIV gag RNA transcripts and intermittent to undetectable blood-derived cell-associated FIV gag RNA. The LTR sequence demonstrated instability in blood-derived cells over time, in spite of low to undetectable viral replication. Sequence variation in the LTR was identified in CD4+ and CD21+ leukocytes from blood and surgically removed lymph nodes. Three single nucleotide polymorphisms (SNPs) in the LTR were commonly identified. Promoter functionality of a common LTR SNP and rare U3 mutation were examined by reporter gene assays and demonstrated either no change or increased basal FIV promoter function, respectively. In conclusion, this cohort of asymptomatic FIV-infected cats demonstrated instability of the LTR and 5' gag sequences during the study period, in spite of undetectable plasma and rare to undetectable viral gag RNA, which suggests that blood may not accurately represent viral activity in asymptomatic FIV-infected cats
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