352 research outputs found

    Applying Organizational Routines in understanding organizational change

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    Organizational routines are considered basic components of organizational behavior and repositories of Organizational capabilities (Nelson and Winter, 1982). They do, therefore, hold one of the keys to understanding organizational change. We identify problems encountered in such research and present proposal for how to deal with them, in order to advance our knowledge of routines and our understanding or organizational change. Developing these themes, we also introduce the articles in the special section 'Towards an Operationalization of the Routines concept'.

    Development of Single- and Double-sided Ladders for the ILD Vertex Detectors

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    We discuss two projects exploring the integration of thin CMOS pixel sensors in order to prototype ladders matching the geometry needed for the ILD vertex detector. The PLUME project has designed and fabricated full-size and fully functional double- sided layers which currently reach 0.6 % X0 and aim for 0.3 % X0 in mid-2012. Another approach, SERNWIETE, consists in wrapping the sensors in a polyimide-based micro-cable to obtain a supportless single-sided ladder with a material budget around 0.15 % X0. First promising samples have been produced and the full-size prototype is expected in spring 2012.Comment: International Workshop on Future Linear Colliders, LCWS 2011, Granada, Spain, 2011, 26-30 Septembe

    Modification of the mycobacteriophage Ms6 attP core allows the integration of multiple vectors into different tRNA(ala )T-loops in slow- and fast-growing mycobacteria

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    BACKGROUND: Mycobacteriophage Ms6 integrates into Mycobacterium smegmatis and M. bovis BCG chromosome at the 3' end of tRNA(ala )genes. Homologous recombination occurs between the phage attP core and the attB site located in the T-loop. Integration-proficient vectors derived from Ms6 are useful genetic tools, but their insertion sites in the BCG chromosome remain poorly defined. The primary objective of this study was to identify Ms6 target genes in M. smegmatis and BCG. We then aimed to modify the attP site in Ms6-derived vectors, to switch integration to other tRNA(ala )loci. This provided the basis for the development of recombinant M. bovis BCG strains expressing several reporter genes inserted into different tRNA(ala )genes. RESULTS: The three tRNA(ala )genes are highly conserved in M. smegmatis and BCG. However, in the T-loop of tRNA(alaU )and tRNA(alaV )containing the attB site, a single base difference was observed between the two species. We observed that the tRNA(alaU )gene was the only site into which Ms6-derived integration-proficient vectors integrated in M. smegmatis, whereas in BCG, the tRNA(alaV )gene was used as the target. No integration occurred in the BCG tRNA(alaU )T-loop, despite a difference of only one base from the 26-base Ms6 attP core. We mutated the attP core to give a perfect match with the other tRNA(ala )T-loops from M. smegmatis and BCG. Modification of the seven-base T-loop decreased integration efficiency, identifying this site as a possible site of strand exchange. Finally, two Ms6 vectors were constructed to integrate two reporter genes into the tRNA(alaU )and tRNA(alaV )T-loops of the same BCG chromosome. CONCLUSION: Small changes in the 7 bp T-loop attP site of Ms6 made it possible to use another attB site, albeit with a lower integration efficiency. These molecular studies on BCG tRNA(ala )genes made it possible to create valuable tools for the site-directed insertion of several genes in the same BCG strain. These tools will be useful for the development of novel multivalent vaccines and genetic studies

    Worms and the treatment of inflammatory bowel disease: are molecules the answer?

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    The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of IBD in the developed world. Epidemiological, experimental, and clinical data sustain the idea that helminths could provide protection against IBD. Studies investigating the underlying mechanisms by which helminths might induce such protection have revealed the importance of regulatory pathways, for example, regulatory T-cells. Further investigation on how helminths influence both innate and adaptive immune reactions will shed more light on the complex pathways used by helminths to regulate the hosts immune system. Although therapy with living helminths appears to be effective in several immunological diseases, the disadvantages of a treatment based on living parasites are explicit. Therefore, the identification and characterization of helminth-derived immunomodulatory molecules that contribute to the protective effect could lead to new therapeutic approaches in IBD and other immune diseases

    Bibliotheca antigua de los escritores aragoneses que florecieron desde la venida de Christo hasta el año 1500

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    Sign.: [ ]4, [asterisco]-2[asterisco]4, 3[asterisco]2, Aa-Zz4AntepLas h. de grab. calc., la primera es retrato de D. Felix de Latassa, entre port. y anteport. ; la segunda es escudo heráldico de D. Juan Martin de Goycoechea y Ciordia, a quien se dedica la obr

    Status of the Micro Vertex Detector of the Compressed Baryonic Matter Experiment

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    The CBM experiment will investigate heavy-ion collisions at beam energies from 8 to 45 AGeV at the future accelerator facility FAIR. The goal of the experiment is to study the QCD phase diagram in the vincinity of the QCD critical point. To do so, CBM aims at measuring rare probes among them open charm. In order to identify those rare and short lived particles despite the rich combinatorial background generated in heavy ion collisions, a micro vertex detector (MVD) providing an unprecedented combination of high rate capability and radiation hardness, very light material budget and excellent granularity is required. In this work, we will discuss the concept of this detector and summarize the status of the R&D

    Towards a macroscope : leveraging technology to transform the breadth, scale and resolution of macroecological data

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    M.D. is grateful for support from the Templeton Foundation (grant #60501, “Putting the Extended Evolutionary Synthesis to the Test”) and from a Leverhulme Trust Fellowship.The problem Earth‐based observations of the biosphere are spatially biased in ways that can limit our ability to detect macroecological patterns and changes in biodiversity. To resolve this problem, we need to supplement the ad hoc data currently collected with planned biodiversity monitoring, in order to approximate global stratified random sampling of the planet. We call this all‐encompassing observational system ‘the macroscope’. The solution With a focus on the marine realm, we identify seven main biosphere observation tools that compose the macroscope: satellites, drones, camera traps, passive acoustic samplers, biologgers, environmental DNA and human observations. By deploying a nested array of these tools that fills current gaps in monitoring, we can achieve a macroscope fit for purpose and turn these existing powerful tools into more than the sum of their parts. An appeal Building a macroscope requires commitment from many fields, together with coordinated actions to attract the level of funding required for such a venture. We call on macroecologists to become advocates for the macroscope and to engage with existing global observation networks.PostprintPeer reviewe

    Validation of risk scores for allograft failure after liver transplantation in Germany: a retrospective cohort analysis

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    A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region
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