1,133 research outputs found

    Aplicabilidad de las TIG en la generación de escenarios de futuro para una gestión integrada de las zonas costeras

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    Para una planificación y gestión coherente de las zonas costeras es fundamental que exista una profunda comprensión de las interacciones entre el hombre y el medio físico, siendo preciso integrar la información sobre el conocimiento del medio natural aportada por las diferentes disciplinas científicas, junto con la información del contexto socio-económico, normativo y cultural. Por tanto, la toma de decisiones en los espacios litorales debe apoyarse en instrumentos interdisciplinares, capaces de operar con distintos tipos de datos y abordar situaciones complejas e impredecibles. La simulación de escenarios es una importante herramienta para evaluar desarrollos futuros en sistemas complejos y dinámicos que poseen un número alto de incertidumbres, y por ello es una técnica muy adecuada para la gestión de las zonas costeras. Los escenarios permiten integrar modelos socioeconómicos con modelos físicos, químicos o biológicos, reflejar una amplia gama de tendencias y dinámicas, y trabajar con distintas escalas temporales y espaciales. En el presente artículo se examina el uso actual y el potencial de las TIG en la generación de escenarios de futuro para la gestión integrada de las zonas costeras. Para ello se ha realizado un análisis de su aplicabilidad de las TIG, identificando en qué fases de la elaboración de escenarios se pueden utilizar. Los resultados indican que estas tecnologías tienen un alto potencial y son aplicables en todas las fases de la generación de los escenarios. Una de las fortalezas identificadas es que las TIG incrementan la transparencia y fiabilidad de la generación de escenarios de futuro facilitando los procesos equitativos y participativos de negociación, toma de decisiones y planificación en las zonas costeras.To achieve a coherent planning and management of coastal areas it is necessary having a deep understanding of the interactions existing between human-being and the physical environment, integrating information from different scientific disciplines (hydrology, morphodynamics, soil science, ecology, etc.) and socio-economic, normative and cultural context information. Therefore decision-making in coastal areas must be based on interdisciplinaryinstruments capable of working with different type of data and dealing with complex and unpredictable situations. Scenario-making is one of the most important tools for assessing future developments in complex and dynamic systems which have a high number of uncertainties; thus it is a very suitable approach for coastal zone management. Scenarios can integrate socio-economic models with physical, chemical or biological models, reflect a broad range of trends and dynamics, and work with different temporal and spatial scales. In this paper the current and potential use of Geographical Information Technologies (GIT) is examined in the generation of future scenarios for an integrated management of coastal areas. An analysis of the applicability of the GIT has been done, identifying at which stage of scenario development GIT can be used. The results indicate that GIT have great potential and are applicable at all stages of the scenarios generation. One of the strengths identified is that GIT increase the transparency and reliability of the generation of future scenarios and facilitate equitable and participatory processes of negotiation, decision making and planning in coastal areas

    Type I Interferon Sensitizes Lymphocytes to Apoptosis and Reduces Resistance to Listeria Infection

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    Infection with Listeria monocytogenes causes lymphocyte apoptosis that is mediated by the actions of the pore-forming virulence factor listeriolysin O (LLO). Previous work showed that activated lymphocytes were highly sensitive to LLO-induced apoptosis, whereas resting lymphocytes were less susceptible. We now show that mice deficient in the type I interferon (IFN) receptor were more resistant to Listeria infection and had less apoptotic lesions than wild-type counterparts. Furthermore, treatment of resting splenic lymphocytes with recombinant IFN-αA enhanced their susceptibility to LLO-induced apoptosis. Together, these data suggest that type I IFN signaling is detrimental to handling of a bacterial pathogen and may enhance the susceptibility of lymphocytes undergoing apoptosis in response to bacterial pore-forming toxins

    Lymphocytes are detrimental during the early innate immune response against Listeria monocytogenes

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    Mice deficient in lymphocytes are more resistant than normal mice to Listeria monocytogenes infection during the early innate immune response. This paradox remains unresolved: lymphocytes are required for sterilizing immunity, but their presence during the early stage of the infection is not an asset and may even be detrimental. We found that lymphocyte-deficient mice, which showed limited apoptosis in infected organs, were resistant during the first four days of infection but became susceptible when engrafted with lymphocytes. Engraftment with lymphocytes from type I interferon receptor–deficient (IFN-αβR−/−) mice, which had reduced apoptosis, did not confer increased susceptibility to infection, even when the phagocytes were IFN-αβR+/+. The attenuation of innate immunity was due, in part, to the production of the antiinflammatory cytokine interleukin 10 by phagocytic cells after the apoptotic phase of the infection. Thus, immunodeficient mice were more resistant relative to normal mice because the latter went through a stage of lymphocyte apoptosis that was detrimental to the innate immune response. This is an example of a bacterial pathogen creating a cascade of events that leads to a permissive infective niche early during infection

    Resident macrophages of pancreatic islets have a seminal role in the initiation of autoimmune diabetes of NOD mice

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    Significance Our studies indicate that the resident macrophages of the pancreatic islets of Langerhans have a seminal role in the initiation and progression of autoimmune diabetes in NOD mice. In this study, islet macrophages were depleted by administration of a monoclonal antibody to the CSF-1 receptor. Macrophage depletion, either at the start of the autoimmune process or when diabetogenesis is active, leads to a significant reduction in diabetes incidence. Depletion of the islet macrophages reduces the entrance of T cells into islets and results in the absence of antigen presentation. Concordantly, a regulatory pathway develops that controls diabetes progression. We conclude that treatments that target the islet macrophages may have important clinical relevance for the control of autoimmune type 1 diabetes.</jats:p

    Recombinant Listeria monocytogenes expressing a cell wall-associated listeriolysin O is weakly virulent but immunogenic

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    Listeriolysin O (LLO) is an essential virulence factor for the gram-positive bacterium Listeria monocytogenes. Our goal was to determine if altering the topology of LLO would alter the virulence and toxicity of L. monocytogenes in vivo. A recombinant strain was generated that expressed a surface-associated LLO (sLLO) variant secreted at 40-fold-lower levels than the wild type. In culture, the sLLO strain grew in macrophages, translocated to the cytosol, and induced cell death. However, the sLLO strain showed decreased infectivity, reduced lymphocyte apoptosis, and decreased virulence despite a normal in vitro phenotype. Thus, the topology of LLO in L. monocytogenes was a factor in the pathogenesis of the infection and points to a role of LLO secretion during in vivo infection. The sLLO strain was cleared by severe combined immunodeficient (SCID) mice. Despite the attenuation of virulence, the sLLO strain was immunogenic and capable of eliciting protec-tive T-cell responses. Listeria monocytogenes is a gram-positive facultative intra-cellular pathogen extensively used to understand host-patho-gen interactions (44, 51, 53). It expresses the highly conserved pore-forming toxin listeriolysin O (LLO), a member of a large family of cholesterol-dependent cytolysins found in many im

    A fully automated flow injection atomic absorption system for the determination of copper traces in waters with on-line pre-concentration in an ion-exchange column

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    The paper describes the development of an automatic on-line column pre-concentration technique using a time based-flow injection atomic absorption spectrometry system. A manifold incorporating a micro-column containing 25 mg of Dowex 50W-X8 was used with a time-based injector for the pre-concentration and determination of copper in natural and drinking waters. The system features depend on the alternate positions of a solenoid valve. The 3σ detection limits, enrichment factors, sampling frequency, relative standard deviations and linear calibration graphs were, respectively, in the range 0.6-1.5 μg/l, 25-60, 15-30 measurements/h, 1.0-3.1% and 1-65 μg/ml for pre-concentration times of 1 min. The procedure was successfully applied to a range of water samples and the accuracy was assessed through recovery experiments, the analysis of certified reference water samples and by independent analysis by atomic absorption spectrometry with electrothermal atomization

    Nuclear Reaction Rates in a Plasma

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    The problem of determining the effects of the surrounding plasma on nuclear reaction rates in stars is formulated ab initio, using the techniques of quantum statistical mechanics. We derive a result that expresses the complete effects of Coulomb barrier penetration and of the influence of the surrounding plasma in terms of matrix elements of well defined operators. We find that possible "dynamical screening" effects that have been discussed in the literature are absent. The form of our results suggests that an approach that relies on numerical calculations of the correlation functions in a classical Coulomb gas, followed by construction of an effective two body potential and a quantum barrier penetration calculation, will miss physics that is as important as the physics that it includes.Comment: 66 pages, revtex, Errors Fixed, Explanation Adde

    Listeriolysin O Is Strongly Immunogenic Independently of Its Cytotoxic Activity

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    The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC) molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC) as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000–7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10–100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells

    Health Care Resource Utilization and Related Costs of Patients With CKD From the United States: A Report From the DISCOVER CKD Retrospective Cohort

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    Introduction: It is well established that chronic kidney disease (CKD) results in a significant burden on patients’ health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers. Methods: Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60−75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR. Results: Overall health care costs ranged from 26,889(A1)to26,889 (A1) to 42,139 (A3), and from 28,627(G2)to28,627 (G2) to 42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure (50,191[A3])andthosecoveredbycommercialpayers(50,191 [A3]) and those covered by commercial payers (55,735 [A3]). Conclusions: Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers
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