Preliminary survey of 21st century civil mission applications of space nuclear power

The purpose was to collect and categorize a forecast of civilian space missions and their power requirements, and to assess the suitability of an SP-100 class space reactor power system to those missions. A wide variety of missions were selected for examination. The applicability of an SP-100 type of nuclear power system was assessed for each of the selected missions; a strawman nuclear power system configuration was drawn up for each mission. The main conclusions are as follows: (1) Space nuclear power in the 50 kW sub e plus range can enhance or enable a wide variety of ambitious civil space mission; (2) Safety issues require additional analyses for some applications; (3) Safe space nuclear reactor disposal is an issue for some applications; (4) The current baseline SP-100 conical radiator configuration is not applicable in all cases; (5) Several applications will require shielding greater than that provided by the baseline shadow-shield; and (6) Long duration, continuous operation, high reliability missions may exceed the currently designed SP-100 lifetime capabilities

Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2

<p>Abstract</p> <p>Background</p> <p>The HIV-1 accessory protein Nef is an important determinant of lentiviral pathogenicity that contributes to disease progression by enhancing viral replication and other poorly understood mechanisms. Nef mediates diverse functions including downmodulation of cell surface CD4 and MHC Class I, enhancement of viral infectivity, and enhancement of T cell activation. Nef interacts with a multiprotein signaling complex that includes Src family kinases, Vav1, CDC42, and activated PAK2 (p21-activated kinase 2). Although previous studies have attempted to identify a biological role for the Nef-PAK2 signaling complex, the importance of this complex and its constituent proteins in Nef function remains unclear.</p> <p>Results</p> <p>Here, we show that Nef mutants defective for PAK2-association, but functional for CD4 and MHC Class I downmodulation and infectivity enhancement, are also defective for the ability to enhance viral replication in primary T cells that are infected and subsequently activated by sub-maximal stimuli (1 μg/ml PHA-P). In contrast, these Nef mutants had little or no effect on HIV-1 replication in T cells activated by stronger stimuli (2 μg/ml PHA-P or anti-CD3/CD28-coated beads). Viruses bearing wild-type Nefs, but not Nef mutants defective for PAK2 association, enhanced NFAT and IL2 receptor promoter activity in Jurkat cells. Moreover, expression of wild-type Nefs, but not mutant Nefs defective for PAK2 association, was sufficient to enhance responsiveness of primary CD4 and CD8 T cells to activating stimuli in Nef-expressing and bystander cells. siRNA knockdown of PAK2 in Jurkat cells reduced NFAT activation induced by anti-CD3/CD28 stimulation both in the presence and absence of Nef, and expression of a PAK2 dominant mutant inhibited Nef-mediated enhancement of CD25 expression.</p> <p>Conclusion</p> <p>Nef-mediated enhancement of cellular activation and viral replication in primary T cells is dependent on PAK2 and on the strength of the activating stimuli, and correlates with the ability of Nef to associate with PAK2. PAK2 is likely to play a role in Nef-mediated enhancement of viral replication and immune activation <it>in vivo</it>.</p

Rejection of randomly coinciding events in ZnMoO4_4 scintillating bolometers

Random coincidence of events (particularly from two neutrino double beta decay) could be one of the main sources of background in the search for neutrinoless double beta decay with cryogenic bolometers due to their poor time resolution. Pulse-shape discrimination by using front edge analysis, mean-time and $\chi^2$ methods was applied to discriminate randomly coinciding events in ZnMoO$_4$ cryogenic scintillating bolometers. These events can be effectively rejected at the level of 99% by the analysis of the heat signals with rise-time of about 14 ms and signal-to-noise ratio of 900, and at the level of 92% by the analysis of the light signals with rise-time of about 3 ms and signal-to-noise ratio of 30, under the requirement to detect 95% of single events. These rejection efficiencies are compatible with extremely low background levels in the region of interest of neutrinoless double beta decay of $^{100}$Mo for enriched ZnMoO$_4$ detectors, of the order of $10^{-4}$ counts/(y keV kg). Pulse-shape parameters have been chosen on the basis of the performance of a real massive ZnMoO$_4$ scintillating bolometer. Importance of the signal-to-noise ratio, correct finding of the signal start and choice of an appropriate sampling frequency are discussed

Longevity Risk Management and Shareholder Value for a Life Annuity Business

The life annuity business is heavily exposed to longevity risk. Risk transfer solutions are not yet fully developed, and when available they are expensive. A significant part of the risk must therefore be retained by the life insurer. So far, most of the research work on longevity risk has been mainly concerned with capital requirements and specific risk transfer solutions. However, the impact of longevity risk on shareholder value also deserves attention. While it is commonly accepted that a market-consistent valuation should be performed in this respect, the definition of a fair shareholder value for a life insurance business is not trivial. In this paper we develop a multi-period market-consistent shareholder value model for a life annuity business. The model allows for systematic and idiosyncratic longevity risk and includes the most significant variables affecting shareholder value: the cost of capital (which in a market-consistent setting must be quantified in terms of frictional and agency costs, net of the value of the limited liability put option), policyholder demand elasticity and the cost of alternative longevity risk management solutions, namely indemnity-based and index-based solutions. We show how the model can be used for assessing the impact of different longevity risk management strategies on life insurer shareholder value and solvency

Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

BACKGROUND: Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron. METHODS: The literature was searched using Medline and all reports addressing the effect of either chelator on hepatic iron were considered. Data were abstracted independently by two investigators. Analyses were performed using reported individual patient data. Hepatic iron concentrations at study end and changes over time were compared using ANCOVA, controlling for initial iron load. Differences in the proportions of patients improving were tested using χ(2). RESULTS: Eight of 11 reports identified provided patient-level data relating to 30 desferrioxamine- and 68 deferiprone-treated patients. Desferrioxamine was more likely than optimal dose deferiprone to decrease hepatic iron over the average follow-up of 45 months (odds ratio, 19.0, 95% CI, 2.4 to 151.4). The degree of improvement was also larger with desferrioxamine. CONCLUSIONS: This analysis suggests that desferrioxamine is more effective than deferiprone in lowering hepatic iron. This comparative analysis – despite its limitations – should prove beneficial to physicians faced with the challenge of selecting the optimal treatment for their patients

Are there functional consequences of a reduction in selenium intake in UK subjects?

Dietary Se levels in the UK have fallen over the last 20 years and recent surveys indicate that average Se intakes are 30-40 microg/d, which is well below the current UK reference nutrient intake for adult men (75 microg/d) or women (60 microg/d). Functional consequences of this decline have not been recognised, although epidemiological data suggest it may contribute to increased risk of infections and incidence of some cancers. Previous data have indicated that biochemical changes in Se-dependent proteins occur in otherwise healthy UK subjects given small Se supplements. The current studies have focused on the effect of small Se supplements on the immune response since there is evidence of specific interactions between Se intake and viral replication, and since the potential anti-cancer effects of Se may be mediated by non-antioxidant effects of Se such as changes in immune function. Data indicate that subjects given small Se supplements (50 or 100 microg Se/d) have changes in the activity of Se-dependent enzymes and evidence of improved immune function and clearance of an administered live attenuated virus in the form of poliovirus vaccine. Responses of individual subjects to Se supplements are variable, and current work is evaluating potential explanations for this variability, including genetic variability and pre-existing Se status

Análisis de Ciclo de Vida para el ecodiseño del sistema Intemper TF de cubierta ecológica aljibe

The construction industry is one of the less sustainable activities on the planet: with a consumption of 40% of the materials entering the global economy and the generation of 40–50% of the global output of greenhouse gases. The biggest environmental impact caused by buildings is generated during their use phase due to the energy consumption for thermal conditioning. Addition of green elements to buildings is used to improve energy efficiency of buildings. In this study Life Cycle Assessment (LCA) methodology has been applied to quantify the environmental impact of the green roofs materials to analyze its environmental profile. The identification of hot spots of the system permits an ecodesign strategy that effectively reduces environmental burdens associated with roof construction, optimizing the environmental performance. The results identify the high environmental impact associated to the structure, the important contribution of the felt wick irrigation system and the extruded polystyrene thermal insulation.El sector de la construcción representa una de las actividades menos sostenibles del planeta: consume el 40% de los materiales de la economía global y genera el 40-50% de las emisiones de gases de efecto invernadero. El mayor impacto ambiental de los edificios se genera durante su fase de uso, debido al gasto energético de su acondicionamiento térmico. El uso de elementos vegetales es una de las estrategias empleadas para aumentar la eficiencia energética. En este trabajo se ha empleado la metodología de Análisis de Ciclo de Vida (ACV) para cuantificar el impacto ambiental de los materiales de la cubierta vegetal. Se han identificado los puntos críticos del sistema para establecer una estrategia de ecodiseño y reducir eficazmente las cargas ambientales. Los resultados obtenidos muestran la importancia del impacto ambiental del soporte estructural, la elevada contribución de la mecha de riego de fieltro y del aislamiento de poliestireno extrudido

Macrophage-Derived Biomarkers of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a severe, rapidly progressive diffuse lung disease. Several pathogenetic mechanisms have been hypothesized on the basis of the fibrotic lung damage occurring in this disease, and a potential profibrotic role of activated alveolar macrophages and their mediators in the pathogenesis of IPF was recently documented. This paper focuses on recent literature on potential biomarkers of IPF derived from activated alveolar macrophages. Biomarker discovery and clinical application are a recent topic of interest in the field of interstitial lung diseases (ILDs). Cytokines, CC-chemokines, and other macrophage-produced mediators are the most promising prognostic biomarkers. Many molecules have been proposed in the literature as potential biomarker of IPF; however, a rigorous validation is needed to confirm their clinical utility