285 research outputs found

    Assessment of the Quality of Safety Cases: A Research Preview

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    Proceedings of the 25th International Working Conference, REFSQ 2019, Essen, Germany, March 18–21, 2019.[Context and motivation] Safety-critical systems in application domains such as aerospace, automotive, healthcare, and railway are subject to assurance processes to provide confidence that the systems do not pose undue risks to people, property, or the environment. The development of safety cases is usually part of these processes to justify that a system satisfies its safety requirements and thus is dependable. [Question/problem] Although safety cases have been used in industry for over two decades, their management still requires improvement. Important weaknesses have been identified and means to assess the quality of safety cases are limited. [Principal ideas/results] This paper presents a research preview on the assessment of the quality of safety cases. We explain how the area should develop and present our preliminary work towards enabling the assessment with Verification Studio, an industrial tool for system artefact quality analysis. [Contribution] The insights provided allow researchers and practitioners to gain an understanding of why safety case quality requires further investigation, what aspects must be considered, and how quality assessment could be performed in practice.The research leading to this paper has received funding from the AMASS project (H2020-ECSEL ID 692474; Spain’s MINECO ref. PCIN-2015-262). We also thank REFSQ reviewers for their valuable comments to improve the paper

    GaAs nanoscale membranes: prospects for seamless integration of III–Vs on silicon

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    The growth of compound semiconductors on silicon has been widely sought after for decades, but reliable methods for defect-free combination of these materials have remained elusive. Recently, interconnected GaAs nanoscale membranes have been used as templates for the scalable integration of nanowire networks on III-V substrates. Here, we demonstrate how GaAs nanoscale membranes can be seamlessly integrated on silicon by controlling the density of nuclei in the initial stages of growth. We also correlate the absence or presence of defects with the existence of a single or multiple nucleation regime for the single membranes. Certain defects exhibit well-differentiated spectroscopic features that we identify with cathodoluminescence and micro-photoluminescence techniques. Overall, this work presents a new approach for the seamless integration of compound semiconductors on silicon

    Synergistic Binding of bHLH Transcription Factors to the Promoter of the Maize NADP-ME Gene Used in C4 Photosynthesis Is Based on an Ancient Code Found in the Ancestral C3 State.

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    C4 photosynthesis has evolved repeatedly from the ancestral C3 state to generate a carbon concentrating mechanism that increases photosynthetic efficiency. This specialized form of photosynthesis is particularly common in the PACMAD clade of grasses, and is used by many of the world's most productive crops. The C4 cycle is accomplished through cell-type-specific accumulation of enzymes but cis-elements and transcription factors controlling C4 photosynthesis remain largely unknown. Using the NADP-Malic Enzyme (NADP-ME) gene as a model we tested whether mechanisms impacting on transcription in C4 plants evolved from ancestral components found in C3 species. Two basic Helix-Loop-Helix (bHLH) transcription factors, ZmbHLH128 and ZmbHLH129, were shown to bind the C4NADP-ME promoter from maize. These proteins form heterodimers and ZmbHLH129 impairs trans-activation by ZmbHLH128. Electrophoretic mobility shift assays indicate that a pair of cis-elements separated by a seven base pair spacer synergistically bind either ZmbHLH128 or ZmbHLH129. This pair of cis-elements is found in both C3 and C4 Panicoid grass species of the PACMAD clade. Our analysis is consistent with this cis-element pair originating from a single motif present in the ancestral C3 state. We conclude that C4 photosynthesis has co-opted an ancient C3 regulatory code built on G-box recognition by bHLH to regulate the NADP-ME gene. More broadly, our findings also contribute to the understanding of gene regulatory networks controlling C4 photosynthesis

    Mifepristone Prevents Stress-Induced Apoptosis in Newborn Neurons and Increases AMPA Receptor Expression in the Dentate Gyrus of C57/BL6 Mice

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    Chronic stress produces sustained elevation of corticosteroid levels, which is why it is considered one of the most potent negative regulators of adult hippocampal neurogenesis (AHN). Several mood disorders are accompanied by elevated glucocorticoid levels and have been linked to alterations in AHN, such as major depression (MD). Nevertheless, the mechanism by which acute stress affects the maturation of neural precursors in the dentate gyrus is poorly understood. We analyzed the survival and differentiation of 1 to 8 week-old cells in the dentate gyrus of female C57/BL6 mice following exposure to an acute stressor (the Porsolt or forced swimming test). Furthermore, we evaluated the effects of the glucocorticoid receptor (GR) antagonist mifepristone on the cell death induced by the Porsolt test. Forced swimming induced selective apoptotic cell death in 1 week-old cells, an effect that was abolished by pretreatment with mifepristone. Independent of its antagonism of GR, mifepristone also induced an increase in the percentage of 1 week-old cells that were AMPA+. We propose that the induction of AMPA receptor expression in immature cells may mediate the neuroprotective effects of mifepristone, in line with the proposed antidepressant effects of AMPA receptor potentiators

    Long -term feeding with high plant protein based diets in gilthead seabream (Sparus aurata, L.) leads to changes in the inflammatory and immune related gene expression at intestinal level

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    [EN] Background: In order to ensure sustainability of aquaculture production of carnivourous fish species such as the gilthead seabream (Sparus aurata, L.), the impact of the inclusion of alternative protein sources to fishmeal, including plants, has been assessed. With the aim of evaluating long-term effects of vegetable diets on growth and intestinal status of the on-growing gilthead seabream (initial weight = 129 g), three experimental diets were tested: a strict plant protein-based diet (VM), a fishmeal based diet (FM) and a plant protein-based diet with 15% of marine ingredients (squid and krill meal) alternative to fishmeal (VM+). Intestines were sampled after 154 days. Besides studying growth parameters and survival, the gene expression related to inflammatory response, immune system, epithelia integrity and digestive process was analysed in the foregut and hindgut sections, as well as different histological parameters in the foregut. Results: There were no differences in growth performance (p = 0.2703) and feed utilization (p = 0.1536), although a greater fish mortality was recorded in the VM group (p = 0.0141). In addition, this group reported a lower expression in genes related to pro-inflammatory response, as Interleukine-1 beta (il1 beta, p = 0.0415), Interleukine-6 (il6, p = 0.0347) and cyclooxigenase-2 (cox2, p = 0.0014), immune-related genes as immunoglobulin M (igm, p = 0.0002) or bacterial defence genes as alkaline phosphatase (alp, p = 0.0069). In contrast, the VM+ group yielded similar survival rate to FM (p = 0.0141) and the gene expression patterns indicated a greater induction of the inflammatory and immune markers (il1 beta, cox2 and igm). However, major histological changes in gut were not detected. Conclusions: Using plants as the unique source of protein on a long term basis, replacing fishmeal in aqua feeds for gilthead seabream, may have been the reason of a decrease in the level of different pro-inflammatory mediators (il1 beta, il6 and cox2) and immune-related molecules (igm and alp), which reflects a possible lack of local immune response at the intestinal mucosa, explaining the higher mortality observed. Krill and squid meal inclusion in vegetable diets, even at low concentrations, provided an improvement in nutrition and survival parameters compared to strictly plant protein based diets as VM, maybe explained by the maintenance of an effective immune response throughout the assay.The research has been partially funded by Vicerrectorat d'Investigacio, Innovacio i Transferencia of the Universitat Politecnica de Valencia, which belongs to the project Aquaculture feed without fishmeal (SP20120603). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.Estruch-Cucarella, G.; Collado, MC.; Monge-Ortiz, R.; Tomas-Vidal, A.; Jover Cerdá, M.; Peñaranda, D.; Perez Martinez, G.... (2018). Long -term feeding with high plant protein based diets in gilthead seabream (Sparus aurata, L.) leads to changes in the inflammatory and immune related gene expression at intestinal level. BMC Veterinary Research. 14. https://doi.org/10.1186/s12917-018-1626-6S14Hardy RW. Utilization of plant proteins in fish diets: effects of global demand and supplies of fishmeal. Aquac Res. 2010;41:770–6.Martínez-Llorens S, Moñino AV, Vidal AT, Salvador VJM, Pla Torres M, Jover Cerdá M, et al. Soybean meal as a protein source in gilthead sea bream (Sparus aurata L.) diets: effects on growth and nutrient utilization. Aquac Res. 2007;38(1):82–90.Tacon AGJ, Metian M. 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    Non-invasive ventilation (NIV) as an aid to rehabilitation in acute respiratory disease

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    <p>Abstract</p> <p>Background</p> <p>Non-invasive ventilation (NIV) can increase exercise tolerance, reduce exercise induced desaturation and improve the outcome of pulmonary rehabilitation in patients with chronic respiratory disease. It is not known whether it can be applied to increase exercise capacity in patients admitted with non-hypercapnic acute exacerbations of COPD (AECOPD). We investigated the acceptability and feasibility of using NIV for this purpose.</p> <p>Methods</p> <p>On a single occasion, patients admitted with an acute exacerbation of chronic respiratory disease who were unable to cycle for five minutes at 20 watts attempted to cycle using NIV and their endurance time (T<sub>lim</sub>) was recorded. To determine feasibility of this approach in clinical practice patients admitted with AECOPD were screened for participation in a trial of regular NIV assisted rehabilitation during their hospital admission.</p> <p>Results</p> <p>In 12 patients tested on a single occasion NIV increased T<sub>lim </sub>from 184(65) seconds to 331(229) seconds (p = 0.04) and patients desaturated less (median difference = 3.5%, p = 0.029). In the second study, 60 patients were admitted to hospital during a three month period of whom only 18(30)% were eligible to participate and of these patients, only four (7%) consented to participate.</p> <p>Conclusion</p> <p>NIV improves exercise tolerance in patients with acute exacerbations of chronic respiratory disease but the applicability of this approach in routine clinical practice may be limited.</p> <p>Trial registration</p> <p><url>http://www.controlled-trials.com/ISRCTN35692743</url></p

    Bronchiolitis: an update on management and prophylaxis.

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    Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children less than 2 years of age in the UK. Respiratory syncytial virus is the most common virus associated with bronchiolitis and has the highest disease severity, mortality and cost. Bronchiolitis is generally a self-limiting condition, but can have serious consequences in infants who are very young, premature, or have underlying comorbidities. Management of bronchiolitis in the UK is guided by the National Institute for Health and Care Excellence (2015) guidance. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Pharmacological interventions including nebulized bronchodilators, steroids and antibiotics generally have limited or no evidence of efficacy and are not advised by National Institute of Health and Care Excellence. Antiviral therapeutics remain in development. As treatments are limited, there have been extensive efforts to develop vaccines, mainly targeting respiratory syncytial virus. At present, the only licensed product is a monoclonal antibody for passive immunisation. Its cost restricts its use to those at highest risk. Vaccines for active immunisation of pregnant women and young infants are also being developed

    Differential overexpression of SERPINA3 in human prion diseases

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    Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans
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