A Lightweight Multilevel Markup Language for Connecting Software Requirements and Simulations

[Context] Simulation is a powerful tool to validate specified requirements especially for complex systems that constantly monitor and react to characteristics of their environment. The simulators for such systems are complex themselves as they simulate multiple actors with multiple interacting functions in a number of different scenarios. To validate requirements in such simulations, the requirements must be related to the simulation runs. [Problem] In practice, engineers are reluctant to state their requirements in terms of structured languages or models that would allow for a straightforward relation of requirements to simulation runs. Instead, the requirements are expressed as unstructured natural language text that is hard to assess in a set of complex simulation runs. Therefore, the feedback loop between requirements and simulation is very long or non-existent at all. [Principal idea] We aim to close the gap between requirements specifications and simulation by proposing a lightweight markup language for requirements. Our markup language provides a set of annotations on different levels that can be applied to natural language requirements. The annotations are mapped to simulation events. As a result, meaningful information from a set of simulation runs is shown directly in the requirements specification. [Contribution] Instead of forcing the engineer to write requirements in a specific way just for the purpose of relating them to a simulator, the markup language allows annotating the already specified requirements up to a level that is interesting for the engineer. We evaluate our approach by analyzing 8 original requirements of an automotive system in a set of 100 simulation runs

Das GRADE-System: Ein internationaler Ansatz zur Vereinheitlichung der Graduierung von Evidenz und Empfehlungen in Leitlinien

Zusammenfassung: Leitlinien haben sich für Ärzte und Patienten zu einer wichtigen Stütze bei diagnostischen und therapeutischen Entscheidungen entwickelt. Um die aktuell verfügbaren methodischen Konzepte der Leitlinienentwicklung zu harmonisieren und die große Heterogenität und oft mangelnde Transparenz existierender Systeme zu überwinden, hat die GRADE (Grading of Recommendations, Assessment, Development and Evaluation) Working Group, eine internationale Kollaboration von Leitlinienentwicklern, Klinikern und Methodikern, die vorhandenen Konzepte weiterentwickelt. Zentrale Bestandteile des GRADE-Systems sind die Unterscheidung zwischen der Qualität der Evidenz und der Stärke einer Empfehlung, die gleichzeitige Betrachtung von Nutzen und Schaden einer Intervention, die Fokussierung auf patientenrelevante Endpunkte, die Abbildung von inhärenten Wertvorstellungen einer Empfehlung und die Integration von Überlegungen zum Ressourcenverbrauch. Unter Berücksichtigung dieser Kriterien werden mit dem GRADE-System starke und abgeschwächte Empfehlungen abgegeben. International befürworten zahlreiche Leitlinienorganisationen und medizinische Fachgesellschaften das System und haben es für die Erstellung der eigenen Leitlinien übernomme

Dogs distinguish human intentional and unintentional action

When dogs interact with humans, they often show appropriate reactions to human intentional action. But it is unclear from these everyday observations whether the dogs simply respond to the action outcomes or whether they are able to discriminate between different categories of actions. Are dogs able to distinguish intentional human actions from unintentional ones, even when the action outcomes are the same? We tested dogs’ ability to discriminate these action categories by adapting the so-called “Unwilling vs. Unable” paradigm. This paradigm compares subjects’ reactions to intentional and unintentional human behaviour. All dogs received three conditions: In the unwilling-condition, an experimenter intentionally withheld a reward from them. In the two unable-conditions, she unintentionally withheld the reward, either because she was clumsy or because she was physically prevented from giving the reward to the dog. Dogs clearly distinguished in their spontaneous behaviour between unwilling- and unable-conditions. This indicates that dogs indeed distinguish intentional actions from unintentional behaviour. We critically discuss our findings with regard to dogs’ understanding of human intentional action.Results - Analysis of waiting - Other behavioural reactions Discussion Methods - Ethical statement - Subjects - Experimental set‑up - Procedure - Codin

Nuclear Resonance Vibrational Spectroscopy of Iron Sulfur Proteins

Nuclear inelastic scattering in conjunction with density functional theory (DFT) calculations has been applied for the identification of vibrational modes of the high-spin ferric and the high-spin ferrous iron-sulfur center of a rubredoxin-type protein from the thermophylic bacterium Pyrococcus abysii

Improving the use of research evidence in guideline development: 13. Applicability, transferability and adaptation

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the thirteenth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on applicability, transferability, and adaptation of guidelines. METHODS: We searched five databases for existing systematic reviews and relevant primary methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We used the definition "coming from, concerning or belonging to at least two or all nations" for the term international. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not identify systematic reviews addressing the key questions. We found individual studies and projects published in the peer reviewed literature and on the Internet. Should WHO develop international recommendations? • Resources for developing high quality recommendations are limited. Internationally developed recommendations can facilitate access to and pooling of resources, reduce unnecessary duplication, and involve international scientists. • Priority should be given to international health problems and problems that are important in low and middle-income countries, where these advantages are likely to be greatest. • Factors that influence the transferability of recommendations across different settings should be considered systematically and flagged, including modifying factors, important variation in needs, values, costs and the availability of resources. What should be done centrally and locally? • The preparation of systematic reviews and evidence profiles should be coordinated centrally, in collaboration with organizations that produce systematic reviews. Centrally developed evidence profiles should be adaptable to specific local circumstances. • Consideration should be given to models that involve central coordination with work being undertaken by centres located throughout the world. • While needs, availability of resources, costs, the presence of modifying factors and values need to be assessed locally, support for undertaking these assessments may be needed to make guidelines applicable. • WHO should provide local support for adapting and implementing recommendations by developing tools, building capacity, learning from international experience, and through international networks that support evidence-informed health policies, such as the Evidence-informed Policy Network (EVIPNet). How should recommendations be adapted? • WHO should provide detailed guidance for adaptation of international recommendations. • Local adaptation processes should be systematic and transparent, they should involve stakeholders, and they should report the key factors that influence decisions, including those flagged in international guidelines, and the reasons for any modifications that are made

A thylakoid membrane-bound and redox-active rubredoxin (RBD1) functions in de novo assembly and repair of photosystem II.

Photosystem II (PSII) undergoes frequent photooxidative damage that, if not repaired, impairs photosynthetic activity and growth. How photosynthetic organisms protect vulnerable PSII intermediate complexes during de novo assembly and repair remains poorly understood. Here, we report the genetic and biochemical characterization of chloroplast-located rubredoxin 1 (RBD1), a PSII assembly factor containing a redox-active rubredoxin domain and a single C-terminal transmembrane α-helix (TMH) domain. RBD1 is an integral thylakoid membrane protein that is enriched in stroma lamellae fractions with the rubredoxin domain exposed on the stromal side. RBD1 also interacts with PSII intermediate complexes containing cytochrome b 559 Complementation of the Chlamydomonas reinhardtii (hereafter Chlamydomonas) RBD1-deficient 2pac mutant with constructs encoding RBD1 protein truncations and site-directed mutations demonstrated that the TMH domain is essential for de novo PSII assembly, whereas the rubredoxin domain is involved in PSII repair. The rubredoxin domain exhibits a redox midpoint potential of +114 mV and is proficient in 1-electron transfers to a surrogate cytochrome c in vitro. Reduction of oxidized RBD1 is NADPH dependent and can be mediated by ferredoxin-NADP+ reductase (FNR) in vitro. We propose that RBD1 participates, together with the cytochrome b 559, in the protection of PSII intermediate complexes from photooxidative damage during de novo assembly and repair. This role of RBD1 is consistent with its evolutionary conservation among photosynthetic organisms and the fact that it is essential in photosynthetic eukaryotes

Importance of correlation effects in hcp iron revealed by a pressure-induced electronic topological transition

We discover that hcp phases of Fe and Fe0.9Ni0.1 undergo an electronic topological transition at pressures of about 40 GPa. This topological change of the Fermi surface manifests itself through anomalous behavior of the Debye sound velocity, c/a lattice parameter ratio and M\"ossbauer center shift observed in our experiments. First-principles simulations within the dynamic mean field approach demonstrate that the transition is induced by many-electron effects. It is absent in one-electron calculations and represents a clear signature of correlation effects in hcp Fe

Beverage specific alcohol intake in a population-based study: Evidence for a positive association between pulmonary function and wine intake

BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA. METHODS: We expressed pulmonary function as percent of predicted normal FEV(1) (FEV(1)%) and FVC (FVC%) after adjustment for height, age, gender and race. To obtain information on alcohol intake we used a questionnaire that reliably queries total alcohol and beverage specific recent (past 30 days) and lifetime alcohol consumption. Results: Using multiple linear regression analysis after adjustment for covariates (pack-years of smoking, weight, smoking status, education, nutritional factors and for FEV(1)%, in addition, eosinophil count), we observed no significant correlation between total alcohol intake and lung function. However, we found positive associations of recent and lifetime wine intake with FEV(1)% and FVC%. When we analyzed white and red wine intake separately, the association of lung function with red wine was weaker than for white wine. CONCLUSION: While total alcohol intake was not related to lung function, wine intake showed a positive association with lung function. Although we cannot exclude residual confounding by healthier lifestyle in wine drinkers, differential effects of alcoholic beverages on lung health may exist

Generation of maghemite nanocrystals from iron–sulfur centres

Iron oxide nano-crystals 0.1–1.1 μm in diameter were generated on sulfur-doped amorphous carbon surfaces by electron beam irradiation of the novel 13e− high-spin complex [Fe(4-methyl-1,2-benzenedithiolate)2][NHEt3] encapsulated in a triblock copolymer. Possible relevance to iron nano-mineralization from Fe–S ferredoxin proteins and iron dysregulation in neurological disorders is discussed. Graphical abstract: Generation of maghemite nanocrystals from iron–sulfur centres Iron is an essential element for mammals and, amongst many other functions, plays an important role in the human brain.1 Recent research has indicated a strong association between iron dysregulation and Alzheimer's disease (AD), although it is unknown how the chemical and magnetic state of iron is linked to AD pathogenesis.2–4 Reports from Collingwood et al., and Dobson et al., for example, have shown the presence of iron oxide as the mixed oxidation state mineral, magnetite (Fe3O4) in AD tissue, a possible source of redox-active iron, but it remains unclear how this kind of iron mineral forms in the tissue.5,6 These unsolved and important questions have led us to consider how atomic resolution microscopy might provide new insight into nanoscale iron mineralization. Recently we reported methodology for studies of the nano-mineralisation of osmium, gold, ruthenium and iridium from their respective 1,2-dicarba-closo-dodecarborane-1,2-dithiolate complexes encapsulated in polymer micelles upon electron beam irradiation.7–9 Here we report the synthesis and characterization of the novel 13e− iron(iii) complex [Fe(4-methyl-1,2-benzenedithiolate)2][NHEt3] (1), containing Fe–S bonds analogous to those in the ubiquitous iron–sulfur ferredoxin proteins. Importantly, recent research has indicated a strong relationship between neurodegenerative disorders and defective Fe–S clusters.10,11 We have characterized complex 1 using Mössbauer, Raman and far-infra red spectroscopy, and investigated the generation of iron nanocrystals from 1 encapsulated in a poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) polymer (Scheme 1) by electron beam irradiation, and used electron energy-loss spectra (EELS) to identify the oxidation state of iron and its coordination environment in the nanocrystals