SPaCIFY: a Formal Model-Driven Engineering for Spacecraft On-Board Software

International audienceThe aim of this article is to present a model- driven approach proposed by the SPaCIFY project for spacecraft on-board software development. This ap- proach is based on a formal globally asynchronous lo- cally synchronous language called Synoptic, and on a set of transformations allowing code generation and model verification

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Threshold/Seuil/Soglia

Il tema scelto per la collaborazione tra due istituzioni europee, solo apparentemente lontane geograficamente e culturalmente, è stato la soglia, o meglio il limen, il poroso confine tra interno ed esterno di un edificio, invitando a ripensare gli infissi a partire dal concetto di “finestra arredata” formulato da Gio Ponti. Un tema divenuto centrale nel progetto contemporaneo, grazie anche alle possibilita offerte dall’uso di attrezzature mobili in grado di ridefinire le gerarchie degli spazi interni. L’insieme dinamico delle esigenze degli utenti di tutti i tipi ambienti suggerisce, infatti, nuove considerazioni su come l’elemento costruttivo possa essere ripensato aggiungendo nuove performance a quelle tradizionali. Finestre, porte, balconi, logge possono diventare cornici per guardare il paesaggio, specchi per catturare la luce, dispositivi per produrre energia, elementi per ombreggiare o per isolare dal rumore o depurare l’aria. Inoltre, possono arrivare a trasformarsi in nuovi volumi: e questo il caso delle “serre abitate” proposte da Umberto Riva, ma anche di alcune riflessioni di Ettore Sottsass sulla possibile evoluzione dell’infisso fino a raggiungere le tre dimensioni. Tali soglie possono integrare le prestazioni per lo spazio interno (monitor, scaffali, librerie) o registrare le condizioni climatiche esterne, confrontandole con quelle interne. Luoghi di piacevole permanenza, potrebbero anche liberare gli ambienti da altri elementi, mostrando nuovi assetti distributivi. La prima parte del Workshop e stata sviluppata in Belgio, la seconda in Italia a Napoli; qui l’attenzione si e concentrata su alcuni edifici del quartiere operaio di via Cocchia a Bagnoli, databile agli inizi del Novecento e adiacente la vasta area all’epoca occupata dall’industria siderurgica ILVA. A differenza delle altre vicine, le palazzine selezionate erano state spogliate delle caratteristiche decorazioni, consentendo cosi al gruppo di studiare nuove soglie, raccogliendo le differenti sollecitazioni dei quattro fronti che affacciano rispettivamente sulla strada, non particolarmente trafficata, sul panorama del magnifico golfo di Pozzuoli, sui giardinetti di quartiere e sul condominio vicino. L’interesse dell’iniziativa e gli incoraggianti risultati stimolano noi tutti curiosi ricercatori a proseguire in tale direzione confortati dall’entusiasmo e l’impegno dei partecipanti

A Novel Mechanism of Inactivating Antibacterial Nitro Compounds in the Human Pathogen Staphylococcus aureus by Overexpression of a NADH-Dependent Flavin Nitroreductase

Recently, the nitro-substituted bisquaternary bisnaphthalimides were reported to have substantial anti-infective activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Here, we selected resistant S. aureus clones by cultivation in increasing concentrations of the most active compound, MT02. Interestingly, MT02-resistant variants induced a diffusible red color of the broth. Chromatographic and spectroscopic investigations revealed a stepwise reduction of the bisquaternary bisnaphthalimides' nitro groups to amino groups. The corresponding derivatives were completely inactive against staphylococci. RNA sequencing experiments revealed a strong overexpression of a novel oxidoreductase in MT02-resistant strains. Deletion mutants of this enzyme did not produce the red color and were not able to develop resistance against bisquaternary bisnaphthalimides. Biochemical reactions confirmed an NADH-dependent deactivation of the nitro-substituted compounds. Thus, this is the first report of a nitroreductase-based antibiotic resistance mechanism in the human pathogen S. aureus