Effective methodologies to derive strategic decisions from ESA technology roadmaps

Top priorities in future international space exploration missions regard the achievement of the necessary matura-tion of enabling technologies, thereby allowing Europe to play a role commensurate with its industrial, operational and scientific capabilities. As part of the actions derived from this commitment, ESA Technology Roadmaps for Exploration represent a powerful tool to prioritise R&D activities in technologies for space exploration and support the preparation of a consistent procurement plan for space exploration technologies in Europe. The roadmaps illus-trate not only the technology procurement (to TRL-8) paths for specific missions envisaged in the present timeframe, but also the achievement for Europe of technological milestones enabling operational capabilities and building blocks, essential for current and future Exploration missions. Coordination of requirements and funding sources among all European stakeholders (ESA, EU, National, Industry) is one of the objectives of these roadmaps, that show also possible application of the technologies beyond space exploration, both at ESA and outside. The present paper describes the activity that supports the work on-going at ESA on the elaboration and update of these roadmaps and related tools, in order to criticise the followed approach and to suggest methodologies of assessment of the Roadmaps, and to derive strategic decision for the advancement of Space Exploration in Europe. After a review of Technology Areas, Missions/Programmes and related building blocks (architectures) and operational capabilities, technology applicability analyses are presented. The aim is to identify if a specific technology is required, applicable or potentially a demonstrator in the building blocks of the proposed mission concepts. In this way, for each technology it is possible to outline one or more specific plans to increase TRL up to the required level. In practice, this translates into two possible solutions: on the one hand, approved mission concepts will be complemented with the required technologies if the latter can be considered as applicable or demo; on the other, if they are neither applicable nor demo, new missions, i.e. technology demonstrators based on multidisciplinary grouping of key technologies, shall be evaluated, so as to proceed through incremental steps. Finally, techniques to determine priorities in technology procurement are identified, and methodologies to rank the required technologies are proposed. In addition, a tool that estimates the percentage of technologies required for the final destination that are implementable in each intermediate destination of the incremental approach is presented

High efficiency regional aircraft conceptual design and on-board systems preliminary study

A conceptual design of a new regional plane has been performed, investigating the application of the three lifting surfaces configuration and laminar fuselage on a larger aircraft. On-board systems have subsequently been sized and their installation validated in a CAD model. Finally, a flight simulation has been executed comparing the new design against a traditional regional aircraft, demonstrating its potential benefit on fuel consumption

Unexpected interfarm transmission dynamics during a highly pathogenic avian influenza epidemic

Next-generation sequencing technology is now being increasingly applied to study the within- and between-host population dynamics of viruses. However, information on avian influenza virus evolution and transmission during a naturally occurring epidemic is still limited. Here, we use deep-sequencing data obtained from clinical samples collected from five industrial holdings and a backyard farm infected during the 2013 highly pathogenic avian influenza (HPAI) H7N7 epidemic in Italy to unravel (i) the epidemic virus population diversity, (ii) the evolution of virus pathogenicity, and (iii) the pathways of viral transmission between different holdings and sheds. We show a high level of genetic diversity of the HPAI H7N7 viruses within a single farm as a consequence of separate bottlenecks and founder effects. In particular, we identified the cocirculation in the index case of two viral strains showing a different insertion at the hemagglutinin cleavage site, as well as nine nucleotide differences at the consensus level and 92 minority variants. To assess interfarm transmission, we combined epidemiological and genetic data and identified the index case as the major source of the virus, suggesting the spread of different viral haplotypes from the index farm to the other industrial holdings, probably at different time points. Our results revealed interfarm transmission dynamics that the epidemiological data alone could not unravel and demonstrated that delay in the disease detection and stamping out was the major cause of the emergence and the spread of the HPAI strain

Selective Recognition of Neutral Guests in an Aqueous Medium by a Biomimetic Calix[6]cryptamide Receptor

The design of artificial receptors that can efficiently work in water is a challenging research area. A possible biomimetic approach for the elaboration of such receptors consists of associating a hydrophobic cavity with a polar polyfunctional binding site. On this basis, a hydrophilic calix[6]cryptamide decorated with oligo(ethylene glycol) units (i.e.) was synthesized through an efficient [1 + 1] macrocyclization reaction as the key-step. The complexation of neutral molecules was evaluated by NMR spectroscopy through competition experiments either in apolar or aqueous media. In both media, host can bind neutral species that display H-bonding acceptor and donor groups such as amides or ureas. Interestingly, the most polar and acidic molecule is the best guest in chloroform and the worst one in an aqueous medium, highlighting the importance of the environment. As shown by NMR and X-ray diffraction data, the mode of recognition involves a complementary DAAAD-ADDDA quintuple H-bonding array between the binding partners as well as multiple CH-π interactions. A comparison of this calix[6]arene-based host-guest system with the binding site of biotin-binding proteins shows strong similarities. Besides, the acid-base control of the binding properties of receptor in aqueous media is highly reminiscent of allosteric processes encountered in natural systems.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Injectable bone-graft substitute for in vivo tissue regeneration

We have demonstrated that using growth factors we can induce the proliferation of human primary osteoblasts but it isn’t enough to form new bone that need also the differentiation of the proliferated osteoblasts [1]. Being these two steps regulated by different pathways and different stimuli, in the same work we have found the combination of a proliferating growth factor (FGF2) with a differentiating stimulus (1,25Vit D3) as an optimal solution. With the aim to develop an injectable medicated scaffold which speeds bone formation in sinus lift augmentation, in bony void and in fracture repair, we have tested in vitro osteoblasts’ behavior in a 3D jelly collagen model (1mg/ml) using soluble native collagen prepared from rat tail tendons [2]. We have seen an osteoblasts’ Rho-kinase mediated contraction of the collagen that causes an approach of bone fragments within a week of culture with the formation of a fibrous bone tissue within 3 weeks of culture. FGF2 addition to the collagen fastened this result by increasing cell proliferation rate while the addition of 1,25Vit D3 to collagen at a concentration of 0,1 mg/mL that shows at HPLC analysis a release of 0,26 mcg/ ml/day during the incubation time studied, favors the mineralization of the new formed tissue that shows also increased tensile strenght. We think that this combination of factors could be used in vivo to accelerate bone growth and fracture healing

A Gut-Ex-Vivo System to Study Gut Inflammation Associated to Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease (IBD) is a complex, chronic, and dysregulated inflammatory condition which etiology is still largely unknown. Its prognosis and disease progression are highly variable and unpredictable. IBD comprises several heterogeneous inflammatory conditions ranging from Ulcerative Colitis (UC) to Crohn's Disease (CD). Importantly, a definite, well-established, and effective clinical treatment for these pathologies is still lacking. The urgent need for treatment is further supported by the notion that patients affected by UC or CD are also at risk of developing cancer. Therefore, a deeper understanding of the molecular mechanisms at the basis of IBD development and progression is strictly required to design new and efficient therapeutic regimens. Although the development of animal models has undoubtedly facilitated the study of IBD, such in vivo approaches are often expensive and time-consuming. Here we propose an organ ex vivo culture (Gut-Ex-Vivo system, GEVS) based on colon from Balb/c mice cultivated in a dynamic condition, able to model the biochemical and morphological features of the mouse models exposed to DNBS (5-12 days), in 5 h. Indeed, upon DNBS exposure, we observed a dose-dependent: (i) up-regulation of the stress-related protein transglutaminase 2 (TG2); (ii) increased intestinal permeability associated with deregulated tight junction protein expression; (iii) increased expression of pro-inflammatory cytokines, such as TNFα, IFNγ, IL1β, IL6, IL17A, and IL15; (iv) down-regulation of the anti-inflammatory IL10; and (v) induction of Endoplasmic Reticulum stress (ER stress), all markers of IBD. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of IBD, in a time- and cost-effective manner

Differential Effects of Dabigatran and Warfarin on Bone Volume and Structure in Rats with Normal Renal Function

Background: Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin) and Matrix Gla Protein (MGP). Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification. Methods: Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically. Results: Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries. Conclusions: These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients.This study was supported by a grant form Boehringer-Ingelheim Pharma, Germany (manufacturer of Dabigatran). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript