Conclusions and perspectives. This deliverable reports on the work done in year one about designing a measurement methodology based both on a state of the art and a state of practice. In this process, we came through a number of problems that we detail hereafter. These are considered as critical, as they might prevent a successful deployment of our measurement methodology. Moreover, they are critical for providing evidence of the impact of formal engineering methods in industrial domains. Two major difficulties are the following: Confidentiality: for marketing purpose, most of the industrial partners have very strict confidentiality policy regarding their own defect rate, quality, etc. This will considerably restrict our ability to perform measurement regarding e.g. dependability. Another consequence is that only very restricted comparison work can be done. Reaching the production team: the currently involved teams are mainly from R&D, so lessons learned from the measurements will have to be validated in the real context of production teams. Such a deployment will be only partly possible and only for some industrial partners. Despite these difficulties, some baseline information could be identified and a measurable set of metrics were provided by the industrial, especially at design level. In addition to this, the measurement workpackage can also give evidence on the factors for adoption of formal engineering methods and in priority for avoiding all “no go” conditions. Such conditions were also identified in the state of practice. Transferability, with its training and tool dimensions seems to be a key issue for adoption of formal methods in industry. Those conditions will also become part of the scope of the measurement workpackage and can rely on some direct monitoring. Appropriate techniques have been described and some work related to this is reported in the training and tooling part of the WP13 yearly assessment deliverable. This report also discussed the development of metrics for formal specification. This proved a more challenging task as the state of the art showed little pre-existing work. An initial set of metrics has been defined, but a deeper understanding of the Event-B language and application of formal methodology is required to define higher level metrics really helping the analyst. This work will be carried out more experimentally together with the development of the related measurement tool, specified in deliverable D10.
Conclusions and perspectives. In this paper, we have studied the impact of a pricing agreement between service and content providers on the Internet users. We have evaluated this impact by mod- eling the system with a hierarchical game in which Inter- net users, called subscribers, split their demand (download traffic) from several content providers depending on costs. Those costs depend on the preference (which depends on the congestion at each CP) and an access price paid to the con- tent provider. At the upper-layer of the hierarchical game, the content providers compete through their prices in or- der to maximize their own revenue. Our first main result is that introducing agreements between service and content providers, causes an impact on the cost perceived by the Internet users. Therefore, it also brings an impact to the revenue of the content providers. In fact, we have proved that such agreements have a positive effect for the Internet users and a negative effect on the content providers. Based on these interesting results, we can think about several ex- tensions. First, we can also introduce quality of service con- trolled by the content provider and/or the service provider. Second we can do again all our computation in the case of an elastic demand.
Conclusions and perspectives. In this chapter, the read alignment algorithm REAL was used to study the ex- pression patterns of isochores and to add to the evidence linking gene expression to the local base composition. To this end, the first transcriptome map of the mouse focused on isochores was produced, for three distinct tissues from adult individuals (brain, liver, muscle) and for two developmental stages of one of these tissues (brain at embryonic day 18 and post-natal day 7) [170, 171]. It is also the first time NGS data has been used for this purpose. The connection between composition and expression has been criticised and questioned, as different methodologies have lead to varying and conflicting re- sults [123, 126, 135, 153, 157]. Much of the controversy stems from the method- ologies used [157]. This study used whole–genome RNA-seq data, which is a more comprehensive and objective method than previously used ones and adds conclusive evidence that there is in fact a positive correlation between the iso- chore composition and the expression level of both genes and entire isochores, as well as a subtle but definite connection between isochore composition and the breadth of gene expression and also between isochore composition and the developmental timing of expression. It has been proposed that the compart- mentalization of the genome into isochores acts as a large–scale gene regulation mechanism acting at the level of chromatin structure [141, 143]. This hypothe- sis offers a plausible and attractive mechanism for the regulation of collocated groups of genes that are not required in all tissues or at all stages of an organ- ism’s or cell’s life. The results of this study can be explained by this hypothesis, but other explanations may also apply. This work also highlights that the correlation between expression and compo- sition is complex and at least partly indirect, with other features that correlate with the composition also being responsible, such as the gene density. In fact, the compartmentalization of the genome into isochores correlates with a large number of features, many of which can affect expression (methylation patterns, different regulatory elements, different functional roles of the genes, chromatin structure), as discussed already, and the causative relationships connecting all these features with one another remain unclear. Thus, more research needs to be directed in deducing how isochores evolved and, more crucially, how the var- ious correlated feature...
Conclusions and perspectives. Incomplete coverage for uses of copper Among the fifty or so uses of copper in France, eleven are partially covered by microbial biocontrol products currently approved for use in France. This coverage is “partial”, because many uses of copper are broad in nature (corresponding to several or even many different pathogens), whereas the effectiveness of biological control organisms is often specific to one or a few pathogens. Moreover, five of the eleven uses are covered by a single product, which could pose problems for the longevity of the product effectiveness. Nineteen additional uses have the potential to be partially covered if products already on the market elsewhere in the EU or elsewhere in the world receive approval for use in France. However, their actual utility as a replacement for copper in France will depend on their efficacy under French production conditions. In some countries, notably in North America, a demonstration of product efficacy is not required for regulatory approval, contrary to the situation in Europe. It is thus possible that some products approved for use in other countries would not receive approval for market introduction in Europe.
Conclusions and perspectives. Currently, two highly requested instruments, GIANO-B and HARPS-N, and their combined observing mode, GIARPS XXXXXXX and NICS available for Gravitational Waves follow-up programs SiFAP2 expected to play a key role in fast photometry (PI Instrument) BATMAN in stand-by mode TNG staff deeply involved in building the WEAVE archive TNG staff (minor) participation in SOXS (visible detector WP) New ideas welcome Working group of instrumentation at the Roque de los Muchachos Observatory
Conclusions and perspectives. Besides their numerous applications in electronic devices, organic materials present a large interest for fundamental investigations of the electrical trans- port mechanisms, as many of these processes are still under discussion. Par- ticularly, the charge injection and charge carrier transport processes in poorly conducting materials are still disputable. Some experimental results point to different possible interpretations and, in some cases, the experimental proce- dures do not allow one to really distinguish between different theoretical mod- els. In this context, using non-conventional tools and methods might bring new insight. We proposed to study these phenomena by means of single- molecule spectroscopy, which is expected to give access to local information at the nanometer scale. In Chapter 2 of this thesis, we studied the photophysics of single terrylene molecules in an anthracene crystal. We showed that the intersystem-crossing can be dramatically enhanced by an intermolecular mechanism when the triplet of the host is in between the singlet and the triplet of the guest. Shifting the energy levels of the chromophore with respect to the matrix, we proposed another guest-host system, which consisted of dibenzoterrylene molecules in an anthracene crystal. We studied the photophysics of these chromophores (Chapter 3) as well as their insertion into the Ac crystal (Chapter 4). This system is very favourable for single-molecule spectroscopy at cryogenic temper- atures, with intense and narrow zero-phonon lines and a very low intersystem- crossing yield. Two dominant insertion sites were found and attributed to the replacement of three molecules of anthracene by one of dibenzoterrylene, almost oriented along the ’b’-axis of the crystal. Finally, we investigated the Stark effect, which turned out to have a strong quadratic component. − We then studied the anthracene field-effect transistor. The obtained I V characterisations follow a power law, which is typical for trap-filling in the space-charge limited conduction regime. We extrapolated a value of the mo- bility and plotted it as a function of temperature (ranging from 4.2 to 290 K). Below 10 K, the mobility reaches a temperature independent plateau, indicat- ing a tunnelling regime. Compared to other systems, the values of the mobility obtained for the anthracene field-effect transistor at low temperatures are rea- sonable and show a substantial amount of mobile charges inside the crystal, indicating ...
Conclusions and perspectives. Conclusions and future perspectives This section presents conclusions and suggestions for future improvements related to the content presented in each chapter. Furthermore, a more general perspective for optimizing and applying metabolomics-based workflows in drug development and clinical studies is discussed. System pharmacology-based strategies, which analyze multiscale networks of disease dynamics and drug action, have shown great value in better understanding pathology and drug action mechanisms. Metabolism-centric methods are frequently used to build and analyze these networks, by connecting metabolic pathways with other omics layers related to the generation of metabolites and/or modulation of their concentrations. In this context, metabolomics-based methods are key to unravel the metabolic pathways involved in disease dynamics and drug action, which represent the foundations of these networks. In this thesis, state-of-the-art metabolomics-based workflows were developed to enable the profiling of metabolites from a wide range of metabolic pathways related to the endocannabinoid system (ECS). The developed workflows were validated for application to a large diversity of biological matrices and used to explore the potential roles of ECS in cardiometabolic health, as well as the mechanisms underlying the positive effects of exercise for cardiometabolic health. Chapter 2 describes the development of a liquid chromatography - mass spectrometry (LC- MS) worklfow, which enables the identification and quantitation of a large number of N- acyl-phosphatidylethanolamines (NAPEs), plasmalogen-NAPEs (pNAPEs), 2-lyso-N- acyl-phosphatidylethanolamines (lyso-NAPEs), glycerol-phospho-acylethanolamines (GP- NAEs), lyso-pNAPEs, N-acylethanolamines (NAEs), diacylglycerols (DAGs), 2-acyl- glycerols (2-AcGs), and free fatty acids (FFAs) in mice brain. Typically, due to their large difference in lipophilicity, these metabolites are measured using multiple runs, which is time consuming. The method described in Chapter 2 relies on the use of a ternary gradient during the chromatographic separation, which enables the resolution of all these metabolites and, in turn, accurate quantitation. Unlike traditional identification methods mostly guided by the fragmentation pattern of analytes, a novel approach based on the retention time (RT) mapping was used for the identification of these metabolites. Using a limited number of (internal) standards, this strategy increased the confid...
Conclusions and perspectives. The French mining law specifically addresses geothermal licensing. It provides for a two-step process requiring an exploration and a production license. In addition, a work permit must be obtained for each work carried out during any of these two phases that can have an environmental impact (drilling, stimulation, etc.). In the framework of this licensing and permitting process, room is left for the geothermal licensing authority to consider all the varied issues that may stem from a geothermal project, including the induced seismicity that may be generated. In this respect, the licensing authority may impose conditions upon geothermal developers to mitigate any adverse effect that may occur. This power entrusted to the geothermal licensing authority ensures that the project fulfils legal, environmental and public acceptance requirements. It should be noted that a public inquiry is organised for each work permit. In this context, the French authorities intend to conduct a reform of mining law. The scope of the reform is not yet known. It is unlikely however that the specific issue of induced seismicity will be of concern, as it is efficiently dealt with in the existing configuration of the licensing system. The reform shall rather deal with better public information (which was, for work permits, lighter for oil & gas than for geothermal and which is not organised for the exploration and production licences); it should also include some further regulatory relief for shallow geothermal projects, qualified as being of ‘minimum significance’, to be understood as being unlikely to have adverse environmental impacts. For the time being, the regulation of these operations is unclear an not appropriate to develop the geothermal applications for the heating and cooling of buildings.
Conclusions and perspectives. The European indicator presented here is based on two metrics representative of the fish abundance. Therefore, it follows partly the requirement of the Water Framework Directive (WFD; 2000/60/EC) since species composition and age structure were not included yet (Annex V 1.2.1 of this directive). Nevertheless, potential abundance fish metrics could also be added in a near future. To do that, more analyses are required, particularly on rules of metrics’ aggregation. Similarly, responses of metrics based on size structure to environmental parameters are currently under analyses by the lake fish group. The interest of the two metrics proposed (CPUE and BPUE) is that they could be easily calculated by the member state and permit an intercalibration at the European scale. Another interesting point could be comparing the data obtained by hydroacoustics and those by gillnetting. The hindcasting model has proved, in our dataset, to be a relevant method for the development of an assessment tool. This method will be used to select metrics responding to pressures on the reservoirs included in the database and on the low species richness lakes. Later, analyse of fish communities of the lakes sampled with other types of multimesh gillnets (included in the database) could also be tried in case no fish based ecological assessment methods were available in the countries using these non standardised sampling protocols. ANNEX 1 Assignment of the 70 fish species (present in the dataset) into reproductive, trophic and habitat guilds used to derive community traits. Two classifications were used, one with a binary code (a) and one with the name (b).
Conclusions and perspectives. In the attempt to strengthen financial discipline and stability in the Euro-zone beyond the Six-Pack, the Draft International Agreement takes the right direc- tion. But it seems to be insufficient with regard to the structural problems of the EMU to be solved in order to bring the crisis to an end and to setting up a sustainable framework for the functioning of the Euro, for stability and growth and economic and social cohesion in the Union (infra 1.). The Agreement seems to be superfluous, on the other hand, with regard to some measures, 10 Case C-70/88 – European Parliamen v. Council (Tschernobyl), para 21 to 27. which could be taken by secondary law (infra 2.). Some of the measures meet serious doubts as to their compliance with the Treaties (infra 3.). With a view to enhancing the effectiveness and democratic legitimacy of the measures en- visage in the Draft, certain questions should be considered (infra. 4.).
