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.).
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.
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. 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. Although it has been known for many years that the ECM is a key component of the stem cell niche, recent advances in analysis at single-cell resolution have provided new information about the underlying mecha- nisms by which the ECM regulates stem cell behaviour. Different types of ECM interactions trigger cell responses via diverse sensing mechanisms and downstream signalling pathways. Nevertheless, the out- come, stem cell renewal or differentiation, may be the same. In addition, the intrinsic transcriptional or epigenetic state of a cell can influence its interaction with the ECM, potentially rendering it more or less sensitive to niche signals. Looking ahead, it will be interesting to couple some of the individual micro- environmental cues, including topography, ECM composition and stiffness, into more complex substrates that may resemble the pressing need to broaden the range of stem cell types being evaluated and to define more rigorously the stem cell populations that are currently being assayed. It is important to distinguish between cells that are undergo- ing fate switching and selective outgrowth of subpopulations of committed progenitors. By drawing together expertise in cell biol- xxx and bioengineering, it will be possible to improve cell-based therapies in humans59 and create ‘tissue chips’ to accurately model human organs for improved evaluation of drug safety60. In particular, there is a growing realization that for cell therapies to succeed, it may not be sufficient to implant cells into the body, as without an appropriate ECM scaffold they are likely to die or differentiate. Xxxxx X. Xxxx is at the King’s College London Centre for Stem Cells and Regenerative Medicine, 28th floor, Guy’s Tower, Great Maze Pond, e-mails: xxxxx.xxxx@xxx.xx.xx; x.xxxx@xxxxxxx.xx.xx doi:10.1038/nrm3620 Published online 10 July 2013
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. Currently, two highly requested instruments, GIANO-B and HARPS-N, and their combined observing mode, GIARPS
Conclusions and perspectives. Incomplete coverage for uses of copper
Conclusions and perspectives. Conclusions and future perspectives 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)
