Service Oriented Architecture: impacts and challenges of an architecture paradigm change

International audienceAutomotive embedded software has relied on signal-based architecture for a long time. This architecture has proven through the last decades its reliability and ability to address complex systems such as a car embedding several tens of processors.Automotive industry foresees a large introduction of Service Oriented Architecture in the car whereas the technology was initially used by information systems and web applications. A complete change of architecture is clearly a challenge considering the number of heterogeneous actors, the heavy legacy of business and the safety constraints.This paper aims at providing feedbacks on the introduction of SOA in automotive industry through the prism of Software architecture and development team

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Recent studies detected genomic aberrations affecting JAK and STAT genes in T-PLL. Due to the limited number of primary patient samples available, genomic analyses of the JAK/STAT pathway have been performed in rather small cohorts. Therefore, we conducted—via a primary-data based pipeline—a meta-analysis that re-evaluated the genomic landscape of T-PLL. It included all available data sets with sequence information on JAK or STAT gene loci in 275 T-PLL. We eliminated overlapping cases and determined a cumulative rate of 62.1% of cases with mutated JAK or STAT genes. Most frequently, JAK1 (6.3%), JAK3 (36.4%), and STAT5B (18.8%) carried somatic single-nucleotide variants (SNVs), with missense mutations in the SH2 or pseudokinase domains as most prevalent. Importantly, these lesions were predominantly subclonal. We did not detect any strong association between mutations of a JAK or STAT gene with clinical characteristics. Irrespective of the presence of gain-of-function (GOF) SNVs, basal phosphorylation of STAT5B was elevated in all analyzed T-PLL. Fittingly, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses (in 71.4% of T-PLL in total, in 68.4% of T-PLL without any JAK or STAT mutations). They included DUSP4, CD45, TCPTP, SHP1, SOCS1, SOCS3, and HDAC9. Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity. In essence, we present a comprehensive meta-analysis on the highly prevalent genomic lesions that affect genes encoding JAK/STAT signaling components. This provides an overview of possible modes of activation of this pathway in a large cohort of T-PLL. In light of new advances in JAK/STAT inhibitor development, we also outline translational contexts for harnessing active JAK/STAT signaling, which has emerged as a ‘secondary’ hallmark of T-PLL

The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

We describe the design and data sample from the DEEP2 Galaxy Redshift Survey, the densest and largest precision-redshift survey of galaxies at z ~ 1 completed to date. The survey has conducted a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude M_B = -20 at z ~ 1 via ~90 nights of observation on the DEIMOS spectrograph at Keck Observatory. DEEP2 covers an area of 2.8 deg^2 divided into four separate fields, observed to a limiting apparent magnitude of R_AB=24.1. Objects with z < 0.7 are rejected based on BRI photometry in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted ~2.5 times more efficiently than in a purely magnitude-limited sample. Approximately sixty percent of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets which fail to yield secure redshifts are blue objects that lie beyond z ~ 1.45. The DEIMOS 1200-line/mm grating used for the survey delivers high spectral resolution (R~6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. DEEP2 surpasses other deep precision-redshift surveys at z ~ 1 in terms of galaxy numbers, redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the publicly-available DEEP2 DEIMOS data reduction pipelines. [Abridged]Comment: submitted to ApJS; data products available for download at http://deep.berkeley.edu/DR4

Polychromatic guide star: feasibility study

International audienceAdaptive optics at astronomical telescopes aims at correcting in real time the phase corrugations of incoming wavefronts caused by the turbulent atmosphere, as early proposed by Babcock. Measuring the phase errors requires a bright source located within the isoplanatic patch of the program source. The probability that such a reference source exists is a function of the wavelength, of the required image quality (Strehl ratio), of the turbulence optical properties, and of the direction of the observation. It turns out that the sky coverage is disastrously low in particular in the visible wavelength range where, unfortunately, the gain in spatial resolution brought by adaptive optics is the largest. Foy and Labeyrie have proposed to overcome this difficulty by creating an artificial point source in the sky in the direction of the observation relying on the backscattered light due to a laser beam. This laser guide star (hereinafter referred to as LGS) can be bright enough to allow us to accurately measure the wavefront phase errors, except for two modes which are the piston (not relevant in this case) and the tilt. Pilkington has emphasized that the round trip time of the laser beam to the mesosphere, where the LGS is most often formed, is significantly shorter than the typical tilt coherence time; then the inverse-return-of-light principle causes deflections of the outgoing and the ingoing beams to cancel. The apparent direction of the LGS is independent of the tilt. Therefore the tilt cannot be measured only from the LGS. Until now, the way to overcome this difficulty has been to use a natural guide star to sense the tilt. Although the tilt is sensed through the entire telescope pupil, one cannot use a faint source because $APEX 90% of the variance of the phase error is in the tilt. Therefore, correcting the tilt requires a higher accuracy of the measurements than for higher orders of the wavefront. Hence current adaptive optics devices coupled with a LGS face low sky coverage. Several methods have been proposed to get a partial sky coverage for the tilt. The only one providing us with a full sky coverage is the polychromatic LGS (hereafter referred to as PLGS). We present here a progress report of the R&D; program Etoile Laser Polychromatique et Optique Adaptative (ELP-OA) carried out in France to develop the PLGS concept. After a short recall of the principles of the PLGS, we will review the goal of ELP-OA and the steps to get over to bring it into play. We finally shortly described the effort in Europe to develop the LGS

Polychromatic guide star: feasibility study

International audienceAdaptive optics at astronomical telescopes aims at correcting in real time the phase corrugations of incoming wavefronts caused by the turbulent atmosphere, as early proposed by Babcock. Measuring the phase errors requires a bright source located within the isoplanatic patch of the program source. The probability that such a reference source exists is a function of the wavelength, of the required image quality (Strehl ratio), of the turbulence optical properties, and of the direction of the observation. It turns out that the sky coverage is disastrously low in particular in the visible wavelength range where, unfortunately, the gain in spatial resolution brought by adaptive optics is the largest. Foy and Labeyrie have proposed to overcome this difficulty by creating an artificial point source in the sky in the direction of the observation relying on the backscattered light due to a laser beam. This laser guide star (hereinafter referred to as LGS) can be bright enough to allow us to accurately measure the wavefront phase errors, except for two modes which are the piston (not relevant in this case) and the tilt. Pilkington has emphasized that the round trip time of the laser beam to the mesosphere, where the LGS is most often formed, is significantly shorter than the typical tilt coherence time; then the inverse-return-of-light principle causes deflections of the outgoing and the ingoing beams to cancel. The apparent direction of the LGS is independent of the tilt. Therefore the tilt cannot be measured only from the LGS. Until now, the way to overcome this difficulty has been to use a natural guide star to sense the tilt. Although the tilt is sensed through the entire telescope pupil, one cannot use a faint source because $APEX 90% of the variance of the phase error is in the tilt. Therefore, correcting the tilt requires a higher accuracy of the measurements than for higher orders of the wavefront. Hence current adaptive optics devices coupled with a LGS face low sky coverage. Several methods have been proposed to get a partial sky coverage for the tilt. The only one providing us with a full sky coverage is the polychromatic LGS (hereafter referred to as PLGS). We present here a progress report of the R&D; program Etoile Laser Polychromatique et Optique Adaptative (ELP-OA) carried out in France to develop the PLGS concept. After a short recall of the principles of the PLGS, we will review the goal of ELP-OA and the steps to get over to bring it into play. We finally shortly described the effort in Europe to develop the LGS

JAK/STAT-Activating Genomic Alterations Are a Hallmark of T-PLL

T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Recent studies detected genomic aberrations affecting JAK and STAT genes in T-PLL. Due to the limited number of primary patient samples available, genomic analyses of the JAK/STAT pathway have been performed in rather small cohorts. Therefore, we conducted-via a primary-data based pipeline-a meta-analysis that re-evaluated the genomic landscape of T-PLL. It included all available data sets with sequence information on JAK or STAT gene loci in 275 T-PLL. We eliminated overlapping cases and determined a cumulative rate of 62.1% of cases with mutated JAK or STAT genes. Most frequently, JAK1 (6.3%), JAK3 (36.4%), and STAT5B (18.8%) carried somatic single-nucleotide variants (SNVs), with missense mutations in the SH2 or pseudokinase domains as most prevalent. Importantly, these lesions were predominantly subclonal. We did not detect any strong association between mutations of a JAK or STAT gene with clinical characteristics. Irrespective of the presence of gain-of-function (GOF) SNVs, basal phosphorylation of STAT5B was elevated in all analyzed T-PLL. Fittingly, a significant proportion of genes encoding for potential negative regulators of STAT5B showed genomic losses (in 71.4% of T-PLL in total, in 68.4% of T-PLL without any JAK or STAT mutations). They included DUSP4, CD45, TCPTP, SHP1, SOCS1, SOCS3, and HDAC9. Overall, considering such losses of negative regulators and the GOF mutations in JAK and STAT genes, a total of 89.8% of T-PLL revealed a genomic aberration potentially explaining enhanced STAT5B activity. In essence, we present a comprehensive meta-analysis on the highly prevalent genomic lesions that affect genes encoding JAK/STAT signaling components. This provides an overview of possible modes of activation of this pathway in a large cohort of T-PLL. In light of new advances in JAK/STAT inhibitor development, we also outline translational contexts for harnessing active JAK/STAT signaling, which has emerged as a 'secondary' hallmark of T-PLL

Recreational sea fishing in Europe in a global contextParticipation rates, fishing effort, expenditure, and implications for monitoring and assessment

Marine recreational fishing (MRF) is a high-participation activity with large economic value and social benefits globally, and it impacts on some fish stocks. Although reporting MRF catches is a European Union legislative requirement, estimates are only available for some countries. Here, data on numbers of fishers, participation rates, days fished, expenditures, and catches of two widely targeted species were synthesized to provide European estimates of MRF and placed in the global context. Uncertainty assessment was not possible due to incomplete knowledge of error distributions; instead, a semi-quantitative bias assessment was made. There were an estimated 8.7 million European recreational sea fishers corresponding to a participation rate of 1.6%. An estimated 77.6 million days were fished, and expenditure was Euro5.9 billion annually. There were higher participation, numbers of fishers, days fished and expenditure in the Atlantic than the Mediterranean, but the Mediterranean estimates were generally less robust. Comparisons with other regions showed that European MRF participation rates and expenditure were in the mid-range, with higher participation in Oceania and the United States, higher expenditure in the United States, and lower participation and expenditure in South America and Africa. For both northern European sea bass (Dicentrarchus labrax, Moronidae) and western Baltic cod (Gadus morhua, Gadidae) stocks, MRF represented 27% of the total removals. This study highlights the importance of MRF and the need for bespoke, regular and statistically sound data collection to underpin European fisheries management. Solutions are proposed for future MRF data collection in Europe and other regions to support sustainable fisheries management.Institut Francais de Recherche pour l'Exploitation de la Mer; French Ministry of Fisheries Management; Greek National Data Collection Programme; European Commission, Data Collection Framework; Department for Environment, Food and Rural Affairs [MF1221, MF1230, MI001]; Norges Forskningsrad [267808]; State Department of Agriculture, Food Security and Fisheries Mecklenburg-Western Pomerania; Interreg IVa 2 Seas; Dutch Ministry of Economic Affairs; European Fishery Fund; Government of Galicia [ED481B2014/034-0

An international comparative analysis and roadmap to sustainable biosimilar markets

Background: Although biosimilar uptake has increased (at a variable pace) in many countries, there have been recent concerns about the long-term sustainability of biosimilar markets. The aim of this manuscript is to assess the sustainability of policies across the biosimilar life cycle in selected countries with a view to propose recommendations for supporting biosimilar sustainability.Methods: The study conducted a comparative analysis across 17 countries from North America, South America, Asia-Pacific, Europe and the Gulf Cooperation Council. Biosimilar policies were identified and their sustainability was assessed based on country-specific reviews of the scientific and grey literature, validation by industry experts and 23 international and local non-industry experts, and two advisory board meetings with these non-industry experts.Results: Given that European countries tend to have more experience with biosimilars and more developed policy frameworks, they generally have higher sustainability scores than the other selected countries. Existing approaches to biosimilar manufacturing and R&amp;D, policies guaranteeing safe and high-quality biosimilars, exemption from the requirement to apply health technology assessment to biosimilars, and initiatives counteracting biosimilar misconceptions are considered sustainable. However, biosimilar contracting approaches, biosimilar education and understanding can be ameliorated in all selected countries. Also, similar policies are sometimes perceived to be sustainable in some markets, but not in others. More generally, the sustainability of the biosimilar landscape depends on the nature of the healthcare system and existing pharmaceutical market access policies, the experience with biosimilar use and policies. This suggests that a general biosimilar policy toolkit that ensures sustainability does not exist, but varies from country to country.Conclusion: This study proposes a set of elements that should underpin sustainable biosimilar policy development over time in a country. At first, biosimilar policies should guarantee the safety and quality of biosimilars, healthy levels of supply and a level of cost savings. As a country gains experience with biosimilars, policies need to optimise uptake and combat any misconceptions about biosimilars. Finally, a country should implement biosimilar policies that foster competition, expand treatment options and ensure a sustainable market environment

Economic benefits of methylmercury exposure control in Europe : monetary value of neurotoxicity prevention

© 2013 Bellanger et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Due to global mercury pollution and the adverse health effects of prenatal exposure to methylmercury (MeHg), an assessment of the economic benefits of prevented developmental neurotoxicity is necessary for any cost-benefit analysis. Methods: Distributions of hair-Hg concentrations among women of reproductive age were obtained from the DEMOCOPHES project (1,875 subjects in 17 countries) and literature data (6,820 subjects from 8 countries). The exposures were assumed to comply with log-normal distributions. Neurotoxicity effects were estimated from a linear dose-response function with a slope of 0.465 Intelligence Quotient (IQ) point reduction per μg/g increase in the maternal hair-Hg concentration during pregnancy, assuming no deficits below a hair-Hg limit of 0.58 μg/g thought to be safe. A logarithmic IQ response was used in sensitivity analyses. The estimated IQ benefit cost was based on lifetime income, adjusted for purchasing power parity. Results: The hair-mercury concentrations were the highest in Southern Europe and lowest in Eastern Europe. The results suggest that, within the EU, more than 1.8 million children are born every year with MeHg exposures above the limit of 0.58 μg/g, and about 200,000 births exceed a higher limit of 2.5 μg/g proposed by the World Health Organization (WHO). The total annual benefits of exposure prevention within the EU were estimated at more than 600,000 IQ points per year, corresponding to a total economic benefit between €8,000 million and €9,000 million per year. About four-fold higher values were obtained when using the logarithmic response function, while adjustment for productivity resulted in slightly lower total benefits. These calculations do not include the less tangible advantages of protecting brain development against neurotoxicity or any other adverse effects. Conclusions: These estimates document that efforts to combat mercury pollution and to reduce MeHg exposures will have very substantial economic benefits in Europe, mainly in southern countries. Some data may not be entirely representative, some countries were not covered, and anticipated changes in mercury pollution all suggest a need for extended biomonitoring of human MeHg exposure.Exposure data were contributed from the DEMOCOPHES project (LIFE09 ENV/BE/000410) carried out thanks to joint financing of 50% from the European Commission programme LIFE + along with 50% from each participating country (see the national implementation websites accessible via http://www.eu-hbm.info/democophes/project-partners). Special thanks go to the national implementation teams. The COPHES project that provided the operational and scientific framework was funded by the European Community's Seventh Framework Programme - DG Research (Grant Agreement Number 244237). Additional exposure data were supported by the PHIME project (FOOD-CT-2006-016253) and ArcRisk (GA 226534). We are grateful to Yue Gao and colleagues for sharing Flanders exposure data from the Flemish Center of Expertise on Environment and Health, financed and steered by the Ministry of the Flemish Community. National exposure data from the 2006–2007 French national survey on nutrition and health (Etude Nationale Nutrition Santé) were made available by Nadine Fréry, French Institute for Public Health Surveillance. Data from the Norwegian Mother and Child Cohort Study (a validation sample) were kindly provided by Anne Lise Brantsæter, National Institute of Public Health, Oslo. The UK mercury data were obtained from the ALSPAC pregnancy blood analyses carried out at the Centers for Disease Control and Prevention with funding from NOAA (the US National Oceanographic and Atmospheric Administration). The studies in the Faroe Islands were supported by the US National Institutes of Health (ES009797 and ES012199). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies