A generic framework for context-sensitive analysis of modular programs

Context-sensitive analysis provides information which is potentially more accurate than that provided by context-free analysis. Such information can then be applied in order to validate/debug the program and/or to specialize the program obtaining important improvements. Unfortunately, context-sensitive analysis of modular programs poses important theoretical and practical problems. One solution, used in several proposals, is to resort to context-free analysis. Other proposals do address context-sensitive analysis, but are only applicable when the description domain used satisfies rather restrictive properties. In this paper, we argüe that a general framework for context-sensitive analysis of modular programs, Le., one that allows using all the domains which have proved useful in practice in the non-modular setting, is indeed feasible and very useful. Driven by our experience in the design and implementation of analysis and specialization techniques in the context of CiaoPP, the Ciao system preprocessor, in this paper we discuss a number of design goals for context-sensitive analysis of modular programs as well as the problems which arise in trying to meet these goals. We also provide a high-level description of a framework for analysis of modular programs which does substantially meet these objectives. This framework is generic in that it can be instantiated in different ways in order to adapt to different contexts. Finally, the behavior of the different instantiations w.r.t. the design goals that motivate our work is also discussed

A mesocosm experiment investigating the effects of substratum quality and wave exposure on the survival of fish eggs

In a mesocosm experiment, the attachment of bream (Abramis brama) eggs to spawning substrata with and without periphytic biofilm coverage and their subsequent survival with and without low-intensity wave exposure were investigated. Egg attachment was reduced by 73% on spawning substrata with a natural periphytic biofilm, compared to clean substrata. Overall, this initial difference in egg numbers persisted until hatching. The difference in egg numbers was even increased in the wave treatment, while it was reduced in the no-wave control treatment. Exposure to a low-intensity wave regime affected egg development between the two biofilm treatments differently. Waves enhanced egg survival on substrata without a biofilm but reduced the survival of eggs on substrata with biofilm coverage. In the treatment combining biofilm-covered substrata and waves, no attached eggs survived until hatching. In all treatments, more than 75% of the eggs became detached from the spawning substrata during the egg incubation period, an

SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome.

International audienceBACKGROUND: Mutations in SCN5A are identified in approximately 20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood. The aim of this study was to investigate the association of SCN5A mutations and BrS in a group of large genotyped families. METHODS AND RESULTS: Families were included if at least 5 family members were carriers of the SCN5A mutation, which was identified in the proband. Thirteen large families composed of 115 mutation carriers were studied. The signature type I ECG was present in 54 mutation carriers (BrS-ECG+; 47%). In 5 families, we found 8 individuals affected by BrS but with a negative genotype (mutation-negative BrS-ECG+). Among these 8 mutation-negative BrS-ECG+ individuals, 3, belonging to 3 different families, had a spontaneous type I ECG, whereas 5 had a type I ECG only after the administration of sodium channel blockers. One of these 8 individuals had also experienced syncope. Mutation carriers had, on average, longer PR and QRS intervals than noncarriers, demonstrating that these mutations exerted functional effects. CONCLUSIONS: Our results suggest that SCN5A mutations are not directly causal to the occurrence of a BrS-ECG+ and that genetic background may play a powerful role in the pathophysiology of BrS. These findings add further complexity to concepts regarding the causes of BrS, and are consistent with the emerging notion that the pathophysiology of BrS includes various elements beyond mutant sodium channels

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Technical guidance on monitoring for the Marine Stategy Framework Directive

The Marine Directors of the European Union (EU), Acceding Countries, Candidate Countries and EFTA Countries have jointly developed a common strategy for supporting the implementation of the Directive 2008/56/EC, “the Marine Strategy Framework Directive” (MSFD). The main aim of this strategy is to allow a coherent and harmonious implementation of the Directive. Focus is on methodological questions related to a common understanding of the technical and scientific implications of the Marine Strategy Framework Directive. In particular, one of the objectives of the strategy is the development of non-legally binding and practical documents, such as this technical guidance on monitoring for the MSFD. These documents are targeted to those experts who are directly or indirectly implementing the MSFD in the marine regions. The document has been prepared by the Joint Research Centre of the European Commission (JRC) with the contribution of experts from Member States, Regional Seas Conventions and ICES and following consultation of the Working Group on Good Environmental Status.JRC.H.1-Water Resource

Analysis of the capacity of google trends to measure interest in conservation topics and the role of online news

With the continuous growth of internet usage, Google Trends has emerged as a source of information to investigate how social trends evolve over time. Knowing how the level of interest in conservation topics--approximated using Google search volume--varies over time can help support targeted conservation science communication. However, the evolution of search volume over time and the mechanisms that drive peaks in searches are poorly understood. We conducted time series analyses on Google search data from 2004 to 2013 to investigate: (i) whether interests in selected conservation topics have declined and (ii) the effect of news reporting and academic publishing on search volume. Although trends were sensitive to the term used as benchmark, we did not find that public interest towards conservation topics such as climate change, ecosystem services, deforestation, orangutan, invasive species and habitat loss was declining. We found, however, a robust downward trend for endangered species and an upward trend for ecosystem services. The quantity of news articles was related to patterns in Google search volume, whereas the number of research articles was not a good predictor but lagged behind Google search volume, indicating the role of news in the transfer of conservation science to the public

Class III myosins shape the auditory hair bundles by limiting microvilli and stereocilia growth.

International audienceThe precise architecture of hair bundles, the arrays of mechanosensitive microvilli-like stereocilia crowning the auditory hair cells, is essential to hearing. Myosin IIIa, defective in the late-onset deafness form DFNB30, has been proposed to transport espin-1 to the tips of stereocilia, thereby promoting their elongation. We show that Myo3a(-/-)Myo3b(-/-) mice lacking myosin IIIa and myosin IIIb are profoundly deaf, whereas Myo3a-cKO Myo3b(-/-) mice lacking myosin IIIb and losing myosin IIIa postnatally have normal hearing. Myo3a(-/-)Myo3b(-/-) cochlear hair bundles display robust mechanoelectrical transduction currents with normal kinetics but show severe embryonic abnormalities whose features rapidly change. These include abnormally tall and numerous microvilli or stereocilia, ungraded stereocilia bundles, and bundle rounding and closure. Surprisingly, espin-1 is properly targeted to Myo3a(-/-)Myo3b(-/-) stereocilia tips. Our results uncover the critical role that class III myosins play redundantly in hair-bundle morphogenesis; they unexpectedly limit the elongation of stereocilia and of subsequently regressing microvilli, thus contributing to the early hair bundle shaping

Strong Coupling Between Whispering Gallery Photons and Spin States of Iron Group Impurity Ions

Interaction of Whispering Gallery Modes (WGM) with dilute spin ensembles in solids is an interesting paradigm of Hybrid Quantum Systems potentially beneficial for Quantum Signal Processing applications. In the present work, WGM spectroscopy of Rare-Earth doped YSO crystal reveals the existence of Iron Group Ion (IGI) co-dopings with concentration levels of order 100 ppb. The IGI spin ensembles demonstrate large Zero Field Splittings at 14.7GHz, 18.4GHz and 25.4GHz, considerable anisotropy of the \textrm{g}-tensors, as well as two inequivalent lattice sites. Strong coupling regimes between an ensemble of IGI spins and WGM photons have been demonstrated at $18.4$ GHz and near zero field. This approach together with useful optical properties of these ions opens a new avenue for 'spins-in-solids' Quantum Electrodynamics