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Showing papers by "University of Rennes published in 2012"


Journal ArticleDOI
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

4,316 citations


Journal ArticleDOI
TL;DR: New T-statistics ('T' for trait) are introduced, based on the comparison of intraspecific and interspecific variances of functional traits across organizational levels, to operationally incorporate intrapecific variability into community ecology theory.
Abstract: Despite being recognized as a promoter of diversity and a condition for local coexistence decades ago, the importance of intraspecific variance has been neglected over time in community ecology. Recently, there has been a new emphasis on intraspecific variability. Indeed, recent developments in trait-based community ecology have underlined the need to integrate variation at both the intraspecific as well as interspecific level. We introduce new T-statistics ('T' for trait), based on the comparison of intraspecific and interspecific variances of functional traits across organizational levels, to operationally incorporate intraspecific variability into community ecology theory. We show that a focus on the distribution of traits at local and regional scales combined with original analytical tools can provide unique insights into the primary forces structuring communities.

1,304 citations


Journal ArticleDOI
TL;DR: This review focuses on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes, and provides critical information on diagnostic methods according to the patient's background.
Abstract: Summary: The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last 40 years. This obligate intracellular parasite was identified early as a pathogen responsible for congenital infection, but its clinical expression and the importance of reactivations of infections in immunocompromised patients were recognized later, in the era of organ transplantation and HIV infection. Recent knowledge of host cell-parasite interactions and of parasite virulence has brought new insights into the comprehension of the pathophysiology of infection. In this review, we focus on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes. In particular, we provide critical information on diagnostic methods according to the patient's background and discuss the implementation of screening tools for congenital toxoplasmosis according to health policies.

1,261 citations


Journal ArticleDOI
TL;DR: Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus-related tumors, led to impaired TP53 function, and association of mutations in specific genes suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways.
Abstract: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcohol-related tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors.

1,195 citations


Journal ArticleDOI
TL;DR: The symposium includes articles from 10 urban analysts working on 30 cities around the globe whose collaborative work aims to understand different types of city shrinkage and the role that different approaches, policies and strategies have played in the regeneration of these cities.
Abstract: Urban shrinkage is not a new phenomenon. It has been documented in a large literature analyzing the social and economic issues that have led to population flight, resulting, in the worse cases, in the eventual abandonment of blocks of housing and neighbourhoods. Analysis of urban shrinkage should take into account the new realization that this phenomenon is now global and multidimensional — but also little understood in all its manifestations. Thus, as the world's population increasingly becomes urban, orthodox views of urban decline need redefinition. The symposium includes articles from 10 urban analysts working on 30 cities around the globe. These analysts belong to the Shrinking Cities International Research Network (SCIRN), whose collaborative work aims to understand different types of city shrinkage and the role that different approaches, policies and strategies have played in the regeneration of these cities. In this way the symposium will inform both a rich diversity of analytical perspectives and country-based studies of the challenges faced by shrinking cities. It will also disseminate SCIRN's research results from the last 3 years. Resume La decroissance urbaine n'est pas un phenomene nouveau. De nombreux travaux ont analyse les problemes sociaux et economiques conduisant au depart de populations et resultant dans les pires des cas a l'abandon d'ilots d'habitat et de quartiers entiers. Cependant, l'etude de la decroissance urbaine doit aujourd'hui tenir compte du constat recent selon lequel ce phenomene est desormais global et multidimensionnel, tout en restant peu apprehende dans toutes ses composantes. Ainsi, alors que la population mondiale est de plus en plus urbaine, les conceptions classiques du declin urbain meritent d'etre reexaminees. Ce symposium inclut des articles de dix chercheurs travaillant sur trente villes a travers le monde. Ils appartiennent au Shrinking Cities International Research Netwok (SCIRN), dont le travail collectif a pour objectif d'analyser differents types de decroissance urbaine et le role que les multiples approches, politiques et strategies ont joue dans la regeneration des villes touchees par ce processus. Ce numero s'appuie sur une diversite d'approches et sur l'etude de contextes urbains varies, ayant pour point commun d'etre concernes par les enjeux de la decroissance urbaine. Il permet de diffuser les resultats des recherches menees au sein du SCIRN au cours des trois dernieres annees.

570 citations


Journal ArticleDOI
TL;DR: Plasma NTBI and especially labile plasma iron determinations represent a new important biological tool since elimination of this toxic iron species is a major therapeutic goal.

533 citations


Journal ArticleDOI
19 Jan 2012-PLOS ONE
TL;DR: A fast mapping-based algorithm is presented to compute the mappability of each region of a reference genome up to a specified number of mismatches, highlighting mappable as an important concept which deserves to be taken into full account when massively parallel sequencing technologies are employed.
Abstract: We present a fast mapping-based algorithm to compute the mappability of each region of a reference genome up to a specified number of mismatches. Knowing the mappability of a genome is crucial for the interpretation of massively parallel sequencing experiments. We investigate the properties of the mappability of eukaryotic DNA/RNA both as a whole and at the level of the gene family, providing for various organisms tracks which allow the mappability information to be visually explored. In addition, we show that mappability varies greatly between species and gene classes. Finally, we suggest several practical applications where mappability can be used to refine the analysis of high-throughput sequencing data (SNP calling, gene expression quantification and paired-end experiments). This work highlights mappability as an important concept which deserves to be taken into full account, in particular when massively parallel sequencing technologies are employed. The GEM mappability program belongs to the GEM (GEnome Multitool) suite of programs, which can be freely downloaded for any use from its website (http://gemlibrary.sourceforge.net).

526 citations


Journal ArticleDOI
TL;DR: The method uses Bayesian transdimensional Markov Chain Monte Carlo and allows a wide range of possible thermal history models to be considered as general prior information on time, temperature (and temperature offset for multiple samples in a vertical profile).
Abstract: [1] A new approach for inverse thermal history modeling is presented. The method uses Bayesian transdimensional Markov Chain Monte Carlo and allows us to specify a wide range of possible thermal history models to be considered as general prior information on time, temperature (and temperature offset for multiple samples in a vertical profile). We can also incorporate more focused geological constraints in terms of more specific priors. The Bayesian approach naturally prefers simpler thermal history models (which provide an adequate fit to the observations), and so reduces the problems associated with over interpretation of inferred thermal histories. The output of the method is a collection or ensemble of thermal histories, which quantifies the range of accepted models in terms a (posterior) probability distribution. Individual models, such as the best data fitting (maximum likelihood) model or the expected model (effectively the weighted mean from the posterior distribution) can be examined. Different data types (e.g., fission track, U-Th/He, 40Ar/39Ar) can be combined, requiring just a data-specific predictive forward model and data fit (likelihood) function. To demonstrate the main features and implementation of the approach, examples are presented using both synthetic and real data.

514 citations


Proceedings ArticleDOI
10 Apr 2012
TL;DR: This work extends a mobility model called Mobility Markov Chain in order to incorporate the n previous visited locations and develops a novel algorithm for next location prediction based on this mobility model that is coined as n-MMC.
Abstract: In this paper, we address the issue of predicting the next location of an individual based on the observations of his mobility behavior over some period of time and the recent locations that he has visited. This work has several potential applications such as the evaluation of geo-privacy mechanisms, the development of location-based services anticipating the next movement of a user and the design of location-aware proactive resource migration. In a nutshell, we extend a mobility model called Mobility Markov Chain (MMC) in order to incorporate the n previous visited locations and we develop a novel algorithm for next location prediction based on this mobility model that we coined as n-MMC. The evaluation of the efficiency of our algorithm on three different datasets demonstrates an accuracy for the prediction of the next location in the range of 70% to 95% as soon as n = 2.

485 citations


Journal ArticleDOI
TL;DR: The KInetic Database for Astrochemistry (KIDA) as mentioned in this paper is a database of gas-phase reactions with rate coefficients and uncertainties that will be vetted to the greatest extent possible.
Abstract: We present a novel chemical database for gas-phase astrochemistry. Named the KInetic Database for Astrochemistry (KIDA), this database consists of gas-phase reactions with rate coefficients and uncertainties that will be vetted to the greatest extent possible. Submissions of measured and calculated rate coefficients are welcome, and will be studied by experts before inclusion into the database. Besides providing kinetic information for the interstellar medium, KIDA is planned to contain such data for planetary atmospheres and for circumstellar envelopes. Each year, a subset of the reactions in the database (kida.uva) will be provided as a network for the simulation of the chemistry of dense interstellar clouds with temperatures between 10 K and 300 K. We also provide a code, named Nahoon, to study the time-dependent gas-phase chemistry of zero-dimensional and one-dimensional interstellar sources.

483 citations


Journal ArticleDOI
TL;DR: A literature review on QAC chemical structure, fields of application, mechanism of action, susceptibility testing, prevalence, and co- or cross-resistance to antibiotics found that there is a lack of standardised procedures for interpreting susceptibility test results.

Journal ArticleDOI
TL;DR: It is demonstrated that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities and generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chemical testing, tissue engineering, and cell therapy.

Journal ArticleDOI
TL;DR: EDCs, from varied sources, may have organisational effects during development and/or activational effects in adulthood that influence sexually‐dimorphic, reproductively‐relevant processes or other functions, by mimicking, antagonising or altering steroidal actions.
Abstract: Some environmental contaminants interact with hormones and may exert adverse consequences as a result of their actions as endocrine disrupting chemicals (EDCs). Exposure in people is typically a result of contamination of the food chain, inhalation of contaminated house dust or occupational exposure. EDCs include pesticides and herbicides (such as dichlorodiphenyl trichloroethane or its metabolites), methoxychlor, biocides, heat stabilisers and chemical catalysts (such as tributyltin), plastic contaminants (e.g. bisphenol A), pharmaceuticals (i.e. diethylstilbestrol; 17α-ethinylestradiol) or dietary components (such as phytoestrogens). The goal of this review is to address the sources, effects and actions of EDCs, with an emphasis on topics discussed at the International Congress on Steroids and the Nervous System. EDCs may alter reproductively-relevant or nonreproductive, sexually-dimorphic behaviours. In addition, EDCs may have significant effects on neurodevelopmental processes, influencing the morphology of sexually-dimorphic cerebral circuits. Exposure to EDCs is more dangerous if it occurs during specific 'critical periods' of life, such as intrauterine, perinatal, juvenile or puberty periods, when organisms are more sensitive to hormonal disruption, compared to other periods. However, exposure to EDCs in adulthood can also alter physiology. Several EDCs are xenoestrogens, which can alter serum lipid concentrations or metabolism enzymes that are necessary for converting cholesterol to steroid hormones. This can ultimately alter the production of oestradiol and/or other steroids. Finally, many EDCs may have actions via (or independent of) classic actions at cognate steroid receptors. EDCs may have effects through numerous other substrates, such as the aryl hydrocarbon receptor, the peroxisome proliferator-activated receptor and the retinoid X receptor, signal transduction pathways, calcium influx and/or neurotransmitter receptors. Thus, EDCs, from varied sources, may have organisational effects during development and/or activational effects in adulthood that influence sexually-dimorphic, reproductively-relevant processes or other functions, by mimicking, antagonising or altering steroidal actions.

Journal ArticleDOI
TL;DR: Direct activation of allylic alcohols in the presence of transition metal catalysts leading to electrophilic π-allyl metal intermediates represents such a promising target in the field of nucleophilic allylation reactions.
Abstract: Modern organic synthesis now requires efficient atom economical synthetic methods operating under greener pathways to achieve C–C and C–heteroatom bond formation. Direct activation of allylic alcohols in the presence of transition metal catalysts leading to electrophilic π-allyl metal intermediates represents such a promising target in the field of nucleophilic allylation reactions. During the last decade, this topic of recognized importance has become an emerging area, and selected transition metals, sometimes associated with alcohol activators, have brought elegant solutions for performing allylic substitution directly from alcohols in a regio, stereo and enantioselective manner.

Journal ArticleDOI
TL;DR: This work presents a novel method for joint inversion of receiver functions and surface wave dispersion data, using a transdimensional Bayesian formulation and shows that the Hierarchical Bayes procedure is a powerful tool in this situation, able to evaluate the level of information brought by different data types in the misfit, thus removing the arbitrary choice of weighting factors.
Abstract: We present a novel method for joint inversion of receiver functions and surface wave dispersion data, using a transdimensional Bayesian formulation. This class of algorithm treats the number of model parameters (e.g. number of layers) as an unknown in the problem. The dimension of the model space is variable and a Markov chain Monte Carlo (McMC) scheme is used to provide a parsimonious solution that fully quantifies the degree of knowledge one has about seismic structure (i.e constraints on the model, resolution, and trade-offs). The level of data noise (i.e. the covariance matrix of data errors) effectively controls the information recoverable from the data and here it naturally determines the complexity of the model (i.e. the number of model parameters). However, it is often difficult to quantify the data noise appropriately, particularly in the case of seismic waveform inversion where data errors are correlated. Here we address the issue of noise estimation using an extended Hierarchical Bayesian formulation, which allows both the variance and covariance of data noise to be treated as unknowns in the inversion. In this way it is possible to let the data infer the appropriate level of data fit. In the context of joint inversions, assessment of uncertainty for different data types becomes crucial in the evaluation of the misfit function. We show that the Hierarchical Bayes procedure is a powerful tool in this situation, because it is able to evaluate the level of information brought by different data types in the misfit, thus removing the arbitrary choice of weighting factors. After illustrating the method with synthetic tests, a real data application is shown where teleseismic receiver functions and ambient noise surface wave dispersion measurements from the WOMBAT array (South-East Australia) are jointly inverted to provide a probabilistic 1D model of shear-wave velocity beneath a given station.

Journal ArticleDOI
T. Accadia1, Fausto Acernese2, M. Alshourbagy3, P. Amico4  +338 moreInstitutions (20)
TL;DR: Virgo as discussed by the authors is a very large Michelson interferometer with 3 km-long arms, built at Cascina, near Pisa (Italy), with a detailed description of all its different elements is given.
Abstract: This paper presents a complete description of Virgo, the French-Italian gravitational wave detector. The detector, built at Cascina, near Pisa (Italy), is a very large Michelson interferometer, with 3 km-long arms. In this paper, following a presentation of the physics requirements, leading to the specifications for the construction of the detector, a detailed description of all its different elements is given. These include civil engineering infrastructures, a huge ultra-high vacuum (UHV) chamber (about 6000 cubic metres), all of the optical components, including high quality mirrors and their seismic isolating suspensions, all of the electronics required to control the interferometer and for signal detection. The expected performances of these different elements are given, leading to an overall sensitivity curve as a function of the incoming gravitational wave frequency. This description represents the detector as built and used in the first data-taking runs. Improvements in different parts have been and continue to be performed, leading to better sensitivities. These will be detailed in a forthcoming paper.

Journal ArticleDOI
TL;DR: In this article, the authors compare updated estimates of groundwater storage changes in the California Central Valley using GRACE satellites with storage changes from groundwater level data, and apply a new processing approach that optimally uses available GRACE and water balance component data to extract changes in groundwater storage.
Abstract: [1] There is increasing interest in using Gravity Recovery and Climate Experiment (GRACE) satellite data to remotely monitor groundwater storage variations; however, comparisons with ground-based well data are limited but necessary to validate satellite data processing, especially when the study area is close to or below the GRACE footprint. The Central Valley is a heavily irrigated region with large-scale groundwater depletion during droughts. Here we compare updated estimates of groundwater storage changes in the California Central Valley using GRACE satellites with storage changes from groundwater level data. A new processing approach was applied that optimally uses available GRACE and water balance component data to extract changes in groundwater storage. GRACE satellites show that groundwater depletion totaled $31.0 6 3.0 km 3 for Groupe de Recherche de Geodesie Spatiale (GRGS) satellite data during the drought from October 2006 through March 2010. Groundwater storage changes from GRACE agreed with those from well data for the overlap period (April 2006 through September 2009) (27 km 3 for both). General correspondence between GRACE and groundwater level data validates the methodology and increases confidence in use of GRACE satellites to monitor groundwater storage changes.

Journal ArticleDOI
TL;DR: An evidence-based assessment demonstrates which parts of Antarctica are at growing risk from alien species that may become invasive and provides the means to mitigate this threat now and into the future as the continent's climate changes.
Abstract: Invasive alien species are among the primary causes of biodiversity change globally, with the risks thereof broadly understood for most regions of the world. They are similarly thought to be among the most significant conservation threats to Antarctica, especially as climate change proceeds in the region. However, no comprehensive, continent-wide evaluation of the risks to Antarctica posed by such species has been undertaken. Here we do so by sampling, identifying, and mapping the vascular plant propagules carried by all categories of visitors to Antarctica during the International Polar Year's first season (2007–2008) and assessing propagule establishment likelihood based on their identity and origins and on spatial variation in Antarctica's climate. For an evaluation of the situation in 2100, we use modeled climates based on the Intergovernmental Panel on Climate Change's Special Report on Emissions Scenarios Scenario A1B [Nakicenovic N, Swart R, eds (2000) Special Report on Emissions Scenarios: A Special Report of Working Group III of the Intergovernmental Panel on Climate Change (Cambridge University Press, Cambridge, UK)]. Visitors carrying seeds average 9.5 seeds per person, although as vectors, scientists carry greater propagule loads than tourists. Annual tourist numbers (∼33,054) are higher than those of scientists (∼7,085), thus tempering these differences in propagule load. Alien species establishment is currently most likely for the Western Antarctic Peninsula. Recent founder populations of several alien species in this area corroborate these findings. With climate change, risks will grow in the Antarctic Peninsula, Ross Sea, and East Antarctic coastal regions. Our evidence-based assessment demonstrates which parts of Antarctica are at growing risk from alien species that may become invasive and provides the means to mitigate this threat now and into the future as the continent's climate changes.

Journal ArticleDOI
TL;DR: Investigation of the role of RIPK1, RIPK3 and PARP-1 in TRAIL-induced necroptosis in vitro and in concanavalin A-induced murine hepatitis suggests that pharmacological inhibitors ofRIPKs and PARp-1 could be new treatment options for immune-mediated hepatitis.
Abstract: Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAIL-induced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis.

Journal ArticleDOI
TL;DR: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p´-DDE does not.
Abstract: Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contr...

Journal ArticleDOI
TL;DR: Germline mutations in MAX are responsible for 1.12% of PCC/PGL in patients without evidence of other known mutations and should be considered in the genetic work-up of these patients.
Abstract: PURPOSE: Pheochromocytomas (PCC) and paragangliomas (PGL) are genetically heterogeneous neural crest-derived neoplasms. Recently we identified germline mutations in a new tumor suppressor susceptibility gene, MAX (MYC-associated factor X), which predisposes carriers to PCC. How MAX mutations contribute to PCC/PGL and associated phenotypes remain unclear. This study aimed to examine the prevalence and associated phenotypic features of germline and somatic MAX mutations in PCC/PGL. Design: We sequenced MAX in 1,694 patients with PCC or PGL (without mutations in other major susceptibility genes) from 17 independent referral centers. We screened for large deletions/duplications in 1,535 patients using a multiplex PCR-based method. Somatic mutations were searched for in tumors from an additional 245 patients. The frequency and type of MAX mutation was assessed overall and by clinical characteristics. RESULTS: Sixteen MAX pathogenic mutations were identified in 23 index patients. All had adrenal tumors, including 13 bilateral or multiple PCCs within the same gland (P < 0.001), 15.8% developed additional tumors at thoracoabdominal sites, and 37% had familial antecedents. Age at diagnosis was lower (P = 0.001) in MAX mutation carriers compared with nonmutated cases. Two patients (10.5%) developed metastatic disease. A mutation affecting MAX was found in five tumors, four of them confirmed as somatic (1.65%). MAX tumors were characterized by substantial increases in normetanephrine, associated with normal or minor increases in metanephrine. CONCLUSIONS: Germline mutations in MAX are responsible for 1.12% of PCC/PGL in patients without evidence of other known mutations and should be considered in the genetic work-up of these patients.

Journal ArticleDOI
TL;DR: The role of out-of-phase firing in neuronal clusters, the importance of strong excitatory AMPA-synaptic currents and recurrent inhibitory connectivity in combination with the fast time scales of IPSPs, ephaptic coupling and the contribution of interneuronal coupling through gap junctions are considered.

Journal ArticleDOI
TL;DR: In this article, the authors analyzed records of daily precipitation and discharge within twelve catchments in Nepal over about 30 years, and inferred that water is stored temporarily in a reservoir with characteristic response time of about 45 days, suggesting a diffusivity typical of fractured basement aquifers.
Abstract: In the course of the transfer of precipitation into rivers, water is temporarily stored in reservoirs with different residence times such as soils, groundwater, snow and glaciers. In the central Himalaya, the water budget is thought to be primarily controlled by monsoon rainfall, snow and glacier melt, and secondarily by evapotranspiration. An additional contribution from deep groundwater has been deduced from the chemistry of Himalayan rivers, but its importance in the annual water budget remains to be evaluated. Here we analyse records of daily precipitation and discharge within twelve catchments in Nepal over about 30 years. We observe annual hysteresis loops--that is, a time lag between precipitation and discharge--in both glaciated and unglaciated catchments and independent of the geological setting. We infer that water is stored temporarily in a reservoir with characteristic response time of about 45 days, suggesting a diffusivity typical of fractured basement aquifers. We estimate this transient storage capacity at about 28km3 for the three main Nepal catchments; snow and glacier melt contribute around 14km3yr-1, about 10% of the annual river discharge. We conclude that groundwater storage in a fractured basement influences significantly the Himalayan river discharge cycle.

Journal ArticleDOI
01 Jan 2012
TL;DR: DAGuE is presented, a generic framework for architecture aware scheduling and management of micro-tasks on distributed many-core heterogeneous architectures and uses a dynamic, fully-distributed scheduler based on cache awareness, data-locality and task priority.
Abstract: The frenetic development of the current architectures places a strain on the current state-of-the-art programming environments. Harnessing the full potential of such architectures is a tremendous task for the whole scientific computing community. We present DAGuE a generic framework for architecture aware scheduling and management of micro-tasks on distributed many-core heterogeneous architectures. Applications we consider can be expressed as a Direct Acyclic Graph of tasks with labeled edges designating data dependencies. DAGs are represented in a compact, problem-size independent format that can be queried on-demand to discover data dependencies, in a totally distributed fashion. DAGuE assigns computation threads to the cores, overlaps communications and computations and uses a dynamic, fully-distributed scheduler based on cache awareness, data-locality and task priority. We demonstrate the efficiency of our approach, using several micro-benchmarks to analyze the performance of different components of the framework, and a linear algebra factorization as a use case.

Journal ArticleDOI
TL;DR: The effects of three different means of alcohol consumption are reviewed: light, heavy, and binge drinking; the roles of reduced total fat mass, increased lipid content in bone marrow, and a hypoleptinemia are discussed.
Abstract: Alcohol is widely consumed across the world. It is consumed in both social and cultural settings. Until recently, two types of alcohol consumption were recognized: heavy chronic alcohol consumption or light consumption. Today, there is a new pattern of consumption among teenagers and young adults namely: binge drinking. Heavy alcohol consumption is detrimental to many organs and tissues, including bones, and is known to induce secondary osteoporosis. Some studies, however, have reported benefits from light alcohol consumption on bone parameters. To date, little is known regarding the effects of binge drinking on bone health. Here, we review the effects of three different means of alcohol consumption: light, heavy, and binge drinking. We also review the detailed literature on the different mechanisms by which alcohol intake may decrease bone mass and strength. The effects of alcohol on bone are thought to be both direct and indirect. The decrease in bone mass and strength following alcohol consumption is mainly due to a bone remodeling imbalance, with a predominant decrease in bone formation. Recent studies, however, have reported new mechanisms by which alcohol may act on bone remodeling, including osteocyte apoptosis, oxidative stress, and Wnt signalling pathway modulation. The roles of reduced total fat mass, increased lipid content in bone marrow, and a hypoleptinemia are also discussed.

Journal ArticleDOI
TL;DR: In this paper, the authors present a review of the research endeavor in this area and underline related applications in nonlinear optics, where the direct lanthanide sensitization from charge transfer excited state appears as an alternative process resulting in a redshift of the excitation wavelength far in the visible thanks to the design of ligands with appropriate donor-acceptor charge transfer transitions.

Journal ArticleDOI
14 Sep 2012-Cell
TL;DR: It is found that transcription of two long noncoding RNAs (lncRNAs) mediates mating-type control of sporulation in yeast and abolishes sporulations in MATa/α diploids.

Journal ArticleDOI
TL;DR: This work presents an oxyhydride of the perhaps most well-known perovskite, BaTiO(3), as an O(2-)/H(-) solid solution with hydride concentrations up to 20% of the anion sites, which is electronically conducting, and stable in air and water at ambient conditions.
Abstract: In oxides, the substitution of non-oxide anions (F(-),S(2-),N(3-) and so on) for oxide introduces many properties, but the least commonly encountered substitution is where the hydride anion (H(-)) replaces oxygen to form an oxyhydride. Only a handful of oxyhydrides have been reported, mainly with electropositive main group elements or as layered cobalt oxides with unusually low oxidation states. Here, we present an oxyhydride of the perhaps most well-known perovskite, BaTiO(3), as an O(2-)/H(-) solid solution with hydride concentrations up to 20% of the anion sites. BaTiO(3-x)H(x) is electronically conducting, and stable in air and water at ambient conditions. Furthermore, the hydride species is exchangeable with hydrogen gas at 400 °C. Such an exchange implies diffusion of hydride, and interesting diffusion mechanisms specific to hydrogen may be at play. Moreover, such a labile anion in an oxide framework should be useful in further expanding the mixed-anion chemistry of the solid state.

Journal ArticleDOI
J. Abadie1, B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2  +881 moreInstitutions (88)
TL;DR: In this paper, the authors report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010.
Abstract: We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.

Journal ArticleDOI
TL;DR: This cavity–nanoparticle system effectively combines the advantages of Fabry–Perot microresonators with those of plasmonic nanoparticles, providing interesting features such as remote-sensing ability, incident-angle independent resonances, strong polarization dependence, lateral ultra small sensing volume and strongly improved detection resolution.
Abstract: Plasmonic nanoparticles are useful as optical sensors, but their spectral resolution is hindered by the linewidth of the plasmon resonance. Schmidt et al. find that coupling this resonance to a microcavity creates hybrid modes with enhanced sensing figure-of-merit and improved frequency resolution.