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Showing papers by "University of Bordeaux 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
01 Apr 2012-Europace
TL;DR: This 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure.
Abstract: During the past decade, catheter ablation of atrial fibrillation (AF) has evolved rapidly from an investigational procedure to its current status as a commonly performed ablation procedure in many major hospitals throughout the world. Surgical ablation of AF, using either standard or minimally invasive techniques, is also performed in many major hospitals throughout the world. In 2007, an initial Consensus Statement on Catheter and Surgical AF Ablation was developed as a joint effort of the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society.1 The 2007 document was also developed in collaboration with the Society of Thoracic Surgeons and the American College of Cardiology. Since the publication of the 2007 document, there has been much learned about AF ablation, and the indications for these procedures have changed. Therefore the purpose of this 2012 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a Task Force, convened by the Heart Rhythm Society, the European Heart Rhythm Association, and the European Cardiac Arrhythmia Society and charged with defining the indications, techniques, and outcomes of this procedure. Included within this document are recommendations pertinent to the design of clinical trials in the field of AF ablation, including definitions relevant to this topic. This statement summarizes the opinion of the Task Force members based on an extensive literature review as well as their own experience. It is directed to all health care professionals who are involved in the care of patients with AF, particularly those who are undergoing, or are being considered for, catheter or surgical ablation procedures for AF. This statement is not intended to recommend or promote catheter ablation of AF. Rather the ultimate judgment regarding care of a particular patient …

2,754 citations


Journal ArticleDOI
TL;DR: It is demonstrated that aflibercept is an effective treatment for AMD, with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring.

1,894 citations


Journal ArticleDOI
29 Nov 2012-Nature
TL;DR: In this article, the authors draw together published and unpublished data on the vulnerability of the transport system to drought-induced embolism for a large number of woody species, with a view to examining the likely consequences of climate change for forest biomes.
Abstract: Shifts in rainfall patterns and increasing temperatures associated with climate change are likely to cause widespread forest decline in regions where droughts are predicted to increase in duration and severity(1). One primary cause of productivity loss and plant mortality during drought is hydraulic failure(2-4). Drought stress creates trapped gas emboli in the water transport system, which reduces the ability of plants to supply water to leaves for photosynthetic gas exchange and can ultimately result in desiccation and mortality. At present we lack a clear picture of how thresholds to hydraulic failure vary across a broad range of species and environments, despite many individual experiments. Here we draw together published and unpublished data on the vulnerability of the transport system to drought-induced embolism for a large number of woody species, with a view to examining the likely consequences of climate change for forest biomes. We show that 70% of 226 forest species from 81 sites worldwide operate with narrow (<1 megapascal) hydraulic safety margins against injurious levels of drought stress and therefore potentially face long-term reductions in productivity and survival if temperature and aridity increase as predicted for many regions across the globe(5,6). Safety margins are largely independent of mean annual precipitation, showing that there is global convergence in the vulnerability of forests to drought, with all forest biomes equally vulnerable to hydraulic failure regardless of their current rainfall environment. These findings provide insight into why drought-induced forest decline is occurring not only in arid regions but also in wet forests not normally considered at drought risk(7,8).

1,864 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present a systematic review of research on academic scientists' involvement in collaborative research, contract research, consulting and informal relationships for university-industry knowledge transfer, which they refer as academic engagement.
Abstract: A considerable body of work highlights the relevance of collaborative research, contract research, consulting and informal relationships for university-industry knowledge transfer. We present a systematic review of research on academic scientists’ involvement in these activities to which we refer as ‘academic engagement’. Apart from extracting findings that are generalisable across studies, we ask how academic engagement differs from commercialization, defined as intellectual property creation and academic entrepreneurship. We identify the individual, organizational and institutional antecedents and consequences of academic engagement, and then compare these findings with the antecedents and consequences of commercialization. Apart from being more widely practiced, academic engagement is distinct from commercialization in that it is closely aligned with traditional academic research activities, and pursued by academics to access resources supporting their research agendas. We conclude by identifying future research needs, opportunities for methodological improvement and policy interventions. (Published version available via open access)

1,589 citations


Journal ArticleDOI
P. L. Nolan1, A. A. Abdo2, A. A. Abdo3, Markus Ackermann  +290 moreInstitutions (53)
TL;DR: The second Fermi-LAT catalog (2FGL) as mentioned in this paper includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms either power-law, exponentially cutoff power law, or log-normal forms.
Abstract: We present the second catalog of high-energy γ-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), derived from data taken during the first 24 months of the science phase of the mission, which began on 2008 August 4. Source detection is based on the average flux over the 24 month period. The second Fermi-LAT catalog (2FGL) includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms of power-law, exponentially cutoff power-law, or log-normal forms. Also included are flux measurements in five energy bands and light curves on monthly intervals for each source. Twelve sources in the catalog are modeled as spatially extended. We provide a detailed comparison of the results from this catalog with those from the first Fermi-LAT catalog (1FGL). Although the diffuse Galactic and isotropic models used in the 2FGL analysis are improved compared to the 1FGL catalog, we attach caution flags to 162 of the sources to indicate possible confusion with residual imperfections in the diffuse model. The 2FGL catalog contains 1873 sources detected and characterized in the 100 MeV to 100 GeV range of which we consider 127 as being firmly identified and 1171 as being reliably associated with counterparts of known or likely γ-ray-producing source classes.

1,541 citations


Journal ArticleDOI
TL;DR: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), was published in this paper.

1,271 citations


Journal ArticleDOI
Markus Ackermann, Marco Ajello1, W. B. Atwood2, Luca Baldini3  +176 moreInstitutions (36)
TL;DR: In this paper, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmicray confinement volume (halo), and distribution of interstellar gas.
Abstract: The gamma-ray sky >100 MeV is dominated by the diffuse emissions from interactions of cosmic rays with the interstellar gas and radiation fields of the Milky Way. Observations of these diffuse emissions provide a tool to study cosmic-ray origin and propagation, and the interstellar medium. We present measurements from the first 21 months of the Fermi-LAT mission and compare with models of the diffuse gamma-ray emission generated using the GALPROP code. The models are fitted to cosmic-ray data and incorporate astrophysical input for the distribution of cosmic-ray sources, interstellar gas and radiation fields. To assess uncertainties associated with the astrophysical input, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmic-ray confinement volume (halo), and the distribution of interstellar gas. An all-sky maximum-likelihood fit is used to determine the Xco-factor, the ratio between integrated CO-line intensity and molecular hydrogen column density, the fluxes and spectra of the gamma-ray point sources from the first Fermi-LAT catalogue, and the intensity and spectrum of the isotropic background including residual cosmic rays that were misclassified as gamma rays, all of which have some dependency on the assumed diffuse emission model. The models are compared on the basis of their maximum likelihood ratios as well as spectra, longitude, and latitude profiles. We also provide residual maps for the data following subtraction of the diffuse emission models. The models are consistent with the data at high and intermediate latitudes but under-predict the data in the inner Galaxy for energies above a few GeV. Possible explanations for this discrepancy are discussed, including the contribution by undetected point source populations and spectral variations of cosmic rays throughout the Galaxy.

686 citations


Journal ArticleDOI
Markus Ackermann1, Marco Ajello1, Alice Allafort1, W. B. Atwood2  +155 moreInstitutions (31)
TL;DR: The Fermi Large Area Telescope measured separate cosmic-ray electron and positron spectra to distinguish the two species by exploiting Earth's shadow, and it is confirmed that the fraction rises with energy in the 20-100 GeV range.
Abstract: We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting the Earth's shadow, which is offset in opposite directions for opposite charges due to the Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 GeV and 200 GeV. We confirm that the fraction rises with energy in the 20--100 GeV range and determine for the first time that it continues to rise between 100 and 200 GeV.

651 citations


Journal ArticleDOI
TL;DR: A brief cognitive assessment for multiple sclerosis that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use is recommended.
Abstract: Background: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and spe...

635 citations


Journal ArticleDOI
03 Aug 2012-Cell
TL;DR: It is demonstrated that long-term potentiation and NMDA-induced neurotoxicity rely on synaptic NMDARs only, and long- term depression requires both synaptic and extrasynaptic receptors.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, Andrea Albert2, Alice Allafort1  +220 moreInstitutions (42)
TL;DR: The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the FermI Gamma-ray Space Telescope (fermi) mission, is an imaging, wide field-of-view, high-energy \gamma-ray telescope, covering the energy range from 20 MeV to more than 300 GeV as discussed by the authors.
Abstract: The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy \gamma-ray telescope, covering the energy range from 20 MeV to more than 300 GeV. During the first years of the mission the LAT team has gained considerable insight into the in-flight performance of the instrument. Accordingly, we have updated the analysis used to reduce LAT data for public release as well as the Instrument Response Functions (IRFs), the description of the instrument performance provided for data analysis. In this paper we describe the effects that motivated these updates. Furthermore, we discuss how we originally derived IRFs from Monte Carlo simulations and later corrected those IRFs for discrepancies observed between flight and simulated data. We also give details of the validations performed using flight data and quantify the residual uncertainties in the IRFs. Finally, we describe techniques the LAT team has developed to propagate those uncertainties into estimates of the systematic errors on common measurements such as fluxes and spectra of astrophysical sources.

Journal ArticleDOI
TL;DR: Almost 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of inflixIMab, however, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers.

Journal ArticleDOI
TL;DR: Analysis of data on the extent of long-distance gene flow and theory that allows us to predict evolutionary responses of trees to climate change suggest that the positive effects of gene flow on adaptation may dominate in many instances.
Abstract: Forest trees are the dominant species in many parts of the world and predicting how they might respond to climate change is a vital global concern. Trees are capable of long-distance gene flow, which can promote adaptive evolution in novel environments by increasing genetic variation for fitness. It is unclear, however, if this can compensate for maladaptive effects of gene flow and for the long-generation times of trees. We critically review data on the extent of long-distance gene flow and summarise theory that allows us to predict evolutionary responses of trees to climate change. Estimates of long-distance gene flow based both on direct observations and on genetic methods provide evidence that genes can move over spatial scales larger than habitat shifts predicted under climate change within one generation. Both theoretical and empirical data suggest that the positive effects of gene flow on adaptation may dominate in many instances. The balance of positive to negative consequences of gene flow may, however, differ for leading edge, core and rear sections of forest distributions. We propose future experimental and theoretical research that would better integrate dispersal biology with evolutionary quantitative genetics and improve predictions of tree responses to climate change.

Journal ArticleDOI
TL;DR: A multidisciplinary group of 63 experts from 24 countries developed evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach by means of repeat online voting and a meeting in June 2011 in Porto, Portugal.
Abstract: Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter Study Group (EHSG), the European Society of Pathology (ESP) and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach (termed MAPS). A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia, and the need for adequate staging in the case of high grade dysplasia, and they focus on treatment and surveillance indications and methods.

Journal ArticleDOI
TL;DR: An adaptive SMC algorithm is proposed which admits a computational complexity that is linear in the number of samples and adaptively determines the simulation parameters.
Abstract: Approximate Bayesian computation (ABC) is a popular approach to address inference problems where the likelihood function is intractable, or expensive to calculate To improve over Markov chain Monte Carlo (MCMC) implementations of ABC, the use of sequential Monte Carlo (SMC) methods has recently been suggested Most effective SMC algorithms that are currently available for ABC have a computational complexity that is quadratic in the number of Monte Carlo samples (Beaumont et al, Biometrika 86:983---990, 2009; Peters et al, Technical report, 2008; Toni et al, J Roy Soc Interface 6:187---202, 2009) and require the careful choice of simulation parameters In this article an adaptive SMC algorithm is proposed which admits a computational complexity that is linear in the number of samples and adaptively determines the simulation parameters We demonstrate our algorithm on a toy example and on a birth-death-mutation model arising in epidemiology

Journal ArticleDOI
TL;DR: The genomic signature defined predicted BRCA1/2 inactivation in BLCs with 100% sensitivity and 90% specificity (97% accuracy) may ease the challenge of selecting patients for genetic testing or recruitment to clinical trials of novel emerging therapies that target DNA repair deficiencies in cancer.
Abstract: BRCA1 inactivation is a frequent event in basal-like breast carcinomas (BLC). However, BRCA1 can be inactivated by multiple mechanisms and determining its status is not a trivial issue. As an alternate approach, we profiled 65 BLC cases using single-nucleotide polymorphism arrays to define a signature of BRCA1-associated genomic instability. Large-scale state transitions (LST), defined as chromosomal break between adjacent regions of at least 10 Mb, were found to be a robust indicator of BRCA1 status in this setting. Two major ploidy-specific cutoffs in LST distributions were sufficient to distinguish highly rearranged BLCs with 85% of proven BRCA1-inactivated cases from less rearranged BLCs devoid of proven BRCA1-inactivated cases. The genomic signature we defined was validated in a second independent series of 55 primary BLC cases and 17 BLC-derived tumor cell lines. High numbers of LSTs resembling BRCA1-inactivated BLC were observed in 4 primary BLC cases and 2 BLC cell lines that harbored BRCA2 mutations. Overall, the genomic signature we defined predicted BRCA1/2 inactivation in BLCs with 100% sensitivity and 90% specificity (97% accuracy). This assay may ease the challenge of selecting patients for genetic testing or recruitment to clinical trials of novel emerging therapies that target DNA repair deficiencies in cancer.

Journal ArticleDOI
TL;DR: A review of brain operation in health and disease can be found in this article, which not only sheds new light on the brain operation, but also points to many unknowns, such as how gliotransmitters can modulate synaptic plasticity and cause changes in behavior.
Abstract: Neuroglial cells define brain homeostasis and mount defense against pathological insults. Astroglia regulate neurogenesis and development of brain circuits. In the adult brain, astrocytes enter into intimate dynamic relationship with neurons, especially at synaptic sites where they functionally form the tripartite synapse. At these sites, astrocytes regulate ion and neurotransmitter homeostasis, metabolically support neurons and monitor synaptic activity; one of the readouts of the latter manifests in astrocytic intracellular Ca(2+) signals. This form of astrocytic excitability can lead to release of chemical transmitters via Ca(2+) -dependent exocytosis. Once in the extracellular space, gliotransmitters can modulate synaptic plasticity and cause changes in behavior. Besides these physiological tasks, astrocytes are fundamental for progression and outcome of neurological diseases. In Alzheimer's disease, for example, astrocytes may contribute to the etiology of this disorder. Highly lethal glial-derived tumors use signaling trickery to coerce normal brain cells to assist tumor invasiveness. This review not only sheds new light on the brain operation in health and disease, but also points to many unknowns.

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.

Journal ArticleDOI
TL;DR: The heterostructure SnO(2)-ZnO photocatalyst showed much higher photocatalytic activities for the degradation of methylene blue than those of individual Sno(2) and ZnO nanomaterials and could be easily recycled several times opening new avenues for potential industrial applications.
Abstract: Nanoporous SnO2–ZnO heterojunction nanocatalyst was prepared by a straightforward two-step procedure involving, first, the synthesis of nanosized SnO2 particles by homogeneous precipitation combined with a hydrothermal treatment and, second, the reaction of the as-prepared SnO2 particles with zinc acetate followed by calcination at 500 °C. The resulting nanocatalysts were characterized by X-ray diffraction (XRD), FTIR, Raman, X-ray photoelectron spectroscopy (XPS), nitrogen adsorption–desorption analyses, transmission electron microscopy (TEM), and UV–vis diffuse reflectance spectroscopy. The SnO2–ZnO photocatalyst was made of a mesoporous network of aggregated wurtzite ZnO and cassiterite SnO2 nanocrystallites, the size of which was estimated to be 27 and 4.5 nm, respectively, after calcination. According to UV–visible diffuse reflectance spectroscopy, the evident energy band gap value of the SnO2–ZnO photocatalyst was estimated to be 3.23 eV to be compared with those of pure SnO2, that is, 3.7 eV, and Z...


Journal ArticleDOI
Roger C. Wiens1, Sylvestre Maurice2, Sylvestre Maurice3, B. L. Barraclough1, B. L. Barraclough4, Muriel Saccoccio5, Walter Barkley1, James F. Bell6, S. Bender1, S. Bender4, John D. Bernardin1, Diana L. Blaney7, Jennifer G. Blank8, Marc Bouyé3, Marc Bouyé2, Nathan T. Bridges9, Nathan K. Bultman1, Phillippe Caïs10, Robert C. Clanton1, Benton C. Clark11, Samuel M. Clegg1, Agnès Cousin2, Agnès Cousin3, David A. Cremers, Alain Cros3, Alain Cros2, Lauren DeFlores7, Dorothea Delapp1, Robert Dingler1, Claude d’Uston2, Claude d’Uston3, M. Darby Dyar12, Tom Elliott7, Don Enemark1, Cécile Fabre, Mike Flores1, Olivier Forni3, Olivier Forni2, Olivier Gasnault2, Olivier Gasnault3, Thomas Chatters Hale1, Charles C. Hays6, K. E. Herkenhoff13, Ed Kan7, L. E. Kirkland14, Driss Kouach2, Driss Kouach3, David Landis15, Yves Langevin16, Nina Lanza17, Nina Lanza1, Frank LaRocca18, Jérémie Lasue1, Jérémie Lasue2, Jérémie Lasue3, Joseph Latino1, Daniel Limonadi7, Chris Lindensmith7, Cynthia K. Little1, Nicolas Mangold19, Gérard Manhès20, Patrick Mauchien21, Christopher P. McKay8, Edward A. Miller7, Joe Mooney, Richard V. Morris, Leland Jean Morrison1, T. Nelson1, Horton E. Newsom17, Ann Ollila17, Melanie N. Ott18, L. Parès3, L. Parès2, R. Perez5, Franck Poitrasson2, Franck Poitrasson3, Cheryl Provost, Joseph W. Reiter7, Tom Roberts7, Frank Patrick Romero1, V. Sautter, Steven Salazar1, John J. Simmonds7, Ralph Stiglich1, S. A. Storms1, Nicolas Striebig3, Nicolas Striebig2, Jean Jacques Thocaven2, Jean Jacques Thocaven3, Tanner Trujillo1, Mike Ulibarri1, David T. Vaniman4, David T. Vaniman1, Noah Warner7, Rob Waterbury, Robert Whitaker1, James Witt1, Belinda Wong-Swanson 
TL;DR: The first laser-induced breakdown spectrometer (LIBS) was used on the Mars Science Laboratory (MSL) rover Curiosity for remote compositional information using the first LIBS on a planetary mission, and provided sample texture and morphology data using a remote micro-imager.
Abstract: The ChemCam instrument suite on the Mars Science Laboratory (MSL) rover Curiosity provides remote compositional information using the first laser-induced breakdown spectrometer (LIBS) on a planetary mission, and provides sample texture and morphology data using a remote micro-imager (RMI). Overall, ChemCam supports MSL with five capabilities: remote classification of rock and soil characteristics; quantitative elemental compositions including light elements like hydrogen and some elements to which LIBS is uniquely sensitive (e.g., Li, Be, Rb, Sr, Ba); remote removal of surface dust and depth profiling through surface coatings; context imaging; and passive spectroscopy over the 240–905 nm range. ChemCam is built in two sections: The mast unit, consisting of a laser, telescope, RMI, and associated electronics, resides on the rover’s mast, and is described in a companion paper. ChemCam’s body unit, which is mounted in the body of the rover, comprises an optical demultiplexer, three spectrometers, detectors, their coolers, and associated electronics and data handling logic. Additional instrument components include a 6 m optical fiber which transfers the LIBS light from the telescope to the body unit, and a set of onboard calibration targets. ChemCam was integrated and tested at Los Alamos National Laboratory where it also underwent LIBS calibration with 69 geological standards prior to integration with the rover. Post-integration testing used coordinated mast and instrument commands, including LIBS line scans on rock targets during system-level thermal-vacuum tests. In this paper we describe the body unit, optical fiber, and calibration targets, and the assembly, testing, and verification of the instrument prior to launch.

Journal ArticleDOI
TL;DR: It is shown that the type-1 cannabinoid receptor (CB1) is present at the membranes of mouse neuronal mitochondria, where it directly controls cellular respiration and energy production, revealing a new mechanism of action of G protein–coupled receptor signaling in the brain.
Abstract: The mammalian brain is one of the organs with the highest energy demands, and mitochondria are key determinants of its functions. Here we show that the type-1 cannabinoid receptor (CB(1)) is present at the membranes of mouse neuronal mitochondria (mtCB(1)), where it directly controls cellular respiration and energy production. Through activation of mtCB(1) receptors, exogenous cannabinoids and in situ endocannabinoids decreased cyclic AMP concentration, protein kinase A activity, complex I enzymatic activity and respiration in neuronal mitochondria. In addition, intracellular CB(1) receptors and mitochondrial mechanisms contributed to endocannabinoid-dependent depolarization-induced suppression of inhibition in the hippocampus. Thus, mtCB(1) receptors directly modulate neuronal energy metabolism, revealing a new mechanism of action of G protein-coupled receptor signaling in the brain.

Journal ArticleDOI
TL;DR: During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research, agreeing that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably.
Abstract: During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner's phenomenon (KP); and 'autoimmune vitiligo'. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term 'vitiligo' be used as an umbrella term for all non-segmental forms of vitiligo, including 'mixed vitiligo' in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that 'autoimmune vitiligo' should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.

Journal ArticleDOI
TL;DR: This is a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA).
Abstract: This is a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). This is endorsed by the governing bodies of the ACC Foundation, the AHA, the ECAS, the EHRA, the STS, the APHRS, and the HRS.

Journal ArticleDOI
TL;DR: The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia and the need for adequate staging in the case of high-grade dysplasia, and they focus on treatment and surveillance indications and methods.
Abstract: Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy, the European Helicobacter Study Group, the European Society of Pathology, and the Sociedade Portuguesa de Endoscopia Digestiva have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach. A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia and the need for adequate staging in the case of high-grade dysplasia, and they focus on treatment and surveillance indications and methods.

Journal ArticleDOI
TL;DR: The goal of this technical note is to design interval observers for a class of nonlinear continuous-time systems and shows that it is usually possible to design an interval observer for linear systems by means of linear time-invariant changes of coordinates even if the system is not cooperative.
Abstract: The goal of this technical note is to design interval observers for a class of nonlinear continuous-time systems. The first part of this work shows that it is usually possible to design an interval observer for linear systems by means of linear time-invariant changes of coordinates even if the system is not cooperative. This result is extended to a class of nonlinear systems using partial exact linearisations. The proposed observers guarantee to enclose the set of system states that is consistent with the model, the disturbances and the measurement noise. Moreover, it is only assumed that the measurement noise and the disturbances are bounded without any additional information such as stationarity, uncorrelation or type of distribution. The proposed observer is illustrated through numerical simulations.


Journal ArticleDOI
17 May 2012-Nature
TL;DR: This approach provides a general tool for time-resolving multi-electron rearrangements in atoms and molecules—one of the key challenges in ultrafast science.
Abstract: A method of laser-induced recollision permits measurement with attosecond resolution of the times at which the electron leaves the tunnelling barrier and discriminates between the ionization times of two carbon dioxide orbitals. Tunnelling of a particle through a barrier is one of the most fundamental and ubiquitous quantum processes. One issue much debated since the early days of quantum mechanics is the link between tunnelling and the dynamics of the particle outside the barrier. Shafir et al. explore this topic by inducing electron tunnelling from atoms and molecules with a strong laser field and then using a weaker probe field to steer the tunnelled electrons in the lateral direction. The liberated electrons emit an attosecond light burst when they re-encounter their parent ions; the effect of the steering on this light burst provides a measure of the time at which the electrons first exited from the tunnelling barrier, with a sensitivity that is sufficient to resolve subtle differences. This work provides a general approach to the direct resolution of multi-electron rearrangements in atoms and molecules in both space and time. The tunnelling of a particle through a barrier is one of the most fundamental and ubiquitous quantum processes. When induced by an intense laser field, electron tunnelling from atoms and molecules initiates a broad range of phenomena such as the generation of attosecond pulses1, laser-induced electron diffraction2,3 and holography2,4. These processes evolve on the attosecond timescale (1 attosecond ≡ 1 as = 10−18 seconds) and are well suited to the investigation of a general issue much debated since the early days of quantum mechanics5,6,7—the link between the tunnelling of an electron through a barrier and its dynamics outside the barrier. Previous experiments have measured tunnelling rates with attosecond time resolution8 and tunnelling delay times9. Here we study laser-induced tunnelling by using a weak probe field to steer the tunnelled electron in the lateral direction and then monitor the effect on the attosecond light bursts emitted when the liberated electron re-encounters the parent ion10. We show that this approach allows us to measure the time at which the electron exits from the tunnelling barrier. We demonstrate the high sensitivity of the measurement by detecting subtle delays in ionization times from two orbitals of a carbon dioxide molecule. Measurement of the tunnelling process is essential for all attosecond experiments where strong-field ionization initiates ultrafast dynamics10. Our approach provides a general tool for time-resolving multi-electron rearrangements in atoms and molecules11,12,13—one of the key challenges in ultrafast science.