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Showing papers by "Paul Sabatier University 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: In this paper, Li insertion into a 2D layered Ti-C-based material (MXene) with an oxidized surface, formed by etching Al from Ti₂AlC in HF at room temperature, was reported.

1,165 citations


Journal ArticleDOI
13 Sep 2012-Nature
TL;DR: These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.
Abstract: The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve 'health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

962 citations


Journal ArticleDOI
TL;DR: This work provides the first quantitative picture of the structure of an ionic liquid adsorbed inside realistically modelled microporous carbon electrodes and shows how the separation of the positive and negative ions occurs inside the porous disordered carbons, yielding much higher capacitance values than with simpler electrode geometries.
Abstract: Lightweight, low-cost supercapacitors with the capability of rapidly storing a large amount of electrical energy can contribute to meeting continuous energy demands and effectively levelling the cyclic nature of renewable energy sources1. The excellent electrochemical performance of supercapacitors is due to a reversible ion adsorption in porous carbon electrodes. Recently, it was demonstrated that ions from the electrolyte could enter sub nanometre pores, greatly increasing the capacitance2, 3, 4. However, the molecular mechanism of this enhancement remains poorly understood. Here we provide the first quantitative picture of the structure of an ionic liquid adsorbed inside realistically modelled microporous carbon electrodes. We show how the separation of the positive and negative ions occurs inside the porous disordered carbons, yielding much higher capacitance values (125 F g−1) than with simpler electrode geometries5. The proposed mechanism opens the door for the design of materials with improved energy storage capabilities. It also sheds new light on situations where ion adsorption in porous structures or membranes plays a role.

883 citations


Journal ArticleDOI
15 Feb 2012-PLOS ONE
TL;DR: Though these and other commonly-used decomposition methods returned many similar components, across 18 ICA/BSS algorithms mean dipolarity varied linearly with both MIR and with PMI remaining between the resulting component time courses, a result compatible with an interpretation of many maximally independent EEG components as being volume-conducted projections of partially-synchronous local cortical field activity within single compact cortical domains.
Abstract: Independent component analysis (ICA) and blind source separation (BSS) methods are increasingly used to separate individual brain and non-brain source signals mixed by volume conduction in electroencephalographic (EEG) and other electrophysiological recordings. We compared results of decomposing thirteen 71-channel human scalp EEG datasets by 22 ICA and BSS algorithms, assessing the pairwise mutual information (PMI) in scalp channel pairs, the remaining PMI in component pairs, the overall mutual information reduction (MIR) effected by each decomposition, and decomposition 'dipolarity' defined as the number of component scalp maps matching the projection of a single equivalent dipole with less than a given residual variance. The least well-performing algorithm was principal component analysis (PCA); best performing were AMICA and other likelihood/mutual information based ICA methods. Though these and other commonly-used decomposition methods returned many similar components, across 18 ICA/BSS algorithms mean dipolarity varied linearly with both MIR and with PMI remaining between the resulting component time courses, a result compatible with an interpretation of many maximally independent EEG components as being volume-conducted projections of partially-synchronous local cortical field activity within single compact cortical domains. To encourage further method comparisons, the data and software used to prepare the results have been made available (http://sccn.ucsd.edu/wiki/BSSComparison).

702 citations


Journal ArticleDOI
David Reich1, David Reich2, Nick Patterson2, Desmond Campbell3, Desmond Campbell4, Arti Tandon2, Arti Tandon1, Stéphane Mazières5, Stéphane Mazières4, Nicolas Ray6, María Victoria Parra4, María Victoria Parra7, Winston Rojas4, Winston Rojas7, Constanza Duque7, Constanza Duque4, Natalia Mesa7, Natalia Mesa4, Luis F. García7, Omar Triana7, Silvia Blair7, Amanda Maestre7, Juan Carlos Dib, Claudio M. Bravi4, Claudio M. Bravi8, Graciela Bailliet8, Daniel Corach9, Tábita Hünemeier4, Tábita Hünemeier10, Maria Cátira Bortolini10, Francisco M. Salzano10, Maria Luiza Petzl-Erler11, Victor Acuña-Alonzo, Carlos A. Aguilar-Salinas, Samuel Canizales-Quinteros12, Teresa Tusié-Luna12, Laura Riba12, Maricela Rodríguez-Cruz13, Mardia López-Alarcón13, Ramón Mauricio Coral-Vázquez14, Thelma Canto-Cetina, Irma Silva-Zolezzi15, Juan Carlos Fernández-López, Alejandra V. Contreras, Gerardo Jimenez-Sanchez15, María José Gómez-Vázquez16, Julio Molina, Angel Carracedo17, Antonio Salas17, Carla Gallo18, Giovanni Poletti18, David B. Witonsky19, Gorka Alkorta-Aranburu19, Rem I. Sukernik20, Ludmila P. Osipova20, Sardana A. Fedorova, René Vasquez, Mercedes Villena, Claudia Moreau21, Ramiro Barrantes22, David L. Pauls1, Laurent Excoffier23, Laurent Excoffier24, Gabriel Bedoya7, Francisco Rothhammer25, Jean-Michel Dugoujon26, Georges Larrouy26, William Klitz27, Damian Labuda21, Judith R. Kidd28, Kenneth K. Kidd28, Anna Di Rienzo19, Nelson B. Freimer29, Alkes L. Price2, Alkes L. Price1, Andres Ruiz-Linares4 
16 Aug 2012-Nature
TL;DR: It is shown that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America.
Abstract: The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

696 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
Roger C. Wiens1, Sylvestre Maurice2, Sylvestre Maurice3, B. L. Barraclough4, B. L. Barraclough1, Muriel Saccoccio5, Walter Barkley1, James F. Bell6, S. Bender4, S. Bender1, John D. Bernardin1, Diana L. Blaney7, Jennifer G. Blank8, Marc Bouyé2, Marc Bouyé3, Nathan T. Bridges9, Nathan K. Bultman1, Phillippe Caïs10, Robert C. Clanton1, Benton C. Clark11, Samuel M. Clegg1, Agnès Cousin3, Agnès Cousin2, David A. Cremers, Alain Cros2, Alain Cros3, Lauren DeFlores7, Dorothea Delapp1, Robert Dingler1, Claude d’Uston3, Claude d’Uston2, M. Darby Dyar12, Tom Elliott7, Don Enemark1, Cécile Fabre, Mike Flores1, Olivier Forni3, Olivier Forni2, Olivier Gasnault3, Olivier Gasnault2, Thomas Chatters Hale1, Charles C. Hays6, K. E. Herkenhoff13, Ed Kan7, L. E. Kirkland14, Driss Kouach3, Driss Kouach2, David Landis15, Yves Langevin16, Nina Lanza1, Nina Lanza17, Frank LaRocca18, Jérémie Lasue2, Jérémie Lasue1, 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. Parès2, L. Parès3, R. Perez5, Franck Poitrasson3, Franck Poitrasson2, 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 Thocaven3, Jean Jacques Thocaven2, Tanner Trujillo1, Mike Ulibarri1, David T. Vaniman1, David T. Vaniman4, 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.

482 citations


Journal ArticleDOI
TL;DR: It is suggested that posterior alpha oscillations (8-13Hz) provide a mechanism for prioritizing and ordering unattended visual input according to 'relevance' within an alpha cycle, producing a temporal phase code for saliency.

426 citations


Journal ArticleDOI
Ted R. Feldpausch1, Jon Lloyd2, Jon Lloyd1, Simon L. Lewis3, Simon L. Lewis1, Roel J. W. Brienen1, Manuel Gloor1, A. Monteagudo Mendoza, G. Lopez-Gonzalez1, Lindsay F. Banin1, Lindsay F. Banin4, K. Abu Salim5, Kofi Affum-Baffoe6, Miguel Alexiades7, Samuel Almeida8, Iêda Leão do Amaral, Ana Andrade, Luiz E. O. C. Aragão9, A. Araujo Murakami10, Eric Arets11, Luzmila Arroyo10, Timothy R. Baker1, Olaf Bánki12, Nicholas J. Berry13, Nallarett Davila Cardozo14, Jérôme Chave15, James A. Comiskey16, Esteban Álvarez, A. A. R. de Oliveira, A. Di Fiore17, Gloria Djagbletey18, Tomas F. Domingues19, Terry L. Erwin20, Philip M. Fearnside, Mabiane Batista França, Maria Aparecida Freitas8, Niro Higuchi, Yoshiko Iida21, E. M. Jimenez22, Abdul Rahman Kassim23, Timothy J. Killeen24, William F. Laurance2, Jon C. Lovett25, Yadvinder Malhi26, Beatriz Schwantes Marimon27, Ben Hur Marimon-Junior27, Eddie Lenza27, Andrew R. Marshall28, Casimiro Mendoza, Daniel J. Metcalfe29, Edward T. A. Mitchard13, David A. Neill, Bruce Walker Nelson, Reuben Nilus, Euler Melo Nogueira, Alexander Parada10, Kelvin S.-H. Peh30, A. Peña Cruz, M. C. Peñuela22, Nigel C. A. Pitman31, Adriana Prieto22, Carlos A. Quesada, Fredy Ramírez14, Hirma Ramírez-Angulo32, Jan Reitsma, Agustín Rudas22, Gustavo Saiz33, Rafael de Paiva Salomão8, Michael P. Schwarz1, Natalino Silva, Javier E. Silva-Espejo, Marcos Silveira34, Bonaventure Sonké35, Juliana Stropp, Hermann Taedoumg35, Sylvester Tan, H. ter Steege36, John Terborgh31, Mireia Torello-Raventos2, G. M. F. van der Heijden37, G. M. F. van der Heijden38, R. Vásquez, Emilio Vilanova32, Vincent A. Vos, Lee J. T. White39, Simon Willcock1, Hannsjorg Woell, Oliver L. Phillips1 
TL;DR: In this article, the effect of tree height (H) on tropical forest biomass and carbon storage estimates was investigated using data from 20 sites across four continents, and the results showed that tree H is an important allometric factor that needs to be included in future forest biomass estimates to reduce error in estimates of tropical carbon stocks and emissions.
Abstract: . Aboveground tropical tree biomass and carbon storage estimates commonly ignore tree height (H). We estimate the effect of incorporating H on tropics-wide forest biomass estimates in 327 plots across four continents using 42 656 H and diameter measurements and harvested trees from 20 sites to answer the following questions: 1. What is the best H-model form and geographic unit to include in biomass models to minimise site-level uncertainty in estimates of destructive biomass? 2. To what extent does including H estimates derived in (1) reduce uncertainty in biomass estimates across all 327 plots? 3. What effect does accounting for H have on plot- and continental-scale forest biomass estimates? The mean relative error in biomass estimates of destructively harvested trees when including H (mean 0.06), was half that when excluding H (mean 0.13). Power- and Weibull-H models provided the greatest reduction in uncertainty, with regional Weibull-H models preferred because they reduce uncertainty in smaller-diameter classes (≤40 cm D) that store about one-third of biomass per hectare in most forests. Propagating the relationships from destructively harvested tree biomass to each of the 327 plots from across the tropics shows that including H reduces errors from 41.8 Mg ha−1 (range 6.6 to 112.4) to 8.0 Mg ha−1 (−2.5 to 23.0). For all plots, aboveground live biomass was −52.2 Mg ha−1 (−82.0 to −20.3 bootstrapped 95% CI), or 13%, lower when including H estimates, with the greatest relative reductions in estimated biomass in forests of the Brazilian Shield, east Africa, and Australia, and relatively little change in the Guiana Shield, central Africa and southeast Asia. Appreciably different stand structure was observed among regions across the tropical continents, with some storing significantly more biomass in small diameter stems, which affects selection of the best height models to reduce uncertainty and biomass reductions due to H. After accounting for variation in H, total biomass per hectare is greatest in Australia, the Guiana Shield, Asia, central and east Africa, and lowest in east-central Amazonia, W. Africa, W. Amazonia, and the Brazilian Shield (descending order). Thus, if tropical forests span 1668 million km2 and store 285 Pg C (estimate including H), then applying our regional relationships implies that carbon storage is overestimated by 35 Pg C (31–39 bootstrapped 95% CI) if H is ignored, assuming that the sampled plots are an unbiased statistical representation of all tropical forest in terms of biomass and height factors. Our results show that tree H is an important allometric factor that needs to be included in future forest biomass estimates to reduce error in estimates of tropical carbon stocks and emissions due to deforestation.

426 citations


Journal ArticleDOI
TL;DR: The algorithm can be used to provide an efficient parametric estimation of the quantum state and therefore can be applied as an alternative to full quantum-state tomography given a fault tolerant quantum computer.
Abstract: We provide a new quantum algorithm that efficiently determines the quality of a least-squares fit over an exponentially large data set by building upon an algorithm for solving systems of linear equations efficiently [Harrow et al., Phys. Rev. Lett. 103, 150502 (2009)]. In many cases, our algorithm can also efficiently find a concise function that approximates the data to be fitted and bound the approximation error. In cases where the input data are pure quantum states, the algorithm can be used to provide an efficient parametric estimation of the quantum state and therefore can be applied as an alternative to full quantum-state tomography given a fault tolerant quantum computer.

Journal ArticleDOI
01 Apr 2012
TL;DR: The research described in this paper is focused on analyzing two playful domains of language: humor and irony, in order to identify key values components for their automatic processing in social media, such as ''tweets''.
Abstract: The research described in this paper is focused on analyzing two playful domains of language: humor and irony, in order to identify key values components for their automatic processing. In particular, we are focused on describing a model for recognizing these phenomena in social media, such as ''tweets''. Our experiments are centered on five data sets retrieved from Twitter taking advantage of user-generated tags, such as ''#humor'' and ''#irony''. The model, which is based on textual features, is assessed on two dimensions: representativeness and relevance. The results, apart from providing some valuable insights into the creative and figurative usages of language, are positive regarding humor, and encouraging regarding irony.

Journal ArticleDOI
01 Sep 2012-Diabetes
TL;DR: These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.
Abstract: T-cell regulation in adipose tissue provides a link between inflammation and insulin resistance. Because of alterations in adipose tissue T-cell composition in obesity, we aimed to identify the antigen-presenting cells in adipose tissue of obese mice and patients with insulin resistance. Dendritic cells (DCs) and T cells were studied in mice and in two cohorts of obese patients. In lean mice, only CD11c(+) DCs were detected in adipose tissue. Adoptive transfer of naive CD4(+) T cells in Rag1(-/-) mice led to a predominant Th1 response in adipose tissue. In contrast, during obesity DCs (human CD11c(+)CD1c(+) and mouse CD11c(high)F4/80(low)) accumulated in adipose tissue. CD11c(high)F4/80(low) DCs from obese mice induced Th17 differentiation. In patients, the presence of CD11c(+)CD1c(+) DCs correlated with the BMI and with an elevation in Th17 cells. In addition, these DCs led to ex vivo Th17 differentiation. CD1c gene expression further correlated with homeostatic model assessment-insulin resistance in the subcutaneous adipose tissue of obese patients. We show for the first time the presence and accumulation of specific DCs in adipose tissue in mouse and human obesity. These DCs were functional and could be important regulators of adipose tissue inflammation by regulating the switch toward Th17 cell responses in obesity-associated insulin resistance.

Journal ArticleDOI
TL;DR: Background Interleukin (IL)‐17A has major proinflammatory activity in psoriatic lesional skin and its role in promoting wound healing is still under investigation.
Abstract: Background: Interleukin-17A has major proinflammatory activity in psoriatic lesional skin. Objectives: Assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti-interleukin-17A antibody, in moderate-to-severe plaque psoriasis in a phase II regimen-finding study. Methods: 404 patients were randomised to subcutaneous placebo (67 patients) or one of three secukinumab 150 mg induction regimens: Single (week 0; 66 patients), Early (weeks 0, 1, 2, 4; 133 patients), and Monthly (weeks 0, 4, 8; 138 patients). The primary outcome was ≥75% improvement from baseline Psoriasis Area and Severity Index (PASI) score at week 12. PASI 75 responders from active treatment arms at week 12 were re-randomised to either a fixed-interval (secukinumab 150 mg at weeks 12 and 24; 65 patients) or a treatment-at-start-of-relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; 67 patients). Results: At week 12, Early and Monthly induction regimens resulted in higher PASI 75 response rates versus placebo (54·5% and 42·0% vs. 1·5%; P<0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed-interval regimen (84·6% [n = 55] and 58·5% [n = 38], respectively) versus the start-of-relapse regimen (67·2% [n = 45], P = 0·020 and 20·9% [n = 14], respectively). Fifteen weeks after last study drug administration, <10% of patients in the fixed-interval and start-of-relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection site reactions were reported. Reported cases of neutropaenia were mild-to-moderate (≤grade 2); none were associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long-term safety. Conclusions: Secukinumab shows efficacy for induction and maintenance treatment of moderate-to-severe plaque psoriasis.

Journal ArticleDOI
TL;DR: Using video tracks of fish shoal in a tank, it is shown how a careful, incremental analysis at the local scale allows for the determination of the stimulus/response function governing an individual's moving decisions, yielding a novel schooling model whose parameters are all estimated from data.
Abstract: Collective motion phenomena in large groups of social organisms have long fascinated the observer, especially in cases, such as bird flocks or fish schools, where large-scale highly coordinated actions emerge in the absence of obvious leaders. However, the mechanisms involved in this self-organized behavior are still poorly understood, because the individual-level interactions underlying them remain elusive. Here, we demonstrate the power of a bottom-up methodology to build models for animal group motion from data gathered at the individual scale. Using video tracks of fish shoal in a tank, we show how a careful, incremental analysis at the local scale allows for the determination of the stimulus/response function governing an individual's moving decisions. We find in particular that both positional and orientational effects are present, act upon the fish turning speed, and depend on the swimming speed, yielding a novel schooling model whose parameters are all estimated from data. Our approach also leads to identify a density-dependent effect that results in a behavioral change for the largest groups considered. This suggests that, in confined environment, the behavioral state of fish and their reaction patterns change with group size. We debate the applicability, beyond the particular case studied here, of this novel framework for deciphering interactions in moving animal groups.

Journal ArticleDOI
TL;DR: In this article, the azimuthal orientation of the quasar sight-lines with strong Mg II absorption (withW 2796 r > 0:3 ˚ A) is shown to be bi-modal.
Abstract: Background quasars are potentially sensitive probes of galactic outflows provided that one can determine the origin of the absorbing material since both gaseous disks and strong bipolar outflows can contribute to the absorption cross-section. Using a dozen quasars passing near spectroscopically identified galaxies at z 0:1, we find that the azimuthal orientation of the quasar sight-lines with strong Mg II absorption (withW 2796 r > 0:3 ˚ A) is bi-modal: about half the Mg II sight-lines are aligned with the major axis and the other half are within = 30 of the minor axis, suggesting that bipolar outflows can contribute to the Mg II cross-section. This bi-modality is also present in the instantaneous star-formation rates (SFRs) of the hosts. For the sight-lines aligned along the minor axis, a simple bi-conical wind model is indeed able to reproduce the observed Mg II kinematics and the Mg II dependence with impact parameter b, (W 2796 r / b 1 ). Using our wind model, we can directly extract key wind properties such as the de-projected outflow speed Vout of the cool material traced by Mg II and the outflow rates _ Mout. The outflow speeds Vout are found to be 150-300 kms 1 , i.e. of the order of the circular velocity, and smaller than the escape velocity by a factor of 2. The outflow rates _ Mout are typically two to three times the instantaneous SFRs. Our results demonstrate how background quasars can be used to measure wind properties with high precision.

Journal ArticleDOI
TL;DR: Based on the considerable overlap of genotype and phenotype of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification and other organ pathologies, rather than two distinct disorders.
Abstract: Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive. We hypothesized that GACI and PXE are in a closely related spectrum of disease. We used a standardized questionnaire to retrospectively evaluate the phenotype of 92 probands with a clinical history of GACI. We obtained the ENPP1 genotype by conventional sequencing. In those patients with less than two disease-causing ENPP1 mutations, we sequenced ABCC6. We observed that three GACI patients who carried biallelic ENPP1 mutations developed typical signs of PXE between 5 and 8 years of age; these signs included angioid streaks and pseudoxanthomatous skin lesions. In 28 patients, no disease-causing ENPP1 mutation was found. In 14 of these patients, we detected pathogenic ABCC6 mutations (biallelic mutations in eight patients, monoallelic mutations in six patients). Thus, ABCC6 mutations account for a significant subset of GACI patients, and ENPP1 mutations can also be associated with PXE lesions in school-aged children. Based on the considerable overlap of genotype and phenotype of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification and other organ pathologies, rather than two distinct disorders. ABCC6 and ENPP1 mutations might lead to alterations of the same physiological pathways in tissues beyond the artery.

Journal ArticleDOI
12 Jan 2012-Blood
TL;DR: It is shown, in humanized mice, that the TLR-7-mediated response of human pDCs is increased in female host mice relative to male, and a previously unappreciated role for estrogens in regulating the innate functions of p DCs is uncovered, which may account for sex-based differences in autoimmune and infectious diseases.

Journal ArticleDOI
TL;DR: There is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime with narrowband UV‐B, and there is still controversy regarding the risk of skin cancer with NB‐UVB.
Abstract: BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and narrowband UV-B (NB-UVB or UVB TL-01) are effective and widely used treatments for chronic plaque psoriasis. Although the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated, there is still controversy regarding the risk of skin cancer with NB-UVB. Furthermore, there is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime. OBJECTIVES: To assess the respective cutaneous carcinogenic risks of PUVA or NB-UVB in psoriasis; to estimate the respective dose-relationship between skin cancers and PUVA or NB-UVB; to estimate a maximum number of sessions for PUVA or NB-UVB not to be exceeded in a lifetime. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from1980 to December 2010 in English and French, with the keywords 'Psoriasis' AND 'UVB therapy' AND 'UVA therapy' AND 'cancer' AND 'skin' OR 'neoplasm' OR 'cutaneous carcinoma' OR 'melanoma'. RESULTS: Of 243 identified references, 49 published studies were included. Most of them (45/49) concerned PUVA therapy, with 41 assessing the risk of non-melanoma skin cancers (NMSC) following PUVA. All publications referring to the US prospective PUVA follow-up study revealed an increased risk of NMSC with the following characteristics: risk most pronounced for squamous cell carcinomas developing even with low exposures and increasing linearly with the number of sessions, tumors occurring also on non-exposed skin including invasive penile tumors, risk persisting after cessation of treatment. An increased risk of basal cell carcinomas was observed in patients receiving more than hundred PUVA sessions. The four prospective European studies selected in our review and most of the pre-1990 European and US retrospective studies failed to find a link between exposure to PUVA and skin cancer. Only the most recent cohorts, including three large long-term retrospective European studies comparing records with their respective national cancer registries reported on an independent increased risk of NMSC with PUVA, The risk was lower as compared to the US prospective PUVA follow-up study. Six studies assessed the risk of melanoma following PUVA therapy: two of the three US publications coming from the same PUVA prospective follow-up study revealed an increased risk with more than doubled incidence of both invasive and in situ melanoma among patients exposed to at least 200 PUVA treatments compared with patients exposed to lower doses, whereas the three retrospectives European studies, comparing the incidence of melanoma in PUVA users with national cancer registers, did not find any increased risk of melanoma. No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB. CONCLUSION: There is an increased risk of skin cancer following PUVA, shown by both US and European studies. The greater risk measured by the US studies may be at least partly explained by high UVA dose exposure and the lighter phototypes of the treated patients. The lack of prospective studies in psoriasis patients treated with NB-UVB constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy technique.

01 Aug 2012
TL;DR: In this article, the quality of a least-squares fit over an exponentially large data set was determined by building upon an algorithm for solving systems of linear equations efficiently, which can be used to provide an efficient parametric estimation of the quantum state and therefore can be applied as an alternative to full quantum-state tomography given a fault tolerant quantum computer.
Abstract: We provide a new quantum algorithm that efficiently determines the quality of a least-squares fit over an exponentially large data set by building upon an algorithm for solving systems of linear equations efficiently [Harrow et al., Phys. Rev. Lett. 103, 150502 (2009)]. In many cases, our algorithm can also efficiently find a concise function that approximates the data to be fitted and bound the approximation error. In cases where the input data are pure quantum states, the algorithm can be used to provide an efficient parametric estimation of the quantum state and therefore can be applied as an alternative to full quantum-state tomography given a fault tolerant quantum computer.

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12 Oct 2012-Cell
TL;DR: It is shown that hedgehog signaling rewires cellular metabolism and is identified a cilium-dependent Smo-Ca(2+)-Ampk axis that triggers rapid Warburg-like metabolic reprogramming within minutes of activation and is required for proper metabolic selectivity and flexibility.

Journal ArticleDOI
TL;DR: In this paper, the authors performed a uniform analysis of 22 stars with the highest signal-to-noise ratio observed for 1 month each during the first year of the Kepler space telescope and quantified the precision and relative accuracy of asteroseismic determinations of the stellar radius, mass and age that are possible using various methods.
Abstract: Asteroseismology with the Kepler space telescope is providing not only an improved characterization of exoplanets and their host stars, but also a new window on stellar structure and evolution for the large sample of solar-type stars in the field. We perform a uniform analysis of 22 of the brightest asteroseismic targets with the highest signal-to-noise ratio observed for 1 month each during the first year of the mission, and we quantify the precision and relative accuracy of asteroseismic determinations of the stellar radius, mass, and age that are possible using various methods. We present the properties of each star in the sample derived from an automated analysis of the individual oscillation frequencies and other observational constraints using the Asteroseismic Modeling Portal (AMP), and we compare them to the results of model-grid-based methods that fit the global oscillation properties. We find that fitting the individual frequencies typically yields asteroseismic radii and masses to ~1% precision, and ages to ~2.5% precision (respectively, 2, 5, and 8 times better than fitting the global oscillation properties). The absolute level of agreement between the results from different approaches is also encouraging, with model-grid-based methods yielding slightly smaller estimates of the radius and mass and slightly older values for the stellar age relative to AMP, which computes a large number of dedicated models for each star. The sample of targets for which this type of analysis is possible will grow as longer data sets are obtained during the remainder of the mission.

Journal ArticleDOI
TL;DR: Positron emission tomography with florbetapir is a safe and suitable biomarker for AD that can be used routinely in a clinical environment, however, the low specificity of the visual PET scan assessment could be improved by the use of specific training and automatic or semiautomatic quantification tools.
Abstract: Purpose Positron emission tomography (PET) imaging of brain amyloid load has been suggested as a core biomarker for Alzheimer’s disease (AD). The aim of this study was to test the feasibility of using PET imaging with 18F-AV-45 (florbetapir) in a routine clinical environment to differentiate between patients with mild to moderate AD and mild cognitive impairment (MCI) from normal healthy controls (HC).

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TL;DR: In this paper, a very short (usually <100 base pairs) but informative DNA fragment was extracted from dead material in soil to assess biodiversity in different biomes, including boreal soil.
Abstract: Ecosystems across the globe are threatened by climate change and human activities. New rapid survey approaches for monitoring biodiversity would greatly advance assessment and understanding of these threats. Taking advantage of next-generation DNA sequencing, we tested an approach we call metabarcoding: high-throughput and simultaneous taxa identification based on a very short (usually <100 base pairs) but informative DNA fragment. Short DNA fragments allow the use of degraded DNA from environmental samples. All analyses included amplification using plant-specific versatile primers, sequencing and estimation of taxonomic diversity. We tested in three steps whether degraded DNA from dead material in soil has the potential of efficiently assessing biodiversity in different biomes. First, soil DNA from eight boreal plant communities located in two different vegetation types (meadow and heath) was amplified. Plant diversity detected from boreal soil was highly consistent with plant taxonomic and growth form diversity estimated from conventional above-ground surveys. Second, we assessed DNA persistence using samples from formerly cultivated soils in temperate environments. We found that the number of crop DNA sequences retrieved strongly varied with years since last cultivation, and crop sequences were absent from nearby, uncultivated plots. Third, we assessed the universal applicability of DNA metabarcoding using soil samples from tropical environments: a large proportion of species and families from the study site were efficiently recovered. The results open unprecedented opportunities for large-scale DNA-based biodiversity studies across a range of taxonomic groups using standardized metabarcoding approaches.

Journal ArticleDOI
TL;DR: The possibility of interfacial storage at low potential for electrode materials reacting through conversion reactions was evaluated in this paper, where the amount of charge that could be stored through the proposed interfacial mechanism was estimated for a range of different materials and was much lower than those observed experimentally.

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TL;DR: Oral treatment with Elafin-expressing food-grade bacteria protected the gut from inflammatory damage and restored intestinal homeostasis in mouse models of acute and chronic colitis, and suggested that oral delivery of LAB secreting ElafIn may be useful for treating IBD in humans.
Abstract: Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has pleiotropic anti-inflammatory properties in vitro and in animal models. We found that mucosal expression of Elafin is diminished in patients with inflammatory bowel disease (IBD). This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue. We engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the site of inflammation in the colon to assess the potential therapeutic benefits of the Elafin-expressing LAB. In mouse models of acute and chronic colitis, oral administration of Elafin-expressing LAB decreased elastolytic activity and inflammation and restored intestinal homeostasis. Furthermore, when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD. Together, these results suggest that oral delivery of LAB secreting Elafin may be useful for treating IBD in humans.


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TL;DR: A set of paradigmatic modelling assumptions whose validity remains unclear are emphasized, both from a behavioural point of view and in terms of quantitative agreement between model outcome and empirical data, for a specific and biologically oriented re-examination of these assumptions through experimental-based behavioural analysis and modelling.
Abstract: Fish schooling is a phenomenon of long-lasting interest in ethology and ecology, widely spread across taxa and ecological contexts, and has attracted much interest from statistical physics and theoretical biology as a case of self-organized behaviour. One topic of intense interest is the search of specific behavioural mechanisms at stake at the individual level and from which the school properties emerges. This is fundamental for understanding how selective pressure acting at the individual level promotes adaptive properties of schools and in trying to disambiguate functional properties from non-adaptive epiphenomena. Decades of studies on collective motion by means of individual-based modelling have allowed a qualitative understanding of the self-organization processes leading to collective properties at school level, and provided an insight into the behavioural mechanisms that result in coordinated motion. Here, we emphasize a set of paradigmatic modelling assumptions whose validity remains unclear, both from a behavioural point of view and in terms of quantitative agreement between model outcome and empirical data. We advocate for a specific and biologically oriented re-examination of these assumptions through experimental-based behavioural analysis and modelling.

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TL;DR: This work provides the most comprehensive examination to date of the relative importance of environmental filtering and limiting similarity in structuring tropical tree communities and confirms that environmental filtering is the overriding influence on community assembly in these species-rich systems.
Abstract: 1 Niche theory proposes that species differences underlie both coexistence within communities and the differentiation in species composition among communities via limiting similarity and environmental filtering However, it has been difficult to extend niche theory to species-rich communities because of the empirical challenge of quantifying niches for many species This has motivated the development of functional and phylogeny-based approaches in community ecology, which represent two different means of approximating niche attributes 2 Here, we assess the utility of plant functional traits and phylogenetic relationships in predicting community assembly processes using the largest trait and phylogenetic data base to date for any set of species-rich communities 3 We measured 17 functional traits for all 4672 individuals of 668 tree species co-occurring in nine tropical rain forest plots in French Guiana Trait variation was summarized into two ordination axes that reflect species niche overlap 4 We also generated a dated molecular phylogenetic tree based on DNA sequencing of two plastid loci (rbcL and matK) comprising 97% of the individuals and 91% of the species in the plots 5 We found that, on average, co-occurring species had greater functional and, to a lesser extent, phylogenetic similarity than expected by chance 6 We also found that functional traits and their ordination loadings showed significant, albeit weak, phylogenetic signal, suggesting that phylogenetic distance provides pertinent information on niche overlap in tropical tree communities 7 Synthesis We provide the most comprehensive examination to date of the relative importance of environmental filtering and limiting similarity in structuring tropical tree communities Our results confirm that environmental filtering is the overriding influence on community assembly in these species-rich systems

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TL;DR: In this paper, the electrochemical determination of Hg(II) at trace level using gold nanoparticles-modified glassy carbon (AuNPs-GC) electrodes is described.