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Showing papers by "University of Göttingen published in 2016"


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy 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. For example, 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 versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase 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. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. 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. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. 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 assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
TL;DR: In this article, a game theoretic approach for computation offloading in a distributed manner was adopted to solve the multi-user offloading problem in a multi-channel wireless interference environment.
Abstract: Mobile-edge cloud computing is a new paradigm to provide cloud computing capabilities at the edge of pervasive radio access networks in close proximity to mobile users. In this paper, we first study the multi-user computation offloading problem for mobile-edge cloud computing in a multi-channel wireless interference environment. We show that it is NP-hard to compute a centralized optimal solution, and hence adopt a game theoretic approach for achieving efficient computation offloading in a distributed manner. We formulate the distributed computation offloading decision making problem among mobile device users as a multi-user computation offloading game. We analyze the structural property of the game and show that the game admits a Nash equilibrium and possesses the finite improvement property. We then design a distributed computation offloading algorithm that can achieve a Nash equilibrium, derive the upper bound of the convergence time, and quantify its efficiency ratio over the centralized optimal solutions in terms of two important performance metrics. We further extend our study to the scenario of multi-user computation offloading in the multi-channel wireless contention environment. Numerical results corroborate that the proposed algorithm can achieve superior computation offloading performance and scale well as the user size increases.

2,013 citations


Journal ArticleDOI
25 Aug 2016-Nature
TL;DR: Observations reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units.
Abstract: At a distance of 1.295 parsecs, the red dwarf Proxima Centauri (α Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref. 3) and its quiescent activity levels and X-ray luminosity are comparable to those of the Sun. Here we report observations that reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units. Its equilibrium temperature is within the range where water could be liquid on its surface.

1,052 citations


Journal ArticleDOI
TL;DR: Recent progress in the field of organometallic cobalt-catalyzed C–H activation is reviewed until November 2015.
Abstract: Catalytic C–H activation has emerged as a powerful tool for sustainable syntheses. In the recent years, notable success was achieved with the development of cobalt-catalyzed C–H functionalizations with either in situ generated or single-component cobalt-complexes under mild reaction conditions. Herein, recent progress in the field of organometallic cobalt-catalyzed C–H activation is reviewed until November 2015.

953 citations


Journal ArticleDOI
TL;DR: This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches to help the reader to appropriately design and conduct studies involving these brain stimulation techniques.

942 citations


Journal ArticleDOI
TL;DR: Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches, and validates that collaborative data analyses can readily be used across brain phenotypes and disorders.
Abstract: The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

919 citations


Journal ArticleDOI
Jingjing Liang1, Thomas W. Crowther2, Nicolas Picard3, Susan K. Wiser4, Mo Zhou1, Giorgio Alberti5, Ernst Detlef Schulze6, A. David McGuire7, Fabio Bozzato, Hans Pretzsch8, Sergio de-Miguel, Alain Paquette9, Bruno Hérault10, Michael Scherer-Lorenzen11, Christopher B. Barrett12, Henry B. Glick2, Geerten M. Hengeveld13, Gert-Jan Nabuurs13, Sebastian Pfautsch14, Helder Viana15, Helder Viana16, Alexander Christian Vibrans, Christian Ammer17, Peter Schall17, David David Verbyla7, N. M. Tchebakova18, Markus Fischer19, James V. Watson1, Han Y. H. Chen20, Xiangdong Lei, Mart-Jan Schelhaas13, Huicui Lu13, Damiano Gianelle, Elena I. Parfenova18, Christian Salas21, Eungul Lee1, Boknam Lee22, Hyun-Seok Kim, Helge Bruelheide23, David A. Coomes24, Daniel Piotto, Terry Sunderland25, Terry Sunderland26, Bernhard Schmid27, Sylvie Gourlet-Fleury, Bonaventure Sonké28, Rebecca Tavani3, Jun Zhu29, Susanne Brandl8, Jordi Vayreda, Fumiaki Kitahara, Eric B. Searle20, Victor J. Neldner30, Michael R. Ngugi30, Christopher Baraloto31, Christopher Baraloto32, Lorenzo Frizzera, Radomir Bałazy33, Jacek Oleksyn34, Jacek Oleksyn35, Tomasz Zawiła-Niedźwiecki36, Olivier Bouriaud37, Filippo Bussotti38, Leena Finér, Bogdan Jaroszewicz39, Tommaso Jucker24, Fernando Valladares40, Fernando Valladares41, Andrzej M. Jagodziński34, Pablo Luis Peri42, Pablo Luis Peri43, Pablo Luis Peri44, Christelle Gonmadje28, William Marthy45, Timothy G. O'Brien45, Emanuel H. Martin46, Andrew R. Marshall47, Francesco Rovero, Robert Bitariho, Pascal A. Niklaus27, Patricia Alvarez-Loayza48, Nurdin Chamuya49, Renato Valencia50, Frédéric Mortier, Verginia Wortel, Nestor L. Engone-Obiang51, Leandro Valle Ferreira52, David E. Odeke, R. Vásquez, Simon L. Lewis53, Simon L. Lewis54, Peter B. Reich14, Peter B. Reich35 
West Virginia University1, Yale University2, Food and Agriculture Organization3, Landcare Research4, University of Udine5, Max Planck Society6, University of Alaska Fairbanks7, Technische Universität München8, Université du Québec à Montréal9, University of the French West Indies and Guiana10, University of Freiburg Faculty of Biology11, Cornell University12, Wageningen University and Research Centre13, University of Sydney14, Polytechnic Institute of Viseu15, University of Trás-os-Montes and Alto Douro16, University of Göttingen17, Russian Academy of Sciences18, Oeschger Centre for Climate Change Research19, Lakehead University20, University of La Frontera21, Seoul National University22, Martin Luther University of Halle-Wittenberg23, University of Cambridge24, James Cook University25, Center for International Forestry Research26, University of Zurich27, University of Yaoundé I28, University of Wisconsin-Madison29, Queensland Government30, Florida International University31, Institut national de la recherche agronomique32, Forest Research Institute33, Polish Academy of Sciences34, University of Minnesota35, Warsaw University of Life Sciences36, Ştefan cel Mare University of Suceava37, University of Florence38, University of Warsaw39, King Juan Carlos University40, Spanish National Research Council41, International Trademark Association42, National Scientific and Technical Research Council43, National University of Austral Patagonia44, Wildlife Conservation Society45, College of African Wildlife Management46, University of York47, Durham University48, Ontario Ministry of Natural Resources49, Pontificia Universidad Católica del Ecuador50, Centre national de la recherche scientifique51, Museu Paraense Emílio Goeldi52, University of Leeds53, University College London54
14 Oct 2016-Science
TL;DR: A consistent positive concave-down effect of biodiversity on forest productivity across the world is revealed, showing that a continued biodiversity loss would result in an accelerating decline in forest productivity worldwide.
Abstract: The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone-US$166 billion to 490 billion per year according to our estimation-is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities.

889 citations


Journal ArticleDOI
TL;DR: Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities that are over an order of magnitude above those produced by conventional tDCS.

874 citations


Journal ArticleDOI
TL;DR: This paper features the first comprehensive and critical account of European syntaxa and synthesizes more than 100 yr of classification effort by European phytosociologists.
Abstract: Aims: Vegetation classification consistent with the Braun-Blanquet approach is widely used in Europe for applied vegetation science, conservation planning and land management. During the long history of syntaxonomy, many concepts and names of vegetation units have been proposed, but there has been no single classification system integrating these units. Here we (1) present a comprehensive, hierarchical, syntaxonomic system of alliances, orders and classes of Braun-Blanquet syntaxonomy for vascular plant, bryophyte and lichen, and algal communities of Europe; (2) briefly characterize in ecological and geographic terms accepted syntaxonomic concepts; (3) link available synonyms to these accepted concepts; and (4) provide a list of diagnostic species for all classes. LocationEuropean mainland, Greenland, Arctic archipelagos (including Iceland, Svalbard, Novaya Zemlya), Canary Islands, Madeira, Azores, Caucasus, Cyprus. Methods: We evaluated approximately 10000 bibliographic sources to create a comprehensive list of previously proposed syntaxonomic units. These units were evaluated by experts for their floristic and ecological distinctness, clarity of geographic distribution and compliance with the nomenclature code. Accepted units were compiled into three systems of classes, orders and alliances (EuroVegChecklist, EVC) for communities dominated by vascular plants (EVC1), bryophytes and lichens (EVC2) and algae (EVC3). Results: EVC1 includes 109 classes, 300 orders and 1108 alliances; EVC2 includes 27 classes, 53 orders and 137 alliances, and EVC3 includes 13 classes, 24 orders and 53 alliances. In total 13448 taxa were assigned as indicator species to classes of EVC1, 2087 to classes of EVC2 and 368 to classes of EVC3. Accepted syntaxonomic concepts are summarized in a series of appendices, and detailed information on each is accessible through the software tool EuroVegBrowser. Conclusions: This paper features the first comprehensive and critical account of European syntaxa and synthesizes more than 100 yr of classification effort by European phytosociologists. It aims to document and stabilize the concepts and nomenclature of syntaxa for practical uses, such as calibration of habitat classification used by the European Union, standardization of terminology for environmental assessment, management and conservation of nature areas, landscape planning and education. The presented classification systems provide a baseline for future development and revision of European syntaxonomy.

817 citations


Journal ArticleDOI
TL;DR: It is shown that CHELSA climatological data has a similar accuracy as other products for temperature, but that its predictions of precipitation patterns are better and can increase the accuracy of species range predictions.
Abstract: High resolution information on climatic conditions is essential to many applications in environmental and ecological sciences. Here we present the CHELSA Climatologies at high resolution for the earths land surface areas data of downscaled model output temperature and precipitation estimates of the ERA Interim climatic reanalysis to a high resolution of 30 arc seconds. The temperature algorithm is based on statistical downscaling of atmospheric temperatures. The precipitation algorithm incorporates orographic predictors including wind fields, valley exposition, and boundary layer height with a subsequent bias correction. The resulting data consist of a monthly temperature and precipitation climatology for the years 1979 to 2013. We compare the data derived from the CHELSA algorithm with other standard gridded products and station data from the Global Historical Climate Network. We compare the performance of the new climatologies in species distribution modelling and show that we can increase the accuracy of species range predictions. We further show that CHELSA climatological data has a similar accuracy as other products for temperature but that its predictions of precipitation patterns are better.

809 citations


Journal ArticleDOI
TL;DR: In this article, a general framework for smoothing parameter estimation for models with regular likelihoods constructed in terms of unknown smooth functions of covariates is discussed, where the smoothing parameters controlling the extent of penalization are estimated by Laplace approximate marginal likelihood.
Abstract: This article discusses a general framework for smoothing parameter estimation for models with regular likelihoods constructed in terms of unknown smooth functions of covariates. Gaussian random effects and parametric terms may also be present. By construction the method is numerically stable and convergent, and enables smoothing parameter uncertainty to be quantified. The latter enables us to fix a well known problem with AIC for such models, thereby improving the range of model selection tools available. The smooth functions are represented by reduced rank spline like smoothers, with associated quadratic penalties measuring function smoothness. Model estimation is by penalized likelihood maximization, where the smoothing parameters controlling the extent of penalization are estimated by Laplace approximate marginal likelihood. The methods cover, for example, generalized additive models for nonexponential family responses (e.g., beta, ordered categorical, scaled t distribution, negative binomial a...

Posted ContentDOI
23 Feb 2016-bioRxiv
TL;DR: A collaborative effort in which a centralized analysis pipeline is applied to a SCZ cohort, finding support at a suggestive level for nine additional candidate susceptibility and protective loci, which consist predominantly of CNVs mediated by non-allelic homologous recombination (NAHR).
Abstract: Genomic copy number variants (CNVs) have been strongly implicated in the etiology of schizophrenia (SCZ). However, apart from a small number of risk variants, elucidation of the CNV contribution to risk has been difficult due to the rarity of risk alleles, all occurring in less than 1% of cases. We sought to address this obstacle through a collaborative effort in which we applied a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. We observed a global enrichment of CNV burden in cases (OR=1.11, P=5.7e-15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7e-6). CNV burden is also enriched for genes associated with synaptic function (OR = 1.68, P = 2.8e-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3e-5). We identified genome-wide significant support for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. We find support at a suggestive level for nine additional candidate susceptibility and protective loci, which consist predominantly of CNVs mediated by non-allelic homologous recombination (NAHR).

Journal ArticleDOI
TL;DR: Three-dimensional brain magnetic resonance imaging data was meta-analyzed to identify subcortical brain volumes that robustly discriminate major depressive disorder patients from healthy controls and showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
Abstract: The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Journal ArticleDOI
TL;DR: The new ICD‐10‐CM (M62.84) code for sarc Openia represents a major step forward in recognizing sarcopenia as a disease and should lead to an increase in availability of diagnostic tools and the enthusiasm for pharmacological companies to develop drugs for sarc openia.
Abstract: The new ICD-10-CM (M62.84) code for sarcopenia represents a major step forward in recognizing sarcopenia as a disease. This should lead to an increase in availability of diagnostic tools and the enthusiasm for pharmacological companies to develop drugs for sarcopenia.

Journal ArticleDOI
TL;DR: In this article, a meta-analysis of the biochar decomposition in soil was performed and the authors concluded that only a small part of biochar is bioavailable and that the remaining 97% contribute directly to long-term carbon sequestration in soil.
Abstract: The stability and decomposition of biochar are fundamental to understand its persistence in soil, its contribution to carbon (C) sequestration, and thus its role in the global C cycle. Our current knowledge about the degradability of biochar, however, is limited. Using 128 observations of biochar-derived CO2 from 24 studies with stable (13C) and radioactive (14C) carbon isotopes, we meta-analyzed the biochar decomposition in soil and estimated its mean residence time (MRT). The decomposed amount of biochar increased logarithmically with experimental duration, and the decomposition rate decreased with time. The biochar decomposition rate varied significantly with experimental duration, feedstock, pyrolysis temperature, and soil clay content. The MRTs of labile and recalcitrant biochar C pools were estimated to be about 108 days and 556 years with pool sizes of 3% and 97%, respectively. These results show that only a small part of biochar is bioavailable and that the remaining 97% contribute directly to long-term C sequestration in soil. The second database (116 observations from 21 studies) was used to evaluate the priming effects after biochar addition. Biochar slightly retarded the mineralization of soil organic matter (SOM; overall mean: −3.8%, 95% CI = −8.1–0.8%) compared to the soil without biochar addition. Significant negative priming was common for studies with a duration shorter than half a year (−8.6%), crop-derived biochar (−20.3%), fast pyrolysis (−18.9%), the lowest pyrolysis temperature (−18.5%), and small application amounts (−11.9%). In contrast, biochar addition to sandy soils strongly stimulated SOM mineralization by 20.8%. This indicates that biochar stimulates microbial activities especially in soils with low fertility. Furthermore, abiotic and biotic processes, as well as the characteristics of biochar and soils, affecting biochar decomposition are discussed. We conclude that biochar can persist in soils on a centennial scale and that it has a positive effect on SOM dynamics and thus on C sequestration.

Journal ArticleDOI
Dominik Sturm1, Dominik Sturm2, Brent A. Orr3, Umut H. Toprak2, Volker Hovestadt2, David T.W. Jones2, David Capper2, David Capper1, Martin Sill2, Ivo Buchhalter2, Paul A. Northcott2, Irina Leis1, Marina Ryzhova, Christian Koelsche1, Christian Koelsche2, Elke Pfaff1, Elke Pfaff2, Sariah Allen3, Gnanaprakash Balasubramanian2, Barbara C. Worst2, Barbara C. Worst1, Kristian W. Pajtler2, Sebastian Brabetz2, Pascal Johann1, Pascal Johann2, Felix Sahm2, Felix Sahm1, Jüri Reimand4, Jüri Reimand5, Alan Mackay6, Diana Carvalho6, Marc Remke5, Joanna J. Phillips7, Arie Perry7, Cynthia Cowdrey7, Rachid Drissi8, Maryam Fouladi8, Felice Giangaspero9, Maria Łastowska10, Wiesława Grajkowska10, Wolfram Scheurlen11, Torsten Pietsch12, Christian Hagel13, Johannes Gojo14, Daniela Lötsch14, Walter Berger14, Irene Slavc14, Christine Haberler14, Anne Jouvet15, Stefan Holm16, Silvia Hofer, Marco Prinz17, Catherine Keohane18, Iris Fried19, Christian Mawrin20, David Scheie21, Bret C. Mobley22, Matthew Schniederjan, Mariarita Santi23, Anna Maria Buccoliero11, Sonika Dahiya24, Christof M. Kramm25, André O. von Bueren25, Katja von Hoff13, Stefan Rutkowski13, Christel Herold-Mende1, Michael C. Frühwald26, Till Milde1, Till Milde2, Martin Hasselblatt27, Pieter Wesseling28, Pieter Wesseling29, Jochen Rößler30, Ulrich Schüller31, Martin Ebinger, Jens Schittenhelm32, Stephan Frank33, Rainer Grobholz, Istvan Vajtai, Volkmar Hans, Reinhard Schneppenheim13, Karel Zitterbart34, V. Peter Collins35, Eleonora Aronica36, Pascale Varlet, Stéphanie Puget37, Christelle Dufour38, Jacques Grill38, Dominique Figarella-Branger39, Marietta Wolter40, Martin U. Schuhmann32, Tarek Shalaby11, Michael A. Grotzer11, Timothy E. Van Meter41, Camelia M. Monoranu42, Jörg Felsberg40, Guido Reifenberger40, Matija Snuderl43, Lynn Ann Forrester43, Jan Koster36, Rogier Versteeg36, Richard Volckmann36, Peter van Sluis36, Stephan Wolf2, Tom Mikkelsen44, Amar Gajjar3, Kenneth Aldape45, Andrew S. Moore46, Michael D. Taylor5, Chris Jones6, Nada Jabado47, Matthias A. Karajannis43, Roland Eils, Matthias Schlesner2, Peter Lichter2, Andreas von Deimling2, Andreas von Deimling1, Stefan M. Pfister1, Stefan M. Pfister2, David W. Ellison3, Andrey Korshunov1, Andrey Korshunov2, Marcel Kool2 
25 Feb 2016-Cell
TL;DR: It is demonstrated that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors.

Journal ArticleDOI
TL;DR: In this article, the authors reviewed soil emission studies involving the most important land-cover types and climate zones and introduced important measuring systems for soil emissions, which leads to global annual net soil emissions of ≥ 350 Pg CO 2 e (CO 2 e = CO 2 equivalents = total effect of all GHG normalized to CO 2 ).
Abstract: Soils act as sources and sinks for greenhouse gases (GHG) such as carbon dioxide (CO 2 ), methane (CH 4 ), and nitrous oxide (N 2 O). Since both storage and emission capacities may be large, precise quantifications are needed to obtain reliable global budgets that are necessary for land-use management (agriculture, forestry), global change and for climate research. This paper discusses exclusively the soil emission-related processes and their influencing parameters. It reviews soil emission studies involving the most important land-cover types and climate zones and introduces important measuring systems for soil emissions. It addresses current shortcomings and the obvious bias towards northern hemispheric data. When using a conservative average of 300 mg CO 2 e m −2 h −1 (based on our literature review), this leads to global annual net soil emissions of ≥350 Pg CO 2 e (CO 2 e = CO 2 equivalents = total effect of all GHG normalized to CO 2 ). This corresponds to roughly 21% of the global soil C and N pools. For comparison, 33.4 Pg CO 2 are being emitted annually by fossil fuel combustion and the cement industry.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4, Baptiste Abeloos5, Rosemarie Aben6, Ossama AbouZeid7, N. L. Abraham8, Halina Abramowicz9, Henso Abreu10, Ricardo Abreu11, Yiming Abulaiti12, Bobby Samir Acharya13, Bobby Samir Acharya14, Leszek Adamczyk15, David H. Adams16, Jahred Adelman17, Stefanie Adomeit18, Tim Adye19, A. A. Affolder20, Tatjana Agatonovic-Jovin21, Johannes Agricola22, Juan Antonio Aguilar-Saavedra23, Steven Ahlen24, Faig Ahmadov25, Faig Ahmadov4, Giulio Aielli26, Henrik Akerstedt12, T. P. A. Åkesson27, Andrei Akimov, Gian Luigi Alberghi28, Justin Albert29, S. Albrand30, M. J. Alconada Verzini31, Martin Aleksa32, Igor Aleksandrov25, Calin Alexa, Gideon Alexander9, Theodoros Alexopoulos33, Muhammad Alhroob2, Malik Aliev34, Gianluca Alimonti, John Alison35, Steven Patrick Alkire36, Bmm Allbrooke8, Benjamin William Allen11, Phillip Allport37, Alberto Aloisio38, Alejandro Alonso39, Francisco Alonso31, Cristiano Alpigiani40, Mahmoud Alstaty1, B. Alvarez Gonzalez32, D. Álvarez Piqueras41, Mariagrazia Alviggi38, Brian Thomas Amadio42, K. Amako, Y. Amaral Coutinho43, Christoph Amelung44, D. Amidei45, S. P. Amor Dos Santos46, António Amorim47, Simone Amoroso32, Glenn Amundsen44, Christos Anastopoulos48, Lucian Stefan Ancu49, Nansi Andari17, Timothy Andeen50, Christoph Falk Anders51, G. Anders32, John Kenneth Anders20, Kelby Anderson35, Attilio Andreazza52, Andrei51, Stylianos Angelidakis53, Ivan Angelozzi6, Philipp Anger54, Aaron Angerami36, Francis Anghinolfi32, Alexey Anisenkov55, Nuno Anjos56 
Aix-Marseille University1, University of Oklahoma2, University of Iowa3, Azerbaijan National Academy of Sciences4, Université Paris-Saclay5, University of Amsterdam6, University of California, Santa Cruz7, University of Sussex8, Tel Aviv University9, Technion – Israel Institute of Technology10, University of Oregon11, Stockholm University12, International Centre for Theoretical Physics13, King's College London14, AGH University of Science and Technology15, Brookhaven National Laboratory16, Northern Illinois University17, Ludwig Maximilian University of Munich18, Rutherford Appleton Laboratory19, University of Liverpool20, University of Belgrade21, University of Göttingen22, University of Granada23, Boston University24, Joint Institute for Nuclear Research25, University of Rome Tor Vergata26, Lund University27, University of Bologna28, University of Victoria29, University of Grenoble30, National University of La Plata31, CERN32, National Technical University of Athens33, University of Salento34, University of Chicago35, Columbia University36, University of Birmingham37, University of Naples Federico II38, University of Copenhagen39, University of Washington40, University of Valencia41, Lawrence Berkeley National Laboratory42, Federal University of Rio de Janeiro43, Brandeis University44, University of Michigan45, University of Coimbra46, University of Lisbon47, University of Sheffield48, University of Geneva49, University of Texas at Austin50, Heidelberg University51, University of Milan52, National and Kapodistrian University of Athens53, Dresden University of Technology54, Novosibirsk State University55, IFAE56
TL;DR: In this article, a combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented.
Abstract: Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a $W$ or a $Z$ boson or a pair of top quarks, and of the six decay modes $H \to ZZ, WW$, $\gamma\gamma, \tau\tau, bb$, and $\mu\mu$. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton--proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb$^{-1}$ at $\sqrt{s}=7$ TeV and 20 fb$^{-1}$ at $\sqrt{s} = 8$ TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 $\pm$ 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the $H \to \tau\tau$ decay of $5.4$ and $5.5$ standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.

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TL;DR: Li et al. as discussed by the authors showed that the short circuit formation was not due to the low relative density of the samples nor the reduction of Li-Al glassy phase at grain boundaries, but was caused by Li dendrite formation inside HP-LLZ:Ta, which took place along the grain boundaries.
Abstract: Al-contaminated Ta-substituted Li7La3Zr2O12 (LLZ:Ta), synthesized via solid-state reaction, and Al-free Ta-substituted Li7La3Zr2O12, fabricated by hot-press sintering (HP-LLZ:Ta), have relative densities of 92.7% and 99.0%, respectively. Impedance spectra show the total conductivity of LLZ:Ta to be 0.71 mS cm–1 at 30 °C and that of HP-LLZ:Ta to be 1.18 mS cm–1. The lower total conductivity for LLZ:Ta than HP-LLZ:Ta was attributed to the higher grain boundary resistance and lower relative density of LLZ:Ta, as confirmed by their microstructures. Constant direct current measurements of HP-LLZ:Ta with a current density of 0.5 mA cm–2 suggest that the short circuit formation was neither due to the low relative density of the samples nor the reduction of Li–Al glassy phase at grain boundaries. TEM, EELS, and MAS NMR were used to prove that the short circuit was from Li dendrite formation inside HP-LLZ:Ta, which took place along the grain boundaries. The Li dendrite formation was found to be mostly due to the i...

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07 Apr 2016-Nature
TL;DR: A fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans was identified in this article, which directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity.
Abstract: Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name 'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.

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TL;DR: The mechanical power equation may help estimate the contribution of the different ventilator-related causes of lung injury and of their variations.
Abstract: We hypothesized that the ventilator-related causes of lung injury may be unified in a single variable: the mechanical power. We assessed whether the mechanical power measured by the pressure–volume loops can be computed from its components: tidal volume (TV)/driving pressure (∆P aw), flow, positive end-expiratory pressure (PEEP), and respiratory rate (RR). If so, the relative contributions of each variable to the mechanical power can be estimated. We computed the mechanical power by multiplying each component of the equation of motion by the variation of volume and RR: $${\text{Power}}_{\text{rs}} = {\text{RR}} \cdot \left\{ {\Delta V^{2} \cdot \left[ {\frac{1}{2} \cdot {\text{EL}}_{\text{rs}} + {\text{RR}} \cdot \frac{{\left( {1 + I:E} \right)}}{60 \cdot I:E} \cdot R_{\text{aw}} } \right] + \Delta V \cdot {\text{PEEP}}} \right\},$$ where ∆V is the tidal volume, ELrs is the elastance of the respiratory system, I:E is the inspiratory-to-expiratory time ratio, and R aw is the airway resistance. In 30 patients with normal lungs and in 50 ARDS patients, mechanical power was computed via the power equation and measured from the dynamic pressure–volume curve at 5 and 15 cmH2O PEEP and 6, 8, 10, and 12 ml/kg TV. We then computed the effects of the individual component variables on the mechanical power. Computed and measured mechanical powers were similar at 5 and 15 cmH2O PEEP both in normal subjects and in ARDS patients (slopes = 0.96, 1.06, 1.01, 1.12 respectively, R 2 > 0.96 and p < 0.0001 for all). The mechanical power increases exponentially with TV, ∆P aw, and flow (exponent = 2) as well as with RR (exponent = 1.4) and linearly with PEEP. The mechanical power equation may help estimate the contribution of the different ventilator-related causes of lung injury and of their variations. The equation can be easily implemented in every ventilator’s software.

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TL;DR: The European Society of Cardiology Heart Failure Long‐Term Registry (ESC‐HF‐LT‐R) was set up with the aim of describing the clinical epidemiology and the 1‐year outcomes of patients with heart failure with the added intention of comparing differences between countries.
Abstract: Aims The European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. Methods and results The ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12 440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1 year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. Conclusion The ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.

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25 Aug 2016-Nature
TL;DR: It is demonstrated that primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services.
Abstract: Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.

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TL;DR: The versatile manganese catalysis largely operates by an isohypsic, thus redox-neutral, mode of action through chelation assistance, and provided step-economical access to structurally divers compounds of relevance to inter alia bioorganic, agrochemical, and medicinal chemistry as well as the material sciences.
Abstract: Manganese is found in the active center of numerous enzymes that operate by an outer-sphere homolytic C–H cleavage. Thus, a plethora of bioinspired radical-based C–H functionalizations by manganese catalysis have been devised during the past decades. In contrast, organometallic C–H activation by means of manganese catalysis has emerged only recently as an increasingly viable tool in organic synthesis. These manganese(I)-catalyzed processes enabled a variety of C–H functionalizations with ample scope, which very recently set the stage for substitutive C–H functionalizations. The versatile manganese catalysis largely operates by an isohypsic, thus redox-neutral, mode of action through chelation assistance, and provided step-economical access to structurally divers compounds of relevance to inter alia bioorganic, agrochemical, and medicinal chemistry as well as the material sciences.

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TL;DR: In this paper, the authors suggest that up to 6% of continental groundwater is modern and that modern groundwater is the largest component of the active hydrologic cycle, and that groundwater recharged less than 50 years ago is vulnerable to contamination and land-use changes.
Abstract: Groundwater recharged less than 50 years ago is vulnerable to contamination and land-use changes. Data and simulations suggest that up to 6% of continental groundwater is modern—forming the largest component of the active hydrologic cycle.

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TL;DR: The prevalence and significance of pulmonary hypertension and RV dysfunction in patients with both HF with reduced ejection fraction and HF with preserved ejections fraction are highlighted, and insights are provided into the complex pathophysiology of cardiopulmonary interaction in LHD which may lead to the evolution from a ‘left ventricular phenotype’ to a “right ventricular physique’ across the natural history of HF.
Abstract: In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65-80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a 'left ventricular phenotype' to a 'right ventricular phenotype' across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context.

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Marco Ajello1, Andrea Albert2, W. B. Atwood3, Guido Barbiellini4  +155 moreInstitutions (45)
TL;DR: The Fermi Large Area Telescope (LAT) has provided the most detailed view to date of the emission toward the Galactic center (GC) in high-energy gamma-rays as mentioned in this paper.
Abstract: The Fermi Large Area Telescope (LAT) has provided the most detailed view to date of the emission toward the Galactic center (GC) in high-energy gamma-rays. This paper describes the analysis of data ...

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Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +2828 moreInstitutions (191)
TL;DR: In this article, the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015 was evaluated using the Monte Carlo simulations.
Abstract: This article documents the performance of the ATLAS muon identification and reconstruction using the first LHC dataset recorded at s√ = 13 TeV in 2015. Using a large sample of J/ψ→μμ and Z→μμ decays from 3.2 fb−1 of pp collision data, measurements of the reconstruction efficiency, as well as of the momentum scale and resolution, are presented and compared to Monte Carlo simulations. The reconstruction efficiency is measured to be close to 99% over most of the covered phase space (|η| 2.2, the pT resolution for muons from Z→μμ decays is 2.9% while the precision of the momentum scale for low-pT muons from J/ψ→μμ decays is about 0.2%.

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TL;DR: While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments.
Abstract: Mycotoxins are fungal metabolites commonly occurring in food, which pose a health risk to the consumer. Maximum levels for major mycotoxins allowed in food have been established worldwide. Good agricultural practices, plant disease management, and adequate storage conditions limit mycotoxin levels in the food chain yet do not eliminate mycotoxins completely. Food processing can further reduce mycotoxin levels by physical removal and decontamination by chemical or enzymatic transformation of mycotoxins into less toxic products. Physical removal of mycotoxins is very efficient: manual sorting of grains, nuts, and fruits by farmers as well as automatic sorting by the industry significantly lowers the mean mycotoxin content. Further processing such as milling, steeping, and extrusion can also reduce mycotoxin content. Mycotoxins can be detoxified chemically by reacting with food components and technical aids; these reactions are facilitated by high temperature and alkaline or acidic conditions. Detoxification of mycotoxins can also be achieved enzymatically. Some enzymes able to transform mycotoxins naturally occur in food commodities or are produced during fermentation but more efficient detoxification can be achieved by deliberate introduction of purified enzymes. We recommend integrating evaluation of processing technologies for their impact on mycotoxins into risk management. Processing steps proven to mitigate mycotoxin contamination should be used whenever necessary. Development of detoxification technologies for high-risk commodities should be a priority for research. While physical techniques currently offer the most efficient post-harvest reduction of mycotoxin content in food, biotechnology possesses the largest potential for future developments.

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TL;DR: Across 48 nations, and consistent with previous research, a large Internet sample is used to provide the first large-scale systematic cross-cultural examination of gender and age differences in self-esteem, finding age-related increases inSelf-esteem from late adolescence to middle adulthood and significant gender gaps.
Abstract: Research and theorizing on gender and age differences in self-esteem have played a prominent role in psychology over the past 20 years. However, virtually all empirical research has been undertaken in the United States or other Western industrialized countries, providing a narrow empirical base from which to draw conclusions and develop theory. To broaden the empirical base, the present research uses a large Internet sample (N = 985,937) to provide the first large-scale systematic cross-cultural examination of gender and age differences in self-esteem. Across 48 nations, and consistent with previous research, we found age-related increases in self-esteem from late adolescence to middle adulthood and significant gender gaps, with males consistently reporting higher self-esteem than females. Despite these broad cross-cultural similarities, the cultures differed significantly in the magnitude of gender, age, and Gender × Age effects on self-esteem. These differences were associated with cultural differences in socioeconomic, sociodemographic, gender-equality, and cultural value indicators. Discussion focuses on the theoretical implications of cross-cultural research on self-esteem. (PsycINFO Database Record