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Showing papers by "University of Lisbon published in 2015"


Journal ArticleDOI
01 Jan 2015
TL;DR: This paper presents an in-depth analysis of the hardware infrastructure, southbound and northbound application programming interfaces (APIs), network virtualization layers, network operating systems (SDN controllers), network programming languages, and network applications, and presents the key building blocks of an SDN infrastructure using a bottom-up, layered approach.
Abstract: The Internet has led to the creation of a digital society, where (almost) everything is connected and is accessible from anywhere. However, despite their widespread adoption, traditional IP networks are complex and very hard to manage. It is both difficult to configure the network according to predefined policies, and to reconfigure it to respond to faults, load, and changes. To make matters even more difficult, current networks are also vertically integrated: the control and data planes are bundled together. Software-defined networking (SDN) is an emerging paradigm that promises to change this state of affairs, by breaking vertical integration, separating the network's control logic from the underlying routers and switches, promoting (logical) centralization of network control, and introducing the ability to program the network. The separation of concerns, introduced between the definition of network policies, their implementation in switching hardware, and the forwarding of traffic, is key to the desired flexibility: by breaking the network control problem into tractable pieces, SDN makes it easier to create and introduce new abstractions in networking, simplifying network management and facilitating network evolution. In this paper, we present a comprehensive survey on SDN. We start by introducing the motivation for SDN, explain its main concepts and how it differs from traditional networking, its roots, and the standardization activities regarding this novel paradigm. Next, we present the key building blocks of an SDN infrastructure using a bottom-up, layered approach. We provide an in-depth analysis of the hardware infrastructure, southbound and northbound application programming interfaces (APIs), network virtualization layers, network operating systems (SDN controllers), network programming languages, and network applications. We also look at cross-layer problems such as debugging and troubleshooting. In an effort to anticipate the future evolution of this new paradigm, we discuss the main ongoing research efforts and challenges of SDN. In particular, we address the design of switches and control platforms—with a focus on aspects such as resiliency, scalability, performance, security, and dependability—as well as new opportunities for carrier transport networks and cloud providers. Last but not least, we analyze the position of SDN as a key enabler of a software-defined environment.

3,589 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +5117 moreInstitutions (314)
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.

1,567 citations


Journal ArticleDOI
TL;DR: In this article, a catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory is presented, and the current understanding of the structure and dynamics of compact objects in these theories is summarized.
Abstract: One century after its formulation, Einstein's general relativity (GR) has made remarkable predictions and turned out to be compatible with all experimental tests. Most of these tests probe the theory in the weak-field regime, and there are theoretical and experimental reasons to believe that GR should be modified when gravitational fields are strong and spacetime curvature is large. The best astrophysical laboratories to probe strong-field gravity are black holes and neutron stars, whether isolated or in binary systems. We review the motivations to consider extensions of GR. We present a (necessarily incomplete) catalog of modified theories of gravity for which strong-field predictions have been computed and contrasted to Einstein's theory, and we summarize our current understanding of the structure and dynamics of compact objects in these theories. We discuss current bounds on modified gravity from binary pulsar and cosmological observations, and we highlight the potential of future gravitational wave measurements to inform us on the behavior of gravity in the strong-field regime.

1,066 citations


Journal ArticleDOI
Lorenzo Galluzzi1, J M Bravo-San Pedro2, Ilio Vitale, Stuart A. Aaronson3, John M. Abrams4, Dieter Adam5, Emad S. Alnemri6, Lucia Altucci7, David W. Andrews8, Margherita Annicchiarico-Petruzzelli, Eric H. Baehrecke9, Nicolas G. Bazan10, Mathieu J.M. Bertrand11, Mathieu J.M. Bertrand12, Katiuscia Bianchi13, Katiuscia Bianchi14, Mikhail V. Blagosklonny15, Klas Blomgren16, Christoph Borner17, Dale E. Bredesen18, Dale E. Bredesen19, Catherine Brenner20, Catherine Brenner21, Michelangelo Campanella22, Eleonora Candi23, Francesco Cecconi23, Francis Ka-Ming Chan9, Navdeep S. Chandel24, Emily H. Cheng25, Jerry E. Chipuk3, John A. Cidlowski26, Aaron Ciechanover27, Ted M. Dawson28, Valina L. Dawson28, V De Laurenzi29, R De Maria, Klaus-Michael Debatin30, N. Di Daniele23, Vishva M. Dixit31, Brian David Dynlacht32, Wafik S. El-Deiry33, Gian Maria Fimia34, Richard A. Flavell35, Simone Fulda36, Carmen Garrido37, Marie-Lise Gougeon38, Douglas R. Green, Hinrich Gronemeyer39, György Hajnóczky6, J M Hardwick28, Michael O. Hengartner40, Hidenori Ichijo41, Bertrand Joseph16, Philipp J. Jost42, Thomas Kaufmann43, Oliver Kepp2, Daniel J. Klionsky44, Richard A. Knight22, Richard A. Knight45, Sharad Kumar46, Sharad Kumar47, John J. Lemasters48, Beth Levine49, Beth Levine50, Andreas Linkermann5, Stuart A. Lipton, Richard A. Lockshin51, Carlos López-Otín52, Enrico Lugli, Frank Madeo53, Walter Malorni54, Jean-Christophe Marine55, Seamus J. Martin56, J-C Martinou57, Jan Paul Medema58, Pascal Meier, Sonia Melino23, Noboru Mizushima41, Ute M. Moll59, Cristina Muñoz-Pinedo, Gabriel Núñez44, Andrew Oberst60, Theocharis Panaretakis16, Josef M. Penninger, Marcus E. Peter24, Mauro Piacentini23, Paolo Pinton61, Jochen H. M. Prehn62, Hamsa Puthalakath63, Gabriel A. Rabinovich64, Kodi S. Ravichandran65, Rosario Rizzuto66, Cecília M. P. Rodrigues67, David C. Rubinsztein68, Thomas Rudel69, Yufang Shi70, Hans-Uwe Simon43, Brent R. Stockwell50, Brent R. Stockwell71, Gyorgy Szabadkai22, Gyorgy Szabadkai66, Stephen W.G. Tait72, H. L. Tang28, Nektarios Tavernarakis73, Nektarios Tavernarakis74, Yoshihide Tsujimoto, T Vanden Berghe11, T Vanden Berghe12, Peter Vandenabeele11, Peter Vandenabeele12, Andreas Villunger75, Erwin F. Wagner76, Henning Walczak22, Eileen White77, W. G. Wood78, Junying Yuan79, Zahra Zakeri80, Boris Zhivotovsky81, Boris Zhivotovsky16, Gerry Melino45, Gerry Melino23, Guido Kroemer1 
Paris Descartes University1, Institut Gustave Roussy2, Mount Sinai Hospital3, University of Texas Southwestern Medical Center4, University of Kiel5, Thomas Jefferson University6, Seconda Università degli Studi di Napoli7, University of Toronto8, University of Massachusetts Medical School9, Louisiana State University10, Ghent University11, Flanders Institute for Biotechnology12, Queen Mary University of London13, Cancer Research UK14, Roswell Park Cancer Institute15, Karolinska Institutet16, University of Freiburg17, Buck Institute for Research on Aging18, University of California, San Francisco19, French Institute of Health and Medical Research20, Université Paris-Saclay21, University College London22, University of Rome Tor Vergata23, Northwestern University24, Memorial Sloan Kettering Cancer Center25, National Institutes of Health26, Technion – Israel Institute of Technology27, Johns Hopkins University28, University of Chieti-Pescara29, University of Ulm30, Genentech31, New York University32, Pennsylvania State University33, University of Salento34, Yale University35, Goethe University Frankfurt36, University of Burgundy37, Pasteur Institute38, University of Strasbourg39, University of Zurich40, University of Tokyo41, Technische Universität München42, University of Bern43, University of Michigan44, Medical Research Council45, University of Adelaide46, University of South Australia47, Medical University of South Carolina48, University of Texas at Dallas49, Howard Hughes Medical Institute50, St. John's University51, University of Oviedo52, University of Graz53, Istituto Superiore di Sanità54, Katholieke Universiteit Leuven55, Trinity College, Dublin56, University of Geneva57, University of Amsterdam58, Stony Brook University59, University of Washington60, University of Ferrara61, Royal College of Surgeons in Ireland62, La Trobe University63, University of Buenos Aires64, University of Virginia65, University of Padua66, University of Lisbon67, University of Cambridge68, University of Würzburg69, Soochow University (Suzhou)70, Columbia University71, University of Glasgow72, University of Crete73, Foundation for Research & Technology – Hellas74, Innsbruck Medical University75, Carlos III Health Institute76, Rutgers University77, University of Minnesota78, Harvard University79, City University of New York80, Moscow State University81
TL;DR: The Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Abstract: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.

809 citations


Journal ArticleDOI
TL;DR: This work is funded by the European Commission (Marie Curie CIG) and Ministerio de Ciencia e Innovacion, Spain (Juan de la Cierva Fellowship).
Abstract: O.B. thanks the European Commission (Marie Curie CIG) and Ministerio de Ciencia e Innovacion, Spain (Juan de la Cierva Fellowship). G.J.L.B. thanks his generous sources of funding: Royal Society, FCT Portugal (FCT Investigator), European Commission (Marie Curie CIG), and the EPSRC. G.J.L.B. is a Royal Society University Research Fellow. The authors thank Paula Boutureira Regla and Francisco Pinteus da Cruz Lopes Bernardes for inspiration.

781 citations


Journal ArticleDOI
TL;DR: It is concluded that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
Abstract: Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.

635 citations


Journal ArticleDOI
Marnix H. Medema1, Marnix H. Medema2, Renzo Kottmann1, Pelin Yilmaz1  +161 moreInstitutions (84)
TL;DR: This work proposes the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard, to facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters.
Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

633 citations


Journal ArticleDOI
TL;DR: An innovative and comprehensive theoretical model that combines the extended unified theory of acceptance and use of technology (UTAUT2) of Venkatesh, Thong, and Xu, with cultural moderators from Hofstede is proposed, providing new insights into factors affecting the acceptation and how culture influences individual use behaviour.

593 citations


Journal ArticleDOI
TL;DR: Boys were less sedentary and more active than girls at all ages, and overweight/obese participants were less active than their normal weight counterparts from age seven onwards.
Abstract: Physical activity and sedentary behaviour in youth have been reported to vary by sex, age, weight status and country. However, supporting data are often self-reported and/or do not encompass a wide range of ages or geographical locations. This study aimed to describe objectively-measured physical activity and sedentary time patterns in youth. The International Children’s Accelerometry Database (ICAD) consists of ActiGraph accelerometer data from 20 studies in ten countries, processed using common data reduction procedures. Analyses were conducted on 27,637 participants (2.8–18.4 years) who provided at least three days of valid accelerometer data. Linear regression was used to examine associations between age, sex, weight status, country and physical activity outcomes. Boys were less sedentary and more active than girls at all ages. After 5 years of age there was an average cross-sectional decrease of 4.2 % in total physical activity with each additional year of age, due mainly to lower levels of light-intensity physical activity and greater time spent sedentary. Physical activity did not differ by weight status in the youngest children, but from age seven onwards, overweight/obese participants were less active than their normal weight counterparts. Physical activity varied between samples from different countries, with a 15–20 % difference between the highest and lowest countries at age 9–10 and a 26–28 % difference at age 12–13. Physical activity differed between samples from different countries, but the associations between demographic characteristics and physical activity were consistently observed. Further research is needed to explore environmental and sociocultural explanations for these differences.

558 citations


Journal ArticleDOI
TL;DR: A new unified method for testing dissolution rates of bioactive glasses and their variants, and the formation of calcium phosphate layer formation on their surface, which is an indicator of bioactivity is proposed and validated.
Abstract: The aim of this study was to propose and validate a new unified method for testing dissolution rates of bioactive glasses and their variants, and the formation of calcium phosphate layer formation on their surface, which is an indicator of bioactivity At present, comparison in the literature is difficult as many groups use different testing protocols An ISO standard covers the use of simulated body fluid on standard shape materials but it does not take into account that bioactive glasses can have very different specific surface areas, as for glass powders Validation of the proposed modified test was through round robin testing and comparison to the ISO standard where appropriate The proposed test uses fixed mass per solution volume ratio and agitated solution The round robin study showed differences in hydroxyapatite nucleation on glasses of different composition and between glasses of the same composition but different particle size The results were reproducible between research facilities Researchers should use this method when testing new glasses, or their variants, to enable comparison between the literature in the future

524 citations


Journal ArticleDOI
TL;DR: Despite limited evidence, higher autonomous motivation, self-efficacy, and self-regulation skills emerged as the best predictors of beneficial weight and physical activity outcomes; for weight control, positive body image and flexible eating restraint may additionally improve outcomes.
Abstract: Relapse is high in lifestyle obesity interventions involving behavior and weight change. Identifying mediators of successful outcomes in these interventions is critical to improve effectiveness and to guide approaches to obesity treatment, including resource allocation. This article reviews the most consistent self-regulation mediators of medium- and long-term weight control, physical activity, and dietary intake in clinical and community behavior change interventions targeting overweight/obese adults. A comprehensive search of peer-reviewed articles, published since 2000, was conducted on electronic databases (for example, MEDLINE) and journal reference lists. Experimental studies were eligible if they reported intervention effects on hypothesized mediators (self-regulatory and psychological mechanisms) and the association between these and the outcomes of interest (weight change, physical activity, and dietary intake). Quality and content of selected studies were analyzed and findings summarized. Studies with formal mediation analyses were reported separately. Thirty-five studies were included testing 42 putative mediators. Ten studies used formal mediation analyses. Twenty-eight studies were randomized controlled trials, mainly aiming at weight loss or maintenance (n = 21). Targeted participants were obese (n = 26) or overweight individuals, aged between 25 to 44 years (n = 23), and 13 studies targeted women only. In terms of study quality, 13 trials were rated as “strong”, 15 as “moderate”, and 7 studies as “weak”. In addition, methodological quality of formal mediation analyses was “medium”. Identified mediators for medium-/long-term weight control were higher levels of autonomous motivation, self-efficacy/barriers, self-regulation skills (such as self-monitoring), flexible eating restraint, and positive body image. For physical activity, significant putative mediators were high autonomous motivation, self-efficacy, and use of self-regulation skills. For dietary intake, the evidence was much less clear, and no consistent mediators were identified. This is the first systematic review of mediational psychological mechanisms of successful outcomes in obesity-related lifestyle change interventions. Despite limited evidence, higher autonomous motivation, self-efficacy, and self-regulation skills emerged as the best predictors of beneficial weight and physical activity outcomes; for weight control, positive body image and flexible eating restraint may additionally improve outcomes. These variables represent possible targets for future lifestyle interventions in overweight/obese populations.

Journal ArticleDOI
TL;DR: The role of neuroinflammation in the emergence of depression is discussed, namely dynamic alterations in the status of microglia response to stimulation, and how their activation phenotypes may have an etiological role in neurodegeneneration, in particular in depressive-like behavior.
Abstract: Patients with chronic inflammation are often associated with the emergence of depression symptoms, while diagnosed depressed patients show increased levels of circulating cytokines. Further studies revealed the activation of the brain immune cell microglia in depressed patients with a greater magnitude in individuals that committed suicide, indicating a crucial role for neuroinflammation in depression brain pathogenesis. Rapid advances in the understanding of microglial and astrocytic neurobiology were obtained in the past fifteen to twenty years. Indeed, recent data reveal that microglia play an important role in managing neuronal cell death, neurogenesis, and synaptic interactions, besides their involvement in immune-response generating cytokines. The communication between microglia and neurons is essential to synchronize these diverse functions with brain activity. Evidence is accumulating that secreted extracellular vesicles (EVs), comprising ectosomes and exosomes with a size ranging from 0.1 to 1 μm, are key players in intercellular signaling. These EVs may carry specific proteins, mRNAs and microRNAs (miRNAs). Transfer of exosomes to neurons was shown to be mediated by oligodendrocytes, microglia and astrocytes that may either be supportive to neurons, or instead disseminate the disease. Interestingly, several recent reports have identified changes in miRNAs in depressed patients, which target not only crucial pathways associated with synaptic plasticity, learning and memory but also the production of neurotrophic factors and immune cell modulation. In this article, we discuss the role of neuroinflammation in the emergence of depression, namely dynamic alterations in the status of microglia response to stimulation, and how their activation phenotypes may have an etiological role in neurodegeneneration, in particular in depressive-like behavior. We will overview the involvement of miRNAs, exosomes, ectosomes and microglia in regulating critical pathways associated with depression and how they may contribute to other brain disorders including amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson disease, which share several neuroinflammatory-associated processes. Specific reference will be made to EVs as potential biomarkers and disease monitoring approaches, focusing on their potentialities as drug delivery vehicles and on putative therapeutic strategies using autologous exosome-based delivery systems to treat neurodegenerative and psychiatric disorders.

Journal ArticleDOI
TL;DR: It is concluded that periods of economic recession are possibly associated with a higher prevalence of mental health problems, including common mental disorders, substance disorders, and ultimately suicidal behaviour.
Abstract: Countries in recession experience high unemployment rates and a decline in living conditions, which, it has been suggested, negatively influences their populations’ health. The present review examines the recent evidence of the possible association between economic recessions and mental health outcomes. Literature review of records identified through Medline, PsycINFO, SciELO, and EBSCO Host. Only original research papers, published between 2004 and 2014, peer-reviewed, non-qualitative research, and reporting on associations between economic factors and proxies of mental health were considered. One-hundred-one papers met the inclusion criteria. The evidence was consistent that economic recessions and mediators such as unemployment, income decline, and unmanageable debts are significantly associated with poor mental wellbeing, increased rates of common mental disorders, substance-related disorders, and suicidal behaviours. On the basis of a thorough analysis of the selected investigations, we conclude that periods of economic recession are possibly associated with a higher prevalence of mental health problems, including common mental disorders, substance disorders, and ultimately suicidal behaviour. Most of the research is based on cross-sectional studies, which seriously limits causality inferences. Conclusions are summarised, taking into account international policy recommendations concerning the cost-effective measures that can possibly reduce the occurrence of negative mental health outcomes in populations during periods of economic recession.

Journal ArticleDOI
TL;DR: The CHEMDNER corpus is presented, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task.
Abstract: The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/

Journal ArticleDOI
TL;DR: In this article, the authors present follow-up observations of the two most luminous z~6.6 Ly$\alpha$ candidates in the COSMOS field: ''MASOSA'' and ''CR7'' to confirm both candidates beyond any doubt.
Abstract: Faint Lyman-$\alpha$ (Ly$\alpha$) emitters become increasingly rarer towards the re-ionisation epoch (z~6-7). However, observations from a very large (~5deg$^2$) Ly$\alpha$ survey at z=6.6 (Matthee et al. 2015) show that this is not the case for the most luminous emitters. Here we present follow-up observations of the two most luminous z~6.6 Ly$\alpha$ candidates in the COSMOS field: `MASOSA' and `CR7'. We used X-SHOOTER, SINFONI and FORS2 (VLT), and DEIMOS (Keck), to confirm both candidates beyond any doubt. We find redshifts of z=6.541 and z=6.604 for MASOSA and CR7, respectively. MASOSA has a strong detection in Ly$\alpha$ with a line width of $386\pm30$ km/s (FWHM) and with high EW$_0$ (>200 \AA), but it is undetected in the continuum. CR7, with an observed Ly$\alpha$ luminosity of $10^{43.93\pm0.05}$erg/s is the most luminous Ly$\alpha$ emitter ever found at z>6. CR7 reveals a narrow Ly$\alpha$ line with $266\pm15$ km/s FWHM, being detected in the NIR (rest-frame UV, with $\beta=-2.3\pm0.1$) with an excess in $J$, and also strongly detected in IRAC/Spitzer. We detect a narrow HeII1640$\AA$ emission line ($6\sigma$) which explains the excess seen in the $J$ band photometry (EW$_0$~80 \AA). We find no other emission lines from the UV to the NIR in our X-SHOOTER spectra, nor any signatures of Wolf-Rayet (WR) stars. We find that CR7 is best explained by a combination of a PopIII-like population which dominates the rest-frame UV and the nebular emission, and a more normal stellar population which dominates the mass. HST/WFC3 observations show that the light is indeed spatially separated between a very blue component, coincident with Ly$\alpha$ and HeII emission, and two red components (~5 kpc away), which dominate the mass. Our findings are consistent with theoretical predictions of a PopIII wave, with PopIII star formation migrating away from the original sites of star formation.

Journal ArticleDOI
TL;DR: In this article, a generic multi-objective mathematical programming model for the design and planning of supply chains, integrating the three dimensions of sustainability is presented, and a social indicator appropriate to assess strategic decisions is proposed.

Journal ArticleDOI
24 Sep 2015-Cell
TL;DR: It is found that sympathetic nerve fibers establish neuro-adipose junctions, necessary and sufficient for the induction of lipolysis in white adipose tissue and are an efferent effector of leptin action.

Journal ArticleDOI
TL;DR: Models ranging from simple 2D visualization and solar constant methods, to more sophisticated 3D representation and analysis, are reviewed and web-based solar maps, which rely on the previous features to successfully communicate the benefits of the solar resource to the public and support in the policy-making process, are addressed.
Abstract: Cityscapes provide a complex environment, where solar radiation is unevenly distributed, especially since urban features started to propagate more and more vertically. Due to the dynamic overshadowing effects present on building surfaces, quantifying these phenomena is essential for predicting reductions in solar radiation availability that can significantly affect potential for solar energy use. Numerical radiation algorithms coupled with GIS tools are a pathway to evaluate those complex effects. Accurate representation of the terrain, vegetation canopy and building structures allows better estimation of shadow patterns. Higher spatial and temporal resolutions deliver more detailed results, but models must compromise between accuracy and computation time. In this paper, models ranging from simple 2D visualization and solar constant methods, to more sophisticated 3D representation and analysis, are reviewed. Web-based solar maps, which rely on the previous features to successfully communicate the benefits of the solar resource to the public and support in the policy-making process, are also addressed.

Journal ArticleDOI
TL;DR: In this paper, the authors analyzed the mechanical performance of concrete with recycled aggregates from construction and demolition waste (CDW) from various locations in Portugal and concluded that the use of RA worsens most of the properties tested, especially when fine RA are used.

Journal ArticleDOI
TL;DR: An overview of the most important pretreatment methods available, including those that are based on the use of green solvents (supercritical fluids and ionic liquids) and those that have a lower impact on the environment.
Abstract: Lignocellulosic materials, such as forest, agriculture, and agroindustrial residues, are among the most important resources for biorefineries to provide fuels, chemicals, and materials in such a way to substitute for, at least in part, the role of petrochemistry in modern society. Most of these sustainable biorefinery products can be produced from plant polysaccharides (glucans, hemicelluloses, starch, and pectic materials) and lignin. In this scenario, cellulosic ethanol has been considered for decades as one of the most promising alternatives to mitigate fossil fuel dependence and carbon dioxide accumulation in the atmosphere. However, a pretreatment method is required to overcome the physical and chemical barriers that exist in the lignin-carbohydrate composite and to render most, if not all, of the plant cell wall components easily available for conversion into valuable products, including the fuel ethanol. Hence, pretreatment is a key step for an economically viable biorefinery. Successful pretreatment method must lead to partial or total separation of the lignocellulosic components, increasing the accessibility of holocellulose to enzymatic hydrolysis with the least inhibitory compounds being released for subsequent steps of enzymatic hydrolysis and fermentation. Each pretreatment technology has a different specificity against both carbohydrates and lignin and may or may not be efficient for different types of biomasses. Furthermore, it is also desirable to develop pretreatment methods with chemicals that are greener and effluent streams that have a lower impact on the environment. This paper provides an overview of the most important pretreatment methods available, including those that are based on the use of green solvents (supercritical fluids and ionic liquids).

Journal ArticleDOI
TL;DR: A library predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains, and in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases.
Abstract: Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing.

Journal ArticleDOI
TL;DR: The human health risk assessment performed showed that appreciable risks to the consumer's health arising from exposure to trace levels of pharmaceuticals in drinking water are extremely unlikely, as RQs values were all below 0.001.

Journal ArticleDOI
01 May 2015-Brain
TL;DR: The use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage and the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis are supported.
Abstract: Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, Ovsat Abdinov4  +2827 moreInstitutions (148)
TL;DR: The Standard Model (SM) Higgs boson hypothesis is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons, and the observed distributions of variables sensitive to the non- SM tensor couplings are compatible with the SM predictions.
Abstract: Studies of the spin, parity and tensor couplings of the Higgs boson in the [Formula: see text], [Formula: see text] and [Formula: see text] decay processes at the LHC are presented. The investigations are based on [Formula: see text] of pp collision data collected by the ATLAS experiment at [Formula: see text] TeV and [Formula: see text] TeV. The Standard Model (SM) Higgs boson hypothesis, corresponding to the quantum numbers [Formula: see text], is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons. All tested alternative models are excluded in favour of the SM Higgs boson hypothesis at more than 99.9 % confidence level. Using the [Formula: see text] and [Formula: see text] decays, the tensor structure of the interaction between the spin-0 boson and the SM vector bosons is also investigated. The observed distributions of variables sensitive to the non-SM tensor couplings are compatible with the SM predictions and constraints on the non-SM couplings are derived.

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TL;DR: The selection of implementation framework(s) should be based not solely on the healthcare innovation to be implemented, but include other aspects of the framework’s orientation, e.g., the setting and end-user, as well as the degree of inclusion and depth of analysis of the implementation concepts.
Abstract: Implementation science and knowledge translation have developed across multiple disciplines with the common aim of bringing innovations to practice. Numerous implementation frameworks, models, and theories have been developed to target a diverse array of innovations. As such, it is plausible that not all frameworks include the full range of concepts now thought to be involved in implementation. Users face the decision of selecting a single or combining multiple implementation frameworks. To aid this decision, the aim of this review was to assess the comprehensiveness of existing frameworks. A systematic search was undertaken in PubMed to identify implementation frameworks of innovations in healthcare published from 2004 to May 2013. Additionally, titles and abstracts from Implementation Science journal and references from identified papers were reviewed. The orientation, type, and presence of stages and domains, along with the degree of inclusion and depth of analysis of factors, strategies, and evaluations of implementation of included frameworks were analysed. Frameworks were assessed individually and grouped according to their targeted innovation. Frameworks for particular innovations had similar settings, end-users, and ‘type’ (descriptive, prescriptive, explanatory, or predictive). On the whole, frameworks were descriptive and explanatory more often than prescriptive and predictive. A small number of the reviewed frameworks covered an implementation concept(s) in detail, however, overall, there was limited degree and depth of analysis of implementation concepts. The core implementation concepts across the frameworks were collated to form a Generic Implementation Framework, which includes the process of implementation (often portrayed as a series of stages and/or steps), the innovation to be implemented, the context in which the implementation is to occur (divided into a range of domains), and influencing factors, strategies, and evaluations. The selection of implementation framework(s) should be based not solely on the healthcare innovation to be implemented, but include other aspects of the framework’s orientation, e.g., the setting and end-user, as well as the degree of inclusion and depth of analysis of the implementation concepts. The resulting generic structure provides researchers, policy-makers, health administrators, and practitioners a base that can be used as guidance for their implementation efforts.

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TL;DR: This review focuses on the most important aspects currently recognized as key factors for the regulation of nanomedicines, discussing the efforts under development by industry and regulatory agencies to promote their translation into the market.

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TL;DR: There was evidence that it is possible to intervene to reduce SB in adults and Lifestyle and SB only interventions may be promising approaches.
Abstract: Context Time spent in sedentary behaviours (SB) is associated with poor health, irrespective of the level of physical activity. The aim of this study was to evaluate the effect of interventions which included SB as an outcome measure in adults. Methods Thirteen databases, including The Cochrane Library, MEDLINE and SPORTDiscus, trial registers and reference lists, were searched for randomised controlled trials until January 2014. Study selection, data extraction and quality assessment were performed independently. Primary outcomes included SB, proxy measures of SB and patterns of accumulation of SB. Secondary outcomes were cardiometabolic health, mental health and body composition. Intervention types were categorised as SB only, physical activity (PA) only, PA and SB or lifestyle interventions (PA/SB and diet). Results Of 8087 records, 51 studies met the inclusion criteria. Meta-analysis of 34/51 studies showed a reduction of 22 min/day in sedentary time in favour of the intervention group (95% CI −35 to −9 min/day, n=5868). Lifestyle interventions reduced SB by 24 min/day (95% CI −41 to −8 min/day, n=3981, moderate quality) and interventions focusing on SB only by 42 min/day (95% CI −79 to −5 min/day, n=62, low quality). There was no evidence of an effect of PA and combined PA/SB interventions on reducing sedentary time. Conclusions There was evidence that it is possible to intervene to reduce SB in adults. Lifestyle and SB only interventions may be promising approaches. More high quality research is needed to determine if SB interventions are sufficient to produce clinically meaningful and sustainable reductions in sedentary time.

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TL;DR: In this paper, the authors present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed.
Abstract: A frequent suggestion to increase individuals' willingness to take action on climate change and to support relevant policies is to highlight its proximal consequences, that is, those that are close in space and time. But previous studies that have tested this proximizing approach have not revealed the expected positive effects on individual action and support for addressing climate change. We present three lines of psychological reasoning that provide compelling arguments as to why highlighting proximal impacts of climate change might not be as effective a way to increase individual mitigation and adaptation efforts as is often assumed. Our contextualization of the proximizing approach within established psychological research suggests that, depending on the particular theoretical perspective one takes on this issue, and on specific individual characteristics suggested by these perspectives, proximizing can bring about the intended positive effects, can have no (visible) effect or can even backfire. Thus, the effects of proximizing are much more complex than is commonly assumed. Revealing this complexity contributes to a refined theoretical understanding of the role that psychological distance plays in the context of climate change and opens up further avenues for future research and for interventions.

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TL;DR: It is demonstrated that by-product streams from the biodiesel industry and waste streams from confectionery industries could be used as the sole source of nutrients for the production of bacterial cellulose with similar properties as those produced with commercial sources of nutrients.
Abstract: The utilization of fermentation media derived from waste and by-product streams from biodiesel and confectionery industries could lead to highly efficient production of bacterial cellulose. Batch fermentations with the bacterial strain Komagataeibacter sucrofermentans DSM (Deutsche Sammlung von Mikroorganismen) 15973 were initially carried out in synthetic media using commercial sugars and crude glycerol. The highest bacterial cellulose concentration was achieved when crude glycerol (3.2 g/L) and commercial sucrose (4.9 g/L) were used. The combination of crude glycerol and sunflower meal hydrolysates as the sole fermentation media resulted in bacterial cellulose production of 13.3 g/L. Similar results (13 g/L) were obtained when flour-rich hydrolysates produced from confectionery industry waste streams were used. The properties of bacterial celluloses developed when different fermentation media were used showed water holding capacities of 102–138 g·water/g·dry bacterial cellulose, viscosities of 4.7–9.3 dL/g, degree of polymerization of 1889.1–2672.8, stress at break of 72.3–139.5 MPa and Young’s modulus of 0.97–1.64 GPa. This study demonstrated that by-product streams from the biodiesel industry and waste streams from confectionery industries could be used as the sole sources of nutrients for the production of bacterial cellulose with similar properties as those produced with commercial sources of nutrients.