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Showing papers by "Ben-Gurion University of the Negev published in 2017"


Journal ArticleDOI
Andrew I R Maas1, David K. Menon2, P. David Adelson3, Nada Andelic4  +339 moreInstitutions (110)
TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators

1,354 citations


Journal ArticleDOI
TL;DR: This comprehensive meta-regression analysis reports a significant decline in sperm counts between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand.
Abstract: BACKGROUND Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality. OBJECTIVE AND RATIONALE To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group. SEARCH METHODS PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models. OUTCOMES SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively). WIDER IMPLICATIONS This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

794 citations


Journal ArticleDOI
07 Jul 2017-Science
TL;DR: A 10.1-gigabase assembly of the 14 chromosomes of wild tetraploid wheat, as well as analyses of gene content, genome architecture, and genetic diversity reveal genomic regions bearing the signature of selection under domestication.
Abstract: Wheat (Triticum spp.) is one of the founder crops that likely drove the Neolithic transition to sedentary agrarian societies in the Fertile Crescent more than 10,000 years ago. Identifying genetic modifications underlying wheat's domestication requires knowledge about the genome of its allo-tetraploid progenitor, wild emmer (T. turgidum ssp. dicoccoides). We report a 10.1-gigabase assembly of the 14 chromosomes of wild tetraploid wheat, as well as analyses of gene content, genome architecture, and genetic diversity. With this fully assembled polyploid wheat genome, we identified the causal mutations in Brittle Rachis 1 (TtBtr1) genes controlling shattering, a key domestication trait. A study of genomic diversity among wild and domesticated accessions revealed genomic regions bearing the signature of selection under domestication. This reference assembly will serve as a resource for accelerating the genome-assisted improvement of modern wheat varieties.

622 citations


Journal ArticleDOI
21 Jun 2017-Nature
TL;DR: Analytical tools developed develop a distance measure on the space of TCRs that permits clustering and visualization, a robust repertoire diversity metric that accommodates the low number of paired public receptors observed when compared to single-chain analyses, and a distance-based classifier that can assign previously unobserved T CRs to characterized repertoires with robust sensitivity and specificity.
Abstract: T cells are defined by a heterodimeric surface receptor, the T cell receptor (TCR), that mediates recognition of pathogen-associated epitopes through interactions with peptide and major histocompatibility complexes (pMHCs). TCRs are generated by genomic rearrangement of the germline TCR locus, a process termed V(D)J recombination, that has the potential to generate marked diversity of TCRs (estimated to range from 1015 (ref. 1) to as high as 1061 (ref. 2) possible receptors). Despite this potential diversity, TCRs from T cells that recognize the same pMHC epitope often share conserved sequence features, suggesting that it may be possible to predictively model epitope specificity. Here we report the in-depth characterization of ten epitope-specific TCR repertoires of CD8+ T cells from mice and humans, representing over 4,600 in-frame single-cell-derived TCRαβ sequence pairs from 110 subjects. We developed analytical tools to characterize these epitope-specific repertoires: a distance measure on the space of TCRs that permits clustering and visualization, a robust repertoire diversity metric that accommodates the low number of paired public receptors observed when compared to single-chain analyses, and a distance-based classifier that can assign previously unobserved TCRs to characterized repertoires with robust sensitivity and specificity. Our analyses demonstrate that each epitope-specific repertoire contains a clustered group of receptors that share core sequence similarities, together with a dispersed set of diverse 'outlier' sequences. By identifying shared motifs in core sequences, we were able to highlight key conserved residues driving essential elements of TCR recognition. These analyses provide insights into the generalizable, underlying features of epitope-specific repertoires and adaptive immune recognition.

595 citations


Journal ArticleDOI
TL;DR: Modeling shows that the small thermal inertia of a globally frozen surface reverses the annual mean tropical atmospheric circulation, producing an equatorial desert and net snow and frost accumulation elsewhere, and that the evolutionary legacy of Snowball Earth is perceptible in fossils and living organisms.
Abstract: Geological evidence indicates that grounded ice sheets reached sea level at all latitudes during two long-lived Cryogenian (58 and ≥5 My) glaciations. Combined uranium-lead and rhenium-osmium dating suggests that the older (Sturtian) glacial onset and both terminations were globally synchronous. Geochemical data imply that CO2 was 102 PAL (present atmospheric level) at the younger termination, consistent with a global ice cover. Sturtian glaciation followed breakup of a tropical supercontinent, and its onset coincided with the equatorial emplacement of a large igneous province. Modeling shows that the small thermal inertia of a globally frozen surface reverses the annual mean tropical atmospheric circulation, producing an equatorial desert and net snow and frost accumulation elsewhere. Oceanic ice thickens, forming a sea glacier that flows gravitationally toward the equator, sustained by the hydrologic cycle and by basal freezing and melting. Tropical ice sheets flow faster as CO2 rises but lose mass and become sensitive to orbital changes. Equatorial dust accumulation engenders supraglacial oligotrophic meltwater ecosystems, favorable for cyanobacteria and certain eukaryotes. Meltwater flushing through cracks enables organic burial and submarine deposition of airborne volcanic ash. The subglacial ocean is turbulent and well mixed, in response to geothermal heating and heat loss through the ice cover, increasing with latitude. Terminal carbonate deposits, unique to Cryogenian glaciations, are products of intense weathering and ocean stratification. Whole-ocean warming and collapsing peripheral bulges allow marine coastal flooding to continue long after ice-sheet disappearance. The evolutionary legacy of Snowball Earth is perceptible in fossils and living organisms.

408 citations


Journal ArticleDOI
TL;DR: A holistic view of surface reconstruction is considered, which shows a detailed characterization of the field, highlights similarities between diverse reconstruction techniques and provides directions for future work in surface reconstruction.
Abstract: The area of surface reconstruction has seen substantial progress in the past two decades. The traditional problem addressed by surface reconstruction is to recover the digital representation of a physical shape that has been scanned, where the scanned data contain a wide variety of defects. While much of the earlier work has been focused on reconstructing a piece-wise smooth representation of the original shape, recent work has taken on more specialized priors to address significantly challenging data imperfections, where the reconstruction can take on different representations-not necessarily the explicit geometry. We survey the field of surface reconstruction, and provide a categorization with respect to priors, data imperfections and reconstruction output. By considering a holistic view of surface reconstruction, we show a detailed characterization of the field, highlight similarities between diverse reconstruction techniques and provide directions for future work in surface reconstruction.

405 citations


Journal ArticleDOI
Maxime Cailleret1, Steven Jansen2, Elisabeth M. R. Robert3, Elisabeth M. R. Robert4, Lucía DeSoto5, Tuomas Aakala6, Joseph A. Antos7, Barbara Beikircher8, Christof Bigler1, Harald Bugmann1, Marco Caccianiga9, Vojtěch Čada10, J. Julio Camarero11, Paolo Cherubini12, Hervé Cochard13, Marie R. Coyea14, Katarina Čufar15, Adrian J. Das16, Hendrik Davi13, Sylvain Delzon13, Michael Dorman17, Guillermo Gea-Izquierdo18, Sten Gillner19, Sten Gillner20, Laurel J. Haavik21, Laurel J. Haavik22, Henrik Hartmann23, Ana-Maria Hereş24, Kevin R. Hultine25, Pavel Janda10, Jeffrey M. Kane26, Vyacheslav I. Kharuk27, Thomas Kitzberger28, Thomas Kitzberger29, Tamir Klein30, Koen Kramer31, Frederic Lens32, Tom Levanič, Juan Carlos Linares Calderón33, Francisco Lloret34, Raquel Lobo-do-Vale35, Fabio Lombardi36, Rosana López Rodríguez37, Rosana López Rodríguez38, Harri Mäkinen, Stefan Mayr8, Ilona Mészáros39, Juha M. Metsaranta40, Francesco Minunno6, Walter Oberhuber8, Andreas Papadopoulos41, Mikko Peltoniemi, Any Mary Petritan12, Brigitte Rohner1, Brigitte Rohner12, Gabriel Sangüesa-Barreda11, Dimitrios Sarris42, Dimitrios Sarris43, Dimitrios Sarris44, Jeremy M. Smith45, Amanda B. Stan46, Frank J. Sterck31, Dejan Stojanović47, Maria Laura Suarez28, Miroslav Svoboda10, Roberto Tognetti48, José M. Torres-Ruiz13, Volodymyr Trotsiuk10, Ricardo Villalba28, Floor Vodde49, Alana R. Westwood50, Peter H. Wyckoff51, Nikolay Zafirov52, Jordi Martínez-Vilalta34 
ETH Zurich1, University of Ulm2, Vrije Universiteit Brussel3, Royal Museum for Central Africa4, University of Coimbra5, University of Helsinki6, University of Victoria7, University of Innsbruck8, University of Milan9, Czech University of Life Sciences Prague10, Spanish National Research Council11, Swiss Federal Institute for Forest, Snow and Landscape Research12, Institut national de la recherche agronomique13, Laval University14, University of Ljubljana15, United States Geological Survey16, Ben-Gurion University of the Negev17, Center for International Forestry Research18, Dresden University of Technology19, Technical University of Berlin20, University of Kansas21, University of Arkansas22, Max Planck Society23, National Museum of Natural History24, Desert Botanical Garden25, Humboldt State University26, Sukachev Institute of Forest27, National Scientific and Technical Research Council28, National University of Comahue29, Agricultural Research Organization, Volcani Center30, Wageningen University and Research Centre31, Naturalis32, Pablo de Olavide University33, Autonomous University of Barcelona34, University of Lisbon35, Mediterranean University36, University of Western Sydney37, Technical University of Madrid38, University of Debrecen39, Natural Resources Canada40, American Hotel & Lodging Educational Institute41, University of Patras42, University of Cyprus43, Open University of Cyprus44, University of Colorado Boulder45, Northern Arizona University46, University of Novi Sad47, European Forest Institute48, Estonian University of Life Sciences49, University of Alberta50, University of Minnesota51, University of Forestry, Sofia52
TL;DR: The results imply that growth-based mortality algorithms may be a powerful tool for predicting gymnosperm mortality induced by chronic stress, but not necessarily so for angiosperms and in case of intense drought or bark-beetle outbreaks.
Abstract: Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-conti- nental tree-ring width database from sites where both dead and living trees were sampled (2970 dead and 4224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca. 84% of the mortality events. The extent and duration of these reductions were highly variable (1–100 years in 96% of events) due to the complex interactions among study species and the source(s) of mortality. Strong and long-lasting declines were found for gymnosperms, shade- and drought-tolerant species, and trees that died from competition. Angiosperms and trees that died due to biotic attacks (especially bark-beetles) typically showed relatively small and short-term growth reductions. Our analysis did not highlight any universal trade-off between early growth and tree longevity within a species, although this result may also reflect high variability in sampling design among sites. The intersite and interspecific variability in growth patterns before mortality provides valuable information on the nature of the mortality process, which is consistent with our understanding of the physiological mechanisms leading to mortality. Abrupt changes in growth immediately before death can be associated with generalized hydraulic failure and/or bark-beetle attack, while long-term decrease in growth may be associated with a gradual decline in hydraulic performance coupled with depletion in carbon reserves. Our results imply that growth-based mortality algorithms may be a powerful tool for predicting gymnosperm mortality induced by chronic stress, but not necessarily so for angiosperms and in case of intense drought or bark-beetle outbreaks.

367 citations


Journal ArticleDOI
01 Jun 2017-Gut
TL;DR: It is concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory, and future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology.
Abstract: Objectives The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community-based studies on IBS prevalence. Design Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages. Pooled prevalence rates were calculated by combining separate population survey prevalence estimates to generate an overall combined metaprevalence estimate. The heterogeneity of studies was assessed. Results 1451 papers were returned and 83, including 288 103 participants in 41 countries, met inclusion criteria. The mean prevalence among individual countries ranged from 1.1% in France and Iran to 35.5% in Mexico. There was significant variance in pooled regional prevalence rates ranging from 17.5% (95% CI 16.9% to 18.2%) in Latin America, 9.6% (9.5% to 9.8%) in Asia, 7.1% (8.0% to 8.3%) in North America/ Europe/Australia/New Zealand, to 5.8% (5.6% to 6.0%) in the Middle East and Africa. There was a significant degree of heterogeneity with the percentage of residual variation due to heterogeneity at 99.9%. Conclusions The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology.

365 citations


Journal ArticleDOI
TL;DR: Antiwear properties of hydroxyl-terminated rGO were significantly enhanced compared to epoxy-hydroxyl functionalized rGO due to the integrity of graphene sheet clusters, and the friction coefficient was unaffected when hydroxy-terminate rGO was coupled with PEG.
Abstract: Functionalized and fully characterized graphene-based lubricant additives are potential 2D materials for energy-efficient tribological applications in machine elements, especially at macroscopic contacts. Two different reduced graphene oxide (rGO) derivatives, terminated by hydroxyl and epoxy-hydroxyl groups, were prepared and blended with two different molecular weights of polyethylene glycol (PEG) for tribological investigation. Epoxy-hydroxyl-terminated rGO dispersed in PEG showed significantly smaller values of the friction coefficient. In this condition, PEG chains intercalate between the functionalized graphene sheets, and shear can take place between the PEG and rGO sheets. However, the friction coefficient was unaffected when hydroxyl-terminated rGO was coupled with PEG. This can be explained by the strong coupling between graphene sheets through hydroxyl units, causing the interaction of PEG with the rGO to be non- effective for lubrication. On the other hand, antiwear properties of hydroxyl-terminated rGO were significantly enhanced compared to epoxy-hydroxyl functionalized rGO due to the integrity of graphene sheet clusters.

355 citations


Journal ArticleDOI
TL;DR: It is shown that additional conservation actions are needed to effectively protect reptiles, particularly lizards and turtles, and that adding reptile knowledge to a global complementarity conservation priority scheme identifies many locations that consequently become important.
Abstract: The distributions of amphibians, birds and mammals have underpinned global and local conservation priorities, and have been fundamental to our understanding of the determinants of global biodiversity. In contrast, the global distributions of reptiles, representing a third of terrestrial vertebrate diversity, have been unavailable. This prevented the incorporation of reptiles into conservation planning and biased our understanding of the underlying processes governing global vertebrate biodiversity. Here, we present and analyse the global distribution of 10,064 reptile species (99% of extant terrestrial species). We show that richness patterns of the other three tetrapod classes are good spatial surrogates for species richness of all reptiles combined and of snakes, but characterize diversity patterns of lizards and turtles poorly. Hotspots of total and endemic lizard richness overlap very little with those of other taxa. Moreover, existing protected areas, sites of biodiversity significance and global conservation schemes represent birds and mammals better than reptiles. We show that additional conservation actions are needed to effectively protect reptiles, particularly lizards and turtles. Adding reptile knowledge to a global complementarity conservation priority scheme identifies many locations that consequently become important. Notably, investing resources in some of the world’s arid, grassland and savannah habitats might be necessary to represent all terrestrial vertebrates efficiently.

354 citations


BookDOI
01 Jan 2017
TL;DR: This in-depth survey of salutogenesis shows the breadth and strengths of this innovative perspective on health promotion, health care, and wellness and summarizes an increasingly salient field for graduate and professional students of public health, nursing, psychology, and medicine, and for their instructors.
Abstract: This in-depth survey of salutogenesis shows the breadth and strengths of this innovative perspective on health promotion, health care, and wellness. Background and historical chapters trace the development of the salutogenic model of health, and flesh out the central concepts, most notably generalized resistance resources and the sense of coherence, that differentiate it from pathogenesis. From there, experts describe a range of real-world applications within and outside health contexts, from positive psychology to geriatrics, from small towns to corrections facilities, and from school and workplace to professional training. Perspectives from scholars publishing in languages other than English show the global relevance of the field.Among the topics in the Handbook: Emerging ideas relevant to the salutogenic model of health Specific resistance resources in the salutogenic model of health The sense of coherence and its measurement The application of salutogenesis in communities and neighborhoods The application of salutogenesis to health development in youth with chronic conditions The application of salutogenesis in mental health care settings The Handbook of Salutogenesis summarizes an increasingly salient field for graduate and professional students of public health, nursing, psychology, and medicine, and for their instructors. It will also appeal to health-related academicians and professionals who wish to have a thorough grounding in the topic.

Journal ArticleDOI
TL;DR: Findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan, using a well-established, validated, publicly available analysis pipeline.
Abstract: Objective:Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group.Method:The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2–64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was mo...

Journal ArticleDOI
09 Mar 2017-Nature
TL;DR: In this article, a detailed view of the organization of the lamin meshwork within the lamina was obtained using cryo-electron tomography, which showed that A-and B-type lamins assemble into tetrameric filaments of 3.5 nm thickness.
Abstract: The nuclear lamina is a fundamental constituent of metazoan nuclei. It is composed mainly of lamins, which are intermediate filament proteins that assemble into a filamentous meshwork, bridging the nuclear envelope and chromatin. Besides providing structural stability to the nucleus, the lamina is involved in many nuclear activities, including chromatin organization, transcription and replication. However, the structural organization of the nuclear lamina is poorly understood. Here we use cryo-electron tomography to obtain a detailed view of the organization of the lamin meshwork within the lamina. Data analysis of individual lamin filaments resolves a globular-decorated fibre appearance and shows that A- and B-type lamins assemble into tetrameric filaments of 3.5 nm thickness. Thus, lamins exhibit a structure that is remarkably different from the other canonical cytoskeletal elements. Our findings define the architecture of the nuclear lamin meshworks at molecular resolution, providing insights into their role in scaffolding the nuclear lamina.

Journal ArticleDOI
TL;DR: The conclusion is that there is not enough convincing evidence to support the number sense theory anymore, and researchers are encouraged not to assume that number sense is simply innate, but to put this hypothesis to the test and consider whether such an assumption is even testable in the light of the correlation of numerosity and continuous magnitudes.
Abstract: In this review, we are pitting two theories against each other: the more accepted theory, the number sense theory, suggesting that a sense of number is innate and non-symbolic numerosity is being processed independently of continuous magnitudes (e.g., size, area, and density); and the newly emerging theory suggesting that (1) both numerosities and continuous magnitudes are processed holistically when comparing numerosities and (2) a sense of number might not be innate. In the first part of this review, we discuss the number sense theory. Against this background, we demonstrate how the natural correlation between numerosities and continuous magnitudes makes it nearly impossible to study non-symbolic numerosity processing in isolation from continuous magnitudes, and therefore, the results of behavioral and imaging studies with infants, adults, and animals can be explained, at least in part, by relying on continuous magnitudes. In the second part, we explain the sense of magnitude theory and review studies that directly demonstrate that continuous magnitudes are more automatic and basic than numerosities. Finally, we present outstanding questions. Our conclusion is that there is not enough convincing evidence to support the number sense theory anymore. Therefore, we encourage researchers not to assume that number sense is simply innate, but to put this hypothesis to the test and consider whether such an assumption is even testable in the light of the correlation of numerosity and continuous magnitudes.

Proceedings ArticleDOI
03 Apr 2017
TL;DR: This work trained a multi-stage meta classifier that can distinguish between traffic generated by IoT and non-IoT devices, and collected and labeled network traffic data from nine distinct IoT devices and PCs and smartphones.
Abstract: In this work we apply machine learning algorithms on network traffic data for accurate identification of IoT devices connected to a network To train and evaluate the classifier, we collected and labeled network traffic data from nine distinct IoT devices, and PCs and smartphones Using supervised learning, we trained a multi-stage meta classifier; in the first stage, the classifier can distinguish between traffic generated by IoT and non-IoT devices In the second stage, each IoT device is associated a specific IoT device class The overall IoT classification accuracy of our model is 99281+

Journal ArticleDOI
20 Mar 2017
TL;DR: The nonlinear Fourier transform is a transmission and signal processing technique that makes positive use of the Kerr nonlinearity in optical fibre channels.
Abstract: Fiber-optic communication systems are nowadays facing serious challenges due to the fast growing demand on capacity from various new applications and services. It is now well recognized that nonlinear effects limit the spectral efficiency and transmission reach of modern fiber-optic communications. Nonlinearity compensation is therefore widely believed to be of paramount importance for increasing the capacity of future optical networks. Recently, there has been steadily growing interest in the application of a powerful mathematical tool—the nonlinear Fourier transform (NFT)—in the development of fundamentally novel nonlinearity mitigation tools for fiber-optic channels. It has been recognized that, within this paradigm, the nonlinear crosstalk due to the Kerr effect is effectively absent, and fiber nonlinearity due to the Kerr effect can enter as a constructive element rather than a degrading factor. The novelty and the mathematical complexity of the NFT, the versatility of the proposed system designs, and the lack of a unified vision of an optimal NFT-type communication system, however, constitute significant difficulties for communication researchers. In this paper, we therefore survey the existing approaches in a common framework and review the progress in this area with a focus on practical implementation aspects. First, an overview of existing key algorithms for the efficacious computation of the direct and inverse NFT is given, and the issues of accuracy and numerical complexity are elucidated. We then describe different approaches for the utilization of the NFT in practical transmission schemes. After that we discuss the differences, advantages, and challenges of various recently emerged system designs employing the NFT, as well as the spectral efficiency estimates available up-to-date. With many practical implementation aspects still being open, our mini-review is aimed at helping researchers assess the perspectives, understand the bottlenecks, and envision the development paths in the upcoming NFT-based transmission technologies.

Journal ArticleDOI
TL;DR: The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization.
Abstract: Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials.

Proceedings ArticleDOI
09 Oct 2017
TL;DR: This article found that experienced drivers learn to avoid hazards to which inexperienced drivers must respond, resulting in a more focused, goal-directed visual search and a higher sensitivity to potential hazards, and observed six hazard perception movies (four movies included one planned hazardous event and two movies served as control).
Abstract: Twenty-one young-inexperienced drivers (17-18 years old, 2.7 months of driving license), 19 experienced drivers (22-30, 7.3 years of driving license) and 16 elderly-experienced drivers (65-72, 37.5 years of driving license) observed six hazard perception movies (four movies included one planned hazardous event and two movies served as control) and were instructed to press a button each time they recognized a hazard. Participants’ eye movements were recorded. Young drivers were the least sensitive in responding to immaterialized unplanned hazards, which occurred after the planned hazardous events. When the hazard was imminent, however, all drivers responded at the same time. Eye movement analysis revealed that all drivers detected the elements in the environment when they were salient, but gazing towards the right at T-intersections characterized only the more experienced drivers. The young drivers tended to gaze straight ahead. This study shows that experienced drivers learn to avoid hazards to which inexperienced drivers must respond. Responding to more hazardous situations, drivers’ knowledge base expands, resulting in a more focused, goal-directed visual search and a higher sensitivity to potential hazards.

Journal ArticleDOI
TL;DR: In this article, the authors examined whether the cognitive, affective and overall image of tourists in the resort city of Eilat can be used to predict behavioral intentions of local residents and tourists.

Journal ArticleDOI
TL;DR: Applications of the superhydrophobic LIG are shown in oil/water separation as well as anti-icing surfaces, while the versatility of the controlled atmosphere chamber fabrication method is demonstrated through the improved microsupercapacitor performance generated from LIG films prepared in an O2 atmosphere.
Abstract: The modification of graphene-based materials is an important topic in the field of materials research. This study aims to expand the range of properties for laser-induced graphene (LIG), specifically to tune the hydrophobicity and hydrophilicity of the LIG surfaces. While LIG is normally prepared in the air, here, using selected gas atmospheres, a large change in the water contact angle on the as-prepared LIG surfaces has been observed, from 0° (superhydrophilic) when using O2 or air, to >150° (superhydrophobic) when using Ar or H2. Characterization of the newly derived surfaces shows that the different wetting properties are due to the surface morphology and chemical composition of the LIG. Applications of the superhydrophobic LIG are shown in oil/water separation as well as anti-icing surfaces, while the versatility of the controlled atmosphere chamber fabrication method is demonstrated through the improved microsupercapacitor performance generated from LIG films prepared in an O2 atmosphere.

Journal ArticleDOI
Jens P. Dreier1, Martin Fabricius2, Cenk Ayata3, Oliver W. Sakowitz4, C. William Shuttleworth5, Christian Dohmen6, Christian Dohmen7, Rudolf Graf7, Peter Vajkoczy1, Raimund Helbok8, Michiyasu Suzuki9, Alois Josef Schiefecker8, Sebastian Major1, Maren K.L. Winkler1, Eun Jeung Kang1, Denny Milakara1, Ana I Oliveira-Ferreira1, Clemens Reiffurth1, Gajanan S. Revankar1, Kazutaka Sugimoto9, Nora F. Dengler1, Nils Hecht1, Brandon Foreman10, Bart Feyen11, Daniel Kondziella2, Christian K. Friberg2, Henning Piilgaard2, Eric Rosenthal3, M. Brandon Westover3, Anna Maslarova12, Edgar Santos4, Daniel N. Hertle4, Renán Sánchez-Porras4, Sharon L. Jewell13, Baptiste Balança14, Baptiste Balança15, Johannes Platz16, Jason M. Hinzman10, Janos Luckl1, Karl Schoknecht1, Michael Schöll4, Christoph Drenckhahn1, Delphine Feuerstein7, Nina Eriksen2, Viktor Horst1, Julia S. Bretz1, Paul Jahnke1, Michael Scheel1, Georg Bohner1, Egill Rostrup2, Bente Pakkenberg2, Uwe Heinemann1, Jan Claassen17, Andrew P. Carlson5, Christina M. Kowoll6, Christina M. Kowoll7, Svetlana Lublinsky18, Yoash Chassidim18, Ilan Shelef18, Alon Friedman19, Gerrit Brinker6, Michael Reiner6, Sergei A. Kirov20, R. David Andrew21, Eszter Farkas22, Erdem Güresir12, Hartmut Vatter12, Lee S Chung23, Kc Brennan23, Thomas Lieutaud15, Thomas Lieutaud14, Stéphane Marinesco14, Andrew I R Maas11, Juan Sahuquillo24, Markus Dahlem25, Frank Richter26, Oscar Herreras27, Martyn G. Boutelle28, David O. Okonkwo29, M. Ross Bullock30, Otto W. Witte26, Peter Martus31, Arn M. J. M. van den Maagdenberg32, Michel D. Ferrari32, Rick M. Dijkhuizen33, Lori Shutter29, Norberto Andaluz10, André P. Schulte, Brian A. MacVicar34, Tomas Watanabe, Johannes Woitzik1, Martin Lauritzen2, Anthony J. Strong13, Jed A. Hartings10 
TL;DR: Consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions are provided, which offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.
Abstract: Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Journal ArticleDOI
30 May 2017
TL;DR: A very clean definition of privacy---now known as differential privacy---and measure of its loss are provided, proving that privacy can be preserved by calibrating the standard deviation of the noise according to the {\em sensitivity} of the function $f$.
Abstract: We continue a line of research initiated in Dinur and Nissim (2003); Dwork and Nissim (2004); and Blum et al. (2005) on privacy-preserving statistical databases. Consider a trusted server that holds a database of sensitive information. Given a query function $f$ mapping databases to reals, the so-called {\em true answer} is the result of applying $f$ to the database. To protect privacy, the true answer is perturbed by the addition of random noise generated according to a carefully chosen distribution, and this response, the true answer plus noise, is returned to the user. Previous work focused on the case of noisy sums, in which $f = \sum_i g(x_i)$, where $x_i$ denotes the $i$th row of the database and $g$ maps database rows to $[0,1]$. We extend the study to general functions $f$, proving that privacy can be preserved by calibrating the standard deviation of the noise according to the {\em sensitivity} of the function $f$. Roughly speaking, this is the amount that any single argument to $f$ can change its output. The new analysis shows that for several particular applications substantially less noise is needed than was previously understood to be the case. The first step is a very clean definition of privacy---now known as differential privacy---and measure of its loss. We also provide a set of tools for designing and combining differentially private algorithms, permitting the construction of complex differentially private analytical tools from simple differentially private primitives. Finally, we obtain separation results showing the increased value of interactive statistical release mechanisms over non-interactive ones.

Journal ArticleDOI
Federica Barzaghi, Laura C. Amaya Hernandez1, Benedicte Neven2, Silvia Ricci3, Zeynep Yesim Kucuk4, Jack J. Bleesing4, Zohreh Nademi3, Mary Slatter3, Erlinda R. Ulloa3, Anna Shcherbina, Anna Roppelt, Austen Worth5, Juliana Silva5, Alessandro Aiuti6, Luis Murguia-Favela7, Carsten Speckmann8, Magda Carneiro-Sampaio9, Juliana Folloni Fernandes9, Safa Baris10, Ahmet Ozen10, Elif Karakoc-Aydiner10, Ayca Kiykim10, Ansgar Schulz11, Sandra Steinmann11, Lucia Dora Notarangelo3, Eleonora Gambineri3, Paolo Lionetti12, William T. Shearer13, Lisa R. Forbes13, Caridad Martinez13, Despina Moshous2, Stéphane Blanche2, Alain Fisher2, Frank M. Ruemmele2, Come Tissandier2, Marie Ouachée-Chardin, Frédéric Rieux-Laucat14, Marina Cavazzana2, Waseem Qasim15, Barbarella Lucarelli3, Michael H. Albert16, Ichiro Kobayashi, Laura C. Alonso, Cristina Díaz de Heredia, Hirokazu Kanegane17, Anita Lawitschka3, Jong Jin Seo18, Marta González-Vicent, Miguel Angel Diaz, Rakesh K. Goyal19, Martin Sauer20, Akif Yesilipek, Minsoo Kim, Yesim Yilmaz-Demirdag, Monica Bhatia, Julie Khlevner, Erick J. Richmond Padilla3, Silvana Martino3, Davide Montin3, Olaf Neth21, Agueda Molinos-Quintana21, Justo Valverde-Fernandez21, Arnon Broides22, Vered Pinsk22, Antje Ballauf3, Filomeen Haerynck23, Victoria Bordon23, Catharina Dhooge23, Maria Laura Garcia-Lloret24, Robbert G. M. Bredius25, Krzysztof Kałwak26, Elie Haddad27, Markus G. Seidel28, Gregor Dückers3, Sung-Yun Pai3, Sung-Yun Pai29, Christopher C. Dvorak30, Stephan Ehl8, Franco Locatelli3, Frederick D. Goldman31, Andrew R. Gennery3, M.J. Cowan30, Maria Grazia Roncarolo1, Rosa Bacchetta1 
TL;DR: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long‐term disease‐free survival, and when performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.
Abstract: Background Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant ( P = .035) but not under IS. Conclusions Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.

Journal ArticleDOI
24 Mar 2017-Science
TL;DR: A mechanism that controls the activation of ER by the posttranslational modification of epigenetic regulators is uncovered, providing a rationale for epigenetic therapy in ER-positive breast cancer.
Abstract: Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)–positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples. KMT2D, a histone H3 lysine 4 methyltransferase, is required for FOXA1, PBX1, and ER recruitment and activation. AKT binds and phosphorylates KMT2D, attenuating methyltransferase activity and ER function, whereas PI3Kα inhibition enhances KMT2D activity. These findings uncover a mechanism that controls the activation of ER by the posttranslational modification of epigenetic regulators, providing a rationale for epigenetic therapy in ER-positive breast cancer.

Journal ArticleDOI
TL;DR: The changes in the epidemiology of this disease, the underlying prenatal mechanisms, and possible treatments that may reduce the prevalence of CP and alter the course of the disease are described.
Abstract: Cerebral palsy (CP) is the most common motor disability in childhood. This syndrome is the manifestation of intrauterine pathologies, intrapartum complications and post-natal sequel, especially among preterm neonates. A double hit model theory is proposed suggesting that an intrauterine condition along with intrapartum or postnatal insult lead to the development of CP. Recent reports demonstrated that treatment during the process of preterm birth like magnesium sulfate and post-natal modalities such as cooling may prevent or reduce the prevalence of this syndrome. Moreover, animal model demonstrated that post-natal treatment with anti-inflammatory drugs coupled with nanoparticles may affect the course of the disease in pups with neuroinflammation. The current review would describe the changes in the epidemiology of this disease, the underlying prenatal mechanisms, and possible treatments that may reduce the prevalence of CP and alter the course of disease.

Journal ArticleDOI
TL;DR: It is hypothesized that H2O2 activates a transcription factor which in turn up-regulates tpxD expression, which triggers a conformational change in CodY, resulting in enhanced binding to DNA and a schematic model illustrating the contribution of TpxD and CodY to pneumococcal global transcriptional response to H2 O2 is proposed.
Abstract: Streptococcus pneumoniae is a facultative anaerobic pathogen Although it maintains fermentative metabolism, during aerobic growth pneumococci produce high levels of H2O2, which can have adverse effects on cell viability and DNA, and influence pneumococcal interaction with its host The pneumococcus is unusual in its dealing with toxic reactive oxygen species in that it neither has catalase nor the global regulators of peroxide stress resistance Previously, we identified pneumococcal thiol peroxidase (TpxD) as the key enzyme for enzymatic removal of H2O2, and showed that TpxD synthesis is up-regulated upon exposure to H2O2 This study aimed to reveal the mechanism controlling TpxD expression under H2O2 stress We hypothesize that H2O2 activates a transcription factor which in turn up-regulates tpxD expression Microarray analysis revealed a pneumococcal global transcriptional response to H2O2 Mutation of tpxD abolished H2O2-mediated response to high H2O2 levels, signifying the need for an active TpxD under oxidative stress conditions Bioinformatic tools, applied to search for a transcription factor modulating tpxD expression, pointed towards CodY as a potential candidate Indeed, a putative 15-bp consensus CodY binding site was found in the proximal region of tpxD-coding sequence Binding of CodY to this site was confirmed by EMSA, and genetic engineering techniques demonstrated that this site is essential for TpxD up-regulation under H2O2 stress Furthermore, tpxD expression was reduced in a codY mutant These data indicate that CodY is an activator of tpxD expression, triggering its up-regulation under H2O2 stress In addition we show that H2O2 specifically oxidizes the 2 CodY cysteines This oxidation may trigger a conformational change in CodY, resulting in enhanced binding to DNA A schematic model illustrating the contribution of TpxD and CodY to pneumococcal global transcriptional response to H2O2 is proposed

Journal ArticleDOI
TL;DR: A comprehensive overview of the AAL domain is provided, presenting a systematic analysis of over 10 years of relevant literature focusing on the stakeholders’ needs, bridging the gap of existing reviews which focused on technologies.
Abstract: Ambient assisted living (AAL) is focused on providing assistance to people primarily in their natural environment. Over the past decade, the AAL domain has evolved at a fast pace in various directions. The stakeholders of AAL are not only limited to patients, but also include their relatives, social services, health workers, and care agencies. In fact, AAL aims at increasing the life quality of patients, their relatives and the health care providers with a holistic approach. This paper aims at providing a comprehensive overview of the AAL domain, presenting a systematic analysis of over 10 years of relevant literature focusing on the stakeholders’ needs, bridging the gap of existing reviews which focused on technologies. The findings of this review clearly show that until now the AAL domain neglects the view of the entire AAL ecosystem. Furthermore, the proposed solutions seem to be tailored more on the basis of the available existing technologies, rather than supporting the various stakeholders’ needs. Another major lack that this review is pointing out is a missing adequate evaluation of the various solutions. Finally, it seems that, as the domain of AAL is pretty new, it is still in its incubation phase. Thus, this review calls for moving the AAL domain to a more mature phase with respect to the research approaches.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the fatigue resistance of AM-SLM AlSi10Mg samples built in the Z direction after various heat treatments and established a relation between the yield stress and fatigue resistance.
Abstract: The fatigue resistance of AM-SLM AlSi10Mg samples built in the Z direction after various heat treatments was investigated. Specimens were tested in the as-built (AB) condition, after stress relief (SR) treatment and after SR and hot isostatic pressing (HIP) at either 250 °C or 500 °C. The AB machined and polished specimens displayed the highest fatigue limit ( S f = 125 MPa, N f = 10 7 cycles). SR and HIP cycles decrease the yield strength, hardness and fatigue limit. The SR and HIP treatment at 500 °C resulted in the lowest fatigue resistance due to significant microstructural changes. A relation between the yield stress and fatigue resistance was established. Linear elastic fracture mechanics were employed for evaluating fracture surface morphology. Based on the results of fracture surface characterization, values of the critical stress intensity factor ( K cr ) for AM-SLM AlSi10Mg specimens after various heat treatments were estimated.

Journal ArticleDOI
TL;DR: TGF-β1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy and the trial was terminated 4 months early for futility on the basis of their recommendation.
Abstract: TGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1-specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3-3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or eGFR of 20-60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-β1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-β1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-β1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.

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TL;DR: The question of whether WGS can entirely replace routine microbiology in the future and the tension between the fact that most sequencers are designed to process multiple samples in parallel whereas for optimal diagnosis a one-by-one processing of the samples is preferred are speculated.