scispace - formally typeset
Search or ask a question

Showing papers by "Bar-Ilan University published in 2015"


Journal ArticleDOI
TL;DR: It is revealed that much of the performance gains of word embeddings are due to certain system design choices and hyperparameter optimizations, rather than the embedding algorithms themselves, and these modifications can be transferred to traditional distributional models, yielding similar gains.
Abstract: Recent trends suggest that neural-network-inspired word embedding models outperform traditional count-based distributional models on word similarity and analogy detection tasks. We reveal that much of the performance gains of word embeddings are due to certain system design choices and hyperparameter optimizations, rather than the embedding algorithms themselves. Furthermore, we show that these modifications can be transferred to traditional distributional models, yielding similar gains. In contrast to prior reports, we observe mostly local or insignificant performance differences between the methods, with no global advantage to any single approach over the others.

1,374 citations


Journal ArticleDOI
05 Mar 2015-Nature
TL;DR: Results support the emerging concept that perturbed host–microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects and suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.
Abstract: The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

1,362 citations


Journal ArticleDOI
27 Feb 2015-Science
TL;DR: It is shown that N6-methyladenosine (m6A), a messenger RNA (mRNA) modification present on transcripts of pluripotency factors, drives this transition from the pluripotent to the differentiated state.
Abstract: Naive and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naive pluripotency. Mettl3 knockout preimplantation epiblasts and naive embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naive state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naive pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naive and primed pluripotency in an opposing manner.

1,181 citations


Journal ArticleDOI
TL;DR: The data support a model of animal circRNA biogenesis in which competing RNA-RNA interactions of introns form larger structures that promote circularization of embedded exons, whereas ADAR1 antagonizes circRNA expression by melting stems within these interactions.

826 citations


Journal ArticleDOI
TL;DR: Li-sulfur batteries have high theoretical energy density that can revolutionize electrochemical propulsion capability Consequently, in recent years there has been much work throughout the world related to these systems as mentioned in this paper.
Abstract: The development and commercialization of Li ion batteries during recent decades is one of the great successes of modern electrochemistry The increasing reliability of Li ion batteries makes them natural candidates as power sources for electric vehicles However, their current energy density, which can reach an average of 200 Wh kg−1 on the single cell level, limits the possible driving range of electric cars propelled by Li-ion batteries Thereby, there is a strong driving force to develop power sources technologies beyond Li-ion batteries that will mark breakthroughs in energy density capabilities Li-sulfur batteries have high theoretical energy density that can revolutionize electrochemical propulsion capability Consequently, in recent years there has been much work throughout the world related to these systems The scope of work on this topic justifies frequent publications of review articles that summarize recent extensive work and provide guidelines and direction for focused future work Here, a comprehensive, systematic work related to Li-sulfur battery systems is described, beginning with the Li anode challenges, carbon-encapsulated sulfur cathodes, and various kinds of relevant electrolyte solutions Based on the work described and parallel recent studies by other groups, important and comprehensive guidelines for further research and development efforts in this field are provided

611 citations


Journal ArticleDOI
TL;DR: A suite of utilities, Change-O, which provides tools for advanced analyses of large-scale Ig repertoire sequencing data, and enables the seamless integration of multiple analyses into a single workflow.
Abstract: Advances in high-throughput sequencing technologies now allow for large-scale characterization of B cell immunoglobulin (Ig) repertoires. The high germline and somatic diversity of the Ig repertoire presents challenges for biologically meaningful analysis, which requires specialized computational methods. We have developed a suite of utilities, Change-O, which provides tools for advanced analyses of large-scale Ig repertoire sequencing data. Change-O includes tools for determining the complete set of Ig variable region gene segment alleles carried by an individual (including novel alleles), partitioning of Ig sequences into clonal populations, creating lineage trees, inferring somatic hypermutation targeting models, measuring repertoire diversity, quantifying selection pressure, and calculating sequence chemical properties. All Change-O tools utilize a common data format, which enables the seamless integration of multiple analyses into a single workflow. Availability and implementation Change-O is freely available for non-commercial use and may be downloaded from http://clip.med.yale.edu/changeo. Contact steven.kleinstein@yale.edu.

549 citations


Journal ArticleDOI
Hou-Feng Zheng1, Vincenzo Forgetta1, Yi-Hsiang Hsu2, Yi-Hsiang Hsu3  +171 moreInstitutions (55)
01 Oct 2015-Nature
TL;DR: Evidence is provided that low‐frequency non‐coding variants have large effects on BMD and fracture, thereby providing rationale for whole‐genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

410 citations


Journal ArticleDOI
TL;DR: The crucial role of the crystal water was revealed by directly visualizing its presence and dynamic rearrangement using scanning transmission electron microscopy (STEM), and the importance of lowering desolvation energy penalty at the cathode-electrolyte interface was elucidated by working with water containing nonaqueous electrolytes.
Abstract: Rechargeable magnesium batteries have lately received great attention for large-scale energy storage systems due to their high volumetric capacities, low materials cost, and safe characteristic. However, the bivalency of Mg2+ ions has made it challenging to find cathode materials operating at high voltages with decent (de)intercalation kinetics. In an effort to overcome this challenge, we adopt an unconventional approach of engaging crystal water in the layered structure of Birnessite MnO2 because the crystal water can effectively screen electrostatic interactions between Mg2+ ions and the host anions. The crucial role of the crystal water was revealed by directly visualizing its presence and dynamic rearrangement using scanning transmission electron microscopy (STEM). Moreover, the importance of lowering desolvation energy penalty at the cathode–electrolyte interface was elucidated by working with water containing nonaqueous electrolytes. In aqueous electrolytes, the decreased interfacial energy penalty ...

394 citations


Journal ArticleDOI
TL;DR: Deep sequencing, proteomic profiling of autoantibodies and single-cell analysis demonstrated highly diversified ASCs punctuated by clones expressing the variable heavy-chain region VH4-34 that produced dominant serum autoantIBodies, shed light on the pathogenesis of SLE and explain the benefit of agents that target B cells and should facilitate the design of future therapies.
Abstract: Acute systemic lupus erythematosus (SLE) courses with surges of antibody-secreting cells (ASCs) whose origin, diversity and contribution to serum autoantibodies remain unknown. Here, deep sequencing, proteomic profiling of autoantibodies and single-cell analysis demonstrated highly diversified ASCs punctuated by clones expressing the variable heavy-chain region VH4-34 that produced dominant serum autoantibodies. A fraction of ASC clones contained autoantibodies without mutation, a finding consistent with differentiation outside the germinal centers. A substantial ASC segment was derived from a distinct subset of newly activated naive cells of considerable clonality that persisted in the circulation for several months. Thus, selection of SLE autoreactivities occurred during polyclonal activation, with prolonged recruitment of recently activated naive B cells. Our findings shed light on the pathogenesis of SLE, help explain the benefit of agents that target B cells and should facilitate the design of future therapies.

392 citations


Journal ArticleDOI
TL;DR: The conclusions reached by a diverse group of scientists who attended an intense 2-day workshop on hybrid organic-inorganic perovskites are presented, including their thoughts on the most burning fundamental and practical questions regarding this unique class of materials.
Abstract: The conclusions reached by a diverse group of scientists who attended an intense 2-day workshop on hybrid organic-inorganic perovskites are presented, including their thoughts on the most burning fundamental and practical questions regarding this unique class of materials, and their suggestions on various approaches to resolve these issues.

381 citations


Journal ArticleDOI
TL;DR: The links between the endocrine system and the gut microbiota are summarized, with interactions by the different functions of the hormones, including those affecting behavior, sexual attraction, appetite and metabolism, gender and immunity.
Abstract: The new field of microbiome research studies the microbes within multicellular hosts and the many effects of these microbes on the host's health and well-being. We now know that microbes influence metabolism, immunity and even behavior. Essential questions, which are just starting to be answered, are what are the mechanisms by which these bacteria affect specific host characteristics. One important but understudied mechanism appears to involve hormones. Although the precise pathways of microbiota-hormonal signaling have not yet been deciphered, specific changes in hormone levels correlate with the presence of the gut microbiota. The microbiota produces and secretes hormones, responds to host hormones and regulates expression levels of host hormones. Here, we summarize the links between the endocrine system and the gut microbiota. We categorize these interactions by the different functions of the hormones, including those affecting behavior, sexual attraction, appetite and metabolism, gender and immunity. Future research in this area will reveal additional connections, and elucidate the pathways and consequences of bacterial interactions with the host endocrine system.

Journal ArticleDOI
TL;DR: In this article, the authors characterize the traffic percolation process as a transition between isolated local flows and global flows, where the giant cluster of local flows disintegrates when the second largest cluster reaches its maximum.
Abstract: A critical phenomenon is an intrinsic feature of traffic dynamics, during which transition between isolated local flows and global flows occurs. However, very little attention has been given to the question of how the local flows in the roads are organized collectively into a global city flow. Here we characterize this organization process of traffic as “traffic percolation,” where the giant cluster of local flows disintegrates when the second largest cluster reaches its maximum. We find in real-time data of city road traffic that global traffic is dynamically composed of clusters of local flows, which are connected by bottleneck links. This organization evolves during a day with different bottleneck links appearing in different hours, but similar in the same hours in different days. A small improvement of critical bottleneck roads is found to benefit significantly the global traffic, providing a method to improve city traffic with low cost. Our results may provide insights on the relation between traffic dynamics and percolation, which can be useful for efficient transportation, epidemic control, and emergency evacuation.

Journal ArticleDOI
TL;DR: The precise direction of metastatic spread is revealed across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours and analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations.
Abstract: Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

Journal ArticleDOI
TL;DR: To the best of the knowledge, this represents the first demonstration of the successful isolation of mutation-reactive T cells from patients' peripheral blood prior to immune therapy, potentially providing the basis for designing personalized immunotherapies to treat patients with advanced cancer.
Abstract: Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. Here, in an attempt to develop a strategy for facilitating the isolation, expansion, and study of mutated antigen-specific T cells, we performed whole-exome sequencing on matched tumor and normal DNA isolated from 8 patients with metastatic melanoma. Candidate mutated epitopes were identified using a peptide-MHC-binding algorithm, and these epitopes were synthesized and used to generate panels of MHC tetramers that were evaluated for binding to tumor digests and cultured TILs used for the treatment of patients. This strategy resulted in the identification of 9 mutated epitopes from 5 of the 8 patients tested. Cells reactive with 8 of the 9 epitopes could be isolated from autologous peripheral blood, where they were detected at frequencies that were estimated to range between 0.4% and 0.002%. To the best of our knowledge, this represents the first demonstration of the successful isolation of mutation-reactive T cells from patients' peripheral blood prior to immune therapy, potentially providing the basis for designing personalized immunotherapies to treat patients with advanced cancer.

Journal ArticleDOI
10 Nov 2015-PLOS ONE
TL;DR: These investigations are initial steps in building a first atlas of dynamic interactions among organ systems, which demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems.
Abstract: We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems.

Journal ArticleDOI
TL;DR: It turns out that the extent to which one can exercise control via manipulation of a subset of nodes depends sensitively on the number of nodes perturbed.
Abstract: Recent studies have made important advances in identifying sensor or driver nodes, through which we can observe or control a complex system. But the observational uncertainty induced by measurement noise and the energy required for control continue to be significant challenges in practical applications. Here we show that the variability of control energy and observational uncertainty for different directions of the state space depend strongly on the number of driver nodes. In particular, we find that if all nodes are directly driven, control is energetically feasible, as the maximum energy increases sublinearly with the system size. If, however, we aim to control a system through a single node, control in some directions is energetically prohibitive, increasing exponentially with the system size. For the cases in between, the maximum energy decays exponentially when the number of driver nodes increases. We validate our findings in several model and real networks, arriving at a series of fundamental laws to describe the control energy that together deepen our understanding of complex systems. The complex interactions inherent in real-world networks grant us precise system control via manipulation of a subset of nodes. It turns out that the extent to which we can exercise this control depends sensitively on the number of nodes perturbed.

Journal ArticleDOI
TL;DR: It is demonstrated that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats, and the ease of implantation of these wireless and modular arrays opens the door to the functional restoration of sight in patients blinded by retinal degeneration.
Abstract: Patients with retinal degeneration lose sight due to the gradual demise of photoreceptors. Electrical stimulation of surviving retinal neurons provides an alternative route for the delivery of visual information. We demonstrate that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats. The electrical receptive fields recorded in retinal ganglion cells were similar in size to the natural visual receptive fields. Similarly to normal vision, the retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images and nonlinear spatial summation. In rats with retinal degeneration, these photovoltaic arrays elicited retinal responses with a spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in healthy rats. The ease of implantation of these wireless and modular arrays, combined with their high resolution, opens the door to the functional restoration of sight in patients blinded by retinal degeneration.

Journal ArticleDOI
TL;DR: In this article, a carbon-coated NaCrO2 cathode material was synthesized via an emulsion-drying method, which was modified using pitch as a carbon source and the products were tested in half and full cells using a NaPF6-based nonaqueous electrolyte solution.
Abstract: Sodium-ion batteries offer a potential alternative or complementary system to lithium-ion batteries, which are widely used in many applications. For this purpose, layered O3-type NaCrO2 for use as a cathode material in sodium-ion batteries was synthesized via an emulsion-drying method. The produced NaCrO2 was modified using pitch as a carbon source and the products were tested in half and full cells using a NaPF6-based non-aqueous electrolyte solution. The carbon-coated NaCrO2 cathode material exhibits excellent capacity retention with superior rate capability up to a rate of 150 C (99 mA h (g oxide)−1), which corresponds to full discharge during 27 s. The surface conducting carbon layer plays a critically important role in the excellent performance of this cathode material. We confirmed the reaction process with sodium using X-ray diffraction and X-ray absorption spectroscopy. Thermal analysis using time-resolved X-ray diffraction also demonstrated the structural stability of carbon-coated Na0.5CrO2. Due to the excellent performance of the cathode material described herein, this study has the potential to promote the accelerated development of sodium-ion batteries for a large number of applications.

Journal ArticleDOI
TL;DR: In this article, the deformation of 2D Ti3C2Tx (MXene) electrode materials at various states-of-charge with a variety of cations (Li, Na, K, Cs, Mg, Ca, Ba, and three tetra-alkylammonium cations) during cycling by electrochemical quartz-crystal admittance was analyzed.
Abstract: Fast ion adsorption processes in supercapacitors enable quick storage/delivery of significant amounts of energy, while ion intercalation in battery materials leads to even larger amounts of energy stored, but at substantially lower rates due to diffusional limitations. Intercalation of ions into the recently discovered 2D Ti3C2Tx (MXene) occurs with a very high rate and leads to high capacitance, posing a paradox. Herein, by characterizing the mechanical deformations of MXene electrode materials at various states-of-charge with a variety of cations (Li, Na, K, Cs, Mg, Ca, Ba, and three tetra­alkylammonium cations) during cycling by electrochemical quartz-crystal admittance (EQCA, quartz-crystal microbalance with dissipation monitoring) combined with in situ electronic conductance and electrochemical impedance, light is shone on this paradox. Based on this work, it appears that the capacitive paradox stems from cationic insertion, accompanied by significant deformation of the MXene particles, that occurs so rapidly so as to resemble 2D ion adsorption at solid-liquid interfaces. The latter is greatly facilitated by the presence of water molecules between the MXene sheets.

Journal ArticleDOI
Ruth Feldman1
TL;DR: A global 'parental caregiving' network is chart that integrates conserved structures supporting mammalian caregiving with later-evolving networks and implicates parenting in the evolution of higher order social functions aimed at maximizing infant survival.

Journal ArticleDOI
TL;DR: In this article, the performance of the MgTFSI2/MgCl2 (DME) solutions through chemical and electrochemical conditioning and demonstrate the effect on the solutions' electrochemical characteristics.
Abstract: MgTFSI2 is the only ether-soluble "simple" magnesium salt. The poor electrochemical performance of Mg electrodes in its solutions hinders its practicality as a viable electrolyte for Mg batteries. MgTFSI2/DME solutions were demonstrated to dissolve large quantities of MgCl2 and produce electrolyte solutions with superior performance, though the electrochemical performance, mainly in terms of reversibility, of MgTFSI2/MgCl2 (DME) solutions cannot yet compete with that of organometallic based electrolyte solutions. We believe that the solutions' purity level governs the overall electrochemical performance, especially in solutions where a strong reductant (i.e Grignard reagent) is not present to act as an impurity scavenger. In this work, we alter the performance of the MgTFSI2/MgCl2 (DME) solutions through chemical and electrochemical conditioning and demonstrate the effect on the solutions' electrochemical characteristics. We demonstrate relatively high reversible behavior of Mg deposition/dissolution with crystalline uniformity of the Mg deposits, complemented by a fully reversible intercalation/de-intercalation process of Mg ions into Mo6S8 cathodes. We also investigated LiTFSI/MgCl2 solutions which exhibited even higher reversibility than MgTFSI2/MgCl2 (DME) solutions, which we attribute to the higher purity level available for the LiTFSI salt.

Proceedings ArticleDOI
01 Jan 2015
TL;DR: This work investigates a collection of distributional representations of words used in supervised settings for recognizing lexical inference relations between word pairs, and shows that they do not actually learn a relation between two words, but an independent property of a single word in the pair.
Abstract: Distributional representations of words have been recently used in supervised settings for recognizing lexical inference relations between word pairs, such as hypernymy and entailment. We investigate a collection of these state-of-the-art methods, and show that they do not actually learn a relation between two words. Instead, they learn an independent property of a single word in the pair: whether that word is a “prototypical hypernym”.

Journal ArticleDOI
TL;DR: It is shown that A-to-I editing and the enzymes mediating this modification are significantly altered, usually elevated, in most cancer types, and increased editing activity is found to be associated with patient survival.

Journal ArticleDOI
TL;DR: By tracking trajectories of fluorescently labelled individuals within such dense swarms, it is found that the bacteria are performing super-diffusion, consistent with Lévy walks.
Abstract: Levy walks have been found in the motion of large animals such as birds and fish in search of sparsely and randomly distributed food. Here, Ariel et al. observe, by tracking long-duration trajectories of fluorescently labelled bacteria, similar walks in bacterial swarms for the first time.

Journal ArticleDOI
TL;DR: Recommendations on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men are focused on.
Abstract: Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

Journal ArticleDOI
TL;DR: The prevalence, course, and comorbidities of war-zone posttraumatic stress disorder (PTSD) across a 25-year interval are determined and underscore the need for mental health services for many decades for veterans with PTSD symptoms.
Abstract: Importance The long-term course of readjustment problems in military personnel has not been evaluated in a nationally representative sample. The National Vietnam Veterans Longitudinal Study (NVVLS) is a congressionally mandated assessment of Vietnam veterans who underwent previous assessment in the National Vietnam Veterans Readjustment Study (NVVRS). Objective To determine the prevalence, course, and comorbidities of war-zone posttraumatic stress disorder (PTSD) across a 25-year interval. Design, Setting, and Participants The NVVLS survey consisted of a self-report health questionnaire (n = 1409), a computer-assisted telephone survey health interview (n = 1279), and a telephone clinical interview (n = 400) in a representative national sample of veterans who served in the Vietnam theater of operations (theater veterans) from July 3, 2012, through May 17, 2013. Of 2348 NVVRS participants, 1920 were alive at the outset of the NVVLS, and 81 died during recruitment; 1450 of the remaining 1839 (78.8%) participated in at least 1 NVVLS study phase. Data analysis was performed from May 18, 2013, through January 9, 2015, with further analyses continued through April 13, 2015. Main Outcomes and Measures Study instruments included the Mississippi Scale for Combat-Related PTSD, PTSD Checklist for DSM-IV supplemented with PTSD Checklist for DSM-5 items (PCL-5+), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and Structured Clinical Interview for DSM-IV , Nonpatient Version. Results Among male theater veterans, we estimated a prevalence (95% CI) of 4.5% (1.7%-7.3%) based on CAPS-5 criteria for a current PTSD diagnosis; 10.8% (6.5%-15.1%) based on CAPS-5 full plus subthreshold PTSD; and 11.2% (8.3%-14.2%) based on PCL-5+ criteria for current war-zone PTSD. Among female veterans, estimates were 6.1% (1.8%-10.3%), 8.7% (3.8%-13.6%), and 6.6% (3.5%-9.6%), respectively. The PCL-5+ prevalence (95% CI) of current non–war-zone PTSD was 4.6% (2.6%-6.6%) in male and 5.1% (2.3%-8.0%) in female theater veterans. Comorbid major depression occurred in 36.7% (95% CI, 6.2%-67.2%) of veterans with current war-zone PTSD. With regard to the course of PTSD, 16.0% of theater veterans reported an increase and 7.6% reported a decrease of greater than 20 points in Mississippi Scale for Combat-Related PTSD symptoms. The prevalence (95% CI) of current PCL-5+–derived PTSD in study respondents was 1.2% (0.0%-3.0%) for male and 3.9% (0.0%-8.1%) for female Vietnam veterans. Conclusions and Relevance Approximately 271 000 Vietnam theater veterans have current full PTSD plus subthreshold war-zone PTSD, one-third of whom have current major depressive disorder, 40 or more years after the war. These findings underscore the need for mental health services for many decades for veterans with PTSD symptoms.

Journal ArticleDOI
TL;DR: This study demonstrates that SGD is a volumetrically important process in the MS, is of a larger magnitude than riverine discharge, and also represents a major source of dissolved inorganic nitrogen, phosphorous, and silica to the MS.
Abstract: The Mediterranean Sea (MS) is a semienclosed basin that is considered one of the most oligotrophic seas in the world. In such an environment, inputs of allochthonous nutrients and micronutrients play an important role in sustaining primary productivity. Atmospheric deposition and riverine runoff have been traditionally considered the main external sources of nutrients to the MS, whereas the role of submarine groundwater discharge (SGD) has been largely ignored. However, given the large Mediterranean shore length relative to its surface area, SGD may be a major conveyor of dissolved compounds to the MS. Here, we used a 228Ra mass balance to demonstrate that the total SGD contributes up to (0.3–4.8)⋅1012 m3⋅y−1 to the MS, which appears to be equal or larger by a factor of 16 to the riverine discharge. SGD is also a major source of dissolved inorganic nutrients to the MS, with median annual fluxes of 190⋅109, 0.7⋅109, and 110⋅109 mol for nitrogen, phosphorous, and silica, respectively, which are comparable to riverine and atmospheric inputs. This corroborates the profound implications that SGD may have for the biogeochemical cycles of the MS. Inputs of other dissolved compounds (e.g., iron, carbon) via SGD could also be significant and should be investigated.

Journal ArticleDOI
TL;DR: The inability to find new associations with survival to ages ≥90 years is because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.
Abstract: Background. The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies. Methods. We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity. Results. In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10-7) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10-8) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10-10). Conclusions. We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

Journal ArticleDOI
TL;DR: It is shown that the genome has highly constrained dynamics, and suggested that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.
Abstract: Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.

Journal ArticleDOI
TL;DR: In this paper, the responses of phytoplankton growth rates to ocean acidification were investigated in a meta-analysis and a marine ecosystem model calibrated with the results indicated that these different responses will result in changes in community structure.
Abstract: The responses of phytoplankton growth rates to ocean acidification were investigated in a meta-analysis. A marine ecosystem model calibrated with the results indicates that these different responses will result in changes in community structure.