Showing papers by "Cornell University published in 2013"
Max Planck Society1, Yale University2, Space Telescope Science Institute3, Harvard University4, University of Colorado Boulder5, Columbia University6, University of Toronto7, Argonne National Laboratory8, Ohio State University9, European Southern Observatory10, Aix-Marseille University11, ETH Zurich12, California Institute of Technology13, New York University14, Louisiana State University15, Australian National University16, Cornell University17, University College London18, Goddard Space Flight Center19, Leibniz Institute for Astrophysics Potsdam20
TL;DR: Astropy as discussed by the authors is a Python package for astronomy-related functionality, including support for domain-specific file formats such as flexible image transport system (FITS) files, Virtual Observatory (VO) tables, common ASCII table formats, unit and physical quantity conversions, physical constants specific to astronomy, celestial coordinate and time transformations, world coordinate system (WCS) support, generalized containers for representing gridded as well as tabular data, and a framework for cosmological transformations and conversions.
Abstract: We present the first public version (v02) of the open-source and community-developed Python package, Astropy This package provides core astronomy-related functionality to the community, including support for domain-specific file formats such as flexible image transport system (FITS) files, Virtual Observatory (VO) tables, and common ASCII table formats, unit and physical quantity conversions, physical constants specific to astronomy, celestial coordinate and time transformations, world coordinate system (WCS) support, generalized containers for representing gridded as well as tabular data, and a framework for cosmological transformations and conversions Significant functionality is under activedevelopment, such as a model fitting framework, VO client and server tools, and aperture and point spread function (PSF) photometry tools The core development team is actively making additions and enhancements to the current code base, and we encourage anyone interested to participate in the development of future Astropy versions
9,720 citations
Ohio State University1, Stanford University2, North Carolina State University3, Pennsylvania State University4, Columbia University5, Northwestern University6, University of Texas at Austin7, University of Notre Dame8, Cornell University9, University of California, Berkeley10, Case Western Reserve University11
TL;DR: The properties and advantages of single-, few-, and many-layer 2D materials in field-effect transistors, spin- and valley-tronics, thermoelectrics, and topological insulators, among many other applications are highlighted.
Abstract: Graphene’s success has shown that it is possible to create stable, single and few-atom-thick layers of van der Waals materials, and also that these materials can exhibit fascinating and technologically useful properties. Here we review the state-of-the-art of 2D materials beyond graphene. Initially, we will outline the different chemical classes of 2D materials and discuss the various strategies to prepare single-layer, few-layer, and multilayer assembly materials in solution, on substrates, and on the wafer scale. Additionally, we present an experimental guide for identifying and characterizing single-layer-thick materials, as well as outlining emerging techniques that yield both local and global information. We describe the differences that occur in the electronic structure between the bulk and the single layer and discuss various methods of tuning their electronic properties by manipulating the surface. Finally, we highlight the properties and advantages of single-, few-, and many-layer 2D materials in...
4,123 citations
TL;DR: This work quantifies the kinetics of charge storage in T-Nb2O5: currents that vary inversely with time, charge-storage capacity that is mostly independent of rate, and redox peaks that exhibit small voltage offsets even at high rates.
Abstract: Pseudocapacitance is commonly associated with surface or near-surface reversible redox reactions, as observed with RuO2·xH2O in an acidic electrolyte. However, we recently demonstrated that a pseudocapacitive mechanism occurs when lithium ions are inserted into mesoporous and nanocrystal films of orthorhombic Nb2O5 (T-Nb2O5; refs 1, 2). Here, we quantify the kinetics of charge storage in T-Nb2O5: currents that vary inversely with time, charge-storage capacity that is mostly independent of rate, and redox peaks that exhibit small voltage offsets even at high rates. We also define the structural characteristics necessary for this process, termed intercalation pseudocapacitance, which are a crystalline network that offers two-dimensional transport pathways and little structural change on intercalation. The principal benefit realized from intercalation pseudocapacitance is that high levels of charge storage are achieved within short periods of time because there are no limitations from solid-state diffusion. Thick electrodes (up to 40 μm thick) prepared with T-Nb2O5 offer the promise of exploiting intercalation pseudocapacitance to obtain high-rate charge-storage devices.
3,725 citations
TL;DR: In graphene heterostructures, the edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials, and enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-tem temperature mobility comparable to the theoretical phonon-scattering limit.
Abstract: Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the 1D edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
2,606 citations
Chad J. Creighton1, Margaret Morgan1, Preethi H. Gunaratne1, Preethi H. Gunaratne2 +288 more•Institutions (27)
TL;DR: Remodelling cellular metabolism constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
Abstract: Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
2,548 citations
TL;DR: The authors showed that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages.
Abstract: Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.
2,504 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston Medical Center3, University of Zurich4, University of Missouri–Kansas City5, University of Oslo6, International Olympic Committee7, University of Toronto8, University of Michigan9, Vanderbilt University Medical Center10, University of Washington11, University of North Carolina at Chapel Hill12, University of British Columbia13, Burke Rehabilitation Hospital14, Cornell University15, University of Ottawa16, Medical College of Wisconsin17, Monash University18, University of New South Wales19, University of Melbourne20, McMaster University21, University of Medicine and Dentistry of New Jersey22, Princeton University23
TL;DR: The 4th International Conference on Concussion in Sport held in Zurich, November 2012 was attended by Paul McCrory, Willem H Meeuwisse, Mark Aubry, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills and Kathryn Schneider.
2,293 citations
University of Wisconsin-Madison1, University of Hawaii2, University of Kiel3, Cornell University4, Max Planck Society5, Pasteur Institute6, Stanford University7, University of Helsinki8, University of Würzburg9, University of California, Berkeley10, University of New South Wales11, Harvard University12, California Institute of Technology13, University of Colorado Boulder14, University of Southern California15, University of North Carolina at Chapel Hill16, University of Connecticut17, Duke University18
TL;DR: Recent technological and intellectual advances that have changed thinking about five questions about how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; and how is homeostasis maintained between animals and their symbionts are highlighted.
Abstract: In the last two decades, the widespread application of genetic and genomic approaches has revealed a bacterial world astonishing in its ubiquity and diversity. This review examines how a growing knowledge of the vast range of animal–bacterial interactions, whether in shared ecosystems or intimate symbioses, is fundamentally altering our understanding of animal biology. Specifically, we highlight recent technological and intellectual advances that have changed our thinking about five questions: how have bacteria facilitated the origin and evolution of animals; how do animals and bacteria affect each other’s genomes; how does normal animal development depend on bacterial partners; how is homeostasis maintained between animals and their symbionts; and how can ecological approaches deepen our understanding of the multiple levels of animal–bacterial interaction. As answers to these fundamental questions emerge, all biologists will be challenged to broaden their appreciation of these interactions and to include investigations of the relationships between and among bacteria and their animal partners as we seek a better understanding of the natural world.
2,103 citations
National Center for Atmospheric Research1, Pacific Northwest National Laboratory2, University of Toronto3, Los Alamos National Laboratory4, Cornell University5, University of Wisconsin-Madison6, Lawrence Livermore National Laboratory7, Lawrence Berkeley National Laboratory8, Oak Ridge National Laboratory9, University of Calgary10
TL;DR: The Community Earth System Model (CESM) as discussed by the authors is a community tool used to investigate a diverse set of Earth system interactions across multiple time and space scales, including biogeochemical cycles, a variety of atmospheric chemistry options, the Greenland Ice Sheet, and an atmosphere that extends to the lower thermosphere.
Abstract: The Community Earth System Model (CESM) is a flexible and extensible community tool used to investigate a diverse set of Earth system interactions across multiple time and space scales. This global coupled model significantly extends its predecessor, the Community Climate System Model, by incorporating new Earth system simulation capabilities. These comprise the ability to simulate biogeochemical cycles, including those of carbon and nitrogen, a variety of atmospheric chemistry options, the Greenland Ice Sheet, and an atmosphere that extends to the lower thermosphere. These and other new model capabilities are enabling investigations into a wide range of pressing scientific questions, providing new foresight into possible future climates and increasing our collective knowledge about the behavior and interactions of the Earth system. Simulations with numerous configurations of the CESM have been provided to phase 5 of the Coupled Model Intercomparison Project (CMIP5) and are being analyzed by the broad com...
2,075 citations
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
2,058 citations
TL;DR: Ibrutinib was associated with a high frequency of durable remissions in patients with relapsed or refractory CLL and small lymphocytic lymphoma, including patients with high-risk genetic lesions.
Abstract: Background The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell–receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells. Methods We conducted a phase 1b–2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma. A total of 85 patients, the majority of whom were considered to have high-risk disease, received ibrutinib orally once daily; 51 received 420 mg, and 34 received 840 mg. Results Toxic effects were predominantly grade 1 or 2 and included transient diarrhea, fatigue, and upper respiratory tract infection; thus, patients could receive extended treatment with minimal hematologic toxic effects. The...
Max Planck Society1, Yale University2, Space Telescope Science Institute3, Harvard University4, University of Colorado Boulder5, Columbia University6, University of Toronto7, Argonne National Laboratory8, Ohio State University9, European Southern Observatory10, Aix-Marseille University11, ETH Zurich12, California Institute of Technology13, New York University14, Louisiana State University15, Australian National University16, Cornell University17, University College London18, Goddard Space Flight Center19, Leibniz Institute for Astrophysics Potsdam20
TL;DR: Astropy as mentioned in this paper provides core astronomy-related functionality to the community, including support for domain-specific file formats such as Flexible Image Transport System (FITS) files, Virtual Observatory (VO) tables, and common ASCII table formats, unit and physical quantity conversions, physical constants specific to astronomy, celestial coordinate and time transformations, world coordinate system (WCS) support, generalized containers for representing gridded as well as tabular data, and a framework for cosmological transformations and conversions.
Abstract: We present the first public version (v0.2) of the open-source and community-developed Python package, Astropy. This package provides core astronomy-related functionality to the community, including support for domain-specific file formats such as Flexible Image Transport System (FITS) files, Virtual Observatory (VO) tables, and common ASCII table formats, unit and physical quantity conversions, physical constants specific to astronomy, celestial coordinate and time transformations, world coordinate system (WCS) support, generalized containers for representing gridded as well as tabular data, and a framework for cosmological transformations and conversions. Significant functionality is under active development, such as a model fitting framework, VO client and server tools, and aperture and point spread function (PSF) photometry tools. The core development team is actively making additions and enhancements to the current code base, and we encourage anyone interested to participate in the development of future Astropy versions.
TL;DR: In this paper, single-crystal islands and polycrystals containing tilt and mirror twin grain boundaries are characterized, and the influence of the grain boundaries on the material properties of molybdenum disulphide is assessed.
Abstract: Despite recent progress in the synthesis and characterization of molybdenum disulphide, little is yet known about its microstructure. Using refined chemical vapour deposition synthesis, high-quality crystals of monolayer molybdenum disulphide have now been grown. Single-crystal islands and polycrystals containing tilt and mirror twin grain boundaries are characterized, and the influence of the grain boundaries on the material properties of molybdenum disulphide is assessed.
TL;DR: It is found that microglia could be specifically depleted from the brain upon diphtheria toxin administration and removal of brain-derived neurotrophic factor (BDNF) frommicroglia largely recapitulated the effects of microglian depletion.
National University of Río Negro1, University of Würzburg2, Rutgers University3, National University of Comahue4, Swedish University of Agricultural Sciences5, Commonwealth Scientific and Industrial Research Organisation6, University of California, Berkeley7, University of Leeds8, Naturalis9, University of Calgary10, Hebrew University of Jerusalem11, Lüneburg University12, ETH Zurich13, National University of Tucumán14, Federal University of Ceará15, Federal University of Bahia16, Plant & Food Research17, Michigan State University18, Agriculture and Agri-Food Canada19, The Nature Conservancy20, University of Göttingen21, University of Queensland22, Cornell University23, University of Reading24, Stockholm University25, University of Vermont26, Lund University27, University of Bern28, University of Koblenz and Landau29, Jagiellonian University30, Universidad de las Américas Puebla31, University of California, Davis32
TL;DR: Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation.
Abstract: The diversity and abundance of wild insect pollinators have declined in many agricultural landscapes. Whether such declines reduce crop yields, or are mitigated by managed pollinators such as honey bees, is unclear. We found universally positive associations of fruit set with flower visitation by wild insects in 41 crop systems worldwide. In contrast, fruit set increased significantly with flower visitation by honey bees in only 14% of the systems surveyed. Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation. Visitation by wild insects and honey bees promoted fruit set independently, so pollination by managed honey bees supplemented, rather than substituted for, pollination by wild insects. Our results suggest that new practices for integrated management of both honey bees and diverse wild insect assemblages will enhance global crop yields.
TL;DR: A test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens is described.
Abstract: As more clinically relevant cancer genes are identified, comprehensive diagnostic approaches are needed to match patients to therapies, raising the challenge of optimization and analytical validation of assays that interrogate millions of bases of cancer genomes altered by multiple mechanisms. Here we describe a test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens. We implemented a practical validation strategy with reference samples of pooled cell lines that model key determinants of accuracy, including mutant allele frequency, indel length and amplitude of copy change. Test sensitivity achieved was 95-99% across alteration types, with high specificity (positive predictive value >99%). We confirmed accuracy using 249 FFPE cancer specimens characterized by established assays. Application of the test to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumors, three times the number of actionable alterations detected by current diagnostic tests.
University of Texas Health Science Center at San Antonio1, Casa Sollievo della Sofferenza2, University of California, San Diego3, Henry Ford Health System4, University of Otago5, Arrowhead Regional Medical Center6, University of Pennsylvania7, Cornell University8, Virginia Mason Medical Center9, Kaiser Permanente10, Inova Fairfax Hospital11, Auckland City Hospital12
TL;DR: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks.
Abstract: Background In phase 2 trials, the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus (HCV) genotype 1, 2, or 3 infection. Methods We conducted two phase 3 studies in previously untreated patients with HCV infection. In a single-group, open-label study, we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1, 4, 5, or 6 (of whom 98% had genotype 1 or 4). In a noninferiority trial, 499 patients with HCV genotype 2 or 3 infection were randomly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks. In the two studies, the primary end point was a sustained virologic response at 12 weeks after the end of therapy. Results In the single-group study, a sustained virologic response was reported in 90% of patients (95% confidence interval, 87 to 93). In the noninferiority trial, a sustained response was reported in 67% of ...
TL;DR: A new class of Pt-Co nanocatalysts composed of ordered Pt(3)Co intermetallic cores with a 2-3 atomic-layer-thick platinum shell with high activity and stability are described, providing a new direction for catalyst performance optimization for next-generation fuel cells.
Abstract: To enhance and optimize nanocatalyst performance and durability for the oxygen reduction reaction in fuel-cell applications, we look beyond Pt-metal disordered alloys and describe a new class of Pt-Co nanocatalysts composed of ordered Pt(3)Co intermetallic cores with a 2-3 atomic-layer-thick platinum shell. These nanocatalysts exhibited over 200% increase in mass activity and over 300% increase in specific activity when compared with the disordered Pt(3)Co alloy nanoparticles as well as Pt/C. So far, this mass activity for the oxygen reduction reaction is the highest among the Pt-Co systems reported in the literature under similar testing conditions. Stability tests showed a minimal loss of activity after 5,000 potential cycles and the ordered core-shell structure was maintained virtually intact, as established by atomic-scale elemental mapping. The high activity and stability are attributed to the Pt-rich shell and the stable intermetallic Pt(3)Co core arrangement. These ordered nanoparticles provide a new direction for catalyst performance optimization for next-generation fuel cells.
University of Bologna1, University of Utah2, University of Jena3, Imperial College London4, University of Barcelona5, Royal Liverpool and Broadgreen University Hospital NHS Trust6, University of Texas MD Anderson Cancer Center7, University of Poitiers8, Norwegian University of Science and Technology9, University of Adelaide10, Catholic University of Korea11, University of Chicago12, University of Toronto13, University of Bordeaux14, Masaryk University15, Heidelberg University16, Leipzig University17, University of Naples Federico II18, Fred Hutchinson Cancer Research Center19, University of Turin20, Wayne State University21, Cornell University22, Uppsala University23
TL;DR: Optimal responders to chronic myeloid leukemia treatment should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
Royal Hallamshire Hospital1, Memorial Sloan Kettering Cancer Center2, University of Texas MD Anderson Cancer Center3, Université de Montréal4, McGill University5, Radboud University Nijmegen6, Mario Negri Institute for Pharmacological Research7, Cornell University8, University of Texas Southwestern Medical Center9
TL;DR: UBC is a frequently occurring malignancy with a significant impact on public health and will remain so because of the high prevalence of smoking and the importance of primary prevention must be stressed and smoking cessation programs need to be encouraged and supported.
National Oceanography Centre, Southampton1, Stanford University2, Bar-Ilan University3, Centre national de la recherche scientifique4, University of Otago5, University of Tasmania6, McGill University7, University of Essex8, Pierre-and-Marie-Curie University9, ETH Zurich10, University of East Anglia11, University of Exeter12, Cornell University13, University of Vigo14, University of Pennsylvania15, University of California, Irvine16, Nagoya University17, Leibniz Institute of Marine Sciences18, Woods Hole Oceanographic Institution19, University of Bergen20, University of Tokyo21, University of Concepción22
TL;DR: In this paper, the authors reveal two broad regimes of phytoplankton nutrient limitation in the modern upper ocean: Nitrogen availability tends to limit productivity throughout much of the surface low-latitude ocean, where the supply of nutrients from the subsurface is relatively slow.
Abstract: Microbial activity is a fundamental component of oceanic nutrient cycles. Photosynthetic microbes, collectively termed phytoplankton, are responsible for the vast majority of primary production in marine waters. The availability of nutrients in the upper ocean frequently limits the activity and abundance of these organisms. Experimental data have revealed two broad regimes of phytoplankton nutrient limitation in the modern upper ocean. Nitrogen availability tends to limit productivity throughout much of the surface low-latitude ocean, where the supply of nutrients from the subsurface is relatively slow. In contrast, iron often limits productivity where subsurface nutrient supply is enhanced, including within the main oceanic upwelling regions of the Southern Ocean and the eastern equatorial Pacific. Phosphorus, vitamins and micronutrients other than iron may also (co-)limit marine phytoplankton. The spatial patterns and importance of co-limitation, however, remain unclear. Variability in the stoichiometries of nutrient supply and biological demand are key determinants of oceanic nutrient limitation. Deciphering the mechanisms that underpin this variability, and the consequences for marine microbes, will be a challenge. But such knowledge will be crucial for accurately predicting the consequences of ongoing anthropogenic perturbations to oceanic nutrient biogeochemistry.
TL;DR: The identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells is reported and it is established that the reprogramming of glutamines metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway.
Abstract: Cancer cells have metabolic dependencies that distinguish them from their normal counterparts. Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes. Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into α-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.
TL;DR: In patients with chronic HBV infection, up to 5 years of treatment with tenofovir DF was safe and effective, and long-term suppression of HBV can lead to regression of fibrosis and cirrhosis.
TL;DR: The presence of Prevotella copri is identified as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients and uniquePrevotella genes that correlate with disease are identified.
Abstract: Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.
University of Texas MD Anderson Cancer Center1, Cornell University2, Rutgers University3, Barts Health NHS Trust4, Jagiellonian University5, University of Wisconsin-Madison6, Stanford University7, University of Virginia8, Hofstra University9, University of Manchester10, University of Ulm11, Ludwig Maximilian University of Munich12, Medical University of Warsaw13, University of Southampton14, Oregon Health & Science University15, Ohio State University16
TL;DR: Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma and is enrolled into two groups: patients who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles.
Abstract: rolled into two groups: those who had previously received at least 2 cycles of bor - tezomib therapy and those who had received less than 2 complete cycles of bortezo - mib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression- free survival, overall survival, and safety. RESULTS The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytope - nia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treat - ment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval (CI), 15.8 to not reached), the estimated median progression- free survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. CONCLUSIONS Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.)
TL;DR: The results of this study should facilitate expanded studies to identify robust heritable plant–microbe interactions at the level of individual polymorphisms by genome wide association, so that plant-microbiome interactions can ultimately be incorporated into plant breeding.
Abstract: The rhizosphere is a critical interface supporting the exchange of resources between plants and their associated soil environment. Rhizosphere microbial diversity is influenced by the physical and chemical properties of the rhizosphere, some of which are determined by the genetics of the host plant. However, within a plant species, the impact of genetic variation on the composition of the microbiota is poorly understood. Here, we characterized the rhizosphere bacterial diversity of 27 modern maize inbreds possessing exceptional genetic diversity grown under field conditions. Randomized and replicated plots of the inbreds were planted in five field environments in three states, each with unique soils and management conditions. Using pyrosequencing of bacterial 16S rRNA genes, we observed substantial variation in bacterial richness, diversity, and relative abundances of taxa between bulk soil and the maize rhizosphere, as well as between fields. The rhizospheres from maize inbreds exhibited both a small but significant proportion of heritable variation in total bacterial diversity across fields, and substantially more heritable variation between replicates of the inbreds within each field. The results of this study should facilitate expanded studies to identify robust heritable plant–microbe interactions at the level of individual polymorphisms by genome wide association, so that plant-microbiome interactions can ultimately be incorporated into plant breeding.
TL;DR: This review will examine how vascular damage disrupts vital homeostatic interactions in brain health, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer's disease.
Duke University1, University of Melbourne2, Université de Montréal3, Royal College of Surgeons in Ireland4, University of Pennsylvania5, University of Washington6, Emory University7, Cincinnati Children's Hospital Medical Center8, Royal Children's Hospital9, Imperial College London10, New York University11, University of California, San Francisco12, University of Liverpool13, Royal Melbourne Hospital14, Columbia University15, Harvard University16, Vanderbilt University17, Cleveland Clinic18, Yeshiva University19, Mayo Clinic20, University of Pittsburgh21, University of Minnesota22, University of Virginia23, Saint Barnabas Medical Center24, University of Michigan25, Kaiser Permanente26, University of Chicago27, University of Texas Health Science Center at Houston28, Johns Hopkins University29, Children's Hospital Oakland Research Institute30, Boston Children's Hospital31, Oregon Health & Science University32, Cornell University33, United States Department of Veterans Affairs34, Washington University in St. Louis35
TL;DR: In this paper, a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms and Lennox-Gastaut syndrome (n = 115) was performed.
Abstract: Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.
Paris Descartes University1, University of Toronto2, Radboud University Nijmegen3, Royal Devon and Exeter Hospital4, Columbia University Medical Center5, University of Bordeaux6, Beatson West of Scotland Cancer Centre7, RWTH Aachen University8, University of Lyon9, Cornell University10, Lund University11, Hannover Medical School12, Alexion Pharmaceuticals13, Mario Negri Institute for Pharmacological Research14, Necker-Enfants Malades Hospital15, Newcastle University16, Istituto Giannina Gaslini17
TL;DR: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome and was also associated with improvement in health-related quality of life.
Abstract: A b s t r ac t Background Atypical hemolytic–uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. Methods We conducted two prospective phase 2 trials in which patients with atypical hemo lytic–uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infu sion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event–free status (no de crease in the platelet count of >25%, no plasma exchange or infusion, and no initia tion of dialysis) (in trial 2). Results A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10 9 per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event–free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculiz umab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in healthrelated quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the exten
TL;DR: In this paper, the authors review recent progress in non-silicon CMOS-compatible platforms for nonlinear optics, with a focus on Si3N4 and Hydex®.
Abstract: Nonlinear photonic chips can generate and process signals all-optically with far superior performance to that possible electronically — particularly with respect to speed. Although silicon-on-insulator has been the leading platform for nonlinear optics, its high two-photon absorption at telecommunication wavelengths poses a fundamental limitation. We review recent progress in non-silicon CMOS-compatible platforms for nonlinear optics, with a focus on Si3N4 and Hydex®. These material systems have opened up many new capabilities such as on-chip optical frequency comb generation and ultrafast optical pulse generation and measurement. We highlight their potential future impact as well as the challenges to achieving practical solutions for many key applications. This article reviews recent progress in the use of silicon nitride and Hydex as non-silicon-based CMOS-compatible platforms for nonlinear optics. New capabilities such as on-chip optical frequency comb generation, ultrafast optical pulse generation and measurement using these materials, and their potential future impact and challenges are covered.