Showing papers by "Cornell University published in 2011"

Integrated genomic analyses of ovarian carcinoma

Abstract: A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

MATPOWER: Steady-State Operations, Planning, and Analysis Tools for Power Systems Research and Education

Abstract: MATPOWER is an open-source Matlab-based power system simulation package that provides a high-level set of power flow, optimal power flow (OPF), and other tools targeted toward researchers, educators, and students. The OPF architecture is designed to be extensible, making it easy to add user-defined variables, costs, and constraints to the standard OPF problem. This paper presents the details of the network modeling and problem formulations used by MATPOWER, including its extensible OPF architecture. This structure is used internally to implement several extensions to the standard OPF problem, including piece-wise linear cost functions, dispatchable loads, generator capability curves, and branch angle difference limits. Simulation results are presented for a number of test cases comparing the performance of several available OPF solvers and demonstrating MATPOWER's ability to solve large-scale AC and DC OPF problems.

A Robust, Simple Genotyping-by-Sequencing (GBS) Approach for High Diversity Species

Abstract: Advances in next generation technologies have driven the costs of DNA sequencing down to the point that genotyping-by-sequencing (GBS) is now feasible for high diversity, large genome species. Here, we report a procedure for constructing GBS libraries based on reducing genome complexity with restriction enzymes (REs). This approach is simple, quick, extremely specific, highly reproducible, and may reach important regions of the genome that are inaccessible to sequence capture approaches. By using methylation-sensitive REs, repetitive regions of genomes can be avoided and lower copy regions targeted with two to three fold higher efficiency. This tremendously simplifies computationally challenging alignment problems in species with high levels of genetic diversity. The GBS procedure is demonstrated with maize (IBM) and barley (Oregon Wolfe Barley) recombinant inbred populations where roughly 200,000 and 25,000 sequence tags were mapped, respectively. An advantage in species like barley that lack a complete genome sequence is that a reference map need only be developed around the restriction sites, and this can be done in the process of sample genotyping. In such cases, the consensus of the read clusters across the sequence tagged sites becomes the reference. Alternatively, for kinship analyses in the absence of a reference genome, the sequence tags can simply be treated as dominant markers. Future application of GBS to breeding, conservation, and global species and population surveys may allow plant breeders to conduct genomic selection on a novel germplasm or species without first having to develop any prior molecular tools, or conservation biologists to determine population structure without prior knowledge of the genome or diversity in the species.

Persistence of soil organic matter as an ecosystem property

Abstract: Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily—and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming.

Biochar effects on soil biota – A review

Abstract: Soil amendment with biochar is evaluated globally as a means to improve soil fertility and to mitigate climate change. However, the effects of biochar on soil biota have received much less attention than its effects on soil chemical properties. A review of the literature reveals a significant number of early studies on biochar-type materials as soil amendments either for managing pathogens, as inoculant carriers or for manipulative experiments to sorb signaling compounds or toxins. However, no studies exist in the soil biologyliterature that recognize the observed largevariations ofbiochar physico-chemical properties. This shortcoming has hampered insight into mechanisms by which biochar influences soil microorganisms, fauna and plant roots. Additional factors limiting meaningful interpretation of many datasets are the clearly demonstrated sorption properties that interfere with standard extraction procedures for soil microbial biomass or enzyme assays, and the confounding effects of varying amounts of minerals. In most studies, microbial biomass has been found to increase as a result of biochar additions, with significant changes in microbial community composition and enzyme activities that may explain biogeochemical effects of biochar on element cycles, plant pathogens, and crop growth. Yet, very little is known about the mechanisms through which biochar affects microbial abundance and community composition. The effects of biochar on soil fauna are even less understood than its effects on microorganisms, apart from several notable studies on earthworms. It is clear, however, that sorption phenomena, pH and physical properties of biochars such as pore structure, surface area and mineral matter play important roles in determining how different biochars affect soil biota. Observations on microbial dynamics lead to the conclusion of a possible improved resource use due to co-location of various resources in and around biochars. Sorption and therebyinactivation of growth-inhibiting substances likelyplaysa rolefor increased abundance of soil biota. No evidence exists so far for direct negative effects of biochars on plant roots. Occasionally observed decreases in abundance of mycorrhizal fungi are likely caused by concomitant increases in nutrient availability,reducing theneedfor symbionts.Inthe shortterm,therelease ofavarietyoforganic molecules from fresh biochar may in some cases be responsible for increases or decreases in abundance and activity of soil biota. A road map for future biochar research must include a systematic appreciation of different biochar-types and basic manipulative experiments that unambiguously identify the interactions between biochar and soil biota.

The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know

Abstract: This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range...

Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection

Abstract: A B S T R AC T Background In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients. Methods In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon–ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon–ribavirin for 8 weeks and placebo with peginterferon–ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon–ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon–ribavirin for 12 weeks, followed by 36 weeks of peginterferon–ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response). Results Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon–ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group. Conclusions Telaprevir with peginterferon–ribavirin, as compared with peginterferon–ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.)

Colloquium: Nonequilibrium dynamics of closed interacting quantum systems

Abstract: This Colloquium gives an overview of recent theoretical and experimental progress in the area of nonequilibrium dynamics of isolated quantum systems There is particularly a focus on quantum quenches: the temporal evolution following a sudden or slow change of the coupling constants of the system Hamiltonian Several aspects of the slow dynamics in driven systems are discussed and the universality of such dynamics in gapless systems with specific focus on dynamics near continuous quantum phase transitions is emphasized Recent progress on understanding thermalization in closed systems through the eigenstate thermalization hypothesis is also reviewed and relaxation in integrable systems is discussed Finally key experiments probing quantum dynamics in cold atom systems are overviewed and put into the context of our current theoretical understanding

Succession of microbial consortia in the developing infant gut microbiome

Abstract: The colonization process of the infant gut microbiome has been called chaotic, but this view could reflect insufficient documentation of the factors affecting the microbiome. We performed a 2.5-y case study of the assembly of the human infant gut microbiome, to relate life events to microbiome composition and function. Sixty fecal samples were collected from a healthy infant along with a diary of diet and health status. Analysis of >300,000 16S rRNA genes indicated that the phylogenetic diversity of the microbiome increased gradually over time and that changes in community composition conformed to a smooth temporal gradient. In contrast, major taxonomic groups showed abrupt shifts in abundance corresponding to changes in diet or health. Community assembly was nonrandom: we observed discrete steps of bacterial succession punctuated by life events. Furthermore, analysis of ≈500,000 DNA metagenomic reads from 12 fecal samples revealed that the earliest microbiome was enriched in genes facilitating lactate utilization, and that functional genes involved in plant polysaccharide metabolism were present before the introduction of solid food, priming the infant gut for an adult diet. However, ingestion of table foods caused a sustained increase in the abundance of Bacteroidetes, elevated fecal short chain fatty acid levels, enrichment of genes associated with carbohydrate utilization, vitamin biosynthesis, and xenobiotic degradation, and a more stable community composition, all of which are characteristic of the adult microbiome. This study revealed that seemingly chaotic shifts in the microbiome are associated with life events; however, additional experiments ought to be conducted to assess how different infants respond to similar life events.

The immunology of stroke: from mechanisms to translation

Abstract: Immunity and inflammation are key elements of the pathobiology of stroke, a devastating illness second only to cardiac ischemia as a cause of death worldwide. The immune system participates in the brain damage produced by ischemia, and the damaged brain, in turn, exerts an immunosuppressive effect that promotes fatal infections that threaten the survival of people after stroke. Inflammatory signaling is involved in all stages of the ischemic cascade, from the early damaging events triggered by arterial occlusion to the late regenerative processes underlying post-ischemic tissue repair. Recent developments have revealed that stroke engages both innate and adaptive immunity. But adaptive immunity triggered by newly exposed brain antigens does not have an impact on the acute phase of the damage. Nevertheless, modulation of adaptive immunity exerts a remarkable protective effect on the ischemic brain and offers the prospect of new stroke therapies. As immunomodulation is not devoid of deleterious side effects, a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.

The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI): a completed reference database of lung nodules on CT scans.

Abstract: Purpose: The development of computer-aided diagnostic (CAD) methods for lung nodule detection, classification, and quantitative assessment can be facilitated through a well-characterized repository of computed tomography (CT) scans. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI) completed such a database, establishing a publicly available reference for the medical imaging research community. Initiated by the National Cancer Institute (NCI), further advanced by the Foundation for the National Institutes of Health (FNIH), and accompanied by the Food and Drug Administration (FDA) through active participation, this public-private partnership demonstrates the success of a consortium founded on a consensus-based process. Methods: Seven academic centers and eight medical imaging companies collaborated to identify, address, and resolve challenging organizational, technical, and clinical issues to provide a solid foundation for a robust database. The LIDC/IDRI Database contains 1018 cases, each of which includes images from a clinical thoracic CT scan and an associated XML file that records the results of a two-phase image annotation process performed by four experienced thoracic radiologists. In the initial blinded-read phase, each radiologist independently reviewed each CT scan and marked lesions belonging to one of three categories (" nodule�3 mm," " nodule<3 mm," and "non- nodule�3 mm "). In the subsequent unblinded-read phase, each radiologist independently reviewed their own marks along with the anonymized marks of the three other radiologists to render a final opinion. The goal of this process was to identify as completely as possible all lung nodules in each CT scan without requiring forced consensus. Results: The Database contains 7371 lesions marked "nodule" by at least one radiologist. 2669 of these lesions were marked " nodul�3 mm " by at least one radiologist, of which 928 (34.7) received such marks from all four radiologists. These 2669 lesions include nodule outlines and subjective nodule characteristic ratings. Conclusions: The LIDC/IDRI Database is expected to provide an essential medical imaging research resource to spur CAD development, validation, and dissemination in clinical practice. © 2011 U.S. Government.

Differences Between Tight and Loose Cultures: A 33-Nation Study

Abstract: With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated multilevel system that comprises distal ecological and historical threats (e.g., high population density, resource scarcity, a history of territorial conflict, and disease and environmental threats), broad versus narrow socialization in societal institutions (e.g., autocracy, media regulations), the strength of everyday recurring situations, and micro-level psychological affordances (e.g., prevention self-guides, high regulatory strength, need for structure). This research advances knowledge that can foster cross-cultural understanding in a world of increasing global interdependence and has implications for modeling cultural change.

Grains and grain boundaries in single-layer graphene atomic patchwork quilts

Abstract: The properties of polycrystalline materials are often dominated by the size of their grains and by the atomic structure of their grain boundaries. These effects should be especially pronounced in two-dimensional materials, where even a line defect can divide and disrupt a crystal. These issues take on practical significance in graphene, which is a hexagonal, two-dimensional crystal of carbon atoms. Single-atom-thick graphene sheets can now be produced by chemical vapour deposition on scales of up to metres, making their polycrystallinity almost unavoidable. Theoretically, graphene grain boundaries are predicted to have distinct electronic, magnetic, chemical and mechanical properties that strongly depend on their atomic arrangement. Yet because of the five-order-of-magnitude size difference between grains and the atoms at grain boundaries, few experiments have fully explored the graphene grain structure. Here we use a combination of old and new transmission electron microscopy techniques to bridge these length scales. Using atomic-resolution imaging, we determine the location and identity of every atom at a grain boundary and find that different grains stitch together predominantly through pentagon-heptagon pairs. Rather than individually imaging the several billion atoms in each grain, we use diffraction-filtered imaging to rapidly map the location, orientation and shape of several hundred grains and boundaries, where only a handful have been previously reported. The resulting images reveal an unexpectedly small and intricate patchwork of grains connected by tilt boundaries. By correlating grain imaging with scanning probe and transport measurements, we show that these grain boundaries severely weaken the mechanical strength of graphene membranes but do not as drastically alter their electrical properties. These techniques open a new window for studies on the structure, properties and control of grains and grain boundaries in graphene and other two-dimensional materials.

Porous Hollow Carbon@Sulfur Composites for High‐Power Lithium–Sulfur Batteries

Abstract: C @ S nanocomposites based on mesoporous hollow carbon capsules were prepared by a template approach. Their excellent properties as a cathode material in a lithium secondary battery of S-sequestration of elemental sulfur in the carbon capsules, a restricted polysulfide shuttling and an improved electron transport on sulfur are attributed.

Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease

Abstract: Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.

Spin-Torque Ferromagnetic Resonance Induced by the Spin Hall Effect

Abstract: We demonstrate that the spin Hall effect in a thin film with strong spin-orbit scattering can excite magnetic precession in an adjacent ferromagnetic film. The flow of alternating current through a Pt/NiFe bilayer generates an oscillating transverse spin current in the Pt, and the resultant transfer of spin angular momentum to the NiFe induces ferromagnetic resonance dynamics. The Oersted field from the current also generates a ferromagnetic resonance signal but with a different symmetry. The ratio of these two signals allows a quantitative determination of the spin current and the spin Hall angle.

Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study

Abstract: Purpose Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. Patients and Methods Patients age 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P .001).

Heavy quarkonium: progress, puzzles, and opportunities

Abstract: A golden age for heavy-quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the B-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations at BESIII, the LHC, RHIC, FAIR, the Super Flavor and/or Tau-Charm factories, JLab, the ILC, and beyond. The list of newly found conventional states expanded to include h(c)(1P), chi(c2)(2P), B-c(+), and eta(b)(1S). In addition, the unexpected and still-fascinating X(3872) has been joined by more than a dozen other charmonium- and bottomonium-like "XYZ" states that appear to lie outside the quark model. Many of these still need experimental confirmation. The plethora of new states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c (c) over bar, b (b) over bar, and b (c) over bar bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. Lattice QCD has grown from a tool with computational possibilities to an industrial-strength effort now dependent more on insight and innovation than pure computational power. New effective field theories for the description of quarkonium in different regimes have been developed and brought to a high degree of sophistication, thus enabling precise and solid theoretical predictions. Many expected decays and transitions have either been measured with precision or for the first time, but the confusing patterns of decays, both above and below open-flavor thresholds, endure and have deepened. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.

Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

Abstract: Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects.

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4

Abstract: We conducted a combined genome-wide association study (GWAS) of 7,481 individuals with bipolar disorder (cases) and 9,250 controls as part of the Psychiatric GWAS Consortium. Our replication study tested 34 SNPs in 4,496 independent cases with bipolar disorder and 42,422 independent controls and found that 18 of 34 SNPs had P < 0.05, with 31 of 34 SNPs having signals with the same direction of effect (P = 3.8 × 10−7). An analysis of all 11,974 bipolar disorder cases and 51,792 controls confirmed genome-wide significant evidence of association for CACNA1C and identified a new intronic variant in ODZ4. We identified a pathway comprised of subunits of calcium channels enriched in bipolar disorder association intervals. Finally, a combined GWAS analysis of schizophrenia and bipolar disorder yielded strong association evidence for SNPs in CACNA1C and in the region of NEK4-ITIH1-ITIH3-ITIH4. Our replication results imply that increasing sample sizes in bipolar disorder will confirm many additional loci.

Building Rome in a day

Abstract: We present a system that can reconstruct 3D geometry from large, unorganized collections of photographs such as those found by searching for a given city (e.g., Rome) on Internet photo-sharing sites. Our system is built on a set of new, distributed computer vision algorithms for image matching and 3D reconstruction, designed to maximize parallelism at each stage of the pipeline and to scale gracefully with both the size of the problem and the amount of available computation. Our experimental results demonstrate that it is now possible to reconstruct city-scale image collections with more than a hundred thousand images in less than a day.

Unravelling the effects of the environment and host genotype on the gut microbiome

Abstract: To what extent do host genetics control the composition of the gut microbiome? Studies comparing the gut microbiota in human twins and across inbred mouse lines have yielded inconsistent answers to this question. However, candidate gene approaches, in which one gene is deleted or added to a model host organism, show that a single host gene can have a tremendous effect on the diversity and population structure of the gut microbiota. Now, quantitative genetics is emerging as a highly promising approach that can be used to better understand the overall architecture of host genetic influence on the microbiota, and to discover additional host genes controlling microbial diversity in the gut. In this Review, we describe how host genetics and the environment shape the microbiota, and how these three factors may interact in the context of chronic disease.

Methane and the greenhouse-gas footprint of natural gas from shale formations

Abstract: We evaluate the greenhouse gas footprint of natural gas obtained by high- volume hydraulic fracturing from shale formations, focusing on methane emissions. Natural gas is composed largely of methane, and 3.6% to 7.9% of the methane from shale-gas production escapes to the atmosphere in venting and leaks over the life- time of a well. These methane emissions are at least 30% more than and perhaps more than twice as great as those from conventional gas. The higher emissions from shale gas occur at the time wells are hydraulically fractured—as methane escapes from flow-back return fluids—and during drill out following the fracturing. Methane is a powerful greenhouse gas, with a global warming potential that is far greater than that of carbon dioxide, particularly over the time horizon of the first few decades following emission. Methane contributes substantially to the greenhouse gas footprint of shale gas on shorter time scales, dominating it on a 20-year time horizon. The footprint for shale gas is greater than that for conventional gas or oil when viewed on any time horizon, but particularly so over 20 years. Compared to coal, the footprint of shale gas is at least 20% greater and perhaps more than twice as great on the 20-year horizon and is comparable when compared over 100 years.

Oxidation resistance of graphene-coated Cu and Cu/Ni alloy

Abstract: The ability to protect refined metals from reactive environments is vital to many industrial and academic applications. Current solutions, however, typically introduce several negative effects, including increased thickness and changes in the metal physical properties. In this paper, we demonstrate for the first time the ability of graphene films grown by chemical vapor deposition to protect the surface of the metallic growth substrates of Cu and Cu/Ni alloy from air oxidation. In particular, graphene prevents the formation of any oxide on the protected metal surfaces, thus allowing pure metal surfaces only one atom away from reactive environments. SEM, Raman spectroscopy, and XPS studies show that the metal surface is well protected from oxidation even after heating at 200 °C in air for up to 4 h. Our work further shows that graphene provides effective resistance against hydrogen peroxide. This protection method offers significant advantages and can be used on any metal that catalyzes graphene growth.

The genomic complexity of primary human prostate cancer

Abstract: Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, ‘copy-neutral’) rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2–ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms. Prostate cancer is a common cause of male cancer-related deaths. Complete genome sequencing of seven 'high-risk' primary prostate cancers and their paired normal counterparts now reveals previously unknown balanced rearrangements, at which multiple intra- and inter-chromosomal loci exchange their breakpoint arms without any loss of genetic material. The anomalies seem to arise through errors in transcription or abnormal chromatin structure, and genes affected include the known prostate tumour suppressor PTEN as well as MAG12, a gene not previously implicated in prostate tumorigenesis. Prostate cancer is a common cause of male cancer-related deaths. Complete sequencing of prostate cancer genomes now reveals previously unknown balanced rearrangements. Single-nucleotide resolution afforded by sequencing indicates that complex rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.

Genome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa

Abstract: Asian rice, Oryza sativa is a cultivated, inbreeding species that feeds over half of the world ’ s population. Understanding the genetic basis of diverse physiological, developmental, and morphological traits provides the basis for improving yield, quality and sustainability of rice. Here we show the results of a genome-wide association study based on genotyping 44,100 SNP variants across 413 diverse accessions of O. sativa collected from 82 countries that were systematically phenotyped for 34 traits. Using cross-population-based mapping strategies, we identifi ed dozens of common variants infl uencing numerous complex traits. Signifi cant heterogeneity was observed in the genetic architecture associated with subpopulation structure and response to environment. This work establishes an open-source translational research platform for genome-wide association studies in rice that directly links molecular variation in genes and metabolic pathways with the germplasm resources needed to accelerate varietal development and crop improvement.

Differences in the mechanics of information diffusion across topics: idioms, political hashtags, and complex contagion on twitter

Abstract: There is a widespread intuitive sense that different kinds of information spread differently on-line, but it has been difficult to evaluate this question quantitatively since it requires a setting where many different kinds of information spread in a shared environment. Here we study this issue on Twitter, analyzing the ways in which tokens known as hashtags spread on a network defined by the interactions among Twitter users. We find significant variation in the ways that widely-used hashtags on different topics spread.Our results show that this variation is not attributable simply to differences in "stickiness," the probability of adoption based on one or more exposures, but also to a quantity that could be viewed as a kind of "persistence" - the relative extent to which repeated exposures to a hashtag continue to have significant marginal effects. We find that hashtags on politically controversial topics are particularly persistent, with repeated exposures continuing to have unusually large marginal effects on adoption; this provides, to our knowledge, the first large-scale validation of the "complex contagion" principle from sociology, which posits that repeated exposures to an idea are particularly crucial when the idea is in some way controversial or contentious. Among other findings, we discover that hashtags representing the natural analogues of Twitter idioms and neologisms are particularly non-persistent, with the effect of multiple exposures decaying rapidly relative to the first exposure.We also study the subgraph structure of the initial adopters for different widely-adopted hashtags, again finding structural differences across topics. We develop simulation-based and generative models to analyze how the adoption dynamics interact with the network structure of the early adopters on which a hashtag spreads.