Showing papers by "Max Planck Society published in 2014"

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Abstract: In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html .

Trimmomatic: a flexible trimmer for Illumina sequence data

Abstract: Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: ed.nehcaa-htwr.1oib@ledasu Supplementary information: Supplementary data are available at Bioinformatics online.

Review of Particle Physics

Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.

Planck 2013 results. XVI. Cosmological parameters

Abstract: This paper presents the first cosmological results based on Planck measurements of the cosmic microwave background (CMB) temperature and lensing-potential power spectra. We find that the Planck spectra at high multipoles (l ≳ 40) are extremely well described by the standard spatially-flat six-parameter ΛCDM cosmology with a power-law spectrum of adiabatic scalar perturbations. Within the context of this cosmology, the Planck data determine the cosmological parameters to high precision: the angular size of the sound horizon at recombination, the physical densities of baryons and cold dark matter, and the scalar spectral index are estimated to be θ∗ = (1.04147 ± 0.00062) × 10-2, Ωbh2 = 0.02205 ± 0.00028, Ωch2 = 0.1199 ± 0.0027, and ns = 0.9603 ± 0.0073, respectively(note that in this abstract we quote 68% errors on measured parameters and 95% upper limits on other parameters). For this cosmology, we find a low value of the Hubble constant, H0 = (67.3 ± 1.2) km s-1 Mpc-1, and a high value of the matter density parameter, Ωm = 0.315 ± 0.017. These values are in tension with recent direct measurements of H0 and the magnitude-redshift relation for Type Ia supernovae, but are in excellent agreement with geometrical constraints from baryon acoustic oscillation (BAO) surveys. Including curvature, we find that the Universe is consistent with spatial flatness to percent level precision using Planck CMB data alone. We use high-resolution CMB data together with Planck to provide greater control on extragalactic foreground components in an investigation of extensions to the six-parameter ΛCDM model. We present selected results from a large grid of cosmological models, using a range of additional astrophysical data sets in addition to Planck and high-resolution CMB data. None of these models are favoured over the standard six-parameter ΛCDM cosmology. The deviation of the scalar spectral index from unity isinsensitive to the addition of tensor modes and to changes in the matter content of the Universe. We find an upper limit of r0.002< 0.11 on the tensor-to-scalar ratio. There is no evidence for additional neutrino-like relativistic particles beyond the three families of neutrinos in the standard model. Using BAO and CMB data, we find Neff = 3.30 ± 0.27 for the effective number of relativistic degrees of freedom, and an upper limit of 0.23 eV for the sum of neutrino masses. Our results are in excellent agreement with big bang nucleosynthesis and the standard value of Neff = 3.046. We find no evidence for dynamical dark energy; using BAO and CMB data, the dark energy equation of state parameter is constrained to be w = -1.13-0.10+0.13. We also use the Planck data to set limits on a possible variation of the fine-structure constant, dark matter annihilation and primordial magnetic fields. Despite the success of the six-parameter ΛCDM model in describing the Planck data at high multipoles, we note that this cosmology does not provide a good fit to the temperature power spectrum at low multipoles. The unusual shape of the spectrum in the multipole range 20 ≲ l ≲ 40 was seen previously in the WMAP data and is a real feature of the primordial CMB anisotropies. The poor fit to the spectrum at low multipoles is not of decisive significance, but is an “anomaly” in an otherwise self-consistent analysis of the Planck temperature data.

Biological insights from 108 schizophrenia-associated genetic loci

Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

Ammonia as a case study for the spontaneous ionization of a simple hydrogen-bonded compound

Abstract: Ionization of highly compressed ammonia has previously been predicted by computation. Here, the authors provide experimental evidence for this autoionization process at high pressures, showing the transformation of molecular ammonia into ammonium amide.

Transiting Exoplanet Survey Satellite

Abstract: The Transiting Exoplanet Survey Satellite (TESS) will search for planets transiting bright and nearby stars. TESS has been selected by NASA for launch in 2017 as an Astrophysics Explorer mission. The spacecraft will be placed into a highly elliptical 13.7-day orbit around the Earth. During its 2-year mission, TESS will employ four wide-field optical charge-coupled device cameras to monitor at least 200,000 main-sequence dwarf stars with I C ≈4−13 for temporary drops in brightness caused by planetary transits. Each star will be observed for an interval ranging from 1 month to 1 year, depending mainly on the star’s ecliptic latitude. The longest observing intervals will be for stars near the ecliptic poles, which are the optimal locations for follow-up observations with the James Webb Space Telescope. Brightness measurements of preselected target stars will be recorded every 2 min, and full frame images will be recorded every 30 min. TESS stars will be 10 to 100 times brighter than those surveyed by the pioneering Kepler mission. This will make TESS planets easier to characterize with follow-up observations. TESS is expected to find more than a thousand planets smaller than Neptune, including dozens that are comparable in size to the Earth. Public data releases will occur every 4 months, inviting immediate community-wide efforts to study the new planets. The TESS legacy will be a catalog of the nearest and brightest stars hosting transiting planets, which will endure as highly favorable targets for detailed investigations.

2D Human Pose Estimation: New Benchmark and State of the Art Analysis

Abstract: Human pose estimation has made significant progress during the last years. However current datasets are limited in their coverage of the overall pose estimation challenges. Still these serve as the common sources to evaluate, train and compare different models on. In this paper we introduce a novel benchmark "MPII Human Pose" that makes a significant advance in terms of diversity and difficulty, a contribution that we feel is required for future developments in human body models. This comprehensive dataset was collected using an established taxonomy of over 800 human activities [1]. The collected images cover a wider variety of human activities than previous datasets including various recreational, occupational and householding activities, and capture people from a wider range of viewpoints. We provide a rich set of labels including positions of body joints, full 3D torso and head orientation, occlusion labels for joints and body parts, and activity labels. For each image we provide adjacent video frames to facilitate the use of motion information. Given these rich annotations we perform a detailed analysis of leading human pose estimation approaches and gaining insights for the success and failures of these methods.

The SILVA and "All-species Living Tree Project (LTP)" taxonomic frameworks.

Abstract: SILVA (from Latin silva, forest, http://www.arb-silva.de) is a comprehensive resource for up-to-date quality-controlled databases of aligned ribosomal RNA (rRNA) gene sequences from the Bacteria, Archaea and Eukaryota domains and supplementary online services. SILVA provides a manually curated taxonomy for all three domains of life, based on representative phylogenetic trees for the small- and large-subunit rRNA genes. This article describes the improvements the SILVA taxonomy has undergone in the last 3 years. Specifically we are focusing on the curation process, the various resources used for curation and the comparison of the SILVA taxonomy with Greengenes and RDP-II taxonomies. Our comparisons not only revealed a reasonable overlap between the taxa names, but also points to significant differences in both names and numbers of taxa between the three resources.

Liquid-liquid phase separation in biology.

Abstract: Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary to understand the consequences of liquid-like states for biological functions.

deepTools: a flexible platform for exploring deep-sequencing data

Abstract: We present a Galaxy based web server for processing and visualizing deeply sequenced data. The web server’s core functionality consists of a suite of newly developed tools, called deepTools, that enable users with little bioinformatic background to explore the results of their sequencing experiments in a standardized setting. Users can upload pre-processed files with continuous data in standard formats and generate heatmaps and summary plots in a straightforward, yet highly customizable manner. In addition, we offer several tools for the analysis of files containing aligned reads and enable efficient and reproducible generation of normalized coverage files. As a modular and open-source platform, deepTools can easily be expanded and customized to future demands and developments. The deepTools webserver is freely available at http://deeptools.ie-freiburg.mpg. de and is accompanied by extensive documentation and tutorials aimed at conveying the principles of deep-sequencing data analysis. The web server can be used without registration. deepTools can be installed locally either stand-alone or as part of Galaxy.

Carbon and Other Biogeochemical Cycles

Abstract: For base year 2010, anthropogenic activities created ~210 (190 to 230) TgN of reactive nitrogen Nr from N2. This human-caused creation of reactive nitrogen in 2010 is at least 2 times larger than the rate of natural terrestrial creation of ~58 TgN (50 to 100 TgN yr−1) (Table 6.9, Section 1a). Note that the estimate of natural terrestrial biological fixation (58 TgN yr−1) is lower than former estimates (100 TgN yr−1, Galloway et al., 2004), but the ranges overlap, 50 to 100 TgN yr−1 vs. 90 to 120 TgN yr−1, respectively). Of this created reactive nitrogen, NOx and NH3 emissions from anthropogenic sources are about fourfold greater than natural emissions (Table 6.9, Section 1b). A greater portion of the NH3 emissions is deposited to the continents rather than to the oceans, relative to the deposition of NOy, due to the longer atmospheric residence time of the latter. These deposition estimates are lower limits, as they do not include organic nitrogen species. New model and measurement information (Kanakidou et al., 2012) suggests that incomplete inclusion of emissions and atmospheric chemistry of reduced and oxidized organic nitrogen components in current models may lead to systematic underestimates of total global reactive nitrogen deposition by up to 35% (Table 6.9, Section 1c). Discharge of reactive nitrogen to the coastal oceans is ~45 TgN yr−1 (Table 6.9, Section 1d). Denitrification converts Nr back to atmospheric N2. The current estimate for the production of atmospheric N2 is 110 TgN yr−1 (Bouwman et al., 2013).

First-principles calculations for point defects in solids

Abstract: Point defects and impurities strongly affect the physical properties of materials and have a decisive impact on their performance in applications. First-principles calculations have emerged as a powerful approach that complements experiments and can serve as a predictive tool in the identification and characterization of defects. The theoretical modeling of point defects in crystalline materials by means of electronic-structure calculations, with an emphasis on approaches based on density functional theory (DFT), is reviewed. A general thermodynamic formalism is laid down to investigate the physical properties of point defects independent of the materials class (semiconductors, insulators, and metals), indicating how the relevant thermodynamic quantities, such as formation energy, entropy, and excess volume, can be obtained from electronic structure calculations. Practical aspects such as the supercell approach and efficient strategies to extrapolate to the isolated-defect or dilute limit are discussed. Recent advances in tractable approximations to the exchange-correlation functional ($\mathrm{DFT}+U$, hybrid functionals) and approaches beyond DFT are highlighted. These advances have largely removed the long-standing uncertainty of defect formation energies in semiconductors and insulators due to the failure of standard DFT to reproduce band gaps. Two case studies illustrate how such calculations provide new insight into the physics and role of point defects in real materials.

Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences

Abstract: Publicly available sequence databases of the small subunit ribosomal RNA gene, also known as 16S rRNA in bacteria and archaea, are growing rapidly, and the number of entries currently exceeds 4 million. However, a unified classification and nomenclature framework for all bacteria and archaea does not yet exist. In this Analysis article, we propose rational taxonomic boundaries for high taxa of bacteria and archaea on the basis of 16S rRNA gene sequence identities and suggest a rationale for the circumscription of uncultured taxa that is compatible with the taxonomy of cultured bacteria and archaea. Our analyses show that only nearly complete 16S rRNA sequences give accurate measures of taxonomic diversity. In addition, our analyses suggest that most of the 16S rRNA sequences of the high taxa will be discovered in environmental surveys by the end of the current decade.

Planck 2013 results. I. Overview of products and scientific results

Abstract: The European Space Agency’s Planck satellite, dedicated to studying the early Universe and its subsequent evolution, was launched 14 May 2009 and has been scanning the microwave and submillimetre sky continuously since 12 August 2009. In March 2013, ESA and the Planck Collaboration released the initial cosmology products based on the first 15.5 months of Planck data, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the mission and its performance, the processing, analysis, and characteristics of the data, the scientific results, and the science data products and papers in the release. The science products include maps of the cosmic microwave background (CMB) and diffuse extragalactic foregrounds, a catalogue of compact Galactic and extragalactic sources, and a list of sources detected through the Sunyaev-Zeldovich effect. The likelihood code used to assess cosmological models against the Planck data and a lensing likelihood are described. Scientific results include robust support for the standard six-parameter ΛCDM model of cosmology and improved measurements of its parameters, including a highly significant deviation from scale invariance of the primordial power spectrum. The Planck values for these parameters and others derived from them are significantly different from those previously determined. Several large-scale anomalies in the temperature distribution of the CMB, first detected by WMAP, are confirmed with higher confidence. Planck sets new limits on the number and mass of neutrinos, and has measured gravitational lensing of CMB anisotropies at greater than 25σ. Planck finds no evidence for non-Gaussianity in the CMB. Planck’s results agree well with results from the measurements of baryon acoustic oscillations. Planck finds a lower Hubble constant than found in some more local measures. Some tension is also present between the amplitude of matter fluctuations (σ8) derived from CMB data and that derived from Sunyaev-Zeldovich data. The Planck and WMAP power spectra are offset from each other by an average level of about 2% around the first acoustic peak. Analysis of Planck polarization data is not yet mature, therefore polarization results are not released, although the robust detection of E-mode polarization around CMB hot and cold spots is shown graphically.

The complete genome sequence of a Neanderthal from the Altai Mountains

Abstract: We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Abstract: We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55–4.30; P = 2 × 10−16). We also show six risk loci associated with proximal gene expression or DNA methylation.

EURO-CORDEX : new high-resolution climate change projections for European impact research

Abstract: A new high-resolution regional climate change ensemble has been established for Europe within the World Climate Research Program Coordinated Regional Downscaling Experiment (EURO-CORDEX) initiative. The first set of simulations with a horizontal resolution of 12.5 km was completed for the new emission scenarios RCP4.5 and RCP8.5 with more simulations expected to follow. The aim of this paper is to present this data set to the different communities active in regional climate modelling, impact assessment and adaptation. The EURO-CORDEX ensemble results have been compared to the SRES A1B simulation results achieved within the ENSEMBLES project. The large-scale patterns of changes in mean temperature and precipitation are similar in all three scenarios, but they differ in regional details, which can partly be related to the higher resolution in EURO-CORDEX. The results strengthen those obtained in ENSEMBLES, but need further investigations. The analysis of impact indices shows that for RCP8.5, there is a substantially larger change projected for temperature-based indices than for RCP4.5. The difference is less pronounced for precipitation-based indices. Two effects of the increased resolution can be regarded as an added value of regional climate simulations. Regional climate model simulations provide higher daily precipitation intensities, which are completely missing in the global climate model simulations, and they provide a significantly different climate change of daily precipitation intensities resulting in a smoother shift from weak to moderate and high intensities.

Lattice Light Sheet Microscopy: Imaging Molecules to Embryos at High Spatiotemporal Resolution

Abstract: Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and the complexity of living systems.

Growth of CH3NH3PbI3 cuboids with controlled size for high-efficiency perovskite solar cells.

Abstract: Perovskite solar cells with submicrometre-thick CH(3)NH(3)PbI(3) or CH(3)NH(3)PbI(3-x)Cl(x) active layers show a power conversion efficiency as high as 15%. However, compared to the best-performing device, the average efficiency was as low as 12%, with a large standard deviation (s.d.). Here, we report perovskite solar cells with an average efficiency exceeding 16% and best efficiency of 17%. This was enabled by the growth of CH(3)NH(3)PbI(3) cuboids with a controlled size via a two-step spin-coating procedure. Spin-coating of a solution of CH(3)NH(3)I with different concentrations follows the spin-coating of PbI(2), and the cuboid size of CH(3)NH(3)PbI(3) is found to strongly depend on the concentration of CH(3)NH(3)I. Light-harvesting efficiency and charge-carrier extraction are significantly affected by the cuboid size. Under simulated one-sun illumination, average efficiencies of 16.4% (s.d. ± 0.35), 16.3% (s.d. ± 0.44) and 13.5% (s.d. ± 0.34) are obtained from solutions of CH(3)NH(3)I with concentrations of 0.038 M, 0.050 M and 0.063 M, respectively. By controlling the size of the cuboids of CH(3)NH(3)PbI(3) during their growth, we achieved the best efficiency of 17.01% with a photocurrent density of 21.64 mA cm(-2), open-circuit photovoltage of 1.056 V and fill factor of 0.741.

Attribute-Based Classification for Zero-Shot Visual Object Categorization

Abstract: We study the problem of object recognition for categories for which we have no training examples, a task also called zero--data or zero-shot learning. This situation has hardly been studied in computer vision research, even though it occurs frequently; the world contains tens of thousands of different object classes, and image collections have been formed and suitably annotated for only a few of them. To tackle the problem, we introduce attribute-based classification: Objects are identified based on a high-level description that is phrased in terms of semantic attributes, such as the object's color or shape. Because the identification of each such property transcends the specific learning task at hand, the attribute classifiers can be prelearned independently, for example, from existing image data sets unrelated to the current task. Afterward, new classes can be detected based on their attribute representation, without the need for a new training phase. In this paper, we also introduce a new data set, Animals with Attributes, of over 30,000 images of 50 animal classes, annotated with 85 semantic attributes. Extensive experiments on this and two more data sets show that attribute-based classification indeed is able to categorize images without access to any training images of the target classes.

The man behind the curtain: x-rays drive the uv through nir variability in the 2013 active galactic nucleus outburst in ngc 2617

Abstract: After the All-Sky Automated Survey for SuperNovae discovered a significant brightening of the inner region of NGC 2617, we began a ∼70 day photometric and spectroscopic monitoring campaign from the X-ray through near-infrared (NIR) wavelengths. We report that NGC 2617 went through a dramatic outburst, during which its X-ray flux increased by over an order of magnitude followed by an increase of its optical/ultraviolet (UV) continuum flux by almost an order of magnitude. NGC 2617, classified as a Seyfert 1.8 galaxy in 2003, is now a Seyfert 1 due to the appearance of broad optical emission lines and a continuum blue bump. Such 'changing look active galactic nuclei (AGNs)' are rare and provide us with important insights about AGN physics. Based on the Hβ line width and the radius-luminosity relation, we estimate the mass of central black hole (BH) to be (4 ± 1) × 10{sup 7} M {sub ☉}. When we cross-correlate the light curves, we find that the disk emission lags the X-rays, with the lag becoming longer as we move from the UV (2-3 days) to the NIR (6-9 days). Also, the NIR is more heavily temporally smoothed than the UV. This can largely be explained bymore » a simple model of a thermally emitting thin disk around a BH of the estimated mass that is illuminated by the observed, variable X-ray fluxes.« less

Antibiotics and Bacterial Resistance in the 21st Century

Abstract: Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed.

Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells.

Abstract: Mass spectrometry (MS)-based proteomics typically employs multistep sample-preparation workflows that are subject to sample contamination and loss. We report an in-StageTip method for performing sample processing, from cell lysis through elution of purified peptides, in a single, enclosed volume. This robust and scalable method largely eliminates contamination or loss. Peptides can be eluted in several fractions or in one step for single-run proteome analysis. In one day, we obtained the largest proteome coverage to date for budding and fission yeast, and found that protein copy numbers in these cells were highly correlated (R(2) = 0.78). Applying the in-StageTip method to quadruplicate measurements of a human cell line, we obtained copy-number estimates for 9,667 human proteins and observed excellent quantitative reproducibility between replicates (R(2) = 0.97). The in-StageTip method is straightforward and generally applicable in biological or clinical applications.

Planck 2013 results. XXII. Constraints on inflation

Abstract: We present the implications for cosmic inflation of the Planck measurements of the cosmic microwave background (CMB) anisotropies in both temperature and polarization based on the full Planck survey, which includes more than twice the integration time of the nominal survey used for the 2013 release papers. The Planck full mission temperature data and a first release of polarization data on large angular scales measure the spectral index of curvature perturbations to be ns = 0.968 ± 0.006 and tightly constrain its scale dependence to dns/ dlnk = −0.003 ± 0.007 when combined with the Planck lensing likelihood. When the Planck high-l polarization data are included, the results are consistent and uncertainties are further reduced. The upper bound on the tensor-to-scalar ratio is r0.002< 0.11 (95% CL). This upper limit is consistent with the B-mode polarization constraint r< 0.12 (95% CL) obtained from a joint analysis of the BICEP2/Keck Array and Planck data. These results imply that V(φ) ∝ φ2 and natural inflation are now disfavoured compared to models predicting a smaller tensor-to-scalar ratio, such as R2 inflation. We search for several physically motivated deviations from a simple power-law spectrum of curvature perturbations, including those motivated by a reconstruction of the inflaton potential not relying on the slow-roll approximation. We find that such models are not preferred, either according to a Bayesian model comparison or according to a frequentist simulation-based analysis. Three independent methods reconstructing the primordial power spectrum consistently recover a featureless and smooth over the range of scales 0.008 Mpc-1 ≲ k ≲ 0.1 Mpc-1. At large scales, each method finds deviations from a power law, connected to a deficit at multipoles l ≈ 20−40 in the temperature power spectrum, but at an uncompelling statistical significance owing to the large cosmic variance present at these multipoles. By combining power spectrum and non-Gaussianity bounds, we constrain models with generalized Lagrangians, including Galileon models and axion monodromy models. The Planck data are consistent with adiabatic primordial perturbations, and the estimated values for the parameters of the base Λ cold dark matter (ΛCDM) model are not significantly altered when more general initial conditions are admitted. In correlated mixed adiabatic and isocurvature models, the 95% CL upper bound for the non-adiabatic contribution to the observed CMB temperature variance is | αnon - adi | < 1.9%, 4.0%, and 2.9% for CDM, neutrino density, and neutrino velocity isocurvature modes, respectively. We have tested inflationary models producing an anisotropic modulation of the primordial curvature power spectrum findingthat the dipolar modulation in the CMB temperature field induced by a CDM isocurvature perturbation is not preferred at a statistically significant level. We also establish tight constraints on a possible quadrupolar modulation of the curvature perturbation. These results are consistent with the Planck 2013 analysis based on the nominal mission data and further constrain slow-roll single-field inflationary models, as expected from the increased precision of Planck data using the full set of observations.

The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition

Abstract: Given the trillions of microbes that inhabit the mammalian intestines, the host immune system must constantly maintain a balance between tolerance to commensals and immunity against pathogens to avoid unnecessary immune responses against otherwise harmless bacteria. Misregulated responses can lead to inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. The mechanisms by which the immune system maintains this critical balance remain largely undefined. Here, we demonstrate that the short-chain fatty acid n-butyrate, which is secreted in high amounts by commensal bacteria, can modulate the function of intestinal macrophages, the most abundant immune cell type in the lamina propria. Treatment of macrophages with n-butyrate led to the down-regulation of lipopolysaccharide-induced proinflammatory mediators, including nitric oxide, IL-6, and IL-12, but did not affect levels of TNF-α or MCP-1. These effects were independent of toll-like receptor signaling and activation of G-protein-coupled receptors, two pathways that could be affected by short-chain fatty acids. In this study, we provide several lines of evidence that suggest that these effects are due to the inhibition of histone deacetylases by n-butyrate. These findings elucidate a pathway in which the host may maintain tolerance to intestinal microbiota by rendering lamina propria macrophages hyporesponsive to commensal bacteria through the down-regulation of proinflammatory effectors.

Trigonometric parallaxes of high mass star forming regions: the structure and kinematics of the milky way

Abstract: Over 100 trigonometric parallaxes and proper motions for masers associated with young, high- mass stars have been measured with the Bar and Spiral Structure Legacy Survey, a Very Long Baseline Array key science project, the European VLBI Network, and the Japanese VLBI Exploration of Radio Astrometry project. These measurements provide strong evidence for the existence of spiral arms in the MilkyWay, accurately locating many arm segments and yielding spiral pitch angles ranging from about 7 degrees to 20 degrees. The widths of spiral arms increase with distance from the Galactic center. Fitting axially symmetric models of the MilkyWay with the three- dimensional position and velocity information and conservative priors for the solar and average source peculiar motions, we estimate the distance to the Galactic center, R-0, to be 8.34 +/- 0.16 kpc, a circular rotation speed at the Sun, Theta(0), to be 240 +/- 8 km s(-1), and a rotation curve that is nearly flat ( i. e., a slope of -0.2 +/- 0.4 km s(-1) kpc(-1)) between Galactocentric radii of approximate to 5 and 16 kpc. Assuming a " universal" spiral galaxy form for the rotation curve, we estimate the thin disk scale length to be 2.44 +/- 0.16 kpc. With this large data set, the parameters R-0 and Theta(0) are no longer highly correlated and are relatively insensitive to different forms of the rotation curve. If one adopts a theoretically motivated prior that high- mass star forming regions are in nearly circular Galactic orbits, we estimate a global solar motion component in the direction of Galactic rotation, V-circle dot = 14.6 +/- 5.0 km s(-1). While Theta(0) and V-circle dot are significantly correlated, the sum of these parameters is well constrained, Theta(0) + V circle dot = 255.2 +/- 5.1 km s(-1), as is the angular speed of the Sun in its orbit about the Galactic center, ( Theta(0) + V-circle dot)/R-0 = 30.57 +/- 0.43 km s(-1) kpc(-1). These parameters improve the accuracy of estimates of the accelerations of the Sun and the Hulse-Taylor binary pulsar in their Galactic orbits, significantly reducing the uncertainty in tests of gravitational radiation predicted by general relativity.