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Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma wakefield

Nature - Tue, 08/25/2015 - 23:00

Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma wakefield

Nature 524, 7566 (2015). doi:10.1038/nature14890

Authors: S. Corde, E. Adli, J. M. Allen, W. An, C. I. Clarke, C. E. Clayton, J. P. Delahaye, J. Frederico, S. Gessner, S. Z. Green, M. J. Hogan, C. Joshi, N. Lipkowitz, M. Litos, W. Lu, K. A. Marsh, W. B. Mori, M. Schmeltz, N. Vafaei-Najafabadi, D. Walz, V. Yakimenko & G. Yocky

Electrical breakdown sets a limit on the kinetic energy that particles in a conventional radio-frequency accelerator can reach. New accelerator concepts must be developed to achieve higher energies and to make future particle colliders more compact and affordable. The plasma wakefield accelerator (PWFA) embodies one such concept, in which the electric field of a plasma wake excited by a bunch of charged particles (such as electrons) is used to accelerate a trailing bunch of particles. To apply plasma acceleration to electron–positron colliders, it is imperative that both the electrons and their antimatter counterpart, the positrons, are efficiently accelerated at high fields using plasmas. Although substantial progress has recently been reported on high-field, high-efficiency acceleration of electrons in a PWFA powered by an electron bunch, such an electron-driven wake is unsuitable for the acceleration and focusing of a positron bunch. Here we demonstrate a new regime of PWFAs where particles in the front of a single positron bunch transfer their energy to a substantial number of those in the rear of the same bunch by exciting a wakefield in the plasma. In the process, the accelerating field is altered—‘self-loaded’—so that about a billion positrons gain five gigaelectronvolts of energy with a narrow energy spread over a distance of just 1.3 metres. They extract about 30 per cent of the wake’s energy and form a spectrally distinct bunch with a root-mean-square energy spread as low as 1.8 per cent. This ability to transfer energy efficiently from the front to the rear within a single positron bunch makes the PWFA scheme very attractive as an energy booster to an electron–positron collider.

Categories: Journal Articles

Atomic inner-shell laser at 1.5-ångström wavelength pumped by an X-ray free-electron laser

Nature - Tue, 08/25/2015 - 23:00

Atomic inner-shell laser at 1.5-ångström wavelength pumped by an X-ray free-electron laser

Nature 524, 7566 (2015). doi:10.1038/nature14894

Authors: Hitoki Yoneda, Yuichi Inubushi, Kazunori Nagamine, Yurina Michine, Haruhiko Ohashi, Hirokatsu Yumoto, Kazuto Yamauchi, Hidekazu Mimura, Hikaru Kitamura, Tetsuo Katayama, Tetsuya Ishikawa & Makina Yabashi

Since the invention of the first lasers in the visible-light region, research has aimed to produce short-wavelength lasers that generate coherent X-rays; the shorter the wavelength, the better the imaging resolution of the laser and the shorter the pulse duration, leading to better temporal resolution in probe measurements. Recently, free-electron lasers based on self-amplified spontaneous emission have made it possible to generate a hard-X-ray laser (that is, the photon energy is of the order of ten kiloelectronvolts) in an ångström-wavelength regime, enabling advances in fields from ultrafast X-ray spectrosopy to X-ray quantum optics. An atomic laser based on neon atoms and pumped by a soft-X-ray (that is, a photon energy of less than one kiloelectronvolt) free-electron laser has been achieved at a wavelength of 14 nanometres. Here, we use a copper target and report a hard-X-ray inner-shell atomic laser operating at a wavelength of 1.5 ångströms. X-ray free-electron laser pulses with an intensity of about 1019 watts per square centimetre tuned to the copper K-absorption edge produced sufficient population inversion to generate strong amplified spontaneous emission on the copper Kα lines. Furthermore, we operated the X-ray free-electron laser source in a two-colour mode, with one colour tuned for pumping and the other for the seed (starting) light for the laser.

Categories: Journal Articles

Substitutional doping in nanocrystal superlattices

Nature - Tue, 08/25/2015 - 23:00

Substitutional doping in nanocrystal superlattices

Nature 524, 7566 (2015). doi:10.1038/nature14872

Authors: Matteo Cargnello, Aaron C. Johnston-Peck, Benjamin T. Diroll, Eric Wong, Bianca Datta, Divij Damodhar, Vicky V. T. Doan-Nguyen, Andrew A. Herzing, Cherie R. Kagan & Christopher B. Murray

Doping is a process in which atomic impurities are intentionally added to a host material to modify its properties. It has had a revolutionary impact in altering or introducing electronic, magnetic, luminescent, and catalytic properties for several applications, for example in semiconductors. Here we explore and demonstrate the extension of the concept of substitutional atomic doping to nanometre-scale crystal doping, in which one nanocrystal is used to replace another to form doped self-assembled superlattices. Towards this goal, we show that gold nanocrystals act as substitutional dopants in superlattices of cadmium selenide or lead selenide nanocrystals when the size of the gold nanocrystal is very close to that of the host. The gold nanocrystals occupy random positions in the superlattice and their density is readily and widely controllable, analogous to the case of atomic doping, but here through nanocrystal self-assembly. We also show that the electronic properties of the superlattices are highly tunable and strongly affected by the presence and density of the gold nanocrystal dopants. The conductivity of lead selenide films, for example, can be manipulated over at least six orders of magnitude by the addition of gold nanocrystals and is explained by a percolation model. As this process relies on the self-assembly of uniform nanocrystals, it can be generally applied to assemble a wide variety of nanocrystal-doped structures for electronic, optical, magnetic, and catalytic materials.

Categories: Journal Articles

Western US intermountain seismicity caused by changes in upper mantle flow

Nature - Tue, 08/25/2015 - 23:00

Western US intermountain seismicity caused by changes in upper mantle flow

Nature 524, 7566 (2015). doi:10.1038/nature14867

Authors: Thorsten W. Becker, Anthony R. Lowry, Claudio Faccenna, Brandon Schmandt, Adrian Borsa & Chunquan Yu

Understanding the causes of intraplate earthquakes is challenging, as it requires extending plate tectonic theory to the dynamics of continental deformation. Seismicity in the western United States away from the plate boundary is clustered along a meandering, north–south trending ‘intermountain’ belt. This zone coincides with a transition from thin, actively deforming to thicker, less tectonically active crust and lithosphere. Although such structural gradients have been invoked to explain seismicity localization, the underlying cause of seismicity remains unclear. Here we show results from improved mantle flow models that reveal a relationship between seismicity and the rate change of ‘dynamic topography’ (that is, vertical normal stress from mantle flow). The associated predictive skill is greater than that of any of the other forcings we examined. We suggest that active mantle flow is a major contributor to seismogenic intraplate deformation, while gravitational potential energy variations have a minor role. Seismicity localization should occur where convective changes in vertical normal stress are modulated by lithospheric strength heterogeneities. Our results on deformation processes appear consistent with findings from other mobile belts, and imply that mantle flow plays a significant and quantifiable part in shaping topography, tectonics, and seismic hazard within intraplate settings.

Categories: Journal Articles

Structure Learning in Bayesian Sensorimotor Integration

PLoS Computational Biology - Tue, 08/25/2015 - 16:00

by Tim Genewein, Eduard Hez, Zeynab Razzaghpanah, Daniel A. Braun

Previous studies have shown that sensorimotor processing can often be described by Bayesian learning, in particular the integration of prior and feedback information depending on its degree of reliability. Here we test the hypothesis that the integration process itself can be tuned to the statistical structure of the environment. We exposed human participants to a reaching task in a three-dimensional virtual reality environment where we could displace the visual feedback of their hand position in a two dimensional plane. When introducing statistical structure between the two dimensions of the displacement, we found that over the course of several days participants adapted their feedback integration process in order to exploit this structure for performance improvement. In control experiments we found that this adaptation process critically depended on performance feedback and could not be induced by verbal instructions. Our results suggest that structural learning is an important meta-learning component of Bayesian sensorimotor integration.
Categories: Journal Articles

Fluorescence Turn-On Folding Sensor To Monitor Proteome Stress in Live Cells

Journal of American Chemical Society - Tue, 08/25/2015 - 14:05

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b04366
Categories: Journal Articles

Molecular simulations study of novel 1,4-dihydropyridines derivatives with a high selectivity for Cav3.1 calcium channel

Protein Science - Tue, 08/25/2015 - 05:45
Abstract

1,4-Dihydropyridines (DHPs) have been developed to treat hypertension, angina, and nerve system disease. They are thought to mainly target the L-type calcium channels, but low selectivity prompts them to block Cav1.2 and Cav3.1 channels simultaneously. Recently, some novel DHPs with different hydrophobic groups have been synthesized and among them M12 has a higher selectivity for Cav3.1. However, the structural information about Cav3.1-DHPs complexes is not available in the experiment. Thus, we combined homology modeling, molecular docking, molecular dynamics simulations, and binding free energy calculations to quantitatively elucidate the inhibition mechanism of DHPs. The calculated results indicate that our model is in excellent agreement with experimental results. On the basis of conformational analysis, we identify the main interactions between DHPs and calcium channels and further elaborate on the different selectivity of ligands from the micro perspective. In conjunction with energy distribution, we propose that the binding sites of Cav3.1-DHPs is characterized by several interspersed hydrophobic amino acid residues on the IIIS6 and IVS6 segments. We also speculate the favorable function groups on prospective DHPs. Besides, our model provides important information for further mutagenesis experiments.

Categories: Journal Articles

Differential backbone dynamics of companion helices in the extended helical coiled-coil domain of a bacterial chemoreceptor

Protein Science - Tue, 08/25/2015 - 05:28
Abstract

Cytoplasmic domains of transmembrane bacterial chemoreceptors are largely extended four-helix coiled coils. Previous observations suggested the domain was structurally dynamic. We probed directly backbone dynamics of this domain of the transmembrane chemoreceptor Tar from Escherichia coli using site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. Spin labels were positioned on solvent-exposed helical faces because EPR spectra for such positions reflect primarily polypeptide backbone movements. We acquired spectra for spin-labeled, intact receptor homodimers solubilized in detergent or inserted into native E. coli lipid bilayers in Nanodiscs, characterizing 16 positions distributed throughout the cytoplasmic domain and on both helices of its helical hairpins, one amino terminal to the membrane-distal tight turn (N-helix), and the other carboxyl terminal (C-helix). Detergent solubilization increased backbone dynamics for much of the domain, suggesting that loss of receptor activities upon solubilization reflects wide-spread destabilization. For receptors in either condition, we observed an unanticipated difference between the N- and C-helices. For bilayer-inserted receptors, EPR spectra from sites in the membrane-distal protein-interaction region and throughout the C-helix were typical of well-structured helices. In contrast, for approximately two-thirds of the N-helix, from its origin as the AS-2 helix of the membrane-proximal HAMP domain to the beginning of the membrane-distal protein-interaction region, spectra had a significantly mobile component, estimated by spectral deconvolution to average approximately 15%. Differential helical dynamics suggests a four-helix bundle organization with a pair of core scaffold helices and two more dynamic partner helices. This newly observed feature of chemoreceptor structure could be involved in receptor function.

Categories: Journal Articles

Heroism in Syria

Nature - Mon, 08/24/2015 - 23:00

Heroism in Syria

Nature 524, 7566 (2015). doi:10.1038/524387b

A tribute to scholars of extraordinary courage.

Categories: Journal Articles

Minnesota bog study turns up the heat on peat

Nature - Mon, 08/24/2015 - 23:00

Minnesota bog study turns up the heat on peat

Nature 524, 7566 (2015). http://www.nature.com/doifinder/10.1038/524397a

Author: Alexandra Witze

Experiment boosts temperature and carbon dioxide to gauge global-warming response.

Categories: Journal Articles

Ecologists embrace their urban side

Nature - Mon, 08/24/2015 - 23:00

Ecologists embrace their urban side

Nature 524, 7566 (2015). http://www.nature.com/doifinder/10.1038/524399a

Author: Daniel Cressey

Climate change and the rise of cities have broadened what it means to study ecosystems.

Categories: Journal Articles

The growing global battle against blood-sucking ticks

Nature - Mon, 08/24/2015 - 23:00

The growing global battle against blood-sucking ticks

Nature 524, 7566 (2015). http://www.nature.com/doifinder/10.1038/524406a

Author: Melinda Wenner Moyer

Scientists have no shortage of ideas about how to stop tick-borne illnesses. What is holding them back?

Categories: Journal Articles

Heavy metal transport by the CusCFBA efflux system

Protein Science - Mon, 08/24/2015 - 22:47
Abstract

It is widely accepted that the increased use of antibiotics has resulted in bacteria with developed resistance to such treatments. These organisms are capable of forming multi-protein structures that bridge both the inner and outer membrane to expel diverse toxic compounds directly from the cell. Proteins of the resistance nodulation cell division (RND) superfamily typically assemble as tripartite efflux pumps, composed of an inner membrane transporter, a periplasmic membrane fusion protein, and an outer membrane factor channel protein. These machines are the most powerful antimicrobial efflux machinery available to bacteria. In Escherichia coli, the CusCFBA complex is the only known RND transporter with a specificity for heavy metals, detoxifying both Cu+ and Ag+ ions. In this review, we discuss the known structural information for the CusCFBA proteins, with an emphasis on their assembly, interaction, and the relationship between structure and function.

Categories: Journal Articles

Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals a noncanonical CTD-interacting domain fold

ABSTRACT

CTDK-I is a yeast kinase complex that phosphorylates the C-terminal repeat domain (CTD) of RNA polymerase II (Pol II) to promote transcription elongation. CTDK-I contains the cyclin-dependent kinase Ctk1 (homologous to human CDK9/CDK12), the cyclin Ctk2 (human cyclin K), and the yeast-specific subunit Ctk3, which is required for CTDK-I stability and activity. Here we predict that Ctk3 consists of a N-terminal CTD-interacting domain (CID) and a C-terminal three-helix bundle domain. We determine the X-ray crystal structure of the N-terminal domain of the Ctk3 homologue Lsg1 from the fission yeast Schizosaccharomyces pombe at 2.0 Å resolution. The structure reveals eight helices arranged into a right-handed superhelical fold that resembles the CID domain present in transcription termination factors Pcf11, Nrd1, and Rtt103. Ctk3 however shows different surface properties and no binding to CTD peptides. Together with the known structure of Ctk1 and Ctk2 homologues, our results lead to a molecular framework for analyzing the structure and function of the CTDK-I complex. Proteins 2015; 83:1849–1858. © 2015 Wiley Periodicals, Inc.

Categories: Journal Articles

Large oligomeric complex structures can be computationally assembled by efficiently combining docked interfaces

ABSTRACT

Macromolecular oligomeric assemblies are involved in many biochemical processes of living organisms. The benefits of such assemblies in crowded cellular environments include increased reaction rates, efficient feedback regulation, cooperativity and protective functions. However, an atom-level structural determination of large assemblies is challenging due to the size of the complex and the difference in binding affinities of the involved proteins. In this study, we propose a novel combinatorial greedy algorithm for assembling large oligomeric complexes from information on the approximate position of interaction interfaces of pairs of monomers in the complex. Prior information on complex symmetry is not required but rather the symmetry is inferred during assembly. We implement an efficient geometric score, the transformation match score, that bypasses the model ranking problems of state-of-the-art scoring functions by scoring the similarity between the inferred dimers of the same monomer simultaneously with different binding partners in a (sub)complex with a set of pregenerated docking poses. We compiled a diverse benchmark set of 308 homo and heteromeric complexes containing 6 to 60 monomers. To explore the applicability of the method, we considered 48 sets of parameters and selected those three sets of parameters, for which the algorithm can correctly reconstruct the maximum number, namely 252 complexes (81.8%) in, at least one of the respective three runs. The crossvalidation coverage, that is, the mean fraction of correctly reconstructed benchmark complexes during crossvalidation, was 78.1%, which demonstrates the ability of the presented method to correctly reconstruct topology of a large variety of biological complexes. Proteins 2015; 83:1887–1899. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Categories: Journal Articles

Fast gap-free enumeration of conformations and sequences for protein design

ABSTRACT

Despite significant successes in structure-based computational protein design in recent years, protein design algorithms must be improved to increase the biological accuracy of new designs. Protein design algorithms search through an exponential number of protein conformations, protein ensembles, and amino acid sequences in an attempt to find globally optimal structures with a desired biological function. To improve the biological accuracy of protein designs, it is necessary to increase both the amount of protein flexibility allowed during the search and the overall size of the design, while guaranteeing that the lowest-energy structures and sequences are found. DEE/A*-based algorithms are the most prevalent provable algorithms in the field of protein design and can provably enumerate a gap-free list of low-energy protein conformations, which is necessary for ensemble-based algorithms that predict protein binding. We present two classes of algorithmic improvements to the A* algorithm that greatly increase the efficiency of A*. First, we analyze the effect of ordering the expansion of mutable residue positions within the A* tree and present a dynamic residue ordering that reduces the number of A* nodes that must be visited during the search. Second, we propose new methods to improve the conformational bounds used to estimate the energies of partial conformations during the A* search. The residue ordering techniques and improved bounds can be combined for additional increases in A* efficiency. Our enhancements enable all A*-based methods to more fully search protein conformation space, which will ultimately improve the accuracy of complex biomedically relevant designs. Proteins 2015; 83:1859–1877. © 2015 Wiley Periodicals, Inc.

Categories: Journal Articles

Using combined evidence from replicates to evaluate ChIP-seq peaks

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) detects genome-wide DNA–protein interactions and chromatin modifications, returning enriched regions (ERs), usually associated with a significance score. Moderately significant interactions can correspond to true, weak interactions, or to false positives; replicates of a ChIP-seq experiment can provide co-localised evidence to decide between the two cases. We designed a general methodological framework to rigorously combine the evidence of ERs in ChIP-seq replicates, with the option to set a significance threshold on the repeated evidence and a minimum number of samples bearing this evidence.

Results: We applied our method to Myc transcription factor ChIP-seq datasets in K562 cells available in the ENCODE project. Using replicates, we could extend up to 3 times the ER number with respect to single-sample analysis with equivalent significance threshold. We validated the ‘rescued’ ERs by checking for the overlap with open chromatin regions and for the enrichment of the motif that Myc binds with strongest affinity; we compared our results with alternative methods (IDR and jMOSAiCS), obtaining more validated peaks than the former and less peaks than latter, but with a better validation.

Availability and implementation: An implementation of the proposed method and its source code under GPLv3 license are freely available at http://www.bioinformatics.deib.polimi.it/MSPC/ and http://mspc.codeplex.com/, respectively.

Contact: marco.morelli@iit.it

Supplementary information: Supplementary Material are available at Bioinformatics online.

Categories: Journal Articles

Data-dependent bucketing improves reference-free compression of sequencing reads

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: The storage and transmission of high-throughput sequencing data consumes significant resources. As our capacity to produce such data continues to increase, this burden will only grow. One approach to reduce storage and transmission requirements is to compress this sequencing data.

Results: We present a novel technique to boost the compression of sequencing that is based on the concept of bucketing similar reads so that they appear nearby in the file. We demonstrate that, by adopting a data-dependent bucketing scheme and employing a number of encoding ideas, we can achieve substantially better compression ratios than existing de novo sequence compression tools, including other bucketing and reordering schemes. Our method, Mince, achieves up to a 45% reduction in file sizes (28% on average) compared with existing state-of-the-art de novo compression schemes.

Availability and implementation: Mince is written in C++11, is open source and has been made available under the GPLv3 license. It is available at http://www.cs.cmu.edu/~ckingsf/software/mince.

Contact: carlk@cs.cmu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Categories: Journal Articles

Polyester: simulating RNA-seq datasets with differential transcript expression

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: Statistical methods development for differential expression analysis of RNA sequencing (RNA-seq) requires software tools to assess accuracy and error rate control. Since true differential expression status is often unknown in experimental datasets, artificially constructed datasets must be utilized, either by generating costly spike-in experiments or by simulating RNA-seq data.

Results: Polyester is an R package designed to simulate RNA-seq data, beginning with an experimental design and ending with collections of RNA-seq reads. Its main advantage is the ability to simulate reads indicating isoform-level differential expression across biological replicates for a variety of experimental designs. Data generated by Polyester is a reasonable approximation to real RNA-seq data and standard differential expression workflows can recover differential expression set in the simulation by the user.

Availability and implementation: Polyester is freely available from Bioconductor (http://bioconductor.org/).

Contact: jtleek@gmail.com

Supplementary information: Supplementary data are available at Bioinformatics online.

Categories: Journal Articles

RVD2: an ultra-sensitive variant detection model for low-depth heterogeneous next-generation sequencing data

Bioinformatics Journal - Mon, 08/24/2015 - 09:21

Motivation: Next-generation sequencing technology is increasingly being used for clinical diagnostic tests. Clinical samples are often genomically heterogeneous due to low sample purity or the presence of genetic subpopulations. Therefore, a variant calling algorithm for calling low-frequency polymorphisms in heterogeneous samples is needed.

Results: We present a novel variant calling algorithm that uses a hierarchical Bayesian model to estimate allele frequency and call variants in heterogeneous samples. We show that our algorithm improves upon current classifiers and has higher sensitivity and specificity over a wide range of median read depth and minor allele fraction. We apply our model and identify 15 mutated loci in the PAXP1 gene in a matched clinical breast ductal carcinoma tumor sample; two of which are likely loss-of-heterozygosity events.

Availability and implementation: http://genomics.wpi.edu/rvd2/.

Contact: pjflaherty@wpi.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Categories: Journal Articles
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