bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of water‐soluble and biocompatible graphene
Authors: Hu Xiaohong , Ma Xiaohan , Tan Huaping , Li Dan
Published: June 2013

Graphene as a two‐dimensional material is particularly attractive because of its excellent electrical conductivity, mechanical properties, large surface area, low coefficient of thermal expansion and very high aspect ratio. However, the water insoluble property of graphene restricts its application in biomedical fields. Therefore the objective of this reported work is to find an efficient way to synthesise water‐soluble and biocompatible graphene for biomedical applications. A stable aqueous graphene oxide (GO) solution was first obtained in the presence of non‐ionic Pluronic copolymer. The GO‐tripolymer showed good solubility in phosphate buffered saline (PBS) and the same UV absorption peaks as GO. Since a traditional reducing agent such as hydrazine had large toxicity, reduced GO (RGO) obtained by hydrazine reduction has some toxicity. In this work, a non‐toxic reducing agent of ascorbic acid, galactose or bovine serum albumin was used as a RGO‐tripolymer solution. The RGO‐tripolymer exhibited good solubility in PBS. Finally, the cytotoxicity of RGO‐tripolymers was investigated. Any RGO‐tripolymer showed low cytotoxicity.
High-resolution laser spectroscopy between 0.9 and 14.3 THz in a supersonic beam: Rydberg-Rydberg transitions of atomic Xe at intermediate n values
Authors: Haase Christa , Agner Josef A. , Merkt Frédéric
Published: June 2013

A laser-based, pulsed, narrow-band source of submillimeter-wave radiation has been developed that is continuously tunable from 0.1 THz to 14.3 THz. The source is based on difference-frequency mixing in the nonlinear crystal trans-4′-(dimethylamino)-N-methyl-4-stilbazolium tosylate. By varying the pulse length, the bandwidth of the submillimeter-wave radiation can be adjusted between 85 MHz and 2.8 MHz. This new radiation source has been integrated in a vacuum-ultraviolet–submillimeter-ware double-resonance spectrometer, with which low-frequency transitions of atoms and molecules in supersonic beams can be detected mass-selectively by photoionization and time-of-flight mass spectrometry. The properties of the radiation source and spectrometer are demonstrated in a study of 33f ← nd Rydberg-Rydberg transitions in Xe with n in the range 16–31. The frequency calibration of the submillimeter-wave radiation was performed with an accuracy of 2.8 MHz. The narrowest lines observed experimentally have a full-width at half-maximum of ∼3 MHz, which is sufficient to fully resolve the hyperfine structure of the Rydberg-Rydberg transitions of 129Xe and 131Xe. A total of 72 transitions were measured in the range between 0.937 THz and 14.245 THz and their frequencies are compared with frequencies calculated by multichannel quantum defect theory.
The coupling between translation and rotation for monomeric water in noble gas matrices
Authors: Ceponkus J. , Uvdal P. , Nelander B.
Published: June 2013

The rotation of water in noble gas matrices has been studied. It is shown that the rotation-translation coupling model of Friedmann and Kimel predicts rotation line spacings, which are close to the experimental observations for H2O, D2O, and HDO, when gas phase rotation constants are used. The model gives intensity estimates in reasonable agreement with the observations for the local oscillator bands, which accompany the rotation spectrum. It also predicts the intensity variations in the bending region of H2O between neon, argon, and krypton matrices.
Growing bubbles in a slightly supersaturated liquid solution
Authors: Enríquez Oscar R. , Hummelink Christian , Bruggert Gert-Wim , Lohse Detlef , Prosperetti Andrea , van der Meer Devaraj , Sun Chao
Published: June 2013

We have designed and constructed an experimental system to study gas bubble growth in slightly supersaturated liquids. This is achieved by working with carbon dioxide dissolved in water, pressurized at a maximum of \documentclass[12pt]{minimal}\begin{document}$\mathrm{1\;\mathrm{M}\mathrm{Pa}}$\end{document}1M Pa and applying a small pressure drop from saturation conditions. Bubbles grow from hydrophobic cavities etched on silicon wafers, which allows us to control their number and position. Hence, the experiment can be used to investigate the interaction among bubbles growing in close proximity when the main mass transfer mechanism is diffusion and there is a limited availability of the dissolved species.
A unifying model for non-adiabatic coupling at metallic surfaces beyond the local harmonic approximation: From vibrational relaxation to scanning tunneling microscopy
Authors: Tremblay Jean Christophe
Published: June 2013

A model for treating excitation and relaxation of adsorbates at metallic surfaces induced by non-adiabatic coupling is developed. The derivation is based on the concept of resonant electron transfer, where the adsorbate serves as a molecular bridge for the inelastic transition between an electron source and a sink. In this picture, energy relaxation and scanning tunneling microscopy (STM) at metallic surfaces are treated on an equal footing as a quasi-thermal process. The model goes beyond the local harmonic approximation and allows for an unbiased description of floppy systems with multiple potential wells. Further, the limitation of the product ansatz for the vibronic wave function to include the position-dependence of the non-adiabatic couplings is avoided by explicitly enforcing detailed balance. The theory is applied to the excitation of hydrogen on palladium, which has multiple local potential minima connected by low energy barriers. The main aspects investigated are the lifetimes of adsorbate vibrations in different adsorption sites, as well as the dependence of the excitation, response, and transfer rates on an applied potential bias. The excitation and relaxation simulations reveal intricate population dynamics that depart significantly from the simplistic tunneling model in a truncated harmonic potential. In particular, the population decay from an initially occupied local minimum induced by the contact with an STM tip is found to be better described by a double exponential. The two rates are interpreted as a response to the system perturbation and a transfer rate following the perturbation. The transfer rate is found to obey a power law, as was the case in previous experimental and theoretical work.
Is quantum mechanics exact?
Authors: Kapustin Anton
Published: June 2013

We formulate physically motivated axioms for a physical theory which for systems with a finite number of degrees of freedom uniquely lead to quantum mechanics as the only nontrivial consistent theory. Complex numbers and the existence of the Planck constant common to all systems arise naturally in this approach. The axioms are divided into two groups covering kinematics and basic measurement theory, respectively. We show that even if the second group of axioms is dropped, there are no deformations of quantum mechanics which preserve the kinematic axioms. Thus, any theory going beyond quantum mechanics must represent a radical departure from the usual a priori assumptions about the laws of nature.
Electrical resistance relaxation induced by high pressure in single crystals of YBa2Cu3O7−δ
Authors: Khadzhai G. Ya. , Vovk R. V. , Vovk N. R.
Published: June 2013

An effect of high hydrostatic pressure on the electrical resistance in the ab-plane of single crystals of YBa2Cu3O7−δ with oxygen deficiency is investigated. It is found that the temperature dependence of the electrical resistance is determined by the fluctuation conductivity near Tc and by the scattering of electrons by phonons in a normal state. A high pressure causes the redistribution of labile oxygen, increasing a phase separation. The depressuriazation is accompanied by relaxation processes in both the phonon and the electronic subsystems, the characteristic times of which are significantly different from each other.
Diffusion model of the thermal conductivity plateau of weak solid solutions of neon in parahydrogen
Authors: Zholonko N. N.
Published: June 2013

The diffusion kinetic of classic impurity particles has been investigated in the framework of the one-dimensional two-level model and applied for the explanation of solid hydrogen thermal conductivity data with extremely low concentrations of neon impurity in samples grown at different crystallization rates, at which the plateau effect was observed. The main idea is that heavy isotopic impurities could segregate into thin long chains near dislocation cores if the growth rate is slow. Neon impurity chains can persist for a long time. Such rigid linear objects ensure inelastic scattering of phonons. The diffusion coefficient of neon atoms in (p-H2)1−cNec mixtures was estimated for the experimental conditions with c = 0.0001 at. % and c = 0.0002 at. %.
Tuning of barrier crossing time of a particle by time dependent magnetic field
Authors: Baura Alendu , Ray Somrita , Bag Bidhan Chandra
Published: June 2013

We have studied the effect of time dependent magnetic field on the barrier crossing dynamics of a charged particle. An interplay of the magnetic field induced electric field and the applied field reveals several interesting features. For slowly oscillating field the barrier crossing rate increases remarkably particularly at large amplitude of the field. For appreciably large frequency a generically distinct phenomenon appears by virtue of parametric resonance manifested in multiple peaks appearing in the variation of the mean first passage time as a function of the amplitude. The parametric resonance is more robust against the variation of amplitude of the oscillating field compared to the case of variation of frequency. The barrier crossing time of a particle can be tuned para-metrically by appropriate choice of amplitude and frequency of the oscillating magnetic field.
More mathematics for pseudo-bosons
Authors: Bagarello F.
Published: June 2013

We propose an alternative definition for pseudo-bosons. This simplifies the mathematical structure, minimizing the required assumptions. Some physical examples are discussed, as well as some mathematical results related to the biorthogonal sets arising out of our framework. We also briefly extend the results to the so-called nonlinear pseudo-bosons.
An efficient many-body potential for the interaction of transition and noble metal nano-objects with an environment
Authors: Cortes-Huerto Robinson , Goniakowski Jacek , Noguera Claudine
Published: June 2013

We present a mean-field model for the description of transition or noble metal nano-objects interacting with an environment. It includes a potential given by the second-moment approximation to the tight-binding Hamiltonian for metal-metal interactions, and an additional many-body potential that depends on the local atomic coordination for the metal-environment interaction. The model does not refer to a specific type of chemical conditions, but rather provides trends as a function of a limited number of parameters. The capabilities of the model are highlighted by studying the relative stability of semi-infinite gold surfaces of various orientations and formation energies of a restricted set of single-faceted gold nanoparticles. It is shown that, with only two parameters and in a very efficient way, it is able to generate a great variety of stable structures and shapes, as the nature of the environment varies. It is thus expected to account for formation energies of nano-objects of various dimensionalities (surfaces, thin films, nano-rods, nano-wires, nanoparticles, nanoribbons, etc.) according to the environment.
Charged colloidal model systems under confinement in slit geometry: A new setup for optical microscopic studies
Authors: Reinmüller A. , Palberg T. , Schöpe H. J.
Published: June 2013

A new experimental setup for optical microscopic studies of charged colloidal model systems under confinement between two flat walls is presented. The measurement cell consists of optically flat quartz substrates attached to piezo actuators. Those facilitate fast and flexible adjustment of the confining geometry. Optionally, the local cell height can be quantitatively controlled by in situ interferometric measurements. Proper choice of materials guarantees sufficient chemical inertia against contamination with salt ions. For efficient preparation of charged colloidal suspensions under strongly deionized conditions, the cell can be connected to a conventional pump circuit including a mixed bed ion exchanger column. The usefulness of this setup, in particular for investigating the equilibrium phase behavior of colloids at low background salt concentrations, is demonstrated recalling recent experiments.
Balance between light trapping and charge carrier collection: Electro-photonic optimization of organic photovoltaics with ridge-patterned back electrodes
Authors: Liu Yingchi , Tippets Cary A. , Kirsch Christoph , Mitran Sorin , Samulski Edward T. , Lopez Rene
Published: June 2013

Light trapping strategies are frequently suggested to improve organic photovoltaic (OPV) cell efficiencies. However, one cannot overlook the side-effects to charge carrier collection which are introduced when seeking optical enhancements. A comprehensive electro-photonic model is utilized to study the optical and electrical effects of patterning poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b′]dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] and poly(3-hexylthiophene) based solar cells with simple optical grating structures. It is found that for the most part, optical absorption improvements are attenuated by enhanced electrical losses. Optimized device structures that overcome this tradeoff are proposed and their detailed electro-optical characteristics are discussed. When the hole mobility is smaller than the electron mobility, the results suggest that in general, an inverted structure has a better chance to outperform a flat active layer than a conventional architecture in an OPV cell with the ridge-patterned back electrode.
Separation of variables in an asymmetric cyclidic coordinate system
Authors: Cohl H. S. , Volkmer H.
Published: June 2013

A global analysis is presented of solutions for Laplace's equation on three-dimensional Euclidean space in one of the most general orthogonal asymmetric confocal cyclidic coordinate systems which admit solutions through separation of variables. We refer to this coordinate system as five-cyclide coordinates since the coordinate surfaces are given by two cyclides of genus zero which represent inversions of each other with respect to the unit sphere, a cyclide of genus one, and two disconnected cyclides of genus zero. This coordinate system is obtained by stereographic projection of sphero-conal coordinates on four-dimensional Euclidean space. The harmonics in this coordinate system are given by products of solutions of second-order Fuchsian ordinary differential equations with five elementary singularities. The Dirichlet problem for the global harmonics in this coordinate system is solved using multiparameter spectral theory in the regions bounded by the asymmetric confocal cyclidic coordinate surfaces.
Excitation of terahertz plasmon-polariton in a grating coupled two-dimensional electron gas with a Fabry-Pérot cavity
Authors: Huang Yongdan , Qin Hua , Zhang Baoshun , Wu Jingbo , Zhou Gaochao , Jin Biaobing
Published: June 2013

Terahertz plasmon-polariton modes are excited and probed in a grating coupled GaN/AlGaN two-dimensional electron gas embedded in a Fabry-Pérot cavity using a terahertz time-domain spectroscopy at 8 K. A strong coupling between the plasmon modes and the cavity modes was observed. Electromagnetic simulations confirmed that both the cavity and the grating coupler play important roles in coupling the terahertz field and the plasmons. The finding suggests that the manipulation of terahertz plasmon-polariton could be achieved by engineering the Q-factor and the mode number of the cavity to further enhance the coupling strength.
Three dimensional effects on proton acceleration by intense laser solid target interaction
Authors: Liu Jin-Lu , Chen Min , Zheng Jun , Sheng Zheng-Ming , Liu Chuan-Sheng
Published: June 2013

Multi-dimensional effects on ion acceleration by a normally incident linearly polarized intense laser pulse interacting with a thin solid target have been investigated numerically, where the laser has the peak intensity of 1.37×1020 W/cm2, focused spot size of 6 μm, pulse duration of 33 fs, and total pulse energy about 3 J, which are commercially available now. We have checked the effects of simulation geometries by running one, two, and three dimensional (1D, 2D, 3D) particle-in-cell simulations. 3D simulation results show that, in the case of using a relatively thick target (in the opaque regime, i.e., 2 μm) with the so-called target normal sheath field acceleration mechanism, electrons spread almost uniformly along two transverse directions. While in the case of using an ultra-thin target (in the relativistic-induced transparent regime, i.e., 100 nm) with the so-called break-out afterburner mechanism, electrons spread more quickly along the direction orthogonal to the laser polarization direction especially at the early stage. The transverse spreading of electrons strongly decreases the electron density at the rear side of the target. Such an effect causes different estimation of electron temperatures in different simulation geometries. Usually, 1D and 2D simulations overestimate the temperature; and as a result, the maximum proton energy observed in 1D and 2D simulations is, respectively, about 3 and 2 times of that observed in 3D simulation.
Electrical studies and plasma characterization of an atmospheric pressure plasma jet operated at low frequency
Authors: Giuliani L. , Xaubet M. , Grondona D. , Minotti F. , Kelly H.
Published: June 2013

Low-temperature, high-pressure plasma jets have an extensive use in medical and biological applications. Much work has been devoted to study these applications while comparatively fewer studies appear to be directed to the discharge itself. In this work, in order to better understand the kind of electrical discharge and the plasma states existing in those devices, a study of the electrical characteristics of a typical plasma jet, operated at atmospheric pressure, using either air or argon, is reported. It is found that the experimentally determined electrical characteristics are consistent with the model of a thermal arc discharge, with a highly collisional cathode sheet. The only exception is the case of argon at the smallest electrode separation studied, around 1 mm in which case the discharge is better modeled as either a non-thermal arc or a high-pressure glow. Also, variations of the electrical behavior at different gas flow rates are interpreted, consistently with the arc model, in terms of the development of fluid turbulence in the external jet.
Wetting of soap bubbles on hydrophilic, hydrophobic, and superhydrophobic surfaces
Authors: Arscott Steve
Published: June 2013

Wetting of sessile bubbles on various wetting surfaces (solid and liquid) has been studied. A model is presented for the apparent contact angle of a sessile bubble based on a modified Young's equation––the experimental results agree with the model. Wetting a hydrophilic surface results in a bubble contact angle of 90° whereas using a superhydrophobic surface one observes 134°. For hydrophilic surfaces, the bubble angle diminishes with bubble radius whereas on a superhydrophobic surface, the bubble angle increases. The size of the plateau borders governs the bubble contact angle, depending on the wetting of the surface.
Two-dimensional Green's functions for fluid and thermoelastic two-phase plane
Authors: Hou Peng-Fei , Tong Jie , Li Qiu-Hua
Published: June 2013

The two-dimensional Green's functions for a steady-state line heat source in the interior of fluid and thermoelastic two-phase plane are derived in this paper. By virtue of the compact two-dimensional general solutions which are expressed in harmonic functions, four newly introduced harmonic functions with undetermined constants are constructed. Then, all the thermoelastic components in the fluid and thermoelastic two-phase plane can be derived by substituting these harmonic functions into the corresponding general solutions. And the undetermined constants can be obtained by the corresponding conditions of compatibility, boundary and equilibrium. Numerical results are given graphically by contours.
Feasibility of atomic layer etching of polymer material based on sequential O2 exposure and Ar low-pressure plasma-etching
Authors: Vogli Evelina , Metzler Dominik , Oehrlein Gottlieb S.
Published: June 2013

We describe controlled, self-limited etching of a polystyrene polymer using a composite etching cycle consisting of sequential deposition of a thin reactive layer from precursors produced from a polymer-coated electrode within the etching chamber, modification using O2 exposure, and subsequent low-pressure Ar plasma etching, which removes the oxygen-modified deposited reactive layer along with ≈0.1 nm unmodified polymer. Deposition prevents net etching of the unmodified polymer during the etching step and enables self-limited etch rates of 0.1 nm/cycle.
Dissecting genealogy and cell cycle as sources of cell-to-cell variability in MAPK signaling using high-throughput lineage tracking
Authors: Ricicova Marketa , Hamidi Mani , Quiring Adam , Niemistö Antti , Emberly Eldon , Hansen Carl L.
Published: June 2013

Cells, even those having identical genotype, exhibit variability in their response to external stimuli. This variability arises from differences in the abundance, localization, and state of cellular components. Such nongenetic differences are likely heritable between successive generations and can also be influenced by processes such as cell cycle, age, or interplay between different pathways. To address the contribution of nongenetic heritability and cell cycle in cell-to-cell variability we developed a high-throughput and fully automated microfluidic platform that allows for concurrent measurement of gene expression, cell-cycle periods, age, and lineage information under a large number of temporally changing medium conditions and using multiple strains. We apply this technology to examine the role of nongenetic inheritance in cell heterogeneity of yeast pheromone signaling. Our data demonstrate that the capacity to respond to pheromone is passed across generations and that the strength of the response correlations between related cells is affected by perturbations in the signaling pathway. We observe that a
ste50Δ
mutant strain exhibits highly heterogeneous response to pheromone originating from a unique asymmetry between mother and daughter response. On the other hand,
fus3Δ
cells were found to exhibit an unusually high correlation between mother and daughter cells that arose from a combination of extended cell-cycle periods of
fus3Δ
mothers, and decreased cell-cycle modulation of the pheromone pathway. Our results contribute to the understanding of the origins of cell heterogeneity and demonstrate the importance of automated platforms that generate single-cell data on several parameters.
Olfactory searches with limited space perception
Authors: Masson Jean-Baptiste
Published: June 2013

Various insects and small animals can navigate in turbulent streams to find their mates (or food) from sparse pheromone (odor) detections. Their access to internal space perception and use of cognitive maps still are heavily debated, but for some of them, limited space perception seems to be the rule. However, this poor space perception does not prevent them from impressive search capacities. Here, as an attempt to model these behaviors, we propose a scheme that can perform, even without a detailed internal space map, searches in turbulent streams. The algorithm is based on a standardized projection of the probability of the source position to remove space perception and on the evaluation of a free energy, whose minimization along the path gives direction to the searcher. An internal “temperature” allows active control of the exploration/exploitation balance during the search. We demonstrate the efficiency of the scheme numerically, with a computational model of odor plume propagation, and experimentally, with robotic searches of thermal sources in turbulent streams. In addition to being a model to describe animals’ searches, this scheme may be applied to robotic searches in complex varying media without odometry error corrections and in problems in which active control of the exploration/exploitation balance is profitable.
Comparative transcriptomics reveals patterns of selection in domesticated and wild tomato
Authors: Koenig Daniel , Jiménez-Gómez José M. , Kimura Seisuke , Fulop Daniel , Chitwood Daniel H. , Headland Lauren R. , Kumar Ravi , Covington Michael F. , Devisetty Upendra Kumar , Tat An V. , Tohge Takayuki , Bolger Anthony , Schneeberger Korbinian , Ossowski Stephan , Lanz Christa , Xiong Guangyan , Taylor-Teeples Mallorie , Brady Siobhan M. , Pauly Markus , Weigel Detlef , Usadel Björn , Fernie Alisdair R. , Peng Jie , Sinha Neelima R. , Maloof Julin N.
Published: June 2013

Significance

One of the most important technological advances by humans is the domestication of plant species for the production of food. We have used high-throughput sequencing to identify changes in DNA sequence and gene expression that differentiate cultivated tomato and its wild relatives. We also identify hundreds of candidate genes that have evolved new protein sequences or have changed expression levels in response to natural selection in wild tomato relatives. Taken together, our analyses provide a snapshot of genome evolution under artificial and natural conditions.
Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers
Authors: Pourdehnad Michael , Truitt Morgan L. , Siddiqi Imran N. , Ducker Gregory S. , Shokat Kevan M. , Ruggero Davide
Published: June 2013

Myc
is one of the most commonly deregulated oncogenes in human cancer, yet therapies directly targeting Myc hyperactivation are not presently available in the clinic. The evolutionarily conserved function of Myc in modulating protein synthesis control is critical to the Myc oncogenic program. Indeed, enhancing the protein synthesis capacity of cancer cells directly contributes to their survival, proliferation, and genome instability. Therefore, inhibiting enhanced protein synthesis may represent a highly relevant strategy for the treatment of Myc-dependent human cancers. However, components of the translation machinery that can be exploited as therapeutic targets for Myc-driven cancers remain poorly defined. Here, we uncover a surprising and important functional link between Myc and mammalian target of rapamycin (mTOR)-dependent phosphorylation of eukaryotic translation initiation factor 4E binding protein-1 (4EBP1), a master regulator of protein synthesis control. Using a pharmacogenetic approach, we find that mTOR-dependent phosphorylation of 4EBP1 is required for cancer cell survival in Myc-dependent tumor initiation and maintenance. We further show that a clinical mTOR active site inhibitor, which is capable of blocking mTOR-dependent 4EBP1 phosphorylation, has remarkable therapeutic efficacy in Myc-driven hematological cancers. Additionally, we demonstrate the clinical implications of these results by delineating a significant link between Myc and mTOR-dependent phosphorylation of 4EBP1 and therapeutic response in human lymphomas. Together, these findings reveal that an important mTOR substrate is found hyperactivated downstream of Myc oncogenic activity to promote tumor survival and confers synthetic lethality, thereby revealing a unique therapeutic approach to render Myc druggable in the clinic.
Admission Surveillance for Carbapenamase-Producing Enterobacteriaceae at a Long-Term Acute Care Hospital
Authors: Lewis Jessica D. , Bishop Matthew , Heon Brenda , Mathers Amy J. , Enfield Kyle B. , Sifri Costi D.
Published: June 2013

Carbapenemase-producing Enterobacteriaceae (CPE) are of increasing prevalence worldwide, and long-term acute care hospitals (LTACHs) have been implicated in several outbreaks in the United States. This prospective study of routine screening for CPE on admission to a LTACH demonstrates a high prevalence of CPE colonization in central Virginia.
Predicting protein contact map using evolutionary and physical constraints by integer programming
Authors: Wang Zhiyong , Xu Jinbo
Published: June 2013

Motivation: Protein contact map describes the pairwise spatial and functional relationship of residues in a protein and contains key information for protein 3D structure prediction. Although studied extensively, it remains challenging to predict contact map using only sequence information. Most existing methods predict the contact map matrix element-by-element, ignoring correlation among contacts and physical feasibility of the whole-contact map. A couple of recent methods predict contact map by using mutual information, taking into consideration contact correlation and enforcing a sparsity restraint, but these methods demand for a very large number of sequence homologs for the protein under consideration and the resultant contact map may be still physically infeasible.

Results: This article presents a novel method PhyCMAP for contact map prediction, integrating both evolutionary and physical restraints by machine learning and integer linear programming. The evolutionary restraints are much more informative than mutual information, and the physical restraints specify more concrete relationship among contacts than the sparsity restraint. As such, our method greatly reduces the solution space of the contact map matrix and, thus, significantly improves prediction accuracy. Experimental results confirm that PhyCMAP outperforms currently popular methods no matter how many sequence homologs are available for the protein under consideration.

Availability: http://raptorx.uchicago.edu.

Contact: jinboxu@gmail.com
A high-throughput framework to detect synapses in electron microscopy images
Authors: Navlakha Saket , Suhan Joseph , Barth Alison L. , Bar-Joseph Ziv
Published: June 2013

Motivation: Synaptic connections underlie learning and memory in the brain and are dynamically formed and eliminated during development and in response to stimuli. Quantifying changes in overall density and strength of synapses is an important pre-requisite for studying connectivity and plasticity in these cases or in diseased conditions. Unfortunately, most techniques to detect such changes are either low-throughput (e.g. electrophysiology), prone to error and difficult to automate (e.g. standard electron microscopy) or too coarse (e.g. magnetic resonance imaging) to provide accurate and large-scale measurements.

Results: To facilitate high-throughput analyses, we used a 50-year-old experimental technique to selectively stain for synapses in electron microscopy images, and we developed a machine-learning framework to automatically detect synapses in these images. To validate our method, we experimentally imaged brain tissue of the somatosensory cortex in six mice. We detected thousands of synapses in these images and demonstrate the accuracy of our approach using cross-validation with manually labeled data and by comparing against existing algorithms and against tools that process standard electron microscopy images. We also used a semi-supervised algorithm that leverages unlabeled data to overcome sample heterogeneity and improve performance. Our algorithms are highly efficient and scalable and are freely available for others to use.

Availability: Code is available at http://www.cs.cmu.edu/∼saketn/detect_synapses/

Contact: zivbj@cs.cmu.edu
Integrating sequence, expression and interaction data to determine condition-specific miRNA regulation
Authors: Le Hai-Son , Bar-Joseph Ziv
Published: June 2013

Motivation: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. MiRNAs were shown to play an important role in development and disease, and accurately determining the networks regulated by these miRNAs in a specific condition is of great interest. Early work on miRNA target prediction has focused on using static sequence information. More recently, researchers have combined sequence and expression data to identify such targets in various conditions.

Results: We developed the Protein Interaction-based MicroRNA Modules (PIMiM), a regression-based probabilistic method that integrates sequence, expression and interaction data to identify modules of mRNAs controlled by small sets of miRNAs. We formulate an optimization problem and develop a learning framework to determine the module regulation and membership. Applying PIMiM to cancer data, we show that by adding protein interaction data and modeling cooperative regulation of mRNAs by a small number of miRNAs, PIMiM can accurately identify both miRNA and their targets improving on previous methods. We next used PIMiM to jointly analyze a number of different types of cancers and identified both common and cancer-type-specific miRNA regulators.

Contact:  zivbj@cs.cmu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A framework for scalable parameter estimation of gene circuit models using structural information
Authors: Kuwahara Hiroyuki , Fan Ming , Wang Suojin , Gao Xin
Published: June 2013

Motivation: Systematic and scalable parameter estimation is a key to construct complex gene regulatory models and to ultimately facilitate an integrative systems biology approach to quantitatively understand the molecular mechanisms underpinning gene regulation.

Results: Here, we report a novel framework for efficient and scalable parameter estimation that focuses specifically on modeling of gene circuits. Exploiting the structure commonly found in gene circuit models, this framework decomposes a system of coupled rate equations into individual ones and efficiently integrates them separately to reconstruct the mean time evolution of the gene products. The accuracy of the parameter estimates is refined by iteratively increasing the accuracy of numerical integration using the model structure. As a case study, we applied our framework to four gene circuit models with complex dynamics based on three synthetic datasets and one time series microarray data set. We compared our framework to three state-of-the-art parameter estimation methods and found that our approach consistently generated higher quality parameter solutions efficiently. Although many general-purpose parameter estimation methods have been applied for modeling of gene circuits, our results suggest that the use of more tailored approaches to use domain-specific information may be a key to reverse engineering of complex biological systems.

Availability:  http://sfb.kaust.edu.sa/Pages/Software.aspx

Contact:  xin.gao@kaust.edu.sa

Supplementary information:  Supplementary data are available at Bioinformatics online.
IBD-Groupon: an efficient method for detecting group-wise identity-by-descent regions simultaneously in multiple individuals based on pairwise IBD relationships
Authors: He Dan
Published: June 2013

Motivation: Detecting IBD tracts is an important problem in genetics. Most of the existing methods focus on detecting pairwise IBD tracts, which have relatively low power to detect short IBD tracts. Methods to detect IBD tracts among multiple individuals simultaneously, or group-wise IBD tracts, have better performance for short IBD tracts detection. Group-wise IBD tracts can be applied to a wide range of applications, such as disease mapping, pedigree reconstruction and so forth. The existing group-wise IBD tract detection method is computationally inefficient and is only able to handle small datasets, such as 20, 30 individuals with hundreds of SNPs. It also requires a previous specification of the number of IBD groups, or partitions of the individuals where all the individuals in the same partition are IBD with each other, which may not be realistic in many cases. The method can only handle a small number of IBD groups, such as two or three, because of scalability issues. What is more, it does not take LD (linkage disequilibrium) into consideration.

Results: In this work, we developed an efficient method IBD-Groupon, which detects group-wise IBD tracts based on pairwise IBD relationships, and it is able to address all the drawbacks aforementioned. To our knowledge, our method is the first practical group-wise IBD tracts detection method that is scalable to very large datasets, for example, hundreds of individuals with thousands of SNPs, and in the meanwhile, it is powerful to detect short IBD tracts. Our method does not need to specify the number of IBD groups, which will be detected automatically. And our method takes LD into consideration, as it is based on pairwise IBD tracts where LD can be easily incorporated.

Contact: dhe@us.ibm.com
Efficient network-guided multi-locus association mapping with graph cuts
Authors: Azencott Chloé-Agathe , Grimm Dominik , Sugiyama Mahito , Kawahara Yoshinobu , Borgwardt Karsten M.
Published: June 2013

Motivation: As an increasing number of genome-wide association studies reveal the limitations of the attempt to explain phenotypic heritability by single genetic loci, there is a recent focus on associating complex phenotypes with sets of genetic loci. Although several methods for multi-locus mapping have been proposed, it is often unclear how to relate the detected loci to the growing knowledge about gene pathways and networks. The few methods that take biological pathways or networks into account are either restricted to investigating a limited number of predetermined sets of loci or do not scale to genome-wide settings.

Results: We present SConES, a new efficient method to discover sets of genetic loci that are maximally associated with a phenotype while being connected in an underlying network. Our approach is based on a minimum cut reformulation of the problem of selecting features under sparsity and connectivity constraints, which can be solved exactly and rapidly.

SConES outperforms state-of-the-art competitors in terms of runtime, scales to hundreds of thousands of genetic loci and exhibits higher power in detecting causal SNPs in simulation studies than other methods. On flowering time phenotypes and genotypes from Arabidopsis thaliana, SConES detects loci that enable accurate phenotype prediction and that are supported by the literature.

Availability: Code is available at http://webdav.tuebingen.mpg.de/u/karsten/Forschung/scones/.

Contact:  chloe-agathe.azencott@tuebingen.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cake: a bioinformatics pipeline for the integrated analysis of somatic variants in cancer genomes
Authors: Rashid Mamunur , Robles-Espinoza Carla Daniela , Rust Alistair G. , Adams David J.
Published: June 2013

Summary: We have developed Cake, a bioinformatics software pipeline that integrates four publicly available somatic variant-calling algorithms to identify single nucleotide variants with higher sensitivity and accuracy than any one algorithm alone. Cake can be run on a high-performance computer cluster or used as a stand-alone application.

Availabilty: Cake is open-source and is available from http://cakesomatic.sourceforge.net/

Contact:  da1@sanger.ac.uk

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Known and missing left ventricular ejection fraction and survival in patients with heart failure: a MAGGIC meta‐analysis report
Authors: Poppe Katrina K. , Squire Iain B. , Whalley Gillian A. , Køber Lars , McAlister Finlay A. , McMurray John J.V. , Pocock Stuart , Earle Nikki J. , Berry Colin , Doughty Robert N. ,   on behalf of the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC)
Published: June 2013

Aims

Treatment of patients with heart failure (HF) relies on measurement of LVEF. However, the extent to which EF is recorded varies markedly. We sought to characterize the patient group that is missing a measure of EF, and to explore the association between missing EF and outcome.

Methods and results

Individual data on 30 445 patients from 28 observational studies in the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) project were used to compare the prevalence of co‐morbidities and outcome across three groups of HF patients: those with missing EF (HF‐mEF), reduced EF (HF‐REF), and preserved EF (HF‐PEF). A total of 29% had HF‐mEF, 52% HF‐REF, and 19% HF‐PEF. Compared with patients in whom EF was known, patients with HF‐mEF were older, had a greater prevalence of COPD and previous stroke, and were smokers. Patients with HF‐mEF were less likely to receive evidence‐based treatment than those with HF‐REF. Adjusted mortality in HF‐mEF was similar to that in HF‐REF and greater than that in HF‐PEF at 3 years [HF‐REF, hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.95–1.12); HF‐PEF, HR 0.78, 95% CI 0.71–0.86].

Conclusion

Missing EF is common. The short‐ and long‐term outcome of patients with HF‐mEF is poor and they exhibit different co‐morbidity profiles and treatment patterns compared with patients with known EF. HF patients with missing EF represent a high risk group.
Computational Advances in Maximum Likelihood Methods for Molecular Phylogeny
Authors: Schadt Eric E. , Sinsheimer Janet S. , Lange Kenneth
Published: June 2013

We have developed a generalization of Kimura’s Markov chain model for base substitution at a single nucleotide site. This generalized model incorporates more flexible transition rates and consequently allows irreversible as well as reversible chains. Because the model embodies just the right amount of symmetry, it permits explicit calculation of finite-time transition probabilities and equilibrium distributions. The model also meshes well with maximum likelihood methods for phylogenetic analysis. Quick calculation of likelihoods and their derivatives can be carried out by adapting Baum’s forward and backward algorithms from the theory of hidden Markov chains. Analysis of HIV sequence data illustrates the speed of the algorithms on trees with many contemporary taxa. Analysis of some of Lake’s data on the origin of the eukaryotic nucleus contrasts the reversible and irreversible versions of the model.
Alternative Gene Form Discovery and Candidate Gene Selection from Gene Indexing Projects
Authors: Burke John , Wang Hui , Hide Winston , Davison Daniel B.
Published: June 2013

Several efforts are under way to partition single-read expressed sequence tag (EST), as well as full-length transcript data, into large-scale gene indices, where transcripts are in common index classes if and only if they share a common progenitor gene. Accurate gene indexing facilitates gene expression studies, as well as inexpensive and early gene sequence discovery through assembly of ESTs that are derived from genes that have not been sequenced by classical methods. We extend, correct, and enhance the information obtained from index groups by splitting index classes into subclasses based on sequence dissimilarity (diversity). Two applications of this are highlighted in this report. First it is shown that our method can ameliorate the damage that artifacts, such as chimerism, inflict on index integrity. Additionally, we demonstrate how the organization imposed by an effective subpartition can greatly increase the sensitivity of gene expression studies by accounting for the existence and tissue- or pathology-specific regulation of novel gene isoforms and polymorphisms. We apply our subpartitioning treatment to the UniGene gene indexing project to measure a marked increase in information quality and abundance (in terms of assembly length and insertion/deletion error) after treatment and demonstrate cases where new levels of information concerning differential expression of alternate gene forms, such as regulated alternative splicing, are discovered.

[Tables 2and 3 can be viewed in their entirety as Online Supplements athttp://www.genome.org.]
A portable application for supporting ABA intervention
Authors: Artoni Silvia , Claudia Buzzi Maria , Buzzi Marina , Fenili Claudia , Leporini Barbara , Mencarini Simona , Senette Caterina
Published: June 2013

Purpose

Applied Behavior Analysis (ABA) is a scientific method for modelling human behavior, successfully applied in the context of Autism. Recording and sharing measurable data (on subjects’ performance) between caregivers guarantees consistency of learning programs and allows monitoring the learning enhancements. Data are usually recorded on paper, which requires considerable effort and is subject to error. The purpose of this paper is to describe a portable application developed to support ABA tutors in their work with autistic subjects. It allows gathering data from ABA sessions, giving tutors rapid access to information, also in graphical formats.

Design/methodology/approach

The tool was designed via participatory design. Various ABA team members were involved, in order to make the application respond perfectly to their needs. The approach aims to ensure maximum usability, while minimizing errors and ambient interference.

Findings

The use of mobile devices (i.e. tablets or smartphones) allows mobility and ease of interaction, enabling efficient data collection and processing. Data plotting allows one to easily interpret gathered data.

Social implications

The proposed application, free open source software, can be a valuable aid for supporting the ABA intervention and favor the inclusion of children with autism.

Originality/value

Available software to assist tutors during therapy sessions is often proprietary, and research prototypes are not freely available, so paper forms are still widespread. Besides, without attention to usability requirements, assisting tools would be comparable in efficiency with data insertion on paper. Our software was specifically designed following ABA principles and favors efficient data entry allowing natural interaction with touch screen interfaces: drag and drop, taps and gestures. Furthermore, it is shared in the public domain.
Visual noun navigation framework for the blind
Authors: Molina Edgardo , Diallo Alpha , Zhu Zhigang
Published: June 2013

Propose

The purpose of this paper is to propose a local orientation and navigation framework based on visual features that provide location recognition, context augmentation, and viewer localization information to a blind or low‐vision user.

Design/methodology/approach

The authors consider three types of “visual noun” features: signage, visual‐text, and visual‐icons that are proposed as a low‐cost method for augmenting environments. These are used in combination with an RGB‐D sensor and a simplified SLAM algorithm to develop a framework for navigation assistance suitable for the blind and low‐vision users.

Findings

It was found that signage detection cannot only help a blind user to find a location, but can also be used to give accurate orientation and location information to guide the user navigating a complex environment. The combination of visual nouns for orientation and RGB‐D sensing for traversable path finding can be one of the cost‐effective solutions for navigation assistance for blind and low‐vision users.

Research limitations/implications

This is the first step for a new approach in self‐localization and local navigation of a blind user using both signs and 3D data. The approach is meant to be cost‐effective but it only works in man‐made scenes where a lot of signs exist or can be placed and are relatively permanent in their appearances and locations.

Social implications

Based on 2012 World Health Organization, 285 million people are visually impaired, of which 39 million are blind. This project will have a direct impact on this community.

Originality/value

Signage detection has been widely studied for assisting visually impaired people in finding locations, but this paper provides the first attempt to use visual nouns as visual features to accurately locate and orient a blind user. The combination of visual nouns with 3D data from an RGB‐D sensor is also new.