bluuebunny/crossref_metadata_2025 huggingface dataset:
Solvent annealing induced phase separation and dewetting in PMMA/SAN blend film: Film thickness and solvent dependence
Authors: You Jichun , Zhang Shuangshuang , Huang Gang , Shi Tongfei , Li Yongjin
Published: June 2013

The competition between “dewetting” and “phase separation” behaviors in polymer blend films attracts significant attention in the last decade. The simultaneous phase separation and dewetting in PMMA/SAN [poly(methyl methacrylate) and poly(styrene-ran-acrylonitrile)] blend ultrathin films upon solvent annealing have been observed for the first time in our previous work. In this work, film thickness and annealing solvent dependence of phase behaviors in this system has been investigated using atomic force microscopy and grazing incidence small-angle X-ray scattering (GISAXS). On one hand, both vertical phase separation and dewetting take place upon selective solvent vapor annealing, leading to the formation of droplet/mimic-film structures with various sizes (depending on original film thickness). On the other hand, the whole blend film dewets the substrate and produces dispersed droplets on the silicon oxide upon common solvent annealing. GISAXS results demonstrate the phase separation in the big dewetted droplets resulted from the thicker film (39.8 nm). In contrast, no period structure is detected in small droplets from the thinner film (5.1 nm and 9.7 nm). This investigation indicates that dewetting and phase separation in PMMA/SAN blend film upon solvent annealing depend crucially on the film thickness and the atmosphere during annealing.
Lithium pellet production (LiPP): A device for the production of small spheres of lithium
Authors: Fiflis P. , Andrucyzk D. , Roquemore A. L. , McGuire M. , Curreli D. , Ruzic D. N.
Published: June 2013

With lithium as a fusion material gaining popularity, a method for producing lithium pellets relatively quickly has been developed for NSTX. The Lithium Pellet Production device is based on an injector with a sub-millimeter diameter orifice and relies on a jet of liquid lithium breaking apart into small spheres via the Plateau-Rayleigh instability. A prototype device is presented in this paper and for a pressure difference of ΔP = 5 Torr, spheres with diameters between 0.91 < D < 1.37 mm have been produced with an average diameter of D = 1.14 mm, which agrees with the developed theory. Successive tests performed at Princeton Plasma Physics Laboratory with Wood's metal have confirmed the dependence of sphere diameter on pressure difference as predicted.
Interaction of a synthetic jet with the flow over a low aspect ratio cylinder
Authors: DeMauro E. P. , Leong C. M. , Amitay M.
Published: June 2013

This paper discusses the interaction of a single synthetic jet with the flow over a finite span low aspect ratio cylinder. The synthetic jet was located at the mid-span of the cylinder, and was oriented such that the length of the jet orifice was parallel to the freestream direction. The investigation incorporated experimental techniques such as stereoscopic particle image velocimetry (SPIV) and hot-wire anemometry. The near wake of the cylinder was dominated by a non-negligible spanwise velocity, or downwash, from the cylinder's free-end that interacted with the near wake resulting in a highly three-dimensional flow field with a strong spanwise dependence. SPIV measurements within the near wake showed that, due to the actuation of the synthetic jet, the wake was vectored and narrowed, resulting in a redirection of the downwash behind the cylinder. Furthermore, the synthetic jet actuation resulted in a localized region of inward-directed flow at a spanwise location outboard of the jet orifice leading to a breakdown of the streamwise vorticity field within the near wake. Measurements obtained near the surface of the cylinder demonstrated that the synthetic jet created an elongated vortex ring that redirected the upwash flow away from the cylinder surface inboard of the jet orifice and entrained flow back towards the surface outboard of the orifice. The result was a three-dimensional separation line along the span of the cylinder that gave rise to the spanwise dependency seen in the near wake. Finally, it was shown, using a stability theory analysis that the near surface interaction of the synthetic jet with the separated mixing layer did not result in excitation of the mixing layer instability.
Self-ordered magnetic α-FeSi2 nano-stripes on Si(111)
Authors: Tripathi J. K. , Markovich G. , Goldfarb I.
Published: June 2013

We fabricated self-assembled one-dimensional α-FeSi2 magnetic nano-stripes, using solid phase epitaxy of ∼1 monolayer Fe on vicinal Si(111) surfaces followed by a 550 °C annealing. Structural and magnetic properties were investigated by scanning tunneling microscopy and superconducting quantum interference device magnetometry, respectively. The nano-stripes show superparamagnetism at room-temperature and at 4 K coercivity about 3 times higher along the long nano-stripe [112¯] direction than along the perpendicular [1¯10] one. The calculated magnetic moment at 4 K was ∼3.3 μB/Fe atom, implying a significant ferromagnetic coupling of the Fe atoms in the system. Such nano-stripes may be useful in high-density magnetic memory storage and spintronics devices.
Giant magneto-impedance effect in amorphous ferromagnetic wire with a weak helical anisotropy: Theory and experiment
Authors: Usov N. A. , Gudoshnikov S. A.
Published: June 2013

An adequate description of the results of experimental measurement of both diagonal and off-diagonal Giant magneto-impedance (GMI) components has been obtained for Co-rich amorphous microwire at moderate frequencies assuming the existence of a small off-diagonal tensor component of the residual quenching stress. The latter is the origin of a weak helical anisotropy of amorphous microwire. The micromagnetic simulation of the magnetization reversal process in the microwire under the influence of the applied magnetic field and dc bias current has been carried out. It is shown that due to the influence of the magneto–elastic interaction in a wire with a weak helical anisotropy, the behavior of the longitudinal and circular magnetization components is significantly correlated. Namely, the change of the sign of the longitudinal magnetization component under the influence of the axial magnetic field leads to a subsequent jump of the circular magnetization component at some critical value of the applied magnetic field. As a result of the jump of the circular magnetization, the off-diagonal GMI component also changes sign during the wire magnetization reversal. This effect is confirmed experimentally for a Co-rich wire with a small negative magnetostriction. It is also shown that the jump of the circular magnetization can be eliminated by a circular magnetic field of a weak dc bias current flowing along the wire. This effect allows one to design sensitive magnetic field sensor based on the measurement of the off-diagonal GMI component.
A hybrid symplectic principal component analysis and central tendency measure method for detection of determinism in noisy time series with application to mechanomyography
Authors: Xie Hong-Bo , Dokos Socrates
Published: June 2013

We present a hybrid symplectic geometry and central tendency measure (CTM) method for detection of determinism in noisy time series. CTM is effective for detecting determinism in short time series and has been applied in many areas of nonlinear analysis. However, its performance significantly degrades in the presence of strong noise. In order to circumvent this difficulty, we propose to use symplectic principal component analysis (SPCA), a new chaotic signal de-noising method, as the first step to recover the system dynamics. CTM is then applied to determine whether the time series arises from a stochastic process or has a deterministic component. Results from numerical experiments, ranging from six benchmark deterministic models to 1/f noise, suggest that the hybrid method can significantly improve detection of determinism in noisy time series by about 20 dB when the data are contaminated by Gaussian noise. Furthermore, we apply our algorithm to study the mechanomyographic (MMG) signals arising from contraction of human skeletal muscle. Results obtained from the hybrid symplectic principal component analysis and central tendency measure demonstrate that the skeletal muscle motor unit dynamics can indeed be deterministic, in agreement with previous studies. However, the conventional CTM method was not able to definitely detect the underlying deterministic dynamics. This result on MMG signal analysis is helpful in understanding neuromuscular control mechanisms and developing MMG-based engineering control applications.
In situ electron-beam lithography of deterministic single-quantum-dot mesa-structures using low-temperature cathodoluminescence spectroscopy
Authors: Gschrey M. , Gericke F. , Schüßler A. , Schmidt R. , Schulze J.-H. , Heindel T. , Rodt S. , Strittmatter A. , Reitzenstein S.
Published: June 2013

We report on the deterministic fabrication of sub-μm mesa-structures containing single quantum dots (QDs) by in situ electron-beam lithography. The fabrication method is based on a two-step lithography process: After detecting the position and spectral features of single InGaAs QDs by cathodoluminescence (CL) spectroscopy, circular sub-μm mesa-structures are defined by high-resolution electron-beam lithography and subsequent etching. Micro-photoluminescence spectroscopy demonstrates the high optical quality of the single-QD mesa-structures with emission linewidths below 15 μeV and g(2)(0) = 0.04. Our lithography method has an alignment precision better than 100 nm which paves the way for a fully deterministic device technology using in situ CL lithography.
Temperature dependence of mode conversion in warm, unmagnetized plasmas with a linear density profile
Authors: Yu Dae Jung , Kim Kihong , Lee Dong-Hun
Published: June 2013

We study theoretically the linear mode conversion between electromagnetic waves and Langmuir waves in warm, stratified, and unmagnetized plasmas, using a numerically precise calculation based on the invariant imbedding method. We verify that the principle of reciprocity for the forward and backward mode conversion coefficients holds precisely regardless of temperature. We also find that the temperature dependence of the mode conversion coefficient is substantially stronger than that previously reported. Depending on the wave frequency and the incident angle, the mode conversion coefficient is found to increase or decrease with the increase of temperature.
Assessing diffusion barriers for phase change memory devices using the magnetization of Fe
Authors: Huang J. C. , Bain J. A. , Song W. D. , Li M. H. , Shi L. P. , Schlesinger T. E. , Chong T. C.
Published: June 2013

We show a method for studying diffusion barriers for phase change memory devices. The method involves placing a barrier layer between a phase change material like Ge2Sb2Te5 and Fe and taking note of the magnetization changes of the Fe layer before and after anneal. This results in a fast, sensitive but qualitative measure of various diffusion barriers. Based on this analysis, Ru was found to be good diffusion barrier comparable to the conventional TiW, while Pt is a poor barrier. These results were then reconfirmed by X-ray photoelectron spectroscopy depth studies.
Visibility graph analysis on heartbeat dynamics of meditation training
Authors: Jiang Sen , Bian Chunhua , Ning Xinbao , Ma Qianli D. Y.
Published: June 2013

We apply the visibility graph analysis to human heartbeat dynamics by constructing the complex networks of heartbeat interval time series and investigating the statistical properties of the network before and during chi and yoga meditation. The experiment results show that visibility graph analysis can reveal the dynamical changes caused by meditation training manifested as regular heartbeat, which is closely related to the adjustment of autonomous neural system, and visibility graph analysis is effective to evaluate the effect of meditation.
Angular dependence and symmetry of Rashba spin torque in ferromagnetic heterostructures
Authors: Ortiz Pauyac Christian , Wang Xuhui , Chshiev Mairbek , Manchon Aurelien
Published: June 2013

In a ferromagnetic heterostructure, the interplay between Rashba spin-orbit coupling and exchange splitting gives rise to a current-driven spin torque. In a realistic device setup, we investigate the Rashba spin torque in the diffusive regime and report two major findings: (i) a nonvanishing torque exists at the edges of the device even when the magnetization and effective Rashba field are aligned; (ii) anisotropic spin relaxation rates driven by the Rashba spin-orbit coupling assign the spin torque a general expression T=T∥y(θ)m×(ŷ×m)+T⊥y(θ)ŷ×m+T∥z(θ)m×(ẑ×m)+T⊥z(θ)ẑ×m, where the coefficients T∥,⊥y,z depend on the magnetization direction. Our results agree with recent experiments.
Hydrogenation induced reversible modulation of perpendicular magnetic coercivity in Pd/Co/Pd films
Authors: Lin Wen-Chin , Tsai Cheng-Jui , Wang Bo-Yao , Kao Chao-Hung , Pong Way-Faung
Published: June 2013

In perpendicularly magnetized Pd/Co/Pd trilayers, the hydrogenation not only increased Kerr signal but also significantly enhanced the magnetic coercivity (HC) by 17%. The reversibility was demonstrated by cyclic H2 exposure. The time constants of hydrogen absorption and desorption effect on HC range from tens to hundreds seconds, depending on the H2 gas pressure. The magneto-optical Kerr signal and magnetic coercivity was simultaneously recorded during H2 absorption and desorption. These multifarious signals respond differently and provide a detailed understanding of hydrogenation effect on the functional Pd/Co/Pd trilayers.
Highly tunable Terahertz filter with magneto-optical Bragg grating formed in semiconductor-insulator-semiconductor waveguides
Authors: Li Kangwen , Ma Xunpeng , Zhang Zuyin , Wang Lina , Hu Haifeng , Xu Yun , Song Guofeng
Published: June 2013

A highly tunable terahertz (THz) filter with magneto-optical Bragg grating formed in semiconductor-insulator-semiconductor waveguides is proposed and demonstrated numerically by means of the Finite Element Method. The results reveal that a sharp peak with high Q-value presents in the band gap of Bragg grating waveguide with a defect, and the position of the sharp peak can be modified greatly by changing the intensity of the transverse magnetic field applied to the device. Compared to the situation without magnetic field applied, the shift of the filtered frequency (wavelength) reaches up to 36.1 GHz (11.4 μm) when 1 T magnetic field is applied. In addition, a simple model to predict the filtered frequency and an effective way to improve the Q-value of the filter are proposed by this paper.
Effect of potential fluctuations on shot noise suppression in mesoscopic cavities
Authors: Marconcini P. , Totaro M. , Basso G. , Macucci M.
Published: June 2013

We perform a numerical investigation of the effect of the disorder associated with randomly located impurities on shot noise in mesoscopic cavities. We show that such a disorder becomes dominant in determining the noise behavior when the amplitude of the potential fluctuations is comparable to the value of the Fermi energy and for a large enough density of impurities. In contrast to existing conjectures, random potential fluctuations are shown not to contribute to achieving the chaotic regime whose signature is a Fano factor of 1/4, but, rather, to the diffusive behavior typical of disordered conductors. In particular, the 1/4 suppression factor expected for a symmetric cavity can be achieved only in high-quality material, with a very low density of impurities. As the disorder strength is increased, a relatively rapid transition of the suppression factor from 1/4 to values typical of diffusive or quasi-diffusive transport is observed. Finally, on the basis of a comparison between a hard-wall and a realistic model of the cavity, we conclude that the specific details of the confinement potential have a minor influence on noise.
Room temperature wafer direct bonding of smooth Si surfaces recovered by Ne beam surface treatments
Authors: Kurashima Yuichi , Maeda Atsuhiko , Takagi Hideki
Published: June 2013

We examined the applicability of a Ne fast atom beam (FAB) to surface activated bonding of Si wafers at room temperature. With etching depth more than 1.5 nm, the bonding strength comparable to Si bulk strength was attained. Moreover, we found the improvement of the bonding strength by surface smoothing effect of the Ne FAB. Silicon surface roughness decreased from 0.40 to 0.17 nm rms by applying a Ne FAB of 30 nm etching depth. The bonding strength between surfaces recovered by Ne FAB surface smoothing was largely improved and finally became equivalent to Si bulk strength.
The influence of interface bonding on thermal transport through solid–liquid interfaces
Authors: Harikrishna Hari , Ducker William A. , Huxtable Scott T.
Published: June 2013

We use time-domain thermoreflectance to show that interface thermal conductance, G, is proportional to the thermodynamic work of adhesion between gold and water, WSL, for a series of five alkane-thiol monolayers at the gold-water interface. WSL is a measure of the bond strength across the solid-liquid interface. Differences in bond strength, and thus differences in WSL, are achieved by varying the terminal group (ω-group) of the alkane-thiol monolayers on the gold. The interface thermal conductance values were in the range 60–190 MW m−2 K−1, and the solid-liquid contact angles span from 25° to 118°.
Synthesis and Reactivity of Half-Sandwich Ruthenium κ2-Aminoborane Complexes
Authors: Addy David A. , Bates Joshua I. , Kelly Michael J. , Abdalla Joseph , Phillips Nicholas , Riddlestone Ian M. , Aldridge Simon
Published: June 2013

Cationic half-sandwich ruthenium complexes featuring κ2-bound aminoborane ligands can readily be accessed from 16-electron precursors via chloride abstraction in the presence of H2BNR2 (R = iPr, Cy). Complexes [Cp*Ru(L)(κ2-H2BNR2)][BArf4] (2a: R = iPr, L = PCy3; 2b: R = iPr, L = PPh3; 2c: R = iPr, L = 1,3-bis-(2,4,6-trimethylphenyl)-imidazol-2-ylidene; 3a: R = Cy, L = PCy3; Arf = C6H3(CF3)2‐3,5) were isolated in yields of ~60 %, and characterised in the solid state by X-ray crystallography (for 2a, 2c, and 3a). Low-field 11B NMR shifts for the coordinated aminoborane fragment, together with short Ru⋯B contacts (of the order of 1.97 Å) imply a relatively tightly bound borane ligand, a finding which is given further credence by the results of density functional theory studies (e.g. bond dissociation energies in the range 24 kcal mol–1; 1 kcal mol–1 = 4.186 kJ mol–1). In terms of reactivity, κ2 systems of this type, while potentially offering a versatile route to asymmetric κ1 systems, in fact undergo borane extrusion even in the presence of a single equivalent of added ligand.
Consequences of elevated temperatures on legume biomass and nitrogen cycling in a field warming and biodiversity experiment in a North American prairie
Authors: Whittington Heather R. , Tilman David , Powers Jennifer S.
Published: June 2013

Increases in global temperature are likely to have effects on the nitrogen cycle, including those mediated through effects on legumes, which have a role in the N cycle by fixing N2. These effects may alter plant functioning and community structure, especially in N-limited ecosystems. We manipulated temperature and plant diversity in the field to investigate the effects of elevated temperature on aboveground biomass, shoot N concentration ([N]), and reliance on N2 fixation of four prairie legumes (Amorpha canescens Pursh., Dalea purpurea Vent., Lespedeza capitata Michx. and Lupinus perennis L.) planted in plots of varying species numbers. We monitored the effect of warming on soil microclimate and net N mineralisation rates, as these variables may mediate the effect of warming on legumes. Warming decreased soil moisture and increased soil temperature, but had no effect on net N mineralisation. Warming increased the aboveground biomass of D. purpurea and L. perennis, but decreased shoot [N] for all species in one year. Though the data were not optimal for quantifying N2 fixation using stable isotopes, they suggest that warming did not affect the reliance on N2 fixation. Species diversity did not have strong effects on the response to warming. These results suggest that legume-mediated effects of temperature on N cycling will arise from changes in biomass and tissue chemistry, not N2 fixation. We observed strong interannual variation between a wet and dry year for N mineralisation, shoot [N] and reliance on N2 fixation, suggesting that these may be more responsive to precipitation changes than elevated temperature.
Global patterns of terrestrial vertebrate diversity and conservation
Authors: Jenkins Clinton N. , Pimm Stuart L. , Joppa Lucas N.
Published: June 2013

Significance

Identifying priority areas for biodiversity is essential for directing conservation resources. We mapped global priority areas using the latest data on mammals, amphibians, and birds at a scale 100 times finer than previous assessments. Priority areas have a higher—but still insufficient—rate of protection than the global average. We identify several important areas currently ignored by biodiversity hotspots, the current leading priority map. As the window of opportunity for expanding the global protected area network begins to close, identifying priorities at a scale practical for local action ensures our findings will help protect biodiversity most effectively.
Discontinuation of Reflex Testing of Stool Samples for Vancomycin-Resistant Enterococci Resulted in Increased Prevalence
Authors: Bodily Mandy , McMullen Kathleen M. , Russo Anthony J. , Kittur Nupur D. , Hoppe-Bauer Joan , Warren David K.
Published: June 2013

Discontinuation of reflex testing of stool submitted forClostridium difficiletesting for vancomycin-resistant enterococci (VRE) led to an increase in the number of patients with healthcare-associated VRE bacteremia and bacteriuria (0.21 vs 0.36 cases per 1,000 patient-days;P< .01). Cost-benefit analysis showed reflex screening and isolation of VRE reduced hospital costs.
Specialized sorting of GLUT4 and its recruitment to the cell surface are independently regulated by distinct Rabs
Authors: Sadacca L. Amanda , Bruno Joanne , Wen Jennifer , Xiong Wenyong , McGraw Timothy E.
Published: June 2013

Adipocyte glucose uptake in response to insulin is essential for physiological glucose homeostasis: stimulation of adipocytes with insulin results in insertion of the glucose transporter GLUT4 into the plasma membrane and subsequent glucose uptake. Here we establish that RAB10 and RAB14 are key regulators of GLUT4 trafficking that function at independent, sequential steps of GLUT4 translocation. RAB14 functions upstream of RAB10 in the sorting of GLUT4 to the specialized transport vesicles that ferry GLUT4 to the plasma membrane. RAB10 and its GTPase-activating protein (GAP) AS160 comprise the principal signaling module downstream of insulin receptor activation that regulates the accumulation of GLUT4 transport vesicles at the plasma membrane. Although both RAB10 and RAB14 are regulated by the GAP activity of AS160 in vitro, only RAB10 is under the control of AS160 in vivo. Insulin regulation of the pool of RAB10 required for GLUT4 translocation occurs through regulation of AS160, since activation of RAB10 by DENND4C, its GTP exchange factor, does not require insulin stimulation.
Automated annotation of gene expression image sequences via non-parametric factor analysis and conditional random fields
Authors: Pruteanu-Malinici Iulian , Majoros William H. , Ohler Uwe
Published: June 2013

Motivation: Computational approaches for the annotation of phenotypes from image data have shown promising results across many applications, and provide rich and valuable information for studying gene function and interactions. While data are often available both at high spatial resolution and across multiple time points, phenotypes are frequently annotated independently, for individual time points only. In particular, for the analysis of developmental gene expression patterns, it is biologically sensible when images across multiple time points are jointly accounted for, such that spatial and temporal dependencies are captured simultaneously.

Methods: We describe a discriminative undirected graphical model to label gene-expression time-series image data, with an efficient training and decoding method based on the junction tree algorithm. The approach is based on an effective feature selection technique, consisting of a non-parametric sparse Bayesian factor analysis model. The result is a flexible framework, which can handle large-scale data with noisy incomplete samples, i.e. it can tolerate data missing from individual time points.

Results: Using the annotation of gene expression patterns across stages of Drosophila embryonic development as an example, we demonstrate that our method achieves superior accuracy, gained by jointly annotating phenotype sequences, when compared with previous models that annotate each stage in isolation. The experimental results on missing data indicate that our joint learning method successfully annotates genes for which no expression data are available for one or more stages.

Contact: uwe.ohler@duke.edu
Using state machines to model the Ion Torrent sequencing process and to improve read error rates
Authors: Golan David , Medvedev Paul
Published: June 2013

Motivation: The importance of fast and affordable DNA sequencing methods for current day life sciences, medicine and biotechnology is hard to overstate. A major player is Ion Torrent, a pyrosequencing-like technology which produces flowgrams – sequences of incorporation values – which are converted into nucleotide sequences by a base-calling algorithm. Because of its exploitation of ubiquitous semiconductor technology and innovation in chemistry, Ion Torrent has been gaining popularity since its debut in 2011. Despite the advantages, however, Ion Torrent read accuracy remains a significant concern.

Results: We present FlowgramFixer, a new algorithm for converting flowgrams into reads. Our key observation is that the incorporation signals of neighboring flows, even after normalization and phase correction, carry considerable mutual information and are important in making the correct base-call. We therefore propose that base-calling of flowgrams should be done on a read-wide level, rather than one flow at a time. We show that this can be done in linear-time by combining a state machine with a Viterbi algorithm to find the nucleotide sequence that maximizes the likelihood of the observed flowgram. FlowgramFixer is applicable to any flowgram-based sequencing platform. We demonstrate FlowgramFixer’s superior performance on Ion Torrent Escherichia coli data, with a 4.8% improvement in the number of high-quality mapped reads and a 7.1% improvement in the number of uniquely mappable reads.

Availability: Binaries and source code of FlowgramFixer are freely available at: http://www.cs.tau.ac.il/~davidgo5/flowgramfixer.html.

Contact: davidgo5@post.tau.ac.il
A weighted sampling algorithm for the design of RNA sequences with targeted secondary structure and nucleotide distribution
Authors: Reinharz Vladimir , Ponty Yann , Waldispühl Jérôme
Published: June 2013

Motivations: The design of RNA sequences folding into predefined secondary structures is a milestone for many synthetic biology and gene therapy studies. Most of the current software uses similar local search strategies (i.e. a random seed is progressively adapted to acquire the desired folding properties) and more importantly do not allow the user to control explicitly the nucleotide distribution such as the GC-content in their sequences. However, the latter is an important criterion for large-scale applications as it could presumably be used to design sequences with better transcription rates and/or structural plasticity.

Results: In this article, we introduce IncaRNAtion, a novel algorithm to design RNA sequences folding into target secondary structures with a predefined nucleotide distribution. IncaRNAtion uses a global sampling approach and weighted sampling techniques. We show that our approach is fast (i.e. running time comparable or better than local search methods), seedless (we remove the bias of the seed in local search heuristics) and successfully generates high-quality sequences (i.e. thermodynamically stable) for any GC-content. To complete this study, we develop a hybrid method combining our global sampling approach with local search strategies. Remarkably, our glocal methodology overcomes both local and global approaches for sampling sequences with a specific GC-content and target structure.

Availability:  IncaRNAtion is available at csb.cs.mcgill.ca/incarnation/

Contact:  jeromew@cs.mcgill.ca or yann.ponty@lix.polytechnique.fr

Supplementary Information:  Supplementary data are available at Bioinformatics online.
Predicting protein interactions via parsimonious network history inference
Authors: Patro Rob , Kingsford Carl
Published: June 2013

Motivation: Reconstruction of the network-level evolutionary history of protein–protein interactions provides a principled way to relate interactions in several present-day networks. Here, we present a general framework for inferring such histories and demonstrate how it can be used to determine what interactions existed in the ancestral networks, which present-day interactions we might expect to exist based on evolutionary evidence and what information extant networks contain about the order of ancestral protein duplications.

Results: Our framework characterizes the space of likely parsimonious network histories. It results in a structure that can be used to find probabilities for a number of events associated with the histories. The framework is based on a directed hypergraph formulation of dynamic programming that we extend to enumerate many optimal and near-optimal solutions. The algorithm is applied to reconstructing ancestral interactions among bZIP transcription factors, imputing missing present-day interactions among the bZIPs and among proteins from five herpes viruses, and determining relative protein duplication order in the bZIP family. Our approach more accurately reconstructs ancestral interactions than existing approaches. In cross-validation tests, we find that our approach ranks the majority of the left-out present-day interactions among the top 2 and 17% of possible edges for the bZIP and herpes networks, respectively, making it a competitive approach for edge imputation. It also estimates relative bZIP protein duplication orders, using only interaction data and phylogenetic tree topology, which are significantly correlated with sequence-based estimates.

Availability: The algorithm is implemented in C++, is open source and is available at http://www.cs.cmu.edu/ckingsf/software/parana2.

Contact:  robp@cs.cmu.edu or carlk@cs.cmu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Automated target segmentation and real space fast alignment methods for high-throughput classification and averaging of crowded cryo-electron subtomograms
Authors: Xu Min , Alber Frank
Published: June 2013

Motivation: Cryo-electron tomography allows the imaging of macromolecular complexes in near living conditions. To enhance the nominal resolution of a structure it is necessary to align and average individual subtomograms each containing identical complexes. However, if the sample of complexes is heterogeneous, it is necessary to first classify subtomograms into groups of identical complexes. This task becomes challenging when tomograms contain mixtures of unknown complexes extracted from a crowded environment. Two main challenges must be overcomed: First, classification of subtomograms must be performed without knowledge of template structures. However, most alignment methods are too slow to perform reference-free classification of a large number of (e.g. tens of thousands) of subtomograms. Second, subtomograms extracted from crowded cellular environments, contain often fragments of other structures besides the target complex. However, alignment methods generally assume that each subtomogram only contains one complex. Automatic methods are needed to identify the target complexes in a subtomogram even when its shape is unknown.

Results: In this article, we propose an automatic and systematic method for the isolation and masking of target complexes in subtomograms extracted from crowded environments. Moreover, we also propose a fast alignment method using fast rotational matching in real space. Our experiments show that, compared with our previously proposed fast alignment method in reciprocal space, our new method significantly improves the alignment accuracy for highly distorted and especially crowded subtomograms. Such improvements are important for achieving successful and unbiased high-throughput reference-free structural classification of complexes inside whole-cell tomograms.

Contact:  alber@usc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
CAMPways: constrained alignment framework for the comparative analysis of a pair of metabolic pathways
Authors: Abaka Gamze , Bıyıkoğlu Türker , Erten Cesim
Published: June 2013

Motivation: Given a pair of metabolic pathways, an alignment of the pathways corresponds to a mapping between similar substructures of the pair. Successful alignments may provide useful applications in phylogenetic tree reconstruction, drug design and overall may enhance our understanding of cellular metabolism.

Results: We consider the problem of providing one-to-many alignments of reactions in a pair of metabolic pathways. We first provide a constrained alignment framework applicable to the problem. We show that the constrained alignment problem even in a primitive setting is computationally intractable, which justifies efforts for designing efficient heuristics. We present our Constrained Alignment of Metabolic Pathways (CAMPways) algorithm designed for this purpose. Through extensive experiments involving a large pathway database, we demonstrate that when compared with a state-of-the-art alternative, the CAMPways algorithm provides better alignment results on metabolic networks as far as measures based on same-pathway inclusion and biochemical significance are concerned. The execution speed of our algorithm constitutes yet another important improvement over alternative algorithms.

Availability: Open source codes, executable binary, useful scripts, all the experimental data and the results are freely available as part of the Supplementary Material at http://code.google.com/p/campways/.

Contact:  cesim@khas.edu.tr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pipit: visualizing functional impacts of structural variations
Authors: Sakai Ryo , Moisse Matthieu , Reumers Joke , Aerts Jan
Published: June 2013

Summary: Pipit is a gene-centric interactive visualization tool designed to study structural genomic variations. Through focusing on individual genes as the functional unit, researchers are able to study and generate hypotheses on the biological impact of different structural variations, for instance, the deletion of dosage-sensitive genes or the formation of fusion genes. Pipit is a cross-platform Java application that visualizes structural variation data from Genome Variation Format files.

Availability: Executables, source code, sample data, documentation and screencast are available at https://bitbucket.org/biovizleuven/pipit.

Contact:  ryo.sakai@esat.kuleuven.be

Supplementary information:  Supplementary data are available at Bioinformatics online.
Hypermethylation reduces expression of tumor‐suppressor PLZF and regulates proliferation and apoptosis in non‐small‐cell lung cancers
Authors: Wang Xiaotian , Wang Lei , Guo Shicheng , Bao Yang , Ma Yanyun , Yan Fengyang , Xu Kuan , Xu Zhiyun , Jin Li , Lu Daru , Xu Jibin , Wang Jiu‐Cun
Published: June 2013

Deregulation of promyelocytic leukemia zinc finger protein (PLZF), a tumor suppressor gene, was reported in different types of solid tumors. This study for the first time explored the reduced expression of PLZF and its effects in non‐small‐cell lung cancer (NSCLC) carcinogenesis. PLZF was found to be downregulated by 62.8% in 87.1% of 154 paired NSCLC samples by quantitative real‐time PCR, and its expression was found to be associated with the sex of the patient (P=0.02). Further analysis showed that down‐regulation of PLZF in 35.6% NSCLC samples (31 out of 87) was triggered by hypermethylation in the promoter region. This was validated by demethylation analysis using the A549 cell line. Dual‐luciferase reporter assay indicated that CTCF binding to the promoter region could activate PLZF transcription. Overexpression of PLZF in both A549 and LTEP lung cancer cell lines was found to inhibit proliferation and increase apoptosis. Therefore, reduced expression of PLZF was found to be common in NSCLC. PLZF down‐regulation was partially correlated with hypermethylation in the promoter region. Decreased levels of PLZF expression may contribute to the pathogenesis of NSCLC by promoting cell survival. Therefore, the restoration of PLZF expression may serve as a new strategy for NSCLC therapy.—Wang, X., Wang, L., Guo, S., Bao, Y., Ma, Y., Yan, F., Xu, K., Xu, Z., Jin, L., Lu, D., Xu, J., Wang, J.‐C. Hypermethylation reduces expression of tumor‐suppressor PLZF and regulates proliferation and apoptosis in non‐small‐cell lung cancers. FASEBJ. 27, 4194‐4203 (2013). www.fasebj.org
Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age
Authors: Bui Tammy , Kocher Jacob , Li Yanru , Wen Ke , Li Guohua , Liu Fangning , Yang Xingdong , LeRoith Tanya , Tan Ming , Xia Ming , Zhong Weiming , Jiang Xi , Yuan Lijuan
Published: June 2013

Human noroviruses (NoVs), a major cause of viral gastroenteritis, are difficult to study due to the lack of a cell-culture and a small-animal model. Pigs share with humans the types A and H histo-blood group antigens on the intestinal epithelium and have been suggested as a potential model for studies of NoV pathogenesis, immunity and vaccines. In this study, the effects of age and a cholesterol-lowering drug, simvastatin, on the susceptibility of pigs to NoV infection were evaluated. The median infectious dose (ID50) of a genogroup II, genotype 4 (GII.4) 2006b variant was determined. The ID50 in neonatal (4–5 days of age) pigs was ≤2.74×103 viral RNA copies. In older pigs (33–34 days of age), the ID50 was 6.43×104 but decreased to <2.74×103 in simvastatin-fed older pigs. Evidence of NoV infection was obtained by increased virus load in the intestinal contents, cytopathological changes in the small intestine, including irregular microvilli, necrosis and apoptosis, and detection of viral antigen in the tip of villi in duodenum. This GII.4 variant was isolated in 2008 from a patient from whom a large volume of stool was collected. GII.4 NoVs are continuously subjected to selective pressure by human immunity, and antigenically different GII.4 NoV variants emerge every 1–2 years. The determination of the ID50 of this challenge virus is valuable for evaluation of protection against different GII.4 variants conferred by NoV vaccines in concurrence with other GII.4 variants in the gnotobiotic pig model.
Sympatric chimpanzees and gorillas harbor convergent gut microbial communities
Authors: Moeller Andrew H. , Peeters Martine , Ndjango Jean-Basco , Li Yingying , Hahn Beatrice H. , Ochman Howard
Published: June 2013

The gut microbial communities within great apes have been shown to reflect the phylogenetic history of their hosts, indicating codiversification between great apes and their gut microbiota over evolutionary timescales. But because the great apes examined to date represent geographically isolated populations whose diets derive from different sources, it is unclear whether this pattern of codiversification has resulted from a long history of coadaptation between microbes and hosts (heritable factors) or from the ecological and geographic separation among host species (environmental factors). To evaluate the relative influences of heritable and environmental factors on the evolution of the great ape gut microbiota, we assayed the gut communities of sympatric and allopatric populations of chimpanzees, bonobos, and gorillas residing throughout equatorial Africa. Comparisons of these populations revealed that the gut communities of different host species can always be distinguished from one another but that the gut communities of sympatric chimpanzees and gorillas have converged in terms of community composition, sharing on average 53% more bacterial phylotypes than the gut communities of allopatric hosts. Host environment, independent of host genetics and evolutionary history, shaped the distribution of bacterial phylotypes across the Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria, the four most common phyla of gut bacteria. Moreover, the specific patterns of phylotype sharing among hosts suggest that chimpanzees living in sympatry with gorillas have acquired bacteria from gorillas. These results indicate that geographic isolation between host species has promoted the evolutionary differentiation of great ape gut bacterial communities.
Sequence Assembly with CAFTOOLS
Authors: Dear Simon , Durbin Richard , Hillier LaDeana , Marth Gabor , Thierry-Mieg Jean , Mott Richard
Published: June 2013

Large-scale genomic sequencing requires a software infrastructure to support and integrate applications that are not directly compatible. We describe a suite of software tools built around the Common Assembly Format (CAF), a comprehensive representation of a sequence assembly as a text file. These tools form the backbone of sequencing informatics at the Sanger Centre and the Genome Sequencing Center. The CAF format is intentionally flexible, and our Perl and C libraries, which parse and manipulate it, provide powerful tools for creating new applications as well as wrappers to incorporate other software. The tools are available free by anonymous FTP from ftp://ftp.sanger.ac.uk/pub/badger/.
EbEST: An Automated Tool Using Expressed Sequence Tags to Delineate Gene Structure
Authors: Jiang Jian , Jacob Howard J.
Published: June 2013

Large numbers of expressed sequence tags (ESTs) continue to fill public and private databases with partial cDNA sequences. However, using this huge amount of ESTs to facilitate gene finding in genomic sequence imposes a challenge, especially to wet-lab scientists who often have limited computing resources. In an effort to consolidate the information hidden in the vast number of ESTs into a readable and manageable format, we have developed EbEST—a program that automates the process of using ESTs to help delineate gene structure in long stretches of genomic sequence. The EbEST program consists of three functional modules—the first module separates homologous ESTs into clusters and identifies the most informative ESTs within each cluster; the second module uses the informative ESTs to perform gapped alignment and to predict the exon–intron boundary; and the third module generates text file and graphic outputs that illustrate the orientation, exonic structure, and untranslated regions (UTRs) of putative genes in the genomic sequence being analyzed. Evaluation of EbEST with 176 human genes from the ALLSEQ set indicated that it performed in-line with several existing gene finding programs, but was more tolerant to sequencing errors. Furthermore, when EbEST was challenged with query sequences that harbor more than one gene, it suffered only a slight drop in performance, whereas the performance of the other programs evaluated decreased more. EbEST may be used as a stand-alone tool to annotate human genomic sequences with EST-derived gene elements, or can be used in conjunction with computational gene-recognition programs to increase the accuracy of gene prediction.

[EbBEST is available athttp://EbEST.ifrc.mcw.edu]
Exponential stability for impulsive Cohen‐Grossberg neural networks with time‐varying delays and distributed delays
Authors: Zheng Cheng‐De , Sun Ri‐Ming , Wang Zhanshan
Published: June 2013

Purpose

The purpose of this paper is to develop a methodology for the existence and global exponential stability of the unique equilibrium point of a class of impulsive Cohen‐Grossberg neural networks.

Design/methodology/approach

The authors perform M‐matrix theory and homeomorphism mapping principle to investigate a class of impulsive Cohen‐Grossberg networks with time‐varying delays and distributed delays. The approach builds on new sufficient criterion without strict conditions imposed on self‐regulation functions.

Findings

The authors' approach results in new sufficient criteria easy to verify but without the usual assumption that the activation functions are bounded and the time‐varying delays are differentiable. An example shows the effectiveness and superiority of the obtained results over some previously known results.

Originality/value

The novelty of the proposed approach lies in removing the usual assumption that the activation functions are bounded and the time‐varying delays are differentiable, and the use of M‐matrix theory and homeomorphism mapping principle for the existence and global exponential stability of the unique equilibrium point of a class of impulsive Cohen‐Grossberg neural networks.
Impact of bundling of ICT services on regulation
Authors: García Zaballos Antonio
Published: June 2013

Purpose

Operators are launching bundles of services to retain customers and improve ARPU but regulators and competition authorities need to ensure fair competition. The objectives of this article are to present the reasonability of ex‐ante and ex‐post intervention and the methodologies and imputation test that might be considered by national regulatory agencies (NRAs) and national competition authorities (NCAs) to guarantee effective competition.

Design/methodology/approach

The methodology from a regulatory standpoint consists of analyzing the impact that margin squeeze might have on the level of competition. It is based on estimating how costs and retail prices will evolve over time. The methodology aims to predict how margins will evolve taking into consideration the number of subscribers and network costs.

Findings

The increasing number of convergent offers, the roll out of new technologies that allows the commercialization of new services and applications and the transformation in the access network means that the methodology used by the NRAs/NCAs to analyze the offers of vertically integrated operators should be revised.

Originality/value

The paper highlights the need for a new methodology to assess anti‐competitive behavior arising from bundling and identifies factors that should be taken into account.