bluuebunny/crossref_metadata_2025 huggingface dataset:
Discrete‐rate adaptive modulation with optimum switching thresholds for space‐time coded multiple‐input multiple‐output system with imperfect channel state information
Authors: Yu Xiangbin , Tan Wenting , Leung Shu‐Hung , Rui Yun , Yin Xin , Liu Xiaoshuai
Published: June 2013

The performance analysis of a space‐time coded multiple‐input multiple‐output (MIMO) system with variable‐rate adaptive modulation over flat Rayleigh fading channels for both perfect and imperfect channel state information (CSI) is presented. In this study, the optimum fading gain switching thresholds for attaining maximum spectrum efficiency (SE) subject to an average bit error rate (BER) constraint are derived. The existence and uniqueness of the Lagrange multiplier in the constrained SE optimisation is studied. It is shown that the Lagrange multiplier does exist and is unique for imperfect CSI. On the other hand, the Lagrange multiplier will be unique if the existence condition for MIMO under perfect CSI is satisfied. A practical iterative algorithm based on Newton's method for finding the Lagrange multiplier is proposed. By the switching thresholds, closed‐form expressions of the SE and average BER are obtained. Simulation results for SE and BER are in good agreement with the theoretical analysis. The results show that the space‐time block coded MIMO system using adaptive modulation (AM‐STBC‐MIMO) with average BER constraint provides SE better than AM‐STBC‐MIMO with fixed thresholds, and AM‐STBC‐MIMO using a BER upper bound, but it has performance degradation in SE for imperfect CSI.
Flow‐lysometry for cytoplasmic analysis of single cells in large populations
Authors: Lee Won Chul , Pisano Albert P. , Cho Young‐Ho , Kuypers Frans A.
Published: June 2013

Presented is a single‐cell analyser to measure cytoplasmic components in large cell populations. This technology, flow‐lysometry, uses a flow‐cell that performs three functions (cell detection, cell lysis and component sensing) in a continuous microfluidic channel. This flow‐cell can be coupled and synchronised with classical flowcytometry, thus offering high‐throughput measurements of various cytoplasmic compounds in combination with cell‐surface markers. The measurement of cytoplasmic markers in the cytosol of red blood cells was shown to verify population analysis of individual cells in mixed‐cell populations. This work presents an approach to characterise complex cell populations to extend measurements in cell biology.
Development of seed layer deposition and fast copper electroplating into deep microvias for three‐dimensional integration
Authors: Chen Xiao , Xu Gaowei , Luo Le
Published: June 2013

Increasing demands for electronic devices with superior performance and functionality while reducing their sizes and weight has driven the semiconductor industry to develop towards three‐dimensional integration using through a silicon via (TSV) copper interconnect. In this Letter, the key enabling technologies such as barrier and seed layers preparation by electron beam evaporation and copper fast‐filling into deep microvias that are void‐free are investigated. The deep vertical microvias filled by copper that are void‐free are achieved by a multi‐step electroplating process. Also, the resistance of single vertical TSVs is tested. Furthermore, the cross‐sections and the scanning electron microscopy of vertical microvias are provided and examined.
Synthesis of three‐dimensional porous Cu2O microspheres by template‐free solvothermal method
Authors: Zou Jing , Ma Jinai , Jiang Jizhou , Zhang Yuanxiao , Li Lu , Wan Qijin
Published: June 2013

Three‐dimensional (3D) porous Cu2O microspheres were successfully synthesised by a simple template‐free solvothermal method. Systematic studies showed that solvent, precipitator and temperature reaction parameters played a key role in controlling the morphology and structure of Cu2O. The crystallisation, morphology and composition of the as‐prepared Cu2O was characterised by X‐ray diffraction, a scanning electron microscope and energy‐dispersive spectroscopy, respectively. It revealed that the 3D porous Cu2O microspheres were built from small 2D nanosheets with a thickness of 50–80 nm. Cyclic voltammetry was applied to investigate the electrochemical performance of the products. It was found that the 3D porous Cu2O microspheres possessed high electrocatalytic activity. The growth mechanism of the 3D porous Cu2O microspheres was proposed with a 3D molecule model.
Effects of milling and subsequent heat treatment on preparation of mullite–zirconia nanocomposites
Authors: Ghaffari Somaye , Alizadeh Masoud , Asadian Keivan , Ebadzadeh Touradj , Ghanbari Arezoo
Published: June 2013

Mullite–zirconia composites were fabricated through reaction sintering of mechanically activated alumina and zircon powder mixtures. X‐ray diffraction results showed that increasing milling time resulted in gradual weakening and broadening of alumina and zircon peaks. For the sample milled for 70 h in which there are no peaks present from zircon, heating at 1200°C resulted in the reappearance of the zircon peaks. Samples sintered at 1500°C achieved complete formation of mullite and zirconia. These samples exhibited the following physical and mechanical properties: density 3.87 g/cm3, open porosity 3.45%, hardness 11.44 ± 0.3 GPa and fracture toughness 4.7 Mpam1/2.
Comparative study of structural, mechanical and electrical properties of Ni0.8Co0.1Cu0.05Mn0.05Fe2O4 prepared from different combustion routes
Authors: Jadhav P.S. , Patankar Ketaki K. , Mathe V.L. , Puri V.
Published: June 2013

Comparative studies on the structural, mechanical and electric properties of Ni0.8Co0.1Cu0.05Mn0.05Fe2O4 prepared by solid state combustion and solution combustion routes were studied. The X‐ray diffraction patterns reveal the cubic spinel phase formation with an extra Fe2O3 phase for Ni0.8Co0.1Cu0.05Mn0.05Fe2O4 prepared by the solid state combustion method in contrast to the single cubic spinel phase formation for ferrites obtained from other routes. Scanning electron microscopic images show loosely agglomerated grains with comparatively large grain size for Ni0.8Co0.1Cu0.05Mn0.05Fe2O4 prepared by solid state combustion, whereas there are well defined grains with distinct grain boundaries and smaller grain size for solution combustion route ferrite. Micro‐strains calculated from XRD show a higher value for ferrite obtained from the solution combustion method route. The Young's modulus also show higher values for ferrite prepared from solution combustion, asserting comparatively high spontaneous magnetostriction in the magnetic domains of these ferrite particles. The fourier transform infrared study reveals the octahedral and tetrahedral bond formation in the authors’ ferrites prepared by both methods. Despite comparatively higher values of electric resistivity for solid combustion route ferrite, the authors’ combustion route ferrite can serve as a competent phase for application in transducer or sensor devices.
High resolution electron microscopy of Ag-clusters in crystalline and non-crystalline morphologies grown inside superfluid helium nanodroplets
Authors: Volk Alexander , Thaler Philipp , Koch Markus , Fisslthaler Evelin , Grogger Werner , Ernst Wolfgang E.
Published: June 2013

We present a first investigation of structural properties of Ag clusters with a diameter of up to 5.5 nm grown inside superfluid helium nanodroplets (HeN) and deposited on an amorphous C surface. With high resolution transmission electron microscope images we are able to show that in addition to the crystalline face centered cubic (fcc) structure, noncrystalline icosahedral (Ih), and decahedral (Dh) morphologies are grown. Relative abundances (56% fcc, 31% Dh, and 13% Ih) as well as the size distribution of each morphology (mean diameters \documentclass[12pt]{minimal}\begin{document}$\bar{d}_{\rm fcc}=2.62(5)$\end{document}d¯ fcc =2.62(5) nm, \documentclass[12pt]{minimal}\begin{document}$\bar{d}_{\rm Dh}= 3.34(7)$\end{document}d¯ Dh =3.34(7) nm, and \documentclass[12pt]{minimal}\begin{document}$\bar{d}_{\rm Ih}= 3.93(2)$\end{document}d¯ Ih =3.93(2) nm) do not reflect the situation expected from pure energetic considerations, where small Ihs should be followed by medium sized Dhs and large fccs. Instead, kinetic factors seem to play an important role in the formation of these structures, as it appears to be the case for clusters formed by inert gas aggregation. Considering the low temperatures (0.37 K) and extremely high cooling rates, we discuss basic ideas that might lead to a qualitative picture of the cluster formation process inside HeN.
In what time scale proton transfer takes place in a live CHO cell?
Authors: Mojumdar Supratik Sen , Chowdhury Rajdeep , Mandal Amit Kumar , Bhattacharyya Kankan
Published: June 2013

Excited state proton transfer (ESPT) of pyranine (8-hydroxypyrene-1,3,6-trisulfonate, HPTS) in a live Chinese hamster ovary (CHO) cell is studied by time resolved confocal microscopy. The cytoplasm region of the cell is stained by a photoacid, HPTS (HA). The time constant of initial proton transfer (τPT) in the cell is found to be ∼10 times longer than that in bulk water, while the time constants of recombination (τrec) and dissociation (τdiss) in the cell are ∼3 times and ∼2 times longer, respectively. The slower rate of proton transfer (∼10 times) inside the CHO cell compared to that in bulk water is ascribed to slower solvation dynamics, lower availability of free water molecules, and disruption of hydrogen-bond network inside the cell. Translational and rotational diffusion of HPTS inside a single CHO cell have been investigated by fluorescence correlation spectroscopy (FCS) and picosecond anisotropy measurement, respectively. Both the translational and rotational diffusion slow down inside the live cell. FCS studies indicate that HPTS remains tightly bound to a macromolecule inside the cell.
Electron reemission processes following photoelectron recapture due to post-collision interaction in inner-shell photoionization of water molecules
Authors: Hikosaka Y. , Sawa M. , Nakano M. , Soejima K. , Lablanquie P. , Penent F. , Ito K.
Published: June 2013

Electron reemission following photoelectron recapture due to post-collision interaction has been studied at 0.7 eV the inner-shell photoionization threshold of water molecules, using a multi-electron coincidence method. Electron reemissions after single Auger decay occur from O and OH fragments which are produced by the dissociations of high-n Rydberg H2O+ states populated through photoelectron recapture. In addition, electron reemissions after double Auger decay are identified in triple coincidence events, where autoionization lines from O and O+ fragments are observed.
Path-breaking schemes for nonequilibrium free energy calculations
Authors: Chelli Riccardo , Gellini Cristina , Pietraperzia Giangaetano , Giovannelli Edoardo , Cardini Gianni
Published: June 2013

We propose a path-breaking route to the enhancement of unidirectional nonequilibrium simulations for the calculation of free energy differences via Jarzynski's equality [C. Jarzynski, Phys. Rev. Lett. 78, 2690 (1997)]10.1103/PhysRevLett.78.2690. One of the most important limitations of unidirectional nonequilibrium simulations is the amount of realizations necessary to reach suitable convergence of the work exponential average featuring the Jarzynski's relationship. In this respect, a significant improvement of the performances could be obtained by finding a way of stopping trajectories with negligible contribution to the work exponential average, before their normal end. This is achieved using path-breaking schemes which are essentially based on periodic checks of the work dissipated during the pulling trajectories. Such schemes can be based either on breaking trajectories whose dissipated work exceeds a given threshold or on breaking trajectories with a probability increasing with the dissipated work. In both cases, the computer time needed to carry out a series of nonequilibrium trajectories is reduced up to a factor ranging from 2 to more than 10, at least for the processes under consideration in the present study. The efficiency depends on several aspects, such as the type of process, the number of check-points along the pathway and the pulling rate as well. The method is illustrated through radically different processes, i.e., the helix-coil transition of deca-alanine and the pulling of the distance between two methane molecules in water solution.
High quality transparent TiO2/Ag/TiO2 composite electrode films deposited on flexible substrate at room temperature by sputtering
Authors: Dhar Aritra , Alford T. L.
Published: June 2013

Multilayer structures of TiO2/Ag/TiO2 have been deposited onto flexible substrates by room temperature sputtering to develop indium-free transparent composite electrodes. The effect of Ag thicknesses on optical and electrical properties and the mechanism of conduction have been discussed. The critical thickness (tc) of Ag mid-layer to form a continuous conducting layer is 9.5 nm and the multilayer has been optimized to obtain a sheet resistance of 5.7 Ω/sq and an average optical transmittance of 90% at 590 nm. The Haacke figure of merit (FOM) for tc has one of the highest FOMs with 61.4 × 10−3 Ω−1/sq.
Reversible luminance decay in polymer light-emitting electrochemical cells
Authors: Li Xiaoyu , Gao Jun , Liu Guojun
Published: June 2013

The luminance decay of generic sandwich polymer light-emitting electrochemical cells has been investigated. Under constant current operation, the apparent luminance decay is caused by both the formation of non-emitting black spots, which decreases the active emitting area, and the in situ electrochemical doping, which quenches the luminescence of the light-emitting electrochemical cell film. The latter's effect on luminance, however, can be mostly reversed by letting the electrochemical doping relax. A dramatic recovery of luminance is observed when the device is stored without voltage bias and/or moderately heated between consecutive operations. The decay/recovery cycle can be repeated multiple times with little loss of luminance despite the high current density (167 mA/cm2) applied. At lower current density, a freshly made device loses less than 10% of its peak luminance after over 200 h of continuous operation. Polymer light-emitting electrochemical cells therefore possess vastly longer operating lifetime if allowed to recover from the effect of reversible doping.
Broadband microwave absorption of CoNi@C nanocapsules enhanced by dual dielectric relaxation and multiple magnetic resonances
Authors: Wang Han , Dai Yingying , Gong Wenjie , Geng Dianyu , Ma Song , Li Da , Liu Wei , Zhang Zhidong
Published: June 2013

Dual dielectric relaxation of the permittivity and multiple magnetic resonances of the permeability (including one natural resonance and two exchange resonance modes) are observed in CoNi@C nanocapsules in the same 5–17 GHz frequency range which leads to a better electromagnetic-wave absorption than earlier reported for nanocomposites. A reflection loss (RL) exceeding −25 dB is obtained in a wide frequency range of 5–17 GHz when an appropriate absorber thickness between 2 and 4.8 mm is chosen. For a 2 mm absorber layer, a RL value exceeding −10 dB is achieved in the broad frequency range 12–18 GHz, which covers the whole Ku-band.
A microelectromechanically tunable microring resonator composed of freestanding silicon photonic waveguide couplers
Authors: Ikeda Taro , Hane Kazuhiro
Published: June 2013

A tunable silicon photonic microring resonator using a microelectromechanical actuator is proposed. The tunable microring consists of freestanding submicron-wide single-mode waveguides and air-gap couplers. The waveguides are 320 nm in width and 340 nm in thickness. The optical path length of the microring is varied by a displacement of the actuator. The round-trip length of the microring was modulated by 1.7% with the displacement of 1.0 μm, which corresponded to the resonant wavelength shift of 10.0 nm around 1.5 μm wavelength. The rate of the resonant wavelength shift was 1.1 nm/V. The quality factor of the fabricated microring was about 4000. The whole size of the tunable microring with actuator was about 80 μm × 100 μm and the power consumption is negligibly small due to the capacitive operation.
Spatial modulation of critical current density in niobium based Josephson junctions induced by selective heating
Authors: Granata C. , Petti L. , Rippa M. , Rombetto S. , Ruggiero B. , Russo M. , Russo R. , Vettoliere A.
Published: June 2013

Results about induced spatial modulation of critical current density in niobium based Josephson devices by a selective radiation heating are presented. The localized heating inside a single circuit element with a good spatial resolution (less than 1 μm) is made possible by depositing a carbon film on the desired region exploiting the larger absorbance coefficient of carbon (close to 1) with respect to niobium (about 0.2). Measurements of critical current as a function of the external magnetic field on high quality Josephson junctions at T = 4.2 K evidenced that the critical current density was changed only in the absorber covered region, leaving unchanged the critical current density outside that region and ensuring the capability to locally modify the Josephson critical current density. The experimental data have been compared with theoretical predictions obtained by using a suitable junction barrier model based on step-like barrier shape. Such results are very interesting in view of applications in quantum computing, Majorana fermions detection, and superconducting magnetic sensors.
Lattice positions of Sn in Cu2ZnSnS4 nanoparticles and thin films studied by synchrotron X-ray absorption near edge structure analysis
Authors: Zillner E. , Paul A. , Jutimoosik J. , Chandarak S. , Monnor T. , Rujirawat S. , Yimnirun R. , Lin X. Z. , Ennaoui A. , Dittrich Th. , Lux-Steiner M.
Published: June 2013

Lattice positions of Sn in kesterite Cu2ZnSnS4 and Cu2SnS3 nanoparticles and thin films were investigated by XANES (x-ray absorption near edge structure) analysis at the S K-edge. XANES spectra were analyzed by comparison with simulations taking into account anti-site defects and vacancies. Annealing of Cu2ZnSnS4 nanoparticle thin films led to a decrease of Sn at its native and defect sites. The results show that XANES analysis at the S K-edge is a sensitive tool for the investigation of defect sites, being critical in kesterite thin film solar cells.
Aharonov-Bohm oscillations and weak antilocalization in topological insulator Sb2Te3 nanowires
Authors: Hamdou Bacel , Gooth Johannes , Dorn August , Pippel Eckhard , Nielsch Kornelius
Published: June 2013

Recently, it has been theoretically predicted that Sb2Te3 and related materials are 3D topological insulators, a phase of matter that has a bulk bandgap and gapless electronic surface states protected by time-reversal symmetry. We report on low temperature magnetoresistance measurements on single crystalline Sb2Te3 nanowires with different cross sectional areas and high surface-to-volume ratios, synthesized via catalytic growth. The observation of Aharonov-Bohm oscillations and weak antilocalization indicates the presence of topological surface states.
Tensile-strained germanium microdisks
Authors: Ghrib A. , El Kurdi M. , de Kersauson M. , Prost M. , Sauvage S. , Checoury X. , Beaudoin G. , Sagnes I. , Boucaud P.
Published: June 2013

We show that a strong tensile strain can be applied to germanium microdisks using silicon nitride stressors. The transferred strain allows one to control the direct band gap emission that is shifted from 1550 nm up to 2000 nm, corresponding to a biaxial tensile strain around 1%. Both Fabry-Perot and whispering gallery modes are evidenced by room temperature photoluminescence measurements. Quality factors up to 1350 and limited by free carrier absorption of the doped layer are observed for the whispering gallery modes. We discuss the strain profile in the microdisks as a function of the disk geometry. These tensile-strained microdisks are promising candidates to achieve Ge laser emission in compact microresonators.
A Southern Hemisphere Survey of the Galactic Plane at 5 GHz
Authors: Haynes RF , Caswell JL , Simons LWJ
Published: June 2013

Seventy five maps are presented showing the 5 GHz emission from the galactic plane in the range I = 190� ~ 360� .... 40� for - 2� < b < 2� (an area of approximately 600 square egrees). The method of observing and the computer reduction of the data are discussed. the telescope resolution is 4'�1 arc to half-power points and the detection limit for point sources is better than 0�5 Jy.
A Monte Carlo Investigation of E x B Discharges in Molecular Nitrogen
Authors: J Brennan Michael , M Garvie Andrew , J Kelly Lesley
Published: June 2013

A Monte Carlo simulation method has been developed and tested using the ramp model gas proposed by Reid (1979). This method is particularly useful for investigations in gases which must be modelled using many cross sections. This paper reports various phenomena associated with Townsend discharges in ExB fields in nitrogen. Of particular interest is the relative importance of terms in the density gradient expansion of the electron energy distribution function. Simulations are conducted to assist in the interpretation of data from experimental techniques, particularly the 'photon flux' method.
Positronium-Proton Scattering at Low Energies
Authors: Mitroy Jim
Published: June 2013

Calculations of low energy positronium-proton scattering using the close coupling approach are reported at energies below the three-body breakup energy of 0�5 Rydberg. The channel space includes nine physical hydrogen and positronium states and in addition twelve hydrogen and positronium pseudo-states. Total elastic and electron-transfer cross sections are reported at incident energies below the ionisation threshold. Cross sections for electron transfer to the H(n=2) and H(n=3) levels are also reported.
Transport, Quantum Interference and Localisation in Ultrathin Systems with Randomly Corrugated Walls and Interfaces
Authors: Meyerovich A. E. , Stepaniants A.
Published: June 2013

Comparative effects of elastic scattering by random surface inhomogeneities
and bulk impurities are discussed for ultrathin quantised systems. A simple
general surface collision operator is derived outside of the quantum resonance
domain. Analytical and semi-analytical applications to corrugation-defined
localisation and transport in various types of physical systems are presented.
Reduced levels of intracellular reactive oxygen species and apoptotic status are not correlated with increases in cryotolerance of bovine embryos produced in vitro in the presence of antioxidants
Authors: Rocha-Frigoni Nathália A. S. , Leão Beatriz C. S. , Nogueira Ériklis , Accorsi Mônica F. , Mingoti Gisele Z.
Published: June 2013

The effects of intracellular (cysteine and β-mercaptoethanol) and extracellular (catalase) antioxidant supplementation at different times during in vitro production (IVM and/or in vitro culture (IVC)) on bovine embryo development, intracellular reactive oxygen species (ROS) levels, apoptosis and re-expansion rates after a vitrification–thawing process were examined. Blastocyst frequencies were not affected by either antioxidant supplementation (40.5%–56.4%) or the timing of supplementation (41.7%–55.4%) compared with control (48.7%; P > 0.05). Similarly, antioxidants and the moment of supplementation did not affect (P > 0.05) the total number of blastomeres (86.2–90.5 and 84.4–90.5, respectively) compared with control (85.7). However, the percentage of apoptotic cells was reduced (P < 0.05) in groups supplemented during IVM (1.7%), IVC (2.0%) or both (1.8%) compared with control (4.3%). Intracellular ROS levels measured in Day 7 blastocysts were reduced (P < 0.05) in all groups (0.60–0.78), with the exception of the group supplemented with β-mercaptoethanol during IVC (0.88), which did not differ (P > 0.05) from that in the control group (1.00). Re-expansion rates were not affected (P > 0.05) by the treatments (50.0%–93.0%). In conclusion, antioxidant supplementation during IVM and/or IVC reduces intracellular ROS and the rate of apoptosis; however, supplementation does not increase embryonic development and survival after vitrification.
Negotiating narrative
Authors: Philip Gill , Bongelli Ramona , Canestrari Carla , Riccioni Ilaria , Zuczkowski Andrzej
Published: June 2013

Within the framework of KUB Theory (Bongelli and Zuczkowski 2008, Zuczkowski et al. 2011), information communicated verbally can ultimately be reduced to one of three categories: what the speaker knows (Known), what the speaker does not know (Unknown) and what the speaker believes (Believed). Dialogic communication can be considered as an exchange of information originating in one of these categories and directed towards another. The present study investigates the interaction of Known, Unknown and Believed information in the dialogues found in Chapter 10 of Harry Potter and the Deathly Hallows. It demonstrates how these three categories of information can contribute to a reading of the plot and its progression, and also how aspects of the protagonists’ characters emerge through the language they use in their dialogic communication.
Politeness and social utopia in Friedrich Schiller’s Wilhelm Tell
Authors: Björkstrand Christel
Published: June 2013

This paper is an interdisciplinary analysis of Friedrich Schiller’s play Wilhelm Tell (1804). An initial study of its dramatic structure suggests a change in the relationship between the Swiss peasants and nobles. A further analysis, based on Brown’s and Levinson’s politeness theory confirms the development of a social utopia in the play, but also reveals that Wilhelm Tell plays a minor role in the social development described. The comparison of the play with earlier versions of the Tell legend highlights the roles of peasants and nobles in the establishment of the Swiss Confederation and suggests that Schiller elaborated extensively on the idea of a ‘common ground’ among the Swiss from different classes. The comparison between Schiller’s play and the contemporary German philosopher Johann Benjamin Erhard’s essay Über das Recht des Volks zu einer Revolution illustrates that Schiller’s social utopia develops in accordance with contemporary social visions. However, Tell’s act of murder separates him from the other Swiss protagonists in Schiller’s attempt to outline a righteous revolution, different from the one in France.
How to distinguish hypothetical from actual speech in fiction
Authors: Karttunen Laura
Published: June 2013

This paper investigates the connection between counterfactuality and stereotypicality in direct speech representation. In Monika Fludernik’s theory of schematic language representation, quotations typify rather than reproduce, and typicality coincides with stereotypical expressivity in the form discourse particles, among other features. By distinguishing hypothetical speech proper from the more general concept of typifying direct speech, we can see that in fiction hypothetical speech is not always stereotypically expressive. In conversational storytelling, discourse markers serve the functions of source-tracking, emplotment, and expressing the quoter’s emotions and evaluation. I discuss reasons why fiction differs from conversational storytelling in this respect. Fludernik’s treatment of discourse markers or ‘typicality markers’ in direct speech representation is here complemented with Bakhtinian notions of dual expressiveness, speech genres, and the responsive quality of utterances. The arguments presented are illustrated by passages from the fiction of Carol Shields, Peter Bichsel, and Junot Díaz.
Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45
Authors: Roccisana Jennifer , Sadler Jessica B. A. , Bryant Nia J. , Gould Gwyn W.
Published: June 2013

Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target–soluble N-ethylmaleimide–sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using sub­cellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment.
Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
Authors: Weflen Andrew W. , Baier Nina , Tang Qing-Juan , Van den Hof Malon , Blumberg Richard S. , Lencer Wayne I. , Massol Ramiro H.
Published: June 2013

The neonatal receptor for immunoglobulin G (IgG; FcRn) prevents IgG degradation by efficiently sorting IgG into recycling endosomes and away from lysosomes. When bound to IgG-opsonized antigen complexes, however, FcRn traffics cargo into lysosomes, where antigen processing can occur. Here we address the mechanism of sorting when FcRn is bound to multivalent IgG-opsonized antigens. We find that only the unbound receptor or FcRn bound to monomeric IgG is sorted into recycling tubules emerging from early endosomes. Cross-linked FcRn is never visualized in tubules containing the unbound receptor. Similar results are found for transferrin receptor, suggesting a general mechanism of action. Deletion or replacement of the FcRn cytoplasmic tail does not prevent diversion of trafficking to lysosomes upon cross-linking. Thus physical properties of the lumenal ligand–receptor complex appear to act as key determinants for sorting between the recycling and lysosomal pathways by regulating FcRn entry into recycling tubules.
opm: an R package for analysing OmniLog® phenotype microarray data
Authors: Vaas Lea A. I. , Sikorski Johannes , Hofner Benjamin , Fiebig Anne , Buddruhs Nora , Klenk Hans-Peter , Göker Markus
Published: June 2013

Summary:  opm is an R package designed to analyse multidimensional OmniLog® phenotype microarray (PM) data. opm provides management, visualization and statistical analysis of PM data, including curve-parameter estimation and discretization, dedicated and customizable plots, metadata management, automated generation of textual and tabular reports, mapping of substrates to databases, batch conversion of files and export to phylogenetic software in the YAML markup language.

Availability:  opm is distributed under the GPL through the Comprehensive R Archive Network (http://cran.r-project.org/package=opm) along with a comprehensive manual and a user-friendly tutorial. Further information may be found at http://www.dsmz.de/research/microorganisms/projects/.

Contact:  johannes.sikorski@dsmz.de
Triplex-Inspector: an analysis tool for triplex-mediated targeting of genomic loci
Authors: Buske Fabian A. , Bauer Denis C. , Mattick John S. , Bailey Timothy L.
Published: June 2013

Summary: At the heart of many modern biotechnological and therapeutic applications lies the need to target specific genomic loci with pinpoint accuracy. Although landmark experiments demonstrate technological maturity in manufacturing and delivering genetic material, the genomic sequence analysis to find suitable targets lags behind. We provide a computational aid for the sophisticated design of sequence-specific ligands and selection of appropriate targets, taking gene location and genomic architecture into account.

Availability: Source code and binaries are downloadable from www.bioinformatics.org.au/triplexator/inspector.

Contact:  t.bailey@uq.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
An image-based multi-label human protein subcellular localization predictor (iLocator) reveals protein mislocalizations in cancer tissues
Authors: Xu Ying-Ying , Yang Fan , Zhang Yang , Shen Hong-Bin
Published: June 2013

Motivation: Human cells are organized into compartments of different biochemical cellular processes. Having proteins appear at the right time to the correct locations in the cellular compartments is required to conduct their functions in normal cells, whereas mislocalization of proteins can result in pathological diseases, including cancer.

Results: To reveal the cancer-related protein mislocalizations, we developed an image-based multi-label subcellular location predictor, iLocator, which covers seven cellular localizations. The iLocator incorporates both global and local image descriptors and generates predictions by using an ensemble multi-label classifier. The algorithm has the ability to treat both single- and multiple-location proteins. We first trained and tested iLocator on 3240 normal human tissue images that have known subcellular location information from the human protein atlas. The iLocator was then used to generate protein localization predictions for 3696 protein images from seven cancer tissues that have no location annotations in the human protein atlas. By comparing the output data from normal and cancer tissues, we detected eight potential cancer biomarker proteins that have significant localization differences with P-value < 0.01.

Availability:  http://www.csbio.sjtu.edu.cn/bioinf/iLocator/

Contact:  hbshen@sjtu.edu.cn or zhng@umich.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Insights into polypharmacology from drug-domain associations
Authors: Moya-García Aurelio A. , Ranea Juan A. G.
Published: June 2013

Motivation: Polypharmacology (the ability of a single drug to affect multiple targets) is a key feature that may explain part of the decreasing success of conventional drug discovery strategies driven by the quest for drugs to act selectively on a single target. Most drug targets are proteins that are composed of domains (their structural and functional building blocks).

Results: In this work, we model drug–domain networks to explore the role of protein domains as drug targets and to explain drug polypharmacology in terms of the interactions between drugs and protein domains. We find that drugs are organized around a privileged set of druggable domains.

Conclusions: Protein domains are a good proxy for drug targets, and drug polypharmacology emerges as a consequence of the multi-domain composition of proteins.

Contact:  amoyag@uma.es

Supplementary information: Supplementary data are available at Bioinformatics online.
DIGEP-Pred: web service for in silico prediction of drug-induced gene expression profiles based on structural formula
Authors: Lagunin Alexey , Ivanov Sergey , Rudik Anastasia , Filimonov Dmitry , Poroikov Vladimir
Published: June 2013

Summary: Experimentally found gene expression profiles are used to solve different problems in pharmaceutical studies, such as drug repositioning, resistance, toxicity and drug–drug interactions. A special web service, DIGEP-Pred, for prediction of drug-induced changes of gene expression profiles based on structural formulae of chemicals has been developed. Structure–activity relationships for prediction of drug-induced gene expression profiles were determined by Prediction of Activity Spectra for Substances (PASS) software. Comparative Toxicogenomics Database with data on the known drug-induced gene expression profiles of chemicals was used to create mRNA- and protein-based training sets. An average prediction accuracy for the training sets (ROC AUC) calculated by leave-one-out cross-validation on the basis of mRNA data (1385 compounds, 952 genes, 500 up- and 475 down-regulations) and protein data (1451 compounds, 139 genes, 93 up- and 55 down-regulations) exceeded 0.85.

Availability: Freely available on the web at http://www.way2drug.com/GE.

Contact:  alexey.lagunin@ibmc.msk.ru

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Amsterdam Chamber of Insurance and Average: A New Phase in Formal Contract Enforcement (Late Sixteenth and Seventeenth Centuries)
Authors: Go Sabine C. P. J.
Published: June 2013

There is an on-going debate among scholars from various disciplines about economic institutions and their impact on economic development. The case of the Amsterdam Chamber of Insurance is relevant to this discussion and in particular to the part that focuses on the nature and development of contract enforcement mechanisms. Marine insurance was introduced in Amsterdam in the mid-sixteenth century and soon the insurance industry developed into a prospering business. Its development was of great importance to the expansion of long-distance trade as it reduced the financial consequences of risks inherent to maritime trade. However, the new industry with its complex contracts was prone to misunderstandings, fraud and deception, creating the need for an independent, specialised court. The Chamber of Insurance was established as a generalised court, rather than a particularised court as was the case in cities that preceded Amsterdam’s trade dominance. Why did the Amsterdam municipality choose to set up this court and what were the implications? A recently discovered Statute Book of the Chamber gives insight into why the Chamber was established, how it functioned within the setting of Europe’s dominant trade centre and how it has affected the development of similar courts in the Netherlands.
Assembly and characterization of foot-and-mouth disease virus empty capsid particles expressed within mammalian cells
Authors: Gullberg Maria , Muszynski Bartosz , Organtini Lindsey J. , Ashley Robert E. , Hafenstein Susan L. , Belsham Graham J. , Polacek Charlotta
Published: June 2013

The foot-and-mouth disease virus (FMDV) structural protein precursor, P1-2A, is cleaved by the virus-encoded 3C protease (3Cpro) into the capsid proteins VP0, VP1 and VP3 (and 2A). In some systems, it is difficult to produce large amounts of these processed capsid proteins since 3Cpro can be toxic for cells. The expression level of 3Cpro activity has now been reduced relative to the P1-2A, and the effect on the yield of processed capsid proteins and their assembly into empty capsid particles within mammalian cells has been determined. Using a vaccinia-virus-based transient expression system, P1-2A (from serotypes O and A) and 3Cpro were expressed from monocistronic cDNA cassettes as P1-2A-3C, or from dicistronic cassettes with the 3Cpro expression dependent on a mutant FMDV internal ribosome entry site (IRES) (designated P1-2A-mIRES-3C). The effects of using a mutant 3Cpro with reduced catalytic activity or using two different mutant IRES elements (the wt GNRA tetraloop sequence GCGA converted, in the cDNA, to GAGA or GTTA) were analysed. For both serotypes, the P1-2A-mIRES-3C construct containing the inefficient GTTA mutant IRES produced the highest amount of processed capsid proteins. These products self-assembled to form FMDV empty capsid particles, which have a related, but distinct, morphology (as determined by electron microscopy and reconstruction) from that determined previously by X-ray crystallography. The assembled empty capsids bind, in a divalent cation-dependent manner, to the RGD-dependent integrin αvβ6, a cellular receptor for FMDV, and are recognized appropriately in serotype-specific antigen ELISAs.
An interaction between the methyltransferase and RNA dependent RNA polymerase domains of the West Nile virus NS5 protein
Authors: Tan Cindy S. E. , Hobson-Peters Jody M. , Stoermer Martin J. , Fairlie David P. , Khromykh Alexander A. , Hall Roy A.
Published: June 2013

The flavivirus nonstructural protein 5 (NS5) is a large protein that is structurally conserved among members of the genus, making it an attractive target for antiviral drug development. The protein contains a methyltransferase (MTase) domain and an RNA dependent RNA polymerase (POL) domain. Previous studies with dengue viruses have identified a genetic interaction between residues 46–49 in the αA3-motif in the MTase and residue 512 in POL. These genetic interactions are consistent with structural modelling of these domains in West Nile virus (WNV) NS5 that predict close proximity of these regions of the two domains, and potentially a functional interaction mediated via the αA3-motif. To demonstrate an interaction between the MTase and POL domains of the WNV NS5 protein, we co-expressed affinity-tagged recombinant MTase and POL proteins in human embryonic kidney cells with simian virus 40 large T antigen (HEK293T cells) and performed pulldown assays using an antibody to the flag tag on POL. Western blot analysis with an anti-MTase mAb revealed that the MTase protein was specifically co-immunoprecipitated with POL, providing the first evidence of a specific interaction between these domains. To further assess the role of the αA3 helix in this interaction, selected residues in this motif were mutated in the recombinant MTase and the effect on POL interaction determined by the pulldown assay. These mutations were also introduced into a WNV infectious clone (FLSDX) and the replication properties of these mutant viruses assessed. While none of the αA3 mutations had a significant effect on the MTase–POL association in pulldown assays, suggesting that these residues were not specific to the interaction, an E46L mutation completely abolished virus viability indicating a critical requirement of this residue in replication. Failure to generate compensatory mutations in POL to rescue replication, even after several passages of the transfection supernatant in Vero cells, precluded further conclusion of the role of this residue in the context of MTase–POL interactions.
Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population
Authors: Schmitz Robert J. , He Yupeng , Valdés-López Oswaldo , Khan Saad M. , Joshi Trupti , Urich Mark A. , Nery Joseph R. , Diers Brian , Xu Dong , Stacey Gary , Ecker Joseph R.
Published: June 2013

Cytosine DNA methylation is one avenue for passing information through cell divisions. Here, we present epigenomic analyses of soybean recombinant inbred lines (RILs) and their parents. Identification of differentially methylated regions (DMRs) revealed that DMRs mostly cosegregated with the genotype from which they were derived, but examples of the uncoupling of genotype and epigenotype were identified. Linkage mapping of methylation states assessed from whole-genome bisulfite sequencing of 83 RILs uncovered widespread evidence for local methylQTL. This epigenomics approach provides a comprehensive study of the patterns and heritability of methylation variants in a complex genetic population over multiple generations, paving the way for understanding how methylation variants contribute to phenotypic variation.
The maize methylome influences mRNA splice sites and reveals widespread paramutation-like switches guided by small RNA
Authors: Regulski Michael , Lu Zhenyuan , Kendall Jude , Donoghue Mark T.A. , Reinders Jon , Llaca Victor , Deschamps Stephane , Smith Andrew , Levy Dan , McCombie W. Richard , Tingey Scott , Rafalski Antoni , Hicks James , Ware Doreen , Martienssen Robert A.
Published: June 2013

The maize genome, with its large complement of transposons and repeats, is a paradigm for the study of epigenetic mechanisms such as paramutation and imprinting. Here, we present the genome-wide map of cytosine methylation for two maize inbred lines, B73 and Mo17. CG (65%) and CHG (50%) methylation (where H = A, C, or T) is highest in transposons, while CHH (5%) methylation is likely guided by 24-nt, but not 21-nt, small interfering RNAs (siRNAs). Correlations with methylation patterns suggest that CG methylation in exons (8%) may deter insertion of Mutator transposon insertion, while CHG methylation at splice acceptor sites may inhibit RNA splicing. Using the methylation map as a guide, we used low-coverage sequencing to show that parental methylation differences are inherited by recombinant inbred lines. However, frequent methylation switches, guided by siRNA, persist for up to eight generations, suggesting that epigenetic inheritance resembling paramutation is much more common than previously supposed. The methylation map will provide an invaluable resource for epigenetic studies in maize.
A Common Fungal Associate of the Spruce Bark Beetle Metabolizes the Stilbene Defenses of Norway Spruce
Authors: Hammerbacher Almuth , Schmidt Axel , Wadke Namita , Wright Louwrance P. , Schneider Bernd , Bohlmann Joerg , Brand Willi A. , Fenning Trevor M. , Gershenzon Jonathan , Paetz Christian
Published: June 2013

Norway spruce (Picea abies) forests suffer periodic fatal attacks by the bark beetle Ips typographus and its fungal associate, Ceratocystis polonica. Norway spruce protects itself against fungal and bark beetle invasion by the production of terpenoid resins, but it is unclear whether resins or other defenses are effective against the fungus. We investigated stilbenes, a group of phenolic compounds found in Norway spruce bark with a diaryl-ethene skeleton with known antifungal properties. During C. polonica infection, stilbene biosynthesis was up-regulated, as evidenced by elevated transcript levels of stilbene synthase genes. However, stilbene concentrations actually declined during infection, and this was due to fungal metabolism. C. polonica converted stilbenes to ring-opened, deglycosylated, and dimeric products. Chromatographic separation of C. polonica protein extracts confirmed that these metabolites arose from specific fungal enzyme activities. Comparison of C. polonica strains showed that rapid conversion of host phenolics is associated with higher virulence. C. polonica is so well adapted to its host’s chemical defenses that it is even able to use host phenolic compounds as its sole carbon source.
Cross-Repressive Interactions between SOC1 and the GATAs GNC and GNL/CGA1 in the Control of Greening, Cold Tolerance, and Flowering Time in Arabidopsis
Authors: Richter René , Bastakis Emmanouil , Schwechheimer Claus
Published: June 2013

The paralogous and functionally redundant GATA transcription factors GNC (for GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM INVOLVED) and GNL/CGA1 (for GNC-LIKE/CYTOKININ-RESPONSIVE GATA FACTOR1) from Arabidopsis (Arabidopsis thaliana) promote greening and repress flowering downstream from the phytohormone gibberellin. The target genes of GNC and GNL with regard to flowering time control have not been identified as yet. Here, we show by genetic and molecular analysis that the two GATA factors act upstream from the flowering time regulator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) to directly repress SOC1 expression and thereby repress flowering. Interestingly, this analysis inversely also reveals that the MADS box transcription factor SOC1 directly represses GNC and GNL expression to control cold tolerance and greening, two further physiological processes that are under the control of SOC1. In summary, these findings support the case of a cross-repressive interaction between the GATA factors GNC and GNL and the MADS box transcription factor SOC1 in flowering time control on the one side and greening and cold tolerance on the other that may be governed by the various signaling inputs that are integrated at the level of SOC1 expression.