bluuebunny/crossref_metadata_2025 huggingface dataset:
High-density Two-Dimensional Small Polaron Gas in a Delta-Doped Mott Insulator
Authors: Ouellette Daniel G. , Moetakef Pouya , Cain Tyler A. , Zhang Jack Y. , Stemmer Susanne , Emin David , Allen S. James
Published: November 2013

Heterointerfaces in complex oxide systems open new arenas in which to test models of strongly correlated material, explore the role of dimensionality in metal-insulator-transitions (MITs) and small polaron formation. Close to the quantum critical point Mott MITs depend on band filling controlled by random disordered substitutional doping. Delta-doped Mott insulators are potentially free of random disorder and introduce a new arena in which to explore the effect of electron correlations and dimensionality. Epitaxial films of the prototypical Mott insulator GdTiO3 are delta-doped by substituting a single (GdO)+1 plane with a monolayer of charge neutral SrO to produce a two-dimensional system with high planar doping density. Unlike metallic SrTiO3 quantum wells in GdTiO3 the single SrO delta-doped layer exhibits thermally activated DC and optical conductivity that agree in a quantitative manner with predictions of small polaron transport but with an extremely high two-dimensional density of polarons, ~7 × 1014 cm−2.
Coexistence of sexual individuals and genetically isolated asexual counterparts in a thrips
Authors: Kobayashi Kazuya , Yoshimura Jin , Hasegawa Eisuke
Published: November 2013

Sex is a paradoxical phenomenon because it is less efficient compared with asexual reproduction. To resolve this paradox we need a direct comparison between sexual and asexual forms. In many organisms, however, sexual and asexual forms do not occur in the same habitat, or at the same time. In a few cases where sexual and asexual forms are found in a single population, some (though rare) genetic exchange is usually detected between the two forms. When genetic exchange occurs a direct comparison is impossible. Here we investigate a thrips exhibiting both sexual and asexual forms (lineages) that are morphologically indistinguishable. We examine if the two forms are genetically isolated. Phylogeny based on nuclear genes confirms that the sexual and asexual lineages are genetically differentiated. Thus we demonstrate that the current system has certain advantages over existing and previously used model systems in the evolution of sexual reproduction.
Behavior of surfactants in aqueous dispersions of single-walled carbon nanotubes
Authors: Kato Haruhisa , Nakamura Ayako , Horie Masanori
Published: November 2013

Industrial surfactants were strongly adsorbed on the surface of the SWCNTs, and did not readily exchange with artificial lung surfactant.
Dependence of the electron transfer capacity on the kinetics of quinone-mediated Fe(iii) reduction by two iron/humic reducing bacteria
Authors: Li Xiaomin , Liu Tongxu , Liu Liang , Li Fangbai
Published: November 2013

The quinone-mediated microbial Fe(iii) reduction is strongly related to their electron transfer capacities and redox equilibria.
The beam diagnostic instruments in Beijing radioactive ion-beam facilities isotope separator on-line
Authors: Ma Y. , Cui B. , Ma R. , Tang B. , Chen L. , Huang Q. , Jiang W.
Published: November 2013

The beam diagnostic instruments for Beijing Radioactive Ion-beam Facilities Isotope Separator On-Line are introduced [B. Q. Cui, Z. H. Peng, Y. J. Ma, R. G. Ma, B. Tang, T. Zhang, and W. S. Jiang, Nucl. Instrum. Methods 266, 4113 (2008); T. J. Zhang, X. L. Guan, and B. Q. Cui, in Proceedings of APAC 2004, Gyeongju, Korea, 2004, http://www.jacow.org, p. 267]. For low intensity ion beam [30–300 keV/1 pA–10 μA], the beam profile monitor, the emittance measurement unit, and the analyzing slit will be installed. For the primary proton beam [100 MeV/200 μA], the beam profile scanner will be installed. For identification of the nuclide, a beam identification unit will be installed. The details of prototype of the beam diagnostic units and some experiment results will be described in this article.
Multiscale multiphysics and multidomain models—Flexibility and rigidity
Authors: Xia Kelin , Opron Kristopher , Wei Guo-Wei
Published: November 2013

The emerging complexity of large macromolecules has led to challenges in their full scale theoretical description and computer simulation. Multiscale multiphysics and multidomain models have been introduced to reduce the number of degrees of freedom while maintaining modeling accuracy and achieving computational efficiency. A total energy functional is constructed to put energies for polar and nonpolar solvation, chemical potential, fluid flow, molecular mechanics, and elastic dynamics on an equal footing. The variational principle is utilized to derive coupled governing equations for the above mentioned multiphysical descriptions. Among these governing equations is the Poisson-Boltzmann equation which describes continuum electrostatics with atomic charges. The present work introduces the theory of continuum elasticity with atomic rigidity (CEWAR). The essence of CEWAR is to formulate the shear modulus as a continuous function of atomic rigidity. As a result, the dynamics complexity of a macromolecular system is separated from its static complexity so that the more time-consuming dynamics is handled with continuum elasticity theory, while the less time-consuming static analysis is pursued with atomic approaches. We propose a simple method, flexibility-rigidity index (FRI), to analyze macromolecular flexibility and rigidity in atomic detail. The construction of FRI relies on the fundamental assumption that protein functions, such as flexibility, rigidity, and energy, are entirely determined by the structure of the protein and its environment, although the structure is in turn determined by all the interactions. As such, the FRI measures the topological connectivity of protein atoms or residues and characterizes the geometric compactness of the protein structure. As a consequence, the FRI does not resort to the interaction Hamiltonian and bypasses matrix diagonalization, which underpins most other flexibility analysis methods. FRI's computational complexity is of \documentclass[12pt]{minimal}\begin{document}${\cal O}(N^2)$\end{document}O(N2) at most, where N is the number of atoms or residues, in contrast to \documentclass[12pt]{minimal}\begin{document}${\cal O}(N^3)$\end{document}O(N3) for Hamiltonian based methods. We demonstrate that the proposed FRI gives rise to accurate prediction of protein B-Factor for a set of 263 proteins. We show that a parameter free FRI is able to achieve about 95% accuracy of the parameter optimized FRI. An interpolation algorithm is developed to construct continuous atomic flexibility functions for visualization and use with CEWAR.
A density functional theory study of magneto-electric Jones birefringence of noble gases, furan homologues, and mono-substituted benzenes
Authors: Fahleson Tobias , Norman Patrick , Coriani Sonia , Rizzo Antonio , Rikken Geert L. J. A.
Published: November 2013

We report on the results of a systematic ab initio study of the Jones birefringence of noble gases, of furan homologues, and of monosubstituted benzenes, in the gas phase, with the aim of analyzing the behavior and the trends within a list of systems of varying size and complexity, and of identifying candidates for a combined experimental/theoretical study of the effect. We resort here to analytic linear and nonlinear response functions in the framework of time-dependent density functional theory. A correlation is made between the observable (the Jones constant) and the atomic radius for noble gases, or the permanent electric dipole and a structure/chemical reactivity descriptor as the para Hammett constant for substituted benzenes.
Reconfigurable acquisition system with integrated optics for a portable flow cytometer
Authors: Kirleis Matthew A. , Mathews Scott A. , Verbarg Jasenka , Erickson Jeffrey S. , Piqué Alberto
Published: November 2013

Portable and inexpensive scientific instruments that are capable of performing point of care diagnostics are needed for applications such as disease detection and diagnosis in resource-poor settings, for water quality and food supply monitoring, and for biosurveillance activities in autonomous vehicles. In this paper, we describe the development of a compact flow cytometer built from three separate, customizable, and interchangeable modules. The instrument as configured in this work is being developed specifically for the detection of selected Centers for Disease Control (CDC) category B biothreat agents through a bead-based assay: E. coli O157:H7, Salmonella, Listeria, and Shigella. It has two-color excitation, three-color fluorescence and light scattering detection, embedded electronics, and capillary based flow. However, these attributes can be easily modified for other applications such as cluster of differentiation 4 (CD4) counting. Proof of concept is demonstrated through a 6-plex bead assay with the results compared to a commercially available benchtop-sized instrument.
Large magnetocapacitance in electronic ferroelectric manganite systems
Authors: Chowdhury Ujjal , Goswami Sudipta , Bhattacharya Dipten , Midya Arindam , Mandal P. , Das Pintu , Mukovskii Ya. M.
Published: November 2013

We have observed a sizable positive magnetocapacitance (∼5%–90%) in perovskite Pr0.55Ca0.45MnO3 and bilayer Pr(Sr0.1Ca0.9)2Mn2O7 system under 5 T magnetic field across 20–100 K below the magnetic transition point TN. The magnetodielectric effect, on the other hand, exhibits a crossover: (a) from positive to negative for the perovskite system and (b) from negative to positive for the bilayer system over the same temperature range. The bilayer Pr(Sr0.1Ca0.9)2Mn2O7 system exhibits a sizable anisotropy as well. We have also noticed the influence of magnetic field on the dielectric relaxation characteristics of these systems. These systems belong to a class of improper ferroelectrics and are expected to exhibit charge/orbital order driven ferroelectric polarization below the transition point TCO. Large magnetocapacitance in these systems shows a typical multiferroic behavior even though the ferroelectric polarization is small in comparison to that of other ferroelectrics.
Mimic synaptic behavior with a single floating gate transistor: A MemFlash synapse
Authors: Ziegler Martin , Kohlstedt Hermann
Published: November 2013

Memristive devices are promising candidates for artificial synapses in neuromorphic circuits. We provide evidence that a single floating gate transistor operating in a memristive mode can be used to mimic synaptic functionality. To ensure the memristive operation mode, the three-terminal device is reduced to a two-terminal device in such a way that the device resistance varied accordingly to the charge flow through the device during source-drain voltage application. Furthermore, based on Hebbian learning, a synaptic analytical expression for the learning rate of this device is derived. The experimental findings are theoretically supported by a capacitive based model. The presented two-terminal MemFlash-synapse can be considered as a potential substitute for any memristive synapses in neuromorphic circuits, cross bar arrays, or reconfigurable logics, and is compatible with state-of-the-art Si-fabrication technology.
Intermolecular potentials and the accurate prediction of the thermodynamic properties of water
Authors: Shvab I. , Sadus Richard J.
Published: November 2013

The ability of intermolecular potentials to correctly predict the thermodynamic properties of liquid water at a density of 0.998 g/cm3 for a wide range of temperatures (298–650 K) and pressures (0.1–700 MPa) is investigated. Molecular dynamics simulations are reported for the pressure, thermal pressure coefficient, thermal expansion coefficient, isothermal and adiabatic compressibilities, isobaric and isochoric heat capacities, and Joule-Thomson coefficient of liquid water using the non-polarizable SPC/E and TIP4P/2005 potentials. The results are compared with both experiment data and results obtained from the ab initio-based Matsuoka-Clementi-Yoshimine non-additive (MCYna) [J. Li, Z. Zhou, and R. J. Sadus, J. Chem. Phys. 127, 154509 (2007)] potential, which includes polarization contributions. The data clearly indicate that both the SPC/E and TIP4P/2005 potentials are only in qualitative agreement with experiment, whereas the polarizable MCYna potential predicts some properties within experimental uncertainty. This highlights the importance of polarizability for the accurate prediction of the thermodynamic properties of water, particularly at temperatures beyond 298 K.
Electronic band structure imaging of three layer twisted graphene on single crystal Cu(111)
Authors: Marquez Velasco J. , Kelaidis N. , Xenogiannopoulou E. , Raptis Y. S. , Tsoutsou D. , Tsipas P. , Speliotis Th. , Pilatos G. , Likodimos V. , Falaras P. , Dimoulas A.
Published: November 2013

Few layer graphene (FLG) is grown on single crystal Cu(111) by Chemical Vapor Deposition, and the electronic valence band structure is imaged by Angle-Resolved Photo-Emission Spectroscopy. It is found that graphene essentially grows polycrystalline. Three nearly ideal Dirac cones are observed along the Cu Γ¯K¯ direction in k-space, attributed to the presence of ∼4° twisted three layer graphene with negligible interlayer coupling. The number of layers and the stacking order are compatible with Raman data analysis demonstrating the complementarity of the two techniques for a more accurate characterization of FLG.
In vitro thermal diffusivity measurements as aging process study in human tooth hard tissues
Authors: Carvalho A. P. N. , Dias D. T. , Bedeschi V. C. , Nakamura O. , Oliveira M. Q.
Published: November 2013

In the present work, the Open Photoacoustic Cell Technique was used to find effective thermal diffusivity of human tooth hard tissues, a thermal variable of great interest in the biological science, and inorganic materials. The aging process of the tooth enamel and dentin was analyzed through its effective thermal diffusivity. The study in vitro of these samples showed an increase and posterior decrease with aging of the samples. The values found for the enamel and dentin samples, varied from (36−55)×10−4 cm2 s−1 and (20−32)×10−4 cm2 s−1, respectively.
Metal-like self-organization of periodic nanostructures on silicon and silicon carbide under femtosecond laser pulses
Authors: Gemini Laura , Hashida Masaki , Shimizu Masahiro , Miyasaka Yasuhiro , Inoue Shunsuke , Tokita Shigeki , Limpouch Jiri , Mocek Tomas , Sakabe Shuji
Published: November 2013

Periodic structures were generated on Si and SiC surfaces by irradiation with femtosecond laser pulses. Self-organized structures with spatial periodicity of approximately 600 nm appear on silicon and silicon carbide in the laser fluence range just above the ablation threshold and upon irradiation with a large number of pulses. As in the case of metals, the dependence of the spatial periodicity on laser fluence can be explained by the parametric decay of laser light into surface plasma waves. The results show that the proposed model might be universally applicable to any solid state material.
Role of flexoelectricity in electro-optical properties of hybrid aligned nematic layers
Authors: Buczkowska M. , Derfel G.
Published: November 2013

The electro-optical effects occurring under the action of AC and DC electric field in hybrid aligned nematic layers placed between crossed polarizers were simulated numerically. Switching between dark and bright states of such systems was analyzed. The role of flexoelectricity in the behavior of the layers was studied, thanks to the fact that the flexoelectric contribution to switching was present in the DC case and cancelled in the AC case. It was found that fast switching was favored by negative flexoelectric parameters or by large difference between voltages at which the both states existed.
Multilevel and long retentive resistive switching in low temperature nanostructured Cu/SiOx-W-SiOx/Pt
Authors: Wang Jinzhi , Chen Renjie , Wang Fang , Yan Aru , Hu Guoqi , Li Runwei , Liu Xianglian , Chi Zhenhua
Published: November 2013

Amorphous SiOx-based memory films are fabricated at room temperature, and study on their resistive switching characteristics and improvement approaches is performed. Multilevel resistive states with large ratio 1: ∼102: 3 × 105 and long retention exceeding 2 × 106 s at ambient temperature and humidity are observed in Cu/SiOx (9 nm)-W (∼2 nm)-SiOx (9 nm)/Pt ultrathin stack. Nonvolatile switching is consistently realized in microscopy. Based on investigations of microscopic conduction and microstructure, tungsten incorporation with copper as relay bridges for conducting filaments is proposed to attribute to the performance improvement and the multilevel switching mechanism.
Frequency conversion in magnetoelectric composites for quasi-static magnetic field detection
Authors: Liu Yuting , Jiao Jie , Ma Jiashuai , Ren Bo , Li Lingying , Zhao Xiangyong , Luo Haosu , Shi Ling
Published: November 2013

We present the detection of quasi-static magnetic fields in Metglas/piezofiber magnetoelectric (ME) composites through frequency conversion. The nonlinear coefficient over wide frequency range (1–30 kHz) was measured, and the noise behavior at sideband was also studied. It was found that the major part of the sideband noise originated from the driven current. Due to the characteristic of the driven current, the sideband noise increased with the increase of the frequency. The ME sensor exhibited excellent performance at low frequencies, sensitivities of 10 mHz, 100 mHz, and 1 Hz were 200 pT, 150 pT, and 20 pT, respectively.
Strong interference in ultrathin semiconducting layers on a wide variety of substrate materials
Authors: Schlich Franziska F. , Spolenak Ralph
Published: November 2013

Optical coatings based on ultrathin highly absorbing dielectrics on metals are attractive because of the considerable reduction of their thickness compared to conventional dielectric coatings. We demonstrate that the underlying material of these optical coatings is not limited only to metals as assumed previously. Instead, it can be replaced by any material if several layers are used such that the effective optical constant resembles that of a highly reflective metal. Consequently, the optical properties are tunable by the choice of material, the number of layers, and the layer thickness and are hence more adaptable to the potential application.
Photothermal mapping and free-space laser tuning of toroidal optical microcavities
Authors: Heylman Kevin D. , Goldsmith Randall H.
Published: November 2013

We report a tuning method for ultrahigh-quality factor toroidal optical microcavities capable of rapid modulation and resonance position control over multiple decades. A free-space laser is focused onto the resonator's silicon support pillar, rapidly heating the mode-containing silica. Microcavity photothermal response is spatially mapped. Resonance shift varies inversely with pillar diameter, reaching 1.5 × 105 fm/mW at 2 μm diameter, allowing switching with 1 μW control power. Larger pillar resonators can be modulated at high speeds (>4 kHz). Heat flow simulations accurately model observed shifts. This versatile approach fulfills an outstanding need for fast, flexible control over toroid resonances.
On the stability analysis of a pair of van der Pol oscillators with delayed self-connection, position and velocity couplings
Authors: Hu Kun , Chung Kwok-wai
Published: November 2013

In this paper, we perform a stability analysis of a pair of van der Pol oscillators with delayed self-connection, position and velocity couplings. Bifurcation diagram of the damping, position and velocity coupling strengths is constructed, which gives insight into how stability boundary curves come into existence and how these curves evolve from small closed loops into open-ended curves. The van der Pol oscillator has been considered by many researchers as the nodes for various networks. It is inherently unstable at the zero equilibrium. Stability control of a network is always an important problem. Currently, the stabilization of the zero equilibrium of a pair of van der Pol oscillators can be achieved only for small damping strength by using delayed velocity coupling. An interesting question arises naturally: can the zero equilibrium be stabilized for an arbitrarily large value of the damping strength? We prove that it can be. In addition, a simple condition is given on how to choose the feedback parameters to achieve such goal. We further investigate how the in-phase mode or the out-of-phase mode of a periodic solution is related to the stability boundary curve that it emerges from a Hopf bifurcation. Analytical expression of a periodic solution is derived using an integration method. Some illustrative examples show that the theoretical prediction and numerical simulation are in good agreement.
Light focusing using epsilon-near-zero metamaterials
Authors: Zhu Weiren , Si Li-Ming , Premaratne Malin
Published: November 2013

We present a strategy of focusing light using epsilon-near-zero metamaterials with embedded dielectric cylinder. The focusing mechanism is analytically investigated, and its accuracy is substantiated by rigorous full-wave simulations. It is found that the focusing intensity is highly depend on the embedded medium and its size, and the magnetic field amplitude of the focused beam itself can reach as high as 98.2 times the incident field. Owing to its versatility, the proposed light focusing system is sure to find applications in fields such as bio-sensing and in nonlinear optics.
Anisotropic thermal conductivity of thin polycrystalline oxide samples
Authors: Tiwari A. , Boussois K. , Nait-Ali B. , Smith D. S. , Blanchart P.
Published: November 2013

This paper reports about the development of a modified laser-flash technique and relation to measure the in-plane thermal diffusivity of thin polycrystalline oxide samples. Thermal conductivity is then calculated with the product of diffusivity, specific heat and density. Design and operating features for evaluating in-plane thermal conductivities are described. The technique is advantageous as thin samples are not glued together to measure in-plane thermal conductivities like earlier methods reported in literature. The approach was employed to study anisotropic thermal conductivity in alumina sheet, textured kaolin ceramics and montmorillonite. Since it is rare to find in-plane thermal conductivity values for such anisotropic thin samples in literature, this technique offers a useful variant to existing techniques.
A Sensitive Catalytic Wave Formed by Electrochemical Reduction of Morin in the Presence of an Oxidant KIO3
Authors: Cheng Sikun , Dong Yanhua , Wu Yayan , Song Junfeng , Zhao Chuan
Published: November 2013

The investigation of the electrogenerated free radical of morin reacting with an oxidant is helpful in understanding its antioxidant pharmacology. In phosphate buffer (pH 5.6 ± 0.1), the reduction of morin proceeds with a one-electron transfer of the C=O double bond into a free radical intermediate, which then delivers the final primary alcohol via a one-electron reduction. When an oxidant KIO3 is present, the free radical intermediate of morin is oxidized to regenerate the original ‘C=O’ bond. Further reduction processes are effectively inhibited, resulting in a sensitive catalytic peak, with the peak current enhanced 70 times.
24. Successful treatment of anal intraepithelial neoplasia by CO2 laser in a sexual health service
Authors: McCloskey Jenny , Hall Janelle , Phillips Michael , Metcalf Cecily
Published: November 2013

Background
Treatments for anal intraepithelial neoplasia (AIN) are still being established. Methods: An audit of patients referred for treatment of anal disease by CO2 laser at a Perth SHS was performed. Patient demographics including sex, sexual preference, age, and HIV status were documented. Anal cytology, histopathology, and HPV testing before and after treatment were reviewed in this preliminary analysis. Initial diagnosis of anal disease including AIN was made by high-resolution anoscopy (HRA) and by histological examination. Patients were then referred for treatment. Six-monthly HRA review occurred after treatment and the original site of HGAIN was biopsied. Results: Preliminary analysis of 28 patients included 16 patients with AIN 2 and 12 with AIN 3. After laser treatment, 7 patients had no AIN, 3 had AIN 1, 10 had AIN 2 and 4 had AIN 3, indicating successful reduction in AIN status (Pearson χ2 = 15.2, P = 0.002). The incidence of AIN decreased over the 18 months of follow-up. Conclusions: Studies of CO2 laser ablation of the anal canal are ongoing and need further study.
Table 1. High-resolution anoscopy follow up Rx, treatment
30. Recognising and treating anal cancer: training medical students and physicians in Puerto Rico
Authors: Ortiz Ana P. , Guiot Humberto M. , Díaz-Miranda Olga L. , Romáán Leticia , Palefsky Joel , Colon-Lopez Vivian
Published: November 2013

Background
Knowledge about epidemiology, diagnosis and treatment of anal neoplasia is limited among medical students and physicians from Puerto Rico (PR). Methods: Educational activity (1.5 contact hours) about anal cancer for a group of medical students, residents and faculty from the University of PR (n = 50). A 6-item pre- and post-test on anal cancer was given to assess the change in knowledge. Results: Thirty-four participants (68%) answered the survey. Overall, 78.8% had not received training in anal cancer screening and 93.9% were interested in receiving this training. Most (75.8%) were interested in participating in a clinical trial. An increase in the test scores was observed after the activity (pre-test: 3.4 ± 1.2; post-test: 4.7 ± 0.71). Three items showed an increment in the post-test that assessed participants’ knowledge regarding: (1) current status of guidelines for the screening/treatment of patients with HPV-related anal disease; (2) that anal intraepithelial neoplasia (AIN) 2 is considered to be a form of high-grade AIN (HGAIN); and (3) that warty growths in the anus are not necessarily a manifestation of HGAIN. Conclusions: This educational activity increased the participants’ knowledge of anal cancer and revealed that most of them were interested in future training and in collaborating in clinical trials. Training physicians from PR on anal cancer and clinical trials is essential to encourage recruitment of Hispanic patients in these studies now that the guidelines in anal cancer screening and treatment are on their way to being defined.
46. HIV-induced epithelial–mesenchymal transition in mucosal epithelium facilitates HPV paracellular penetration
Authors: Tugizov Sharof M. , Herrera Rossana , Veluppillai Piri , Greenspan Deborah , Palefsky Joel M.
Published: November 2013

Background
The incidence of human papillomavirus (HPV)-associated epithelial lesions in HIV-infected individuals is substantially higher than in HIV-negative individuals. HIV may increase the risk of mucosal HPV infection by induction of an epithelial–mesenchymal transition (EMT) phenotype that leads to reduced epithelial barrier functions. Methods: To model the effect of EMT on HPV entry, we used oral epithelial biopsies, and oral and anal keratinocytes from HIV-infected and HIV-uninfected individuals. EMT was defined as loss of adherens and tight junctions, and induction of vimentin expression. To study epithelial HPV entry we used HPV-16 pseudovirions (PsVs) containing a plasmid expressing red fluorescent protein (RFP). PsV penetration was evaluated using confocal microscopy to detect RFP-generated fluorescence. Results: Compared with oral epithelia from HIV-uninfected individuals, oral epithelia from HIV-infected individuals had reduced adherens and tight junctions and expressed vimentin. Keratinocytes isolated from oral and anal tissues of HIV-infected individuals also showed loss of E-cadherin and induction of vimentin expression. Exposure of oral epithelial cells from HIV-uninfected individuals to HIV and HIV tat, gp120, and nef proteins induced EMT with reduced cell junctions and epithelial polarity, and allowed paracellular passage of HPV-16 PsV. Oral mucosal epithelial tissues treated with HIV tat and gp120 also lost tight junctions and allowed PsV paracellular penetration, leading to PsV entry into basal/parabasal cells. Conclusions: HIV-associated EMT in oral epithelia, and oral and anal keratinocytes leads to impaired barrier function. This facilitates entry of HPV/PsV into basal/parabasal cells, and may contribute to the increased incidence of HPV-associated malignancy in HIV-infected individuals.
7. High prevalence of human papillomavirus (HPV) infection and high-grade anal intraepithelial neoplasia in HIV-seropositive women, the EVVA study
Authors: Coutlée Francois , Rodrigues-Coutlée Sophie , Munoz Marie , Mayrand Marie Helene , Charest Louise , Auger Manon , Marcus Martin , Burchell Ann , Klein Marina , De Castro Christina , Preziosi Helen , de Pokomandy Alexandra
Published: November 2013

Background
Women living with HIV are at increased risk of anal HPV infection, anal intraepithelial neoplasia (AIN) and anal cancer. This study will describe the burden of infection and of high-grade AIN (AIN-2,3) in a population of HIV-infected women living in Montreal, Canada. Methods: HIV-seropositive women aged ≥18 years old are recruited in the cohort study EVVA. Participants are followed every 6 months for 2 years with questionnaires, cervical/anal HPV testing, cervical/anal cytology and high-resolution anoscopy (HRA). Results: Of the 116 first participants, 88 (75.9%, 95% confidence interval (CI) 67.3–82.8) were infected by HPV in the anal canal. In contrast, 58 of these participants (50%, 95% CI 41.1–59.0) had cervical HPV infection). The most frequent types were HPV16 (n = 19), HPV51 (n = 18), HPV81 and HPV62 (n = 15 each), and HPV45 and HPV58 (n = 14 for each). An average of 2.3 ± 3.1 HPV types (median of 1) were detected per anal sample. Of the 89 participants with satisfactory cytology, 5 had high-grade squamous intraepithelial lesions. HRA from 95 women revealed 17 AIN2,3 (17.9%, 95% confidence interval (CI) 11.4–26.9), 43 AIN1 (45.3%, 95% CI 35.6–55.3), and only 35 without AIN (36.8%, 95% CI 27.8–46.9). Biopsies from 4 women gave undetermined results. Conclusions: Our study revealed that anal HPV infection was more frequently detected than cervical infection in HIV-seropositive women. Prevalent AIN2,3 is a significant problem in women infected with HIV. Prospective follow-up of women with AIN1 will disclose the proportion of women with progressive AIN.
Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells
Authors: Gallego-Paez Lina Marcela , Tanaka Hiroshi , Bando Masashige , Takahashi Motoko , Nozaki Naohito , Nakato Ryuichiro , Shirahige Katsuhiko , Hirota Toru
Published: November 2013

The structural maintenance of chromosomes (SMC) proteins constitute the core of critical complexes involved in structural organization of chromosomes. In yeast, the Smc5/6 complex is known to mediate repair of DNA breaks and replication of repetitive genomic regions, including ribosomal DNA loci and telomeres. In mammalian cells, which have diverse genome structure and scale from yeast, the Smc5/6 complex has also been implicated in DNA damage response, but its further function in unchallenged conditions remains elusive. In this study, we addressed the behavior and function of Smc5/6 during the cell cycle. Chromatin fractionation, immunofluorescence, and live-cell imaging analyses indicated that Smc5/6 associates with chromatin during interphase but largely dissociates from chromosomes when they condense in mitosis. Depletion of Smc5 and Smc6 resulted in aberrant mitotic chromosome phenotypes that were accompanied by the abnormal distribution of topoisomerase IIα (topo IIα) and condensins and by chromosome segregation errors. Importantly, interphase chromatin structure indicated by the premature chromosome condensation assay suggested that Smc5/6 is required for the on-time progression of DNA replication and subsequent binding of topo IIα on replicated chromatids. These results indicate an essential role of the Smc5/6 complex in processing DNA replication, which becomes indispensable for proper sister chromatid assembly in mitosis.
Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data
Authors: Okada Hiroki , Ohnuki Shinsuke , Roncero Cesar , Konopka James B. , Ohya Yoshikazu
Published: November 2013

The cell wall of budding yeast is a rigid structure composed of multiple components. To thoroughly understand its involvement in morphogenesis, we used the image analysis software CalMorph to quantitatively analyze cell morphology after treatment with drugs that inhibit different processes during cell wall synthesis. Cells treated with cell wall–affecting drugs exhibited broader necks and increased morphological variation. Tunicamycin, which inhibits the initial step of N-glycosylation of cell wall mannoproteins, induced morphologies similar to those of strains defective in α-mannosylation. The chitin synthase inhibitor nikkomycin Z induced morphological changes similar to those of mutants defective in chitin transglycosylase, possibly due to the critical role of chitin in anchoring the β-glucan network. To define the mode of action of echinocandin B, a 1,3-β-glucan synthase inhibitor, we compared the morphology it induced with mutants of Fks1 that contains the catalytic domain for 1,3-β-glucan synthesis. Echinocandin B exerted morphological effects similar to those observed in some fks1 mutants, with defects in cell polarity and reduced glucan synthesis activity, suggesting that echinocandin B affects not only 1,3-β-glucan synthesis, but also another functional domain. Thus our multivariate analyses reveal discrete functions of cell wall components and increase our understanding of the pharmacology of antifungal drugs.
Lipid droplet autophagy in the yeastSaccharomyces cerevisiae
Authors: van Zutphen Tim , Todde Virginia , de Boer Rinse , Kreim Martin , Hofbauer Harald F. , Wolinski Heimo , Veenhuis Marten , van der Klei Ida J. , Kohlwein Sepp D.
Published: November 2013

Cytosolic lipid droplets (LDs) are ubiquitous organelles in prokaryotes and eukaryotes that play a key role in cellular and organismal lipid homeostasis. Triacylglycerols (TAGs) and steryl esters, which are stored in LDs, are typically mobilized in growing cells or upon hormonal stimulation by LD-associated lipases and steryl ester hydrolases. Here we show that in the yeast Saccharomyces cerevisiae, LDs can also be turned over in vacuoles/lysosomes by a process that morphologically resembles microautophagy. A distinct set of proteins involved in LD autophagy is identified, which includes the core autophagic machinery but not Atg11 or Atg20. Thus LD autophagy is distinct from endoplasmic reticulum–autophagy, pexophagy, or mitophagy, despite the close association between these organelles. Atg15 is responsible for TAG breakdown in vacuoles and is required to support growth when de novo fatty acid synthesis is compromised. Furthermore, none of the core autophagy proteins, including Atg1 and Atg8, is required for LD formation in yeast.
Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development
Authors: Nakamoto Chizu , Kuan Soh-Leh , Findlay Amy S. , Durward Elaine , Ouyang Zhufeng , Zakrzewska Ewa D. , Endo Takuma , Nakamoto Masaru
Published: November 2013

For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development.
Mutations in the lipoyltransferaseLIPT1gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes
Authors: Tort Frederic , Ferrer-Cortès Xènia , Thió Marta , Navarro-Sastre Aleix , Matalonga Leslie , Quintana Ester , Bujan Núria , Arias Angela , García-Villoria Judit , Acquaviva Cecile , Vianey-Saban Christine , Artuch Rafael , García-Cazorla Àngels , Briones Paz , Ribes Antonia
Published: November 2013

Cofactor disorders of mitochondrial energy metabolism are a heterogeneous group of diseases with a wide variety of clinical symptoms, particular metabolic profiles and variable enzymatic defects. Mutations in NFU1, BOLA3, LIAS and IBA57 have been identified in patients with deficient lipoic acid-dependent enzymatic activities and defects in the assembly and activity of the mitochondrial respiratory chain complexes. Here, we report a patient with an early onset fatal lactic acidosis presenting a biochemical phenotype compatible with a combined defect of pyruvate dehydrogenase (PDHC) and 2-ketoglutarate dehydrogenase (2-KGDH) activities, which suggested a deficiency in lipoic acid metabolism. Immunostaining analysis showed that lipoylated E2-PDH and E2-KGDH were extremely reduced in this patient. However, the absence of glycine elevation, the normal activity of the glycine cleavage system and the normal lipoylation of the H protein suggested a defect of lipoic acid transfer to particular proteins rather than a general impairment of lipoic acid biosynthesis as the potential cause of the disease. By analogy with yeast metabolism, we postulated LIPT1 as the altered candidate gene causing the disease. Sequence analysis of the human LIPT1 identified two heterozygous missense mutations (c.212C>T and c.292C>G), segregating in different alleles. Functional complementation experiments in patient's fibroblasts demonstrated that these mutations are disease-causing and that LIPT1 protein is required for lipoylation and activation of 2-ketoacid dehydrogenases in humans. These findings expand the spectrum of genetic defects associated with lipoic acid metabolism and provide the first evidence of a lipoic acid transfer defect in humans.
UnSplicer: mapping spliced RNA-seq reads in compact genomes and filtering noisy splicing
Authors: Burns Paul D. , Li Yang , Ma Jian , Borodovsky Mark
Published: November 2013

Accurate mapping of spliced RNA-Seq reads to genomic DNA has been known as a challenging problem. Despite significant efforts invested in developing efficient algorithms, with the human genome as a primary focus, the best solution is still not known. A recently introduced tool, TrueSight, has demonstrated better performance compared with earlier developed algorithms such as TopHat and MapSplice. To improve detection of splice junctions, TrueSight uses information on statistical patterns of nucleotide ordering in intronic and exonic DNA. This line of research led to yet another new algorithm, UnSplicer, designed for eukaryotic species with compact genomes where functional alternative splicing is likely to be dominated by splicing noise. Genome-specific parameters of the new algorithm are generated by GeneMark-ES, an ab initio gene prediction algorithm based on unsupervised training. UnSplicer shares several components with TrueSight; the difference lies in the training strategy and the classification algorithm. We tested UnSplicer on RNA-Seq data sets of Arabidopsis thaliana, Caenorhabditis elegans, Cryptococcus neoformans and Drosophila melanogaster. We have shown that splice junctions inferred by UnSplicer are in better agreement with knowledge accumulated on these well-studied genomes than predictions made by earlier developed tools.
Globulin Expression in Grain of Australian Hard Wheat Cultivars Is Affected by Growth Environment
Authors: Hasniza M. Z. Noor , Copeland Les , Wilkes Meredith A.
Published: November 2013

Our aim was to study changes in wheat proteomes across different growth locations as the first step in linking protein composition with functional changes in grains produced with commercial production systems. Soluble and insoluble proteins were extracted sequentially from grain of three commercial wheat cultivars grown at four locations in New South Wales, Australia, during a single season. Bands were separated with SDS‐PAGE and identified by peptide mass fingerprinting. Quantitative changes in the electrophoretic patterns were observed mainly in the insoluble polypeptides of molecular mass 40,000–70,000 for all three cultivars grown at two of the four locations. These proteins were identified as mainly globulin and serpin isoforms, as well as triticin. Other proteins with changed expression included disease‐resistance proteins, class III peroxidase, starch branching enzyme I, β‐amylase, and storage proteins. Two‐dimensional electrophoretic analysis was performed on two of the same wheat cultivars grown at one of the locations during two consecutive seasons. Protein spots that varied between seasons consisted of globulin and serpin isoforms, triticin, HMW glutenin, γ‐gliadin, starch branching enzyme IIb, and α‐amylase. The implications of the upregulation of globulin and triticin on whole meal flour quality, through their participation in polymerization of the gluten network, are considered.
Novel Molecular Targets of Dezocine and Their Clinical Implications
Authors: Liu Renyu , Huang Xi-Ping , Yeliseev Alexei , Xi Jin , Roth Bryan L.
Published: November 2013

Background:

Although dezocine is a partial μ-opioid receptor agonist, it is not a controlled substance. Thus, the characterization of the molecular targets of dezocine is critical for scientific and clinical implications. The goal of this study is to characterize molecular targets for dezocine and determine their implications.

Methods:

A binding screen for dezocine was performed on 44 available receptors and transporter proteins. Functional assays for the novel targets were performed along with computation calculations to locate the binding site. A G protein activation study was performed for the human κ opioid receptor to determine whether dezocine is a κ-antagonist. Data are presented as mean ± standard error.

Results:

The affinities for dezocine were 3.7 ± 0.7 nM for the μ receptor, 527 ± 70 nM for the δ-receptor, and 31.9 ± 1.9 nM for the κ-receptor. Dezocine failed to induce G protein activation with κ-opioid receptor and concentration dependently inhibited κ-agonist (salvinorin A and nalbuphine)–induced receptor activation, indicating that dezocine is a κ-antagonist. Two novel molecular targets (norepinephrine transporter and serotonin transporter) were identified. Dezocine concentration-dependently inhibited norepinephrine and serotonin reuptake in vitro. The half maximal inhibitory concentrations (expressed as pIC50) were 5.68 ± 0.11 for norepinephrine transporter and 5.86 ± 0.17 for serotonin transporter. Dezocine occupied the binding site for known norepinephrine transporter and serotonin transporter inhibitors.

Conclusions:

The unique molecular pharmacological profile of dezocine as a partial μ-receptor agonist, a κ-receptor antagonist, and a norepinephrine and serotonin reuptake inhibitor (via norepinephrine transporter and serotonin transporter) was revealed. These discoveries reveal potentially important novel clinical implications and drug interactions of dezocine.
RNA-binding protein GLD-1/quaking genetically interacts with themir-35andthe let-7 miRNA pathways inCaenorhabditis elegans
Authors: Akay Alper , Craig Ashley , Lehrbach Nicolas , Larance Mark , Pourkarimi Ehsan , Wright Jane E. , Lamond Angus , Miska Eric , Gartner Anton
Published: November 2013

Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-binding protein GLD-1 as a translational repressor is well studied duringCaenorhabditis elegansgermline development and maintenance. Possible functions of GLD-1 during somatic development and the mechanism of how GLD-1 acts as a translational repressor are not known. Its human homologue, quaking (QKI), is essential for embryonic development. Here, we report that the RNA-binding protein GLD-1 inC. elegansaffects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found thatnhl-2andvig-1, two known modulators of miRNA function, genetically interact with GLD-1.gld-1mutations enhance multiple phenotypes conferred bymir-35andlet-7family mutants during somatic development. We used stable isotope labelling with amino acids in cell culture to globally analyse the changes in the proteome conferred bylet-7andgld-1during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed inlet-7andgld-1mutants. The link between GLD-1 and miRNA-mediated gene regulation is further supported by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins implicated in miRNA regulation. Overall, we have uncovered genetic and biochemical interactions between GLD-1 and miRNA pathways.
Expression of the six chromate ion transporter homologues of Burkholderia xenovorans LB400
Authors: Acosta-Navarrete Yaned M. , León-Márquez Yhoana L. , Salinas-Herrera Karina , Jácome-Galarza Irvin E. , Meza-Carmen Víctor , Ramírez-Díaz Martha I. , Cervantes Carlos
Published: November 2013

The chromate ion transporter (CHR) superfamily comprises transporters that confer chromate resistance by extruding toxic chromate ions from cytoplasm.Burkholderia xenovoransstrain LB400 has been reported to encode six CHR homologues in its multireplicon genome. We found that strain LB400 displays chromate-inducible resistance to chromate. Susceptibility tests ofEscherichia colistrains transformed with clonedB. xenovorans chrgenes indicated that the six genes confer chromate resistance, although under different growth conditions, and suggested that expression ofchrgenes is regulated by sulfate. Expression ofchrgenes was measured by quantitative reverse transcription-PCR (RT-qPCR) from total RNA ofB. xenovoransLB400 grown under different concentrations of sulfate and exposed or not to chromate. Thechrhomologues displayed distinct expression levels, but showed no significant differences in transcription under the various sulfate concentrations tested, indicating that sulfate does not regulatechrgene expression inB. xenovorans. ThechrA2gene, encoded in the megaplasmid, was the onlychrgene whose expression was induced by chromate and it was shown to constitute the chromate-responsivechrBACFoperon. These data suggest that this determinant is mainly responsible for theB. xenovoransLB400 chromate resistance phenotype.