bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of new antimalarial chemotypes through chemical methodology and library development
Authors: Brown Lauren E. , Chih-Chien Cheng Ken , Wei Wan-Guo , Yuan Pingwei , Dai Peng , Trilles Richard , Ni Feng , Yuan Jing , MacArthur Ryan , Guha Rajarshi , Johnson Ronald L. , Su Xin-zhuan , Dominguez Melissa M. , Snyder John K. , Beeler Aaron B. , Schaus Scott E. , Inglese James , Porco John A.
Published: April 2011

In an effort to expand the stereochemical and structural complexity of chemical libraries used in drug discovery, the Center for Chemical Methodology and Library Development at Boston University has established an infrastructure to translate methodologies accessing diverse chemotypes into arrayed libraries for biological evaluation. In a collaborative effort, the NIH Chemical Genomics Center determined IC
50
’s for
Plasmodium falciparum
viability for each of 2,070 members of the CMLD-BU compound collection using quantitative high-throughput screening across five parasite lines of distinct geographic origin. Three compound classes displaying either differential or comprehensive antimalarial activity across the lines were identified, and the nascent structure activity relationships (SAR) from this experiment used to initiate optimization of these chemotypes for further development.
Antennal transcriptome of
Manduca sexta
Authors: Grosse-Wilde Ewald , Kuebler Linda S. , Bucks Sascha , Vogel Heiko , Wicher Dieter , Hansson Bill S.
Published: April 2011

In recent years, considerable progress has been made in understanding the molecular mechanisms underlying olfaction in insects. Because of the diverse nature of the gene families involved, this process has largely relied on genomic data. As a consequence, studies have focused on a small subset of species with extensive genomic information. For Lepidoptera, a large order historically crucial to olfactory research, this circumstance has mostly limited advances to the domesticated species
Bombyx mori
, with some progress in the noctuid
Heliothis virescens
based on a nonpublic partial genome database. Because of the limited behavioral repertoire and nonexistent ecological importance of
Bombyx
, molecular data on the tobacco hornworm
Manduca sexta
are of utmost importance, especially with regards to its position as a classical olfactory model and its complex natural behavior. Here we present the use of transcriptomic and microarray data to identify members of the main olfactory gene families of
Manduca.
To assess the quality of our data, we correlate information on expressed receptor genes with detailed morphological data on the antennal lobe. Finally, we compare the expression of the near-complete transcript sets in male and female antennae.
Direct observation of Young’s double-slit interferences in vibrationally resolved photoionization of diatomic molecules
Authors: Canton Sophie E. , Plésiat Etienne , Bozek John D. , Rude Bruce S. , Decleva Piero , Martín Fernando
Published: April 2011

Vibrationally resolved valence-shell photoionization spectra of H
2
, N
2
and CO have been measured in the photon energy range 20–300 eV using third-generation synchrotron radiation. Young’s double-slit interferences lead to oscillations in the corresponding vibrational ratios, showing that the molecules behave as two-center electron-wave emitters and that the associated interferences leave their trace in the angle-integrated photoionization cross section. In contrast to previous work, the oscillations are directly observable in the experiment, thereby removing any possible ambiguity related to the introduction of external parameters or fitting functions. A straightforward extension of an original idea proposed by Cohen and Fano [Cohen HD, Fano U (1966)
Phys Rev
150:30] confirms this interpretation and shows that it is also valid for diatomic heteronuclear molecules. Results of accurate theoretical calculations are in excellent agreement with the experimental findings.
Becoming a problem: Behaviour and reputation in the early years classroom
Authors: MacLure Maggie , Jones Liz , Holmes Rachel , MacRae Christina
Published: April 2011

How does it happen that some children acquire a reputation as a ‘problem’ in school? The article discusses some findings of a qualitative study involving children in the Reception year (ages 4–5). The research focused on problematic behaviour as this emerged within, and was shaped by, the culture of the classroom. A key question for the research was: what makes it difficult for some children to be, and to be recognised as, good students? Using an analytic framework derived from discourse and conversation analysis, we identify some critical factors in the production of reputation, including: the ‘discursive framing’ of behaviour; the public nature of classroom discipline; the linking of behaviour, learning and emotions; the interactional complexities of being (seen to be) good, and the demands on children of passing as the ‘proper child’ required by prevailing discourses of normal development, as coded in UK early years curriculum policy and pedagogy.
The association between mathematics pedagogy and learners’ dispositions for university study
Authors: Pampaka Maria , Williams Julian , Hutcheson Graeme , Wake Geoff , Black Laura , Davis Pauline , Hernandez‐Martinez Paul
Published: April 2011

We address the current concerns about teaching‐to‐the‐test and its association with declining dispositions towards further study of mathematics and the consequences for choice of STEM subjects at university. In particular, through a mixed study including a large survey sample of over 1000 students and their teachers, and focussed qualitative case studies, we explored the impact of ‘transmissionist’ pedagogic practices on learning outcomes. We report on the construction and validation of a scale to measure teachers’ self‐reported pedagogy. We then use this measure in combination with the students’ survey data and through regression modelling we illustrate significant associations between the pedagogic measure and students’ mathematics dispositions. Finally, we discuss the potential implications of these results for mathematics education and the STEM agenda.
What every worker wants? Evidence about employee demand for learning
Authors: Findlay Jeanette , Findlay Patricia , Warhurst Chris
Published: April 2011

In order to boost learning, recent UK governments have invested in trade union‐led workplace learning. Investing in the supply of learning is useful but ignores the demand for learning by workers, about which there is little research. This paper addresses this lacunae by analysing worker demand for learning, which workers want learning, what learning is demanded and why, and what factors might best lever learning. Data come from two surveys of potential learners and union learning representatives. Findings reveal a large demand for learning and that unions can lever this learning. Findings also suggest further policy development to address problems associated with union‐led learning.
Multi‐directional creative transfer between practice‐based arts education and work
Authors: Shreeve Alison , Smith Catherine
Published: April 2011

In this article we examine how 19 students in creative arts disciplines in two universities experience work in not‐for‐profit and public sectors. We explore the notion of transfer from university education and suggest that ‘creative transfer’ is taking place, often in more than one direction. Students draw on their life‐wide experiences as they deem appropriate in new situations and also vicarious learning from university settings. The extent to which creative transfer happens is, we suggest, tempered by relational affordances between the individual, the people they encounter, the opportunities they perceive in new situations and the value or reward perceived in the new work environment. These findings have implications for supporting students in practice‐based learning and work settings and we provide some recommendations for maximising the potential for multi‐directional transfer.
Surface effect in antiferromagnetic Ba6Mn24O48 nanoribbons
Authors: Zhang Xianke , Tang Shaolong , Du Youwei
Published: April 2011

The magnetic properties of Ba6Mn24O48 nanoribbons and bulk are studied by zero-field-cooled and field-cooled magnetization, and ac susceptibility. Upon cooling, we find that both nanoribbons and bulk experience multiple magnetic phase transitions, i.e. paramagnetic, antiferromagnetic and re-entrant spin glass (RSG) phases at a low temperature. The main focus of this work is to understand the origin of RSG behaviour and to investigate the surface effect on magnetism in Ba6Mn24O48 nanoribbons. The dc susceptibility measurement shows that the paramagnetism in these nanoribbons involves the Curie–Weiss paramagnetism and temperature-independent contributions to magnetic susceptibility due to Pauli and Van Vleck paramagnetism. The Pauli paramagnetic contribution to susceptibility might give rise to uncompensated spins due to the breaking of sublattice pairing on the surface of nanoribbons. An exchange bias phenomenon is found in both Ba6Mn24O48 nanoribbons and bulk. The exchange field (H
E) in the nanoribbons is larger than that of the corresponding bulk, which may also be induced by the uncompensated surface spins. The resistivity of Ba6Mn24O48 bulk presents the relation ln(ρ) ∝ T
−1/2, and the possible conduction mechanism is suggested.
Resonant nano-antennas for light trapping in plasmonic solar cells
Authors: Mokkapati S , Beck F J , de Waele R , Polman A , Catchpole K R
Published: April 2011

We investigate the influence of nanoparticle height on light trapping in thin-film solar cells covered with metal nanoparticles. We show that in taller nanoparticles the scattering cross-section is enhanced by resonant excitation of plasmonic standing waves. Tall nanoparticles have higher coupling efficiency when placed on the illuminated surface of the cell than on the rear of the cell due to their forward scattering nature. One of the major factors affecting the coupling efficiency of these particles is the phase shift of surface plasmon polaritons propagating along the nanoparticle due to reflection from the Ag/Si or Ag/air interface. The high scattering cross-sections of tall nanoparticles on the illuminated surface of the cell could be exploited for efficient light trapping by modifying the coupling efficiency of nanoparticles by engineering this phase shift. We demonstrate that the path length enhancement (with a nanoparticle of height 500 nm) at an incident wavelength of 700 nm can be increased from ∼6 to ∼16 by modifying the phase shift at the Ag/air interface by coating the surface of the nanoparticle with a layer of Si.
Magnetohydrodynamic electrical power generation using convexly divergent channel: I. Experimental demonstration
Authors: Murakami Tomoyuki , Okuno Yoshihiro
Published: April 2011

We describe shock-tunnel-based experiments carried out to evaluate a magnetohydrodynamic electrical power generator equipped with a convexly divergent supersonic channel. Two-dimensional structure of the streaming MHD plasma and the temporal behaviour of electron temperature are examined. The spatial profile of MHD power-generating plasma and the energy-conversion efficiency in the convexly divergent channel are compared with those from a linearly divergent channel. For an understanding of the basic scaling of the channel geometry modification effect, a convexity parameter is proposed. With this simple and fundamental scaling parameter, the dependence of plasma–fluid properties and energy-conversion efficiency on the channel convexity is quantitatively examined. The quality of MHD plasma and the generator performance are improved at the convexity parameter of 0.35 (a slight enhancement of the channel convexity) rather than at the convexity parameter of zero (no convexity or concavity). This paper is the first part of a duology.
Magnetohydrodynamic electrical power generation using convexly divergent channel: II. Numerical simulation
Authors: Murakami Tomoyuki , Okuno Yoshihiro
Published: April 2011

We describe quasi-three-dimensional numerical calculations based on large eddy simulation model for magnetohydrodynamic (MHD) electrical power generators equipped with modified wall configurations. The wall profile of the MHD channel is finely tuned in four types of geometry, that is, a concavely divergent channel, a linearly divergent channel, a convexly divergent channel and a highly convexed channel. The plasma–fluid properties and energy conversion efficiency are examined in detail. Although the deterioration in the plasma–fluid behaviour is not completely overcome, the advantages of the convexly divergent channel are notable. The convexly divergent channel exhibits the highest energy conversion performance, which is followed by the highly convexed, linearly and concavely divergent channels in order. The effect of the channel geometry modification on the generator performance is clearly quantified using a convexity parameter. This paper is the second part of a duology.
Effects of hydrogen plasma treatment on the structural and electrical properties of sputter-deposited SnO2 thin films
Authors: Kim Hye-Ri , Lee Gun-Hwan , Kim Dong-Ho
Published: April 2011

In this paper, we report the effects of hydrogen plasma treatment on the structural and electrical properties of SnO2 thin films prepared by the sputtering method. Whereas the hydrogen plasma treatment led to etching of SnO2 films and subsequent degradation of crystalline quality and optical transmittance, the plasma-treated films exhibited an improvement in the electrical conductivity. Hall measurements indicated an increase in the carrier concentration of SnO2 films which, following x-ray diffraction and secondary ion mass spectrometry measurements, was attributed to the generation of oxygen vacancies rather than the incorporation of hydrogen shallow donors in undoped SnO2 films.
Shear strength measurements in a shock loaded commercial silastomer
Authors: Millett J C F , Whiteman G , Stirk S M , Bourne N K
Published: April 2011

The shock-induced shear strength of a commercial silastomer, trade name Sylgard 184™, has been determined using laterally mounted manganin stress gauges. Shear strength has been observed to increase with increasing shock amplitude, in common with many other materials. Shear strength has also been observed to increase slightly behind the shock front as well. It is believed that a combination of polymer chain entanglement and cross linking between chains is responsible. Finally, a ramp on the leading edge of the lower amplitude stress traces has been observed. It has been suggested that this is due to shock-induced collapse of free space between the polymer chains. Similar explanations have been used to explain the apparent non-linearity of the shock velocity with particle velocity at low shock amplitudes.
Raman scattering of monolayer graphene: the temperature and oxygen doping effects
Authors: Zhou Haiqing , Qiu Caiyu , Yu Fang , Yang Huaichao , Chen Minjiang , Hu Lijun , Guo Yanjun , Sun Lianfeng
Published: April 2011

Raman spectra of monolayer graphene at various temperatures (303–473 K) are measured. In Raman scattering with wave numbers ranging from 1200 to 3400 cm−1, the four main Raman peaks (G, 2D, T + D and 2D′) show temperature-dependent behaviour, but have different frequency shifts with increase in temperature. We propose that the peak frequency shift is related mainly to the elongation of C–C bond due to thermal expansion or anharmonic coupling of phonon modes, and oxygen-induced strong hole doping on the graphene surface. The doping effect can be confirmed from the frequency shifts, full-width at half-maximum as well as the area and intensity ratios of G and 2D peaks in temperature-dependent Raman scattering of graphene, room-temperature Raman spectra of pristine graphene and graphene cooled down after Raman measurement at 473 K in air. Therefore, the oxygen doping effect and temperature effect coexist in temperature-dependent Raman scattering of monolayer graphene.
Investigation of the surface properties of CaF2 layers on (1 1 1) Si as a function of growth temperature
Authors: Suela J , Abramof E , Rappl P H O , Freitas F E , Closs H , Boschetti C
Published: April 2011

This work reports on the study of surface properties of CaF2 films (30 and 10 nm thick) grown on (1 1 1) Si by molecular beam epitaxy at substrate temperatures from 400 to 700 °C. Reflection high-energy electron diffraction (RHEED) analysis indicated that CaF2 films with smooth surfaces were obtained in temperature ranges 500–550 °C and 620–700 °C, while at temperatures from 400 to 500 °C and in the vicinity of 600 °C the films showed grains randomly oriented on top of the surface. Atomic force microscopy (AFM) investigation corroborated with the RHEED results and confirmed the presence of grains on the film surface, with an evident transition near 600 °C. The dependence of grain density on the growth temperature followed the expectation from the RHEED analysis. The arithmetical average roughness of the CaF2 surface obtained from the AFM images remained below 1 nm for the best quality films. The x-ray reflectivity curves of all samples exhibited well-defined interference fringes, whose oscillation damping behaviour agreed with the RHEED and AFM results. The CaF2 layer thickness and roughness were accurately determined by a best-fit procedure applied to the x-ray reflectivity data. By combining all results, the temperature range between 525 and 550 °C was found to be the most suitable to grow CaF2 layers on (1 1 1) Si. For growth temperatures above 650 °C, pinholes and cracks started to reduce the CaF2 surface quality.
Combined unfolding and spatial inversion of neutron camera measurements for ion temperature profile determination in ITER
Authors: Marocco D. , Esposito B. , Moro F.
Published: April 2011

Measurements of the core ion temperature profile are required in ITER with ±10% accuracy and 100 ms time resolution. The ITER radial neutron camera (RNC), with 45 collimated lines of sight (spanning almost completely a poloidal plasma section) equipped with compact neutron spectrometers, has the potential to provide such spatially resolved temperature information. In this paper a novel technique for the ion temperature profile measurement based on the combination of unfolding and spatial inversion of RNC measurements is presented and applied to the ITER full power standard H-mode deuterium–tritium scenario, assuming the RNC to be equipped with liquid scintillators. Results based on synthetic data suggest that the target accuracy could be reached with a time resolution ⩾200 ms.
Residual analysis of the equilibrium reconstruction quality on JET
Authors: Murari A. , Mazon D. , Gelfusa M. , Folschette M. , Quilichini T.
Published: April 2011

An extended set of statistical tests, aimed at assessing the quality of the magnetic reconstructions in JET, obtained with the code EFIT using the external magnetic measurements, is described and the results reported in detail. In addition to the traditional analysis of the global distributions of the residuals (the difference between the actual measurements and their reconstructions from the equilibrium), to determine to what extent they approximate a Gaussian, more sophisticated correlation tests have been performed. Since EFIT solves a highly non-linear equation, tests adequate for multi-input multi-output, non-linear systems have been implemented. Not only the reconstruction of the pickup coil signals but also the accuracy of the plasma boundary has been investigated. The results indicate quite clearly that the errors in the reconstruction of the pickup coils are not negligible. The coils, whose residuals present skewed monomodal distributions (distributions asymmetric with respect to their maximum value), are affected by average errors of the order of more than one millitesla and multimodal distributions of the residuals (distributions presenting more than one local maximum) are quite common. Also the correlation of the residuals is typically outside the 95% limits for a good model in typically more than 70% of the cases. With regard to the plasma boundary, the situation is better since the errors in the distances of the plasma from the wall are typically of the order of 1 cm. On the other hand, in this case the autocorrelations of the residuals are also well outside the 95% confidence interval for random residuals. A detailed analysis of the correlations indicates that the main reasons for the imperfections in the magnetic reconstructions do not reside in the measurements, since there is no evidence of systematic errors or problems with the calibrations. Therefore, the main improvements are to be expected by refinements in the used equilibrium code EFIT, whose constraints and boundary conditions are probably not the most appropriate to model H mode plasmas.
Influence of plasma flow shear on tearing in DIII-D hybrids
Authors: La Haye R.J. , Petty C.C. , Politzer P.A.
Published: April 2011

That plasma flow shear has a stabilizing effect on tearing stability is a new insight found from experiments on DIII-D, JET and NSTX. High-order (m/n = 4/3 or 3/2) tearing modes are a key beneficial feature in hybrid scenarios that act to regulate the q-profile to keep q(0) ∼ 1 with the absence of large m/n = 1/1 sawteeth. The destabilization of low-order (m/n = 2/1) tearing acts as the limit on achievable beta. Hybrid discharges in DIII-D with 4/3 tearing modes under large co- (to I
p) neutral-beam torque can be run steadily just below the 2/1 tearing beta limit. However, reducing the torque has consequences on both the existing 4/3 tearing mode amplitude and the beta at which the 2/1 tearing mode destabilizes. It is found that flow shear at a rational surface is well correlated with both decreased 4/3 mode amplitude and higher beta 2/1 mode onset. The working physics model is that flow shear is classically stabilizing, i.e. makes the tearing stability index Δ′ more negative; this both reduces the amplitude of neoclassical tearing modes and makes mode destabilization more difficult (requiring higher beta). However, a detailed understanding of the effects of flow shear on tearing stability remains a challenge for theory and modelling. The classically stabilizing effect of flow shear in DIII-D (and indeed future larger tokamaks) is in the regime of large magnetic Prandtl and very large Lundquist numbers; this is significant for sorting out which physical effects of flow and flow shear are relevant and would be stabilizing or even destabilizing. Experimental data with applied torque varied from all co- to near-balanced neutral beams in the DIII-D hybrid scenario with 4/3 mode ‘regulation’ is analysed for 4/3 mode amplitude, 2/1 onset and criticality for 2/1 mode locking. For both existing m/n = 4/3 modes and for the onset of m/n = 2/1 modes, a local flow shear of the order of
is found to have a significant stabilizing effect on tearing. In addition, a flow shear effect increasing local viscosity is suggested in order to explain the behaviour of mode locking to the resistive wall.
Effects of transient heating events on tungsten plasma-facing materials in a steady-state divertor-plasma environment*
Authors: Umstadter K.R. , Doerner R. , Tynan G.R.
Published: April 2011

Nearly all heat-pulse tests of plasma-facing materials (PFMs) have been completed in vacuum environments without the presence of a background plasma. Thus, combined effects of thermal transients on materials undergoing plasma exposure need to be explored. Heat-pulse experiments have been conducted in the PISCES-A device using a pulsed laser in a divertor-like plasma background. The results indicate that the erosion of PFMs is enhanced as compared with transient-only or plasma-only experiments, and the threshold energy for material removal by a transient heat pulse in a steady-state plasma background is reduced. There appears to be a minimum ion fluence to the surface needed to cause these effects. Initial experiments with pre-loaded material samples exposed to plasmas and heat pulsed in the lower divertor of the DIII-D tokamak using the Divertor Material Evaluation System indicate that similar effects occur in confinement devices.
Modelling of the neoclassical toroidal plasma viscosity torque in tokamaks
Authors: Sun Y. , Liang Y. , Shaing K.C. , Koslowski H.R. , Wiegmann C. , Zhang T.
Published: April 2011

Neoclassical toroidal plasma viscosity (NTV) torque induced by non-axisymmetric magnetic perturbation in the collisionless regimes in tokamaks is modelled by solving the bounce-averaged drift kinetic equation numerically. The detailed comparison between the numerical and the analytic solutions of NTV is discussed in this paper. In different asymptotic limits of the collisionless regimes, the numerical solutions are in good agreement with the analytic results. The numerical results are different from the analytic results calculated from the smoothly connected formula in the transit regimes. The pitch angle scattering is especially important in the
regime. The final difference between the numerical and the analytic results can be up to a factor of 2 near the transition between the non-resonant and resonant regimes. This reveals the importance of the boundary condition of the pitch angle space. The sign of the electric field is found to be important in the calculation of the NTV torque. It shows that the effect of the resonant particles makes the NTV torque more important for the lower collisionality and lower rotation cases, which are the International Thermonuclear Experimental Reactor relevant conditions. It also shows that the electron NTV torque is important in the low collisionality case. This numerical method can be applied for modelling the NTV torque in different collisionality regimes and their transitions in tokamaks without additional approximations.
A Conceptional Analysis of Dynamics and Production in Bioeconomic Models
Authors: Steinshamn Stein Ivar
Published: April 2011

Harvesting functions and stock dynamic equations in age‐structured bioeconomic models are generalized in order to incorporate density dependence. Using this generalization, anything from completely uniformly distributed fish to extreme schooling can be analyzed. The classical Beverton–Holt model comes out as a special case of the generalized model. The generalization can be applied both for simulation as well as for optimization purposes given appropriate software. Conceptual analysis indicates that pulse fishing seems to become less and less economically profitable as we move from uniformly distributed fish to schooling species. This has important implications for how fish stocks ought to be managed.
datPAV—an online processing, analysis and visualization tool for exploratory investigation of experimental data
Authors: Biswas Ambarish , Rao Raghuraj , Umashankar Shivshankar , Mynampati Kalyan C. , Reuben Sheela , Parab Gauri , Swarup Sanjay
Published: April 2011

Summary:Data processing, analysis and visualization (datPAV) is an exploratory tool that allows experimentalist to quickly assess the general characteristics of the data. This platform-independent software is designed as a generic tool to process and visualize data matrices. This tool explores organization of the data, detect errors and support basic statistical analyses. Processed data can be reused whereby different step-by-step data processing/analysis workflows can be created to carry out detailed investigation. The visualization option provides publication-ready graphics. Applications of this tool are demonstrated at the web site for three cases of metabolomics, environmental and hydrodynamic data analysis.

Availability: datPAV is available free for academic use at http://www.sdwa.nus.edu.sg/datPAV/.

Contact:  sanjay@nus.edu.sg
Normalizing bead-based microRNA expression data: a measurement error model-based approach
Authors: Wang Bin , Wang Xiao−Feng , Xi Yaguang
Published: April 2011

Motivation: Compared with complementary DNA (cDNA) or messenger RNA (mRNA) microarray data, microRNA (miRNA) microarray data are harder to normalize due to the facts that the total number of miRNAs is small, and that the majority of miRNAs usually have low expression levels. In bead-based microarrays, the hybridization is completed in several pools. As a result, the number of miRNAs tested in each pool is even smaller, which poses extra difficulty to intrasample normalization and ultimately affects the quality of the final profiles assembled from various pools. In this article, we consider a measurement error model-based method for bead-based microarray intrasample normalization.

Results: In this study, results from quantitative real-time PCR (qRT-PCR) assays are used as ‘gold standards’ for validation. The performance of the proposed measurement error model-based method is evaluated via a simulation study and real bead-based miRNA expression data. Simulation results show that the new method performs well to assemble complete profiles from subprofiles from various pools. Compared with two intrasample normalization methods recommended by the manufacturer, the proposed approach produces more robust final complete profiles and results in better agreement with the qRT-PCR results in identifying differentially expressed miRNAs, and hence improves the reproducibility between the two microarray platforms. Meaningful results are obtained by the proposed intrasample normalization method, together with quantile normalization as a subsequent complemental intersample normalization method.

Availability: Datasets and R package are available at http://gauss.usouthal.edu/publ/beadsme/.

Contact:  bwang@jaguar1.usouthal.edu
BACOM: in silico detection of genomic deletion types and correction of normal cell contamination in copy number data
Authors: Yu Guoqiang , Zhang Bai , Bova G. Steven , Xu Jianfeng , Shih Ie−Ming , Wang Yue
Published: April 2011

Motivation: Identification of somatic DNA copy number alterations (CNAs) and significant consensus events (SCEs) in cancer genomes is a main task in discovering potential cancer-driving genes such as oncogenes and tumor suppressors. The recent development of SNP array technology has facilitated studies on copy number changes at a genome-wide scale with high resolution. However, existing copy number analysis methods are oblivious to normal cell contamination and cannot distinguish between contributions of cancerous and normal cells to the measured copy number signals. This contamination could significantly confound downstream analysis of CNAs and affect the power to detect SCEs in clinical samples.

Results: We report here a statistically principled in silico approach, Bayesian Analysis of COpy number Mixtures (BACOM), to accurately estimate genomic deletion type and normal tissue contamination, and accordingly recover the true copy number profile in cancer cells. We tested the proposed method on two simulated datasets, two prostate cancer datasets and The Cancer Genome Atlas high-grade ovarian dataset, and obtained very promising results supported by the ground truth and biological plausibility. Moreover, based on a large number of comparative simulation studies, the proposed method gives significantly improved power to detect SCEs after in silico correction of normal tissue contamination. We develop a cross-platform open-source Java application that implements the whole pipeline of copy number analysis of heterogeneous cancer tissues including relevant processing steps. We also provide an R interface, bacomR, for running BACOM within the R environment, making it straightforward to include in existing data pipelines.

Availability: The cross-platform, stand-alone Java application, BACOM, the R interface, bacomR, all source code and the simulation data used in this article are freely available at authors' web site: http://www.cbil.ece.vt.edu/software.htm.

Contact:  yuewang@vt.edu

Supplementary Information:  Supplementary data are available at Bioinformatics online.
PathScan: a tool for discerning mutational significance in groups of putative cancer genes
Authors: Wendl Michael C. , Wallis John W. , Lin Ling , Kandoth Cyriac , Mardis Elaine R. , Wilson Richard K. , Ding Li
Published: April 2011

Motivation: The expansion of cancer genome sequencing continues to stimulate development of analytical tools for inferring relationships between somatic changes and tumor development. Pathway associations are especially consequential, but existing algorithms are demonstrably inadequate.

Methods: Here, we propose the PathScan significance test for the scenario where pathway mutations collectively contribute to tumor development. Its design addresses two aspects that established methods neglect. First, we account for variations in gene length and the consequent differences in their mutation probabilities under the standard null hypothesis of random mutation. The associated spike in computational effort is mitigated by accurate convolution-based approximation. Second, we combine individual probabilities into a multiple-sample value using Fisher–Lancaster theory, thereby improving differentiation between a few highly mutated genes and many genes having only a few mutations apiece. We investigate accuracy, computational effort and power, reporting acceptable performance for each.

Results: As an example calculation, we re-analyze KEGG-based lung adenocarcinoma pathway mutations from the Tumor Sequencing Project. Our test recapitulates the most significant pathways and finds that others for which the original test battery was inconclusive are not actually significant. It also identifies the focal adhesion pathway as being significantly mutated, a finding consistent with earlier studies. We also expand this analysis to other databases: Reactome, BioCarta, Pfam, PID and SMART, finding additional hits in ErbB and EPHA signaling pathways and regulation of telomerase. All have implications and plausible mechanistic roles in cancer. Finally, we discuss aspects of extending the method to integrate gene-specific background rates and other types of genetic anomalies.

Availability: PathScan is implemented in Perl and is available from the Genome Institute at: http://genome.wustl.edu/software/pathscan.

Contact:  mwendl@wustl.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
OTUbase: an R infrastructure package for operational taxonomic unit data
Authors: Beck Daniel , Settles Matt , Foster James A.
Published: April 2011

Summary: OTUbase is an R package designed to facilitate the analysis of operational taxonomic unit (OTU) data and sequence classification (taxonomic) data. Currently there are programs that will cluster sequence data into OTUs and/or classify sequence data into known taxonomies. However, there is a need for software that can take the summarized output of these programs and organize it into easily accessed and manipulated formats. OTUbase provides this structure and organization within R, to allow researchers to easily manipulate the data with the rich library of R packages currently available for additional analysis.

Availability: OTUbase is an R package available through Bioconductor. It can be found at http://www.bioconductor.org/packages/release/bioc/html/OTUbase.html.

Contact:  msettles@uidaho.edu
MAISTAS: a tool for automatic structural evaluation of alternative splicing products
Authors: Floris Matteo , Raimondo Domenico , Leoni Guido , Orsini Massimiliano , Marcatili Paolo , Tramontano Anna
Published: April 2011

Motivation: Analysis of the human genome revealed that the amount of transcribed sequence is an order of magnitude greater than the number of predicted and well-characterized genes. A sizeable fraction of these transcripts is related to alternatively spliced forms of known protein coding genes. Inspection of the alternatively spliced transcripts identified in the pilot phase of the ENCODE project has clearly shown that often their structure might substantially differ from that of other isoforms of the same gene, and therefore that they might perform unrelated functions, or that they might even not correspond to a functional protein. Identifying these cases is obviously relevant for the functional assignment of gene products and for the interpretation of the effect of variations in the corresponding proteins.

Results: Here we describe a publicly available tool that, given a gene or a protein, retrieves and analyses all its annotated isoforms, provides users with three-dimensional models of the isoform(s) of his/her interest whenever possible and automatically assesses whether homology derived structural models correspond to plausible structures. This information is clearly relevant. When the homology model of some isoforms of a gene does not seem structurally plausible, the implications are that either they assume a structure unrelated to that of the other isoforms of the same gene with presumably significant functional differences, or do not correspond to functional products. We provide indications that the second hypothesis is likely to be true for a substantial fraction of the cases.

Availability:  http://maistas.bioinformatica.crs4.it/.

Contact:  anna.tramontano@uniromal.it
An overview of global catch statistics for inland fish
Authors: Welcomme Robin L.
Published: April 2011

Welcomme, R. L. 2011. An overview of global catch statistics for inland fish. – ICES Journal of Marine Science, 68: 1751–1756. The reported global inland fish catch passed 10 million tonnes in 2008, after almost linear growth from the early 1950s. The rise coincides with an increasing number of reports of falling catches resulting from environmental degradation. It is thought that catches from inland waters were underreported in the past because of constraints on collecting the relevant data. National approaches to data collection are not generally comparable and their accuracy not usually assessed. National data processing and reporting should be audited, and training undertaken to harmonize these activities. The apparently bigger catches probably result from better reporting of actual catches rather than any increase in the amount of fish landed. Current data are sufficient only for a general overview of global inland catches of fish, rather than for the detailed analysis needed for management, policy formulation, and the valuation of inland fisheries. There is a need for improved approaches to data collection and for historical catches to be corrected to account for changes in methodologies and reporting procedures.
Salinicoccus qingdaonensis sp. nov., isolated from coastal seawater during a bloom of green algae
Authors: Qu Zhe , Li Zhao , Zhang Xiuming , Zhang Xiao-Hua
Published: April 2011

A novel Gram-stain-positive, white-pigmented, non-motile, non-sporulating, catalase- and oxidase-positive, strictly aerobic coccus, designated strain ZXM223T, was isolated from a seawater sample collected from the coast of Qingdao, PR China, during a green algal bloom. It grew at pH 6.0–10.5 and 0–25.0 % (w/v) NaCl, with optimum growth at pH 8.5 and 3.0 % (w/v) NaCl. Growth occurred at 16–42 °C (optimum at 28 °C). The major fatty acids were anteiso-C15 : 0 and iso-C15 : 0. Menaquinone 6 (MK-6) was the major respiratory quinone. The polar lipids were phosphatidylglycerol, three unidentified phospholipids and two unknown glycolipids. The peptidoglycan type was l-Lys–Gly5–6. The genomic DNA G+C content was 43.5 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed strain ZXM223T within the genus Salinicoccus, with sequence similarity of 92.2–97.1 % between ZXM223T and the type strains of this genus. The closest relatives were Salinicoccus kunmingensis YIM Y15T, ‘S. salitudinis’ YIM-C678 and S. alkaliphilus T8T. The DNA–DNA relatedness between strain ZXM223T and S. kunmingensis CGMCC 1.6302T and ‘S. salitudinis’ CGMCC 1.6299 ( = YIM-C678) was 37±3 and 30±2 %, respectively. The phenotypic, chemotaxonomic and phylogenetic characteristics and low DNA–DNA relatedness support the proposal of a novel species of the genus Salinicoccus, Salinicoccus qingdaonensis sp. nov., with the type strain ZXM223T ( = LMG 24855T  = CGMCC 1.8895T).
Mariniflexile aquimaris sp. nov., isolated from seawater, and emended description of the genus Mariniflexile Nedashkovskaya et al. 2006
Authors: Jung Yong-Taek , Kim Ji-Hoon , Oh Tae-Kwang , Yoon Jung-Hoon
Published: April 2011

A Gram-staining-negative, non-flagellated, non-gliding and rod-shaped bacterial strain, designated HWR-17T, was isolated from seawater of the Yellow Sea in Korea. Strain HWR-17T grew optimally at pH 7.0–8.0, at 30 °C and in the presence of 2 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain HWR-17T clustered with the two Mariniflexile species in the family Flavobacteriaceae, exhibiting 16S rRNA gene sequence similarity of 97.1–97.2 % to their type strains and less than 95.7 % sequence similarity to other members of the family Flavobacteriaceae. Strain HWR-17T contained MK-6 as the predominant menaquinone and iso-C15 : 0 as the major fatty acid. The polar lipid profile of strain HWR-17T contained phosphatidylethanolamine, an unidentified aminolipid and four unidentified lipids. The DNA G+C content of strain HWR-17T was 35.7 mol% and it exhibited 11 and 10 % DNA–DNA relatedness, respectively, with Mariniflexile
gromovii KCTC 12570T and Mariniflexile
fucanivorans DSM 18792T. The phylogenetic and genetic distinctiveness and differential phenotypic properties revealed that strain HWR-17T is distinguishable from the two recognized Mariniflexile species. On the basis of the data presented, strain HWR-17T is considered to represent a novel species of the genus Mariniflexile, for which the name Mariniflexile aquimaris sp. nov. is proposed. The type strain is HWR-17T ( = KCTC 23346T  = CCUG 60529T). An emended description of the genus Mariniflexile is also proposed.
Kazachstania ichnusensis sp. nov., a diploid homothallic ascomycetous yeast from Sardinian lentisk rhizosphere
Authors: Cardinali Gianluigi , Antonielli Livio , Corte Laura , Roscini Luca , Bagnetti Ambra , Pelliccia Cristina , Puddu Gianfranco
Published: April 2011

During an investigation of yeast biota in the rhizosphere of lentisk in Sardinian semi-arid areas, a strain was isolated that could not be assigned to any known species. The sequence of the D1/D2 domain of the large subunit rDNA gene revealed that the strain belonged to the genus Kazachstania and was phylogenetically related to a clade including Kazachstania aerobia, Kazachstania servazzii, Kazachstania solicola and Kazachstania unispora. The novel isolate differed from members of this clade in its ability to assimilate d-glucono-1,5-lactone and its very weak fermentation of glucose and sucrose; its assimilation profile was unique within the genus Kazachstania. Monosporal colonies were able to sporulate, indicating that the species is homothallic. It is proposed that the isolate represents a novel species, Kazachstania ichnusensis sp. nov., with LCF 1675T ( = CBS 11859T) as type strain.
Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: Testing the AMPA receptor hypothesis in an appetitive learning model
Authors: Cui Wen , Darby-King Andrea , Grimes Matthew T. , Howland John G. , Wang Yu Tian , McLean John H. , Harley Carolyn W.
Published: April 2011

An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in the neonate rat. Rat pups were given a single pairing of peppermint and 2 mg/kg isoproterenol, which produces a 24-h, but not a 48-h, peppermint preference in the 7-d-old rat pup. GluA1 PKA-dependent phosphorylation peaked 10 min after the 10-min training trial and returned to baseline within 90 min. At 24 h, GluA1 subunits did not change overall but were significantly increased in synaptoneurosomes, consistent with increased membrane insertion. Immunohistochemistry revealed a significant increase in GluA1 subunits in olfactory bulb glomeruli, the targets of olfactory nerve axons. Glomerular increases were seen at 3 and 24 h after odor exposure in trained pups, but not in control pups. GluA1 increases were not seen as early as 10 min after training and were no longer observed 48 h after training when odor preference is no longer expressed behaviorally. Thus, the pattern of increased GluA1 membrane expression closely follows the memory timeline. Further, blocking GluA1 insertion using an interference peptide derived from the carboxyl tail of the GluA1 subunit inhibited 24 h odor preference memory providing causative support for our hypothesis. PKA-mediated GluA1 phosphorylation and later GluA1 insertion could, conjointly, provide increased AMPA function to support both short-term and long-term appetitive memory.
Systemic 5-bromo-2-deoxyuridine induces conditioned flavor aversion and c-Fos in the visceral neuraxis
Authors: Kimbrough Adam , Kwon Bumsup , Eckel Lisa A. , Houpt Thomas A.
Published: April 2011

5-bromo-2-deoxyuridine (BrdU) is often used in studies of adult neurogenesis and olfactory learning, but it can also have toxic effects on highly proliferative tissue. We found that pairing Kool-Aid flavors with acute systemic injections of BrdU induced strong conditioned flavor aversions. Intermittent injections during Kool-Aid-glucose conditioning interfered with learning of a conditioned flavor-nutrient preference. Acute injection of BrdU also elevated plasma corticosterone levels and induced c-Fos in the visceral neuraxis. Thus, acute or intermittent systemic injections of BrdU (50–200 mg/kg) have aversive effects that may interfere with learning.
Photoprotective Energy Dissipation Involves the Reorganization of Photosystem II Light-Harvesting Complexes in the Grana Membranes of Spinach Chloroplasts
Authors: Johnson Matthew P. , Goral Tomasz K. , Duffy Christopher D.P. , Brain Anthony P.R. , Mullineaux Conrad W. , Ruban Alexander V.
Published: April 2011

Plants must regulate their use of absorbed light energy on a minute-by-minute basis to maximize the efficiency of photosynthesis and to protect photosystem II (PSII) reaction centers from photooxidative damage. The regulation of light harvesting involves the photoprotective dissipation of excess absorbed light energy in the light-harvesting antenna complexes (LHCs) as heat. Here, we report an investigation into the structural basis of light-harvesting regulation in intact spinach (Spinacia oleracea) chloroplasts using freeze-fracture electron microscopy, combined with laser confocal microscopy employing the fluorescence recovery after photobleaching technique. The results demonstrate that formation of the photoprotective state requires a structural reorganization of the photosynthetic membrane involving dissociation of LHCII from PSII and its aggregation. The structural changes are manifested by a reduced mobility of LHC antenna chlorophyll proteins. It is demonstrated that these changes occur rapidly and reversibly within 5 min of illumination and dark relaxation, are dependent on ΔpH, and are enhanced by the deepoxidation of violaxanthin to zeaxanthin.