bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective Cost-Effectiveness Analysis of Treatments for Aphasia: An Approach Using Experimental Data
Authors: Ellis Charles , Lindrooth Richard C. , Horner Jennifer
Published: February 2014

Purpose

Evidence supports the effectiveness of speech-language treatment for individuals with aphasia, yet less is known about the cost-effectiveness of such treatments. The purpose of this study was to examine the incremental cost and cost-effectiveness of aphasia treatment using previously published data.

Method

The authors completed a retrospective cost-effectiveness analysis using experimental data that they extracted from 19 previously published aphasia treatment studies. Average and incremental cost-effectiveness ratios were calculated based on participants' pre- and posttreatment proficiency scores.

Results

The average cost-effectiveness ratio for all sessions was $9.54 for each 1% increase in the outcome of interest. Measures of incremental cost-effectiveness indicated that aphasia treatments resulted in statistically significant improvements up to and including 17 treatment sessions. Increases in proficiency occurred at a cost of approximately $7.00 per 1% increase for the first 3 sessions to more than $20.00 in the 14th session; the ratio was either not statistically significant or dominated (more costly and less effective) in later sessions.

Conclusions

This cost-effectiveness analysis demonstrated that initial aphasia treatment sessions resulted in relatively larger and more cost-effective benefits than did later aphasia treatment sessions. The findings reported here are preliminary and have limitations. Prospective studies are needed to examine the cost-effectiveness of speech-language treatment for individuals with aphasia.
Cognitive opportunistic relaying systems with mobile nodes: average outage rates and outage durations
Authors: Jia Xiangdong , Yang Longxiang , Zhu Hongbo
Published: February 2014

In the existing literature about cognitive radio opportunistic relaying (CR‐OR) systems, the first‐order statistics such as outage probability are investigated widely. However, for the second‐order statistics, such as average outage duration (AOD) and average outage rate (AOR), there is not open works, still. To obtain a comprehensive cognition on the behaviour of mobile communication systems, this study focuses on the second‐order statistical properties of CR‐OR systems. There are two CR‐OR schemes considered, in which the canonical amplify‐and‐forward (AF) and reactive decode‐and‐forward (RDF) are employed, respectively. Since the equivalent end‐to‐end signal‐to‐noise ratio (SNR) of AF CR‐OR is complicated such that it is very difficult to obtain the closed‐form solution to AOR of AF CR‐OR schemes, the high SNR approximation in AF CR‐OR schemes is employed. For the two schemes, first the closed‐form solutions to AORs and AODs are obtained by using appropriate mathematical proof. Based on the derivations, the comparison analyses about AORs and AODs of the two schemes are provided. The comparison results show that, under high SNR approximation, the AF CR‐OR scheme achieves the same AOR and AOD as RDF CR‐OR. Finally, the impact of system parameters on AORs and AODs is provided.
Empirical analysis of the causes of stop‐and‐go waves at sags
Authors: Goñi Ros Bernat , Knoop Victor L. , van Arem Bart , Hoogendoorn Serge P.
Published: February 2014

Stop‐and‐go waves are spatially‐confined regions of low traffic speed that propagate upstream at a constant velocity. The occurrence of stop‐and‐go waves on freeways has negative impacts on both travel time and traffic safety. Sags are freeway sections along which gradient changes significantly from downwards to upwards. Stop‐and‐go waves often emerge on the uphill section of sags, both in uncongested and congested traffic conditions. According to previous studies, the formation of stop‐and‐go waves at sags can be caused by local changes in car‐following behaviour as well as disruptive lane changes. However, it is not clear which of those two causes is more frequent. This paper aims to identify the primary factor triggering stop‐and‐go waves at sags. To this end, the authors analyse vehicle trajectories collected by means of video cameras on a three‐lane sag of the Tomei Expressway (Japan), identifying the causes of formation and growth of stop‐and‐go waves on the study site. The results show that the primary factor triggering stop‐and‐go waves is related to car‐following behaviour. This finding shows the relevance of developing systems to assist drivers in performing the acceleration task at sags.
Third order susceptibilities in supercooled liquids and the “box model” theory versus experiments
Authors: Pick R. M.
Published: February 2014

We give here the exact expression of the time dependent third order polarization predicted by the “box model” when a supercooled liquid is permanently subjected since time t = 0 to a strong electric field ${\rm E}( {\rm t}) = \begin{array}{*{20}c} {{\rm E}_0 } & {\sin ( {{\rm \omega t}} )} \end{array}$E(t)=E0sin(ωt), Dielectric Hole Burning experiment. We derive different forms of the time dependent susceptibilities, both at frequencies ω and 3ω, and examine particularly one of them. We also show that its susceptibility at ω should exhibit, at short times, presently undetected oscillations at frequency 2ω that are a signature of the “box model.” We finally compare, for a large frequency range, the ω and 3ω time independent susceptibilities with the corresponding measurements on glycerol at 204.7 K. The agreement is good at frequency ω but, as already shown in Ladieu et al. [J. Chem. Phys. 134, 194507 (2011)], it is not the case at 3ω.
Charge-displacement analysis for excited states
Authors: Ronca Enrico , Pastore Mariachiara , Belpassi Leonardo , De Angelis Filippo , Angeli Celestino , Cimiraglia Renzo , Tarantelli Francesco
Published: February 2014

We extend the Charge-Displacement (CD) analysis, already successfully employed to describe the nature of intermolecular interactions [L. Belpassi et al., J. Am. Chem. Soc. 132, 13046 (2010)] and various types of controversial chemical bonds [L. Belpassi et al., J. Am. Chem. Soc. 130, 1048 (2008); N. Salvi et al., Chem. Eur. J. 16, 7231 (2010)], to study the charge fluxes accompanying electron excitations, and in particular the all-important charge-transfer (CT) phenomena. We demonstrate the usefulness of the new approach through applications to exemplary excitations in a series of molecules, encompassing various typical situations from valence, to Rydberg, to CT excitations. The CD functions defined along various spatial directions provide a detailed and insightful quantitative picture of the electron displacements taking place.
The Golden-Thompson inequality: Historical aspects and random matrix applications
Authors: Forrester Peter J. , Thompson Colin J.
Published: February 2014

The Golden-Thompson inequality, Tr (eA+B) ⩽ Tr (eAeB) for A, B Hermitian matrices, appeared in independent works by Golden and Thompson published in 1965. Both of these were motivated by considerations in statistical mechanics. In recent years the Golden-Thompson inequality has found applications to random matrix theory. In this article, we detail some historical aspects relating to Thompson's work, giving in particular a hitherto unpublished proof due to Dyson, and correspondence with Pólya. We show too how the 2 × 2 case relates to hyperbolic geometry, and how the original inequality holds true with the trace operation replaced by any unitarily invariant norm. In relation to the random matrix applications, we review its use in the derivation of concentration type lemmas for sums of random matrices due to Ahlswede-Winter, and Oliveira, generalizing various classical results.
Discriminating trpzip2 and trpzip4 peptides’ folding landscape using the two-dimensional infrared spectroscopy: A simulation study
Authors: Wu Tianmin , Zhang Ruiting , Li Huanhuan , Yang Lijiang , Zhuang Wei
Published: February 2014

We analyzed, based on the theoretical spectroscopic modeling, how the differences in the folding landscapes of two β-hairpin peptides trpzip2 and trpzip4 are reflected in their thermal unfolding infrared measurements. The isotope-edited equilibrium FTIR and two dimensional infrared spectra of the two peptides were calculated, using the nonlinear exciton propagation method, at a series of temperatures. The spectra calculations were based on the configuration distributions generated using the GBOBC implicit solvent MD simulation and the integrated tempering sampling technique. Conformational analysis revealed the different local thermal stabilities for these two peptides, which suggested the different folding landscapes. Our study further suggested that the ellipticities of the isotope peaks in the coherent IR signals are more sensitive to these local stability differences compared with other spectral features such as the peak intensities. Our technique can thus be combined with the relevant experimental measurements to achieve a better understanding of the peptide folding behaviors.
Molecular properties of excited electronic state: Formalism, implementation, and applications of analytical second energy derivatives within the framework of the time-dependent density functional theory/molecular mechanics
Authors: Zeng Qiao , Liu Jie , Liang WanZhen
Published: February 2014

This work extends our previous works [J. Liu and W. Z. Liang, J. Chem. Phys. 135, 014113 (2011); J. Liu and W. Z. Liang, J. Chem. Phys. 135, 184111 (2011)] on analytical excited-state energy Hessian within the framework of time-dependent density functional theory (TDDFT) to couple with molecular mechanics (MM). The formalism, implementation, and applications of analytical first and second energy derivatives of TDDFT/MM excited state with respect to the nuclear and electric perturbations are presented. Their performances are demonstrated by the calculations of adiabatic excitation energies, and excited-state geometries, harmonic vibrational frequencies, and infrared intensities for a number of benchmark systems. The consistent results with the full quantum mechanical method and other hybrid theoretical methods indicate the reliability of the current numerical implementation of developed algorithms. The computational accuracy and efficiency of the current analytical approach are also checked and the computational efficient strategies are suggested to speed up the calculations of complex systems with many MM degrees of freedom. Finally, we apply the current analytical approach in TDDFT/MM to a realistic system, a red fluorescent protein chromophore together with part of its nearby protein matrix. The calculated results indicate that the rearrangement of the hydrogen bond interactions between the chromophore and the protein matrix is responsible for the large Stokes shift.
Diverse and tunable electronic structures of single-layer metal phosphorus trichalcogenides for photocatalytic water splitting
Authors: Liu Jian , Li Xi-Bo , Wang Da , Lau Woon-Ming , Peng Ping , Liu Li-Min
Published: February 2014

The family of bulk metal phosphorus trichalcogenides (APX3, A = MII, ${\rm M}_{0.5}^{\rm I}{\rm M}_{0.5}^{{\rm III}}$M0.5IM0.5 III ; X = S, Se; MI, MII, and MIII represent Group-I, Group-II, and Group-III metals, respectively) has attracted great attentions because such materials not only own magnetic and ferroelectric properties, but also exhibit excellent properties in hydrogen storage and lithium battery because of the layered structures. Many layered materials have been exfoliated into two-dimensional (2D) materials, and they show distinct electronic properties compared with their bulks. Here we present a systematical study of single-layer metal phosphorus trichalcogenides by density functional theory calculations. The results show that the single layer metal phosphorus trichalcogenides have very low formation energies, which indicates that the exfoliation of single layer APX3 should not be difficult. The family of single layer metal phosphorus trichalcogenides exhibits a large range of band gaps from 1.77 to 3.94 eV, and the electronic structures are greatly affected by the metal or the chalcogenide atoms. The calculated band edges of metal phosphorus trichalcogenides further reveal that single-layer ZnPSe3, CdPSe3, Ag0.5Sc0.5PSe3, and Ag0.5In0.5PX3 (X = S and Se) have both suitable band gaps for visible-light driving and sufficient over-potentials for water splitting. More fascinatingly, single-layer Ag0.5Sc0.5PSe3 is a direct band gap semiconductor, and the calculated optical absorption further convinces that such materials own outstanding properties for light absorption. Such results demonstrate that the single layer metal phosphorus trichalcogenides own high stability, versatile electronic properties, and high optical absorption, thus such materials have great chances to be high efficient photocatalysts for water-splitting.
Magnetization dynamics and interface studies in ion-beam sputtered Si/CoFeB(8)/MgO(4)/CoFeB(8)/Ta(5) structures
Authors: Raju M. , Behera Nilamani , Pandya Dinesh K. , Chaudhary Sujeet
Published: February 2014

The interface roughness, Boron distribution in bulk CoFeB and at interface, Gilbert damping constant (α), and inhomogeneous broadening in ion-beam sputtered Si/CoFeB(8)/MgO(4)/CoFeB(8)/Ta(5) structures are found to be sensitive to the MgO growth process. The ion-assist and reactive growth processes that result in sharper interfaces of width ∼0.5 nm lead to smaller α of 0.0050 ± 0.0003 and 0.0060 ± 0.0002 and inhomogeneous broadening ΔH0 of 3 ± 0.3 and 1 ± 0.3 Oe, respectively. On the other hand, the post-oxidation method results in rough interface and higher retention of Boron in CoFeB leading to higher values for α and ΔH0 as 0.0080 ± 0.0006 and 5 ± 0.3 Oe, respectively.
Self-organized internal architectures of chiral micro-particles
Authors: Provenzano Clementina , Mazzulla Alfredo , Pagliusi Pasquale , De Santo Maria P. , Desiderio Giovanni , Perrotta Ida , Cipparrone Gabriella
Published: February 2014

The internal architecture of polymeric self-assembled chiral micro-particles is studied by exploring the effect of the chirality, of the particle sizes, and of the interface/surface properties in the ordering of the helicoidal planes. The experimental investigations, performed by means of different microscopy techniques, show that the polymeric beads, resulting from light induced polymerization of cholesteric liquid crystal droplets, preserve both the spherical shape and the internal self-organized structures. The method used to create the micro-particles with controlled internal chiral architectures presents great flexibility providing several advantages connected to the acquired optical and photonics capabilities and allowing to envisage novel strategies for the development of chiral colloidal systems and materials.
Polymer escape from a confining potential
Authors: Mökkönen Harri , Ikonen Timo , Jónsson Hannes , Ala-Nissila Tapio
Published: February 2014

The rate of escape of polymers from a two-dimensionally confining potential well has been evaluated using self-avoiding as well as ideal chain representations of varying length, up to 80 beads. Long timescale Langevin trajectories were calculated using the path integral hyperdynamics method to evaluate the escape rate. A minimum is found in the rate for self-avoiding polymers of intermediate length while the escape rate decreases monotonically with polymer length for ideal polymers. The increase in the rate for long, self-avoiding polymers is ascribed to crowding in the potential well which reduces the free energy escape barrier. An effective potential curve obtained using the centroid as an independent variable was evaluated by thermodynamic averaging and Kramers rate theory then applied to estimate the escape rate. While the qualitative features are well reproduced by this approach, it significantly overestimates the rate, especially for the longer polymers. The reason for this is illustrated by constructing a two-dimensional effective energy surface using the radius of gyration as well as the centroid as controlled variables. This shows that the description of a transition state dividing surface using only the centroid fails to confine the system to the region corresponding to the free energy barrier and this problem becomes more pronounced the longer the polymer is. A proper definition of a transition state for polymer escape needs to take into account the shape as well as the location of the polymer.
A modified Bitter-type electromagnet and control system for cold atom experiments
Authors: Luan Tian , Zhou Tianwei , Chen Xuzong , Ma Zhaoyuan
Published: February 2014

We present a modified Bitter-type electromagnet which features high magnetic field, fine electronic properties and efficient heat removal. The electromagnet is constructed from a stack of copper layers separated by mica layers that have the same shape. A distinctive design of cooling channels on the insulating layers and the parallel ducts between the layers ensures low resistance for cooling water to flow. A continuous current control system is also made to regulate the current through the electromagnet. In our experiment, versatile electromagnets are applied to generate magnetic field and gradient field. From our measurements, a peak magnetic field of 1000 G and a peak gradient field of 80 G/cm are generated in the center of the apparatuses which are 7 cm and 5 cm away from the edge of each electromagnet with a current of 230 A and 120 A, respectively. With the effective feedback design in the current control system and cooling water flow of 3.8 l/min, the stability of the current through the electromagnets can reach 10−5.
High-performance ferroelectric memory based on fully patterned tunnel junctions
Authors: Boyn S. , Girod S. , Garcia V. , Fusil S. , Xavier S. , Deranlot C. , Yamada H. , Carrétéro C. , Jacquet E. , Bibes M. , Barthélémy A. , Grollier J.
Published: February 2014

In tunnel junctions with ferroelectric barriers, switching the polarization direction modifies the electrostatic potential profile and the associated average tunnel barrier height. This results in strong changes of the tunnel transmission and associated resistance. The information readout in ferroelectric tunnel junctions (FTJs) is thus resistive and non-destructive, which is an advantage compared to the case of conventional ferroelectric memories (FeRAMs). Initially, endurance limitation (i.e., fatigue) was the main factor hampering the industrialization of FeRAMs. Systematic investigations of switching dynamics for various ferroelectric and electrode materials have resolved this issue, with endurance now reaching 1014 cycles. Here we investigate data retention and endurance in fully patterned submicron Co/BiFeO3/Ca0.96Ce0.04MnO3 FTJs. We report good reproducibility with high resistance contrasts and extend the maximum reported endurance of FTJs by three orders of magnitude (4 × 106 cycles). Our results indicate that here fatigue is not limited by a decrease of the polarization or an increase of the leakage but rather by domain wall pinning. We propose directions to access extreme and intermediate resistance states more reliably and further strengthen the potential of FTJs for non-volatile memory applications.
Magnetic field assisted self-assembly of ferrite-ferroelectric core-shell nanofibers and studies on magneto-electric interactions
Authors: Sreenivasulu G. , Popov Maksym , Zhang Ru , Sharma K. , Janes C. , Mukundan A. , Srinivasan G.
Published: February 2014

Core-shell nanofibers of nickel ferrite and lead zirconate titanate have been synthesized by electrospinning, assembled into superstructure in uniform or non-uniform magnetic fields, and have been characterized in terms of ferroic order parameters and strain mediated magneto-electric (ME) coupling. The core-shell structure was confirmed by electron microscopy and scanning probe microscopy. Studies on magnetic field induced polarization P in assembled samples showed a decrease or increase in P, depending on the nature of fibers and strengthening of ME coupling with change in remnant-P as high as 32%. Strong ME interactions were evident from H-induced variation in permittivity at 20–22 GHz.
Study of deep hole trap levels associated with bias-induced metastabilities in Cu(In,Ga)Se2 thin films using isothermal capacitance transient spectroscopy
Authors: Okada Hiroshi , Minemoto Takashi
Published: February 2014

The origins of bias-induced metastabilities in Cu(In,Ga)Se2 thin film samples were investigated using isothermal capacitance transient spectroscopy. We confirmed that these metastabilities are associated with deep hole trap levels, and examined these levels in detail. The trap has multiple charge states, tentatively assigned to a double acceptor, where the first (−1/0) acceptor level has an apparent activation energy of 0.72 eV and the second acceptor level (−2/−1) has an apparent activation energy of 0.51 eV, indicating negative-U-like properties. The metastable behavior becomes prominent on forward biasing of the junction, which was attributed to the slow hole-capture rate of the first (−1/0) acceptor level. This slow rate is probably because of a large lattice relaxation associated with the hole-capture process, as well as depletion of free holes because of the excess concentration of the deep level compared with the net concentration of shallow acceptors.
Magnetic properties of transition metal doped AlN nanosheet: First-principle studies
Authors: Shi Changmin , Qin Hongwei , Zhang Yongjia , Hu Jifan , Ju Lin
Published: February 2014

We carry out our first-principles calculations within density functional theory to study the 3d transition metal (TM) doped AlN nanosheets. The calculated results indicate that a stoichiometric AlN nanosheet is graphene-like structure and nonmagnetic. The TM impurities can induce magnetic moments, localized mainly on the 3d TM atoms and neighboring N atoms. Our calculated results of TM-doped nanosheet systems indicate a strong interaction between 3d orbit of TM atom and the 2p orbit of N atoms. In addition, the Mn- and Ni-doped AlN nanosheet with half-metal characters seems to be good candidates for spintronic applications. When substituting two Al atoms, the relative energies of the states between ferromagnetic and antiferromagnetic coupling are investigated sufficiently. The exchange coupling of Co- and Ni-doped AlN nanosheets exhibits a transformation with different distances of two TM atoms and that of Cr-, Mn-, and Fe-doped AlN nanosheets is not changed.
Size effect on transfection and cytotoxicity of nanoscale plasmid DNA/polyethyleneimine complexes for aerosol gene delivery
Authors: Hoon Byeon Jeong , Kim Jang-Woo
Published: February 2014

Nanoscale plasmid DNA (pDNA)/polyethyleneimine (PEI) complexes were fabricated in the aerosol state using a nebulization system consisting of a collison atomizer and a cool-walled diffusion dryer. The aerosol fabricated nanoscale complexes were collected and employed to determine fundamental properties of the complexes, such as size, structure, surface charge, and in vitro gene transfection efficiency and cytotoxicity. The results showed that mass ratio between pDNA and PEI should be optimized to enhance gene transfection efficiency without a significant loss of cell viability. These findings may support practical advancements in the field of nonviral gene delivery.
Active and silent chromophore isoforms for phytochrome Pr photoisomerization: An alternative evolutionary strategy to optimize photoreaction quantum yields
Authors: Yang Yang , Linke Martin , von Haimberger Theodore , Matute Ricardo , González Leticia , Schmieder Peter , Heyne Karsten
Published: February 2014

Photoisomerization of a protein bound chromophore is the basis of light sensing of many photoreceptors. We tracked Z-to-E photoisomerization of Cph1 phytochrome chromophore PCB in the Pr form in real-time. Two different phycocyanobilin (PCB) ground state geometries with different ring D orientations have been identified. The pre-twisted and hydrogen bonded PCBa geometry exhibits a time constant of 30 ps and a quantum yield of photoproduct formation of 29%, about six times slower and ten times higher than that for the non-hydrogen bonded PCBb geometry. This new mechanism of pre-twisting the chromophore by protein-cofactor interaction optimizes yields of slow photoreactions and provides a scaffold for photoreceptor engineering.
i-Review: Sharing Code
Authors: Kubilius Jonas
Published: February 2014

Sharing code is becoming increasingly important in the wake of Open Science. In this review I describe and compare two popular code-sharing utilities, GitHub and Open Science Framework (OSF). GitHub is a mature, industry-standard tool but lacks focus towards researchers. In comparison, OSF offers a one-stop solution for researchers but a lot of functionality is still under development. I conclude by listing alternative lesser-known tools for code and materials sharing.
A review of the genetic and epigenetic factors affecting lamb survival
Authors: Brien F. D. , Cloete S. W. P. , Fogarty N. M. , Greeff J. C. , Hebart M. L. , Hiendleder S. , Edwards J. E. Hocking , Kelly J. M. , Kind K. L. , Kleemann D. O. , Plush K. L. , Miller D. R.
Published: February 2014

Poor lamb survival pre-weaning is a major source of reproductive inefficiency in Australian sheep flocks. While nutrition and management options have been extensively researched and promoted to improve lamb survival, the present review focuses on the prospects for obtaining genetic gain and helps identify selection strategies for boosting such gains to improve overall reproductive efficiency in the Australian sheep industry. Estimated heritability for lamb survival using linear model analysis is low, although use of threshold models suggests that heritability could be higher, which, if true, could help explain the substantial genetic gains obtained in long-term selection experiments. Epigenetic mechanisms may hinder selection and quantitative trait-loci identification through confounding and/or masking genetic variances and co-variances. With sufficient information, these effects could be considered in genetic evaluations by identifying those components that are amenable to selection. Regarding indirect selection, finding effective criteria for improving lamb survival has proved elusive. Most measures of maternal behaviour, temperament and lambing difficulty researched are poorly correlated genetically with lamb survival. Of lamb behaviours and thermo-genic indicators studied, latency to bleat following handling by humans is moderately genetically correlated with lamb survival, as is neonatal rectal temperature. Industry application remains to be adequately explored for the more promising of these measures. Finally, in lieu of direct selection for lamb survival, there is merit in selecting for multiple-rearing ability or its equivalent, possibly with additional selection criteria for lamb survival and reproductive efficiency.
Vitamin E status and reproduction in sheep: potential implications for Australian sheep production
Authors: Liu Shimin , Masters David , Ferguson Mark , Thompson Andrew
Published: February 2014

Vitamin E concentrations in dried pastures, stubble and most grains are below the recommended requirement of 10–25 mg/kg dry matter (DM). Sheep grazing in an environment when dry pastures and cereal crop stubbles are their primary source of nutrients for a few months have a high risk of developing vitamin E deficiency. If the low vitamin E status coincides with late gestation, the neonate is likely to have a deficiency of vitamin E. Some of the consequences of this are well known, with nutritional myopathy (with high mortality) a risk in young growing sheep unless vitamin E supplements are provided. Vitamin E plays an important role in the management of oxidative stress. Sperm are subject to oxidative damage due to high metabolic rate and high concentration of polyunsaturated fatty acids in their membranes. Oxidative stress may also compromise follicular development and ovarian activity. Vitamin E is also involved with improvement in immune response. For these reasons, vitamin E status is important for reproductive efficiency in both males and females and in the survival of lambs and weaners. In addition, vitamin E deficiency is potentially exacerbated by a lack of other nutrients involved in the management of oxidative stress and immune function, such as selenium (Se) and sulfur amino acids. A Se concentration of 0.1 mg/kg DM in feedstuffs is required to maintain immune competency in sheep. In considering possible consequences for reproduction, further investigation is justified into: (i) effects of low vitamin E, in combination with low levels of other natural antioxidants, on the quality and quantity of sperm produced before and during mating; (ii) follicle development, fertilisation and embryonic mortality in Se-supplemented ewes; (iii) assessment of supplementing formulated antioxidants to rams and ewes during the mating season; (iv) managing oxidative stress in the newborn – consequences of large doses of vitamin E to ewes before parturition to boost lamb reserves; (v) potential benefits to lamb survival through boosting maternal innate immunity; (vi) choices for boosting antioxidant and immune function in ewes and lambs through ‘immune pack’ nutrient options that may target nutrients lacking in dry grass pastures; (vii) the potential role of heat stress in modifying the requirements for, and responses to, vitamin E in extensive grazing systems.
Morpho-physiological and adaptive variation of Italian germplasm of sulla (Hedysarum coronarium L.)
Authors: Annicchiarico P. , Ruisi P. , Di Miceli G. , Pecetti L.
Published: February 2014

Sulla is a biennial forage legume native to the central-western Mediterranean Basin and has increasing interest for regions with Mediterranean-climate. The Italian germplasm is a reservoir of variation for important agronomic traits. This study aimed to support breeding programs by investigating patterns of agronomic, adaptive and morpho-physiological variation among ecotypes collected from the three main Italian regions of species cultivation: central Italy, and the two islands of Sicily and Sardinia. Forage yield and morpho-physiological traits were evaluated at a site with Mediterranean climate in Sicily. Forage yield and cold tolerance in a cold-prone site of northern Italy were also assessed, to locate useful germplasm for widening crop resilience and climatic adaptability. Collection regions, and ecotypes within regions, differed for total forage yield and final plant survival, but their responses were subjected to interactions with test location. Specific adaptation dominated the adaptive responses of ecotypes and elite commercial varieties. Ecotype adaptation to cold winter was associated with latitude and, more specifically, the extent of cold stress in collecting sites. The ecotype collection region had a bearing also on morpho-physiological characteristics. A few ecotypes from central Italy performed outstandingly with respect to elite varieties, displaying wide adaptation across cold-prone and drought-prone environments.
Host plant peptides elicit a transcriptional response to control theSinorhizobium meliloticell cycle during symbiosis
Authors: Penterman Jon , Abo Ryan P. , De Nisco Nicole J. , Arnold Markus F. F. , Longhi Renato , Zanda Matteo , Walker Graham C.
Published: February 2014

Significance

Sinorhizobium melilotiand its legume hosts establish a symbiosis in which bacterial fixed nitrogen is exchanged for plant carbon compounds. We study this symbiosis because it is agriculturally and ecologically important and to identify mechanisms used in host–microbe interactions.S. melilotiis internalized in specialized host nodule cells that then use small, cysteine-rich peptides to drive their differentiation into polyploid cells that fix nitrogen. We found that a representative host peptide blocks cell division, in part by eliciting significant changes in the expression of genes that regulate the cell cycle and mediate cell division. We also found that the peptide activated pathways conserved in related pathogens. Our study provides insights into how host peptides cause differentiation ofS. melilotiduring symbiosis.
Can Approximate Mental Calculation Account for Operational Momentum in Addition and Subtraction?
Authors: Knops André , Dehaene Stanislas , Berteletti Ilaria , Zorzi Marco
Published: February 2014

The operational momentum (OM) effect describes a cognitive bias whereby we overestimate the results of mental addition problems while underestimating for subtraction. To test whether the OM emerges from psychophysical characteristics of the mental magnitude representation we measured two basic parameters (Weber fraction and numerical estimation accuracy) characterizing the mental magnitude representation and participants’ performance in cross-notational addition and subtraction problems. Although participants were able to solve the cross-notational problems, they consistently chose relatively larger results in addition problems than in subtraction problems, thus replicating and extending previous results. Combining the above measures in a psychophysical model allowed us to partially predict the chosen results. Most crucially, however, we were not able to fully model the OM bias on the basis of these psychophysical parameters. Our results speak against the idea that the OM is due to basic characteristics of the mental magnitude representation. In turn, this might be interpreted as evidence for the assumption that the OM effect is better explained by attentional shifts along the mental magnitude representation during mental calculation.
Symmetric Whitney tower cobordism for bordered 3-manifolds and links
Authors: Cha Jae Choon
Published: February 2014

We introduce the notion of a symmetric Whitney tower cobordism between bordered 3-manifolds, aiming at the study of homology cobordism and link concordance. It is motivated by the symmetric Whitney tower approach to slicing knots and links initiated by T. Cochran, K. Orr, and P. Teichner. We give amenable Cheeger-Gromov

ρ
\rho

-invariant obstructions to bordered 3-manifolds being Whitney tower cobordant. Our obstruction is related to and generalizes several prior known results, and also gives new interesting cases. As an application, our method applied to link exteriors reveals new structures on (Whitney tower and grope) concordance between links with nonzero linking number, including the Hopf link.
New single-molecule speckle microscopy reveals modification of the retrograde actin flow by focal adhesions at nanometer scales
Authors: Yamashiro Sawako , Mizuno Hiroaki , Smith Matthew B. , Ryan Gillian L. , Kiuchi Tai , Vavylonis Dimitrios , Watanabe Naoki
Published: February 2014

Speckle microscopy directly visualizes the retrograde actin flow, which is believed to promote cell-edge protrusion when linked to focal adhesions (FAs). However, it has been argued that, due to rapid actin turnover, the use of green fluorescent protein–actin, the lack of appropriate analysis algorithms, and technical difficulties, speckle microscopy does not necessarily report the flow velocities of entire actin populations. In this study, we developed a new, user-friendly single-molecule speckle (SiMS) microscopy using DyLight dye-labeled actin. Our new SiMS method enables in vivo nanometer-scale displacement analysis with a low localization error of ±8–8.5 nm, allowing accurate flow-velocity measurement for actin speckles with lifetime <5 s. In lamellipodia, both short- and long-lived F-actin molecules flow with the same speed, indicating they are part of a single actin network. These results do not support coexistence of F-actin populations with different flow speeds, which is referred to as the lamella hypothesis. Mature FAs, but not nascent adhesions, locally obstruct the retrograde flow. Interestingly, the actin flow in front of mature FAs is fast and biased toward FAs, suggesting that mature FAs attract the flow in front and actively remodel the local actin network.
miR-218 regulates focal adhesion kinase–dependent TGFβ signaling in fibroblasts
Authors: Guo Fen , Carter David E. , Leask Andrew
Published: February 2014

Scarring, which occurs in essentially all adult tissue, is characterized by the excessive production and remodeling of extracellular matrix by α-smooth muscle actin (SMA)–expressing myofibroblasts located within connective tissue. Excessive scarring can cause organ failure and death. Oral gingivae do not scar. Compared to dermal fibroblasts, gingival fibroblasts are less responsive to transforming growth factor β (TGFβ) due to the reduced expression, due to the reduced expression and activity of focal adhesion kinase (FAK) by this cell type. Here we show that, compared with dermal fibroblasts, gingival fibroblasts show reduced expression of miR-218. Introduction of pre–miR-218 into gingival fibroblasts elevates FAK expression and, via a FAK/src-dependent mechanism, results in the ability of TGFβ to induce α-SMA. The deubiquitinase cezanne is a direct target of miR-218 and has increased expression in gingival fibroblasts compared with dermal fibroblasts. Knockdown of cezanne in gingival fibroblasts increases FAK expression and causes TGFβ to induce α-smooth muscle actin (α-SMA). These results suggest that miR-218 regulates the ability of TGFβ to induce myofibroblast differentiation in fibroblasts via cezanne/FAK.
Caenorhabditis elegansHOPS and CCZ-1 mediate trafficking to lysosome-related organelles independently of RAB-7 and SAND-1
Authors: Delahaye Jared L. , Foster Olivia K. , Vine Annalise , Saxton Daniel S. , Curtin Thomas P. , Somhegyi Hannah , Salesky Rebecca , Hermann Greg J.
Published: February 2014

As early endosomes mature, the SAND-1/CCZ-1 complex acts as a guanine nucleotide exchange factor (GEF) for RAB-7 to promote the activity of its effector, HOPS, which facilitates late endosome–lysosome fusion and the consumption of AP-3–containing vesicles. We show that CCZ-1 and the HOPS complex are essential for the biogenesis of gut granules, cell type–specific, lysosome-related organelles (LROs) that coexist with conventional lysosomes in Caenorhabditis elegans intestinal cells. The HOPS subunit VPS-18 promotes the trafficking of gut granule proteins away from lysosomes and functions downstream of or in parallel to the AP-3 adaptor. CCZ-1 also acts independently of AP-3, and ccz-1 mutants mistraffic gut granule proteins. Our results indicate that SAND-1 does not participate in the formation of gut granules. In the absence of RAB-7 activity, gut granules are generated; however, their size and protein composition are subtly altered. These observations suggest that CCZ-1 acts in partnership with a protein other than SAND-1 as a GEF for an alternate Rab to promote gut granule biogenesis. Point mutations in GLO-1, a Rab32/38-related protein, predicted to increase spontaneous guanine nucleotide exchange, specifically suppress the loss of gut granules by ccz-1 and glo-3 mutants. GLO-3 is known to be required for gut granule formation and has homology to SAND-1/Mon1–related proteins, suggesting that CCZ-1 functions with GLO-3 upstream of the GLO-1 Rab, possibly as a GLO-1 GEF. These results support LRO formation occurring via processes similar to conventional lysosome biogenesis, albeit with key molecular differences.
Relative Preferences for Soil Conservation Incentives among Smallholder Farmers: Evidence from Malawi
Authors: Marenya Paswel , Smith Vincent H. , Nkonya Ephraim
Published: February 2014

This paper uses framed choice experiments to examine the preferences of smallholder farmers in Malawi regarding alternative policy‐based incentives to adopt conservation practices that reduce soil erosion and increase yields. The policy incentives offered in the choice experiments included an ideal index‐based crop insurance contract, an index insurance contract with basis risk, cash payments, and fertilizer subsidies. Prior to implementing the choice experiments, the farmers participated in a workshop utilizing small group‐based dynamic learning games that demonstrated how index‐based crop insurance contracts function. The choice experiment results indicate that most farmers preferred cash payments to index insurance contracts, even when the insurance contracts offered substantially higher expected returns. Further, more risk averse farmers were more likely to prefer cash payments than less risk averse and risk loving farmers.
Learning phenotype densities conditional on many interacting predictors
Authors: Kessler David C. , Taylor Jack A. , Dunson David B.
Published: February 2014

Motivation: Estimating a phenotype distribution conditional on a set of discrete-valued predictors is a commonly encountered task. For example, interest may be in how the density of a quantitative trait varies with single nucleotide polymorphisms and patient characteristics. The subset of important predictors is not usually known in advance. This becomes more challenging with a high-dimensional predictor set when there is the possibility of interaction.

Results: We demonstrate a novel non-parametric Bayes method based on a tensor factorization of predictor-dependent weights for Gaussian kernels. The method uses multistage predictor selection for dimension reduction, providing succinct models for the phenotype distribution. The resulting conditional density morphs flexibly with the selected predictors. In a simulation study and an application to molecular epidemiology data, we demonstrate advantages over commonly used methods.

Availability and implementation: MATLAB code available at https://googledrive.com/host/0Bw6KIFB-k4IOOWQ0dFJtSVZxNE0/ktdctf.html

Contact:  dave.kessler@gmail.com
Visualization and probability-based scoring of structural variants within repetitive sequences
Authors: Halper-Stromberg Eitan , Steranka Jared , Burns Kathleen H. , Sabunciyan Sarven , Irizarry Rafael A.
Published: February 2014

Motivation: Repetitive sequences account for approximately half of the human genome. Accurately ascertaining sequences in these regions with next generation sequencers is challenging, and requires a different set of analytical techniques than for reads originating from unique sequences. Complicating the matter are repetitive regions subject to programmed rearrangements, as is the case with the antigen-binding domains in the Immunoglobulin (Ig) and T-cell receptor (TCR) loci.

Results: We developed a probability-based score and visualization method to aid in distinguishing true structural variants from alignment artifacts. We demonstrate the usefulness of this method in its ability to separate real structural variants from false positives generated with existing upstream analysis tools. We validated our approach using both target-capture and whole-genome experiments. Capture sequencing reads were generated from primary lymphoid tumors, cancer cell lines and an EBV-transformed lymphoblast cell line over the Ig and TCR loci. Whole-genome sequencing reads were from a lymphoblastoid cell-line.

Availability: We implement our method as an R package available at https://github.com/Eitan177/targetSeqView. Code to reproduce the figures and results are also available.

Contact:  ehalper2@jhmi.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
A dual promoter system regulating λ DNA replication initiation
Authors: Olszewski Paweł , Szambowska Anna , Barańska Sylwia , Narajczyk Magdalena , Węgrzyn Grzegorz , Glinkowska Monika
Published: February 2014

Transcription and DNA replication are tightly regulated to ensure coordination of gene expression with growth conditions and faithful transmission of genetic material to progeny. A large body of evidence has accumulated, indicating that encounters between protein machineries carrying out DNA and RNA synthesis occur in vivo and may have important regulatory consequences. This feature may be exacerbated in the case of compact genomes, like the one of bacteriophage λ, used in our study. Transcription that starts at the rightward pR promoter and proceeds through the λ origin of replication and downstream of it was proven to stimulate the initiation of λ DNA replication. Here, we demonstrate that the activity of a convergently oriented pO promoter decreases the efficiency of transcription starting from pR. Our results show, however, that a lack of the functional pO promoter negatively influences λ phage and λ-derived plasmid replication. We present data, suggesting that this effect is evoked by the enhanced level of the pR-driven transcription, occurring in the presence of the defective pO, which may result in the impeded formation of the replication initiation complex. Our data suggest that the cross talk between the two promoters regulates λ DNA replication and coordinates transcription and replication processes.
Direct activation of human and mouse Oct4 genes using engineered TALE and Cas9 transcription factors
Authors: Hu Jiabiao , Lei Yong , Wong Wing-Ki , Liu Senquan , Lee Kai-Chuen , He Xiangjun , You Wenxing , Zhou Rui , Guo Jun-Tao , Chen Xiongfong , Peng Xianlu , Sun Hao , Huang He , Zhao Hui , Feng Bo
Published: February 2014

The newly developed transcription activator-like effector protein (TALE) and clustered regularly interspaced short palindromic repeats/Cas9 transcription factors (TF) offered a powerful and precise approach for modulating gene expression. In this article, we systematically investigated the potential of these new tools in activating the stringently silenced pluripotency gene Oct4 (Pou5f1) in mouse and human somatic cells. First, with a number of TALEs and sgRNAs targeting various regions in the mouse and human Oct4 promoters, we found that the most efficient TALE-VP64s bound around −120 to −80 bp, while highly effective sgRNAs targeted from −147 to −89-bp upstream of the transcription start sites to induce high activity of luciferase reporters. In addition, we observed significant transcriptional synergy when multiple TFs were applied simultaneously. Although individual TFs exhibited marginal activity to up-regulate endogenous gene expression, optimized combinations of TALE-VP64s could enhance endogenous Oct4 transcription up to 30-fold in mouse NIH3T3 cells and 20-fold in human HEK293T cells. More importantly, the enhancement of OCT4 transcription ultimately generated OCT4 proteins. Furthermore, examination of different epigenetic modifiers showed that histone acetyltransferase p300 could enhance both TALE-VP64 and sgRNA/dCas9-VP64 induced transcription of endogenous OCT4. Taken together, our study suggested that engineered TALE-TF and dCas9-TF are useful tools for modulating gene expression in mammalian cells.
DNA-PKcs is required to maintain stability of Chk1 and Claspin for optimal replication stress response
Authors: Lin Yu-Fen , Shih Hung-Ying , Shang Zengfu , Matsunaga Shinji , Chen Benjamin PC
Published: February 2014

The ataxia telangiectasia mutated and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) axis is the major signaling pathway activated in response to replication stress and is essential for the intra-S checkpoint. ATR phosphorylates and activates a number of molecules to coordinate cell cycle progression. Chk1 is the major effector downstream from ATR and plays a critical role in intra-S checkpoint on replication stress. Activation of Chk1 kinase also requires its association with Claspin, an adaptor protein essential for Chk1 protein stability, recruitment and ATR-dependent Chk1 phosphorylation. We have previously reported that, on replication stress, the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is rapidly phosphorylated by ATR at the stalled replication forks and is required for cellular resistance to replication stresses although the impact of DNA-PKcs onto the ATR signaling pathway remains elusive. Here we report that ATR-dependent Chk1 phosphorylation and Chk1 signaling are compromised in the absence of DNA-PKcs. Our investigation reveals that DNA-PKcs is required to maintain Chk1–Claspin complex stability and transcriptional regulation of Claspin expression. The impaired Chk1 activity results in a defective intra-S checkpoint response in DNA-PKcs–deficient cells. Taken together, these results suggest that DNA-PKcs, in addition to its direct role in DNA damage repair, facilitates ATR-Chk1 signaling pathway in response to replication stress.