bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking for the party? The effects of partisan change on issue attention in UK Acts of Parliament
Authors: Bevan Shaun , Greene Zachary
Published: December 2014

Political parties matter for government outcomes. Despite this general finding for political science research, recent work on public policy and agenda-setting has found just the opposite; parties generally do not matter when it comes to explaining government attention. While the common explanation for this finding is that issue attention is different than the location of policy, this explanation has never truly been tested. Through the use of data on nearly 65 years of UK Acts of Parliament, this paper presents a detailed investigation of the effect parties have on issue attention in UK Acts of Parliament. It demonstrates that elections alone do not explain changes in the distribution of policies across issues. Instead, the parties’ organizations, responses to economic conditions, and size of the parliamentary delegation influence the stability of issue attention following a party transition.
Pilot Study of Appetite Monitoring at a Family-Based Camp for Obese Youth
Authors: Marx Lauren S. , Reddy Sheethal D. , Welsh Jean A. , Craighead Linda W.
Published: December 2014

Self-monitoring of food intake is a core strategy in cognitive–behavioral therapy (CBT) for weight management, but some concerns have been raised about the use of food monitoring (FM), particularly with youth. Appetite monitoring (AM), a form of self-monitoring in which participants track their appetite cues, has shown promise as a potentially acceptable and equally useful alternative. This pilot study implemented AM at a residential camp for overweight and obese youth (ages 9–14) that promotes family based healthy lifestyle habits. Campers and their families were taught to rate their appetite (using a form called the “Hunger Scale”) at family weekends in the spring, and were encouraged to use the scale at home. During the children’s 5-day summertime overnight camp, they were prompted to attend to their appetite cues before all meals. At the end of the camp week, counselor and camper ratings indicated that the AM intervention was feasible, acceptable, helpful, and utilized. At the fall reunion weekends, campers and parents reported remembering the Hunger Scale and continued to rate the intervention positively. On average, campers reported improved awareness of their appetite cues at the end of camper week, which was maintained at the fall reunion weekend. The most improvement was reported by campers identified by parents at baseline as having objective overeating episodes (i.e., eating clearly large amounts). These results are preliminary and warrant further investigation, but suggest that AM could be a promising alternative or additional self-monitoring strategy within camps and other interventions for overweight and obese youth.
Systematic, Theoretically Grounded Development and Feasibility Testing of an Innovative, Preventive Web-Based Game for Children Exposed to Acute Trauma
Authors: Marsac Meghan L. , Winston Flaura K. , Hildenbrand Aimee K. , Kohser Kristen L. , March Sonja , Kenardy Justin , Kassam-Adams Nancy
Published: December 2014

Millions of children are affected by acute medical events annually, creating a need for resources to promote recovery. Although web-based interventions promise wide reach and low cost for users, development can be time- and cost-intensive. A systematic approach to intervention development can help to minimize costs and increase the likelihood of effectiveness. Using a systematic approach, our team integrated evidence on the etiology of traumatic stress, an explicit program theory, and a user-centered design process to intervention development. This study describes evidence and the program theory model applied to the Coping Coach intervention and presents pilot data evaluating intervention feasibility and acceptability. Informed by empirical evidence on traumatic stress prevention, an overarching program theory model was articulated to delineate pathways from specific intervention content to program targets and proximal outcomes to key longer-term health outcomes. Systematic user-testing with children ages 8–12 years ( N = 42) exposed to an acute medical event and their parents was conducted throughout intervention development. Functionality challenges in early prototypes necessitated revisions. Child engagement was positive throughout revisions to the Coping Coach intervention. Final pilot-testing demonstrated promising feasibility and high user-engagement and satisfaction. In conclusion, applying a systematic approach to the development of Coping Coach led to the creation of a functional intervention that is accepted by children and parents. Development of new e-health interventions may benefit from a similar approach. Future research should evaluate the efficacy of Coping Coach in achieving targeted outcomes of reduced trauma symptoms and improved health-related quality of life.
Lewis Sheiner ISoP/UCSF Lecturer Award: From Drug Use to Statistical Models and Vice Versa
Authors: Mentré F
Published: December 2014

I was very honored to receive the University of California, San Francisco, and the International Society of Pharmacometrics Lewis Sheiner lecturer award in May 2013. In the present perspective, I outline the main points of my lecture at the American Conference of Pharmacometrics (slides in Supplementary Material 1). I first emphasize the scientific contributions of Lewis Sheiner as a quantitative pharmacologist toward the better use of drugs. I then focus on three statistical topics in pharmacometrics, describing Lewis Sheiner's impact and my own contributions and interactions with him.

CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e154; doi:10.1038/psp.2014.52; published online 29 December 2014
Directional self-assembly of permanently magnetised nanocubes in quasi two dimensional layers
Authors: Donaldson Joe G. , Kantorovich Sofia S.
Published: December 2014

Our theoretical study shows how directional interactions offer various pathways for the self-assembly of permanently magnetised nanocubes.
In search of the X2BO and X2BS (X = H, F) free radicals: Ab initio studies of their spectroscopic signatures
Authors: Clouthier Dennis J.
Published: December 2014

The F2BO free radical is a known, although little studied, species but similar X2BY (X = H, D, F; Y = O, S) molecules are largely unknown. High level ab initio methods have been used to predict the molecular structures, vibrational frequencies (in cm−1), and relative energies of the ground and first two excited electronic states of these free radicals, as an aid to their eventual spectroscopic identification. The chosen theoretical methods and basis sets were tested on F2BO and found to give good agreement with the known experimental quantities. In particular, complete basis set extrapolations of coupled-cluster single and doubles with perturbative triple excitations/aug-cc-pVXZ (X = 3, 4, 5) energies gave excellent electronic term values, due to small changes in geometry between states and the lack of significant multireference character in the wavefunctions. The radicals are found to have planar C2v geometries in the X̃2B2 ground state, the low-lying Ã2B1 first excited state, and the higher B̃2A1 state. Some of these radicals have very small ground state dipole moments hindering microwave measurements. Infrared studies in matrices or in the gas phase may be possible although the fundamentals of H2BO and H2BS are quite weak. The most promising method of identifying these species in the gas phase appears to be absorption or laser-induced fluorescence spectroscopy through the allowed B̃-X̃ transitions which occur in the visible-near UV region of the electromagnetic spectrum. The ab initio results have been used to calculate the Franck-Condon profiles of the absorption and emission spectra, and the rotational structure of the B̃-X̃000 bands has been simulated. The calculated single vibronic level emission spectra provide a unique, readily recognizable fingerprint of each particular radical, facilitating the experimental identification of new X2BY species in the gas phase.
A transferable force field for CdS-CdSe-PbS-PbSe solid systems
Authors: Fan Zhaochuan , Koster Rik S. , Wang Shuaiwei , Fang Changming , Yalcin Anil O. , Tichelaar Frans D. , Zandbergen Henny W. , van Huis Marijn A. , Vlugt Thijs J. H.
Published: December 2014

A transferable force field for the PbSe-CdSe solid system using the partially charged rigid ion model has been successfully developed and was used to study the cation exchange in PbSe-CdSe heteronanocrystals [A. O. Yalcin et al., “Atomic resolution monitoring of cation exchange in CdSe-PbSe heteronanocrystals during epitaxial solid-solid-vapor growth,” Nano Lett. 14, 3661–3667 (2014)]. In this work, we extend this force field by including another two important binary semiconductors, PbS and CdS, and provide detailed information on the validation of this force field. The parameterization combines Bader charge analysis, empirical fitting, and ab initio energy surface fitting. When compared with experimental data and density functional theory calculations, it is shown that a wide range of physical properties of bulk PbS, PbSe, CdS, CdSe, and their mixed phases can be accurately reproduced using this force field. The choice of functional forms and parameterization strategy is demonstrated to be rational and effective. This transferable force field can be used in various studies on II-VI and IV-VI semiconductor materials consisting of CdS, CdSe, PbS, and PbSe. Here, we demonstrate the applicability of the force field model by molecular dynamics simulations whereby transformations are initiated by cation exchange.
Study of photon–magnon coupling in a YIG-film split-ring resonant system
Authors: Bhoi B. , Cliff T. , Maksymov I. S. , Kostylev M. , Aiyar R. , Venkataramani N. , Prasad S. , Stamps R. L.
Published: December 2014

By using the stripline Microwave Vector–Network Analyser Ferromagnetic Resonance and Time Domain spectroscopy techniques, we study a strong coupling regime of magnons to microwave photons in the planar geometry of a lithographically formed split-ring resonator (SRR) loaded by a single-crystal epitaxial yttrium–iron–garnet (YIG) film. Strong anti-crossing of the photon modes of SRR and of the magnon modes of the YIG film is observed in the applied-magnetic-field resolved measurements. The coupling strength extracted from the experimental data reaches 9% at 3 GHz. Theoretically, we propose an equivalent circuit model of the SRR loaded by a magnetic film. This model follows from the results of our numerical simulations of the microwave field structure of the SRR and of the magnetisation dynamics in the YIG film driven by the microwave currents in the SRR. The results obtained with the equivalent-circuit model are in good agreement with the experiment. This model provides a simple physical explanation of the process of mode anti-crossing. Our findings are important for future applications in microwave quantum photonic devices as well as in nonlinear and magnetically tuneable metamaterials exploiting the strong coupling of magnons to microwave photons.
Deterministic coupling of delta-doped nitrogen vacancy centers to a nanobeam photonic crystal cavity
Authors: Lee Jonathan C. , Bracher David O. , Cui Shanying , Ohno Kenichi , McLellan Claire A. , Zhang Xingyu , Andrich Paolo , Alemán Benjamin , Russell Kasey J. , Magyar Andrew P. , Aharonovich Igor , Bleszynski Jayich Ania , Awschalom David , Hu Evelyn L.
Published: December 2014

The negatively charged nitrogen vacancy center (NV) in diamond has generated significant interest as a platform for quantum information processing and sensing in the solid state. For most applications, high quality optical cavities are required to enhance the NV zero-phonon line (ZPL) emission. An outstanding challenge in maximizing the degree of NV-cavity coupling is the deterministic placement of NVs within the cavity. Here, we report photonic crystal nanobeam cavities coupled to NVs incorporated by a delta-doping technique that allows nanometer-scale vertical positioning of the emitters. We demonstrate cavities with Q up to ∼24 000 and mode volume V ∼ 0.47(λ/n)3 as well as resonant enhancement of the ZPL of an NV ensemble with Purcell factor of ∼20. Our fabrication technique provides a first step towards deterministic NV-cavity coupling using spatial control of the emitters.
Sulfur vacancies in photorefractive Sn2P2S6 crystals
Authors: Golden E. M. , Basun S. A. , Grabar A. A. , Stoika I. M. , Giles N. C. , Evans D. R. , Halliburton L. E.
Published: December 2014

A photoinduced electron paramagnetic resonance (EPR) spectrum in single crystals of Sn2P2S6 (SPS) is assigned to an electron trapped at a sulfur vacancy. These vacancies are unintentionally present in undoped SPS crystals and are expected to play an important role in the photorefractive behavior of the material. Nonparamagnetic sulfur vacancies are formed during the initial growth of the crystal. Subsequent illumination below 100 K with 442 nm laser light easily converts these vacancies to EPR-active defects. The resulting S = 1/2 spectrum shows well-resolved and nearly isotropic hyperfine interactions with two P ions and two Sn ions. Partially resolved interactions with four additional neighboring Sn ions are also observed. Principal values of the g matrix are 1.9700, 1.8946, and 1.9006, with the corresponding principal axes along the a, b, and c directions in the crystal. The isotropic parts of the two primary 31P hyperfine interactions are 19.5 and 32.6 MHz and the isotropic parts of the two primary Sn hyperfine interactions are 860 and 1320 MHz (the latter values are each an average for 117Sn and 119Sn). These hyperfine results suggest that singly ionized sulfur vacancies have a diffuse wave function in SPS crystals, and thus are shallow donors. Before illumination, sulfur vacancies are in the doubly ionized charge state because of compensation by unidentified acceptors. They then trap an electron during illumination. The EPR spectrum from the sulfur vacancy is destroyed when a crystal is heated above 120 K in the dark and reappears when the crystal is illuminated again at low temperature.
Theoretical investigation on the barocaloric and magnetocaloric properties in the Gd5Si2Ge2 compound
Authors: Alvaranega T. S. T. , Alho B. P. , Nobrega E. P. , Ribeiro P. O. , Caldas A. , de Sousa V. S. R. , Magnus A. , Carvalho G. , de Oliveira N. A. , von Ranke P. J.
Published: December 2014

We report a theoretical microscopic model to discuss the barocaloric and magnetocaloric effects in the Gd5Si2Ge2 compound based on the recent experimental data by Yuce et al. [Appl. Phys. Lett. 101, 071906 (2012)]. For this purpose, our model Hamiltonian includes three interactions: Zeeman, magnetoelastic, and exchange interactions, considering the magnetic field dependence of phonons entropy. Using this model, the combined magnetocaloric and barocaloric effects were calculated in Gd5Si2Ge2 compound showing satisfactory agreement with the experimental data. Besides, a high entropy change was predicted for simultaneous changes in the applied magnetic field and pressure (the combined magnetocaloric and barocaloric effects).
Atomistic mechanism of perfect alignment of nitrogen-vacancy centers in diamond
Authors: Miyazaki Takehide , Miyamoto Yoshiyuki , Makino Toshiharu , Kato Hiromitsu , Yamasaki Satoshi , Fukui Takahiro , Doi Yuki , Tokuda Norio , Hatano Mutsuko , Mizuochi Norikazu
Published: December 2014

Nitrogen-vacancy (NV) centers in diamond have attracted a great deal of attention because of their possible use in information processing and electromagnetic sensing technologies. We examined the atomistic generation mechanism for the NV defect aligned in the [111] direction of C(111) substrates. We found that N is incorporated in the C bilayers during the lateral growth arising from a sequence of kink propagation along the step edge down to [1¯1¯2]. As a result, the atomic configuration with the N-atom lone-pair pointing in the [111] direction is formed, which causes preferential alignment of NVs. Our model is consistent with recent experimental data for perfect NV alignment in C(111) substrates.
Thermoelectric and mechanical properties of spark plasma sintered Cu3SbSe3 and Cu3SbSe4: Promising thermoelectric materials
Authors: Tyagi Kriti , Gahtori Bhasker , Bathula Sivaiah , Toutam Vijaykumar , Sharma Sakshi , Singh Niraj Kumar , Dhar Ajay
Published: December 2014

We report the synthesis of thermoelectric compounds, Cu3SbSe3 and Cu3SbSe4, employing the conventional fusion method followed by spark plasma sintering. Their thermoelectric properties indicated that despite its higher thermal conductivity, Cu3SbSe4 exhibited a much larger value of thermoelectric figure-of-merit as compared to Cu3SbSe3, which is primarily due to its higher electrical conductivity. The thermoelectric compatibility factor of Cu3SbSe4 was found to be ∼1.2 as compared to 0.2 V−1 for Cu3SbSe3 at 550 K. The results of the mechanical properties of these two compounds indicated that their microhardness and fracture toughness values were far superior to the other competing state-of-the-art thermoelectric materials.
Microstructure from joint analysis of experimental data and ab initio interactions: Hydrogenated amorphous silicon
Authors: Biswas Parthapratim , Drabold D. A. , Atta-Fynn Raymond
Published: December 2014

A study of the formation of voids and molecular hydrogen in hydrogenated amorphous silicon is presented based upon a hybrid approach that involves inversion of experimental nuclear magnetic resonance data in conjunction with ab initio total-energy relaxations in an augmented solution space. The novelty of this approach is that the voids and molecular hydrogen appear naturally in the model networks unlike conventional approaches, where voids are created artificially by removing silicon atoms from the networks. Two representative models with 16 and 18 at. % of hydrogen are studied in this work. The result shows that the microstructure of the a-Si:H network consists of several microvoids and few molecular hydrogen for concentration above 15 at. % H. The microvoids are highly irregular in shape and size, and have a linear dimension of 5–7 Å. The internal surface of a microvoid is found to be decorated with 4–9 hydrogen atoms in the form of monohydride Si–H configurations as observed in nuclear magnetic resonance experiments. The microstructure consists of (0.9–1.4)% hydrogen molecules of total hydrogen in the networks. These observations are consistent with the outcome of infrared spectroscopy, nuclear magnetic resonance, and calorimetry experiments.
Planar Hall effect in Y3Fe5O12/IrMn films
Authors: Zhang X. , Zou L. K.
Published: December 2014

The planar Hall effect of IrMn on an yttrium iron garnet (YIG = Y3Fe5O12) was measured in the magnetic field rotating in the film plane. The magnetic field angular dependence of planar Hall resistance (PHR) was observed in YIG/IrMn bilayer at different temperatures, while the Gd3Ga5O12/IrMn film shows constant PHR for different magnetic field angles at both 10 K and 300 K. This provides evidence that IrMn has interfacial spins which can be led by ferrimagnetic layer in YIG/IrMn structure. A hysteresis can be observed in PHR-magnetic field angle loop of YIG/IrMn film at 10 K, indicative of the irreversible switching of IrMn interfacial spins at low temperature.
Super-resolution nanofabrication with metal-ion doped hybrid material through an optical dual-beam approach
Authors: Cao Yaoyu , Li Xiangping , Gu Min
Published: December 2014

We apply an optical dual-beam approach to a metal-ion doped hybrid material to achieve nanofeatures beyond the optical diffraction limit. By spatially inhibiting the photoreduction and the photopolymerization, we realize a nano-line, consisting of polymer matrix and in-situ generated gold nanoparticles, with a lateral size of sub 100 nm, corresponding to a factor of 7 improvement compared to the diffraction limit. With the existence of gold nanoparticles, a plasmon enhanced super-resolution fabrication mechanism in the hybrid material is observed, which benefits in a further reduction in size of the fabricated feature. The demonstrated nanofeature in hybrid materials paves the way for realizing functional nanostructures.
Frequency sweep rates of rising tone electromagnetic ion cyclotron waves: Comparison between nonlinear theory and Cluster observation
Authors: He Zhaoguo , Zong Qiugang , Liu Siqing , Wang Yongfu , Lin Ruilin , Shi Liqin
Published: December 2014

Resonant pitch angle scattering by electromagnetic ion cyclotron (EMIC) waves has been suggested to account for the rapid loss of ring current ions and radiation belt electrons. For the rising tone EMIC wave (classified as triggered EMIC emission), its frequency sweep rate strongly affects the efficiency of pitch-angle scattering. Based on the Cluster observations, we analyze three typical cases of rising tone EMIC waves. Two cases locate at the nightside (22.3 and 22.6 magnetic local time (MLT)) equatorial region and one case locates at the duskside (18MLT) higher magnetic latitude (λ = –9.3°) region. For the three cases, the time-dependent wave amplitude, cold electron density, and cold ion density ratio are derived from satellite data; while the ambient magnetic field, thermal proton perpendicular temperature, and the wave spectral can be directly provided by observation. These parameters are input into the nonlinear wave growth model to simulate the time-frequency evolutions of the rising tones. The simulated results show good agreements with the observations of the rising tones, providing further support for the previous finding that the rising tone EMIC wave is excited through the nonlinear wave growth process.
Linear electrostatic waves in a three-component electron-positron-ion plasma
Authors: Mugemana A. , Lazarus I. J. , Moolla S.
Published: December 2014

Analytical linear electrostatic waves in a magnetized three-component electron-positron-ion plasma are studied in the low-frequency limit. By using the continuity and momentum equations with Poisson's equation, the dispersion relation for the electron-positron-ion plasma consisting of cool ions, and hot Boltzmann electrons and positrons is derived. In the linear regime, the propagation of two possible modes and their evolution are studied. In the cases of parallel and perpendicular propagation, it is shown that these two possible modes are always stable. The present investigation contributes to nonlinear propagation of electrostatic waves in space and the laboratory.
Plasma response measurements of non-axisymmetric magnetic perturbations on DIII-D via soft x-ray imaging
Authors: Shafer M. W. , Unterberg E. A. , Wingen A. , Battaglia D. J. , Evans T. E. , Ferraro N. M. , Harris J. H. , Hillis D. L. , Nazikian R.
Published: December 2014

Recent observations on DIII-D have advanced the understanding of plasma response to applied resonant magnetic perturbations (RMPs) in both H-mode and L-mode plasmas. Three distinct 3D features localized in minor radius are imaged via filtered soft x-ray emission: (i) the formation of lobes extending from the unperturbed separatrix in the X-point region at the plasma boundary, (ii) helical kink-like perturbations in the steep-gradient region inside the separatrix, and (iii) amplified islands in the core of a low-rotation L-mode plasma. These measurements are used to test and to validate plasma response models, which are crucial for providing predictive capability of edge-localized mode control. In particular, vacuum and two-fluid resistive magnetohydrodynamic (MHD) responses are tested in the regions of these measurements. At the plasma boundary in H-mode discharges with n = 3 RMPs applied, measurements compare well to vacuum-field calculations that predict lobe structures. Yet in the steep-gradient region, measurements agree better with calculations from the linear resistive two-fluid MHD code, M3D-C1. Relative to the vacuum fields, the resistive two-fluid MHD calculations show a reduction in the pitch-resonant components of the normal magnetic field (screening), and amplification of non-resonant components associated with ideal kink modes. However, the calculations still over-predict the amplitude of the measured perturbation by a factor of 4. In a slowly rotating L-mode plasma with n = 1 RMPs, core islands are observed amplified from vacuum predictions. These results indicate that while the vacuum approach describes measurements in the edge region well, it is important to include effects of extended MHD in the pedestal and deeper in the plasma core.
Reversed rainbow with a nonlocal metamaterial
Authors: Morgado Tiago A. , Marcos João S. , Costa João T. , Costa Jorge R. , Fernandes Carlos A. , Silveirinha Mário G.
Published: December 2014

One of the intriguing potentials of metamaterials is the possibility to realize a nonlocal electromagnetic reaction, such that the effective medium response at a given point is fundamentally entangled with the macroscopic field distribution at long distances. Here, it is experimentally and numerically verified that a microwave nonlocal metamaterial formed by crossed metallic wires enables a low-loss broadband anomalous material response such that the refractive index decreases with frequency. Notably, it is shown that an electromagnetic beam refracted by our metamaterial prism creates a reversed microwave rainbow.
Roll-to-roll production of spray coated N-doped carbon nanotube electrodes for supercapacitors
Authors: Karakaya Mehmet , Zhu Jingyi , Raghavendra Achyut J. , Podila Ramakrishna , Parler Samuel G. , Kaplan James P. , Rao Apparao M.
Published: December 2014

Although carbon nanomaterials are being increasingly used in energy storage, there has been a lack of inexpensive, continuous, and scalable synthesis methods. Here, we present a scalable roll-to-roll (R2R) spray coating process for synthesizing randomly oriented multi-walled carbon nanotubes electrodes on Al foils. The coin and jellyroll type supercapacitors comprised such electrodes yield high power densities (∼700 mW/cm3) and energy densities (1 mW h/cm3) on par with Li-ion thin film batteries. These devices exhibit excellent cycle stability with no loss in performance over more than a thousand cycles. Our cost analysis shows that the R2R spray coating process can produce supercapacitors with 10 times the energy density of conventional activated carbon devices at ∼17% lower cost.
Temporally and spatially resolved photoluminescence investigation of (112¯2) semi-polar InGaN/GaN multiple quantum wells grown on nanorod templates
Authors: Liu B. , Smith R. , Athanasiou M. , Yu X. , Bai J. , Wang T.
Published: December 2014

By means of time-resolved photoluminescence (PL) and confocal PL measurements, temporally and spatially resolved optical properties have been investigated on a number of InxGa1−xN/GaN multiple-quantum-well (MQW) structures with a wide range of indium content alloys from 13% to 35% on (112¯2) semi-polar GaN with high crystal quality, obtained through overgrowth on nanorod templates. With increasing indium content, the radiative recombination lifetime initially increases as expected, but decreases if the indium content further increases to 35%, corresponding to emission in the green spectral region. The reduced radiative recombination lifetime leads to enhanced optical performance for the high indium content MQWs as a result of strong exciton localization, which is different from the behaviour of c-plane InGaN/GaN MQWs, where quantum confined Stark effect plays a dominating role in emission process.
Energetic basis for the molecular-scale organization of bone
Authors: Tao Jinhui , Battle Keith C. , Pan Haihua , Salter E. Alan , Chien Yung-Ching , Wierzbicki Andrzej , De Yoreo James J.
Published: December 2014

Significance

The remarkable mechanical properties of bone are determined by the organization and strength of binding at the mineral–collagen interface. Although the process through which collagen becomes mineralized has been extensively studied, little is known about the mechanisms or energetics that underlie the organization of this mineral–matrix composite. Combining molecular-scale imaging and analyses of collagen adsorption on four bone-related calcium phosphate phases, single-molecule force measurements and molecular simulations of collagen binding to hydroxyapatite, and electron microscopy analyses of bone and dentine, we determine the magnitude and chemistry of collagen–hydroxyapatite binding and show that calcium-deficient apatite is the only phase consistent with observed structural relationships.
ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells
Authors: Morita Rimpei , Suzuki Mayu , Kasahara Hidenori , Shimizu Nana , Shichita Takashi , Sekiya Takashi , Kimura Akihiro , Sasaki Ken-ichiro , Yasukawa Hideo , Yoshimura Akihiko
Published: December 2014

Significance

Endothelial cells (ECs) form vasculature to provide vital elements, such as nutrients and oxygen, to tissues and organs in the body. Thus, creating ECs from nonvascular cells by transducing some transcription factors not only leads to the development of new strategies for patient-specific therapeutic angiogenesis, but also facilitates the maintenance of the solid organs that are regenerated from pluripotent stem cells. In this paper, we show that the single transcription factor ETV2, which is lentivirally transduced, induces expression of the multiple EC-specific molecules in coordination with endogenous FOXC2 in the fibroblasts, resulting in the conversion of primary human adult skin fibroblasts into functional ECs that form mature perfused vessels in vivo.
Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation
Authors: Patel Meghana N. , Bernard William G. , Milev Nikolay B. , Cawthorn William P. , Figg Nichola , Hart Dan , Prieur Xavier , Virtue Sam , Hegyi Krisztina , Bonnafous Stephanie , Bailly-Maitre Beatrice , Chu Yajing , Griffin Julian L. , Mallat Ziad , Considine Robert V. , Tran Albert , Gual Philippe , Takeuchi Osamu , Akira Shizuo , Vidal-Puig Antonio , Bennett Martin R. , Sethi Jaswinder K.
Published: December 2014

Significance

Chronic low-grade inflammation plays a causative role in obesity-associated metabolic diseases. However, the mechanisms underlying chronicity of low-grade inflammation remain elusive. Herein, we identify inhibitor of κB kinase epsilon (IKBKE) as a new modulator of chronic inflammation in macrophages. We first show that IKBKE is clinically relevant in distinct tissues associated with metabolic diseases including obesity, nonalcoholic steatohepatitis, and atherosclerosis. In all cases, IKBKE expression predominates in macrophages and associates with chronic inflammation. In macrophages, IKBKE affects chronicity of inflammation by temporally limiting inflammasome priming. Both global IKBKE ablation and reconstitution with hematopoietic IKBKE reciprocally alters metaflammation in adipose tissue, liver, and the composition of advanced atherosclerotic plaques. These findings establish a nonpathogenic role for hematopoietic IKBKE in limiting inflammasome priming and metaflammation.
Arrestins regulate cell spreading and motility via focal adhesion dynamics
Authors: Cleghorn Whitney M. , Branch Kevin M. , Kook Seunghyi , Arnette Christopher , Bulus Nada , Zent Roy , Kaverina Irina , Gurevich Eugenia V. , Weaver Alissa M. , Gurevich Vsevolod V.
Published: December 2014

Focal adhesions (FAs) play a key role in cell attachment, and their timely disassembly is required for cell motility. Both microtubule-dependent targeting and recruitment of clathrin are critical for FA disassembly. Here we identify nonvisual arrestins as molecular links between microtubules and clathrin. Cells lacking both nonvisual arrestins showed excessive spreading on fibronectin and poly-d-lysine, increased adhesion, and reduced motility. The absence of arrestins greatly increases the size and lifespan of FAs, indicating that arrestins are necessary for rapid FA turnover. In nocodazole washout assays, FAs in arrestin-deficient cells were unresponsive to disassociation or regrowth of microtubules, suggesting that arrestins are necessary for microtubule targeting–dependent FA disassembly. Clathrin exhibited decreased dynamics near FA in arrestin-deficient cells. In contrast to wild-type arrestins, mutants deficient in clathrin binding did not rescue the phenotype. Collectively the data indicate that arrestins are key regulators of FA disassembly linking microtubules and clathrin.
Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness
Authors: Meller Julia , Rogozin Igor B. , Poliakov Eugenia , Meller Nahum , Bedanov-Pack Mark , Plow Edward F. , Qin Jun , Podrez Eugene A. , Byzova Tatiana V.
Published: December 2014

Kindlins are integrin-interacting proteins essential for integrin-mediated cell adhesiveness. In this study, we focused on the evolutionary origin and functional specialization of kindlins as a part of the evolutionary adaptation of cell adhesive machinery. Database searches revealed that many members of the integrin machinery (including talin and integrins) existed before kindlin emergence in evolution. Among the analyzed species, all metazoan lineages—but none of the premetazoans—had at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages. Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH domain of separate origin. Sequence analysis identified a member of the actin filament–associated protein 1 (AFAP1) superfamily as the most likely origin of the kindlin PH domain. The functional divergence between kindlin paralogues was assessed using the sequence swap (chimera) approach. Comparison of kindlin 2 (K2)/kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential functional properties of K2 and K3. The presence of this segment enables K2 but not K3 to localize to focal adhesions. Sequence analysis of the C-terminal part of the F2 subdomain of K3 suggests that insertion of a variable glycine-rich sequence in vertebrates contributed to the loss of constitutive K3 targeting to focal adhesions. Thus emergence and subsequent functional specialization of kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness.
Seipin performs dissectible functions in promoting lipid droplet biogenesis and regulating droplet morphology
Authors: Cartwright Bethany R. , Binns Derk D. , Hilton Christopher L. , Han Sungwon , Gao Qiang , Goodman Joel M.
Published: December 2014

Seipin is necessary for both adipogenesis and lipid droplet (LD) organization in nonadipose tissues; however, its molecular function is incompletely understood. Phenotypes in the seipin-null mutant of Saccharomyces cerevisiae include aberrant droplet morphology (endoplasmic reticulum–droplet clusters and size heterogeneity) and sensitivity of droplet size to changes in phospholipid synthesis. It has not been clear, however, whether seipin acts in initiation of droplet synthesis or at a later step. Here we utilize a system of de novo droplet formation to show that the absence of seipin results in a delay in droplet appearance with concomitant accumulation of neutral lipid in membranes. We also demonstrate that seipin is required for vectorial budding of droplets toward the cytoplasm. Furthermore, we find that the normal rate of droplet initiation depends on 14 amino acids at the amino terminus of seipin, deletion of which results in fewer, larger droplets that are consistent with a delay in initiation but are otherwise normal in morphology. Importantly, other functions of seipin, namely vectorial budding and resistance to inositol, are retained in this mutant. We conclude that seipin has dissectible roles in both promoting early LD initiation and in regulating LD morphology, supporting its importance in LD biogenesis.
Insights into the cellular mechanism of the yeast ubiquitin ligase APC/C-Cdh1 from the analysis of in vivo degrons
Authors: Arnold Lea , Höckner Sebastian , Seufert Wolfgang
Published: December 2014

In vivo analysis in budding yeast identifies APC/C-Cdh1–specific minimal degrons carrying either a D or a KEN box and a nuclear localization sequence. APC/C-Cdh1 activity is restricted to the nucleus, maximal in the nucleoplasm, and absent from the cytoplasm, allowing for spatiotemporal control of Cdh1 substrate proteolysis.
ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1)
Authors: Shitomi Yasuyuki , Thøgersen Ida B. , Ito Noriko , Leitinger Birgit , Enghild Jan J. , Itoh Yoshifumi
Published: December 2014

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1–dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding-resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1-mediated cell adhesion to achieve efficient cell migration on collagen matrices.
FAP206 is a microtubule-docking adapter for ciliary radial spoke 2 and dynein c
Authors: Vasudevan Krishna Kumar , Song Kangkang , Alford Lea M. , Sale Winfield S. , Dymek Erin E. , Smith Elizabeth F. , Hennessey Todd , Joachimiak Ewa , Urbanska Paulina , Wloga Dorota , Dentler William , Nicastro Daniela , Gaertig Jacek
Published: December 2014

Radial spokes are conserved macromolecular complexes that are essential for ciliary motility. A triplet of three radial spokes, RS1, RS2, and RS3, repeats every 96 nm along the doublet microtubules. Each spoke has a distinct base that docks to the doublet and is linked to different inner dynein arms. Little is known about the assembly and functions of individual radial spokes. A knockout of the conserved ciliary protein FAP206 in the ciliate Tetrahymena resulted in slow cell motility. Cryo–electron tomography showed that in the absence of FAP206, the 96-nm repeats lacked RS2 and dynein c. Occasionally, RS2 assembled but lacked both the front prong of its microtubule base and dynein c, whose tail is attached to the front prong. Overexpressed GFP-FAP206 decorated nonciliary microtubules in vivo. Thus FAP206 is likely part of the front prong and docks RS2 and dynein c to the microtubule.
Stepping stone: a cytohesin adaptor for membrane cytoskeleton restraint in the syncytial Drosophila embryo
Authors: Liu Jiangshu , Lee Donghoon M. , Yu Cao Guo , Angers Stephane , Harris Tony J. C.
Published: December 2014

Cytohesin Arf-GEFs are conserved plasma membrane regulators. The sole Drosophila cytohesin, Steppke, restrains Rho1-dependent membrane cytoskeleton activity at the base of plasma membrane furrows of the syncytial embryo. By mass spectrometry, we identified a single major Steppke-interacting protein from syncytial embryos, which we named Stepping stone (Sstn). By sequence, Sstn seems to be a divergent homologue of the mammalian cytohesin adaptor FRMD4A. Our experiments supported this relationship. Specifically, heterophilic coiled-coil interactions linked Sstn and Steppke in vivo and in vitro, whereas a separate C-terminal region was required for Sstn localization to furrows. Sstn mutant and RNAi embryos displayed abnormal, Rho1-dependent membrane cytoskeleton expansion from the base of pseudocleavage and cellularization furrows, closely mimicking Steppke loss-of-function embryos. Elevating Sstn furrow levels had no effect on the steppke phenotype, but elevating Steppke furrow levels reversed the sstn phenotype, suggesting that Steppke acts downstream of Sstn and that additional mechanisms can recruit Steppke to furrows. Finally, the coiled-coil domain of Steppke was required for Sstn binding and in addition homodimerization, and its removal disrupted Steppke furrow localization and activity in vivo. Overall we propose that Sstn acts as a cytohesin adaptor that promotes Steppke activity for localized membrane cytoskeleton restraint in the syncytial Drosophila embryo.
The QDREC web server: determining dose–response characteristics of complex macroparasites in phenotypic drug screens
Authors: Asarnow Daniel , Rojo-Arreola Liliana , Suzuki Brian M. , Caffrey Conor R. , Singh Rahul
Published: December 2014

Summary: Neglected tropical diseases (NTDs) caused by helminths constitute some of the most common infections of the world’s poorest people. The etiological agents are complex and recalcitrant to standard techniques of molecular biology. Drug screening against helminths has often been phenotypic and typically involves manual description of drug effect and efficacy. A key challenge is to develop automated, quantitative approaches to drug screening against helminth diseases. The quantal dose–response calculator (QDREC) constitutes a significant step in this direction. It can be used to automatically determine quantitative dose–response characteristics and half-maximal effective concentration (EC50) values using image-based readouts from phenotypic screens, thereby allowing rigorous comparisons of the efficacies of drug compounds. QDREC has been developed and validated in the context of drug screening for schistosomiasis, one of the most important NTDs. However, it is equally applicable to general phenotypic screening involving helminths and other complex parasites.

Availability and implementation: QDREC is publically available at: http://haddock4.sfsu.edu/qdrec2/. Source code and datasets are at: http://tintin.sfsu.edu/projects/phenotypicAssays.html.

Contact:  rahul@sfsu.edu.

Supplementary information:  Supplementary data are available at Bioinformatics online.
Knowledge-based modeling of peptides at protein interfaces: PiPreD
Authors: Oliva Baldo , Fernandez-Fuentes Narcis
Published: December 2014

Motivation: Protein–protein interactions (PPIs) underpin virtually all cellular processes both in health and disease. Modulating the interaction between proteins by means of small (chemical) agents is therefore a promising route for future novel therapeutic interventions. In this context, peptides are gaining momentum as emerging agents for the modulation of PPIs.

Results: We reported a novel computational, structure and knowledge-based approach to model orthosteric peptides to target PPIs: PiPreD. PiPreD relies on a precompiled and bespoken library of structural motifs, iMotifs, extracted from protein complexes and a fast structural modeling algorithm driven by the location of native chemical groups on the interface of the protein target named anchor residues. PiPreD comprehensive and systematically samples the entire interface deriving peptide conformations best suited for the given region on the protein interface. PiPreD complements the existing technologies and provides new solutions for the disruption of selected interactions.

Availability and implementation: Database and accessory scripts and programs are available upon request to the authors or at http://www.bioinsilico.org/PIPRED.

Contact:  narcis.fernandez@gmail.com
RRDistMaps: a UCSF Chimera tool for viewing and comparing protein distance maps
Authors: Chen Jonathan E. , Huang Conrad C. , Ferrin Thomas E.
Published: December 2014

Motivation: Contact maps are a convenient method for the structural biologists to identify structural features through two-dimensional simplification. Binary (yes/no) contact maps with a single cutoff distance can be generalized to show continuous distance ranges. We have developed a UCSF Chimera tool, RRDistMaps, to compute such generalized maps in order to analyze pairwise variations in intramolecular contacts. An interactive utility, RRDistMaps, visualizes conformational changes, both local (e.g. binding-site residues) and global (e.g. hinge motion), between unbound and bound proteins through distance patterns. Users can target residue pairs in RRDistMaps for further navigation in Chimera. The interface contains the unique features of identifying long-range residue motion and aligning sequences to simultaneously compare distance maps.

Availability and implementation:  RRDistMaps was developed as part of UCSF Chimera release 1.10, which is freely available at http://rbvi.ucsf.edu/chimera/download.html, and operates on Linux, Windows, and Mac OS.

Contact:  conrad@cgl.ucsf.edu
J-Circos: an interactive Circos plotter
Authors: An Jiyuan , Lai John , Sajjanhar Atul , Batra Jyotsna , Wang Chenwei , Nelson Colleen C
Published: December 2014

Summary: Circos plots are graphical outputs that display three dimensional chromosomal interactions and fusion transcripts. However, the Circos plot tool is not an interactive visualization tool, but rather a figure generator. For example, it does not enable data to be added dynamically nor does it provide information for specific data points interactively. Recently, an R-based Circos tool (RCircos) has been developed to integrate Circos to R, but similarly, Rcircos can only be used to generate plots. Thus, we have developed a Circos plot tool (J-Circos) that is an interactive visualization tool that can plot Circos figures, as well as being able to dynamically add data to the figure, and providing information for specific data points using mouse hover display and zoom in/out functions. J-Circos uses the Java computer language to enable, it to be used on most operating systems (Windows, MacOS, Linux). Users can input data into J-Circos using flat data formats, as well as from the Graphical user interface (GUI). J-Circos will enable biologists to better study more complex chromosomal interactions and fusion transcripts that are otherwise difficult to visualize from next-generation sequencing data.

Availability and implementation: J-circos and its manual are freely available at http://www.australianprostatecentre.org/research/software/jcircos

Contact:  j.an@qut.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
UProC: tools for ultra-fast protein domain classification
Authors: Meinicke Peter
Published: December 2014

Motivation: With rapidly increasing volumes of biological sequence data the functional analysis of new sequences in terms of similarities to known protein families challenges classical bioinformatics.

Results: The ultrafast protein classification (UProC) toolbox implements a novel algorithm (‘Mosaic Matching’) for large-scale sequence analysis. UProC is by three orders of magnitude faster than profile-based methods and in a metagenome simulation study achieved up to 80% higher sensitivity on unassembled 100 bp reads.

Availability and implementation: UProC is available as an open-source software at https://github.com/gobics/uproc. Precompiled databases (Pfam) are linked on the UProC homepage: http://uproc.gobics.de/.

Contact:  peter@gobics.de.

Supplementary information:  Supplementary data are available at Bioinformatics online.