bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear and nonlinear verification of gyrokinetic microstability codes
Authors: Bravenec R. V. , Candy J. , Barnes M. , Holland C.
Published: January 2012

Verification of nonlinear microstability codes is a necessary step before comparisons or predictions of turbulent transport in toroidal devices can be justified. By verification we mean demonstrating that a code correctly solves the mathematical model upon which it is based. Some degree of verification can be accomplished indirectly from analytical instability threshold conditions, nonlinear saturation estimates, etc., for relatively simple plasmas. However, verification for experimentally relevant plasma conditions and physics is beyond the realm of analytical treatment and must rely on code-to-code comparisons, i.e., benchmarking. The premise is that the codes are verified for a given problem or set of parameters if they all agree within a specified tolerance. True verification requires comparisons for a number of plasma conditions, e.g., different devices, discharges, times, and radii. Running the codes and keeping track of linear and nonlinear inputs and results for all conditions could be prohibitive unless there was some degree of automation. We have written software to do just this and have formulated a metric for assessing agreement of nonlinear simulations. We present comparisons, both linear and nonlinear, between the gyrokinetic codes GYRO [J. Candy and R. E. Waltz, J. Comput. Phys. 186, 545 (2003)] and GS2 [W. Dorland, F. Jenko, M. Kotschenreuther, and B. N. Rogers, Phys. Rev. Lett. 85, 5579 (2000)]. We do so at the mid-radius for the same discharge as in earlier work [C. Holland, A. E. White, G. R. McKee, M. W. Shafer, J. Candy, R. E. Waltz, L. Schmitz, and G. R. Tynan, Phys. Plasmas 16, 052301 (2009)]. The comparisons include electromagnetic fluctuations, passing and trapped electrons, plasma shaping, one kinetic impurity, and finite Debye-length effects. Results neglecting and including electron collisions (Lorentz model) are presented. We find that the linear frequencies with or without collisions agree well between codes, as do the time averages of the nonlinear fluxes without collisions. With collisions, the differences between the time-averaged fluxes are larger than the uncertainties defined as the oscillations of the fluxes, with the GS2 fluxes consistently larger (or more positive) than those from GYRO. However, the electrostatic fluxes are much smaller than those without collisions (the electromagnetic energy flux is negligible in both cases). In fact, except for the electron energy fluxes, the absolute magnitudes of the differences in fluxes with collisions are the same or smaller than those without. None of the fluxes exhibit large absolute differences between codes. Beyond these results, the specific linear and nonlinear benchmarks proposed here, as well as the underlying methodology, provide the basis for a wide variety of future verification efforts.
Large amplitude solitary waves in ion-beam plasmas with charged dust impurities
Authors: Misra A. P. , Adhikary N. C.
Published: January 2012

The nonlinear propagation of large amplitude dust ion-acoustic (DIA) solitary waves (SWs) in an ion-beam plasma with stationary charged dusts is investigated. For typical plasma parameters relevant for experiments [Y. Nakamura and K. Komatsuda, J. Plasma Phys. 60, 69 (1998)], when the beam speed is larger than the DIA speed (νb0 ≳ 1.7cs), three stable waves, namely, the “fast” and “slow” ion-beam modes and the plasma DIA wave, are shown to exist. These modes can propagate as SWs in the beam plasmas. However, in the other regime (cs < νb0 < 1.7cs), one of the beam modes when coupled to the DIA mode may become unstable. The SWs with positive (negative) potential may exist when the difference of the nonlinear wave speed (M) and the beam speed is such that 1.2 ≲ M − νb0 ≲ 1.6 (M − νb0 ≳ 1.6). Furthermore, for real density perturbations, the wave potential ( > 0) is found to be limited by a critical value which typically depends on M, νb0 as well as the ion/beam temperature. The conditions for the existence of DIA solitons are obtained, and their properties are analyzed numerically in terms of the system parameters. While the system supports both the compressive and rarefactive large amplitude SWs, the small amplitude solitons exist only of the compressive type. The theoretical results may be useful for observation of soliton excitations in laboratory ion-beam driven plasmas as well as in space plasmas where the charged dusts play as impurities.
On the adsorption and formation of Pt dimers on the CeO2(111) surface
Authors: Bruix Albert , Nazari Fariba , Neyman Konstantin M. , Illas Francesc
Published: January 2012

The direct adsorption of Pt2 dimers on CeO2(111) and their formation from isolated adsorbed Pt atoms have been studied using periodic slab model calculations based on density functional theory and including the so-called on-site Hubbard parameter (GGA + U). In the most stable configuration Pt2 is found to be almost parallel to the surface; the electronic ground state is closed shell and there is no evidence of charge transfer towards or from the surface. The formation of Pt2 from two single adsorbed Pt atoms involves a rather small energy barrier of ∼0.10 eV only. On the contrary, dissociation of adsorbed Pt2 requires to overcome a considerable barrier of ∼1.43 eV. This indicates that once Pt2 is formed it will remain on the surface, thus likely triggering the growth of larger supported Pt particles.
Thermal expansion coefficients of Bi2Se3 and Sb2Te3 crystals from 10 K to 270 K
Authors: Chen X. , Zhou H. D. , Kiswandhi A. , Miotkowski I. , Chen Y. P. , Sharma P. A. , Lima Sharma A. L. , Hekmaty M. A. , Smirnov D. , Jiang Z.
Published: January 2012

Lattice constant of Bi2Se3 and Sb2Te3 crystals is determined by x-ray powder diffraction measurement in a wide temperature range. Linear thermal expansion coefficients (α) of the crystals are extracted, and considerable anisotropy between α|| and α⊥ is observed. The low temperature values of α can be fit well by the Debye model, while an anomalous behavior at above 150 K is evidenced and explained. Grüneisen parameters of the materials are also estimated at room temperature.
The origin and consequences of push-pull breakdown in series connected dielectrics
Authors: Masuduzzaman Muhammad , Varghese Dhanoop , Guo Honglin , Krishnan Srikanth , Alam Muhammad Ashraful
Published: January 2012

Given the extensive literature on the dielectric failure probability (F) of single as well as sandwich capacitors, one might conclude that the overall failure probability of k series connected (SC) capacitors is simply given by the uncorrelated product of failure probabilities of single capacitors, i.e., F=Πi=1i=kFi. Instead, in this paper, we show that the SC capacitors experience non-trivial oscillatory push-pull voltage sequence such that the breakdowns among the capacitors become strongly correlated, with important/nontrivial implications for the overall capacitor lifetime. We use a cell-based Monte Carlo approach to numerically establish the characteristic features of failure distribution associated with such correlated breakdown in the SC capacitors.
Lasing in planar semiconductor diodes
Authors: De Simoni Giorgio , Mahler Lukas , Piazza Vincenzo , Tredicucci Alessandro , Nicoll Christine A. , Beere Harvey E. , Ritchie David A. , Beltram Fabio
Published: January 2012

We present a planar laser diode based on a simple fabrication scheme compatible with virtually any geometry accessible by standard semiconductor lithography technique. We show that our lasers exhibit ∼1 GHz -3 dB-modulation-bandwidth already in this prototypical implementation. Directions for a significant speed increase are discussed.
Estimation of electron temperature and density of the decay plasma in a laser-assisted discharge plasma extreme ultraviolet source by using a modified Stark broadening method
Authors: Zhu Qiushi , Muto Takahiro , Yamada Junzaburo , Kishi Nozomu , Watanabe Masato , Okino Akitoshi , Horioka Kazuhiko , Hotta Eiki
Published: January 2012

In order to investigate the plasma expansion behaviors and the electrical recovery process after the maximum implosion in our tin fueled laser-assisted discharge plasma (LDP) 13.5 nm EUV source, we developed and evaluated a cost-efficient spectroscopic method to determine the electron temperature Te and density ne simultaneously, by using Stark broadenings of two Sn II isolated lines (5s24f2F°5/2 – 5s25d2D3/2 558.9 nm and 5s26d2D5/2 – 5s26p2P°3/2 556.2 nm) spontaneously emitted from the plasma. The spatial-resolved evolutions of Te and ne of the expansion plasma over 50 to 900 ns after the maximum implosion were obtained using this modified Stark broadening method. According to the different ne decay characteristics along the Z-pinch axis, the expansion velocity of the electrons was estimated as ∼1.2 × 104 ms− 1 from the plasma shell between the electrodes towards the cathode and the anode. The decay time constant of ne was measured as 183 ± 24 ns. Based on the theories of plasma adiabatic expansion and electron-impact ionization, the minimum time-span that electrical recovery between the electrodes needs in order to guarantee the next succeeding regular EUV-emitting discharge was estimated to be 70.5 μs. Therefore, the maximum repetition rate of our LDP EUV source is ∼14 kHz, which enables the output to reach 125 W/(2πsr).
Transport properties of superconducting MgB2 composites with carbon-encapsulated Fe nanospheres
Authors: Sandu Viorel , Aldica Gheorghe , Popa Stelian , Badica Petre , Cimpoiasu Elena , Dumitrache Florian , Sandu Elena
Published: January 2012

We present the magnetic and transport properties of superconducting composites fabricated by admixing carbon-encapsulated Fe nanospheres and MgB2 powder. The addition of nanoparticles is expected to enhance the critical current density by carbon-doping the MgB2 matrix and by providing artificial pinning sites. Three samples with estimated amounts of 0.35, 0.6, and 1.0 wt. % metallic Fe were prepared using the spark plasma sintering technique. The average size of these nanoparticles is comparable to the superconducting coherence length of MgB2 at approximately 5 nm. We found that the additions do not significantly alter the critical temperature which is very high, close to that of the pure MgB2 samples. We have also observed improved current densities, as high as 1100 kA/cm2 for the samples with 0.35 wt. % metallic Fe at 5 K and 1 T. A core-shell model for explaining the transport data is presented. The field and temperature dependence of the reduced pinning force is described in terms of pinning on grain boundaries and/or on point defects.
Electrically pumped simultaneous ultraviolet and visible random laser actions from ZnO-CdO interdiffused film
Authors: Tian Ye , Ma Xiangyang , Xiang Luelue , Yang Deren
Published: January 2012

We have demonstrated electrically pumped simultaneous ultraviolet (UV) and visible random laser (RL) actions from ZnO-CdO interdiffused film. The interdiffusion between ZnO and CdO films at 700 °C forms composition-graded CdxZn1−xO alloy within the ZnO-CdO interdiffused film, which is luminescent in both UV and visible regions. A device based on SiO2/ZnO-CdO/SiO2 double-barrier structure on silicon substrate, where SiO2 acts as the barrier, is constructed for electrical pumping of the ZnO-CdO interdiffused film. As the device is applied with sufficiently high forward bias with negative voltage connecting to the silicon substrate, the UV and visible RL actions simultaneously occur. The mechanism for such electrically pumped RL actions has been tentatively elucidated.
Thickness independent magneto-optical coupling constant of nickel films in the visible spectral range
Authors: Mok K. , Scarlat C. , Kovács G. J. , Li L. , Zviagin V. , McCord J. , Helm M. , Schmidt H.
Published: January 2012

Magneto-optical properties of nominally 10, 20, and 30 nm thick ferromagnetic Ni films have been investigated at room temperature by vector-magneto-optical generalized ellipsometry under saturated magnetization conditions in the sample surface plane. The magneto-optical dielectric tensor of Ni has been determined by reflection Mueller matrix ellipsometry in the spectral range from 300 to 1100 nm. Different sets of magnetic field induced Mueller matrix elements enable us to identify the magnetization directions in the sample. The extracted magnetic field and thickness independent magneto-optical coupling constant is useful for modeling the Mueller matrix and complex Kerr angle of magnetized Ni thin films in layered sample systems in dependence of the incident angle of light, wavelength, and magnetization.
Prognostic monitoring of aircraft wiring using electrical capacitive tomography
Authors: McKenzie G. , Record P.
Published: January 2012

Electrical capacitive tomography (ECT) has been used to monitor sections of aircraft wiring, as a tool for prognostic analysis. To apply the principles of ECT across a cross section of only 4 mm, modification of the basic circuit was required. Additionally, a more novel method of placing the necessary electrodes was needed, this being accomplished by etching them from flexible copper sheeting and wrapping them inside the perimeter of an enclosure. Results showed that at this small scale, it was possible to determine the position of a wire-under-test inside the 4 mm diameter enclosure to about 0.1 mm, and that by measuring capacitance between pairs, it was also possible to determine whether or not the insulation of wire passed between the electrodes was damaged. With more than one wire-under-test present, it was possible to determine whether or not damage was present, and if so, which wire was damaged. By detecting insulation damage in this way, ECT has proven to be a useful tool in prognostic monitoring, helping faults to be found before they become safety-critical onboard an aircraft.
Vibrational, magnetic, and dielectric behavior of La-substituted BiFeO3-PbTiO3
Authors: Mishra K. K. , Satya A. T. , Bharathi A. , Sivasubramanian V. , Murthy V. R. K. , Arora A. K.
Published: January 2012

Phonons and magnetic and ferroelectric ordering in La-substituted (Bi1−xLax)0.5Pb0.5Fe0.5Ti0.5O3 for samples with 0.0 ≤ x ≤ 0.5 are investigated using Raman, magnetization, and polarization measurements as a function of temperature. The system is tetragonal for pure Bi0.5Pb0.5Fe0.5Ti0.5O3 with a large c/a ratio. The anisotropy is reduced when Bi is partially replaced by La (0 ≤ x ≤ 0.5), and it turns cubic for x ≥ 0.4. All the properties are found to change significantly with changes in the c/a ratio. Evidence of spin-glass-like magnetic ordering at low temperature is found in the case of x = 0.2. A mechanism for the systematic change of magnetic ordering temperature as a function of doping is also discussed. The phonon frequencies and line widths exhibit discontinuous changes across the tetragonal-cubic transition. Large polarization and forbidden Raman scattering in the cubic phase are explained on the basis of symmetry breaking due to the formation of a polar nano region, which leads to relaxor behavior.
Controlling the conformations and transport of DNA by free energy landscaping
Authors: Shelton Elijah , Jiang Zhijun , Wang Shutong , Stein Derek
Published: January 2012

We demonstrate free energy landscaping, a method for controlling the transport and conformations of DNA in nanofluidic devices with a nanotopography. A device that funnels molecules into traps where they adopt the shapes of letters illustrates the principle. We analyze how the nanotopography establishes regions of lower free energy and how entropic forces compete with advection, Brownian motion, and, importantly, excluded volume interactions; a rise in the density of DNA can be induced to facilitate its escape from a trap at a controlled location. An ability to guide DNA into solvent-permeable traps makes free energy landscaping applicable to genetic analyses.
Transverse thermoelectric response in tilted orientation La1−xSrxCoO3 (0.05 ≤ x ≤ 0.4) thin films
Authors: Wang Y. , Yu L. , Jiang B. , Zhang P. X.
Published: January 2012

La1−xSrxCoO3 (0.05 ≤ x ≤ 0.4) thin films with tilted c-axis have been grown on vicinal cut LaAlO3 (100) substrates by pulse laser deposition. The single phase and the epitaxial growth of these thin films have been checked by x-ray diffraction analysis. Transverse thermoelectric voltage response in these films has been studied at room temperature by using a pulse laser as the thermal source. The maximum voltage response has been observed in La0.7Sr0.3CoO3 films in this series of oxides, with the responsivity of 1.23 V/mJ in 10° tilted film. The resistivity and the thermal diffusivity have been reckoned as the main physical parameters to determine the time response of establishment and decay processes of transverse thermoelectric voltage, respectively. Smaller resistivity leads to fast response speed to establish the voltage, while larger thermal diffusivity results in the fast decay of voltage.
Fire management on private conservation lands: knowledge, perceptions and actions of landholders in eastern Australia
Authors: Halliday Lucy G. , Castley J. Guy , Fitzsimons James A. , Tran Cuong , Warnken Jan
Published: January 2012

Fire is an important natural disturbance process within the Australian landscape, but the complex and hazardous nature of fire creates a conservation management dilemma. For landholders of private conservation lands, management for conservation of biodiversity and risk reduction is complicated. Private conservation landholders in eastern Australia directed far less effort towards fire management than other conservation management actions, despite clearly acknowledging the risk and associated responsibilities of fire management on their lands. Nonetheless, landholders did undertake actions to reduce fuel hazards and prepare for wildfire events on their land. Despite the established role and benefits of fire to many ecosystems in the region, landholder understanding of the ecological role of fire was generally poor. Few landholders were aware of ecologically appropriate fire regimes for the vegetation types on their property, and few undertook fire management actions to achieve ecological outcomes. Site-specific obstacles, lack of fire management knowledge and experience, and legal and containment concerns contributed to the low level of fire management observed. There is a need for property-specific fire management planning across all private conservation lands, to further integrate ecological fire requirements into biodiversity management, and prioritise actions that aim to improve conservation outcomes while safeguarding life and property.
RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway
Authors: Zhang Donglei , Isack Nora R. , Glodowski Doreen R. , Liu Jie , Chen Carlos Chih-Hsiung , Xu X.Z. Shawn , Grant Barth D. , Rongo Christopher
Published: January 2012

Regulated membrane trafficking of AMPA-type glutamate receptors (AMPARs) is a key mechanism underlying synaptic plasticity, yet the pathways used by AMPARs are not well understood. In this paper, we show that the AMPAR subunit GLR-1 in Caenorhabditis elegans utilizes the retrograde transport pathway to regulate AMPAR synaptic abundance. Mutants for rab-6.2, the retromer genes vps-35 and snx-1, and rme-8 failed to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. In contrast, expression of constitutively active RAB-6.2 drove the retrograde transport of GLR-1 from dendrites back to cell body Golgi. We also find that activated RAB-6.2 bound to and colocalized with the PDZ/phosphotyrosine binding domain protein LIN-10. RAB-6.2 recruited LIN-10. Moreover, the regulation of GLR-1 transport by RAB-6.2 required LIN-10 activity. Our results demonstrate a novel role for RAB-6.2, its effector LIN-10, and the retromer complex in maintaining synaptic strength by recycling AMPARs along the retrograde transport pathway.
Ndfip1 regulates nuclear Pten import in vivo to promote neuronal survival following cerebral ischemia
Authors: Howitt Jason , Lackovic Jenny , Low Ley-Hian , Naguib Adam , Macintyre Alison , Goh Choo-Peng , Callaway Jennifer K. , Hammond Vicki , Thomas Tim , Dixon Matthew , Putz Ulrich , Silke John , Bartlett Perry , Yang Baoli , Kumar Sharad , Trotman Lloyd C. , Tan Seong-Seng
Published: January 2012

PTEN (phosphatase and tensin homologue deleted on chromosome TEN) is the major negative regulator of phosphatidylinositol 3-kinase signaling and has cell-specific functions including tumor suppression. Nuclear localization of PTEN is vital for tumor suppression; however, outside of cancer, the molecular and physiological events driving PTEN nuclear entry are unknown. In this paper, we demonstrate that cytoplasmic Pten was translocated into the nuclei of neurons after cerebral ischemia in mice. Critically, this transport event was dependent on a surge in the Nedd4 family–interacting protein 1 (Ndfip1), as neurons in Ndfip1-deficient mice failed to import Pten. Ndfip1 binds to Pten, resulting in enhanced ubiquitination by Nedd4 E3 ubiquitin ligases. In vitro, Ndfip1 overexpression increased the rate of Pten nuclear import detected by photobleaching experiments, whereas Ndfip1−/− fibroblasts showed negligible transport rates. In vivo, Ndfip1 mutant mice suffered larger infarct sizes associated with suppressed phosphorylated Akt activation. Our findings provide the first physiological example of when and why transient shuttling of nuclear Pten occurs and how this process is critical for neuron survival.
dEHBP1 controls exocytosis and recycling of Delta during asymmetric divisions
Authors: Giagtzoglou Nikolaos , Yamamoto Shinya , Zitserman Diana , Graves Hillary K. , Schulze Karen L. , Wang Hao , Klein Hayley , Roegiers Fabrice , Bellen Hugo J.
Published: January 2012

Notch signaling governs binary cell fate determination in asymmetrically dividing cells. Through a forward genetic screen we identified the fly homologue of Eps15 homology domain containing protein-binding protein 1 (dEHBP1) as a novel regulator of Notch signaling in asymmetrically dividing cells. dEHBP1 is enriched basally and at the actin-rich interface of pII cells of the external mechanosensory organs, where Notch signaling occurs. Loss of function of dEHBP1 leads to up-regulation of Sanpodo, a regulator of Notch signaling, and aberrant trafficking of the Notch ligand, Delta. Furthermore, Sec15 and Rab11, which have been previously shown to regulate the localization of Delta, physically interact with dEHBP1. We propose that dEHBP1 functions as an adaptor molecule for the exocytosis and recycling of Delta, thereby affecting cell fate decisions in asymmetrically dividing cells.
The vesicular SNARE Synaptobrevin is required for Semaphorin 3A axonal repulsion
Authors: Zylbersztejn Kathleen , Petkovic Maja , Burgo Andrea , Deck Marie , Garel Sonia , Marcos Séverine , Bloch-Gallego Evelyne , Nothias Fatiha , Serini Guido , Bagnard Dominique , Binz Thomas , Galli Thierry
Published: January 2012

Attractive and repulsive molecules such as Semaphorins (Sema) trigger rapid responses that control the navigation of axonal growth cones. The role of vesicular traffic in axonal guidance is still largely unknown. The exocytic vesicular soluble N-ethylmaleimide sensitive fusion protein attachment protein receptor (SNARE) Synaptobrevin 2 (Syb2) is known for mediating neurotransmitter release in mature neurons, but its potential role in axonal guidance remains elusive. Here we show that Syb2 is required for Sema3A-dependent repulsion but not Sema3C-dependent attraction in cultured neurons and in the mouse brain. Syb2 associated with Neuropilin 1 and Plexin A1, two essential components of the Sema3A receptor, via its juxtatransmembrane domain. Sema3A receptor and Syb2 colocalize in endosomal membranes. Moreover, upon Sema3A treatment, Syb2-deficient neurons failed to collapse and transport Plexin A1 to cell bodies. Reconstitution of Sema3A receptor in nonneuronal cells revealed that Sema3A further inhibited the exocytosis of Syb2. Therefore, Sema3A-mediated signaling and axonal repulsion require Syb2-dependent vesicular traffic.
Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence
Authors: Schulze zur Wiesch Julian , Ciuffreda Donatella , Lewis-Ximenez Lia , Kasprowicz Victoria , Nolan Brian E. , Streeck Hendrik , Aneja Jasneet , Reyor Laura L. , Allen Todd M. , Lohse Ansgar W. , McGovern Barbara , Chung Raymond T. , Kwok William W. , Kim Arthur Y. , Lauer Georg M.
Published: January 2012

Vigorous proliferative CD4+ T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4+ T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4+ T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4+ T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4+ T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4+ T cells. Instead, broadly directed HCV-specific CD4+ T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T cell responses through antiviral therapy.
Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10–producing suppressive CD4+ T cells
Authors: Li Dapeng , Romain Gabrielle , Flamar Anne-Laure , Duluc Dorothée , Dullaers Melissa , Li Xiao-Hua , Zurawski Sandra , Bosquet Nathalie , Palucka Anna Karolina , Le Grand Roger , O’Garra Anne , Zurawski Gerard , Banchereau Jacques , Oh SangKon
Published: January 2012

Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4+ T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3–grabbing nonintegrin favors the generation of antigen-specific suppressive CD4+ T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4+ T cells. The generation of such IL-10–producing CD4+ T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti–DC-ASGPR monoclonal antibody generates antigen-specific CD4+ T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10–producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.
Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis
Authors: Leuschner Florian , Rauch Philipp J. , Ueno Takuya , Gorbatov Rostic , Marinelli Brett , Lee Won Woo , Dutta Partha , Wei Ying , Robbins Clinton , Iwamoto Yoshiko , Sena Brena , Chudnovskiy Aleksey , Panizzi Peter , Keliher Edmund , Higgins John M. , Libby Peter , Moskowitz Michael A. , Pittet Mikael J. , Swirski Filip K. , Weissleder Ralph , Nahrendorf Matthias
Published: January 2012

Monocytes (Mo) and macrophages (MΦ) are emerging therapeutic targets in malignant, cardiovascular, and autoimmune disorders. Targeting of Mo/MΦ and their effector functions without compromising innate immunity’s critical defense mechanisms first requires addressing gaps in knowledge about the life cycle of these cells. Here we studied the source, tissue kinetics, and clearance of Mo/MΦ in murine myocardial infarction, a model of acute inflammation after ischemic injury. We found that a) Mo tissue residence time was surprisingly short (20 h); b) Mo recruitment rates were consistently high even days after initiation of inflammation; c) the sustained need of newly made Mo was fostered by extramedullary monocytopoiesis in the spleen; d) splenic monocytopoiesis was regulated by IL-1β; and e) the balance of cell recruitment and local death shifted during resolution of inflammation. Depending on the experimental approach, we measured a 24 h Mo/MΦ exit rate from infarct tissue between 5 and 13% of the tissue cell population. Exited cells were most numerous in the blood, liver, and spleen. Abrogation of extramedullary monocytopoiesis proved deleterious for infarct healing and accelerated the evolution of heart failure. We also detected rapid Mo kinetics in mice with stroke. These findings expand our knowledge of Mo/MΦ flux in acute inflammation and provide the groundwork for novel anti-inflammatory strategies for treating heart failure.
Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis
Authors: Zhao Bin , Li Li , Wang Lloyd , Wang Cun-Yu , Yu Jindan , Guan Kun-Liang
Published: January 2012

Cell attachment to the extracellular matrix (ECM) is crucial to cell physiology such as polarity, motility, and proliferation. In normal cells, loss of attachment to the ECM induces a specific type of apoptosis, termed anoikis. Resistance to anoikis in cancer cells promotes their survival in circulation and dispersion to distant anatomic sites, leading to tumor metastasis. The Yes-associated protein (YAP) transcription coactivator is a human oncogene and a key regulator of organ size. The Hippo tumor suppressor pathway phosphorylates and inhibits YAP. However, little is known about the signals that regulate the Hippo pathway. Here we report that through cytoskeleton reorganization, cell detachment activates the Hippo pathway kinases Lats1/2 and leads to YAP phosphorylation and inhibition. The detachment-induced YAP inactivation is required for anoikis in nontransformed cells, whereas in cancer cells with deregulation of the Hippo pathway, knockdown of YAP and TAZ restores anoikis. Furthermore, we provided evidence that Lats1/2 expression level is indeed significantly down-regulated in metastatic prostate cancer. Our findings provide a novel connection between cell attachment and anoikis through the Hippo pathway and have important implications in cancer therapeutics.
Spatial arrangement of an RNA zipcode identifies mRNAs under post-transcriptional control
Authors: Patel Vivek L. , Mitra Somdeb , Harris Richard , Buxbaum Adina R. , Lionnet Timothée , Brenowitz Michael , Girvin Mark , Levy Matthew , Almo Steven C. , Singer Robert H. , Chao Jeffrey A.
Published: January 2012

How RNA-binding proteins recognize specific sets of target mRNAs remains poorly understood because current approaches depend primarily on sequence information. In this study, we demonstrate that specific recognition of messenger RNAs (mRNAs) by RNA-binding proteins requires the correct spatial positioning of these sequences. We characterized both thecis-acting sequence elements and the spatial restraints that define the mode of RNA binding of the zipcode-binding protein 1 (ZBP1/IMP1/IGF2BP1) to the β-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element comprised of a 5′ element (CGGAC) followed by a variable 3′ element (C/A-CA-C/U) that must be appropriately spaced. Remarkably, the orientation of these elements is interchangeable within target transcripts bound by ZBP1. The spatial relationship of this consensus binding site identified conserved transcripts that were verified to associate with ZBP1 in vivo. The dendritic localization of one of these transcripts, spinophilin, was found to be dependent on both ZBP1 and the RNA elements recognized by ZBP1 KH34.
Polyploidization of glia in neural development links tissue growth to blood–brain barrier integrity
Authors: Unhavaithaya Yingdee , Orr-Weaver Terry L.
Published: January 2012

Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found theDrosophila melanogastersubperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood–brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential vertebrate examples.
Intronic miR-26b controls neuronal differentiation by repressing its host transcript,ctdsp2
Authors: Dill Holger , Linder Bastian , Fehr Alexander , Fischer Utz
Published: January 2012

Differentiation of neural stem cells (NSCs) to neurons requires the activation of genes controlled by the repressor element 1 (RE1) silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) protein complex. Important components of REST/NRSF are phosphatases (termed RNA polymerase II C-terminal domain small phosphatases [CTDSPs]) that inhibit RNA polymerase II and suppress neuronal gene expression in NSCs. Activation of genes controlled by CTDSPs is required for neurogenesis, but how this is achieved is not fully understood. Here we show thatctdsp2is a target of miR-26b, a microRNA that is encoded in an intron of thectdsp2primary transcript. This intrinsic negative feedback loop is inactive in NSCs because miR-26b biogenesis is inhibited at the precursor level. Generation of mature miR-26b is activated during neurogenesis, where it suppresses Ctdsp2 protein expression and is required for neuronal cell differentiation in vivo.
Structure and operation of the DNA-translocating type I DNA restriction enzymes
Authors: Kennaway Christopher K. , Taylor James E.N. , Song Chun Feng , Potrzebowski Wojciech , Nicholson William , White John H. , Swiderska Anna , Obarska-Kosinska Agnieszka , Callow Philip , Cooper Laurie P. , Roberts Gareth A. , Artero Jean-Baptiste , Bujnicki Janusz M. , Trinick John , Kneale G. Geoff , Dryden David T.F.
Published: January 2012

Type I DNA restriction/modification (RM) enzymes are molecular machines found in the majority of bacterial species. Their early discovery paved the way for the development of genetic engineering. They control (restrict) the influx of foreign DNA via horizontal gene transfer into the bacterium while maintaining sequence-specific methylation (modification) of host DNA. The endonuclease reaction of these enzymes on unmethylated DNA is preceded by bidirectional translocation of thousands of base pairs of DNA toward the enzyme. We present the structures of two type I RM enzymes, EcoKI and EcoR124I, derived using electron microscopy (EM), small-angle scattering (neutron and X-ray), and detailed molecular modeling. DNA binding triggers a large contraction of the open form of the enzyme to a compact form. The path followed by DNA through the complexes is revealed by using a DNA mimic anti-restriction protein. The structures reveal an evolutionary link between type I RM enzymes and type II RM enzymes.
Schizosaccharomyces pombeCcq1 and TER1 bind the 14-3-3-like domain of Est1, which promotes and stabilizes telomerase–telomere association
Authors: Webb Christopher J. , Zakian Virginia A.
Published: January 2012

The telomerase protein Est1 exists in multiple organisms, includingSchizosaccharomyces pombe, humans, andSaccharomyces cerevisiae, but its function has only been closely examined inS. cerevisiae, where it is a recruiter/activator of telomerase. Here, we demonstrate thatS. pombeEst1 was required for the telomere association of the telomerase holoenzyme, suggesting that it too has a recruitment role. Its association with telomeres was dependent on Trt1, the catalytic subunit, and Ccq1, a telomeric protein. Surprisingly, Est1 telomere binding was only partially dependent on TER1, the telomerase RNA, even though Est1 bound nucleotides 415–507 of TER1. Ater1-Δ415–507 strain had short telomeres and very low Est1 and Trt1 telomere association in late S phase but did not senesce. An unbiased search for mutations that reduced Est1–TER1 interaction identified mutations only in the Est1 14-3-3-like domain, a phosphoserine-binding motif, the first example of a 14-3-3-like domain with RNA-binding activity. These mutations also reduced Est1–Ccq1 binding. One such mutant prevented Est1 telomere association and caused telomere loss and slow senescence, similar toccq1Δ. We propose that the Est1–Ccq1 interaction is critical for telomerase recruitment, while the Est1–TER1 interaction acts downstream from Ccq1-mediated recruitment to stabilize the holoenzyme at the telomere.
LhnR and upstream operon LhnABC in Agrobacterium vitis regulate the induction of tobacco hypersensitive responses, grape necrosis and swarming motility
Authors: ZHENG DESEN , HAO GUIXIA , CURSINO LUCIANA , ZHANG HONGSHENG , BURR THOMAS J.
Published: January 2012

The characterization of Tn5 transposon insertional mutants of Agrobacterium vitis strain F2/5 revealed a gene encoding a predicted LysR‐type transcriptional regulator, lhnR (for ‘LysR‐type regulator associated with HR and necrosis’), and an immediate upstream operon consisting of three open reading frames (lhnABC) required for swarming motility, surfactant production and the induction of a hypersensitive response (HR) on tobacco and necrosis on grape. The operon lhnABC is unique to A. vitis among the sequenced members in Rhizobiaceae. Mutagenesis of lhnR and lhnABC by gene disruption and complementation of ΔlhnR and ΔlhnABC confirmed their roles in the expression of these phenotypes. Mutation of lhnR resulted in complete loss of HR, swarming motility, surfactant production and reduced necrosis, whereas mutation of lhnABC resulted in loss of swarming motility, delayed and reduced HR development and reduced surfactant production and necrosis. The data from promoter–green fluorescent protein (gfp) fusions showed that lhnR suppresses the expression of lhnABC and negatively autoregulates its own expression. It was also shown that lhnABC negatively affects its own expression and positively affects the transcription of lhnR. lhnR and lhnABC constitute a regulatory circuit that coordinates the transcription level of lhnR, resulting in the expression of swarming, surfactant, HR and necrosis phenotypes.
Modulatory Effects of Sex Steroid Hormones on Brain‐Derived Neurotrophic Factor‐Tyrosine Kinase B Expression during Adolescent Development in C57Bl/6 Mice
Authors: Hill R. A. , Wu Y. W. C. , Kwek P. , Buuse M. van den
Published: January 2012

Sex steroid hormones and neurotrophic factors are involved in pruning and shaping the adolescent brain and have been implicated in the pathogenesis of neurodevelopmental disorders, including mental illness. We aimed to determine the association between altered levels of sex steroid hormones during adolescent development and neurotrophic signalling in the C57Bl/6 mouse. We first performed a week by week analysis from pre‐pubescence to adulthood in male and female C57Bl/6 mice, measuring serum levels of testosterone and oestradiol in conjunction with western blot analysis of neurotrophin expression in the forebrain and hippocampal regions. Second, we manipulated adolescent sex steroid hormone levels by gonadectomy and hormone replacement at the pre‐pubescent age of 5 weeks. Young‐adult forebrain and hippocampal neurotrophin expression was then determined. Male mice showed significant changes in brain‐derived neurotrophic factor (BDNF) expression in the forebrain regions during weeks 7–10, which corresponded significantly with a surge in serum testosterone. Castration and testosterone or di‐hydrotestosterone replacement experiments revealed an androgen receptor‐dependent effect on BDNF‐tyrosine kinase (Trk) B signalling in the forebrain and hippocampal regions during adolescence. Female mice showed changes in BDNF‐TrkB signalling at a much earlier time point (weeks 4–8) in the forebrain and hippocampal regions and these did not correspond with changes in serum oestradiol. Ovariectomy actually increased BDNF expression but decreased TrkB phosphorylation in the forebrain regions. 17β‐Oestradiol replacement had no effect, suggesting a role for other ovarian hormones in regulating BDNF‐TrkB signalling in the adolescent female mouse brain. These results suggest the differential actions of sex steroid hormones in modulating BDNF‐TrkB signalling during adolescence. These data provide insight into how the male and female brain changes in response to altered levels of circulating sex steroid hormones and could help to explain some of the developmental sex differences in the pathogenesis of neurodevelopmental disorders, including mental illness.
Humour in health‐care interactions: a risk worth taking
Authors: McCreaddie May , Payne Sheila
Published: January 2012

Background  Humour is a complex, dynamic phenomenon that mainly occurs in social situations between two or more people. Most humour research reviews rehearsed as opposed to spontaneous humour and rarely review the patients’ perspective.

Aim  We explore patients’ perspectives on the use of humour in health care. We discuss the asymmetrical and divergent humour use between patients and clinical nurse specialists and posit nurses’ approaches to risk as a contributing factor.

Design  A constructivist grounded theory collated researcher‐provoked (interviews, observation, field notes, pre‐and post‐interaction audio diaries) and non‐researcher‐provoked data (naturally occurring interactions) over 18 months. This paper is based upon four patient focus groups. A constant comparison approach to data collection and analyses was applied using interpretative and illustrative frameworks that balanced what was ‘known’ and ‘unknown’ about humour.

Setting and participants  Patients were recruited from four patient–peer groups. Three audio‐taped (n = 20) and one observed focus group interactions (n = 12) were undertaken at the groups’ regular meeting places.

Results  Patients hold a broad appreciation of humour and recognize it as being evident in subtle and nuanced forms. Patients wish health‐care staff to initiate and reciprocate humour.

Conclusion  A chasm exists between what patients apparently want with regard to humour use in health‐care interactions and what actually transpires. Initiating humour involves risk, and risk‐taking requires a degree of self‐esteem and confidence. Nurses are, arguably, risk‐averse and have low self‐esteem. Future research could review confidence and self‐esteem markers with observed humour use in nurses and their interactions across a range of specialities.
Structural social support predicts functional social support in an online weight loss programme
Authors: Hwang Kevin O. , Etchegaray Jason M. , Sciamanna Christopher N. , Bernstam Elmer V. , Thomas Eric J.
Published: January 2012

Background  Online weight loss programmes allow members to use social media tools to give and receive social support for weight loss. However, little is known about the relationship between the use of social media tools and the perception of specific types of support.

Objective  To test the hypothesis that the frequency of using social media tools (structural support) is directly related to perceptions of Encouragement, Information and Shared Experiences support (functional support).

Design  Online survey.

Participants  Members of an online weight loss programme.

Methods  The outcome was the perception of Encouragement (motivation, congratulations), Information (advice, tips) and Shared Experiences (belonging to a group) social support. The predictor was a social media scale based on the frequency of using forums and blogs within the online weight loss programme (alpha = 0.91). The relationship between predictor and outcomes was evaluated with structural equation modelling (SEM) and logistic regression, adjusted for sociodemographic characteristics, BMI and duration of website membership.

Results  The 187 participants were mostly female (95%) and white (91%), with mean (SD) age 37 (12) years and mean (SD) BMI 31 (8). SEM produced a model in which social media use predicted Encouragement support, but not Information or Shared Experiences support. Participants who used the social media tools at least weekly were almost five times as likely to experience Encouragement support compared to those who used the features less frequently [adjusted OR 4.8 (95% CI 1.8–12.8)].

Conclusions  Using the social media tools of an online weight loss programme at least once per week is strongly associated with receiving Encouragement for weight loss behaviours.
Fish Gills Alterations as Potential Biomarkers of Environmental Quality in a Eutrophized Tropical River in South‐Eastern Brazil
Authors: Nascimento A. A. , Araújo F. G. , Gomes I. D. , Mendes R. M. M. , Sales A.
Published: January 2012

Gill anomalies in three common fish species of different taxonomic order, habitat dwelling and feeding habits (one Characiformes, Oligosarcus hepsetus; one Siluriformes, Hypostomus auroguttatus; and one Perciformes, Geophagus brasiliensis) from a eutrophized tropical river in south‐eastern in Brazil were compared. The aim of this study was to search for sentinel species that could be used as potential biomarkers of environmental quality. Most fish had gills with histological changes, namely epithelial lifting, interstitial oedema, leucocyte infiltration, hyperplasia of the epithelial cells, lamellar fusion, vasodilatation and necrosis. On the other hand, lamellar blood congestion and lamellar aneurysm, which are more serious and often irreversible changes, were recorded for the water column carnivorous O. hepsetus and, to a lesser extent, for the bottom‐dwelling detritivorous H. auroguttatus. A histopathological alteration index (HAI) based on the occurrence and severity of gills anomalies indicated that O. hepsetus (mean score = 11.4) had significantly higher values (Kruskall–Wallis H2,41 = 15.95, P = 0.0003) compared with G. brasiliensis (mean score = 7.0). Overall, the omnivorous G. brasiliensis had comparatively lesser occurrence of most gill anomalies compared with other two species, being less suitable as biomarker of environmental quality. In contrast, the water column–dweller O. hepsetus (water column) and the bottom‐dweller H. auroguttatus had gills most susceptible to changes, making them more suitable for using as histological biomarkers of the environmental quality in entrophized tropical rivers.