bluuebunny/crossref_metadata_2025 huggingface dataset:
Electric-field-tunable defect mode in one-dimensional photonic crystal operating in the terahertz range
Authors: Skoromets V. , Němec H. , Kadlec C. , Fattakhova-Rohlfing D. , Kužel P.
Published: June 2013

A one-dimensional photonic crystal possessing an electric-field-tunable defect mode in the lowest forbidden band is demonstrated. The compact photonic structure consists of two symmetric Bragg mirrors made of alternate quarter-wave layers of SiO2 and CeO2 separated by a defect layer of an incipient ferroelectric SrTiO3 with electrodes transparent for terahertz radiation on its both sides. The applied bias is then perpendicular to the layer and modifies the in-plane dielectric function, which is probed by the transverse terahertz wave. The observed tunable behavior is in agreement with the model of the ferroelectric soft mode behavior in SrTiO3 single crystals. The defect-mode frequency tunability is proportional to that of the soft mode: we achieved a relative tunability of 6.5% at 105 K under an electric bias of 60 kV/cm.
Development of a cryogenic load frame for the neutron diffractometer at Takumi in Japan Proton Accelerator Research Complex
Authors: Jin Xinzhe , Nakamoto Tatsushi , Harjo Stefanus , Hemmi Tsutomu , Umeno Takahiro , Ogitsu Toru , Yamamoto Akira , Sugano Michinaka , Aizawa Kazuya , Abe Jun , Gong Wu , Iwahashi Takaaki
Published: June 2013

To prepare for projects such as the Large Hadron Collider upgrade, International Thermonuclear Experimental Reactor and Demonstration reactor, it is important to form a clear understanding of stress-strain properties of the materials that make up superconducting magnets. Thus, we have been studying the mechanical properties of superconducting wires using neutron diffraction measurements. To simulate operational conditions such as temperature, stress, and strain, we developed a cryogenic load frame for stress-strain measurements of materials using a neutron diffractometer at Japan Proton Accelerator Research Complex (J-PARC) Takumi beam line. The maximum load that can be applied to a sample using an external driving machine is 50 kN. Using a Gifford–MacMahon cryocooler, samples can be measured down to temperatures below 10 K when loaded. In the present paper, we describe the details of the cryogenic load frame with its test results by using type-304 stainless steel wire.
CO2 sensing at room temperature using carbon nanotubes coated core fiber Bragg grating
Authors: Shivananju B. N. , Yamdagni S. , Fazuldeen R. , Sarin Kumar A. K. , Hegde G. M. , Varma M. M. , Asokan S.
Published: June 2013

The sensing of carbon dioxide (CO2) at room temperature, which has potential applications in environmental monitoring, healthcare, mining, biotechnology, food industry, etc., is a challenge for the scientific community due to the relative inertness of CO2. Here, we propose a novel gas sensor based on clad-etched Fiber Bragg Grating (FBG) with polyallylamine-amino-carbon nanotube coated on the surface of the core for detecting the concentrations of CO2 gas at room temperature, in ppm levels over a wide range (1000 ppm–4000 ppm). The limit of detection observed in polyallylamine-amino-carbon nanotube coated core-FBG has been found to be about 75 ppm. In this approach, when CO2 gas molecules interact with the polyallylamine-amino-carbon nanotube coated FBG, the effective refractive index of the fiber core changes, resulting in a shift in Bragg wavelength. The experimental data show a linear response of Bragg wavelength shift for increase in concentration of CO2 gas. Besides being reproducible and repeatable, the technique is fast, compact, and highly sensitive.
Multiscale modeling with smoothed dissipative particle dynamics
Authors: Kulkarni Pandurang M. , Fu Chia-Chun , Shell M. Scott , Gary Leal L.
Published: June 2013

In this work, we consider two issues related to the use of Smoothed Dissipative Particle Dynamics (SDPD) as an intermediate mesoscale model in a multiscale scheme for solution of flow problems when there are local parts of a macroscopic domain that require molecular resolution. The first is to demonstrate that SDPD with different levels of resolution can accurately represent the fluid properties from the continuum scale all the way to the molecular scale. Specifically, while the thermodynamic quantities such as temperature, pressure, and average density remain scale-invariant, we demonstrate that the dynamic properties are quantitatively consistent with an all-atom Lennard-Jones reference system when the SDPD resolution approaches the atomistic scale. This supports the idea that SDPD can serve as a natural bridge between molecular and continuum descriptions. In the second part, a simple multiscale methodology is proposed within the SDPD framework that allows several levels of resolution within a single domain. Each particle is characterized by a unique physical length scale called the smoothing length, which is inversely related to the local number density and can change on-the-fly. This multiscale methodology is shown to accurately reproduce fluid properties for the simple problem of steady and transient shear flow.
Comparison of density functionals for nitrogen impurities in ZnO
Authors: Sakong Sung , Gutjahr Johann , Kratzer Peter
Published: June 2013

Hybrid functionals and empirical correction schemes are compared to conventional semi-local density functional theory (DFT) calculations in order to assess the predictive power of these methods concerning the formation energy and the charge transfer level of impurities in the wide-gap semiconductor ZnO. While the generalized gradient approximation fails to describe the electronic structure of the N impurity in ZnO correctly, methods that widen the band gap of ZnO by introducing additional non-local potentials yield the formation energy and charge transfer level of the impurity in reasonable agreement with hybrid functional calculations. Summarizing the results obtained with different methods, we corroborate earlier findings that the formation of substitutional N impurities at the oxygen site in ZnO from N atoms is most likely slightly endothermic under oxygen-rich preparation conditions, and introduces a deep level more than 1 eV above the valence band edge of ZnO. Moreover, the comparison of methods elucidates subtle differences in the predicted electronic structure, e.g., concerning the orientation of unoccupied orbitals in the crystal field and the stability of the charged triplet state of the N impurity. Further experimental or theoretical analysis of these features could provide useful tests for validating the performance of DFT methods in their application to defects in wide-gap materials.
Active laser ranging over planetary distances with millimeter accuracy
Authors: Chen Yijiang , Birnbaum Kevin M. , Hemmati Hamid
Published: June 2013

Precision laser ranging between planetary bodies will allow advances in the study of fundamental physics and solar system dynamics. Current precision ranging techniques based on retro-reflectors are limited to the Earth-Moon distance. We present a method of active laser ranging over interplanetary distances with asynchronous two-way ranging. The method is validated in real time laboratory experiments and field tests. Sub-millimeter accuracy has been achieved in real-time active laser ranging for interplanetary distances, providing precision improvement well above three orders of magnitude over the current RF techniques. An instrument developed with the approach and deployed in future planetary missions will significantly advance planetary sciences and fundamental physics. For example, implemented in a future Mars lander mission our approach will clarify the Mars interior (liquid or solid), which is still an open question due to limitation of RF ranging precision although extensive efforts have been made over years with numerous missions since 1970s.
Development of multi-hierarchy simulation model with non-uniform space grids for collisionless driven reconnection
Authors: Usami Shunsuke , Horiuchi Ritoku , Ohtani Hiroaki , Den Mitsue
Published: June 2013

A multi-hierarchy simulation model aimed at magnetic reconnection studies has been developed, in which macroscopic and microscopic physics are solved self-consistently and simultaneously. In this work, the previous multi-hierarchy model by these authors is extended to a more realistic one with non-uniform space grids. Based on the domain decomposition method, the multi-hierarchy model consists of three parts: a magnetohydrodynamics algorithm to express the macroscopic global dynamics, a particle-in-cell algorithm to describe the microscopic kinetic physics, and an interface algorithm to interlock macro and micro hierarchies. For its verification, plasma flow injection is simulated in this multi-hierarchy model and it is confirmed that the interlocking method can describe the correct physics. Furthermore, this model is applied to collisionless driven reconnection in an open system. Magnetic reconnection is found to occur in a micro hierarchy by injecting plasma from a macro hierarchy.
Nuclear magnetic resonance reveals structural evolution upon annealing in epitaxial Co2MnSi Heusler films
Authors: Rodan S. , Alfonsov A. , Belesi M. , Ferraro F. , Kohlhepp J. T. , Swagten H. J. M. , Koopmans B. , Sakuraba Y. , Bosu S. , Takanashi K. , Büchner B. , Wurmehl S.
Published: June 2013

Co2MnSi films were recently reported to show a significant increase in current-perpendicular-to-plane-giant-magnetoresistance upon annealing. Here, nuclear magnetic resonance was used to study the impact of annealing on the structure of such films. Below 550 °C, no long-range L21-order is observed, while annealing above 550 °C leads to the formation of the ideal L21 configuration, however, with a distinct degree of off-stoichiometry. Further evidence from restoring field measurements hints that interdiffusion may account for the drop in magnetoresistance observed for samples annealed above 600 °C. These results show that optimizing films for spintronics involves the identification of the best annealing temperature, high enough for long-range order to emerge, but low enough to maintain smooth interfaces.
Effect of thickness on the photoluminescence of silicon quantum dots embedded in silicon nitride films
Authors: Rodriguez-Gómez A. , García-Valenzuela A. , Haro-Poniatowski E. , Alonso-Huitrón J. C.
Published: June 2013

In this work, the effect of film thickness on the photoluminescence (PL) spectra of Si quantum dots embedded in silicon nitride films is investigated experimentally and theoretically. The films were deposited by remote plasma enhanced chemical vapor deposition using the same SiH2Cl2/H2/Ar/NH3 mixture and deposition conditions, in order to obtain films with similar composition and approximately equal average size (∼3.1 nm) of Si quantum dots. Only the deposition times were varied to prepare five samples with different thicknesses ranging from ∼30 nm to 4500 nm. Chemical characterization by Fourier Transform Infrared Spectroscopy and X-ray Photoelectron Spectroscopy were carried out in order to check that the composition in all films was the same. The structure, average size, and size distribution of the Si quantum dots were deduced from High-Resolution Transmission Electron Microscopy. The thickness of the films was determined by ellipsometry and interferometry of UV-Vis transmission spectra. It was found experimentally that the increase of the thickness above a few hundreds of nanometers produces significant distortions of the PL spectra of the films, such as peak shifts and the appearance of shoulders and multiple peaks suggesting interference effects. Comparing the experimental results with theoretical simulations, it is shown that these distortions are mainly due to interference effects and not to intrinsic changes in the films. The approximation used to simulate the PL spectra as a function of film thickness allows improving the fitting between simulated and experimental spectra by changing some optical parameters and can be helpful to further investigate the intrinsic optical properties of the films.
Growth of single-walled Ag and Cu nanotubes confined in carbon nanotubes, studied by molecular dynamics simulations
Authors: Han Yang , Li Rui , Ge Yong , Dong Jinming
Published: June 2013

Growth of single-walled silver and copper nanotubes (Ag- and Cu-SWNTs), confined in carbon nanotubes (CNTs), has been studied by using the classical molecular dynamics method. It is found that: (1) Four kinds of Ag-SWNTs, i.e., (3, 2), (4, 2), (4, 3), and (5, 3) ones, and five kinds of Cu-SWNTs, i.e., (3, 2), (4, 2), (4, 3), (4, 4), and (5, 3) ones, could be formed when the diameters of outside CNT containers are changed from 6.78 to 10.86 Å. (2) The formation of the Ag- and Cu-SWNTs in confined CNTs is less sensitive to the CNTs' tube indices, but heavily influenced by the CNTs’ diameters. And the Ag- and Cu-SWNTs, formed in confined CNTs, are radially compressed, when the CNTs’ diameters are small. (3) The frequencies of the radial breathing modes of Ag- and Cu-SWNTs are approximately to vary linearly with the inverse tube diameters.
Destabilization of low-n peeling modes by trapped energetic particles
Authors: Hao G. Z. , Liu Y. Q. , Wang A. K. , Matsunaga G. , Okabayashi M. , Mou Z. Z. , Qiu X. M.
Published: June 2013

The kinetic effect of trapped energetic particles (EPs), arising from perpendicular neutral beam injection, on the stable low-n peeling modes in tokamak plasmas is investigated, through numerical solution of the mode's dispersion relation derived from an energy principle. A resistive-wall peeling mode with m/n=6/1, with m and n being the poloidal and toroidal mode numbers, respectively, is destabilized by trapped EPs as the EPs' pressure exceeds a critical value βc*, which is sensitive to the pitch angle of trapped EPs. The dependence of βc* on the particle pitch angle is eventually determined by the bounce average of the mode eigenfunction. Peeling modes with higher m and n numbers can also be destabilized by trapped EPs. Depending on the wall distance, either a resistive-wall peeling mode or an ideal-kink peeling mode can be destabilized by EPs.
Influence of A-site doping and strain on the relationship between the anisotropic magneto-resistance and charge localization in films of La0.7−xPrxCa0.3MnO3 manganites
Authors: Alagoz H. S. , Khan M. , Saber M. M. , Mahmud S. T. , Chow K. H. , Jung J.
Published: June 2013

We studied the correlation between the charge carrier localization and the anisotropic magneto-resistance (AMR) of La0.7−xPrxCa0.3MnO3 (0.00≤x≤0.35) epitaxial thin films deposited on SrTiO3 and LaAlO3 substrates. An increase in the carrier localization, as evidenced by the rise of the small polaron activation energy Ea in the paramagnetic state, has been achieved either by increasing the dopant concentration x on the A-site or by decreasing the thickness (increasing the epitaxial lattice strain) in the film. The relationship between the AMRmax (the magnitude of AMR at the maximum near the metal-insulator temperature) and Ea exhibits a trend that is independent of the thickness of the film, the substrate, and the doping concentration x. This implies that knowledge of the value of Ea measured in a film could be sufficient to accurately predict its AMRmax value.
Analytical model for self-heating in nanowire geometries
Authors: Hunley D. Patrick , Johnson Stephen L. , Flores Roel L. , Sundararajan Abhishek , Strachan Douglas R.
Published: June 2013

An analytical closed form diffusive model is developed of Joule heating in a device consisting of a nanowire connected to two contacts on a substrate. This analytical model is compared to finite-element simulations and demonstrates excellent agreement over a wider range of system parameters in comparison to other recent models, with particularly large improvements in cases when the width of the nanowire is less than the thermal healing length of the contacts and when the thermal resistance of the contact is appreciable relative to the thermal resistance of the nanowire. The success of this model is due to more accurately accounting for the heat spreading within the contact region of a device and below the nanowire into a substrate. The heat spreading is achieved by matching the linear heat flow near the nanowire interfaces with a radially symmetric spreading solution through an interpolation function. Additional features of this model are the ability to incorporate contact resistances that may be present at the nanowire-contact interfaces, as well as accommodating materials with a linear temperature-dependent electrical resistivity.
Formation of pure GaAs nanotubes driven by surface stress imbalance
Authors: Chen Min , Ding Yingchun , Wu Wenjuan
Published: June 2013

We demonstrate a mechanism for fabricating pure GaAs nanotubes by molecular dynamics simulation. We show the reconstruction of GaAs(001) surface may induce a large stress imbalance between the top and bottom surfaces in a GaAs nanofilm. Driven by such intrinsic surface-stress imbalance, a flat GaAs nanofilm with reconstructed surfaces may self-bend into a nanotube. Our findings suggest the possibility of using ultrathin single layer of GaAs films alone to fabricate pure GaAs nanotubes by manipulating their surface structure.
Epitaxial growth of multiferroic BiFeO3 thin films with (101) and (111) orientations on (100) Si substrates
Authors: Kyun Lee Sung , Ho Choi Bum , Hesse Dietrich
Published: June 2013

Multiferroic (101)- and (111)-oriented BiFeO3 thin films were grown on heteroepitaxial substrates of (110) SrRuO3/(100) YSZ/(100) Si and (111) SrRuO3/(111) Pt/(100) YSZ/(100) Si, respectively, by pulsed laser deposition. X-ray diffraction θ–2θ scans, ϕ scans, and pole figures showed the well-developed out-of-plane and in-plane orientations of the epitaxial BiFeO3 films. The (111) BiFeO3 films showed ∼3/2 times higher remanent polarization (58.9 μC/cm2) than that of the (101) BiFeO3 films (44.3 μC/cm2), thus revealing the ferroelectric anisotropy. The (101) BiFeO3 films exhibited a good fatigue resistance up to 4.6 × 107 cycles, whereas the (111) BiFeO3 films proved to be vulnerable to fatigue, which is associated with the polarization switching path.
Room temperature molecular resolution nanopatterning of cyclopentene monolayers on Si(100) via feedback controlled lithography
Authors: Karmel Hunter J. , Hersam Mark C.
Published: June 2013

Molecularly precise nanopatterning is demonstrated for a saturated organic monolayer on the Si(100) surface using room temperature ultra-high vacuum scanning tunneling microscopy. In particular, feedback controlled lithography enables the clean desorption of individual molecules from a highly-ordered cyclopentene monolayer at moderate negative sample bias, resulting in the exposure of isolated silicon dimers on an otherwise organically passivated surface. The quality and uniformity of the cyclopentene passivation layer is also quantified with X-ray photoelectron spectroscopy following exposure to ambient conditions, revealing that complete formation of the native oxide on silicon is suppressed for time scales exceeding 100 days.
The impact of negative oxygen ion bombardment on electronic and structural properties of magnetron sputtered ZnO:Al films
Authors: Bikowski André , Welzel Thomas , Ellmer Klaus
Published: June 2013

In order to study the impact of negative oxygen ion bombardment on the electronic transport properties of ZnO:Al films, a systematic magnetron sputtering study from ceramic targets with excitation frequencies from DC to 27 MHz, accompanied by strongly varying discharge voltages, has been performed. Higher plasma excitation frequencies significantly improve the transport properties of ZnO:Al films. The effect of the bombardment of the films by energetic particles (negative oxygen ions) can be explained by the dynamic equilibrium between the formation of acceptor-like oxygen interstitials compensating the extrinsic donors and the self-annealing of the interstitial defects at higher deposition temperatures.
Preparation of residential aged care services for extreme hot weather in Victoria, Australia
Authors: McInnes Judith A. , Ibrahim Joseph E.
Published: June 2013

Objectives. The purpose of this study was to describe preparations for extreme hot weather at Victorian public sector residential aged care services for the 2010−11 summer, and to examine the role of the Residential Aged Care Services Heatwave Ready Resource in this process. Method. Qualitative data was collected through semi-structured interviews of senior staff of Victorian public sector residential aged care services. Interviews were conducted at monthly intervals from November 2010 to March 2011, and data were analysed thematically. Results. All interviewees described pre-summer preparations for hot weather undertaken at the health services they represented. Staff awareness and experience, and having a heatwave plan, were reported to have facilitated heat preparedness, whereas challenges to preparations mainly concerned air conditioning. The Residential Aged Care Services Heatwave Ready Resource was used to inform heatwave plans, for staff and family education, and as an audit tool. Conclusions. An extensive and well-considered approach to minimisation of harm from extreme heat by a sample of residential aged care services is described, and the Residential Aged Care Services Heatwave Ready Resource is reported to have supported the heatwave preparedness process. What is known about the topic? Heatwaves cause illness and death and are likely to become more frequent and severe in the future. Residents of aged care services are particularly vulnerable to harm from heatwaves. The Residential Aged Care Services Heatwave Ready Resource has been developed to support staff of residential aged care services in Victoria to prepare for heatwaves. What does this paper add? This exploratory study provides insight into the types of preparations for extreme hot weather that are undertaken at Victorian residential aged care services before and during summer. What are the implications for practitioners? A combination of staff knowledge and experience, and having a heatwave plan, supported by a publication that includes educational resources and a checklist is reported to facilitate the preparedness of Victorian residential aged care services for extreme hot weather.
Fragment Screening by Native State Mass Spectrometry
Authors: Poulsen Sally-Ann
Published: June 2013

Native state mass spectrometry (MS) has been recognised as a rapid, sensitive, and high throughput method to directly investigate protein-ligand interactions for some time, however there are few examples reporting this approach as a screening method to identify relevant protein–fragment interactions in fragment-based drug discovery (FBDD). In this paper an overview of native state MS will be presented, highlighting the attractive properties of this method within the context of fragment screening applications. A summary of published examples using MS for fragment screening will be described and reflection on the outlook for the future adoption and implementation of native state MS as a complementary fragment screening method will be presented.
Field testing of single-administration porcine zona pellucida contraceptive vaccines in white-tailed deer (Odocoileus virginianus)
Authors: Rutberg Allen T. , Naugle Ricky E. , Turner John W. , Fraker Mark A. , Flanagan Douglas R.
Published: June 2013

Context
Many contraceptive agents have demonstrated effectiveness in wild species, most notably immunocontraceptives such as GnRH conjugates and porcine zona pellucida (PZP). The major challenge in using these agents to control deer and other wildlife populations in the field now lies with safe, effective and efficient delivery to a large-enough proportion of the population to suppress growth.

Aims
Because deer and other wildlife are typically difficult to access for treatment, contraceptives that require multiple or repeated treatments will be of limited management value. To address this constraint, we conducted a field study of white-tailed deer (Odocoileus virginianus) on Fripp Island, SC, USA, to test two different technologies for achieving single-administration, multi-year efficacy in PZP vaccines.

Methods
Between 2005 and 2010, we captured, ear-tagged and blood-sampled a total of 245 individual adult and yearling female deer. Deer were hand-injected at capture with one of two preparations of SpayVac or a combination native PZP–adjuvant emulsion plus PZP–adjuvant incorporated into lactide–glycolide polymer pellets engineered to release at 1, 3 and 12 months post-treatment. Pregnancy was determined from serum assays of pregnancy-specific protein B sampled from captured deer.

Key results
Aqueous SpayVac, and the PZP–adjuvant-containing polymer pellets manufactured through a heat extrusion (H/X) method administered simultaneously with PZP–AdjuVac or modified Freund’s complete adjuvant emulsions reduced pregnancy rates from control levels by 95–100% in the first year after treatment, and by 65–70% in the second year after treatment.

Conclusions
A single, hand-injected vaccination with SpayVac or PZP–adjuvant emulsion combined with H/X PZP pellets reduced fertility for multiple years.

Implications
Single-treatment, multi-year immunocontraceptive vaccines bring contraceptive management of wildlife populations one step closer. Future efforts should focus on improving handling and storage, developing technologies for remote delivery, and addressing remaining regulatory and management concerns.
Observer effects occur when estimating alert but not flight-initiation distances
Authors: Guay P.-J. , McLeod E. M. , Cross R. , Formby A. J. , Maldonado S. P. , Stafford-Bell R. E. , St-James-Turner Z. N. , Robinson R. W. , Mulder R. A. , Weston M. A.
Published: June 2013

Context The estimation of alert (vigilance) and flight-initiation (escape) distances (AD and FID, respectively) has underpinned theoretical and applied studies of the escape behaviour and management of disturbance to wildlife. Many studies use multiple observers, and some conduct meta-analyses; these efforts assume no observer effects in the estimation of these distances. Aims and methods We compared the estimates of FID and AD under ideal conditions (i.e. of black swans, Cygnus atratus, a large species with obvious behaviour, and at a location where swans allowed close approaches in open habitats), by one experienced and four inexperienced observers. Key results FID did not differ among observers but AD differed between the experienced and all inexperienced observers, and among inexperienced observers. Thus, FID estimates appear more repeatable than those of AD. Experience apparently results in more conservative estimates of AD. Conclusions FID represents a repeatable measure that is consistent across observers. This study supports its broad application in the study of wildlife escape behaviour. Implications We recommend the use of FID rather than AD for comparative analyses that involve multiple observers, because FID is more reliably measured.
Feeding activity of threatened black cockatoos in mine-site rehabilitation in the jarrah forest of south-western Australia
Authors: Lee Jessica , Finn Hugh , Calver Michael
Published: June 2013

Land clearing threatens three black cockatoo species (forest red-tailed black cockatoo, (Calyptorhynchus banksii naso), Carnaby’s cockatoo (Calyptorhynchus latirostris), and Baudin’s cockatoo (Calyptorhynchus baudinii) endemic to south-western Australia, so revegetation is important to their recovery. Over three years we studied cockatoo activity in 7–14-year-old mine-site rehabilitation in the region’s jarrah (Eucalyptus marginata)–marri (Corymbia calophylla) forest to give the most detailed description to date of the use of rehabilitation by the birds. Pits varied floristically and structurally (despite similar rehabilitation prescriptions), but interior and exterior plots (100 m2) were similar within pits. Using feeding traces (e.g. chewed husks), and behavioural observations we confirmed feeding within eight years of revegetation. Plots containing feeding trace were similar to plots without, so factors determining black cockatoo feeding may not be apparent at small scales. Returning food resources reflected vegetation succession, with regenerating marri and fast-maturing proteaceous species providing most food. Carnaby’s cockatoo ate Banksia and Hakea seeds and Baudin’s cockatoo and the forest red-tailed black cockatoo consumed marri seeds. Banksia squarrosa, Hakea undulata, H. prostrata and marri were common foods in all years. Revegetation efforts elsewhere should consider these species, within the constraints of rehabilitation protocols addressing multiple aims.
Inositol kinase and its product accelerate wound healing by modulating calcium levels, Rho GTPases, and F-actin assembly
Authors: Soto Ximena , Li Jingjing , Lea Robert , Dubaissi Eamon , Papalopulu Nancy , Amaya Enrique
Published: June 2013

Wound healing is essential for survival. We took advantage of the
Xenopus
embryo, which exhibits remarkable capacities to repair wounds quickly and efficiently, to investigate the mechanisms responsible for wound healing. Previous work has shown that injury triggers a rapid calcium response, followed by the activation of Ras homolog (Rho) family guanosine triphosphatases (GTPases), which regulate the formation and contraction of an F-actin purse string around the wound margin. How these processes are coordinated following wounding remained unclear. Here we show that inositol-trisphosphate 3-kinase B (Itpkb) via its enzymatic product inositol 1,3,4,5-tetrakisphosphate (InsP
4
) plays an essential role during wound healing by modulating the activity of Rho family GTPases and F-actin ring assembly. Furthermore, we show that Itpkb and InsP
4
modulate the speed of the calcium wave, which propagates from the site of injury into neighboring uninjured cells. Strikingly, both overexpression of
itpkb
and exogenous application of InsP
4
accelerate the speed of wound closure, a finding that has potential implications in our quest to find treatments that improve wound healing in patients with acute or chronic wounds.
Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes
Authors: Iqbal Jameel , Sun Li , Cao Jay , Yuen Tony , Lu Ping , Bab Itai , Leu N. Adrian , Srinivasan Satish , Wagage Sagie , Hunter Christopher A. , Nebert Daniel W. , Zaidi Mone , Avadhani Narayan G.
Published: June 2013

Smoking is a major risk factor for osteoporosis and fracture, but the mechanism through which smoke causes bone loss remains unclear. Here, we show that the smoke toxins benzo(
a
)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-
p
-dioxin (TCDD) interact with the aryl hydrocarbon receptor (Ahr) to induce osteoclastic bone resorption through the activation of cytochrome P450 1a/1b (Cyp1) enzymes. BaP and TCDD enhanced osteoclast formation in bone marrow cell cultures and gavage with BaP stimulated bone resorption and osteoclastogenesis in vivo. The osteoclastogenesis triggered by BaP or RANK-L was reduced in
Ahr

−/−

cells, consistent with the high bone mass noted in
Ahr

−/−

male mice. The receptor activator of NF-κB ligand (RANK-L) also failed to induce the expression of Cyp1 enzymes in
Ahr

−/−

cells. Furthermore, the osteoclastogenesis induced by TCDD was lower in
Cyp1a1/1a2

−/−

and
Cyp1a1/1a2/1b1

−/−

cultures, indicating that Ahr was upstream of the Cyp enzymes. Likewise, the pharmacological inhibition of the Cyp1 enzymes with tetramethylsilane or proadifen reduced osteoclastogenesis. Finally, deletion of the
Cyp1a1
,
Cyp1a2
, and
Cyp1b1
in triple knockout mice resulted in reduced bone resorption and recapitulated the high bone mass phenotype of
Ahr

−/−

mice. Overall, the data identify the Ahr and Cyp1 enzymes not only in the pathophysiology of smoke-induced osteoporosis, but also as potential targets for selective modulation by new therapeutics.
Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber–Purkinje cell synapses via cannabinoid signaling
Authors: Rinaldo Lorenzo , Hansel Christian
Published: June 2013

Muscarinic acetylcholine receptors (mAChRs) are known to modulate synaptic plasticity in various brain areas. A signaling pathway triggered by mAChR activation is the production and release of endocannabinoids that bind to type 1 cannabinoid receptors (CB1R) located on synaptic terminals. Using whole-cell patch-clamp recordings from rat cerebellar slices, we have demonstrated that the muscarinic agonist oxotremorine-m (oxo-m) blocks the induction of presynaptic long-term potentiation (LTP) at parallel fiber (PF)–Purkinje cell synapses in a CB1R-dependent manner. Under control conditions, LTP was induced by delivering 120 PF stimuli at 8 Hz. In contrast, no LTP was observed when oxo-m was present during tetanization. PF-LTP was restored when the CB1R antagonist N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251) was coapplied with oxo-m. Furthermore, the suppressive effect of oxo-m on PF-LTP was abrogated by the GDP analog GDP-β-S (applied intracellularly), the phospholipase C inhibitor U-73122, and the diacylglycerol lipase inhibitor tetrahydrolipstatin (THL), suggesting that cannabinoid synthesis results from the activation of G
q
-coupled mAChRs present on Purkinje cells. The oxo-m–mediated suppression of LTP was also prevented in the presence of the M3 receptor antagonist DAU 5884, and was absent in M1/M3 receptor double-KO mice, identifying M3 receptors as primary oxo-m targets. Our findings allow for the possibility that cholinergic signaling in the cerebellum—which may result from long-term depression (LTD)-related disinhibition of cholinergic neurons in the vestibular nuclei—suppresses presynaptic LTP to prevent an up-regulation of transmitter release that opposes the reduction of postsynaptic responsiveness. This modulatory capacity of mAChR signaling could promote the functional penetrance of LTD.
CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer
Authors: Loi Sherene , Pommey Sandra , Haibe-Kains Benjamin , Beavis Paul A. , Darcy Phillip K. , Smyth Mark J. , Stagg John
Published: June 2013

Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative breast cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy. In TNBC patients treated with anthracycline-only preoperative chemotherapy, high CD73 gene expression was significantly associated with a lower rate of pathological complete response or the disappearance of invasive tumor at surgery. Using mouse models of breast cancer, we demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. Targeted blockade of CD73 enhanced doxorubicin-mediated antitumor immune responses and significantly prolonged the survival of mice with established metastatic breast cancer. Taken together, our data suggest that CD73 constitutes a therapeutic target in TNBC.
Crystal structure of the high-affinity Na
+
,K
+
-ATPase–ouabain complex with Mg
2+
bound in the cation binding site
Authors: Laursen Mette , Yatime Laure , Nissen Poul , Fedosova Natalya U.
Published: June 2013

The Na
+
,K
+
-ATPase maintains electrochemical gradients for Na
+
and K
+
that are critical for animal cells. Cardiotonic steroids (CTSs), widely used in the clinic and recently assigned a role as endogenous regulators of intracellular processes, are highly specific inhibitors of the Na
+
,K
+
-ATPase. Here we describe a crystal structure of the phosphorylated pig kidney Na
+
,K
+
-ATPase in complex with the CTS representative ouabain, extending to 3.4 Å resolution. The structure provides key details on CTS binding, revealing an extensive hydrogen bonding network formed by the β-surface of the steroid core of ouabain and the side chains of αM1, αM2, and αM6. Furthermore, the structure reveals that cation transport site II is occupied by Mg
2+
, and crystallographic studies indicate that Rb
+
and Mn
2+
, but not Na
+
, bind to this site. Comparison with the low-affinity [K
2
]E2–MgF
x
–ouabain structure [Ogawa et al. (2009)
Proc Natl Acad Sci USA
106(33):13742–13747) shows that the CTS binding pocket of [Mg]E2P allows deep ouabain binding with possible long-range interactions between its polarized five-membered lactone ring and the Mg
2+
. K
+
binding at the same site unwinds a turn of αM4, dragging residues Ile318–Val325 toward the cation site and thereby hindering deep ouabain binding. Thus, the structural data establish a basis for the interpretation of the biochemical evidence pointing at direct K
+
–Mg
2+
competition and explain the well-known antagonistic effect of K
+
on CTS binding.
Detection of atomic spin labels in a lipid bilayer using a single-spin nanodiamond probe
Authors: Kaufmann Stefan , Simpson David A. , Hall Liam T. , Perunicic Viktor , Senn Philipp , Steinert Steffen , McGuinness Liam P. , Johnson Brett C. , Ohshima Takeshi , Caruso Frank , Wrachtrup Jörg , Scholten Robert E. , Mulvaney Paul , Hollenberg Lloyd
Published: June 2013

Magnetic field fluctuations arising from fundamental spins are ubiquitous in nanoscale biology, and are a rich source of information about the processes that generate them. However, the ability to detect the few spins involved without averaging over large ensembles has remained elusive. Here, we demonstrate the detection of gadolinium spin labels in an artificial cell membrane under ambient conditions using a single-spin nanodiamond sensor. Changes in the spin relaxation time of the sensor located in the lipid bilayer were optically detected and found to be sensitive to near-individual (4 ± 2) proximal gadolinium atomic labels. The detection of such small numbers of spins in a model biological setting, with projected detection times of 1 s [corresponding to a sensitivity of ∼5 Gd spins per Hz
1/2
], opens a pathway for in situ nanoscale detection of dynamical processes in biology.
Mechanistic and structural studies on legumain explain its zymogenicity, distinct activation pathways, and regulation
Authors: Dall Elfriede , Brandstetter Hans
Published: June 2013

The cysteine protease legumain plays important functions in immunity and cancer at different cellular locations, some of which appeared conflicting with its proteolytic activity and stability. Here, we report crystal structures of legumain in the zymogenic and fully activated form in complex with different substrate analogs. We show that the eponymous asparagine-specific endopeptidase activity is electrostatically generated by pH shift. Completely unexpectedly, the structure points toward a hidden carboxypeptidase activity that develops upon proteolytic activation with the release of an activation peptide. These activation routes reconcile the enigmatic pH stability of legumain, e.g., lysosomal, nuclear, and extracellular activities with relevance in immunology and cancer. Substrate access and turnover is controlled by selective protonation of the S1 pocket (
K
M
) and the catalytic nucleophile (
k
cat
), respectively. The multibranched and context-dependent activation process of legumain illustrates how proteases can act not only as signal transducers but as decision makers.
Zinc finger protein ZBTB20 promotes toll-like receptor-triggered innate immune responses by repressing
IκBα
gene transcription
Authors: Liu Xingguang , Zhang Peng , Bao Yan , Han Yanmei , Wang Yan , Zhang Qian , Zhan Zhenzhen , Meng Jun , Li Yingke , Li Nan , Zhang Weiping J. , Cao Xuetao
Published: June 2013

Toll-like receptor (TLR) signaling is critical in innate response against invading pathogens. However, the molecular mechanisms for full activation of TLR-triggered innate immunity need to be fully elucidated. The broad complex tramtrack bric-a-brac/poxvirus and zinc finger (BTB/POZ) family is a class of transcription factors involved in many biological processes. However, few BTB/POZ proteins were reported to function in innate immune response. Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses α-fetoprotein gene transcription in liver. However, the immunological functions of ZBTB20 remain unknown. Here, we found that myeloid cell-specific ZBTB20 KO mice were resistant to endotoxin shock and
Escherichia coli
-caused sepsis. ZBTB20 deficiency attenuated TLR-triggered production of proinflammatory cytokines and type I IFN in macrophages, which attributed to higher abundance of IκBα protein and impaired activity of NF-κB. Furthermore, ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to
IκBα
gene promoter (+1 to +60 region) after TLR activation. ZBTB20 could inhibit
IκBα
gene transcription, govern IκBα protein expression, and then promote NF-κB activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor
IκBα
gene transcription.
Reduced calcification and lack of acclimatization by coral colonies growing in areas of persistent natural acidification
Authors: Crook Elizabeth D. , Cohen Anne L. , Rebolledo-Vieyra Mario , Hernandez Laura , Paytan Adina
Published: June 2013

As the surface ocean equilibrates with rising atmospheric CO
2
, the pH of surface seawater is decreasing with potentially negative impacts on coral calcification. A critical question is whether corals will be able to adapt or acclimate to these changes in seawater chemistry. We use high precision CT scanning of skeletal cores of
Porites astreoides
, an important Caribbean reef-building coral, to show that calcification rates decrease significantly along a natural gradient in pH and aragonite saturation (Ω
arag
). This decrease is accompanied by an increase in skeletal erosion and predation by boring organisms. The degree of sensitivity to reduced Ω
arag
measured on our field corals is consistent with that exhibited by the same species in laboratory CO
2
manipulation experiments. We conclude that the
Porites
corals at our field site were not able to acclimatize enough to prevent the impacts of local ocean acidification on their skeletal growth and development, despite spending their entire lifespan in low pH, low Ω
arag
seawater.
Molecular hyperdiversity defines populations of the nematode
Caenorhabditis brenneri
Authors: Dey Alivia , Chan Cecilia K. W. , Thomas Cristel G. , Cutter Asher D.
Published: June 2013

The biology of Sydney Brenner’s eponymous species of nematode,
Caenorhabditis brenneri
, is little known to science, despite its famous sibling
Caenorhabditis elegans
. Here we demonstrate that
C. brenneri
harbors the most molecular diversity of any eukaryote, with its 14.1% of polymorphic synonymous sites between individuals being 150-fold greater than humans and most comparable to hyperdiverse bacteria. This diversity is not an artifact of cryptic species divergence but reflects an enormous pan-tropical population, confirmed by fully viable genetic crosses between continents, extensive intralocus recombination, selection on codon use, and only weak geographic genetic structure. These findings in an animal galvanize tests of theory about the evolution of complexity in genomes and phenotypes and enable molecular population genetics methods to finely resolve uncharacterized functional noncoding elements.
Role of sortase-dependent pili ofBifidobacterium bifidumPRL2010 in modulating bacterium–host interactions
Authors: Turroni Francesca , Serafini Fausta , Foroni Elena , Duranti Sabrina , O’Connell Motherway Mary , Taverniti Valentina , Mangifesta Marta , Milani Christian , Viappiani Alice , Roversi Tommaso , Sánchez Borja , Santoni Andrea , Gioiosa Laura , Ferrarini Alberto , Delledonne Massimo , Margolles Abelardo , Piazza Laura , Palanza Paola , Bolchi Angelo , Guglielmetti Simone , van Sinderen Douwe , Ventura Marco
Published: June 2013

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling ofBifidobacterium bifidumPRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of theseB. bifidumPRL2010 appendages in nonpiliatedLactococcus lactisenhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliatedL. lactiscells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity.
Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss
Authors: Talantova Maria , Sanz-Blasco Sara , Zhang Xiaofei , Xia Peng , Akhtar Mohd Waseem , Okamoto Shu-ichi , Dziewczapolski Gustavo , Nakamura Tomohiro , Cao Gang , Pratt Alexander E. , Kang Yeon-Joo , Tu Shichun , Molokanova Elena , McKercher Scott R. , Hires Samuel Andrew , Sason Hagit , Stouffer David G. , Buczynski Matthew W. , Solomon James P. , Michael Sarah , Powers Evan T. , Kelly Jeffery W. , Roberts Amanda , Tong Gary , Fang-Newmeyer Traci , Parker James , Holland Emily A. , Zhang Dongxian , Nakanishi Nobuki , Chen H.-S. Vincent , Wolosker Herman , Wang Yuqiang , Parsons Loren H. , Ambasudhan Rajesh , Masliah Eliezer , Heinemann Stephen F. , Piña-Crespo Juan C. , Lipton Stuart A.
Published: June 2013

Significance

Communication between nerve cells occurs at specialized cellular structures known as synapses. Loss of synaptic function is associated with cognitive decline in Alzheimer’s disease (AD). However, the mechanism of synaptic damage remains incompletely understood. Here we describe a pathway for synaptic damage whereby amyloid-β
1–42
peptide (Aβ
1–42
) releases, via stimulation of α7 nicotinic receptors, excessive amounts of glutamate from astrocytes, in turn activating extrasynaptic NMDA-type glutamate receptors (eNMDARs) to mediate synaptic damage. The Food and Drug Administration-approved drug memantine offers some beneficial effect, but the improved eNMDAR antagonist NitroMemantine completely ameliorates Aβ-induced synaptic loss, providing hope for disease-modifying intervention in AD.