bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic quadrupole doublet focusing system for high energy ions
Authors: Glass Gary A. , Dymnikov Alexander D. , Rout Bibhudutta , Dias Johnny F. , Houston Louis M. , LeBlanc Jared
Published: March 2008

A high energy focused ion beam microprobe using a doublet arrangement of short magnetic quadrupole lenses was used to focus 1–3MeV protons to spot sizes of 1×1μm2 and 1–4.5MeV carbon and silicon ion beams to spot sizes of 1.5×1.5μm2. The results presented clearly demonstrate that this simple doublet configuration can provide high energy microbeams for microananalysis and microfabrication applications.
Magnetodipolar interlayer interaction effect on the magnetization dynamics of a trilayer square element with the Landau domain structure
Authors: Berkov D. V. , Gorn N. L.
Published: March 2008

We present a detailed numerical simulation study of the effects caused by the magnetodipolar interaction between ferromagnetic (FM) layers of a trilayer magnetic nanoelement on its magnetization dynamics. As an example, we use a Co∕Cu∕Ni80Fe20 element with a square lateral shape where the magnetization of FM layers forms a closed Landau-like domain pattern. First, we show that when the thickness of the nonmagnetic (NM) spacer is in the technology relevant region h∼10nm, magnetodipolar interaction between 90° Neel domain walls in FM layers qualitatively changes the equilibrium magnetization state of these layers. In the main part of the paper, we compare the magnetization dynamics induced by a sub-nsec field pulse in a single-layer Ni80Fe20 (Py) element and in the Co∕Cu∕Py trilayer element. Here, we show that (i) due to the spontaneous symmetry breaking of the Landau state in the FM/NM/FM trilayer, its domains and domain walls oscillate with different frequencies and have different spatial oscillation patterns; (ii) magnetization oscillations of the trilayer domains are strongly suppressed due to different oscillation frequencies of domains in Co and Py; (iii) magnetization dynamics qualitatively depends on the relative rotation sense of magnetization states in Co and Py layers and on the magnetocrystalline anisotropy kind of Co crystallites. Finally, we discuss the relation of our findings with experimental observations of magnetization dynamics in magnetic trilayers, performed using the element-specific time-resolved x-ray microscopy.
Method of measurements with random perturbation: Application in photoemission experiments
Authors: Fedin D. S. , Granichin O. N. , Dedkov Yu. S. , Molodtsov S. L.
Published: March 2008

We report on an application of a simultaneous perturbation stochastic approximation (SPSA) algorithm to filtering systematic noise (SN) with nonzero mean value in photoemission data. In our analysis, we have used a series of 50 single-scan photoemission spectra of W(110) surface where different SNs were added. It was found that the SPSA-evaluated spectrum is in good agreement with the spectrum measured without SN. On the basis of our results, a wide application of SPSA algorithm for evaluation of experimental data is anticipated.
Growth and thermal properties of Ga3PO7 bulk single crystals
Authors: Xu Guogang , Li Jing , Wang Jiyang , Zhao Hongyang , Cheng Xiufeng , Gao Wenlan
Published: March 2008

Ga 3 P O 7 crystal with large size and good optical quality has been grown by the top-seeded solution growth slow-cooling method from a Li2O–3MoO3 flux system. Thermal properties of the as-grown Ga3PO7 crystal have been carefully studied by measuring the anisotropic thermal expansion, specific heat, thermal diffusion, and thermal conductivity. The results show that Ga3PO7 crystal possesses low thermal expansion coefficients and good thermal conductivity. The calculated average thermal expansion coefficients along a and c axes are αa=1.66×10−6 and αc=3.53×10−6K−1 from 293.15to773.15K. The thermal conductivities along a and c axes are up to 6.34 and 6.18Wm−1K−1 at the temperature of 303.15K.
Calculated temperature rise in midinfrared laser irradiated Hg0.72Cd0.28Te
Authors: Storeboe Asta Katrine , Brudevoll Trond , Stenersen Knut
Published: March 2008

We present results from a numerical study on heating in a 10μm thick layer of Hg0.72Cd0.28Te induced by 1μs long laser pulses at photon energies close to the band gap of the material. A number of highly nonlinear mechanisms contribute to the heating, their relative importance being dependent on laser wavelength, instantaneous irradiance, and material temperature. Mechanisms studied include one- and two-photon absorptions across the band gap, intervalence band absorption between light- and heavy hole bands, electron-hole recombination, free-carrier absorption, excess carrier temperatures, and refractive index changes. The increase in band gap with temperature eventually terminates one-photon absorption from the valence to the conduction band, and further heating is driven by much weaker absorption processes. The varying band gap also introduces changes in electron- and light hole masses and thereby in the separation between the light- and heavy hole bands, thus strongly affecting intervalence band absorption. At the shortest laser wavelength of 3.8μm, the simulations indicate that surface melting will occur at fluence levels in the range of 2–3J∕cm2, while more than 10J∕cm2 will be required for melting at wavelengths beyond 5μm.
A scanning near-field middle-infrared microscope for the study of objects submerged in water
Authors: Platkov Max , Tsun Alexander , Nagli Lev , Katzir Abraham
Published: March 2008

We had developed a scanning near-field middle-infrared microscope, based on AgClBr probes, which has a subwavelength resolution in air. We adapted this microscope for imaging of samples submerged in water. Toward this goal, we had to develop a theoretical model for the mechanical vibration of the probes in water and use it for the construction of an improved microscope. Using this system, we obtained infrared and topographic images of polymer beads of subwavelength diameters. This microscope will be particularly useful for high resolution spectral imaging of living biological cells in the middle infrared.
Surface enhanced Raman scattering analyses of individual silver nanoaggregates on living single yeast cell wall
Authors: Sujith Athiyanathil , Itoh Tamitake , Abe Hiroko , Anas Abdul Aziz , Yoshida Kenichi , Biju Vasudevanpillai , Ishikawa Mitsuru
Published: March 2008

We labeled the living yeast cell surface (Saccharomyces cerevisiae strain W303-1A) by silver nanoparticles which can form nanoaggregates and found to show surface enhanced Raman scattering (SERS) activity. Blinking of SERS and its polarization dependence reveal that SERS signals are from amplified electromagnetic field at nanometric Ag nanoparticles gaps with single or a few molecules sensitivity. We tentatively assigned SERS spectra from a yeast cell wall to mannoproteins. Nanoaggregate-by-nanoaggregate variations and temporal fluctuations of SERS spectra are discussed in terms of inhomogeneous mannoprotein distribution on a cell wall and possible ways of Ag nanoaggregate adsorption, respectively.
Drift mobility and the frequency response of diode connected organic transistors
Authors: Cobb Brian , Jeong Yeon Taek , Dodabalapur Ananth
Published: March 2008

A method to characterize the frequency response of an organic field effect transistor (FET) is presented. Analysis then shows a method to calculate the average drift mobility from the frequency at which a pole appears in the response. This pole is believed to appear at the point where charge carriers can no longer fully traverse the channel in one period of the input signal. The dc output characteristics of the device are also described, and saturation mobility values are derived. This saturation mobility and the drift mobility calculated from the frequency response are comparable. This method can be used in determining the drift mobility in other materials such as single nanowires in the FET configuration.
Control of the nanoscale crystallinity and phase separation in polymer solar cells
Authors: Chu Chih-Wei , Yang Hoichang , Hou Wei-Jen , Huang Jinsong , Li Gang , Yang Yang
Published: March 2008

Grazing-incidence x-ray diffraction and atomic force microscopy were performed on bulk heterojunction regioregular poly(3-hexylthiophene) (RR-P3HT) [6,6]-phenyl-C71-butyric acid methyl esters spin-cast films with different film processing conditions to correlate the crystalline nanostructure of P3HT with the corresponding solar cell performance. The increase in long wavelength absorption for solvent annealed films is related to highly conjugated crystal structure of RR-P3HT phase-separated in the active layer. Upon thermal annealing, the solvent annealed 50-nm-thick device shows high solar cell performance with fill factor up to 73% and power conversion efficiency of 3.80%.
Ultrathin responsive polyelectrolyte brushes studied by infrared synchrotron mapping ellipsometry
Authors: Roodenko Katy , Mikhaylova Yulia , Ionov Leonid , Gensch Michael , Stamm Manfred , Minko Sergiy , Schade Ulrich , Eichhorn Klaus-Jochen , Esser Norbert , Hinrichs Karsten
Published: March 2008

An infrared microfocus spectroscopic mapping ellipsometer was set up at the Berlin electron synchrotron storage ring and used to study ultrathin polyacrylic acid brush films with 3nm thickness. The pH-responsive properties of the brush on a gold-coated glass substrate were investigated. The chemical structure of the brush was resolved with a spatial resolution of 300μm using the synchrotron mapping ellipsometer.
Angular spectrum tailoring in solid immersion microscopy for circuit analysis
Authors: Ippolito S. B. , Song P. , Miles D. L. , Sylvestri J. D.
Published: March 2008

We present a technique that involves tailoring the angular spectrum in optical microscopy of silicon integrated circuits, with a solid immersion lens. Spatial light modulation to select only supercritical light at the substrate/dielectric interface yields only evanescent and scattered light in the interconnect layers. We demonstrated the technique in optical excitation microscopy of 65nm silicon-on-insulator circuits, which enabled localization of a fault during microprocessor development. Acquiring images with and without angular spectrum tailoring allowed longitudinal localization of the electrical response to optical excitation. Lateral registration of electrical response and confocal reflection images to the circuit layout was also significantly improved.
Submicron silicon waveguide optical switch driven by microelectromechanical actuator
Authors: Bulgan Erdal , Kanamori Yoshiaki , Hane Kazuhiro
Published: March 2008

A submicron silicon waveguide optical switch driven by a microelectromechanical actuator is fabricated. The switch is composed of single-mode silicon input and output waveguides and a movable waveguide suspended by silicon springs. Switching occurs when the air gap between input and output waveguides is closed by displacing the movable waveguide 540±20nm by an electrostatic comb actuator. The switch, fabricated on a silicon-on-insulator wafer, is monolithic, and active switching region is as small as about 40×60μm2. An extinction ratio of 15±2dB is experimentally obtained between switch off and on states at 1.55μm wavelength.
Polyfluorene-based light-emitting diodes with an azide photocross-linked poly(3,4-ethylene dioxythiophene):(polystyrene sulfonic acid) hole-injecting layer
Authors: Winroth Gustaf , Latini Gianluca , Credgington Dan , Wong Loke-Yuen , Chua Lay-Lay , Ho Peter K.-H. , Cacialli Franco
Published: March 2008

We used a water-soluble bis(fluorinated phenyl azide) to cross-link a poly(ethylene dioxythiophene):poly(styrene sulphonic acid) (PEDOT:PSS), hole-injection layer, with a view to its future use with water-soluble emitters. To enable direct comparison with conventional PEDOT:PSS, we studied the cross-linked films in diodes incorporating the organic-solvent soluble polymer poly(9,9′-dioctylfluorene-alt-benzothiadiazole). Kelvin probe characterization of the PEDOT:PSS and electroabsorption measurements of the devices consistently show a 0.2eV increase of the PEDOT:PSS work function upon cross-linking. We also observe a 70-fold reduction in resistivity, an increase of the current above threshold and a decrease of the “leakage” current below threshold.
Polymeric tandem organic light-emitting diodes using a self-organized interfacial layer
Authors: Ryu Seung Yoon , Kim Jong Tae , Noh Joo Hyon , Hwang Byoung Har , Kim Chang Su , Jo Sung Jin , Hwang Hyeon Seok , Kang Seok Ju , Baik Hong Koo , Lee Chang Ho , Song Seung Yong , Lee Se Jong
Published: March 2008

The authors have demonstrated efficient polymeric tandem organic light-emitting diodes (OLEDs) with a self-organized interfacial layer, which was formed by differences in chemical surface energy. Hydrophilic poly(styrene sulfonate)-doped poly(3,4-ethylene dioxythiophene) (PEDOT:PSS) was spin coated onto the hydrophobic poly(9,9-dyoctilfluorene) (PFO) surface and a PEDOT:PSS bubble or dome was built as an interfacial layer. The barrier heights of PEDOT:PSS and PFO in the two-unit tandem OLED induced a charge accumulation at the interface in the heterojunction and thereby created exciton recombination at a much higher level than in the one-unit reference. This effect was confirmed in both the hole only and the electron only devices.
Constrained ferroelectricity in BaTiO3∕BaZrO3 superlattices
Authors: Roy Choudhury Palash , Krupanidhi S. B.
Published: March 2008

Ba Ti O 3 ∕ Ba Zr O 3 superlattices with varying periodicities were grown on SrRuO3 buffered MgO (001) substrates by pulsed laser ablation. Ferroelectric measurements were done and correlated to the strain in the heterostructures. The results of ferroelectric measurements indicate an apparent suppression of polarization in the low period superlattices and the onset of weakly ferroelectric behavior in higher period superlattices. Measured switchable polarization values indicate that contribution is primarily from the BaTiO3 in the structure. These results have been correlated to the interfacial strain and the critical thickness of BaTiO3 when grown over tensile substrates such as MgO.
Theoretical investigation of shock wave stability in metals
Authors: Lomonosov I. V. , Tahir N. A.
Published: March 2008

Shock adiabats of metals with different initial volumes and pressures have been calculated with the use of multiphase equation of state. The stability of shock wave has been investigated using the known criteria. We found two types of instabilities occurring in the vicinity and inside two-phase liquid-gas region. They are the specific sound instability arising as a spontaneous sound emission from the shock discontinuity and two-wave configuration. The position of the instability region and its dependence on initial pressure and volume has been analyzed. Discussed are regularities obtained for 30 metals.
Structure and magnetic properties of the self-assembled Co52Pt48 nanowire arrays
Authors: Gao Jian-Hua , Sun Da-Li , Zhang Xiang-Qun , Zhan Qing-Feng , He Wei , Sun Young , Cheng Zhao-Hua
Published: March 2008

Co 52 Pt 48 nanowire arrays with diameter of about 10nm have been fabricated by electrodeposition into the anodic aluminum oxide templates. The as-deposited nanowire arrays exhibit fcc structure with [110]-preferred texture along the wire axes. The nanowire arrays present both large magnetocrystalline anisotropy along the [111] direction and strong shape anisotropy along the wire axis, resulting in high coercive fields parallel and perpendicular to the wire axes, respectively. From experimental results and micromagnetic simulation, the coercive field variation as a function of the angles evidenced that the [111] magnetocrystalline anisotropy plays important role besides shape magnetic anisotropy.
Acoustic monitoring of microplasma formation and filamentation of tightly focused femtosecond laser pulses in silica glass
Authors: Kudryashov Sergey I. , Zvorykin Vladimir D. , Ionin Andrei A. , Mizeikis Vygantas , Juodkazis Saulius , Misawa Hiroaki
Published: March 2008

Contact acoustic technique has been employed to perform spatially resolved in situ detection of microplasma formation and filamentation of tightly focused femtosecond laser pulses with supercritical pulse powers in bulk dielectrics, via corresponding acoustic emission. Investigation of acoustic generation mechanisms related to the plasma formation and filamentation effects reveals the critical character of the opaque microplasma and provides estimates of its gigapascal-level pressures and energy densities of a few kJ∕cm3. The acoustic measurement enables real-time in situ monitoring and revealing of basic mechanisms of ionization and filamentation in bulk dielectrics.
Monte Carlo study of GaN versus GaAs terahertz quantum cascade structures
Authors: Bellotti Enrico , Driscoll Kristina , Moustakas Theodore D. , Paiella Roberto
Published: March 2008

Due to their large optical phonon energies, nitride semiconductors are promising for the development of terahertz quantum cascade lasers with dramatically improved high-temperature performance relative to existing GaAs devices. Here, we present a rigorous Monte Carlo study of carrier dynamics in two structures based on the same design scheme for emission at 2THz, consisting of GaN∕AlGaN or GaAs∕AlGaAs quantum wells. The population inversion and hence the gain coefficient of the nitride device are found to exhibit a much weaker (by a factor of over 3) temperature dependence and to remain large enough for laser action even without cryogenic cooling.
Control of quantum-confined Stark effect in InGaN∕GaN multiple quantum well active region by p-type layer for III-nitride-based visible light emitting diodes
Authors: Ryou J.-H. , Lee W. , Limb J. , Yoo D. , Liu J. P. , Dupuis R. D. , Wu Z. H. , Fischer A. M. , Ponce F. A.
Published: March 2008

We demonstrate the control of the quantum-confined Stark effect in InGaN∕GaN quantum wells (QWs), grown along the [0001] direction as part of the active region of visible light emitting diodes (LEDs). The effect can be altered by modifying the strain applied to the active region by the hole injection and contact layers. The optical characteristics and electrostatic potentials of the active region of the visible LEDs with different p-type layers are compared. LEDs with p-InGaN on top of the active region show a reduced blueshift in the peak wavelength with increasing injection current and a lower potential difference across the QW than those with p-GaN layers. The electrostatic potentials across the QW have estimated average values of ∼0.8 and ∼1.3MV∕cm for the active region of LEDs of current study with p-InGaN and p-GaN layers, respectively.
Directional growth of Ge on GaAs at 175°C using plasma-generated nanocrystals
Authors: Johnson Erik V. , Patriarche Gilles , Roca i Cabarrocas Pere
Published: March 2008

We demonstrate the directional growth of Ge on a GaAs {100} wafer at 175°C using radio-frequency plasma-enhanced chemical vapor deposition at 13.56MHz under conditions where nanocrystals are the primary contributors to film growth. High resolution transmission electron microscopy (HRTEM) verifies the transport of plasma-formed nanocrystals to the substrate surface where they are initially mobile. Furthermore, cross-sectional HRTEM images show directional growth on the GaAs wafer, wherein the incident Ge nanocrystals have adopted the orientation of the underlying lattice.
Anisotropic lattice behavior in elasticoluminescent material SrAl2O4:Eu2+
Authors: Yamada Hiroshi , Kusaba Hajime , Xu Chao-Nan
Published: March 2008

We report that the elasticoluminescent (elastico-L) material SrAl2O4:Eu2+ (SAO-E) shows an extraordinarily anisotropic thermal expansion: the linear thermal expansion coefficient in the c axis was one order of magnitude smaller than those in the a and b axes in the monoclinic phase. This anisotropic lattice behavior was attributed to the development of the spontaneous shear strain e5 upon lowering the temperature, indicating that SAO-E is preferentially deformed by a shear stress. This suggests that controlling the crystal orientation is important for developing elastico-L devices.
Temperature dependence on current-voltage characteristics of Ni∕Au–Al0.45Ga0.55N Schottky photodiode
Authors: Cheng C. J. , Zhang X. F. , Lu Z. X. , Ding J. X. , Zhang L. , Zhao L. , Si J. J. , Sun W. G. , Sang L. W. , Qin Z. X. , Zhang G. Y.
Published: March 2008

Temperature dependence on electrical characteristics of a Ni∕Au–Al0.45Ga0.55N Schottky photodiode is investigated in a temperature range of 198–323K. The ideality factor decreases from 2.57 to 1.75, while the barrier height increases from 0.75to1.14eV in this temperature range. The ln(I)-V curves at a small forward current are intersectant at 273, 298, and 323K and are almost parallel at 198, 223, and 248K. This crossing of the ln(I)-V curves is an inherent property of Schottky diodes, and the almost parallel curves can be well explained by thermionic field emission theory.
Kernel weight dependence upon plant growth at different grain-filling stages in maize and sorghum
Authors: Gambín Brenda L. , Borrás Lucas , Otegui María E.
Published: March 2008

In the present study we tested how assimilate availability per kernel at different grain-filling stages may affect maize (Zea mays L.) and sorghum (Sorghum bicolor L. Moench) individual kernel weight (KW). These two species have shown a contrasting KW response to increased assimilate availability at similar seed developmental stages. Plant growth rate (PGR) per kernel was used to estimate the assimilate availability per kernel at two stages: around the early grain-filling period when kernel number per plant is also being established, and around the effective grain-filling period. We tested 3 commercial genotypes from each species, and modified the PGR by thinning or shading the stand at different developmental stages. In both species, each genotype showed a particular relationship between PGR around flowering and kernel number, which gave a range of responses in the PGR per kernel set around flowering. Final KW always increased whenever PGR per kernel around flowering was enhanced. Only sorghum showed a consistent KW increase when PGR per kernel during the effective grain-filling period was enhanced. Results confirmed that increasing assimilate availability per kernel will affect maize kernel size only if the potential set early in development is altered. Most important, we showed that linking specific KW sensibility across species at different seed developmental stages using a simple estimate of assimilate availability per seed (i.e. PGR per kernel) at each grain-filling stage helped explain most of the explored genotypic and environmental variability in final kernel size.
Identifying chickpea homoclimes using the APSIM chickpea model
Authors: Chauhan Yash , Wright Graeme , Rachaputi Nageswararao , McCosker Kevin
Published: March 2008

Chickpea (Cicer arietinum L.) has been traditionally grown in India but is a relatively new export crop in Australia where its cultivation is expanding into new areas. The objective of this study was to identify homoclimes (i.e. similar chickpea-growing environments) in the major chickpea-growing areas of the 2 countries, using the Agricultural Production Systems Simulator (APSIM) chickpea model. The model, which processes climatic, soil, and plant information on a daily time step, was first validated and then used to simulate flowering, maturity, and grain yield of Amethyst, a mid-season cultivar, and Barwon, a full-season cultivar, on low (100 mm), medium (150 mm), and high (190 mm) water-holding capacity soils, using historical climatic data of 67 Australian and 24 Indian locations. The mean of annual outputs of flowering, maturity, and grain yield of the 2 cultivars on 3 soils was then clustered using Ward’s hierarchical complete linkage clustering procedure. At a 90% level of similarity, all the locations could be grouped into 6 homoclime clusters. The Australian locations appeared more diverse as they were present in all the clusters, whereas the Indian locations were present only in clusters 1, 2, and 6. While there were clear geographical patterns of spread of these clusters, in Australia they were not entirely related to latitude. The cluster 1 and 2 locations, which represent the largest chickpea-growing area in Australia, had homoclime locations in common with northern India. The clustering of locations appeared generally consistent with the known adaptation of chickpea in different environments of the 2 countries and therefore suggests that the methodology could be potentially used for complementing conventional approaches of introducing or exchanging germplasm, as well as determining appropriateness of breeding/testing sites.
Embryo-endometrial expression of leukemia inhibitory factor in the golden hamster (Mesocricetus auratus): increased expression during proestrous and window of implantation stages
Authors: Rao Rajnish P. , Fischer Bernd , Seshagiri Polani B.
Published: March 2008

Leukemia inhibitory factor (LIF) is a pleiotropic IL-6 family cytokine and its maternal uterine expression is critical for mouse blastocyst implantation. In the golden hamster (Mesocricetus auratus), although the blastocyst hatching phenomenon is quite interesting and LIF is shown to regulate hatching, information is not available on the embryonic and uterine expression of LIF and hormonal regulation of LIF expression during the peri-implantation period. The present investigation is aimed at studying embryonic and uterine expression of LIF during preimplantation hamster development. We observed embryonic expression of LIF mRNA and protein in the 8-cell, morula and blastocyst stages. In cycling females, uterine LIF mRNA expression was maximal during the oestrogen-dominant phase of the oestrous cycle, i.e. proestrous stage. Interestingly, during pregnancy, both LIF mRNA and protein were highly upregulated on Days 3.5 and 4 (‘window of implantation’), implying a role for this cytokine in blastocyst hatching and implantation. Cell type-specific localisation of LIF mRNA and protein was observed predominantly in luminal epithelium and uterine glands with faint staining being detected in the stroma. The hamster uterus encoded a ~4.2 kb LIF transcript whose coding region, when cloned and sequenced, showed a high degree of identity to the murine cDNA counterpart. These data demonstrate that: (1) hamster preimplantation embryos show LIF mRNA and protein expression; (2) uterine expression of LIF mRNA and protein was dependent on elevated levels of circulating oestrogen, and (3) there is a possible functional association of LIF with the peri-implantation development in the golden hamster.
Homeodomain protein HLX is expressed primarily in cytotrophoblast cell types in the early pregnancy human placenta
Authors: Rajaraman Gayathri , Murthi Padma , Quinn Leonie , Brennecke Shaun P. , Kalionis Bill
Published: March 2008

Homeobox genes are a large family of transcription factors. Of these, the HLX homeobox gene (previously known as HLX1 and HB24) is important for normal placentation. We have previously shown that HLX mRNA expression is significantly reduced in fetal growth-restricted human placentae compared with control placentae. In this study, a rabbit polyclonal antibody to the homeodomain protein HLX was raised and characterised. Western analysis revealed a protein of 50 kDa. HLX protein was detected in cellular nuclei in the cytotrophoblast-derived cell lines HTR8/SVneo, SGHPL-4, JEG-3, JAR and BeWo. Dual labelling with cytokeratin 7 was used to determine the spatial distribution of HLX in the early placenta and fetal membranes, showing both a perinuclear and punctate nuclear distribution for HLX. In the early pregnancy placenta HLX was localised to villous cytotrophoblast, and extravillous cytotrophoblast nuclei in the proximal regions of the cytotrophoblast cell columns, but was not detected at significant levels in the syncytiotrophoblast. In first trimester placental bed biopsies, HLX expression was not localised to the nucleus but instead was found in the cytoplasm. We conclude that HLX is primarily expressed in cytotrophoblast cell types in the human placenta and propose that HLX is involved in cytotrophoblast proliferation and downregulation of cell differentiation.
Effect of increasing progesterone concentration from Day 3 of pregnancy on subsequent embryo survival and development in beef heifers
Authors: Carter F. , Forde N. , Duffy P. , Wade M. , Fair T. , Crowe M. A. , Evans A. C. O. , Kenny D. A. , Roche J. F. , Lonergan P.
Published: March 2008

Higher systemic progesterone in the immediate post-conception period is associated with an increase in embryonic growth rate, interferon-tau production and pregnancy rate in cattle. The objective of this study was to examine the effect of increasing progesterone concentration on Day 3 on subsequent embryo survival and development. Oestrus (Day 0) was synchronised in beef-cross heifers (n = 210) and approximately two-thirds of the heifers were inseminated with semen from a proven sire, while the remainder were not inseminated. In order to produce animals with divergent progesterone concentrations, half of the animals received a progesterone-releasing intravaginal device (PRID) on Day 3 of the oestrous cycle, which was left in situ until slaughter. The four treatment groups were: (i) pregnant, high progesterone; (ii) pregnant, normal progesterone; (iii) non-pregnant, high progesterone; and (iv) non-pregnant, normal progesterone. Animals were blood-sampled twice daily from Days 0 to 8 and once daily thereafter until slaughter on Days 5, 7, 13 or 16, corresponding to the 16-cell stage, the blastocyst stage, the beginning of elongation and the day of maternal recognition of pregnancy, respectively. Embryos were recovered by flushing the tract with phosphate-buffered saline and characterised by stage of development and, in the case of Days 13 and 16, measured. Data were analysed by mixed models ANOVA, Chi-square analysis and Student’s t-test where appropriate. Insertion of a PRID on Day 3 increased (P < 0.05) progesterone concentrations from Day 3.5 onwards. There was no difference between treatments in the proportion of embryos at the expected stage of development on Days 5 or 7 (P > 0.05). While not significantly different, the proportion of viable embryos recovered was numerically greater in the high progesterone group on both Day 13 (58 v. 43%) and Day 16 (90 v. 50%). Elevation of progesterone significantly increased embryonic length on Day 13 (2.24 ± 0.51 mm v. 1.15 ± 0.16 mm, P = 0.034) and Day 16 (14.06 ± 1.18 cm v. 5.97 ± 1.18 cm, P = 0.012). In conclusion, insertion of a PRID on Day 3 of the oestrous cycle increased serum progesterone concentrations on subsequent days, which, while having no phenotypic effect on embryonic development on Days 5 or 7, was associated with an increase in embryonic size on Days 13 and 16.
Modeling targeted layered containment of an influenza pandemic in the United States
Authors: Halloran M. Elizabeth , Ferguson Neil M. , Eubank Stephen , Longini Ira M. , Cummings Derek A. T. , Lewis Bryan , Xu Shufu , Fraser Christophe , Vullikanti Anil , Germann Timothy C. , Wagener Diane , Beckman Richard , Kadau Kai , Barrett Chris , Macken Catherine A. , Burke Donald S. , Cooley Philip
Published: March 2008

Planning a response to an outbreak of a pandemic strain of influenza is a high public health priority. Three research groups using different individual-based, stochastic simulation models have examined the consequences of intervention strategies chosen in consultation with U.S. public health workers. The first goal is to simulate the effectiveness of a set of potentially feasible intervention strategies. Combinations called targeted layered containment (TLC) of influenza antiviral treatment and prophylaxis and nonpharmaceutical interventions of quarantine, isolation, school closure, community social distancing, and workplace social distancing are considered. The second goal is to examine the robustness of the results to model assumptions. The comparisons focus on a pandemic outbreak in a population similar to that of Chicago, with ≈8.6 million people. The simulations suggest that at the expected transmissibility of a pandemic strain, timely implementation of a combination of targeted household antiviral prophylaxis, and social distancing measures could substantially lower the illness attack rate before a highly efficacious vaccine could become available. Timely initiation of measures and school closure play important roles. Because of the current lack of data on which to base such models, further field research is recommended to learn more about the sources of transmission and the effectiveness of social distancing measures in reducing influenza transmission.
Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss
Authors: Sun Li , Vukicevic Slobodan , Baliram Ramkumarie , Yang Guozhe , Sendak Rebecca , McPherson John , Zhu Ling-Ling , Iqbal Jameel , Latif Rauf , Natrajan Arjun , Arabi Ario , Yamoah Kosj , Moonga Baljit S. , Gabet Yankel , Davies Terry F. , Bab Itai , Abe Etsuko , Sampath Kuber , Zaidi Mone
Published: March 2008

We recently described the direct effects of thyroid-stimulating hormone (TSH) on bone and suggested that the bone loss in hyperthyroidism, hitherto attributed solely to elevated thyroid hormone levels, could at least in part arise from accompanying decrements in serum TSH. Recent studies on both mice and human subjects provide compelling evidence that thyroid hormones and TSH have the opposite effects on the skeleton. Here, we show that TSH, when injected intermittently into rodents, even at intervals of 2 weeks, displays a powerful antiresorptive action
in vivo
. By virtue of this action, together with the possible anabolic effects shown earlier, TSH both prevents bone loss and restores the lost bone after ovariectomy. Importantly, the osteoclast inhibitory action of TSH persists
ex vivo
even after therapy is stopped for 4 weeks. This profound and lasting antiresorptive action of TSH is mimicked in cells that genetically overexpress the constitutively active ligand-independent TSH receptor (TSHR). In contrast, loss of function of a mutant TSHR (Pro → Leu at 556) in congenital hypothyroid mice activates osteoclast differentiation, confirming once again our premise that TSHRs have a critical role in regulating bone remodeling.
Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy
Authors: Palmer Sarah , Maldarelli Frank , Wiegand Ann , Bernstein Barry , Hanna George J. , Brun Scott C. , Kempf Dale J. , Mellors John W. , Coffin John M. , King Martin S.
Published: March 2008

Residual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter. Single-copy assay results revealed that 77% of the patient samples had detectable low-level viremia (≥1 copy per ml), and all patients had at least one sample with detectable viremia. A nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39 weeks and a subsequent phase with no perceptible decay. The level of pretherapy viremia extrapolated for each phase of decay was significantly correlated with total baseline viremia for each patient (
R
2
= 0.27,
P
= 0.001 and
R
2
= 0.19,
P
< 0.005, respectively), supporting a biological link between the extent of overall baseline viral infection and the infection of long-lived reservoirs. These data suggest that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years.
Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome
Authors: Kim Soong Ho , Markham Julie A. , Weiler Ivan Jeanne , Greenough William T.
Published: March 2008

Fragile X syndrome (FXS) has so far resisted efforts to define the basic cellular defects caused by the absence of a single protein, fragile X mental retardation protein (FMRP), because the patients have a wide variety of symptoms of varying severity. Immature-appearing dendritic spines on neurons found in FXS patients and
fmr1
-KO mice suggest a role for FMRP in modulating production of synaptic structural proteins. We isolated cortical synaptoneurosomes from WT and KO mice and studied MAPK pathway activation after group I metabotropic glutamate receptor (mGluR) stimulation. Here, we show that ERK in KO synaptoneurosomes is rapidly dephosphorylated upon mGluR1/5 stimulation, whereas it is phosphorylated in WT mice, suggesting that aberrant activation of phosphatases occurs in KO synapses in response to synaptic stimulation. In KO synapses, protein phosphatase 2A (PP2A) is overactivated after mGluR1 stimulation, and tyrosine phosphatase is overactivated after mGluR5 stimulation, causing the rapid deactivation of ERK. ERK activation can be restored in KO by pretreatment with phosphatase blockers; blocking of PP2A by okadaic acid could successfully restore normal ERK activation in KO synaptoneurosomes. We propose that overactivation of phosphatases in synapses may be a key deficit in FXS, which affects synaptic translation, transcription, and synaptic receptor regulation.
Helicobacter pylorievolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells
Authors: Giannakis Marios , Chen Swaine L. , Karam Sherif M. , Engstrand Lars , Gordon Jeffrey I.
Published: March 2008

We have characterized the adaptations ofHelicobacter pylorito a rarely captured event in the evolution of its impact on host biology—the transition from chronic atrophic gastritis (ChAG) to gastric adenocarcinoma—and defined the impact of these adaptations on an intriguing but poorly characterized interaction between this bacterium and gastric epithelial stem cells. Bacterial isolates were obtained from a single human host colonized with a single dominant strain before and after his progression from ChAG to gastric adenocarcinoma during a 4-year interval. Draft genome assemblies were generated from two isolates, one ChAG-associated, the other cancer-associated. The cancer-associated strain was less fit in a gnotobiotic transgenic mouse model of human ChAG and better able to establish itself within a mouse gastric epithelial progenitor-derived cell line (mGEP) that supports bacterial attachment. GeneChip-based comparisons of the transcriptomes of mGEPs and a control mouse gastric epithelial cell line revealed that, upon infection, the cancer-associated strain regulates expression of GEP-associated signaling and metabolic pathways, and tumor suppressor genes associated with development of gastric cancer in humans, in a manner distinct from the ChAG-associated isolate. The effects on GEP metabolic pathways, some of which were confirmed in gnotobiotic mice, together with observed changes in the bacterial transcriptome are predicted to support aspects of an endosymbiosis between this microbe and gastric stem cells. These results provide insights about howH. pylorimay adapt to and influence stem cell biology and how its intracellular residency could contribute to gastric tumorigenesis.
‘Governance of’ and ‘Governance by’: Implementing a Clinical Governance Framework in an Area Mental Health Service
Authors: O'Connor Nick , Paton Michael
Published: March 2008

Objective: A framework developed to promote the understanding and application of clinical governance principles in an area mental health service is described. The framework is operationalized through systems, processes, roles and responsibilities.

Methods: The development of an explicit and operationalizable framework for clinical governance arose from the authors' experiences in leading and managing mental health services. There is a particular emphasis on improvement of quality of care and patient safety. The framework is informed by recent developments in thinking about clinical governance, including key documents from Australia and the United Kingdom.

Results: The operational nature of the framework allows for key components of clinical governance to be described explicitly, communicated effectively, and continually tested and improved. Further consideration and assessment of the value of differing approaches to this task are required. For example, a general, illustrative approach to raise clinician awareness can be contrasted with prescriptive and specified approaches which progressively encompass the many functions and processes of a mental health service.

Conclusions: Mental health clinicians and managers can be guided by a framework that will ensure safe, high quality and continually improving processes of care.
Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion
Authors: Cortesio Christa L. , Chan Keefe T. , Perrin Benjamin J. , Burton Nicholas O. , Zhang Sheng , Zhang Zhong-Yin , Huttenlocher Anna
Published: March 2008

Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel function for calpain 2 in the formation of invadopodia and in the invasive abilities of breast cancer cells through the modulation of endogenous c-Src activity. Calpain-deficient breast cancer cells show impaired invadopodia formation that is rescued by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B) corresponding to the calpain proteolytic fragment, which indicates that calpain modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for efficient invadopodia formation and breast cancer invasion, which suggests that PTP1B may modulate breast cancer progression through its effects on invadopodia. Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion.
A gammaherpesvirus-secreted activator of Vβ4+ CD8+ T cells regulates chronic infection and immunopathology
Authors: Evans Andrew G. , Moser Janice M. , Krug Laurie T. , Pozharskaya Veranika , Mora Ana L. , Speck Samuel H.
Published: March 2008

Little is known about herpesvirus modulation of T cell activation in latently infected individuals or the implications of such for chronic immune disorders. Murine gammaherpesvirus 68 (MHV68) elicits persistent activation of CD8+ T cells bearing a Vβ4+ T cell receptor (TCR) by a completely unknown mechanism. We show that a novel MHV68 protein encoded by the M1 gene is responsible for Vβ4+ CD8+ T cell stimulation in a manner reminiscent of a viral superantigen. During infection, M1 expression induces a Vβ4+ effector T cell response that resists functional exhaustion and appears to suppress virus reactivation from peritoneal cells by means of long-term interferon-γ (IFNγ) production. Mice lacking an IFNγ receptor (IFNγR−/−) fail to control MHV68 replication, and Vβ4+ and CD8+ T cell activation by M1 instead contributes to severe inflammation and multiorgan fibrotic disease. Thus, M1 manipulates the host CD8+ T cell response in a manner that facilitates latent infection in an immunocompetent setting, but promotes disease during a dysregulated immune response. Identification of a viral pathogenecity determinant with superantigen-like activity for CD8+ T cells broadens the known repertoire of viral immunomodulatory molecules, and its function illustrates the delicate balance achieved between persistent viruses and the host immune response.
Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus
Authors: Yager Eric J. , Ahmed Mushtaq , Lanzer Kathleen , Randall Troy D. , Woodland David L. , Blackman Marcia A.
Published: March 2008

A diverse T cell repertoire is essential for a vigorous immune response to new infections, and decreasing repertoire diversity has been implicated in the age-associated decline in CD8 T cell immunity. In this study, using the well-characterized mouse influenza virus model, we show that although comparable numbers of CD8 T cells are elicited in the lung and lung airways of young and aged mice after de novo infection, a majority of aged mice exhibit profound shifts in epitope immunodominance and restricted diversity in the TCR repertoire of responding cells. A preferential decline in reactivity to viral epitopes with a low naive precursor frequency was observed, in some cases leading to “holes” in the T cell repertoire. These effects were also seen in young thymectomized mice, consistent with the role of the thymus in maintaining naive repertoire diversity. Furthermore, a decline in repertoire diversity generally correlated with impaired responses to heterosubtypic challenge. This study formally demonstrates in a mouse infection model that naturally occurring contraction of the naive T cell repertoire can result in impaired CD8 T cell responses to known immunodominant epitopes and decline in heterosubtypic immunity. These observations have important implications for the design of vaccine strategies for the elderly.
IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection
Authors: Brooks David G. , Lee Andrew M. , Elsaesser Heidi , McGavern Dorian B. , Oldstone Michael B.A.
Published: March 2008

Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate persistent viral infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established persistent lymphocytic choriomeningitis virus (LCMV) infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.
Fixing DNA breaks during class switch recombination
Authors: Jolly Christopher J. , Cook Adam J.L. , Manis John P.
Published: March 2008

Immunoglobulin (Ig) class switch recombination (CSR) involves the breakage and subsequent repair of two DNA sequences, known as switch (S) regions, which flank IgH constant region exons. The resolution of CSR-associated breaks is thought to require the nonhomologous end-joining (NHEJ) DNA repair pathway, but the role of the NHEJ factor DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in this process has been unclear. A new study, in which broken IgH-containing chromosomes in switching B cells were visualized directly, clearly demonstrated that DNA-PKcs and, unexpectedly, the nuclease Artemis are involved in the resolution of switch breaks.