bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of solar wind‐magnetosphere coupling functions during geomagnetic storms with the WINDMI model
Authors: Spencer E. , Rao A. , Horton W. , Mays M. L.
Published: February 2009

We evaluate the performance of three solar wind‐magnetosphere coupling functions in training the physics‐based WINDMI model on the 3–7 October 2000 geomagnetic storm and predicting the geomagnetic Dst and AL indices during the 15–24 April 2002 geomagnetic storm. The rectified solar wind electric field, a coupling function by Siscoe, and a recent formula proposed by Newell are evaluated. The Newell coupling function performed best in both the training and prediction phases for Dst prediction. The Siscoe formula performed best during the training phase in reproducing the AL faithfully and capturing storm time events. The rectified driver was discovered to be the best in overall performance during both training as well as prediction phases, even though the other two coupling functions outperform it in the training phase. The results indicate that multiple drivers need to be concurrently employed in space weather models to yield different possible levels of geomagnetic activity.
95‐GHz Doppler radar and lidar synergy for simultaneous ice microphysics and in‐cloud vertical air motion retrieval
Authors: Sato Kaori , Okamoto Hajime , Yamamoto Masayuki K. , Fukao Shoichiro , Kumagai Hiroshi , Ohno Yuichi , Horie Hiroaki , Abo Makoto
Published: February 2009

We introduce a combined 95‐GHz radar multi‐parameter (radar reflectivity Ze, Doppler velocity VD, and/or linear depolarization ratio LDR) and lidar backscatter coefficient βbk algorithm for the simultaneous retrieval of ice cloud microphysics and in‐cloud vertical air motion Vair within a single radar volume. Unlike earlier methods, our new approach is not limited to a specific temporal or spatial scale of Vair, which makes it applicable to the interaction between cloud dynamics and ice cloud microphysics on various scales. Full one‐to‐one validation of the retrieved Vair was performed, for the first time, by collocated VHF Doppler radar measurement (Equatorial Atmospheric Radar) every 3 min for a cloud observed on 14 November 2005, at Kototabang, West Sumatra, Indonesia. The spatial structure of the retrieved up‐/downward Vair in cloud agreed closely with direct measurements, with an average difference of −0.009 ± 0.119 ms−1. The frequency distributions for the retrieved and measured Vair also agreed closely, with peaks of similar width observed around 0 ms−1. A large improvement in the microphysical retrieval was achieved due to the accurate estimation of the Ze‐weighted particle fall velocity Vtz from VD. The correlation coefficient between ice water content retrieved with the estimated Vair and that retrieved with the Vair measured by the EAR improved to 0.70 from values as low as 0.28 without the Vair retrieval.
Characteristics and sources of non‐methane hydrocarbons in background atmospheres of eastern, southwestern, and southern China
Authors: Tang J. H. , Chan L. Y. , Chang C. C. , Liu Shaw , Li Y. S.
Published: February 2009

Non‐methane hydrocarbons (NMHCs) play very important roles in atmospheric chemistry, yet little is known about their abundance in the atmosphere of China, especially in the background atmospheres. Measurements of C2‐C10 NMHCs were concurrently carried out at two remote background sites and one rural background site in April and May 2004 in this study: Tengchong Mountain (TM) in Yunnan province on the border of southwestern China; Jianfeng Mountain (JM) on the southwest coast of Hainan Island, southern China; and Lin'an (LA) in Zhejiang province in eastern China. Additional samples were collected at an urban site, Tengyue Town (TT, about 10 km from TM), to obtain local urban NMHC profiles. NMHC levels in these background sites were compared with other rural and remote sites in Asia and other global background stations. In the urban site of TT, local biofuel combustion was the major contributor to the high levels of ethene, ethyne, and ethane. In LA, the major sources of NMHCs were the emissions from fossil fuel and biofuel combustion and from industrial solvent use. Compared with another study conducted in 2001, toluene levels had increased by 75% in 2004 in this study, whereas the levels of other anthropogenic hydrocarbons remained at the same levels. Local industrial emissions and transports from the Yangtze River Delta were the major sources of toluene, ethylbenzene, and xylenes in LA. While in TM, the major sources were regional biofuel combustions and biomass burning emissions from Southeast Asia. Long‐range transport of air masses from Southeast Asia was the major source of NMHCs in JM in spring. JM showed the lowest levels of most hydrocarbons among the three background sites. Several hydrocarbon molar ratios, such as benzene/toluene and ethane/propane, were used to characterize the signatures of air masses from different regions.
Hemodynamic Etiology of Elevated Flow Velocity and Stroke in Sickle-Cell Disease
Authors: Prohovnik Isak , Hurlet-Jensen Anne , Adams Robert , De Vivo Darryl , Pavlakis Steven G
Published: February 2009

Elevation of blood flow velocity in the large cerebral vessels is known to be of substantial pathophysiologic and prognostic significance in sickle-cell disease (SCD). Its precise cause is not established, but the two obvious proximal mechanisms are obstructive vascular stenosis and hemodynamic dilatation. Here we revisit this distinction by analyzing cerebrovascular reserve capacity. Forty-two patients with SCD underwent measurements of global cerebral blood flow in grey matter by the 133Xe inhalation method during normocapnia and hypercapnia to quantify cerebrovascular reactivity. Cerebral blood flow was significantly higher in SCD patients (120±31 ml/100 g/min) than in controls (76±20 ml/100 g/min). Reactivity was significantly lower in SCD patients (1.06±1.92 versus 2.16±1.15%/mm Hg). Stepwise multiple regressions within the SCD sample determined that normocapnic cerebral blood flow was largely predicted by hematocrit ( r =–0.59; P > 0.0001), whereas hypercapnic reactivity was only predicted by normocapnic flow across all subjects ( r =–0.52; P > 0.0001). None of the controls, but 24% of the SCD patients showed ‘steal’ (negative reactivity, χ2 = 6.05; P > 0.02). This impairment of vasodilatory capacity, occurring at perfusion levels above 150 ml/100 g/min, may reflect intrinsic limitations of the human cerebrovascular system and can explain both the elevated blood flow velocities and the high risk of stroke observed in such patients.
Characterization of the catalytic activity of the membrane-anchored metalloproteinase ADAM15 in cell-based assays
Authors: Maretzky Thorsten , Yang Guangli , Ouerfelli Ouathek , Overall Christopher M. , Worpenberg Susanne , Hassiepen Ulrich , Eder Joerg , Blobel Carl P.
Published: February 2009

ADAM15 (a disintegrin and metalloproteinase 15) is a membrane-anchored metalloproteinase, which is overexpressed in several human cancers and has been implicated in pathological neovascularization and prostate cancer metastasis. Yet, little is known about the catalytic properties of ADAM15. Here, we purified soluble recombinant ADAM15 to test for its ability to cleave a library of peptide substrates. However, we found no processing of any of the peptide substrates tested here, and therefore turned to cell-based assays to characterize the catalytic properties of ADAM15. Overexpression of full-length membrane-anchored ADAM15 or the catalytically inactive ADAM15E→A together with various membrane proteins resulted in increased release of the extracellular domain of the fibroblast growth factor receptor 2iiib (FGFR2iiib) by ADAM15, but not ADAM15E→A. This provided a robust assay for a characterization of the catalytic properties of ADAM15 in intact cells. We found that increased expression of ADAM15 resulted in increased FGFR2iiib shedding, but that ADAM15 was not stimulated by phorbol esters or calcium ionophores, two commonly used activators of ectodomain shedding. Moreover, ADAM15-dependent processing of FGFR2iiib was inhibited by the hydroxamate-based metalloproteinase inhibitors marimastat, TAPI-2 and GM6001, and by 50 nM TIMP-3 (tissue inhibitor of metalloproteinases 3), but not by 100 nM TIMP-1, and only weakly by 100 nM TIMP-2. These results define key catalytic properties of ADAM15 in cells and its response to stimulators and inhibitors of ectodomain shedding. A cell-based assay for the catalytic activity of ADAM15 could aid in identifying compounds, which could be used to block the function of ADAM15 in pathological neovascularization and cancer.
Observation and interpretation of the low-temperature features of the phonon thermal conductivity of mercury selenide crystals doped with impurities of 3d transition elements
Authors: Lonchakov A. T. , Okulov V. I. , Paranchich S. Yu.
Published: February 2009

The temperature dependence of the thermal conductivity of mercury selenide containing iron and cobalt impurities is investigated experimentally. An analysis of the phonon contributions to the thermal conductivity at low temperatures in HgSe:Fe crystals reveals a significant impurity-related anomaly of the phonon thermal conductivity—a dip in its temperature dependence near 15K. On the basis of a proposed theoretical description it is shown that this anomaly is explained by the contribution to the thermal conductivity from the scattering of phonons on electrons in hybridized impurity states.
Statistical model structure of A1−xZxB2 Laves phase C15 system—the superconducting alloy Ce1−xLaxRu2
Authors: Robouch B. V. , Marcelli A. , Saini N. L. , Kisiel A.
Published: February 2009

The local structure of the Ce1−xLaxRu2 system measured by EXAFS is re-examined and correlated to the statistical ad hoc model recently applied to the sphalerite, wurtzite, and other intermetallic ternary alloys. Deconvolution of the EXAFS data shows that the Ce1−xLaxRu2 ternary system is essentially a mixture of CeRu2 and LaRu2 binary alloys with a small proportion of the Ce0.5La0.5Ru2 ternary configuration, which is maximum for the intermediate concentration. Moreover, the analysis reveals that while the LaRu2 configuration exhibits a Bernoulli random distribution, the presence of a Ce atom affects both the CeRu2 and Ce0.5La0.5Ru2 distributions, strongly favoring the configuration with the CeCe pair, while keeping rare that with a single Ce ion.
Pinning control of fractional-order weighted complex networks
Authors: Tang Yang , Wang Zidong , Fang Jian-an
Published: February 2009

In this paper, we consider the pinning control problem of fractional-order weighted complex dynamical networks. The well-studied integer-order complex networks are the special cases of the fractional-order ones. The network model considered can represent both directed and undirected weighted networks. First, based on the eigenvalue analysis and fractional-order stability theory, some local stability properties of such pinned fractional-order networks are derived and the valid stability regions are estimated. A surprising finding is that the fractional-order complex networks can stabilize itself by reducing the fractional-order q without pinning any node. Second, numerical algorithms for fractional-order complex networks are introduced in detail. Finally, numerical simulations in scale-free complex networks are provided to show that the smaller fractional-order q, the larger control gain matrix D, the larger tunable weight parameter β, the larger overall coupling strength c, the more capacity that the pinning scheme may possess to enhance the control performance of fractional-order complex networks.
Effect of pretreatment bias on the nucleation and growth mechanisms of ultrananocrystalline diamond films via bias-enhanced nucleation and growth: An approach to interfacial chemistry analysis via chemical bonding mapping
Authors: Zhong X. Y. , Chen Y. C. , Tai N. H. , Lin I. N. , Hiller J. M. , Auciello O.
Published: February 2009

The effect of pretreatment bias on the nucleation and growth mechanisms of the ultrananocrystalline diamond (UNCD) films on the Si substrate via bias-enhanced nucleation and bias-enhanced growth (BEN-BEG) was investigated using cross-sectional high-resolution transmission electron microscopy, chemical bonding mapping, and Raman spectroscopy. The mirror-polished substrate surface showed the formation of a triangular profile produced by a dominant physical sputtering mechanism induced by ion bombardment of ions from the hydrogen plasma accelerated toward the substrate due to biasing and a potential hydrogen-induced chemical reaction component before synthesizing the UNCD films. The BEN-BEG UNCD films grown on the Si substrate with biased and unbiased pretreatments in the hydrogen plasma were compared. In the case of the bias-pretreated substrate, the SiC phases were formed at the peaks of the Si surface triangular profile due to the active unsaturated Si bond and the enhanced local electrical field. The UNCD grains grew preferentially at the peaks of the triangular substrate surface profile and rapidly covered the amorphous carbon (a-C) and oriented graphite phases formed in the valley of the surface profile. In the case of the substrate with unbiased pretreatment, the SiC phases were formed via the reactions between the hydrocarbon species and the active Si atoms released from the substrate with assistance of the hydrogen plasma. The UNCD grains nucleated on the nucleating sites consisting of the SiC, a-C, and graphite phases. Growth mechanisms for the BEN-BEG UNCD films on both Si substrates were proposed to elucidate the different nucleation processes. Applying bias on the Si substrate pretreated in the hydrogen plasma optimized the nucleation sites for growth of UNCD grains, resulting in the low content of the nondiamond phases in UNCD films.
A direct test of the correlation between elastic parameters and fragility of ten glass formers and their relationship to elastic models of the glass transition
Authors: Torchinsky Darius H. , Johnson Jeremy A. , Nelson Keith A.
Published: February 2009

We present an impulsive stimulated scattering test of the “shoving model” of the glass transition and of the correlation between the fragility index and the ratio of instantaneous elastic moduli of eight supercooled liquids. Samples of triphenyl phosphite, DC704 (tetramethyl tetraphenyl trisiloxane), m-fluoroaniline, Ca(NO3)2⋅4H2O, diethyl phthalate, propylene carbonate, m-toluidine, phenyl salicylate (salol), 2-benzylphenol, and Santovac 5 (5-phenyl 4-ether), were cooled to their respective glass transition temperatures and the elastic moduli directly measured at the highest accessible shear frequencies. The shear modulus was then measured every 2 K as deeply as permitted into the liquid state for all liquids except propylene carbonate. Our results, in conjunction with dynamical relaxation data for these liquids obtained from the literature, lend credence to the notion that the dynamics of the glass transition are governed by the evolution of the shear modulus but do not suggest a strong correlation between the fragility index and the ratio of the elastic moduli.
Generalized outer synchronization between complex dynamical networks
Authors: Wu Xiaoqun , Zheng Wei Xing , Zhou Jin
Published: February 2009

In this paper, the problem of generalized outer synchronization between two completely different complex dynamical networks is investigated. With a nonlinear control scheme, a sufficient criterion for this generalized outer synchronization is derived based on Barbalat’s lemma. Two corollaries are also obtained, which contains the situations studied in two lately published papers as special cases. Numerical simulations further demonstrate the feasibility and effectiveness of the theoretical results.
Nonlinear structures of drift waves in pair-ion-electron plasmas
Authors: Saleem H. , Batool N.
Published: February 2009

The Korteweg–de Vries–Burgers equation is derived for drift waves in a partially ionized nonuniform pair-ion-electron (PIE) plasma. The nonlinearity appears due to electron temperature gradient. The analytical solutions in the form of solitons, monotonic shocks, and oscillatory shocks have been obtained. The numerical calculations have also been presented for PIE plasmas of fullerene and hydrogen for illustration keeping in view the recent experiments. This work can be useful for future experimental investigations.
Vanadium oxide nanowire phase and orientation analyzed by Raman spectroscopy
Authors: Chou J. Y. , Lensch-Falk J. L. , Hemesath E. R. , Lauhon L. J.
Published: February 2009

Phase-selective growth of VO2 and V2O5 nanowires was realized via catalyst-free physical vapor deposition from bulk VO2 powder. Single nanowire Raman spectroscopy was used to analyze the distribution of the vanadium oxide phases within the reactor. VO2 (V2O5) nanowires were identified by characteristic peaks at 197, 224, and 620 cm−1 (149, 700, and 994 cm−1). Electron diffraction and polarization-dependent Raman spectra indicated that the growth directions of VO2 and V2O5 nanowires were [100] and [010]. Analysis of Raman spectra in two polarization configurations is sufficient to distinguish between low-index nanowire growth directions for the V2O5 phase. Single nanostructure Raman measurements thus provide a means to rapidly analyze the phase and growth direction of anisotropic nanostructures.
Influence of Sb on the magnetic and magnetocaloric properties of ferromagnetic shape memory alloy NiMnIn
Authors: Liu Z. H. , Aksoy S. , Acet M.
Published: February 2009

We investigate the magnetic properties and the magnetic entropy change around the martensitic transformations in Sb-doped Ni50Mn35In15 ferromagnetic shape memory alloys. We find that the martensitic transformation temperature decreases, and the thermal hysteresis associated with the transition increases when Sb is added. The alloy with 5.5 at. % Sb enhances the ferromagnetism of austenitic phase and improves the field shift martensitic transition ability, resulting in a great increase in magnetic entropy change up to 8 J kg−1 K−1 at 2 T and 21 J kg−1 K−1 at 5 T. This is attributed to magnetic interaction that is sensitive to the variation of p-d hybridization and conduction electron concentration arising from the substitution of sp element.
Stability study and effect of passivation on InP/InGaAs double heterojunction bipolar transistors
Authors: Lin Yu-Shyan , Jou Yu-Jeng , Huang Pin-Chun
Published: February 2009

This work explores the thermal and bias stabilities of composite-collector double heterojunction bipolar transistors (CC-DHBTs) with i-InGaAs/n+-InP in the collector layer, in the temperature range of 300–400 K. Both V-shaped behaviors (observed in dc current gain β against collector current IC and in offset voltage VCE,offset against base current IB plot) of the asymmetric CC-DHBT are studied simultaneously. At high IC, the devices of interest improve the dc current gain temperature stability relative to most HBTs described in the literature. Additionally, unlike that of the abrupt DHBTs in the literature, the β of the CC-DHBTs is independent of VCB, revealing that the effect of the conduction-band barrier in the base-collector junctions may have been eliminated. An analytical expression for the variation in VCE,offset with IB has been developed. Additionally, unlike that of the unpassivated and SiNx-passivated devices, the β of the sulfur-treated device is fairly constant over five decades of IC. The difference among these variously treated devices is striking. X-ray photoelectron spectroscopy was adopted to examine InGaAs surfaces that were (NH4)2Sx and SiNx passivated. The results reveal that passivation effectively suppresses the oxidation of As.
Toward a low-voltage multiferroic transistor: Magnetic (Ga,Mn)As under ferroelectric control
Authors: Riester S. W. E. , Stolichnov I. , Trodahl H. J. , Setter N. , Rushforth A. W. , Edmonds K. W. , Campion R. P. , Foxon C. T. , Gallagher B. L. , Jungwirth T.
Published: February 2009

The persistent field effect control of ferromagnetism in a diluted magnetic semiconductor by low-voltage polarizing pulses is demonstrated in a ferroelectric gate field effect transistor configuration. The Curie temperature of the (Ga,Mn)As channel is unambiguously signaled by a cusp in the temperature derivative of resistance. Polarization reversal in the ferroelectric copolymer polyvinylidene fluoride with trifluoroethylene P(VDF-TrFE) by voltage pulses of less than 10 V results in a reproducible nonvolatile shift in the cusp by as much as 7%–9%. The unique combination of a relatively large spontaneous polarization and low dielectric constant of the P(VDF-TrFE) gate promises a further reduction in the operation voltage.
Pressure induced phase separation in optimally doped bilayer manganites
Authors: Malavasi Lorenzo , Baldini Maria , Zardo Ilaria , Hanfland Michael , Postorino Paolo
Published: February 2009

In this paper, we give a direct experimental evidence of the long hypothesized phase separation scenario in strongly correlated manganite-based systems. High resolution, high-pressure synchrotron x-ray diffraction measurements on La1.4Sr1.6Mn2O7 as a function of temperature reveal the instability with P of the ferromagnetic phase leading, above a threshold P, to a phase separation between two phases with different orbital occupancies.
MoO
3
surface passivation of the transparent anode in organic solar cells using ultrathin films
Authors: Cattin L. , Dahou F. , Lare Y. , Morsli M. , Tricot R. , Houari S. , Mokrani A. , Jondo K. , Khelil A. , Napo K. , Bernède J. C.
Published: February 2009

An original surface passivation technique of indium tin oxide (ITO) used as anode in organic solar cells is proposed. We demonstrate that a thin MoO3 film (3.5±1 nm) at the interface ITO/organic donor allows improving significantly the devices’ performances. The devices are based on the multiheterojunction structure copper phthalocyanine (CuPc)/fullerene (C60)/aluminum tris(8-hydroxyquinoline) (Alq3). The deposition of MoO3 onto ITO improves the charge transfer from CuPc to ITO. The enhancement in the hole collection efficiency in the presence of an oxide layer can be explained in terms of the reduction in the effective barrier against hole transfer from CuPc into the ITO anode. The contact ITO/MoO3/CuPc behaves like a metal-insulator-semiconductor (MIS) structure, which allows reducing the energy barrier due to the difference between the work function of ITO and the highest occupied molecular orbital of CuPc. It is shown that the optimum MoO3 thickness corresponds to a compromise between an optimum ITO coverage and a sufficient transparency of the trapezoidal barrier for the tunneling of the charge carriers. The MoO3 thin films are discontinuous, and the passivation effect is improved when the oxide thin film is covered by an ultrathin gold film. Such behavior is discussed in the light of band scheme structures after contact and of geometrical considerations.
Lateral stress and shear strength behind the shock front in three face centered cubic metals
Authors: Millett J. C. F. , Whiteman G. , Bourne N. K.
Published: February 2009

Lateral stress and shear strength behind the shock front have been measured in three face centered cubic alloys. Results show different behaviors according to microstructure. A hardening response has been shown in pure nickel, while in stainless steel (SS) 304L, hardening has been shown to be minimal. This has been explained in terms of the stacking fault energy effecting the motion and generation of dislocations. In the high stacking fault energy nickel, dislocation motion is comparatively easy, and hence the microstructure consists of dislocation cells, with a pronounced hardening postshock. In SS 304L with its lower stacking fault energy, dislocation motion is more restricted, and hence deformation is dominated by deformation twins. The behavior behind the shock front correlates with the low degree of hardening observed by others during mechanical testing of preshocked samples. The aluminum alloy 6082-T6 also shows a low degree of hardening behind the shock front. This is believed to occur due to the presence of fine intermetallic particles suppressing the formation of dislocation cells but rather forming a random distribution throughout the microstructure.
Localized microwave heating in microwells for parallel DNA amplification applications
Authors: Kempitiya A. , Borca-Tasciuc Diana A. , Mohamed Hisham S. , Hella Mona M.
Published: February 2009

This work explores the potential of microwave heating for applications requiring parallel DNA amplification platforms. Device characterization and thermal modeling is performed on 4.1μl microfluidic chamber fabricated in polycarbonate. Microwave power at 6GHz is delivered to the chamber via copper transmission line in a microstrip configuration. Microwave power reflection coefficient and temperature measurements are performed to characterize the power coupled to the chamber and rate of change in temperature. Temperatures up to 72°C are achieved with less than 400mW power applied at the input of the transmission line. Initial heating and cooling rates measured experimentally are ∼7 and ∼6°C∕s, respectively. These results suggest that microwave heating is an efficient, rapid heating technique suitable for programmable, parallel DNA amplification platforms to be empolyed in future genetic analysis systems.
Effect of doping on the amorphous to microcrystalline transition in a hydrogenated amorphous silicon under hydrogen plasma treatment
Authors: Hadjadj A. , Pham N. , Roca i Cabarrocas P. , Jbara O.
Published: February 2009

Just after their deposition, we have exposed intrinsic and doped hydrogenated amorphous silicon (a-Si:H) films to a hydrogen plasma. We have investigated, by in situ spectroscopic ellipsometry measurements, the structural evolution of the film during the amorphous to microcrystalline phase transition. To take into account the complex morphological development of microcrystalline silicon (μc-Si:H), the grown film is modeled by a graded layer with a linear index variation along the growth direction. By comparing the time evolution of the structural parameters of the deposited μc-Si:H layer, we have observed a particular behavior in the case of boron-doped a-Si:H. Despite a faster and deeper hydrogen diffusion from the beginning of hydrogen plasma exposure, and a later nucleation, a compact μc-Si:H layer is obtained. In the case of intrinsic and n-type a-Si:H the nucleation is faster and leads to a thin and very porous μc-Si:H layer. The particular behavior of the p-type material is attributed to the effects of boron, which, on the one hand, enhances the deposition of the Si precursors and, on the other hand, reduces the etching rate.
Diffusion and interaction studied nondestructively and in real-time with depth-resolved low energy ion spectroscopy
Authors: de Rooij-Lohmann V. I. T. A. , Kleyn A. W. , Bijkerk F. , Brongersma H. H. , Yakshin A. E.
Published: February 2009

An analysis procedure was developed that enables studying diffusion in ultrathin films by utilizing the depth-resolved information that is contained in the background of low energy ion scattering (LEIS) spectra. Using a high-sensitivity analyzer/detector combination allows for such a low ion dose that the ion-induced perturbation caused by this technique is negligible and not measurable with LEIS. The developed analysis procedure provides a unique opportunity to study diffusion processes in nanoscaled systems. It was applied to the Mo/Si system, a system that is relevant for extreme ultraviolet optics.
Bidirectional direct-current electroluminescence from i-MgxZn1−xO/n-ZnO/SiOx double-barrier heterostructures on Si
Authors: Chen Peiliang , Ma Xiangyang , Li Dongsheng , Zhang Yuanyuan , Yang Deren
Published: February 2009

We report bidirectional direct-current electroluminescence (EL) from i-MgxZn1−xO/n-ZnO/SiOx double-barrier heterostructures on Si. When the heterostructure-based device is forward biased with negative voltage applied on Si, ultraviolet (UV) emission is more intense than visible emissions. The visible emissions appear only at sufficiently high currents. As the device is reverse biased, the visible emissions dominate the EL at low currents. However, they are gradually overridden by the UV emission with increasing current. The EL mechanism has been discussed in terms of energy band structures of the device under forward and reverse biases.
Haploinsufficiency forPtenandSerotonin transportercooperatively influences brain size and social behavior
Authors: Page Damon T. , Kuti Orsolya J. , Prestia Chrysa , Sur Mriganka
Published: February 2009

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that share deficits in sociability, communication, and restrictive and repetitive interests. ASD is likely polygenic in origin in most cases, but we presently lack an understanding of the relationships between ASD susceptibility genes and the neurobiological and behavioral phenotypes of ASD. Two genes that have been implicated as conferring susceptibility to ASD arePTENandSerotonin transporter(SLC6A4). The PI3K and serotonin pathways, in which these genes respectively act, are both potential biomarkers for ASD diagnosis and treatment. Biochemical evidence exists for an interaction between these pathways; however, the relevance of this for the pathogenesis of ASD is unclear. We find thatPtenhaploinsufficient (Pten+/−) mice are macrocephalic, and this phenotype is exacerbated inPten+/−;Slc6a4+/−mice. Furthermore, femalePten+/−mice are impaired in social approach behavior, a phenotype that is exacerbated in femalePten+/−;Slc6a4+/−mice. While increased brain size correlates with decreased sociability across these genotypes in females, within each genotype increased brain size correlates with increased sociability, suggesting that epigenetic influences interact with genetic factors in influencing the phenotype. These findings provide insight into an interaction between two ASD candidate genes during brain development and point toward the use of compound mutant mice to validate biomarkers for ASD against biological and behavioral phenotypes.
Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase
Authors: Chen Yu , Cai Hui , Pan Ji'an , Xiang Nian , Tien Po , Ahola Tero , Guo Deyin
Published: February 2009

The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3′-to-5′ exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.
Rubisco in complex with Rubisco large subunit methyltransferase
Authors: Raunser Stefan , Magnani Roberta , Huang Zhong , Houtz Robert L. , Trievel Raymond C. , Penczek Pawel A. , Walz Thomas
Published: February 2009

SET domain protein lysine methyltransferases (PKMT) are a structurally unique class of enzymes that catalyze the specific methylation of lysine residues in a number of different substrates. Especially histone-specific SET domain PKMTs have received widespread attention because of their roles in the regulation of epigenetic gene expression and the development of some cancers. Rubisco large subunit methyltransferase (RLSMT) is a chloroplast-localized SET domain PKMT responsible for the formation of trimethyl-lysine-14 in the large subunit of Rubisco, an essential photosynthetic enzyme. Here, we have used cryoelectron microscopy to produce an 11-Å density map of the Rubisco–RLSMT complex. The atomic model of the complex, obtained by fitting crystal structures of Rubisco and RLSMT into the density map, shows that the extensive contact regions between the 2 proteins are mainly mediated by hydrophobic residues and leucine-rich repeats. It further provides insights into potential conformational changes that may occur during substrate binding and catalysis. This study presents the first structural analysis of a SET domain PKMT in complex with its intact polypeptide substrate.
Two-state selection of conformation-specific antibodies
Authors: Gao Junjun , Sidhu Sachdev S. , Wells James A.
Published: February 2009

We present a general strategy for identification of conformation-specific antibodies using phage display. Different covalent probes were used to trap caspase-1 into 2 alternative conformations, termed the on-form and the off-form. These conformation-trapped forms of the protease were used as antigens in alternating rounds of selection and antiselection for antibody antigen-binding fragments (Fabs) displayed on phage. After affinity maturation, 2 Fabs were isolated withKDvalues ranging from 2 to 5 nM, and each bound to their cognate conformer 20- to 500-fold more tightly than their noncognate conformer. Kinetic analysis of the Fabs indicated that binding was conformation dependent, and that the wild-type caspase-1 sits much closer to the off-form than the on-form. Bivalent IgG forms of the Fabs were used to localize the different states in cells and revealed the activated caspase-1 is concentrated in a central structure in the cytosol, similar to what has been described as the pyroptosome. These studies demonstrate a general strategy for producing conformation-selective antibodies and show their utility for probing the distribution of caspase-1 conformational states in vitro and in cells.
Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19
Authors: Napetschnig Johanna , Kassube Susanne A. , Debler Erik W. , Wong Richard W. , Blobel Günter , Hoelz André
Published: February 2009

Key steps in the export of mRNA from the nucleus to the cytoplasm are the transport through the nuclear pore complex (NPC) and the subsequent remodeling of messenger RNA-protein (mRNP) complexes that occurs at the cytoplasmic side of the NPC. Crucial for these events is the recruitment of the DEAD-box helicase Ddx19 to the cytoplasmic filaments of the NPC that is mediated by the nucleoporin Nup214. Here, we present the crystal structure of the Nup214 N-terminal domain in complex with Ddx19 in its ADP-bound state at 2.5 Å resolution. Strikingly, the interaction surfaces are not only evolutionarily conserved but also exhibit strongly opposing surface potentials, with the helicase surface being positively and the Nup214 surface being negatively charged. We speculate that the positively charged surface of the interacting ADP-helicase binds competitively to a segment of mRNA of a linearized mRNP, passing through the NPC on its way to the cytoplasm. As a result, the ADP-helicase would dissociate from Nup214 and replace a single bound protein from the mRNA. One cycle of protein replacement would be accompanied, cooperatively, by nucleotide exchange, ATP hydrolysis, release of the ADP-helicase from mRNA and its rebinding to Nup214. Repeat of these cycles would remove proteins from a mRNP, one at a time, akin to a ratchet mechanism for mRNA export.
Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression
Authors: Auld Douglas S. , Thorne Natasha , Maguire William F. , Inglese James
Published: February 2009

High-throughput screening (HTS) assays used in drug discovery frequently use reporter enzymes such as firefly luciferase (FLuc) as indicators of target activity. An important caveat to consider, however, is that compounds can directly affect the reporter, leading to nonspecific but highly reproducible assay signal modulation. In rare cases, this activity appears counterintuitive; for example, some FLuc inhibitors, acting through posttranslational Fluc reporter stabilization, appear to activate gene expression. Previous efforts to characterize molecules that influence luciferase activity identified a subset of 3,5-diaryl-oxadiazole-containing compounds as FLuc inhibitors. Here, we evaluate a number of compounds with this structural motif for activity against FLuc. One such compound is PTC124 {3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid}, a molecule originally identified in a cell-based FLuc assay as having nonsense codon suppression activity [Welch EM,et al., Nature (2007) 447:87–91]. We find that the potency of FLuc inhibition for the tested compounds strictly correlates with their activity in a FLuc reporter cell-based nonsense codon assay, with PTC124 emerging as the most potent FLuc inhibitor (IC50= 7 ± 1 nM). However, these compounds, including PTC124, fail to show nonsense codon suppression activity whenRenilla reniformisluciferase (RLuc) is used as a reporter and are inactive against the RLuc enzyme. This suggests that the initial discovery of PTC124 may have been biased by its direct effect on the FLuc reporter, implicating firefly luciferase as a molecular target of PTC124. Our results demonstrate the value of understanding potential interactions between reporter enzymes and chemical compounds and emphasize the importance of implementing the appropriate control assays before interpreting HTS results.
Acute regulation of tight junction ion selectivity in human airway epithelia
Authors: Flynn Andrea N. , Itani Omar A. , Moninger Thomas O. , Welsh Michael J.
Published: February 2009

Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La
3+
movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na
+
conductance, with a smaller increase in Cl
−
conductance. The increase was mediated by histamine H
1
receptors and depended on an increase in intracellular Ca
2+
concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport.
Molecular Dissection of the Checkpoint Kinase Hsl1p
Authors: Crutchley John , King Kindra M. , Keaton Mignon A. , Szkotnicki Lee , Orlando David A. , Zyla Trevin R. , Bardes Elaine S.G. , Lew Daniel J.
Published: February 2009

Cell shape can influence cell behavior. In Saccharomyces cerevisiae, bud emergence can influence cell cycle progression via the morphogenesis checkpoint. This surveillance pathway ensures that mitosis always follows bud formation by linking degradation of the mitosis-inhibitory kinase Swe1p (Wee1) to successful bud emergence. A crucial component of this pathway is the checkpoint kinase Hsl1p, which is activated upon bud emergence and promotes Swe1p degradation. We have dissected the large nonkinase domain of Hsl1p by using evolutionary conservation as a guide, identifying regions important for Hsl1p localization, function, and regulation. An autoinhibitory motif restrains Hsl1p activity when it is not properly localized to the mother-bud neck. Hsl1p lacking this motif is active as a kinase regardless of the assembly state of cytoskeletal septin filaments. However, the active but delocalized Hsl1p cannot promote Swe1p down-regulation, indicating that localization is required for Hsl1p function as well as Hsl1p activation. We also show that the septin-mediated Hsl1p regulation via the novel motif operates in parallel to a previously identified Hsl1p activation pathway involving phosphorylation of the Hsl1p kinase domain. We suggest that Hsl1p responds to alterations in septin organization, which themselves occur in response to the local geometry of the cell cortex.
Renal Colic
Authors: Thornton Andrew
Published: February 2009

Renal colic describes the severe pain felt from ‘loin to groin’ caused by a renal stone obstructing the flow of urine as it passes down through the ureter. It is a very common condition that GPs are increasingly expected to manage in the community.
Childhood Immunization
Authors: Mehrali Tauseef H.
Published: February 2009

Many childhood diseases have been consigned to history and case reports in the UK and most developed countries. Immunization has been a key factor in achieving this. According to the World Health Organization, the two public health interventions that have had the greatest impact on the world's health are the provision of clean water and vaccinations.
MRSA in the Community
Authors: Simon Chantal
Published: February 2009

Staphylococcus aureus ( Fig. 1 ) is a gram-positive bacterium that is a common colonizer of human skin and mucosa. It can cause disease, particularly if there is an opportunity for the bacteria to enter the body. A small proportion of S. aureus bacteria is resistant to methicillin and other beta-lactam antibiotics, including the penicillins and cephalosporins. Infections due to these strains are no more dangerous or virulent than other varieties of S. aureus, but they are much more difficult to treat because the range of effective antibiotics is considerably reduced. These antibiotic-resistant bacteria are termed methicillin-resistant S. aureus (MRSA). The first strain of methicillin resistant S. aureus appeared in Cairo in 1961. Since that time, it has spread to become a worldwide problem. This article aims to provide a practical strategy to enable GPs to manage MRSA colonization and potential or actual MRSA infection in the community.
The Consultation
Authors: Simon Chantal
Published: February 2009

The dictionary definition of a consultation is ‘a meeting for deliberation, discussion, or decision’. In medicine, the consultation is of huge importance. It is the framework within which the doctor and patient interact, and thus forms the platform upon which everything else we do for our patients is built — it is the cornerstone of general practice.
Suspected Food Poisoning
Authors: Melzer Mark , Shah Nirav
Published: February 2009

Food poisoning is defined as ‘any disease of an infective or toxic nature caused by or thought to be caused by the consumption of food and water’. The term ‘food poisoning’ is, in fact, a misnomer and is more accurately described as ‘food-borne infections and intoxications’ ( Collee, 1989 ) or infectious intestinal diseases (IIDs). Data from 2006, released by the Health Protection Agency for England and Wales, totalled 70 603 cases of food-borne illness and 211 deaths (excluding enterocolitis caused by Clostridium difficile). Cohort studies based in general practice found that, of the 9.4 million estimated cases of IID, only 1.5 million will consult their general practitioner approximating to one in six ( Wheeler et al., 1999 ). With total costs to the economy estimated at £1.5 billion a year, the Food Standards Agency launched a strategic campaign in June 2008 to reduce this prevalence, in particular, the high numbers of cases notified during summer months.
The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer
Authors: Fernandez Agustin F. , Rosales Cecilia , Lopez-Nieva Pilar , Graña Osvaldo , Ballestar Esteban , Ropero Santiago , Espada Jesus , Melo Sonia A. , Lujambio Amaia , Fraga Mario F. , Pino Irene , Javierre Biola , Carmona Francisco J. , Acquadro Francesco , Steenbergen Renske D.M. , Snijders Peter J.F. , Meijer Chris J. , Pineau Pascal , Dejean Anne , Lloveras Belen , Capella Gabriel , Quer Josep , Buti Maria , Esteban Juan-Ignacio , Allende Helena , Rodriguez-Frias Francisco , Castellsague Xavier , Minarovits Janos , Ponce Jordi , Capello Daniela , Gaidano Gianluca , Cigudosa Juan Cruz , Gomez-Lopez Gonzalo , Pisano David G. , Valencia Alfonso , Piris Miguel Angel , Bosch Francesc X. , Cahir-McFarland Ellen , Kieff Elliott , Esteller Manel
Published: February 2009

The natural history of cancers associated with virus exposure is intriguing, since only a minority of human tissues infected with these viruses inevitably progress to cancer. However, the molecular reasons why the infection is controlled or instead progresses to subsequent stages of tumorigenesis are largely unknown. In this article, we provide the first complete DNA methylomes of double-stranded DNA viruses associated with human cancer that might provide important clues to help us understand the described process. Using bisulfite genomic sequencing of multiple clones, we have obtained the DNA methylation status of every CpG dinucleotide in the genome of the Human Papilloma Viruses 16 and 18 and Human Hepatitis B Virus, and in all the transcription start sites of the Epstein-Barr Virus. These viruses are associated with infectious diseases (such as hepatitis B and infectious mononucleosis) and the development of human tumors (cervical, hepatic, and nasopharyngeal cancers, and lymphoma), and are responsible for 1 million deaths worldwide every year. The DNA methylomes presented provide evidence of the dynamic nature of the epigenome in contrast to the genome. We observed that the DNA methylome of these viruses evolves from an unmethylated to a highly methylated genome in association with the progression of the disease, from asymptomatic healthy carriers, through chronically infected tissues and pre-malignant lesions, to the full-blown invasive tumor. The observed DNA methylation changes have a major functional impact on the biological behavior of the viruses.
Intervening in Children’s Involvement in Gangs: Views of Cape Town’s Young People
Authors: Ward Catherine L. , Bakhuis Karlijn
Published: February 2009

Gangs have a long history in Cape Town and children tend to begin involvement around age 12. Children’s views on causes of children’s involvement in gangs and appropriate interventions, were sought for inclusion in policy recommendations. Thirty focus group discussions were held with in‐ and out‐of‐school youth in different communities. Participants identified failing social structures as the causes of gangsterism. They recommended interventions to enable social structures to provide a wide range of opportunities for positive youth development, rather than programmes narrowly focused on gangs.