bluuebunny/crossref_metadata_2025 huggingface dataset:
Near‐bed turbulence and relict waveformed sand ripples: Observations from the inner shelf
Authors: Hay Alex E.
Published: April 2008

Results are presented from a field investigation of near‐bed turbulence above degrading waveformed sand ripples in 17‐m water depth on the inner shelf. The heights of the 50‐cm wavelength primary ripples were about 5 cm at the start of the observation period, and decreased by a factor of 2 within 15 days. The principal degradation mechanism involved fish making pits in the seafloor. Near‐bed turbulent kinetic energy dissipation rates are estimated both from the energy spectrum and from the vertical structure function within the inertial subrange, and ranged from 0.1 × 10−6 to 3 × 10−6 W/kg. The friction velocity, u*, at the bed ranged from 0.3 to 0.5 cm/s, and the wave friction factor, fw, from 0.017 to 0.02. The nearbed turbulence intensities and consequently the estimated values of u2* and fw are likely too small by a factor of 2, partly to satisfy the smooth‐wall constraint, and partly to account for the effects of small‐scale turbulence within the finite‐volume range cells of the coherent Doppler system used to make the turbulence estimates. Finally, the results indicate that the hydraulic roughness of relict ripples is likely a function of both ripple height and steepness, and that the relative roughness should also depend on the near‐bed wave orbital excursion. For modeling purposes, Nielsen's ripple roughness formula is recommended, with a reduced proportionality constant to account for the effects of irregular wave forcing and non‐equilibrium ripple history.
Kinematic, microphysical, and electrical aspects of an asymmetric bow‐echo mesoscale convective system observed during STEPS 2000
Authors: Lang Timothy J. , Rutledge Steven A.
Published: April 2008

Five hours of detailed observations of the asymmetric bow‐echo mesoscale convective system on 11–12 June 2000 during the STEPS project are presented. Data sources included polarimetric and Doppler radars, a VHF lightning mapper, and the National Lightning Detection Network. Nearly every (99%) VHF lightning source occurred within 10 km of the convective line. Charge identification within the much of the convective line revealed evolution during the first 3 h from a normal polarity dipole (upper positive charge near 9 km MSL/−30°C, over mid‐level negative charge near 7 km/−16°C) to a normal polarity tripole with the addition of lower positive charge near 4 km (1°C). During the final 2 h, the charge structure resembled an inverted dipole, with negative charge overlaying positive. When the bow echo occurred during hour 2, part of the cells associated with severe winds developed an inverted tripolar charge structure and produced predominantly positive cloud‐to‐ground lightning. Stratiform lightning was infrequent, normally initiating in the convective line and propagating rearward along two pathways: a downward‐sloping upper pathway near 9 km, and a more common constant‐altitude lower pathway near 6 km (−10°C). Some flashes initiated within the stratiform region during this time, but only after stratiform reflectivities increased significantly in the mixed‐phase region. These flashes initiated near the bright band (4 km), and tapped negative charge above and positive charge below. Possible mechanisms to explain the observations are discussed.
Current global plate kinematics from GPS (1995–2007) with the plate‐consistent reference frame
Authors: Kogan Mikhail G. , Steblov Grigory M.
Published: April 2008

We present the vectors of rotation of 10 major lithospheric plates, estimated from continuous GPS observations at 192 globally distributed stations; 71 stations were selected as representing stable plate regions. All days for the period 1995.0–2007.0 were included in the analysis. In contrast to previous GPS plate models, our model is independent of international terrestrial reference frames (ITRF). The origin of our plate‐consistent reference frame is the center of plate rotation (CP) rather than the center of mass of the entire Earth's system (CM) as in recent versions of ITRF. We estimate plate rotations and CP by minimizing the misfit between the horizontal velocities predicted by the plate model and the observed GPS velocities. If any version of ITRF is used as the reference frame, the drift of the ITRF origin relative to CP cannot be neglected in estimation of plate rotation vectors and plate‐residual station velocities. The model of the plate kinematics presented here addresses the problem debated since the beginning of the space geodesy: how big are disagreements between the current plate motions and the motions averaged over several million years? We compare the vectors of relative plate rotations estimated here with the published vectors from GPS and geologic models. We also discuss the integrity of individual plates as exhibited by plate‐residual station velocities. For seven largest plates, the RMS value of plate‐residual station velocities in stable plate interiors is 0.5–0.9 mm/a; this value is an upper bound on deviation of real plates from infinite stiffness.
Mixing across the Arctic Ocean: Microstructure observations during the Beringia 2005 Expedition
Authors: Rainville Luc , Winsor Peter
Published: April 2008

Turbulent‐scale temperature and conductivity were measured during the pan‐arctic Beringia 2005 Expedition. The rates of dissipation of thermal variance and diapycnal diffusivities are calculated along a section from Alaska to the North Pole, across deep flat basins (Canada and Makarov Basins) and steep ridges (Alpha‐Mendeleev and Lomonosov Ridges). The mixing rates are observed to be small relative to lower latitudes but also remarkably non‐uniform. Relatively elevated turbulence is found over deep topography, confirming the dominant role of bottom‐generated internal waves. Measured patterns of mixing in the Arctic are also associated with other mechanisms, such as double‐diffusive structures and deep overflows. A better knowledge of the distribution of mixing is essential to understand the dynamics of the changing Arctic environment.
Progress in direct-drive inertial confinement fusion
Authors: McCrory R. L. , Meyerhofer D. D. , Betti R. , Craxton R. S. , Delettrez J. A. , Edgell D. H. , Glebov V. Yu. , Goncharov V. N. , Harding D. R. , Jacobs-Perkins D. W. , Knauer J. P. , Marshall F. J. , McKenty P. W. , Radha P. B. , Regan S. P. , Sangster T. C. , Seka W. , Short R. W. , Skupsky S. , Smalyuk V. A. , Soures J. M. , Stoeckl C. , Yaakobi B. , Shvarts D. , Frenje J. A. , Li C. K. , Petrasso R. D. , Séguin F. H.
Published: April 2008

Significant progress in direct-drive inertial confinement fusion (ICF) research has been made since the completion of the 60-beam, 30-kJUV OMEGA Laser System [Boehly, Opt. Commun. 133, 495 (1997)] in 1995. A theory of ignition requirements, applicable to any ICF concept, has been developed. Detailed understanding of laser-plasma coupling, electron thermal transport, and hot-electron preheating has lead to the measurement of neutron-averaged areal densities of ∼200mg∕cm2 in cryogenic target implosions. These correspond to an estimated peak fuel density in excess of 100g∕cm3 and are in good agreement with hydrodynamic simulations. The implosions were performed using an 18-kJ drive pulse designed to put the converging fuel on an adiabat of two. The polar-drive concept will allow direct-drive-ignition research on the National Ignition Facility while it is configured for indirect drive. Advanced ICF ignition concepts—fast ignition [Tabak et al., Phys. Plasmas 1, 1626 (1994)] and shock ignition [Betti et al., Phys. Rev. Lett. 98, 155001 (2007)]—have the potential to significantly reduce ignition driver energies and/or provide higher target gain.
Multiscale theory of collective and quasiparticle modes in quantum nanosystems
Authors: Ortoleva P. , Iyengar S. S.
Published: April 2008

A quantum nanosystem (such as a quantum dot, nanowire, superconducting nanoparticle, or superfluid nanodroplet) involves widely separated characteristic lengths. These lengths range from the average nearest-neighbor distance between the constituent fermions or bosons, or the lattice spacing for a conducting metal, to the overall size of the quantum nanosystem (QN). This suggests the wave function has related distinct dependencies on the positions of the constituent fermions and bosons. We show how the separation of scales can be used to generate a multiscale perturbation scheme for solving the wave equation. Results for electrons or other fermions show that, to lowest order, the wave function factorizes into an antisymmetric (fermion) part and a symmetric (bosonlike) part. The former manifests the short-range∕exclusion-principle behavior, while the latter corresponds to collective behaviors, such as plasmons, which have a boson character. When the constituents are bosons, multiscale analysis shows that, to lowest order, the wave function can also factorize into short- and long-scale parts. However, to ensure that the product wave function has overall symmetric particle label exchange behavior, there could, in principle, be states of the boson nanosystem where both the short- and long-scale factors are either boson- or fermionlike; the latter “dual fermion” states are, due to their exclusion-principle-like character, of high energy (i.e., single particle states cannot be multiply occupied). The multiscale perturbation analysis is used to argue for the existence of a coarse-grained wave equation for bosonlike collective behaviors. Quasiparticles, with effective mass and interactions, emerge naturally as consequences of the long-scale dynamics of the constituent particles. The multiscale framework holds promise for facilitating QN computer simulations and novel approximation schemes.
Local domain structure of exchange-coupled NiFe∕CoO nanowire probed by nonlocal spin valve measurement
Authors: Kimura T. , Otani Y.
Published: April 2008

We investigate the local magnetization process in a 100-nm-wide Permalloy/CoO exchange-coupled wire by means of nonlocal spin valve measurements for a structure with lateral geometry. The domain structure in the exchange-coupled wire is found to change with the direction of the exchange bias. When the exchange bias is parallel to the easy axis of the Permalloy wire, the magnetization-reversal process can be expressed by the single domain model. However, when the exchange bias is perpendicular to the easy axis, the magnetization reversal is accompanied by domain nucleation and annihilation processes even in the lateral dimension of 100nm. The reason for the dependence of the domain structure on the direction of the exchange bias is discussed.
High-performance multimedia encryption system based on chaos
Authors: Hasimoto-Beltrán Rogelio
Published: April 2008

Current chaotic encryption systems in the literature do not fulfill security and performance demands for real-time multimedia communications. To satisfy these demands, we propose a generalized symmetric cryptosystem based on N independently iterated chaotic maps (N-map array) periodically perturbed with a three-level perturbation scheme and a double feedback (global and local) to increase the system’s robustness to attacks. The first- and second-level perturbations make cryptosystem extremely sensitive to changes in the plaintext data since the system’s output itself (ciphertext global feedback) is used in the perturbation process. Third-level perturbation is a system reset, in which the system-key and chaotic maps are replaced for totally new values. An analysis of the proposed scheme regarding its vulnerability to attacks, statistical properties, and implementation performance is presented. To the best of our knowledge we provide a secure cryptosystem with one of the highest levels of performance for real-time multimedia communications.
Complex trajectory method in time-dependent WKB
Authors: Goldfarb Yair , Schiff Jeremy , Tannor David J.
Published: April 2008

We present a significant improvement to a complex time-dependent WKB (CWKB) formulation developed by Boiron and Lombardi [J. Chem. Phys. 108, 3431 (1998)] in which the time-dependent WKB equations are solved along classical trajectories that propagate in complex space. Boiron and Lombardi showed that the method gives very good agreement with the exact quantum mechanical result as long as the wavefunction does not exhibit interference effects such as oscillations and nodes. In this paper, we show that this limitation can be overcome by superposing the contributions of crossing trajectories. Secondly, we demonstrate that the approximation improves when incorporating higher order terms in the expansion. Thirdly, equations of motion for caustics and Stokes lines are implemented to help overcome Stokes discontinuities. These improvements could make the CWKB formulation a competitive alternative to current time-dependent semiclassical methods.
Bias temperature instability in metal-oxide-semiconductor field-effect transistors with atomic-layer-deposited Si-nitride/SiO2 stack gate dielectrics
Authors: Zhu Shiyang , Nakajima Anri
Published: April 2008

Bias temperature instability (BTI) in p+ poly-Si gated metal-oxide-semiconductor field-effect transistors (MOSFETs) with atomic-layer-deposited (ALD) Si-nitride/SiO2 stack gate dielectrics was systematically studied using drain current-gate voltage (Id-Vg) and modified direct-current current-voltage (DCIV) measurements. They exhibited quite unique behaviors as compared to the conventional SiON counterpart: turnaround of the threshold voltage shift (ΔVth) during stressing and significant positive BTI in nMOSFETs. The observed phenomena were consistently explained within the framework of conventional reaction-diffusion model for BTI but with two additional assumptions: (1) there exist pre-existing traps in the ALD Si-nitride/SiO2 stack dielectrics and (2) it is the inversion carriers (electrons or holes) rather than the accumulation carriers which effectively dissociate the SiH bonds at the SiO2∕Si interface during BTI stressing. Owing to the absence of nitrogen near the SiO2∕Si interface and the compensation effect on ΔVth between the charge trapping in the pre-existing traps and the dissociation of the SiH bonds under small voltage stress, the ALD Si-nitride/SiO2 stack dielectrics at the operating voltage may have similar or even longer BTI lifetime than the pure SiO2.
First-principles local density approximation (generalized gradient approximation) +U study of catalytic CenOm clusters: U value differs from bulk
Authors: Li S. F. , Lu Heqiang , Li Pinglin , Yang Zongxian , Guo Z. X.
Published: April 2008

Ceria possesses strong catalytic properties for CO∕NOx removal and H2 production. Clusters often show more intriguing functionalities than their bulk counterparts. Here, the geometric and electronic structures of CenOm (n=1–4,m=2n−1,2n) clusters are studied for the first time using the projected augmented wave method in density functional theory with detailed assessment of the exchange-correlation functional and the Hubbard parameter U. We note that the U value strongly affects the electronic structures of the oxygen-deficient CenO2n−1 clusters, though less so on the stoichiometric CenO2n. Furthermore, the local density approximation (LDA)+U method is more accurate than the generalized gradient approximation+U in describing the localization of the 4f electrons of the CenOm clusters. The calculated vibration frequency of the CeO molecule with the LDA+U (U=4eV) is 818.4cm−1, in close agreement with experimental values of 820–825cm−1 for the low lying states. Different optimal U values were noted for the ceria cluster (4eV) and its bulk (6eV), due to quantum-size and geometric effects. The largely reduced formation energy of an oxygen vacancy indicates that the catalytic effect of the CenOm clusters are far greater than bulk CeO2.
Nonassociativity, supersymmetry, and hidden variables
Authors: Dzhunushaliev Vladimir
Published: April 2008

It is shown that the supersymmetric quantum mechanics has an octonionic generalization. The generalization is based on the inclusion of quaternions into octonions. The elements from the coset octonions∕quaternions are unobservables because they cannot be considered as quantum operators as a consequence of their nonassociative properties. The idea that the octonionic generalization of the supersymmetric quantum mechanics describes an observable particle formed with unobservable “particles” is presented.
Nanocavity strengthening: Impact of the broken bonds at the negatively curved surfaces
Authors: Ding Yu , Sun Chang Q. , Zhou Y. C.
Published: April 2008

The atomistic origin of the atomic vacancy or nanocavity induced hardening in hollow nanotubes and nanoporous structures has long been a puzzle. An analysis from the perspective of bond-order–length-strength correlation mechanism [C. Q. Sun, Prog. Solid State Chem. 35, 1 (2007)] has led to solutions that show that the shortened and strengthened bonds between the undercoordinated atoms in the negatively curved surface skins dominate the observed nanocavity strengthening and thermal instability of the porous structures. It is suggested that the broken bond derived local strain and quantum trapping and the associated energy densification provide pinning centers for inhibiting atomic dislocations and that the broken bond induced cohesive energy dropping dominate the thermal instability. On the other hand, nanocavities also provide sites that initiate the structure failure under plastic deformation. The agreement between predictions and the experimentally observed size dependence of mechanical strength of some nanoporous materials and the well-known phenomenon of hollow tube strengthening evidences for the proposed mechanism.
Effects of active atomic sinks and reservoirs on the reliability of Cu∕low-k interconnects
Authors: Wei Frank L. , Hau-Riege Christine S. , Marathe Amit P. , Thompson Carl V.
Published: April 2008

Electromigration experiments using Cu∕low-k interconnect tree structures were carried out in order to study the effects of active atomic sinks and reservoirs on interconnect reliability. In all cases, failures occurred after a long period of void growth. Kinetic parameters were extracted from resistance versus time data, giving (Dz*)0,eff=3.9×10−10m2∕s and z*=0.40±0.12. By using these values, the evolution of stress in each of the interconnect tree segments could be calculated and correlated with the rate of void growth and failure times for all test configurations. It is demonstrated that segments that serve as atomic sinks and reservoirs for the failing segments affect the lifetime by modifying the conditions for stress induced migration. Reservoirs can lead to increased lifetimes, while sinks can lead to reduced lifetimes. Quantitative predictions of the times required for failure for Cu∕low-k interconnect trees as a function of the effective bulk elastic modulus of the interconnect system, B, are made. As Young’s modulus of the interlevel dielectric films decreases, B decreases, and the positive effects of reservoirs are diminished and the negative effects of sinks are amplified.
Thermal conductivity of single crystal and ceramic AlN
Authors: AlShaikhi A. , Srivastava G. P.
Published: April 2008

We have applied the Callaway theory and used a detailed account of three-phonon scattering processes to calculate the thermal conductivity of three AlN single crystal samples containing different amounts of oxygen and two AlN ceramic samples with different grain sizes and oxygen contamination levels. The N-drift contribution to the total conductivity has been quantified. The influence on the thermal conductivity of oxygen-related defects, and grain boundaries in ceramic samples, has been investigated. The theoretical results obtained from this work are in good agreement with available experimental data. Our calculations suggest that the “effective” boundary length is greater than the reported grain size for each of the two ceramic samples studied by Watari et al. [J. Mater. Res. 17, 2940 (2002)].
Is the trend of the polarizability per atom for all small 3d transition metal clusters the same? The case of Nin (n⩽5) clusters
Authors: Calaminici Patrizia
Published: April 2008

The first theoretical study on static polarizability and polarizability anisotropy of small nickel clusters up to the pentamer is presented. All-electron-type calculations were performed using a finite field approach as implemented in the density functional program deMon2K. A newly developed first-order field-induced basis set for density functional calculations was employed. For the static polarizability per atom of these clusters, a different trend to the one reported in the literature for other transition metal cluster systems of similar size, is observed.
Phase transformations in annealed PZN-4.5%PT single crystals
Authors: Lim L. C. , Chang W. S. , Rajan K. K. , Shanthi M. , Yang P. , Moser H. O. , Tu C.-S. , Wang F.-T. , Tseng C.-T. , Bhalla A. S. , Guo R.
Published: April 2008

Phase transformations of annealed bulk 0.955Pb(Zn1/3Nb2/3)O3–0.045PbTiO3 (PZN-4.5%PT) single crystals have been examined by means of dielectric permittivity, thermal current, domain structure, and high-resolution synchrotron x-ray diffraction as a function of temperature. The result shows that annealed (unpoled) bulk PZN-4.5%PT single crystal undergoes an R-T-C transformation sequence upon zero-field heating, where R, T, and C are the rhombohedral, tetragonal, and cubic phases, respectively. Diffractions pertaining to rhombohedral and tetragonal nanotwins are detected. These diffractions can easily be mistaken as the monoclinic diffractions, which, however, are not supported by our thermal current measurement. The nanotwin structure plays an important role in bridging the R-T and T-C transformations, possibly by alleviating the accompanying transformation stresses.
Thermosolutal convection in a horizontal porous layer heated from below in the presence of a horizontal through flow
Authors: Lyubimov D. V. , Lyubimova T. P. , Mojtabi A. , Sadilov E. S.
Published: April 2008

In this paper, we study the effect of a homogeneous longitudinal through flow on the onset of convection in a horizontal porous layer saturated by a binary fluid and heated from below or above. The layer boundaries are subjected to a constant heat flux. The investigation is made by taking the Soret effect into account. It is found that in the case of positive separation ratio when the denser component moves toward the cooler wall, through flow has no effect on the stability threshold but exerts an orientating effect on the convective patterns. For negative separation ratio, a strong destabilization occurs of the spatially homogeneous state with respect to long-wave disturbances. The stability range for long-wavelength convective rolls is defined.
Amorphous phase formation, spinodal decomposition, and fractal growth of nanocrystals in an immiscible Hf–Nb system studied by ion beam mixing and atomistic modeling
Authors: Tai K. P. , He X. , Liu B. X.
Published: April 2008

In the equilibrium immiscible Hf–Nb system characterized by a positive heat of formation, five Hf–Nb metallic glasses with overall compositions of Hf84Nb16, Hf65Nb35, Hf45Nb55, Hf38Nb62, and Hf20Nb80 are obtained by ion beam mixing with properly designed Hf–Nb multilayered films, suggesting a glass-forming composition range of 16–80 at.% of Nb. For the special case of Hf45Nb55 located at the ridge point on the convex free energy curve, dual-glass phases are formed at a dose of 2×1015 Xe+/cm2, which results from a spinodal decomposition of the expected Hf45Nb55 amorphous phase. With increasing irradiation dose, fractal growth of nanocrystals (around 20 nm) appears in the major glass phase and the dimension is determined to be from 1.70 to 1.84 within a dose range of (4–7)×1015 Xe+/cm2. In atomistic modeling, a n-body Hf–Nb potential is first constructed with the aid of ab initio calculations. Applying the constructed potential, molecular dynamics simulations using the hcp and bcc solid solution models, reveals an intrinsic glass-forming range to be within 15–83 at.% of Nb, which is compatible with the ion beam mixing experiments. Moreover, the formation of the metallic glasses and the fractal growth in association with the amorphous spinodal decomposition are also discussed in terms of the atomic collision theory and cluster-diffusion-limited-aggregation model.
Electrotunable polarization of surface-emitting distributed feedback laser with nematic liquid crystals
Authors: Jeong Soon Moon , Ha Na Young , Araoka Fumito , Ishikawa Ken , Takezoe Hideo
Published: April 2008

The authors have demonstrated nanoimprinted polarization-tunable surface-emitting distributed feedback laser by using an aligned dye-doped nematic liquid crystal (NLC) as a tunable phase retarder. Because the lasing emission from nanoimprinted layer is a highly transverse electric mode, the polarization is continuously tunable by electrically controlling NLC orientation. The presented polarization-tunable lasing device will give rise to various opportunities in optical device application and its simple fabrication process can be readily used for large area geometries from the viewpoint of practical application.
Magnetoelastic domains and magnetic field-induced strains in ferromagnetic shape memory alloys by phase-field simulation
Authors: Li L. J. , Li J. Y. , Shu Y. C. , Chen H. Z. , Yen J. H.
Published: April 2008

Magnetoelastic domains in ferromagnetic shape memory alloys evolve through either variant rearrangement or magnetization rotation, resulting in a large or a small magnetic field-induced strain depending on the magnitude of applied compressive stress. These phenomena are simulated in this letter using an unconventional phase-field model motivated by energy-minimizing multirank laminated domain structures. The results agree well with experiments, and confirm the analysis of Ma and Li [Appl. Phys. Lett. 90, 172504 (2007)] based on an energy minimization theory.
On the possibility of degradation-free field effect transistors
Authors: Islam Ahmad Ehteshamul , Alam Muhammad Ashraful
Published: April 2008

Time-dependent change in threshold voltage, due to generation of interface/bulk traps, degrades drain current of field effect transistors. In this paper, we show—both theoretically and experimentally—the intriguing possibility of designing degradation-free transistors (with time-invariant drain current), where the degradation in threshold voltage is exactly compensated by improvement in mobility. Such transistors would reduce parametric reliability being a key concern for supply voltage scaling and thereby improve integrated circuit performance by minimizing the guard band voltage used in very large scale integrated circuit design.
Anemia and splenomegaly in cGKI-deficient mice
Authors: Föller Michael , Feil Susanne , Ghoreschi Kamran , Koka Saisudha , Gerling Andrea , Thunemann Martin , Hofmann Franz , Schuler Beat , Vogel Johannes , Pichler Bernd , Kasinathan Ravi S. , Nicolay Jan P. , Huber Stephan M. , Lang Florian , Feil Robert
Published: April 2008

To explore the functional significance of cGMP-dependent protein kinase type I (cGKI) in the regulation of erythrocyte survival, gene-targeted mice lacking cGKI were compared with their control littermates. By the age of 10 weeks, cGKI-deficient mice exhibited pronounced anemia and splenomegaly. Compared with control mice, the cGKI mutants had significantly lower red blood cell count, packed cell volume, and hemoglobin concentration. Anemia was associated with a higher reticulocyte number and an increase of plasma erythropoietin concentration. The spleens of cGKI mutant mice were massively enlarged and contained a higher fraction of Ter119
+
erythroid cells, whereas the relative proportion of leukocyte subpopulations was not changed. The Ter119
+
cGKI-deficient splenocytes showed a marked increase in annexin V binding, pointing to phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis. Compared with control erythrocytes, cGKI-deficient erythrocytes exhibited
in vitro
a higher cytosolic Ca
2+
concentration, a known trigger of eryptosis, and showed increased PS exposure, which was paralleled by a faster clearance
in vivo
. Together, these results identify a role of cGKI as mediator of erythrocyte survival and extend the emerging concept that cGMP/cGKI signaling has an antiapoptotic/prosurvival function in a number of cell types
in vivo
.
Mathematical modeling identifies Smad nucleocytoplasmic shuttling as a dynamic signal-interpreting system
Authors: Schmierer Bernhard , Tournier Alexander L. , Bates Paul A. , Hill Caroline S.
Published: April 2008

TGF-β-induced Smad signal transduction from the membrane into the nucleus is not linear and unidirectional, but rather a dynamic network that couples Smad phosphorylation and dephosphorylation through continuous nucleocytoplasmic shuttling of Smads. To understand the quantitative behavior of this network, we have developed a tightly constrained computational model, exploiting the interplay between mathematical modeling and experimental strategies. The model simultaneously reproduces four distinct datasets with excellent accuracy and provides mechanistic insights into how the network operates. We use the model to make predictions about the outcome of fluorescence recovery after photobleaching experiments and the behavior of a functionally impaired Smad2 mutant, which we then verify experimentally. Successful model performance strongly supports the hypothesis of a dynamic maintenance of Smad nuclear accumulation during active signaling. The presented work establishes Smad nucleocytoplasmic shuttling as a dynamic network that flexibly transmits quantitative features of the extracellular TGF-β signal, such as its duration and intensity, into the nucleus.
Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in
Saccharomyces cerevisiae
Authors: Puria Rekha , Zurita-Martinez Sara A. , Cardenas Maria E.
Published: April 2008

The yeast
Saccharomyces cerevisiae
has developed specialized mechanisms that enable growth on suboptimal nitrogen sources. Exposure of yeast cells to poor nitrogen sources or treatment with the Tor kinase inhibitor rapamycin elicits activation of Gln3 and transcription of nitrogen catabolite-repressed (NCR) genes whose products function in scavenging and metabolizing nitrogen. Here, we show that mutations in class C and D Vps components, which mediate Golgi-to-endosome vesicle transport, impair nuclear translocation of Gln3, NCR gene activation, and growth in poor nitrogen sources. In nutrient-replete conditions, a significant fraction of Gln3 is peripherally associated with light membranes and partially colocalizes with Vps10-containing foci. These results reveal a role for Golgi-to-endosome vesicular trafficking in TORC1-controlled nuclear translocation of Gln3 and support a model in which Tor-mediated signaling in response to nutrient cues occurs in these compartments. These findings have important implications for nutrient sensing and growth control via mTor pathways in metazoans.
Strengthening prevention programs to eliminate cervical cancer in the Nordic countries
Authors: DILLNER LENA , PAGLIUSI SONIA , BRAY FREDDIE , LORINCZ ATTILA , KJAER SUSANNE K. , ANTTILA AHTI , ERIC IVERSEN OLE , DILLNER JOAKIM , LEHTINEN MATTI , PAAVONEN JORMA
Published: April 2008

Disease trend studies based on birth cohort analysis and serological studies indicate that recent generations have a higher prevalence of oncogenic Human Papilloma Virus (HPV) types, and are likely to be at higher risk of cancer than previous generations. This implies that prevention strategies to protect young populations from HPV‐associated cancers need to be strengthened, and hence organized implementation of vaccination and better screening programs are being considered. In this context, randomized large‐scale policy evaluations will be instrumental in accelerating disease control and improve effective prevention programs. This report shares experiences from Nordic countries with examples of prevention strategies through vaccination and cervical screening. The same principles as set up for organized programs and new HPV technologies may apply for screening and vaccination as key tools to eliminate cervical cancer in the Nordic countries and globally.
Moderate neonatal encephalopathy: Pre‐ and perinatal risk factors and long‐term outcome
Authors: LINDSTRÖM KATARINA , HALLBERG BOUBOU , BLENNOW MATS , WOLFF KERSTIN , FERNELL ELISABETH , WESTGREN MAGNUS
Published: April 2008

Background. The aim was to describe pre‐ and perinatal data and long‐term neurodevelopmental outcome (15–19 years) in children born at term with Apgar score <7 at 5 min and moderate neonatal encephalopathy. Methods. The study is based on a population‐based birth‐cohort of children born in Sweden in 1985. Maternal, delivery, neonatal, and neuropaediatric data were compiled. Neurodevelopmental status was classified according to the presence of 1. cerebral palsy or other major impairments, 2. exclusively cognitive impairments, and 3. no impairments. Results. The majority of the children (81%) had cognitive dysfunctions, with or without other impairments, such as cerebral palsy. The rates of post‐term birth (19% versus 8%) and breech presentation (12% versus 3%) were significantly higher than in the general Swedish population. Pre‐ and perinatal data did not differ notably between the three outcome groups. Questionable or suboptimal obstetric care was common (55%). Conclusions. The study shows that children born at term with moderate neonatal encephalopathy have a high rate of cognitive dysfunctions with or without cerebral palsy at long‐term follow‐up. Our pre‐ and perinatal data did not correlate with outcome.
Effects of pre‐pregnancy physical activity and maternal BMI on gestational weight gain and birth weight
Authors: LÖF MARIE , HILAKIVI‐CLARKE LEENA , SANDIN SVEN , WEIDERPASS ELISABETE
Published: April 2008

Background. Western women frequently exhibit excessive gestational weight gain (GWG). The effects of maternal physical activity level (PAL) and body mass index (BMI) on the timing of GWG are insufficiently known.Purpose. To assess the impact of pre‐pregnancy PAL and BMI on GWG during the second and third trimester and on birth weight.Methods. Body weight was measured in 223 healthy Swedish women in gestational weeks 12, 25 and 33, and GWG during the second (weeks 12–25) and third trimesters (weeks 25–33) was determined (kg/week). PAL was assessed using a questionnaire. Birth weights were obtained from birth records. The results were evaluated by the fitting of linear statistical models.Results.Some 50 and 80% of the women exhibited excessive GWG during the second and third trimesters, respectively. Women with a high pre‐pregnancy PAL gained 0.10 kg/week (p= 0.04) less weight during the third trimester than women with a medium PAL. A 5 kg/m2higher BMI was associated with a 0.06 kg/week lower GWG in the second trimester (p= 0.005), but with a 0.05 higher GWG in the third trimester (p= 0.03). Maternal BMI (p= 0.014) and total GWG (p= 0.05) correlated with birth weight.Conclusions.High BMI and low pre‐pregnancy PAL were associated with excessive GWG. BMI and GWG, but not pre‐pregnancy PAL, were linked to birth weight. However, together with smoking, parity, education and age, pre‐pregnancy PAL and BMI explained only 4% of the variation in GWG. Thus, identification of other factors that could explain excessive GWG is an important area of future research.
Interobserver agreement in the assessment of intrapartum automated fetal electrocardiography in singleton pregnancies
Authors: OJALA KATI , MÄKIKALLIO KAARIN , HAAPSAMO MERVI , IJÄS HILKKA , TEKAY AYDIN
Published: April 2008

Objective. To study interobserver agreement in the assessment of intrapartum automated fetal electrocardiogram ST interval analysis (STAN). Design. Observational study. Setting. Labor ward in tertiary level university hospital. Sample. Two hundred (140 reassuring and 60 non‐reassuring) STAN recordings on non‐selected women with singleton, vertex, term pregnancies were selected from our archive. Samples of 60‐min were analysed from the end of each recording, excluding the last 30 min before delivery. Methods. Three consultants, who had undergone STAN training and had clinical experience in using STAN, reviewed the recordings using cardiotocography (CTG) and ST information with no clinical data. The reviewers were asked to follow STAN guidelines and (1) to classify the CTG as normal, intermediary, abnormal, or preterminal, and (2) to make a clinical decision on labor management. Main outcome measures. Interobserver agreement evaluated by weighted kappa (κw) values and the proportion of agreement. Results. In CTG classification, the interobserver agreement between three observers was moderate (κw, 0.47–0.48). The proportion of agreement was 56–59%. In clinical decision‐making, κw values varied from 0.47 to 0.60, and the proportion of agreement was 80–86%. Conclusions. In non‐selected term pregnancies, the interobserver agreement among experienced obstetricians in the classification of CTG and clinical decision‐making according to STAN guidelines is moderate at best.
Term perinatal mortality and morbidity in monochorionic and dichorionic twin pregnancies: A retrospective study
Authors: LOPRIORE ENRICO , STROEKEN HISKE , SUETERS MARIEKE , MEERMAN ROBERT‐JAN , WALTHER FRANS , VANDENBUSSCHE FRANK
Published: April 2008

Aim. Perinatal mortality and morbidity in monochorionic (MC) twins appears to be increasing compared to dichorionic (DC) twins. The aim of our study was to determine the difference in perinatal mortality and morbidity in MC and DC twins born after 37 weeks’ gestation. Design. A retrospective, cross‐sectional study of medical records. Setting. Large tertiary care centre in the Netherlands. Population. All twins delivered ≥37 gestational weeks at the Leiden University Medical Centre between 1988 and 2004 were included in the study. Methods. Perinatal outcome was assessed in all term twins. Differentiation between a MC study group and a DC control group was made based on gender, intertwin membrane histology, or first trimester ultrasound. Main outcome measures. Perinatal mortality and morbidity was assessed. Morbidity was defined as admission to the neonatal nursery. Results. We included 383 DC and 74 MC twin pregnancies. Three fetuses died in utero in two MC pregnancies at 38 gestational weeks. One surviving MC co‐twin had a right‐sided hemiparesis due to a large parenchymal defect in the left cerebral hemisphere. Perinatal mortality was 2% (3/148) in MC and 0% (0/766) in DC twins (p = 0.004). The admission rate to the neonatal nursery was 27% in MC and 19% in DC twins (p = 0.031). Conclusions. At term, MC twins have a higher risk for perinatal mortality and a higher admission rate to the neonatal nursery compared to DC twins. Given the increased mortality, a prospective study is needed to determine the effects of elective delivery in uncomplicated MC twin pregnancies at around 37 weeks’ gestation.
Mapping practice onto theory: the speech and language practitioner's construction of receptive language impairment
Authors: Law J. , Campbell C. , Roulstone S. , Adams C. , Boyle J.
Published: April 2008

Background:Receptive language impairment (RLI) is one of the most significant indicators of negative sequelae for children with speech and language disorders. Despite this, relatively little is known about the most effective treatments for these children in the primary school period.

Aims:To explore the relationship between the reported practice of speech and language practitioners and the underlying rationales for the therapy that they provide.

Methods & Procedures:A phenomenological approach was adopted, drawing on the experiences of speech and language practitioners. Practitioners completed a questionnaire relating to their practice for a single child with receptive language impairment within the 5–11 age range, providing details and rationales for three recent therapy activities. The responses of 56 participants were coded. All the children described experienced marked receptive language impairments, in the main associated with expressive language difficulties and/or social communication problems.

Outcome & Results:The relative homogeneity of the presenting symptoms in terms of test performance was not reflected in the highly differentiated descriptions of intervention. One of the key determinants of how therapists described their practice was the child's age. As the child develops the therapists appeared to shift from a ‘skills acquisition’ orientation to a ‘meta‐cognitive’ orientation, that is they move away from teaching specific linguistic behaviours towards teaching children strategies for thinking and using their language. A third of rationales refer to explicit theories but only half of these refer to the work of specific authors. Many of these were theories of practice rather than theories of deficit, and of those that do cite specific theories, no less than 29 different authors were cited many of whom might best be described as translators of existing theories rather than generators of novel theories.

Conclusions:While theories of the deficit dominate the literature they appear to play a relatively small part in the eclectic practice of speech and language therapists. Theories of therapy may develop relatively independent of theories of deficit. While this may not present a problem for the practitioner, whose principal focus is remediation, it may present a problem for the researcher developing intervention efficacy studies, where the theory of the deficit will need to be well‐defined in order to describe both the subgroup of children under investigation and the parameters of the deficit to be targeted in intervention.
Ability of children with language impairment to understand emotion conveyed by prosody in a narrative passage
Authors: Fujiki Martin , Spackman Matthew P. , Brinton Bonnie , Illig Tori
Published: April 2008

Background: Several recent studies have indicated that children with language impairment experience difficulty with various aspects of emotion understanding. Because emotion understanding skills are critical to successful social interaction, it is possible that these deficits play a role in the social problems frequently experienced by children with language difficulties.

Aims: To explore further the emotion understanding skills of children with language impairment, the investigation examined the ability of these children to understand emotion conveyed by prosody in a narrative passage.

Methods & Procedures: Nineteen children with language impairment and their chronological age‐matched peers served as participants. Children were sampled from the age range of 8–10;10 years. These children were presented with a seven‐sentence narrative read by actors to express happiness, anger, sadness, and fear. They were then asked to indicate what emotion the speaker expressed.

Outcomes & Results: Children with language impairment performed significantly more poorly than their typical peers in identifying the emotion expressed in the passage. There were also differences between emotions, with happiness being the easiest emotion to identify and fear the most difficult. The interaction between group and emotion type was not statistically significant.

Conclusions: The results provide additional evidence that children with language impairment may have impairments in emotion understanding. If these findings are replicated, interventions designed to facilitate emotion understanding as an aspect of social communication should be considered for some children with language impairment.
Telomere dysfunction and cell survival: roles for distinct TIN2-containing complexes
Authors: Kim Sahn-ho , Davalos Albert R. , Heo Seok-Jin , Rodier Francis , Zou Ying , Beausejour Christian , Kaminker Patrick , Yannone Steven M. , Campisi Judith
Published: April 2008

Telomeres are maintained by three DNA-binding proteins (telomeric repeat binding factor 1 [TRF1], TRF2, and protector of telomeres 1 [POT1]) and several associated factors. One factor, TRF1-interacting protein 2 (TIN2), binds TRF1 and TRF2 directly and POT1 indirectly. Along with two other proteins, TPP1 and hRap1, these form a soluble complex that may be the core telomere maintenance complex. It is not clear whether subcomplexes also exist in vivo. We provide evidence for two TIN2 subcomplexes with distinct functions in human cells. We isolated these two TIN2 subcomplexes from nuclear lysates of unperturbed cells and cells expressing TIN2 mutants TIN2-13 and TIN2-15C, which cannot bind TRF2 or TRF1, respectively. In cells with wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere uncapping and eventual growth arrest. In cells lacking p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere dysfunction and cell death. Our findings suggest that distinct TIN2 complexes exist and that TIN2-15C–sensitive subcomplexes are particularly important for cell survival in the absence of functional p53.
All quiet on the neuronal front: NMDA receptor inhibition by prion protein
Authors: Steele Andrew D.
Published: April 2008

The normal function of the prion protein (PrP)—the causative agent of mad cow or prion disease—has long remained out of reach. Deciphering PrP's function may help to unravel the complex chain of events triggered by PrP misfolding during prion disease. In this issue of the JCB, an exciting paper (Khosravani, H., Y. Zhang, S. Tsutsui, S. Hameed, C. Altier, J. Hamid, L. Chen, M. Villemaire, Z. Ali, F.R. Jirik, and G.W. Zamponi. 2008. J. Cell Biol. 181:551–565) connects diverse observations regarding PrP into a coherent framework whereby PrP dampens the activity of an N-methyl-d-aspartate (NMDA) receptor (NMDAR) subtype and reduces excitotoxic lesions. The findings of this study suggest that understanding the normal function of proteins associated with neurodegenerative disease may elucidate the molecular pathogenesis.
MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells
Authors: Huang Shouxiong , Gilfillan Susan , Kim Sojung , Thompson Bruce , Wang Xiaoli , Sant Andrea J. , Fremont Daved H. , Lantz Olivier , Hansen Ted H.
Published: April 2008

Like CD1d-restricted iNKT cells, mucosal-associated invariant T cells (MAITs) are “innate” T cells that express a canonical TCRα chain, have a memory phenotype, and rapidly secrete cytokines upon TCR ligation. Unlike iNKT cells, MAIT cells require the class Ib molecule MHC-related protein I (MR1), B cells, and gut flora for development and/or expansion, and they preferentially reside in the gut lamina propria. Evidence strongly suggests that MAIT cell activation is ligand-dependent, but the nature of MR1 ligand is unknown. In this study, we define a mechanism of endogenous antigen presentation by MR1 to MAIT cells. MAIT cell activation was dependent neither on a proteasome-processed ligand nor on the chaperoning by the MHC class I peptide loading complex. However, MAIT cell activation was enhanced by overexpression of MHC class II chaperones Ii and DM and was strikingly diminished by silencing endogenous Ii. Furthermore, inhibiting the acidification of the endocytic compartments reduced MR1 surface expression and ablated MAIT cell activation. The importance of the late endosome for MR1 antigen presentation was further corroborated by the localization of MR1 molecules in the multivesicular endosomes. These findings demonstrate that MR1 traffics through endocytic compartments, thereby allowing MAIT cells to sample both endocytosed and endogenous antigens.