bluuebunny/crossref_metadata_2025 huggingface dataset:
Decadal variations of temperature and geopotential height over the Tibetan Plateau and their relations with Tibet ozone depletion
Authors: Zhou Shunwu , Zhang Renhe
Published: September 2005

The Total Ozone Mapping Spectrometer/Solar Backscatter Ultraviolet (TOMS/SBUV) merged total ozone data, and the Tibetan Plateau radiosonde reports during the period from 1979 to 2002 are used in this paper, we study the decadal variations of temperature and geopotential height over the Tibetan Plateau and their relationship with changes of Tibet total ozone. It is found that temperature and geopotential height over the Tibetan Plateau have displayed declining trends in the stratosphere and positive trends in the troposphere since the late 1970s, well consistent with Tibet total ozone depletion. The possible role of ozone in long‐term changes of temperature and geopotential height is proposed.
Attribution studies of observed land precipitation changes with nine coupled models
Authors: Lambert F. Hugo , Gillett Nathan P. , Stone Dáithí A. , Huntingford Chris
Published: September 2005

Global‐land mean observations of 20th century precipitation are compared to modelled values using an optimal regression technique for nine general circulation models. The combined influence of major anthropogenic and natural forcings is detected in five cases. Comparing the accuracy of precipitation and temperature simulation of each model, we find that low temperature simulation accuracy produces low precipitation simulation accuracy, but temperature accuracy does not determine precipitation accuracy in general. Model formulation appears to be more important for accurate precipitation simulation than inclusion of a more complete set of forcings. The implications for possible constraints on land precipitation are discussed.
Meaning in the Context of Stress and Coping
Authors: Park Crystal L. , Folkman Susan
Published: September 2005

Although theoretical and empirical work on topics related to meaning and meaning making proliferate, careful evaluation and integration of this area have not been carried out. Toward this end, this article has 3 goals: (a) to elaborate the critical dimensions of meaning as it relates to stressful life events and conditions, (b) to extend the transactional model of stress and coping to include these dimensions, and (c) to provide a framework for understanding current research and directions for future research within this extended model. First, the authors present a framework for understanding diverse conceptual and operational definitions of meaning by distinguishing 2 levels of meaning, termed global meaning and situationalmeaning. Second, the authors use this framework to review and synthesize the literature on the functions of meaning in the coping process and propose a definition of meaningmaking that highlights the critical role of reappraisal. The authors specify the roles of attributions throughout the coping process and discuss implications for future research.
Aesthetics and the Environment
Authors: Averill James R. , Stanat Petra , More Thomas A.
Published: September 2005

This article presents a framework for understanding aesthetic experience, with special reference to the natural environment. The framework entails 2 broad perspectives. First, from a functional perspective, aesthetic experiences are analyzed in terms of biological, sociocultural, and psychological systems of behavior; succinctly stated, objects are experienced aesthetically if they activate cognitive representations of response patterns that do or did contribute to the survival or enhancement of the species, society, or the self. Second, from the perspective of mediating mechanisms, the cognitive processes that enable aesthetic experiences are examined. The mechanisms discussed range from simple sensory processes to the activation and transformation of complex schemas. To the extent that cognitive representations of behavioral systems are flexible and subject to elaboration and refinement, aesthetic experience is a creative, skillful act.
Laboratory Research on Self-Control: Applications to Administration
Authors: Logue A. W.
Published: September 2005

Administrators must sometimes choose between a less delayed but ultimately less valued outcome (impulsiveness) and a more delayed but ultimately more valued outcome (self-control). Which choice is made can affect the long-term health of an administrator's organization. Self-control laboratory research and analysis can be useful in understanding and possibly modifying these choices. This article describes some of the extensive basic laboratory research and analysis concerning self-control and applies this information to specific situations in administration, particularly higher education administration. It discusses the various factors that affect self-control and examines choices between negative, as well as positive, outcomes. Laboratory and nonlaboratory investigations can benefit from attending to information obtained from the other domain.
Interfacial electron dynamics and hot-electron-driven surface photochemistry of carbon tetrachloride on Ag(111)
Authors: Ryu Sunmin , Chang Jinyoung , Kim Seong Keun
Published: September 2005

We used time-resolved two-photon photoemission (2PPE) spectroscopy to investigate the photochemical behavior, the interfacial electronic structure, and the fate of photogenerated hot electron for carbon tetrachloride adsorbed on Ag(111). The photodissociation cross section was determined over a wide range of photon energy from 1.62to5.69eV, which suggested a low-lying electron affinity level of adsorbed CCl4. A CCl4-derived unoccupied state located at 3.41eV above the Fermi level was attributed to an image potential (IP) state based on its binding energy and effective mass. Polarization dependence of the 2PPE signal revealed that the IP state was populated by an indirect excitation process involving scattering of photoexcited hot electrons rather than direct electronic transition from a bulk band. The lifetime of the IP state was much shorter on the CCl4-covered Ag(111) surface than on the clean one, implying that the electron in the IP state is scavenged effectively by CCl4, probably through dissociative attachment to it. These results are significant in the sense that they provide dynamical evidence for a new relaxation pathway of the IP state in addition to the more common pathway involving back transfer of electron to the substrate.
Multi-keV x-ray conversion efficiencies of laser-preexploded titanium foils
Authors: Girard F. , Jadaud J. P. , Naudy M. , Villette B. , Babonneau D. , Primout M. , Miller M. C. , Kauffman R. L. , Suter L. J. , Grun J. , Davis J.
Published: September 2005

In the context of target design for multi-keV x-ray laser-produced experiments, the concept of exploding metallic thin foils by two laser pulses delayed in time has been tested at the OMEGA laser facility [J. M. Soures, R. L. McCrory, C. P. Verdon et al., Phys. Plasma 3, 2108 (1996)]. The first laser pulse creates an underdense plasma (ne∕nc≈0.2), and the second laser pulse heats the plasma plume which produces strong line emission from the titanium K shell (Heα at 4.7 keV and Hα at 4.9 keV). Six OMEGA beams (500-ps duration) for the prepulse and nine beams (1-ns duration) for the heating pulse irradiate one side of the foil. Different experimental conditions have been investigated in order to optimize the conversion efficiency enhancement on titanium foils. The influences of the foil thicknesses (5 and 6 μm), the delays (3, 4, and 5 ns) between the laser pulses, and the laser intensities (1.3 and 2.2×1015Wcm−2) have been tested. The absolute output power was measured by a set of filtered x-ray diodes, giving conversion efficiencies (CEs) up to 3.6% in 2π for energies above 4 keV with a preformed plasma, to be compared to the case without a prepulse where the CE is 1.5%. This double-pulse concept in this case shows an increase of CE by a factor of 2.4 for titanium thin foils. CE up to 4.9% has been reached with a laser intensity of 2.2×1015Wcm−2.
Condensed-to-atoms electronic Fukui functions within the framework of spin-polarized density-functional theory
Authors: Chamorro Eduardo , Pérez Patricia
Published: September 2005

A simple formalism devised to calculate the condensed-to-atoms Fukui function [R. R. Contreras, P. Fuentealba, M. Galván, and P. Pérez, Chem. Phys. Lett. 304, 405 (1999)] has been further analyzed within a spin-polarized density-functional theory framework. The model is based on a frozen-core approximation to these local reactivity indices [M. Galván, A. Vela, and J. L. Gázquez, J. Phys. Chem. 92, 6470 (1988)], giving us an extended local reactivity description of systems based on the frontier spin-up and spin-down molecular orbitals. Degenerate molecular spin orbitals have been explicitly included in our model equations. Computational results for the nitric oxide (NO) and some simple carbene systems are presented in order to test the model. These quantities have been discussed in the context of changes both in charge density and spin density within the context of electron charge transfer or spin-polarization processes.
Convective particle transport arising from poloidal inhomogeneity in tokamak H mode
Authors: Kasuya N. , Itoh K.
Published: September 2005

In tokamak high-confinement modes (H modes), a large poloidal flow exists within an edge transport barrier, and the electrostatic potential and density profiles can be steep both in the radial and poloidal directions. The two-dimensional structures of the electrostatic potential, density, and flow velocity near the edge of a tokamak plasma are investigated. The analysis is carried out with the momentum conservation law using the shock ordering. For the case with a strong radial electric field (H-mode case), a particle flux is induced from asymmetry of the poloidal electric field in the transport barrier. This convective transport is found to depend weakly on collisionality, and changes its direction in accordance with the direction of the radial electric field, the toroidal magnetic field, and the plasma current. The divergence of a particle flux is a source of temporal variation of the density, and there are negative divergence regions both in the inward and outward flux cases. Thus this convective particle flux is a new candidate for the cause of the rapid establishment of the density pedestal after the onset of low to high confinement mode (L∕H) transition.
Basic turbulence studies on TORPEX and challenges in the theory-experiment comparison
Authors: Müller S. H. , Fasoli A. , Labit B. , McGrath M. , Pisaturo O. , Plyushchev G. , Podestà M. , Poli F. M.
Published: September 2005

TORPEX [A. Fasoli, B. Labit, M. McGrath, S. H. Müller, M. Podestà, and F. M. Poli, Bull. Am. Phys. Soc. 48, 119 (2003)] is dedicated to the study of electrostatic instabilities, turbulence, and transport. Plasmas are produced by waves in the electron cyclotron frequency range and are confined by a toroidal magnetic field of about 0.1T to which a small vertical component Bz is added. The crucial role of Bz for the basic confinement scheme through the generation of parallel flows has been studied previously. This paper focuses on the effects of Bz on turbulence. The observed strong dependence indicates an intrinsic coupling between average profiles, confinement, and turbulence regulated by the action of Bz. Two approaches to characterize turbulence are adopted, via time series statistics and via the direct measurement of spatiotemporal structures, made possible by the novel hexagonal turbulence imaging probe diagnostic, which is described in detail. Analysis methods to condense the large amount of data of such imaging diagnostics are proposed.
Correlation effects and electronic properties of Cr-substituted SZn with an intermediate band
Authors: Tablero C.
Published: September 2005

A study using first principles of the electronic properties of S32Zn31Cr, a material derived from the SZn host semiconductor where a Cr atom has been substituted for each of the 32 Zn atoms, is presented. This material has an intermediate band sandwiched between the valence and conduction bands of the host semiconductor, which in a formal band-theoretic picture is metallic because the Fermi energy is located within the impurity band. The potential technological application of these materials is that when they are used to absorb photons in solar cells, the efficiency increases significantly with respect to the host semiconductor. An analysis of the gaps, bandwidths, density of states, total and orbital charges, and electronic density is carried out. The main effects of the local-density approximation with a Hubbard term corrections are an increase in the bandwidth, a modification of the relative composition of the five d and p transition-metal orbitals, and a splitting of the intermediate band. The results demonstrate that the main contribution to the intermediate band is the Cr atom. For values of U greater than 6 eV, where U is the empirical Hubbard term U parameter, this band is unfolded, thus creating two bands, a full one below the Fermi energy and an empty one above it, i.e., a metal-insulator transition.
Reaction barrier heights from an exact-exchange-based density-functional correlation model
Authors: Dickson Ross M. , Becke Axel D.
Published: September 2005

A recent exact-exchange-based density-functional model of nondynamical and dynamical correlation [A.D. Becke, J. Chem. Phys. 122, 064101 (2005)] is tested on 70 barrier heights for a variety of reaction types: hydrogen transfer reactions, heavy-atom transfer reactions, nucleophilic substitutions, association reactions, and unimolecular rearrangements, including both even- and odd-electron systems. The mean absolute error with respect to accurate reference data is 1.4kcal∕mol. This is achieved without any refitting of the parameters of the model to the barrier height data.
Imaging the doping and electroluminescence in extremely large planar polymer light-emitting electrochemical cells
Authors: Gao Jun , Dane Justin
Published: September 2005

An extremely large planar polymer light-emitting electrochemical cell with an interelectrode spacing of 11mm has been demonstrated. The large planar device structure allows for the imaging of doping propagation, photoluminescence, and electroluminescence (EL) with high spatial and temporal resolutions. Several unconventional EL modes have been observed based on the direct imaging of these devices with an interelectrode spacing ranging from 0.6to11mm. These include transient EL in a dynamic-junction device, EL from planar polymer/polymer heterojunction devices, and anomalous reverse-bias EL in a frozen-junction device. Transient EL occurs when the polarity of the applied bias is reversed after the device is fully turned on. The reversal of the applied bias causes the initiation and uneven propagation of fresh p doping within previously n-doped regions, and vise versa. This leads to the formation of transient, discrete, light-emitting p-n junctions near the electrodes before a continuous light-emission zone is formed by the complete reversal of the doping profile. In addition, planar cells consisting of a side-by-side polymer/polymer heterojunction have been demonstrated and imaged. The heterojunction in all working devices is found to be electronically conductive, but exhibits different ion-transport properties. Three types of polymer/polymer interface have been identified based on the imaging of doping and EL profiles. Finally, an anomalous reverse-bias EL mode has been observed in a planar frozen-junction device. The device was turned on at elevated temperature and then cooled to 200K. Stress under a constant reverse bias leads to the activation of anomalous EL that originates from the same region as forward-bias EL. Furthermore, both forward- and reverse-bias EL have been found to increase with time under reverse-bias stress.
Molecular size effect in NCO and NCS dianion resonances
Authors: Svendsen A. , El Ghazaly M. O. A. , Andersen L. H.
Published: September 2005

Cross sections for electron-impact detachment and electron-impact dissociation of NCO− and NCS− were measured from about 3 to about 40 eV. The former are found to follow a classical prediction with a threshold energy of 9.1±0.1eV for NCO− and 8.9±0.2eV for NCS−. When the incoming electron binds to the monoanion, a short-lived dianion complex is formed, which is revealed as a resonance in the cross section. For NCO− a resonance is evident at 9.3±0.2eV, which implies that the dianion lies above the monoanion by this amount of energy. In the case of NCS− two resonances are evident at 8.4±0.2 and 19.0±0.5eV, respectively. The low-energy NCS dianion is less unstable than the dianion of NCO, which in turn is less unstable than the CN dianion (10-eV resonance). Thus the resonance shifts down in energy with the increasing size of the anion, a fact which is attributed to a decrease in Coulomb energy between the spatially separated electrons.
Dynamic studies of small animals with a four-color diffuse optical tomography imager
Authors: Schmitz Christoph H. , Graber Harry L. , Pei Yaling , Farber Mark , Stewart Mark , Levina Rita D. , Levin Mikhail B. , Xu Yong , Barbour Randall L.
Published: September 2005

We present newly developed instrumentation for full-tomographic four-wavelength, continuous wave, diffuse optical tomography (DOT) imaging on small animals. A small-animal imaging stage was constructed, from materials compatible with in-magnet studies, which offers stereotaxic fixation of the animal and precise, stable probe positioning. Instrument performance, based on calibration and phantom studies, demonstrates excellent long-term signal stability. DOT measurements of the functional rat brain response to electric paw stimulation are presented, and these demonstrate high data quality and excellent sensitivity to hemodynamic changes. A general linear model analysis on individual trials is used to localize and quantify the occurrence of functional behavior associated with the different hemoglobin state responses. Statistical evaluation of outcomes of individual trials is employed to identify significant regional response variations for different stimulation sites. Image results reveal a diffuse cortical response and a strong reaction of the thalamus, both indicative of activation of pain pathways by the stimulation. In addition, a weaker lateralized functional component is observed in the brain response, suggesting presence of motor activation. An important outcome of the experiment is that it shows that reactions to individual provocations can be monitored, without having to resort to signal averaging. Thus the described technology may be useful for studies of long-term trends in hemodynamic response, as would occur, for example, in behavioral studies involving freely moving animals.
Locating the lowest free-energy point on conical intersection in polar solvent: Reference interaction site model self-consistent field study of ethylene and CH2NH2+
Authors: Yamazaki Shohei , Kato Shigeki
Published: September 2005

We present a theoretical method for locating the lowest free-energy points on conical intersections (CIs) in solution using the reference interaction site model self-consistent field (RISM-SCF) theory. Based on the linear-response theory, the nonequilibrium free energy is defined as a quadratic function of solvation coordinates, the parameters in which are directly obtained by ab initio RISM-SCF calculations. This free energy is easily incorporated into an efficient CI optimization procedure in gas phase. The present method is applied to the cis-trans photoisomerizations of ethylene and methaniminium cation (CH2NH2+) in polar solvents. We show that the geometries and energies of CIs are largely affected by the solute-solvent electrostatic interaction. In particular, the hydrogen migration of ethylene observed at CIs in the gas phase disappears in protic solvents due to the large stabilization of the zwitterionic state.
Role of effective potential barriers in the nonlinear screening regime: Grain charging and ion drag force
Authors: Tsytovich V. N. , de Angelis U. , Ivlev A. V. , Morfill G. E. , Khrapak S. A.
Published: September 2005

The effects of barriers in the effective potential of ion-grain interaction on grain charging and ion drag force are investigated in the nonlinear regime of grain screening. The use of analytical fittings of the numerical solutions to the Poisson’s equation for the electrostatic potential around a dust grain assuming nonlinear dependence of polarization charge around the grain on electrostatic potential allows us to present the results in analytical form. This can be useful since the previous investigations use complex numerical calculations.
Rayleigh-Taylor and Richtmyer-Meshkov instabilities and mixing in stratified cylindrical shells
Authors: Mikaelian Karnig O.
Published: September 2005

We study the linear stability of an arbitrary number N of cylindrical concentric shells undergoing a radial implosion or explosion.We derive the evolution equation for the perturbation ηi at interface i; it is coupled to the two adjacent interfaces via ηi±1. For N=2, where there is only one interface, we verify Bell’s conjecture as to the form of the evolution equation for arbitrary ρ1 and ρ2, the fluid densities on either side of the interface. We obtain several analytic solutions for the N=2 and 3 cases. We discuss freeze-out, a phenomenon that can occur in all three geometries (planar, cylindrical, or spherical), and “critical modes” that are stable for any implosion or explosion history and occur only in cylindrical or spherical geometries. We present numerical simulations of possible gelatin-ring experiments illustrating perturbation feedthrough from one interface to another. We also develop a simple model for the evolution of turbulent mix in cylindrical geometry and define a geometrical factor G as the ratio hcylindrical∕hplanar between the cylindrical and planar mixing layers. We find that G is a decreasing function of R∕R0 implying that in our model hcylindrical evolves faster (slower) than hplanar during an implosion (explosion).
Orientation distribution of cylindrical particles suspended in a turbulent pipe flow
Authors: Zhang Ling-Xin , Lin Jian-Zhong , Chan T. L.
Published: September 2005

A model of turbulent cylindrical particle suspensions is proposed to predict the orientation distribution of particles. The fluctuating equation for the orientation distribution function (ODF) of cylindrical particles is theoretically solved using the method of characteristics. The orientation-correlated terms in the mean equation for the ODF due to the random motion of cylindrical particles are related to the correlations of the mean ODF and the fluid velocity gradient. Thus, the evolution of the mean ODF is described by a modified convection-dispersion equation. The model and modified equation are used to calculate the ODF in a pipe flow numerically. The results compare qualitatively with the experimental data and show that the turbulent dispersion makes cylindrical particles have a broad orientation distribution, while the velocity gradient plays an opposite role. The increase of the particle aspect ratio leads to a less aligned distribution in the vicinity of the axis and a narrower orientation distribution at positions far from the axis.
Internal kink mode stabilization and the properties of auxiliary heated ions
Authors: Graves Jonathan P.
Published: September 2005

The stability of the internal kink mode is analyzed in terms of the essential properties of auxiliary heated ions. A fundamental difference between fusion born alpha particles and auxiliary heated ions is that the latter are typically anisotropically distributed. The effect of anisotropy, which is usually ignored in the fluid contribution of hybrid kinetic-magnetohydrodynamic codes, provides a stabilizing effect for populations that have a large passing fraction. The effect on internal kink mode stability is further modified by crucial finite orbit effects if the distribution is asymmetric in v‖, such as for unbalanced beam ion populations. Additionally, such heating scenarios transfer momentum to the background plasma thereby especially modifying the kinetic response of thermal ions. In contrast, anisotropic distributions with large trapped fractions incur improved kinetic stability, but at the cost of increased fluid instability, which is partially due to the effect of anisotropy on the equilibrium.
Linear forcing in numerical simulations of isotropic turbulence: Physical space implementations and convergence properties
Authors: Rosales Carlos , Meneveau Charles
Published: September 2005

Numerical simulations of forced isotropic turbulence are most often formulated in Fourier space, where forcing is applied to low-wavenumber modes. For applications in physical space, low-wavenumber forcing is difficult to implement. The linear forcing recently proposed by Lundgren [“Linearly forced isotropic turbulence,” in Annual Research Briefs (Center for Turbulence Research, Stanford, 2003), pp. 461–473], where a force proportional to velocity is applied, is an attractive alternative but not much is known about its properties. Using numerical experimentation, various properties of the linear forcing are explored: (i) it is shown that when implemented in physical space, linear forcing gives the same results as in spectral implementations; (ii) it is shown that the linearly forced system converges to a stationary state that depends on domain size and Reynolds number, but not on the spectral shape of the initial condition; (iii) it is also shown that the extent of Kolmogorov −5∕3 range is similar to that achieved using the standard band-limited forcing schemes but the integral length scale l=urms3∕ε is smaller, thus reducing the effective scaling range for a given resolution. It is concluded that linear forcing is a useful alternative method that does not require transformation to Fourier space and is easily integrated into physical-space numerical codes.
Saturation of the magnetorotational instability
Authors: Knobloch Edgar , Julien Keith
Published: September 2005

An analytical theory is developed that describes asymptotically exactly the process of nonlinear saturation of the magnetorotational instability in a model problem employing a linear shear flow in a uniformly rotating channel. The theory shows that the instability saturates by modifying the shear responsible for it. The saturation process requires both viscous and Ohmic dissipation. The theory also describes the approach from small-amplitude perturbations to the final strongly nonlinear saturated state.
On spectral scaling laws for incompressible anisotropic magnetohydrodynamic turbulence
Authors: Galtier Sébastien , Pouquet Annick , Mangeney André
Published: September 2005

A heuristic model is given for anisotropic magnetohydrodynamics turbulence in the presence of a uniform external magnetic field B0ê‖. The model is valid for both moderate and strong B0 and is able to describe both the strong and weak wave turbulence regimes as well as the transition between them. The main ingredient of the model is the assumption of constant ratio at all scales between the linear wave period and the nonlinear turnover time scale. Contrary to the model of critical balance introduced by Goldreich and Sridhar [Astrophys. J. 438, 763 (1995)], it is not assumed, in addition, that this ratio be equal to unity at all scales. This allows us to make use of the Iroshnikov–Kraichnan phenomenology; it is then possible to recover the widely observed anisotropic scaling law k‖∝k⊥2∕3 between parallel and perpendicular wave numbers (with reference to B0ê‖) and to obtain for the total-energy spectrum E(k⊥,k‖)∼k⊥−αk‖−β the universal prediction, 3α+2β=7. In particular, with such a prediction, the weak Alfvén wave turbulence constant-flux solution is recovered and, for the first time, a possible explanation to its precursor found numerically by Galtier et al. [J. Plasma Phys. 63, 447 (2000)] is given.
Scanning resonant tunneling spectroscopy of fullerene molecules on Si surfaces for carrier density profiling across p-n junctions
Authors: Bolotov Leonid , Okui Toshiko , Kanayama Toshihiko
Published: September 2005

Scanning tunneling microscopy and spectroscopy were used to investigate a variation of resonant electron tunneling peaks of C60 molecules placed on oxidized Si(100) surfaces that had different impurity profiles. C60-derived resonance peak energy systematically varied depending on the position in the depletion region of lateral Si p-n junctions, indicating that the peak energy can be used for carrier density profiling. The peak energy was determined for uniformly doped substrates with a wide range of phosphorus and boron concentrations. The results were supported by a simple calculation of a one-dimensional tunnel diode.
Defective osteogenesis of the stromal stem cells predisposes CD18-null mice to osteoporosis
Authors: Miura Yasuo , Miura Masako , Gronthos Stan , Allen Matthew R. , Cao Chunzhang , Uveges Thomas E. , Bi Yanming , Ehirchiou Driss , Kortesidis Angela , Shi Songtao , Zhang Li
Published: September 2005

Osteogenesis by the bone marrow stromal stem cells (BMSSCs) supports continuous bone formation and the homeostasis of the bone marrow microenvironment. The mechanism that controls the proliferation and differentiation of BMSSCs is not fully understood. Here, we report that CD18, a surface protein present primarily on hematopoietic cells, but not on differentiated mesenchymal cells, is expressed by the stromal stem cells and plays a critical role in the osteogenic process. Constitutive expression of CD18 on BMSSCs using a retroviral promoter significantly enhances bone formation
in vivo
, whereas genetic inactivation of CD18 in mice leads to defective osteogenesis due to decreased expression of the osteogenic master regulator Runx2/Cbfa1. The defective osteogenesis of the CD18-null BMSSCs can be restored by expressing full-length, but not cytoplasmic domain-truncated, CD18. Radiographic analyses with dual-energy x-ray absorptiometry and 3D microcomputed tomography show that mice lacking CD18 have decreased bone mineral density and exhibit certain features of osteoporosis. Altogether, this work demonstrates that CD18 functions critically in the osteogenesis of BMSSCs, and thus lack of CD18 expression in the leukocyte adhesion deficiency patients may predispose them to osteoporosis.
An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase
Authors: Budovskaya Yelena V. , Stephan Joseph S. , Deminoff Stephen J. , Herman Paul K.
Published: September 2005

Protein kinases are important mediators of much of the signal transduction that occurs in eukaryotic cells. Unfortunately, the identification of protein kinase substrates has proven to be a difficult task, and we generally know few, if any, of the physiologically relevant targets of any particular kinase. Here, we describe a sequence-based approach that simplified this substrate identification process for the cAMP-dependent protein kinase (PKA) in
Saccharomyces cerevisiae
. In this method, the evolutionary conservation of all PKA consensus sites in the
S. cerevisiae
proteome was systematically assessed within a group of related yeasts. The basic premise was that a higher degree of conservation would identify those sites that are functional
in vivo
. This method identified 44 candidate PKA substrates, 5 of which had been described. A phosphorylation analysis showed that all of the identified candidates were phosphorylated by PKA and that the likelihood of phosphorylation was strongly correlated with the degree of target site conservation. Finally, as proof of principle, the activity of one particular target, Atg1, a key regulator of autophagy, was shown to be controlled by PKA phosphorylation
in vivo
. These data therefore suggest that this evolutionary proteomics approach identified a number of PKA substrates that had not been uncovered by other methods. Moreover, these data show how this approach could be generally used to identify the physiologically relevant occurrences of any protein motif identified in a eukaryotic proteome.
Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation
Authors: Measday Vivien , Baetz Kristin , Guzzo Julie , Yuen Karen , Kwok Teresa , Sheikh Bilal , Ding Huiming , Ueta Ryo , Hoac Trinh , Cheng Benjamin , Pot Isabelle , Tong Amy , Yamaguchi-Iwai Yuko , Boone Charles , Hieter Phil , Andrews Brenda
Published: September 2005

Accurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosome stability by performing genome-wide screens employing synthetic genetic array methodology. Two genetic approaches (a series of synthetic lethal and synthetic dosage lethal screens) isolated 211 nonessential deletion mutants that were unable to tolerate defects in kinetochore function. Although synthetic lethality and synthetic dosage lethality are thought to be based upon similar genetic principles, we found that the majority of interactions associated with these two screens were nonoverlapping. To functionally characterize genes isolated in our screens, a secondary screen was performed to assess defects in chromosome segregation. Genes identified in the secondary screen were enriched for genes with known roles in chromosome segregation. We also uncovered genes with diverse functions, such as
RCS1
, which encodes an iron transcription factor.
RCS1
was one of a small group of genes identified in all three screens, and we used genetic and cell biological assays to confirm that it is required for chromosome stability. Our study shows that systematic genetic screens are a powerful means to discover roles for uncharacterized genes and genes with alternative functions in chromosome maintenance that may not be discovered by using proteomics approaches.
ADP-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic activity on mammalian cells
Authors: Basile Giovanna , Taglialatela-Scafati Orazio , Damonte Gianluca , Armirotti Andrea , Bruzzone Santina , Guida Lucrezia , Franco Luisa , Usai Cesare , Fattorusso Ernesto , De Flora Antonio , Zocchi Elena
Published: September 2005

ADP-ribosyl cyclases are ubiquitous enzymes responsible for synthesis from NAD+of the intracellular calcium-releasing signal molecules cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP+). Here, we show that cyclases from lower and higher Metazoa also synthesize three adenylic dinucleotides from cADPR and adenine: diadenosine diphosphate and two isomers thereof. These dinucleotides are present and metabolized in mammalian cells and affect intracellular calcium and cell proliferation. The diadenosine diphosphate isomers are naturally occurring nucleotides containing an N-glycosidic bond different from the usual C1′-N9. The identification of these members of the family of NAD+-derived, calcium-active nucleotides opens new areas of investigation into their functional cooperation with cADPR and NAADP+and into their involvement in the physiology and pathology of calcium-controlled cell functions.
Collagen triple-helix formation in
all-trans
chains proceeds by a nucleation/growth mechanism with a purely entropic barrier
Authors: Bachmann Annett , Kiefhaber Thomas , Boudko Sergei , Engel Jürgen , Bächinger Hans Peter
Published: September 2005

Collagen consists of repetitive Gly–Xaa–Yaa tripeptide units with proline and hydroxyproline frequently found in the Xaa and Yaa position, respectively. This sequence motif allows the formation of a highly regular triple helix that is stabilized by steric (entropic) restrictions in the constituent polyproline-II-helices and backbone hydrogen bonds between the three strands. Concentration-dependent association reactions and slow prolyl isomerization steps have been identified as major rate-limiting processes during collagen folding. To gain information on the dynamics of triple-helix formation in the absence of these slow reactions, we performed stopped-flow double-jump experiments on cross-linked fragments derived from human type III collagen. This technique allowed us to measure concentration-independent folding kinetics starting from unfolded chains with all peptide bonds in the
trans
conformation. The results show that triple-helix formation occurs with a rate constant of 113 ± 20 s
–1
at 3.7°C and is virtually independent of temperature, indicating a purely entropic barrier. Comparison of the effect of guanidinium chloride on folding kinetics and stability reveals that the rate-limiting step is represented by bringing 10 consecutive tripeptide units (3.3 per strand) into a triple-helical conformation. The following addition of tripeptide units occurs on a much faster time scale and cannot be observed experimentally. These results support an entropy-controlled zipper-like nucleation/growth mechanism for collagen triple-helix formation.
Abstract number and arithmetic in preschool children
Authors: Barth Hilary , La Mont Kristen , Lipton Jennifer , Spelke Elizabeth S.
Published: September 2005

Educated humans use language to express abstract number, applying the same number words to seven apples, whistles, or sins. Is language or education the source of numerical abstraction? Claims to the contrary must present evidence for numerical knowledge that applies to disparate entities, in people who have received no formal mathematics instruction and cannot express such knowledge in words. Here we show that preschool children can compare and add large sets of elements without counting, both within a single visual-spatial modality (arrays of dots) and across two modalities and formats (dot arrays and tone sequences). In two experiments, children viewed animations and either compared one visible array of dots to a second array or added two successive dot arrays and compared the sum to a third array. In further experiments, a dot array was replaced by a sequence of sounds, so that participants had to integrate quantity information presented aurally and visually. Children performed all tasks successfully, without resorting to guessing strategies or responding to continuous variables. Their accuracy varied with the ratio of the two quantities: a signature of large, approximate number representations in adult humans and animals. Addition was as accurate as comparison, even though children showed no relevant knowledge when presented with symbolic versions of the addition tasks. Abstract knowledge of number and addition therefore precedes, and may guide, language-based instruction in mathematics.
DNA polymerase θ contributes to the generation of C/G mutations during somatic hypermutation of Ig genes
Authors: Masuda Keiji , Ouchida Rika , Takeuchi Arata , Saito Takashi , Koseki Haruhiko , Kawamura Kiyoko , Tagawa Masatoshi , Tokuhisa Takeshi , Azuma Takachika , O-Wang Jiyang
Published: September 2005

Somatic hypermutation of Ig variable region genes is initiated by activation-induced cytidine deaminase; however, the activity of multiple DNA polymerases is required to ultimately introduce mutations. DNA polymerase η (Polη) has been implicated in mutations at A/T, but polymerases involved in C/G mutations have not been identified. We have generated mutant mice expressing DNA polymerase (Polθ) specifically devoid of polymerase activity. Compared with WT mice, Polq-inactive (Polq, the gene encoding Polθ) mice exhibited a reduced level of serum IgM and IgG1. The mutant mice mounted relatively normal primary and secondary immune responses to a T-dependent antigen, but the production of high-affinity specific antibodies was partially impaired. Analysis of the J
H
4 intronic sequences revealed a slight reduction in the overall mutation frequency in Polq-inactive mice. Remarkably, although mutations at A/T were unaffected, mutations at C/G were significantly decreased, indicating an important, albeit not exclusive, role for Polθ activity. The reduction of C/G mutations was particularly focused on the intrinsic somatic hypermutation hotspots and both transitions and transversions were similarly reduced. These findings, together with the recent observation that Polθ efficiently catalyzes the bypass of abasic sites, lead us to propose that Polθ introduces mutations at C/G by replicating over abasic sites generated via uracil-DNA glycosylase.
Divergent responses of chondrocytes and endothelial cells to shear stress: Cross-talk among COX-2, the phase 2 response, and apoptosis
Authors: Healy Zachary R. , Lee Norman H. , Gao Xiangqun , Goldring Mary B. , Talalay Paul , Kensler Thomas W. , Konstantopoulos Konstantinos
Published: September 2005

Fluid shear exerts anti-inflammatory and anti-apoptotic effects on endothelial cells by inducing the coordinated expression of phase 2 detoxifying and antioxidant genes. In contrast, high shear is pro-apoptotic in chondrocytes and promotes matrix degradation and cartilage destruction. We have analyzed the mechanisms regulating shear-mediated chondrocyte apoptosis by cDNA microarray technology and bioinformatics. We demonstrate that shear-induced cyclooxygenase (COX)-2 suppresses phosphatidylinositol 3-kinase (PI3-K) activity, which represses antioxidant response element (ARE)/NF-E2 related factor 2 (Nrf2)-mediated transcriptional response in human chondrocytes. The resultant decrease in antioxidant capacity of sheared chondrocytes contributes to their apoptosis. Phase 2 inducers, and to a lesser extent COX-2-selective inhibitors, negate the shear-mediated suppression of ARE-driven phase 2 activity and apoptosis. The abrogation of shear-induced COX-2 expression by PI3-K activity and/or stimulation of the Nrf2/ARE pathway suggests the existence of PI3-K/Nrf2/ARE negative feedback loops that potentially interfere with c-Jun N-terminal kinase 2 activity upstream of COX-2. Reconstructing the signaling network regulating shear-induced chondrocyte apoptosis may provide insights to optimize conditions for culturing artificial cartilage in bioreactors and for developing therapeutic strategies for arthritic disorders.
The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice
Authors: Pieper Andrew A. , Wu Xinle , Han Tina W. , Estill Sandi Jo , Dang Quyen , Wu Leeju C. , Reece-Fincanon Sarah , Dudley Carol A. , Richardson James A. , Brat Daniel J. , McKnight Steven L.
Published: September 2005

The neuronal PAS domain protein 3 (
NPAS3
) gene encoding a brain-enriched transcription factor was recently found to be disrupted in a family suffering from schizophrenia. Mice harboring compound disruptions in the
NPAS3
and related
NPAS1
genes manifest behavioral and neuroanatomical abnormalities reminiscent of schizophrenia. Herein we demonstrate that
Npas3
-/-
mice are deficient in expression of hippocampal FGF receptor subtype 1 mRNA, most notably in the dentate gyrus.
In vivo
BrdUrd-labeling shows that basal neural precursor cell proliferation in the dentate gyrus of
Npas3
-/-
mice is reduced by 84% relative to wild-type littermates. We propose that a deficiency in adult neurogenesis may cause the behavioral and neuroanatomical abnormalities seen in
Npas3
-/-
mice, and we speculate that impaired neurogenesis may be involved in the pathophysiology of schizophrenia.
HLA class I-restricted responses to vaccinia recognize a broad array of proteins mainly involved in virulence and viral gene regulation
Authors: Oseroff Carla , Kos Ferdynand , Bui Huynh-Hoa , Peters Bjoern , Pasquetto Valerie , Glenn Jean , Palmore Tara , Sidney John , Tscharke David C. , Bennink Jack R. , Southwood Scott , Grey Howard M. , Yewdell Jonathan W. , Sette Alessandro
Published: September 2005

We have analyzed byex vivoELISPOT the anti-vaccinia cytotoxic T lymphocyte responses of peripheral blood mononuclear cells from humans vaccinated with Dryvax vaccine. More than 6,000 peptides from 258 putative vaccinia ORFs predicted to bind the common molecules of the HLA A1, A2, A3, A24, B7, and B44 supertypes were screened with peripheral blood mononuclear cells of 31 vaccinees. A total of 48 epitopes derived from 35 different vaccinia antigens were identified, some of which (B8R, D1R, D5R, C10L, C19L, C7L, F12, and O1L) were recognized by multiple donors and contain multiple epitopes recognized in the context of different HLA types. The antigens recognized tend to be >100 residues in length and are expressed predominantly in the early phases of infection, although some late antigens were also recognized. Viral genome regulation and virulence factor were recognized most frequently, whereas few structural proteins were immunogenic. Finally, most epitopes were highly conserved among vaccinia virus Western Reserve, variola major and modified vaccinia Ankara, supporting their potential use in vaccine and diagnostic applications.
Social Identification versus Regionalism in Contemporary Ukraine
Authors: Malanchuk Oksana
Published: September 2005

Because of the historic separation of western and eastern Ukraine under Polish and Russian spheres of influence, respectively, regional subpopulations have been seen as an important factor in Ukrainian politics. Arel and Wilson argue that the division on the all-important “Russian question” in Ukraine (relations with Russia and with the Russian-speaking minority) is increasingly regional: east and south versus the center and west. Hesli calculated the level of russification and industrialization in the various regions of Ukraine and concluded that both, together with geographic location, although interrelated, have their own bearing on variation in public opinion. Markus, however, has argued that despite economic, political and ethnic differences among Ukraine's regions, these differences pose less of a threat to reform than has sometimes been suggested. She further points out that speculation that the Donbass wants to unite with Russia “stems more from Russian claims to the area than from genuine indigenous sentiment.” Miller and colleagues, on the other hand, dispute the notion of regional differences independent of the socio-demographic characteristics of the local populations, challenging the conventional wisdom that there are regional political cultures that supersede any underlying demographic differences. They argue that national, political, economic and class identities represent the important cleavages in post-communist societies. The regional divide in Ukraine is thus not a foregone conclusion but a factor that bears closer examination.
Becoming an Agent of Change: Analyzing Narratives by Leaders in Post-Soviet Ukraine
Authors: Susak Victor
Published: September 2005

This paper is about the life experiences of selected individuals who, five years after Ukrainian independence, had emerged as key leaders in post-Soviet Ukraine, a society undergoing deep social and political transformations. In this paper, I argue that under these circumstances, these individuals became both the “children” and “agents” of change. In exploring this idea, I will focus on the moment in their life stories when each narrator identifies the moment when he or she began to act as an “agent” of change. More specifically, I will examine circumstances that transformed these individuals into new leaders at this unique social and political juncture in Ukraine's history. My working hypothesis is that, in addition to direct factors and a certain element of chance, other factors in their earlier biographies, during the Soviet period, have had lasting importance on these leaders' development.