bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum wave-packet dynamics of H+HLi scattering: Reaction cross section and thermal rate constant
Authors: Padmanaban R. , Mahapatra S.
Published: October 2004

The channel specific and initial state-selected reaction cross section and temperature-dependent rate constant for the title system is calculated with the aid of a time-dependent wave-packet approach and using the ab initio potential energy surface of Dunne et al. [Chem. Phys. Lett. 336, 1 (2001)]. All partial-wave contributions up to the total angular momentum J=74 are explicitly calculated within the coupled states (CS) approximation. Companion calculations are also carried out employing the standard as well as the uniform J-shifting (JS) approximation. The overall variation of reaction cross sections corresponds well to the behavior of a barrierless reaction. The hydrogen exchange channel yielding HLi+H products is seen to be more favored over the HLi depletion channel yielding Li+H2 products at low and moderate collision energies. Sharp resonance features are observed in the cross-section results for the HLi depletion channel at low energies. Resonance features in the reaction cross sections average out with various partial-wave contributions, when compared to the same observed in the individual reaction probability curve. Except near the onset of the reaction, the vibrational and rotational excitation of the reagent HLi, in general, does not dramatically influence the reactivity of either channel. The thermal rate constants calculated up to 4000 K show nearly Arrhenius type behavior. The rate constant decreases with vibrational excitation of the reagent HLi, indicating that the cold HLi molecules are efficiently depleted in the reactive encounter with H at relatively low temperatures. The results obtained from the JS approximation are found to agree well qualitatively with the CS results.
New approximations for calculating dispersion coefficients
Authors: Cybulski Sławomir M. , Haley Terence P.
Published: October 2004

Improved approaches for finding approximate values of dispersion coefficients are proposed. They are based on scaling the values of time-dependent Hartree–Fock (TDHF) dispersion coefficients by factors that use the ratio of the estimated true value and the TDHF value of static dipole polarizabilities. It is shown that for a set of 14 atoms and molecules the average absolute-value deviation of the estimated two-body isotropic dispersion coefficients with respect to the dipole oscillator strength distribution results is smaller than 1.0% for two of our approaches. For three-body isotropic dispersion coefficients the corresponding deviations are smaller than 1.2%. Our approximations work particularly well compared to approximations proposed by other researchers in cases where the TDHF results differ from the reference values by more than 10%.
Dissociative multiphoton ionization of NO2 studied by time-resolved imaging
Authors: Eppink André T. J. B. , Whitaker Benjamin J. , Gloaguen Eric , Soep Benoit , Coroiu A. Marcela , Parker David H.
Published: October 2004

We have studied dissociative multiphoton ionization of NO2 by time-resolved velocity map imaging in a two-color pump-probe experiment using the 400 and 266 nm harmonics of a regeneratively amplified titanium-sapphire laser. We observe that most of the ion signal appears as NO+ with ∼0.28 eV peak kinetic energy. Approximately 600 fs period oscillations indicative of wave packet motion are also observed in the NO+ decay. We attribute the signal to two competitive mechanisms. The first involving three-photon 400 nm absorption followed by dissociative ionization of the pumped state by a subsequent 266 nm photon. The second involving one-photon 400 nm absorption to the B22 state of NO2 followed by two-photon dissociative ionization at 266 nm. This interpretation is derived from the observation that the total NO+ ion signal exhibits biexponential decay, 0.72 exp(−t/90±10)+0.28 exp(−t/4000±400), where t is the 266 nm delay in femtoseconds. The fast decay of the majority of the NO+ signal suggests a direct dissociation via the bending mode of the pumped state.
Single molecule photon emission statistics in the slow modulation limit
Authors: Zheng Yujun , Brown Frank L. H.
Published: October 2004

A framework for calculating photon emission statistics for single chromophores perturbed by slow environmental fluctuations is introduced. When internal chromophore dynamics are significantly faster than time scales for environmental modulation it becomes possible to invoke a type of adiabatic approximation, allowing for straightforward calculation of photon counting moments including explicitly quantum effects. Unlike previous exact treatments, the present methodology involves calculation of dynamics reflecting only the modulation characteristics of the environment and quantum dynamics of an isolated chromophore separately, i.e., the complicated intermingling of chromophore quantum dynamics and the environmental modulation are suppressed via the adiabatic approximation. This leads to significant conceptual and computational simplifications. Within its regime of applicability, the present approximation reproduces exact calculations quantitatively. We demonstrate this accuracy explicitly for the case of a two-level chromophore modulated by a number of different stochastic models.
Why hyperpolarizabilities fall short of the fundamental quantum limits
Authors: Tripathy Kakoli , Moreno Javier Pérez , Kuzyk Mark G. , Coe Benjamin J. , Clays Koen , Kelley Anne Myers
Published: October 2004

Quantum sum rules impose limits on the hyperpolarizability, β. A survey of the largest second-order molecular susceptibilities finds what appears to be a universal gap between the experimental results and the fundamental limits. In this work, we use theory, linear spectroscopy, Raman spectroscopy, and measured values of β (using hyper-Rayleigh scattering and Stark Spectroscopy) to show that this gap is due to an unfavorable arrangement of excited state energies. The question of whether this result is a universal property of a quantum system or a matter of present paradigms for making molecules is discussed.
Molecular beam investigation of hydrogen dissociation on Si(001) and Si(111) surfaces
Authors: Dürr M. , Höfer U.
Published: October 2004

The influence of molecular vibrations on the reaction dynamics of H2 on Si(001) as well as isotopic effects have been investigated by means of optical second-harmonic generation and molecular beam techniques. Enhanced dissociation of vibrationally excited H2 on Si(001)2×1 has been found corresponding to a reduction of the mean adsorption barrier to 390 meV and 180 meV for ν=1 and ν=2, respectively. The adsorption dynamics of the isotopes H2 and D2 show only small differences in the accessible range of beam energies between 50 meV and 350 meV. They are traced back to different degrees of vibrational excitation and do not point to an important influence of quantum tunneling in crossing the adsorption barrier. The sticking probability of H2 on the 7×7-reconstructed Si(111) surface was found to be activated both by H2 kinetic energy and surface temperature in a qualitatively similar fashion as H2/Si(001)2×1. Quantitatively, the overall sticking probabilities of H2 on the Si(111) surface are about one order of magnitude lower than on Si(001), the influence of surface temperature is generally stronger.
Equation of state and liquid-vapor equilibria of one- and two-Yukawa hard-sphere chain fluids: Theory and simulation
Authors: Kalyuzhnyi Yurij V. , McCabe Clare , Whitebay Eric , Cummings Peter T.
Published: October 2004

The accuracy of several theories for the thermodynamic properties of the Yukawa hard-sphere chain fluid are studied. In particular, we consider the polymer mean spherical approximation (PMSA), the dimer version of thermodynamic perturbation theory (TPTD), and the statistical associating fluid theory for potentials of variable attractive range (SAFT-VR). Since the original version of SAFT-VR for Yukawa fluids is restricted to the case of one-Yukawa tail, we have extended SAFT-VR to treat chain fluids with two-Yukawa tails. The predictions of these theories are compared with Monte Carlo (MC) simulation data for the pressure and phase behavior of the chain fluid of different length with one- and two-Yukawa tails. We find that overall the PMSA and TPTD give more accurate predictions than SAFT-VR, and that the PMSA is slightly more accurate than TPTD.
Identifiability analysis of models for reversible intermolecular two-state excited-state processes coupled with species-dependent rotational diffusion monitored by time-resolved fluorescence depolarization
Authors: Szubiakowski Jacek P. , Dale Robert E. , Boens Noël , Ameloot Marcel
Published: October 2004

A deterministic identifiability analysis of the kinetic model for a reversible intermolecular two-state excited-state process with species-dependent rotational diffusion described by Brownian reorientation is presented. The cases of both spherically and cylindrically symmetric rotors, with no change in the principal axes of rotation on interconversion in the latter case, are specifically considered. The identifiability analysis is carried out in terms of compartmental modeling based on the S(t)≡I∥(t)+2I⊥(t) and D(t)≡I∥(t)−I⊥(t) functions, where I∥(t) and I⊥(t) are the δ-response functions for fluorescence, polarized, respectively, parallel and perpendicular to the electric vector of linearly polarized excitation. It is shown that, from polarized time-resolved fluorescence data collected at two concentrations of coreactant and three appropriately chosen emission wavelengths, (a) a unique set of rate constants for the overall excited-state process is always obtained by making use of polarized measurements and (b) the rotational diffusion constants and geometrical factors associated with the different anisotropy decay components can be uniquely determined and assigned to each species. The geometrical factors are determined by the absorption and emission transitions in the two rotating species. For spherical rotors, these factors depend directly on the relative orientations of the transition moments, while for cylindrically symmetric rotors they depend on the orientations with respect to each other and to the symmetry axis.
Radial subshell splittings and double-zeta functions in many-electron atoms
Authors: Koga Toshikatsu , Matsuyama Hisashi
Published: October 2004

When the electron–electron interaction is explicitly considered in many-electron atoms, the average subshell radius 〈r〉nl splits into two different radii, inner radius 〈r<〉nl and outer radius 〈r>〉nl, where n and l are the principal and azimuthal quantum numbers. For the 102 atoms He through Lr in their ground states, the radii 〈r<〉nl and 〈r>〉nl are systematically examined at the Hartree–Fock limit level. For a subshell nl, two exponents ζnl(est) estimated from these radii have good linear correlations with variationally determined exponents ζnl(var) of double-ζ Slater-type functions.
Importance of chain–chain interactions on the band gap of trans-polyacetylene as predicted by second-order perturbation theory
Authors: Pino Ramiro , Scuseria Gustavo E.
Published: October 2004

We employ the Laplace-transformed second-order Møller–Plesset perturbation theory for periodic systems in its atomic orbital basis formulation to determine the geometric structure and band gap of interacting polyacetylene chains. We have studied single, double, and triple chains, and also two-dimensional crystals. We estimate from first principles the equilibrium interchain distance and setting angle, along with binding energy between trans-polyacetylene chains due to dispersion interactions. The dependence of the correlation corrected quasiparticle band gap on the intrachain and interchain geometric parameters is studied, obtaining that the gap of the compound structures is substantially reduced with respect to the single chain polymer.
A three-dimensional He-NaH potential energy surface for rovibrational energy transfer studies
Authors: Taylor Brian K.
Published: October 2004

A three-dimensional potential energy surface for the He-NaH van der Waals complex is calculated at the coupled cluster singles-and-doubles with noniterative inclusion of connected triples [CCSD(T)] level of theory. Estimates of CCSD(T) interaction energies for an infinitely large basis set is obtained using a basis set extrapolation scheme. The He-NaH potential energy surface is much different than the He-LiH surface. In particular, the He-NaH system has a binding energy of De=19.73 cm−1 in comparison to De=176.7 cm−1 for He-LiH. These minima are at the θ=180° linear geometry where the helium is located at the metal end of the metal hydride. The He-NaH and He-LiH potentials are very similar for the θ=0° linear geometry. The He-NaH potential energy surface supports one vibrational bound state with E=−1.48 cm−1. Since this energy is smaller than the accuracy of the potential energy surface, the existence of a bound He-NaH complex is questionable.
Adsorption and dissociation of NO on stepped Pt (533)
Authors: Backus Ellen H. G. , Eichler Andreas , Grecea Mihail L. , Kleyn Aart W. , Bonn Mischa
Published: October 2004

We present an experimental and theoretical investigation of the adsorption, desorption, and dissociation of NO on the stepped Pt (533) surface. By combining temperature programmed desorption and reflection absorption infrared spectroscopy, information about the adsorption sites at different temperatures is obtained. Surprisingly, metastable adsorption structures of NO can be produced through variation of the dosing temperature. We also show that part of the NO molecules adsorbed on the step sites dissociates around 450 K. After dissociation the N atoms can desorb either by combining with an O fragment, or with another N atom, resulting in NO and N2. The N2 production can be enhanced by coadsorbing CO on the surface: CO scavenges the oxygen atom, thereby suppressing associative recombinative desorption of N and O atoms. Density functional theory calculations are used to reveal the adsorption energies and vibrational frequencies of adsorbed NO as well as barriers for dissociation of NO and for diffusion of N atoms. The combined experimental results and theoretical calculations reveal that dissociation of NO is the rate limiting step in the formation of N2.
Equilibrium and kinetics: Water confined in carbon nanotubes as one-dimensional lattice gas
Authors: Zhou Xin , Li Cheng-Quan , Iwamoto Mitsumasa
Published: October 2004

We present a simple one-dimensional lattice gas model, which describes very well the equilibrium and kinetic behaviors of water confined in a thin carbon nanotube found in an atomistic molecular dynamics simulation [G. Hummer, J. C. Rasaiah, and J. P. Noworyta, Nature (London), 414, 188 (2001)]. The model parameters correspond to various physical interactions and can be calculated or estimated by using statistical mechanics. Then, the roles of all interactions in the water filling, emptying, and transporting processes are clearly understood. Our results indicate that the interaction from the water molecules outside the nanotube plays a key role in these processes and the interaction can be simply treated as an average effect of the bulk water.
Temperature dependence of the structure of Langmuir films of normal-alkanes on liquid mercury
Authors: Kraack H. , Ocko B. M. , Pershan P. S. , Tamam L. , Deutsch M.
Published: October 2004

The temperature dependent phase behavior of Langmuir films of n-alkanes [CH3(CH2)n−2CH3, denote Cn] on mercury was studied for chain lengths 19⩽n⩽22 and temperatures 15⩽T⩽44 °C, using surface tensiometry and surface x-ray diffraction methods. In contrast with Langmuir films on water, where molecules invariably orient roughly surface normal, alkanes on mercury are always oriented surface parallel and show no long-range in-plane order at any surface pressure. A gas and several condensed phases of single, double, and triple layers of lying-down molecules are found, depending on n and T. At high coverages, the alkanes studied here show transitions from a triple to a double to a single layer with increasing temperature. The transition temperature from a double to a single layer is found to be ∼5 °C, lower than the bulk rotator-to-liquid melting temperature, while the transition from a triple to a double layer is about as much below the double-to-single layer transition. Both monolayer and bulk transition temperatures show a linear increase with n with identical slopes of ∼4.5 °C/CH2 within the range of n values addressed here. It is suggested that the film and bulk transitions are both driven by a common cause: the proliferation of gauche defects in the chain with increasing temperature.
Libration induced stretching mode excitation for pump-probe spectroscopy in pure liquid water
Authors: Amir Wafa , Gallot Guilhem , Hache François
Published: October 2004

We developed an experimental approach to study pure liquid water in the infrared and avoid thermal effects. This technique is based on libration induced stretching excitation of water molecules. A direct correspondence between frequencies within the libration and OH stretching bands is demonstrated. Energy diffusion is studied in pure liquid water by measuring wave packet dynamics of OH stretching vibrator with infrared femtosecond spectroscopy. Wave packet dynamics reveals ultrafast energy dynamics and reflects 130 fs intermolecular energy transfer between water vibrators. Energy diffusion is almost two orders of magnitude faster than self diffusion in water.
Chain conformation in two-dimensional dense state
Authors: Wang Xiaorong , Foltz Victor J.
Published: October 2004

In an effort to provide evidence concerning the conformation of many chains in strict two-dimensional (2D) dense state, we synthesized polymer chains of diameter of nanometers through an anionic polymerization process. The conformational characteristics of the long chain molecules in films of thickness h corresponding to the chain diameter a were directly obtained from atomic force microscopy observations. In 2D dispersed state, the conformations of the long chain molecules were typical Gaussian. However, in 2D dense state the long chain molecules were strongly interpenetrated. Their conformations were largely perturbed by the presence of neighbor chains and were not Gaussian. This result was in contradiction with the segregated globule model predicted by de Gennes. The central reason is that 2D space cannot be filled to normal density with 2D Gaussian globules; either the area must be greatly increased with consequently large voids, or the globule conformation must be expanded by allowing chains to interpenetrate each other.
Optimal linearized Poisson–Boltzmann theory applied to the simulation of flexible polyelectrolytes in solution
Authors: Bathe M. , Grodzinsky A. J. , Tidor B. , Rutledge G. C.
Published: October 2004

Optimal linearized Poisson–Boltzmann (OLPB) theory is applied to the simulation of flexible polyelectrolytes in solution. As previously demonstrated in the contexts of the cell model [H. H. von Grünberg, R. van Roij, and G. Klein, Europhys. Lett. 55, 580 (2001)] and a particle-based model [B. Beresfordsmith, D. Y. C. Chan, and D. J. Mitchell, J. Colloid Interface Sci. 105, 216 (1985)] of charged colloids, OLPB theory is applicable to thermodynamic states at which conventional, Debye–Hückel (DH) linearization of the Poisson–Boltzmann equation is rendered invalid by violation of the condition that the electrostatic coupling energy of a mobile ion be much smaller than its thermal energy throughout space, |ναeψ(r)|≪kBT. As a demonstration of its applicability to flexible polyelectrolytes, OLPB theory is applied to a concentrated solution of freely jointed chains. The osmotic pressure is computed at various reservoir ionic strengths and compared with results from the conventional DH model for polyelectrolytes. Through comparison with the cylindrical cell model for polyelectrolytes, it is demonstrated that the OLPB model yields the correct osmotic pressure behavior with respect to nonlinear theory where conventional DH theory fails, namely at large ratios of mean counterion density to reservoir salt density, when the Donnan potential is large.
On the influence of the water electrostatic field on the amide group vibrational frequencies
Authors: Bouř Petr
Published: October 2004

For clusters of N-methylacetamide and water molecules the performance of the fixed-charged approximation was tested against continuum and explicit ab initio models. The dispersion of the vibrational frequencies when constant electrostatic potential was maintained at the solute atoms was compared to the distribution caused by geometry fluctuations.
Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice
Authors: Fenske Timothy S. , Pengue Gina , Mathews Vikram , Hanson Piia T. , Hamm Sarah E. , Riaz Noor , Graubert Timothy A.
Published: October 2004

The t(8;21)(q22;q22) translocation, present in 10-15% of acute myeloid leukemia (AML) cases, generates the AML1/ETO fusion protein. To study the role of AML1/ETO in the pathogenesis of AML, we used the
Ly6A
locus that encodes the well characterized hematopoietic stem cell marker, Sca1, to target expression of AML1/ETO to the hematopoietic stem cell compartment in mice. Whereas germ-line expression of AML1/ETO from the
AML1
promoter results in embryonic lethality, heterozygous
Sca1
+/AML1-ETO ires EGFP
(abbreviated
Sca
+/AE
) mutant mice are born in Mendelian ratios with no apparent abnormalities in growth or fertility. Hematopoietic cells from
Sca
+/AE
mice have markedly extended survival
in vitro
and increasing myeloid clonogenic progenitor output over time.
Sca
+/AE
mice develop a spontaneous myeloproliferative disorder with a latency of 6 months and a penetrance of 82% at 14 months. These results reinforce the notion that the phenotype of murine transgenic models of human leukemia is critically dependent on the cellular compartment targeted by the transgene. This model should provide a useful platform to analyze the effect of AML1/ETO on hematopoiesis and its potential cooperation with other mutations in the pathogenesis of leukemia.
Assigning African elephant DNA to geographic region of origin: Applications to the ivory trade
Authors: Wasser Samuel K. , Shedlock Andrew M. , Comstock Kenine , Ostrander Elaine A. , Mutayoba Benezeth , Stephens Matthew
Published: October 2004

Resurgence of illicit trade in African elephant ivory is placing the elephant at renewed risk. Regulation of this trade could be vastly improved by the ability to verify the geographic origin of tusks. We address this need by developing a combined genetic and statistical method to determine the origin of poached ivory. Our statistical approach exploits a smoothing method to estimate geographic-specific allele frequencies over the entire African elephants' range for 16 microsatellite loci, using 315 tissue and 84 scat samples from forest (
Loxodonta africana cyclotis
) and savannah (
Loxodonta africana africana
) elephants at 28 locations. These geographic-specific allele frequency estimates are used to infer the geographic origin of DNA samples, such as could be obtained from tusks of unknown origin. We demonstrate that our method alleviates several problems associated with standard assignment methods in this context, and the absolute accuracy of our method is high. Continent-wide, 50% of samples were located within 500 km, and 80% within 932 km of their actual place of origin. Accuracy varied by region (median accuracies: West Africa, 135 km; Central Savannah, 286 km; Central Forest, 411 km; South, 535 km; and East, 697 km). In some cases, allele frequencies vary considerably over small geographic regions, making much finer discriminations possible and suggesting that resolution could be further improved by collection of samples from locations not represented in our study.
Nucleotide diversity and linkage disequilibrium in loblolly pine
Authors: Brown Garth R. , Gill Geoffrey P. , Kuntz Robert J. , Langley Charles H. , Neale David B.
Published: October 2004

Outbreeding species with large, stable population sizes, such as widely distributed conifers, are expected to harbor relatively more DNA sequence polymorphism. Under the neutral theory of molecular evolution, the expected heterozygosity is a function of the product 4
N
e
μ, where
N
e
is the effective population size and μ is the per-generation mutation rate, and the genomic scale of linkage disequilibrium is determined by 4
N
e
r
, where
r
is the per-generation recombination rate between adjacent sites. These parameters were estimated in the long-lived, outcrossing gymnosperm loblolly pine (
Pinus taeda
L.) from a survey of single nucleotide polymorphisms across ≈18 kb of DNA distributed among 19 loci from a common set of 32 haploid genomes. Estimates of 4
N
e
μ at silent and nonsynonymous sites were 0.00658 and 0.00108, respectively, and both were statistically heterogeneous among loci. By Tajima's
D
statistic, the site frequency spectrum of no locus was observed to deviate from that predicted by neutral theory. Substantial recombination in the history of the sampled alleles was observed and linkage disequilibrium declined within several kilobases. The composite likelihood estimate of 4
N
e
r
based on all two-site sample configurations equaled 0.00175. When geological dating, an assumed generation time (25 years), and an estimated divergence from
Pinus pinaster
Ait. are used, the effective population size of loblolly pine should be 5.6 × 10
5
. The emerging narrow range of estimated silent site heterozygosities (relative to the vast range of population sizes) for humans,
Drosophila
, maize, and pine parallels the paradox described earlier for allozyme polymorphism and challenges simple equilibrium models of molecular evolution.
The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development
Authors: Lu Robert , Wang Houping , Liang Zhe , Ku Li , O'Donnell William T. , Li Wen , Warren Stephen T. , Feng Yue
Published: October 2004

The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein implicated in regulating translation of its mRNA ligands. The absence of FMRP results in fragile X syndrome, one of the leading causes of inherited mental retardation. Delayed dendritic spine maturation was found in fragile X mental retardation patients as well as inFmr1knockout (KO) mice, indicating the functional requirement of FMRP in synaptic development. However, the biochemical link between FMRP deficiency and the neuronal impairment during brain development has not been defined. How FMRP governs normal synapse development in the brain remains elusive. We report here that the developmentally programmed FMRP expression represses the translation of microtubule associated protein 1B (MAP1B) and is required for the accelerated decline of MAP1B during active synaptogenesis in neonatal brain development. The lack of FMRP results in misregulated MAP1B translation and delayed MAP1B decline in theFmr1KO brain. Furthermore, the aberrantly elevated MAP1B protein expression leads to abnormally increased microtubule stability inFmr1KO neurons. Together, these results indicate that FMRP plays critical roles in controlling cytoskeleton organization during neuronal development, and the abnormal microtubule dynamics is a conceivable underlying factor for the pathogenesis of fragile X mental retardation.
Mediation of Af4 protein function in the cerebellum by Siah proteins
Authors: Oliver Peter L. , Bitoun Emmanuelle , Clark Joanne , Jones Emma L. , Davies Kay E.
Published: October 2004

We have established that the gene
AF4
, which had long been recognized as disrupted in childhood leukemia, also plays a role in the CNS.
Af4
is mutated in the robotic mouse that is characterized by ataxia and Purkinje cell loss. To determine the molecular basis of this mutation, we carried out a yeast two-hybrid screen and show that Af4 binds the E3 ubiquitin ligases
Drosophila seven in absentia
(sina) homologues (Siah)-1a and Siah-2 in the brain.
Siah-1a
and
Af4
are expressed in Purkinje cells and colocalize in the nucleus of human embryonic kidney 293T and P19 cells.
In vitro
binding assays and coimmunoprecipitation reveal a significant reduction in affinity between Siah-1a and robotic mutant Af4 compared with wild-type, which correlates with the almost complete abolition of mutant Af4 degradation by Siah-1a. These data strongly suggest that an accumulation of mutant Af4 occurs in the robotic mouse due to a reduction in its normal turnover by the proteasome. A significant increase in the transcriptional activity of mutant Af4 relative to wild-type was obtained in mammalian cells, suggesting that the activity of Af4 is controlled through Siah-mediated degradation. Another member of the Af4 family, Fmr2, which is involved in mental handicap in humans, binds Siah proteins in a similar manner. These results provide evidence that a common regulatory mechanism exists that controls levels of the Af4/Fmr2 protein family. The robotic mouse thus provides a unique opportunity to understand how these proteins play a role in disorders as diverse as leukemia, mental retardation, and neurodegenerative disease.
Prion protein gene (PRNP) variants and evidence for strong purifying selection in functionally important regions of bovine exon 3
Authors: Seabury Christopher M. , Honeycutt Rodney L. , Rooney Alejandro P. , Halbert Natalie D. , Derr James N.
Published: October 2004

Amino acid replacements encoded by the prion protein gene (PRNP) have been associated with transmissible and hereditary spongiform encephalopathies in mammalian species. However, an association between bovine spongiform encephalopathy (BSE) and bovinePRNPexon 3 has not been detected. Moreover, little is currently known regarding the mechanisms of evolution influencing the bovinePRNPgene. Therefore, in this study we evaluated the patterns of nucleotide variation associated withPRNPexon 3 for 36 breeds of domestic cattle and representative samples for 10 additional species of Bovinae. The results of our study indicate that strong purifying selection has intensely constrainedPRNPover the long-term evolutionary history of the subfamily Bovinae, especially in regions considered to be of functional, structural, and pathogenic importance in humans as well as other mammals. The driving force behind this intense level of purifying selection remains to be explained.
Regulation of the endogenous VEGF-A gene by exogenous designed regulatory proteins
Authors: Tachikawa Kiyoshi , Schröder Oliver , Frey Gerhard , Briggs Steven P. , Sera Takashi
Published: October 2004

We describe a facile method to activate or repress transcription of endogenous genes in a quantitative and specific manner by treatment with designed regulatory proteins (DRPs), in which artificial transcription factors (ATFs) are fused to cell-penetrating peptides (CPPs). Penetration of DRPs into cells is mediated by an N-terminal CPP fused to a nuclear localization signal; a DNA-binding domain and a transactivation domain follow. The DNA-binding domain was targeted to the vascular endothelial growth factor (VEGF)-A gene. An agonist DRP was rapidly taken up by cells and transported to the nucleus; soon after, the cells began transcribing the gene and secreting VEGF-A protein in a dose-dependent manner. Multiple copies of a short oligopeptide derived from a minimal transactivation domain of human β-catenin was stronger than VP-16. The SRDX domain from the plant transcription factor, SUPERMAN, changed the DRP to a hypoxia-induced antagonist of VEGF-A. DRPs combine many of the potential benefits of transgenes with those of recombinant proteins.
The rate and equilibrium constants for a multistep reaction sequence for the aggregation of superoxide dismutase in amyotrophic lateral sclerosis
Authors: Khare Sagar D. , Caplow Michael , Dokholyan Nikolay V.
Published: October 2004

Mutation-induced aggregation of the dimeric enzyme Cu, Zn superoxide dismutase 1 (SOD1) has been implicated in the familial form of the disease amyotrophic lateral sclerosis, but the mechanism of aggregation is not known. Here, we show that
in vitro
SOD1 aggregation is a multistep reaction that minimally consists of dimer dissociation, metal loss from the monomers, and oligomerization of the apo-monomers:

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\begin{equation*}\;D_{{\mathrm{holo}}}{ \,\substack{ ^{k_{{\mathrm{off}}}} \\ {\rightleftharpoons} \\ _{k_{{\mathrm{on}}}} }\, }2M_{{\mathrm{holo}}}{ \,\substack{ ^{k_{{\mathrm{m}}}^{-}} \\ {\rightleftharpoons} \\ _{k_{{\mathrm{m}}}^{+}} }\, }2M_{{\mathrm{apo}}}{ \,\substack{ ^{k_{{\mathrm{agg}}}} \\ {\rightarrow} \\ }\, }A,\;\end{equation*}\end{document}

where
D
holo
,
M
holo
,
M
apo
, and
A
are the holo-dimer, holo-monomer, apo-monomer, and aggregate, respectively. Under aggregation-promoting conditions (pH 3.5), the rate and equilibrium constants corresponding to each step are: (
i
) dimer dissociation,
K
d
≈1 μM;
k
off
≈ 1 × 10
–3
s
–1
,
k
on
≈1 × 10
3
M
–1
·s
–1
; (
ii
) metal loss,
K
m
≈0.1 μM,

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\begin{document}
\begin{equation*}k_{{\mathrm{m}}}^{-}\approx 1{\times}10^{-3}{\mathrm{s}}^{-1}\end{equation*}\end{document}

,

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\begin{equation*}k_{{\mathrm{m}}}^{+}\approx 1{\times}10^{4}{\mathrm{M}}^{-1}{\cdot}{\mathrm{s}}^{-1}\end{equation*}\end{document}

; and (
iii
) assembly (rate-limiting step),
k
agg
≈1 × 10
3
M
–1
·s
–1
. In contrast, under near-physiological conditions (pH 7.8), where aggregation is drastically reduced, dimer dissociation is less thermodynamically favorable:
K
d
≈ 0.1 nM, and extremely slow:
k
off
≈3 × 10
–5
s
–1
,
k
on
≈3 × 10
5
M
–1
·s
–1
. Our results suggest that familial amyotrophic lateral sclerosis-linked SOD1 aggregation occurs by a mutation-induced increase in dimer dissociation and/or increase in apomonomer formation.
The Microcirculation in Severe Malaria
Authors: ROGERSON STEPHEN J , GRAU GEORGES E. , HUNT NICHOLAS H.
Published: October 2004

Severe malaria in humans and animals is initiated by interactions between malaria‐infected cells, host blood cells (including monocytes, T cells and platelets) and endothelial cells of the microcirculation. Adhesion to vascular cells, and possible vascular obstruction in severe human disease, involves interaction between host receptors and parasite‐derived proteins, such as the variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Our understanding of how different PfEMP1 variants may target infected erythrocytes to specific sites, such as the placenta, is rapidly increasing. However, in most instances downstream immune‐mediated inflammatory processes appear more central than parasite accumulation to development of severe malaria. Using genetically‐manipulated animal models of severe malaria, key roles for CD8 T cells and mediators such as lymphotoxin in the pathogenesis of murine disease have been established. Experimental and human studies suggest vascular deposition of activated platelets may have a central role. Here, we review some recent advances in the understanding of severe malaria pathogenesis from human and animal studies, focusing on events at the level of the microcirculation, and highlight the role for activated host cells in initiating the pathology of the disease.
Hypercholesterolemia Promotes Leukocyte‐Dependent Platelet Adhesion in Murine Postcapillary Venules
Authors: TAILOR ANITABEN , GRANGER D. NEIL
Published: October 2004

Objective: Leukocyte‐platelet aggregates form in blood during the development of cardiovascular diseases, including atherosclerosis. The study determined whether leukocytes contribute to the platelet adhesion induced by hypercholesterolemia in postcapillary venules.

Methods: Wild‐type (WT) C57Bl/6 or CD18‐deficient (CD18−/−) mice were placed on a normal (ND) or high‐cholesterol (HC) diet for 2 weeks. Platelets isolated from ND, HC, or CD18−/− mice were fluorescently labeled with CFSE, and administered to either ND, HC, HC‐CD18−/− or anti‐neutrophil serum (HC‐ANS)‐treated mice. Rhodamine 6G was administered to label and visualize leukocytes. Intravital fluorescence microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules.

Results: HC increased both leukocyte and platelet adhesion (relative to ND). Greater than 50% of adherent platelets in HC mice were bound to adherent leukocytes. When HC platelets were examined in HC‐ANS‐treated or HC‐CD18−/− mice, leukocyte‐dependent platelet adhesion was significantly attenuated. Conversely, when HC‐CD18−/− platelets were observed in HC recipients both leukocyte‐dependent and endothelium‐dependent platelet adhesion was comparable to HC mice receiving WT platelets.

Conclusions: The findings demonstrate that the pro‐thrombogenic phenotype assumed in the microvasculature during hypercholesterolemia is largely attributed to leukocyte‐dependent platelet adhesion.
Hypophosphorylated SR splicing factors transiently localize around active nucleolar organizing regions in telophase daughter nuclei
Authors: Bubulya Paula A. , Prasanth Kannanganattu V. , Deerinck Thomas J. , Gerlich Daniel , Beaudouin Joel , Ellisman Mark H. , Ellenberg Jan , Spector David L.
Published: October 2004

Upon completion of mitosis, daughter nuclei assemble all of the organelles necessary for the implementation of nuclear functions. We found that upon entry into daughter nuclei, snRNPs and SR proteins do not immediately colocalize in nuclear speckles. SR proteins accumulated in patches around active nucleolar organizing regions (NORs) that we refer to as NOR-associated patches (NAPs), whereas snRNPs were enriched at other nuclear regions. NAPs formed transiently, persisting for 15–20 min before dissipating as nuclear speckles began to form in G1. In the absence of RNA polymerase II transcription, NAPs increased in size and persisted for at least 2 h, with delayed localization of SR proteins to nuclear speckles. In addition, SR proteins in NAPs are hypophosphorylated, and the SR protein kinase Clk/STY colocalizes with SR proteins in NAPs, suggesting that phosphorylation releases SR proteins from NAPs and their initial target is transcription sites. This work demonstrates a previously unrecognized role of NAPs in splicing factor trafficking and nuclear speckle biogenesis.
A standardized kinesin nomenclature
Authors: Lawrence Carolyn J. , Dawe R. Kelly , Christie Karen R. , Cleveland Don W. , Dawson Scott C. , Endow Sharyn A. , Goldstein Lawrence S.B. , Goodson Holly V. , Hirokawa Nobutaka , Howard Jonathon , Malmberg Russell L. , McIntosh J. Richard , Miki Harukata , Mitchison Timothy J. , Okada Yasushi , Reddy Anireddy S.N. , Saxton William M. , Schliwa Manfred , Scholey Jonathan M. , Vale Ronald D. , Walczak Claire E. , Wordeman Linda
Published: October 2004

In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered.
ADAP–SLP-76 Binding Differentially Regulates Supramolecular Activation Cluster (SMAC) Formation Relative to T Cell–APC Conjugation
Authors: Wang Hongyan , McCann Fiona E. , Gordan John D. , Wu Xiang , Raab Monika , Malik Talat H. , Davis Daniel M. , Rudd Christopher E.
Published: October 2004

T cell–APC conjugation as mediated by leukocyte function-associated antigen-1 (LFA-1)–intercellular adhesion molecule (ICAM)-1 binding is followed by formation of the supramolecular activation cluster (SMAC) at the immunological synapse. The intracellular processes that regulate SMAC formation and its influence on T cell function are important questions to be addressed. Here, using a mutational approach, we demonstrate that binding of adaptor adhesion and degranulation promoting adaptor protein (ADAP) to SLP-76 differentially regulates peripheral SMAC (pSMAC) formation relative to conjugation. Although mutation of the YDDV sites (termed M12) disrupted SLP-76 SH2 domain binding and prevented the ability of ADAP to increase conjugation and LFA-1 clustering, M12 acted selectively as a dominant negative (DN) inhibitor of pSMAC formation, an effect that was paralleled by a DN effect on interleukin-2 production. ADAP also colocalized with LFA-1 at the immunological synapse. Our findings identify ADAP–SLP-76 binding as a signaling event that differentially regulates SMAC formation, and support a role for SMAC formation in T cell cytokine production.
Negative Regulation of Mast Cell Signaling and Function by the Adaptor LAB/NTAL
Authors: Volná Petra , Lebduška Pavel , Dráberová Lubica , Šímová Šárka , Heneberg Petr , Boubelík Michael , Bugajev Viktor , Malissen Bernard , Wilson Bridget S. , Hořejší Václav , Malissen Marie , Dráber Petr
Published: October 2004

Engagement of the Fcε receptor I (FcεRI) on mast cells and basophils initiates signaling pathways leading to degranulation. Early activation events include tyrosine phosphorylation of two transmembrane adaptor proteins, linker for activation of T cells (LAT) and non–T cell activation linker (NTAL; also called LAB; a product of Wbscr5 gene). Previous studies showed that the secretory response was partially inhibited in bone marrow–derived mast cells (BMMCs) from LAT-deficient mice. To clarify the role of NTAL in mast cell degranulation, we compared FcεRI-mediated signaling events in BMMCs from NTAL-deficient and wild-type mice. Although NTAL is structurally similar to LAT, antigen-mediated degranulation responses were unexpectedly increased in NTAL-deficient mast cells. The earliest event affected was enhanced tyrosine phosphorylation of LAT in antigen-activated cells. This was accompanied by enhanced tyrosine phosphorylation and enzymatic activity of phospholipase C γ1 and phospholipase C γ2, resulting in elevated levels of inositol 1,4,5-trisphosphate and free intracellular Ca2+. NTAL-deficient BMMCs also exhibited an enhanced activity of phosphatidylinositol 3-OH kinase and Src homology 2 domain–containing protein tyrosine phosphatase-2. Although both LAT and NTAL are considered to be localized in membrane rafts, immunogold electron microscopy on isolated membrane sheets demonstrated their independent clustering. The combined data show that NTAL is functionally and topographically different from LAT.
Positive and Negative Regulation of FcεRI-Mediated Signaling by the Adaptor Protein LAB/NTAL
Authors: Zhu Minghua , Liu Yan , Koonpaew Surapong , Granillo Olivia , Zhang Weiguo
Published: October 2004

Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcεRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcεRI-mediated signaling than LAT−/− mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcεRI-mediated signaling.
Willow genotype, but not drought treatment, affects foliar phenolic concentrations and leaf‐beetle resistance
Authors: Glynn Carolyn , Rönnberg‐Wästljung Ann‐Christin , Julkunen‐Tiitto Riitta , Weih Martin
Published: October 2004

In a greenhouse experiment we examined the effect of willow genotype and irrigation regime (moderate drought and well‐watered) on plant growth parameters, foliar nitrogen, and phenolic concentrations, as well as on the preference and performance of the blue leaf beetle, Phratora vulgatissima (L.) (Coleoptera: Chrysomelidae). The 10 vegetatively propagated willow genotypes in the experiments were F2 full‐sibling hybrids, originated from a cross between Salix viminalis (L.) (Salicaceae) (high in condensed tannins) and Salix dasyclados (L.) (Salicaceae) (rich in phenolic glycosides). Insect bioassays were conducted on detached leaves in Petri dishes as well as with free‐living insects on intact potted plants. The 10‐week long irrigation treatments caused statistically significant phenotypic differences in the potted willow saplings. Total biomass was somewhat higher in the well‐watered treatment. The root to total biomass ratio was higher in the drought‐treatment plants. There was significant genotypic variation in foliar nitrogen concentrations, and they were higher in the drought‐treatment plants. There was also a strong genotypic variation in each of the phenolic substances analyzed. Condensed tannins, which accounted for the greatest proportion of total phenolic mass, were higher in the well‐watered treatment. There was, however, no difference in levels of the other phenolics (salicylates, cinnamic acid, flavonoids, and chlorogenic acid) between irrigation treatments. The sum of these phenolics was higher in the well‐watered treatment. There was a strong variation in P. vulgatissima larval development on different willow genotypes, and larval performance was negatively correlated with levels of salicylates and cinnamic acid. There was, however, no effect of irrigation treatment on larval performance. Phratora vulgatissima preferred to feed on well‐watered plants, and we found a preference for oviposition there, but neither feeding nor oviposition site preference was affected by willow genotype. Adult feeding and oviposition preferences were not correlated with larval performance.
The deinstitutionalization of American marriage
Authors: Cherlin Andrew J.
Published: October 2004

This article argues that marriage has undergone a process of deinstitutionalization—a weakening of the social norms that define partners' behavior—over the past few decades. Examples are presented involving the increasing number and complexity of cohabiting unions and the emergence of same‐sex marriage. Two transitions in the meaning of marriage that occurred in the United States during the 20th century have created the social context for deinstitutionalization. The first transition, noted by Ernest Burgess, was from the institutional marriage to the companionate marriage. The second transition was to the individualized marriage in which the emphasis on personal choice and self‐development expanded. Although the practical importance of marriage has declined, its symbolic significance has remained high and may even have increased. It has become a marker of prestige and personal achievement. Examples of its symbolic significance are presented. The implications for the current state of marriage and its future direction are discussed.