bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurements of low-level prepulse on Nike KrF laser
Authors: Karasik Max , Mostovych A. N. , Lehmberg R. H. , Chan Y. , Weaver J. L. , Obenschain S. P.
Published: September 2005

The krypton fluoride (KrF) laser is a leading candidate driver for inertial fusion energy. Some of the current fusion target designs call for targets with thin metallic coatings. These targets could be particularly susceptible to preheat by a low-level laser prepulse. Knowledge of the prepulse can be important in understanding and modeling the behavior of such targets. This paper presents measurements of low-level prepulse on target with the Nike KrF laser. Sources of prepulse are discussed and measurements are performed under several specific laser conditions in order to evaluate the relative contribution of these sources to the overall prepulse. Prepulse is found to be ∼2×10−7 from peak intensity for approximately 120ns prior to the main laser pulse. Prepulse energy density on target is ∼2J∕cm2. The first laser amplifier in the time- and angle-multiplexed section of the laser is found to be the dominant source of prepulse.
Influence of germanium on the formation of NiSi1−xGex on (111)-oriented Si1−xGex
Authors: Jarmar T. , Ericson F. , Smith U. , Seger J. , Zhang S.-L.
Published: September 2005

The formation of NiSi1−xGex on Si1−xGex(111) substrates with x=0, 0.05, and 0.20 at an annealing temperature of 500°C has been studied by x-ray diffraction, transmission electron microscopy, and pole-figure measurements. NiSi formed preferentially oriented on Si, with (100), (001), and (102) parallel to Si(111) and NiSi[010]‖Si⟨211⟩. In NiSi0.95Ge0.05, (001) and (102) maintained their preferential orientations, whereas NiSi0.95Ge0.05(100) was rotated by 30°, so that NiSi0.95Ge0.05[010]‖Si0.95Ge0.05⟨011⟩. An epitaxial alignment in the form of a double axiotaxy, with NiSi0.95Ge0.05(2±11) as well as (20−2)‖Si0.95Ge0.05{220}, simultaneously with NiSi0.95Ge0.05(0±13) as well as (020)‖Si0.95Ge0.05{022}, caused NiSi0.95Ge0.05(100) to tilt over the range of 0°–7.5°. The Ge addition also enhanced the preferentially oriented structure by reinforcing NiSi0.95Ge0.05(123)‖Si0.95Ge0.05(111) through the axiotaxial alignments, NiSi0.95Ge0.05(211) and (−112)‖Si0.95Ge0.05{220}. Observed was also the presence of NiSi0.95Ge0.05(011)‖Si0.95Ge0.05(111), with NiSi0.95Ge0.05[100]‖Si0.95Ge0.05⟨011⟩. In the case of NiSi0.80Ge0.20, the preferential orientations were sharply reduced in favor of NiSi0.80Ge0.20(100)‖Si0.80Ge0.20(111), with NiSi0.80Ge0.20[010]‖Si0.80Ge0.20⟨011⟩ and the 30° rotation thus preserved. The observed Ge influence is shown to be consistent with a model suggested earlier for Si1−xGex(001) substrates, which is based on the nonexistence of Ni(Si1−xGex)2 for all except the smallest values of x. High-resolution transmission electron microscopy was used to show that the surface steps typical of molecular-beam-deposited epitaxial Si1−xGex substrate films do not influence the growth of the NiSi1−xGex.
Experimental and theoretical study of bulk light scattering in CaF2 monocrystals
Authors: Logunov Stephan , Kuchinsky Sergey
Published: August 2005

A variety of different types of light scattering (Rayleigh, Brillouin, Raman, and Mie scatterings), which may contribute to the transmission losses in the bulk of high-quality CaF2 monocrystals, have been investigated experimentally and theoretically. The angular distribution of Rayleigh and Mie scatterings in the visible spectral range has been measured using an imaging technique. An effective technique for scattering measurements in the uv spectral range has also been implemented. Measurement of Raman scattering has shown that its contribution to the total scattering loss is negligible. In order to estimate the scattering from thermal fluctuations versus that from crystalline defects, a measurement of the temperature dependence of the scattering at the scattering angle of 90° has been performed. It has been shown that scatterings from thermal fluctuations and defects are of the same order of magnitude. Taking into account the dependence of the Brillouin scattering on the direction of the incident beam relative to crystalline axes, an upper limit of scattering loss due to thermal fluctuation in the perfect crystal has been evaluated theoretically. At 193nm this limit appeared to be 2.6×10−5cm−1, which is about two orders of magnitude less than the scattering loss in fused silica. Measured values of Rayleigh and Mie scatterings are in reasonable agreement with theoretical evaluation. Scattering measured in high-quality samples are comparable with the scattering calculated from thermodynamic fluctuations, indicating that the transmission of these samples is approaching the theoretical limit.
Vacuum ultraviolet circular dichroism spectroscopy using an ac-modulated polarizing undulator
Authors: Yamada Toru , Yagi-Watanabe Kazutoshi , Tanaka Masahito , Kaneko Fusae , Kitada Tomo , Ohta Yoshimi , Nakagawa Kazumichi
Published: September 2005

To obtain vacuum ultraviolet (VUV) circular dichroism (CD) measurements, an Onuki-type crossed undulator in an electron storage ring (TERAS) at the National Institute of Advanced Industrial Science and Technology (AIST) was used as a light source and a polarization modulator was used instead of a photoelastic modulator (PEM). Polarization modification through the beam-line optics was theoretically considered and experimentally examined by polarization analysis. The modulation frequency of 2Hz was chosen to optimize the signal-to-noise ratio. On this basis, VUV-CD spectra of alanine films were measured and calibrated. The resulting CD spectra were consistent with other data obtained that was measured by a conventional CD spectropolarimeter (JASCO, J720WI) at a wavelength range of 190–210nm. The spectra of L- and D-alanine films showed an obvious symmetry with respect to the baseline at a wavelength range of 120–210nm. These results proved that the true CD of the samples was measured. The present technique successfully extended the wavelength coverage of CD measurements to a shorter range than the practical limit of PEMs.
Photodissociation dynamics in “hyper-rovibronic” detail: Exploring the potential of millimeter/submillimeter-wave spectroscopy in molecular reaction dynamics experiments
Authors: Duffy Liam M.
Published: September 2005

Over the years, many techniques for studying molecular reaction dynamics have been developed and fine-tuned to probe chemical dynamics at an ever-increasing level of detail. Unfortunately, this progress has frequently come at the price of high experimental cost and great complexity. In this regard experiments employing direct absorption have a distinct advantage in that they are comparatively simple in setup and they probe nascent product distributions directly. Even though the low product number densities in molecular-beam experiments put severe constraints on the noise and sensitivity requirements of detectors, Nesbitt and co-workers [J. Chem. Phys. 86, 3151 (1987); Rev. Sci. Instrum. 58, 807 (1987); J. Chem. Phys. 85, 4890 (1986); J. Chem. Phys. 107, 5661 (1997); Chem. Phys. Lett. 258, 207 (1996)] have demonstrated the use of direct infrared absorption in a variety of molecular reaction dynamics studies. In analogous experiments, this article explores the use of millimeter- and submillimeter-wavelength radiation in direct absorption experiments in a molecular beam. The comparatively simple and inexpensive setup demonstrates the utility of combining new commercial solid-state millimeter/submillimeter-wavelength sources with hot-electron bolometer detectors to directly probe parent and product hyperfine rovibronic levels and their Doppler-resolved velocity distributions in a molecular beam. For example, in open-shell products with nuclear spin, the ultrahigh energy resolution of the rotational spectroscopy easily resolves nuclear quadrupole hyperfine structure and lambda doublets in both ground and excited spin-orbit states as well as in ground and excited vibrational levels. Two molecular beam examples are given: (1) detection of “hyper-rovibronic” structure in ClO (ΠΩ=3∕2,1∕22, ν=0–8, J=112–712, Λ,F) following the mode-specific photodissociation of OClO (AA22←XB12, ν1=14–15), and (2) coherent transient absorption of HCN following the 266 nm photodissociation of sym-triazine/argon clusters.
Subnanosecond Thomson scattering setup for space and time resolved measurements with reduced background signal
Authors: Kieft E. R. , Groothuis C. H. J. M. , van der Mullen J. J. A. M. , Banine V.
Published: September 2005

In order to reduce the level of recorded background radiation in Thomson scattering (TS) experiments, we have designed and built a new setup for time and space resolved subnanosecond TS. Compared to our old setup, the new one is based on a faster camera, a laser with shorter pulse duration, and an optical delay line in the laser path. It has been characterized both by ray-trace simulations of the spectrograph and test experiments using Rayleigh and rotational Raman scattering on atmospheric pressure nitrogen gas. Although it was designed in the first place for experiments on a vacuum arc discharge in tin vapor for production of extreme ultraviolet light, our setup can also be applied to other plasmas that emit high levels of radiation or in which fast phenomena play a role.
Epitaxial Heusler alloy Co2FeSi∕GaAs(001) hybrid structures
Authors: Hashimoto M. , Herfort J. , Schönherr H.-P. , Ploog K. H.
Published: August 2005

We found that Co2FeSi layers on GaAs(001) grown by molecular-beam epitaxy with high crystal and interface perfection as well as smooth surfaces can be obtained in the low-growth-temperature regime. The layers are thermally robust up to 250°C. They have long-range order and crystallize in the Heusler-type L21 structure. The easy axis of magnetization is along the [110] direction caused by a dominating uniaxial in-plane magnetic anisotropy component which has an easy axis different from that of the magnetocrystalline anisotropy component.
Studies of the annihilation mechanism of threading dislocation in AlN films grown on vicinal sapphire (0001) substrates using transmission electron microscopy
Authors: Shen X. Q. , Okumura H. , Matsuhata H.
Published: September 2005

Annihilation phenomena of threading dislocations (TDs) in AlN films grown on vicinal sapphire (0001) substrates are investigated by transmission electron microscopy. It is found that the dislocation density is greatly reduced when the AlN is grown on a 2°-cut vicinal sapphire substrate. Two different types of the annihilation mechanisms of TDs were observed: (i) The coalescence of two TDs with opposite Burger’s vectors b to form a dislocation loop with one b, and (ii) the formation of one TD from the combination of two TDs with different Burger’s vectors, such as [1¯21¯0]+[21¯1¯0]→[112¯0]. These interactions between TDs are caused by the formation of inclined TDs (ITDs), where ITDs are locked and dragged by the macrosteps on the surface during the growth.
Is Curie–Weiss law valid in every ferro-to-para transition?
Authors: Kaur S. , Thakur A. K. , Choudhary A. , Bawa S. S. , Biradar A. M. , Annapoorni S.
Published: August 2005

The Curie–Weiss law is obeyed where there is a change in the order parameter and the symmetry of molecules at the transition temperature (Tc) of ferro-to-para phase. The ferroelectric transition is not strictly governed by the Curie–Weiss law. In fact, a number of solid ferroelectrics show deviation from the Curie–Weiss law. It has been shown in the present letter that the de-Vries electroclinic liquid crystals, with a wide smectic A (Sm-A) phase and a high electroclinic effect, do not obey the Curie–Weiss law. The nonlayer shrinkage leads to symmetry conservation that makes the observance of soft mode impossible and hence the deviation.
Temperature dependence of terahertz optical transitions from boron and phosphorus dopant impurities in silicon
Authors: Lynch S. A. , Townsend P. , Matmon G. , Paul D. J. , Bain M. , Gamble H. S. , Zhang J. , Ikonic Z. , Kelsall R. W. , Harrison P.
Published: September 2005

There has been considerable interest in using impurity dopants in silicon, such as boron and phosphorus, since it was demonstrated that such materials can show emission in the THz region of the electromagnetic spectrum. The measured temperature dependence of these transitions in this letter shows that the most optimistic maximum operating temperature of such an impurity-based laser is 90 K. In a real device with current flowing and associated Joule heating, the actual operating range is likely to be much narrower and it is therefore unlikely that such a device would have a maximum operating temperature above 40 K.
All-optical spin-dependent polarization switching in Bragg-spaced quantum well structures
Authors: Johnston W. J. , Yildirim M. , Prineas J. P. , Smirl Arthur L. , Gibbs H. M. , Khitrova G.
Published: September 2005

All-optical polarization switching is demonstrated in a resonant photonic band-gap structure consisting of Bragg-spaced quantum wells (BSQWs). The switch takes advantage of the large spin-dependent optical nonlinearities and the ultrafast recovery present in BSQWs to produce large throughputs (greater than 40%), high contrast ratios (greater than 40 dB), and large optical bandwidths (∼0.6THz), where both switching time and sample recovery time are control-pulse-width limited.
BaTiO
3
–
(
Bi
1
∕
2
Na
1
∕
2
)
TiO
3
solid-solution semiconducting ceramics with Tc>130°C
Authors: Takeda Hiroaki , Aoto Wataru , Shiosaki Tadashi
Published: September 2005

As a candidate of a lead-free positive temperature coefficient of resistivity (PTCR) material, barium titanate (BaTiO3)-based solid-solution ceramics, Ba1−x(Bi1∕2Na1∕2)xTiO3 with x=0.05 (BBNT5), have been synthesized by an ordinary sintering technique. Temperature dependences of the dielectric and ferroelectric properties show ferroelectric and paraelectric phase transition of the ceramics with the Curie temperature of Tc=170°C, which is higher than that of BaTiO3 (130°C). The La-doped BBNT5 ceramics display low ρ values of 102–103Ωcm at room temperature and their abrupt changes of 102–104 at about 220 °C. The reduced BBNT5 ceramics show small PTCR characteristics compared to the La-doped ones.
Polarization enhancement in two- and three-component ferroelectric superlattices
Authors: Nakhmanson S. M. , Rabe K. M. , Vanderbilt David
Published: September 2005

Composition-dependent structural and polar properties of epitaxial short-period CaTiO3∕-SrTiO3∕BaTiO3 superlattices grown on a SrTiO3 substrate are investigated with first-principles density-functional theory computational techniques. Polarization enhancement with respect to bulk tetragonal BaTiO3 is found for two- and three-component superlattices with a BaTiO3 concentration of more than 30%. Individual BaTiO3 layer thickness is identified as an important factor governing the polarization improvement. In addition, the degree of inversion-symmetry breaking in three-component superlattices can be controlled by varying the thicknesses of the component layers. The flexibility allowed within this large family of structures makes them highly suitable for various applications in modern nanoelectromechanical devices.
Crystal structure of the high-temperature paraelectric phase in barium titanate BaTi2O5
Authors: Yashima Masatomo , Tu Rong , Goto Takashi , Yamane Hisanori
Published: August 2005

Crystal structure of a ferroelectric barium titanate BaTi2O5 was investigated by the Rietveld analysis of neutron powder diffraction data measured at 706°C. The crystal structure of BaTi2O5 at 706°C was refined assuming the centrosymmetric monoclinic A2∕m space group. The crystal structures of the high-temperature A2∕m and low-temperature A2 phases are similar. The displacement of atoms along the b axis is accompanied by the paraelectric A2∕m to ferroelectric A2 phase transformation. The A2∕m-A2 transition is not reconstructive but displacive.
Self assembled nanoparticle wires by discontinuous vertical colloidal deposition
Authors: Diao J. J. , Sun Jianwei , Hutchison J. B. , Reeves M. E.
Published: September 2005

We report a simple, one-step method for assembling spherical nanoparticles into wires without the need for lithographic templating. It is effective for a variety of conducting and nonconducting nanoparticles and substrates, and the only material requirement is that the nanoparticles be placed in a colloidal suspension that is wettable on the desired substrate. The shape of the meniscus defines the wire’s geometry, and we report the synthesis and physical properties of wires several millimeters long by a few micrometers wide. As we demonstrate here, the technique is fast and easily controlled, and can be used to make integrated nanoparticle wire arrays.
Antiferromagnetic coupling and perpendicular anisotropy in TbFeCo∕NiO multilayers
Authors: Shan R. , Du J. , Zhang X. X. , Sun L. , Lin W. W. , Sang H. , Gao T. R. , Zhou S. M.
Published: August 2005

For Tbx(Fe90Co10)100−x(40nm)∕NiO(3.3nm) multilayers with x=17 and 19, antiferromagnetic coupling is revealed by both in-plane and out-of-plane hysteresis loops at low temperatures. Magnetic perpendicular anisotropy and out-of-plane coercivity of multilayers are enhanced, in comparison to those of TbFeCo single layer films. The strength of the antiferromagnetic coupling, the perpendicular anisotropy, and out-of-plane coercivity are all reduced at high temperatures. These results can be ascribed to the weakening of antiferromagnetic ordering of NiO spins.
Design of β-Secretase Inhibitors by Introduction of a Mandelyl Moiety in DAPT Analogues
Authors: Pietrancosta Nicolas , Quéléver Gilles , Laras Younes , Garino Cédrik , Burlet Stéphane , Kraus Jean Louis
Published: September 2005

We report the synthesis of two series of compounds with 3,5-difluoromandelyl-alanyl or 3,5-difluorophenylacetyl-alanyl backbones coupled to various heterocyclic or peptidic moieties. These two series of compounds were evaluated for their inhibitory properties on β-secretase (BACE-1) enzymatic assay, a target enzyme for Alzheimer’s disease (AD) pathology. We found that both diastereomers obtained from the racemic mixture 7 of the coumarin derivative bearing a mandelyl moiety were the most potent BACE-1 inhibitors studied in this work (IC50 = 1 × 10−6 M). Analysis of the obtained results led to the hypothesis that introduction of a difluoromandelyl residue in place of a difluorophenylacetyl moiety may induce β-secretase inhibitory activity.
Crystal structure of dihydrofolate reductase from
Plasmodium vivax
: Pyrimethamine displacement linked with mutation-induced resistance
Authors: Kongsaeree Palangpon , Khongsuk Puttapol , Leartsakulpanich Ubolsree , Chitnumsub Penchit , Tarnchompoo Bongkoch , Walkinshaw Malcolm D. , Yuthavong Yongyuth
Published: September 2005

Pyrimethamine (Pyr) targets dihydrofolate reductase of
Plasmodium vivax
(PvDHFR) as well as other malarial parasites, but its use as antimalarial is hampered by the widespread high resistance. Comparison of the crystal structures of PvDHFR from wild-type and the Pyr-resistant (SP21, Ser-58 → Arg + Ser-117 → Asn) strain as complexes with NADPH and Pyr or its analog lacking
p
-Cl (Pyr20) clearly shows that the steric conflict arising from the side chain of Asn-117 in the mutant enzyme, accompanied by the loss of binding to Ser-120, is mainly responsible for the reduction in binding of Pyr. Pyr20 still effectively inhibits both the wild-type and SP21 proteins, and the x-ray structures of these complexes show how Pyr20 fits into both active sites without steric strain. These structural insights suggest a general approach for developing new generations of antimalarial DHFR inhibitors that, by only occupying substrate space of the active site, would retain binding affinity with the mutant enzymes.
Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome
Authors: Kalanithi Paul S. A. , Zheng Wei , Kataoka Yuko , DiFiglia Marian , Grantz Heidi , Saper Clifford B. , Schwartz Michael L. , Leckman James F. , Vaccarino Flora M.
Published: August 2005

Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterized by motor and vocal tics. Imaging studies found alterations in caudate (Cd) and putamen volumes. To investigate possible alterations in cell populations, postmortem basal ganglia tissue from individuals with TS and normal controls was analyzed by using unbiased stereological techniques. A markedly higher total neuron number was found in the globus pallidus pars interna (GPi) of TS. In contrast, a lower neuron number and density was observed in the globus pallidus pars externa and in the Cd. An increased number and proportion of the GPi neurons were positive for the calcium-binding protein parvalbumin in tissue from TS subjects, whereas lower densities of parvalbumin-positive interneurons were observed in both the Cd and putamen of TS subjects. This change is consistent with a developmental defect in tangential migration of some GABAergic neurons. The imbalance in striatal and GPi inhibitory neuron distribution suggests that the functional dynamics of cortico-striato-thalamic circuitry are fundamentally altered in severe, persistent TS.
Structure and mechanism of the reversible photoswitch of a fluorescent protein
Authors: Andresen Martin , Wahl Markus C. , Stiel André C. , Gräter Frauke , Schäfer Lars V. , Trowitzsch Simon , Weber Gert , Eggeling Christian , Grubmüller Helmut , Hell Stefan W. , Jakobs Stefan
Published: September 2005

Proteins that can be reversibly photoswitched between a fluorescent and a nonfluorescent state bear enormous potential in diverse fields, such as data storage,
in vivo
protein tracking, and subdiffraction resolution light microscopy. However, these proteins could hitherto not live up to their full potential because the molecular switching mechanism is not resolved. Here, we clarify the molecular photoswitching mechanism of asFP595, a green fluorescent protein (GFP)-like protein that can be transferred from a nonfluorescent “off” to a fluorescent “on” state and back again, by green and blue light, respectively. To this end, we establish reversible photoswitching of fluorescence in whole protein crystals and show that the switching kinetics in the crystal is identical with that in solution. Subsequent x-ray analysis demonstrated that upon the absorption of a green photon, the chromophore isomerizes from a trans (off) to a cis (on) state. Molecular dynamics calculations suggest that isomerization occurs through a bottom hula twist mechanism with concomitant rotation of both bonds of the chromophoric methine ring bridge. This insight into the switching mechanism should facilitate the targeted design of photoswitchable proteins. Reversible photoswitching of the protein chromophore system within intact crystals also constitutes a step toward the use of fluorescent proteins in three-dimensional data recording.
Identification of a peptide fragment of DSCR1 that competitively inhibits calcineurin activityin vitroandin vivo
Authors: Chan Betty , Greenan Garrett , McKeon Frank , Ellenberger Tom
Published: August 2005

Calcineurin phosphatase activity regulates the nuclear localization of the nuclear factor of activated T cells (NFAT) family of transcription factors during immune challenge. Calcineurin inhibitors, such as the cyclosporin A–cyclophilin A and FK506–FKBP12 complexes, regulate this enzymatic activity noncompetitively by binding at a site distinct from the enzyme active site. A family of endogenous protein inhibitors of calcineurin was recently identified and shown to block calcineurin-mediated NFAT nuclear localization and transcriptional activation. One such inhibitor, Down Syndrome Critical Region 1 (DSCR1), functions in T cell activation, cardiac hypertrophy, and angiogenesis. We have identified a small region of DSCR1 that is a potent inhibitor of calcineurin activityin vitroandin vivo.
Hydrogen bonds in liquid water are broken only fleetingly
Authors: Eaves J. D. , Loparo J. J. , Fecko C. J. , Roberts S. T. , Tokmakoff A. , Geissler P. L.
Published: September 2005

Although it is widely accepted that the local structure of liquid water has tetrahedral arrangements of molecules ordered by hydrogen bonds, the mechanism by which water molecules switch hydrogen-bonded partners remains unclear. In this mechanism, the role of nonhydrogen-bonded configurations (NHBs) between adjacent molecules is of particular importance. A molecule may switch hydrogen-bonding partners either (
i
) through thermally activated breaking of a hydrogen bond that creates a dangling hydrogen bond before finding a new partner or (
ii
) by infrequent but rapid switching events in which the NHB is a transition state. Here, we report a combination of femtosecond 2D IR spectroscopy and molecular dynamics simulations to investigate the stability of NHB species in an isotopically dilute mixture of HOD in D
2
O. Measured 2D IR spectra reveal that hydrogen-bonded configurations and NHBs undergo qualitatively different relaxation dynamics, with NHBs returning to hydrogen-bonded frequencies on the time scale of water's fastest intermolecular motions. Simulations of an atomistic model for the OH vibrational spectroscopy of water yield qualitatively similar 2D IR spectra to those measured experimentally. Analysis of NHBs in simulations by quenching demonstrates that the vast majority of NHBs are in fact part of a hydrogen-bonded well of attraction and that virtually all molecules return to a hydrogen-bonding partner within 200 fs. The results from experiment and simulation demonstrate that NHBs are intrinsically unstable and that dangling hydrogen bonds are an insignificant species in liquid water.
Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cells
Authors: Werz Oliver , Tretiakova Irina , Michel Angela , Ulke-Lemee Annegret , Hörnig Michael , Franke Lutz , Schneider Gisbert , Samuelsson Bengt , Rådmark Olof , Steinhilber Dieter
Published: September 2005

5-Lipoxygenase (5-LO) is a tightly regulated enzyme in the synthesis of bioactive lipids from arachidonic acid. Here, we demonstrate that 5-LO is regulated by caspases, which are signaling molecules that control critical biological processes by means of specific limited proteolysis. Cell splitting of the Epstein–Barr virus-transformed B lymphocytic cell line BL41-E95-A caused a pronounced, but transient, reduction of functional 5-LO protein, ac-companied by the appearance of a 62-kDa 5-LO cleavage product. In parallel, splitting of BL41-E95-A cells induced activation of caspase-6 (casp-6) and casp-8. Caspase activation and 5-LO degradation were blocked by the protein-synthesis inhibitor cycloheximide, and cell-permeable peptide inhibitors of casp-6 and casp-8 prevented 5-LO cleavage. Activation of casp-6 and casp-8 was connected to subsequent enhancement of cell proliferation, whereas selective caspase inhibition blocked cell growth. Last, isolated human 5-LO was cleaved by recombinant casp-6
in vitro
to a 58-kDa fragment. Based on site-directed mutagenesis studies, 5-LO is cleaved by casp-6 after Asp-170, which in a homology-based 3D model of 5-LO is located on the enzyme periphery. We suggest that splitting of BL41-E95-A cells induces
de novo
synthesis of a protein involved in the activation of casp-6, which cleaves 5-LO.
Statistical coil model of the unfolded state: Resolving the reconciliation problem
Authors: Jha Abhishek K. , Colubri Andrés , Freed Karl F. , Sosnick Tobin R.
Published: August 2005

An unfolded state ensemble is generated by using a self-avoiding statistical coil model that is based on backbone conformational frequencies in a coil library, a subset of the Protein Data Bank. The model reproduces two apparently contradicting behaviors observed in the chemically denatured state for a variety of proteins, random coil scaling of the radius of gyration and the presence of significant amounts of local backbone structure (NMR residual dipolar couplings). The most stretched members of our unfolded ensemble dominate the residual dipolar coupling signal, whereas the uniformity of the sign of the couplings follows from the preponderance of polyproline II and β conformers in the coil library. Agreement with the NMR data substantially improves when the backbone conformational preferences include correlations arising from the chemical and conformational identity of neighboring residues. Although the unfolded ensembles match the experimental observables, they do not display evidence of native-like topology. By providing an accurate representation of the unfolded state, our statistical coil model can be used to improve thermodynamic and kinetic modeling of protein folding.
Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP
Authors: Cary Stephen P. L. , Winger Jonathan A. , Marletta Michael A.
Published: August 2005

Nitric oxide (NO) affects many physiological systems by activating cGMP signaling cascades through soluble guanylate cyclase (sGC). In the accepted model, NO binds to the sGC heme, activating the enzyme. Here, we report that in the presence of physiological concentrations of ATP and GTP, NO dissociation from the sGC heme is ≈160 times slower than the rate of enzyme deactivation
in vitro
. Deactivated sGC still has NO bound to the heme, and full activation requires additional NO. We propose an activation model where, in the presence of both ATP and GTP, tonic NO forms a stable heme complex with low sGC activity; acute production of NO transiently and fully activates this NO-bound sGC.
The adjuvant activity of CpG DNA requires T-bet expression in dendritic cells
Authors: Lugo-Villarino Geanncarlo , Ito Shu-Ichi , Klinman Dennis M. , Glimcher Laurie H.
Published: September 2005

Treatment with synthetic oligodeoxynucleotides containing CpG motifs (CpG ODNs) is remarkably protective against otherwise lethal infection. Here, we describe an essential role for the transcription factor T-bet in mediating the protective function of CpG ODNs. Loss of T-bet in conventional CD11chidendritic cells (DCs) and in plasmacytoid DCs impaired production of IFNs. Strikingly, in contrast toRag2-/-mice,Rag2-/-mice that also lacked T-bet (DKO) could not be rescued from lethalListeria monocytogenesinfection by prior treatment with CpG ODN. Rescue was achieved by adoptive transfer of CD11chiDCs from WT, but notT-bet-/-, CpG ODN-treated donor mice. We conclude that T-bet in DCs is required for the adjuvant activity of CpG ODN in infection, revealing its vital role in innate immunity.
Divergent Roles of c-Src in Controlling Platelet-derived Growth Factor-dependent Signaling in Fibroblasts
Authors: Shah Kavita , Vincent Fabien
Published: September 2005

The vast complexity of platelet-derived growth factor (PDGF)-induced downstream signaling pathways is well known, but the precise roles of critical players still elude us due to our lack of specific and temporal control over their activities. Accordingly, although Src family members are some of the better characterized effectors of PDGFβ signaling, considerable controversy still surrounds their precise functions. To address these questions and limitations, we applied a chemical–genetic approach to study the role of c-Src at the cellular level, in defined signaling cascades; we also uncovered novel phosphorylation targets and defined its influence on transcriptional events. The spectacular control of c-Src on actin reorganization and chemotaxis was delineated by global substrate labeling and transcriptional analysis, revealing multiple cytoskeletal proteins and chemotaxis promoting genes to be under c-Src control. Additionally, this tool revealed the contrasting roles of c-Src in controlling DNA synthesis, where it transmits conflicting inputs via the phosphatidylinositol 3 kinase and Ras pathways. Finally, this study reveals a mechanism by which Src family kinases may control PDGF-mediated responses both at transcriptional and translational levels.
Poly(ADP-ribosyl)ation by PARP-1: `PAR-laying' NAD+ into a nuclear signal
Authors: Kim Mi Young , Zhang Tong , Kraus W. Lee
Published: September 2005

Poly(ADP-ribose) (PAR) and the PAR polymerases (PARPs) that catalyze its synthesis from donor nicotinamide adenine dinucleotide (NAD+) molecules have received considerable attention in the recent literature. Poly(ADP-ribosyl)ation (PARylation) plays diverse roles in many molecular and cellular processes, including DNA damage detection and repair, chromatin modification, transcription, cell death pathways, insulator function, and mitotic apparatus function. These processes are critical for many physiological and pathophysiological outcomes, including genome maintenance, carcinogenesis, aging, inflammation, and neuronal function. This review highlights recent work on the biochemistry, molecular biology, physiology, and pathophysiology of PARylation, focusing on the activity of PARP-1, the most abundantly expressed member of a family of PARP proteins. In addition, connections between nuclear NAD+ metabolism and nuclear signaling through PARP-1 are discussed.
Centronuclear myopathy in mice lacking a novel muscle-specific protein kinase transcriptionally regulated by MEF2
Authors: Nakagawa Osamu , Arnold Michael , Nakagawa Masayo , Hamada Hideaki , Shelton John M. , Kusano Hajime , Harris Thomas M. , Childs Geoffrey , Campbell Kevin P. , Richardson James A. , Nishino Ichizo , Olson Eric N.
Published: September 2005

Myocyte enhancer factor 2 (MEF2) plays essential roles in transcriptional control of muscle development. However, signaling pathways acting downstream of MEF2 are largely unknown. Here, we performed a microarray analysis using Mef2c-null mouse embryos and identified a novel MEF2-regulated gene encoding a muscle-specific protein kinase, Srpk3, belonging to the serine arginine protein kinase (SRPK) family, which phosphorylates serine/arginine repeat-containing proteins. The Srpk3 gene is specifically expressed in the heart and skeletal muscle from embryogenesis to adulthood and is controlled by a muscle-specific enhancer directly regulated by MEF2. Srpk3-null mice display a new entity of type 2 fiber-specific myopathy with a marked increase in centrally placed nuclei; while transgenic mice overexpressing Srpk3 in skeletal muscle show severe myofiber degeneration and early lethality. We conclude that normal muscle growth and homeostasis require MEF2-dependent signaling by Srpk3.
Reinforcement of silencing at transposons and highly repeated sequences requires the concerted action of two distinct RNA polymerases IV in Arabidopsis
Authors: Pontier Dominique , Yahubyan Galina , Vega Danielle , Bulski Agnès , Saez-Vasquez Julio , Hakimi Mohamed-Ali , Lerbs-Mache Silva , Colot Vincent , Lagrange Thierry
Published: September 2005

Recent genetic and biochemical studies have revealed the existence in plants of a fourth RNA polymerase, RNAPIV, which mediates siRNA accumulation and DNA methylation-dependent silencing of endogenous repeated sequences. Here, we show that Arabidopsis expresses, in fact, two evolutionarily related forms of RNAPIV, hereafter referred to as RNAPIVa and RNAPIVb. These two forms contain the same second-largest subunit (NRPD2), but differ at least by their largest subunit, termed NRPD1a and NRPD1b. Unlike NRPD1a, NRPD1b possesses a reiterated CTD, a feature that also characterizes the largest subunit of RNAPII. Our data indicate that RNAPIVb is the most abundant form of RNAPIV in Arabidopsis. Selective disruption of either form of RNAPIV indicates that RNAPIVa-dependent siRNA accumulation is not sufficient per se to drive robust silencing at endogenous loci and that high levels of DNA methylation and silencing depend on siRNA that are accumulated through a pathway involving the concerted action of both RNAPIV forms. Taken together, our results imply the existence of a novel two-step mechanism in siRNA synthesis at highly methylated loci, with RNAPIVb being an essential component of a self-reinforcing loop coupling de novo DNA methylation to siRNA production.
Why do human diversity levels vary at a megabase scale?
Authors: Hellmann Ines , Prüfer Kay , Ji Hongkai , Zody Michael C. , Pääbo Svante , Ptak Susan E.
Published: September 2005

Levels of diversity vary across the human genome. This variation is caused by two forces: differences in mutation rates and the differential impact of natural selection. Pertinent to the question of the relative importance of these two forces is the observation that both diversity within species and interspecies divergence increase with recombination rates. This suggests that mutation and recombination are either directly coupled or linked through some third factor. Here, we test these possibilities using the recently generated sequence of the chimpanzee genome and new estimates of human diversity. We find that measures of GC and CpG content, simple-repeat structures, as well as the distance from the centromeres and the telomeres predict diversity as well as divergence. After controlling for these factors, large-scale recombination rates measured from pedigrees are still significant predictors of human diversity and human-chimpanzee divergence. Furthermore, the correlation between human diversity and recombination remains significant even after controlling for human-chimpanzee divergence. Two plausible and non-mutually exclusive explanations are, first, that natural selection has shaped the patterns of diversity seen in humans and, second, that recombination rates across the genome have changed since humans and chimpanzees shared a common ancestor, so that current recombination rates are a better predictor of diversity than of divergence. Because there are indications that recombination rates may have changed rapidly during human evolution, we favor the latter explanation.
Ancient haplotypes of the HLA Class II region
Authors: Raymond Christopher K. , Kas Arnold , Paddock Marcia , Qiu Ruolan , Zhou Yang , Subramanian Sandhya , Chang Jean , Palmieri Anthony , Haugen Eric , Kaul Rajinder , Olson Maynard V.
Published: September 2005

Allelic variation in codons that specify amino acids that line the peptide-binding pockets of HLA's Class II antigen-presenting proteins is superimposed on strikingly few deeply diverged haplotypes. These haplotypes appear to have been evolving almost independently for tens of millions of years. By complete resequencing of 20 haplotypes across the ∼100-kbp region that spans theHLA-DQA1, -DQB1, and -DRB1genes, we provide a detailed view of the way in which the genome structure at this locus has been shaped by the interplay of selection, gene-gene interaction, and recombination.
Genomic deletions and precise removal of transposable elements mediated by short identical DNA segments in primates
Authors: van de Lagemaat Louie N. , Gagnier Liane , Medstrand Patrik , Mager Dixie L.
Published: September 2005

Insertion of transposable elements is a major cause of genomic expansion in eukaryotes. Less is understood, however, about mechanisms underlying contraction of genomes. In this study, we show that retroelements can, in rare cases, be precisely deleted from primate genomes, most likely via recombination between 10- to 20-bp target site duplications (TSDs) flanking the retroelement. The deleted loci are indistinguishable from pre-integration sites, effectively reversing the insertion. Through human-chimpanzee-Rhesus monkey genomic comparisons, we estimate that 0.5%-1% of apparent retroelement “insertions” distinguishing humans and chimpanzees actually represent deletions. Furthermore, we demonstrate that 19% of genomic deletions of 200-500 bp that have occurred since the human-chimpanzee divergence are associated with flanking identical repeats of at least 10 bp. A large number of deletions internal to Alu elements were also found flanked by homologies. These results suggest that illegitimate recombination between short direct repeats has played a significant role in human genome evolution. Moreover, this study lends perspective to the view that insertions of retroelements represent unidirectional genetic events.
The New Entrepreneur Scholarships: self‐employment as a means to tackle social deprivation
Authors: Slack Jonathan
Published: September 2005

Purpose

The purpose of this paper is to investigate New Entrepreneur Scholarships, a government‐funded programme that aims to help people from disadvantaged backgrounds to become self‐employed.

Design/methodology/approach

A case study methodology is employed.

Findings

The programme has been very effective in helping people who would not otherwise overcome the barriers in setting up a business to establish themselves in self‐employment.

Originality/value

Tacking the issue of qualifications remains an issue as there is no clear demand for a qualification. Resources are also needed to further promote the success of New Entrepreneur scholars within their own areas to that they can be role models to others and so that enterprise can be seen as a viable option for other members of their communities.
The changing role of education on managerial career attainment
Authors: Hurley‐Hanson Amy E. , Wally Stefan , Segrest Purkiss Sharon L. , Sonnenfeld Jeffrey A.
Published: September 2005

Purpose

This study aims to explore the role of formal education in managerial career attainment and how this role has changed over time.

Design/methodology/approach

The personnel records of two cohorts of managers who entered the firm at different times in a large internal labor market company were examined. The study encompassed years of education, subject of degree, timing of degree conferral, and quality of educational institution. Career attainment was regressed on the control variables and the hypothesized predictor variables using hierarchical multiple regression analysis.

Findings

The research suggests that the importance of having an undergraduate degree seems to be increasing, while the importance of the selectivity of the university seems to be decreasing with respect to career attainment. Also, majoring in business continues to be an important factor related to career attainment.

Research limitations/implications

Future research focusing specifically on the differences in managerial career attainment of individuals who stay with their initial firm versus those who change employers would be beneficial. It would also be interesting to focus on the different reasons why people go back to school to obtain a degree.

Practical implications

Obtaining a degree after entering the firm was not related to career attainment. Universities have advocated the benefits of obtaining a degree to students who are already in the workforce. These results must be investigated further.

Originality/value

The data for this study were obtained from occupational records and allowed a more detailed analysis of an actual internal labor market organization and a longitudinal look at the changing role of education in relationship to career attainment.
Prudence vs professionalism
Authors: Kakabadse Nada K. , Kakabadse Andrew
Published: September 2005

Purpose

This paper seeks to report original research examining how effectively board members of occupational pension trusts administer pension plan assets on behalf of their respective members. The concept of the concerned lay board member (the “prudent person”) is increasingly under attack from the media, government and professional bodies. The proposition is that lay members should be replaced by professionals. Aims to explore the prudence vs professionalism theme through an examination of trustee profile, trustee financial competence and trustee performance effectiveness.

Design/methodology/approach

The study adopts demographic theory from the perspective that group demographics are a critical focus of analysis due to their potent impact on organisational outcomes. A qualitative approach was initially pursued in order to capture trustee views which formed the platform for the second quantitative phase of the study.

Findings

The study concludes that lay trustees display comparable capacity to professional trustees and emerge as equally able to positively respond to the future challenges facing pension boards.

Practical implications

The study highlights that HR practitioners can make a significant impact on the selection and development of pension board trustees.

Originality/value

Rather than continuing with the unhelpful, historically based distinction between lay and professional pension board trustees, this original study identifies the growing complexities of managing pension trusts, whilst emphasising the capabilities required to pursue innovative investment practice in the future. This paper is likely to be of value to researchers in the areas of board and pension trust performance, fund trustees, actuaries, trust fund managers, employee benefits consultancies, the Treasury and HR professionals.
A note on occupational variations in the returns to education in the US labor market
Authors: Gabriel Paul E. , Schmitz Susanne
Published: September 2005

Purpose

Seeks to answer the question: “do certain occupations offer lower financial benefits to acquiring years of formal schooling than others?”.

Design/methodology/approach

This study uses data from the 2003 Current Population Survey to estimate rates of return to education across occupational categories in the US labor market. The wage model employed is based on the human capital model of income determination.

Findings

The analysis suggests that additional schooling has a positive impact on the weekly earnings of men and women in both white‐ and blue‐collar occupations – with the highest returns accruing to sales, managerial, and professional workers. Although returns are generally higher for white‐collar workers, no link is found between the returns to schooling and the propensity of occupations to be comprised of “primary” or “secondary” sector jobs.

Originality/value

Supports the notion that additional schooling increases the earnings of men and women in both blue‐ and white‐collar occupations.
Analysis of team effectiveness in software development teams working on hardware and software environments using Belbin Self‐perception Inventory
Authors: Rajendran Mazhil
Published: September 2005

Purpose

Aims to present a team effectiveness analysis of software development teams and one means of improving the effectiveness of software development teams in quite an innovative manner, namely, by forming teams based on who can work effectively together.

Design/methodology/approach

The team roles described by R. Meredith Belbin are utilized to improve the effectiveness of software development teams The procedure used in these analyses consists of: finding teams that indicate a commitment to, or interest in, participating in an analysis of their team; having all team members fill out the Belbin Self‐perception Inventory in order to gather data for analysis; interviewing the leader of the team in order to obtain an independent analysis and verification of the self‐perception data; analyzing the self‐perception data, looking for trends in the data from which subjective assessments can be made; Comparing the Belbin analysis with the interview information, identifying similarities and differences between the two, thus providing verification of the Belbin analysis.

Findings

Analyses of software development teams from within the industry demonstrate that Belbin's roles and the Belbin self‐perception inventory can be used to recognize important positive and negative features of a team. Thus, positive features can be encouraged, and negative features can be avoided or remedied.

Originality/value

This paper would be useful to managers and team leaders of software development industries to analyze their team and to bring out superior efforts of forming the team to get the work done.