bluuebunny/crossref_metadata_2025 huggingface dataset:
Z pinches as intense x-ray sources for high-energy density physics applications
Authors: Matzen M. Keith
Published: July 2002

Fast Z-pinch implosions can efficiently convert the stored electrical energy in a pulsed-power accelerator into x rays. These x rays are produced when an imploding cylindrical plasma, driven by the magnetic field pressure associated with very large axial currents, stagnates upon the cylindrical axis of symmetry. On the Saturn pulsed-power accelerator [R. B. Spielman et al., in Proceedings of the 2nd International Conference on Dense Z Pinches, Laguna Beach, CA, 1989, edited by N. R. Pereira, J. Davis, and N. Rostoker (American Institute of Physics, New York, 1989), p. 3] at Sandia National Laboratories, for example, currents of 6–8 MA with a rise time of less than 50 ns are driven through cylindrically symmetric loads, producing implosion velocities as high as 108 cm/s and x-ray energies exceeding 400 kJ. Hydromagnetic Rayleigh–Taylor instabilities and cylindrical load symmetry are critical, limiting factors in determining the assembled plasma densities and temperatures, and thus in the x-ray energies and pulse widths that can be produced on these accelerators. In recent experiments on the Saturn accelerator, these implosion nonuniformities have been minimized by using wire arrays with as many as 192 wires. Increasing the wire number produced significant improvements in the pinched plasma quality, reproducibility, and x-ray output power. X-ray pulse widths of less than 5 ns and peak powers of 75±10 TW have been achieved with arrays of 120 tungsten wires. Similar loads have recently been fielded on the Particle Beam Fusion Accelerator (PBFA II), producing x-ray energies in excess of 1.8 MJ at powers in excess of 160 TW. These intense x-ray sources offer the potential for performing many new basic physics and fusion-relevant experiments.
Fluid equations governing the dynamics and energetics of partially ionized dusty magnetoplasmas
Authors: Kopp A. , Schröer A. , Birk G. T. , Shukla P. K.
Published: July 2002

A set of nonlinear equations for multi-component partially ionized dusty magnetoplasmas is developed, taking into account the contributions of frictional thermalization, collisional heating in the energy equations on one hand, and those of ionization and recombination in the continuity equations on the other hand. The present nonlinear equations form a tool for numerical simulation studies of various collective effects in the presence of sources and sinks. However, in order to illustrate possible applications of the present system of equations, two examples of thermal condensation instabilities are discussed.
A unified theory of transport barriers and of subneoclassical transport
Authors: Rogister André L.
Published: July 2002

“Subneoclassical” heat fluxes are shown to be rigorous consequences of the revisited neoclassical theory published earlier [Phys. Plasmas 1, 619 (1994)]. Including finite Larmor radius and inertia effects, this theory also provides a nondegenerate ambipolarity constraint, which, together with the parallel momentum equation, defines unambiguously the radial electric field Er and the parallel velocity U∥,i. It is shown that the stationary solution of those equations features, under conditions that are discussed, highly sheared Er profiles as observed in edge transport barriers. The operation regime is determined by a competition between nonlinear spin up of the rotation (which is interpreted) and momentum loss via charge exchange neutrals. The position of the transport barrier—near the last closed magnetic surface (LCMS)—is explained. The local threshold condition is analyzed, including the role of recycling neutrals and of the isotope mass. The width of the shear layer, as well as the predicted jumps and negative values of Er in front of the LCMS, agrees with experimental data. The time-dependent equations have solutions propagating from the edge to the core; the time scale associated with the toroidal rotation scales as and is usually comparable to the neoclassical heat transport time scale. Although the theory is so far limited to the high collisionality regime, a clear physical interpretation of the results allows extrapolation to low collisionality plasmas.
A nonlinear dynamic model of relaxation oscillations in tokamaks
Authors: Thyagaraja A. , Haas F. A. , Harvey D. J.
Published: July 2002

Tokamaks exhibit several types of relaxation oscillations such as sawteeth, fishbones and Edge Localized Modes (ELMs) under appropriate conditions. Several authors have introduced model nonlinear dynamic systems with a small number of degrees of freedom which can illustrate the generic characteristics of such oscillations. In these models, one focuses on physically “relevant” degrees of freedom, without attempting to simulate all the myriad details of the fundamentally nonlinear tokamak phenomena. Such degrees of freedom often involve the plasma macroscopic quantities such as pressure or density and also some measure of the plasma turbulence, which is thought to control transport. In addition, “coherent” modes may be involved in the dynamics of relaxation, as well as radial electric fields, sheared flows, etc. In the present work, an extension of an earlier sawtooth model (which involved only two degrees of freedom) due to the authors is presented. The dynamical consequences of a pressure-driven “coherent” mode, which interacts with the turbulence in a specific manner, are investigated. Varying only the two parameters related to the coherent mode, the bifurcation properties of the system have been studied. These turn out to be remarkably rich and varied and qualitatively similar to the behavior found experimentally in actual tokamaks. The dynamic model presented involves only continuous nonlinearities and is the simplest known to the authors that can yield features such as sawteeth, “compound sawteeth” with partial crashes, “monster” sawteeth, metastability, intermittency, chaos, periodic and “grassy” ELMing in appropriate regions of parameter space. The results suggest that linear stability analysis of systems, while useful in elucidating instability drives, can be misleading in understanding the dynamics of nonlinear systems over time scales much longer than linear growth times and states far from stable equilibria.
Local transit-time dissipation and Landau damping
Authors: Skjæraasen O. , Robinson P. A. , Melatos A.
Published: July 2002

A generalization of local transit-time dissipation theory to coherent electrostatic wave packets with nonzero mean wave number is presented. The connection between Landau damping and transit time damping is derived in a concise, mathematically rigorous manner, settling a longstanding controversy. It is shown that transit time dissipation involves both Landau-type resonant damping and nonresonant damping. For small wave packets with nonzero mean wave number or asymmetric incident particle distributions, the nonresonant damping can dominate over Landaudamping. In the opposite extreme of infinitely large, constant-amplitude wave packets, the nonresonant part of transit time dissipation vanishes, and only Landau damping remains. All the analytical results presented are verified independently by numerical test-particle calculations.
Radiative properties of high wire number tungsten arrays with implosion times up to 250 ns
Authors: Deeney C. , Coverdale C. A. , Douglas M. R. , Struve K. W. , Spielman R. B. , Stygar W. A. , Peterson D. L. , Roderick N. F. , Haines M. G. , Beg F. N. , Ruiz-Camacho J.
Published: July 2002

High wire number, 25-mm-diameter tungsten wire arrays have been imploded on the 8-MA Saturn generator [R. B. Spielman et al., AIP Conference Proceeding 195, 3 (American Institute of Physics, Woodbury, NY 1989)], operating in a long-pulse mode. By varying the mass of the arrays from 710 to 6140 μg/cm, implosion times of 130–250 ns have been obtained with implosion velocities of 50–25 cm/μs, respectively. These Z-pinch implosions produced plasmas with millimeter diameters that radiated 600–800 kJ of x-rays, with powers of 20–49 TW; the corresponding pulsewidths were 19–7.5 ns, with risetimes ranging from 6.5 to 4.0 ns. These powers and pulsewidths are similar to those achieved with 50-ns implosion times on Saturn. Two-dimensional, radiation-magnetohydrodynamic calculations indicate that the imploding shells in these long implosion time experiments are comparable in width to those in the short-pulse cases. This can be due to lower initial perturbations. A heuristic wire array model suggests that the reduced perturbations, in the long-pulse cases, may be due to the individual wire merger occurring well before the acceleration of the shell. The experiments and modeling suggest that 150–200 ns implosion time Z-pinches could be employed for high-power, x-ray source applications.
Theory of high-frequency waves in a coaxial plasma wave guide
Authors: Maraghechi B. , Farrokhi B. , Willett J. E.
Published: July 2002

An analysis of the high-frequency eigenmodes of a coaxial wave guide containing a magnetized annular plasma column is presented. A transcendental equation is derived from the boundary conditions in the form of an eighth-order determinant equated to zero. Simultaneous solution of this determinantal equation and a polynomial equation derived from the wave equation yields the dispersion relations for the eigenmodes. By reduction of the order of the determinant the appropriate transcendental equation is easily obtained for some special cases, e.g., partially filled coaxial wave guide. The electrostatic treatment of a coaxial cylindrical wave guide is also presented. The corresponding transcendental equation is reduced to some special cases, e.g., conventional wave guide containing an annular plasma column under electrostatic approximation. Numerical solutions are obtained for some azimuthally symmetric EH (perturbed TM) and HE (perturbed TE) wave guide modes, cyclotron modes, and space-charge modes. A strong dependence of the frequencies of these electromagnetic–electrostatic waves on the radii of the coaxial wave guide and the plasma column is revealed.
Transistor action in Si/CoSi2/Si heterostructures
Authors: Hensel J. C. , Levi A. F. J. , Tung R. T. , Gibson J. M.
Published: July 2002

We report transistor action in a Si/CoSi2/Si structure. The thin silicide layer (<100 Å), which acts as the base, is a single-crystal metal, essentially continuous and locally exhibiting atomically perfect interfaces with Si. The transistor action is manifested by a common base current gain α as high as 0.6 and a voltage gain greater than 10.
Infrared absorption band for substitutional nitrogen in silicon
Authors: Stein H. J.
Published: July 2002

Formation and annealing characteristics for an infrared absorption band at 653 cm−1 in 14N-implanted Si have been correlated with those for a distorted substitutional N center identified previously in electron paramagnetic resonance studies. It is concluded from this correlation and the observed frequency shift upon isotopic substitution of 15N that the 653 cm−1 band is a localized vibrational mode for substitutional 14N in Si.
Dependence of hole transport on Ga doping in Si molecular beam epitaxy layers
Authors: Casel A. , Jorke H. , Kasper E. , Kibbel H.
Published: July 2002

Ga-doped silicon layers with constant profiles were grown by molecular beam epitaxy (MBE) at 650 °C and by solid phase epitaxy in the MBE system at a regrowth temperature 600 °C. By the latter technique, doping levels up to 2×1020 cm−3 were achieved. The electrical properties were investigated by temperature-dependent Hall measurements. The resulting hole concentration was compared with the Ga concentration, determined by neutron activation analysis: At room temperature the ionization of the Ga acceptor was concentration dependent and exhibited a minimum of 50% at 1019 cm−3. Comparison with B-doped silicon showed a significant lower mobility for carrier concentration above 1019 cm−3.
A method of poling LiNbO3 and LiTaO3 below T
c
Authors: Haycock P. W. , Townsend P. D.
Published: July 2002

A method of poling LiNbO3 and LiTaO3 significantly below their Curie temperatures is proposed and results are presented. The technique involves excitation of the crystal lattice by an energetic beam of electrons while applying an electron field along the c axis. The lowest temperatures and fields successfully used so far are 600 °C with 10 V cm−1 for LiNbO3 and 400 °C with 900 V cm−1 for LiTaO3. These do not necessarily define lower limits for the process.
Optically detected carrier confinement to one and zero dimension in GaAs quantum well wires and boxes
Authors: Cibert J. , Petroff P. M. , Dolan G. J. , Pearton S. J. , Gossard A. C. , English J. H.
Published: July 2002

Carrier confinement to one and zero degrees of freedom has been achieved in artificial quantum well wires and boxes fabricated in the GaAs-GaAlAs system. Low-temperature cathodoluminescence measurements show new luminescence lines attributed to transitions arising from ground and excited levels of electrons within these low dimensional structures.
Surface stoichiometry and reaction kinetics of molecular beam epitaxially grown (001) CdTe surfaces
Authors: Benson J. D. , Wagner B. K. , Torabi A. , Summers C. J.
Published: July 2002

Reflection high-energy electron diffraction desorption studies have been performed on epitaxial (001) CdTe surfaces. Both Cd and Te desorption from CdTe were observed to follow a simple first order rate law. Activation energies of 1.95 and 7.70 eV were found for Te and Cd, respectively, on the CdTe surface. The congruent evaporation temperature was determined to be 340 °C. Under normal growth conditions (a substrate temperature of 300 °C and growth rate of 1 μm/h) a Te-stabilized surface of (001) CdTe was found. The implications of these findings on high-quality crystalline growth are discussed.
Chemically induced high-tilt surfaces for liquid crystals
Authors: Filas Robert W. , Patel J. S.
Published: July 2002

A method for producing high-tilt boundary conditions for liquid crystals has been developed which requires only chemical treatment followed by conventional rubbing techniques. The basic concept involves two chemicals: one which, by itself, produces homogeneous orientation, and the other which, by itself, gives homeotropic orientation. By varying the relative concentrations of the two components, it is possible to balance the surface forces to give any desired tilt angle. The chemicals chosen were two silanes: N-methylaminopropyltrimethoxysilane and octadecyltriethoxysilane, where the former is the homogeneous component and the latter is the homeotropic component. Although the system has some practical limitations, such as time-dependent solution behavior and high-temperature instability, it is possible to produce the entire range of tilt angles from homogeneous to homeotropic.
Nature of the E′ deep hole trap in metal-oxide-semiconductor oxides
Authors: Witham H. S. , Lenahan P. M.
Published: July 2002

We have found through a sequence of ultraviolet illuminations, electron spin resonance measurements, and capacitance versus voltage measurements, that the E′ deep hole trap in metal-oxide-semiconductor silicon dioxide is a fundamentally reversible defect. Our results are totally consistent with an oxygen vacancy model for the E′ deep hole trap, but our results are inconsistent with the bond strain gradient model for the deep hole trap in metal-oxide-semiconductor silicon dioxide.
Gate oxide integrity and minority-carrier lifetime correlated with Si wafer polish damage
Authors: Lee J. , Wong C.-C. D. , Tung C. Y. , Smith W. Lee , Hahn S. , Arst M.
Published: July 2002

This study investigated the effects of Si wafer polish damage on the electrical performance and integrated circuits, using metal-oxide-semiconductor capacitors as the test structures. These test capacitors were fabricated with 100 or 250 Å oxide layers thermally grown on wafers having varied polish-damaged surfaces. Field-dependent and time-dependent breakdown data were measured and correlated with the surface polish quality as characterized by thermal wave (TW) modulated reflectance measurements. To study the effects of damage remaining in the silicon beneath the Si/SiO2 interface after the formation of the capacitors, the minority-carrier lifetime was measured and also correlated with the TW values obtained on the starting (nonprocessed) wafer surfaces. The results of this study established that increased polish damage, indicated by higher TW values, adversely affects thin oxide breakdown integrity and reduces the minority-carrier lifetime.
Direct writing of GaAs monolayers by laser-assisted atomic layer epitaxy
Authors: Karam N. H. , Liu H. , Yoshida I. , Bedair S. M.
Published: July 2002

Direct writing of GaAs epitaxial monolayers has been achieved by laser-assisted atomic layer epitaxy (LALE) technique on GaAs substrates. Sequential exposures of the substrate to trimethylgallium (TMG) and arsine (AsH3) were separated by periods of hydrogen purging to prevent mixing. Laser beam scanning of the samples took place either during the flow of TMG or AsH3. The selectively grown films at the one monolayer per cycle condition have a mirrorlike surface and a flat top thickness profile. LALE has been realized at temperatures as low as 300 °C and over a wide range of TMG flux and laser power densities. Photoluminescence results of the deposited films show that their quality are comparable to those achieved by conventional ALE.
Investigation of the opacity of hot, dense aluminum in the region of its K edge
Authors: Davidson S. J. , Foster J. M. , Smith C. C. , Warburton K. A. , Rose S. J.
Published: July 2002

We report the application of a technique for performing opacity measurements on hot, dense plasmas. Plasmas were generated by using the x rays emitted from a laser-produced gold plasma to heat an aluminum sample. Observations were made using the technique of point projection spectroscopy. The distribution of ion stages observed is compared with predictions based on Saha distributions, at densities and temperatures deduced from hydrodynamic simulations.
Surface acoustic wave propagation on lead zirconate titanate thin films
Authors: Sreenivas K. , Sayer M. , Baar D. J. , Nishioka M.
Published: July 2002

Piezoelectric activity in reactively sputtered lead zirconate titanate [Pb(Zr,Ti)O3 or PZT] thin films has been confirmed through the fabrication of surface acoustic wave delay lines on poled polycrystalline films of PZT deposited on glass substrates. Films of varying thickness ranging from 3.4 to 6 μm show a dispersion in resonant frequency for interdigital transducers designed to resonate at 44 MHz on bulk PZT material. The electromechanical coupling coefficient k2 was in the range 0.57–0.79% for hk=0.21–0.37.
Gene expression profiles in normal and
Otx2
−/−
early gastrulating mouse embryos
Authors: Zakin Lise , Reversade Bruno , Virlon Bérangère , Rusniok Christophe , Glaser Philippe , Elalouf Jean-Marc , Brûlet Philippe
Published: July 2002

The mouse
Otx2
gene is a homeobox transcription
factor required as early as gastrulation for the proper development of
the head. We compared gene expression profiles in wild-type and
Otx2
−/−
6.5 days postcoitum embryos by
using a serial analysis of gene expression assay adapted to
microdissected structures. Among a broader list, the study of six genes
found to be differentially expressed allows defining a role for
Otx2
in the orchestration of cell movements leading to
the adequate organization of the embryo before gastrulation.
A stochastic algorithm for global optimization and for best populations: A test case of side chains in proteins
Authors: Glick Meir , Rayan Anwar , Goldblum Amiram
Published: July 2002

The problem of global optimization is pivotal in a variety of scientific fields. Here, we present a robust stochastic search method that is able to find the global minimum for a given cost function, as well as, in most cases, any number of best solutions for very large combinatorial “explosive” systems. The algorithm iteratively eliminates variable values that contribute consistently to the highest end of a cost function's spectrum of values for the full system. Values that have not been eliminated are retained for a full, exhaustive search, allowing the creation of an ordered population of best solutions, which includes the global minimum. We demonstrate the ability of the algorithm to explore the conformational space of side chains in eight proteins, with 54 to 263 residues, to reproduce a population of their low energy conformations. The 1,000 lowest energy solutions are identical in the stochastic (with two different seed numbers) and full, exhaustive searches for six of eight proteins. The others retain the lowest 141 and 213 (of 1,000) conformations, depending on the seed number, and the maximal difference between stochastic and exhaustive is only about 0.15 Kcal/mol. The energy gap between the lowest and highest of the 1,000 low-energy conformers in eight proteins is between 0.55 and 3.64 Kcal/mol. This algorithm offers real opportunities for solving problems of high complexity in structural biology and in other fields of science and technology.
Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes
Authors: Hagglund Ryan , Van Sant Charles , Lopez Pascal , Roizman Bernard
Published: July 2002

Infected cell protein 0 (ICP0) of herpes simplex virus 1, a multifunctional ring finger protein, enhances the expression of genes introduced into cells by infection or transfection, interacts with numerous cellular and viral proteins, and is associated with the degradation of several cellular proteins. Sequences encoded by exon 2 of ICP0 (residues 20–241) bind the UbcH3 (cdc34) ubiquitin-conjugating enzyme, and its carboxy terminus expresses a ubiquitin ligase activity demonstrable by polyubiquitylation of cdc34
in vitro
. We report that: (
i
) The physical interaction of cdc34 and ICP0 leads to its degradation. Thus, substitution of ICP0 aspartate 199 with alanine attenuates the degradation of cdc34 and its binding to the ICP0 ring finger domain. (
ii
) Substitution of residue 620 reported to abolish the interaction with a ubiquitin-specific protease has no effect on the function of ubiquitin ligase. (
iii
) ICP0 contains an additional distinct E3 ligase activity specific for the UbcH5a- and UbcH6 E2-conjugating enzymes mapping to the ring finger domain. This is, to our knowledge, the first identification of a viral protein with at least two physically separated E3 ligase activities with different E2 specificities. The results suggest that each activity may target different proteins.
Impact of folivory on photosynthesis is greater than the sum of its holes
Authors: Zangerl A. R. , Hamilton J. G. , Miller T. J. , Crofts A. R. , Oxborough K. , Berenbaum M. R. , de Lucia E. H.
Published: July 2002

The effects of herbivores on plant production and fitness may not relate directly to the quantity of biomass removed because folivory may alter photosynthetic rates at a considerable distance from the damaged tissue [Welter, S. C. (1989) in
Insect-Plant Interactions,
ed. Bernays, E. A. (CRC, Boca Raton), pp. 135–151.]. An impediment to understanding the effects of leaf damage on photosynthesis has been an inability to map photosynthetic function within a single leaf. We developed an instrument for imaging chlorophyll fluorescence and used it to map the effects of caterpillar feeding on whole-leaf photosynthesis in wild parsnip. The adverse effects of caterpillar feeding on photosynthesis were found to extend well beyond the areas of the leaflet in which caterpillars removed tissue. These “indirectly” affected areas remained impaired for at least 3 days after the caterpillars were removed and were six times as large as the area directly damaged by the caterpillars. Although photosynthesis in indirectly affected areas was reduced and not eliminated, these areas accounted for three times as much of the overall reduction in photosynthesis as the area removed by the caterpillars. The size of the indirect effects was positively correlated with defense-related synthesis of furanocoumarins, suggesting that costs of chemical defense may be one factor that accounts for the indirect effects of herbivory on plants.
Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion
Authors: Jenkins Scott M. , Bennett Vann
Published: July 2002

Nodes of Ranvier are excitable regions of axonal membranes highly enriched in voltage-gated sodium channels that propagate action potentials. The mechanism of protein clustering at nodes has been a source of controversy. In this study, developmental analysis of nodes of Ranvier in optic nerve axons reveals that early node intermediates are defined by ankyrin-G. Other node components, including beta IV spectrin, voltage-gated sodium channels, and the L1 cell adhesion molecule neurofascin, are subsequently recruited to sites of ankyrin-G clustering. The role of intact paranodes in protein clustering was examined in the dysmyelinating mouse mutant
jimpy. Jimpy
mice do not have intact paranodal axoglial contacts, which is indicated by a complete lack of neurexin/contactin-associated protein/paranodin clustering in paranodes. In the absence of intact paranodes, ankyrin-G was still able to cluster, although fewer ankyrin clusters were seen in
jimpy
optic nerves than in wild-type optic nerves. Recruitment of Na
v
1.2, Na
v
1.6, beta IV spectrin, and neurofascin to sites of ankyrin-G clustering is unimpaired in
jimpy
mice, indicating that node formation occurs independent of intact paranodal axoglial contacts.
HNF-1α G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community
Authors: Triggs-Raine Barbara L. , Kirkpatrick Robert D. , Kelly Sherrie L. , Norquay Lisa D. , Cattini Peter A. , Yamagata Kazuya , Hanley Anthony J. G. , Zinman Bernard , Harris Stewart B. , Barrett P. Hugh , Hegele Robert A.
Published: July 2002

The prevalence of type 2 diabetes mellitus in the Oji-Cree of northwestern Ontario is the third highest in the world. A private mutation, G319S, in
HNF1A
, which encodes hepatic nuclear factor-1α (HNF-1α), was associated with Oji-Cree type 2 diabetes and was found in ≈40% of affected subjects. The G319S mutation reduced the
in vitro
ability of HNF-1α to activate transcription by ≈50%, with no effect on DNA binding or protein stability. There was no evidence of a dominant negative effect of the mutant protein. The impact of the G319S mutation at the population level was assessed by classifying subjects with type 2 diabetes according to
HNF1A
genotype and plotting the cumulative age of onset of diabetes. Disease onset was modeled satisfactorily by two-parameter sigmoidal functions for all diabetic subjects and all three
HNF1A
genotypes. Pairwise statistical comparisons showed significant between-genotype differences in
t
50
(all
P
< 0.00001), corresponding to the age at which half the subjects had become diabetic. Each dose of G319S accelerated median disease onset by ≈7 years. Thus, the transactivation-deficient
HNF1A
G319S mutation affects the dynamics of disease onset. The demonstration of a functional consequence for
HNF1A
G319S provides a mechanistic basis for its strong association with Oji-Cree type 2 diabetes and its unparalleled specificity for diabetes prediction in these people, in whom diabetes presents a significant public health dilemma. The findings also show that
HNF1A
mutations can be associated with typical adult-onset insulin-resistant obesity-related diabetes in addition to maturity-onset diabetes of the young.
Electric and magnetic phenomena observed before the volcano-seismic activity in 2000 in the Izu Island Region, Japan
Authors: Uyeda S. , Hayakawa M. , Nagao T. , Molchanov O. , Hattori K. , Orihara Y. , Gotoh K. , Akinaga Y. , Tanaka H.
Published: July 2002

Significant anomalous changes in the ultra low frequency range (≈0.01 Hz) were observed in both geoelectric and geomagnetic fields before the major volcano-seismic activity in the Izu Island region, Japan. The spectral intensity of the geoelectric potential difference between some electrodes on Niijima Island and the third principal component of geomagnetic field variations at an array network in Izu Peninsula started to increase from a few months before the onset of the volcano-seismic activity, culminating immediately before nearby magnitude 6 class earthquakes. Appearance of similar changes in two different measurements conducted at two far apart sites seems to provide information supporting the reality of preseismic electromagnetic signals.
Reverse engineering gene networks using singular value decomposition and robust regression
Authors: Yeung M. K. Stephen , Tegnér Jesper , Collins James J.
Published: July 2002

We propose a scheme to reverse-engineer gene networks on a genome-wide scale using a relatively small amount of gene expression data from microarray experiments. Our method is based on the empirical observation that such networks are typically large and sparse. It uses singular value decomposition to construct a family of candidate solutions and then uses robust regression to identify the solution with the smallest number of connections as the most likely solution. Our algorithm has
O
(log
N
) sampling complexity and
O
(
N
4
) computational complexity. We test and validate our approach in a series of
in numero
experiments on model gene networks.
Regulation of the p21-activated kinase (PAK) by a human Gβ-like WD-repeat protein, hPIP1
Authors: Xia Chunzhi , Ma Wenbin , Stafford Lewis Joe , Marcus Stevan , Xiong Wen-Cheng , Liu Mingyao
Published: July 2002

The family of p21-activated protein kinases (PAKs) is composed of
serine–threonine kinases whose activity is regulated by the small
guanosine triphosphatases (GTPases) Rac and Cdc42. In mammalian cells,
PAKs have been implicated in the regulation of mitogen-activated
protein cascades, cellular morphological and cytoskeletal changes,
neurite outgrowth, and cell apoptosis. Although the ability of
Cdc42 and Rac GTPases to activate PAK is well established, relatively
little is known about the negative regulation of PAK or the identity of
PAK cellular targets. Here, we describe the identification and
characterization of a human PAK-interacting protein, hPIP1. hPIP1
contains G protein β-like WD repeats and shares sequence homology
with the essential fission yeast PAK regulator, Skb15, as well as the
essential budding yeast protein, MAK11. Interaction of hPIP1 with PAK1
inhibits the Cdc42/Rac-stimulated kinase activity through the
N-terminal regulatory domains of PAK1. Cotransfection of hPIP1 in
mammalian cells inhibits PAK-mediated c-Jun N-terminal kinase and
nuclear factor κ B signaling pathways. Our results demonstrate that
hPIP1 is a negative regulator of PAK and PAK signaling pathways.
Symptomatic and asymptomatic benign prostatic hyperplasia: Molecular differentiation by using microarrays
Authors: Prakash Kulkarni , Pirozzi Gregorio , Elashoff Michael , Munger William , Waga Iwao , Dhir Rajiv , Kakehi Yoshiyuki , Getzenberg Robert H.
Published: July 2002

Benign prostatic hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed by using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not seem to change with age. These data could provide novel approaches for alleviating symptoms and hyperplasia in BPH.
B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1
Authors: Shu Hong-Bing , Johnson Holly
Published: July 2002

TALL-1 is a recently identified member of the tumor necrosis factor (TNF) family that costimulates B lymphocyte proliferation. Here we show that B cell maturation protein (BCMA), a member of the TNF receptor family that is expressed only by B lymphocytes, specifically binds to TALL-1. A soluble receptor containing the extracellular domain of BCMA blocks the binding of TALL-1 to its receptor on the plasma membrane and inhibits TALL-1-triggered B lymphocyte costimulation. Overexpression of BCMA activates NF-κB, and this activation is potentiated by TALL-1. Moreover, BCMA-mediated NF-κB activation is inhibited by dominant negative mutants of TNF receptor-associated factor 5 (TRAF5), TRAF6, NF-κB-inducing kinase (NIK), and IκB kinase (IKK). These data indicate that BCMA is a receptor for TALL-1 and BCMA activates NF-κB through a TRAF5-, TRAF6-, NIK-, and IKK-dependent pathway. The identification of BCMA as a NF-κB-activating receptor for TALL-1 suggests molecular targets for drug development against certain immunodeficient or autoimmune diseases.
Antisense DNAs as multisite genomic modulators identified by DNA microarray
Authors: Cho Yee Sook , Kim Meyoung-Kon , Cheadle Chris , Neary Catherine , Becker Kevin G. , Cho-Chung Yoon S.
Published: July 2002

Antisense oligodeoxynucleotides can selectively block
disease-causing genes, and cancer genes have been chosen as potential
targets for antisense drugs to treat cancer. However, nonspecific side
effects have clouded the true antisense mechanism of action and
hampered clinical development of antisense therapeutics. Using DNA
microarrays, we have conducted a systematic characterization of gene
expression in cells exposed to antisense, either exogenously or
endogenously. Here, we show that in a sequence-specific
manner, antisense targeted to protein kinase A RIα alters expression
of the clusters of coordinately expressed genes at a specific stage of
cell growth, differentiation, and activation. The genes that define the
proliferation-transformation signature are down-regulated, whereas
those that define the differentiation-reverse transformation signature
are up-regulated in antisense-treated cancer cells and tumors, but not
in host livers. In this differentiation signature, the genes showing
the highest induction include genes for the G proteins Rap1 and Cdc42.
The expression signature induced by the exogenously supplied antisense
oligodeoxynucleotide overlaps strikingly with that induced by
endogenous antisense gene overexpression. Defining
antisense DNAs on the basis of their effects on global gene
expression can lead to identification of clinically relevant
antisense therapeutics and can identify which molecular and
cellular events might be important in complex biological processes,
such as cell growth and differentiation.
Cooperative regulation of light-harvesting complex II phosphorylation via the plastoquinol and ferredoxin-thioredoxin system in chloroplasts
Authors: Rintamäki E. , Martinsuo P. , Pursiheimo S. , Aro E.-M.
Published: July 2002

Light induces phosphorylation of photosystem II (PSII) proteins in
chloroplasts by activating the protein kinase(s) via reduction of
plastoquinone and the cytochrome
b
6
f
complex. The recent
finding of high-light-induced inactivation of the phosphorylation of
chlorophyll a/b-binding proteins (LHCII) of the PSII antenna in
floated leaf discs, but not
in vitro
, disclosed a second
regulatory mechanism for LHCII phosphorylation. Here we show that this
regulation of LHCII phosphorylation is likely to be mediated by the
chloroplast ferredoxin–thioredoxin system. We present a cooperative
model for the function of the two regulation mechanisms that determine
the phosphorylation level of the LHCII proteins
in vivo
,
based on the following results: (
i
) Chloroplast
thioredoxins f and m efficiently inhibit LHCII phosphorylation.
(
ii
) A disulfide bond in the LHCII kinase, rather than
in its substrate, may be a target component regulated by thioredoxin.
(
iii
) The target disulfide bond in inactive LHCII kinase
from dark-adapted leaves is exposed and easily reduced by external
thiol mediators, whereas in the activated LHCII kinase the regulatory
disulfide bond is hidden. This finding suggests that the activation of
the kinase induces a conformational change in the enzyme. The active
state of LHCII kinase prevails in chloroplasts under low-light
conditions, inducing maximal phosphorylation of LHCII proteins
in vivo
. (
iv
) Upon high-light
illumination of leaves, the target disulfide bond becomes exposed and
thus is made available for reduction by thioredoxin, resulting in a
stable inactivation of LHCII kinase.
SBE-TAGS: An array-based method for efficient single-nucleotide polymorphism genotyping
Authors: Hirschhorn Joel N. , Sklar Pamela , Lindblad-Toh Kerstin , Lim Yin-Mei , Ruiz-Gutierrez Melisa , Bolk Stacey , Langhorst Bradley , Schaffner Steven , Winchester Ellen , Lander Eric S.
Published: July 2002

Generating human single-nucleotide polymorphisms (SNPs) is no
longer a rate-limiting step for genetic studies of disease. The number
of SNPs in public databases already exceeds 200,000, and the total is
expected to exceed 1,000,000 within a year. Rather, progress is limited
by the inability to genotype large numbers of SNPs. Current genotyping
methods are suitable for studying individual loci or at most a handful
at a time. Here, we describe a method for parallel genotyping of SNPs,
called single base extension–tag array on glass slides, SBE-TAGS. The
principle is as follows. SNPs are genotyped by single base extension
(SBE), using bifunctional primers carrying a unique sequence tag in
addition to a locus-specific sequence. Because each locus has a
distinct tag, the genotyping reactions can be performed in a highly
multiplexed fashion, and the resulting product can then be
“demultiplexed” by hybridization to the reverse complements of
the sequence tags arrayed on a glass slide. SBE-TAGS is simple and
inexpensive because of the high degree of multiplexing and the use of
an easily generated, generic tag array. The method is also highly
accurate: we genotyped over 100 SNPs, obtaining over 5,000 genotypes,
with approximately 99% accuracy.
Proteomic method identifies proteins nitrated
in vivo
during inflammatory challenge
Authors: Aulak Kulwant S. , Miyagi Masaru , Yan Lin , West Karen A. , Massillon Duna , Crabb John W. , Stuehr Dennis J.
Published: July 2002

Inflammation in asthma, sepsis, transplant rejection, and many neurodegenerative diseases associates an up-regulation of NO synthesis with increased protein nitration at tyrosine. Nitration can cause protein dysfunction and is implicated in pathogenesis, but few proteins that appear nitrated
in vivo
have been identified. To understand how this modification impacts physiology and disease, we used a proteomic approach toward targets of protein nitration in both
in vivo
and cell culture inflammatory disease models. This approach identified more than 40 nitrotyrosine-immunopositive proteins, including 30 not previously identified, that became modified as a consequence of the inflammatory response. These targets include proteins involved in oxidative stress, apoptosis, ATP production, and other metabolic functions. Our approach provides a means toward obtaining a comprehensive view of the nitroproteome and promises to broaden understanding of how NO regulates cellular processes.
Body patterning
Authors: Takahashi Yoshiko , Osumi Noriko , Patel Nipam H.
Published: July 2002

Early patterning of the body during animal development is a fundamental process to subsequent events including cell differentiation, tissue and organ formation, and correct function of the adult body. We focused on two major topics: body segmentation and brain patterning, both of which are essential for conferring a functional complexity to the body, repetition of skeletal elements and complex neural network, respectively.
The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis
Authors: Jiang Xin , Buxbaum Joel N. , Kelly Jeffery W.
Published: July 2002

The transthyretin (TTR) amyloid diseases are of keen
interest, because there are >80 mutations that cause, and a few
mutations that suppress, disease. The V122I variant is the most common
amyloidogenic mutation worldwide, producing familial amyloidotic
cardiomyopathy primarily in individuals of African descent. The
substitution shifts the tetramer-folded monomer equilibrium toward
monomer (lowers tetramer stability) and lowers the kinetic barrier
associated with rate-limiting tetramer dissociation (pH 7; relative to
wild-type TTR) required for amyloid fibril formation. Fibril formation
is also accelerated because the folded monomer resulting from the
tetramer-folded monomer equilibrium rapidly undergoes partial
denaturation and self-assembles into amyloid (
in vitro
)
when subjected to a mild denaturation stress (e.g., pH 4.8).
Incorporation of the V122I mutation into a folded monomeric variant of
transthyretin reveals that this mutation does not destabilize the
tertiary structure or alter the rate of amyloidogenesis relative to the
wild-type monomer. The increase in the velocity of rate-limiting
tetramer dissociation coupled with the lowered tetramer stability
(increasing the mol fraction of folded monomer present at equilibrium)
may explain why V122I confers an apparent absolute anatomic risk for
cardiac amyloid deposition.
Mutational analysis of NM23-H2/NDP kinase identifies the structural domains critical to recognition of a c-myc regulatory element.
Authors: Postel E H , Weiss V H , Beneken J , Kirtane A
Published: July 2002

NM23-H2, a presumed regulator of tumor metastasis in humans, is a hexameric protein with both enzymatic (NDP kinase) and regulatory (transcriptional activation) activity. While the structure and catalytic mechanisms have been well characterized, the mode of DNA binding is not known. We examined this latter function in a site-directed mutational study and identified residues and domains essential for the recognition of a c-myc regulatory sequence. Three amino acids, Arg-34, Asn-69, and Lys-135, were found among 30 possibilities to be critical for DNA binding. Two of these, Asn-69 and Lys-135, are not conserved between NM23 variants differing in DNA-binding potential, suggesting that DNA recognition resides partly in nonconserved amino acids. All three DNA-binding defective mutant proteins are active enzymatically and appear to be stable hexamers, suggesting that they perform at the level of DNA recognition and that separate functional domains exist for enzyme catalysis and DNA binding. In the context of the known crystal structure of NM23-H2, the DNA-binding residues are located within distinct structural motifs in the monomer, which are exposed to the surface near the 2-fold axis of adjacent subunits in the hexamer. These findings are explained by a model in which NM23-H2 binds DNA with a combinatorial surface consisting of the "outer" face of the dimer. Chemical crosslinking data support a dimeric DNA-binding mode by NM23-H2.
Stepwise assembly of the lipid-linked oligosaccharide in the endoplasmic reticulum of Saccharomyces cerevisiae: identification of the ALG9 gene encoding a putative mannosyl transferase.
Authors: Burda P , te Heesen S , Brachat A , Wach A , Düsterhöft A , Aebi M
Published: July 2002

The core oligosaccharide Glc3Man9GlcNAc2 is assembled at the membrane of the endoplasmic reticulum on the lipid carrier dolichyl pyrophosphate and transferred to selected asparagine residues of nascent polypeptide chains. This transfer is catalyzed by the oligosaccharyl transferase complex. Based on the synthetic phenotype of the oligosaccharyl transferase mutation wbp1 in combination with a deficiency in the assembly pathway of the oligosaccharide in Saccharomyces cerevisiae, we have identified the novel ALG9 gene. We conclude that this locus encodes a putative mannosyl transferase because deletion of the gene led to accumulation of lipid-linked Man6GlcNAc2 in vivo and to hypoglycosylation of secreted proteins. Using an approach combining genetic and biochemical techniques, we show that the assembly of the lipid-linked core oligosaccharide in the lumen of the endoplasmic reticulum occurs in a stepwise fashion.
Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.
Authors: Pedersen W A , Kloczewiak M A , Blusztajn J K
Published: July 2002

The characteristic features of a brain with Alzheimer disease (AD) include the presence of neuritic plaques composed of amyloid beta-protein (Abeta) and reductions in the levels of cholinergic markers. Neurotoxic responses to Abeta have been reported in vivo and in vitro, suggesting that the cholinergic deficit in AD brain may be secondary to the degeneration of cholinergic neurons caused by Abeta. However, it remains to be determined if Abeta contributes to the cholinergic deficit in AD brain by nontoxic effects. We examined the effects of synthetic Abeta peptides on the cholinergic properties of a mouse cell line, SN56, derived from basal forebrain cholinergic neurons. Abeta 1-42 and Abeta 1-28 reduced the acetylcholine (AcCho) content of the cells in a concentration-dependent fashion, whereas Abeta 1-16 was inactive. Maximal reductions of 43% and 33% were observed after a 48-h treatment with 100 nM of Abeta 1-42 and 50 pM of Abeta 1-28, respectively. Neither Abeta 1-28 nor Abeta 1-42 at a concentration of 100 nM and a treatment period of 2 weeks was toxic to the cells. Treatment of the cells with Abeta 25-28 (48 h; 100 nM) significantly decreased AcCho levels, suggesting that the sequence GSNK (aa 25-28) is responsible for the AcCho-reducing effect of Abeta. The reductions in AcCho levels caused by Abeta 1-42 and Abeta 1-28 were accompanied by proportional decreases in choline acetyltransferase activity. In contrast, acetylcholinesterase activity was unaltered, indicating that Abeta specifically reduces the synthesis of AcCho in SN56 cells. The reductions in AcCho content caused by Abeta 1-42 could be prevented by a cotreatment with all-trans-retinoic acid (10 nM), a compound previously shown to increase choline acetyltransferase mRNA expression in SN56 cells. These results demonstrate a nontoxic, suppressive effect of Abeta on AcCho synthesis, an action that may contribute to the cholinergic deficit in AD brain.
Evidence for aminoacylation-induced conformational changes in human mitochondrial tRNAs.
Authors: Enríquez J A , Attardi G
Published: July 2002

Analysis by acid polyacrylamide/urea gel electrophoresis of 14 individual mitochondrial tRNAs (mt-tRNAs) from human cells has revealed a variable decrease in mobility of the aminoacylated relative to the nonacylated form, with the degree of separation of the two forms not being correlated with the mass, polar character, or charge of the amino acid. Separation of the charged and uncharged species has been found to be independent of tRNA denaturation, being observed also in the absence of urea. In another approach, electrophoresis through a perpendicular denaturing gradient gel of several individual mt-tRNAs has shown a progressive unfolding of the tRNA with increasing denaturant concentration, which is consistent with an initial disruption of tertiary interactions, followed by the sequential melting of the four stems of the cloverleaf structure. A detailed analysis of the unfolding process of charged and uncharged tRNALys and tRNALeu(UUR) has revealed that the separation of the two forms of these tRNAs persisted throughout the almost entire range of denaturant concentrations used and was lost upon denaturation of the last helical domain(s), which most likely included the amino acid acceptor stem. These observations strongly suggest that the electrophoretic retardation of the charged species reflects an aminoacylation-induced conformational change of the 3'-end of these mt-tRNAs, with possible significant implications in connection with the known role of the acceptor end in tRNA interactions with the ribosomal peptidyl transferase center and the elongation factor Tu.