bluuebunny/crossref_metadata_2025 huggingface dataset:
The barrier to linearity of water
Authors: Tarczay György , Császár Attila G. , Klopper Wim , Szalay Viktor , Allen Wesley D. , Schaefer Henry F.
Published: July 2002

High-quality ab initio quantum chemical methods, including higher-order coupled cluster (CC) and many-body perturbation (MP) theory, explicitly correlated (linear R12) techniques, and full configuration interaction (FCI) benchmarks, with basis sets ranging from [O/H] [3s2p1d/2s1p] to [8s7p6d5f4g3h2i/7s6p5d4f3g2h] have been employed to obtain the best possible value for the barrier to linearity of water. Attention is given to the degree of accord among extrapolations of conventional MP2, CCSD, and CCSD(T) energies to the complete basis set (CBS) limit and corresponding linear R12 schemes for these correlation methods. Small corrections due to one- and two-particle relativistic terms, core correlation effects, and the diagonal Born–Oppenheimer correction (DBOC) have been incorporated. The final electronic (vibrationless) extrapolated barrier height of this study is 11 127±35 cm−1. Anharmonic force fields have been determined at the aug-cc-pCVTZ CCSD(T) level at equilibrium and at a linear reference geometry. These and previous sextic force fields are in general accord with the expansion terms of recent global potential energy hypersurfaces but also highlight some of their weaknesses.
Physical and mathematical content of coupled-cluster equations. IV. Impact of approximations to the cluster operator on the structure of solutions
Authors: Jankowski K. , Kowalski K.
Published: July 2002

The impact of approximations to the form of the cluster operator on the structure and physical significance of the complete set of geometrically isolated solutions to the coupled-cluster (CC) equations has been studied for the first time. To systematically study the correspondence of solutions obtained at various levels of the approximation process, a continuation procedure based on a set of β-nested equations (β-NE) has been proposed and applied. Numerical studies based on a homotopy method for obtaining full solutions to sets of polynomial equations have been performed for the H4 and P4 models which belong to the simplest realistic many-electron model systems. Two examples of approximation procedures have been considered. The first one involved, for the P4 model, the approximation leading from the full CC (FCC) method to the CC method based on double excitations (CCD). As a result of this approximations the number of solutions has increased from 8 to 20. In the second example, for H4, we have studied the approximation leading from the CCSD method to the CCD one. To complete these studies, we have for the first time obtained the full set of geometrically isolated solutions for a CCSD equations which consists of 60 solutions. Only a small subset of this set might have some physical significance. During the approximation process considered, the number of solution decreases from 60 to 12. This radical drop of the numbers of solutions is a consequence of the absence of the third and fourth powers of the unknowns in the CCD equations.
A test of the accuracy of the partially-separable time-dependent self-consistent-field approach
Authors: Garcı́a-Vela A.
Published: July 2002

The accuracy of the time-dependent self-consistent-field (TDSCF) approach assuming partial factorization of the total wave packet is tested against an exact treatment, when applied to calculate asymptotic properties. The test is carried out in the framework of a three-dimensional simulation of the Ar–HCl UV photodissociation dynamics. All the partially-separable TDSCF ansatzs possible for this problem are investigated. The quality of the TDSCF results is found to be strongly dependent on the specific partially-separable ansatzs applied. In general, the TDSCF predictions are in very good (even quantitative) agreement with the exact ones for magnitudes associated with direct photodissociation dynamics, and are qualitative in the case of indirect photodissociation. The deviation of the TDSCF results from the exact dynamics is interpreted in terms of an error operator defined as the difference between the exact and the TDSCF Hamiltonians. The analysis of this operator also explains the different accuracy of the partially-separable ansatzs investigated. Based on this analysis, a simple procedure is suggested to estimate the relative average quality of the different TDSCF ansatzs.
Search for “quadrupole-bound” anions. I
Authors: Gutsev Gennady L. , Jena Puru , Bartlett Rodney J.
Published: July 2002

In a classical model, some anions exist due to the attraction between an electron and a molecule’s dipole moment. When the dipole moment is sufficiently large (μcrit>2.5 D), an electron can be trapped. Can a sufficiently large quadrupole moment produce the same effect? To help answer this question, we can search for molecules with a large quadrupole moment and use predictive, ab initio, correlated quantum chemistry methods to assess whether an anion forms and, if it does, to discover its nature. For this purpose, coupled-cluster calculations are reported for the structure and properties of KnClm and KnClm− (n,m=0–2). The KCl2 superhalogen was found to have an electron affinity of 4.2 eV and is stable towards dissociation by 26 kcal/mol. The (KCl)2 dimer has a rhombic ground state with a large electric quadrupole moment. Rhombic and linear configurations of the (KCl)2− anion correspond to stationary states that are nearly degenerate in total energy. The rhombic anion has a single, weakly bound state that could be a “quadrupole-bound” state on the basis of a comparison of its characteristics with those of dipole-bound states. Linear KClKCl− has seven excited states; four of them can be identified as dipole-bound states. KCl and KCl2 possess rather similar dipole moments and their anions have two excited dipole-bound states each.
Time-resolved photoelectron angular distributions as a means of studying polyatomic nonadiabatic dynamics
Authors: Seideman Tamar
Published: July 2002

We propose based on theoretical arguments, and illustrate numerically the possibility of using time-resolved photoelectron angular distributions to follow the dynamics of nonradiative transitions in large polyatomic systems.
Geometric quantization and constrained systems
Authors: Ashtekar Abhay , Stillerman Matthew
Published: July 2002

The problem of obtaining the quantum theory of systems with first class constraints is discussed in the context of geometric quantization. The precise structure needed on the constraint surface of the full phase space to obtain a polarization on the reduced phase space is displayed in a form that is particularly convenient for applications. For unconstrained systems, any polarization on the phase space leads to a mathematically consistent quantum description, although not all of these descriptions may be viable from a physical standpoint. It is pointed out that the situation is worse in the presence of constraints: a general polarization on the full phase space need not lead to even a mathematically consistent quantum theory. Examples are given to illustrate the general constructions as well as the subtle difficulties.
Quantum mechanics as an infinite-dimensional Hamiltonian system with uncertainty structure: Part II
Authors: Cirelli Renzo , Manià Alessandro , Pizzocchero Livio
Published: July 2002

Making reference to the formalism developed in Part I to formulate Schrödinger quantum mechanics, the properties of Kählerian functions in general, almost Kählerian manifolds, are studied.
Three-dimensional quantum groups from contractions of SU(2)q
Authors: Celeghini Enrico , Giachetti Riccardo , Sorace Emanuele , Tarlini Marco
Published: July 2002

Contractions of Lie algebras and of their representations are generalized to define new quantum groups. An explicit and complete exposition is made for the one-dimensional Heisenberg H(1)q and the two-dimensional Euclidean quantum group E(2)q obtained by contracting SU(2)q.
A new description of force-free magnetic fields
Authors: MacLeod Malcolm A.
Published: July 2002

The Moses curl eigenfunctions are used to describe linear force-free magnetic fields, enabling a proof that such fields are defined entirely by the value of their curl transform on the unit hemisphere in transform space. This change of viewpoint suggests an orderly approach to the exploration and classification of the properties of such fields, which is briefly sketched. The simplest force-free fields defined on zero- , one- , and two-dimensional sets on the transform sphere are exhibited, and the possibility of fields with fractal support sets suggested. Connections with other mathematical descriptions are pointed out, as well as several promising directions for further exploration. All results apply equally well to the description of the Trkalian subset of Beltrami fields in fluid dynamics.
Statistical interpretation of p-adic quantum theories with p-adic valued wave functions
Authors: Khrennikov Andrew
Published: July 2002

The development of p-adic quantum mechanics has made it necessary to construct a probability theory in which the probabilities of events are p-adic numbers. The foundations of this theory are developed here. The frequency definition of probability is used. A general principle of statistical stabilization of relative frequencies is formulated. By virtue of this principle, statistical stabilization of relative frequencies, which are, like all experimental data, rational numbers, can be considered not only in the real topology but also in p-adic topologies.
Maximal localization in the presence of minimal uncertainties in positions and in momenta
Authors: Hinrichsen Haye , Kempf Achim
Published: July 2002

Small corrections to the uncertainty relations, with effects in the ultraviolet and/or infrared, have been discussed in the context of string theory and quantum gravity. Such corrections lead to small but finite minimal uncertainties in position and/or momentum measurements. It has been shown that these effects could indeed provide natural cutoffs in quantum field theory. The corresponding underlying quantum theoretical framework includes small ‘‘noncommutative geometric’’ corrections to the canonical commutation relations. In order to study the full implications on the concept of locality, it is crucial to find the physical states of then maximal localization. These states and their properties have been calculated for the case with minimal uncertainties in positions only. Here we extend this treatment, though still in one dimension, to the general situation with minimal uncertainties both in positions and in momenta.
Relativistic gas: Moment equations and maximum wave velocity
Authors: Boillat Guy , Ruggeri Tommaso
Published: July 2002

For a rarefied relativistic gas we consider the N-moment equations associated with the relativistic Boltzmann–Chernikov equation and we require the compatibility with the entropy principle thus obtaining a closed symmetric hyperbolic system. This interesting form permits one to deduce a lower and an upper bound for the maximum velocity of a wave propagating in a monoatomic or a degenerate gas of fermions or bosons and to prove that when this number N increases this velocity tends to the speed of light.
Classical and quantum probability
Authors: Streater R. F.
Published: July 2002

We follow the development of probability theory from the beginning of the last century, emphasizing that quantum theory is really a generalization of this theory. The great achievements of probability theory, such as the theory of processes, generalized random fields, estimation theory, and information geometry, are reviewed. Their quantum versions are then described.
Comments on a paper by Sakuma and Ghil
Authors: Ripa P.
Published: July 2002

New stability criteria, for steady nonparallel solutions of the shallow-water equations, are shown to be incorrect through the use of a counterexample: the sine profile in an f-plane channel. If the channel is wide enough and the Coriolis parameter does not vanish, the conditions in question predict stability but the flow is found to be unstable to quasigeostrophic normal modes.
Raman sidescattering in laser-produced plasmas
Authors: Menyuk C. R. , El-Siragy N. M. , Manheimer W. M.
Published: July 2002

The theory of the Raman sidescattering instability in an inhomogeneous plasma is revisited. The growth rate is found from the eigenvalue of a second-order ordinary differential equation in the Fourier domain. Under certain, rather easily satisfied constraints, the normalized growth rate depends on a single parameter involving laser strength, gradient scale length, and resonant density.
Corner flow in the sliding plate problem
Authors: Koplik Joel , Banavar Jayanth R.
Published: July 2002

The usual formulation of the well-studied sliding plate problem of driven cavity flow involves an unphysical boundary velocity discontinuity at the corners where moving and fixed boundary surfaces intersect. Molecular dynamics simulations of a Lennard-Jones liquid in a cavity driven by the motion of realistic atomic walls at several Reynolds numbers are used to explore the small-scale structure of this flow. The results indicate that slip occurs in the corner region, removing the stress singularity which would otherwise occur, and furthermore that the fluid has non-Newtonian behavior there. Elsewhere, at least at low Reynolds numbers, the overall flow field is consistent with continuum calculations which do not allow for slip. As the Reynolds number increases, the slip region grows in size, and eventually extends across the entire moving boundary. The often-cited Navier slip boundary condition is shown to be incorrect. The mechanism for the avoidance of singular behavior here is generally similar to that of the moving contact line case.
Isotopological relaxation, coherent structures, and Gaussian turbulence in two-dimensional (2-D) magnetohydrodynamics (MHD)
Authors: Isichenko M. B. , Gruzinov A. V.
Published: July 2002

The long-time relaxation of ideal two-dimensional (2-D) magnetohydrodynamic (MHD) turbulence subject to the conservation of two infinite families of constants of motion—the magnetic and the ‘‘cross’’ topology invariants—is examined. The analysis of the Gibbs ensemble, where all integrals of motion are respected, predicts the initial state to evolve into an equilibrium, stable coherent structure (the most probable state) and decaying Gaussian turbulence (fluctuations) with a vanishing, but always positive temperature. The nondissipative turbulence decay is accompanied by decrease in both the amplitude and the length scale of the fluctuations, so that the fluctuation energy remains finite. The coherent structure represents a set of singular magnetic islands with plasma flow whose magnetic topology is identical to that of the initial state, while the energy and the cross topology invariants are shared between the coherent structure and the Gaussian turbulence. These conservation laws suggest the variational principle of isotopological relaxation that allows one to predict the appearance of the final state from a given initial state. For a generic initial condition having x points in the magnetic field, the coherent structure has universal types of singularities: current sheets terminating at Y points. These structures, which are similar to those resulting from the 2-D relaxation of magnetic field frozen into an ideally conducting viscous fluid, are observed in the numerical experiment of D. Biskamp and H. Welter [Phys. Fluids B 1, 1964 (1989)] and are likely to form during the nonlinear stage of the kink tearing mode in tokamaks. The Gibbs ensemble method developed in this work admits extension to other Hamiltonian systems with invariants not higher than quadratic in the highest-order-derivative variables. The turbulence in 2-D Euler fluid is of a different nature: there the coherent structures are also formed, but the fluctuations about these structures are non-Gaussian.
Investigation of the formation of a fully pressure-driven tokamak*
Authors: Forest C. B. , Hwang Y. S. , Ono M. , Greene G. , Jones T. , Choe W. , Schaffer M. , Hyatt A. , Osborne T. , Pinsker R. I. , Petty C. C. , Lohr J. , Lippmann S.
Published: July 2002

A noninductive current drive concept, based on internal pressure-driven currents in a low-aspect-ratio toroidal geometry, has been demonstrated on the Current Drive Experiment Upgrade (CDX-U) [Forest et al., Phys. Rev. Lett. 68, 3559 (1992)] and further tested on DIII-D [in Plasma Physics and Controlled Nuclear Fusion Research, 1986, Proceedings of the 11th International Conference, Kyoto (International Atomic Energy Agency, Vienna, 1987), Vol. 1, p. 159]. For both experiments, electron cyclotron power provided the necessary heating to breakdown and maintain a plasma with high-βp and low collisionality (εβp∼1, ν*≤1). A poloidal vacuum field similar to a simple magnetic mirror is superimposed on a much stronger toroidal field to provide the initial confinement for a hot, trapped electron species. With application of electron cyclotron heating (ECH), toroidal currents spontaneously flow within the plasma and increase with applied ECH power. The direction of the generated current is independent of the toroidal field direction and depends only on the direction of the poloidal field, scaling inversely with magnitude of the later. On both CDX-U and DIII-D, these currents were large enough that stationary closed flux surfaces were observed to form with no additional Ohmic heating. The existence of such equilibria provides further evidence for the existence of some type of bootstrap current. Equilibrium reconstructions show the resulting plasma exhibits properties similar to more conventional tokamaks, including a peaked current density profile which implies some form of current on axis or nonclassical current transport.
Plasma discharge current–beam current relation for different gases in large-volume magnetic multipole ion sources
Authors: Uhlemann R.
Published: July 2002

Production of a certain extracted particle beam current requires for different gases different discharge currents in the ion source plasma generated by an arc discharge. Experimental data of hydrogen, deuterium, helium-3, and helium-4 particle beams extracted from large-volume ion sources with permanent magnet multipole confinement show that higher arc currents are required for the particles of higher atomic mass. These differences can be understood by considering the particle loss mechanisms in the ion source plasma. The differences in plasma leakage can be described by the particle loss area in the magnetic multipole cusp field. Such loss area is higher for the particles with higher mass. The size of loss channels is found to be proportional to the ion Larmor radius.
Solitary potentials in dusty plasmas
Authors: Mamun A. A. , Cairns R. A. , Shukla P. K.
Published: July 2002

It is found that a dusty plasma with inertial dust fluid and Boltzmann distributed ions admits only negative solitary potentials associated with nonlinear dust-acoustic waves. The dynamics of small-amplitude disturbances is governed by the Korteweg–de Vries (KdV) equation, the stationary solution of which assumes the inverted bell-shaped secant hyperbolic squared profile. The associated dust and ion density perturbations are, on the other hand, positive. The solitary potentials can be identified as nonlinear structures in low-temperature dusty plasmas such as those in laboratory and astrophysical environments.
The chirped-pulse inverse free-electron laser: A high-gradient vacuum laser accelerator
Authors: Hartemann F. V. , Landahl E. C. , Troha A. L. , Van Meter J. R. , Baldis H. A. , Freeman R. R. , Luhmann N. C. , Song L. , Kerman A. K. , Yu D. U. L.
Published: July 2002

The inverse free-electron laser (IFEL) interaction is studied theoretically and computationally in the case where the drive laser intensity approaches the relativistic regime, and the pulse duration is only a few optical cycles long. The IFEL concept has been demonstrated as a viable vacuum laser acceleration process; it is shown here that by using an ultrashort, ultrahigh-intensity drive laser pulse, the IFEL interaction bandwidth and accelerating gradient are increased considerably, thus yielding large energy gains. Using a chirped pulse and negative dispersion focusing optics allows one to take further advantage of the laser optical bandwidth and produce a chromatic line focus maximizing the gradient. The combination of these novel ideas results in a compact vacuum laser accelerator capable of accelerating picosecond electron bunches with a high gradient (GeV/m) and very low energy spread.
Temperature dependence of the energy gap of InSb using nonlinear optical techniques
Authors: Littler C. L. , Seiler D. G.
Published: July 2002

We report the first use of the resonant two-photon photo-Hall effect as a nonlinear optical technique to measure the temperature dependence of the energy gap of InSb. Values of Eg for the temperature range 2–210 K are determined and compared with theoretical predictions and past experimental work. The technique is shown to provide an accurate, straightforward means of measuring Eg as a function of temperature in semiconductor materials.
14.5% conversion efficiency GaAs solar cell fabricated on Si substrates
Authors: Itoh Yoshio , Nishioka Takashi , Yamamoto Akio , Yamaguchi Masafumi
Published: July 2002

AlGaAs-GaAs heteroface p+-p-n solar cells have been fabricated directly on Si substrates using metalorganic chemical vapor deposition. GaAs on Si solar cell efficiency as high as exceeding 14.5% at AM1.5 was obtained by cleaning the substrate surface and repeating GaAs film growth interruption. This value is the highest ever reported for GaAs solar cells on Si substrates. Defects, which could not be observed in homoepitaxially grown GaAs film, were observed in the heteroepitaxial GaAs films through electron beam induced current image. Relatively low conversion efficiency of the GaAs cell on Si compared to the GaAs can be attributed to these defects.
Cascade four-wave mixing in semiconductor lasers
Authors: Nietzke R. , Fenz P. , Elsässer W. , Göbel E. O.
Published: July 2002

Highly efficient cascade frequency mixing signals are generated in a nearly degenerate intracavity four-wave mixing experiment in a GaAs/(GaAl)As semiconductor laser. This method allows a consistent quantitative determination of the third-order nonlinear optical susceptibility within the gain bandwidth of a semiconductor laser. The dependence of this susceptibility on light intensity reveals the contribution of the free-carrier plasma.
Simultaneous, multiple wavelength lasing of (Ho, Nd):Y3Al5O12
Authors: Machan J. , Kurtz R. , Bass M. , Birnbaum M. , Kokta M.
Published: July 2002

Simultaneous lasing of both Ho3+ and Nd3+ in the same crystal of yttrium aluminum garnet (YAG) is reported. The crystal was doped with 10% Ho3+ and 1% Nd3+ ions. Lasing occurred at 2.940 and 3.011 μm due to Ho3+ ion transitions and at 1.064 μm due to a Nd3+ transition. Appropriate mirrors produced simultaneous lasing at 1.064 and 1.339 μm due to Nd3+ ion transitions. The fluorescent lifetimes of both the Nd3+ 4F3/2 and Ho3+ 5I7 states were significantly lower in the doubly doped material than in Nd:YAG and Ho:YAG. This indicates very strong ion-ion interactions in the (Ho, Nd):YAG crystal.
Decreased intracellular calcium mediates the histamine H
3
-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings
Authors: Silver Randi B. , Poonwasi Kumar S. , Seyedi Nahid , Wilson Sandy J. , Lovenberg Timothy W. , Levi Roberto
Published: July 2002

Activation of presynatic histamine H
3
receptors
(H
3
R) down-regulates norepinephrine exocytosis from cardiac
sympathetic nerve terminals, in both normal and ischemic
conditions. Analogous to the effects of
α
2
-adrenoceptors, which also act prejunctionally to
inhibit norepinephrine release, H
3
R-mediated antiexocytotic
effects could result from a decreased Ca
2+
influx into
nerve endings. We tested this hypothesis in sympathetic nerve terminals
isolated from guinea pig heart (cardiac synaptosomes) and in a model
human neuronal cell line (SH-SY5Y), which we stably transfected with
human H
3
R cDNA (SH-SY5Y-H
3
). We found that
reducing Ca
2+
influx in response to membrane depolarization
by inhibiting N-type Ca
2+
channels with ω-conotoxin
(ω-CTX) greatly attenuated the exocytosis of
[
3
H]norepinephrine from both SH-SY5Y and
SH-SY5Y-H
3
cells, as well as the exocytosis of
endogenous norepinephrine from cardiac synaptosomes.
Similar to ω-CTX, activation of H
3
R with the selective
H
3
R-agonist imetit also reduced both the rise in
intracellular Ca
2+
concentration (Ca
i
) and
norepinephrine exocytosis in response to membrane depolarization. The
selective H
3
R antagonist thioperamide prevented this effect
of imetit. In the parent SH-SY5Y cells lacking H
3
R, imetit
affected neither the rise in Ca
i
nor
[
3
H]norepinephrine exocytosis, demonstrating that the
presence of H
3
R is a prerequisite for a decrease in
Ca
i
in response to imetit and that H
3
R
activation modulates norepinephrine exocytosis by limiting the
magnitude of the increase in Ca
i
. Inasmuch as excessive
norepinephrine exocytosis is a leading cause of cardiac dysfunction and
arrhythmias during acute myocardial ischemia, attenuation of
norepinephrine release by H
3
R agonists may offer a novel
therapeutic approach to this condition.
Biosensors from conjugated polyelectrolyte complexes
Authors: Wang Deli , Gong Xiong , Heeger Peter S. , Rininsland Frauke , Bazan Guillermo C. , Heeger Alan J.
Published: July 2002

A charge neutral complex (CNC) was formed in aqueous solution by combining an orange light emitting anionic conjugated polyelectrolyte and a saturated cationic polyelectrolyte at a 1:1 ratio (per repeat unit). Photoluminescence (PL) from the CNC can be quenched by both the negatively charged dinitrophenol (DNP) derivative, (DNP-BS−), and positively charged methyl viologen (MV2+). Use of the CNC minimizes nonspecific interactions (which modify the PL) between conjugated polyelectrolytes and biopolymers. Quenching of the PL from the CNC by the DNP derivative and specific unquenching on addition of anti-DNP antibody (anti-DNP IgG) were observed. Thus, biosensing of the anti-DNP IgG was demonstrated.
Gonadotropin-releasing hormone neurons in the preoptic-hypothalamic region of the rat contain lamprey gonadotropin-releasing hormone III, mammalian luteinizing hormone-releasing hormone, or both peptides
Authors: Hiney J. K. , Sower S. A. , Yu W. H. , McCann S. M. , Dees W. L.
Published: July 2002

This study utilized a newly developed antiserum, specific for lamprey gonadotropin-releasing hormone III (l-GnRH-III), to determine the following: in which regions of the rat hypothalamus the neuronal perikarya producing l-GnRH-III are localized; and whether this peptide, known to selectively induce follicle-stimulating hormone release, is coexpressed in neurons containing mammalian luteinizing hormone-releasing hormone (m-LHRH). Double-label immunocytochemistry was performed by using an l-GnRH-III polyclonal antiserum and an LHRH monoclonal antiserum. Immunopositive neurons for l-GnRH-III, m-LHRH, or neurons coexpressing both peptides were detected within the organum vasculosum lamina terminalis (OVLT) region of the preoptic area (POA). Caudal to the OVLT, l-GnRH-III-positive neurons were also observed dorso-medially, above the third ventricle in the medial POA. The m-LHRH neurons were not observed in this area. The lateral POA region contained neurons positive for both peptides along with single-labeled neurons for each peptide. Importantly, neurons that expressed l-GnRH-III, m-LHRH, or both peptides were also detected in the ventral regions of the rostral hypothalamus, dorsolateral to the borders of the supraoptic nuclei. In both of these latter areas, neurons containing l-GnRH-III were slightly dorsal to neurons containing only m-LHRH. The l-GnRH-III perikarya and fibers were eliminated by absorption of the primary antiserum with l-GnRH-III, but not by l-GnRH-I, chicken-GnRH-II, or m-LHRH. These results indicate that, unlike other isoforms of GnRH found in the mammalian brain, l-GnRH-III neurons not only are observed in regions that control follicle-stimulating hormone release but also are colocalized with m-LHRH neurons in areas primarily controlling LH release. These findings suggest an interrelationship between these two peptides in the control of gonadotropin secretion.
Riding the ice age El Niño? Pacific biogeography and evolution of
Metrosideros
subg.
Metrosideros
(Myrtaceae) inferred from nuclear ribosomal DNA
Authors: Wright S. D. , Yong C. G. , Dawson J. W. , Whittaker D. J. , Gardner R. C.
Published: July 2002

Metrosideros
subg.
Metrosideros
(Myrtaceae) comprises ≈26 species distributed widely across the Pacific basin. They occur on the ancient Gondwanan landmasses of New Zealand and New Caledonia, as well as on the volcanic islands of the remote Pacific, from Melanesia to tropical Polynesia and the Bonin Island. Phylogenetic analysis based on nuclear ribosomal DNA spacer sequences from all named species showed
Metrosideros
umbellata
of New Zealand as basal in the subgenus, with the remaining species falling into three monophyletic clades. One includes the seven New Caledonian species together with three daughters in western Oceania that probably dispersed during the mid/late Tertiary. A second contains six taxa located in east Melanesia and Samoa that may also have arisen from a mid/late Tertiary dispersal, in this instance from New Zealand. The third includes three New Zealand endemics along with all of the taxa in remote Polynesia and accounts for much of the total range of the subgenus. These dispersed taxa in Polynesia either are identical to the New Zealand species
Metrosideros excelsa
or differ by a single nucleotide change. We suggest that they are all derived from a Pleistocene dispersal out of New Zealand. A relatively recent dispersal is surprising, given that this wind-dispersed genus has occupied New Zealand for much of the Tertiary and that some of the islands in remote Polynesia date to at least the Miocene. We attribute this dramatic range expansion to climate change—specifically changes in wind flow patterns—in the southern hemisphere during worldwide glaciation.
Chemical synthesis gets a fillip from molecular recognition and self-assembly processes
Authors: Stoddart J. Fraser , Tseng Hsian-Rong
Published: July 2002

By drawing on nature conceptually, the practice of chemical synthesis can now be broadened in scope to include the supramolecular synthesis of supermolecules and their postassembly covalent modification to form mechanically interlocked molecules, which the chemist can use to build functioning nanosystems after the style of those found in the living world.
Cytotoxic T cell immunity against telomerase reverse transcriptase in humans
Authors: Minev Boris , Hipp Jason , Firat Huseyin , Schmidt Joseph D. , Langlade-Demoyen Pierre , Zanetti Maurizio
Published: July 2002

Telomerase is a ribonucleoprotein enzyme which has been linked to malignant transformation in human cells. Telomerase activity is increased in the vast majority of human tumors, making its gene product the first molecule common to all human tumors. The generation of endogenously processed telomerase peptides bound to Class I MHC molecules could therefore target cytotoxic T lymphocytes (CTL) to tumors of different origins. This could advance vaccine therapy against cancer provided that precursor CTL recognizing telomerase peptides in normal adults and cancer patients can be expanded through immunization. We demonstrate here that the majority of normal individuals and patients with prostate cancer immunizedin vitroagainst two HLA-A2.1 restricted peptides from telomerase reverse transcriptase (hTRT) develop hTRT-specific CTL. This suggests the existence of precursor CTL for hTRT in the repertoire of normal individuals and in cancer patients. Most importantly, the CTL of cancer patients specifically lysed a variety of HLA-A2+cancer cell lines, demonstrating immunological recognition of endogenously processed hTRT peptides. Moreover,in vivoimmunization of HLA-A2.1 transgenic mice generated a specific CTL response against both hTRT peptides. Based on the induction of CTL responsesin vitroandin vivo, and the susceptibility to lysis of tumor cells of various origins by hTRT CTL, we suggest that hTRT could serve as a universal cancer vaccine for humans.
Extracellular matrix composition determines the transcriptional response to epidermal growth factor receptor activation
Authors: Yarwood Stephen J. , Woodgett James R.
Published: July 2002

The transcriptional response to epidermal growth factor (EGF) was
examined in a cultured cell model of adhesion. Gene expression was
monitored in human embryonic kidney cells (HEK293) after attachment of
cells to the extracellular matrix (ECM) proteins, laminin, and
fibronectin, by using complementary DNA micorarrays printed with 1,718
individual human genes. Cluster analysis revealed that the influence of
EGF on gene expression, either positive or negative, was largely
independent of ECM composition. However, clusters of EGF-regulated
genes were identified that were diagnostic of the type of ECM proteins
to which cells were attached. In these clusters, attachment of cells to
a laminin or fibronectin substrata specifically modified the direction
of gene expression changes in response to EGF stimulation. For example,
in HEK293 cells attached to fibronectin, EGF stimulated an increase in
the expression of some genes; however, genes in the same group were
nonresponsive or even suppressed in cells attached to laminin. Many of
the genes regulated by EGF and ECM proteins in this manner are involved
in ECM and cytoskeletal architecture, protein synthesis, and cell cycle
control, indicating that cell responses to EGF stimulation can be
dramatically affected by ECM composition.
Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells
Authors: Taneja Samir , MacGregor Jennifer , Markus Steven , Ha Susan , Mohr Ian
Published: July 2002

Replication-competent, attenuated herpes simplex virus-1 (HSV-1) derivatives that contain engineered mutations into the viral γ34.5 virulence gene have been used as oncolytic agents. However, as attenuated mutants often grow poorly, they may not completely destroy some tumors and surviving cancer cells simply regrow. Thus, although HSV-1 γ34.5 mutants can reduce the growth of human tumor xenografts in mice and have passed phase I safety studies, their efficacy is limited because they replicate poorly in many human tumor cells. Previously, we selected for a γ34.5 deletion mutant variant that regained the ability to replicate efficiently in tumor cells. Although this virus contains an extragenic suppressor mutation that confers enhanced growth in tumor cells, it remains attenuated. Here, we demonstrate that the suppressor virus replicates to greater levels in prostate carcinoma cells and, importantly, is a more potent inhibitor of tumor growth in an animal model of human prostate cancer than the γ34.5 parent virus. Thus, genetic selection in cancer cells can be used as a tool to enhance the antitumor activity of a replication-competent virus. The increased therapeutic potency of this oncolytic virus may be useful in the treatment of a wide variety of cancers.
Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer
Authors: Hu Zhiwei , Garen Alan
Published: July 2002

The efficacy and safety of an immunoconjugate (icon) molecule, composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient (SCID) mouse model of human prostatic cancer and an immunocompetent mouse model of mouse prostatic cancer. The SCID mice were first injected s.c. with a human prostatic tumor line, forming a skin tumor that produces a high blood titer of prostate-specific antigen and metastasizes to bone. The icon was encoded in a replication-incompetent adenoviral vector that was injected directly into the skin tumor. The tumor cells infected by the vector synthesize and secrete the icon into the blood, and the blood-borne icon binds with high affinity and specificity to mouse tissue factor expressed on endothelial cells lining the lumen of the tumor vasculature and to human tissue factor expressed on the tumor cells. The Fc domain of the icon activates a cytolytic immune attack against cells that bind the icon. The immunotherapy tests in SCID mice demonstrated that intratumoral injections of the adenoviral vector encoding the mfVII/human Fc icon resulted in long-term regression of the injected human prostatic tumor and also of a distant uninjected tumor, without associated toxicity to the mice. Comparable results were obtained with a SCID mouse model of human melanoma. At the end of the experiments the mice appeared to be free of viable tumor cells. This protocol also could be efficacious for treating cancer patients who have vascularized tumors.
The NMR structure of the 47-kDa dimeric enzyme 3,4-dihydroxy-2-butanone-4-phosphate synthase and ligand binding studies reveal the location of the active site
Authors: Kelly Mark J. S. , Ball Linda J. , Krieger Cornelia , Yu Yihua , Fischer Markus , Schiffmann Susanne , Schmieder Peter , Kühne Ronald , Bermel Wolfgang , Bacher Adelbert , Richter Gerald , Oschkinat Hartmut
Published: July 2002

Recent developments in NMR have extended the size range of proteins amenable to structural and functional characterization to include many larger proteins involved in important cellular processes. By applying a combination of residue-specific isotope labeling and protein deuteration strategies tailored to yield specific information, we were able to determine the solution structure and study structure–activity relationships of 3,4-dihydroxy-2-butanone-4-phosphate synthase, a 47-kDa enzyme from the
Escherichia coli
riboflavin biosynthesis pathway and an attractive target for novel antibiotics. Our investigations of the enzyme's ligand binding by NMR and site-directed mutagenesis yields a conclusive picture of the location and identity of residues directly involved in substrate binding and catalysis. Our studies illustrate the power of state-of-the-art NMR techniques for the structural characterization and investigation of ligand binding in protein complexes approaching the 50-kDa range in solution.
Insulin can regulate GLUT4 internalization by signaling to Rab5 and the motor protein dynein
Authors: Huang Jie , Imamura Takeshi , Olefsky Jerrold M.
Published: July 2002

Insulin stimulates glucose transport by promoting translocation of the insulin-sensitive glucose transporter isoform 4 (GLUT4) from an intracellular compartment to the cell surface. This movement is accomplished by stimulation of GLUT4 exocytosis as well as inhibition of endocytosis. However, the molecular mechanisms for these effects remain unclear. In this study, we found that the GTP-binding protein Rab5 physically associated with the motor protein dynein in immunoprecipitants from both untransfected cells and cells transfected with GFP-Rab5 constructs. Microinjection of anti-Rab5 or anti-dynein antibody into 3T3-L1 adipocytes increased the basal level of surface GLUT4, did not change the insulin-stimulated surface GLUT4 level, and inhibited GLUT4 internalization after the removal of insulin. Photoaffinity labeling of Rab5 with [γ-
32
P]GTP-azidoanilide showed that insulin inhibited Rab5-GTP loading. By using microtubule-capture assays, we found that insulin also caused a significant decrease in the binding of dynein to microtubules. Furthermore, pretreatment of cells with the PI3-kinase inhibitor LY294002 inhibited the effects of insulin on both Rab5-GTP loading and dynein binding to microtubules. In conclusion, these data indicate that insulin signaling inhibits Rab5 activity and the interaction of dynein with microtubules in a PI3-kinase-dependent manner, and that these effects may inhibit the rate of GLUT4 internalization. As such, our results present a previously uncharacterized insulin-signaling pathway involving Rab5, the motor protein dynein, and the cytoskeleton to regulate directional GLUT4 movement, facilitating GLUT4 distribution to the cell surface.
The ionic layer is required for efficient dissociation of the SNARE complex by α-SNAP and NSF
Authors: Scales Suzie J. , Yoo Bryan Y. , Scheller Richard H.
Published: July 2002

The four-helical bundle soluble
N
-ethylmaleimide-sensitive fusion protein (NSF)
attachment protein receptor (SNARE) complex that mediates intracellular
membrane fusion events contains a highly conserved ionic layer at the
center of an otherwise hydrophobic core. This layer has an undetermined
function; it consists of glutamine (Q) residues in syntaxin and the two
synaptosomal-associated protein of 25 kDa (SNAP-25) family helices, and
an arginine (R) in vesicle-associated membrane protein (a 3Q:1R
ratio). Here, we show that the ionic-layer glutamine of syntaxin is
required for efficient α-SNAP and NSF-mediated dissociation of the
complex. When this residue is mutated, the SNARE complex still binds to
α-SNAP and NSF and is released through ATP hydrolysis by NSF, but the
complex no longer dissociates into SNARE monomers. Thus, one function
of the ionic layer—in particular, the glutamine of syntaxin—is to
couple ATP hydrolysis by NSF to the dissociation of the fusion complex.
We propose that α-SNAP and NSF drive conformational changes at the
ionic layer through specific interactions with the syntaxin glutamine,
resulting in the dissociation of the SNARE complex.
Binding specificity of
Escherichia coli
trigger factor
Authors: Patzelt Holger , Rüdiger Stefan , Brehmer Dirk , Kramer Günter , Vorderwülbecke Sonja , Schaffitzel Elke , Waitz Andreas , Hesterkamp Thomas , Dong Liying , Schneider-Mergener Jens , Bukau Bernd , Deuerling Elke
Published: July 2002

The ribosome-associated chaperone trigger factor (TF)
assists the folding of newly synthesized cytosolic proteins in
Escherichia coli
. Here, we determined the substrate
specificity of TF by examining its binding to 2842 membrane-coupled
13meric peptides. The binding motif of TF was identified as a stretch
of eight amino acids, enriched in basic and aromatic residues and with
a positive net charge. Fluorescence spectroscopy verified that TF
exhibited a comparable substrate specificity for peptides in solution.
The affinity to peptides in solution was low, indicating that TF
requires ribosome association to create high local concentrations of
nascent polypeptide substrates for productive interaction
in
vivo
. Binding to membrane-coupled peptides occurred through the
central peptidyl-prolyl-
cis
/
trans
isomerase (PPIase) domain of TF, however, independently of prolyl
residues. Crosslinking experiments showed that a TF fragment containing
the PPIase domain linked to the ribosome via the N-terminal domain is
sufficient for interaction with nascent polypeptide substrates.
Homology modeling of the PPIase domain revealed a conserved
FKBP(FK506-binding protein)-like binding pocket composed of exposed
aromatic residues embedded in a groove with negative surface charge.
The features of this groove complement well the determined substrate
specificity of TF. Moreover, a mutation (E178V) in this putative
substrate binding groove known to enhance PPIase activity also enhanced
TF's association with a prolyl-free model peptide in solution and with
nascent polypeptides. This result suggests that both
prolyl-independent binding of peptide substrates and peptidyl-prolyl
isomerization involve the same binding site.
Ice as a matrix for IR-matrix-assisted laser desorption/ionization: mass spectra from a protein single crystal.
Authors: Berkenkamp S , Karas M , Hillenkamp F
Published: July 2002

Lasers emitting in the ultraviolet wavelength range of 260-360 nm are almost exclusively used for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of macromolecules. Reports about the use of lasers emitting in the infrared first appeared in 1990/1991. In contrast to MALDI in the ultraviolet, a very limited number of reports on IR-MALDI have since been published. Several matrices have been identified for infrared MALDI yielding spectra of a quality comparable to those obtained in the ultraviolet. Water (ice) was recognized early as a potential matrix because of its strong O-H stretching mode near 3 microm. Interest in water as matrix derives primarily from the fact that it is the major constituent of most biological tissues. If functional as matrix, it might allow the in situ analysis of macromolecular constituents in frozen cell sections without extraction or exchanging the water. We present results that show that IR-MALDI of lyophilized proteins, air dried protein solutions, or protein crystals up to a molecular mass of 30 kDa is possible without the addition of any separate matrix. Samples must be frozen to retain a sufficient fraction of the water of hydration in the vacuum. The limited current sensitivity, requiring at least 10 pmol of protein for a successful analysis needs to be further improved.
Manipulation and potentiation of antimycobacterial immunity using recombinant bacille Calmette-Guérin strains that secrete cytokines.
Authors: Murray P J , Aldovini A , Young R A
Published: July 2002

Bacille Calmette-Guérin (BCG) is a live, attenuated strain of Mycobacterium bovis used widely for tuberculosis prophylaxis and bladder cancer immunotherapy, although it has limitations in both contexts. To investigate whether BCG's immunostimulatory properties could be modified, and to gain insight into the interaction between mycobacteria and their hosts, we constructed recombinant BCG strains that secrete functional murine cytokines and studied their properties in mouse models of experimental infection. Cell-mediated immune responses to mycobacterial antigen (purified protein derivative) were assayed using splenocytes from mice inoculated with various BCG recombinants. Antigen-specific proliferation and cytokine release were found to be substantially greater with splenocytes derived from mice injected with cytokine-secreting BCG than with splenocytes from mice injected with BCG lacking cytokines. The most profound effects were induced by BCG secreting interleukin 2, interferon gamma, or granulocyte-macrophage colony-stimulating factor. Thus, cytokine-secreting BCG can enhance immune responses to mycobacterial antigens and may be improved reagents for tuberculosis prophylaxis and cancer immunotherapy.