bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotope effects associated with tunneling and double proton transfer in the hydrogen bonds of benzoic acid
Authors: Xue Q. , Horsewill A. J. , Johnson M. R. , Trommsdorff H. P.
Published: May 2004

The isotope effects associated with double proton transfer in the hydrogen bonds of benzoic acid (BA) dimers have been measured using field-cycling H1 NMR relaxometry and quasielastic neutron scattering. By studying mixed isotope (hydrogen and deuterium) samples, the dynamics of three isotopologues, BA-HH, BA-HD, and BA-DD, have been investigated. Low temperature measurements provide accurate measurements of the incoherent tunneling rate, k0. This parameter scales accurately with the mass number, m, according to the formula k0=(E/m)e−Fm providing conclusive evidence that the proton transfer process is a strongly correlated motion of two hydrons. Furthermore, we conclude that the tunneling pathway is the same for the three isotopologue species. Measurements at higher temperatures illuminate the through barrier processes that are mediated via intermediate or excited vibrational states. In parallel with the investigation of proton transfer dynamics, the theoretical and experimental aspects of studying spin-lattice relaxation in single crystals of mixed isotope samples are investigated in depth. Heteronuclear dipolar interactions between H1 and H2 isotopes contribute significantly to the overall proton spin-lattice relaxation and it is shown that these must be modeled correctly to obtain accurate values for the proton transfer rates. Since the sample used in the NMR measurements was a single crystal, full account of the orientation dependence of the spin-lattice relaxation with respect to the applied B field was incorporated into the data analysis.
Plasticity and strength of metal oxide high-temperature superconductors (Review)
Authors: Lubenets S. V. , Natsik V. D. , Fomenko L. S.
Published: May 2004

The results of research on the plasticity and strength of a wide class of metal oxide perovskite-like compounds which have the property of high-temperature superconductivity or which can be used as base compounds for making high-temperature superconductors (HTSCs) are systematized and presented from a unified point of view. The mechanical properties of materials with different morphology—single crystals, polycrystals, and composites,—measured by different methods of mechanical testing in the low-temperature, room-temperature, and high-temperature regions, are discussed. The characteristic defects of the crystal structure for these compounds are considered, the crystallography of two modes of plastic deformation—slip and twinning—is described, and the stress-induced structural rearrangement of the twin structure that appears at a high-temperature phase transformation is discussed. The features of plastic deformation and fracture of metal oxide materials due to structural microdefects (dislocations, impurities, twin and grain boundaries) and macrodefects (voids, cracks, heterophase inclusions) are noted, and the role of heavy-cation diffusion in the kinetics of high-temperature deformation is discussed. The influence of structural phase transformations and the superconducting transition on the mechanical properties of metal oxides is considered. This review is a continuation of a review of the elastic and acoustic properties of HTSCs published earlier by the authors in Fiz. Nizk. Temp. 21, 475 (1995) [Low Temp. Phys. 21, 367 (1995)].
Study of the spectra of electron–ripplon oscillations and dissipation processes in a two-dimensional electron crystal over liquid helium
Authors: Syvokon V. E.
Published: May 2004

The resonance spectrum of coupled electron–ripplon oscillations in two-dimensional electron crystals over liquid helium are investigated in the range of surface electron densities ns=(3.2–10.8)×108 cm−2 at holding electric fields E⊥=300–1150 V/cm, and in the temperature interval T=0.08–0.4 K. As a result of an analysis of the spectra, the real χ1 and imaginary χ2 parts of the inverse conductivity σ−1 of the crystals are obtained as functions of T, ns, and E⊥. The value found for χ2 is in good agreement with the theoretical estimates. Analysis of the dependences of χ1 suggests that the energy losses in the electron crystal are due to defects of its crystal structure.
Electronic topological transition in Re1−xMox alloys and its influence on the temperature of the superconducting transition
Authors: Ignatyeva T. A. , Velikodny A. N.
Published: May 2004

The features of the variation in the superconducting transition temperature Tc of Re1−xMox alloys in the interval of Mo concentrations C up to 5 at. % (within the solid solution region) are investigated at pressures P of up to 10 kbar. A nonlinear increase of Tc to ≈5 K is observed when an impurity of C≈4.7 at. % Mo is added, and an inflection point is observed at C≈2.35 at. % Mo. The dependence (∂Tc/∂P)(C) has a minimum at the same Mo concentration. This attests to the presence of a critical energy Ec<EF0 in the electron spectrum of Re. An Mo impurity, which is electronegative relative to Re, lowers the Fermi energy EF0 of Re, and when it crosses the level Ec of the top of the filled d band, which lies below the Fermi energy, an electronic topological transition (ETT) occurs under the influence of the Mo impurity at a concentration C≈2.35 at. %. The minimum and asymmetry of (1/Tc)(∂Tc/∂P)(C) correspond to the appearance of a new hole pocket of the Fermi surface. The d electrons, with a high electronic density of states, emerge on the Fermi level; this gives a substantial contribution to the increase of Tc. In a quantitative comparison of the theory with experiment the difference EF0−Ec≈0.017 eV and other parameters of the ETT are determined.
Anomalous diamagnetism in aluminum–lithium alloys
Authors: Desnenko V. A. , Dolya S. N. , Isaev N. V. , Svechkarev I. V. , Fedorchenko A. V.
Published: May 2004

In the region of the equilibrium solid solutions of lithium in aluminum an anomalous low-temperature peak of diamagnetism is observed which is due to the presence of a boundary point on a line of band degeneracy directly below the Fermi level. The position and structure of the peak in the average valence function are analogous to those studied previously in the aging systems Al–Mg and Al–Zn under suitable heat treatment. The value of the lithium impurity scattering parameter for the electron states in the vicinity of the point of degeneracy mentioned is estimated, and the linear relation of that parameter with impurity-related electrical resistance in aluminum alloys is established.
Above the surface multifragmentation of surface scattered fullerenes
Authors: Bekkerman A. , Kaplan A. , Gordon E. , Tsipinyuk B. , Kolodney E.
Published: May 2004

C 60 − ions were scattered from a gold surface at impact energies of 80–900 eV. The Cn− fragments abundance distribution (odd and even) and the sharp fragmentation threshold observed, point at a prompt shattering event. The measured angle and energy distributions of the Cn− fragments (n=2–12) provide clear evidence for a multifragmentation process where the superheated fullerenes leave the surface “intact” and disintegrate away from the surface.
A high-resolution pulsed field ionization-photoelectron-photoion coincidence study of vinyl bromide
Authors: Qian X. M. , Lau K. C. , Ng C. Y.
Published: May 2004

By employing the high-resolution pulsed field ionization-photoelectron (PFI-PE)-photoion coincidence method, we have examined the unimolecular dissociation reaction of energy-selected C2H3Br+ to form C2H3++Br near its threshold. The analysis of the breakdown curves for C2H3Br+ and C2H3+ yields a value of 11.9010±0.0015 eV for the 0 K dissociative photoionization threshold or appearance energy (AE) for C2H3+ from C2H3Br. This AE(C2H3+) value, together with the ionization energy (IE) for C2H3Br (9.8200±0.0015 eV) obtained by PFI-PE and threshold photoelectron (TPE) measurements, has allowed the determination of the 0 K dissociation energy (D0) for the C2H3+–Br bond to be 2.081±0.002 eV. The 0 K AE(C2H3+) from C2H3Br obtained in this study corresponds to ΔHf0∘(C2H3+)=1123.7±1.9 kJ/mol. Combining the latter value and the known ΔHf0∘(C2H3)=306.7±2.1 kJ/mol, we calculated a value of 8.468±0.029 eV for the IE(C2H3), which is in accord with the result obtained in the previous photoionization efficiency study. We have also carried out high-level ab initio calculations for the IE(C2H3) at the Gaussian-3 and the CCSD(T,full)/CBS level of theory. The CCSD(T,full)/CBS prediction of 8.487 eV for the IE(C2H3→bridged-C2H3+) is in good agreement with the IE(C2H3) value derived in the present experiment. Combining the 0 K AE(C2H3+)=11.9010±0.0015 eV and the IE(C2H3)=8.468±0.029 eV yields the value of 3.433±0.029 eV for D0(C2H3–Br). We have also recorded the TPE spectrum of C2H3Br in the energy range of 9.80–12.20 eV. Members (n=5–14) of four autoionizing Rydberg series converging to the C2H3Br+(Ã 2A′) state are observed in the TPE spectrum. The analysis of the converging limit of these Rydberg series and the vibrational TPE bands for C2H3Br+(Ã 2A′) has provided more precise values for the ν6+ (1217±10 cm−1) and ν8+ (478±8 cm−1) modes and the IE (10.9156±0.0010 eV) for the formation of C2H3Br+(Ã 2A′) from C2H3Br.
New results for phase transitions from catastrophe theory
Authors: Bogdan Tetyana V. , Wales David J.
Published: May 2004

Catastrophe theory predicts that in certain limits universal relations should exist between barrier heights, curvatures and the positions of local maxima and minima on a potential or free energy surface. In the present work we investigate these relations for both first- and second-order phase transitions, revealing that the ideal ratios often hold quite well over a wide range of conditions. This elementary catastrophe theory is illustrated for the melting transition of an atomic cluster, the isotropic-to-nematic transition in a liquid crystal, and the ferromagnetic-to-paramagnetic phase transition in the two-dimensional Ising model.
The hardness profile as a tool to detect spurious stationary points in the potential energy surface
Authors: Torrent-Sucarrat Miquel , Luis Josep M. , Duran Miquel , Solà Miquel
Published: May 2004

In the present work, we have computed the energy and hardness profiles for a series of inter and intramolecular conformational changes at several levels of calculation. All processes studied have in common the fact that the choice of a weak methodology or a poor basis set results in the presence of spurious stationary points in the energy profile. At variance with the energy profiles, the hardness profiles calculated as the difference between the vertical ionization potential and electron affinity always show the correct number of stationary points independently of the basis set and methodology used. For this reason, we have concluded that hardness profiles can be used to check the reliability of the energy profiles for those chemical systems that, because of their size, cannot be treated with high level ab initio methods.
In search of temporal power laws in the orientational relaxation near isotropic–nematic phase transition in model nematogens
Authors: Jose Prasanth P. , Bagchi Biman
Published: May 2004

Recent Kerr relaxation experiments by Gottke et al. [J. Chem. Phys. 116, 360 (2002); 116, 6339 (2002)] have revealed the existence of a pronounced temporal power law decay in the orientational relaxation near the isotropic–nematic phase transition (INPT) of nematogens of rather small aspect ratio, κ (κ≃3–4). We have carried out very long (50 ns) molecular dynamics simulations of model (Gay–Berne) prolate ellipsoids with aspect ratio 3 in order to investigate the origin of this power law. The model chosen is known to undergo an isotropic to nematic phase transition for a range of density and temperature. The distance dependence of the calculated angular pair correlation function correctly shows the emergence of a long range correlation as the INPT is approached along the density axis. In the vicinity of INPT, the single particle second rank orientational time correlation function exhibits power law decay, (t−α) with exponent α∼2/3. More importantly, we find the sudden appearance of a pronounced power-law decay in the collective part of the second rank orientational time correlation function at short times when the density is very close to the transition density. The power law has an exponent close to unity, that is, the correlation function decays almost linearly with time. At long times, the decay is exponential-like, as predicted by Landau–de Gennes mean field theory. Since Kerr relaxation experiments measure the time derivative of the collective second rank orientational pair correlation function, the simulations recover the near independence of the signal on time observed in experiments. In order to capture the microscopic essence of the dynamics of pseudonematic domains inside the isotropic phase, we introduce and calculate a dynamic orientational pair correlation function (DOPCF) obtained from the coefficients in the expansion of the distinct part of orientational van Hove time correlation function in terms of spherical harmonics. The DOPCF exhibits power law relaxation when the pair separation length is below certain critical length. The orientational relaxation of a local director, defined in terms of the sum of unit vectors of all the ellipsoidal molecules, is also found to show slow power law relaxation over a long time scale. These results have been interpreted in terms of a newly developed mode coupling theory of orientational dynamics near the INPT. In the present case, the difference between the single particle and the collective orientational relaxation is huge which can be explained by the frequency dependence of the memory kernel, calculated from the mode coupling theory. The relationship of this power law with the one observed in a supercooled liquid near its glass transition temperature is explored.
Exponential probe rotation in glass-forming liquids
Authors: Wang Li-Min , Richert Ranko
Published: May 2004

Using time resolved optical depolarization, we have studied the rotational behavior of molecular probes in supercooled liquids near the glass transition temperature Tg. Simultaneously, the dynamics of the liquid immediately surrounding these rigid probes is measured by triplet state solvation experiments. This direct comparison of solute and solvent dynamics is particularly suited for assessing the origin of exponential orientational correlation functions of probe molecules embedded in liquids which exhibit highly nonexponential structural relaxation. Polarization angle dependent Stokes shift correlation functions demonstrate that probe rotation time and solvent response time are locally correlated quantities in the case of smaller probe molecules. Varying the size of both guest and host molecules shows that the size ratio determines the rotational behavior of the probes. The results are indicative of time averaging being at the origin of exponential rotation of probes whose rotational time constant is slower than solvent relaxation by a factor of 20 or more.
Optimized Jastrow–Slater wave functions for ground and excited states: Application to the lowest states of ethene
Authors: Schautz Friedemann , Filippi Claudia
Published: May 2004

A quantum Monte Carlo method is presented for determining multideterminantal Jastrow–Slater wave functions for which the energy is stationary with respect to the simultaneous optimization of orbitals and configuration interaction coefficients. The approach is within the framework of the so-called energy fluctuation potential method which minimizes the energy in an iterative fashion based on Monte Carlo sampling and a fitting of the local energy fluctuations. The optimization of the orbitals is combined with the optimization of the configuration interaction coefficients through the use of additional single excitations to a set of external orbitals. A new set of orbitals is then obtained from the natural orbitals of this enlarged configuration interaction expansion. For excited states, the approach is extended to treat the average of several states within the same irreducible representation of the pointgroup of the molecule. The relationship of our optimization method with the stochastic reconfiguration technique by Sorella et al. is examined. Finally, the performance of our approach is illustrated with the lowest states of ethene, in particular with the difficult case of the 11B1u state.
Induced thermal stress fields for three-dimensional distortion control of Si wafer topography
Authors: Schaper Charles D. , Chen Been-Der , Pease R. Fabian W.
Published: May 2004

Localized, controlled heating can induce a thermal stress field in silicon wafers and displace the surface topography in three dimensions, which is useful for nanoscale regulation of overlay in microcontact printing systems. Simulation and experimental results are presented to demonstrate the use of a thermal array consisting of a dense distribution of independent heating elements to locally displace silicon wafer alignment microstructures. An experimental apparatus comprised of a 7×7 array of thermal cycling sources is used to control the absolute three-dimensional position of surface microstructures. The system is used to demonstrate out-of-plane sensitivity of 1.4 μm/°C by thermomechanical displacement contributions from thermal expansion of the heating element. Rolloff in out-of-plane displacement of 200 nm/mm/°C in silicon at the boundary between heated and nonheated regions in this apparatus is exhibited. Dynamic real-time control of the substrate flatness is thus feasible and is demonstrated with the apparatus using feedback from three alignment microscopes, to sub-100 nm levels of regulation. Control of the in-plane microstructure position is achieved by stabilizing the vertical displacement with a mechanical nanopositioning stage, while establishing a thermal stress field to produce displacement sensitivity of 70 nm/°C. Real-time feedback control of the in-plane microstructure position is demonstrated, also within sub-100 nm of the target regulation level.
New method to estimate the frequency stability of laser signals
Authors: McFerran J. J. , Maric M. , Luiten A. N.
Published: May 2004

A frequent challenge in the scientific and commercial use of lasers is the need to determine the frequency stability of the output optical signal. In this article we present a new method to estimate this quantity while avoiding the complexity of the usual technique. The new technique displays the result in terms of the usual time domain measure of frequency stability: the square root Allan variance.
Experimental setup for mobile detection of electromagnetic fields in populated regions
Authors: Bellia P. , Carrubba S. , Falciglia F. , Gulino M. , Triglia A.
Published: May 2004

The mobile measurement of electromagnetic fields (emf) allows us to constantly monitor a wide part of the territory very quickly and cut the price. The study of an experimental apparatus designed for such kind of measurements will be presented. The experimental setup uses broadband instruments for emf measurements synchronized with GPS-GIS (global position system—geographic information systems) systems. The apparatus is installed on a vehicle in motion in order to measure continuously at the same time the position of the probe and the correspondent emf value. The results, however, are affected by many factors, as vehicle presence, probe position, and field frequency. Using a metallic shield with known geometric and dielectric properties it is possible to overcome these problems. Moreover the effect of the metallic shield on the emf measured value can be easily simulated and reproduced in laboratory. Some laboratory measurements are performed in order to optimize the experimental apparatus for the measure of emf of interest.
Rapid cryofixation/freeze fracture for the study of nanobubbles at solid–liquid interfaces
Authors: Switkes M. , Ruberti J. W.
Published: May 2004

A technique borrowed from biology, rapid cryofixation/freeze fracture, has been adapted for the study of liquid–solid interfaces. This technique allows high-resolution imaging of the interfaces between water and substrates with varying degrees of hydrophobicity. The interface between gas-saturated water and hydrophobic surfaces is covered with a network of 100 nm scale features similar to those previously reported, while degassed water produces smooth interfaces. We thus confirm that the features are indeed nanobubbles which form spontaneously from dissolved gas in the liquid. The interface of gas-saturated water and a hydrophilic surface, while showing no evidence of nanobubbles, is not as smooth as the degassed interface.
Distributive and analytic properties of lattice sums
Authors: McPhedran R. C. , Smith G. H. , Nicorovici N. A. , Botten L. C.
Published: May 2004

We use sums over Bessel functions of the first kind to derive a convenient form of the Poisson summation identity relating sums over direct lattices in two dimensions to sums over reciprocal lattices. After three simple examples of the use of the identity, we consider sums over complex powers of the radial distance to lattice points, and also sums incorporating factors exp(4imφp) depending on angles of lattice points. We study the distribution of zeros of lattice sums, and show two which seemingly obey the Riemann hypothesis, and a third which does not. We provide a reflection formula for angular lattice sums, and a Macdonald function sum for the lowest order angular lattice sum.
Suppression of subcutaneous oxidation during the deposition of amorphous lanthanum aluminate on silicon
Authors: Edge L. F. , Schlom D. G. , Brewer R. T. , Chabal Y. J. , Williams J. R. , Chambers S. A. , Hinkle C. , Lucovsky G. , Yang Y. , Stemmer S. , Copel M. , Holländer B. , Schubert J.
Published: May 2004

Amorphous LaAlO3 thin films have been deposited by molecular beam deposition directly on silicon without detectable oxidation of the underlying substrate. We have studied these abrupt interfaces by Auger electron spectroscopy, high-resolution transmission electron microscopy, medium-energy ion scattering, transmission infrared absorption spectroscopy, and x-ray photoelectron spectroscopy. Together these techniques indicate that the films are fully oxidized and have less than 0.2 Å of SiO2 at the interface between the amorphous LaAlO3 and silicon. These heterostructures are being investigated for alternative gate dielectric applications and provide an opportunity to control the interface between the silicon and the gate dielectric.
Measurement of polarization charge and conduction-band offset at InxGa1−xN/GaN heterojunction interfaces
Authors: Zhang H. , Miller E. J. , Yu E. T. , Poblenz C. , Speck J. S.
Published: May 2004

The spontaneous and piezoelectric polarization fields in group-III nitride semiconductors lead to the presence of large electrostatic sheet charge densities at nitride semiconductor heterojunction interfaces. Precise quantitative knowledge of these polarization-induced charge densities and of the band-edge discontinuities at nitride heterojunction interfaces is therefore essential in nitride semiconductor device design and analysis. We have used capacitance–voltage profiling to measure the conduction-band offset and polarization charge density at InxGa1−xN/GaN heterojunction interfaces with x=0.054 and x=0.09. We obtain conduction-band offsets ΔEC=0.09±0.07 eV for x=0.054 and ΔEC=0.22±0.05 eV for x=0.09, corresponding to an averaged conduction-to-valence-band offset ratio ΔEC:ΔEV of 58:42. Our measurements yield polarization charge densities of (1.80±0.32)×1012 e/cm2 for x=0.054 and (4.38±0.36)×1012 e/cm2 for x=0.09. These values are smaller than those predicted by recent theoretical calculations, but in good agreement with values inferred from a number of optical experiments.
Magnetization dependence on strain in the Ni–Mn–Ga magnetic shape memory material
Authors: Suorsa I. , Pagounis E. , Ullakko K.
Published: May 2004

Magnetic shape memory (MSM) materials can generate up to 10% strain when exposed to a magnetic field. The magnetization of the MSM material is closely related to its strain level. Modeling this relationship is of prime importance, especially in sensor and motion generation applications. In the present work, the magnetization curve of a Ni2MnGa MSM material was measured at different strain levels. The measurements were performed at magnetic fields of up to 130 kA/m, which includes the range used in most sensor applications. The measurement setup is described, and the results are compared with two models of magnetization dependence on strain, a linear and a nonlinear model. It is demonstrated that at high magnetic field strength values the relationship is linear, while at low fields (H<40 kA/m) the dependence between the strain and the magnetization is nonlinear.
Comprehensive analysis of the internal losses in 2.0μm (AlGaIn)(AsSb) quantum-well diode lasers
Authors: Rattunde M. , Schmitz J. , Kiefer R. , Wagner J.
Published: May 2004

We have fabricated and characterized high-power 2.0 μm-wavelength (AlGaIn)(AsSb) quantum-well diode lasers emitting a power of 1.7 W in continuous-wave operation and over 9 W in pulsed operation at 300 K heat sink temperature. For potential further improvement of laser performance, the different contribution to the internal losses αi has been analyzed in detail for the present laser structure. Consistent results have been obtained for a series of samples, for which different design parameters were varied systematically: As expected, the losses in the cladding layers are dominated by free carrier absorption in the p-doped cladding. The cross section for free-hole absorption in Al0.84Ga0.16As0.06Sb0.94 is determined to σP=4.6×10−17 cm2, which is comparable to values reported in the literature for (AlGaIn)(AsP)-based lasers emitting at 1.5 μm. The losses in the active region were found to increase linearly with increasing number of quantum wells at a rate of 1.5 cm−1 per quantum well, whereas the losses in the separate confinement layers are negligible.
Silver nanoparticle array structures that produce remarkably narrow plasmon lineshapes
Authors: Zou Shengli , Janel Nicolas , Schatz George C.
Published: May 2004

Using electrodynamics calculations, we have discovered one dimensional array structures built from spherical silver nanoparticles that produce remarkably narrow (∼ meV or less) plasmon resonance spectra upon irradiation with light that is polarized perpendicular to the array axis. The narrow lines require a minimum particle radius of about 30 nm to achieve. Variations of the plasmon resonance wavelength, extinction efficiency and width with particle size, array structure, interparticle distance and polarization direction are examined, and conditions which lead to the smallest widths are demonstrated. A simple analytical expression valid for infinite lattices shows that the sharp resonance arises from cancellation between the single particle width and the imaginary part of the radiative dipolar interaction.
Er
3+
-doped BaTiO3 nanocrystals for thermometry: Influence of nanoenvironment on the sensitivity of a fluorescence based temperature sensor
Authors: Alencar Márcio A. R. C. , Maciel Glauco S. , de Araújo Cid B. , Patra Amitava
Published: May 2004

Frequency upconverted emissions centered at 526 and 547 nm from two thermodynamically coupled excited states of Er3+ doped in BaTiO3 nanocrystals were recorded in the temperature range from 322 to 466 K using a diode laser emitting at 980 nm as the excitation source. The ensemble measurements of the fluorescence intensity ratio (FIR) of the signals at 526 and 547 nm as a function of the temperature showed that the sensitivity (the rate in which the FIR changes with the temperature) of such sensor depends on the size of the nanocrystal. This is explained taking into consideration modifications of nonraditive relaxation mechanisms with the size of the nanocrystals.
Thermal and Base-Induced Cyclizations of N-Heteroarylamidinopropanoates
Authors: Clark Adrian , Prager Rolf H.
Published: May 2004

The potential cyclization of N-heteroarylamidines to annelated pyrimidines by flash vacuum pyrolysis or by treatment with bases has been investigated. The pyrolytic process with the title compounds is complicated by competing formation and rearrangement of an imidoylketene. The major pyrolysis products, the 4-aminopyrimidin-6-ones, were best prepared from the title compounds by reaction with hindered alkoxides, while the pyrolysis byproducts, the 4-alkoxypyrimidin-6-ones, were conveniently prepared from the appropriate isoxazol-5(2H)-one by reaction with the appropriate alkoxide, followed by acidic workup.
Modeling first-hit functions of the t(12;21)TEL-AML1translocation in mice
Authors: Tsuzuki Shinobu , Seto Masao , Greaves Mel , Enver Tariq
Published: May 2004

The t(12;21) translocation, which generates theTEL-AML1(ETV6-RUNX1) fusion gene, is the most common structural chromosome change in childhood cancer and is exclusively associated with the common B cell precursor subset of acute lymphoblastic leukemia (ALL). Evidence suggests that the translocation usually occursin uteroduring fetal hemopoiesis and most probably constitutes an initiating or first-hit mutation that is necessary but insufficient for the development of overt, clinical leukemia. The mechanism by whichTEL-AML1contributes to this early stage of leukemogenesis is unknown. To address this question we have analyzed hemopoiesis in mice syngeneically transplanted withTEL-AML1-transduced bone marrow stem cells.TEL-AML1expression was associated with an accumulation/expansion of primitive c-kit-positive multipotent progenitors and a modest increase in myeloid colony-forming cells.TEL-AML1expression was, however, permissive for myeloid differentiation. Analysis of B lymphopoiesis revealed an increase in early, pro-B cells but a differentiation deficit beyond that stage, resulting in reduced B cell production in the marrow. TEL-AML1-positive B cell progenitors exhibited reduced expression of the surrogate light-chain component λ5 and the IL-7 receptor, both of which may contribute to impedance of differentiationin vivoand account for their reducedin vitroclonogenicity in IL-7. A selective differentiation deficit of B lineage progenitors (i) is consistent with the phenotype ofTEL-AML1-associated leukemia in children and (ii) provides a potential mechanism for the protracted preleukemic state that often precedes ALL. These results provide mechanistic insight into the role of the t(12;21) translocation in the initiation of common B cell precursor ALL.
Dynamic fMRI and EEG Recordings during Spike-Wave Seizures and Generalized Tonic-Clonic Seizures in WAG/Rij Rats
Authors: Nersesyan Hrachya , Hyder Fahmeed , Rothman Douglas L. , Blumenfeld Hal
Published: May 2004

Generalized epileptic seizures produce widespread physiological changes in the brain. Recent studies suggest that “generalized” seizures may not involve the whole brain homogeneously. For example, electrophysiological recordings in WAG/Rij rats, an established model of human absence seizures, have shown that spike-and-wave discharges are most intense in the perioral somatosensory cortex and thalamus, but spare the occipital cortex. Is this heterogeneous increased neuronal activity matched by changes in local cerebral blood flow sufficient to meet or exceed cerebral oxygen consumption? To investigate this, we performed blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measurements at 7T with simultaneous electroencephalogram recordings. During spontaneous spike-wave seizures in WAG/Rij rats under fentanylhaloperidol anesthesia, we found increased fMRI signals in focal regions including the perioral somatosensory cortex, known to be intensely involved during seizures, whereas the occipital cortex was spared. For comparison, we also studied bicuculline-induced generalized tonic-clonic seizures under the same conditions, and found fMRI increases to be larger and more widespread than during spike-and-wave seizures. These findings suggest that even in regions with intense neuronal activity during epileptic seizures, oxygen delivery exceeds metabolic needs, enabling fMRI to be used for investigation of dynamic cortical and subcortical network involvement in this disorder.
Glucosylceramide Synthase Activity and Ceramide Levels are Modulated during Cerebral Ischemia after Ischemic Preconditioning
Authors: Takahashi Kenzo , Ginis Irene , Nishioka Ryoji , Klimanis Dace , Barone Frank C. , White Raymond F. , Chen Yong , Hallenbeck John M.
Published: May 2004

After 24-hour middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats, brain ceramide level increased from baseline reached 595% (ischemic core) and 460% (perifocal/penumbral areas); brain glucosylceramide synthase (GCS) activities in these areas simultaneously decreased by 70% and 50%, respectively. Ten-minute MCAO preconditioning significantly attenuated 24-hour MCAO-induced ceramide accumulation by 40% to 60% in ischemic core and perifocal areas, and GCS activities improved by 60% to 70% in both areas. Thus, potentially toxic levels of brain ceramide induced by MCAO were attenuated to intermediate levels in preconditioned animals; brain GCS activity was relatively preserved. In ischemic tolerance, GCS appears to modulate otherwise high levels of brain ceramide.
Epsilon Protein Kinase C Mediated Ischemic Tolerance Requires Activation of the Extracellular Regulated Kinase Pathway in the Organotypic Hippocampal Slice
Authors: Lange-Asschenfeldt Christian , Raval Ami P. , Dave Kunjan R. , Mochly-Rosen Daria , Sick Thomas J. , Pérez-Pinzón Miguel A.
Published: May 2004

Ischemic preconditioning (IPC) promotes brain tolerance against subsequent ischemic insults. Using the organotypic hippocampal slice culture, we conducted the present study to investigate (1) the role of adenosine A1 receptor (A1AR) activation in IPC induction, (2) whether epsilon protein kinase C (ɛPKC) activation after IPC is mediated by the phosphoinositol pathway, and (3) whether ɛPKC protection is mediated by the extracellular signal-regulated kinase (ERK) pathway. Our results demonstrate that activation of A1AR emulated IPC, whereas blockade of the A1AR during IPC diminished neuroprotection. The neuroprotection promoted by the A1AR was also reduced by the ɛPKC antagonist. To determine whether ɛPKC activation in IPC and A1AR preconditioning is mediated by activation of the phosphoinositol pathway, we incubated slices undergoing IPC or adenosine treatment with a phosphoinositol phospholipase C inhibitor. In both cases, preconditioning neuroprotection was significantly attenuated. To further characterize the subsequent signal transduction pathway that ensues after ɛPKC activation, mitogen-activated protein kinase kinase was blocked during IPC and pharmacologic preconditioning (PPC) (with ɛPKC, NMDA, or A1AR agonists). This treatment significantly attenuated IPC- and PPC-induced neuroprotection. In conclusion, we demonstrate that ɛPKC activation after IPC/PPC is essential for neuroprotection against oxygen/glucose deprivation in organotypic slice cultures and that the ERK pathway is downstream to ɛPKC.
Neuroprotection of Ischemic Brain by Vascular Endothelial Growth Factor is Critically Dependent on Proper Dosage and May Be Compromised by Angiogenesis
Authors: Manoonkitiwongsa Panya S. , Schultz Robert L. , McCreery Douglas B. , Whitter Ernest F. , Lyden Patrick D.
Published: May 2004

Vascular endothelial growth factor (VEGF) is currently considered a potential pharmacologic agent for stroke therapy because of its strong neuroprotective and angiogenic capacities. Nonetheless, it is unclear how neuroprotection and angiogenesis by exogenous VEGF are related and whether they are concurrent events. In this study, the authors evaluated by stereology the effect of VEGF on neuronal and vascular volume densities of normal and ischemic brain cortices of adult male Sprague-Dawley rats. Ischemia was induced by a 4-hour occlusion of the middle cerebral artery. Low, intermediate, and high doses of VEGF165 were infused through the internal carotid artery for 7 days by an indwelling osmotic pump. The low and intermediate doses, which did not induce angiogenesis, significantly promoted neuroprotection of ischemic brains and did not damage neurons of normal brains. In contrast, the high dose that induced angiogenesis showed no neuroprotection of ischemic brains and damaged neurons of normal brains. These findings suggest that in vivo neuroprotection of ischemic brains by exogenous VEGF does not necessarily occur simultaneously with angiogenesis. Instead, neuroprotection may be greatly compromised by doses of VEGF capable of inducing angiogenesis. Stroke intervention efforts attempting to induce neuroprotection and angiogenesis concurrently through VEGF monotherapy should be approached with caution.
Augmented Inverse Probability Weighted Estimator for Cox Missing Covariate Regression
Authors: Wang C. Y. , Chen Hua Yun
Published: May 2004

Summary.This article investigates an augmented inverse selection probability weighted estimator for Cox regression parameter estimation when covariate variables are incomplete. This estimator extends the Horvitz and Thompson (1952,Journal of the American Statistical Association47, 663–685) weighted estimator. This estimator is doubly robust because it is consistent as long as either the selection probability model or the joint distribution of covariates is correctly specified. The augmentation term of the estimating equation depends on the baseline cumulative hazard and on a conditional distribution that can be implemented by using an EM‐type algorithm. This method is compared with some previously proposed estimators via simulation studies. The method is applied to a real example.
Nonoverlapping Clusters: Approximate Distribution and Application to Molecular Biology
Authors: Su Xiaoping , Wallenstein Sylvan , Bishop David
Published: May 2004

Summary. An approach is developed for the screening of genomic sequence data to identify gene regulatory regions. This approach is based on deciding if putative transcription factor binding sites are clustered together to a greater extent than one would expect by chance. Given n events occurring on an interval of width L (L base pairs), an r:w cluster is defined as r+ 1 consecutive events all contained within a window of length wL. Accurate and easily computable approximations are derived for the distribution of the number of nonoverlapping r:w clusters under the model that the positions of the n events have a uniform distribution. Simulations demonstrate that these approximations have greater accuracy than existing methods. The approximation is applied to detect erythroid‐specific regulatory regions in genomic DNA sequences, first in an artificial case where r is specified a priori and then as part of an exploratory approach.
Identifying Chromosomal Fragile Sites from a Hierarchical‐Clustering Point of View
Authors: Hou Chia‐Ding , Chiang Jengtung , Tai John Jen
Published: May 2004

Summary. Identification of fragile sites is a way to investigate the genetic abnormalities that are the hallmark of cancer and play an important role in carcinogenesis. Manifestation of nonrandom breakage at a chromosome band is an essential criterion for determination of the fragility of the band. In this article, a new detection procedure is proposed. This new procedure takes the relationship of one site with the others into consideration and can be applied to tests of the randomness of breakpoints under either the proportional probability model (PPM) or the equiprobability model (EPM). The procedure can form a grouping structure that classifies all sites into several clusters. It is applied to identification of fragile sites for a real data set for Chinese patients with colorectal carcinoma for illustration of the proposed method.
Unbiased Confidence Intervals for the Odds Ratio of Two Independent Binomial Samples with Application to Case–Control Data
Authors: Troendle James F. , Frank Jennifer
Published: May 2004

Summary. The problem of confidence interval construction for the odds ratio of two independent binomial samples is considered. Two methods of eliminating the nuisance parameter from the exact likelihood, conditioning and maximization, are described. A conditionally exact tail method exists by putting together upper and lower bounds. A shorter interval can be obtained by simultaneous consideration of both tails. We present here new methods that extend the tail and simultaneous approaches to the maximized likelihood. The methods are unbiased and applicable to case‐control data, for which the odds ratio is important. The confidence interval procedures are compared unconditionally for small sample sizes in terms of their expected length and coverage probability. A Bayesian confidence interval method and a large‐sample χ2 procedure are included in the comparisons.
Testing Local Independence between Two Point Processes
Authors: Allard Denis , Brix Anders , Chadoeuf Joël
Published: May 2004

Summary.Dependencies between two types of points in a spatial point process can be due either to a real dependence between the two types or to the dependence on common underlying variables. We propose a global test for dependence between two point processes that is valid for a wide range of models. In contrast with previously proposed methods, it is based on a number of local test statistics, which makes it possible to map the local association between the two processes. The behavior of the test is evaluated by a simulation study. It is then applied to a vegetation pattern data set from Burkina Faso.
Simple Incorporation of Interactions into Additive Models
Authors: Coull Brent A. , Ruppert David , Wand M. P.
Published: May 2004

Summary.Often, the functional form of covariate effects in an additive model varies across groups defined by levels of a categorical variable. This structure represents a factor‐by‐curve interaction. This article presents penalized spline models that incorporate factor‐by‐curve interactions into additive models. A mixed model formulation for penalized splines allows for straightforward model fitting and smoothing parameter selection. We illustrate the proposed model by applying it to pollen ragweed data in which seasonal trends vary by year.
Analyte Identification in Multivariate Calibration
Authors: Jones Geoffrey , Rocke David M.
Published: May 2004

Summary.In calibration experiments, an estimated relationship between covariate information for a sample and an observed response is used to infer the covariate information for unknown samples from their responses. In some ituations, this covariate information comprises a nominal variable (e.g., identity of a chemical, sex of an animal) and a real‐valued variable (e.g., concentration of the chemical, age of animal). If the calibrating relationship can be estimated separately for each candidate identity, the first step in analyzing unknown samples is to correctly determine their identity. A discrimination statistic is suggested for use in this situation and its asymptotic distribution is derived. The investigation is motivated by the possibility of using multiple immunoassays in environmental monitoring to identify and quantitate contaminated samples in situations where there are several candidate pollutants that cross‐react significantly to single assays. An example is given of the use of a four‐antibody assay for the simultaneous monitoring of the levels in water samples of several of the commonly used triazine herbicides and their derivatives.
Model‐Checking Techniques Based on Cumulative Residuals
Authors: Lin D. Y. , Wei L. J. , Ying Z.
Published: May 2004

Summary.Residuals have long been used for graphical and numerical examinations of the adequacy of regression models. Conventional residual analysis based on the plots of raw residuals or their smoothed curves is highly subjective, whereas most numerical goodness‐of‐fit tests provide little information about the nature of model misspecification. In this paper, we develop objective and informative model‐checking techniques by taking the cumulative sums of residuals over certain coordinates (e.g., covariates or fitted values) or by considering some related aggregates of residuals, such as moving sums and moving averages. For a variety of statistical models and data structures, including generalized linear models with independent or dependent observations, the distributions of these stochastic processes under the assumed model can be approximated by the distributions of certain zero‐mean Gaussian processes whose realizations can be easily generated by computer simulation. Each observed process can then be compared, both graphically and numerically, with a number of realizations from the Gaussian process. Such comparisons enable one to assess objectively whether a trend seen in a residual plot reflects model misspecification or natural variation. The proposed techniques are particularly useful in checking the functional form of a covariate and the link function. Illustrations with several medical studies are provided.
Monitoring the Rates of Composite Events with Censored Data in Phase II Clinical Trials
Authors: Cheung Ying Kuen , Thall Peter F.
Published: May 2004

Summary. In many phase II clinical trials, interim monitoring is based on the probability of a binary event, response, defined in terms of one or more time‐to‐event variables within a time period of fixed length. Such outcome‐adaptive methods may require repeated interim suspension of accrual in order to follow each patient for the time period required to evaluate response. This may increase trial duration, and eligible patients arriving during such delays either must wait for accrual to reopen or be treated outside the trial. Alternatively, monitoring may be done continuously by ignoring censored data each time the stopping rule is applied, which wastes information. We propose an adaptive Bayesian method that eliminates these problems. At each patient's accrual time, an approximate posterior for the response probability based on all of the event‐time data is used to compute an early stopping criterion. Application to a leukemia trial with a composite event shows that the method can reduce trial duration substantially while maintaining the reliability of interim decisions.
Combining Complete Multivariate Outcomes with Incomplete Covariate Information: A Latent Class Approach
Authors: Xue Qian‐Li , Bandeen‐Roche Karen
Published: May 2004

Summary.This work was motivated by the need to combine outcome information from a reference population with risk factor information from a screened subpopulation in a setting where the analytic goal was to study the association between risk factors and multiple binary outcomes. To achieve such an analytic goal, this article proposes a two‐stage latent class procedure that first summarizes the commonalities among outcomes using a reference population sample, then analyzes the association between outcomes and risk factors. It develops a pseudo‐maximum likelihood approach to estimating model parameters. The performance of the proposed method is evaluated in a simulation study and in an illustrative analysis of data from the Women's Health and Aging Study, a recent investigation of the causes and course of disability in older women. Combining information in the proposed way is found to improve both accuracy and precision in summarizing multiple categorical outcomes, which effectively diminishes ambiguity and bias in making risk factor inferences.