bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of sodium‐independent β‐alanine binding to cerebral cortical membranes from 7‐day‐old and adult mice
Authors: Saransaari Pirjo , Oja Simo S.
Published: April 2003

The sodium‐independent binding of β‐alanine to cerebral cortical membranes from adult (3‐ and 12‐month‐old) and developing (7‐day‐old) mice was characterized for the first time. The binding was saturable in each age group, consisting of only one component. The affinity for β‐alanine was highest and the number of available binding sites greatest in young animals. The binding was not affected by strychnine, but inhibited by β‐alanine itself, glycine, l‐alanine and l‐serine, the IC50 values being lower in immature mice. Glycine was shown to be a competitive inhibitor. The binding was also inhibited, albeit only in adults, by N‐methyl‐d‐aspartate receptor antagonists acting at the glycine modulatory site and by some GABAergic substances. It is concluded that even though β‐alanine may possess binding sites of its own, particularly in the immature cerebral cortex, β‐alanine could at least partly bind to strychnine‐insensitive glycine sites in the N‐methyl‐d‐aspartate receptor complex.
Growth factor‐induced neurite growth in primary neuronal cultures of dogs with neuronal ceroid lipofuscinosis
Authors: Dunn William A. , Raizada Mohan K. , Vogt E.Suzanne , Brown Elizabeth A.
Published: April 2003

Neuronal ceroid lipofuscinosis (NCL) is a type of lysosomal storage disease resulting in the progressive deterioration of neuronal function. Little is known about the genetics, pathophysiology and biochemical basis of this disease. This is, in part, due to the complexity of the central nervous system and the lack of an in vitro model. In this report, we describe the conditions to establish neuronal cells in primary culture from the brains of newborn English setters with NCL, a canine model for this disease. Over 80% of the neuronal cells from normal dog brain establish well‐developed interconnecting networks of long neurites. On the contrary, approximately 50% of the neurons cultured from NCL dog brains do not assemble neurites. Of those NCL neurons with processes, the neurites are routinely shorter and fewer in number than those seen in normal cultures. In addition, the characteristic inclusion bodies, pathological markers for this disease in vivo, are prevalent in the soma of cultured neuronal cells isolated from NCL dog brain. A time‐dependent maturation of the inclusion bodies suggests a progression of the disease state in culture. The reduced ability of the NCL neurons to establish neurites prompted us to examine the effects of growth factors on neurite assembly. Our data show that insulin‐like growth factor I, epidermal growth factor and platelet‐derived growth factor are capable of stimulating neurite outgrowth of NCL neurons.

We report the establishment and morphological characterization of neuronal cultures from normal and NCL dog brains. The abnormal morphology of cultured NCL neurons can, in part, be alleviated by supplementing the medium with growth factors. The results suggest that this cellular model of NCL will be useful to study the molecular and physiological mechanisms of NCL disease, as well as to test potential therapeutic agents and candidate genes.
Expression of amyloid precursor protein (APP) in rat brain and cultured neural cells
Authors: Gegelashvili Georgi , Schousboe Arne , Linnemann Dorte
Published: April 2003

Cell type‐specific and developmental patterns of APP expression were investigated in rat brain and cultured neural cells. Nearly all astrocytes were APP‐positive, whereas only selected population of neurons appeared to express APP. In these neurons, APP immunoreactivity was preferentially restricted to single processes. mRNAs encoding the major APP isoforms, APP695 and APP770, were co‐expressed as 3.4–3.6 kb transcripts both in astrocytes and neurons. In addition, an unusual 2.8 kb mRNA size class was revealed in cultured cerebellar granule neurons by means of the probe recognizing APP770 mRNA. Also, for the first time, APP714 mRNA was detected in rat brain by northern blotting. The steady‐state levels of these transcripts were increased from birth up to postnatal day 20, whereas no apparent changes were observed after reaching adulthood. These data hint at the involvement of APP in the major morphogenetic events taking place in rat brain during the first three postnatal weeks.
Brain‐derived neurotrophic factor and neurotrophin‐4 increase neurotrophin‐3 expression in the rat hippocampus
Authors: Lindholm Dan , da Penha Berzaghi Maria , Cooper Jonathan , Thoenen Hans , Castrén Eero
Published: April 2003

Hippocampal levels of mRNA encoding nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) are rapidly induced by enhanced neuronal activity following seizures and glutamate or muscarinic receptor activation. However, the levels of neurotrophin‐3 (NT‐3) mRNA acutely decrease after limbic seizures suggesting that a different mode of regulation may exist for these neurotrophins. Here we show that BDNF and neurotrophin‐4 (NT‐4), but not NT‐3 itself, up‐regulate NT‐3 mRNA in cultured hippocampal neurons. In the rat hippocampus, the muscarinic receptor agonist, pilocarpine increased BDNF mRNA levels rapidly and those of NT‐3 with a delay of several hours. Injection of BDNF into neonatal rats elevated NT‐3 mRNA in the hippocampus which demonstrates that BDNF is able to enhance NT‐3 expression in vivo. The regulation of NT‐3 by BDNF and NT‐4 enlargens the neurotrophic spectrum of these neurotrophins to include neuron populations responsive primarily to NT‐3.
Growth of trigeminal neurites and interactions with corneal cells in embryonic chick organ cultures
Authors: Pavlidis Christos , Steuhl Klaus‐Peter , Thanos Solon
Published: April 2003

The investigation of interactions between growing neurites and target cells during the development of the sensible corneal innervation is of crucial importance for understanding certain corneal diseases which are related to abnormal patterns of innervation. The purpose of the present work was to establish a culture system of cornea and trigeminal neurons and to examine interactions between these tissues. The responses of neurons derived from explanted embryonic chick trigeminal ganglia to co‐explanted slices prepared from embryonic cornea were monitored over several days in culture. The growth of trigeminal fibers, but not of neurites derived from control tissues such as trigeminal mesencephalic nucleus or ciliary ganglion, was preferentially directed towards the co‐cultured corneal slices. The ingrowth of trigeminal axons into the cornea was followed by formation of elaborate axonal terminal branches. Individual dissociated trigeminal neurons of pseudo‐unipolar or bipolar classes developed their typical morphologies in culture. In co‐cultures with corneal slices, they reacted to the corneal co‐explant by frequently retracting some branches and forming or elongating other ones, which were predominantly directed towards the target tissue. In addition, the presence of a co‐explanted trigeminal ganglion increased the rate of growth in the dissociated trigeminal neurons. The effect was not additive when cornea was present. Antibodies against nerve growth factor (NGF) and the low‐affinity p75‐NGF receptor (LANGFR) revealed that trigeminal ganglion cells support neuritic growth by secreting NGF, whereas corneal cells secrete additional factor(s) which act via the LANGFR.
Norepinephrine modulates excitatory amino acid‐induced responses in developing human and adult rat cerebral cortex
Authors: Radisavljevic Zivotije , Cepeda Carlos , Peacock Warwick , Buchwald Nathaniel A. , Levine Michael S.
Published: April 2003

These experiments were designed to assess the ability of norepinephrine and its β‐receptor agonist, isoproterenol, to modulate responses induced by activation of excitatory amino acid receptors in brain slices obtained from developing human cortex or adult rat cortex. Human cortical slices were obtained from children undergoing surgery for intractable epilepsy (9 months to 10 yr of age). For comparison, slices were also obtained from rats (2–3 months of age). Iontophoretic application of glutamate, N‐methyl‐d‐aspartate or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) produced excitatory responses consisting of membrane depolarizations accompanied by action potentials. Iontophoretic or bath application of norepinephrine or isoproterenol enhanced responses evoked by glutamate or N‐methyl‐d‐aspartate. Depolarizations occurred with shorter latencies and their amplitudes increased. Action potential frequency was also increased and responses were of longer duration. In contrast, norepinephrine or isoproterenol had no effect on responses induced by AMPA. The enhancement of responses induced by N‐methyl‐d‐aspartate or glutamate was antagonized by the β‐adrenergic receptor antagonist propranolol. Similar findings were obtained from neurons in humans or rats.

These results suggest that norepinephrine, possibly via β‐receptors, potentiates responses mediated by glutamate and N‐methyl‐d‐aspartate receptors without affecting those mediated by AMPA receptors. These effects were observed at all ages studied, indicating that the ability of norepinephrine to modulate excitatory neuronal transmission is well developed in human cortex by 9 months of age.
Developmental profiles of ornithine decarboxylase activity in the hippocampus, neocortex and cerebellum: Modulation following lead exposure
Authors: Zawia N.H. , Evers L.B. , Harry G.J.
Published: April 2003

Ornithine decarboxylase (ODC) is a growth‐associated enzyme which is critical for cell growth and transformation. ODC activity follows a specific ontogenetic pattern of activity in distinct brain regions according to their developmental stage. Perturbations in the pattern of ODC activity have been associated with brain damage including arrested cerebral growth. Modulations in the pattern of ODC activity were examined in the hippocampus, neocortex and cerebellum of neonatal rats (PND 3, 6, 9, 15) exposed via the dam to 0.2% lead‐acetate (Pb2+ prenatally (gestational day 13 to birth), postnatally (PND 1–15) or perinatally (gestational day 13 to PND 15). Prenatal exposure to Pb2+ perturbed the profile of ODC activity in all three brain regions examined, while postnatal exposure to Pb2+ resulted in prolonged stimulations of ODC activity in the cerebellum. Following prenatal exposure, these effects were manifested as a stimulation of ODC activity in the hippocampus, a repression of activity in the neocortex and a combination of these effects in the cerebellum. Perinatal exposure to Pb2+ transiently modulated the pattern of ODC activity similarly in all three brain regions, in a characteristic manner irrespective of their developmental stage. These Pb2+‐induced modulations of ODC activity suggest that polyamine‐dependent processes may play a significant role in the manifestation of Pb2+‐induced neurotoxicity dependent upon developmental factors at specific exposure periods.
Characterization of the response of growth and differentiation to lipoproteins and agents affecting cholesterol metabolism in murine neuroblastoma cells
Authors: Castellano F. , Bruscalupi G. , Columba S. , Di Croce L. , Trentalance A. , Augusti‐Tocco G.
Published: April 2003

Treatment with mevinolin, a competitive inhibitor of HMGCoAR, the key enzyme of isoprenoid metabolism, causes the arrest of proliferation and the differentiation of a neuroblastoma cell line (N18TG2). Mevalonate and high density lipoproteins partially restore growth.

Cholesterol synthesis in the presence of mevinolin remains active, because in these cells the key enzyme HMG‐CoA reductase is not completely inhibited by this drug. The fact that cell growth is reduced, while cholesterogenesis remains active, suggests that mevinolin acts by interfering with the synthesis of some unknown compound, other than cholesterol, which is necessary for proliferation.
Gender, anxiety-depressivity and self-image among adolescents
Authors: Kirkcaldy Bruce , Siefen Georg , Furnham Adrian
Published: April 2003

Two groups of non- and “quasi-depressives”—the latter corresponding to high depression scorers—German adolescents were examined to determine the effect of gender and depression in predicting physical ailments, self-image and attitudes towards parents. Quasi-depressive adolescents displayed higher frequencies of physical complaints across all five subscales of the Giessen physical complaints inventory compared to the non-depressive counterparts. Females generally reported more ailments (exhaustion, gastrointestinal, circulatory, and colds) than males. In contrast to males who showed scarce difference between depressives and non-depressives, female depressives exhibited substantially higher gastrointestinal ailments than non-depressive females. Depressives emerged as displaying inferior self-images, lower paternal acceptance, and somewhat higher maternal rejection, compared to non-depressives. Female adolescents displayed lower self-image, lower paternal acceptance (but not maternal rejection/acceptance), lower mathematical competency, and higher linguistic competency, when compared to male adolescents.
Influence of magnetoelastic coupling on the formation of a spatially inhomogeneous phase in two-dimensional ferromagnets
Authors: Fridman Yu. A. , Spirin D. V. , Klevets Ph. N.
Published: April 2003

The influence of magnetoelastic coupling on the existence region of a spatially inhomogeneous state in a two-dimensional anisotropic ferromagnet is investigated. The phase transitions to the spatially inhomogeneous state under the influence of magnetic field and upon a change in the single-ion anisotropy constant are examined. It is shown that the magnetoelastic coupling enlarges the existence region of this phase substantially and also increases the domain width.
Self-consistent, two-dimensional, magnetohydrodynamic simulations of magnetically driven flyer plates
Authors: Lemke R. W. , Knudson M. D. , Robinson A. C. , Haill T. A. , Struve K. W. , Asay J. R. , Mehlhorn T. A.
Published: April 2003

The intense magnetic field generated by the 20 megaampere Z machine [R. B. Spielman et al., Phys. Plasmas 5, 2105 (1998)] at Sandia National Laboratories is being used as a pressure source for material science studies. An application we have studied in great detail involves using the intense magnetic field to accelerate flyer plates (small metal disks) to very high velocities (>20 km/s) for use in shock loading experiments. We have used two-dimensional (2D) magnetohydrodynamic (MHD) simulation to investigate the physics of accelerating flyer plates using multi-megabar magnetic drive pressures. A typical shock physics load is comprised of conducting electrodes that are highly compressible at multi-megabar pressures. Electrode deformation that occurs during the rise time of the current pulse causes significant inductance increase, which reduces the peak current (drive pressure) relative to a static geometry. This important dynamic effect is modeled self-consistently by driving the MHD simulation with an accurate circuit model of Z. Self-consistent, 2D, MHD simulations are able to produce and predict time resolved velocity interferometry measurements when the drive circuit includes models of current losses and short circuiting in Z. Simulation results elucidate the phenomena contributing to the flyer velocity history, and show that electrical and hydrodynamic optimization of the load are necessary to minimize effects of time varying inductance. Details of the modeling, the physics, and comparisons with experiment are presented.
Why current-carrying magnetic flux tubes gobble up plasma and become thin as a result
Authors: Bellan P. M.
Published: April 2003

Suppose an electric current I flows along a magnetic flux tube that has poloidal flux ψ and radius a=a(z), where z is the axial position along the flux tube. This current creates a toroidal magnetic field Bφ. It is shown that, in such a case, nonlinear, nonconservative J×B forces accelerate plasma axially from regions of small a to regions of large a and that this acceleration is proportional to ∂I2/∂z. Thus, if a current-carrying flux tube is bulged at, say, z=0 and constricted at, say, z=±h, then plasma will be accelerated from z=±h towards z=0 resulting in a situation similar to two water jets pointed at each other. The ingested plasma convects embedded, frozen-in toroidal magnetic flux from z=±h to z=0. The counterdirected flows collide and stagnate at z=0 and in so doing (i) convert their translational kinetic energy into heat, (ii) increase the plasma density at z≈0, and (iii) increase the embedded toroidal flux density at z≈0. The increase in toroidal flux density at z≈0 increases Bφ and hence increases the magnetic pinch force at z≈0 and so causes a reduction of a(0). Thus, the flux tube develops an axially uniform cross section, a decreased volume, an increased density, and an increased temperature. This model is proposed as a likely hypothesis for the long-standing mystery of why solar coronal loops are observed to be axially uniform, hot, and bright. It is furthermore argued that a small number of tail particles bouncing between the approaching counterstreaming plasma jets should be Fermi accelerated to extreme energies. Finally, analytic solution of the Grad–Shafranov equation predicts that a flux tube becomes axially uniform when the ingested plasma becomes hot and dense enough to have 2μ0nκT/Bpol2=(μ0Ia(0)/ψ)2/2; observed coronal loop parameters are in reasonable agreement with this relationship which is analogous to having βpol=1 in a tokamak.
Laser plasma interactions with intensities from 1012–1021 W/cm2
Authors: Kruer William L.
Published: April 2003

A tutorial introduction is given to some important physics and current challenges in laser plasma interactions. The topics are chosen to illustrate a few of John Dawson’s many pioneering contributions to the physics and modeling of plasmas. In each case, a current frontier is also briefly discussed, including the 0.53 μm option for laser fusion, kinetic inflation of instability levels, and new regimes accessed with ultra-high-power lasers.
Progress in understanding turbulent mixing induced by Rayleigh–Taylor and Richtmyer–Meshkov instabilities
Authors: Zhou Ye , Remington B. A. , Robey H. F. , Cook A. W. , Glendinning S. G. , Dimits A. , Buckingham A. C. , Zimmerman G. B. , Burke E. W. , Peyser T. A. , Cabot W. , Eliason D.
Published: April 2003

Turbulent hydrodynamic mixing induced by the Rayleigh–Taylor (RT) and Richtmyer–Meshkov (RM) instabilities occurs in settings as varied as exploding stars (supernovae), inertial confinement fusion (ICF) capsule implosions, and macroscopic flows in fluid dynamics facilities such as shock tubes. Turbulence theory and modeling have been applied to RT and RM induced flows and developed into a quantitative description of turbulence from the onset to the asymptotic end-state. The treatment, based on a combined approach of theory, direct numerical simulation (DNS), and experimental data analysis, has broad generality. Three areas of progress will be reported. First, a robust, easy to apply criteria will be reported for the mixing transition in a time-dependent flow. This allows an assessment of whether flows, be they from supernova explosions or ICF experiments, should be mixed down to the molecular scale or not. Second, through DNS, the structure, scaling, and spectral evolution of the RT instability induced flow will be inspected. Finally, using these new physical insights, a two-scale, dynamic mix model has been developed that can be applied to simulations of ICF experiments and astrophysics situations alike.
Periodic driving of plasma turbulence
Authors: Baptista M. S. , Caldas I. L. , Heller M. V. A. P. , Ferreira A. A.
Published: April 2003

Tools to characterize three important characteristics of turbulence are proposed: Structures-within-structures, intermittent amplitude bursting, and turbulence complexity. These tools are applied to show that the injection of a rf wave into the plasma confined on the Tokamak Chauffage Alfvén Bresilién (TCABR) [R. M. O. Galvao, V. Bellintani, Jr., R. D. Bengtson et al., Plasma Phys. Controlled Fusion 43, A299 (2001)] decreases plasma edge turbulence, although not completely destroy it, by destroying the only two types of time structures found in the data. Both structures present multiscaling spectra, with infinitely many possible scalings. So, according to this analysis, complexity of this turbulence is mainly due to the multiscaling character of the oscillations.
Self-modulated wakefield and forced laser wakefield acceleration of electrons
Authors: Najmudin Z. , Krushelnick K. , Clark E. L. , Mangles S. P. D. , Walton B. , Dangor A. E. , Fritzler S. , Malka V. , Lefebvre E. , Gordon D. , Tsung F. S. , Joshi C.
Published: April 2003

The interaction of intense laser pulses (power>30 TW) with underdense plasmas has been studied. In the regime where the pulse length is much longer than the plasma period (τl≫2πωp−1), the laser pulse is found to be self-modulated at the plasma frequency by the forward Raman scattering instability. Wavebreaking of the resulting plasma wave results in energetic electrons being accelerated to more than 100 MeV. Reducing the pulse length so that τl∼2πωp−1, but retaining the same power, also leads to wavebreaking. This is a direct result of a combination of laser beam self-focusing, front-edge laser pulse steepening and relativistic lengthening of the plasma wave wavelength, which can result in a forced growth of the wakefield plasma wave, even for initially nonresonant laser pulses (τl≠πωp−1). Since, in this forced laser wakefield regime, the interaction of the plasma wave and the bunch of accelerated electrons with the laser pulse is reduced, this can result in higher energy gain (to beyond 200 MeV) and better beam quality.
Nonthermal effects on occurrence scattering time in generalized Lorentzian distribution plasmas
Authors: Jung Young-Dae
Published: April 2003

Nonthermal effects on the occurrence time advance for the elastic electron–ion collisions in generalized Lorentzian (kappa) distribution plasmas are investigated using the first-order eikonal analysis. The electron–ion interaction potential in the Lorentzian plasmas is obtained by the introduction of the plasma dielectric function (εκ). The semiclassical straight-line trajectory method is applied to the path of the projectile electron in order to obtain the eikonal phase and the scattering amplitude as functions of the impact parameter, Debye length, and spectral index (κ), and collision energy. The occurrence time advance is found to be increased with the increasing scattering angle. It is found that the occurrence time advance has the maximum value for the case of the thermal Maxwellian distribution plasmas. It is also found that the occurrence time advance decreases with the decreasing spectral index, i.e., increasing the nonthermal character of the plasma.
Saddles and dynamics in a solvable mean-field model
Authors: Angelani L. , Ruocco G. , Zamponi F.
Published: April 2003

We use the saddle-approach, recently introduced in the numerical investigation of simple model liquids, in the analysis of a mean-field solvable system. The investigated system is the k-trigonometric model, a k-body interaction mean field system, that generalizes the trigonometric model introduced by Madan and Keyes [J. Chem. Phys. 98, 3342 (1993)] and that has been recently introduced to investigate the relationship between thermodynamics and topology of the configuration space. We find a close relationship between the properties of saddles (stationary points of the potential energy surface) visited by the system and the dynamics. In particular the temperature dependence of saddle order follows that of the diffusivity, both having an Arrhenius behavior at low temperature and a similar shape in the whole temperature range. Our results confirm the general usefulness of the saddle-approach in the interpretation of dynamical processes taking place in interacting systems.
Global-gyrokinetic study of finite β effects on linear microinstabilities
Authors: Falchetto G. L. , Vaclavik J. , Villard L.
Published: April 2003

Electromagnetic microinstabilities in tokamak plasmas are studied by means of a linear global eigenvalue numerical code. Ion dynamics is described by the gyrokinetic equation, so that finite ion Larmor radius effects are taken into account to all orders. Nonadiabatic electrons are included in the model, with passing particles described by the drift-kinetic equation and trapped particles through the bounce averaged drift-kinetic equation. A large aspect ratio plasma with circular shifted surfaces is considered for the numerical implementation. The effects of an electromagnetic perturbation on toroidal ion temperature gradient driven modes are studied, confirming the stabilization of these modes with increasing β (parameter identifying the ratio of the plasma pressure to the magnetic pressure). The threshold for the destabilization of an electromagnetic mode, the so-called kinetic ballooning mode or Alfvénic ion temperature gradient mode is identified. Moreover, owing to the global formulation, the radial structure of these electromagnetic modes is observed for the first time. Finally, the contributions of trapped electron dynamics and the effects of the Shafranov shift are addressed.
Blending of plasma and neutral gas in the Sun, the heliosphere, and the interstellar medium
Authors: Spangler Steven R.
Published: April 2003

This paper summarizes a minisymposium devoted to the physics of partially ionized plasmas in astrophysics. The theme of the minisymposium is that the presence of neutrals in a plasma can be more than just a detail, but can introduce new and significant internal dynamics. The symposium considered partial ionization effects in the solar atmosphere, the solar wind, the region of interaction between the solar wind and the interstellar medium, and the interstellar medium itself. Papers in the symposium dealt with theory, astronomical observations, and laboratory measurements.
Anisotropic fluid turbulence in the interstellar medium and solar wind
Authors: Ng C. S. , Bhattacharjee A. , Germaschewski K. , Galtier S.
Published: April 2003

The interstellar medium and solar wind is permeated by a magnetic field that renders magnetohydrodynamic turbulence anisotropic. In the classic work of Iroshnikov [Astron. Zh. 40, 742 (1963)] and Kraichnan [Phys. Fluids 8, 1385 (1965)], it is assumed that the turbulence is isotropic, and an inertial range energy spectrum that scales as k−3/2 is deduced based on the nonlinear interaction of Alfvén wave packets. Much insight can be gained by analysis and high-resolution numerical simulations of such interactions. In the weak-turbulence limit in which three-wave interactions dominate, analytical and high-resolution numerical results based on random scattering of shear-Alfvén waves propagating parallel to a large-scale magnetic field demonstrate an anisotropic energy spectrum that scales as k⊥−2. Even in the absence of a background magnetic field, when the energy spectrum is globally isotropic, anisotropy is found to develop with respect to the local magnetic field. The two-dimensional case is studied by means of simulations and phenomenological arguments. Despite the presence of local anisotropy, we obtain the Iroshnikov–Kraichnan spectrum, rather than the Kolmogorov spectrum. The same techniques are used to study turbulence in electron magnetohydrodynamics where whistler waves mediate the energy cascade, and comparisons are made with turbulence in magnetohydrodynamics.
Tuning of the blue emission from europium-doped alkaline earth chloroborate thin films activated in air
Authors: Hao Jianhua , Gao J. , Cocivera Michael
Published: April 2003

Thin films of M2B5O9Cl:Eu (M=Ca, Sr, Ba) were prepared on glass substrates using spray pyrolysis. Blue cathodoluminescence due to the abnormal reduction of Eu3+→Eu2+ was obtained by annealing films in air. The cation of the host lattice was found to affect the effectiveness of the reduction process, which could result in influencing the emission band. By selecting types and composition of alkaline cation, it was possible to tune the dominant emitting wavelength between 435 to 465 nm. Activation of the films occurred at temperatures suitable for the use of glass substrates.
p-type conductivity in wide-band-gap BaCuQF (Q=S,Se)
Authors: Yanagi Hiroshi , Tate Janet , Park Sangmoon , Park Cheol-Hee , Keszler Douglas A.
Published: April 2003

BaCuQF (Q=S,Se) materials, candidate transparent p-type conductors, were prepared by solid-state reaction, and their bulk electrical and optical properties were evaluated. The room-temperature Seebeck coefficient and electrical conductivity of undoped BaCuQF pellets were +56 μV/K and 0.088 S/cm, respectively, for the sulfide fluoride, and +32 μV/K and 0.061 S/cm, respectively, for the selenide fluoride. The conductivity was greatly enhanced by the substitution of several percent of K for Ba; the highest conductivities were 82 S/cm for Ba0.9K0.1CuSF and 43 S/cm for Ba0.9K0.1SeF. The band gaps for Q=S and Q=Se were measured to be 3.2 and 3.0 eV, respectively. Undoped BaCuSF exhibits strong red luminescence near 630 nm under ultraviolet excitation.
Role of histidine interruption in mitigating the pathological effects of long polyglutamine stretches in SCA1: A molecular approach
Authors: Sen Somdutta , Dash Debasis , Pasha Santosh , Brahmachari Samir K.
Published: April 2003

Polyglutamine expansions, leading to aggregation, have been implicated in various neurodegenerative disorders. The range of repeats observed in normal individuals in most of these diseases is 19–36, whereas mutant proteins carry 40–81 repeats. In one such disorder, spinocerebellar ataxia (SCA1), it has been reported that certain individuals with expanded polyglutamine repeats in the disease range (Q12HQHQ12HQHQ14/15) but with histidine interruptions were found to be phenotypically normal. To establish the role of histidine, a comparative study of conformational properties of model peptide sequences with (Q12HQHQ12HQHQ12) and without (Q42) interruptions is presented here. Q12HQHQ12HQHQ12 displays greater solubility and lesser aggregation propensity compared to uninterrupted Q42 as well as much shorter Q22. The solvent and temperature‐driven conformational transitions (β structure ↔ random coil → α helix) displayed by these model polyQ stretches is also discussed in the present report. The study strengthens our earlier hypothesis of the importance of histidine interruptions in mitigating the pathogenicity of expanded polyglutamine tract at the SCA1 locus. The relatively lower propensity for aggregation observed in case of histidine interrupted stretches even in the disease range suggests that at a very low concentration, the protein aggregation in normal cells, is possibly not initiated at all or the disease onset is significantly delayed. Our present study also reveals that besides histidine interruption, proline interruption in polyglutamine stretches can lower their aggregation propensity.
Synthesis and Structure of New Macrocyclic Bisindolylmaleimides
Authors: Mandl Christian , Zabel Manfred , König Burkhard
Published: April 2003

We report synthesis and structure of three new macrocyclic bisindolylmaleimides. The UV spectra of the xylene-bridged compounds4and6show significant differences. A dependence of the absorption properties on the maleimide-indole torsion angles is likely. A first attempt to use induced changes in ring conformation of the more flexible macrocyclic crown ether derivative8to signal the presence of metal cations failed.
Synthesis of Optically Active N6-Alkyl Derivatives of (R)-3-(Adenin-9-yl)-2-hydroxypropanoic Acid and Related Compounds
Authors: Krečmerová Marcela , Buděšínský Miloš , Masojídková Milena , Holý Antonín
Published: April 2003

Reaction of ethyl (R)-oxiranecarboxylate (2a) with various nucleobases (adenine, 6-chloropurine, thymine, cytosine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one and 4-methoxypyrimidin-2(1H)-one) afforded ethyl 3-substituted-2-hydroxypropanoates 4-10. Enantioselectivity of this reaction is dependent on the type of the base: 6-chloropurine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one, thymine and cytosine gave optically pure R enantiomers. In other cases, partial or complete racemization occurred. Optically pure ethyl (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoate (5a) was hydrolyzed to give (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoic acid (11). Reactions of 11 with various primary or secondary amines led to N6-substituted (R)-3-(adenin-9-yl)-2-hydroxypropanoic acids 14-19. Enantiomeric purity was determined from 1H NMR spectra measured in the presence of (-)-(R)-1-(9-anthryl)-2,2,2-trifluoroethan-1-ol.
Novel 6-Azapteridines from Bifunctional 1,2,4-Triazines
Authors: Wamhoff Heinrich , Tzanova Milena
Published: April 2003

The convergent synthesis of ethyl 5-chloro- and 5-amino-3-aryl-1,2,4-triazinecarboxylates 9a-9d and 10a-10d as well as of 5-amino-3-aryl-1,2,4-triazine-6-carboxamides 11a-11d is described. Compounds 9, 10 and 11 are powerful key compounds for cyclization reactions to the novel pyrimido[4,5-e][1,2,4]triazines 13d, 14c, 14d, 15c and 17a, 17d.
HOW PENGUINS STARTED TO FLY
Authors: VAINSHTEIN ARKADY
Published: April 2003

A mechanism explaining a strong enhancement of nonleptonic weak decays was suggested in 1975, later to be dubbed the penguin. This mechanism extends Wilson's ideas about the operator product expansion at short distances and reveals an intricate interplay of subtle features of the theory such as heavy quark masses in Glashow–Iliopoulos–Maini cancellation, light quarks shaping the chiral properties of QCD, etc. The penguins have subsequently evolved to play a role in a variety of fields in present-day particle phenomenology. I will describe the history of this idea and review its subsequent development. The recent measurement of direct CP violation in K decays gives a new confirmation of the penguin mechanism.
NUMERICAL INSTABILITIES IN BUBBLE TRACKING IN TWO-PHASE FLOW SIMULATIONS
Authors: LAÍN S. , GÖZ M. F.
Published: April 2003

One way to model and simulate the dispersed phase in a two-phase flow is to track the discrete elements through a fluctuating fluid field by solving their equations of motion. It is shown that widely used and physically motivated discretization methods for the particle equation may lead to artificial instabilities yielding spurious oscillations and chaotic behavior via period-doubling bifurcations. This effect depends strongly on the form of the drag force exerted by the fluid on a discrete element, and is particularly pronounced in the case of bubbly flows.
GENERALIZED SYNCHRONIZATION, FREQUENCY-LOCKING AND PHASE-LOCKING OF COUPLED SINE CIRCLE MAPS
Authors: QIN WEN-XIN
Published: April 2003

Applying invariant manifold theorem, we study the existence of generalized synchronization of a coupled system, with local systems being different sine circle maps. We specify a range of parameters for which the coupled system achieves generalized synchronization. We also investigate the relation between generalized synchronization, predictability and equivalence of dynamical systems. If the parameters are restricted in the specified range, then all the subsystems are topologically equivalent, and each subsystem is predictable from any other subsystem. Moreover, these subsystems are frequency locked even if the frequencies are greatly different in the absence of coupling. If the local systems are identical without coupling, then the widths of the phase-locked intervals of the coupled system are the same as those of the individual map and are independent of the coupling strength.
ON THE FRACTAL NATURE OF ECOLOGICAL AND MACROEVOLUTIONARY DYNAMICS
Authors: SOLÉ RICARD V. , ALONSO DAVID , BASCOMPTE JORDI , MANRUBIA SUSANNA C.
Published: April 2003

In recent studies, a new class of models dealing with evolutionary processes on the large timescale have shown that many of the general traits of the fossil record can be reproduced under some simple assumptions. Additionally, the study of living ecosystems and their network organization, as well as the time series analysis of population fluctuations, points in the direction that complex ecosystems are organized close to instability points where extinction of species and ecological turnover would be the rule. In this paper, we further explore these ideas and their implications for our understanding of evolution as a complex dynamical process with some universal features linked with network-level properties. In particular, a source for the decoupling between micro- and macroevolutionary mechanisms is provided.
Parietal Lobe Contribution to Mental Rotation Demonstrated with rTMS
Authors: Harris Irina M. , Miniussi Carlo
Published: April 2003

A large number of imaging studies have identified a role for the posterior parietal lobe, in particular Brodmann's area 7 and the intraparietal sulcus (IPS), in mental rotation. Here we investigated whether neural activity in the posterior parietal lobe is essential for successful mental rotation performance by observing the effects of interrupting this activity during the execution of a mental rotation task. Repetitive transcranial magnetic stimulation (rTMS) was applied to posterior parietal locations estimated to overlie Brodmann's area 7 in the right and the left hemisphere, or to a posterior midline location (sham condition). In three separate experiments, rTMS (four pulses, 20 Hz) was delivered at these locations either 200–400, 400–600, or 600–800 msec after the onset of a mental rotation trial. Disrupting neural activity in the right parietal lobe interfered with task performance, but only when rTMS was delivered 400 to 600 msec after stimulus onset. Stimulation of the left parietal lobe did not reliably affect mental rotation performance at any of the time points investigated. The time-limited effect of rTMS was replicated in a fourth experiment that directly compared the effects of rTMS applied to the right parietal lobe either 200–400 or 400–600 msec into the mental rotation trial. The results indicate that the right superior posterior parietal lobe plays an essential role in mental rotation, consistent with its involvement in a variety of visuospatial and visuomotor transformations.
The Pleasure of Believing: Toward a naturalistic explanation of religious conversions
Authors: Clément Fabrice
Published: April 2003

From a cognitive point of view, the adhesion to religious beliefs, especially those involving adult subjects, are quite mysterious. Religious representations entail paradoxical claims that should imply skepticism or cautious doubts in any rational mind. Nevertheless, it is not rare that they prompt an act of total commitment from the converts. The aim of this paper is to propose a naturalist explanation of the conversion phenomenon. The argument relies on the postulated existence of an emotional signal selected by evolution to motivate the child to look for the underlying structure of the world by providing a strong positive feeling when a solution is found. By the use of different examples of historical conversions, the author shows how this emotional mechanism can be triggered in the presence of religious representations, causing in the subjects the feeling that they have discovered a good solution to problems they were confronted with.
Simulations of the glaciation of a frontal mixed‐phase cloud with the Explicit Microphysics Model
Authors: Phillips V. T. J. , Choularton T. W. , Illingworth A. J. , Hogan R. J. , Field P. R.
Published: April 2003

Simulations with the Explicit Microphysics Model (EMM) of a case of lightly precipitating, glaciated stratiform cloud are presented. This frontal cloud was observed by the UK Met Office C‐130 aircraft and the dual‐polarization radar at Chilbolton in southern England.

The Hallett–Mossop (H‐M) process was found to cause extremely high number concentrations of crystal columns of up to almost 1000 l−1 in the H‐M region (−3 to −8°C) of the updraught in the EMM control simulation. Similarly high number concentrations of ice particles were seen in, and in the vicinity of, ascending thermals in the aircraft observations. Such concentrations are orders of magnitude higher than the ice nucleus (IN) concentration. Moreover, the dendritic growth of highly planar particles of primary ice produces a peak in differential reflectivity of almost 4 dB just below the cloud top (−15°C). Primary ice particles are generally larger than H‐M splinters and mostly determine the simulated radar properties of the model cloud.

Tests with the EMM revealed significant sensitivities of the average ice number concentration, the cloud‐ and ice‐water paths, and the surface precipitation rate, to atmospheric concentrations of IN and cloud condensation nuclei for this frontal‐cloud case. The layer of supercooled cloud‐water located just below cloud top in the control is depleted by evaporation when the IN concentration is augmented. © Royal Meteorological Society, 2003. P. R. Field's contribution is Crown copyright
Solar radiative biases in deep convective regimes: Possible implications for dynamical feedback
Authors: Tompkins A. M. , Di Giuseppe F.
Published: April 2003

There is increasing evidence that interactions between radiation and convectively determined water vapour and cloud fields can have a significant dynamical impact on the tropical circulation. However, the use of a one‐dimensional (1D) independent column method for the calculation of solar fluxes in cloud‐resolving or mesoscale models could possibly misrepresent this feedback. This is investigated by calculating 1D and full three‐dimensional (3D) solar fluxes through a 3D field of deep convective clouds generated using a high‐resolution cloud‐resolving model, and diagnosing the clear‐sky subsidence velocities required to balance this if a state of radiative convective equilibrium were to exist. The mean clear‐sky solar radiative heating rate is found to change by up to 15%. At low sun angles the shading of the clear‐sky regions implies a reduction of net clear‐sky heating rates. In contrast, at higher solar elevations the scattering effect dominates shading and the clear‐sky heating rates are enhanced, implying an enhancement of the diurnal cycle. However, since the 1D/3D heating‐rate differences in the clear sky increase smoothly from zero at the tropopause to their maximum value near the surface, the vertical gradient and thus the impact on the vertical profile of entrainment and detrainment into the convective regions is negligibly small. This implies that the strong radiative dynamical feedbacks so far documented in cloud‐ensemble models cannot be discounted on the grounds of their use of an independent column calculation for the solar radiative transfer. That said, the substantial bias noted in surface downward solar fluxes could result in a substantial impact in convective organization if an interactive land surface were used as a lower boundary condition. Copyright © 2003 Royal Meteorological Society
Background error covariance functions for Doppler radial‐wind analysis
Authors: Xu Qin , Gong Jiandong
Published: April 2003

Under the assumption that the vector field of the background wind error is Gaussian random, homogeneous and isotropic in the horizontal, a two‐dimensional form of error covariance function is derived for the radial component of the background wind projected onto the direction of radar beam at a low elevation. The derived covariance function is homogeneous but non‐isotropic in the horizontal, and approximately homogeneous on the conical surface of low‐elevation radar scans. This covariance function can be applied directly to statistical interpolation of radar‐observed radial winds on the conical surface, although the true optimality of the analysis depends on the underlying assumption. It can also be used as an influence function for the radial‐wind analysis with zero background. The structure of this covariance function is interpreted in terms of the influence of a single point observation on the radial‐wind analysis. The utility and merits of this covariance function are demonstrated by numerical experiments. Copyright © 2003 Royal Meteorological Society
Severe Hypocalcemia With Denosumab Among Older Female Dialysis-Dependent Patients
Authors: Bird Steven T. , Smith Elizabeth R. , Gelperin Kate , Jung Tae Hyun , Thompson Aliza , Kambhampati Rekha , Lyu Hai , Zhao Henu , Zhao Yueqin , Zhu Yunfan , Easley Olivia , Niak Ali , Wernecke Michael , Chillarige Yoganand , Zemskova Marina , Kelman Jeffrey A. , Graham David J.
Published: January 2024

Importance

Dialysis-dependent patients experience high rates of morbidity from fractures, yet little evidence is available on optimal treatment strategies. Chronic kidney disease–mineral and bone disorder is nearly universal in dialysis-dependent patients, complicating diagnosis and treatment of skeletal fragility.

Objective

To examine the incidence and comparative risk of severe hypocalcemia with denosumab compared with oral bisphosphonates among dialysis-dependent patients treated for osteoporosis.

Design, Setting, and Participants

Retrospective cohort study of female dialysis-dependent Medicare patients aged 65 years or older who initiated treatment with denosumab or oral bisphosphonates from 2013 to 2020. Clinical performance measures including monthly serum calcium were obtained through linkage to the Consolidated Renal Operations in a Web-Enabled Network database.

Exposures

Denosumab, 60 mg, or oral bisphosphonates.

Main Outcomes and Measures

Severe hypocalcemia was defined as total albumin-corrected serum calcium below 7.5 mg/dL (1.88 mmol/L) or a primary hospital or emergency department hypocalcemia diagnosis (emergent care). Very severe hypocalcemia (serum calcium below 6.5 mg/dL [1.63 mmol/L] or emergent care) was also assessed. Inverse probability of treatment-weighted cumulative incidence, weighted risk differences, and weighted risk ratios were calculated during the first 12 treatment weeks.

Results

In the unweighted cohorts, 607 of 1523 denosumab-treated patients and 23 of 1281 oral bisphosphonate–treated patients developed severe hypocalcemia. The 12-week weighted cumulative incidence of severe hypocalcemia was 41.1% with denosumab vs 2.0% with oral bisphosphonates (weighted risk difference, 39.1% [95% CI, 36.3%-41.9%]; weighted risk ratio, 20.7 [95% CI, 13.2-41.2]). The 12-week weighted cumulative incidence of very severe hypocalcemia was also increased with denosumab (10.9%) vs oral bisphosphonates (0.4%) (weighted risk difference, 10.5% [95% CI, 8.8%-12.0%]; weighted risk ratio, 26.4 [95% CI, 9.7-449.5]).

Conclusions and Relevance

Denosumab was associated with a markedly higher incidence of severe and very severe hypocalcemia in female dialysis-dependent patients aged 65 years or older compared with oral bisphosphonates. Given the complexity of diagnosing the underlying bone pathophysiology in dialysis-dependent patients, the high risk posed by denosumab in this population, and the complex strategies required to monitor and treat severe hypocalcemia, denosumab should be administered after careful patient selection and with plans for frequent monitoring.
AI’s Threat to the Medical Profession
Authors: Fogo Agnes B. , Kronbichler Andreas , Bajema Ingeborg M.
Published: January 2024

This Viewpoint discusses the potential drawbacks of the use of artificial intelligence (AI) in medicine, for example, the loss of certain skills due to the reliance on AI, and how physicians should consider how to take advantage of the potential benefits of AI without losing control over their profession.