bluuebunny/crossref_metadata_2025 huggingface dataset:
Capsaicin activation of glutamatergic synaptic transmission in the rat locus coeruleus In vitro
Authors: Marinelli Silvia , Vaughan Christopher W. , Christie MacDonald J. , Connor Mark
Published: August 2002

The vanilloid receptor protein (VR1) is a well‐characterised integrator of noxious stimuli in peripheral sensory neurones. There is evidence for the presence of VR1 in the central nervous system, but little information as to its role there. In this study we have examined the actions of agonists for VR1 receptors in the rat locus coeruleus (LC), using whole‐cell patch‐clamp recordings from acutely isolated neurones and neurones in slices. Superfusion with capsaicin resulted in a concentration‐dependent increase in the frequency of isolated miniature excitatory postsynaptic currents (mEPSCs) in LC neurones. The mean amplitude of the mEPSCs was not affected by capsaicin. The effects of capsaicin (1 μM) were abolished by the VR1 receptor antagonists capsazepine (10 μM) and iodoresiniferatoxin (300 nm). Removal of extracellular Ca2+ abolished the capsaicin‐induced increase in frequency of mEPSCs. Capsaicin superfusion had no consistent effects on evoked excitatory postsynaptic currents. Capsaicin superfusion also resulted in the release of an adrenoceptor agonist in the LC but did not affect the membrane currents of acutely isolated LC neurones. These data demonstrate that the VR1 receptor appears to be located presynaptically on afferents to the LC, and that activation of VR1 may serve to potentiate the release of glutamate and adrenaline/noradrenaline in this brain region.
Sleep‐waking discharge patterns of median preoptic nucleus neurons in rats
Authors: Suntsova Natalia , Szymusiak Ronald , Md. Alam Noor , Guzman‐Marin Ruben , McGinty Dennis
Published: August 2002

Several lines of evidence show that the preoptic area (POA) of the hypothalamus is critically implicated in the regulation of sleep. Functionally heterogeneous cell groups with sleep‐related discharge patterns are located both in the medial and lateral POA. Recently a cluster of neurons showing sleep‐related c‐Fos immunoreactivity was found in the median preoptic nucleus (MnPN). To determine the specificity of the state‐related behaviour of MnPN neurons we have undertaken the first study of their discharge patterns across the sleep‐waking cycle. Nearly 76% of recorded cells exhibited elevated discharge rates during sleep. Sleep‐related units showed several distinct types of activity changes across sleep stages. Two populations included cells displaying selective activation during either non‐rapid eye movement (NREM) sleep (10%) or REM sleep (8%). Neurons belonging to the predominant population (58%) exhibited activation during both phases of sleep compared to wakefulness. Most of these cells showed a gradual increase in their firing rates prior to sleep onset, elevated discharge during NREM sleep and a further increase during REM sleep. This specific sleep‐waking discharge profile is opposite to that demonstrated by wake‐promoting monoaminergic cell groups and was previously found in cells localized in the ventrolateral preoptic area (vlPOA). We hypothesize that these vlPOA and MnPN neuronal populations act as parts of a GABAergic/galaninergic sleep‐promoting (‘anti‐waking’) network which exercises inhibitory control over waking‐promoting systems. MnPN neurons that progressively increase activity during sustained waking and decrease activity during sustained sleep states may be involved in homeostatic regulation of sleep.
Discrete store‐operated calcium influx into an intracellular compartment in rabbit arteriolar smooth muscle
Authors: Flemming R. , Cheong A. , Dedman A. M. , Beech D. J.
Published: August 2002

This study tested the hypothesis that store‐operated channels (SOCs) exist as a discrete population of Ca2+ channels activated by depletion of intracellular Ca2+ stores in cerebral arteriolar smooth muscle cells and explored their direct contractile function. Using the Ca2+ indicator fura‐PE3 it was observed that depletion of sarcoplasmic reticulum (SR) Ca2+ by inhibition of SR Ca2+‐ATPase (SERCA) led to sustained elevation of [Ca2+]i that depended on extracellular Ca2+ and slightly enhanced Mn2+ entry. Enhanced background Ca2+ influx did not explain the raised [Ca2+]i in response to SERCA inhibitors because it had marked gadolinium (Gd3+) sensitivity, which background pathways did not. Effects were not secondary to changes in membrane potential. Thus SR Ca2+ depletion activated SOCs. Strikingly, SOC‐mediated Ca2+ influx did not evoke constriction of the arterioles, which were in a resting state. This was despite the fura‐PE3‐indicated [Ca2+]i rise being greater than that evoked by 20 mm[K+]o (which did cause constriction). Release of endothelial vasodilators did not explain the absence of SOC‐mediated constriction, nor did a change in Ca2+ sensitivity of the contractile proteins. We suggest SOCs are a discrete subset of Ca2+ channels allowing Ca2+ influx into a ‘non‐contractile’ compartment in cerebral arteriolar smooth muscle cells.
Ca2+ current‐gated focal and local ca2+ release in rat atrial myocytes: evidence from rapid 2‐d confocal imaging
Authors: Woo Sun‐Hee , Cleemann Lars , Morad Martin
Published: August 2002

In atrial myocytes immunocytochemistry has shown two groups of ryanodine receptors (RyRs): those at the periphery colocalized with dihydropyridine receptors (DHPRs) and those at the cell interior not associated with DHPRs. The extent to which the two sets of RyRs are controlled by Ca2+ current (ICa) or Ca2+ diffusion remains to be determined. Here, using rapid (240 Hz) two‐dimensional confocal Ca2+ imaging in rat atrial myocytes, we examine directly the role of ICa on the two‐dimensional patterns of local and focal Ca2+ releases. ICa evoked peripheral Ca2+ release within 1–4 ms, causing a rapid monophasic local rise of Ca2+, which then propagated into the cell interior along sarcomeric lines (∼2 μm) with a velocity of ∼230 μm s−1, even though we found no evidence for organized t‐tubules using di‐8‐ANEPPS staining. ICa‐triggered Ca2+ release in the cell centre, on the other hand, had both a rapid (≤12 ms) and slower delayed components (12–50 ms). The voltage dependence of peripheral Ca2+ release and the two components of central release was bell shaped, and the magnitude of each release component was linearly related to ICa. Premature termination (2–10 ms) of ICa was equally effective in abbreviating both the peripheral and slow central Ca2+ release. High concentration of Ca2+ buffers (2–5 mm EGTA plus 1 mm fluo‐3) completely abolished the ICa‐gated propagation wave and the slow delayed component of Ca2+ release, but had little or no effect on the rapid component of central release. The efficacy of ICa to trigger Ca2+ release in periphery of the myocyte was ∼5 times higher than in the centre, consistent with the smaller measured central Ca2+ release. The quantification of central Ca2+ release as a function of peripheral release suggests a cooperative gating mechanism(s) for central release. These findings indicate that both ICa and diffusion of Ca2+ from the peripheral sites contribute to the gating of Ca2+ release from central SR. How in fact the ICa‐dependent fast component of central release is activated remains to be determined.
Cytosolic Ca2+ triggers early afterdepolarizations and torsade de pointes in rabbit hearts with type 2 long QT syndrome
Authors: Choi Bum‐Rak , Burton Francis , Salama Guy
Published: August 2002

The role of intracellular Ca2+ (Ca12+) in triggering early afterdepolarizations (EADs), the origins of EADs and the mechanisms underlying Torsade de Pointes (TdP) were investigated in a model of long QT syndrome (Type 2). Perfused rabbit hearts were stained with RH327 and Rhod‐2/AM to simultaneously map membrane potential (Vm) and Ca12+ with two photodiode arrays. The IKr blocker E4031 (0.5 μM) together with 50% reduction of [K+]o and [Mg2+]o elicited long action potentials (APs), Vm oscillations on AP plateaux (EADs) then ventricular tachycardia (VT). Cryoablation of both ventricular chambers eliminated Purkinje fibres as sources of EADs. E4031 prolonged APs (0.28 to 2.3 s), reversed repolarization sequences (base→apex) and enhanced repolarization gradients (30 to 230 ms, n= 12) indicating a heterogeneous distribution of IKr. At low [K+]o and [Mg2+]o, E4031 elicited spontaneous Ca12+and Vm spikes or EADs (3.5 ± 1.9 Hz) during the AP plateau (n= 6). EADs fired ‘out‐of‐phase’ from several sites, propagated, collided then evolved to TdP. Phase maps (Ca12+vs. Vm) had counterclockwise trajectories shaped like a ‘boomerang’ during an AP and like ellipses during EADs, with Vm preceding Ca12+ by 9.2 ± 1.4 (n= 6) and 7.2 ± 0.6 ms (n= 5/6), respectively. After cryoablation, EADs from surviving epicardium (∼1 mm) fired at the same frequency (3.4 ± 0.35 Hz, n= 6) as controls. At the origins of EADs, Ca12+ preceded Vm and phase maps traced clockwise ellipses. Away from EAD origins, Vm coincided with or preceded Ca12+. In conclusion, overload elicits EADs originating from either ventricular or Purkinje fibres and ‘out‐of‐phase’ EAD activity from multiple sites generates TdP, evident in pseudo‐ECGs.
Inverse calculation of material parameters for a thin-layer system using transient elastic waves
Authors: Ma Chien-Ching , Liu Shaw-Wen , Chang Chen-Ming
Published: September 2002

The inverse calculation of material parameters of a thin-layer system is investigated using transient elastic waves. The inverse problem is formulated as an optimization problem in which the norm of the discrepancies between the calculated and measured normal surface displacements is minimized through the simplex algorithm. The theoretical result is first solved using the Laplace transform and the transient response is then implemented analytically by Cagniard’s method. In the experiment, the source time function is generated by the brittle fracture of a pencil lead on the surface of the thin-layer system, and a National Bureau of Standards (NBS) conical transducer is used to record the surface responses. To obtain reliable inverse results for material parameters, a two-step inverse calculation procedure is proposed. The recovered material parameters of the specimens agree well with the theoretical values and experimental results.
Diffraction correction for precision surface acoustic wave velocity measurements
Authors: Ruiz M. Alberto , Nagy Peter B.
Published: September 2002

Surface wave dispersion measurements can be used to nondestructively characterize shot-peened, laser shock-peened, burnished, and otherwise surface-treated specimens. In recent years, there have been numerous efforts to separate the contribution of surface roughness from those of near-surface material variations, such as residual stress, texture, and increased dislocation density. As the accuracy of the dispersion measurements was gradually increased using state-of-the-art laser-ultrasonic scanning and sophisticated digital signal processing methods, it was recognized that a perceivable dispersive effect, similar to the one found on rough shot-peened specimens, is exhibited by untreated smooth surfaces as well. This dispersion effect is on the order of 0.1%, that is significantly higher than the experimental error associated with the measurements and comparable to the expected velocity change produced by near-surface compressive residual stresses in metals below their yield point. This paper demonstrates that the cause of this apparent dispersion is the diffraction of the surface acoustic wave (SAW) as it travels over the surface of the specimen. The results suggest that a diffraction correction may be introduced to increase the accuracy of surface wave dispersion measurements. A simple diffraction correction model was developed for surface waves and this correction was subsequently validated by laser-interferometric velocity measurements on aluminum specimens.
A speech enhancement scheme incorporating spectral expansion evaluated with simulated loss of frequency selectivity
Authors: Lyzenga J. , Festen J. M. , Houtgast T.
Published: September 2002

Hearing-impaired listeners often suffer from supra-threshold speech perception deficits. One such deficit is reduced frequency selectivity. We applied a speech enhancement scheme that incorporated spectral expansion in an attempt to reduce the effects of this deficit. The speech processing could contain up to three stages, a first in which the peak–valley ratio of the speech spectrum was enlarged to counteract the broadening of the auditory filtering, and a second in which the overall speech spectrum was modified to counteract the effects of upward-spread-of-masking, using a linear filter. The third stage was a noise suppression stage, applied before the spectral enhancement. The effectiveness of the speech processing with and without noise suppression was evaluated for various parameter settings by measuring the speech reception threshold (SRT) in noise, i.e., the signal-to-noise ratio at which listeners repeat 50% of presented sentences correctly. We used normal-hearing subjects. To simulate the loss of frequency selectivity we applied spectral smearing to the stimuli presented to the subjects. The speech material of the SRT tests was mixed with the noise before processing, and, when present, the smearing was applied last. The results indicated that for one specific parameter setting the SRT values decreased (i.e., improved) by approximately 1 dB when incorporating the spectral expansion together with the linear filtering. Employing either of these two stages separately did not improve the SRT. The application of the noise suppression stage did not further improve the SRT. A pilot study using hearing-impaired listeners showed more promising results for a female than for a male speaker.
Guided wave modes in porous cylinders: Experimental results
Authors: Wisse C. J. , Smeulders D. M. J. , van Dongen M. E. H. , Chao G.
Published: September 2002

In this paper guided wave modes in porous media are investigated. A water-saturated porous cylinder is mounted in the test section of a shock tube. Between the porous sample and the wall of the shock tube a water-filled annulus exists. For very small annulus width, bulk waves are generated and one-dimensional modeling is sufficient. Otherwise two-dimensional effects become important and multiple guided wave modes occur. Using a newly developed traversable positioning system in the shock tube, the frequency-dependent phase velocities and damping coefficients in the 1–120 kHz frequency range were measured. Prony’s method was used for data processing. Agreement was found between the experimental data and the two-dimensional modeling of the shock tube which was based on Biot’s theory.
A dimensionless mobility formulation for evaluation of force and moment excitation of structures
Authors: Moorhouse A. T.
Published: September 2002

The problem addressed is the simultaneous excitation of a structure by a force and moment. These two forms of excitation are dimensionally incompatible, and so their relative importance is normally difficult to assess. Here, a dimensionless form of the mobility matrix is developed thereby allowing proper comparison. The off-diagonal elements of the matrix quantify the coupling between two excitations of whatever dimensions, in other words the extent to which an applied force or moment affects the power input by another force or moment. It is shown that off-diagonals of unit magnitude indicate the maximum possible extent of coupling between the corresponding excitations. A precise definition of weak and strong coupling is therefore possible. Illustrative examples of dimensionless mobilities for infinite, semi-infinite, and finite plates are given. It is also shown that the eigenvalues of the dimensionless mobility matrix relate the actual delivered power to the “point-by-point” power input. The results are shown to have wider relevance than originally intended; specifically, the dimensionless mobilities provide a measure of the suitability for active vibration control of different points on a structure, or mixed excitations.
The significance of shape and orientation in single-particle weak-scatterer models
Authors: Coussios Constantin-C.
Published: September 2002

Particles that have a density and compressibility comparable to those of the surrounding medium (weak scatterers) are often modeled as spherical scatterers of equivalent volume. The simplicity and symmetry of the spherical model does not however account for the effect of the angle of incidence of the incident field onto the particle. By performing a comparative study of scattering models for the case of a fluid sphere, it is shown that models derived using the Born approximation closely match the exact solution for weak scatterers. This approximation is therefore applied to produce a model for the fluid disk, which is used to investigate the significance of particle shape and orientation. Scattering by a red blood cell of given volume modeled as a sphere is compared to the result obtained by approximating its shape as a disk of varying aspect ratio and orientation. The spherical model is shown to provide a good description for frequencies up to 20 MHz, beyond which particle shape becomes significant. This effect could go undetected if the scattered field is only observed at 90° relative to the direction of the incident field. Nevertheless, the significance of particle shape and orientation might form the basis of a novel detection technique.
Effects of low pass filtering on the intelligibility of speech in noise for people with and without dead regions at high frequencies
Authors: Baer Thomas , Moore Brian C. J. , Kluk Karolina
Published: September 2002

People with high-frequency sensorineural hearing loss differ in the benefit they gain from amplification of high frequencies when listening to speech. Using vowel–consonant–vowel (VCV) stimuli in quiet that were amplified and then low pass filtered with various cutoff frequencies, Vickers et al. [J. Acoust. Soc. Am. 110, 1164–1175 (2001)] found that the benefit from amplification of high-frequency components was related to the presence or absence of a cochlear dead region at high frequencies. For hearing-impaired subjects without dead regions, performance improved with increasing cutoff frequency up to 7.5 kHz (the highest value tested). Subjects with high-frequency dead regions showed no improvement when the cutoff frequency was increased above about 1.7 times the edge frequency of the dead region. The present study was similar to that of Vickers et al. but used VCV stimuli presented in background noise. Ten subjects with high-frequency hearing loss, including eight from the study of Vickers et al., were tested. Five had dead regions starting below 2 kHz, and five had no dead regions. Speech stimuli at a nominal level of 65 dB were mixed with spectrally matched noise, amplified according to the “Cambridge” prescriptive formula for each subject and then low pass filtered. The noise level was chosen separately for each subject to give a moderate reduction in intelligibility relative to listening in quiet. For subjects without dead regions, performance generally improved with increasing cutoff frequency up to 7.5 kHz, on average more so in noise than in quiet. For most subjects with dead regions, performance improved with cutoff frequency up to 1.5–2 times the edge frequency of the dead region, but hardly changed with further increases. Calculations of speech audibility using a modified version of the articulation index showed that application of the Cambridge formula was at least partially successful in making high-frequency components of the speech audible for subjects with dead regions, and that such subjects often failed to benefit from increased audibility of the speech at high frequencies.
Floquet wave ultrasonic method for determination of single ply moduli in multidirectional composites
Authors: Wang L. , Rokhlin S. I.
Published: September 2002

An inversion method based on Floquet wave velocity in a periodic medium has been introduced to determine the single ply elastic moduli of a multi-ply composite. The stability of this algorithm is demonstrated by numerical simulation. The applicability of the plane wave approximation to the velocity measurement in the double-through-transmission self-reference method has been analyzed using a time-domain beam model. It shows that the finite width of the transmitter affects only the amplitudes of the signals and has almost no effect on the time delay. Using this method, the ply moduli for a multiply composite have been experimentally determined. While the paper focuses on elastic constant reconstruction from phase velocity measurements by the self-reference double-through-transmission method, the reconstruction methodology is also applicable to assessment of data collected by other methods.
Theory of elastic wave propagation in anisotropic film on anisotropic substrate: TiN film on single-crystal Si
Authors: Tewary V. K.
Published: September 2002

The delta-function representation of the elastodynamic Green’s function is used to derive an expression for the elastic wave forms on the surface of an anisotropic thin film on an anisotropic substrate due to a point or a line source located at the surface of the film. The dispersion relation for surface acoustic waves (SAWs) is obtained from the poles of the Green’s function. A computationally efficient algorithm is formulated to obtain the elastic constants and the density of the film from the SAW dispersion data. The theory is used to analyze measured SAW dispersion relations in a titanium nitride film on silicon. The analysis yields values of the elastic constants and the density of the film. Excellent agreement is obtained between the theoretical and experimental dispersion results. Calculated wave forms for the surface wave due to a pulsed line source on the surface of the film are reported.
Perception of synthesized voice quality in connected speech by Cantonese speakers
Authors: Yiu Edwin M-L. , Murdoch Bruce , Hird Kathryn , Lau Polly
Published: September 2002

Perceptual voice analysis is a subjective process. However, despite reports of varying degrees of intrajudge and interjudge reliability, it is widely used in clinical voice evaluation. One of the ways to improve the reliability of this procedure is to provide judges with signals as external standards so that comparison can be made in relation to these “anchor” signals. The present study used a Klatt speech synthesizer to create a set of speech signals with varying degree of three different voice qualities based on a Cantonese sentence. The primary objective of the study was to determine whether different abnormal voice qualities could be synthesized using the “built-in” synthesis parameters using a perceptual study. The second objective was to determine the relationship between acoustic characteristics of the synthesized signals and perceptual judgment. Twenty Cantonese-speaking speech pathologists with at least three years of clinical experience in perceptual voice evaluation were asked to undertake two tasks. The first was to decide whether the voice quality of the synthesized signals was normal or not. The second was to decide whether the abnormal signals should be described as rough, breathy, or vocal fry. The results showed that signals generated with a small degree of aspiration noise were perceived as breathiness while signals with a small degree of flutter or double pulsing were perceived as roughness. When the flutter or double pulsing increased further, tremor and vocal fry, rather than roughness, were perceived. Furthermore, the amount of aspiration noise, flutter, or double pulsing required for male voice stimuli was different from that required for the female voice stimuli with a similar level of perceptual breathiness and roughness. These findings showed that changes in perceived vocal quality could be achieved by systematic modifications of synthesis parameters. This opens up the possibility of using synthesized voice signals as external standards or “anchors” to improve the reliability of clinical perceptual voice evaluation.
Effect of overpressure and pulse repetition frequency on cavitation in shock wave lithotripsy
Authors: Sapozhnikov Oleg A. , Khokhlova Vera A. , Bailey Michael R. , Williams James C. , McAteer James A. , Cleveland Robin O. , Crum Lawrence A.
Published: September 2002

Cavitation appears to contribute to tissue injury in lithotripsy. Reports have shown that increasing pulse repetition frequency [(PRF) 0.5–100 Hz] increases tissue damage and increasing static pressure (1–3 bar) reduces cell damage without decreasing stone comminution. Our hypothesis is that overpressure or slow PRF causes unstabilized bubbles produced by one shock pulse to dissolve before they nucleate cavitation by subsequent shock pulses. The effects of PRF and overpressure on bubble dynamics and lifetimes were studied experimentally with passive cavitation detection, high-speed photography, and B-mode ultrasound and theoretically. Overpressure significantly reduced calculated (100–2 s) and measured (55–0.5 s) bubble lifetimes. At 1.5 bar static pressure, a dense bubble cluster was measured with clinically high PRF (2–3 Hz) and a sparse cluster with clinically low PRF (0.5–1 Hz), indicating bubble lifetimes of 0.5–1 s, consistent with calculations. In contrast to cavitation in water, high-speed photography showed that overpressure did not suppress cavitation of bubbles stabilized on a cracked surface. These results suggest that a judicious use of overpressure and PRF in lithotripsy could reduce cavitation damage of tissue while maintaining cavitation comminution of stones.
Combined feedback–feedforward active noise-reducing headset—The effect of the acoustics on broadband performance
Authors: Rafaely Boaz , Jones Matthew
Published: September 2002

Active noise-reducing headsets that employ analog feedback control and provide good broadband attenuation are commercially available for a wide range of applications. Recent studies have explored the integration of an adaptive digital feedforward controller with the analog feedback controller to provide additional attenuation of periodic noise components. This paper presents an experimental study of such a combined control system, but with both feedback- and feedforward controllers attenuating broadband noise. Good performance is demonstrated in a reverberant sound field, while under direct sound-field conditions the attenuation performance of the feedforward controller is shown to be dependent on head position. The paper concludes with an analysis of the forward path delay showing how the passive attenuation mechanism improves broadband performance.
Diamond Genesis, Seismic Structure, and Evolution of the Kaapvaal-Zimbabwe Craton
Authors: Shirey Steven B. , Harris Jeffrey W. , Richardson Stephen H. , Fouch Matthew J. , James David E. , Cartigny Pierre , Deines Peter , Viljoen Fanus
Published: September 2002

The lithospheric mantle beneath the Kaapvaal-Zimbabwe craton of southern Africa shows variations in seismic P-wave velocity at depths within the diamond stability field that correlate with differences in the composition of diamonds and their syngenetic inclusions. Middle Archean mantle depletion events initiated craton keel formation and early harzburgitic diamond formation. Late Archean accretionary events involving an oceanic lithosphere component stabilized the craton and contributed a younger Archean generation of eclogitic diamonds. Subsequent Proterozoic tectonic and magmatic events altered the composition of the continental lithosphere and added new lherzolitic and eclogitic diamonds to the Archean diamond suite.
Representation of the Quantity of Visual Items in the Primate Prefrontal Cortex
Authors: Nieder Andreas , Freedman David J. , Miller Earl K.
Published: September 2002

Deriving the quantity of items is an abstract form of categorization. To explore it, monkeys were trained to judge whether successive visual displays contained the same quantity of items. Many neurons in the lateral prefrontal cortex were tuned for quantity irrespective of the exact physical appearance of the displays. Their tuning curves formed overlapping filters, which may explain why behavioral discrimination improves with increasing numerical distance and why discrimination of two quantities with equal numerical distance worsens as their numerical size increases. A mechanism that extracts the quantity of visual field items could contribute to general numerical ability.
Structure, Mechanism, and Regulation of the
Neurospora
Plasma Membrane H
+
-ATPase
Authors: Kühlbrandt Werner , Zeelen Johan , Dietrich Jens
Published: September 2002

Proton pumps in the plasma membrane of plants and yeasts maintain the intracellular pH and membrane potential. To gain insight into the molecular mechanisms of proton pumping, we built an atomic homology model of the proton pump based on the 2.6 angstrom x-ray structure of the related Ca
2+
pump from rabbit sarcoplasmic reticulum. The model, when fitted to an 8 angstrom map of the
Neurospora
proton pump determined by electron microscopy, reveals the likely path of the proton through the membrane and shows that the nucleotide-binding domain rotates by ∼70° to deliver adenosine triphosphate (ATP) to the phosphorylation site. A synthetic peptide corresponding to the carboxyl-terminal regulatory domain stimulates ATPase activity, suggesting a mechanism for proton transport regulation.
Mast Cells: A Cellular Link Between Autoantibodies and Inflammatory Arthritis
Authors: Lee David M. , Friend Daniel S. , Gurish Michael F. , Benoist Christophe , Mathis Diane , Brenner Michael B.
Published: September 2002

Previous studies have revealed that autoantibodies, complement components, and Fc receptors each participate in the pathogenesis of erosive arthritis in K/BxN mice. However, it is not known which cellular populations are responsive to these inflammatory signals. We find that two strains of mice deficient in mast cells, W/W
v
and Sl/Sl
d
, were resistant to development of joint inflammation and that susceptibility was restored in the W/W
v
strain by mast cell engraftment. Thus, mast cells may function as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis.
The Role of Sea Spray in Cleansing Air Pollution over Ocean via Cloud Processes
Authors: Rosenfeld Daniel , Lahav Ronen , Khain Alexander , Pinsky Mark
Published: September 2002

Particulate air pollution has been shown to strongly suppress precipitation from convective clouds over land. New observations show that precipitation from similar polluted clouds over oceans is much less affected, because large sea salt nuclei override the precipitation suppression effect of the large number of small pollution nuclei. Raindrops initiated by the sea salt grow by collecting small cloud droplets that form on the pollution particles, thereby cleansing the air. Therefore, sea salt helps cleanse the atmosphere of the air pollution via cloud processes. This implies that over oceans, the climatic aerosol indirect effects are significantly smaller than current estimates.
Nitrogenase MoFe-Protein at 1.16 Å Resolution: A Central Ligand in the FeMo-Cofactor
Authors: Einsle Oliver , Tezcan F. Akif , Andrade Susana L. A. , Schmid Benedikt , Yoshida Mika , Howard James B. , Rees Douglas C.
Published: September 2002

A high-resolution crystallographic analysis of the nitrogenase MoFe-protein reveals a previously unrecognized ligand coordinated to six iron atoms in the center of the catalytically essential FeMo-cofactor. The electron density for this ligand is masked in structures with resolutions lower than 1.55 angstroms, owing to Fourier series termination ripples from the surrounding iron and sulfur atoms in the cofactor. The central atom completes an approximate tetrahedral coordination for the six iron atoms, instead of the trigonal coordination proposed on the basis of lower resolution structures. The crystallographic refinement at 1.16 angstrom resolution is consistent with this newly detected component being a light element, most plausibly nitrogen. The presence of a nitrogen atom in the cofactor would have important implications for the mechanism of dinitrogen reduction by nitrogenase.
Inhibition of Retroviral RNA Production by ZAP, a CCCH-Type Zinc Finger Protein
Authors: Gao Guangxia , Guo Xuemin , Goff Stephen P.
Published: September 2002

Cells have evolved multiple mechanisms to inhibit viral replication. To identify previously unknown antiviral activities, we screened mammalian complementary DNA (cDNA) libraries for genes that prevent infection by a genetically marked retrovirus. Virus-resistant cells were selected from pools of transduced clones, and an active antiviral cDNA was recovered. The gene encodes a CCCH-type zinc finger protein designated ZAP. Expression of the gene caused a profound and specific loss of viral messenger RNAs (mRNAs) from the cytoplasm without affecting the levels of nuclear mRNAs. The finding suggests the existence of a previously unknown machinery for the inhibition of virus replication, targeting a step in viral gene expression.
Down with the Kingdom (Phylum, Class, and Order Too)
Authors: Moore Gerry
Published: September 2002

The Poverty of the Linnaean Hierarchy
A Philosophical Study of Biological Taxonomy. Marc Ereshefsky. Cambridge University Press, Cambridge, 2001. 326 pp. $65, £40. ISBN 0-521-78170-1.

Ereshefsky argues that the Linnaean system hampers our ability to classify the organic world and should be replaced by one more in line with evolutionary theory.
High Carrier Mobility in Single-Crystal Plasma-Deposited Diamond
Authors: Isberg Jan , Hammersberg Johan , Johansson Erik , Wikström Tobias , Twitchen Daniel J. , Whitehead Andrew J. , Coe Steven E. , Scarsbrook Geoffrey A.
Published: September 2002

Room-temperature drift mobilities of 4500 square centimeters per volt second for electrons and 3800 square centimeters per volt second for holes have been measured in high-purity single-crystal diamond grown using a chemical vapor deposition process. The low-field drift mobility values were determined by using the time-of-flight technique on thick, intrinsic, freestanding diamond plates and were verified by current-voltage measurements onp-ijunction diodes. The improvement of the electronic properties of single-crystal diamond and the reproducibility of those properties are encouraging for research on, and development of, high-performance diamond electronics.
New Directions in Neuronal Migration
Authors: Hatten Mary E.
Published: September 2002

Over the past decade, genetic analyses have yielded a more molecular view of neuronal migration and its role in central nervous system development. We now realize that many of the molecular mechanisms that guide migrations in invertebrates are recapitulated in the vertebrate nervous system. These mechanisms guide dorsoventral and anterior-posterior migrations and merge with radial migratory pathways that are prominent in the development of the mammalian cortex. This review discusses the choreography of these different migratory mechanisms within the context of genetic approaches that have defined their molecular mechanisms.
Identification of a DNA Nonhomologous End-Joining Complex in Bacteria
Authors: Weller Geoffrey R. , Kysela Boris , Roy Rajat , Tonkin Louise M. , Scanlan Elizabeth , Della Marina , Devine Susanne Krogh , Day Jonathan P. , Wilkinson Adam , di Fagagna Fabrizio d'Adda , Devine Kevin M. , Bowater Richard P. , Jeggo Penny A. , Jackson Stephen P. , Doherty Aidan J.
Published: September 2002

In eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by the pathway of homologous recombination or by DNA nonhomologous end joining (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution, but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ pathway requires a DNA end-binding component called Ku. We have identified bacterial Ku homologs and show that these proteins retain the biochemical characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation in
Bacillus subtilis
. These data provide evidence that many bacteria possess a DNA DSB repair apparatus that shares many features with the NHEJ system of eukarya and suggest that this DNA repair pathway arose before the prokaryotic and eukaryotic lineages diverged.
Internal Olefins to Linear Amines
Authors: Seayad A. , Ahmed M. , Klein H. , Jackstell R. , Gross T. , Beller M.
Published: September 2002

The selective synthesis of linear amines from internal olefins or olefin mixtures was
achieved through a catalytic one-pot reaction consisting of an initial olefin
isomerization followed by hydroformylation and reductive amination. Key to the success is
the use of specially designed phosphine ligands in the presence of rhodium catalysts. This
reaction constitutes an economically attractive and environmentally favorable synthesis of
linear aliphatic amines.
Model Representations
Authors: Uglow Jenny
Published: September 2002

Embryos in Wax
Models from the Ziegler Studio. Nick Hopwood. Whipple Museum of the History of Science, University of Cambridge, and the Institute of the History of Medicine, University of Bern, Switzerland, 2002. 216 pp. Paper, $19.50, £13.50. ISBN 0-906271-18-5.

In this profusely illustrated account of these classic three-dimensional models of developing embryos from the 19th century, Hopwood discusses how the models were built and how they were used in teaching, research, and museums.
Comparison of In-House and Commercial Slides for Detection by Immunofluorescence of Immunoglobulins G and M againstBartonella henselaeandBartonella quintana
Authors: Maurin M. , Rolain J. M. , Raoult D.
Published: August 2002

We compared the sensitivities and specificities of indirect fluorescent antibody tests developed in our laboratory and commercially available from Focus Technologies (FT; formerly MRL Diagnostic) for detection of serum antibodies toBartonellaspp. Serum samples tested were from patients with culture- or PCR-confirmedBartonella quintanaorB. henselaeinfections causing cat scratch disease (CSD), chronic bacteremia, or endocarditis. At a cutoff titer of 64, the FT test had higher sensitivity than our in-house test in detecting anti-B. henselaeimmunoglobulin G (IgG) antibodies in CSD patients (91.2 versus 52.9%;P< 0.001). The specificity in serum samples from 85 control patients was, however, lower with the FT test (87%) than with the in-house test (98.8%) (P= 0.002). A cutoff titer of 128 improves the specificity for the FT test but lowers the sensitivity to 85%. For patients infected withB. henselae, our in-house test, but not the FT test, enabled endocarditis to be detected more reliably. With the in-house test, titers of IgG againstB. henselaeof ≥1,024 were found only in endocarditis patients and not in CSD patients. With the FT test, 19.1% of CSD patients had titers of IgG againstB. henselaeof ≥1,024 (P< 0.001). Our in-house technique also improved detection of anti-B. quintanaantibodies in homeless patients with endocarditis. IgG titers of ≥1,024 were present in 75% of serum samples, but only in 16.7% of serum samples with the FT test (P= 0.004). Since each test has advantages over the other, the serological diagnosis ofBartonellainfections would benefit if both tests were used concurrently.
Antibody Responses of Cattle with Respiratory Coronavirus Infections during Pathogenesis of Shipping Fever Pneumonia Are Lower with Antigens of Enteric Strains than with Those of a Respiratory Strain
Authors: Lin Xiao-Qing , O'Reilly Kathy L. , Storz Johannes
Published: August 2002

The serum antibody responses of cattle with respiratory coronavirus infections during the pathogenesis of shipping fever pneumonia were analyzed with different bovine coronavirus antigens, including those from a wild-type respiratory bovine coronavirus (RBCV) strain (97TXSF-Lu 15-2) directly isolated from lung tissue from a fatally infected bovine, a wild-type enteropathogenic bovine coronavirus (EBCV) strain (Ly 138-3), and the highly cell culture-adapted, enteric prototype strain (EBCV L9-81). Infectivity-neutralizing (IN) and hemagglutinin-inhibiting (HAI) activities were tested. Sequential serum samples, collected during the onset of the respiratory coronavirus infection and at weekly intervals for 5 weeks thereafter, had significantly higher IN and HAI titers for antigens of RBCV strain 97TXSF-Lu15-2 than for the wild-type and the highly cell culture-adapted EBCV strains, with
P
values ranging from <0.0001 to 0.0483. The IN and HAI antibody responses against the two EBCV strains did not differ significantly, but the lowest titers were detected with EBCV strain L9-81.
Serodiagnosis of Mice Minute Virus and Mouse Parvovirus Infections in Mice by Enzyme-Linked Immunosorbent Assay with Baculovirus-Expressed Recombinant VP2 Proteins
Authors: Livingston Robert S. , Besselsen David G. , Steffen Earl K. , Besch-Williford Cynthia L. , Franklin Craig L. , Riley Lela K.
Published: August 2002

Mice minute virus (MMV) and mouse parvovirus (MPV) type 1 are the two parvoviruses known to naturally infect laboratory mice and are among the most prevalent infectious agents found in contemporary laboratory mouse colonies. Serologic assays are commonly used to diagnose MMV and MPV infections in laboratory mice; however, highly accurate, high-throughput serologic assays for the detection of MMV- and MPV-infected mice are needed. To this end, the major capsid viral protein (VP2) genes of MMV and MPV were cloned and MMV recombinant VP2 (rVP2) and MPV rVP2 proteins were expressed by using a baculovirus system. MMV rVP2 and MPV rVP2 spontaneously formed virus-like particles that were morphologically similar to empty parvovirus capsids. These proteins were used as antigens in enzyme-linked immunosorbent assays (ELISAs) to detect anti-MMV or anti-MPV antibodies in the sera of infected mice. Sera from mice experimentally infected with MMV (n= 43) or MPV (n= 35) and sera from uninfected mice (n= 30) were used to evaluate the ELISAs. The MMV ELISA was 100% sensitive and 100% specific in detecting MMV-infected mice, and the MPV ELISA was 100% sensitive and 98.6% specific in detecting MPV-infected mice. Both assays outperformed a parvovirus ELISA that uses a recombinant nonstructural protein (NS1) of MMV as antigen. The MMV rVP2 and MPV rVP2 proteins provide a ready source of easily produced antigen, and the ELISAs developed provide highly accurate, high-throughput assays for the serodiagnosis of MMV and MPV infections in laboratory mice.
In Vitro Whole-Blood Analysis of Cellular Immunity in Patients with Active Coccidioidomycosis by Using the Antigen Preparation T27K
Authors: Ampel Neil M. , Kramer Larissa A. , Li Lijin , Carroll Deborah S. , Kerekes Kathleen M. , Johnson Suzanne M. , Pappagianis Demosthenes
Published: August 2002

Measurement of cellular immunity in human coccidioidomycosis has important diagnostic and prognostic implications. The coccidioidin skin test has been the standard for the measurement of this, but it is not available in the United States. We examined the utility of measuring surface expression of CD69 on T lymphocytes in whole blood incubated with the coccidioidal antigen preparation T27K as an alternative to the skin test. Seventy donors with active coccidioidomycosis were studied. The mean fluorescent intensity (MFI) of CD69 expression on CD3 lymphocytes in response to T27K was 28.61 ± 1.77, significantly greater than the control response of 11.45 ± 0.78 (
P
< 0.001). The MFI CD69 response to T27K above that for the control (MFI CD69 above control) was 6.35 ± 2.18 for seven subjects with disseminated coccidioidomycosis who were studied within 5 months of diagnosis. This was significantly below the value of 20.17 ± 3.17 for 18 subjects with pulmonary coccidioidomycosis studied within 5 months of diagnosis and the value of 19.58 ± 2.91 for 27 subjects with disseminated coccidioidomycosis studied after 5 months of diagnosis (for both,
P
< 0.05). There was an inverse correlation between coccidioidal clinical score and MFI CD69 above control for all 34 subjects with disseminated coccidioidomycosis (
r
= 0.362;
P
= 0.036) but not for the 36 subjects with pulmonary disease (
r
< 0.001;
P
= 0.993). Among 30 subjects for whom data were available, there was a highly significant association between the MFI CD69 above control and the supernatant concentrations of gamma interferon, interleukin-2 (IL-2), and tumor necrosis factor alpha (for all,
P
< 0.001), but not for IL-4, IL-5, or IL-10. These data indicate that in vitro assessment of CD69 expression on T lymphocytes by using T27K may be a useful measure of cellular immune response among subjects with active coccidioidomycosis.
Immunoglobulin G Antibody against
Helicobacter pylori
: Clinical Implications of Levels Found in Serum
Authors: Chen Tseng-Shing , Li Fen-Yau , Chang Full-Young , Lee Shou-Dong
Published: August 2002

The clinical significance of high levels of antibody against
Helicobacter pylori
is still unclear. We sought to evaluate whether the serum antibody levels could predict the presence of macroscopic gastroduodenal disease, to identify factors that correlate with antibody levels in a multivariate context, and to determine the predictive value of antibody levels for diagnosing
H. pylori
infection. The grades of gastritis and density of
H. pylori
colonization were scored separately using the updated Sydney system for antral and body mucosa. An enzyme-linked immunosorbent assay (ELISA) for the quantitative detection in serum of IgG antibodies to
H. pylori
was performed. Of the 170 dyspeptic patients, 105 (62%) had
H. pylori
infection. There was no difference in antibody levels among endoscopic findings of normal mucosa, chronic gastritis, and duodenal ulcer. On multivariate linear regression analysis, the status of
H. pylori
infection, mononuclear cell infiltration of body mucosa, and age correlated with antibody levels. The negative predictive value for antibody levels of <30 U/ml is 94%, and the positive predictive value of antibody levels of >70 U/ml is 98%. We conclude that serum antibody levels do not predict the severity of gastroduodenal diseases or the density of
H. pylori
colonization in
H. pylori
-infected dyspeptic patients. Higher levels are associated with the presence of
H. pylori
infection, the chronic gastritis score of the corpus, and older age. Setting a gray zone is necessary for ELISA, since the accuracy in this zone does not allow a precise determination of
H. pylori
status.