bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperative Control of Vehicle Swarms for Acoustic Target Localization by Energy Flows
Authors: Dohner and J. L. , Eisler G. R. , Driessen B. J. , Hurtado J.
Published: March 2005

A control algorithm has been developed and experimentally validated for guiding swarms of robotic vehicles to acoustic targets. This novel algorithm uses pressure measurements from a set of sensors, each attached to a vehicle of the swarm, to deduce energy flows from the environment, and to move in the direction of maximum reflected intensity while controlling constraints between vehicles. The algorithm was validated using a collective of eight hand-placed microphones in an open-space area with a 50-m separation between an emitter and scatterer.
String Instabilities in Formation Flight: Limitations Due to Integral Constraints
Authors: Seiler P. , Pant A. , Hedrick J. K.
Published: March 2005

Flying in formation improves aerodynamic efficiency and, consequently, leads to an energy savings. One strategy for formation control is to follow the preceding vehicle. Many researchers have shown through simulation results and analysis of specific control laws that this strategy leads to amplification of disturbances as they propagate through the formation. This effect is known as string instability. In this paper, we show that string instability is due to a fundamental constraint on coupled feedback loops. The tradeoffs imposed by this constraint imply that predecessor following is an inherently poor strategy for formation flight control. Finally, we present two examples that demonstrate the theoretical results.
Finite elements methods for modeling the guided waves propagation in structures with weak interfaces
Authors: Hosten Bernard , Castaings Michel
Published: March 2005

This paper describes two methods using a finite element (FE) code for modeling the effects of weak interfaces on the propagation of low-order Lamb modes. The variable properties of the interfaces are modeled by either a thin layer or a uniform repartition of compression and shear springs that insure the continuity of the stresses and impose a discontinuity in the displacement field. The method is tested by comparison with measurements that were presented in a previous paper [J. Acoust. Soc. Am. 113(6) 3161–3170 (2003)]. The interface was the contact between a rough elastomer with high internal damping loaded against one surface of a glass plate. Both normal and shear stiffnesses of the interface were quantified from the attenuation of A0 and S0 Lamb waves caused by leakage of energy from the plate into the elastomer and measured at each step of a compressive loading. The FE model is made in the frequency domain, thus allowing the viscoelastic properties of the elastomer to be modeled by using complex moduli as input data. By introducing the interface stiffnesses in the code, the predicted guided waves attenuations are compared to the experimental results to validate the numerical FE methods.
Measurements of glottal structure dynamics
Authors: Holzrichter John F. , Ng Lawrence C. , Burke Gerry J. , Champagne Nathan J. , Kallman Jeffrey S. , Sharpe Robert M. , Kobler James B. , Hillman Robert E. , Rosowski John J.
Published: March 2005

Low power, radarlike electromagnetic (EM) wave sensors, operating in a homodyne interferometric mode, are being used to measure tissue motions in the human vocal tract during speech. However, when these and similar sensors are used in front of the laryngeal region during voiced speech, there remains an uncertainty regarding the contributions to the sensor signal from vocal fold movements versus those from pressure induced trachea-wall movements. Several signal-source hypotheses are tested by performing experiments with a subject who had undergone tracheostomy, and who still was able to phonate when her stoma was covered (e.g., with a plastic plate). Laser-doppler motion-measurements of the subject’s posterior trachea show small tissue movements, about 15 microns, that do not contribute significantly to signals from presently used EM sensors. However, signals from the anterior wall do contribute. EM sensor and air-pressure measurements, together with 3-D EM wave simulations, show that EM sensors measure movements of the vocal folds very well. The simulations show a surprisingly effective guiding of EM waves across the vocal fold membrane, which, upon glottal opening, are interrupted and reflected. These measurements are important for EM sensor applications to speech signal de-noising, vocoding, speech recognition, and diagnostics.
Estimation of sound pressure levels of voiced speech from skin vibration of the neck
Authors: Švec Jan G. , Titze Ingo R. , Popolo Peter S.
Published: March 2005

How accurately can sound pressure levels (SPLs) of speech be estimated from skin vibration of the neck? Measurements using a small accelerometer were carried out in 27 subjects (10 males and 17 females) who read Rainbow and Marvin Williams passages in soft, comfortable, and loud voice, while skin acceleration levels (SALs) and SPLs were simultaneously registered and analyzed every 30 ms. The results indicate that the mean SPL of voiced speech can be estimated with accuracy better than ±2.8 dB in 95% of the cases when the subjects are individually calibrated. This makes the accelerometer an interesting sensor for SPL measurement of speech when microphones are problematic to use (e.g., noisy environments or in voice dosimetry). The estimates of equivalent SPL, which is the logarithm of averaged relative energy of voiced speech, were found to be up to 1.5 dB less accurate than the mean SPL. The estimation accuracy for instantaneous SPLs was worse than for the mean and equivalent SPLs (on average ±6 and ±5 dB for males and females, respectively).
Dominance region for pitch: Effects of duration and dichotic presentation
Authors: Gockel Hedwig , Carlyon Robert P. , Plack Christopher J.
Published: March 2005

The dominance region (DR) for pitch was determined for 16- and 200-ms complex tones containing the first seven harmonics of a fundamental frequency (F0) of 250 Hz. A tone was presented with one of the harmonics mistuned upwards or downwards by 3%, followed 500 ms later by a perfectly harmonic tone of the same duration. Listeners adjusted the F0 of the harmonic tone so that its pitch matched that of the mistuned complex. In experiment 1, stimuli were presented monaurally. The DR was significantly higher in harmonic number for the short than for the long duration. The overall sum of the pitch shifts produced by all harmonics was significantly larger for the short than for the long duration, presumably due to stronger perceptual fusion for the former. In experiment 2, the mistuned harmonic was presented only contralaterally to the remainder of the complex. A similar shift in the DR with duration was observed, although the pitch shifts were smaller than for monaural presentation. There was no significant effect of duration on the overall pitch shifts. The results are discussed in terms of pattern recognition and autocorrelation models of pitch perception, and a role of attention in pitch matching is suggested.
On the large-scale spectral structure of otoacoustic emissions
Authors: Sisto Renata , Moleti Arturo
Published: March 2005

Transient evoked and distortion product otoacoustic emission data, showing a characteristic slowly oscillating spectral shape, are presented. Such peculiar behavior had also been observed in earlier studies, and deserves some theoretical explanation. A simple model of the cochlear reflectivity, based on the analogy between the cochlear transmission line equations and the Schrödinger wave equation for the motion of an elementary particle above a one-dimensional potential well, is presented. Wave mechanics predicts indeed reflection from a negative potential well, which is quasiperiodically dependent on the width and depth of the well, i.e., on the quality factor of the cochlear resonance. The model, whose quantitative predictions are dependent on the rather uncertain level and slope of the cochlear tuning curve, proves capable of explaining, at least qualitatively, the observed experimental behavior.
Distortion-product otoacoustic emission measured with continuously varying stimulus level
Authors: Neely Stephen T. , Johnson Tiffany A. , Gorga Michael P.
Published: March 2005

Distortion-product otoacoustic emissions (DPOAE) are measured by stimulating the ear with two simultaneous tones. A novel method for measuring DPOAEs has been developed in which the tone levels vary continuously instead of in discrete steps. Varying the tone levels continuously may offer advantages for characterizing DPOAE level as a function of stimulus level. For equivalent primary levels, DPOAE levels measured with the continuous-level method were the same as levels obtained with the discrete-level method, thus validating the new method. Continuous-level measurements were used to determine the optimal L1 for each L2 in individual subjects (N=20) at f2=1, 2, 4, and 8 kHz by using a Lissajous path that covered a wide range of stimulus levels. The optimal L1 (defined as the L1 that resulted in the largest DPOAE for each L2) varied across subjects and across frequency. The optimal difference between L1 and L2 decreased with increasing L2 at all frequencies, and increased with frequency when L2 was low. When the optimal L1 was determined individually for each ear, the DPOAE levels were larger and less variable than those obtained using the equation for L1 suggested by Kummer et al. [J. Acoust. Soc. Am. 103, 3431–3444 (1998)].
Detection-theoretic analysis of same–different judgments for the amplitude discrimination of acoustic sinusoids
Authors: Wang Miao-Fen , Irwin R. John , Hautus Michael J.
Published: March 2005

Three methods were applied to determine which decision model best accounted for same–different judgments about the amplitude of acoustic sinusoids. The methods were (1) analysis of the shape of the receiver operating characteristic; (2) analysis of an observer’s decision space; and (3) a correlation method based on the conditional-on-single-stimulus procedure. In one experiment, observers rated their confidence that a pair of 1-kHz sinusoids was drawn from the same or from different sets. The two sets had identical Gaussian distributions of decibel amplitudes, but their mean amplitudes differed by 3 dB. The differencing model, in which observers base their decision on the absolute difference between the two observations, accounted for the data better than the independent-observation model, in which observers compute independent likelihood ratios for each observation. A second experiment added to every trial an interval that contained a 1-kHz sinusoid whose amplitude equaled the grand mean of both stimulus sets. Despite this additional information, which is needed to adopt the independent-observation model, the differencing model again better accounted for the data.
Investigation of potential effects of cellular phones on human auditory function by means of distortion product otoacoustic emissions
Authors: Janssen Thomas , Boege Paul , von Mikusch-Buchberg Jutta , Raczek Johannes
Published: March 2005

Outer hair cells (OHC) are thought to act like piezoelectric transducers that amplify low sounds and hence enable the ear’s exquisite sensitivity. Distortion product otoacoustic emissions (DPOAE) reflect OHC function. The present study investigated potential effects of electromagnetic fields (EMF) of GSM (Global System for Mobile Communication) cellular phones on OHCs by means of DPOAEs. DPOAE measurements were performed during exposure, i.e., between consecutive GSM signal pulses, and during sham exposure (no EMF) in 28 normally hearing subjects at tone frequencies around 4 kHz. For a reliable DPOAE measurement, a 900-MHz GSM-like signal was used where transmission pause was increased from 4.034 ms (GSM standard) to 24.204 ms. Peak transmitter power was set to 20 W, corresponding to a specific absorption rate (SAR) of 0.1 W/kg. No significant change in the DPOAE level in response to the EMF exposure was found. However, when undesired side effects on DPOAEs were compensated, in some subjects an extremely small EMF-exposure-correlated change in the DPOAE level (<1 dB) was observed. In view of the very large dynamic range of hearing in humans (120 dB), it is suggested that this observation is physiologically irrelevant.
The effect of bottom interaction on transmissions from the North Pacific Acoustic Laboratory Kauai source
Authors: Vera Michael D. , Heaney Kevin D. ,   The NPAL Group
Published: March 2005

Acoustic signals transmitted from a 75-Hz broadband source near Kauai as part of the North Pacific Acoustic Laboratory (NPAL) experiment were recorded on an array of receivers near California at a range of 3890 km, and on a vertical line array at a range of 3336 km in the Gulf of Alaska. Because the source is approximately 2 m above the seafloor, and the bottom depth at the receivers near California is approximately 1800 m, acoustic interaction with the bathymetry complicates the identification of the recorded arrivals with those present in numerical simulations of the experiment. Ray methods were used to categorize acoustic energy according to interactions with the sea bottom and surface and to examine the significance of seafloor geometry. A modal decomposition was also used to examine the role of range-dependent bathymetry and to associate the effects on the acoustic field with seafloor features at specific ranges. Parabolic-equation simulations were performed in order to investigate the sensitivity of the received signal to geoacoustic parameters; shear excitations within the seafloor were modeled using a complex-density, equivalent-fluid technique. Incorporation of bottom interaction into models of the propagation enables an identification between experimental and simulated arrivals.
Ray chaos, travel time modulation, and sensitivity to the initial conditions
Authors: Smirnov I. P. , Virovlyansky A. L. , Zaslavsky G. M.
Published: March 2005

Using a model of underwater acoustic waveguide with a periodic range dependence, travel times of chaotic rays at long-range sound propagation in the ocean are studied. It is shown that the travel time as a function of the initial momentum and propagation range in the unperturbed (range-independent) waveguide displays a scaling law. Some properties predicted by this law still persist in periodically nonuniform waveguides with chaotic ray trajectories. Ray tracing has demonstrated that the coexistence of chaotic and regular rays causes an appearance of a gap in the timefront, representing ray arrivals in the time–depth plane. Besides the gap, a “focusing” of ray travel times has been found within a comparatively small temporal interval preceding the gap. In numerical simulation of a sound pulse propagation this phenomenon reveals itself in the appearance of a bright spot in the distribution of acoustic energy in the time–depth plane. It has been shown that the effect of focusing is a manifestation of the so-called stickiness, i.e., the presence of such parts of the chaotic trajectory where the latter exhibits an almost regular behavior.
Numerical study of broadband sound pulse propagation in three-dimensional oceanic waveguides
Authors: Sturm Frédéric
Published: March 2005

In this paper, the propagation of a broadband sound pulse in three-dimensional (3D) shallow water waveguides is investigated numerically. Two cases are examined: (i) the 3D ASA benchmark wedge, and (ii) the 3D Gaussian canyon. The numerical method used to solve the four-dimensional acoustic problem is based on a Fourier synthesis technique. The frequency-domain calculations are carried out using the fully 3D parabolic equation based model 3DWAPE, recently modified to include a wide-angle paraxial approximation for the azimuthal component. A broadband sound pulse with a central frequency of 25 Hz and a bandwith of 40 Hz is considered. For both test cases, 3D results corresponding to a 25 Hz cw point source are first presented and compared with predictions from a 3D adiabatic modal model. Then, the acoustic problem is solved considering the broadband source pulse. The modal structure of the received signals is analyzed and exhibits multiple mode arrivals of the propagating signal.
The Allen-Fahey experiment extended
Authors: de Boer Egbert , Nuttall Alfred L. , Hu Ning , Zou Yuan , Zheng Jiefu
Published: March 2005

An ingenious experiment has been performed by Allen and Fahey [J. Acoust. Soc. Am. 92, 178–188 (1992)], in which they attempted to estimate the gain of the cochlear amplifier by comparing responses to the 2 f1–f2 distortion product (DP) in the outer ear canal (otoacoustic emissions) and from an auditory-nerve fiber. Results were essentially negative: no evidence of cochlear amplification was found in that experiment. A variation of that experiment is reported here, where DP responses in the outer ear canal are compared with mechanical responses of the basilar membrane. This variation does not suffer from the major limitation in the original experiment in the choice of possible frequency ratios. Results confirm and extend those of Allen and Fahey entirely. Apparently, the gain of the cochlear amplifier cannot be measured in this way. It is argued that the retrograde wave going to the stapes is most likely reduced in magnitude by wave interference when the two primary frequencies approach each other. Such a reduction does not take place in the forward-going wave to the location tuned to the DP frequency. This explanation is illustrated on the basis of results of earlier experiments on the movements of the basilar membrane.
Speech and melody recognition in binaurally combined acoustic and electric hearing
Authors: Kong Ying-Yee , Stickney Ginger S. , Zeng Fan-Gang
Published: March 2005

Speech recognition in noise and music perception is especially challenging for current cochlear implant users. The present study utilizes the residual acoustic hearing in the nonimplanted ear in five cochlear implant users to elucidate the role of temporal fine structure at low frequencies in auditory perception and to test the hypothesis that combined acoustic and electric hearing produces better performance than either mode alone. The first experiment measured speech recognition in the presence of competing noise. It was found that, although the residual low-frequency (<1000 Hz) acoustic hearing produced essentially no recognition for speech recognition in noise, it significantly enhanced performance when combined with the electric hearing. The second experiment measured melody recognition in the same group of subjects and found that, contrary to the speech recognition result, the low-frequency acoustic hearing produced significantly better performance than the electric hearing. It is hypothesized that listeners with combined acoustic and electric hearing might use the correlation between the salient pitch in low-frequency acoustic hearing and the weak pitch in the envelope to enhance segregation between signal and noise. The present study suggests the importance and urgency of accurately encoding the fine-structure cue in cochlear implants.
Ultrasonic excitation of a bubble near a rigid or deformable sphere: Implications for ultrasonically induced hemolysis
Authors: Gracewski Sheryl M. , Miao Hongyu , Dalecki Diane
Published: March 2005

A number of independent studies have reported increased ultrasound bioeffects, such as hemolysis and hemorrhage, when ultrasound contrast agents are present. To better understand the role of cavitation in these bioeffects, one- and two-dimensional models have been developed to investigate the interactions between ultrasonically excited bubbles and model “cells.” First, a simple one-dimensional model based on the Rayleigh–Plesset equation was developed to estimate upper bounds for strain, strain rate, and areal expansion of a simulated red blood cell. Then, two-dimensional boundary element models were developed (with DynaFlow Inc.) to obtain simulations of asymmetric bubble dynamics in the presence of rigid and deformable spheres. The deformable spherical “cell” was modeled using Tait’s equation of state for water, with a membrane approximated by surface tension that increases linearly with areal expansion. The presence of a rigid or deformable sphere had little effect on the bubble expansion, but caused an asymmetric collapse and jetting for the conditions considered. Predicted membrane areal expansions were found to be below critical values for hemolysis reported in the literature for the cases considered near the inertial cavitation threshold.
Whistles of tucuxi dolphins (Sotalia fluviatilis) in Brazil: Comparisons among populations
Authors: Azevedo Alexandre F. , Van Sluys Monique
Published: March 2005

A quantitative and comparative analysis of the acoustic whistles parameters of tucuxi dolphins (Sotalia fluviatilis) from eight areas in Brazilian waters were conducted. Tucuxi produced mainly upsweep whistles, and despite their similar characteristics to other delphinids, whistles were shorter and less complex in shape. Some signals had fundamental frequency components above 24 kHz, and a broader band system may be useful in further studies concerning tucuxi whistles. The frequency parameters of the whistles had the lowest variation coefficients, whereas the duration and number of inflections had the highest variation coefficients. About 65% of all whistles had common characteristics between study localities, but SF, MinF, MeF, F1/4, F1/2, and F3/4 increased in frequency from southern to northern populations. The magnitude of the whistle characteristics variation was comparatively smaller between adjacent sites areas than between nonadjacent ones. However, for some pairwise comparisons the whistles were more similar between nonadjacent areas than between adjacent ones, indicating that other factors besides genetic and mixing affected tucuxi whistle characteristics. Only a few numbers of whistle variables were significantly different between adjacent areas and the parameter ranges of whistles overlapped, which made it difficult to discriminate whistles between adjacent tucuxi populations.
The relative importance of spectral tilt in monophthongs and diphthongs
Authors: Kiefte Michael , Kluender Keith R.
Published: March 2005

Ito et al. [J. Acoust. Soc. Am. 110, 1141–1149 (2001)] demonstrated that listeners can reliably identify vowel stimuli on the basis of relative formant amplitude in the absence of, or in spite of, F2 peak frequency. In the present study, formant frequencies and global spectral tilt are manipulated independently in synthetic steady-state vowels. Listeners’ identification of these sounds demonstrate strong perceptual effects for both local (formant frequency) and global (spectral tilt) acoustic characteristics. Subsequent experiments reveal that effects of spectral tilt are attenuated in synthetic stimuli for which formant center frequencies change continuously. When formant peaks are kinematic, perceptual salience of the relative amplitudes of low- and high-frequency formants (as determined by spectral tilt) is mitigated. Because naturally produced English vowels are rarely spectrally static, one may conclude that gross spectral properties may play only a limited role in perception of fluently produced vowel sounds.
GENE THERAPY: Twenty-First Century Medicine
Authors: Verma Inder M. , Weitzman Matthew D.
Published: March 2005

▪ Abstract  Broadly defined, the concept of gene therapy involves the transfer of genetic material into a cell, tissue, or whole organ, with the goal of curing a disease or at least improving the clinical status of a patient. A key factor in the success of gene therapy is the development of delivery systems that are capable of efficient gene transfer in a variety of tissues, without causing any associated pathogenic effects. Vectors based upon many different viral systems, including retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses, currently offer the best choice for efficient gene delivery. Their performance and pathogenicity has been evaluated in animal models, and encouraging results form the basis for clinical trials to treat genetic disorders and acquired diseases. Despite some initial success in these trials, vector development remains a seminal concern for improved gene therapy technologies.
Kenneth Frank Baker—Pioneer Leader in Plant Pathology
Authors: Cook R. James
Published: March 2005

Kenneth F. Baker (1908–1996) made major contributions to understanding diseases of ornamental plants, seed pathology, soilborne plant pathogens, biological control, and history of plant pathology. His work set the stage for the success of today's ornamentals and nursery industries. His leadership and writings created the scientific framework for research and teaching on soilborne plant pathogens and biological control. After B.Sc. and Ph.D. degrees from Washington State University in 1930 and 1934, respectively, and one year as a National Research Council Fellow with B.M. Dugger at Wisconsin, he took jobs in 1935 with the U.S. Department of Agriculture in Nebraska on establishment of shelter belts and 1936–39 with the Pineapple Producers Cooperative Association in Hawaii. He worked on diseases of ornamental plants at the University of California, Los Angeles, starting in 1939, moving to Berkeley in 1961 when the UCLA program closed. He retired in 1975 and moved to Corvallis, OR, as Emeritus Professor, Oregon State University, and Collaborator, U.S. Department of Agriculture, Agricultural Research Service. He spent four sabbatical leaves in Australia, and was elected fellow of the American Association for the Advancement of Science in 1950, fellow of the American Phytopathological Society in 1969, and the Horticultural Hall of Fame in 1976.
New Directions in Corporate Governance
Authors: Davis Gerald F.
Published: March 2005

Corporate governance describes the structures, processes, and institutions within and around organizations that allocate power and resource control among participants. Law and economics scholars have developed a view of the public corporation as a nexus-of-contracts whose structure is driven by the requirements of financial markets, and thus features of the corporation and its surrounding institutions are theorized in terms of their function in directing corporations toward share price as a criterion of value. Working from this base, more recent research has studied historical and cross-national variation in governance institutions, producing highly varied interpretations of their sources and function. Sociological work, particularly within organization theory, has critiqued this functionalist view and provided alternative interpretations based on networks, power, and culture. The most promising contemporary work seeks to analyze governance in terms of the dynamics of institutions—where they originate, how they operate, how they change, and how they spread beyond their original purposes.
Signal-Transduction Pathways that Regulate Smooth Muscle Function II. Receptor-ion channel coupling mechanisms in gastrointestinal smooth muscle
Authors: Akbarali Hamid I.
Published: March 2005

Regulation of membrane ion channels by second messengers is an important mechanism by which gastrointestinal smooth muscle excitability is controlled. Receptor-mediated phosphorylation of Ca2+channels has been known for some time; however, recent findings indicate that these channels may also modulate intracellular signaling. The plasmalemma ion channels may also function as a point of convergence between different receptor types. In this review, the molecular mechanisms that link channel function and signal transduction are discussed. Emerging evidence also indicates altered second-messenger modulation of the Ca2+channel in the pathophysiology of smooth muscle dysmotility.
Influence of substrate supply on cardiac efficiency, as measured by pressure-volume analysis in ex vivo mouse hearts
Authors: How Ole-Jakob , Aasum Ellen , Kunnathu Stanley , Severson David L. , Myhre Eivind S. P. , Larsen Terje S.
Published: March 2005

In the present study, we tested the reliability of measurements of pressure-volume area (PVA) and oxygen consumption (MV̇o2) in ex vivo mouse hearts, combining the use of a miniaturized conductance catheter and a fiber-optic oxygen sensor. Second, we tested whether we could reproduce the influence of increased myocardial fatty acid (FA) metabolism on cardiac efficiency in the isolated working mouse heart model, which has already been documented in large animal models. The hearts were perfused with crystalloid buffer containing 11 mM glucose and two different concentrations of FA bound to 3% BSA. The initial concentration was 0.3 ± 0.1 mM, which was subsequently raised to 0.9 ± 0.1 mM. End-systolic and end-diastolic pressure-volume relationships were assessed by temporarily occluding the preload line. Different steady-state PVA-MV̇o2relationships were obtained by changing the loading conditions (pre- and afterload) of the heart. There were no apparent changes in baseline cardiac performance or contractile efficiency (slope of the PVA-MV̇o2regression line) in response to the elevation of the perfusate FA concentration. However, all hearts ( n = 8) showed an increase in the y-intercept of the PVA-MV̇o2regression line after elevation of the palmitate concentration, indicating an FA-induced increase in the unloaded MV̇o2. Therefore, in the present model, unloaded MV̇o2is not independent of metabolic substrate. This is, to our knowledge, the first report of a PVA-MV̇o2relationship in ex vivo perfused murine hearts, using a pressure-volume catheter. The methodology can be an important tool for phenotypic assessment of the relationship among metabolism, contractile performance, and cardiac efficiency in various mouse models.
Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply
Authors: Tokarska-Schlattner Malgorzata , Zaugg Michael , da Silva Rafaela , Lucchinetti Eliana , Schaub Marcus C. , Wallimann Theo , Schlattner Uwe
Published: March 2005

Doxorubicin (DXR) is a widely used and efficient anticancer drug. However, its application is limited by the risk of severe cardiotoxicity. Impairment of cardiac high-energy phosphate homeostasis is an important manifestation of both acute and chronic DXR cardiotoxic action. Using the Langendorff model of the perfused rat heart, we characterized the acute effects of 1-h perfusion with 2 or 20 μM DXR on two key kinases in cardiac energy metabolism, creatine kinase (CK) and AMP-activated protein kinase (AMPK), and related them to functional responses of the perfused heart and structural integrity of the contractile apparatus as well as drug accumulation in cardiomyocytes. DXR-induced changes in CK were dependent on the isoenzyme, with a shift in protein levels of cytosolic isoenzymes from muscle-type CK to brain-type CK, and a destabilization of octamers of the mitochondrial isoenzyme (sarcometric mitochondiral CK) accompanied by drug accumulation in mitochondria. Interestingly, DXR rapidly reduced the protein level and phosphorylation of AMPK as well as phosphorylation of its target, acetyl-CoA-carboxylase. AMPK was strongly affected already at 2 μM DXR, even before substantial cardiac dysfunction occurred. Impairment of CK isoenzymes was mostly moderate but became significant at 20 μM DXR. Only at 2 μM DXR did upregulation of brain-type CK compensate for inactivation of other isoenzymes. These results suggest that an impairment of kinase systems regulating cellular energy homeostasis is involved in the development of DXR cardiotoxicity.
Hemoglobin oxygen saturation measurements using resonance Raman intravital microscopy
Authors: Torres Filho Ivo P. , Terner James , Pittman Roland N. , Somera Leonardo G. , Ward Kevin R.
Published: March 2005

A system is described for in vivo noninvasive measurements of hemoglobin oxygen saturation (HbO2Sat) at the microscopic level. The spectroscopic basis for the application is resonant Raman enhancement of Hb in the violet/ultraviolet region, allowing simultaneous identification of oxy- and deoxyhemoglobin with the same excitation wavelength. The heme vibrational bands are well known, but the technique has never been used to determine microvascular HbO2Sat in vivo. A diode laser light (power: 0.3 mW) was focused onto sample areas 15–30 μm in diameter. Raman spectra were obtained in backscattering geometry by using a microscope coupled to a spectrometer and a cooled detector. Calibration was performed in vitro by using glass capillaries containing blood at several Hb concentrations, equilibrated at various oxygen tensions. HbO2Sat was estimated using the Raman band intensities at 1,360 and 1,375 cm−1. Glass capillary path length and Hb concentration had no effect on HbO2Sat estimated from Raman spectra. In vivo observations were made in blood flowing in microvessels of the rat mesentery. The Hb Raman peaks observed in oxygenated and deoxygenated blood were consistent with earlier Raman studies that used Hb solutions and isolated cells. The method allowed HbO2Sat determinations in the whole range of arterioles, venules, and capillaries. Tissue transillumination allowed diameter and erythrocyte velocity measurements in the same vessels. Raman microspectroscopy offers distinct advantages over other currently used techniques by providing noninvasive and reliable in vivo determinations of HbO2Sat in thin tissues as well as in solid organs and tissues, which are unsuitable for techniques requiring transillumination.
K+-dependent regulation of matrix volume improves mitochondrial function under conditions mimicking ischemia-reperfusion
Authors: Korge Paavo , Honda Henry M. , Weiss James N.
Published: March 2005

To delineate the role of mitochondrial K+fluxes in cardioprotection, we investigated the effect of extramitochondrial K+on the ability of mitochondria to support membrane potential (ΔΨ), regulate matrix volume, consume oxygen, and phosphorylate ADP under conditions mimicking key elements of ischemia-reperfusion. Isolated energized mitochondria responded to ADP addition with depolarization, increased O2consumption, and matrix shrinkage. The time required for full recovery of ΔΨ, signaling the completion of ADP phosphorylation, was used to evaluate the rate of ATP synthesis during repeated ADP pulses. In mitochondria with a decreased ability to support ΔΨ, the rate of ADP phosphorylation was significantly improved by extramitochondrial K+> Na+> Li+, especially at higher buffer osmolarity, which promotes matrix shrinkage. K+-induced improvement in ΔΨ recovery after ADP pulses was accompanied by more rapid and complete matrix volume recovery and enhanced O2consumption. Manipulations expected to affect matrix swelling by regulating K+fluxes or water distribution indicate that matrix volume regulation by external factors becomes increasingly important in mitochondria with decreased ability to support ΔΨ in the face of a high ADP load. Under these conditions, opening of K+influx pathways improved mitochondrial function and delayed failure. This may be an important factor in the mechanism of diaxozide-induced cardioprotection.
TGF-α perturbs surfactant homeostasis in vivo
Authors: Ikegami Machiko , Le Cras Timothy D. , Hardie William D. , Stahlman Mildred T. , Whitsett Jeffrey A. , Korfhagen Thomas R.
Published: March 2005

To determine potential relationships between transforming growth factor (TGF)-α and surfactant homeostasis, the metabolism, function, and composition of surfactant phospholipid and proteins were assessed in transgenic mice in which TGF-α was expressed in respiratory epithelial cells. Secretion of saturated phosphatidylcholine was decreased 40–60% by expression of TGF-α. Although SP-A, SP-B, and SP-C mRNA levels were unchanged by expression of TGF-α, SP-A and SP-B content in bronchoalveolar lavage fluid was decreased. The minimum surface tension of surfactant isolated from the transgenic mice was significantly increased. Incubation of cultured normal mice type II cells with TGF-α in vitro did not change secretion of surfactant phosphatidylcholine and SP-B, indicating that TGF-α does not directly influence surfactant secretion. Expression of a dominant negative (mutant) EGF receptor in the respiratory epithelium blocked the TGF-α-induced changes in lung morphology and surfactant secretion, indicating that EGF receptor signaling in distal epithelial cells was required for TGF-α effects on surfactant homeostasis. Because many epithelial cells were embedded in fibrotic lesions caused by TGF-α, changes in surfactant homeostasis may at least in part be influenced by tissue remodeling that results in decreased surfactant secretion. The number of nonembedded type II cells was decreased 30% when TGF-α was expressed during development and was increased threefold by TGF-α expression in adulthood, suggesting possible alteration of type II cells on surfactant metabolism in the adult lung. Abnormalities in surfactant function and decreased surfactant level in the airways may contribute to the pathophysiology induced by TGF-α in both the developing and adult lung.
Evolutionary sequence analysis of complete eukaryote genomes
Authors: Blair Jaime E , Shah Prachi , Hedges S Blair
Published: March 2005

Background

Gene duplication and gene loss during the evolution of eukaryotes have hindered attempts to estimate phylogenies and divergence times of species. Although current methods that identify clusters of orthologous genes in complete genomes have helped to investigate gene function and gene content, they have not been optimized for evolutionary sequence analyses requiring strict orthology and complete gene matrices. Here we adopt a relatively simple and fast genome comparison approach designed to assemble orthologs for evolutionary analysis. Our approach identifies single-copy genes representing only species divergences (panorthologs) in order to minimize potential errors caused by gene duplication. We apply this approach to complete sets of proteins from published eukaryote genomes specifically for phylogeny and time estimation.

Results

Despite the conservative criterion used, 753 panorthologs (proteins) were identified for evolutionary analysis with four genomes, resulting in a single alignment of 287,000 amino acids. With this data set, we estimate that the divergence between deuterostomes and arthropods took place in the Precambrian, approximately 400 million years before the first appearance of animals in the fossil record. Additional analyses were performed with seven, 12, and 15 eukaryote genomes resulting in similar divergence time estimates and phylogenies.

Conclusion

Our results with available eukaryote genomes agree with previous results using conventional methods of sequence data assembly from genomes. They show that large sequence data sets can be generated relatively quickly and efficiently for evolutionary analyses of complete genomes.
Two new plumage mutations in the Japanese quail: "curly" feather and "rusty" plumage
Authors: Minvielle Francis , Gourichon David , Moussu Chantal
Published: March 2005

Background

The genetics of plumage of Japanese quail is of interest both from a biological standpoint, for comparative studies between avian species, and from a zootechnical standpoint, for identifying commercial selection lines or crosses. There are only few plumage mutations reported in quail, and the present work describes a new color variant "rusty" and a new feather structure "curly", and their heredity from an F1 and F2 segregation experiment.

Results

Curly feathers result from abnormal early growth caused by transient joining of follicle walls of adjacent feathers around 10 days of age, but the expression of the trait is variable. Rusty plumage color results from the replacement of the wild-type plumage pattern on the tip of the feather by a reddish coloration, but the pigmentation of the bottom part of the feather is not affected. Two lines breeding true for the curly or the rusty phenotype were developed. Both characters are determined by autosomal recessive mutations which are independent. The curly mutation has also a positive effect on body weight at 5 weeks of age.

Conclusion

The curly line is a new model which may be used for further work on the growth of the feather, and the rusty mutation is a new addition to the panel of plumage mutations available for comparative studies in poultry, and more generally among avian species.
A qualitative assessment of direct-labeled cDNA products prior to microarray analysis
Authors: Grissom Sherry F , Lobenhofer Edward K , Tucker Charles J
Published: March 2005

Background

The success of the microarray process in determining differential gene expression of thousands of genes is dependent upon the quality and integrity of the starting RNA, this being particularly true of direct labeling via a reverse transcription procedure. Furthermore, an RNA of reasonable quality still may not yield reliable hybridization data if the labeling efficiency was poor.

Results

Here we present a novel assay for assessing the quality of directly labeled fluorescent cDNA prior to microarray hybridization utilizing the Agilent 2100 Bioanalyzer, which employs microfluidic technology for the analysis of nucleic acids and proteins. Using varying amounts of RNase to simulate RNA degradation, we show the strength of this un-advertised assay in determining the relative amounts of cDNA obtained from a direct labeling reaction.

Conclusion

Utilization of this method in the lab will help to prevent the costly mistake of hybridizing poor quality direct labeled products to expensive arrays.
Chronic ethanol exposure increases microtubule content in PC12 cells
Authors: Reiter-Funk Cindy K , Dohrman Douglas P
Published: March 2005

Background

Chronic ethanol exposure has been shown to result in changes in neuronal cyto-architecture such as aberrant sprouting and alteration of neurite outgrowth. In PC12 cells, chronic ethanol treatment produces an increase in Nerve Growth Factor (NGF)-induced neurite outgrowth that appears to require the epsilon, but not delta, isoform of Protein Kinase C (PKC). Neurites contain a core of microtubules that are formed from polymerization of free-tubulin. Therefore, it would be expected that an increase in neurite outgrowth would correlate with an increase in microtubule content. We examined the effect of chronic ethanol exposure on microtubule content in PC12 cells and the role of PKC epsilon and delta in ethanol's effect on microtubule levels.

Results

Chronic ethanol exposure of wild-type and vector control PC12 cells resulted in a significant increase in microtubule content and a corresponding decrease in free tubulin. There was also a significant increase in microtubule content in PC12 cells expressing a dominate-negative inhibitor of epsilon PKC; cells which have previously been shown to have no ethanol-induced increase in neurite outgrowth. In contrast, ethanol had no effect on microtubule content in PC12 cells expressing a dominate-negative inhibitor of delta PKC.

Conclusion

These results suggest that chronic ethanol exposure alters the relative ratio of free tubulin to microtubule-associated tubulin, an important component of the cytoskeleton. Further, the data from the PKC dominant-negative cell lines suggest that the effects of ethanol on microtubule content do not correlate with the effects of ethanol on neurite outgrowth. The delta isoform of PKC appears to be necessary for the ethanol-induced increase in microtubule content. These studies demonstrate an effect of chronic ethanol exposure which may contribute to previously documented alterations of neuronal cyto-architecture.
Immunogenetics of Hashimoto's thyroiditis
Authors: Chistiakov Dimitry A
Published: March 2005

Hashimoto's thyroiditis (HT) is an organ-specific T-cell mediated disease. It is a complex disease, with a strong genetic component. To date, significant progress has been made towards the identification and functional characterization of HT susceptibility genes. In this review, we will summarize the recent advances in our understanding of the genetic input to the pathogenesis of HT.
The levels of plasma low density lipoprotein are independent of cholesterol ester transfer protein in fish-oil fed F1B hamsters
Authors: de Silva Pujitha P , Agarwal-Mawal Alka , Davis Phillip J , Cheema Sukhinder Kaur
Published: March 2005

Background

Cholesterol ester transfer protein (CETP) plays a major role in regulating the levels of LDL- and HDL-cholesterol. We previously observed a fish-oil-induced elevation of low-density lipoprotein (LDL)-and very-low-density lipoprotein (VLDL)-cholesterol concentrations and a decrease in high-density lipoprotein (HDL)-cholesterol concentration in F1B hamsters. The molecular mechanism/s by which fish oil induces hyperlipidaemic effect was investigated in this study. We examined whether the effects of dietary fish oil on plasma lipoprotein concentrations are due to fish-oil-induced alterations in plasma CETP activity. MIX diet, a diet supplemented with a mixture of lard and safflower oil, was used as the control diet.

Results

We found that fish oil feeding in hamsters reduced CETP mass as well as CETP activity. Increasing the dietary fat level of fish-oil from 5% to 20% (w/w) led to a further decrease in CETP mass. Supplementation with dietary cholesterol increased both CETP mass and CETP activity in fish-oil and MIX-diet fed hamsters. However, there was no correlation between CETP mass as well as CETP activity and LDL-cholesterol concentrations.

Conclusion

These findings suggest that cholesterol ester transfer between HDL and LDL is not likely to play a major role in determining fish-oil-induced changes in LDL- and HDL-cholesterol concentrations in F1B hamsters. A possible role of reduced clearance of LDL-particles as well as dietary fat level and dietary cholesterol dependent changes in LDL-lipid composition have been discussed.
A case-control study of the HER2 Ile655Val polymorphism in relation to risk of invasive breast cancer
Authors: Nelson Stephanie E , Gould Michael N , Hampton John M , Trentham-Dietz Amy
Published: March 2005

Background

Overexpression of the HER2 proto-oncogene in human cancer cells has been associated with a poor prognosis, and survival improves with therapy targeting the HER2 gene. Animal studies and protein modeling suggest that the Ile655Val polymorphism located in the transmembrane domain of the HER2 protein might influence breast cancer development by altering the efficiency of homodimerization.

Methods

To investigate this genetic polymorphism, incident cases of invasive breast cancer (N = 1,094) and population controls of a similar age (N = 976) were interviewed during 2001 to 2003 regarding their risk factors for breast cancer. By using DNA collected from buccal samples mailed by the participants, the HER2 Ile655Val polymorphism was evaluated with the Applied Biosystems allelic discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression adjusted for numerous breast cancer risk factors. Analysis was restricted to women with self-reported European descent.

Results

Prevalence of the Val/Val genotype was 5.6% in cases and 7.1% in controls. In comparison with the Ile/Ile genotype, the Ile/Val genotype was not significantly associated with breast cancer risk (OR 0.97, 95% CI 0.79 to 1.18), whereas the Val/Val genotype was associated with a reduced risk (OR 0.63, 95% CI 0.42 to 0.92). This inverse association seemed strongest in older women (OR 0.51, 95% CI 0.29 to 0.89 for women aged more than 55 years), women without a family history of breast cancer (OR 0.54, 95% CI 0.35 to 0.84), postmenopausal women with greater body mass index (OR 0.43, 95% CI 0.20 to 0.91 for a body mass index of 25.3 kg/m2 or more), and cases diagnosed with non-localized breast cancer (OR 0.49, 95% CI 0.26 to 0.90).

Conclusion

Although results from our population-based case-control study show an inverse association between the HER2 Ile655Val polymorphism and risk of invasive breast cancer, most other studies of this single-nucleotide polymorphism suggest an overall null association. Any further study of this polymorphism should involve sample populations with complete risk factor information and sufficient power to evaluate gene-environment interactions between the HER2 polymorphism and factors such as age and family history of breast cancer.