bluuebunny/crossref_metadata_2025 huggingface dataset:
A model of the VU (volume-unit) meter, with speech applications
Authors: Lobdell Bryce E. , Allen Jont B.
Published: January 2007

The Volume-Unit (VU) meter, used in speech research prior to the advent of computers and modern signal processing methods, is described in signal processing terms. There are no known software implementations of this meter, which meet the 1954 ASA standard and provide the instantaneous needle level. Important speech applications will be explored, such as making comparisons of speech levels to earlier classic works, and measuring speech levels using traditional methods on modern computers. It is our intention to make this venerable method of measuring speech levels available once again. The VU meter is simulated and its properties are studied. A 1950s vintage and a recent vintage VU meter are studied by comparing the transient responses to tones and measurement of speech levels. Based on these measurements, a software VU meter (henceforth referred to as VUSOFT) is simulated, and verified. The method for reading the meter is explained, and simulated in software. The VU level for speech is shown to depend on the reading duration. The relationship between the root-mean-squared (rms) level of a signal and the VU level of a signal is determined, as a function of the meter-reading time.
Sound localization with a preceding distractor
Authors: Kopčo Norbert , Best Virginia , Shinn-Cunningham Barbara G.
Published: January 2007

Experiments explored how a distractor coming from a known location influences the localization of a subsequent sound, both in a classroom and in an anechoic chamber. Listeners localized a target click preceded by a distractor click coming from a location fixed throughout a run of trials (either frontal or lateral). The stimulus onset asynchrony (SOA) between distractor and target was relatively long (25–400ms); control trials presented the target alone. The distractor induced bias and variability in target localization responses even at the longest SOA, with the specific pattern of effects differing between the two rooms. Furthermore, the presence of the distractor caused target responses to be displaced away from the distractor location in that run, even on trials with no distractor. This contextual bias built up anew in each run, over the course of minutes. The different effects illustrate that (a) sound localization is a dynamic process that depends on both the context and on the level of reverberation in the environment, and (b) interactions between sequential sound sources occur on time scales from hundreds of milliseconds to as long as minutes.
Automatic acoustic synthesis of human-like laughter
Authors: Sundaram Shiva , Narayanan Shrikanth
Published: January 2007

A technique to synthesize laughter based on time-domain behavior of real instances of human laughter is presented. In the speech synthesis community, interest in improving the expressive quality of synthetic speech has grown considerably. While the focus has been on the linguistic aspects, such as precise control of speech intonation to achieve desired expressiveness, inclusion of nonlinguistic cues could further enhance the expressive quality of synthetic speech. Laughter is one such cue used for communicating, say, a happy or amusing context. It can be generated in many varieties and qualities: from a short exhalation to a long full-blown episode. Laughter is modeled at two levels, the overall episode level and at the local call level. The first attempts to capture the overall temporal behavior in a parametric model based on the equations that govern the simple harmonic motion of a mass-spring system is presented. By changing a set of easily available parameters, the authors are able to synthesize a variety of laughter. At the call level, the authors relied on a standard linear prediction based analysis-synthesis model. Results of subjective tests to assess the acceptability and naturalness of the synthetic laughter relative to real human laughter samples are presented.
Distortion product otoacoustic emission of symphony orchestra musicians before and after rehearsal
Authors: Reuter Karen , Hammershøi Dorte
Published: January 2007

The 2f1−f2 distortion product otoacoustic emission (DPOAE) and hearing levels are obtained for 12 normal-hearing symphony orchestra musicians both before and after their rehearsal. The DPOAE fine structures are determined and analyzed according to the character and prevalence of ripples. Hearing levels, DPOAE levels, and DPOAE fine structures before and after rehearsal are similar, indicating that no or marginal temporary change of the state of hearing were caused by the exposure. The data were further compared to similar data for occupationally nonexposed subjects, one group which was age and gender matched, and other two groups of younger individuals (one group with better hearing levels than the other). The data for the age and gender matched group compared well with the musicians data (and the data for the group of better-hearing younger individuals). In general, the analyses of hearing thresholds and DPOAE data thus lead to the same conclusions concerning the state of hearing.
Properties of transparent sound-absorbing panels for use in noise barriers
Authors: Asdrubali Francesco , Pispola Giulio
Published: January 2007

Sound absorption and optical transparency are among the most useful properties of noise barriers. While the latter is required to reduce visual impact and for aesthetical reasons, the former is required whenever conditions of multiple reflections and presence of close, high receivers occur. The technical feasibility of a transparent, sound-absorbing panel for outdoor antinoise devices is investigated in this paper. An analysis of acoustical performance of multiple perforated plates is performed employing an existing theory for microperforated absorbers under normal incidence and diffused sound field. An optimization of the geometrical parameters is carried out on the basis of the European classification criteria of noise barriers for roadways. An optimized three-layer configuration can achieve sound-absorption properties similar to nontransparent products with only a limited loss of visual transparency and appropriate mechanical strength. Experimental data obtained with an impedance tube on small test samples made of transparent polycarbonate and in a reverberation room on full-scale prototypes are reported, showing a rather good agreement with the theoretical predictions. The optical performance of a multilayered configuration is evaluated also.
Acoustic positioning using a tetrahedral ultrashort baseline array of an acoustic modem source transmitting frequency-hopped sequences
Authors: Beaujean Pierre-Philippe J. , Mohamed Asif I. , Warin Raphael
Published: January 2007

Acoustic communications and positioning are vital aspects of unmanned underwater vehicle operations. The usage of separate units on each vehicle has become an issue in terms of frequency bandwidth, space, power, and cost. Most vehicles rely on acoustic modems transmitting frequency-hopped multiple frequency-shift keyed sequences for command-and-control operations, which can be used to locate the vehicle with a good level of accuracy without requiring extra signal transmission. In this paper, an ultrashort baseline acoustic positioning technique has been designed, simulated, and tested to locate an acoustic modem source in three dimensions using a tetrahedral, half-wavelength acoustic antenna. The position estimation is performed using the detection sequence contained in each message, which is a series of frequency-hopped pulses. Maximum likelihood estimation of azimuth and elevation estimation is performed using a varying number of pulse and various signal-to-noise ratios. Simulated and measured position estimation error match closely, and indicate that the accuracy of this system improves dramatically as the number of pulses processed increases, given a fixed signal-to-noise ratio.
Coherent backscattering and far-field beamforming in acoustics
Authors: Aubry Alexandre , Derode Arnaud , Roux Philippe , Tourin Arnaud
Published: January 2007

Coherent backscattering of waves by a random medium is spectacular evidence of interference effects despite disorder and multiple scattering. It manifests itself as a doubling of the wave intensity reflected exactly in the backward direction. This phenomenon has been observed experimentally in optics, acoustics, or seismology. While optical measurements are realized in far-field conditions with a plane wave illumination and a beamwidth much larger than the wavelength, ultrasonic experiments are carried out with wideband controllable arrays of (nearly) pointlike transducers that directly record the wave field, in amplitude and phase. Therefore it is possible to perform beamforming of the incoming and outgoing wave fields before computing the average backscattered intensity. In this paper, the advantages of plane wave beamforming applied to the study of the coherent backscattering effect are shown. Particularly, the angular resolution, the signal-to-noise ratio, as well as the estimation of the enhancement factor can be improved by beamforming. Experimental results are presented with ultrasonic pulses, in the 2.5–3.5MHz range, propagating in random collections of scatterers. Since the coherent backscattering effect can be taken advantage of to measure diffusive parameters (transport mean free path, diffusion constant), plane-wave beamforming can be applied to the characterization of highly scattering media.
The response of rectangular piezoelectric sensors to Rayleigh and Lamb ultrasonic waves
Authors: Lanza di Scalea Francesco , Matt Howard , Bartoli Ivan
Published: January 2007

A fundamental understanding of the response of piezoelectric transducer patches to ultrasonic waves is of increasing interest to the field of structural health monitoring. While analytical solutions exist on the interaction of a piezoelectric actuator with the generated Lamb waves, the behavior of a piezoelectric sensor has only been examined for the limited case of a piezo-actuated Lamb wave in a pitch-catch configuration. This paper focuses on the fundamental response of surface-bonded piezoelectric sensors to ultrasonic waves. The response to both Rayleigh waves and Lamb waves is examined, starting with harmonic excitation fields and moving to broadband and narrowband excitation fields. General oblique incidence of the wave on rectangular sensors is treated first; parallel incidence is then derived as a particular case. The solutions are developed analytically for the harmonic and the narrowband excitations, and semianalytically for the broadband excitation. The results obtained can be used to design ultrasonic sensors that are either particularly sensitive to a given mode or possess unique directivity behavior which, in turn, can greatly simplify current algorithms for damage detection and localization.
The binaural temporal window in adults and children
Authors: Hall Joseph W. , Buss Emily , Grose John H.
Published: January 2007

This study investigated the binaural temporal window in adults and children 5–10.5 years of age. Detection thresholds were estimated for a brief, interaurally out-of-phase (Sπ) 500Hz pure tone signal masked by bandpass, 100–2000Hz Gaussian noise. In one set of conditions, the masker was consistently either in phase (No) or out of phase (Nπ). In another set of conditions, the masker changed abruptly in interaural phase (NoNπ or NπNo), and threshold was estimated at a range of delays with respect to the phase transition. Masked thresholds were also obtained in further conditions where the masker interaural phase was steady and the signal was of long duration. Age effects obtained with dynamic maskers could be accounted for by positing that children have a binaural temporal window with a relatively prolonged leading edge or that the children position the binaural temporal window relatively late with respect to the signal. Modeling of the reduced masking-level difference shown by children for a brief Sπ signal presented in a steady No or Nπ masker was more consistent with late placement of a symmetrical binaural temporal window than a binaural temporal window having a relatively prolonged leading edge.
The fluid and elastic nature of nucleated cells: Implications from the cellular backscatter response
Authors: Baddour Ralph E. , Kolios Michael C.
Published: January 2007

In a previous experiment [Baddour et al., J. Acoust. Soc. Am. 117(2), 934–943 (2005)] it was shown that it is possible to deduce the ultrasound backscatter transfer function from single, subresolution cells in vitro, across a broad, continuous range of frequencies. Additional measurements have been performed at high frequencies (10–65MHz) on cells with different relative nucleus sizes. It was found that for cells with a nucleus to cell volume ratio of 0.50, the backscatter response was better modeled as an elastic sphere. For the cells in which the ratio was 0.33, the backscatter showed good agreement with the theoretical solution for a fluid sphere.
Why do transposed stimuli enhance binaural processing?: Interaural envelope correlation vs envelope normalized fourth moment
Authors: Bernstein Leslie R. , Trahiotis Constantine
Published: January 2007

High-frequency, “transposed” stimuli have been shown to yield enhanced processing of ongoing interaural temporal disparities (ITDs). This paper concerns determining which aspect or aspects of the envelopes of such stimuli mediate enhanced resolution of ITD. Behavioral measures and quantitative analyses utilizing special classes of transposed stimuli show that the “internal” interaural envelope correlation accounts both qualitatively and quantitatively for the enhancement. In contrast, the normalized fourth moment of the envelope (Y), which provides an index of the degree to which the envelopes of high-frequency stimuli fluctuate, does not lead to a successful accounting of the data.
Auditory efferent activation in CBA mice exceeds that of C57s for varying levels of noise
Authors: Frisina Robert D. , Newman S. R. , Zhu Xiaoxia
Published: January 2007

The medial olivocochlear efferent (MOC) system enhances signals in noise and helps mediate auditory attention. Contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAEs) has revealed age-related MOC declines. Here, differences in CS as a function of contralateral noise intensity (43–67dB sound pressure level) were measured; 2f1-f2 DPOAE grams were recorded for young adult CBA and C57 mice. In CBAs, CS was a monotonic function of contralateral noise level. The C57s showed normal hearing, measured with DPOAE amplitudes and auditory brainstem response thresholds, but showed little CS, suggesting a loss of efferent dynamics preceding any deficiencies of the afferent auditory system.
The acoustic signature of marine seep bubbles
Authors: Leifer Ira , Tang Dajun
Published: January 2007

Observations of seabed bubbles (62m depth) at a natural marine hydrocarbon seep by passive acoustic and optical approaches are compared. The acoustic and optical methods observed a bimodal distribution with peaks at 1500 and 1750Hz, and 2200 and 2800μm radius, respectively. Radii were ~20% lower than predicted by the Minnaert formula. Frequency shifts were observed for bubbles emitted within a few milliseconds and were attributed to coupling between nearby bubbles. Surfactants also may have played a role.
Instantaneous orifice discharge coefficient of a physical, driven model of the human larynx
Authors: Park Jong Beom , Mongeau Luc
Published: January 2007

The quasisteady approximation is often made in the study of phonatory aerodynamics to facilitate the modeling of time-varying air flows through the self-oscillating vocal folds. The unsteady, pulsating flow is approximated by a sequence of steady flows through representative configurations of the vocal folds at rest. Previous studies have discussed the accuracy of this approximation for a range of orifice geometries, and flow conditions. The purpose of the present study was to further evaluate the quasisteady approximation experimentally using an improved procedure, from a direct comparison between the discharge coefficients of steady jets through fixed orifices and unsteady jets through modulated orifices of identical shape, area, and transglottal pressures at a given time. Life-scale convergent and divergent glottis-shaped rubber orifices were used in a rigid-walled tube and a low Mach number flow representative of human phonation. It was found that the quasisteady approximation is valid during 70% of the duty cycle, when the Reynolds number was above 3000, for a frequency of oscillations of 100Hz. The steady form of Bernoulli’s equation along a streamline, and Bernoulli’s flow obstruction theory were found to be reasonably accurate for the unsteady flows. These models break down at low Reynolds numbers, near the beginning and the end of the duty cycle, due to viscous effects and to the influence of flow displaced by the motion of the walls.
The acoustic and perceptual effects of two noise-suppression algorithms
Authors: Zakis Justin A. , Wise Christi
Published: January 2007

Internal noise generated by hearing-aid circuits can be audible and objectionable to aid users, and may lead to the rejection of hearing aids. Two expansion algorithms were developed to suppress internal noise below a threshold level. The multiple-channel algorithm’s expansion thresholds followed the 55-dB SPL long-term average speech spectrum, while the single-channel algorithm suppressed sounds below 45dBA. With the recommended settings in static conditions, the single-channel algorithm provided lower noise levels, which were perceived as quieter by most normal-hearing participants. However, in dynamic conditions “pumping” noises were more noticeable with the single-channel algorithm. For impaired-hearing listeners fitted with the ADRO® amplification strategy, both algorithms maintained speech understanding for words in sentences presented at 55dB SPL in quiet (99.3% correct). Mean sentence reception thresholds in quiet were 39.4, 40.7, and 41.8dB SPL without noise suppression, and with the single- and multiple-channel algorithms, respectively. The increase in the sentence reception threshold was statistically significant for the multiple-channel algorithm, but not the single-channel algorithm. Thus, both algorithms suppressed noise without affecting the intelligibility of speech presented at 55dB SPL, with the single-channel algorithm providing marginally greater noise suppression in static conditions, and the multiple-channel algorithm avoiding pumping noises.
Effects of accent-reduction techniques for the treatment of an individual with foreign accent syndrome
Authors: Katz William F. , Garst Diane M. , Kaplan Karen E. , Frisch Emily J.
Published: January 2007

Foreign accent syndrome (FAS) is a rare speech motor disorder characterized by the emergence of a perceived foreign accent following brain damage. Although FAS has received increased attention in recent years, the issue of intervention for this disorder has not been systematically explored. In this study, an English-speaking female patient with FAS thought to sound Swedish was given short-term accent reduction treatment for selected front vowels (/i/, /■/, /ε/), back vowels (/u/, /■/, /o/), and inter-dental consonants (/θ/, /■/). Therapy consisted of structured practice on word lists containing targeted phonemes. A list of compound nouns was included as untreated control items. A multiple-baseline across behaviors design was used to determine treatment efficacy. Probes were included for response generalization, maintenance, and long-term retention. Digitally-recorded productions by the FAS talker were played in randomized order to a phonetically-trained listener who rated a targeted sound in each word as foreign-sounding or not. Results indicated highly variable performance on treated items, generalization probes, and control probes throughout the course of the experiment, with no apparent acquisition or maintenance resulting from the intervention. These findings suggest that structured intervention techniques were not successful for this patient.
Acoustic emission mechanism from scuba diving equipment
Authors: Donskoy Dimitri M.
Published: January 2007

The energy-based analysis of the underwater acoustic emission mechanism from scuba diving equipment shows that the primary originating source of acoustic emission is turbulent air flow pressure fluctuations during the inhale phase of breathing. A scuba air tank contains a substantial amount of energy in the form of compressed air. This energy is gradually released as the air is consumed during breathing. As air expands from high pressure in the tank to lower pressure supplied to the second stage regulator, it rushes through the first stage regulator’s valve and channels creating highly turbulent air flow. The turbulent pressure fluctuations excite structural vibrations of the valve housing and connected air tank and piping in a very broad frequency range spreading above 100 kHz. In turn, vibration causes sound emission into surrounding medium (water). [Work supported by ONR].
Hygromycin B Inhibition of Protein Synthesis and Ribosome Biogenesis in
Escherichia coli
Authors: McGaha Susan M. , Champney W. Scott
Published: January 2007

The aminoglycoside antibiotic hygromycin B was examined in
Escherichia coli
cells for inhibitory effects on translation and ribosomal-subunit formation. Pulse-chase labeling experiments were performed, which verified lower rates of ribosomal-subunit synthesis in drug-treated cells. Hygromycin B exhibited a concentration-dependent inhibitory effect on viable-cell numbers, growth rate, protein synthesis, and 30S and 50S subunit formation. Unlike other aminoglycosides, hygromycin B was a more effective inhibitor of translation than of ribosomal-subunit formation in
E. coli
. Examination of total RNA from treated cells showed an increase in RNA corresponding to a precursor to the 16S rRNA, while mature 16S rRNA decreased. Northern hybridization to rRNA in cells treated with hygromycin B showed that RNase II- and RNase III-deficient strains of
E. coli
accumulated 16S rRNA fragments upon treatment with the drug. The results indicate that hygromycin B targets protein synthesis and 30S ribosomal-subunit assembly.
DEVELOPMENT OF SIMPLE FUZZY LOGIC CONTROLLER FOR EXTENDED PERIOD-ZCS/ZVS-QUASI RESONANT CONVERTER: DESIGN, SIMULATION, AND EXPERIMENTATION
Authors: ARULSELVI S. , GOVINDARAJAN UMA
Published: January 2007

This paper describes the design and implementation of simple fuzzy logic controller (SFLC) for a nonlinear quasi-resonant converter (QRC). It is shown that the two-dimensional rule table of conventional FLCs (CFLCs) used in power converters can be reduced to one-dimensional rule table using SFLC. The proposed SFLC reduces the memory space and computing time of the fuzzy algorithm. The tuning of scaling factors and the generation of fuzzy rules are also easier when compared with CFLC. As a result, realizing SFLC in a Microcontroller or Digital Signal Processor (DSP) is made simple. The proposed controller structure is universal and it can be directly applied to any of the dc–dc converter topologies. In this paper, the application of SFLC is successfully verified for the voltage control of Extended Period (EP)-ZCS/ZVS-QRC through simulation and experimental studies using TMS320F2407A Processor. The ability of SFLC, compared to CFLC, to achieve good transient response for load variations and supply disturbances is demonstrated.
HIGH-FREQUENCY LINEAR MULTIPLE-OUTPUT CMOS TRANSCONDUCTANCE AMPLIFIER FOR CURRENT-MODE FILTERS
Authors: SU HSIAO WEI , SUN YICHUANG
Published: January 2007

A high-frequency highly linear tunable CMOS multiple-output operational transconductance amplifier (MO-OTA) for fully balanced current-mode OTA and capacitor (OTA-C) filters is presented. The MO-OTA is based on the cross-coupled pairs at the input and provides two pairs of differential outputs. A simple common-mode feedback (CMFB) circuit to stabilize the DC output levels of the MO-OTA is also proposed and two such CMFB circuits are used by the MO-OTA. The proposed MO-OTA is suitable for relatively low voltage (2.5 V) applications as its circuit has only two MOS transistors between the supply and ground rails. Simulated in a TSMC 0.25 μm CMOS process using PSpice, the MO-OTA has at least ± 0.3 V linear differential input signal swing with a single 2.5 V power supply and operates up to 1 GHz frequency. The MO-OTA has a THD less than -46 dB for a differential input voltage of 0.9 Vp-p at 10 MHz, dynamic range (DR) at THD = -46 dB is over 50 dB, and power consumption (with the common-mode feedback circuit) is below 8 mW for the whole tuning range. A fully balanced multiple loop feedback current-mode OTA-C filter example using the proposed MO-OTA is presented. This example also shows that the current-mode follow-the-leader-feedback (FLF) structure can achieve good performances for OTA-C filter design.
Adequate oral threonine is critical for mucin production and gut function in neonatal piglets
Authors: Law Garson K. , Bertolo Robert F. , Adjiri-Awere Alfred , Pencharz Paul B. , Ball Ronald O.
Published: January 2007

In previous experiments, we found that the threonine requirement of neonatal piglets fed parenterally was 40% of that when fed intragastrically; we hypothesized that much of the oral supply of threonine is being used for mucin production. To investigate this hypothesis, intragastrically fed 2-day-old piglets were fed one of three treatments for 8 days: 1) a threonine-adequate diet (IG-A; 0.6 g threonine·kg−1·day−1 fed intragastrically); 2) a threonine-deficient diet (IG-D; 0.1 g threonine·kg−1·day−1 fed intragastrically); or 3) a threonine-deficient diet with adequate threonine delivered parenterally (IV-A; 0.5 g threonine·kg−1·day−1 fed parenterally plus 0.1 g threonine·kg−1·day−1 fed intragastrically). IG-D piglets experienced higher nitrogen excretion, higher plasma urea, and lower plasma threonine concentrations versus both of the other groups ( P < 0.05), indicating profound threonine deficiency. Mucosal mass and total crude mucin content were lower in the colons of IG-D pigs ( P < 0.05). Histopathological analysis showed lower numbers of acidic mucin-producing goblet cells in the duodenum and ileum of IG-D pigs. In IG-D pigs, acidic mucin subtypes were lower in the small intestine but higher in the colon, which corresponded with persistent diarrhea. The parenteral supply of threonine was adequate to maintain most outcome parameters, although IV-A pigs did have smaller colonic goblet cells with more acidic mucins compared with IG-A pigs. Overall, our results suggest that adequate dietary threonine was critical in the production of mucus and that a parenteral threonine supply can ameliorate most of the symptoms of oral threonine deficiency.
Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis
Authors: He Min , Horuk Richard , Moochhala Shabbir M. , Bhatia Madhav
Published: January 2007

Sepsis is a complex clinical syndrome resulting from a harmful host inflammatory response to infection. Chemokines and their receptors play a key role in the pathogenesis of sepsis. BX471 is a potent nonpeptide CC chemokine receptor-1 (CCR1) antagonist in both human and mouse. The aim of the present study was to evaluate the effect of prophylactic and therapeutic treatment with BX471 on cecal ligation and puncture-induced sepsis in the mouse and to investigate the underlying mechanisms. In sepsis induced by cecal ligation and puncture, treatment with BX471 significantly protected mice against lung and liver injury by attenuating MPO activity, an indicator of neutrophil recruitment in lungs and livers and attenuating lung and liver morphological changes in histological sections. Blocking CCR1 by BX471 also downregulated ICAM-1, P-selectin, and E-selectin expression at mRNA and protein levels in lungs and livers compared with placebo-treated groups. These findings suggest that blockage of CCR1 by specific antagonist may represent a promising strategy to prevent disease progression in sepsis.
IL-1β inhibits intestinal smooth muscle proliferation in an organ culture system: involvement of COX-2 and iNOS induction in muscularis resident macrophages
Authors: Ohama Takashi , Hori Masatoshi , Momotani Eiichi , Elorza Margaret , Gerthoffer William T. , Ozaki Hiroshi
Published: January 2007

Intestinal inflammation causes hyperplasia of smooth muscle that leads to thickening of the smooth muscle layer, resulting in dysmotility. IL-1β is a proinflammatory cytokine that plays a central role in intestinal inflammation. In this study, to evaluate the effect of IL-1β on proliferation of ileal smooth muscle cells in vivo, we utilized an organ culture system. When rat ileal smooth muscle tissue was cultured under serum-free conditions for 3 days, most smooth muscle cells maintained their arrangement and kept their contractile phenotype. When 10% FBS was added, an increased number of smooth muscle cells per unit area was observed. Moreover, immunohistochemical staining for PCNA demonstrated that FBS induced proliferation of smooth muscle cells. IL-1β inhibited the proliferative effect of FBS. Furthermore, IL-1β upregulated inducible nitric oxide (NO) synthase and cyclooxygenase-2 mRNA and protein and thus stimulated NO and PGE2productions. Moreover, exogenously applied NO and PGE2inhibited the increase of bromodeoxyuridine-positive cells stimulated with FBS. Immunostaining revealed that the majority of cyclooxygenase-2 and inducible NO synthase was located in the dense network of macrophages resident in the muscularis, which were immunoreactive to ED2. Based on these findings, IL-1β acts as an anti-proliferative mediator, which acts indirectly through the production of PGE2and NO from resident macrophage within ileal smooth muscle tissue.
Nitric oxide-dependent and -independent mechanisms are involved in TNF-α-induced depression of cardiac myocyte contractility
Authors: Kumar Anand , Paladugu Bhanu , Mensing Joel , Kumar Aseem , Parrillo Joseph E.
Published: January 2007

Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This response is mediated, in part, through circulating TNF-α-induced, nitric oxide-dependent, depression of basal myocyte contractility. Other mechanisms of early myocardial dysfunction involving decreased response to adrenergic stimulation may exist. This study evaluated the presence and nitric oxide dependence of impaired adrenergic response to TNF-α in in vitro cardiac myocytes. The contraction of electrically paced neonatal rat cardiac myocytes in tissue culture was quantified using a closed-loop video tracking system. TNF-α induced depression of baseline contractility over the first 20 min of cardiac myocyte exposure. This effect was blocked by N-methyl-arginine (NMA), a nitric oxide synthase inhibitor, in all studies. Contractile and cAMP response to increasing concentrations of isoproterenol was deficient in cardiac myocytes exposed to TNF-α regardless of the presence of NMA. In contrast, increasing concentrations of forskolin (a direct stimulant of adenylate cyclase) and dibutyryl cAMP (a metabolically active membrane-soluble analog of cAMP) completely reversed TNF-α-mediated depression, though only in the presence of NMA. Forskolin-stimulated cAMP generation remained intact regardless of NMA. Increasing concentrations of exogenous calcium chloride, unlike other inotropic agents, corrected TNF-α-mediated defects of contractility independent of the presence of NMA. These data suggest that TNF-α exposure is associated with a second nitric oxide-independent but calcium-dependent early depressant mechanism that is manifested by reduced contractile and cAMP response to β-adrenergic stimulation.
Metabolic rate does not scale with body mass in cultured mammalian cells
Authors: Brown Melanie F. , Gratton Tyson P. , Stuart Jeffrey. A.
Published: January 2007

The allometric scaling of metabolic rate with organism body mass can be partially accounted for by differences in cellular metabolic rates. For example, hepatocytes isolated from horses consume almost 10-fold less oxygen per unit time as mouse hepatocytes [Porter and Brand, Am J Physiol Regul Integr Comp Physiol 269: R226–R228, 1995]. This could reflect a genetically programmed, species-specific, intrinsic metabolic rate set point, or simply the adaptation of individual cells to their particular in situ environment (i.e., within the organism). We studied cultured cell lines derived from 10 mammalian species with donor body masses ranging from 5 to 600,000 g to determine whether cells propagated in an identical environment (media) exhibited metabolic rate scaling. Neither metabolic rate nor the maximal activities of key enzymes of oxidative or anaerobic metabolism scaled significantly with donor body mass in cultured cells, indicating the absence of intrinsic, species-specific, cellular metabolic rate set points. Furthermore, we suggest that changes in the metabolic rates of isolated cells probably occur within 24 h and involve a reduction of cellular metabolism toward values observed in lower metabolic rate organisms. The rate of oxygen delivery has been proposed to limit cellular metabolic rates in larger organisms. To examine the effect of oxygen on steady-state cellular respiration rates, we grew cells under a variety of physiologically relevant oxygen regimens. Long-term exposure to higher medium oxygen levels increased respiration rates of all cells, consistent with the hypothesis that higher rates of oxygen delivery in smaller mammals might increase cellular metabolic rates.
Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers
Authors: Stocker Claire J. , Wargent Ed , O'Dowd Jacqueline , Cornick Claire , Speakman John R. , Arch Jonathan R. S. , Cawthorne Michael A.
Published: January 2007

Absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. We investigated whether administration of leptin to normally nourished rats affects energy balance in their offspring. Leptin (2 mg·kg−1·day−1) was administered from day 14 of pregnancy and throughout lactation. Male and female offspring were fed either on chow or on high-fat diets that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age. Treatment of the dams with leptin prevented diet-induced increases in the rate of weight gain, retroperitoneal fat pad weight, area under the intraperitoneal glucose tolerance curve, and fasting plasma insulin concentration in female offspring. In the male offspring, the diet-induced increase in weight gain was prevented and increased fat pad weight was reduced. Energy intake per rat was higher in response to the obesogenic diet in male offspring of saline-treated but not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring. Energy expenditure at 3 mo of age was higher for a given body weight in female offspring of leptin-treated compared with saline-treated dams when these animals were fed on the obesogenic diet. A similar trend was seen for male rats fed on the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.
Glutamine's protection against sepsis and lung injury is dependent on heat shock protein 70 expression
Authors: Singleton Kristen D. , Wischmeyer Paul E.
Published: January 2007

Glutamine (GLN) has been shown to protect against inflammatory injury and illness in experimental and clinical settings. The mechanism of this protection is unknown; however, laboratory and clinical trial data have indicated a relationship between GLN-mediated protection and enhanced heat shock protein 70 (HSP70) expression. The aim of this study was to examine the hypothesis that GLN's beneficial effect on survival, tissue injury, and inflammatory response after inflammatory injury is dependent on HSP70 expression. Mice with a specific deletion of the HSP70 gene underwent cecal ligation and puncture (CLP)-induced sepsis and were treated with GLN (0.75 g/kg) or a saline placebo 1 h post-CLP. Lung tissue NF-κB activation, inflammatory cytokine response, and lung injury were assessed post-CLP. Survival was assessed for 5 days post-CLP. Our results indicate that GLN administration improved survival in Hsp70+/+mice vs. Hsp70+/+mice not receiving GLN; however, GLN exerted no survival benefit in Hsp70−/−mice. This was accompanied by a significant decrease in lung injury, attenuation of NF-κB activation, and proinflammatory cytokine expression in GLN-treated Hsp70+/+mice vs. Hsp70+/+mice not receiving GLN. In the Hsp70−/−mice, GLN's attenuation of lung injury, NF-κB activation, and proinflammatory cytokine expression was lost. These results confirm our hypothesis that HSP70 expression is required for GLN's effects on survival, tissue injury, and the inflammatory response after global inflammatory injury.
Influence of acute inspiratory loading upon diaphragm motor-evoked potentials in healthy humans
Authors: Ross Emma Z. , Nowicky Alexander V. , McConnell Alison K.
Published: January 2007

Acute prior activity of the inspiratory muscles can enhance inspiratory muscle strength and reduce effort perception during subsequent inspiratory efforts. However, the mechanisms subserving these changes are poorly understood. Responses to magnetic stimulation in 10 subjects were studied after an acute bout of nonfatiguing inspiratory muscle loading (IML), corresponding to 40% of subjects’ initial maximal inspiratory pressure (MIP), and after an acute bout of nonloaded, forced inspiration (NLF). Motor-evoked potentials elicited by cortical stimulation (MEPc) and by phrenic nerve stimulation (MEPp) were recorded transcutaneously from the diaphragm before, immediately after, and 15 min after two sets of 30 inspiratory efforts, at rest and during an MIP effort. After IML, MIP increased to 113 ± 3% (SE) of baseline and diaphragm MEPp (during MIP) significantly increased (129 ± 10% of baseline). Diaphragmatic MEPc (during MIP), expressed as a percentage of maximal MEPp, decreased after IML (from 29 ± 9% to 20 ± 6%; P = 0.017) and after NLF (from 43 ± 5% to 31 ± 5%; P = 0.032). Observations from the biceps brachi demonstrated that changes after IML and NLF were specific to the inspiratory muscle, since no significant changes were observed in biceps force generation or in MEPp or MEPc amplitudes. These data indicate that after IML increased global inspiratory strength is accompanied by increased peripheral excitability and by a dampening of corticospinal excitability of the diaphragm.
Sex Determination and Gonadal Development in Mammals
Authors: Wilhelm Dagmar , Palmer Stephen , Koopman Peter
Published: January 2007

Arguably the most defining moment in our lives is fertilization, the point at which we inherit either an X or a Y chromosome from our father. The profoundly different journeys of male and female life are thus decided by a genetic coin toss. These differences begin to unfold during fetal development, when the Y-chromosomal Sry (“sex-determining region Y”) gene is activated in males and acts as a switch that diverts the fate of the undifferentiated gonadal primordia, the genital ridges, towards testis development. This sex-determining event sets in train a cascade of morphological changes, gene regulation, and molecular interactions that directs the differentiation of male characteristics. If this does not occur, alternative molecular cascades and cellular events drive the genital ridges toward ovary development. Once testis or ovary differentiation has occurred, our sexual fate is further sealed through the action of sex-specific gonadal hormones. We review here the molecular and cellular events (differentiation, migration, proliferation, and communication) that distinguish testis and ovary during fetal development, and the changes in gene regulation that underpin these two alternate pathways. The growing body of knowledge relating to testis development, and the beginnings of a picture of ovary development, together illustrate the complex mechanisms by which these organ systems develop, inform the etiology, diagnosis, and management of disorders of sexual development, and help define what it is to be male or female.
Mitochondrial Membrane Permeabilization in Cell Death
Authors: Kroemer Guido , Galluzzi Lorenzo , Brenner Catherine
Published: January 2007

Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.
Transcriptional Control of Lung Morphogenesis
Authors: Maeda Yutaka , Davé Vrushank , Whitsett Jeffrey A.
Published: January 2007

The vertebrate lung consists of multiple cell types that are derived primarily from endodermal and mesodermal compartments of the early embryo. The process of pulmonary organogenesis requires the generation of precise signaling centers that are linked to transcriptional programs that, in turn, regulate cell numbers, differentiation, and behavior, as branching morphogenesis and alveolarization proceed. This review summarizes knowledge regarding the expression and proposed roles of transcription factors influencing lung formation and function with particular focus on knowledge derived from the study of the mouse. A group of transcription factors active in the endodermally derived cells of the developing lung tubules, including thyroid transcription factor-1 (TTF-1), β-catenin, Forkhead orthologs (FOX), GATA, SOX, and ETS family members are required for normal lung morphogenesis and function. In contrast, a group of distinct proteins, including FOXF1, POD1, GLI, and HOX family members, play important roles in the developing lung mesenchyme, from which pulmonary vessels and bronchial smooth muscle develop. Lung formation is dependent on reciprocal signaling among cells of both endodermal and mesenchymal compartments that instruct transcriptional processes mediating lung formation and adaptation to breathing after birth.
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Authors: Bedard Karen , Krause Karl-Heinz
Published: January 2007

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the phagocyte NADPH oxidase itself (NOX2/gp91phox), the homologs are now referred to as the NOX family of NADPH oxidases. These enzymes share the capacity to transport electrons across the plasma membrane and to generate superoxide and other downstream reactive oxygen species (ROS). Activation mechanisms and tissue distribution of the different members of the family are markedly different. The physiological functions of NOX family enzymes include host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. NOX enzymes also contribute to a wide range of pathological processes. NOX deficiency may lead to immunosuppresion, lack of otoconogenesis, or hypothyroidism. Increased NOX actvity also contributes to a large number or pathologies, in particular cardiovascular diseases and neurodegeneration. This review summarizes the current state of knowledge of the functions of NOX enzymes in physiology and pathology.
The role of autophagy in the death of L1210 leukemia cells initiated by the new antitumor agents, XK469 and SH80
Authors: Kessel David , Reiners John J. , Hazeldine Stuart T. , Polin Lisa , Horwitz Jerome P.
Published: January 2007

The phenoxypropionic acid derivative 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469) and an analogue termed 2-{4-[(7-bromo-2-quinalinyl)oxy]phenoxy}propionic acid (SH80) can eradicate malignant cell types resistant to many common antitumor agents. Colony formation assays indicated that a 24 h exposure of L1210 cells to XK469 or SH80 inhibited clonogenic growth with CI90 values of 10 and 13 μmol/L, respectively. This effect was associated with G2-M arrest and the absence of any detectable markers of apoptosis (i.e., plasma membrane blebbing, procaspase 3 activation, loss of mitochondrial membrane potential, and formation of condensed chromatin). Drug-treated cells increased in size and eventually exhibited the characteristics of autophagy (i.e., appearance of autophagosomes and conversion of microtubule-associated protein light chain 3-I to 3-II). The absence of apoptosis was not related to an inhibition of the apoptotic program. Cultures treated with XK469 or SH80 readily underwent apoptosis upon exposure to the Bcl-2/Bcl-xL antagonist ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate. Continued incubation of drug-treated cells led to a reciprocal loss of large autophagic cells and the appearance of smaller cells that could not be stained with Höechst dye HO33342, had a chaotic morphology, were trypan blue–permeable, and lacked mitochondrial membrane potential. L1210 cells cotreated with the phosphatidylinositol-3-kinase inhibitor wortmannin, or having reduced Atg7 protein content, underwent G2-M arrest, but not autophagy, following XK469 treatment. Hence, the therapeutic actions of XK469/SH80 with L1210 cultures reflect both the initiation of a cell cycle arrest as well as the initiation of autophagy. [Mol Cancer Ther 2007;6(1):370–9]