bluuebunny/crossref_metadata_2025 huggingface dataset:
Central giant cell granuloma of the jaws: assessment of cell cycle proteins
Authors: Kauzman Adel , Li Shu Qiu , Bradley Grace , Bell Robert S. , Wunder Jay S. , Kandel Rita
Published: February 2004

Background:  Several reports have demonstrated the presence of a high proliferative activity in central giant cell granuloma, raising the possibility that deregulation of the cell cycle may contribute to its pathogenesis. As we identified alterations of cyclin D1 in giant cell tumor of bone, and as there are histologic similarities between central giant cell granuloma and giant cell tumor, we assessed jaw lesions for the presence of similar alterations.

Methods:  Formalin‐fixed, paraffin‐embedded tissue from 29 cases of central giant cell granuloma was assessed for the expression of cyclin D1, cyclin B1, and MIB‐1 (Ki‐67) using immunohistochemistry. In addition, differential polymerase chain reaction (PCR) was used to determine whether there was cyclin D1 gene amplification.

Results:  The cyclin D1 gene copy number appeared to be minimally elevated in 31% of the cases. Cyclin D1 protein overexpression was observed in 28 of 29 cases (96.5%). Immunostaining was present predominantly in the nuclei of the giant cells. Cyclin B1 and MIB‐1 immunoreactivity was restricted to the mononuclear cells with no staining present in the giant cells.

Conclusions:  Cyclin D1 protein overexpression may be involved in the formation of the giant cells and the pathogenesis of central giant cell granuloma. As the distribution of immunostaining is identical to that observed in giant cell tumor of bone, our results support the possibility that central giant cell granuloma of the jaws and giant cell tumor of bone represent a similar disease process that clinically and histologically may have somewhat different features because of differences in the anatomical site of involvement.
Immunohistochemical localization of tissue‐type plasminogen activator and type I plasminogen activator inhibitor in radicular cysts
Authors: Tsai Chung‐Hung , Weng Sheng‐Feng , Yang Li‐Chiu , Huang Fu‐Mei , Chen Yi‐Juai , Chang Yu‐Chao
Published: February 2004

Background:  The plasminogen/plasmin proteolytic system participates in a wide variety of extracellular matrix degradation. Detailed knowledge of plasminogen activators (PAs) and their inhibitors may be important for understanding the pathogenesis of radicular cysts. The purpose of this study was to investigate the in situ localization of tissue‐type PA (t‐PA) and type I PA inhibitor (PAI‐1) in radicular cysts.

Methods:  Thirty formalin‐fixed, paraffin‐embedded specimens of radicular cysts were examined using immunohistochemistry. In addition, another section from each radicular cyst specimen was stained with hematoxylin and eosin to assess the presence of inflammatory infiltrates. Differences in t‐PA and PAI‐1 expression between tissues with low and high levels of inflammation were subsequently analyzed using Fisher's exact test.

Results:  Both t‐PA‐ and PAI‐1‐positive cells were detected in the lining epithelium, connective tissue, inflammatory infiltrates, and endothelium. In addition, the t‐PA signal was mainly expressed in epithelial cells. However, the PAI‐1 signal was mainly expressed in fibroblasts. Moreover, significantly greater t‐PA as well as PAI‐1 expression was noted in radicular cysts with high levels of inflammation as compared to tissues with low levels of inflammatory cell infiltrates (P < 0.05).

Conclusions:  The present study confirms earlier indications of local production of PA and its inhibitor in radicular cysts. In addition, this study further shows the tissue localization of the antigens for t‐PA as well as PAI‐1, and demonstrates that the expression of both t‐PA and PAI‐1 increases with the grade of inflammation in radicular cysts.
Web‐based Assessment and Test Analyses (WATA) system: development and evaluation
Authors: Wang T. H. , Wang K. H. , Wang W. L. , Huang S. C. , Chen S. Y.
Published: February 2004

This study introduces the development of a Web‐based assessment system, the Web‐based Assessment and Test Analyses (WATA) system, and examines its impacts on teacher education. The WATA system is a follow‐on system, which applies the Triple‐A Model (assembling, administering, and appraising). Its functions include (1) an engine for teachers to administer and manage testing, (2) an engine for students to apply tests, and (3) an engine for generating test results and analyses for teachers. Two studies were undertaken to assess the usefulness and potential benefits of the WATA system for teacher education. In the first study, 47 in‐service teachers were asked to assess the functions of the WATA system. The results indicated that they were satisfied with the Triple‐A Model of the WATA system. In the second study, 30 pre‐service teachers were required to use the WATA system during the teacher‐training program. After 4 months of experience in using the WATA system, the pre‐service teachers' perspectives of assessment have been changed significantly. The findings of these two studies might provide some guidance to help those who are interested in the development of Web‐based assessment and intend to infuse information technology into teacher education.
A structured dialogue tool for argumentative learning
Authors: Hirsch L. , Saeedi M. , Cornillon J. , Litosseliti L.
Published: February 2004

This paper presents a structured environment for Computer‐Supported Collaborative Argumentation, which we call the Argumentative Learning Experience (ALEX). The system aims to improve understanding of argumentation and to widen and deepen the space of debate among 16–18‐year‐old students. To use ALEX users make arguments by selecting and completing partial sentences. An automatically created visual representation of the argument is displayed and personalised advice on the argumentation is provided to each user.
Political Institutions and Policy Volatility
Authors: Henisz Witold Jerzy
Published: February 2004

Checks and balances that limit the discretion of policy‐makers reduce the volatility of government expenditure and revenue. While this assumption is at the heart of a large body of empirical work, the association between political institutions and policy volatility has itself been the focus of only limited empirical testing. The results presented here support the existence of this link, allow for a comparison between two prominent measures of checks and balances and provide insight into the relative impact of checks and balances on the volatility of nine different types of fiscal policy both during times of macroeconomic stability and upheaval.
Intense exercise up‐regulates Na+,K+‐ATPase isoform mRNA, but not protein expression in human skeletal muscle
Authors: Murphy K. T. , Snow R. J. , Petersen A. C. , Murphy R. M. , Mollica J. , Lee J. S. , Garnham A. P. , Aughey R. J. , Leppik J. A. , Medved I. , Cameron‐Smith D. , McKenna M. J.
Published: February 2004

Characterization of expression of, and consequently also the acute exercise effects on, Na+,K+‐ATPase isoforms in human skeletal muscle remains incomplete and was therefore investigated. Fifteen healthy subjects (eight males, seven females) performed fatiguing, knee extensor exercise at ∼40% of their maximal work output per contraction. A vastus lateralis muscle biopsy was taken at rest, fatigue and 3 and 24 h postexercise, and analysed for Na+,K+‐ATPase α1, α2, α3, β1, β2 and β3 mRNA and crude homogenate protein expression, using Real‐Time RT‐PCR and immunoblotting, respectively. Each individual expressed gene transcripts and protein bands for each Na+,K+‐ATPase isoform. Each isoform was also expressed in a primary human skeletal muscle cell culture. Intense exercise (352 ± 69 s; mean ±s.e.m.) immediately increased α3 and β2 mRNA by 2.4‐ and 1.7‐fold, respectively (P < 0.05), whilst α1 and α2 mRNA were increased by 2.5‐ and 3.5‐fold at 24 h and 3 h postexercise, respectively (P < 0.05). No significant change occurred for β1 and β3 mRNA, reflecting variable time‐dependent responses. When the average postexercise value was contrasted to rest, mRNA increased for α1, α2, α3, β1, β2 and β3 isoforms, by 1.4‐, 2.2‐, 1.4‐, 1.1‐, 1.0‐ and 1.0‐fold, respectively (P < 0.05). However, exercise did not alter the protein abundance of the α1–α3 and β1–β3 isoforms. Thus, human skeletal muscle expresses each of the Na+,K+‐ATPase α1, α2, α3, β1, β2 and β3 isoforms, evidenced at both transcription and protein levels. Whilst brief exercise increased Na+,K+‐ATPase isoform mRNA expression, there was no effect on isoform protein expression, suggesting that the exercise challenge was insufficient for muscle Na+,K+‐ATPase up‐regulation.
Effect of acute and chronic ascorbic acid on flow‐mediated dilatation with sedentary and physically active human ageing
Authors: Eskurza Iratxe , Monahan Kevin D. , Robinson Jed A. , Seals Douglas R.
Published: February 2004

Peripheral conduit artery flow‐mediated dilatation decreases with ageing in humans. The underlying mechanisms and efficacy of preventive strategies are unknown. Brachial artery flow‐mediated dilatation was determined at baseline and after ascorbic acid (vitamin C) intravenous infusion and chronic supplementation (500 mg day−1 for 30 days) in three groups of healthy men: young sedentary (n= 11; 25 ± 1 years, mean ±s.e.m.), older sedentary (n= 9; 64 ± 2), and older endurance‐exercise trained (n= 9; 64 ± 2). At baseline, flow‐mediated dilatation (normalized for the hyperaemic stimulus) was ∼45% lower in the older (0.015 ± 0.001) versus young (0.028 ± 0.004) sedentary men (P < 0.01), but was preserved in older exercising men (0.028 ± 0.004). Ascorbic acid infusion increased plasma concentrations > 15‐fold in all groups and restored flow‐mediated dilatation in the sedentary older men (to 0.023 ± 0.002; P > 0.1 versus other groups), with no effects in the other two groups. Oral ascorbic acid supplementation did not affect flow‐mediated dilatation in any group. Brachial artery endothelium‐independent dilatation (sublingual nitroglycerin) did not differ among the groups at baseline nor change with ascorbic acid administration. These results provide the first evidence for an important role of oxidative stress in both the impairment in peripheral conduit artery flow‐mediated dilatation with sedentary human ageing and the preservation of flow‐mediated dilatation with physically active ageing.
Induction, modification and accumulation of HSP70s in the rat liver after acute exercise: early and late responses
Authors: González Beatriz , Manso Rafael
Published: February 2004

Liver cells synthesize HSP72, the cytosolic highly stress‐inducible member of the 70 kDa family of heat‐shock proteins (HSP70s), in response to acute exercise. This study was aimed at obtaining further insight into the physiological relevance of the hepatic stress response to exercise by investigating the induction and long‐term maintenance of increased levels of HSP70s of the HSP and glucose‐regulated protein (GRP) families, their post‐translational modifications during or after exercise and the possible relation of HSP induction to oxidative stress. In a running rat model, acute exercise activated the synthesis and accumulation of HSP72, GRP75 and GRP78 in liver cells, pointing towards a multifactorial origin of this response. A peak HSP72 accumulation was observed shortly after exercise as a result of transcriptional activation. HSP72 was reduced shortly after exercise preceding the disappearance of its mRNA. Two further waves of HSP72 accumulation peaked 8 and 48 h after exercise without transcriptional activation. A transient increase in the proportion of acidic variants of HSP72 and HSP73 was also observed shortly after exercise as a result, at least in part, of protein phosphorylation. Free and protein‐bound lipid peroxidation derivatives (TBARS) showed a tendency to increase in the early post‐exercise and the free‐to‐protein‐bound TBARS ratio decreased significantly after 2 h. During the early post‐exercise period, protein‐bound TBARS correlated positively with HSP72 and 73, but not with GRP75 or GRP78. Altogether, the reported results indicate that the early induction and post‐translational modification of HSP70s in liver cells following exercise is a preliminary step of a series of long‐lasting HSP70‐related events, possibly designed to preserve liver cell homeostasis and to help provide a concerted response of the whole organism to physical stress.
Inositol‐1,4,5‐trisphosphate‐dependent Ca2+ signalling in cat atrial excitation–contraction coupling and arrhythmias
Authors: Zima Aleksey V. , Blatter Lothar A.
Published: February 2004

Inositol‐1,4,5‐trisphosphate (IP3)‐dependent Ca2+ release represents the major Ca2+ mobilizing pathway responsible for diverse functions in non‐excitable cells. In the heart, however, its role is largely unknown or controversial. In intact cat atrial myocytes, endothelin (ET‐1) increased basal [Ca2+]i levels, enhanced action potential‐evoked [Ca2+]i transients, caused [Ca2+]i transients with alternating amplitudes (Ca2+ alternans), and facilitated spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) in the form of Ca2+ sparks and arrhythmogenic Ca2+ waves. These effects were prevented by the IP3 receptor (IP3R) blocker aminoethoxydiphenyl borate (2‐APB), suggesting the involvement of IP3‐dependent SR Ca2+ release. In saponin‐permeabilized myocytes IP3 and the more potent IP3R agonist adenophostin increased basal [Ca2+]i and the frequency of spontaneous Ca2+ sparks. In the presence of tetracaine to eliminate Ca2+ release from ryanodine receptor (RyR) SR Ca2+ release channels, IP3 and adenophostin triggered unique elementary, non‐propagating IP3R‐dependent Ca2+ release events with amplitudes and kinetics that were distinctly different from classical RyR‐dependent Ca2+ sparks. The effects of IP3 and adenophostin were prevented by heparin and 2‐APB. The data suggest that IP3‐dependent Ca2+ release increases [Ca2+]i in the vicinity of RyRs and thus facilitates Ca2+‐induced Ca2+ release during excitation–contraction coupling. It is concluded that in the adult mammalian atrium IP3‐dependent Ca2+ release enhances atrial Ca2+ signalling and exerts a positive inotropic effect. In addition, by facilitating Ca2+ release, IP3 may also be an important component in the development of Ca2+‐mediated atrial arrhythmias.
The sense of movement elicited by transcranial magnetic stimulation in humans is due to sensory feedback
Authors: Ellaway P. H. , Prochazka A. , Chan M. , Gauthier M. J.
Published: February 2004

It has been claimed that transcranial magnetic stimulation (TMS) of the human motor cortex can produce a sense of movement of the contralateral hand, even when the hand is paralysed. The sense of movement was equated with a ‘corollary discharge’, a nulling mechanism originally posited for maintaining constancy of the visual field during eye movements. Our experiments were designed to test whether the sensation that accompanies TMS‐evoked finger movements is generated centrally or whether it arises as a result of sensory feedback. Matched twitches of the left and right fingers were elicited either by bilateral electrical stimulation of forearm extensor muscles, or by a combination of TMS of left motor cortex (eliciting twitches of the right forefinger), and electrical stimulation of the left forearm muscles (eliciting twitches of the left forefinger). The time interval between stimuli activating left and right twitches was varied randomly (range ± 90 ms) from trial to trial. Subjects reported whether they sensed that the left or the right movement occurred first, or if they could detect no difference. The left and right movements evoked by bilateral electrical stimulation of muscles were sensed as near simultaneous when there was zero delay between them. When TMS was applied in conjunction with unilateral muscle stimulation, the TMS‐evoked movement was felt, on average, 20 ms after the movement evoked by muscle stimulation. Similar results were obtained when the skin under the cathodal electrodes was anaesthetized. Since the TMS‐evoked movements were felt later rather than earlier than the electrically evoked movements, the results do not support the idea that the sensation of movement was elicited centrally by TMS. Rather, they favour sensory feedback as the source of the sense of movement. The earlier perception of electrically evoked versus TMS‐evoked movements was probably due to earlier sensory responses in the periphery rather than a suppression of the excitability of somatosensory cortex.
Experimental study of the Doppler shift generated by a vibrating scatterer
Authors: Wunenburger Régis , Mujica Nicolás , Fauve Stéphan
Published: February 2004

We report an experimental study of the backscattering of a sound wave of frequency f by a surface vibrating harmonically at frequency F (F≪f) and amplitude A in the regime where the Doppler effect overcomes bulk nonlinear effects. When the duration t0 of the analyzed time series of the scattered wave is small compared to the vibration period, the power spectrum of the backscattered wave is proportional to the probability density function of the scatterer velocity, which presents two peaks shifted from f by roughly 2fAΩ/c (Ω=2πF). On the contrary, when t0≫F−1, sidebands at frequencies f±nF (n integer) appear in the power spectrum, which are due to the phase modulation of the backscattered wave induced by its reflection on a moving boundary. We use the backscattered power spectrum to validate the phase modulation theory of the Doppler effect in the latter case for 2kA≪1 and 2kA≳1 (k=2πf/c, where c is the wave velocity) and we test the validity of an acoustic nonintrusive estimator of A as a function of power spectrum bandwidth and of A itself.
Rayleigh–Ritz calculation of the resonant modes of a solid parallelepiped in a pressurizing fluid
Authors: Beck D. E.
Published: February 2004

Resonant ultrasound spectroscopy relies on comparisons of experimentally determined vibrational spectra to theoretically computed spectra for the extraction of the elastic moduli of the solid samples. To determine the pressure dependence of these moduli, resonant spectra are taken for samples pressurized by a surrounding gas and knowledge of the contribution of the surface loading of the sample by the gas is needed in order to extract the intrinsic pressure dependence of the moduli. To facilitate the required comparisons, a Rayleigh–Ritz variational calculation of the vibrational spectrum is formulated which includes the loading of the solid by the pressurizing fluid. This formalism is used to compute the effect of gas loading on the vibrational spectrum of an isotropic, solid parallelepiped.
Longitudinal surveys on effects of changes in road traffic noise—annoyance, activity disturbances, and psycho-social well-being
Authors: Öhrström Evy
Published: February 2004

The adverse effects of long-term exposure to a high volume of road traffic were studied in socio-acoustic surveys in 1997 and in 1999 after a substantial reduction in road traffic. The results obtained in 1997 showed a similar response pattern as in previously performed studies in the area in 1986 [Öhrström, J. Sound Vib. 122, 277–290 (1989)]. In 1999, road traffic had been reduced from 25 000 to 2400 vehicles per day, and this resulted not only in a large decrease in annoyance and activity disturbances, but also in a better general well-being. The results suggest that a reduction in both noise and other pollutants from road traffic contribute to these effects. To be able to use the outdoor environment and to have the possibility to keep windows open is essential for general well-being and daily behavior, which implies that access both to quiet indoor and outdoor sections of the residency is of importance for achievement of a healthy sound environment. More knowledge of long-term health consequences of exposure to noise and simultaneous pollutants from road traffic is needed. Studies should focus more on “softer” health outcomes and well-being than hitherto and preferably be performed in connection with traffic abatement measures.
Experimental validation of a nonparametric probabilistic model of nonhomogeneous uncertainties for dynamical systems
Authors: Chebli Hamid , Soize Christian
Published: February 2004

The paper deals with an experimental validation of a nonparametric probabilistic model of nonhomogeneous uncertainties for dynamical systems. The theory used, recently introduced, allows model uncertainties and data uncertainties to be simultaneously taken into account. An experiment devoted to this validation was specifically developed. The experimental model is constituted of two simple dural rectangular plates connected together with a complex joint. In the mean mechanical model, the complex joint, which is constituted of two additional plates attached with 40 screw-bolts, is modeled by a homogeneous orthotropic continuous plate with constant thickness, as usual. Consequently, the mean model introduces a region (the joint) which has a high level of uncertainties. The objective of the paper is to present the experiment and the comparisons of the theoretical prediction with the experiments.
Coherence function and mean field of plane and spherical sound waves propagating through inhomogeneous anisotropic turbulence
Authors: Ostashev Vladimir E. , Wilson D. Keith
Published: February 2004

Inhomogeneity and anisotropy are intrinsic characteristics of daytime and nighttime atmospheric turbulence. For example, turbulent eddies are often stretched in the direction of the mean wind, and the turbulence statistics depends on the height above the ground. Recent studies have shown that the log-amplitude and phase fluctuations of plane and spherical sound waves are significantly affected by turbulence inhomogeneity and anisotropy. The present paper is devoted to studies of the mean sound field and the coherence functions of plane and spherical sound waves propagating through inhomogeneous anisotropic turbulence with temperature and velocity fluctuations. These statistical moments of a sound field are important in many practical applications, e.g., for source detection, ranging, and recognition. Formulas are derived for the mean sound field and coherence function of initially arbitrary waveform. Using the latter formula, we also obtained formulas for the coherence functions of plane and spherical sound waves. All these formulas coincide with those known in the literature for two limiting cases: homogeneous isotropic turbulence with temperature and wind velocity fluctuations, and inhomogeneous anisotropic turbulence with temperature fluctuations only. Using the formulas obtained, we have numerically shown that turbulence inhomogeneity significantly affects the coherence functions of plane and spherical sound waves.
Acoustical wave propagator for time-domain flexural waves in thin plates
Authors: Peng S. Z. , Pan J.
Published: February 2004

In this paper, an explicit acoustical wave propagator technique is introduced to describe the time-domain evolution of acoustical waves in two-dimensional plates. A combined scheme with Chebyshev polynomial expansion and fast Fourier transformation is used to implement the operation of the acoustical wave propagator. Through this operation, the initial wave packet at t=0 is mapped into the wave packet at any instant t>0. By comparison of the results of the exact analytical solution and the Euler numerical method, we find that this new Chebyshev–Fourier scheme is highly accurate and computationally effective in predicting the acoustical wave propagation in thin plates. This method offers an opportunity for future study of dynamic stress concentration and time-domain energy flow in coupled structures.
Wideband RELAX and wideband CLEAN for aeroacoustic imaging
Authors: Wang Yanwei , Li Jian , Stoica Petre , Sheplak Mark , Nishida Toshikazu
Published: February 2004

Microphone arrays can be used for acoustic source localization and characterization in wind tunnel testing. In this paper, the wideband RELAX (WB-RELAX) and the wideband CLEAN (WB-CLEAN) algorithms are presented for aeroacoustic imaging using an acoustic array. WB-RELAX is a parametric approach that can be used efficiently for point source imaging without the sidelobe problems suffered by the delay-and-sum beamforming approaches. WB-CLEAN does not have sidelobe problems either, but it behaves more like a nonparametric approach and can be used for both point source and distributed source imaging. Moreover, neither of the algorithms suffers from the severe performance degradations encountered by the adaptive beamforming methods when the number of snapshots is small and/or the sources are highly correlated or coherent with each other. A two-step optimization procedure is used to implement the WB-RELAX and WB-CLEAN algorithms efficiently. The performance of WB-RELAX and WB-CLEAN is demonstrated by applying them to measured data obtained at the NASA Langley Quiet Flow Facility using a small aperture directional array (SADA). Somewhat surprisingly, using these approaches, not only were the parameters of the dominant source accurately determined, but a highly correlated multipath of the dominant source was also discovered.
The benefit of binaural hearing in a cocktail party: Effect of location and type of interferer
Authors: Hawley Monica L. , Litovsky Ruth Y. , Culling John F.
Published: February 2004

The “cocktail party problem” was studied using virtual stimuli whose spatial locations were generated using anechoic head-related impulse responses from the AUDIS database [Blauert et al., J. Acoust. Soc. Am. 103, 3082 (1998)]. Speech reception thresholds (SRTs) were measured for Harvard IEEE sentences presented from the front in the presence of one, two, or three interfering sources. Four types of interferer were used: (1) other sentences spoken by the same talker, (2) time-reversed sentences of the same talker, (3) speech-spectrum shaped noise, and (4) speech-spectrum shaped noise, modulated by the temporal envelope of the sentences. Each interferer was matched to the spectrum of the target talker. Interferers were placed in several spatial configurations, either coincident with or separated from the target. Binaural advantage was derived by subtracting SRTs from listening with the “better monaural ear” from those for binaural listening. For a single interferer, there was a binaural advantage of 2–4 dB for all interferer types. For two or three interferers, the advantage was 2–4 dB for noise and speech-modulated noise, and 6–7 dB for speech and time-reversed speech. These data suggest that the benefit of binaural hearing for speech intelligibility is especially pronounced when there are multiple voiced interferers at different locations from the target, regardless of spatial configuration; measurements with fewer or with other types of interferers can underestimate this benefit.
A beam tracing method for interactive architectural acoustics
Authors: Funkhouser Thomas , Tsingos Nicolas , Carlbom Ingrid , Elko Gary , Sondhi Mohan , West James E. , Pingali Gopal , Min Patrick , Ngan Addy
Published: February 2004

A difficult challenge in geometrical acoustic modeling is computing propagation paths from sound sources to receivers fast enough for interactive applications. This paper describes a beam tracing method that enables interactive updates of propagation paths from a stationary source to a moving receiver in large building interiors. During a precomputation phase, convex polyhedral beams traced from the location of each sound source are stored in a “beam tree” representing the regions of space reachable by potential sequences of transmissions, diffractions, and specular reflections at surfaces of a 3D polygonal model. Then, during an interactive phase, the precomputed beam tree(s) are used to generate propagation paths from the source(s) to any receiver location at interactive rates. The key features of this beam tracing method are (1) it scales to support large building environments, (2) it models propagation due to edge diffraction, (3) it finds all propagation paths up to a given termination criterion without exhaustive search or risk of under-sampling, and (4) it updates propagation paths at interactive rates. The method has been demonstrated to work effectively in interactive acoustic design and virtual walkthrough applications.
Transient energy exchange between a primary structure and a set of oscillators: Return time and apparent damping
Authors: Carcaterra Antonio , Akay Adnan
Published: February 2004

In this paper we examine the conditions that influence the return time, the time it takes before energy returns from a set of satellite oscillators attached to a primary structure. Two methods are presented to estimate the return time. One estimate is based on an analysis of the reaction force on a rigid base by a finite number of oscillators as compared with an infinite number of continuously distributed oscillators. The result gives a lower-bound estimate for the return time. A more accurate estimation results from considering the dynamic behavior of a set of oscillators as waves in a waveguide. Such an analogy explains energy flow between a primary structure and the oscillators in terms of pseudowaves and shows that a nonlinear frequency distribution of the oscillators leads to pseudodispersive waves. The resulting approximate expressions show the influence of the natural frequency distribution within the set of oscillators, and of their number, on the return time as compared with the asymptotic case of a continuous set with infinite oscillators. In the paper we also introduce a new method based on a Hilbert envelope to estimate the apparent damping loss factor of the primary structure during the return time considering transient energy flow from the primary structure before any energy reflects back from the attached oscillators. The expressions developed for return time and damping factor show close agreement with direct numerical simulations. The paper concludes with a discussion of the return time and its relation to apparent damping and optimum frequency distribution within a set of oscillators that maximize these quantities.
Better place-coding of the fundamental frequency in cochlear implants
Authors: Geurts Luc , Wouters Jan
Published: February 2004

In current cochlear implant systems, the fundamental frequency F0 of a complex sound is encoded by temporal fluctuations in the envelope of the electrical signals presented on the electrodes. In normal hearing, the lower harmonics of a complex sound are resolved, in contrast with a cochlear implant system. In the present study, it is investigated whether “place-coding” of the first harmonic improves the ability of an implantee to discriminate complex sounds with different fundamental frequencies. Therefore, a new filter bank was constructed, for which the first harmonic is always resolved in two adjacent filters, and the balance between both filter outputs is directly related to the frequency of the first harmonic. The new filter bank was compared with a filter bank that is typically used in clinical processors, both with and without the presence of temporal cues in the stimuli. Four users of the LAURA cochlear implant participated in a pitch discrimination task to determine detection thresholds for F0 differences. The results show that these thresholds decrease noticeably for the new filter bank, if no temporal cues are present in the stimuli. If temporal cues are included, the differences between the results for both filter banks become smaller, but a clear advantage is still observed for the new filter bank. This demonstrates the feasibility of using place-coding for the fundamental frequency.
Acoustical measurements of sound fields between the stage and the orchestra pit inside an historical opera house
Authors: Sato Shin-ichi , Prodi Nicola , Sakai Hiroyuki
Published: February 2004

To clarify the relationship of the sound fields between the stage and the orchestra pit, we conducted acoustical measurements in a typical historical opera house, the Teatro Comunale of Ferrara, Italy. Orthogonal factors based on the theory of subjective preference and other related factors were analyzed. First, the sound fields for a singer on the stage in relation to the musicians in the pit were analyzed. And then, the sound fields for performers in the pit in relation to the singers on the stage were considered. Because physical factors vary depending on the location of the sound source, performers can move on the stage or in the pit to find the preferred sound field.
The fast and the fatal: street racing fatal crashes in the United States
Authors: Knight S , Cook L J , Olson L M
Published: February 2004

The objective of this study was to determine the annual incidence of fatal motor vehicle crashes involving street racing and to describe the characteristics of these crashes compared to other fatal crashes in the United States. The National Highway Traffic Safety Administration Fatality Analysis Reporting System data for 1998–2001 were used for the analyses. There were 149 568 fatal crashes and 315 (0.21%) involved street racing and 399 fatalities occurred in these crashes. In contrast to other fatal crashes, street racing fatal crashes were more likely to occur on urban roadways and were nearly six times more likely to occur at travel speeds ≥65 mph. Compared with other drivers involved in fatal crashes, street racers were more likely to be teenagers, male, and have previous crashes and driving violations. Street racing involves risky driving behaviors and warrants further attention.
Longer term effects of New York State’s law on drivers’ handheld cell phone use
Authors: McCartt A T , Geary L L
Published: February 2004

Objective:To determine whether substantial short term declines in drivers’ use of handheld cell phones, after a state ban, were sustained one year later.

Design:Drivers’ daytime handheld cell phone use was observed in four New York communities and two Connecticut communities. Observations were conducted one month before the ban, shortly after, and 16 months after. Driver gender, estimated age, and vehicle type were recorded for phone users and a sample of motorists.

Intervention:Effective 1 November 2001, New York became the only state in the United States to ban drivers’ handheld cell phone use. Connecticut is an adjacent state without such a law.

Sample:50 033 drivers in New York, 28 307 drivers in Connecticut.

Outcome measures:Drivers’ handheld cell phone use rates in New York and Connecticut and rates by driver characteristics.

Results:Overall use rates in Connecticut did not change. Overall use in New York declined from 2.3% pre-law to 1.1% shortly after (p<0.05). One year later, use was 2.1%, higher than immediately post-law (p<0.05) and not significantly different from pre-law. Initial declines in use followed by longer term increases were observed for males and females, drivers younger than 60, and car and van drivers; use patterns varied among the four communities. Publicity declined after the law’s implementation. No targeted enforcement efforts were evident. Cell phone citations issued during the first 15 months represented 2% of all traffic citations.

Conclusions:Vigorous enforcement campaigns accompanied by publicity appear necessary to achieve longer term compliance with bans on drivers’ cell phone use.
ATP-sensitive potassium channels mediate hyperosmotic stimulation of NKCC in slow-twitch muscle
Authors: Gosmanov Aidar R. , Fan Zheng , Mi Xianqiang , Schneider Edward G. , Thomason Donald B.
Published: February 2004

In mildly hyperosmotic medium, activation of the Na+-K+-2Cl- cotransporter (NKCC) counteracts skeletal muscle cell water loss, and compounds that stimulate protein kinase A (PKA) activity inhibit the activation of the NKCC. The aim of this study was to determine the mechanism for PKA inhibition of NKCC activity in resting skeletal muscle. Incubation of rat slow-twitch soleus and fast-twitch plantaris muscles in isosmotic medium with the PKA inhibitors H-89 and KT-5720 caused activation of the NKCC only in the soleus muscle. NKCC activation caused by PKA inhibition was insensitive to MEK MAPK inhibitors and to insulin but was abolished by the PKA stimulators isoproterenol and forskolin. Furthermore, pinacidil [an ATP-sensitive potassium (KATP) channel opener] or inhibition of glycolysis increased NKCC activity in the soleus muscle but not in the plantaris muscle. Preincubation of the soleus muscle with glibenclamide (a KATP channel inhibitor) prevented the NKCC activation by hyperosmolarity, PKA inhibition, pinacidil, and glycolysis inhibitors. In contrast, glibenclamide stimulated NKCC activity in the plantaris muscle. In cells stably transfected with the Kir6.2 subunit of the of KATP channel, inhibition of glycolysis activated potassium current and NKCC activity. We conclude that activation of KATP channels in slow-twitch muscle is necessary for activation of the NKCC and cell volume restoration in hyperosmotic conditions.
Tumor necrosis factor activates CRE-binding protein through a p38 MAPK/MSK1 signaling pathway in endothelial cells
Authors: Gustin Jason A. , Pincheira Roxana , Mayo Lindsey D. , Ozes Osman Nidai , Kessler Kelly M. , Baerwald Melinda R. , Korgaonkar Chandrashekhar K. , Donner David B.
Published: February 2004

Tumor necrosis factor (TNF) promotes immunity and modulates cell viability, in part, by promoting alterations of cellular gene expression. The mechanisms through which TNF communicates with the nucleus and alters gene expression are incompletely understood. Incubation of human umbilical vein endothelial cells (HUVEC) with TNF induces phosphorylation of the CRE-binding protein (CREB) transcription factor on serine 133 and increases CREB DNA binding and transactivation. Dominant negative CREB, an antagonist antibody directed against the type 1 TNF receptor, or pharmacological inhibition of p38 MAPK signaling blocked TNF-induced CREB activation as determined by phosphorylation and gene reporter assays. From among the kinases that can activate CREB, we found that downstream of p38 MAPK, MSK1 is activated by TNF to promote CREB activation. These observations show that CREB is activated by TNF/TNFR1 signaling through a p38MAPK/MSK1 signaling pathway.
Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of tight junction functional integrity
Authors: Pollack Anne L. , Apodaca Gerard , Mostov Keith E.
Published: February 2004

Hepatocyte growth factor (HGF) induces mitogenesis, motogenesis, and tubulogenesis of cultured Madin-Darby canine kidney (MDCK) epithelial cells. We report that in addition to these effects HGF stimulates morphogenesis of tight, polarized MDCK cell monolayers into pseudostratified layers without loss of tight junction (TJ) functional integrity. We tested TJ functional integrity during formation of pseudostratified layers. In response to HGF, the TJ marker ZO-1 remained in morphologically complete rings and functional barriers to paracellular diffusion of ruthenium red were maintained in pseudostratified layers. Transepithelial resistance (TER) increased transiently two- to threefold during the morphogenetic transition from monolayers to pseudostratified layers and then declined to baseline levels once pseudostratified layers were formed. In MDCK cells expressing the trk/met chimera, both HGF and NGF at concentrations of 2.5 ng/ml induced scattering. However, 2.5 ng/ml HGF did not affect TER. The peak effect of HGF on TER was at a concentration of 100 ng/ml. In contrast, NGF at concentrations as high as 25 μg/ml had no effect on TER or pseudostratified layer morphogenesis of trk/met-expressing cultures. These results suggest that altered presentation of the stimulus, such as through HGF interaction with low-affinity sites, may change the downstream signaling response. In addition, our results demonstrate that HGF stimulates pseudostratified layer morphogenesis while inducing an increase in TER and maintaining the overall tightness of the epithelial layer. Stimulation of epithelial cell movements by HGF without loss of functional TJs may be important for maintaining epithelial integrity during morphogenetic events such as formation of pseudostratified epithelia, organ regeneration, and tissue repair.
Drug discovery in academia
Authors: Verkman A. S.
Published: February 2004

Drug discovery and development is generally done in the commercial rather than the academic realm. Drug discovery involves target discovery and validation, lead identification by high-throughput screening, and lead optimization by medicinal chemistry. Follow-up preclinical evaluation includes analysis in animal models of compound efficacy and pharmacology (ADME: administration, distribution, metabolism, elimination) and studies of toxicology, specificity, and drug interactions. Notwithstanding the high-cost, labor-intensive, and non-hypothesis-driven aspects of drug discovery, the academic setting has a unique and expanding niche in this important area of investigation. For example, academic drug discovery can focus on targets of limited commercial value, such as third-world and rare diseases, and on the development of research reagents such as high-affinity inhibitors for pharmacological “gene knockout” in animal models (“chemical genetics”). This review describes the practical aspects of the preclinical drug discovery process for academic investigators. The discovery of small molecule inhibitors and activators of the cystic fibrosis transmembrane conductance regulator is presented as an example of an academic drug discovery program that has yielded new compounds for physiology research and clinical development.
Chronological changes in metabolism and functions of cultured adipocytes: a hypothesis for cell aging in mature adipocytes
Authors: Yu Yi-Hao , Zhu Huaijie
Published: February 2004

The growth and aging of 3T3-L1 adipocytes were investigated in a synchronized tissue-culture system. We systematically characterized several major aspects of adipocyte metabolism and functions as variables of cell age. We found that terminal differentiation of 3T3-L1 cells is followed by a near-linear hypertrophic growth (increase in triglyceride content) of the cultured adipocytes throughout a 20-day study period. However, three metabolically and functionally distinct stages are recognized. The first stage overlaps with differentiation and is represented by small immature adipocytes. The second stage is characterized by fully mature adipocytes that show peaked overall metabolic activities. The third stage is marked by cell aging, with deterioration in every major aspect of the cell's functionality except for the function of net energy storage, which is preserved even in aged adipocytes. Compared with young mature adipocytes, older cells are increasingly insulin resistant, have decreased glucose uptake and fuel consumption, and show impaired glycerokinase-mediated fatty acid reesterification. Moreover, aged adipocytes show reduced gene expression for adiponectin and leptin, each of which is important in systemic regulation of energy metabolism. The characterization of these cell age-dependent changes in adipocyte functionality provides a model for understanding dynamic changes at the tissue level and suggests that adipose tissue is modifiable via adipocyte aging.
Transgenic complementation of leptin receptor deficiency. II. Increased leptin receptor transgene dose effects on obesity/diabetes and fertility/lactation in lepr-db/db mice
Authors: Chua Streamson C. , Liu Shun Mei , Li Qiong , Sun Aijun , DeNino Walter F. , Heymsfield Steven B. , Guo X. Edward
Published: February 2004

We have generated mice that are homozygous for a leptin receptor transgene that is expressed exclusively in neurons (NSE-LEPR-B). We had previously shown that this transgene in the hemizygous state is effective in ameliorating almost all aspects of leptin receptor deficiency. Now, we show that the transgene, in the homozygous state, almost fully corrects the excess adiposity of LEPR-deficient ( db/db) mice. Body composition analyses indicate that the transgene is able to restrain the massive increase in adiposity observed in LEPR-deficient mice. Examination of hypothalamic agouti gene-related peptide and proopiomelanocortin mRNA shows normalization of these leptin-regulated transcripts. Interestingly, despite normalization of circulating leptin concentrations by the transgene in the fed state, transgenic db3J/db mice did not show fasting-induced reductions of circulating leptin. Increased adiposity of the transgenic db/db mice at 4 wk of age, immediately postweaning, suggests that the transgene is less effective in correcting the preferential fat deposition caused by LEPR deficiency. We noted that the morphology of brown adipose tissue is nearly normal, concordant with the cold tolerance conferred by the transgene. Aspects of the diabetes phenotype are also corrected: glucose and insulin concentrations are nearly normal, and islet hyperplasia is greatly diminished. The transgene also corrects the infertility of db/db females and confers the ability to lactate sufficiently to nurse normal-sized litters. Finally, the slightly increased adiposity and mild insulin resistance of transgenic db/db dams were not a contributory factor to the increased fat content of transgenic db/db male progeny.
Epinephrine-induced hyperpolarization of islet cells without KATPchannels
Authors: Sieg Andrea , Su Jiping , Muñoz Alvaro , Buchenau Michael , Nakazaki Mitsuhiro , Aguilar-Bryan Lydia , Bryan Joseph , Ullrich Susanne
Published: February 2004

This study examines the effect of epinephrine, a known physiological inhibitor of insulin secretion, on the membrane potential of pancreatic islet cells from sulfonylurea receptor-1 (ABCC8)-null mice (Sur1KO), which lack functional ATP-sensitive K+(KATP) channels. These channels have been argued to be activated by catecholamines, but epinephrine effectively inhibits insulin secretion in both Sur1KO and wild-type islets and in mice. Isolated Sur1KO β-cells are depolarized in both low (2.8 mmol/l) and high (16.7 mmol/l) glucose and exhibit Ca2+-dependent action potentials. Epinephrine hyperpolarizes Sur1KO β-cells, inhibiting their spontaneous action potentials. This effect, observed in standard whole cell patches, is abolished by pertussis toxin and blocked by BaCl2. The epinephrine effect is mimicked by clonidine, a selective α2-adrenoceptor agonist and inhibited by α-yohimbine, an α2-antagonist. A selection of K+channel inhibitors, tetraethylammonium, apamin, dendrotoxin, iberiotoxin, E-4130, chromanol 293B, and tertiapin did not block the epinephrine-induced hyperpolarization. Analysis of whole cell currents revealed an inward conductance of 0.11 ± 0.04 nS/pF ( n = 7) and a TEA-sensitive outward conductance of 0.55 ± 0.08 nS/pF ( n = 7) at -60 and 0 mV, respectively. Guanosine 5′- O-(3-thiotriphosphate) (100 μM) in the patch pipette did not significantly alter these currents or activate novel inward-rectifying K+currents. We conclude that epinephrine can hyperpolarize β-cells in the absence of KATPchannels via activation of low-conductance BaCl2-sensitive K+channels that are regulated by pertussis toxin-sensitive G proteins.