bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of wind-generated bubbles on fixed range acoustic attenuation in shallow water at 1–4kHz
Authors: Ainslie Michael A.
Published: December 2005

Long-range acoustic propagation in isothermal conditions is considered, involving multiple reflections from the sea surface. If the sea is calm there is almost perfect reflection and hence little loss of acoustic energy or coherence. The effect of wind is to increase propagation loss due to rough surface scattering and the interaction with near-surface bubble clouds. Previously published measurements of wind-related attenuation in shallow water, at a fixed range of 23km, are converted to surface reflection loss by dividing the total attenuation by the expected number of surface interactions. Theoretical predictions of coherent reflection loss are compared with these measurements in the frequency range 0.9–4.0kHz and wind speeds up to 13m∕s. Apart from an unexplained seasonal dependence, it is shown that the magnitude of the predicted rough surface scattering loss is sufficient to explain the measurements if the effect of bubbles is included, and not otherwise. The bubbles are found to play an important catalytic role, not by scattering or absorbing sound, but by refracting it up towards the sea surface and thus enhancing the scattering loss associated with the rough air–sea boundary. Possible explanations for the apparent seasonal variations in the measurements are explored.
Acoustic eigenvalues of rectangular rooms with arbitrary wall impedances using the interval Newton∕generalized bisection method
Authors: Naka Yusuke , Oberai Assad A. , Shinn-Cunningham Barbara G.
Published: December 2005

Modal analysis of a rectangular room requires evaluation of the eigenvalues of the Helmholtz operator while taking into account the boundary conditions imposed on the walls of the room. When the walls have finite impedances, the acoustic eigenvalue equation becomes complicated and a numerical method that can find all roots within a given interval is required to solve it. In this study, the interval Newton∕generalized bisection (IN∕GB) method is adopted for solving this problem. For an efficient implementation of this method, bounds are derived for the acoustic eigenvalues and their asymptotic behavior explored. The accuracy of the IN∕GB method is verified for a canonical problem by comparing the modal solution with the corresponding finite element solution. Furthermore, reverberation times estimated using the IN∕GB method are compared to those calculated using the finite difference method. Through these examples, it is demonstrated that the IN∕GB method provides a useful and efficient approach for estimating the acoustic responses of rectangular rooms with finite wall impedances.
Dynamic measurements of the elastic constants of glass wool
Authors: Tarnow Viggo
Published: December 2005

The sound wave in the air between the fibers of glass wool exerts an oscillatory viscous drag on the fibers and excites a mechanical wave in the fiber skeleton. Accurate calculations of sound attenuation in glass wool must take the mechanical wave in the fiber skeleton into account, and this requires knowledge of the dynamic elastic constants of the fiber skeleton. The mechanical properties of glass wool are highly anisotropic. Previously only one of the elastic constants has been measured dynamically, but here all the elastic constants are reported. The measurement method is well known. But a new mechanical design, which reduces mechanical resonance, is described. The measurements were carried out in atmospheric air at normal pressure, and this causes an oscillatory airflow in the sample. To obtain the elastic constants, the influence of the airflow was subtracted from the data by a new formula. The elastic constants were measured in the frequency range 20–160Hz for glass wool of mass density 30kg∕m3. The elastic constant C11 depended on the frequency; at 20Hz it was 1.5+0.01iMPa, and at 160Hz it was 2.6+0.06iMPa. The constant C33=12+0.6ikPa did not depend on frequency. The shear constant C44=40+2ikPa was constant. The two constants C12,C13 were zero.
Stiffness matrix method with improved efficiency for elastic wave propagation in layered anisotropic media
Authors: Tan Eng Leong
Published: December 2005

This paper presents the recursive algorithm of stiffness matrix method with improved efficiency for computing the total and surface stiffness matrices for a general multilayered anisotropic media. Based on the eigensolutions commonly available for analysis of such media, the recursive algorithm deals with eigen-submatrices directly and bypasses all intermediate layer stiffness submatrices. The improved algorithm obviates the need to compute certain inverse of the original scheme and makes the stiffness matrix recursion more robust. In situation where transfer matrix is numerically stable and easily accessible, an improved recursive algorithm is also given directly in terms of transfer submatrices without involving their explicit inverse.
Noise levels in Johns Hopkins Hospital
Authors: Busch-Vishniac Ilene J. , West James E. , Barnhill Colin , Hunter Tyrone , Orellana Douglas , Chivukula Ram
Published: December 2005

This article presents the results of a noise survey at Johns Hopkins Hospital in Baltimore, MD. Results include equivalent sound pressure levels (Leq) as a function of location, frequency, and time of day. At all locations and all times of day, the Leq indicate that a serious problem exists. No location is in compliance with current World Health Organization Guidelines, and a review of objective data indicates that this is true of hospitals throughout the world. Average equivalent sound levels are in the 50–60dB(A) range for 1min, 12, and 24h averaging time periods. The spectra are generally flat over the 63–2000Hz octave bands, with higher sound levels at lower frequencies, and a gradual roll off above 2000Hz. Many units exhibit little if any reduction of sound levels in the nighttime. Data gathered at various hospitals over the last 45years indicate a trend of increasing noise levels during daytime and nighttime hours. The implications of these results are significant for patients, visitors, and hospital staff.
The influence of noise on vowel and consonant cues
Authors: Parikh Gaurang , Loizou Philipos C.
Published: December 2005

This study assessed the acoustic and perceptual effect of noise on vowel and stop-consonant spectra. Multi-talker babble and speech-shaped noise were added to vowel and stop stimuli at −5 to +10dB S/N, and the effect of noise was quantified in terms of (a) spectral envelope differences between the noisy and clean spectra in three frequency bands, (b) presence of reliable F1 and F2 information in noise, and (c) changes in burst frequency and slope. Acoustic analysis indicated that F1 was detected more reliably than F2 and the largest spectral envelope differences between the noisy and clean vowel spectra occurred in the mid-frequency band. This finding suggests that in extremely noisy conditions listeners must be relying on relatively accurate F1 frequency information along with partial F2 information to identify vowels. Stop consonant recognition remained high even at −5dB despite the disruption of burst cues due to additive noise, suggesting that listeners must be relying on other cues, perhaps formant transitions, to identify stops.
Equivalence of expressions for the acoustic radiation force on cylinders
Authors: Wei Wei , Marston Philip L.
Published: December 2005

Using an appropriate grouping of terms, a radiation force expression for cylinders in a standing wave based on far-field scattering [Wei et al., J. Acoust. Soc. Am. 116, 202–208 (2004)] is transformed to an expression given elsewhere [F. G. Mitri, Eur. Phys. J. B 44, 71–78 (2005)]. Mitri’s result is from a near-field derivation for the specific case of a circular cylinder. The far-field derivation also applies to noncircular objects having mirror symmetry about the incident wave vector. Some aspects of far-field derivations of optical and acoustical radiation forces are noted as are some implications for the radiation force on cylinders in travelling waves.
Approximate boundary conditions for a fluid-loaded elastic plate
Authors: Johansson M. , Folkow P. D. , Hägglund A. M. , Olsson P.
Published: December 2005

Approximate boundary conditions for an infinite elastic layer immersed in a fluid are derived. By using series expansions in the thickness coordinate of the plate fields, the displacements fields are eliminated, adopting the three-dimensional equations of motion. The sums and differences of the boundary pressure fields and their normal derivatives are related through a set of approximate boundary conditions, one symmetric and one antisymmetric. These equations involve powers in the layer thickness together with partial derivatives with respect to time as well as the spatial variables in the plate plane. The approximate boundary conditions can be truncated to an arbitrary order, and explicit relations are presented including terms of order five. Comparisons are made with effective boundary conditions using classical plate theories. The numerical examples involve reflection and transmission of plane waves incident on the plate at different angles, as well as the pressure fields due to a line force. Three fluid-loading cases are studied: modest, heavy, and light loadings. The results using truncated approximate boundary conditions are compared to exact and classical plate solutions. The examples show that the accuracies of the power series approximations of order three and higher are very good in the frequency interval considered.
Localization of aerial pure tones by pinnipeds
Authors: Holt Marla M. , Schusterman Ronald J. , Kastak David , Southall Brandon L.
Published: December 2005

In this study, minimum audible angles (MAAs) of aerial pure tones were measured in and compared between a northern elephant seal (Mirounga angustirostris), a harbor seal (Phoca vitulina), and a California sea lion (Zalophus californianus). Testing was conducted between 0.8 and 16kHz in the elephant seal and 0.8 and 20kHz in the harbor seal and sea lion in a hemi-anechoic chamber using a left∕right psychophysical procedure. Performance for the same frequencies was also quantified for discrete speaker separation of 5° from the mid-line. For all subjects, MAAs ranged from approximately 3° to 15° and were generally equal to or larger than those previously measured in the same subjects with a broadband signal. Performance at 5° ranged from chance to 97% correct, depending on frequency and subject. Poorest performance in the sea lion and harbor seal occurred at intermediate frequencies, which is consistent with the duplex theory of sound localization. In contrast, the elephant seal’s poorest performance occurred at higher frequencies. The elephant seal’s result suggests an inferior ability to utilize interaural level differences and is perhaps related to best hearing sensitivity shifted toward lower frequencies in this species relative to other pinnipeds.
Psychophysical estimates of nonlinear cochlear processing in younger and older listeners
Authors: Gifford René H. , Bacon Sid P.
Published: December 2005

The primary goal of this project was to compare the performance of younger and older listeners on a number of psychophysical measures thought to be influenced by nonlinear cochlear processing. Younger (mean of 25.6years) and older (mean of 63.8years) listeners with normal hearing were matched (within 5dB) according to their quiet thresholds at the two test frequencies of 1200 and 2400Hz. They were similarly matched at the adjacent octave frequencies of 600 and 4800Hz (within 5dB at one and 9dB at the other). Performance was compared on measures of auditory filter shape, psychophysical suppression, and growth of forward masking. There was no difference between the two age groups on these psychophysical estimates reflecting nonlinear processing, suggesting that aging per se does not affect the cochlear nonlinearity, at least for the ages sampled here. The results did, however, consistently demonstrate an age-related increase in the susceptibility to forward masking.
Kramers-Kronig analysis of attenuation and dispersion in trabecular bone
Authors: Waters Kendall R. , Hoffmeister Brent K.
Published: December 2005

A restricted-bandwidth form of the Kramers-Kronig dispersion relations is applied to in vitro measurements of ultrasonic attenuation and dispersion properties of trabecular bone specimens from bovine tibia. The Kramers-Kronig analysis utilizes only experimentally measured properties and avoids extrapolation of ultrasonic properties beyond the known bandwidth. Compensation for the portions of the Kramers-Kronig integrals over the unknown bandwidth is partially achieved by the method of subtractions, where a subtraction frequency acts as an adjustable parameter. Good agreement is found between experimentally measured and Kramers-Kronig reconstructed dispersions. The restricted-bandwidth approach improves upon other forms of the Kramers-Kronig relations and may provide further insight into how ultrasound interacts with trabecular bone.
Measurements of the frame acoustic properties of porous and granular materials
Authors: Park Junhong
Published: December 2005

For porous and granular materials, the dynamic characteristics of the solid component (frame) are important design factors that significantly affect the material’s acoustic properties. The primary goal of this study was to present an experimental method for measuring the vibration characteristics of this frame. The experimental setup was designed to induce controlled vibration of the solid component while minimizing the influence from coupling between vibrations of the fluid and the solid component. The Biot theory was used to verify this assumption, taking the two dilatational wave propagations and interactions into account. The experimental method was applied to measure the dynamic properties of glass spheres, lightweight microspheres, acoustic foams, and fiberglass. A continuous variation of the frame vibration characteristics with frequency similar to that of typical viscoelastic materials was measured. The vibration amplitude had minimal effects on the dynamic characteristics of the porous material compared to those of the granular material. For the granular material, materials comprised of larger particles and those under larger vibration amplitudes exhibited lower frame wave speeds and larger decay rates.
Doppler-shift compensation in the Taiwanese leaf-nosed bat (Hipposideros terasensis) recorded with a telemetry microphone system during flight
Authors: Hiryu Shizuko , Katsura Koji , Lin Liang-Kong , Riquimaroux Hiroshi , Watanabe Yoshiaki
Published: December 2005

Biosonar behavior was examined in Taiwanese leaf-nosed bats (Hipposideros terasensis; CF-FM bats) during flight. Echolocation sounds were recorded using a telemetry microphone mounted on the bat’s head. Flight speed and three-dimensional trajectory of the bat were reconstructed from images taken with a dual high-speed video camera system. Bats were observed to change the intensity and emission rate of pulses depending on the distance from the landing site. Frequencies of the dominant second harmonic constant frequency component (CF2) of calls estimated from the bats’ flight speed agreed strongly with observed values. Taiwanese leaf-nosed bats changed CF2 frequencies depending on flight speed, which caused the CF2 frequencies of the Doppler-shifted echoes to remain constant. Pulse frequencies were also estimated using echoes returning directly ahead of the bat and from its sides for two different flight conditions: landing and U-turn. Bats in flight may periodically alter their attended angles from the front to the side when emitting echolocation pulses.
Spatial unmasking of birdsong in human listeners: Energetic and informational factors
Authors: Best Virginia , Ozmeral Erol , Gallun Frederick J. , Sen Kamal , Shinn-Cunningham Barbara G.
Published: December 2005

Spatial unmasking describes the improvement in the detection or identification of a target sound afforded by separating it spatially from simultaneous masking sounds. This effect has been studied extensively for speech intelligibility in the presence of interfering sounds. In the current study, listeners identified zebra finch song, which shares many acoustic properties with speech but lacks semantic and linguistic content. Three maskers with the same long-term spectral content but different short-term statistics were used: (1) chorus (combinations of unfamiliar zebra finch songs), (2) song-shaped noise (broadband noise with the average spectrum of chorus), and (3) chorus-modulated noise (song-shaped noise multiplied by the broadband envelope from a chorus masker). The amount of masking and spatial unmasking depended on the masker and there was evidence of release from both energetic and informational masking. Spatial unmasking was greatest for the statistically similar chorus masker. For the two noise maskers, there was less spatial unmasking and it was wholly accounted for by the relative target and masker levels at the acoustically better ear. The results share many features with analogous results using speech targets, suggesting that spatial separation aids in the segregation of complex natural sounds through mechanisms that are not specific to speech.
Interacting effects of syllable and phrase position on consonant articulation
Authors: Byrd Dani , Lee Sungbok , Riggs Daylen , Adams Jason
Published: December 2005

The complexities of how prosodic structure, both at the phrasal and syllable levels, shapes speech production have begun to be illuminated through studies of articulatory behavior. The present study contributes to an understanding of prosodic signatures on articulation by examining the joint effects of phrasal and syllable position on the production of consonants. Articulatory kinematic data were collected for five subjects using electromagnetic articulography (EMA) to record target consonants (labial, labiodental, and tongue tip), located in (1) either syllable final or initial position and (2) either at a phrase edge or phrase medially. Spatial and temporal characteristics of the consonantal constriction formation and release were determined based on kinematic landmarks in the articulator velocity profiles. The results indicate that syllable and phrasal position consistently affect the movement duration; however, effects on displacement were more variable. For most subjects, the boundary-adjacent portions of the movement (constriction release for a preboundary coda and constriction formation for a postboundary onset) are not differentially affected in terms of phrasal lengthening—both lengthen comparably.
The Distance to the Perseus Spiral Arm in the Milky Way
Authors: Xu Y. , Reid M. J. , Zheng X. W. , Menten K. M.
Published: December 2005

We have measured the distance to the massive star–forming region W3OH in the Perseus spiral arm of the Milky Way to be 1.95 ± 0.04 kiloparsecs (5.86 ×10
16
km). This distance was determined by triangulation, with Earth's orbit as one segment of a triangle, using the Very Long Baseline Array. This resolves the long-standing problem that there is a discrepancy of a factor of 2 between different techniques used to determine distances. The reason for the discrepancy is that this portion of the Perseus arm has anomalous motions. The orientation of the anomalous motion agrees with spiral density-wave theory, but the magnitude of the motion is somewhat larger than most models predict.
Asymmetric Hydrogenation of Unfunctionalized, Purely Alkyl-Substituted Olefins
Authors: Bell Sharon , Wüstenberg Bettina , Kaiser Stefan , Menges Frederik , Netscher Thomas , Pfaltz Andreas
Published: December 2005

Asymmetric hydrogenation of olefins is one of the most useful reactions for the synthesis of optically active compounds, especially in industry. However, the application range of the catalysts developed so far is limited to alkenes with a coordinating functional group or an aryl substituent next to the double bond. We have found a class of chiral iridium catalysts that give high enantioselectivity in the hydrogenation of unfunctionalized, trialkyl-substituted olefins. Because these catalysts do not require the presence of any particular functional group or aryl substituent in the substrate, they considerably broaden the scope of asymmetric hydrogenation.
Differences in transport of fatty acids and expression of fatty acid transporting proteins in adipose tissue of obese black and white women
Authors: Bower Joseph F. , Davis Julianne M. , Hao Enhui , Barakat Hisham A.
Published: December 2005

We have reported that the rate of de novo triglyceride (TG) synthesis by omental, but not subcutaneous, adipose tissue was higher in African-American women (AAW) than in Caucasian women (CAW). The purpose of this study was to explore the potential mechanisms underlying this increase. Toward that end, we determined the activities of key enzymes in the pathway of TG synthesis, the rates of uptake of fatty acids by adipocytes, mRNA and protein levels of the fatty acid-transporting proteins FAT/CD36 and FATP, and mRNA and protein levels of PPARγ in omental fat of AAW and CAW. The results showed 1) no difference in the activity of phosphofructokinase, glycerol-3-phosphate dehydrogenase, or diacylglycerol acyltransferase; 2) a higher rate of fatty acid uptake by adipocytes of the AAW; 3) an increase in the mRNA and protein levels of CD36 and FATP4 in the fat of the AAW; and 4) an increase in the mRNA and protein levels of PPARγ, which can stimulate the expression of CD36 and FATP. These results suggest that the increase in the transport of fatty acid, which is mediated by the overexpression of the transport proteins in the omental adipose tissue of the AAW, might contribute to the higher prevalence of obesity in AAW.
Hexosamines, insulin resistance, and the complications of diabetes: current status
Authors: Buse Maria G.
Published: December 2005

The hexosamine biosynthesis pathway (HBP) is a relatively minor branch of glycolysis. Fructose 6-phosphate is converted to glucosamine 6-phosphate, catalyzed by the first and rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase (GFAT). The major end product is UDP- N-acetylglucosamine (UDP-GlcNAc). Along with other amino sugars generated by HBP, it provides essential building blocks for glycosyl side chains, of proteins and lipids. UDP-GlcNAc regulates flux through HBP by regulating GFAT activity and is the obligatory substrate of O-GlcNAc transferase. The latter is a cytosolic and nuclear enzyme that catalyzes a reversible, posttranslational protein modification, transferring GlcNAc in O-linkage ( O-GlcNAc) to specific serine/threonine residues of proteins. The metabolic effects of increased flux through HBP are thought to be mediated by increasing O-GlcNAcylation. Several investigators proposed that HBP functions as a cellular nutrient sensor and plays a role in the development of insulin resistance and the vascular complications of diabetes. Increased flux through HBP is required and sufficient for some of the metabolic effects of sustained, increased glucose flux, which promotes the complications of diabetes, e.g., diminished expression of sarcoplasmic reticulum Ca2+-ATPase in cardiomyocytes and induction of TGF-β and plasminogen activator inhibitor-1 in vascular smooth muscle cells, mesangial cells, and aortic endothelial cells. The mechanism was consistent with enhanced O-GlcNAcylation of certain transcription factors. The role of HBP in the development of insulin resistance has been controversial. There are numerous papers showing a correlation between increased flux through HBP and insulin resistance; however, the causal relationship has not been established. More recent experiments in mice overexpressing GFAT in muscle and adipose tissue or exclusively in fat cells suggest that the latter develop in vivo insulin resistance via cross talk between fat cells and muscle. Although the relationship between HBP and insulin resistance may be quite complex, it clearly deserves further study in concert with its role in the complications of diabetes.
Febrile-range temperature but not heat shock augments the acute phase response to interleukin-6 in human hepatoma cells
Authors: Wigmore Stephen J. , Fearon Kenneth C. H. , Ross James A. , McNally Stephen J. , Welch William J. , Garden O. James
Published: December 2005

The relationship between the stress protein response and the acute phase response (APPR) was studied in human hepatoma cells to investigate the hierarchy of regulation of these survival responses. Huh-7 cells were subjected to heat treatment (febrile-range temperature 40°C or heat shock 43°C) followed by recovery at 37°C in the presence or absence of IL-6 given either before or after heat treatment. The effects on total, fractional, and acute phase protein synthesis were then analyzed by metabolic labeling, ELISA, real-time PCR, Northern blot analysis, and activation of an α1-antitrypsin reporter plasmid. Cell energetics were studied under the same conditions using an index of mitochondrial activity and measurement of cellular ATP levels. Febrile-range temperature (40°C) augmented acute phase protein production when cells had been pretreated with IL-6. Pretreatment of cells with IL-6 also prevented heat shock-induced suppression of α1-antichymotrypsin (ACT) but not transferrin. mRNA expression of ACT and α1-antitrypsin reporter activation studies was consistent with transcriptional regulation of these proteins. Expression of mRNA transcripts for transferrin was increased despite protein expression being reduced by heat shock. The effects of heat shock on acute phase protein synthesis can be modified by preincubation with IL-6, whereas addition of this ligand after heat treatment has no effect on the suppressive effect of heat on the APPR. The mechanism of this action appears to be transcriptionally regulated in the case of ACT, but in the case of transferrin, it may be mediated by another process such as posttranslational modification.
Nitric oxide-cGMP-protein kinase G signaling pathway induces anoxic preconditioning through activation of ATP-sensitive K+ channels in rat hearts
Authors: Cuong Dang Van , Kim Nari , Youm Jae Boum , Joo Hyun , Warda Mohamad , Lee Jae-Wha , Park Won Sun , Kim Taeho , Kang Sunghyun , Kim Hyungkyu , Han Jin
Published: December 2005

Nitric oxide (NO) plays an important role in anoxic preconditioning to protect the heart against ischemia-reperfusion injuries. The present work was performed to study better the NO-cGMP-protein kinase G (PKG) signaling pathway in the activation of both sarcolemmal and mitochondrial ATP-sensitive K+ (KATP) channels during anoxic preconditioning (APC) and final influence on reducing anoxia-reperfusion (A/R)-induced cardiac damage in rat hearts. The upstream regulating elements controlling NO-cGMP-PKG signal-induced KATP channel opening that leads to cardioprotection were investigated. The involvement of both inducible and endothelial NO synthases (iNOS and eNOS) in the progression of this signaling pathway was followed. Final cellular outcomes of ischemia-induced injury after different preconditioning in the form of lactate dehydrogenase release, DNA strand breaks, and malondialdehyde formation as indexes of cell injury and lipid peroxidation, respectively, were investigated. The lactate dehydrogenase and malondialdehyde values decreased in the groups that underwent preconditioning periods with specific mitochondrial KATP channels opener diazoxide (100 μM), nonspecific mitochondrial KATP channels opener pinacidil (50 μM), S-nitroso- N-acetylpenicillamine (SNAP, 300 μM), or β-phenyl-1, N2-etheno-8-bromoguanosine-3′,5′-cyclicmonophosphorothioate, Sp-isomer (10 μM) before the A/R period. Preconditioning with SNAP significantly reduced the DNA damage. The effect was blocked by glibenclamide (50 μM), 5-hydroxydecanoate (100 μM), NG-nitro-l-arginine methyl ester (200 μM), and β-phenyl-1, N2-etheno-8-bromoguanosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (1 μM). The results suggest iNOS, rather than eNOS, as the major contributing NO synthase during APC treatment. Moreover, the PKG shows priority over NO as the upstream regulator of NO-cGMP-PKG signal-induced KATP channel opening that leads to cardioprotection during APC treatment.
Cerebrovascular response to normal pregnancy: a longitudinal study
Authors: Bergersen T. K. , Hartgill T. W. , Pirhonen J.
Published: December 2005

We used a longitudinal study design ( gestational weeks 8, 15, 22, 29, and 36 and 12 wk postpartum ) to investigate the effect of normal pregnancy on cerebral autoregulation and pressor response. Blood flow velocities in the right internal carotid artery, end-tidal CO2, and mean arterial pressure (MAP) were simultaneously and continuously recorded in 16 healthy pregnant women during standardized hyperventilation and handgrip. Blood flow velocities were recorded using Doppler ultrasound sampled beat by beat using the ECG signal. The results demonstrate that the vasoconstrictor response to hyperventilation is unchanged during pregnancy. During standardized handgrip, MAP showed a statistically significant increase during pregnancy that did not affect cerebral blood flow. A statistically significant reduction in the MAP response to handgrip was seen in week 36. In conclusion, pregnancy has no impact on cerebral autoregulation. There is an impact on the pressor response resulting in a blunted reaction at week 36, probably caused by a fall in the baroreflex set point.
Sepsis and inflammatory insults downregulate IGFBP-5, but not IGFBP-4, in skeletal muscle via a TNF-dependent mechanism
Authors: Lang Charles H. , Krawiec Brian J. , Huber Danuta , McCoy Jennifer M. , Frost Robert A.
Published: December 2005

The purpose of the present study was to determine whether catabolic stimuli that induce muscle atrophy alter the muscle mRNA abundance of insulin-like growth factor binding protein (IGFBP)-4 and -5, and if so determine the physiological mechanism for such a change. Catabolic insults produced by endotoxin (LPS) and sepsis decreased IGFBP-5 mRNA time- and dose-dependently in gastrocnemius muscle. This reduction did not result from muscle disuse because hindlimb immobilization increased IGFBP-5. Continuous infusion of a nonlethal dose of tumor necrosis factor-α (TNF-α) decreased IGFBP-5 mRNA 70%, whereas pretreatment of septic rats with a neutralizing TNF binding protein completely prevented the reduction in muscle IGFBP-5. The addition of LPS or TNF-α to cultured C2C12myoblasts also decreased IGFBP-5 expression. Although exogenously administered growth hormone (GH) increased IGFBP-5 mRNA 2-fold in muscle from control rats, muscle from septic animals was GH resistant and no such elevation was detected. In contrast, exogenous administration of IGF-I as part of a binary complex composed of IGF-I/IGFBP-3 produced comparable increases in IGFBP-5 mRNA in both control and septic muscle. Concomitant determinations of IGF-I mRNA content revealed a positive linear relationship between IGF-I and IGFBP-5 mRNA in the same muscle in response to LPS, sepsis, TNF-α, and GH treatment. Although dexamethasone decreased muscle IGFBP-5, pretreatment of rats with the glucocorticoid receptor antagonist RU486 did not prevent the sepsis-induced decrease in IGFBP-5 mRNA. In contrast, muscle IGFBP-4 mRNA abundance was not significantly altered by LPS, sepsis, or hindlimb immobilization. In summary, these data demonstrate that various inflammatory insults decrease muscle IGFBP-5 mRNA, without altering IGFBP-4, by a TNF-dependent glucocorticoid-independent mechanism. Finally, IGF-I appears to be a dominant positive regulator of IGFBP-5 gene expression in muscle under both normal and catabolic conditions.
Tight junction biology and kidney dysfunction
Authors: Lee David B. N. , Huang Edmund , Ward Harry J.
Published: December 2005

The epithelial tight junction (TJ) has three major functions. As a “gate,” it serves as a regulatory barrier separating and maintaining biological fluid compartments of different composition. As a “fence,” it generates and maintains the apicobasal polarity of cells that form the confluent epithelium. Finally, the TJ proteins form a trafficking and signaling platform that regulates cell growth, proliferation, differentiation, and dedifferentiation. Six examples are selected that illustrate the emerging link between TJ dysfunction and kidney disease. First, the glomerular slit diaphragm (GSD) is evolved, in part, from the TJ and, on maturation, exhibits all three functions of the TJ. GSD dysfunction leads to proteinuria and, in some instances, podocyte dedifferentiation and proliferation. Second, accumulating evidence supports epithelial-mesenchymal transformation (EMT) as a major player in renal fibrosis, the final common pathway that leads to end-stage renal failure. EMT is characterized by a loss of cell-cell contact and apicobasal polarity, which are hallmarks of TJ dysfunction. Third, in autosomal dominant polycystic kidney disease, mutations of the polycystins may disrupt their known interactions with the apical junction complex, of which the TJ is a major component. This can lead to disturbances in epithelial polarity regulation with consequent abnormal tubulogenesis and cyst formation. Fourth, evidence for epithelial barrier and polarity dysregulation in the pathogenesis of ischemic acute renal failure will be summarized. Fifth, the association between mutations of paracellin-1, the first TJ channel identified, and clinical disorders of magnesium and calcium wasting and bovine renal fibrosis will be used to highlight an integral TJ protein that can serve multiple TJ functions. Finally, the role of WNK4 protein kinase in shunting chloride across the TJ of the distal nephron will be addressed.
The use of mammalian cortical kidney slices for the study of tubule secretion: a pioneering step toward understanding organic anion transport
Authors: Dantzler William H.
Published: December 2005

This essay examines the historical significance of an APS classic paper that is freely available on line:

Cross RJ and Taggart JV. Renal tubular transport: accumulation of p-aminohippurate by rabbit kidney slices. Am J Physiol 161: 181–190, 1950 ( http://ajplegacy.physiology.org/cgi/reprint/161/1/181 ).
Voluntary muscle activation is impaired by core temperature rather than local muscle temperature
Authors: Thomas Melissa M. , Cheung Stephen S. , Elder Geoff C. , Sleivert Gordon G.
Published: December 2005

Fatigue during hyperthermia may be due in part to a failure of the central nervous system to fully activate the working muscles. We investigated the effects of passive hyperthermia on maximal plantar flexor isometric torque (maximal isometric voluntary contraction) and voluntary activation to determine the roles of local skin temperature, core temperature, and peripheral muscle temperature in fatigue. Nine healthy subjects were passively heated from 37.2 to 39.5°C (core temperature) and then cooled back down to 37.9°C using a liquid-conditioning garment, with the right leg kept at a thermoneutral temperature throughout the protocol, whereas the left leg was allowed to heat and cool. Passive heating resulted in significant decreases in torque from [mean (SD)] 172 N·m (SD 39) to 160 N·m (SD 44) and in voluntary activation from 96% (SD 2) to 91% (SD 5) in the heated leg, and maximal isometric voluntary contraction decreased similarly from 178 N·m (SD 37) to 165 N·m (SD 38) and voluntary activation from 97% (SD 2) to 94% (SD 5) in the thermoneutral leg. The initiation of cooling, which produced a rapid decrease in skin temperature and cardiovascular strain [heart rate reserve decreased from 58% (SD 12) to 31% (SD 12)], did not immediately restore either torque or voluntary activation. However, when core temperature was lowered back to normal, torque and voluntary activation were restored to baseline values. It was concluded that an increase in core temperature is a factor responsible for reducing voluntary activation during brief voluntary isometric contractions and that temperature-induced changes in the contractile properties of muscle and local thermal afferent input from the skin do not contribute significantly to the decrement in torque.
Brisk production of nitric oxide and associated formation ofS-nitrosothiols in early hemorrhage
Authors: Atkins James L. , Day Billy W. , Handrigan Michael T. , Zhang Zhe , Pamnani Motilal B. , Gorbunov Nikolai V.
Published: December 2005

The results of previous inhibitor studies suggest that there is some increase in nitric oxide (NO) production from constitutive NO synthase in early hemorrhage (H), but the magnitude of NO production early after H has not been previously assessed. It is generally believed that only modest production rates are possible from the constitutively expressed NO synthases. To study this, anesthetized male Sprague-Dawley rats were subjected to 90 min of isobaric (40 mmHg) H. During this period of time, the dynamics of accumulation of NO intermediates in the arterial blood was assessed using electron paramagnetic resonance spectroscopy, chemiluminescence, fluorescence imaging, and mass spectrometry. Electron paramagnetic resonance-detectable NO adducts were also measured with spin traps in blood plasma and red blood cells. H led to an increase in the concentration of hemoglobin-NO from 0.9 ± 0.2 to 4.8 ± 0.7 μM. This accumulation was attenuated by a nonselective inhibitor of NO synthase, NG-nitro-l-argininemethyl ester (l-NAME), but not by NG-nitro-d-argininemethyl ester (d-NAME) or 1400W. Administration of l-NAME (but not 1400W or d-NAME) during H produced a short-term increase in mean arterial pressure (∼90%). In H, the level of N oxides in red blood cells increased sevenfold. S-nitrosylation of plasma proteins was revealed with “biotin switch” techniques. The results provide compelling evidence that there is brisk production of NO in early H. The results indicate that the initial compensatory response to H is more complicated than previously realized, and it involves an orchestrated balance between intense vasoconstrictor and vasodilatory components.
Radiological Findings, Pulmonary Function and Dyspnea in Underground Coal Miners
Authors: Bauer Torsten T. , Heyer Christoph M. , Duchna Hans-Werner , Andreas Kirsten , Weber Andreas , Schmidt Ernst-Wilhelm , Ammenwerth Wim , Schultze-Werninghaus Gerhard
Published: December 2005

Background: Respiratory disability induced by dust exposure in coal workers is assessed by pulmonary function tests and radiological evidence of pneumoconiosis. High-resolution computed tomography (HR-CT) improves the visibility of tissue changes, but the value of the findings for the clinical evaluation is controversial. Objectives: It was the aim of this study to evaluate the correlation between the International Labour Office (ILO) classification and the degree of emphysema in HR-CT with self-reported dyspnea and pulmonary function tests including diffusion capacity for CO (DL,CO). Methods: We investigated 87 coal miners (aged 67 ± 6 years), having worked underground for 26 ± 9 years, with pulmonary function tests and HR-CT. Univariate associations were tested with correlation coefficients, and multivariable analyses used a stepwise forward regression model. Results: No aspect of the ILO classification showed a univariate correlation with dyspnea or forced expiratory flow in 1 s (FEV1). Emphysema CT score was strongly associated with DL,CO (rs = –0.40; p < 0.001) and FEV1/maximal vital capacity (r = –0.38; p < 0.001) in univariate analysis, but not with the clinical grade of dyspnea (r = –0.14; p = 0.256). CT emphysema score but not ILO classification was associated with FEV1 in multivariable analyses (rs = –0.37; p < 0.001). Dyspnea was best approximated by DL,CO (r = –0.312; p = 0.008). Conclusion: The clinical grade of breathlessness was best approximated by DL,CO. HR-CT showed a good association with expiratory flow limitation. ILO classification of the chest radiograph may be a marker of exposure but conveys little information about the degree of respiratory impairment.
Conjugated Linoleic Acid Impairs Endothelial Function
Authors: Taylor Justin S.W. , Williams Simon R.P. , Rhys Rhian , James Phillip , Frenneaux Michael P.
Published: December 2005

Objectives—

To determine the effect of dietary supplementation with conjugated linoleic acid (CLA) on body mass index (BMI), body fat distribution, endothelial function, and markers of cardiovascular risk.

Methods and Results—

Forty healthy volunteers with BMI >27 kg/m
2
were randomized to receive a CLA isomeric mixture or olive oil in a 12-week double-blind study. Subcutaneous body fat and abdominal/hepatic fat content were assessed using skin-fold thicknesses and computed tomography scanning, respectively. Endothelial function was assessed by brachial artery flow-mediated dilatation (FMD). Plasma isoprostanes were measured as an index of oxidative stress. CLA supplementation did not result in a significant change in BMI index or total body fat. There was a significant decrease in limb (−7.8 mm,
P
<0.001), but not torso skin-fold thicknesses or abdominal or liver fat content. Brachial artery FMD declined (−1.3%,
P
=0.013), and plasma F2-isoprostanes increased (+91pg/mL,
P
=0.042).

Conclusions—

A CLA isomeric mixture had at most modest effects on adiposity and worsened endothelial function. On the basis of these results, the use of the isomeric mixture of CLA as an aid to weight loss cannot be recommended.
Rho GTPases, Statins, and Nitric Oxide
Authors: Rikitake Yoshiyuki , Liao James K.
Published: December 2005

The lipid-lowering drugs, 3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins, are used in the prevention and treatment of cardiovascular diseases. Recent experimental and clinical studies suggest that statins may exert vascular protective effects beyond cholesterol reduction. For example, statins improve endothelial function by cholesterol-dependent and -independent mechanisms. The cholesterol-independent or “pleiotropic” effects of statins include the upregulation and activation of endothelial NO synthase (eNOS). Because statins inhibit an early step in the cholesterol biosynthetic pathway, they also inhibit the synthesis of isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate, which are important posttranslational lipid attachments for intracellular signaling molecules such as the Rho GTPases. Indeed, decrease in Rho GTPase responses as a consequence of statin treatment increases the production and bioavailability of endothelium-derived NO. The mechanism involves, in part, Rho/Rho-kinase (ROCK)-mediated changes in the actin cytoskeleton, which leads to decreases in eNOS mRNA stability. The regulation of eNOS by Rho GTPases, therefore, may be an important mechanism underlying the cardiovascular protective effect of statins.
Raised Plasma Soluble P-Selectin in Peripheral Arterial Occlusive Disease Enhances Leukocyte Adhesion
Authors: Woollard K.J. , Kling D. , Kulkarni S. , Dart A.M. , Jackson S. , Chin-Dusting J.
Published: December 2005

Raised levels of soluble P-selectin (sP-selectin) have been reported in the plasma of patients with vascular diseases; however, the functional importance of this ligand remains unclear. In this study we have examined a potential role for plasma sP-selectin in regulating neutrophil adhesion in patients with peripheral arterial occlusive disease (PAOD). Patients with PAOD had significantly higher levels of sP-selectin (mean±SD: 73.3±13.0 versus 16.7±6.4 ng/mL) and enhanced whole blood leukocyte adhesion to platelets under shear. To examine whether the raised sP-selectin levels can directly influence leukocyte adhesion, isolated neutrophils were incubated with plasma from PAOD patients before and after immunodepletion of sP-selectin. Neutrophil adhesion to fibrinogen increased 2-fold following incubation with PAOD plasma, which was abrogated on sP-selectin immunodepletion. We subsequently demonstrated that recombinant sP-selectin dose-dependently (75 to 250 ng/mL) increased leukocyte adhesion to fibrinogen and platelet monolayers. This increase was PSGL-1 and Src kinase-dependent and correlated with an increase in sP-selectin-mediated Mac-1 activation. sP-selectin–stimulated neutrophil adhesion to platelet monolayers was inversely correlated with shear, such that at low shear (50 s
−1
) a 92.7%±15.7 increase in adhesion was observed decreasing to 38.5%±11.9 at 150 s
−1
and 10.1%±7.4 at 300 s
−1
. These studies suggest a potentially important role for sP-selectin in modulating neutrophil adhesion in patients with PAOD, particularly at sites of low shear, where it raises the possibility that raised plasma sP-selectin levels may enhance leukocyte recruitment to vascular injury and promote disease progression.
Potential Consequences for Recruitment, Power, and External Validity of Requirements for Additional Risk Factors for Eligibility in Randomized Controlled Trials in Secondary Prevention of Stroke
Authors: Howard Sally C. , Algra Ale , Warlow Charles P. , Rothwell Peter M.
Published: December 2005

Background and Purpose—

Eligibility criteria determine the external validity (generalizability) of the results of randomized controlled trials. To increase the number of outcome events, and hence statistical power, some recent stroke prevention trials have required additional vascular risk factors for eligibility.

Methods—

To assess the merits of additional eligibility criteria in stroke prevention trials, we analyzed data from 3 trials and 1 hospital-referred series of patients with a transient ischemic attack or minor ischemic stroke. Patients were stratified according to 2 sets of additional risk factors similar to those used in recent trials (MATCH, SPORTIF and PRoFESS); risk of stroke, myocardial infarction, or vascular death was calculated in relation to the number of risk factors.

Results—

Although the observed risk during follow-up did increase with the number of risk factors present (
P
<0.01 for both sets), the risks in patients with ≥1 risk factors were not substantially greater than those in all patients. Consequently, although the proportions of patients with no risk factors in the 4 cohorts differed substantially between the 2 sets of eligibility criteria (21% to 28% versus 56% to 73%), in neither case could their exclusion be justified on statistical grounds.

Conclusions—

The degree of patient selection introduced by use of additional vascular risk factors as eligibility criteria for trials can differ substantially between apparently similar sets of risk factors. Given that the potential for additional eligibility criteria to undermine generalizability and prolong recruitment outweighs any benefits in terms of statistical power, the exclusion of patients with no risk factors is difficult to justify.