bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of calcium oscillations by membrane fluxes
Authors: Sneyd J. , Tsaneva-Atanasova K. , Yule D. I. , Thompson J. L. , Shuttleworth T. J.
Published: February 2004

It is known that Ca
2+
influx plays an important role in the modulation of inositol trisphosphate-generated Ca
2+
oscillations, but controversy over the mechanisms underlying these effects exists. In addition, the effects of blocking membrane transport or reducing Ca
2+
entry vary from one cell type to another; in some cell types oscillations persist in the absence of Ca
2+
entry (although their frequency is affected), whereas in other cell types oscillations depend on Ca
2+
entry. We present theoretical and experimental evidence that membrane transport can control oscillations by controlling the total amount of Ca
2+
in the cell (the Ca
2+
load). Our model predicts that the cell can be balanced at a point where small changes in the Ca
2+
load can move the cell into or out of oscillatory regions, resulting in the appearance or disappearance of oscillations. Our theoretical predictions are verified by experimental results from HEK293 cells. We predict that the role of Ca
2+
influx during an oscillation is to replenish the Ca
2+
load of the cell. Despite this prediction, even during the peak of an oscillation the cell or the endoplasmic reticulum may not be measurably depleted of Ca
2+
.
Division of labor among distinct subtypes of inhibitory neurons in a cortical microcircuit of working memory
Authors: Wang X.-J. , Tegnér J. , Constantinidis C. , Goldman-Rakic P. S.
Published: February 2004

A conspicuous feature of cortical organization is the wide diversity of inhibitory interneurons; their differential computational functions remain unclear. Here we propose a local cortical circuit in which three major subtypes of interneurons play distinct roles. In a model designed for spatial working memory, stimulus tuning of persistent activity arises from the concerted action of widespread inhibition mediated by perisoma-targeting (parvalbumin-containing) interneurons and localized disinhibition of pyramidal cells via interneuron-targeting (calretinin-containing) interneurons. Moreover, resistance against distracting stimuli (a fundamental property of working memory) is dynamically controlled by dendrite-targeting (calbindin-containing) interneurons. The experimental observation of inverted tuning curves of monkey prefrontal neurons recorded during working memory supports a key model prediction. This work suggests a framework for understanding the division of labor and cooperation among different inhibitory cell types in a recurrent cortical circuit.
Estimating hydration changes upon biomolecular reactions from osmotic stress, high pressure, and preferential hydration experiments
Authors: Shimizu Seishi
Published: February 2004

How do we estimate, from thermodynamic measurements, the number of water molecules adsorbed or released from biomolecules as a result of a biochemical process such as binding and allosteric effects? Volumetric and osmotic stress analyses are established methods for estimating water numbers; however, these techniques often yield conflicting results. In contrast, Kirkwood–Buff theory offers a novel way to calculate excess hydration number from volumetric data, provides a quantitative condition to gauge the accuracy of osmotic stress analysis, and clarifies the relationship between osmotic and volumetric analyses. I have applied Kirkwood–Buff theory to calculate water numbers for two processes: (
i
) the allosteric transition of hemoglobin and (
ii
) the binding of camphor to cytochrome P450. I show that osmotic stress analysis may overestimate hydration number changes for these processes.
A genomewide oscillation in transcription gates DNA replication and cell cycle
Authors: Klevecz Robert R. , Bolen James , Forrest Gerald , Murray Douglas B.
Published: February 2004

Microarray analysis from a yeast continuous synchrony culture system shows a genomewide oscillation in transcription. Maximums in transcript levels occur at three nearly equally spaced intervals in this ≈40-min cycle of respiration and reduction. Two temporal clusters (4,679 of 5,329) are maximally expressed during the reductive phase of the cycle, whereas a third cluster (650) is maximally expressed during the respiratory phase. Transcription is organized functionally into redox-state superclusters with genes known to be important in respiration or reduction being synthesized in opposite phases of the cycle. The transcriptional cycle gates synchronous bursts in DNA replication in a constant fraction of the population at 40-min intervals. Restriction of DNA synthesis to the reductive phase of the cycle may be an evolutionarily important mechanism for reducing oxidative damage to DNA during replication.
Complement regulation at the molecular level: The structure of decay-accelerating factor
Authors: Lukacik P. , Roversi P. , White J. , Esser D. , Smith G. P. , Billington J. , Williams P. A. , Rudd P. M. , Wormald M. R. , Harvey D. J. , Crispin M. D. M. , Radcliffe C. M. , Dwek R. A. , Evans D. J. , Morgan B. P. , Smith R. A. G. , Lea S. M.
Published: February 2004

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 Å above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.
Normalization and analysis of cDNA microarrays using within-array replications applied to neuroblastoma cell response to a cytokine
Authors: Fan Jianqing , Tam Paul , Woude George Vande , Ren Yi
Published: February 2004

The quantitative comparison of two or more microarrays can reveal, for example, the distinct patterns of gene expression that define different cellular phenotypes or the genes that are induced in the cellular response to certain stimulations. Normalization of the measured intensities is a prerequisite of such comparisons. However, a fundamental problem in cDNA microarray analysis is the lack of a common standard to compare the expression levels of different samples. Several normalization protocols have been proposed to overcome the variabilities inherent in this technology. We have developed a normalization procedure based on within-array replications via a semilinear in-slide model, which adjusts objectively experimental variations without making critical biological assumptions. The significant analysis of gene expressions is based on a weightedtstatistic, which accounts for the heteroscedasticity of the observed log ratios of expressions, and a balanced sign permutation test. We illustrated the use of the techniques in a comparison of the expression profiles of neuroblastoma cells that were stimulated with a growth factor, macrophage migration inhibitory factor (MIF). The analysis of expression changes at mRNA levels showed that ≈99 genes were up-regulated and 24 were reduced significantly (P<0.001) in MIF-stimulated neuroblastoma cells. The regulated genes included several oncogenes, growth-related genes, tumor metastatic genes, and immuno-related genes. The findings provide clues as to the molecular mechanisms of MIF-mediated tumor progression and supply therapeutic targets for neuroblastoma treatment.
DNA–PKcs function regulated specifically by protein phosphatase 5
Authors: Wechsler Thomas , Chen Benjamin P. C. , Harper Ryan , Morotomi-Yano Keiko , Huang Betty C. B. , Meek Katheryn , Cleaver James E. , Chen David J. , Wabl Matthias
Published: February 2004

Unrepaired DNA double-strand breaks can lead to apoptosis or tumorigenesis. In mammals double-strand breaks are repaired mainly by nonhomologous end-joining mediated by the DNA–PK complex. The core protein of this complex, DNA–PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself. Although the (auto)phosphorylation activity has been shown to be essential for repair of both random double-strand breaks and induced breaks at the immunoglobulin locus, the corresponding phosphatase has been elusive. In fact, to date, none of the putative phosphatases in DNA double-strand break repair has been identified. Here we show that protein phosphatase 5 interacts with DNA–PKcs and dephosphorylates with surprising specificity at least two functional sites. Cells with either hypo- or hyperphosphorylation of DNA–PKcs at these sites show increased radiation sensitivity.
Complex nested promoters control tissue-specific expression of acetyl-CoA carboxylase genes in wheat
Authors: Zuther E. , Huang S. , Jelenska J. , Eilenberg H. , Arnold E. M. , Su X. , Sirikhachornkit A. , Podkowinski J. , Zilberstein A. , Haselkorn R. , Gornicki P.
Published: February 2004

Cis-acting regulatory elements of the wheat acetyl-CoA carboxylase (ACC) gene family were identified by comparing the promoter activity of 5′ end gene fragments fused to a reporter gene in two transient expression systems: wheat protoplasts and epidermal cells of mature embryos. Expression of the plastid and the cytosolic ACC genes is each driven by two nested promoters responsible for the synthesis of two transcript types. The internal promoter is located in an intron removed from transcripts originating at the first promoter. These complex promoters, which are different for the cytosolic and plastid ACC genes, control tissue-specific expression of the enzymatic activity supplying cytosolic, plastid, and mitochondrial pools of malonyl-CoA. The activity of one such complex promoter, driving expression of one of the cytosolic ACC genes, was studied throughout development of transgenic wheat plants carrying a full-length promoter–reporter gene fusion. High activity of the promoter was detected in the coleoptile, in the upper sheath section of the leaf, on the top surface of the ovary, in some sections of the main veins in the lemma and glume, and in abaxial epidermis hair cells of the lemma, glume, and rachis. The findings are consistent with the developmental and environmental requirements for very-long-chain fatty acids and flavonoids, whose synthesis begins with the ACC reaction in the cytosol of these specific cell types.
A tautomeric zinc sensor for ratiometric fluorescence imaging: Application to nitric oxide-induced release of intracellular zinc
Authors: Chang Christopher J. , Jaworski Jacek , Nolan Elizabeth M. , Sheng Morgan , Lippard Stephen J.
Published: February 2004

Zinc is an essential metal ion for human growth and development, the disruption of cellular Zn
2+
homeostasis being implicated in several major disorders including Alzheimer's disease, diabetes, and cancer. The molecular mechanisms of Zn
2+
physiology and pathology are insufficiently understood, however, owing in part to the lack of tools for measuring changes in intracellular Zn
2+
concentrations with high spatial and temporal fidelity. To address this critical need, we have synthesized, characterized, and applied an intracellular fluorescent probe for the ratiometric imaging of Zn
2+
based on a tautomeric seminaphthofluorescein platform. Zin-naphthopyr 1 (ZNP1) affords single-excitation, dual-emission ratiometric detection of intracellular Zn
2+
through Zn
2+
-controlled switching between fluorescein and naphthofluorescein tautomeric forms. The probe features visible excitation and emission profiles, excellent selectivity responses for Zn
2+
over competing Ca
2+
and Mg
2+
ions at intracellular concentrations, a dissociation constant (

K
d

) for Zn
2+
of <1 nM, and an 18-fold increase in fluorescence emission intensity ratio (λ
624
/λ
528
) upon zinc binding. We demonstrate the value of the ZNP1 platform for biological applications by imaging changes in intracellular [Zn
2+
] in living mammalian cells. Included is the ratiometric detection of endogenous pools of intracellular Zn
2+
after NO-induced release of Zn
2+
from cellular metalloproteins. We anticipate that ZNP1 and related probes should find utility for interrogating the biology of Zn
2+
.
Duplication, coclustering, and selection of human Alu retrotransposons
Authors: Jurka Jerzy , Kohany Oleksiy , Pavlicek Adam , Kapitonov Vladimir V. , Jurka Michael V.
Published: February 2004

Alu and L1 are families of non-LTR retrotransposons representing ≈30% of the human genome. Genomic distributions of young Alu and L1 elements are quite similar, but over time, Alu densities in GC-rich DNA increase in comparison with L1 densities. Here we analyze two processes that may contribute to this phenomenon. First, DNA duplications in the human genome occur more frequently in Alu- and GC-rich than in AT-rich chromosomal regions. Second, most Alu elements tend to be coclustered with each other, but recently retroposed elements are likely to be inserted outside the existing clusters. These “stand-alone” elements appear to be rapidly eliminated from the genome. We also report that over time, the densities of recently retroposed Alu families on chromosome Y decline rapidly, whereas Alu densities on chromosome X increase relative to autosomal densities. We propose that these changes in the chromosomal proportions of Alu densities and the elimination of stand-alone Alus represent the same process of paternal Alu selection. We also propose that long-term Alu accumulation in GC-rich DNA is associated with DNA duplication initiated by elevated recombinogenic activities in Alu clusters.
A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis
Authors: De Gendt Karel , Swinnen Johannes V. , Saunders Philippa T. K. , Schoonjans Luc , Dewerchin Mieke , Devos Ann , Tan Karen , Atanassova Nina , Claessens Frank , Lécureuil Charlotte , Heyns Walter , Carmeliet Peter , Guillou Florian , Sharpe Richard M. , Verhoeven Guido
Published: February 2004

Androgens control spermatogenesis, but germ cells themselves do not express a functional androgen receptor (AR). Androgen regulation is thought to be mediated by Sertoli and peritubular myoid cells, but their relative roles and the mechanisms involved remain largely unknown. Using Cre/loxPtechnology, we have generated mice with a ubiquitous knockout of the AR as well as mice with a selective AR knockout in Sertoli cells (SC) only. Mice with a floxed exon 2 of the AR gene were crossed with mice expressing Cre recombinase ubiquitously or selectively in SC (under control of the anti-Müllerian hormone gene promoter). AR knockout males displayed a complete androgen insensitivity phenotype. Testes were located abdominally, and germ cell development was severely disrupted. In contrast, SC AR knockout males showed normal testis descent and development of the male urogenital tract. Expression of the homeobox genePem, which is androgen-regulated in SC, was severely decreased. Testis weight was reduced to 28% of that in WT littermates. Stereological analysis indicated that the number of SC was unchanged, whereas numbers of spermatocytes, round spermatids, and elongated spermatids were reduced to 64%, 3%, and 0% respectively of WT. These changes were associated with increased germ cell apoptosis and grossly reduced expression of genes specific for late spermatocyte or spermatid development. It is concluded that cell-autonomous action of the AR in SC is an absolute requirement for androgen maintenance of complete spermatogenesis, and that spermatocyte/spermatid development/survival critically depends on androgens.
Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing
Authors: Li Wan-Xiang , Li Hongwei , Lu Rui , Li Feng , Dus Monica , Atkinson Peter , Brydon Edward W. A. , Johnson Kyle L. , García-Sastre Adolfo , Ball L. Andrew , Palese Peter , Ding Shou-Wei
Published: February 2004

Homology-dependent RNA silencing occurs in many eukaryotic cells. We reported recently that nodaviral infection triggers an RNA silencing-based antiviral response (RSAR) in
Drosophila
, which is capable of a rapid virus clearance in the absence of expression of a virus-encoded suppressor. Here, we present further evidence to show that the
Drosophila
RSAR is mediated by the RNA interference (RNAi) pathway, as the viral suppressor of RSAR inhibits experimental RNAi initiated by exogenous double-stranded RNA and RSAR requires the RNAi machinery. We demonstrate that RNAi also functions as a natural antiviral immunity in mosquito cells. We further show that vaccinia virus and human influenza A, B, and C viruses each encode an essential protein that suppresses RSAR in
Drosophila
. The vaccinia and influenza viral suppressors, E3L and NS1, are distinct double-stranded RNA-binding proteins and essential for pathogenesis by inhibiting the mammalian IFN-regulated innate antiviral response. We found that the double-stranded RNA-binding domain of NS1, implicated in innate immunity suppression, is both essential and sufficient for RSAR suppression. These findings provide evidence that mammalian virus proteins can inhibit RNA silencing, implicating this mechanism as a nucleic acid-based antiviral immunity in mammalian cells.
Digital Detection of Genetic Mutations Using SPC-Sequencing
Authors: Ruparel Hameer , Ulz Michael E. , Kim Sobin , Ju Jingyue
Published: February 2004

Deletion or insertion mutations lead to a frameshift that causes misalignment between wild-type and mutated allele sequences, making it difficult to identify such mutations unambiguously by using electrophoresis-based DNA sequencing. We have previously established the feasibility of an accurate DNA sequencing method using solid-phase capturable (SPC) dideoxynucleotides and MALDI-TOF mass spectrometry on synthetic templates, an approach we refer to as SPC-sequencing. Here, we report the application of SPC-sequencing in characterizing frameshift mutations by using the detection of the BRCA1 gene mutations 185delAG and 5382insC as examples. In this method, Sanger DNA sequencing fragments are generated in one tube by using biotinylated dideoxynucleotides. The sequencing fragments carrying a biotin moiety at the 3′ end are captured on a streptavidin-coated solid phase to eliminate excess primer, primer dimers, and false stops. Only correctly terminated DNA fragments are captured, subsequently released, and analyzed by mass spectrometry to obtain digital DNA sequencing data. This method produces distinct doublet mass peaks at each point in the mass spectrum beyond the mutation site, facilitating the accurate characterization of the mutation. We have compared SPC-sequencing with electrophoresis-based sequencing in characterizing the above BRCA1 mutations, demonstrating the significant advantage offered by SPC-sequencing for the accurate identification of frameshift mutations.
The Genome Sequence of Mycoplasma mycoides subsp. mycoides SC Type Strain PG1T, the Causative Agent of Contagious Bovine Pleuropneumonia (CBPP)
Authors: Westberg Joakim , Persson Anja , Holmberg Anders , Goesmann Alexander , Lundeberg Joakim , Johansson Karl-Erik , Pettersson Bertil , Uhlén Mathias
Published: February 2004

Mycoplasma mycoides subsp. mycoidesSC (MmymySC)is the etiological agent of contagious bovine pleuropneumonia (CBPP), a highly contagious respiratory disease in cattle. The genome of Mmymy SC type strain PG1T has been sequenced to map all the genes and to facilitate further studies regarding the cell function of the organism and CBPP. The genome is characterized by a single circular chromosome of 1,211,703 bp with the lowest G+C content (24 mole%)and the highest density of insertion sequences (13% of the genome size)of all sequenced bacterial genomes. The genome contains 985 putative genes, of which 72 are part of insertion sequences and encode transposases. Anomalies in the GC-skew pattern and the presence of large repetitive sequences indicate a high genomic plasticity. A variety of potential virulence factors was identified, including genes encoding putative variable surface proteins and enzymes and transport proteins responsible for the production of hydrogen peroxide and the capsule, which is believed to have toxic effects on the animal.
Basement membrane‐type heparan sulfate proteoglycan (perlecan) and low‐density lipoprotein (LDL) are co‐localized in granulation tissues: a possible pathogenesis of cholesterol granulomas in jaw cysts
Authors: Yamazaki Manabu , Cheng Jun , Hao Natsuko , Takagi Ritsuo , Jimi Shiro , Itabe Hiroyuki , Saku Takashi
Published: February 2004

Background:  As perlecan contains a low‐density lipoprotein (LDL) receptor‐like repeats in the second domain of its core protein, LDL may be bound to perlecan, which is rich in granulation tissues. We wanted to study if this is the case in the cyst wall of radicular cysts, which are often associated with cholesterol granuloma.

Methods:  Thirty‐three specimens of radicular cyst with cholesterol granulomas were immunohistochemically examined for comparative localizations of perlecan, apoprotein B (apo B), and oxidized LDL (Ox‐LDL), and for mRNA expression levels for perlecan.

Results:  Myxoid or edematous stroma of immature granulation tissues was strongly positive for perlecan and simultaneously for apo B and Ox‐LDL. Macrophages including foamy cells scattered in the granulation tissues were also immunopositive for Ox‐LDL and occasionally for apo B. In situ hybridization showed that fibroblasts, endothelial cells, and pericytes had strong signals for perlecan, which was also confirmed by RT‐PCR.

Conclusion:  These results suggest that perlecan, which is abundantly produced and accumulated in the cyst wall of immature granulation tissue, traps Ox‐LDL locally, and that Ox‐LDL is phagocytosed by macrophages. Thus, LDL‐laden foamy macrophages are aggregated in the granulation tissue, and free cholesterol from ruptured macrophages may be concentrated locally to be crystallized, which may induce foreign body granulomas in the cyst wall.
Could a laptop computer plus the liquid crystal display projector amount to improved multimedia geoscience instruction?
Authors: Chang C.Y.
Published: February 2004

In this study, a multimedia computer‐aided tutorial (MCAT) on the topic of debris‐flow hazards was developed for senior high‐school students in Taiwan. The format of the new course is a blend of whole‐class presentations, interactive discussions among the teacher and students, and classroom activities using the MCAT software. The whole‐class presentation was presented using both a laptop computer and a high‐resolution liquid crystal display projector to display the MCAT contents on a large white screen in front of a whole class. Besides, class discussions between the teacher and the students and among students were also embedded in the teaching format. Students' earth science learning outcomes were evaluated by administering an achievement test and a survey of attitudes towards the earth science subject before and after the course. The results indicated that MCAT accompanied by the current ‘interactive whole‐class teaching’ form could significantly help the students' grasp of earth science concepts and greatly improve their attitudes towards earth science.
Tools for the job: a report of two surveys of information and communications technology training and use for literacy in primary schools in the West of England
Authors: Waite S.
Published: February 2004

Substantial investment has been made in improving computer hardware and raising the profile of information and communications technology (ICT) in English primary schools in recent years, in line with the belief that skills in ICT are essential for our future workforce (DfEE/QCA 2000). This study compares practising teachers' responses in 1998 and 2001 to a questionnaire about the aims and uses of ICT in primary schools for literacy activities. It discusses the changes in what teachers want and their understanding of the task the government has given them to do. A commonly cited problem is finding time to absorb the new technology to maximise its pedagogic potential.
Realism in the design process and credibility of a simulation‐based virtual laboratory
Authors: Couture M.
Published: February 2004

The credibility of an instructional simulation is the most important issue in distance education, where it may replace hands‐on activities. This credibility is based in large part upon verisimilitude, a perception strongly influenced by the simulation's realism. This paper presents a case study encompassing the design process of a simulation‐based virtual laboratory, which was guided by a realism principle, and an investigation of its credibility among potential users. We found that many characteristics of the environment associated with the design principle favoured its credibility, but that others had widely varying, even opposite, effects among users. A user's prior experience was shown to play a crucial but intricate role in verisimilitude and credibility judgements.
Inflation, Inflation Variability, and Corruption
Authors: Braun Miguel , Di tella Rafael
Published: February 2004

We present a model where agents can inflate the cost of goods needed to start an investment project and inflation variability increases monitoring costs. We show that inflation variability can lead to higher corruption and lower investment. We document a positive relationship between corruption and inflation variability in a sample of 75 countries. The effect is robust to the inclusion of country fixed effects, other controls, and 2SLS estimation. The results are economically significant: a one standard deviation increase in inflation variance from the median increases corruption by 12 percent of a standard deviation and reduces growth by 0.33 percentage points. Our paper highlights a new channel through which inflation reduces investment and growth, thus bridging the perception gap over the costs of inflation between economists and the public. We also find evidence that political competition reduces corruption and that corruption is pro‐cyclical.
Interstitial cells of Cajal are functionally innervated by excitatory motor neurones in the murine intestine
Authors: Iino Satoshi , Ward Sean M. , Sanders Kenton M.
Published: February 2004

Recent studies have demonstrated that intramuscular interstitial cells of Cajal (ICC) are preferential targets for neurotransmission in the stomach. Terminals of enteric motor neurones also form tight, synaptic‐like contacts with ICC in the small intestine and colon, but little is known about the role of these cells in neurotransmission. ICC at the deep muscular plexus (ICC‐DMP) of the small intestine express neurokinin 1 receptors (NK1R) and internalize these receptors in response to exogenous substance P. We used NK1R internalization as an assay of functional innervation of ICC‐DMP in the murine small intestine. Under basal conditions NK1R‐like immunoreactivity (NK1R‐LI) was mainly observed in ICC‐DMP (519 cells counted, 100% were positive) and myenteric neurones. ICC‐DMP were closely apposed to substance P‐containing nerve fibres. Of 338 ICC‐DMP examined, 65% were closely associated with at least one substance P‐positive nerve fibre, 32% were associated with at least two, 2% were associated with more than two nerve fibres and 1% with none. After electrical field stimulation (EFS, 10 Hz; 1 min) NK1R‐LI was internalized in more than 80% of ICC‐DMP, as compared to 10% of cells before EFS. Internalization of NK1R was not observed in myenteric ICC or smooth muscle cells in response to nerve stimulation. Internalization of NK1R‐LI was blocked by the specific NK1 receptor antagonist WIN 62577 (1 μm) and by tetrodotoxin (0.3 μm), suggesting that internalization resulted from stimulation of receptors with neurally released neurokinins. These data suggest that ICC‐DMP are primary targets for neurokinins released from enteric motor neurones in the intestine.
Spatiotemporal patterning of IP3‐mediated Ca2+ signals in Xenopus oocytes by Ca2+‐binding proteins
Authors: Dargan Sheila L. , Schwaller Beat , Parker Ian
Published: February 2004

Ca2+‐binding proteins (CaBPs) are expressed in a highly specific manner across many different cell types, yet the physiological basis underlying their selective distribution patterns remains unclear. We used confocal line‐scan microscopy together with photo‐release of IP3 in Xenopus oocytes to investigate the actions of mobile cytosolic CaBPs on the spatiotemporal properties of IP3‐evoked Ca2+ signals. Parvalbumin (PV), a CaBP with slow Ca2+‐binding kinetics, shortened the duration of IP3‐evoked Ca2+ signals and ‘balkanized’ global responses into discrete localized events (puffs). In contrast, calretinin (CR), a presumed fast buffer, prolonged Ca2+ responses and promoted ‘globalization’ of spatially uniform Ca2+ signals at high [IP3]. Oocytes loaded with CR or PV showed Ca2+ puffs following photolysis flashes that were subthreshold in controls, and the spatiotemporal properties of these localized events were differentially modulated by PV and CR. In comparison to results we previously obtained with exogenous Ca2+ buffers, PV closely mimicked the actions of the slow buffer EGTA, whereas CR showed important differences from the fast buffer BAPTA. Most notably, puffs were never observed after loading BAPTA, and this exogenous buffer did not show the marked sensitization of IP3 action evident with CR. The ability of Ca2+ buffers and CaBPs with differing kinetics to fine‐tune both global and local intracellular Ca2+ signals is likely to have significant physiological implications.
Aerobic exercise before diving reduces venous gas bubble formation in humans
Authors: Dujić Željko , Duplančic Darko , Marinovic‐Terzić Ivana , Baković Darija , Ivančev Vladimir , Valic Zoran , Eterović Davor , Petri Nadan M , Wisløff Ulrik , Brubakk Alf O.
Published: February 2004

We have previously shown in a rat model that a single bout of high‐intensity aerobic exercise 20h before a simulated dive reduces bubble formation and after the dive protects from lethal decompression sickness. The present study investigated the importance of these findings in man. Twelve healthy male divers were compressed in a hyperbaric chamber to 280kPa at a rate of 100kPamin−1 breathing air and remaining at pressure for 80min. The ascent rate was 9mmin−1 with a 7min stop at 130kPa. Each diver underwent two randomly assigned simulated dives, with or without preceding exercise. A single interval exercise performed 24h before the dive consisted of treadmill running at 90% of maximum heart rate for 3min, followed by exercise at 50% of maximum heart rate for 2min; this was repeated eight times for a total exercise period of 40min. Venous gas bubbles were monitored with an ultrasonic scanner every 20min for 80min after reaching surface pressure. The study demonstrated that a single bout of strenuous exercise 24h before a dive to 18 m of seawater significantly reduced the average number of bubbles in the pulmonary artery from 0.98 to 0.22 bubbles cm−2(P= 0.006) compared to dives without preceding exercise. The maximum bubble grade was decreased from 3 to 1.5 (P= 0.002) by pre‐dive exercise, thereby increasing safety. This is the first report to indicate that pre‐dive exercise may form the basis for a new way of preventing serious decompression sickness.
Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice
Authors: Martínez Vicente , Wang Lixin , Rivier Jean , Grigoriadis Dimitri , Taché Yvette
Published: February 2004

Recently characterized selective agonists and developed antagonists for the corticotropin releasing factor (CRF) receptors are new tools to investigate stress‐related functional changes. The influence of mammalian CRF and related peptides injected intracerebroventricularly (i.c.v.) on gastric and colonic motility, and the CRF receptor subtypes involved and their role in colonic response to stress were studied in conscious mice. The CRF1/CRF2 agonists rat urocortin 1 (rUcn 1) and rat/human CRF (r/h CRF), the preferential CRF1 agonist ovine CRF (oCRF), and the CRF2 agonist mouse (m) Ucn 2, injected i.c.v. inhibited gastric emptying and stimulated distal colonic motor function (bead transit and defecation) while oCRF9–33OH (devoid of CRF receptor affinity) showed neither effects. mUcn 2 injected peripherally had no colonic effect. The selective CRF2 antagonist astressin2‐B (i.c.v.), at a 20 : 1 antagonist: agonist ratio, blocked i.c.v. r/hCRF and rUcn 1 induced inhibition of gastric transit and reduced that of mUcn 2, while the CRF1 antagonist NBI‐35965 had no effect. By contrast, the colonic motor stimulation induced by i.c.v. r/hCRF and rUcn 1 and 1h restraint stress were antagonized only by NBI‐35965 while stimulation induced by mUcn 2 was equally blocked by both antagonists. None of the CRF antagonists injected i.c.v. alone influenced gut transit. These data establish in mice that brain CRF1 receptors mediate the stimulation of colonic transit induced by central CRF, urocortins (1 and 2) and restraint stress, while CRF2 receptors mediate the inhibitory actions of these peptides on gastric transit.
False beats in coupled piano string unisons
Authors: Capleton Brian
Published: February 2004

The behavior of a unison pair of piano strings coupled by the soundboard bridge, when one string has localized anisotropy in the reactive part of the bridge admittance for a given partial frequency, can be investigated using a theoretical matrix description. The anisotropy can cause what in piano tuning terminology is referred to as “false beating” in a partial of the single string. A mathematical model can be used to illustrate how “mistunings” between the strings of the unison (measured when the strings are sounding in isolation from each other) may theoretically arise as a consequence of the normal practice in piano tuning, of eliminating or reducing audible beating in the unison when both strings are sounding. “False beats” in a single string partial can be “inherited” by a partial of the coupled unison’s spectrum, and mistunings between the strings can eliminate or reduce the appearance of this inheritance.
Real time inverse filter focusing through iterative time reversal
Authors: Montaldo Gabriel , Tanter Mickaël , Fink Mathias
Published: February 2004

In order to achieve an optimal focusing through heterogeneous media we need to build the inverse filter of the propagation operator. Time reversal is an easy and robust way to achieve such an inverse filter in nondissipative media. However, as soon as losses appear in the medium, time reversal is not equivalent to the inverse filter anymore. Consequently, it does not produce the optimal focusing and beam degradations may appear. In such cases, we showed in previous works that the optimal focusing can be recovered by using the so-called spatiotemporal inverse filter technique. This process requires the presence of a complete set of receivers inside the medium. It allows one to reach the optimal focusing even in extreme situations such as ultrasonic focusing through human skull or audible sound focusing in strongly reverberant rooms. But, this technique is time consuming and implied fastidious numerical calculations. In this paper we propose a new way to process this inverse filter focusing technique in real time and without any calculation. The new process is based on iterative time reversal process. Contrary to the classical inverse filter technique, this iteration does not require any computation and achieves the inverse filter in an experimental way using wave propagation instead of computational power. The convergence from time reversal to inverse filter during the iterative process is theoretically explained. Finally, the feasibility of this iterative technique is experimentally demonstrated for ultrasound applications.
Click sounds produced by cod (Gadus morhua)
Authors: Vester Heike I. , Folkow Lars P. , Blix A. S.
Published: February 2004

Conspicuous sonic click sounds were recorded in the presence of cod (Gadus morhua), together with either harp seals (Pagophilus groenlandicus), hooded seals (Cystophora cristata) or a human diver in a pool. Similar sounds were never recorded in the presence of salmon (Salmo salar) together with either seal species, or from either seal or fish species when kept separately in the pool. It is concluded that cod was the source of these sounds and that the clicks were produced only when cod were approached by a swimming predatorlike body. The analyzed click sounds (n=377) had the following characteristics (overall averages ± S.D.): peak frequency=5.95±2.22 kHz; peak-to-peak duration=0.70±0.45 ms; sound pressure level (received level)=153.2±7.0 dB re 1 μPa at 1 m. At present the mechanism and purpose of these clicks is not known. However, the circumstances under which they were recorded and some observations on the behavior of the seals both suggest that the clicks could have a predator startling function.
A tri-modal directional transducer
Authors: Butler John L. , Butler Alexander L. , Rice Joseph A.
Published: February 2004

Acoustic transducers made from piezoelectric ceramic cylinders usually exploit the breathing or omnidirectional (omni) mode of vibration. However, with suitable voltage distribution, higher order extensional modes of the cylinder can be excited which produce directional radiation patterns. These modal radiation patterns can then be combined to synthesize desired beam patterns which may be steered by incrementing the excitation. This paper describes a model for the combined acoustic response of the extensional modes of vibration of a piezoelectric ceramic cylinder, a method of synthesizing a desired radiation pattern, and an experimental implementation of a directional transducer that uses these techniques. This tri-modal transducer is broadband and directional with a frequency independent beam pattern yet simple, small, and lightweight.
Effects of mutual impedance on the radiation characteristics of transducer arrays
Authors: Lee Haksue , Tak Jinhee , Moon Wonkyu , Lim Geunbae
Published: February 2004

The mutual resistance of transducer arrays is investigated in order to design arrays with improved performance for high intensity sounds at a given frequency. This work proposes the theory that the mutual resistance is related to the loading effects of pressure waves propagated from a piston driver on the surface of another driver. Using this interpretation, the important characteristics of the mutual resistance of two piston drivers are explained and the conditions for local maxima in the mutual resistance are easily determined. On the basis of analyses of the interactions between a driver and acoustic pressure waves, we propose a method to determine the driver radius and the distance between two drivers that give maximum mutual radiation resistance. To evaluate the proposed method, the total resistance of a transducer array is calculated using the formulas for mutual and self-resistance established by Pritchard. The results of the calculations of the total resistances of arrays with many drivers show that a transducer array with drivers arranged sparsely can achieve a larger value of the radiation power per unit area as well as better radiation efficiency than an array in which the drivers are in a closely packed arrangement at a given frequency.
Fluid volume displacement at the oval and round windows with air and bone conduction stimulation
Authors: Stenfelt Stefan , Hato Naohito , Goode Richard L.
Published: February 2004

The fluids in the cochlea are normally considered incompressible, and the fluid volume displacement of the oval window (OW) and the round window (RW) should be equal and of opposite phase. However, other channels, such as the cochlear and vestibular aqueducts, may affect the fluid flow. To test if the OW and RW fluid flows are equal and of opposite phase, the volume displacement was assessed by multiple point measurement at the windows with a laser Doppler vibrometer. This was done during air conduction (AC) stimulation in seven fresh human temporal bones, and with bone conduction (BC) stimulation in eight temporal bones and one human cadaver head. With AC stimulation, the average volume displacement of the two windows is within 3 dB, and the phase difference is close to 180° for the frequency range 0.1 to 10 kHz. With BC stimulation, the average volume displacement difference between the two windows is greater: below 2 kHz, the volume displacement at the RW is 5 to 15 dB greater than at the OW and above 2 kHz more fluid is displaced at the OW. With BC stimulation, lesions at the OW caused only minor changes of the fluid flow at the RW.
A simple formula for the longitudinal modes in a cylinder
Authors: Ahmad Faiz
Published: February 2004

For cT<c<cL, the Pochhammer dispersion relation can be replaced by an approximate equation which can be solved to obtain the dimensionless wave number explicitly as a function of the phase velocity. This equation is similar to the corresponding equation for the Lamb modes in plate. The two types of modes are interlaced, i.e., between every pair of modes of the plate there is a longitudinal mode of cylinder and vice versa.
Hands help hearing: Facilitatory audiotactile interaction at low sound-intensity levels
Authors: Schürmann Martin , Caetano Gina , Jousmäki Veikko , Hari Riitta
Published: February 2004

Auditory and vibrotactile stimuli share similar temporal patterns. A psychophysical experiment was performed to test whether this similarity would lead into an intermodal bias in perception of sound intensity. Nine normal-hearing subjects performed a loudness-matching task of faint tones, adjusting the probe tone to sound equally loud as a reference tone. The task was performed both when the subjects were touching and when they were not touching a tube that vibrated simultaneously with the probe tone. The subjects chose on average 12% lower intensities (p<0.01) for the probe tone when they touched the tube, suggesting facilitatory interaction between auditory and tactile senses in normal-hearing subjects.
Data extrapolation method for boundary element method-based near-field acoustical holography
Authors: Saijyou Kenji , Uchida Hiroshi
Published: February 2004

A new data extrapolation method for boundary element method (BEM)-based near-field acoustical holography (NAH) is proposed to reduce an error of the reconstructed result obtained from the pressure measured on an aperture small compared with the structure. The finiteness of the measurement aperture is a serious impediment to actual large-scale implementation of NAH, because NAH requires the measurement of the pressure field over a complete surface of structure. To eliminate the requirement, the wave number-space data extrapolation method for fast Fourier transform (FFT)-based NAH has been proposed. In this paper, the extension of this data extrapolation method to BEM-based NAH is presented. The effectiveness of this method is demonstrated by experiments. The experiment results confirm that the reconstruction error is sufficiently suppressed by the proposed method.
Wave equations, dispersion relations, and van Hove singularities for applications of doublet mechanics to ultrasound propagation in bio- and nanomaterials
Authors: Wu Junru , Layman Christopher , Liu Jun
Published: February 2004

A fundamental mathematical framework for applications of Doublet Mechanics to ultrasound propagation in a discrete material is introduced. A multiscale wave equation, dispersion relation for longitudinal waves, and shear waves are derived. The van Hove singularities and corresponding highest frequency limits for the Mth-order wave equations of longitudinal and shear waves are determined for a widely used microbundle structure. Doublet Mechanics is applied to soft tissue and low-density polyethylene. The experimental dispersion data for soft tissue and low-density polyethylene are compared with results predicted by Doublet Mechanics and an attenuation model based on a Kramers–Kronig relation in classical continuum mechanics.
Response variance prediction in the statistical energy analysis of built-up systems
Authors: Langley Robin S. , Cotoni Vincent
Published: February 2004

In the statistical energy analysis (SEA) of high frequency noise and vibration, a complex engineering structure is represented as an assembly of subsystems. The response of the system to external excitation is expressed in terms of the vibrational energy of each subsystem, and these energies are found by employing the principle of power balance. Strictly the computed energy is an average taken over an ensemble of random structures, and for many years there has been interest in extending the SEA prediction to the variance of the energy. A variance prediction method for a general built-up structure is presented here. Closed form expressions for the variance are obtained in terms of the standard SEA parameters and an additional set of parameters αk that describe the nature of the power input to each subsystem k, and αks that describe the nature of the coupling between subsystems k and s. The theory is validated by comparison with Monte Carlo simulations of plate networks and structural-acoustic systems.
Echolocation signals of free-ranging killer whales (Orcinus orca) and modeling of foraging for chinook salmon (Oncorhynchus tshawytscha)
Authors: Au Whitlow W. L. , Ford John K. B. , Horne John K. , Allman Kelly A. Newman
Published: February 2004

Fish-eating “resident”-type killer whales (Orcinus orca) that frequent the coastal waters off northeastern Vancouver Island, Canada have a strong preference for chinook salmon (Oncorhynchus tshawytscha). The whales in this region often forage along steep cliffs that extend into the water, echolocating their prey. Echolocation signals of resident killer whales were measured with a four-hydrophone symmetrical star array and the signals were simultaneously digitized at a sample rate of 500 kHz using a lunch-box PC. A portable VCR recorded the images from an underwater camera located adjacent to the array center. Only signals emanating from close to the beam axis (1185 total) were chosen for a detailed analysis. Killer whales project very broadband echolocation signals (Q equal 0.9 to 1.4) that tend to have bimodal frequency structure. Ninety-seven percent of the signals had center frequencies between 45 and 80 kHz with bandwidths between 35 and 50 kHz. The peak-to-peak source level of the echolocation signals decreased as a function of the one-way transmission loss to the array. Source levels varied between 195 and 224 dB re:1 μPa. Using a model of target strength for chinook salmon, the echo levels from the echolocation signals are estimated for different horizontal ranges between a whale and a salmon. At a horizontal range of 100 m, the echo level should exceed an Orcinus hearing threshold at 50 kHz by over 29 dB and should be greater than sea state 4 noise by at least 9 dB. In moderately heavy rain conditions, the detection range will be reduced substantially and the echo level at a horizontal range of 40 m would be close to the level of the rain noise.