bluuebunny/crossref_metadata_2025 huggingface dataset:
ENDOW: Efficient Development of Offshore Windfarms
Authors: Barthelmie Rebecca , Larsen Gunner , Bergström Hans , Magnusson Mikael , Schlez Wolfgang , Hassan Garrad ,   Partners Ltd, Rados Kostas , Lange Bernhard , Vølund Per , Neckelmann Søren , Christensen Lars , Schepers Gerard , Hegberg Terry , Folkerts Luuk
Published: October 2002

The objective of the ENDOW project is to evaluate, enhance and interface wake and boundary-layer models for utilisation in developing offshore windfarms. The model hierarchy will form the basis of design tools for use by wind energy developers and turbine manufacturers to optimise power output from offshore wind farms through minimised wake effects immediately downwind of wind turbines and optimal grid connections. The initial focus of the project was to use databases from existing offshore wind farms (Vindeby and Bockstigen) for the first comprehensive evaluation of offshore wake model performances. The six wake models vary in complexity from empirical solutions to the most advanced models based on solutions of the Navier-Stokes equations using eddy viscosity or k-epsilon turbulence closure. One of the wake models is also being coupled with a full aeroelastic model for the calculation of wind loads on the turbines. Parallel research includes comparison of a local-scale stability/roughness model with a mesoscale model focusing on boundary-layer development within and over a large offshore wind farm, and particularly the influence of large scale thermal flows. A new experiment was conducted using SODAR immediately downwind of offshore wind turbines to examine vertical wind speed profiles to hub-height and beyond in near-wake conditions and wake dispersion to assist in model development and evaluation.
Recent Aeroacoustics Research in the United States
Authors: Raman G. , McLaughlin D. K.
Published: October 2002

It is expected that with the projected increase in air travel aeroacoustics research will be very critical in meeting increasingly stringent aircraft noise certification standards. In the United States aeroacoustics research has steadily progressed toward enhanced safety, noise benefits and lower costs. This report provides a brief summary of selected recent aeroacoustics activity in the US. Four topics of great interest to the aerospace industry are: (1) Advanced Subsonic Technology (AST) for future subsonic aircraft, (2) High Speed Research (HSR) for future supersonic commercial aircraft, (3) Rotorcraft noise control efforts, and (4) Weapons bay and other noise control applications for the military. Examples of good progress in the areas of jet, fan, airframe and helicopter noise as well as liner design and weapons bay noise suppression are provided herein. In the next few years we look forward to seeing major strides in noise reduction technology and our ability to predict situations of aeroacoustics interest.
The Characterisation of Fibrous Materials from Measurements of Absorption Using Techniques Based on the Voronina Model
Authors: Alba Jesus , Ramis Jaime , Llinares Jaime
Published: October 2002

In this work we present a method for characterising fibrous materials from absorption measurements in the Kundt tube. One may calculate the structural characteristics, the complex propagation constant and the specific impedance of material using techniques based on the Voronina Model. Furthermore, this method allows one to estimate the diameter of a fibre for its use in other models, and does not require any special equipment.
The Characterisation of Fibrous Materials from Measurements of Absorption Using Techniques Based on Miki's Model
Authors: Alba Jesús , Ramis Jaime
Published: October 2002

In this work the authors present a method for characterizing fibrous materials from absorption measurements in the Kundt tube. Specific Flow Resistance may be calculated, using techniques based on the Miki's model. Using this model and taking measurements of absorption as a starting point, the method presented here enables one to achieve a complete characterisation of a fibrous material, with the added advantage that no special equipment is needed.
Blade and Shaft Crack Detection Using Torsional Vibration Measurements Part 1: Feasibility Studies
Authors: Maynard Kenneth P. , Trethewey Martin
Published: October 2002

The primary goal of the development project was to demonstrate the feasibility of detecting changes in blade natural frequencies (such as those associated with a blade crack) on a turbine using non-contact, non-intrusive measurement methods. The approach was to set up a small experimental apparatus, develop a torsional vibration detection system, and maximize the dynamic range and the signal to noise ratio. The results of the testing and analysis clearly demonstrated the feasibility of using torsional vibration to detect the change in natural frequency of a blade due to a change in stiffness such as those associated with a blade crack.
By-Pass Road Effects on the Traffic Noise in the City of Gandia (Spain)
Authors: Uris Antonio , Cervera Francisco
Published: October 2002

Roads belonging to the national network go through the Mediterranean coastal towns. In this paper, a study carried out in Gandia, a coastal city located 65 km from Valencia, where the local authorities decided to build a by-pass road to reduce the volume of traffic, is presented. Traffic noise levels are measured before and after the by-pass road was built.
Are Normal Hearing Thresholds a Sufficient Condition for Click-Evoked Otoacoustic Emissions?
Authors: Kapadia Sarosh , Lutman Mark E.
Published: October 2002

Transient-evoked otoacoustic emissions (TEOAE) have been reported in several studies as absent in a small minority of normal ears. Other studies have reported TEOAEs in all normal ears. Differences between studies may arise directly from criteria for TEOAE identification, criteria for selection of normals, or statistically due to limited sample sizes. In order to understand and model cochlear processes involved in TEOAE generation, it needs to be known whether the presence of normal hearing leads automatically to generation of TEOAEs. The present study set out to establish in a large sample if any ears could be found that lacked TEOAEs despite normal hearing threshold levels (HTL). A total of 397 ears from highly co-operative adult subjects were examined, under laboratory conditions. Using cross-correlation between replicate nonlinear wave forms as the criterion, TEOAEs were present in of 99.2% of the sample (lower CI 98.1%). However, careful visual assessment of the recorded wave forms for the remaining ears did not unequivocally show absence of TEOAE characteristics in any ear with normal HTLs. Whilst TEOAE strength varies amongst ears, no clear evidence was found to show that TEOAEs can be absent when HTLs are normal.
Vibration Suppression Using Bandpass Absorber
Authors: Filipović Damir
Published: October 2002

A concept for active vibration suppression with a so called bandpass absorber (BPA) is presented. A properly designed compensator in the active feedback converts the well-known passive absorber into a bandpass absorber. Such an absorber amplifies frequencies in a given frequency range, thus producing almost the resonance for all these frequencies. If such an absorber is attached to a vibrating body, it absorbs vibrations at all frequencies that belong to the bandpass range. The presented compensator design guarantees the stability of the system. The proposed concept needs an additional local control of the absorber mass displacement. The paper presents the idea, the design procedure, and the simulation results that prove the relevance of the solution.
Increases in Leukemia in Infants in Wales and Scotland following Chernobyl: Evidence for Errors in Statutory Risk Estimates
Authors: Busby Chris , Cato Molly Scott
Published: October 2002

After the Chernobyl reactor accident in April 1986, rainfall precipitation caused measurable radioactive contamination of Wales and Scotland. Using risk models developed by themselves and by the International Commission on Radiological Protection, the UK National Radiological Protection Board advised that no measurable increase in leukemia was predicted at exposures which they estimated from measurements of contamination. However, cancer registry data from both the Wales and Scotland registries show a sharp increase in cases of infant leukemia age 0–1 in the eighteen month period January 1st 1987 to June 30th 1988. This period is that in which the birth cohort who were in utero in the exposure period following the fallout would be in the age group 0–1. Compared with an ‘unexposed group’ consisting of the period 1975–1986 the Wales exposed group had a relative risk (RR) of 4.4 (p = 0.004), the Scotland group a RR of 3.7 (p = .001) and the combined Wales and Scotland group an RR of 3.87 (p = .0001). A second unexposed group, those aged 0–1 in 1989–91 had no significant increased risk although after 1991 rates increased slightly. This finding supports earlier reports of infant leukemia effects in Greece, Germany and the U.S. following Chernobyl. The data cannot entirely distinguish between pre-conception or in utero effects but also reported here are increases in very low birth-weight births in Wales following Chernobyl, suggesting a genetic component to both effects. The existence of good quality leukemia and exposure data makes it possible to calculate an error in the presently accepted risk factors for radiation induced leukemia following this kind of exposure of about 100-fold or more. The possibility of errors of this magnitude in the contemporary risk estimates of ionizing radiation effects suggests that a more cautious approach should be exercised to policy decisions about nuclear power options.
Bureaucratic Tax-Seeking: The Danish Waste Tax
Authors: Christoffersen Henrik , Svendsen Gert Tinggaard
Published: October 2002

We suggest that when individual ministries are able to add differentiated green taxation on top of traditional taxation, the result is over-taxation. This is so for two reasons. Firstly, budget maximisation leads to overwhelming fiscal pressure because bureaucracies are competing for resources just like fishermen or hunters (here named ‘bureaucratic tax-seeking’). Secondly, the absence of a strong and fully informed ‘troop leader’, i.e. overall budget co-ordinator, prevents the rational co-ordination of collective action. Taxing citizens or firms may then be likened to harvesting rents from a natural resource and we therefore apply a common-pool resource model. These suggestions are confirmed by a case study of the Danish waste tax with its fixed price approach and perverse incentives compared to that of achieving environmental target levels in a cost-minimising way. Thus, we recommend that bureaucratic institutions should coordinate their tax-seeking efforts to maximise budgets in the long run and that the ministries that collect green tax revenues should not be allowed to control these revenues. Furthermore, our results dictate that the postulated effects arising from green tax intervention need to be demonstrated.
Implementing Stronger European Air Pollution Policies: Will High Hopes in Brussels and Geneva Be Dashed in London?
Authors: Wettestad Jørgen
Published: October 2002

The recently adopted National Emission Ceilings (NEC) Directive within the European Union and the 1999 Gothenburg Protocol within the Convention on Long-Range Transboundary Air Pollution (CLRTAP) require a substantial further reduction of emissions. What are the chances for implementation success and what are the determining factors? The earlier central air pollution ‘laggard’ the UK is singled out for specific scrutiny, along with Germany and France. With regard to the UK, it does not seem reasonable to assume that the ‘high hopes’ in Geneva/CLRTAP and Brussels will be dashed in London. Despite a recent worrying increase in the use of coal, the UK as ‘the dirty man of Europe’ seems to be history. The prospects for German implementation are more uncertain, but it seems reasonable to assume that the Germans will do quite well, but be less impressive than in the past. France is even more of an uncertain card here, and its unimpressive NOx and VOC performance so far does not bode well. As these countries are central in both the EU and CLRTAP contexts, the implementation prospects for the new EU and CLRTAP commitments are overall quite promising, even though there are huge uncertainties to be clarified further.
Active Acoustic Control of Sound Transmission through Double Walls: Simulation Results
Authors: Bao C. , Pan J.
Published: October 2002

In this paper, the active control of sound transmission through double-panel partitions by inserting acoustic sources in the air gap between the double panels is studied through a computer simulation. The work is an extension of the previous analytical work in which a theoretical framework was developed to reveal the control mechanisms involved in active acoustic control. In this work, a computer simulation based on the theoretical framework is used to assess the control performance under different conditions. It is shown that the property of the radiating panel plays an important role in active acoustic control. The control performance can be improved by increasing the panel damping or decreasing the panel modal density. The reasons for this are discussed.
Case Study: Acoustic Design of a Restored Theatre in Thessaloniki
Authors: Tsinikas N. P.
Published: October 2002

This paper discusses the acoustics of a restored theatre in Thessaloniki, Greece. The paper presents the acoustic design principles, discusses the employment of these principles and concludes with an assessment of the success of the design. The acoustic design changes included improvement of direct sound, provision of ceiling and walls reflections, positioning of diffusers, optimising reverberation time and minimising background noise levels. Steeper seating rakes were constructed in the stalls, boxes and balconies. Curved ceiling reflectors were positioned in a new wire frame false ceiling. Lateral wall reflectors were introduced, as were curved side walls near the stage to act as diffusers. Diffusers were positioned in the rear walls and in balcony fronts.

Reverberation times were predicted, measured and compared with earlier data, based on the change of volume, the number and design of seats and the volume per seat ratio. Finally, noise level measurements were obtained in most of the spaces in the theatre.

Assessment of the success of the design is based on measurement results and on the subjective acceptance by theatre goers.
On the Performance of Base-Isolated Buildings
Authors: Talbot J.P. , Hunt H.E.M.
Published: October 2002

Base isolation is a means of reducing the transmission of vibration into buildings and was first used in the 1960s. Since then many buildings have been mounted on springs of various types in order to reduce the effects of ground-borne vibration from roads and railways. For most applications, the building rests on steel springs or laminated rubber bearings. A typical objective is a reduction in vibration transmission of at least 10 dB for frequencies above 10 Hz, but, while difficult to verify, such performance is probably rarely ever achieved.

Current practice suggests that the choice of spring type has a significant effect on the efficiency of the vibration isolation, as well as having implications on the cost and implementation of the system. However, there remain unanswered a number of fundamental questions concerning the specification and design of isolation bearings for buildings. For example, what is the most appropriate stiffness of the bearings for a given application and to what extent is damping an important part of a good system?

This paper reviews current methods of predicting isolation performance and introduces an alternative model which aims to model more fully the behaviour of base-isolated buildings. The benefits of a power-flow approach in assessing isolation performance are also discussed and it is argued that this enables a more appropriate measure of performance to be defined than one based on vibration amplitudes alone.
Evaluation and Design of Small Rooms
Authors: Fürjes Andor T. , Arató-Borsi Éva , Augusztinovicz Fülöp
Published: October 2002

Small rooms in the acoustical sense, are the bottlenecks of classical room acoustics. There are practical guidelines for the design and evaluation of such rooms, but still no widely accepted objective numerical criteria and general design method are at hand. This paper presents a uniform evaluation and design approach, based on conventional measurement and computer aided modelling methods of impulse responses or energy decay curves.
Case Study: Laboratory and Field Measurements for Evaluating the Weighted Reduction in Impact Noise Associated with Floor Coverings
Authors: Patrício Jorge
Published: October 2002

In order that impact sound insulation in buildings complies with national regulations, the use of floor coverings needs to be considered, either at the design stage, or as a corrective measure. The improvement of impact sound insulation for floor coverings shown in marketing literature, comes from laboratory tests, expressed as the difference between the values of bare and covered floor noise insulation indices, calculated in accordance with what is prescribed in standard EN ISO 717/2. However, the values of the improvement for the same product are sometimes very different from laboratory to on-site conditions. This problem is more acute for buildings with non-homogenous floors such as beam-block. This case study presents some tests performed on identical horizontal beam-block slabs, in the laboratory and on site, using the same floor coverings. Discrepancies in the values obtained for the characterisation of each floor covering are observed. Assuming that part of the problem could be linked to the type of index used, a comparison is made using the following metrics: ΔdB(A); ΔLn,w (or ΔL3n,w – when on site); and the difference of Loudness Level.
Clarity and Definition in Mudejar-Gothic Churches
Authors: Galindo M. , Zamarreño T. , Girón S.
Published: October 2002

This paper studies the C80 and D50 objective acoustic indices in relation to source-receiver distance for five different octave bands inside Mudejar-Gothic churches. This type of church, eight examples of which we have studied in the city of Seville, is characterised by good acoustic conditions as far as this can be indicated by reverberation times. This article aims to supply more data on these values and to explore the dependence of these measurements on receiver position. Finally, the experimental results have been compared with expected results derived from a semiempirical analytical model proposed.
Physical Properties of Noise Barriers and the Development of an Acoustical Protection Rating Index
Authors: Simón F. , Pfretzschner J.
Published: October 2002

A study into the physical properties of noise barriers has been carried out and a single rating index to characterise the acoustical protection of a barrier has been developed, in terms of the barrier diffraction coefficient. An expression for a single figure rating index may be formulated by assessing the insertion loss at a receiver point far enough from the barrier to make the difference between direct and diffracted sound paths from barrier to receiver negligible. This makes the geometry between the barrier and the receiver point redundant in the calculation of insertion loss and thus allows the barrier to be characterised by a single rating index. In this work the insertion loss is expressed as a function of the barrier diffraction coefficient, applying the same geometry conditions. Subsequently an expression for a single rating index is obtained as a function of the barrier diffraction coefficient.
Is There a Systematic Disagreement between Intensity-Based and Pressure-Based Sound Transmission Loss Measurements?
Authors: Machimbarrena María , Jacobsen Finn
Published: October 2002

Conventional and intensity-based sound transmission loss measurements have frequently been compared in the literature. Looking at published results determined under laboratory conditions, one would come to the conclusion that it is only possible to obtain good agreement between the two methods in a very restricted frequency range. It has often been reported that the intensity method gives lower values of the sound reduction index than the conventional method at low frequencies and higher at high frequencies.

The purpose of this paper is to demonstrate with experimental data that excellent agreement between the two methods can be obtained in a fairly wide frequency range (80 Hz-6.3 kHz), provided that the measurements are carried out under optimum conditions. As pointed out by several authors, the only reason for systematic deviations between the two methods is the effect of having a partition that is highly absorbing in the receiving room.
An Intercomparison of Laboratory Measurements of Airborne Sound Insulation of Lightweight Plasterboard Walls
Authors: Fausti Patrizio , Pompoli Roberto , Smith R. Sean
Published: October 2002

This paper describes the results of the European Inter-Laboratory Test (ILT) program, conducted for the determination of repeatability and reproducibility values for the laboratory measurements of airborne sound insulation of walls. A total of 24 laboratories took part in this ILT, 21 belonging to the European Community. Two test structures were constructed; a double lightweight wall and a single lightweight wall, both built of plasterboard. The sound reduction index values were measured. The main result of the ILT was the significant difference obtained for the reproducibility value, R, for the double lightweight wall with values up to 12 dB at middle-high-frequencies. On the contrary, the reproducibility value for the single wall was very similar to the tentative values indicated in Annex A of ISO 140–2. Good agreement between laboratories was found for both structures in the computed repeatability values, r.
Predicting the Sound Reduction of Building Elements from Material Data
Authors: Gerretsen Eddy
Published: October 2002

The airborne and impact sound reduction of building elements are important quantities to compare the acoustic performance of products and to apply as input for prediction models for the acoustic performance of buildings. Besides using existing measurement methods, it is very useful to have the disposal of calculation models to predict these quantities for various types of elements from data on the design and materials used. Such models provide a quick and easy way to estimate the effect of changes in an element and to check for anomalies in measurement results. For homogeneous elements calculation models are given in an annex to EN 12354–1&2. These models will be discussed and possible extensions to layered, stiffened and double elements will be indicated. Such detailed models are used to give examples of acoustic behaviour of elements and estimations for single number ratings.
New Structural Forms and New Technologies in the Development of Steel Space Structures in China
Authors: Dong Shilin , Zhao Yang , Zhou Dai
Published: October 2002

The last decades have seen major advances in the research, design and construction of steel space structures (space grid structures) in China. This paper provides a review of these developments, with particular attention to the new technologies and new structural forms employed in China. The following topics on new technologies and new structures are given emphasis: long-span and large-area grid structures; composite space trusses; composite reticulated shells; triple-layer space trusses; partial double-layer (single-layer) lattice shells; prestressed grid structures; cable-stayed grid structures; special grid structures; new types of joints; theoretical work and application research. Prospects for steel space structures in the 21st century are presented at the end of this paper.
Buckling Analysis of Multi-Step Non-Uniform Columns
Authors: Li Q.S.
Published: October 2002

An analytical procedure for the elastic buckling of a multi-step nonuniform column subjected to concentrated axial compressive forces is presented in this paper. The governing differential equation for the buckling problem is established. Special solutions of the governing equation for five different types of nonuniform columns are given. The procedure for determining the fundamental solutions that satisfy the normalization conditions is proposed. using the fundamental solutions and a recurrence formula developed in this paper, the bending moment function that includes only one unknown parameter for each step column can be easily determined. Thus, it is convenient to establish the eigenvalue equation for buckling of a multi-step non-uniform column in terms of the normalized fundamental solutions of the governing equation. The eigenvalue equations for three general boundary conditions are given. A numerical example shows that the proposed procedure for determining the critical buckling force of a multi-step non-uniform column with general boundary conditions is a simple, efficient and exact method.
Equilibrium Shapes and Forces Incurred by Lifting a Heavy, Segmented Rod from One End
Authors: Wang C.Y.
Published: October 2002

A segmented rod, composed of heavy rigid links joined by hinges with rotational resistance, is gradually lifted off the ground from one end. The equilibrium shape is governed by a non linear difference equation with two unknown parameters. The solution scheme yields a non linear lifting force–lifted height relation.
Weight Optimization of Steel Frames Using Genetic Algorithm
Authors: Torregosa Ribelito F. , Kanok-Nukulchai Worsak
Published: October 2002

Genetic Algorithm (GA) is a new technique in optimization procedure that works best in design problems with discrete variables. It employs the survival of the fittest philosophy in determining the optimum combination. GA optimization procedure is applied to weight optimization of steel plane frames subjected to different load cases. Database of steel beam sizes is provided as the discrete variables. Both elitist and non-elitist search procedures are used to optimize the total weight of steel frames. Crossover types used are 20- and 50-percent uniform. Optimization result using population sizes 10, 20, and 40 are compared. Elitist search procedure showed superior results when compared to non-elitist for higher population sizes search because of its faster convergence rate. Performance of non-elitist is superior when using lesser population sizes. To examine the performance of genetic algorithms, case studies are conducted by varying material groups and the results are compared with the results from other optimization techniques. Genetic optimization showed superior results when compared to other techniques especially to problems with few material groupings.
Pharmacological characterization of SB‐710411 (Cpa‐c[D‐Cys‐Pal‐D‐Trp‐Lys‐Val‐Cys]‐Cpa‐amide), a novel peptidic urotensin‐II receptor antagonist
Authors: Behm David J , Herold Christopher L , Ohlstein Eliot H , Knight Steven D , Dhanak Dashyant , Douglas Stephen A
Published: October 2002

Human urotensin‐II (hU‐II), a cyclic undecapeptide, is amongst the most potent mammalian vasoconstrictors identified, suggesting that hU‐II and its G‐protein‐coupled receptor (UT) may regulate cardiovascular homeostasis. Such a hypothesis would benefit greatly from the development of selective UT antagonists.

Although the somatostatin (SST) antagonist SB‐710411 (Cpa‐c[D‐Cys‐Pal‐D‐Trp‐Lys‐Val‐Cys]‐Cpa‐amide) is purported to block U‐II‐induced contractions in rat isolated aorta, little is known about its specific pharmacological properties.

SB‐710411 (10 μM) inhibited hU‐II‐induced contraction in rat isolated aorta causing a significant, parallel shift in the agonist concentration‐response curve (pKb 6.28±0.11; n=8) with no suppression of the Emax. In contrast, SB‐710411 did not alter the contractile actions of angiotensin‐II, phenylephrine, or KCl. Paradoxically, however, SB‐710411 potentiated the contractile response to endothelin‐1 (pEC50 8.02±0.16 and 8.54±0.11, P<0.01; n=8). Rather than being specific toSB‐710411, this phenomenon appears to be related to somatostatin receptor affinity and not intrinsic activity since the SST agonist somatostatin‐14 and antagonist cyclo‐somatostatin also potentiated endothelin‐1‐induced contraction.

SB‐710411 (10 μM) did not inhibit carbachol, sodium nitroprusside, IBMX, isoprenaline, and levcromakalim‐induced reversal of tone established with noradrenaline. In contrast, however, SB‐710411 significantly inhibited the reversal of tone established with endothelin‐1 using the same vasorelaxants.

In summary, although SB‐710411 inhibits the vasoconstrictor actions of hU‐II in a competitive, surmountable manner, it also possesses additional pharmacological actions. Thus, whilst the present study is amongst the first to detail the properties of a functional U‐II receptor antagonist, the data suggest caution be used when assessing data generated utilizing this moiety and other SST analogues.

British Journal of Pharmacology (2002) 137, 449–458. doi:10.1038/sj.bjp.0704887
Muscarinic receptors in isolated urinary bladder smooth muscle from different mouse strains
Authors: Choppin A
Published: October 2002

The pharmacological characteristics of muscarinic receptors in male and female mouse urinary bladder smooth muscle from different strains (C57Bl/6, 129/SvJ and hybrid backcross N1F2) were studied.

(+)‐Cis‐dioxolane, oxotremorine‐M, acetylcholine, carbachol and pilocarpine induced concentration‐dependent contractions of the urinary bladder smooth muscle (range for pEC50=6.4–6.6, 6.2–6.7, 6.2–6.4, 5.4–6.0 and 0.0–5.1, Tmax=1.9–4.7 g, 1.3–3.4 g, 1.0–3.0 g, 1.4–2.4 and 0.0–0.3 g, respectively, n=4–6 depending on the gender and the strain). In females, these contractions were competitively antagonized by a range of muscarinic receptor antagonists (pKB value range, depending on the strain): atropine (8.0–8.9), pirenzepine (6.1–6.4), 4‐DAMP (7.6–8.4), methoctramine (5.6–6.1), p‐F‐HHSiD (7.5–7.7), zamifenacin (7.7–8.4) and darifenacin (8.2–8.7).

In recontraction studies, in which the muscarinic M3 receptor population was decreased, and conditions optimized to study M2 receptor activation, methoctramine exhibited an affinity estimate consistent with muscarinic M3 receptors (pKB=6.26±0.08, pA2=6.31±0.07; pKB=6.09±0.22, pA2=6.08±0.01 for female inbred strain 129/SvJ and hybrid backcross N1F2, respectively) or intermediate between the one expected for this compound at M2 and M3 receptors, (pKB=6.66±0.08, pA2=7.00±0.27 for female inbred strain C57BL/6).

These data study suggest that muscarinic M3 receptors are the predominant, if not the exclusive, subtype mediating contractile responses to muscarinic agonists in female mouse urinary bladder smooth muscle, with strain differences.

British Journal of Pharmacology (2002) 137, 522–528. doi:10.1038/sj.bjp.0704897
Efficiency wages in an experimental labor market
Authors: Rigdon Mary L.
Published: October 2002

There has been recent experimental support for efficiency wage theories of the labor market. This short paper initiates the larger process of evaluating the boundary conditions of the gift- exchange phenomenon. In particular, we will see whether behavior consistent with the fair wage–effort hypothesis can emerge and be sustained under conditions in which there is (
i
) a nontrivial marginal cost to providing effort and (
ii
) increased social distance between subject and experimenter.
Minimum molecular architectures for transcription and replication of the influenza virus
Authors: Honda Ayae , Mizumoto Kiyohisa , Ishihama Akira
Published: October 2002

The RNA-dependent RNA polymerase of influenza virus is composed of three viral P proteins (PB1, PB2, and PA) and involved in both transcription and replication of the RNA genome. The PB1 subunit plays a key role in both the assembly of three P protein subunits and the catalytic function of RNA polymerization. We have established a simultaneous expression system of three P proteins in various combinations using recombinant baculoviruses, and isolated the PA–PB1–PB2 ternary (3P) complex and two kinds of the binary (2P) complex, PA–PB1 and PB1–PB2. The affinity-purified 3P complex showed all of the catalytic properties characteristic of the transcriptase, including capped RNA-binding, capped RNA cleavage, model viral RNA binding, model viral RNA-directed RNA synthesis, and polyadenylation of newly synthesized RNA. The PB1–PB2 binary complex showed essentially the same catalytic properties as does the 3P complex, whereas the PA–PB1 complex catalyzed
de novo
initiation of RNA synthesis in the absence of primers. Taken together we propose that the catalytic specificity of PB1 subunit is modulated to the transcriptase by binding PB2 or the replicase by interaction with PA.
Doming modes and dynamics of model heme compounds
Authors: Klug Dennis D. , Zgierski Marek Z. , Tse John S. , Liu Zhenxian , Kincaid James R. , Czarnecki Kazimierz , Hemley Russell J.
Published: October 2002

Synchrotron far-IR spectroscopy and density-functional calculations are used to characterize the low-frequency dynamics of model heme FeCO compounds. The “doming” vibrational mode in which the iron atom moves out of the porphyrin plane while the periphery of this ring moves in the opposite direction determines the reactivity of oxygen with this type of molecule in biological systems. Calculations of frequencies and absorption intensities and the measured pressure dependence of vibrational modes in the model compounds are used to identify the doming and related normal modes.
Intrinsic and extrinsic contributions to stochasticity in gene expression
Authors: Swain Peter S. , Elowitz Michael B. , Siggia Eric D.
Published: October 2002

Gene expression is a stochastic, or “noisy,” process. This noise comes about in two ways. The inherent stochasticity of biochemical processes such as transcription and translation generates “intrinsic” noise. In addition, fluctuations in the amounts or states of other cellular components lead indirectly to variation in the expression of a particular gene and thus represent “extrinsic” noise. Here, we show how the total variation in the level of expression of a given gene can be decomposed into its intrinsic and extrinsic components. We demonstrate theoretically that simultaneous measurement of two identical genes per cell enables discrimination of these two types of noise. Analytic expressions for intrinsic noise are given for a model that involves all the major steps in transcription and translation. These expressions give the sensitivity to various parameters, quantify the deviation from Poisson statistics, and provide a way of fitting experiment. Transcription dominates the intrinsic noise when the average number of proteins made per mRNA transcript is greater than ≃2. Below this number, translational effects also become important. Gene replication and cell division, included in the model, cause protein numbers to tend to a limit cycle. We calculate a general form for the extrinsic noise and illustrate it with the particular case of a single fluctuating extrinsic variable—a repressor protein, which acts on the gene of interest. All results are confirmed by stochastic simulation using plausible parameters for
Escherichia coli.
Neural basis of protracted developmental changes in visuo-spatial working memory
Authors: Kwon H. , Reiss A. L. , Menon V.
Published: October 2002

Developmental studies have shown that visuo-spatial working memory (VSWM) performance improves throughout childhood and adolescence into young adulthood. The neural basis of this protracted development is poorly understood. In this study, we used functional MRI (fMRI) to examine VSWM function in children, adolescents, and young adults, ages 7–22. Subjects performed a 2-back VSWM experiment that required dynamic storage and manipulation of spatial information. Accuracy and response latency on the VSWM task improved gradually, extending into young adulthood. Age-related increases in brain activation were observed in focal regions of the left and right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex (including Broca's area), left premotor cortex, and left and right posterior parietal cortex. Multiple regression analysis was used to examine the relative contributions of age, accuracy, and response latency on activation. Our analysis showed that age was the most significant predictor of activation in these brain regions. These findings provide strong evidence for a process of protracted functional maturation of bilateral fronto-parietal neural networks involved in VSWM development. At least two neural systems involved in VSWM mature together: (
i
) a right hemisphere visuo-spatial attentional system, and (
ii
) a left hemisphere phonological storage and rehearsal system. These observations suggest that visually and verbally mediated mnemonic processes, and their neural representations, develop concurrently during childhood and adolescence and into young adulthood.
The CENP-A homolog CaCse4p in the pathogenic yeastCandida albicansis a centromere protein essential for chromosome transmission
Authors: Sanyal Kaustuv , Carbon John
Published: October 2002

The gene encoding CaCse4p, a homolog of the evolutionarily conserved histone H3-like kinetochore protein CENP-A, has been cloned from the human pathogenic diploid yeastCandida albicans. To study the phenotype ofC. albicansdiploid cells depleted of CaCse4p, we deleted one copy of CaCSE4and brought the other copy under control of a regulatedPCK1promoter (repressed by glucose and induced by succinate). Inability of this strain to grow on glucose medium indicates that CaCse4p is essential for cell viability. Shutdown of CaCSE4expression resulted in a sharp decline of CaCse4p levels with concomitant loss of cell viability. Examination of these CaCse4p-depleted cells revealed a mitosis-specific arrest phenotype with accumulation of large-budded cells containing single G2nuclei at or near the bud neck along with short mitotic spindles. Subcellular localization of CaCse4p by anti-CaCse4p antibodies in both budding and filamentousC. albicanscells revealed an intense dot-like signal always colocalized with 4′,6-diamidino-2-phenylindole-stained nuclei. Unlike higher eukaryotes but similar to the budding yeastSaccharomyces cerevisiae, centromere separation in the budding yeast form ofC. albicansoccurs before anaphase, at a very early stage of the cell cycle. In the filamentous mode of cell division, however, centromere separation appears to occur in early anaphase. Coimmunostaining with anti-CaCse4p and antitubulin antibodies shows that CaCse4p localizes near spindle pole bodies, analogous to the localization pattern observed for kinetochore proteins inS. cerevisiae. CaCse4p promises to be a highly useful reagent for the study of centromere/kinetochore structure inC. albicans.
Amyloid β-peptide inhibition of the PKA/CREB pathway and long-term potentiation: Reversibility by drugs that enhance cAMP signaling
Authors: Vitolo Ottavio V. , Sant'Angelo Antonino , Costanzo Vincenzo , Battaglia Fortunato , Arancio Ottavio , Shelanski Michael
Published: October 2002

Changes in hippocampal function seem critical for cognitive impairment in Alzheimer's disease (AD). Although there is eventual loss of synapses in both AD and animal models of AD, deficits in spatial memory and inhibition of long-term potentiation (LTP) precede morphological alterations in the models, suggesting earlier biochemical changes in the disease. In the studies reported here we demonstrate that amyloid β-peptide (Aβ) treatment of cultured hippocampal neurons leads to the inactivation of protein kinase A (PKA) and persistence of its regulatory subunit PKAIIα. Consistent with this, CREB phosphorylation in response to glutamate is decreased, and the decrease is reversed by rolipram, a phosphodiesterase inhibitor that raises cAMP and leads to the dissociation of the PKA catalytic and regulatory subunits. It is likely that a similar mechanism underlies Αβ inhibition of LTP, because rolipram and forskolin, agents that enhance the cAMP-signaling pathway, can reverse this inhibition. This reversal is blocked by H89, an inhibitor of PKA. These observations suggest that Αβ acts directly on the pathways involved in the formation of late LTP and agents that enhance the cAMP/PKA/CREB-signaling pathway have potential for the treatment of AD.
Dominant-negative inhibition of prion replication in transgenic mice
Authors: Perrier Véronique , Kaneko Kiyotoshi , Safar Jiri , Vergara Julie , Tremblay Patrick , DeArmond Stephen J. , Cohen Fred E. , Prusiner Stanley B. , Wallace Andrew C.
Published: October 2002

Our discovery of dominant-negative inhibition of prion formation in cultured cells provided an explanation for the resistance of some sheep to scrapie and humans to Creutzfeldt–Jakob disease. To determine whether dominant-negative inhibition occurs
in vivo
, we produced transgenic (Tg) mice expressing prion protein (PrP) with either the Q167R or Q218K mutation alone or in combination with wild-type (wt) PrP. Tg(MoPrP,Q167R)
Prnp
0/0
mice expressing mutant PrP at levels equal to non-Tg mice remained healthy for >550 days, indicating that inoculation with prions did not cause disease. Immunoblots of brain homogenates and histologic analysis did not reveal abnormalities. Tg(MoPrP,Q167R)
Prnp
+/+
mice expressing both mutant and wt PrP did not exhibit neurologic dysfunction, but their brains revealed low levels of the PrP pathogenic isoform (PrP
Sc
), and sections showed numerous vacuoles and severe astrocytic gliosis at 300 days after inoculation. Both Tg(MoPrP,Q218K)
Prnp
0/0
and Tg(MoPrP,Q218K)
Prnp
+/+
mice expressing high levels of the transgene product remained healthy for >300 days after inoculation. Neither PrP
Sc
nor neuropathologic changes were found. Our studies demonstrate that although dominant-negative inhibition of wt PrP
Sc
formation occurs, expression of the dominant-negative PrP at the same level as wt PrP does not prevent prion formation completely. However, expression of dominant-negative PrP alone had no deleterious effects on the mice and did not support prion propagation.
Molecular analysis of microscopic ezrin dynamics by two-photon FRAP
Authors: Coscoy Sylvie , Waharte François , Gautreau Alexis , Martin Marianne , Louvard Daniel , Mangeat Paul , Arpin Monique , Amblard François
Published: October 2002

Ezrin plays a key role in coupling signal transduction to cortical cell organization. This actin–membrane linker undergoes a series of conformational changes that modulate its interactions with various partners and its localization in membrane or cytosolic pools. Its mobility and exchange rates within and between these two pools were assessed by two-photon fluorescence recovery after photobleaching in epithelial cell microvilli. Analysis of ezrin mutants with an altered actin-binding site revealed three ezrin membrane states of different mobilities and exchange properties, reflecting sequential association with membrane components and F-actin in the context of a fast overall turnover.
One O-linked sugar can affect the coil-to-β structural transition of the prion peptide
Authors: Chen Pei-Yeh , Lin Chun-Cheng , Chang Yin-Ting , Lin Su-Ching , Chan Sunney I.
Published: October 2002

It has been known that the structural transition from PrP
C
to PrP
Sc
leads to the prion formation. This putative conformational change challenges the central dogma of the protein folding theory—“one sequence, one structure.” Generally, scientists believe that there must be either a posttranslational modification or environmental factors involved in this event. However, all of the efforts to solve the mystery of the PrP
C
to PrP
Sc
transition have ended in vain so far. Here we provide evidence linking O-linked glycosylation to the structural transition based on prion peptide studies. We find that the O-linked α-GalNAc at Ser-135 suppresses the formation of amyloid fibril formation of the prion peptide at physiological salt concentrations, whereas the peptide with the same sugar at Ser-132 shows the opposite effect. Moreover, this effect is sugar specific. Replacing α-GalNAc with β-GlcNAc does not yield the same effect.
Expression of the integrin αEβ7identifies unique subsets of CD25+as well as CD25−regulatory T cells
Authors: Lehmann Joachim , Huehn Jochen , de la Rosa Maurus , Maszyna Frank , Kretschmer Ute , Krenn Veit , Brunner Monika , Scheffold Alexander , Hamann Alf
Published: October 2002

Regulatory CD25+CD4+T cells are considered as important players in T cell homeostasis and self-tolerance. Here we report that the integrin αEβ7, which recognizes epithelial cadherin, identifies the most potent subpopulation of regulatory CD25+T cells. Strikingly, CD25-negative αE+CD4+T cells displayed regulatory activity. Both αE+subsets, CD25+and CD25−, express CTLA-4, suppress T cell proliferationin vitro, and protect mice from colitis in the severe combined immunodeficient model (SCID)in vivo. Whereas αE+CD25+T cells produce almost no cytokines, αE+CD25−T cells represent a unique subset in which high IL-2, IFN-γ and T helper 2-cytokine production is linked with suppressive function. Thus, the integrin αEβ7can be regarded as a novel marker for subsets of highly potent, functionally distinct regulatory T cells specialized for crosstalk with epithelial environments.
Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks
Authors: Bartos Marlene , Vida Imre , Frotscher Michael , Meyer Axel , Monyer Hannah , Geiger Jörg R. P. , Jonas Peter
Published: October 2002

Networks of GABAergic interneurons are of critical importance for the generation of gamma frequency oscillations in the brain. To examine the underlying synaptic mechanisms, we made paired recordings from “basket cells” (BCs) in different subfields of hippocampal slices, using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the parvalbumin promoter. Unitary inhibitory postsynaptic currents (IPSCs) showed large amplitude and fast time course with mean amplitude-weighted decay time constants of 2.5, 1.2, and 1.8 ms in the dentate gyrus, and the cornu ammonis area 3 (CA3) and 1 (CA1), respectively (33–34°C). The decay of unitary IPSCs at BC–BC synapses was significantly faster than that at BC–principal cell synapses, indicating target cell-specific differences in IPSC kinetics. In addition, electrical coupling was found in a subset of BC–BC pairs. To examine whether an interneuron network with fast inhibitory synapses can act as a gamma frequency oscillator, we developed an interneuron network model based on experimentally determined properties. In comparison to previous interneuron network models, our model was able to generate oscillatory activity with higher coherence over a broad range of frequencies (20–110 Hz). In this model, high coherence and flexibility in frequency control emerge from the combination of synaptic properties, network structure, and electrical coupling.