bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity of Ca2+ Signaling in Developing Cardiac Cells
Authors: JANOWSKI EINSLEY , CLEEMANN LARS , SASSE PHILIPP , MORAD MARTIN
Published: November 2006

Abstract:  During embryonic and postnatal development, the mammalian heart undergoes rapid morphological changes with cellular differentiation that at the ultrastructural level encompasses altered expression and organization of the proteins and organelles associated with Ca2+ signaling. Here the development and roles of the releasable Ca2+ stores located within the sarco/endoplasmic reticulum and possibly within the nuclear envelopes are addressed. Confocal Ca2+ imaging experiments were carried out on (i) neonatal rat cardiomyocytes, (ii) pluripotent P19 stem cells, differentiated to a cardiac phenotype by culturing with 1% dimethylsulfoxide (DMSO) in hanging droplets, and (iii) mouse embryonic cardiomyocytes isolated for short‐time culture at embryonic day 9–18. The Ca2+ release channels in neonatal and “cardiac” P19 cell were activated versus inhibited by targeting ryanodine (Ry) receptors with caffeine versus Ry and IP3 receptors with adenosine 5'‐triphosphate (ATP) or histamine versus U‐73122, a phospholipase c (PLC) inhibitor. The neonatal cells displayed four recognizable phenotypes, of which two had specialized Ca2+ stores releasable via either Ry or IP3 receptors, and two had both types of receptors, either controlling functionally separate stores or with some degree of overlap, so that caffeine could deplete the stores releasable by ATP. The P19 cells showed variable presence of IP3‐mediated Ca2+ stores, and caffeine releasable stores that gained prominence in the “cardiac” phenotype, but were absent in a “neuronal” phenotype. The different roles of Ca2+ stores were seen clearly in the mouse embryonic cells. Some cells from early stages of development (E 9–10) had Ca2+ waves that increased in intensity during the diastolic interval and could trigger synchronous electrical excitation (via Na‐Ca exchanger [NCX] and excitatory Ca2+ and Na+ channels). At later stages of development (E 18) we observed diastolic Ca2+ sparks that appeared to originate from the nuclear envelope, while the Ca2+ signals during excitation were faster and stronger in the nuclear region than in the surrounding cytoplasmic regions. However, we also found cells where the nuclear Ca2+ signals were weaker and showed afterglow compared to the cytosolic Ca2+ transients. We conclude that the Ca2+ stores in cardiac cells during embryogenesis and postnatal development, that is, before the maturation of the t‐tubular system and in stem cells with cardiac phenotype, show considerable diversity with respect to the pharmacology of the release channels and that regional differences in Ca2+ signaling are observed centered in, at, and around the nucleus. We suggest that the causal relationship excitation and subcellular Ca2+ signals in developing cardiac cells is different from that of adult cells and that the developing cardiomyocytes show a diversity that in later stages of development may be reflected in the different properties of atrial, ventricular, and pacemaker cells.
The Mechanoelectric Feedback: A Novel “Calcium Clamp” Method, Using Tetanic Contraction, for Testing the Role of the Intracellular Free Calcium
Authors: YANIV YAEL , LEVY CARMIT , LANDESBERG AMIR
Published: November 2006

Abstract:  Mechanical perturbations affect the membrane action potential, a phenomenon denoted as the mechanoelectric feedback (MEF), and may elicit cardiac arrhythmias. Two plausible mechanisms were suggested to explain this phenomenon: (i) stretch‐activated channels (SACs) within the cell membrane and (ii) modulation of the action potential by the intracellular Ca2+ (the Calcium hypothesis). The intracellular Ca2+ varies mainly due to the effects of the mechanical perturbations on the affinity of troponin for calcium. The present study concentrates on the unique experimental methods that allow differentiating between the effects of SAC and Ca2+ on the action potential. This is achieved by controlling the sarcomere lengths (SLs) independently of the intracellular Ca2+ concentration, in the intact fiber. A dedicated experimental setup allowed simultaneous measurements of the membrane potential and the mechanical performance (Force and SL). The action potential was measured by voltage‐sensitive dye (Di‐4‐ANEPPS). The SL was measured by laser diffraction technique and was controlled by a fast servomotor. The intracellular Ca2+ was controlled (calcium clamp) by imposing stable tetanic contractions at various extracellular calcium concentrations ([Ca2+]0s). Tetanus was obtained by 8 Hz stimulation in the presence of cyclopiazonic acid (CPA) (30 μM). Isolated trabeculae from a rat's right ventricle were studied at different SLs and [Ca2+]0s. The experimental data strongly support the calcium hypothesis. Although the action potential duration (APD) decreases at longer SL, the [Ca2+]0 has a significantly larger effect on the APD. The APD decreases as the [Ca2+]0 increases. Understanding the underlying mechanism opens new research avenues for the development of therapeutic modalities for cardiac arrhythmias.
Role of Sarcomere Mechanics and Ca2+ Overload in Ca2+ Waves and Arrhythmias in Rat Cardiac Muscle
Authors: TER KEURS HENK E.D.J. , WAKAYAMA YUJI , SUGAI YOSHINAO , PRICE GUY , KAGAYA YUTAKA , BOYDEN PENELOPE A. , MIURA MASAHITO , STUYVERS BRUNO D.M.
Published: November 2006

Abstract:  Ca2+ release from the sarcoplasmic reticulum (SR) depends on the sarcoplasmic reticulum (SR) Ca2+ load and the cytosolic Ca2+ level. Arrhythmogenic Ca2+ waves underlying triggered propagated contractions arise from Ca2+ overloaded regions near damaged areas in the cardiac muscle. Ca2+ waves can also be induced in undamaged muscle, in regions with nonuniform excitation–contraction (EC) coupling by the cycle of stretch and release in the border zone between the damaged and intact regions. We hypothesize that rapid shortening of sarcomeres in the border zone during relaxation causes Ca2+ release from troponin C (TnC) on thin filaments and initiates Ca2+ waves. Elimination of this shortening will inhibit the initiation of Ca2+ waves, while SR Ca2+ overload will enhance the waves. Force, sarcomere length (SL), and [Ca2+]i were measured and muscle length was controlled. A small jet of Hepes solution with an extracellular [Ca2+] 10 mM (HC), or HC containing BDM, was used to weaken a 300 μm long muscle segment. Trains of electrical stimuli were used to induce Ca2+ waves. The effects of small exponential stretches on triggered propagatory contraction (TPC) amplitude and propagation velocity of Ca2+ waves (Vprop) were studied. Sarcomere shortening was uniform prior to activation. HC induced spontaneous diastolic sarcomere contractions in the jet region and attenuated twitch sarcomere shortening; HC+ butanedione monoxime (BDM) caused stretch only in the jet region. Stimulus trains induced Ca2+ waves, which started inside the HC jet region during twitch relaxation. Ca2+ waves started in the border zone of the BDM jet. The initial local [Ca2+]i rise of the waves by HC was twice that by BDM. The waves propagated at a Vprop of 2.0 ± 0.2 mm/sec. Arrhythmias occurred frequently in trabeculae following exposure to the HC jet. Stretch early during relaxation, which reduced sarcomere shortening in the weakened regions, substantially decreased force of the TPC (FTPC) and delayed Ca2+ waves, and reduced Vprop commensurate with the reduction FTPC. These results are consistent with the hypothesis that Ca2+ release from the myofilaments initiates arrhythmogenic propagating Ca2+ release. Prevention of sarcomere shortening, by itself, did not inhibit Ca2+ wave generation. SR Ca2+ overload potentiated initiation and propagation of Ca2+ waves.
Cellular Basis for the Repolarization Waves of the ECG
Authors: ANTZELEVITCH CHARLES
Published: November 2006

Abstract:  One hundred years after Willem Einthoven first recorded the electrocardiogram (ECG), physicians and scientists are still debating the cellular basis for the various waves of the ECG. In this review, our focus is on the cellular basis for the J, T, and U waves of the ECG. The J wave and T wave are thought to arise as a consequence of voltage gradients that develop as a result of the electrical heterogeneities that exist within the ventricular myocardium. The presence of a prominent action potential notch in epicardium but not endocardium gives rise to a voltage gradient during ventricular activation that inscribes the J wave. Transmural and apico‐basal voltage gradients developing as a result of difference in the time course of repolarization of the epicardial, M, and endocardial cell action potentials, and the more positive plateau potential of the M cell contribute to inscription of the T wave. Amplification of these heterogeneities results in abnormalities of the J wave and T wave, leading to the development of the Brugada, long QT, and short QT syndromes. The basis for the U wave has long been a matter of debate. One theory attributes the U wave to mechanoelectrical feedback. A second theory ascribes it to voltage gradients within ventricular myocardium and a third to voltage gradients between the ventricular myocardium and the His–Purkinje system. Although direct evidence in support of any of these three hypotheses is lacking, recent studies involving the short QT syndrome have generated renewed interest in the mechanoelectrical hypothesis.
Three‐Dimensional Models of Individual Cardiac Histoanatomy: Tools and Challenges
Authors: BURTON REBECCA A.B. , PLANK GERNOT , SCHNEIDER JÜRGEN E. , GRAU VICENTE , AHAMMER HELMUT , KEELING STEPHEN L. , LEE JACK , SMITH NICOLAS P. , GAVAGHAN DAVID , TRAYANOVA NATALIA , KOHL PETER
Published: November 2006

Abstract:  There is a need for, and utility in, the acquisition of data sets of cardiac histoanatomy, with the vision of reconstructing individual hearts on the basis of noninvasive imaging, such as MRI, enriched by reference to detailed atlases of serial histology obtained from representative samples. These data sets would be useful not only as a repository of knowledge regarding the specifics of cardiac histoanatomy, but could form the basis for generation of individualized high‐resolution cardiac structure–function models. The current article presents a step in this general direction: it illustrates how whole‐heart noninvasive imaging can be combined with whole‐heart histology in an approach to achieve automated construction of histoanatomically detailed models of cardiac 3D structure and function at hitherto unprecedented resolution and accuracy (based on 26.4 × 26.4 × 24.4 μm MRI voxel size, and enriched by histological detail). It provides an overview of the tools used in this quest and outlines challenges posed by the approach in the light of applications that may benefit from the availability of such data and tools.
Cardiac β‐Adrenergic Signaling
Authors: SAUCERMAN JEFFREY J. , McCULLOCH ANDREW D.
Published: November 2006

Abstract: β‐adrenergic signaling plays a central role in the neurohumoral regulation of the heart and the progression of heart failure. Initially thought to be a simple linear cascade, this complex network is now recognized to utilize cross‐talk with numerous other pathways, spatial compartmentation, and feedback control to coordinate cardiac electrophysiology, contractility, and adaptive remodeling. Here, we review recent basic insights and novel quantitative approaches that are leading to a more comprehensive understanding of β‐adrenergic signaling and thus motivate new therapeutic strategies for cardiac disease.
Cardiovascular Therapeutic Aspects of Cell Therapy and Stem Cells
Authors: GEPSTEIN LIOR
Published: November 2006

Abstract:  The recent advancements in stem cell biology, molecular and cell biology, and tissue engineering have paved the way to the development of a new biomedical discipline: regenerative medicine. The heart represents an attractive candidate for this emerging discipline since these emerging technologies could be used to potentially treat a variety of myocardial disorders. Here we describe our efforts in using stem cell and cell therapy strategies to restore the myocardial electromechanical properties. Specifically, our research has focused on the potential role of human embryonic stem cells (hESC) for myocardial regeneration (for the treatment of heart failure) and on using genetically engineered cell grafts to modify the myocardial electrophysiological properties (for the treatment of cardiac arrhythmias). The recently described hESC lines are unique pluripotent cell lines that can be propagated in the undifferentiated state in culture and coaxed to differentiate into cell derivatives of all three germ layers, including cardiomyocytes. The current article describes this unique cardiomyocyte differentiating system and details the molecular, ultrastructural, and functional properties of the generated hESC‐derived cardiomyocytes (hESC‐CMs). The ability of the hESC‐CMs to integrate structurally and functionally with host cardiomyocytes in both in vitro and in vivo studies will be described as well as their ability to restore the myocardial electromechanical function in animal models of diseased hearts. We will next present detailed in vitro, in vivo, and computer simulation studies performed in our laboratory testing the hypothesis that cell grafts, engineered to express specific ion channels, can be used to modify the myocardial electrophysiological properties of cardiac tissue. The potential and drawbacks of this novel approach for the treatment of both tachyarrhythmias (using cell grafts expressing potassium channels) and bradyarrhythmias (using hESC coaxed to differentiate into pacemaking cells or conducting tissue) will be described.
Nanomedicine Opportunities in Cardiology
Authors: LANZA GREGORY , WINTER PATRICK , CYRUS TILLMANN , CARUTHERS SHELTON , MARSH JON , HUGHES MICHAEL , WICKLINE SAMUEL
Published: November 2006

Abstract:  Despite myriad advances, cardiovascular‐related diseases continue to remain our greatest health problem. In more than half of patients with atherosclerotic disease, their first presentation to medical attention becomes their last. Patients often survive their first cardiac event through acute revascularization and placement of drug‐eluting stents (DES), but only select coronary lesions are amenable to DES placement, resulting in the use of bare metal or no stent, both of which lack the benefit of antirestenotic therapy. In other patients, transient ischemic attacks (TIAs) and stroke constitute the initial presentation of disease. In these patients, the diagnostic and therapeutic options are woefully inadequate. Nanomedicine offers options to each of these challenges. Antiangiogenic paramagnetic nanoparticles may be used to serially assess the severity of atherosclerotic disease in asymptomatic, high‐risk patients by detecting the development of plaque neovasculature, which reflects the underlying lesion activity and vulnerability to rupture. The nanoparticles can locally deliver antiangiogenic therapy, which may acutely retard plaque progression, allowing aggressive statin therapy to become effective. Moreover, these agents may be useful as a quantitative marker to guide atherosclerotic management in an asymptomatic patient. In those cases proceeding to the catheterization laboratory for revascularization, nanoparticles incorporating antirestenotic drugs can be delivered directly into the wall of lesions not amenable to DES placement. Targeted nanoparticles could help ensure that antirestenotic drugs are available for all lesions. Moreover, displacement of antiproliferative agents from the intimal surface into the vascular wall is likely to improve rehealing of the endothelium, improving postprocedural management of these patients.
Effects of Synchronized Cardiac Assist Device on Cardiac Energetics
Authors: LANDESBERG AMIR , SHENHAV AVSHALOM , SHOFTY RONA , KONYUKHOV EUGENE , LEVY CARMIT , LICHTENSTEIN OSCAR , BEYAR RAFAEL , TER KEURS HENK E.D.J. , LANDESBERG GIORA , CABRERA MARCO , STANLEY WILLIAM , SAIDEL GERALD M.
Published: November 2006

Abstract:  A novel physiological cardiac assist device (PCAD), the LEV RAM assist device, which is synchronized with the failing heart ejection, was developed to improve the failing heart systolic and diastolic functions and cardiac energetics. The PCAD uses a single short cannula, which is inserted into the beating left ventricle (LV) by means of a specially designed device. Blood is ejected from the PCAD into the LV after the opening of the aortic valve and augments the cardiac stroke work. The same amount of blood is withdrawn from the LV into the PCAD, through the same cannula, during the diastole. The study aims to test the effects of the PCAD on cardiac energetics and coronary blood flow. Adult normal sheep were anesthetized and the heart was exposed by left thoracotomy. Pressures transducers (Millar Instruments, Inc., Houston, TX) were inserted into the LV and aorta. LV volume was measured by sonocrystals (Sonometrics Corp., London, Ontario, Canada) and impedance catheter (CD Lycom, Argonstrat 116 Zoetermeer, 2718 SP The Netherlands). Flowmeters (transonic) measured the cardiac output (CO) and the coronary arteries (left anterior descending (LAD) and circumflex) flows. A thin cannula was inserted into the coronary sinus and the oxygen content of the LV and the coronary sinus were determined (AVOXimeter‐1000). Pressure‐volume loops, myocardial energetics, and coronary flow were measured. The displaced PCAD volume was 11 mL. Four different levels of assist were studied by changing the frequency of the assist: (1) assist beat after three successive regular beats [1:4], (2) assist every third beat [1:3], (3) alternate assist and normal beat [1:2], and (4) continuous assist [1:1]. Cardiac output (CO) and stroke volume (SV) increased proportionally with increasing frequency of assist. Systolic mechanical efficiency of the PCAD was above 90%. Simultaneously, the PCAD decreased the end‐diastolic volume (EDV; diastolic unloading). The PCAD increased coronary flow and decreased cardiac arterial–venous O2 difference. We conclude that the PCAD efficiently augments CO and stroke work, decreases preload, and decreases the coronary arterial–venous O2 difference; all these may expedite cardiac reverse remodeling, and promote recovery of function and eventual easy explanation of the device.
Amenorrhea in Premenopausal Women After Adjuvant Chemotherapy for Breast Cancer
Authors: Walshe Janice M. , Denduluri Neelima , Swain Sandra M.
Published: November 2006

Chemotherapy and ovarian ablation both independently improve survival in premenopausal women with hormone-sensitive breast cancer. Amenorrhea is a well-recognized occurrence after chemotherapy. The rate of chemotherapy-induced amenorrhea varies with patient age and chemotherapy regimens administered. However, the impact of chemotherapy-induced amenorrhea on prognosis is still being defined. Older studies in premenopausal women argue that the benefit with chemotherapy is a result of direct cytotoxicity alone. However, studies that restrict outcome analysis to hormone receptor–positive tumors suggest that chemotherapy has a dual mechanism in women with hormone-responsive tumors; indirect endocrine manipulation secondary to chemotherapy-induced ovarian suppression and direct cytotoxicity. The significant health ramifications involved with the induction of premature menopause as well as potential benefits necessitate a comprehensive evaluation of chemotherapy-induced amenorrhea. This review will discuss the incidence of amenorrhea with commonly-used adjuvant chemotherapeutic regimens, the possible benefits of chemotherapy-induced amenorrhea, and the challenges of interpreting the existing data in breast cancer trials.
Single-point likelihood method to determine a generalized S-N surface
Authors: Xiong J J , Shenol R A
Published: November 2006

This paper outlines a new technique to address the paucity of data in determining a generalized S-N surface on the basis of fatigue reliability design. A new single-point likelihood method (SPLM) is presented for estimating a P-S-N curve, dealing with small sample numbers of data. A confidence level formula for P-S-N curve estimated by SPLM is also given. The concepts are then applied for the determination of a generalized S-N surface. Finally, contrast tests for the P-S curve are conducted to examine the presented method, demonstrating the practical and economic use of the proposed technique. It is shown from the results that the P-S-N curve can be obtained realistically using small sample numbers and that the required number of test specimens in this case is less than those for the conventional method.
Microelectromechanical coupled dynamics
Authors: Xu L , Zhu C , Qin L
Published: November 2006

In this paper, a continuous body, electromechanical coupled dynamic model of the micro ring, in an electrical field has been presented and its equations of motion have been given. From the analysis of the system's energy, the electromechanical coupled force has been obtained. The non-linear electromechanical coupled dynamic equations has been linearized and by means of the linear equations, the natural frequencies and vibration modes of the micro ring have been investigated. The dynamic responses of the electrical system and its changes, along with its system parameters have been investigated. These results are useful in the design and manufacture of microelectromechanical systems and can offer some reference for nanomachines.
Finite-element modelling of thermo-mechanical stress distribution in laser beam ceramic tile grout sealing process
Authors: Liaqat A , Safdar S , Sheikh M A
Published: November 2006

Laser tile grout sealing is a special process in which voids between the adjoining ceramic tiles are sealed by a laser beam. This process has been developed by Lawrence and Li using a customized grout material and a high power diode laser (HPDL). The process has been optimally carried out at laser powers of 60–120 W and at scanning speeds of 3–15 mm/s.

Modelling of the laser tile grout sealing process is a complex task as it involves a moving laser beam and five different materials: glazed enamel, grout material, ceramic tile, epoxy bedding, and ordinary Portland cement substrate. This article presents the finite element model (FEM) of the laser tile grout sealing process. The main aim of this model is to accurately predict the thermo-mechanical stress distribution induced by the HPDL beam in the process. For an accurate representation of the process, the laser was modelled as a moving heat source. A three-dimensional transient thermal analysis was carried out to determine the temperature distribution. Temperature-dependent material properties and latent heat effects, due to melting and solidification of the glazed enamel, were taken into account in the FEM, thereby allowing a more realistic and accurate thermal analysis. The results of the thermal analysis were used as an input for the stress analysis with temperature-dependent mechanical properties. The results obtained from the FEM are compared with the published experimental results.
Wave propagation in piezoelectric laminated cylindrical shells under large deformations and rotary inertias
Authors: Dong K , Wang X
Published: November 2006

This article presents an analytical solution for wave propagation in piezoelectric laminated cylindrical shells under large deformation with the effect of rotary inertias. In this research, non-linear dynamic governing equations of piezoelectric laminated cylindrical shells with freely supported end conditions are derived on the basis of the minimum potential energy principle. The effects of piezoelectricity, rotary inertias, and geometrical non-linear deformations on wave propagation are considered in the governing equations. Wave propagation characteristics curves are carried out by solving an eigenvalue problem. In example calculations, the effects of the wave propagation modes, piezoelectric layers, and the stacking sequence on wave propagation in piezoelectric laminated cylindrical shell are obtained and discussed from the wave characteristics curves. The results carried out can be used in the ultrasonic inspection techniques and health monitoring for piezoelectric laminated structures.
Study on the reliability evaluation method of the wear life of roller chains
Authors: Xu S , Wang Y , Meng F
Published: November 2006

Wear resistance property is one of the important characteristics of the intrinsic quality of chains. Formerly, the evaluation index for the quality of roller chains was based on ISO606-94. However, because that version of standardization was mainly related to the exchangeability of dimensional parameters, it was difficult to assess the wear life and reliability of roller chains. The promulgation and implementation of ISO10823-96 makes it now possible to evaluate the life and reliability of roller chains. Based on the sampling theory, this paper discusses in depth the reliability evaluation method of assessing the life of roller chains. A method is proposed to obtain higher quality and reliable roller chains that show good wear properties. A sampling scheme for reliability inspection has also been devised.
Algorithm for dynamics evaluation
Authors: Herman P
Published: November 2006

In this article, an algorithm for the evaluation of unconstrained system dynamics is proposed. The algorithm is based on an optimal motion plan and two first-order equations expressed in terms of generalized velocity components. The equations arise from decomposition of the system mass matrix, and their use gives some insight into internal couplings. The algorithm makes it possible not only to evaluate the couplings but also to change a set of mechanical parameters in order to improve the behaviour of the system and to reduce the control effort. The presented strategy is illustrated in a simulation of a two-degree-of-freedom planar mechanical system.
Modelling of velocity profiles in transient laminar flow in pipes
Authors: Taïeb L. H. , Taïeb E. H.
Published: November 2006

The authors describe a numerical model to compute the radial profiles of axial velocities in transient laminar flow in pipelines by using the Lax-Wendroff scheme. These velocities are expanded into a polynomial of the radial coordinate where the polynomial coefficients are expressed in terms of weighted averaged velocities. The weighted averaged shear stresses representing friction forces are defined in terms of the weighted averaged velocities. Fluid pressure and weighted averaged velocities are, therefore, considered as the principle dependent variables. Computed results show a satisfactory agreement with experimental results and numerical simulations solutions of previous works.
Optimization of cooling load and coefficient of performance for real regenerated air refrigerator
Authors: Tu Y , Chen L , Sun F , Wu C
Published: November 2006

The performance analysis and optimization of a real regenerated air refrigerator is carried out by using finite-time thermodynamic method in this article. To maximize the cooling load and the coefficient of performance of the refrigerator, the heat conductance distribution between the hot- and cold-side exchangers and the regenerator for the fixed total heat exchanger inventory and heat capacitance rate matching between the working fluid and heat reservoirs are optimized, respectively. The influences of the pressure ratio, the total heat exchanger inventory, the efficiencies of the compressor and expander, the pressure recovery coefficient, and the ratio of the heat capacitance rates of heat reservoirs on the optimum characteristic of the refrigerator are shown by detailed numerical examples. The results obtained may provide guidance for the design of practice air refrigeration plants.
Modelling three-dimensional dynamic stall of helicopter blades using computational fluid dynamics and neural networks
Authors: Spentzos A , Barakos G , Badcock K , Richards B
Published: November 2006

Numerical simulation of three-dimensional dynamic stall (DS) of helicopter rotor blades has been undertaken using computational fluid dynamics (CFD) based on the Navier-Stokes equations. The CFD method has been carefully validated against experimental data before being used to study the topology of the three-dimensional DS vortex and the effects of yaw and rotation on its shape and trajectory. The three-dimensional unsteady viscous computations were found to give a wealth of results at the expense of significant amounts of CPU time. To alleviate this problem and to develop a faster model for the aerodynamic loads encountered during three-dimensional DS, a neural network (NN) was put forward. The NN was trained using both CFD and experimental data and was subsequently used as a method for interpolating DS loads between known states for which CFD data were available. The NN was found to work well for such interpolations, although its capability to extrapolate outside the training envelope was somehow limited. Nevertheless, the NN was found to be a very efficient technique for reconstructing three-dimensional DS and has demonstrated great potential as a method for reducing non-linear aerodynamics to a simple computational model.
Continuing evolution of aerodynamic concept development using collaborative numerical and experimental evaluations
Authors: Cummings R M , Morton S A
Published: November 2006

Traditionally, computational predictions and experimental evaluations of aerodynamic concepts have been conducted separately, with little collaboration other than post priori comparisons of results. This has led to distrust and even antagonism between the computational and the experimental communities. These difficulties probably began when early computational fluid dynamic practitioners boasted that wind tunnels would become secondary in aerodynamic concept development within a few short years, a prediction that has not come true. On the contrary, it is believed that a great deal of synergy can be cultivated when computational and experimental evaluations are conducted in an integrative fashion. A variety of projects where this has been done will be reviewed, including a pitching Unmanned Combat Air Vehicle, a delta wing with periodic suction and blowing for aerodynamic control, a missile with drag brakes that caused excessive unsteady flow, a C-130 aircraft configured for airdrop, and closed-loop flow control. Further evolution of the numerical/experimental collaboration will be discussed showing results from the flow control research where the dividing line between numerical predictions and experimental evaluations is becoming blurred. Suggestions for future directions in collaboration will also be made.
Planar visualization of vortical flows
Authors: Knowles R D , Finnis M V , Saddington A J , Knowles K
Published: November 2006

This article presents two over-looked post-processing techniques which provide the investigator with additional tools for data analysis and visualization. Both techniques exploit the trend for planar experimental data collection and are implemented in two-dimensions. Critically, both techniques are suitable for use on computational and experimental datasets, require no a-priori knowledge of the flow-field, and minimal user interaction during processing. Firstly, line integral convolution will be introduced as an alternative to streamline or in-plane velocity vector visualization. Secondly, a feature identification procedure will be outlined that can be used to reduce datasets for clearer visualization and provide quantitative information about topological flow features.
Transition measurement and prediction on a generic high-lift swept wing
Authors: Moens F , Perraud J , Séraudie A , Houdeville R
Published: November 2006

This article presents experimental and numerical studies on the effect of the Reynolds number on transition location for a simplified multi-element wing. The main phases of the test preparation and the main results of the data analysis carried out within the EUROLIFT EC funded programme are given in the first part. In the second part of the article, recent assessments of the ONERA elsA CFD software where transition is computed during the Navier-Stokes calculation are presented for both the effect of change in incidence at a given Reynolds number and the change in Reynolds number at constant angle of attack. The upper slat region is the main concern of this article, as this element was better equipped and analysed after the experiments. Flap transition is also considered in the computations. For themain wing, turbulent flow is imposed in the computations, as leading-edge contamination occurred in the experiments.
Improvement and verification of low-speed aerodynamic characteristics of a supersonic civil transport aircraft
Authors: van Muijden J
Published: November 2006

For supersonic civil transport aircraft, the low-speed aerodynamic characteristics form an important factor in its operational capabilities and in its economic viability. Low drag is a prerequisite to meet the present and future noise and emissions requirements. The application of concepts for leading-edge devices aiming at an improvement of low-speed aerodynamic efficiency is investigated. From computational analysis of a series of leading-edge flap designs, the two most promising devices are selected for experimental verification, viz. a doublehinge leading-edge flap and a deep-hinge leading edge flap design. In the course of comparing experimental and computational results, discrepancies are observed that are satisfactorily dealt with by adding the wind tunnel struts and the strut-wing connections in the computational analysis. Reynolds number extrapolations from wind tunnel scale to full-scale are obtained using computional fluid dynamics (CFD). It is concluded that the design approach based on CFD has significantly contributed to the success of configuration development, meeting the target efficiency improvement. Furthermore, the influences of geometrical details that differ in the design phase and the validation phase have been assessed.
Performance of the piezo-poppet valve. Part 1
Authors: Wong A. P. , Bullough W. A. , Chin S. B. , Chua Y. S.
Published: November 2006

The thermofluid mechanics of inflow (flow-to-close) and outflow (flow-to-open) conical poppet head valves is investigated for the range of small and controllable openings made available from the employment of a practical piezo-electric stack driver. A computational fluid dynamics (CFD) package suite is applied to the above task, the results from which are verified experimentally for several outflow slave valve (a valve with a non-electrical stand-in for the piezo stack) poppet lifts, cone angles, and pressure drops for the steady, non-isothermal flow of a test liquid (Tellus R37). Finally, the inflow valve performance is examined and a simple sizing technique consolidated. The results are compared, as far as is possible (quantitatively), with the findings of previous workers. This is done in order further to justify the use of CFD for the design of valves of small but potentially greater displacement than available from the contemporary piezo drivers and to underpin design exercises that are intended to optimize low lift valves for real operating conditions. In a companion paper unsteady/moving boundary and transient flow is tackled using a fast and precise piezo stack to actuate the same poppet head variations (as in the steady state case) as are the effects of manufacturing tolerances on poppet eccentricity, angular misalignment, and seat chamfering for small displacements.
On the fault diagnosis of uncertain singularly perturbed systems
Authors: Tellili A , Abdelkrim M. N. , Benrejeb M
Published: November 2006

This work aims at the fault diagnosis of two-timescale, singularly perturbed systems (SPSs) and SPSs with a multimodelling structure. The approach of model-based fault detection and isolation using the dynamic parity space to generate singular perturbation parameter free residuals was used. A comparative study of diagnosis of the SPS is carried out considering, in the first case, the SPS as an uncertain system with parameter uncertainties and using, in the second case, the slow subsystem for fault detection and isolation. The results are applied to a power system.
Potential Utility of Plasma Fatty Acid Analysis in the Diagnosis of Cystic Fibrosis
Authors: Batal Ibrahim , Ericsoussi Mhd-Bassel , Cluette-Brown Joanne E , O’Sullivan Brian P , Freedman Steven D , Savaille Juanito E , Laposata Michael
Published: November 2006

Background: An altered distribution of fatty acids in cells and tissues is found in patients with cystic fibrosis (CF). In this study, we assessed the potential role of plasma fatty acid analysis in the diagnosis of CF.

Methods: In this 2-part study, we first used gas chromatography–mass spectrometry to analyze fatty acids in plasma from 13 CF patients and 11 controls without CF. We then used the fatty acid distribution data to identify the fatty acids or multiple fatty acid calculations most effective in identifying CF patients. Part 2 of the study was a blinded analysis of 10 CF patients and 9 controls to directly test the effectiveness of the diagnostic parameters for CF identified from the plasma fatty acid analysis.

Results: In the nonblinded trial, the multiplication product of (18:2 n-6) × (22:6 n-3) (each as percentage of total plasma fatty acid) was the most effective indicator for distinguishing patients with CF from controls (P = 0.0003). In part 2 (the blinded trial), this multiplication product was also the most effective indicator for distinguishing CF patients from controls (P = 0.0008).

Conclusions: The product of (18:2 n-6) × (22:6 n-3) is effective for distinguishing CF patients from persons without CF. This diagnostic marker may have value as an alternative to the sweat chloride test in selected patients being evaluated for CF.
Mitochondrial morphology and distribution in mammalian cells
Authors: Frazier Ann E. , Kiu Clement , Stojanovski Diana , Hoogenraad Nicholas J. , Ryan Michael T.
Published: November 2006

It is now appreciated that mitochondria form tubular networks that adapt to the requirements of the cell by undergoing changes in their shape through fission and fusion. Proper mitochondrial distribution also appears to be required for ATP delivery and calcium regulation, and, in some cases, for cell development. While we now realise the great importance of mitochondria for the cell, we are only beginning to work out how these organelles undergo the drastic morphological changes that are essential for cellular function. Of the few known components involved in shaping mitochondria, some have been found to be essential to life and their gene mutations are linked to neurological disorders, while others appear to be recruited in the activation of cell death pathways. Here we review our current understanding of the functions of the main players involved in mitochondrial fission, fusion and distribution in mammalian cells.
Media repertoires as a result of selective media use. A conceptual approach to the analysis of patterns of exposure
Authors: Hasebrink Uwe , Popp Jutta
Published: November 2006

This article sets out to provide a conceptual contribution to theoretical and empirical work on the level of media repertoires. We will first discuss theoretical approaches which allow for an explanation of media repertoires and relate them to the most prominent approaches to selective audience behavior. Secondly, in order to empirically analyze media repertoires we propose a combination of secondary analyses of existing surveys on media use and qualitative studies on the internal ‘architecture’ of these repertoires and their practical meaning in the user's everyday life. These proposals for secondary analyses are illustrated by two examples based on different data sets and referring to different levels of analysis.
“Play it again, Sam”. A differentiating view on repeated exposure to narrative content in media
Authors: Hoffmann Jella
Published: November 2006

Whereas repeated exposure to communication is a widespread phenomenon, it has so far received little attention in communication research. This article takes a step towards describing, differentiating, and explaining repeated exposure to communication. It discusses different forms of repeated exposure and then focuses on repeated exposure to narrative films. It explores possible motivations for reusing the same media content again and again, while taking processes of repeated exposure as well as situational and personal variables into account. The initially theoretical considerations are then supported, expanded, and specified both by existent empirical evidence and findings from a focus group study. Finally, further questions about repeated exposure to narrative content in media are discussed.
Introduction: Cognitive linguistic approaches to humor
Authors: Brône Geert , Feyaerts Kurt , Veale Tony
Published: November 2006

Ever since the publication of Victor Raskin's seminal work on the
The cognitive mechanisms of adversarial humor
Authors: Veale Tony , Feyaerts Kurt , Brône Geert
Published: November 2006

In this paper, we provide an in-depth cognitive analysis of a specific humor strategy we coin “trumping”, a multi-agent language game that revolves around the subversion of the linguistic forms of exchange. In particular, we illustrate how, in a conversational setting, agents can “reflect” and “distort” the linguistic-conceptual construal of each others' utterances. Because this reflection or parallelism in the trumping game can be situated on different levels of linguistic organization, a multi-dimensional semantic-pragmatic account is proposed. Using insights from cognitive linguistics, we show that adversarial agents exploit the conceptual mechanisms underlying the opponent's utterances in order to turn the tables in the humor game. In doing so, an agent can trump an adversary by demonstrating a “hyper-understanding” of the lexico-conceptual meaning of an opponent's utterance. This subversion of construal operations like metaphor, metonymy and salience leads to a sudden manipulation of the discourse space that has been set up in the previous utterance(s) (Langacker 2001). In general, by providing an analysis in terms of basic principles of semantic construal, we argue that a cognitive linguistic treatment of humor has an ecological validity that is lacking in most linguistic humor research.
Cognitive linguistics and humor
Authors: Attardo Salvatore
Published: November 2006

There are a number of problems with the articles in this issue. As I read the articles in this guest edited issue of
Quality of life in 70 women with disorders of sex development
Authors: Johannsen Trine H , Ripa Caroline P L , Mortensen Erik L , Main Katharina M
Published: November 2006

Objective: The aim of this study was to assess the quality of life and psychosocial well-being in women with disorders of sex development (DSD).

Design: An open case-control study.

Methods: Social and psychiatric information was collected via a structured interview from 70 Danish women diagnosed with DSD, 70 controls matched on sex, age, and school education, and six women with isolated genital malformations. Quality of life and mental distress were assessed by ‘Quality of Life-Assessment of Growth Hormone Deficiency in Adults’ (QoL-AGHDA) and three symptom scales from the ‘Hopkins Symptom Checklist’ (SCL-90-R; i.e. somatization, depression, and anxiety) respectively. For both measures, higher scores reflected poorer outcomes.

Results: Present relationships and having children were less frequent in patients than in controls (P = 0.02 and P < 0.001 respectively). Previous suicidal thoughts (P = 0.002) and a higher frequency of psychological/psychiatric counseling for severe problems (P = 0.06) were more frequently reported in patients than in controls. The mean QoL-AGHDA score was significantly higher in patients than in controls (5.5 vs 2.9; P = 0.002), especially for congenital adrenal hyperplasia (CAH) females (P = 0.01) and virilized 46,XX and 46,XY females (P = 0.04). The total SCL score was higher in patients than in controls (mean 23.2 vs 20.0), reaching significance for anxiety (mean 6.3 vs 4.3, P = 0.03) with highest score in CAH (P = 0.01).

Conclusion: An impaired quality of life and more affective distress were observed especially in CAH patients and virilized 46,XX and 46,XY females. This may be caused by trauma from distressing diagnostic procedures, the chronic illnesses per se, and psychosocial consequences of the disorders.
Remission of Graves’ disease during anti-thyroid drug therapy. Time to reconsider the mechanism?
Authors: Laurberg Peter
Published: November 2006

Therapy of Graves’ hyperthyroidism with thionamide anti-thyroid drugs is accompanied by a gradual remission of the autoimmune aberration in the majority of patients. The most likely mechanism behind this remission has been considered to be a direct immunosuppressive effect of thionamide drugs. However, a number of findings in clinical studies of patients with Graves’ disease indicate that remission is probably not caused by a special effect of thionamide drugs. Many studies have shown that remission is linked to restoration of the euthyroid state, and that it is independent of drug dose and type. Moreover, similar remission is observed when patients become euthyroid after thyroid surgery. In an explanatory model described, it is assumed that the autoimmune aberration of Graves’ disease is often basically quit mild and self-limiting. Patients may become ill by the running of a vicious cycle of hyperthyroidism worsening the autoimmunity, and autoimmunity worsening the hyperthyroidism. Once patients are made euthyroid by one or the other drug or by thyroid surgery, the majority of patients will gradually enter remission of the disease. The conclusion that remission is associated with restoration of the euthyroid state, and that it is not a special drug effect, highlights the importance of making and keeping patients with Graves’ disease euthyroid.
Effect of exogenous glucocorticoid on osmotically stimulated antidiuretic hormone secretion and on water reabsorption in man
Authors: Bähr Volker , Franzen Norma , Oelkers Wolfgang , Pfeiffer Andreas F H , Diederich Sven
Published: November 2006

Objective: Glucocorticoids exert tonic suppression of antidiuretic hormone (ADH) secretion. Hypocortisolism in secondary adrenocortical insufficiency can result in a clinical picture similar to the syndrome of inappropriate ADH secretion. On the other hand,in vitroandin vivoresults provide evidence for ADH suppression in states of hypercortisolism. To test the hypothesis that ADH suppression is of relevance during glucocorticoid therapy, we investigated the influence of prednisolone on the osmotic stimulation of ADH.

Design and methods: Seven healthy men were subjected to water deprivation tests with the measurement of plasma ADH (pADH) and osmolality (posmol) before and after glucocorticoid treatment (5 days 30 mg prednisolone per day).

Results: Before glucocorticoid treatment, the volunteers showed a normal test with an adequate increase of pADH (basal 0.54 ± 0.2 to 1.9 ± 0.72 pg/ml (mean ± S.D.)) in relation to posmol(basal 283.3 ± 8.5 to 293.7 ± 6 mosmol/kg). After prednisolone intake, pADH was attenuated (<0.4 pg/ml) in spite of an increase of posmol from 289.3 ± 3.6 to 297.0 ± 5.5 mosmol/kg. However, urine osmolar concentration increased normally during water deprivation after prednisolone. Urinary cAMP excretion increased during water deprivation without glucocorticoid treatment from 3.56 ± 0.55 to 6.07 ± 0.76 μmol/l, reflecting the increased pADH levels. The rise in cAMP excretion was completely blunted by prednisolone treatment.

Conclusions: We speculate that there may be an ADH-independent stimulation of the formation or function of aquaporin-2 channels by prednisolone and/or a direct osmotic stimulation of water reabsorption independent of ADH and glucocorticoid control.