Determinants of tissue Doppler measures of regional diastolic function during dobutamine stress echocardiography

Background Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutomine echocardiography (DbE). Methods Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter. Results Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs 4.8 +/- 2.2 cm/s, P < .0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P < .0001), Abnormal segments also showed a shorter E deceleration time (51 +/- 27 ms vs 41 +/- 27 ms, P = .0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress. Conclusion Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography.

A monolithic smoothing-gap algorithm for contact-impact based on the signed distance function

A new algorithm has been developed for smoothing the surfaces in finite element formulations of contact-impact. A key feature of this method is that the smoothing is done implicitly by constructing smooth signed distance functions for the bodies. These functions are then employed for the computation of the gap and other variables needed for implementation of contact-impact. The smoothed signed distance functions are constructed by a moving least-squares approximation with a polynomial basis. Results show that when nodes are placed on a surface, the surface can be reproduced with an error of about one per cent or less with either a quadratic or a linear basis. With a quadratic basis, the method exactly reproduces a circle or a sphere even for coarse meshes. Results are presented for contact problems involving the contact of circular bodies. Copyright (C) 2002 John Wiley Sons, Ltd.

Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes

Androgens play an important role in regulating the central obesity that is a strong risk factor for cardiovascular disease and insulin resistance. This study confirms that androgen receptors are present in subcultured human preadipocytes, with androgen receptor gene expression and saturable specific dihydrotestosterone binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 - 55.7 fmol/mg protein. There was an intrinsic regional difference in androgen receptor complement, with more androgen receptors in visceral than in subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human preadipocytes, with more androstanediol produced by subcutaneous than visceral preadipocytes. While dihydrotestosterone metabolism was insufficient to explain the regional variation in androgen binding, both of these differences would reduce the androgen responsiveness of the subcutaneous preadipocytes compared with visceral preadipocytes. There were no gender differences in androgen binding or metabolism. While the direct effects of androgens on human PAS remain uncertain, these regional differences suggest that AR-mediated regulation of certain PA functions influences adipose tissue distribution.

Exercise and T-lymphocyte function: a comparison of proliferation in PBMC and NK cell-depleted PBMC culture

This study utilized recently developed microbead technology to remove natural killer (NK) cells from peripheral blood mononuclear cell (PBMC) preparations to determine the effect of acute exercise on T-lymphocyte function, independent of changes in lymphocyte subpopulations. Twelve well-trained male runners completed a 60-min exercise trial at 95% ventilatory threshold and a no-exercise control trial. Six blood samples were taken at each session: before exercise, midexercise, immediately after exercise, and 30, 60, and 90 min after exercise. Isolated PBMC and NK cell-depleted PBMC were stimulated with the mitogen phytohemagglutinin. Cellular proliferation was assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye uptake. In the PBMC cultures, there was a significantly lower mitogen response to phytohemagglutinin in exercise compared with the control condition immediately postexercise. There were no significant differences between the control and exercise conditions in NK cell-depleted PBMC cultures or in the responses adjusted for the percentage of CD3 cells. The present findings do not support the view that T-lymphocyte function is reduced after exercise.

Coordination and movement pathology: models of structure and function

Here we consider the role of abstract models in advancing our understanding of movement pathology. Models of movement coordination and control provide the frameworks necessary for the design and interpretation of studies of acquired and developmental disorders. These models do not however provide the resolution necessary to reveal the nature of the functional impairments that characterise specific movement pathologies. In addition, they do not provide a mapping between the structural bases of various pathologies and the associated disorders of movement. Current and prospective approaches to the study and treatment of movement disorders are discussed. It is argued that the appreciation of structure-function relationships, to which these approaches give rise, represents a challenge to current models of interlimb coordination, and a stimulus for their continued development. (C) 2002 Elsevier Science B.V. All rights reserved.

Structure and function of plant toxins (with emphasis on cystine knot toxins)

Plant toxins are substances produced and secreted by plants to defend themselves against predators. In a broad sense, this includes all substances that have a toxic effect on targeted organisms, whether they are microbes, other plants, insects, or higher animals. Plant toxins have a diverse range of structures, from small organic molecules through to proteins. This review gives an overview of the various classes of plant toxins but focuses on an interesting class of protein-based plant toxins containing a cystine knot motif. This structural motif confers exceptional stability on proteins containing it and is associated with a wide range of biological activities. The biological activities and structural stability offer many potential applications in the pharmaceutical and agricultural fields. One particularly exciting prospect is in the use of protein-based plant toxins as molecular scaffolds for displaying pharmaceutically important bioactivities. Future applications of plant toxins are likely to involve genetic engineering techniques and molecular pharming approaches.

Single mode Lamb waves in composite laminated plates generated by piezoelectric transducers

The technique of permanently attaching piezoelectric transducers to structural surfaces has demonstrated great potential for quantitative non-destructive evaluation and smart materials design. For thin structural members such as composite laminated plates, it has been well recognized that guided Lamb wave techniques can provide a very sensitive and effective means for large area interrogation. However, since in these applications multiple wave modes are generally generated and the individual modes are usually dispersive, the received signals are very complex and difficult to interpret. An attractive way to deal with this problem has recently been introduced by applying piezoceramic transducer arrays or interdigital transducer (IDT) technologies. In this paper, the acoustic wave field in composite laminated plates excited by piezoceramic transducer arrays or IDT is investigated. Based on dynamic piezoelectricity theory, a discrete layer theory and a multiple integral transform method, an analytical-numerical approach is developed to evaluate the input impedance characteristics of the transducer and the surface velocity response of the plate. The method enables the quantitative evaluation of the influence of the electrical characteristics of the excitation circuit, the geometric and piezoelectric properties of the transducer array, and the mechanical and geometrical features of the laminate. Numerical results are presented to validate the developed method and show the ability of single wave mode selection and isolation. The results show that the interaction between individual elements of the piezoelectric array has a significant influence on the performance of the IDT, and these effects can not be neglected even in the case of low frequency excitation. It is also demonstrated that adding backing materials to the transducer elements can be used to improve the excitability of specific wave modes. (C) 2002 Elsevier Science Ltd. All rights reserved.

Dual mode cooling house in the warm humid tropics

Passive techniques as an alternative to artificial cooling can bring important energy, environmental, financial, operational and qualitative benefits. However, regions such as the wet tropics can reach high levels of thermal stress in which passive means alone are unable to provide appropriate thermal comfort standards for some parts of the year. Despite a great accumulation of empirical information on the passive performance of houses for either free-running or conditioned modes, very little work has been done on the thermal performance of buildings that can operate with a mixed-running strategy in warm-humid climates. Buildings with such design features are able to balance the needs for comfort, privacy, and energy efficiency during different periods of the year. As free-running and conditioned modes are believed by many to be 'opposite' approaches, and have been presented as separate strategies, this paper demonstrates that not all parameters are directly opposite and a possible dual-mode integrated operation can be used for warm-humid locations for maximum comfort and minimum energy requirements. For this purpose, simulation runs using ESP-R (University of Strathclyde, ESRU, UK) were based on the climate data of Darwin (Australia) and on the ventilation styles of the house: free running and conditioned. Design features applicable to both, i.e. for a dual mode operation could be identified and the differences between conditioned and free running were demonstrated and proved not to be totally conflicting and therefore suitable for a dual mode operation. Different daily usage profiles (five use patterns were defined), and zoning of sleeping and living areas are presented. The dual mode use patterns compared to the base case house, for all the user possibilities, had improved performances of 17-52%, when compared to the free-running mode and 66-98% when compared to the conditioned mode. Simulation runs using other warm-humid climates (Miami, USA; Sao Luis, Brazil; Kuala Lumpur, Malaysia) were also conducted and compared to the results found for Darwin. (C) 2002 Elsevier Science Ltd. All rights reserved.

Polyethylene flow prediction with a differential multi-mode Pom-Pom model

We report the first steps of a collaborative project between the University of Queensland, Polyflow, Michelin, SK Chemicals, and RMIT University; on simulation, validation and application of a recently introduced constitutive model designed to describe branched polymers. Whereas much progress has been made on predicting the complex flow behaviour of many - in particular linear - polymers, it sometimes appears difficult to predict simultaneously shear thinning and extensional strain hardening behaviour using traditional constitutive models. Recently a new viscoelastic model based on molecular topology, was proposed by McLeish and Larson (1998). We explore the predictive power of a differential multi-mode version of the pom-pom model for the flow behaviour of two commercial polymer melts: a (long-chain branched) low-density polyethylene (LDPE) and a (linear) high-density polyethylene (HDPE). The model responses are compared to elongational recovery experiments published by Langouche and Debbaut (1999), and start-up of simple shear flow, stress relaxation after simple and reverse step strain experiments carried out in our laboratory.

Modeling of phase equilibrium and vapor adsorption on carbon black based on a combination of a lattice theory and equation of state

A thermodynamic approach is developed in this paper to describe the behavior of a subcritical fluid in the neighborhood of vapor-liquid interface and close to a graphite surface. The fluid is modeled as a system of parallel molecular layers. The Helmholtz free energy of the fluid is expressed as the sum of the intrinsic Helmholtz free energies of separate layers and the potential energy of their mutual interactions calculated by the 10-4 potential. This Helmholtz free energy is described by an equation of state (such as the Bender or Peng-Robinson equation), which allows us a convenient means to obtain the intrinsic Helmholtz free energy of each molecular layer as a function of its two-dimensional density. All molecular layers of the bulk fluid are in mechanical equilibrium corresponding to the minimum of the total potential energy. In the case of adsorption the external potential exerted by the graphite layers is added to the free energy. The state of the interface zone between the liquid and the vapor phases or the state of the adsorbed phase is determined by the minimum of the grand potential. In the case of phase equilibrium the approach leads to the distribution of density and pressure over the transition zone. The interrelation between the collision diameter and the potential well depth was determined by the surface tension. It was shown that the distance between neighboring molecular layers substantially changes in the vapor-liquid transition zone and in the adsorbed phase with loading. The approach is considered in this paper for the case of adsorption of argon and nitrogen on carbon black. In both cases an excellent agreement with the experimental data was achieved without additional assumptions and fitting parameters, except for the fluid-solid potential well depth. The approach has far-reaching consequences and can be readily extended to the model of adsorption in slit pores of carbonaceous materials and to the analysis of multicomponent adsorption systems. (C) 2002 Elsevier Science (USA).

Stress correlation function evolution in lattice solid elasto-dynamic models of shear and fracture zones and earthquake prediction

It has been argued that power-law time-to-failure fits for cumulative Benioff strain and an evolution in size-frequency statistics in the lead-up to large earthquakes are evidence that the crust behaves as a Critical Point (CP) system. If so, intermediate-term earthquake prediction is possible. However, this hypothesis has not been proven. If the crust does behave as a CP system, stress correlation lengths should grow in the lead-up to large events through the action of small to moderate ruptures and drop sharply once a large event occurs. However this evolution in stress correlation lengths cannot be observed directly. Here we show, using the lattice solid model to describe discontinuous elasto-dynamic systems subjected to shear and compression, that it is for possible correlation lengths to exhibit CP-type evolution. In the case of a granular system subjected to shear, this evolution occurs in the lead-up to the largest event and is accompanied by an increasing rate of moderate-sized events and power-law acceleration of Benioff strain release. In the case of an intact sample system subjected to compression, the evolution occurs only after a mature fracture system has developed. The results support the existence of a physical mechanism for intermediate-term earthquake forecasting and suggest this mechanism is fault-system dependent. This offers an explanation of why accelerating Benioff strain release is not observed prior to all large earthquakes. The results prove the existence of an underlying evolution in discontinuous elasto-dynamic, systems which is capable of providing a basis for forecasting catastrophic failure and earthquakes.

The structural and functional diversity of naturally occurring antimicrobial peptides

Antimicrobial peptides occur in a diverse range of organisms from microorganisms to insects, plants and animals. Although they all have the common function of inhibiting or killing invading microorganisms they achieve this function using an extremely diverse range of structural motifs. Their sizes range from approximately 10-90 amino acids. Most carry an overall positive charge, reflecting a preferred mode of electrostatic interaction with negatively charged microbial membranes. This article describes the structural diversity of a representative set of antimicrobial peptides divided into five structural classes: those with agr-helical structure, those with bgr-sheet structure, those with mixed helical / bgr- sheet structure, those with irregular structure, and those incorporating a macrocyclic structure. There is a significant diversity in both the size and charge of molecules within each of these classes and between the classes. The common feature of their three-dimensional structures is, however, that they have a degree of amphipathic character in which there is separate localisation of hydrophobic regions and positively charged regions. An emerging trend amongst antimicrobial proteins is the discovery of more macrocyclic analogues. Cyclisation appears to impart an additional degree of stability on these molecules and minimizes proteolytic cleavage. In conclusion, there appear to be a number of promising opportunities for the development of novel clinically useful antimicrobial peptides based on knowledge of the structures of naturally occurring antimicrobial molecules.