Rate-limiting steps in the development of atherosclerosis: the response-to-influx theory

A large number of processes are involved in the pathogenesis of atherosclerosis but it is unclear which of them play a rate-limiting role. One way of resolving this problem is to investigate the highly non-uniform distribution of disease within the arterial system; critical steps in lesion development should be revealed by identifying arterial properties that differ between susceptible and protected sites. Although the localisation of atherosclerotic lesions has been investigated intensively over much of the 20th century, this review argues that the factor determining the distribution of human disease has only recently been identified. Recognition that the distribution changes with age has, for the first time, allowed it to be explained by variation in transport properties of the arterial wall; hitherto, this view could only be applied to experimental atherosclerosis in animals. The newly discovered transport variations which appear to play a critical role in the development of adult disease have underlying mechanisms that differ from those elucidated for the transport variations relevant to experimental atherosclerosis: they depend on endogenous NO synthesis and on blood flow. Manipulation of transport properties might have therapeutic potential. Copyright (C) 2004 S. Karger AG, Basel.

A novel self-healing supramolecular polymer system

Utilising supramolecular pi-pi stacking interactions to drive miscibility in two-component polymer blends offers a novel approach to producing materials with unique properties. We report in this paper the preparation of a supramolecular polymer network that exploits this principle. A low molecular weight polydiimide which contains multiple pi-electron-poor receptor sites along its backbone forms homogeneous films with a siloxane polymer that features pi-electron-rich pyrenyl end-groups. Compatibility results from a complexation process that involves chain-folding of the polydiimide to create an optimum binding site for the pi-electron-rich chain ends of the polysiloxane. These complementary pi-electron-rich and -poor receptors exhibit rapid and reversible complexation behaviour in solution, and healable characteristics in the solid state in response to temperature. A mechanism is proposed for this thermoreversible healing behaviour that involves disruption of the intermolecular pi-pi stacking cross-links as the temperature of the supramolecular film is increased. The low T-g siloxane component can then flow and as the temperature of the blend is decreased, pi-pi stacking interactions drive formation of a new network and so lead to good damage-recovery characteristics of the two-component blend.

Scanning LDV for vibration measurement of filiform hairs in crickets in response to induced airflow - art. no. 63450E

Cercal hairs represent in cricket a wind sensitive escape system, able to detect the airflow generated from predating species. These sensors have been studied as a biomimetic concept to allow the development of MEMS for biomedical use. In particular, the behaviour of the hairs, including airflow response, resonant frequency and damping, has been investigated up to a frequency of 20 kHz. The microscopic nature of the hairs, the complex vibrations of excited hairs and the high damping of the system suggested that the use of Laser Doppler vibrometry could possibly improve the test performance. Two types of tests were performed: in the first case the hairs were indirectly excited using the signal obtained from a vibrating aluminium plate, whilst in the second case the hairs were directly excited using a white noise chirp. The results from the first experiment indicated that the hairs move in-phase with the exciting signal up to frequencies in the order of 10 kHz, responding to the vibration modes of the plate with a signal attenuation of 12 to 20 dB. The chirp experiment revealed the presence of rotational resonant modes at 6850 and 11300 Hz. No clear effect of hair length was perceivable on the vibration response of the filiform sensors. The obtained results proved promising to support the mechanical and vibration characterisation of the hairs and suggest that scanning Laser vibrometry can be used extensively on highly dampened biological materials.

Lipids and the immune response: from molecular mechanisms to clinical applications

Purpose of review This review critically evaluates recent studies investigating the effects of fatty acids on immune and inflammatory responses in both healthy individuals and in patients with inflammatory diseases, with some reference to animal studies where relevant. It examines recent findings describing the cellular and molecular basis for the modulation of immune function by fatty acids. The newly emerging area of diet-genotype interactions will also be discussed, with specific reference to the anti-inflammatory effects of fish oil. Recent findings Fatty acids are participants in many intracellular signalling pathways. They act as ligands for nuclear receptors regulating a host of cell responses, they influence the stability of lipid rafts, and modulate eicosanoid metabolism in cells of the immune system. Recent findings suggest that some or all of these mechanisms may be involved in the modulation of immune function by fatty acids. Summary Human studies investigating the relationship between dietary fatty acids and some aspects of the immune response have been disappointingly inconsistent. This review presents the argument that most studies have not been adequately powered to take into account the influence of variation (genotypic or otherwise) on parameters of immune function. There is well-documented evidence that fatty acids modulate T lymphocyte activation, and recent findings describe a range of potential cellular and molecular mechanisms. However, there are still many questions remaining, particularly with respect to the roles of nuclear receptors, for which fatty acids act as ligands, and the modulation of eicosanoid synthesis, for which fatty acids act as precursors.

A novel galactooligosaccharide mixture increases the bifidobacterial population numbers in a continuous in vitro fermentation system and in the proximal colonic contents of pigs in vivo

Prebiotics are nondigestible food ingredients that encourage proliferation of selected groups of the colonic microflora, thereby altering the composition toward a more beneficial community. In the present study, the prebiotic potential of a novel galactooligosaccharide (GOS) mixture, produced by the activity of galactosyltransferases from Bifidobacterium bifidum 41171 on lactose, was assessed in vitro and in a parallel continuous randomized pig trial. In situ fluorescent hybridization with 16S rRNA-targeted probes was used to investigate changes in total bacteria, bifidobacteria, lactobacilli, bacteroides, and Clostridium histolyticum group in response to supplementing the novel GOS mixture. In a 3-stage continuous culture system, the bifidobacterial numbers for the first 2 vessels, which represented the proximal and traverse colon, increased (P < 0.05) after the addition of the oligosaccharide mixture. In addition, the oligosaccharide mixture strongly inhibited the attachment of enterohepatic Escherichia coli (P < 0.01) and Salmonella enterica serotype Typhimurium (P < 0.01) to HT29 cells. Addition of the novel mixture at 4% (wt:wt) to a commercial diet increased the density of bificlobacteria (P < 0.001) and the acetate concentration (P < 0.001), and decreased the pH (P < 0.001) compared with the control diet and the control diet supplemented with inulin, suggesting a great prebiotic potential for the novel oligosaccharide mixture. J. Nutr. 135: 1726-1731, 2005.

The role played by the interaction between genetic factors and attachment in the stress response in infancy

Background: The importance of understanding which environmental and biological factors are involved in determining individual differences in physiological response to stress is widely recognized, given the impact that stress has on physical and mental health. Methods: The child-mother attachment relationship and some genetic polymorphisms (5-HTTLPR, COMT and GABRA6) were tested as predictors of salivary cortisol and alpha amylase concentrations, two biomarkers of hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic adrenomedullary (SAM) system activity, during the Strange Situation (SS) procedure in a sample of more than 100 healthy infants, aged 12 to 18 months. Results: Individual differences in alpha amylase response to separation were predicted by security of attachment in interaction with 5-HTTLPR and GABRA6 genetic polymorphisms, whereas alpha amylase basal levels were predicted by COMT x attachment interaction. No significant effect of attachment, genetics and their interaction on cortisol activity emerged. Conclusions: These results help to disentangle the role played by both genetic and environmental factors in determining individual differences in stress response in infancy. The results also shed light on the suggestion that HPA and SAM systems are likely to have different characteristic responses to stress.

Using a RESTful messaging and registry system to support a range a distributed applications

Tycho was conceived in 2003 in response to a need by the GridRM [1] resource-monitoring project for a ldquolight-weightrdquo, scalable and easy to use wide-area distributed registry and messaging system. Since Tycho's first release in 2006 a number of modifications have been made to the system to make it easier to use and more flexible. Since its inception, Tycho has been utilised across a number of application domains including widearea resource monitoring, distributed queries across archival databases, providing services for the nodes of a Cray supercomputer, and as a system for transferring multi-terabyte scientific datasets across the Internet. This paper provides an overview of the initial Tycho system, describes a number of applications that utilise Tycho, discusses a number of new utilities, and how the Tycho infrastructure has evolved in response to experience of building applications with it.

Reach and grasp therapy: effects of the Gentle/G System assessing sub-acute stroke whole-arm rehabilitation

This paper reports preliminary results of a reach and grasp study of robot mediated neurorehabilitation. These results are presented on a case-by-case basis and give a good indication of a positive effect of robot mediated therapy. The study investigated both reach and grasp assistance and although it is not possible to attribute the response to the benefits of providing assistance of both modalities the study is a good indicator that this strategy should be pursued. The paper also reports on the benefits of motivational queues such as exercise scores and on subject attitudes to the robot mediated therapy.

The effect of the GENTLE/s robot-mediated therapy system on arm function after stroke

Objective: To evaluate the effect of robot-mediated therapy on arm dysfunction post stroke. Design: A series of single-case studies using a randomized multiple baseline design with ABC or ACB order. Subjects (n = 20) had a baseline length of 8, 9 or 10 data points. They continued measurement during the B - robot-mediated therapy and C - sling suspension phases. Setting: Physiotherapy department, teaching hospital. Subjects: Twenty subjects with varying degrees of motor and sensory deficit completed the study. Subjects attended three times a week, with each phase lasting three weeks. Interventions: In the robot-mediated therapy phase they practised three functional exercises with haptic and visual feedback from the system. In the sling suspension phase they practised three single-plane exercises. Each treatment phase was three weeks long. Main measures: The range of active shoulder flexion, the Fugl-Meyer motor assessment and the Motor Assessment Scale were measured at each visit. Results: Each subject had a varied response to the measurement and intervention phases. The rate of recovery was greater during the robot-mediated therapy phase than in the baseline phase for the majority of subjects. The rate of recovery during the robot-mediated therapy phase was also greater than that during the sling suspension phase for most subjects. Conclusion: The positive treatment effect for both groups suggests that robot-mediated therapy can have a treatment effect greater than the same duration of non-functional exercises. Further studies investigating the optimal duration of treatment in the form of a randomized controlled trial are warranted.

Comparison of subspace and ARX models of a waveguide's terahertz transient response after optimal wavelet filtering

A quasi-optical deembedding technique for characterizing waveguides is demonstrated using wide-band time-resolved terahertz spectroscopy. A transfer function representation is adopted for the description of the signal in the input and output port of the waveguides. The time-domain responses were discretized and the waveguide transfer function was obtained through a parametric approach in the z-domain after describing the system with an AutoRegressive with eXogenous input (ARX), as well as with a state-space model. Prior to the identification procedure, filtering was performed in the wavelet domain to minimize both signal distortion, as well as the noise propagating in the ARX and subspace models. The optimal filtering procedure used in the wavelet domain for the recorded time-domain signatures is described in detail. The effect of filtering prior to the identification procedures is elucidated with the aid of pole-zero diagrams. Models derived from measurements of terahertz transients in a precision WR-8 waveguide adjustable short are presented.

A statistical mechanical approach for the computation of the climatic response to general forcings

The climate belongs to the class of non-equilibrium forced and dissipative systems, for which most results of quasi-equilibrium statistical mechanics, including the fluctuation-dissipation theorem, do not apply. In this paper we show for the first time how the Ruelle linear response theory, developed for studying rigorously the impact of perturbations on general observables of non-equilibrium statistical mechanical systems, can be applied with great success to analyze the climatic response to general forcings. The crucial value of the Ruelle theory lies in the fact that it allows to compute the response of the system in terms of expectation values of explicit and computable functions of the phase space averaged over the invariant measure of the unperturbed state. We choose as test bed a classical version of the Lorenz 96 model, which, in spite of its simplicity, has a well-recognized prototypical value as it is a spatially extended one-dimensional model and presents the basic ingredients, such as dissipation, advection and the presence of an external forcing, of the actual atmosphere. We recapitulate the main aspects of the general response theory and propose some new general results. We then analyze the frequency dependence of the response of both local and global observables to perturbations having localized as well as global spatial patterns. We derive analytically several properties of the corresponding susceptibilities, such as asymptotic behavior, validity of Kramers-Kronig relations, and sum rules, whose main ingredient is the causality principle. We show that all the coefficients of the leading asymptotic expansions as well as the integral constraints can be written as linear function of parameters that describe the unperturbed properties of the system, such as its average energy. Some newly obtained empirical closure equations for such parameters allow to define such properties as an explicit function of the unperturbed forcing parameter alone for a general class of chaotic Lorenz 96 models. We then verify the theoretical predictions from the outputs of the simulations up to a high degree of precision. The theory is used to explain differences in the response of local and global observables, to define the intensive properties of the system, which do not depend on the spatial resolution of the Lorenz 96 model, and to generalize the concept of climate sensitivity to all time scales. We also show how to reconstruct the linear Green function, which maps perturbations of general time patterns into changes in the expectation value of the considered observable for finite as well as infinite time. Finally, we propose a simple yet general methodology to study general Climate Change problems on virtually any time scale by resorting to only well selected simulations, and by taking full advantage of ensemble methods. The specific case of globally averaged surface temperature response to a general pattern of change of the CO2 concentration is discussed. We believe that the proposed approach may constitute a mathematically rigorous and practically very effective way to approach the problem of climate sensitivity, climate prediction, and climate change from a radically new perspective.

Spectral design and verification of HIRDLS filters and antireflection coatings using an integrated system performance approach

The HIRDLS instrument contains 21 spectral channels spanning a wavelength range from 6 to 18mm. For each of these channels the spectral bandwidth and position are isolated by an interference bandpass filter at 301K placed at an intermediate focal plane of the instrument. A second filter cooled to 65K positioned at the same wavelength but designed with a wider bandwidth is placed directly in front of each cooled detector element to reduce stray radiation from internally reflected in-band signals, and to improve the out-of-band blocking. This paper describes the process of determining the spectral requirements for the two bandpass filters and the antireflection coatings used on the lenses and dewar window of the instrument. This process uses a system throughput performance approach taking the instrument spectral specification as a target. It takes into account the spectral characteristics of the transmissive optical materials, the relative spectral response of the detectors, thermal emission from the instrument, and the predicted atmospheric signal to determine the radiance profile for each channel. Using this design approach an optimal design for the filters can be achieved, minimising the number of layers to improve the in-band transmission and to aid manufacture. The use of this design method also permits the instrument spectral performance to be verified using the measured response from manufactured components. The spectral calculations for an example channel are discussed, together with the spreadsheet calculation method. All the contributions made by the spectrally active components to the resulting instrument channel throughput are identified and presented.

An enhancement of the ionospheric sporadic‐E layer in response to negative polarity cloud‐to‐ground lightning

Lightning data, collected using a Boltek Storm Tracker system installed at Chilton, UK, were used to investigate the mean response of the ionospheric sporadic-E layer to lightning strokes in a superposed epoch study. The lightning detector can discriminate between positive and negative lightning strokes and between cloud-to-ground ( CG) and inter-cloud ( IC) lightning. Superposed epoch studies carried out separately using these subsets of lightning strokes as trigger events have revealed that the dominant cause of the observed ionospheric enhancement in the Es layer is negative cloud-to-ground lightning.

The application of affine projection to the development of a siren noise cancellation system

Emergency vehicles use high-amplitude sirens to warn pedestrians and other road users of their presence. Unfortunately, the siren noise enters the vehicle and corrupts the intelligibility of two-way radio voice com-munications from the emergency vehicle to a control room. Often the siren has to be turned off to enable the control room to hear what is being said which subsequently endangers people's lives. A digital signal processing (DSP) based system for the cancellation of siren noise embedded within speech is presented. The system has been tested with the least mean square (LMS), normalised least mean square (NLMS) and affine projection algorithm (APA) using recordings from three common types of sirens (two-tone, wail and yelp) from actual test vehicles. It was found that the APA with a projection order of 2 gives comparably improved cancellation over the LMS and NLMS with only a moderate increase in algorithm complexity and code size. Therefore, this siren noise cancellation system using the APA offers an improvement in cancellation achieved by previous systems. The removal of the siren noise improves the response time for the emergency vehicle and thus the system can contribute to saving lives. The system also allows voice communication to take place even when the siren is on and as such the vehicle offers less risk of danger when moving at high speeds in heavy traffic.