Wall shear stress and arterial performance: two approaches based on engineering

This is the Abstract of the Article. Copyright @ 2009 Oxford University.This crucially important subject generates a very wide literature and the recent authoritative ‘in vivo’ review of Reneman et al [1] (& [2]), with Vennemann et al [3], are taken as seminal. In this paper we use approaches based on conventional engineering to address two key issues raised in [1]. The first is that of basic theory. To what extent can underlying fluid flow theory complement the in vivo understanding of wall shear stress (WSS)? In [1], which is sub-titled Discrepancies with Theory’, Poiseuille’s Law is used, extended to Murray’s Law in [2]. But they do ’not hold in vivo’ [2] because ‘we are dealing with non-Newtonian fluid, distensible vessels, unsteady flows, and too short entrance lengths’ [1].This comment coincides with the four factors Xu and Collins identified in their early Review of numerical analysis for bifurcations [4]. Subsequently they addressed these factors, with an engineering-based rationale of comparing predictions of Computational Fluid Dynamics (CFD) with Womersley theory, in vitro and in vivo data. This rationale has yet to be widely adopted, possibly due to computing complexities and the wide boundary condition data needed. This is despite uncertainties in current in vivo WSS [2]. Secondly, [1] and [2] focus on endothelial function. WSS is an ‘important determinant of arterial diameter’ and ‘mean (M)WSS is regulated locally’. One pointer is the possible importance of the glycocalyx, so that ‘endothelial cells are not seeing WSS’ and which ‘may be involved in the regulation of the total blood flow’ [3]. A typical glycocalyx is shown in [3]. Such a model should focus on adaptation of arterial diameter by ‘nitric oxide and prostaglandins’ [1]. So, using an engineering approach, can we construct a model for local regulation of MWSS? Again, remarks from [1]-[3] resonate with the conclusions of a review of nanoscale physiological flows [5] undertaken as part of an early Nanotechnology Initiative of the UK’s EPSRC. In [5] is illustrated the fractal nature of the intestinal villi-glycocalyx geometry, together with an engineering-style control loop for nitric oxide release and arterial diameter-flow rate control. Within our discussion we report two studies to obtain CFD predictive data very close to the endothelial surface. In both cases we compared two independent codes, respectively two CFD codes, and CFD and Lattice Boltzmann solvers. We also give an updated version of the endothelium control loop

The thermodynamics of metabolism, cardiovascular performance and exercise, in health and diabetes: The objective of clinical markers

Extensive experience in UK National Health Service metabolic syndrome/type 2 diabetes clinics highlights the need for convenient clinical marker(s) which can be readily used to indicate the success or otherwise of alternative therapies. In this paper we study the metabolic context of the healthy and diseased states, which points to the haemodynamics being a possible key in identifying candidate markers. Human metabolism relates to two elemental thermodynamic systems, the individual cell and the human body in its entirety. The fundamental laws of thermodynamics apply to humans, animals, and their individual cells for both healthy and diseased conditions. as they are to classic heat engines. In compliance with the second law enhanced levels of heat are generated under exercise, heat itself being another factor modulating the cardiovascular response to physical exercise. Nutrients and oxygen uptake occurs via the digestive system and lungs, respectively, leading to ATP production by the established metabolic pathways: this is controlled by insulin. These are then delivered to the cells via the haemodynamic system to satisfy local metabolic need. The supply and demand of oxygen are finely regulated, in part, via oxygen-dependent release of ATP from the circulating erythrocytes. Energy supply and demand are regulated to sustain muscle activity resulting in the body’s output of measurable thermodynamic work—i.e. exercise. Recently a dynamic pathway model allowing quantification of ATP release from the erythrocytes and its contribution to oxygen supply regulation has been published. However, metabolic uptake is well known to be greatly affected by disease such as the highly prevalent diabetes type 2 with insulin resistance and beta cell dysfunction having mechanistic roles. In 2010, over 25% of residents above 65 in the USA had diabetes 2. The complexity of the metabolic pathways means that monitoring of patient-specific treatment would be beneficial from a diabetic marker which may be haemodynamic-related and traceable via the local fluid dynamics

A bifunctional kinase-phosphatase in bacterial chemotaxis.

addresses: Oxford Centre for Integrative Systems Biology and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.notes: PMCID: PMC2587623types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2008, The National Academy of SciencesPhosphorylation-based signaling pathways employ dephosphorylation mechanisms for signal termination. Histidine to aspartate phosphosignaling in the two-component system that controls bacterial chemotaxis has been studied extensively. Rhodobacter sphaeroides has a complex chemosensory pathway with multiple homologues of the Escherichia coli chemosensory proteins, although it lacks homologues of known signal-terminating CheY-P phosphatases, such as CheZ, CheC, FliY or CheX. Here, we demonstrate that an unusual CheA homologue, CheA(3), is not only a phosphodonor for the principal CheY protein, CheY(6), but is also is a specific phosphatase for CheY(6)-P. This phosphatase activity accelerates CheY(6)-P dephosphorylation to a rate that is comparable with the measured stimulus response time of approximately 1 s. CheA(3) possesses only two of the five domains found in classical CheAs, the Hpt (P1) and regulatory (P5) domains, which are joined by a 794-amino acid sequence that is required for phosphatase activity. The P1 domain of CheA(3) is phosphorylated by CheA(4), and it subsequently acts as a phosphodonor for the response regulators. A CheA(3) mutant protein without the 794-amino acid region lacked phosphatase activity, retained phosphotransfer function, but did not support chemotaxis, suggesting that the phosphatase activity may be required for chemotaxis. Using a nested deletion approach, we showed that a 200-amino acid segment of CheA(3) is required for phosphatase activity. The phosphatase activity of previously identified nonhybrid histidine protein kinases depends on the dimerization and histidine phosphorylation (DHp) domains. However, CheA(3) lacks a DHp domain, suggesting that its phosphatase mechanism is different from that of other histidine protein kinases

Neuroprotective Mechanism of Lycium barbarum Polysaccharides against Hippocampal-Dependent Spatial Memory Deficits in a Rat Model of Obstructive Sleep Apnea

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Review of early hospitalisation after percutaneous coronary intervention

Background: Percutaneous coronary intervention (PCI) is the most common modality of revascularization in patients with coronary artery disease. Understanding the readmission rates and reasons for readmission after PCI is important because readmissions are a quality of care indicator, in addition to being a burden to patients and healthcare services. Methods: A literature review was performed. Relevant studies are described by narrative synthesis with the use of tables to summarize study results. Results: Data suggests that 30-day readmissions are not uncommon. The rate of readmission after PCI is highly influenced by the cohort and the healthcare system studied, with 30-day readmission rates reported to be between 4.7‐% and 15.6%. Studies consistently report that a majority of readmissions within 30 days are due to a cardiac-related disorders or complication-related disorders. Female sex, peripheral vascular disease, diabetes mellitus, renal failure and non-elective PCI are predictive of readmission. Studies also suggest that there is greater risk of mortality among patients who are readmitted compared to those who are not readmitted. Conclusion: Readmission after PCI is common and its rate is highly influenced by the type of cohort studied. There is clear evidence that majority of readmissions within 30 days are cardiac related. While there are many predictors of readmission following PCI, it is not known whether targeting patients with modifiable predictors could prevent or reduce the rates of readmission

Spontaneous Parity Violation in SUSY Strong Gauge Theory

We suggest simple models of spontaneous parity violation in supersymmetric strong gauge theory. We focus on left-right symmetric model and investigate vacuum with spontaneous parity violation. Non-perturbative effects are calculable in supersymmetric gauge theory, and we suggest two new models. The first model shows confinement, and the second model has a dual description of the theory. The left-right symmetry breaking and electroweak symmetry breaking are simultaneously occurred with the suitable energy scale hierarchy. The second model also induces spontaneous supersymmetry breaking.Comment: 14 page

Growth and dislocation studies of β-HMX

Background: The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX). Results: The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip. Conclusions: Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b = [010] and pure screw dislocations with b = [010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b = [010]

Probabilistic Guarded P Systems, A New Formal Modelling Framework

Multienvironment P systems constitute a general, formal framework for modelling the dynamics of population biology, which consists of two main approaches: stochastic and probabilistic. The framework has been successfully used to model biologic systems at both micro (e.g. bacteria colony) and macro (e.g. real ecosystems) levels, respectively. In this paper, we extend the general framework in order to include a new case study related to P. Oleracea species. The extension is made by a new variant within the probabilistic approach, called Probabilistic Guarded P systems (in short, PGP systems). We provide a formal definition, a simulation algorithm to capture the dynamics, and a survey of the associated software.Ministerio de Economía y Competitividad TIN2012- 37434Junta de Andalucía P08-TIC-0420