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

Research reports on the diagnosis and detection; environment and infection; and evaluation of interventions on infectious diseases.

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Superposition as memory: unlocking quantum automatic complexity

Imagine a lock with two states, "locked" and "unlocked", which may be manipulated using two operations, called 0 and 1. Moreover, the only way to (with certainty) unlock using four operations is to do them in the sequence 0011, i.e., $0^n1^n$ where $n=2$. In this scenario one might think that the lock needs to be in certain further states after each operation, so that there is some memory of what has been done so far. Here we show that this memory can be entirely encoded in superpositions of the two basic states "locked" and "unlocked", where, as dictated by quantum mechanics, the operations are given by unitary matrices. Moreover, we show using the Jordan--Schur lemma that a similar lock is not possible for $n=60$. We define the semi-classical quantum automatic complexity $Q_{s}(x)$ of a word $x$ as the infimum in lexicographic order of those pairs of nonnegative integers $(n,q)$ such that there is a subgroup $G$ of the projective unitary group PU$(n)$ with $|G|\le q$ and with $U_0,U_1\in G$ such that, in terms of a standard basis $\{e_k\}$ and with $U_z=\prod_k U_{z(k)}$, we have $U_x e_1=e_2$ and $U_y e_1 \ne e_2$ for all $y\ne x$ with $|y|=|x|$. We show that $Q_s$ is unbounded and not constant for strings of a given length. In particular, $$Q_{s}(0^21^2)\le (2,12) < (3,1) \le Q_{s}(0^{60}1^{60})$$ and $Q_s(0^{120})\le (2,121)$.Comment: Lecture Notes in Computer Science, UCNC (Unconventional Computation and Natural Computation) 201

Modelling wall shear stress in small arteries using LBM and FVM

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this study a finite-volume discretisation of a Lattice Boltzmann equation over unstructured grids is presented. The new scheme is based on the idea of placing the unknown fields at the nodes of the mesh and evolve them based on the fluxes crossing the surfaces of the corresponding control volumes. The method, named unstructured Lattice Boltzmann equation (ULBE) is compared with the classical finite volume method (FVM) and is applied here to the problem of blood flow over the endothelium in small arteries. The study shows a significant variation and a high sensitivity of wall shear stress to the endothelium corrugation degree

Optical Coherence Tomography – Variations on a Theme

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.Optical Coherence Tomography (OCT) has developed extensively over the last 23 years. This paper reviews some of the imaging techniques based on OCT with particular reference to the trade-offs between lateral and axial resolution, working distance, imaging depth, acquisition speed (enabling real time observation and 3D imaging), imaged area/volume, contrast enhancement – including velocity measurement, and system complexity – including detectors, light sources and the optical path. The majority of applications of OCT are biomedical, especially ophthalmology, endoscopy and intravascular imaging. However, some industrial applications are emerging particularly for non-destructive testing and quality control, such as in the production of MEMS devices, or the non-destructive detection of sub-surface strain fields in injected moulded polymer parts

Near wall hemodynamics: Modelling the glycocalyx and the endothelial surface

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute.In this paper a coarse-grained model for blood flow in small arteries is presented. Blood is modelled as a two-component incompressible fluid: the plasma and corpuscular elements dispersed in it. The latter are modelled as deformable liquid droplets having greater density and viscosity. Interfacial surface tension and membrane effects are present to mimic key properties and to avoid droplets’ coalescence. The mesoscopic model also includes the presence of the wavy wall, due to the endothelial cells and incorporates a representation of the glycocalyx, covering the vessel wall. The glycocalyx is modelled as a porous medium, the droplets being subjected to a repulsive elastic force when approaching it, during their transit. Preliminary simulations are intended to show the influence of the undulation on the wall together with that of the glycocalyx

Cervical dysplasia in patients with systemic lupus erythematosus

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Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica

The helminth parasite Fasciola hepatica secretes cysteine proteases to facilitate tissue invasion, migration, and development within the mammalian host. The major proteases cathepsin L1 (FheCL1) and cathepsin L2 (FheCL2) were recombinantly produced and biochemically characterized. By using site-directed mutagenesis, we show that residues at position 67 and 205, which lie within the S2 pocket of the active site, are critical in determining the substrate and inhibitor specificity. FheCL1 exhibits a broader specificity and a higher substrate turnover rate compared with FheCL2. However, FheCL2 can efficiently cleave substrates with a Pro in the P2 position and degrade collagen within the triple helices at physiological pH, an activity that among cysteine proteases has only been reported forhuman cathepsin K. The 1.4-Å three-dimensional structure of the FheCL1 was determined by x-ray crystallography, and the three-dimensional structure of FheCL2 was constructed via homology-based modeling. Analysis and comparison of these structures and our biochemical data with those of human cathepsins L and Kprovided an interpretation of the substrate-recognition mechanisms of these major parasite proteases. Furthermore, our studies suggest that a configuration involving residue 67 and the "gatekeeper" residues 157 and 158 situated at the entrance of the active site pocket create a topology that endows FheCL2 with its unusual collagenolytic activity. The emergence of a specialized collagenolytic function in Fasciola likely contributes to the success of this tissue-invasive parasite. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc