An Application of a Second Order Upwinding Scheme for an Implicit LES CFD Solver

The flow past a right square cylinder in a duct at a Reynolds number of 22 x 103 has been employed to validate the use of second order upwinding, instead of a subgrid model in a largeeddy simulation. In this extensively studied problem, all the numerical work has been based on a simplifying assumption that the square cylinder is infinite, which resulted in all previous workers using cyclic boundary conditions so as to reduce the required domain size. It is not clear how the size of the domain had been established and, therefore, whether it was sufficiently large to adequately represent the experimental flow in a duct. The integral quantities of the drag and lift coefficient and the Strouhal number, converged towards the experimental values as the grid resolution is increased. However, the cyclic boundary condition assumption leads to a flow width that provides too small a region of uncorrelated flow. A model of the full duct case, identical to experimental domain, was used to contrast the cyclic domain results. Surprisingly the second order upwind model generates power spectra that appear to correctly capture the energy cascade down to the inertial and viscous ranges

Thermal Conductivity of Graphite Felt at High Temperatures

Thermal conductivity measurements in vacuum, helium and air of WDF graphite felt were conducted at room temperature. It was found that conduction along the solid paths, gas conduction and radiation between fibres are the dominant heat transfer mechanisms. All heat transfer models reviewed indicated that there are geometrical parameters to be determined experimentally in order to be able to quantify the conduction and radiative mechanisms. Experimental results obtained at room temperature were used to calculate the conduction tortuosity, Ï. Results from the literature were used to determine the radiation constant, Cfr. Using these parameters, an equation for the felt thermal conductivity as a function of the absolute temperature was obtained

Syndecan-3 is selectively pro-inflammatory in the joint and contributes to antigen-induced arthritis in mice

INTRODUCTION: Syndecans are heparan sulphate proteoglycans expressed by endothelial cells. Syndecan-3 is expressed by synovial endothelial cells of rheumatoid arthritis (RA) patients where it binds chemokines, suggesting a role in leukocyte trafficking. The objective of the current study was to examine the function of syndecan-3 in joint inflammation by genetic deletion in mice and compare with other tissues. METHODS: Chemokine C-X-C ligand 1 (CXCL1) was injected in the joints of syndecan-3-/-and wild-type mice and antigen-induced arthritis performed. For comparison chemokine was administered in the skin and cremaster muscle. Intravital microscopy was performed in the cremaster muscle. RESULTS: Administration of CXCL1 in knee joints of syndecan-3-/-mice resulted in reduced neutrophil accumulation compared to wild type. This was associated with diminished presence of CXCL1 at the luminal surface of synovial endothelial cells where this chemokine clustered and bound to heparan sulphate. Furthermore, in the arthritis model syndecan-3 deletion led to reduced joint swelling, leukocyte accumulation, cartilage degradation and overall disease severity. Conversely, CXCL1 administration in the skin of syndecan-3 null mice provoked increased neutrophil recruitment and was associated with elevated luminal expression of E-selectin by dermal endothelial cells. Similarly in the cremaster, intravital microscopy showed increased numbers of leukocytes adhering and rolling in venules in syndecan-3-/-mice in response to CXCL1 or tumour necrosis factor alpha. CONCLUSIONS: This study shows a novel role for syndecan-3 in inflammation. In the joint it is selectively pro-inflammatory, functioning in endothelial chemokine presentation and leukocyte recruitment and cartilage damage in an RA model. Conversely, in skin and cremaster it is anti-inflammatory

Mice lacking the syndecan-3 gene are resistant to diet-induced obesity

The accurate matching of caloric intake to caloric expenditure involves a complex system of peripheral signals and numerous CNS neurotransmitter systems. Syndecans are a family of membrane-bound heparan sulfate proteoglycans that modulate ligand-receptor interactions. Syndecan-3 is heavily expressed in several areas of the brain, including hypothalamic nuclei, which are known to regulate energy balance. In particular, syndecans have been implicated in modulation of the activity of the melanocortin system, which potently regulates energy intake, energy expenditure, and peripheral glucose metabolism. Our data demonstrate that syndecan-3-null mice have reduced adipose content compared with wild-type mice. On a high-fat diet, syndecan-3-null male and female mice exhibited a partial resistance to obesity due to reduced food intake in males and increased energy expenditure in females relative to that of wild-type mice. As a result, syndecan-3-null mice on a high-fat diet accumulated less adipose mass and showed improved glucose tolerance compared with wild-type controls. The data implicate syndecan-3 in the regulation of body weight and suggest that inhibition of syndecan-3 may provide a therapeutic approach for the treatment of obesity resulting from exposure to high-fat diets. Introduction Body adipose mass is regulated by matching caloric intake to caloric expenditure over time. The CNS is a critical site where signals of adipose stores are sensed and where appropriate changes in intake and/or expenditure are produced. Over the past decade, a number of proteins have been implicated in the process of sensing peripheral fuel status and the effector mechanisms that defend peripheral adipose mass (1). While most of these proteins are neurotransmitters, receptors, or intracellular signaling molecules, recent data indicate an important role for a unique family of proteins called syndecans. Syndecans are ubiquitous cell surface heparan sulfate proteoglycans (HSPGs; proteins with covalently attached, highly acidic sugar chains), unique in their ability to bind many extracellular peptides, such as hormones and growth factors. Syndecans are found on almost every cell type (2) but are differentially expressed depending on the tissue type. Evidence for the involvement of syndecans in the control of energy balance comes from mice that overexpress syndecan-1 (3). Despite using the pan-selective cytomegalovirus promoter enhancer, Reizes and colleagues showed that mice overexpressing syndecan-1 express transgenic syndecan-1 in a highly unique and circumscribed pattern including expression in regions of the hypothalamus that have long been linked to energy balance regulation, such as the paraventricular nucleus (3, 4). Quite unexpectedly, these mice also show a profound, maturity-onset obesity and type 2 diabetes (3). Although such data indicate a potential role for syndecans in the CNS control of energy balance, syndecan-1 is not normally expressed in the CNS. However, other members of the syndecan family are expressed in the CNS and, most nota

Experimental and numerical investigation of blade–tower interaction noise

© 2018 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (December 2018) in accordance with the publisher’s archiving policyThis paper describes the generation of blade–tower interaction (BTI) noise from upwind turbines and pylon-mounted fans using a combination of experimental and numerical means. An experimental rotor-rig was used in an anechoic chamber to obtain BTI acoustic data under controlled conditions. A computational model, based on the solution of the unsteady Reynolds Averaged Navier Stokes (URANS) equations and Curle's acoustic analogy, was used to describe the generation of fan and simplistic model of wind turbine BTI noise by the rotor-rig. For both the fan and model wind turbine case, the tower was found to be a more significant source of BTI noise than rotor blades. The acoustic waveforms for both turbine and fan are similar; however, in the case of the turbine, the blade contribution reinforces that from the tower, while in the case of a fan, there is some cancellation between the tower source and the blade source. This behavior can be explained by the unsteady aerodynamics occurring during BTI

A novel role for syndecan-3 in angiogenesis.

Syndecan-3 is one of the four members of the syndecan family of heparan sulphate proteoglycans and has been shown to interact with numerous growth factors via its heparan sulphate chains. The extracellular core proteins of syndecan-1,-2 and -4 all possess adhesion regulatory motifs and we hypothesized that syndecan-3 may also possess such characteristics. Here we show that a bacterially expressed GST fusion protein consisting of the entire mature syndecan-3 ectodomain has anti-angiogenic properties and acts via modulating endothelial cell migration. This work identifies syndecan-3 as a possible therapeutic target for anti-angiogenic therapy.This work was funded by Arthritis Research-UK (Grant No. 19207) and funds from the William Harvey Research Foundation both to JRW

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Developing innovative teaching materials that use molecular simulations in engineering thermodynamics

Traditionally, Engineering Thermodynamics is presented to undergraduate mechanical engineering students from a classical viewpoint. The emphasis in the courses is on analyzing processes involving bulk thermodynamic properties of materials to ascertain the performance of systems of significant size such as internal combustion engines, steam boiler power plants, vapour compression refrigeration systems, gas compressors etc. This emphasis may need to change so that mechanical engineers gain a better understanding of areas such as nanotechnology, fuel cells, photovoltaic cells and solid state electronics. A further need for change, is because thermodynamics, as a subject, has a reputation that many students apply formulae in a rote-like manner and struggle to understand the underlying physics and practicalities. One of our innovations is to use simple one and two dimensional hard sphere simulations to demonstrate the validity of such basic constants as Avogadro's Number and the Boltzman constant, and then visually demonstrate the ideal gas equation explaining concepts such as temperature and pressure and the way in which they relate to the volume containing a specified number of molecules. The underlying mechanical/physical reasons for the idealizations and processes of thermodynamics can be visually demonstrated by simple hard sphere models in ways that are related to mechanics. We outline some examples of simple simulations and innovative teaching materials that model the molecular (microscopic) behaviour on which macroscopic thermodynamic behaviour depends. Initial trials of some of the ideas that have appeared in past congress papers have been or are currently being trialed. These trials have revealed how students tend to follow the "rote learning of formulae and procedure approach" rather than the "physical understanding" approach. © 2013 ASME

A Novel Approach to the Teaching of Thermodynamic Cycles and the Laws of Thermodynamics

This paper outlines a simple particle mechanics model in which a single particle represents the thermodynamic fluid (gas) in a heat engine (exemplified by a piston engine). By mechanics based reasoning the model demonstrates the connection between the Carnot efficiency limitation of heat engines and the Kelvin-Planck statement of Second Law requiring only the truth of the Clausius statement