LES of additive and non-additive pulsatile flows in a model arterial stenosis

Transition of additive and non-additive pulsatile flows through a simple 3D model of arterial stenosis is investigated by using a large eddy simulation (LES) technique. We find in both the pulsatile cases that the interaction of the two shear layers, one of which separates from the nose of the stenosis and the another one from its opposite wall, causes recirculation in the flow downstream of the stenosis where the nature of the transient flow becomes turbulent. The strength of this recirculation is found to be quite high from the non-additive pulsations when the flow Reynolds numbers, Re ≥ 1500, for which both the pressure and shearing stresses take on an oscillating form at the post-stenotic region. Potential medical consequences of these results are discussed in the paper. In addition, some comparisons of the non-additive pulsatile results are given with those of both the additive pulsatile and steady flows. The capability of using LES to simulate the pulsatile transitional flow is also assessed, and the present results show that the smaller (subgrid) scales (SGS) contributes about 78% energy dissipation to the flow when the Reynolds number is taken as 2000. The level of SGS dissipation decreases as the Reynolds number is decreased. The numerical results are validated with the experimental data available in literature where a quite good agreement is found

Dot and the Kangaroo

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Large-Eddy simulation of pulsatile blood flow

Large-Eddy simulation (LES) is performed to study pulsatile blood flow through a 3D model of arterial stenosis. The model is chosen as a simple channel with a biological type stenosis formed on the top wall. A sinusoidal non-additive type pulsation is assumed at the inlet of the model to generate time dependent oscillating flow in the channel and the Reynolds number of 1200, based on the channel height and the bulk velocity, is chosen in the simulations. We investigate in detail the transition-to-turbulent phenomena of the non-additive pulsatile blood flow downstream of the stenosis. Results show that the high level of flow recirculation associated with complex patterns of transient blood flow have a significant contribution to the generation of the turbulent fluctuations found in the post-stenosis region. The importance of using LES in modelling pulsatile blood flow is also assessed in the paper through the prediction of its sub-grid scale contributions. In addition, some important results of the flow physics are achieved from the simulations, these are presented in the paper in terms of blood flow velocity, pressure distribution, vortices, shear stress, turbulent fluctuations and energy spectra, along with their importance to the relevant medical pathophysiology

Estimation of surface area and volume of a nematode from morphometric data

Nematode volume and surface area are usually based on the inappropriate assumption that the animal is cylindrical. While nematodes are approximately circular in cross section, the radius varies longitudinally. We use standard morphometric data to obtain improved estimates of volume and surface area based on (i) a geometrical approach and (ii) a Bezier representation of the nematode. These new estimators require only the morphometric data available from Cobb's ratios, but if fewer coordinates are available the geometric approach reduces to the standard estimates. Consequently, these new estimators are better than the standard alternatives

Threats to groundwater supplies from contamination in Sierra Leone, with special reference to Ebola care facilities

The outbreak of Ebola virus disease in West Africa in 2014 is the worst single outbreak recorded, and has resulted in more fatalities than all previous outbreaks combined. This outbreak has resulted in a large humanitarian effort to build new health care facilities, with associated water supplies. Although Ebola is not a water-borne disease, care facilities for Ebola patients may become sources of outbreaks of other, water-borne, diseases spread through shallow groundwater from hazard sources such as open defecation, latrines, waste dumps and burial sites to water supplies. The focus of this rapid desk study is to assess from existing literature the evidence for sub-surface transport of pathogens in the context of the hydrogeological and socio-economic environment of Sierra Leone. In particular, the outputs are to advise on the robustness of the evidence for an effective single minimum distance for lateral spacing between hazard sources and water supply, and provide recommendations for protecting water supplies for care facilities as well as other private and public water supplies in this region. Preliminary conclusions were: Considering the climate (heavy intense rainfall for 8 months), the hydrogeological conditions (prevalent shallow and rapidly fluctuating water tables, permeable tropical soils), the pervasive and widespread sources of hazards (very low improved sanitation coverage), and the widespread use of highly vulnerable water points there is little evidence that simply using an arbitrary lateral spacing between hazard sources and water point of 30 – 50 m would provide effective protection for groundwater points. An alternative framework that considers vertical as well as lateral separation and the integrity of the construction and casing of the deeper water points is recommended to protect water supplies from contamination by pathogens. The shallow aquifer, accessed by wells and springs, must be treated as highly vulnerable to pollution, both from diffuse sources and from localised sources. Diffuse pollution of groundwater from surface-deposited wastes including human excreta is likely to be at least as important as pollution from pit latrines and other point sources, given the low sanitation coverage in Sierra Leone. Even though conditions are not optimal for pathogen survival (e.g. temperatures of >25° C), given the very highly permeable shallow tropical soil zone, and the high potential surface and subsurface loading of pathogens, it is likely that shallow water sources are at risk from pathogen pollution, particularly during periods of intense rainfall and high water table conditions. Extending improved sanitation must be a high priority, in conjunction with improved vertical separation between hazard sources and water points, in order to reduce environmental contamination and provide a basis for improved public health. We recommend that risk assessments of water points are undertaken for health care facilities as soon as possible including: detailed sanitary inspections of water points within the 30 – 50 m radius suggested by the Ministry of Water Resource; assessments of the construction and integrity of the water points; a wider survey of contaminant load and rapid surface / sub surface transit routes within a wider 200 m radius of water points. Analysis of key water quality parameters and monitoring of water levels should be undertaken at each water point in parallel with the risk assessments. The translation of policy on water, sanitation and hygiene into implementation needs complementary research to understand key hydrogeological processes as well as barriers and failings of current practice for reducing contamination in water points. A baseline assessment of water quality status and sanitary risks for e.g. wells vs boreholes, improved vs unimproved sources in Sierra Leone is needed. Understanding the role of the tropical soil zone in the rapid migration of pollutants in the shallow subsurface, i.e. tracing rapid pathways, and quantifying residence times of shallow and deep groundwater systems are key knowledge gaps

Estimation of Surface Area and Volume of a Nematode from Morphometric Data

Nematode volume and surface area are usually based on the inappropriate assumption that the animal is cylindrical. While nematodes are approximately circular in cross section, the radius varies longitudinally. We use standard morphometric data to obtain improved estimates of volume and surface area based on (i) a geometrical approach and (ii) a Bézier representation of the nematode. These new estimators require only the morphometric data available from Cobb's ratios, but if fewer coordinates are available the geometric approach reduces to the standard estimates. Consequently, these new estimators are better than the standard alternatives

Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival

BACKGROUND: The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. METHODS: We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. RESULTS: We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. CONCLUSIONS: Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and in vivo tumor growth

The heats of formation of the haloacetylenes XCCY [X, Y = H, F, Cl]: basis set limit ab initio results and thermochemical analysis

The heats of formation of haloacetylenes are evaluated using the recent W1 and W2 ab initio computational thermochemistry methods. These calculations involve CCSD and CCSD(T) coupled cluster methods, basis sets of up to spdfgh quality, extrapolations to the one-particle basis set limit, and contributions of inner-shell correlation, scalar relativistic effects, and (where relevant) first-order spin-orbit coupling. The heats of formation determined using W2 theory are: \hof(HCCH) = 54.48 kcal/mol, \hof(HCCF) = 25.15 kcal/mol, \hof(FCCF) = 1.38 kcal/mol, \hof(HCCCl) = 54.83 kcal/mol, \hof(ClCCCl) = 56.21 kcal/mol, and \hof(FCCCl) = 28.47 kcal/mol. Enthalpies of hydrogenation and destabilization energies relative to acetylene were obtained at the W1 level of theory. So doing we find the following destabilization order for acetylenes: FCCF $>$ ClCCF $>$ HCCF $>$ ClCCCl $>$ HCCCl $>$ HCCH. By a combination of W1 theory and isodesmic reactions, we show that the generally accepted heat of formation of 1,2-dichloroethane should be revised to -31.8$\pm$0.6 kcal/mol, in excellent agreement with a very recent critically evaluated review. The performance of compound thermochemistry schemes such as G2, G3, G3X and CBS-QB3 theories has been analyzed.Comment: Mol. Phys., in press (E. R. Davidson issue