Hydrodynamic and acoustic pressure fluctuations in water pipes due to an orifice:Comparison of measurements with Large Eddy Simulations

The present article investigates the turbulent wall pressure fluctuations due to flow through single-hole sharp-square-edged orifices (opening area ratios of 11%, 20% and 31%) in a water-filled pipe by means of measurements and incompressible Large Eddy Simulations (LES) for opening area ratios of 20% and 31%. The orifice plate thickness was half the orifice diameter. The static pressure measurements and simulations show that the vena-contracta factors of the orifices are dependent on Reynolds numbers, which is due to the finite thickness of the orifices. These LES simulations provide a good prediction of the near-field hydrodynamic wall pressure fluctuations, which dominate up to the first three pipe diameters downstream of the orifice. Upstream and far downstream wall pressure fluctuations are dominated by acoustic pressure fluctuations. The source of the radiated sound field was estimated from the surface integral of the fluctuations across the orifice in the LES. The sound field was calculated by implementing the sound source in a one dimensional acoustic model of the test section. The power spectrum density (PSD) of the wall pressure fluctuations for pipe Reynolds numbers varying from 4000 to 10000 collapsed when presented in dimensionless form, which uses the dynamic pressure in the orifice as reference pressure and the ratio of cross-sectional averaged orifice velocity and orifice diameter as characteristic frequency. In the inertial range of the turbulence a global decay of the pressure PSD and of the sound source show a power of the Strouhal number between [Formula presented] and −2.8. For higher frequencies the pressure fluctuations were dominated by acoustic resonances. For wider orifices the magnitude of these acoustic pressure fluctuations is predicted within a factor two by the acoustic model. For the narrowest orifice (opening ratio of 11%) the measured PSD of pressure fluctuations displays sharp peaks due to self-sustained oscillations (whistling). A simple power law of the sound source is not accurate due to the unstable hydrodynamic modes related to orifice thickness. However, using the simple model for the sound source the acoustic model predicts the acoustic pressure fluctuations reasonably well for all orifices. At low frequency one observes a peak in the PSD hydrodynamic wall-pressure fluctuations at one pipe diameter downstream of the orifice. It is probably due to an acoustically silent “edge-tone-like” sinusoidal self-sustained motion of the jet.</p

Antimalarial drug discovery - the path towards eradication

Malaria is a disease that still affects a significant proportion of the global human population. Whilst advances have been made in lowering the numbers of cases and deaths, it is clear that a strategy based solely on disease control year on year, without reducing transmission and ultimately eradicating the parasite, is unsustainable. This article highlights the current mainstay treatments alongside a selection of emerging new clinical molecules from the portfolio of Medicines for Malaria Venture (MMV) and our partners. In each case, the key highlights from each research phase are described to demonstrate how these new potential medicines were discovered. Given the increased focus of the community on eradicating the disease, the strategy for next generation combination medicines that will provide such potential is explaine

Realisation of a low frequency SKA Precursor: The Murchison Widefield Array

The Murchison Widefield Array is a low frequency (80 - 300 MHz) SKA Precursor, comprising 128 aperture array elements distributed over an area of 3 km diameter. The MWA is located at the extraordinarily radio quiet Murchison Radioastronomy Observatory in the mid-west of Western Australia, the selected home for the Phase 1 and Phase 2 SKA low frequency arrays. The MWA science goals include: 1) detection of fluctuations in the brightness temperature of the diffuse redshifted 21 cm line of neutral hydrogen from the epoch of reionisation; 2) studies of Galactic and extragalactic processes based on deep, confusion-limited surveys of the full sky visible to the array; 3) time domain astrophysics through exploration of the variable radio sky; and 4) solar imaging and characterisation of the heliosphere and ionosphere via propagation effects on background radio source emission. This paper will focus on a brief discussion of the as-built MWA system, highlighting several novel characteristics of the instrument, and a brief progress report (as of June 2012) on the final construction phase. Practical completion of the MWA is expected in November 2012, with commissioning commencing from approximately August 2012 and operations commencing near mid 2013. A brief description of recent science results from the MWA prototype instrument is given

Identification of Plasmodium PI4 kinase as target of MMV390048 by chemoproteomics

Most antimalarial drugs face decreased efficacy due to the emergence of resistant parasites. Therefore, the discovery of new antimalarial medicines is focused on new drugs that act by novel mechanisms and are active against different P. falciparum development stages. Screening of a focused compound library for antiparasitic activity, lead to identification of a novel class of compounds with activity against P. falciparum, 2-aminopyridines. The selected hits were validated and subjected to a lead optimization program resulting in the pre-clinical candidate MMV390048. Here we report an unbiased chemoproteomics strategy for the identification of targets of MMV390048

TOPOLOGICAL MATTER, MIRROR SYMMETRY AND NON-CRITICAL (SUPER)STRINGS

We study the realization of the (super) conformal topological symmetry in two-dimensional field theories. The mirror automorphism of the topological algebra is represented as a reflection in the space of fields. As a consequence, a double BRST structure for topological matter theories is found. It is shown that the implementation of the topological symmetry in non-critical (super)string theories depends on the matter content of the two realizations connected by the mirror transformation.Comment: 45 pages, phyzzx, no figure

Low serum magnesium and 1-year mortality in alcohol withdrawal syndrome

Background: In 2014, the WHO reported that 6% of all deaths were attributable to excess alcohol consumption. The aim of the present study was to examine the relationship between serum magnesium concentrations and mortality in patients with alcohol withdrawal syndrome (AWS). Materials and methods: A retrospective review of 700 patients with documented evidence of previous AWS indicating a requirement for benzodiazepine prophylaxis or evidence of alcohol withdrawal syndrome between November 2014 and March 2015. Results: Of 380 patients included in the sample analysis, 64 (17%) were dead at 1 year following the time of treatment for AWS. The majority of patients had been prescribed thiamine (77%) and a proton pump inhibitor (66%). In contrast, the majority of patients had low circulating magnesium concentrations (2 (P  50 years (OR 3.37, 95% CI 1.52-7.48, P 2 (OR 3.10, 95% CI 1.38-6.94, P < 0.01) and magnesium < 0.75 mmol/L (OR 4.11, 95% CI 1.3-12.8, P < 0.05) remained independently associated with death at 1 year. Conclusion: Overall, 1-year mortality was significantly higher among those patients who were magnesium deficient (<0.75 mmol/L) when compared to those who were replete (≥0.75 mmol/L; P < 0.001)

Screening a protein kinase inhibitor library against <i>Plasmodium falciparum</i>

Abstract Background Protein kinases have been shown to be key drug targets, especially in the area of oncology. It is of interest to explore the possibilities of protein kinases as a potential target class in Plasmodium spp., the causative agents of malaria. However, protein kinase biology in malaria is still being investigated. Therefore, rather than assaying against individual protein kinases, a library of 4731 compounds with protein kinase inhibitor-like scaffolds was screened against the causative parasite, Plasmodium falciparum. This approach is more holistic and considers the whole kinome, making it possible to identify compounds that inhibit more than one P. falciparum protein kinase, or indeed other malaria targets. Results As a result of this screen, 9 active compound series were identified; further validation was carried out on 4 of these series, with 3 being progressed into hits to lead chemistry. The detailed evaluation of one of these series is described. Discussion This screening approach proved to be an effective way to identify series for further optimisation against malaria. Compound optimisation was carried out in the absence of knowledge of the molecular target. Some of the series had to be halted for various reasons. Mode of action studies to find the molecular target may be useful when problems prevent further chemical optimisation. Conclusions Progressible series were identified through phenotypic screening of a relatively small focused kinase scaffold chemical library

100 million years of turtle paleoniche dynamics enable the prediction of latitudinal range shifts in a warming world

Past responses to environmental change provide vital baseline data for estimating the potential resilience of extant taxa to future change. Here, we investigate the latitudinal range contraction that terrestrial and freshwater turtles (Testudinata) experienced from the Late Cretaceous to the Paleogene (100.5-23.03 mya) in response to major climatic changes. We apply ecological niche modeling (ENM) to reconstruct turtle niches, using ancient and modern distribution data, paleogeographic reconstructions, and the HadCM3L climate model to quantify their range shifts in the Cretaceous and late Eocene. We then use the insights provided by these models to infer their probable ecological responses to future climate scenarios at different representative concentration pathways (RCPs 4.5 and 8.5 for 2100), which project globally increased temperatures and spreading arid biomes at lower to mid-latitudes. We show that turtle ranges are predicted to expand poleward in the Northern Hemisphere, with decreased habitat suitability at lower latitudes, inverting a trend of latitudinal range contraction that has been prevalent since the Eocene. Trionychids and freshwater turtles can more easily track their niches than Testudinidae and other terrestrial groups. However, habitat destruction and fragmentation at higher latitudes will probably reduce the capability of turtles and tortoises to cope with future climate changes

Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2

New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 ( 2 ) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 ( Pf eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline ( 2 ) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency