465 research outputs found

    Evolution of Surface Density Function in an Open Turbulent Jet Spray Flame

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    A three-dimensional Direct Numerical Simulation of an open turbulent jet spray flame representing a laboratory-scale burner configuration has been used to analyse the statistical behaviours of the magnitude of reaction progress variable gradient |∇c| [alternatively known as the Surface Density Function (SDF)] and the strain rates, which affect its evolution. The flame has been found to exhibit fuel-lean combustion close to the jet exit, but fuel-rich conditions have been obtained further downstream due to the evaporation of fuel droplets, which leads to the reduction in the mean value of the SDF in the downstream direction. This change in mixture composition in the axial direction has implications on the statistical behaviours of the SDF and the strain rates affecting its evolution. The mean value of dilatation rate remains positive, whereas the mean normal strain rate assumes positive values where the effects of heat release are strong but becomes negative towards both unburned and burned gas sides. The mean values of dilatation rate, normal strain rate and tangential strain rate decrease downstream of the jet exit. However, the mean behaviours of displacement speed and its components do not change significantly away from the jet exit. The mean values of normal strain rate arising from flame propagation remain positive and thus act to thicken the flame. The mean tangential strain rate due to flame propagation (alternatively the curvature stretch rate) remains negative throughout the flame at all axial locations investigated. The mean effective normal strain rate assumes positive values throughout the flame and it increases in the downstream direction for the present case, which is consistent with the reduction in the peak mean value of the SDF in the axial direction. The mean effective tangential strain rate (alternatively stretch rate) assumes negative values throughout the flame at all axial locations

    Priority diffusion model in lattices and complex networks

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    We introduce a model for diffusion of two classes of particles (AA and BB) with priority: where both species are present in the same site the motion of AA's takes precedence over that of BB's. This describes realistic situations in wireless and communication networks. In regular lattices the diffusion of the two species is normal but the BB particles are significantly slower, due to the presence of the AA particles. From the fraction of sites where the BB particles can move freely, which we compute analytically, we derive the diffusion coefficients of the two species. In heterogeneous networks the fraction of sites where BB is free decreases exponentially with the degree of the sites. This, coupled with accumulation of particles in high-degree nodes leads to trapping of the low priority particles in scale-free networks.Comment: 5 pages, 3 figure

    Supporting User-Defined Functions on Uncertain Data

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    Uncertain data management has become crucial in many sensing and scientific applications. As user-defined functions (UDFs) become widely used in these applications, an important task is to capture result uncertainty for queries that evaluate UDFs on uncertain data. In this work, we provide a general framework for supporting UDFs on uncertain data. Specifically, we propose a learning approach based on Gaussian processes (GPs) to compute approximate output distributions of a UDF when evaluated on uncertain input, with guaranteed error bounds. We also devise an online algorithm to compute such output distributions, which employs a suite of optimizations to improve accuracy and performance. Our evaluation using both real-world and synthetic functions shows that our proposed GP approach can outperform the state-of-the-art sampling approach with up to two orders of magnitude improvement for a variety of UDFs. 1

    Discovery and cardioprotective effects of the first non-peptide agonists of the G protein-coupled prokineticin receptor-1

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    Prokineticins are angiogenic hormones that activate two G protein-coupled receptors: PKR1 and PKR2. PKR1 has emerged as a critical mediator of cardiovascular homeostasis and cardioprotection. Identification of non-peptide PKR1 agonists that contribute to myocardial repair and collateral vessel growth hold promises for treatment of heart diseases. Through a combination of in silico studies, medicinal chemistry, and pharmacological profiling approaches, we designed, synthesized, and characterized the first PKR1 agonists, demonstrating their cardioprotective activity against myocardial infarction (MI) in mice. Based on high throughput docking protocol, 250,000 compounds were computationally screened for putative PKR1 agonistic activity, using a homology model, and 10 virtual hits were pharmacologically evaluated. One hit internalizes PKR1, increases calcium release and activates ERK and Akt kinases. Among the 30 derivatives of the hit compound, the most potent derivative, IS20, was confirmed for its selectivity and specificity through genetic gain- and loss-of-function of PKR1. Importantly, IS20 prevented cardiac lesion formation and improved cardiac function after MI in mice, promoting proliferation of cardiac progenitor cells and neovasculogenesis. The preclinical investigation of the first PKR1 agonists provides a novel approach to promote cardiac neovasculogenesis after MI

    Flame self-interaction during turbulent boundary layer flashback of hydrogen-rich premixed combustion

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    A three-dimensional direct numerical simulation database of turbulent boundary layer flashback of a hydrogen-rich premixed flame with an equivalence ratio of 1.5 has been analyzed to investigate flame self-interaction (FSI) events. The nonreacting turbulence characteristics of the channel flow are representative of the friction-velocity-based Reynolds number, Reτ=120. A skeletal chemical mechanism with nine species and twenty reactions is employed for the representation of hydrogen-air combustion. Three definitions of the reaction progress variable, c, based on the mass fractions of H2, O2, and H2O, have been considered to define the progress variable. It is found that the FSI events predominantly occur close to the burned gas side for all definitions of c at all the wall normal distances. No FSI events adjacent to the wall have been identified for the c definition based on O2 and H2O mass fractions, whereas FSI events occur for c based on H2 in the near-wall region. In the regions further away from the wall, all c definitions show that tunnel formation and tunnel closure type FSI events remain predominant, which is consistent with the earlier findings by Griffiths et al. [Proc. Combust. Inst. 35, 1341 (2015)1540-748910.1016/j.proci.2014.08.003] involving hydrogen-air premixed flame under shear flow conditions. In this work for c based on H2 mass fraction, unburned gas pockets have also been identified at all wall normal distances and are a consequence of the hydrogen-rich nature of the flame. The reason for the variations in topologies with the change in the definition of c based on different species and wall normal distance is a consequence of several factors, including the changes in the level of turbulence within the turbulent boundary layer, heat loss to the isothermal wall in the near-wall region, and the differential diffusion induced by the nonunity Lewis number. The results from the current analysis show that the turbulent boundary layer and heat loss at the wall play important roles in determining the FSI topologies. The differences in the qualitative nature and distributions of the FSI events between different definitions of c have important implications on the possible extension of flame-surface-based modeling methodology for hydrogen-rich flames within turbulent boundary layers

    Variability in organ-specific EGFR mutational spectra in tumour epithelium and stroma may be the biological basis for differential responses to tyrosine kinase inhibitors

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    Organ-specific differences in epidermal growth factor receptor (EGFR) mutational spectra and frequencies were found in lung cancer and sporadic and BRCA1/2-related breast cancers. Additionally, we found a high frequency of EGFR mutations in the tumour stroma of these invasive breast carcinomas. Those organ-specific mutational spectra and potential targets in the cancer-associated stroma might influence the efficacy of TKI therapy

    Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Pregnane X receptor (PXR) is a key transcription factor that regulates drug metabolizing enzymes such as cytochrome P450 (CYP) 3A4, and plays important roles in intestinal first-pass metabolism. Although there is a large inter-individual heterogeneity with intestinal CYP3A4 expression and activity, the mechanism driving these differences is not sufficiently explained by genetic variability of PXR or CYP3A4. We examined whether epigenetic mechanisms are involved in the regulation of PXR/CYP3A4 pathways in colon cancer cells.</p> <p>Methods</p> <p>mRNA levels of PXR, CYP3A4 and vitamin D receptor (VDR) were evaluated by quantitative real-time PCR on 6 colon cancer cell lines (Caco-2, HT29, HCT116, SW48, LS180, and LoVo). DNA methylation status was also examined by bisulfite sequencing of the 6 cell lines and 18 colorectal cancer tissue samples. DNA methylation was reversed by the treatment of these cell lines with 5-aza-2'-deoxycytidine (5-aza-dC).</p> <p>Results</p> <p>The 6 colon cancer cell lines were classified into two groups (high or low expression cells) based on the basal level of PXR/CYP3A4 mRNA. DNA methylation of the CpG-rich sequence of the <it>PXR </it>promoter was more densely detected in the low expression cells (Caco-2, HT29, HCT116, and SW48) than in the high expression cells (LS180 and LoVo). This methylation was reversed by treatment with 5-aza-dC, in association with re-expression of PXR and CYP3A4 mRNA, but not VDR mRNA. Therefore, PXR transcription was silenced by promoter methylation in the low expression cells, which most likely led to downregulation of CYP3A4 transactivation. Moreover, a lower level of <it>PXR </it>promoter methylation was observed in colorectal cancer tissues compared with adjacent normal mucosa, suggesting upregulation of the PXR/CYP3A4 mRNAs during carcinogenesis.</p> <p>Conclusions</p> <p><it>PXR </it>promoter methylation is involved in the regulation of intestinal PXR and CYP3A4 mRNA expression and might be associated with the inter-individual variability of the drug responses of colon cancer cells.</p

    A hop-count based positioning algorithm for wireless ad-hoc networks

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    We propose a range-free localization algorithm for a wireless ad-hoc network utilizing the hop-count metric’s ability to indicate proximity to anchors (i.e., nodes with known positions). In traditional sense, hop-count generally means the number of intermediate routers a datagram has to go through between its source and the destination node. We analytically show that hop-count could be used to indicate proximity relative to an anchor node. Our proposed algorithm is computationally feasible for resource constrained wireless ad-hoc nodes, and gives reasonable accuracy. We perform both real experiments and simulations to evaluate the algorithm’s performance. Experimental results show that our algorithm outperforms similar proximity based algorithms utilizing received signal strength and expected transmission count. We also analyze the impact of various parameters like the number of anchor nodes, placements of anchor nodes and varying transmission powers of the nodes on the hop-count based localization algorithm’s performance through simulation
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