567 research outputs found

    Application of the nonlinear vortex-lattice concept to aircraft-interference problems

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    A discrete-vortex model was developed to account for the hazardous effects of the vortex trail issued from the edges of separation of a large leading wing on a small trailing wing. The model is divided into three main parts: the leading wing and its near wake, the near and far wakes of the leading wing, and the trailing wing and the portion of the far wake in its vicinity. The normal force, pitching moment, and rolling moment coefficients for the trailing wing are calculated. The circulation distribution in the vortex trail is calculated in the first part of the model where the leading wing is far upstream and hence is considered isolated. A numerical example is solved to demonstrate the feasibility of using this method to study interference between aircraft. The numerical results show the correct trends: The following wing experiences a loss in lift between the wing-tip vortex systems of the leading wing, a gain outside this region, and strong rolling moments which can change sign as the lateral relative position changes. All the results are strongly dependent on the vertical relative position

    Unsteady flow past wings having sharp-edge separation

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    A vortex-lattice technique is developed to model unsteady, incompressible flow past thin wings. This technique predicts the shape of the wake as a function of time; thus, it is not restricted by planform, aspect ratio, or angle of attack as long as vortex bursting does not occur and the flow does not separate from the wing surface. Moreover, the technique can be applied to wings of arbitrary curvature undergoing general motion; thus, it can treat rigid-body motion, arbitrary wing deformation, gusts in the freestream, and periodic motions. Numerical results are presented for low-aspect rectangular wings undergoing a constant-rate, rigid-body rotation about the trailing edge. The results for the unsteady motion are compared with those predicted by assuming quasi-steady motion. The present results exhibit hysteretic behavior

    Differential Role of PKC-Induced c-Jun in HTLV-1 LTR Activation by 12-O-Tetradecanoylphorbol-13-acetate in Different Human T-cell Lines

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    We have previously shown that TPA activates HTLV-1 LTR in Jurkat T-cells by inducing the binding of Sp1-p53 complex to the Sp1 site residing within the Ets responsive region 1 (ERR-1) of the LTR and that this activation is inhibited by PKCalpha and PKCepsilon. However, in H9 T-cells TPA has been noted to activate the LTR in two consecutive stages. The first stage is activation is mediated by PKCetta and requires the three 21 bp TRE repeats. The second activation mode resembles that of Jurkat cells, except that it is inhibited by PKCdelta. The present study revealed that the first LTR activation in H9 cells resulted from PKCetta-induced elevation of non-phosphorylated c-Jun which bound to the AP-1 site residing within each TRE. In contrast, this TRE-dependent activation did not occur in Jurkat cells, since there was no elevation of non-phosphorylated c-Jun in these cells. However, we found that PKCalpha and PKCepsilon, in Jurkat cells, and PKCetta and PKCdelta, in H9 cells, increased the level of phosphorylated c-Jun that interacted with the Sp1-p53 complex. This interaction prevented the Sp1-p53 binding to ERR-1 and blocked, thereby, the ERR-1-mediated LTR activation. Therefore, this PKC-inhibited LTR activation started in both cell types after depletion of the relevant PKCs by their downregulation. In view of these variable activating mechanisms we assume that there might be additional undiscovered yet modes of HTLV-1 LTR activation which vary in different cell types. Moreover, in line with this presumption we speculate that in HTLV-1 carriers the LTR of the latent provirus may also be reactivated by different mechanisms that vary between its different host T-lymphocyte subclones. Since this reactivation may initiate the ATL process, understanding of these mechanisms is essential for establishing strategies to block the possibility of reactivating the latent virus as preventive means for ATL development in carriers

    Natural Rolling Responses of a Delta Wing in Transonic and Subsonic Flows

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    The unsteady, three-dimensional, full Navier-Stokes (NS) equations and the Euler equations of rigid-body dynamics are sequentially solved to simulate the natural rolling response of slender delta wings of zero thickness at moderate to high angles of attack, to transonic and subsonic flows. The governing equations of fluid flow and dynamics of the present multi-disciplinary problem are solved using the time-accurate solution of the NS equations with the implicit, upwind, Roe flux-difference splitting, finite-volume scheme and a four-stage Runge-Kutta scheme, respectively. The main focus is to analyze the effect of Mach number and angle of attack on the leading edge vortices and their breakdown, the resultant rolling motion, and overall aerodynamic response of the wing. Three cases demonstrate the natural response of a 65 deg swept, cropped delta wing in a transonic flow with breakdown of the leading edge vortices and an 80 deg swept delta wing in a subsonic flow undergoing either damped or self-excited limit-cycle rolling oscillations as a function of angle of attack. Comparisons with an experimental investigation completes this study, validating the analysis and illustrating the complex details afforded by computational investigations

    Fire detection in color images using Markov random fields

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    Automatic video-based fire detection can greatly reduce fire alert delay in large industrial and commercial sites, at a minimal cost, by using the existing CCTV camera network. Most traditional computer vision methods for fire detection model the temporal dynamics of the flames, in conjunction with simple color filtering. An important drawback of these methods is that their performance degrades at lower framerates, and they cannot be applied to still images, limiting their applicability. Also, real-time operation often requires significant computational resources, which may be unfeasible for large camera networks. This paper presents a novel method for fire detection in static images, based on a Markov Random Field but with a novel potential function. The method detects 99.6% of fires in a large collection of test images, while generating less false positives then a state-of-the-art reference method. Additionally, parameters are easily trained on a 12-image training set with minimal user input

    Evaluation of Galanin Expression in Colorectal Cancer: An Immunohistochemical and Transcriptomic Study

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    Colorectal cancer (CRC) represents around 10% of all cancers, with an increasing incidence in the younger age group. The gut is considered a unique organ with its distinctive neuronal supply. The neuropeptide, human galanin, is widely distributed in the colon and expressed in many cancers, including the CRC. The current study aimed to explore the role of galanin at different stages of CRC. Eighty-one CRC cases (TNM stages I – IV) were recruited, and formalin-fixed paraffin-embedded samples were analyzed for the expression of galanin and galanin receptor 1 (GALR1) by immunohistochemistry (IHC). Galanin intensity was significantly lower in stage IV (n= 6) in comparison to other stages (p= 0.037 using the Mann-Whitney U test). Whole transcriptomics analysis using NGS was performed for selected samples based on the galanin expression by IHC [early (n=5) with high galanin expression and late (n=6) with low galanin expression]. Five differentially regulated pathways (using Absolute GSEA) were identified as drivers for tumor progression and associated with higher galanin expression, namely, cell cycle, cell division, autophagy, transcriptional regulation of TP53, and immune system process. The top shared genes among the upregulated pathways are AURKA, BIRC5, CCNA1, CCNA2, CDC25C, CDK2, CDK6, EREG, LIG3, PIN1, TGFB1, TPX2. The results were validated using real-time PCR carried out on four cell lines [two primaries (HCT116 and HT29) and two metastatic (LoVo and SK-Co-1)]. The current study shows galanin as a potential negative biomarker. Galanin downregulation is correlated with advanced CRC staging and linked to cell cycle and division, autophagy, transcriptional regulation of TP53 and immune system response

    Free energy and molecular dynamics calculations for the cubic-tetragonal phase transition in zirconia

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    The high-temperature cubic-tetragonal phase transition of pure stoichiometric zirconia is studied by molecular dynamics (MD) simulations and within the framework of the Landau theory of phase transformations. The interatomic forces are calculated using an empirical, self-consistent, orthogonal tight-binding (SC-TB) model, which includes atomic polarizabilities up to the quadrupolar level. A first set of standard MD calculations shows that, on increasing temperature, one particular vibrational frequency softens. The temperature evolution of the free energy surfaces around the phase transition is then studied with a second set of calculations. These combine the thermodynamic integration technique with constrained MD simulations. The results seem to support the thesis of a second-order phase transition but with unusual, very anharmonic behaviour above the transition temperature

    Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells

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    Background: Many cancers show aberrant silencing of gene expression and overexpression of histone methyltransferases. The histone methyltransferases (HKMT) EZH2 and EHMT2 maintain the repressive chromatin histone methylation marks H3K27me and H3K9me, respectively, which are associated with transcriptional silencing. Although selective HKMT inhibitors reduce levels of individual repressive marks, removal of H3K27me3 by specific EZH2 inhibitors, for instance, may not be sufficient for inducing the expression of genes with multiple repressive marks. Results: We report that gene expression and inhibition of triple negative breast cancer cell growth (MDA-MB-231) are markedly increased when targeting both EZH2 and EHMT2, either by siRNA knockdown or pharmacological inhibition, rather than either enzyme independently. Indeed, expression of certain genes is only induced upon dual inhibition. We sought to identify compounds which showed evidence of dual EZH2 and EHMT2 inhibition. Using a cell-based assay, based on the substrate competitive EHMT2 inhibitor BIX01294, we have identified proof-of-concept compounds that induce re-expression of a subset of genes consistent with dual HKMT inhibition. Chromatin immunoprecipitation verified a decrease in silencing marks and an increase in permissive marks at the promoter and transcription start site of re-expressed genes, while Western analysis showed reduction in global levels of H3K27me3 and H3K9me3. The compounds inhibit growth in a panel of breast cancer and lymphoma cell lines with low to sub-micromolar IC50s. Biochemically, the compounds are substrate competitive inhibitors against both EZH2 and EHMT1/2. Conclusions: We have demonstrated that dual inhibition of EZH2 and EHMT2 is more effective at eliciting biological responses of gene transcription and cancer cell growth inhibition compared to inhibition of single HKMTs, and we report the first dual EZH2-EHMT1/2 substrate competitive inhibitors that are functional in cells
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