38 research outputs found

    A Numerical and Experimental Evaluation of the Turbulent Heat Flux in a Heated Jet in Crossflow

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    The injection of fully-developed turbulent heated air from a tube into a cooler turbulent duct flow is examined, as an analogy to film cooled turbine blades. Scale Resolving Simulations (SRS) are used to examine the flow numerically. A Detached Eddy Simulation (DES) methodology is examined but found to be ineffective at correctly capturing the physics of the flow. A Large Eddy Simulation (LES) numerical model is developed and applied in which tube and duct turbulence inflow effects are emulated using a divergence-free synthetic eddy method (SEM). The LES sensitivity to the synthetic inflow turbulence is examined with a series of simulations with the SEM inflow toggled on and off. The effects of turbulence in the coolant tube are found to the most critical for accurate prediction. For direct comparison, a hot-wire experiment is conducted within the ERB test cell SW-6 at NASA Glenn Research Center. Excellent agreement is obtained for these numerical and experimental results related to velocity, temperature, and heat flux, for a blowing ratio of 1.2, and involving a 36 K temperature difference. The relative effect on the solutions of tube and duct inflow turbulence is systematically evaluated. The impact of inherent low-pass filtering of temperature measurements and probe wire offset on the experimental results are addressed. The validity of the gradient diffusion hypothesis, fundamental to Reynolds-Averaged Navier-Stokes (RANS) models, is evaluated

    Evaluation of Mixing-Limited Quasi-Global Wind-US Model for HIFiRE 2 Flowpath

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    A Reynolds-averaged Navier-Stokes computational model featuring a mixing-limited, quasi-global chemical kinetics approach for an ethylene-methane fuel mixture is described and used in a validation effort against the Hypersonic International Flight Research Experimentation (HIFiRE) Direct Connect Rig experimental data for flight Mach numbers of 5.84, 6.5, and 8.0. An average error level between the numerical predictions and corresponding experimental measurements for static pressure along the engine flowpath is found to be within approximately 10%, for the two lowest Mach number cases, without calibration. Key features of the numerical flowfield development are identified, including regions within the combustor found to be significantly mixing-limited for each fuel type. The sensitivity of the results to turbulent Schmidt is also briefly examined

    Evidence for natural antisense transcript-mediated inhibition of microRNA function

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    MicroRNAs (miRNAs) have the potential to regulate diverse sets of mRNA targets. In addition, mammalian genomes contain numerous natural antisense transcripts, most of which appear to be non-protein-coding RNAs (ncRNAs). We have recently identified and characterized a highly conserved non-coding antisense transcript for beta-secretase-1 (BACE1), a critical enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript is markedly up-regulated in brain samples from Alzheimer's disease patients and promotes the stability of the (sense) BACE1 transcript. We report here that BACE1-antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed, miR-485-5p and BACE1-antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA. We observed opposing effects of BACE1-antisense and miR-485-5p on BACE1 protein in vitro and showed that Locked Nucleic Acid-antimiR mediated knockdown of miR-485-5p as well as BACE1-antisense over-expression can prevent the miRNA-induced BACE1 suppression. We found that the expression of BACE1-antisense as well as miR-485-5p are dysregulated in RNA samples from Alzheimer's disease subjects compared to control individuals. Our data demonstrate an interface between two distinct groups of regulatory RNAs in the computation of BACE1 gene expression. Moreover, bioinformatics analyses revealed a theoretical basis for many other potential interactions between natural antisense transcripts and miRNAs at the binding sites of the latter

    Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

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    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB

    Highlights from the LHCb experiment

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    We report recent results by the LHCb collaboration in heavy-ion collisions in collider and fixed-target mode at the LHC. A large variety of measurements show the potential of LHCb in nuclear collisions

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

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    AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
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