442 research outputs found
Examination of the material removal mechanisms during the lapping process of advanced ceramic rolling elements
Two types of HIPed Si3N4 bearing ball blanks with different surface hardness and fracture toughness were lapped under various loads, speeds, and lubricants using a novel eccentric lapping machine. The lapped surfaces were examined by optical microscope and SEM. The experimental results show that the material removal rate for type I ball blanks were 3-4-fold of type 2 in most cases. Different lapping fluids affected the material removal rate at lower lapping loads, but they had much less influence on the material removal rate at higher lapping loads. The SEM micrographs reveal that the grain pullout prevailed on the lapped surface of type I ball blanks, and the surface of type 2 featured bulk material removal by microcracking. Under extreme high lapping load, surface cracks and damages were found, and SEM with EDX disclosed steel from the lapping plate had transferred to the ceramic ball surface. The preliminary conclusion is that the material removal mechanism during the lapping process of silicon nitride balls using this eccentric lapping machine is mainly mechanical abrasive wear. Lawn and Wilshaw's indentation model on brittle materials is used to explain the difference in material removal rate for the two types of ball blanks
Large Eddy Simulation of Transonic Flow Field in NASA Rotor 37
The current paper reports on numerical investigations on the flow characteristics in a transonic axial compressor, NASA Rotor 37. The flow field was used previously as a CFD blind test case conducted by American Society of Mechanical Engineers in 1994. Since the CFD blind-test exercise, many numerical studies on the flow field in the NASA Rotor 37 have been reported. Although steady improvements have been reported in both numerical procedure and turbulence closure, it is believed that all the important aspects of the flow field have not been fully explained with numerical studies based on the Reynolds Averaged Navier-Stokes (RANS) solution. Experimental data show large dip in total pressure distribution near the hub at downstream of the rotor at 100% rotor speed. Most original numerical solutions from the blind test exercise did not predict this total pressure deficit correctly. This total pressure deficit at the rotor exit was attributed to a hub corner flow separation by the author. Several subsequent numerical studies with different turbulence closure model also calculated this dip in total pressure rise. Also, several studies attributed this total pressure deficit to a small leakage flow coming from the hub in the test article. As the experimental study cannot be repeated, either explanation cannot be validated. The primary purpose of the current investigation is to investigate the transonic flow field with both RANS and a Large Eddy Simulation (LES). The RANS approach gives similar results presented at the original blind test exercise. Although the RANS calculates higher overall total pressure rise, the total pressure deficit near the hub is calculated correctly. The numerical solution shows that the total pressure deficit is due to a hub corner flow separation. The calculated pressure rise from the LES agrees better with the measured total pressure rise especially near the casing area where the passage shock interacts with the tip clearance vortex and flow becomes unsteady due to this interaction. The LES simulation also calculates the total pressure rise deficit near the hub and it agrees well with the measured data
High repetition-rate neutron generation by several-mJ, 35 fs pulses interacting with free-flowing D2O
Using several-mJ energy pulses from a high-repetition rate (1/2 kHz), ultrashort (35 fs) pulsed laser interacting with a 10 lm diameter stream of free-flowing heavy water (D2O), we demonstrate a 2.45 MeV neutron flux of 105/s. Operating at high intensity (of order 1019W/cm2), laser pulse energy is efficiently absorbed in the pre-plasma, generating energetic deuterons. These collide with deuterium nuclei in both the bulk target and the large volume of low density D2O vapor surrounding the target to generate neutrons through dðd; nÞ3 He reactions. The neutron flux, as measured by a calibrated neutron bubble detector, increases as the laser pulse energy is increased from 6 mJ to 12 mJ. A quantitative comparison between the measured flux and the results derived from 2D-particle-in-cell simulations shows comparable neutron fluxes for laser characteristics similar to the experiment. The simulations reveal that there are two groups of deuterons. Forward moving deuterons generate deuterium–deuterium fusion reactions in the D2O stream and act as a point source of neutrons, while backward moving deuterons propagate through the low-density D2O vapor filled chamber and yield a volumetric source of neutrons
Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.
The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-α and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance
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A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice.
It is well known that the ω-3 fatty acids (ω-3-FAs; also known as n-3 fatty acids) can exert potent anti-inflammatory effects. Commonly consumed as fish products, dietary supplements and pharmaceuticals, ω-3-FAs have a number of health benefits ascribed to them, including reduced plasma triglyceride levels, amelioration of atherosclerosis and increased insulin sensitivity. We reported that Gpr120 is the functional receptor for these fatty acids and that ω-3-FAs produce robust anti-inflammatory, insulin-sensitizing effects, both in vivo and in vitro, in a Gpr120-dependent manner. Indeed, genetic variants that predispose to obesity and diabetes have been described in the gene encoding GPR120 in humans (FFAR4). However, the amount of fish oils that would have to be consumed to sustain chronic agonism of Gpr120 is too high to be practical, and, thus, a high-affinity small-molecule Gpr120 agonist would be of potential clinical benefit. Accordingly, Gpr120 is a widely studied drug discovery target within the pharmaceutical industry. Gpr40 is another lipid-sensing G protein-coupled receptor, and it has been difficult to identify compounds with a high degree of selectivity for Gpr120 over Gpr40 (ref. 11). Here we report that a selective high-affinity, orally available, small-molecule Gpr120 agonist (cpdA) exerts potent anti-inflammatory effects on macrophages in vitro and in obese mice in vivo. Gpr120 agonist treatment of high-fat diet-fed obese mice causes improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity and decreased hepatic steatosis. This suggests that Gpr120 agonists could become new insulin-sensitizing drugs for the treatment of type 2 diabetes and other human insulin-resistant states in the future
Nonlinear fractional differential equations in nonreflexive Banach spaces and fractional calculus
The aim of this paper is to correct some ambiguities and inaccuracies in Agarwal et al. (Commun. Nonlinear Sci. Numer. Simul. 20(1): 59-73, 2015; Adv. Differ. Equ. 2013: 302, 2013, doi:10.1186/1687-1847-2013-302) and to present new ideas and approaches for fractional calculus and fractional differential equations in nonreflexive Banach spaces
Modeling shear waves through a viscoelastic medium induced by acoustic radiation force
In this study, a finite element model of a tissue-mimicking, viscoelastic phantom with a stiffer cylindrical inclusion subjected to an acoustic radiation force (ARF) is presented, and the resulting shear waves through the heterogeneous media are simulated, analyzed, and compared with experimental data. Six different models for the ARF were considered and compared. Each study used the same finite element model, but applied the following: (1) full radiation push; (2) focal region push; (3) single element focal point source; or (4) various thresholds of the full radiation push. For each case, displacements at discrete locations were determined and compared. The finite element simulation results for the full radiation push matched well with the experimental data with respect to replicating the shear wave speed and attenuation in the peak displacements through the background medium and inclusion, but did not illustrate comparable recovery after the peak displacements. As a result of this study, it has been shown that a focal region or point source push is not adequate to accurately model the effects of the full radiation push, but thresholding the full push can produce comparable results and reduce computation time
Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer
In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ≈ 55% of them in extragenic DNA regions and an intriguing involvement of the 5′ domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa
Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations
Limited sensitivity of existing assays has prevented investigation of whether Adriamycin–DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin–DNA adducts/104 bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin–DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [14C]Adriamycin–DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin–DNA adducts at clinically-relevant Adriamycin concentrations. [14C]Adriamycin treatment (25 nM) resulted in 4.4 ± 1.0 adducts/107 bp (∼1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin–DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin–DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues
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