480 research outputs found
A Time-Domain Finite Element Boundary Integration Method for Ultrasonic Nondestructive Evaluation
A 2-D and 3-D numerical modeling approach for calculating the elastic wave scattering signals from complex stress-free defects is evaluated. In this method, efficient boundary integration across the complex boundary of the defect is coupled with a time-domain finite element (FE) solver. The model is designed to simulate time-domain ultrasonic nondestructive evaluation in bulk media. This approach makes use of the hybrid concept of linking a local numerical model to compute the near-field scattering behavior and theoretical mathematical formulas for postprocessing to calculate the received signals. It minimizes the number of monitoring signals from the FE calculation so that the computation effort in postprocessing decreases significantly. In addition, by neglecting the conventional regular monitoring box, the region for FE calculation can be made smaller. In this paper, the boundary integral method is implemented in a commercial FE code, and it is validated by comparing the scattering signals with results from corresponding full FE models. The coupled method is then implemented in real inspection scenarios in both 2-D and 3-D, and the accuracy and the efficiency are demonstrated. The limitations of the proposed model and future works are also discussed. © 2014 IEEE
A generic hybrid model for the simulation of three-dimensional bulk elastodynamics for use in nondestructive evaluation
A three-dimensional (3-D) generic hybrid model is developed for the simulation of elastic waves in applications in nondestructive evaluation (NDE) that efficiently links different solution strategies but, crucially, is independent of the particular schemes employed. This is an important step forward in facilitating rapid and accurate large-scale simulations, and this advances the two-dimensional (2-D) generic hybrid methodology recently developed by the authors. The hybrid model provides an efficient and effective tool for creating highly accurate simulations that model the wave propagation and scattering, enabling the interpretation of inspection data; the new methodology is verified against other numerical simulations. Furthermore, its deployment to simulate wave reflection from side-drilled holes (SDHs), comparing the results with experimental measurements, provides a realistic demonstration as well as further validation
Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer
Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through the secondary T790M EGFR mutation. To overcome this problem, we analysed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M EGFR cells. We also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. Decreased transcription of the GSH-synthesising enzymes (GCLC and GSS) due to the inhibition of NRF2 was responsible for low GSH levels in resistant cells that was directly linked to the T790M mutation. T790M EGFR clinical samples also showed decreased expression of these key enzymes; increasing intra-tumoural GSH levels with a small-molecule GST inhibitor re-sensitised resistant tumours to erlotinib in mice. Thus, we identified a new resistance pathway controlled by EGFR T790M and a therapeutic strategy to tackle this problem in the clinic
James Hutton’s geological tours of Scotland : romanticism, literary strategies, and the scientific quest
This article explores a somewhat neglected part of the story of the emergence of geology as a science and discourse in the late eighteenth century – James Hutton’s posthumously published accounts of the geological tours of Scotland that he undertook in the years 1785 to 1788 in search of empirical evidence in support of his theory of the Earth and that he intended to include in the projected third volume of his Theory of the Earth of 1795. The article brings some of the assumptions and techniques of literary criticism to bear on Hutton’s scientific travel writing in order to open up new connections between geology, Romantic aesthetics and eighteenth-century travel writing about Scotland. Close analysis of Hutton’s accounts of his field trips to Glen Tilt, Galloway and Arran, supplemented by later accounts of the discoveries at Jedburgh and Siccar Point, reveals the interplay between desire, travel and the scientific quest and foregrounds the textual strategies that Hutton uses to persuade his readers that they share in the experience of geological discovery and interpretation as ‘virtual witnesses’. As well as allowing us to revisit the interrelation between scientific theory and discovery, this article concludes that Hutton was a much better writer than he has been given credit for and suggests that if these geological tours had been published in 1795 they would have made it impossible for critics to dismiss him as an armchair geologist
The validity of Kirchhoff theory for scattering of elastic waves from rough surfaces
The Kirchhoff approximation (KA) for elastic wave scattering from two-dimensional (2D) and three-dimensional (3D) rough surfaces is critically examined using finite-element (FE) simulations capable of extracting highly accurate data while retaining a fine-scale rough surface. The FE approach efficiently couples a time domain FE solver with a boundary integration method to compute the scattered signals from specific realizations of rough surfaces. Multiple random rough surfaces whose profiles have Gaussian statistics are studied by both Kirchhoff and FE models and the results are compared; Monte Carlo simulations are used to assess the comparison statistically. The comparison focuses on the averaged peak amplitude of the scattered signals, as it is an important characteristic measured in experiments. Comparisons, in both two dimensions and three dimensions, determine the accuracy of Kirchhoff theory in terms of an empirically estimated parameter
σ
2
/λ
0
(
σ
is the RMS value, and λ
0
is the correlation length, of the roughness), being considered accurate when this is less than some upper bound
c
, (
σ
2
/λ
0
<
c
). The incidence and scattering angles also play important roles in the validity of the Kirchhoff theory and it is found that for modest incidence angles of less than 30°, the accuracy of the KA is improved even when
σ
2
/λ
0
>
c
. In addition, the evaluation results are compared using 3D isotropic rough surfaces and 2D surfaces with the same surface parameters.
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Rough surface reconstruction of real surfaces for numerical simulations of ultrasonic wave scattering
The scattering of waves by rough surfaces plays a significant role in many fields of physical sciences including ultrasonics where failure surfaces are often rough and their accurate identification is critical. The prediction of the strength of scattering can be hampered when the roughness is not adequately characterised and this is a particular issue when the surface roughness is within an order of the incident wavelength. Here we develop a methodology to reconstruct, and accurately represent, rough surfaces using an AutoRegressive (AR) process that then allows for rapid numerical simulations of ultrasonic wave rough surface scattering in three dimensions. Gaussian, exponential and AR surfaces are reconstructed based on real surface data and the statistics of the surfaces are compared with each other. The statistics from the AR surfaces agree well with those from actual rough surfaces, taken from experimental samples, in terms of the heights as well as the gradients, which are the two main factors in accurately predicting the wave scattering intensities. Ultrasonic rough surface scattering is simulated numerically using the Kirchhoff approximation, and comparisons with Gaussian, exponential, AR and real sample surfaces are performed; scattering intensities found using AR surfaces show the best agreement with the real sample surfaces
Determination of Specific Electrocatalytic Sites in the Oxidation of Small Molecules on Crystalline Metal Surfaces
The identification of active sites in electrocatalytic reactions is part of the elucidation of mechanisms of catalyzed reactions on solid surfaces. However, this is not an easy task, even for apparently simple reactions, as we sometimes think the oxidation of adsorbed CO is. For surfaces consisting of non-equivalent sites, the recognition of specific active sites must consider the influence that facets, as is the steps/defect on the surface of the catalyst, cause in its neighbors; one has to consider the electrochemical environment under which the “active sites” lie on the surface, meaning that defects/steps on the surface do not partake in chemistry by themselves. In this paper, we outline the recent efforts in understanding the close relationships between site-specific and the overall rate and/or selectivity of electrocatalytic reactions. We analyze hydrogen adsorption/desorption, and electro-oxidation of CO, methanol, and ammonia. The classical topic of asymmetric electrocatalysis on kinked surfaces is also addressed for glucose electro-oxidation. The article takes into account selected existing data combined with our original works.M.J.S.F. is grateful to PNPD/CAPES (Brazil). J.M.F. thanks the MCINN (FEDER, Spain) project-CTQ-2016-76221-P
Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]
<p>Abstract</p> <p>Background</p> <p>The efficacy and safety of a dietary supplement derived from South American botanicals was compared to glucosamine sulfate in osteoarthritis subjects in a Mumbai-based multi-center, randomized, double-blind study.</p> <p>Methods</p> <p>Subjects (n = 95) were screened and randomized to receive glucosamine sulfate (n = 47, 1500 mg/day) or reparagen (n = 48, 1800 mg/day), a polyherbal consisting of 300 mg of vincaria (<it>Uncaria guianensis</it>) and 1500 mg of RNI 249 (<it>Lepidium meyenii</it>) administered orally, twice daily. Primary efficacy variable was response rate based on a 20% improvement in WOMAC pain scores. Additional outcomes were WOMAC scores for pain, stiffness and function, visual analog score (VAS) for pain, with assessments at 1, 2, 4, 6 and 8 weeks. Tolerability, investigator and subject global assessments and rescue medication consumption (paracetamol) were measured together with safety assessments including vital signs and laboratory based assays.</p> <p>Results</p> <p>Subject randomization was effective: age, gender and disease status distribution was similar in both groups. The response rates (20% reduction in WOMAC pain) were substantial for both glucosamine (89%) and reparagen (94%) and supported by investigator and subject assessments. Using related criteria response rates to reparagen were favorable when compared to glucosamine. Compared to baseline both treatments showed significant benefits in WOMAC and VAS outcomes within one week (P < 0.05), with a similar, progressive improvement over the course of the 8 week treatment protocol (45–62% reduction in WOMAC or VAS scores). Tolerability was excellent, no serious adverse events were noted and safety parameters were unchanged. Rescue medication use was significantly lower in the reparagen group (p < 0.01) at each assessment period. Serum IGF-1 levels were unaltered by treatments.</p> <p>Conclusion</p> <p>Both reparagen and glucosamine sulfate produced substantial improvements in pain, stiffness and function in subjects with osteoarthritis. Response rates were high and the safety profile was excellent, with significantly less rescue medication use with reparagen. Reparagen represents a new natural productive alternative in the management of joint health.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN25438351.</p
The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β
BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases
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