650 research outputs found

    Specimen collection for electron microscopy.

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    Apparatus to control and visualize the impact of a high-energy laser pulse on a liquid target

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    We present an experimental apparatus to control and visualize the response of a liquid target to a laser-induced vaporization. We use a millimeter-sized drop as target and present two liquid-dye solutions that allow a variation of the absorption coefficient of the laser light in the drop by seven orders of magnitude. The excitation source is a Q-switched Nd:YAG laser at its frequency-doubled wavelength emitting nanosecond pulses with energy densities above the local vaporization threshold. The absorption of the laser energy leads to a large-scale liquid motion at timescales that are separated by several orders of magnitude, which we spatiotemporally resolve by a combination of ultra-high-speed and stroboscopic high-resolution imaging in two orthogonal views. Surprisingly, the large-scale liquid motion at upon laser impact is completely controlled by the spatial energy distribution obtained by a precise beam-shaping technique. The apparatus demonstrates the potential for accurate and quantitative studies of laser-matter interactions.Comment: Submitted to Review of Scientific Instrument

    Dimethylarginine Dimethylaminohydrolase-1 Transgenic Mice Are Not Protected from Ischemic Stroke

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    Methylated arginines are endogenous analogues of L-arginine, the substrate for nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) interferes with NO formation, causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in humans. It is eliminated primarily by enzymatic activity of dimethylarginine dimethylaminohydrolase (DDAH).We investigated whether human DDAH-1 (hDDAH-1) transgenicity protects from ischemic tissue damage in temporary middle cerebral artery occlusion (tMCAO) in mice. Infarct sizes did not significantly differ between hDDAH-1 transgenic (TG) mice and wild-type littermates (WT). As expected, ADMA plasma concentrations were significantly decreased, cerebral hDDAH expression and protein significantly increased in transgenic animals. Interestingly, neither brain tissue DDAH activity nor ADMA concentrations were different between TG and WT mice. In contrast, muscular DDAH activity was generally lower than in brain but significantly increased in TG mice.Our study demonstrates that hDDAH-1 transgenic mice are not protected from ischemic cerebral tissue damage in tMCAO. This lack of protection is due to high basal cerebral DDAH activity, which is not further increasable by transgenic overexpression of DDAH

    Which activities threaten independent living of elderly when becoming problematic : inspiration for meaningful service robot functionality

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    Purpose: In light of the increasing elderly population and the growing demand for home care, the potential of robot support is given increasing attention. In this paper, an inventory of activities was made that threaten independent living of elderly when becoming problematic. Results will guide the further development of an existing service robot, the Care-O-bot®. Method: A systematic literature search of PubMed was performed, focused on the risk factors for institutionalization. Additionally, focus group sessions were conducted in the Netherlands, United Kingdom and France. In these focus group sessions, problematic activities threatening the independence of elderly people were discussed. Three separate target groups were included in the focus group sessions: (1) elderly persons (n = 41), (2) formal caregivers (n = 40) and (3) informal caregivers (n = 32). Results: Activities within the International Classification of Functioning domains mobility, self-care, and interpersonal interaction and relationships were found to be the most problematic. Conclusions: A distinct set of daily activities was identified that may threaten independent living, but no single activity could be selected as the main activity causing a loss of independence as it is often a combination of problematic activities that is person-specific. Supporting the problematic activities need not involve a robotic solution Read More: http://informahealthcare.com/doi/abs/10.3109/17483107.2013.840861Peer reviewe

    Analytical and experimental characterization of a miniature calorimetric sensor in pulsatile flow

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    The behaviour of a miniature calorimetric sensor, which is under consideration for catheter-based coronary artery flow assessment, is investigated in both steady and pulsatile tube flow. The sensor is composed of a heating element operated at constant power, and two thermopiles that measure flow-induced temperature differences over the sensor surface. An analytical sensor model is developed, which includes axial heat conduction in the fluid and a simple representation of the solid wall, assuming a quasi-steady sensor response to the pulsatile flow. To reduce the mathematical problem, described by a two-dimensional advection-diffusion equation, a spectral method is applied. A Fourier transform is then used to solve the resulting set of ordinary differential equations and an analytical expression for the fluid temperature is found. To validate the analytical model, experiments with the sensor mounted in a tube have been performed in steady and pulsatile water flow with various amplitudes and Strouhal numbers. Experimental results are generally in good agreement with theory and show a quasi-steady sensor response in the coronary flow regime. The model can therefore be used to optimize the sensor design for coronary flow assessment

    Everolimus pharmacokinetics and its exposure-toxicity relationship in patients with thyroid cancer

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    Contains fulltext : 172498.pdf (publisher's version ) (Open Access)BACKGROUND: Everolimus is a mTOR inhibitor used for the treatment of different solid malignancies. Many patients treated with the registered fixed 10 mg dose once daily are in need of dose interruptions, reductions or treatment discontinuation due to severe adverse events. This study determined the correlation between systemic everolimus exposure and toxicity. Additionally, the effect of different covariates on everolimus pharmacokinetics (PK) was explored. METHODS: Forty-two patients with advanced thyroid carcinoma were treated with 10 mg everolimus once daily. Serial pharmacokinetic sampling was performed on days 1 and 15. Subsequently, a population PK model was developed using NONMEM to estimate individual PK values used for analysis of an exposure-toxicity relationship. Furthermore, this model was used to investigate the influence of patient characteristics and genetic polymorphisms in genes coding for enzymes relevant in everolimus PK. RESULTS: Patients who required a dose reduction (n = 18) due to toxicity at any time during treatment had significant higher everolimus exposures [mean AUC0-24 (SD) 600 (274) vs. 395 (129) microg h/L, P = 0.008] than patients without a dose reduction (n = 22). A significant association between everolimus exposure and stomatitis was found in the four-level ordered logistic regression analysis (P = 0.047). The presence of at least one TTT haplotype in the ABCB1 gene was associated with a 21 % decrease in everolimus exposure. CONCLUSION: The current study showed that dose reductions and everolimus-induced stomatitis were strongly associated with systemic everolimus drug exposure in patients with cancer. Our findings confirm observations from another study in patients with cancer and show us that everolimus is a good candidate for individualized dosing in patients with cancer. CLINICALTRIAL. GOV NUMBER: NCT01118065
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