Vascular endothelial cells (EC)are an important target of estrogen action through both the classical genomic (i.e. nuclear-initiated) activities of estrogen receptors ␣ and ␤ (ER␣ and ER␤) and the rapid "nongenomic" (i.e. membrane-initiated) activation of ER that stimulates intracellular phosphorylation pathways. We tested the hypothesis that the red wine polyphenol trans-resveratrol activates MAPK signaling via rapid ER activation in bovine aortic EC, human umbilical vein EC, and human microvascular EC. We report that bovine aortic EC, human umbilical vein EC, and human microvascular EC express ER␣ and ER␤. We demonstrate that resveratrol and estradiol (E 2 ) rapidly activated MAPK in a MEK-1, Src, matrix metalloproteinase, and epidermal growth factor receptor-dependent manner. Importantly, resveratrol activated MAPK and endothelial nitric-oxide synthase (eNOS) at nM concentrations (i.e. an order of magnitude less than that required for ER genomic activity) and concentrations possibly achieved transiently in serum following oral red wine consumption. Co-treatment with ER antagonists ICI 182,780 or 4-hydroxytamoxifen blocked resveratrol-or E 2 -induced MAPK and eNOS activation, indicating ER dependence. We demonstrate for the first time that ER␣-and ER␤-selective agonists propylpyrazole triol and diarylpropionitrile, respectively, stimulate MAPK and eNOS activity. A red but not a white wine extract also activated MAPK, and activity was directly correlated with the resveratrol concentration. These data suggest that ER may play a role in the rapid effects of resveratrol in EC and that some of the atheroprotective effects of resveratrol may be mediated through rapid activation of ER signaling in EC.Epidemiological studies have indicated that the consumption of red wine reduces the incidence of mortality from coronary heart disease (CHD) 1 (1, 2). The cardioprotective effect has been attributed to the polyphenol fraction of red wine (1). A key polyphenol in red wine is resveratrol, trans-3,5,4Ј-trihydroxystilbene, from grape skin. Red wine contains 1-75 mg of transresveratrol/liter (3). Studies in male rats demonstrated that an alcohol-free red wine extract and resveratrol protect the heart from ischemia reperfusion injury (4). Rodent studies showed that orally administered resveratrol is absorbed in the gut, has high affinity for heart and liver (5, 6), and is metabolized to glucuronides that have a t1 ⁄2 of ϳ1.5 h (7). A recurrent question is whether resveratrol, at concentrations present in red wine, is effective in vivo. The oral absorption of 25 mg of trans-

Using various nanomanipulating instruments, solvated polymers are simultaneously formed into fibers, adhered to solid supports, and interconnected in real-time to create suspended fiber bridges and networks of specified geometries. Fibers from 50 nm to 20 µm diameter have been drawn individually and in parallel using single tips and tip arrays. The speed and ease of producing suspended three-dimensional structures recommends the method for application to custom fabrication of prototype microfluidic and microoptical devices.

Early diagnosis, playing an important role in preventing progress and treating the Alzheimer's disease (AD), is based on classification of features extracted from brain images. The features have to accurately capture main AD-related variations of anatomical brain structures, such as, e.g., ventricles size, hippocampus shape, cortical thickness, and brain volume. This paper proposed to predict the AD with a deep 3D convolutional neural network (3D-CNN), which can learn generic features capturing AD biomarkers and adapt to different domain datasets. The 3D-CNN is built upon a 3D convolutional autoencoder, which is pre-trained to capture anatomical shape variations in structural brain MRI scans. Fully connected upper layers of the 3D-CNN are then fine-tuned for each task-specific AD classification. Experiments on the CADDementia MRI dataset with no skull-stripping preprocessing have shown our 3D-CNN outperforms several conventional classifiers by accuracy. Abilities of the 3D-CNN to generalize the features learnt and adapt to other domains have been validated on the ADNI dataset.Index Terms-Alzheimer's disease, deep learning, 3D convolutional neural network, autoencoder, brain MRI

Microfabricated lab-on-a-chip devices employing a fully integrated electrochemical (EC) detection system have been developed and evaluated. Both capillary electrophoresis (CE) channels and all CE/EC electrodes were incorporated directly onto glass substrates via traditional microfabrication techniques, including photolithographic patterning, wet chemical etching, DC sputtering, and thermal wafer bonding. Unlike analogous CE/EC devices previously reported, no external electrodes were required, and critical electrode characteristics, including size, shape, and placement on the microchip, were established absolutely by the photolithography process. For the model analytes dopamine and catechol, detection limits in the 4-5 microM range (approximately 200 amol injected) were obtained with the Pt EC electrodes employed here, and devices gave stable analytical performance over months of usage.

The micro-Wilhelmy method is a well-established method of determining surface tension by measuring the force of withdrawing a tens of microns to millimeters in diameter cylindrical wire or fiber from a liquid. A comparison of insertion force to retraction force can also be used to determine the contact angle with the fiber. Given the limited availability of atomic force microscope (AFM) probes that have long constant diameter tips, force-distance (F-D) curves using probes with standard tapered tips have been difficult to relate to surface tension. In this report, constant diameter metal alloy nanowires (referred to as "nanoneedles") between 7.2 and 67 microm in length and 108 and 1006 nm in diameter were grown on AFM probes. F-D and Q damping AFM measurements of wetting and drag forces made with the probes were compared against standard macroscopic models of these forces on slender cylinders to estimate surface tension, contact angle, meniscus height, evaporation rate, and viscosity. The surface tensions for several low molecular weight liquids that were measured with these probes were between -4.2% and +8.3% of standard reported values. Also, the F-D curves show well-defined stair-step events on insertion and retraction from partial wetting liquids, compared to the continuously growing attractive force of standard tapered AFM probe tips. In the AFM used, the stair-step feature in F-D curves was repeatably monitored for at least 0.5 h (depending on the volatility of the liquid), and this feature was then used to evaluate evaporation rates (as low as 0.30 nm/s) through changes in the surface height of the liquid. A nanoneedle with a step change in diameter at a known distance from its end produced two steps in the F-D curve from which the meniscus height was determined. The step features enable meniscus height to be determined from distance between the steps, as an alternative to calculating the height corresponding to the AFM measured values of surface tension and contact angle. All but one of the eight measurements agreed to within 13%. The constant diameter of the nanoneedle also is used to relate viscous damping of the vibrating cantilever to a macroscopic model of Stokes drag on a long cylinder. Expected increases in drag force with insertion depth and viscosity are observed for several glycerol-water solutions. However, an additional damping term (associated with drag of the meniscus on the sidewalls of the nanoneedle) limits the sensitivity of the measurement of drag force for low-viscosity solutions, while low values of Q limit the sensitivity for high-viscosity solutions. Overall, reasonable correspondence is found between the macroscopic models and the measurements with the nanoneedle-tipped probes. Tighter environmental control of the AFM and treatments of needles to give them more ideal surfaces are expected to improve repeatability and make more evident subtle features that currently appear to be present on the F-D and Q damping curves.