Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. They are easily functionalized, which allows for the conjugation or encapsulation of important biomolecules. Although recent in vitro studies suggested that silicaderived nanomaterials are nontoxic, in vivo studies of silica nanomaterial toxicity have not been performed. Using the embryonic zebrafish as a model system, we show that silica nanomaterials with aspect ratios greater than 1 are highly toxic (LD 50 = 110 pg/g embryo) and cause embryo deformities, whereas silica nanomaterials with an aspect ratio of 1 are neither toxic nor teratogenic at the same concentrations. Silica nanowires also interfere with neurulation and disrupt expression of sonic hedgehog, which encodes a key midline signaling factor. Our results demonstrate the need for further testing of nanomaterials before they can be used as platforms for drug delivery. From the Clinical Editor:Silica-based nanomaterials show promise for biomedical applications such as cell-selective drug delivery and bioimaging. Using an embryonic zebrafish model system silica nanomaterials with aspect ratios greater than one were found to be highly toxic; whereas silica nanomaterials with an aspect ratio of one are neither toxic nor teratogenic. These results demonstrate the need for testing "nanomaterials" before they can be used as platforms for drug delivery. KeywordsNanowires; Silica; Teratogenic; Toxicity; Zebrafish Nanomaterials show promise for use in biomedical applications including drug delivery and diagnostics due to their size-dependent properties. Many nanomaterials can be functionalized to increase or modify access to specific cells, to deliver molecular payloads to their targets, and/or to report cellular activities. 1-3 Silica-based materials are particularly attractive for biomedical applications because functionalization is readily accomplished, 4-9 and a wide range of sizes and aspect ratios can be fabricated, allowing for control of nanomaterial surface area and therefore the number of sites for the conjugation of biomolecules. 4,10 In addition, fluorescently modified silica nanoparticles are easily tracked in vivo 6, 7 , 11 , 12 targeted to select regions of the body. 13 Silica nanoparticles (those having an aspect ratio of 1) have a tendency to form clumps, whereas silica nanowires (those having an aspect ratio much greater than 1) do not 14, 15 suggesting that silica nanowires may offer a higher degree of functional control for biomedical applications.With the great interest in developing nanomaterial-based drug delivery platforms comes a greater responsibility for testing new nanomaterials for biocompatibility. Several silica-derived nano-materials have been tested for toxicity in cell culture. [16][17][18][19][20][21][22] In these studies, silica nanoparticles were benign, even at very high concentrations. Similarly, silica nanoparticles delivered to the lateral ventricles of the mouse brain were nontoxic and effi...

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Recently, a new type of neural networks called Least Squares Support Vector Machines (LS-SVMs) has been receiving increasing attention in nonlinear system identification and control due to its generalization performance. This paper develops a stable adaptive control scheme using the LS-SVM network. The developed control scheme includes two parts: the identification part that uses a modified structure of LS-SVM neural networks called the multi-resolution wavelet least squares support vector machine network (MRWLS-SVM) as a predictor model, and the controller part that is developed to track a reference trajectory. By means of the Lyapunov stability criterion, stability analysis for the tracking errors is performed. Finally, simulation studies are performed to demonstrate the capability of the developed approach in controlling a pH process.Keywords: least squares support vector machine, multi-resolution wavelet least squares support vector machine neural network, nonlinear system modeling and control, pH control.