Mechanical Engineering - Research Publications
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ItemEffect Of Arm Deweighting Using End-Effector Based Robotic Devices On Muscle Activity.(IEEE, 2018)Deweighting of the limb is commonly performed for patients with a neurological injury, such as stroke, as it allows these patients with limited muscle activity to perform movements. Deweighting has been implemented in exoskeletons and other multi-contact devices, but not on an end-effector based device with single contact point between the assisting robot and the human limb being assisted. This study inves-tigates the effects of deweighting using an end-effector based device on healthy subjects. The muscle activity of five subjects was measured in both static postures and dynamic movements. The results indicate a decrease in the activity of muscles which typically act against gravity - such as the anterior deltoid and the biceps brachii - but also suggest an increase in activity in muscles which act with gravity - such as the posterior deltoid and the lateral triceps. This can be explained by both the change in required muscle-generated torques and a conscious change in approach by the participants. These observations have implications for neurorehabilitation, particularly with respect to the muscle activation patterns which are trained through rehabilitation exercises.
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ItemOptimization Methods on Riemannian Manifolds via Extremum Seeking Algorithms(Society for Industrial and Applied Mathematics, 2018)This paper formulates the problem of extremum seeking for optimization of cost function defined on Riemannian manifolds. We extend the conventional extremum seeking algorithms for optimization problems in Euclidean spaces to optimization of cost functions defined on smooth Riemannian manifolds. This problem falls within the category of online optimization methods. We introduce the notion of geodesic dithers, which is a perturbation of the optimizing trajectory in the tangent bundle of the ambient state manifolds, and obtain the extremum seeking closed loop as a perturbation of the averaged gradient system. The main results are obtained by applying closeness of solutions and averaging theory on Riemannian manifolds. The main results are further extended for optimization on Lie groups. Numerical examples on the Stiefel manifold V3;2 and the Lie group SEp3q are presented at the end of the paper.
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ItemAntiproliferative activities of the second- generation antipsychotic drug sertindole against breast cancers with a potential application for treatment of breast-to-brain metastases(NATURE PORTFOLIO, 2018-10-25)Epidemiological observations have shown that schizophrenia patients after long-term drug treatment exhibited reduced tumor incidences. The potential anticancer effects of antipsychotic drugs are subsequently demonstrated. These drugs are of great interest as agents against untreatable brain metastases because of their ability to traverse the blood-brain barrier (BBB). Most drugs tested thus far are the first-generation antipsychotics (FGAs). But their clinical application may be limited due to high risks of deaths in elderly patients. There is an urgent need to find additional BBB-traversing anticancer agents with lower risks of deaths. In this work, we investigated antitumor activities of eight second-generation-antipsychotic (SGA) drugs, since they exhibit lower mortality rates than FGAs. We discovered that sertindole showed broad antiproliferative activities against seven cancer types including 29 cell-lines and exhibited potent effects toward breast cancer cell-lines, with half maximal concentration to inhibit proliferation by 50% (IC50) as low as 800 nM. We further found that sertindole caused cell death through autophagy-associated apoptosis and its directly-binding inhibition of 5-HT6 involved in this process. In xenotransplant mice, sertindole administration approaching maximal therapeutic dose attenuated breast-tumor growth by 22.7%. Therefore, our study reveals promising anticancer potentials of sertindole against breast cancers, with probable applications for breast-to-brain metastases.
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ItemA New Strategy Involving the Use of Peptides and Graphene Oxide for Fluorescence Turn-on Detection of Proteins(MDPI, 2018-02)The detection of proteins is of great biological significance as disease biomarkers in early diagnosis, prognosis tracking and therapeutic evaluation. Thus, we developed a simple, sensitive and universal protein-sensing platform based on peptide and graphene oxide (GO). The design consists of a fluorophore (TAMRA, TAM), a peptide containing eight arginines and peptide ligand that could recognize the target protein, and GO used as a quencher. To demonstrate the feasible use of the sensor for target detection, Bcl-xL was evaluated as the model target. The sensor was proved to be sensitive and applied for the detection of the target proteins in buffer, 2% serum and living cells.
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ItemNPASS: natural product activity and species source database for natural product research, discovery and tool development(OXFORD UNIV PRESS, 2018-01-04)There has been renewed interests in the exploration of natural products (NPs) for drug discovery, and continuous investigations of the therapeutic claims and mechanisms of traditional and herbal medicines. In-silico methods have been employed for facilitating these studies. These studies and the optimization of in-silico algorithms for NP applications can be facilitated by the quantitative activity and species source data of the NPs. A number of databases collectively provide the structural and other information of ∼470 000 NPs, including qualitative activity information for many NPs, but only ∼4000 NPs are with the experimental activity values. There is a need for the activity and species source data of more NPs. We therefore developed a new database, NPASS (Natural Product Activity and Species Source) to complement other databases by providing the experimental activity values and species sources of 35 032 NPs from 25 041 species targeting 5863 targets (2946 proteins, 1352 microbial species and 1227 cell-lines). NPASS contains 446 552 quantitative activity records (e.g. IC50, Ki, EC50, GI50 or MIC mainly in units of nM) of 222 092 NP-target pairs and 288 002 NP-species pairs. NPASS, http://bidd2.nus.edu.sg/NPASS/, is freely accessible with its contents searchable by keywords, physicochemical property range, structural similarity, species and target search facilities.