Energy-efficient full-range oscillation analysis of parallel-plate electrostatically actuated MEMS resonators

This is the peer reviewed version of the following article: “Fargas Marques, A., Costa Castelló, R. (2017) Energy-efficient full-range oscillation analysis of parallel-plate electrostatically actuated MEMS resonators, 1-13.” which has been published in final form at [doi: 10.1007/s11071-017-3633-8]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Electrostatic parallel-plate actuators are a common way of actuating microelectromechanical systems, both statically and dynamically. Nevertheless, actuation voltages and oscillations are limited by the nonlinearity of the actuator that leads to the pull-in phenomena. This work presents a new approach to obtain the electrostatic parallel-plate actuation voltage, which allows to freely select the desired frequency and amplitude of oscillation. Harmonic Balance analysis is used to determine the needed actuation voltage and to choose the most energy-efficient actuation frequency. Moreover, a new two-sided actuation approach is presented that allows to actuate the device in all the stable range using the Harmonic Balance Voltage.Peer ReviewedPostprint (author's final draft

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

A biological survey of ballast water in container ships entering Hong Kong

The role of ballast water in the introduction of exotic species has recently received extensive attention. The aim of this study is to assess the importance of ballast water discharge as a vector for the introduction of exotic species into Hong Kong waters. Twelve ballast water samples were collected from 5 container ships entering Hong Kong between June 1994 and October 1995. The ballast water originated from ports on both sides of the Pacific Ocean. At least 81 species from 8 animal phyla and 5 protist phyla were found. Most of the major marine taxonomic groups were represented and many planktonic larval stages were included. Species richness in the ballast tanks decreased with the age of ballast water. Copepoda was the most diverse and abundant taxonomic group. The density of calanoid and cyclopoid copepods decreased with the age of ballast water, but that of harpacticoid copepods did not change significantly with time. Bivalve, crustacean, polychaete and ascidian larvae from ballast water samples were observed to settle in laboratory culture tanks. The mussel Mytilopsis sallei which was introduced to I-long Kong in 1980, was one of the bivalves that settled readily. Results of this study indicate that ballast water can be a major source for the introduction of exotic species to Hong Kong waters. Regulatory guidelines on the discharge of ballast water should be established

Multiple diabetic complications, as well as impaired physical and mental function, are associated with declining balance function in older persons with diabetes mellitus

Xiufang Hong,1,2 Xujiao Chen,2 Jiaojiao Chu,2 Shanshan Shen,2 Qichen Chai,2 Gaobo Lou,2 Lingyan Chen2 1Zhejiang Chinese Medical University, 2Department of Geriatrics, Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China Objective: To investigate whether there is a difference in balance function between older persons with and without diabetes mellitus (DM), and to identify whether mediating factors, such as diabetic complications, Instrumental Activities of Daily Living (IADL) score, Mini-Mental State Examination (MMSE) score, as well as hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), are associated with balance function in older persons with DM.Methods: In this cross-sectional study, a total of 208 older persons were divided into a DM group (n=80) and a control group who did not have DM (n=128). Balance function was evaluated with the Tinetti performance-oriented mobility assessment (POMA), which includes balance and gait subscales. Activities of daily living (ADL), IADL, and the MMSE were also measured. Fall incidents in last 12 months, the use of walking aids, fear of falling, comorbidities, and polypharmacy were recorded. Diabetic complications were recorded, and HbA1c, FPG, TC, TG, and LDL were measured in the patients of the DM group.Results: Fall incidents in last 12 months were higher in the DM group than in the control group (P<0.01). POMA score as well as ADL and IADL scores were lower in the diabetic group than the control group (P<0.05). Within the diabetic group, the POMA score was positively related to the ADL score (odds ratio [OR], 11.7; 95% confidence interval [CI], 3.076–44.497; P<0.01), IADL score (OR, 16.286; 95% CI, 4.793–55.333; P<0.01), and MMSE score (OR, 10.524; 95% CI, 2.764–40.074; P<0.01), but was negatively related to age (OR, 7.707; 95% CI, 2.035–29.185; P<0.01) and diabetic complication (OR, 6.667; 95% CI, 2.279–19.504; P<0.01). Also, within the DM group, the decreased POMA score was associated with multiple diabetic complications (OR, 5.977; 95% CI, 1.378–25.926; P<0.05), decreased IADL score (OR, 10.288; 95% CI, 2.410–43.915; P<0.01), and MMSE score (OR, 13.757; 95% CI, 2.556–74.048; P<0.01).Conclusion: Multiple diabetic complications, lower MMSE, ADL, and IADL scores were associated with declining balance function in the older persons with DM. These findings can alert physicians to detect and intervene earlier on declining balance in older persons with DM. Keywords: diabetes mellitus, balance, POMA, fall, elderly, performance-oriented mobility assessmen

Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

Qiuchen Chu,1,* Hong Xu,2,* Meng Gao,1 Xin Guan,1 Hongyan Liu,1 Sa Deng,1 Xiaokui Huo,1 Kexin Liu,1 Yan Tian,1 Xiaochi Ma1 1College of Pharmacy, 2College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and decreased toxicity for the loaded drug RBG, is therefore a promising intravenous dosage form that may be useful in the treatment of liver cancer. Keywords: Resibufogenin, PLGA-TPGS, nanoparticles, liver cancer, HepG2 cells, HCa-F cell