Serial manipulator functional calibration for in vitro biomechanical testing

Serial manipulators are often used in biomechanical testing of human joints because they are precise, repeatable instruments that can create interesting loading scenarios. Unfortunately, commercial serial manipulators often do not have acceptable global positional accuracy due to manufacturing tolerances, assembly errors, and other mechanical imperfections. Numerous calibration methods have been reported which calibrate geometric and non-geometric parameters to reduce static position errors under constant loading conditions. However, the manipulator's global accuracy during continuous motion with time-varying external loading conditions is often not addressed but is necessary for joint biomechanical testing. Using the Mitsubishi PA10-6CE as a case study, a novel functional calibration procedure was developed that performs both static and dynamic calibration. The calibration uses optimization techniques to populate a 34-parameter model that accounts for the robot's geometric and non-geometric parameters and significantly reduces the mean/peak static and dynamic position errors to 0.368/0.67 mm and 0.353/0.81 mm, respectively, while externally loaded.     

Optimization of lipase-catalyzed synthesis of acetylated EGCG by response surface methodology

(−)-Epigallocatechin-3-O-gallate (EGCG) acetylated derivatives, which can be widely used as a natural antioxidant in both lipid containing food and cosmetic applications, were prepared by lipase catalyzed acylation of EGCG with vinyl acetate. Response surface methodology (RSM) and 5-level-4-factor central composite rotatable design (CCRD) were employed to evaluate the effects of synthesis parameters, such as reaction time (6–10 h), temperature (30–50 °C), enzyme amount (1.5–2.5% (w/w) of substrate), and substrate molar ratio of EGCG to vinyl acetate (0.5–1.5) on conversion of EGCG. By using multiple regression analysis, the experimental data were fitted to a second order polynomial model. The most suitable combination of variables was 40 °C, 2.12%, 10 h and 1.13 for the reaction temperature, the enzyme amount, the reaction time, and EGCG/vinyl acetate mole ratio, respectively. At these optimal conditions, the conversion yield reached 87.37%. The presence of mono-, di- and tri-acetylated derivatives in acetylated EGCG was confirmed by LC–MS-MS and identified as 5″-O-acetyl-EGCG, 3″, 5″-2-O-acetyl-EGCG and 5′, 3″, 5″-3-O-acetyl-EGCG by NMR.     

Exploring novel objective functions for simulating muscle coactivation in the neck

Musculoskeletal modeling allows for analysis of individual muscles in various situations. However, current techniques to realistically simulate muscle response when significant amounts of intentional coactivation is required are inadequate. This would include stiffening the neck or spine through muscle coactivation in preparation for perturbations or impacts. Muscle coactivation has been modeled previously in the neck and spine using optimization techniques that seek to maximize the joint stiffness by maximizing total muscle activation or muscle force. These approaches have not sought to replicate human response, but rather to explore the possible effects of active muscle. Coactivation remains a challenging feature to include in musculoskeletal models, and may be improved by extracting optimization objective functions from experimental data. However, the components of such an objective function must be known before fitting to experimental data. This study explores the effect of components in several objective functions, in order to recommend components to be used for fitting to experimental data. Four novel approaches to modeling coactivation through optimization techniques are presented, two of which produce greater levels of stiffness than previous techniques. Simulations were performed using OpenSim and MATLAB cooperatively. Results show that maximizing the moment generated by a particular muscle appears analogous to maximizing joint stiffness. The approach of optimizing for maximum moment generated by individual muscles may be a good candidate for developing objective functions that accurately simulate muscle coactivation in complex joints. This new approach will be the focus of future studies with human subjects.     

A short synthesis of Dronedarone

A modification of the Nenitzescu reaction was used to obtain Dronedarone from quinonimine 20 and 1,3-diketone 14 (R?=?CH₂CH₂CH₂NBu₂) in a two-stage process in almost 55% overall yield. Our results represent significant improvement over other state-of-the-art methods as no extra steps for the decoration of the benzofuran core are required.     

Application of a Life Cycle Model for European Union Policy‐Driven Waste Management Decision Making in Emerging Economies

Solid waste life cycle modeling has predominantly focused on developed countries, but there are significant opportunities to assist developing and transition economies to minimize the environmental impact of solid waste management (SWM). Serbia is representative of a transition country and most (92%) of its waste is landfilled. As a Candidate European Union (EU) country, Serbia is expected to implement SWM strategies that meet EU directives. The Solid Waste Life‐Cycle Optimization Framework (SWOLF) was used to evaluate scenarios that meet EU goals by 2030. Scenarios included combinations of landfills, anaerobic digestion, composting, material recovery facilities (MRFs), waste‐to‐energy (WTE) combustion, and the use of refuse‐derived fuel in cement kilns. Each scenario was evaluated with and without separate collection of recyclables. Modeled impacts included cost, climate change, cumulative fossil energy demand, acidification, eutrophication, photochemical oxidation, total eco‐toxicity, and total human toxicity. Trade‐offs among the scenarios were evaluated because no scenario performed best in every category. In general, SWM strategies that incorporated processes that recover energy and recyclable materials performed well across categories, whereas scenarios that did not include energy recovery performed poorly. Emissions offsets attributable to energy recovery and reduced energy requirements associated with remanufacturing of recovered recyclables had the strongest influence on the results. The scenarios rankings were robust under parametric sensitivity analysis, except when the marginal electricity fuel source changed from coal to natural gas. Model results showed that the use of existing infrastructure, energy recovery, and efficient recovery of recyclables from mixed waste can reduce environmental emissions at relatively low cost.     

南极交替单胞菌R11-5产卡拉胶酶的发酵条件优化

【背景】极地寒冷环境中发现了大量具有潜在应用前景的冷适应酶,同时也存在种类繁多的海藻多糖降解菌,因此极端环境微生物是筛选获得新颖、高效多糖降解酶的重要新源泉。由于筛选培养基通常并非野生菌发酵产酶的最优条件,为了使野生菌的产酶效率达到最高,需要对其培养条件进行优化,从而为其深入研究及开发利用提供依据。【目的】对一株产卡拉胶酶的南极菌株进行种属鉴定,并采用响应面法对该菌的发酵产酶条件进行优化。【方法】通过16SrRNA基因对产卡拉胶酶的南极菌株进行种属鉴定,采用响应面法优化南极菌株产酶发酵条件。【结果】该南极菌属于交替单胞菌属(Alteromonas),命名为交替单胞菌R11-5。发酵条件优化结果显示,7个环境因子影响交替单胞菌R11-5的产酶量。利用Design-Expert软件中的Plackett-Burman设计实验,筛选出影响交替单胞菌R11-5产酶量的4个主要因素分别为培养温度、牛肉膏浓度、卡拉胶浓度和Ca~(2+)浓度。通过Box-Behnken设计和响应面分析得到交替单胞菌R11-5最佳产酶发酵条件为:温度15.0°C,牛肉膏浓度11.0 g/L,卡拉胶浓度3.0 g/L,Ca~(2+)浓度5.0 mmol/L。优化后发酵上清液酶产量达到87.193 U/mL,与优化前相比提高了1.8倍。【结论】响应面法提高了南极交替单胞菌R11-5卡拉胶酶的产量,为其开发应用提供了科学依据。     

Indole acids as a novel PDE2 inhibitor chemotype that demonstrate pro-cognitive activity in multiple species

An internal HTS effort identified a novel PDE2 inhibitor series that was subsequently optimized for improved PDE2 activity and off-target selectivity. The optimized lead, compound 4, improved cognitive performance in a rodent novel object recognition task as well as a non-human primate object retrieval task. In addition, co-crystallization studies of close analog of 4 in the PDE2 active site revealed unique binding interactions influencing the high PDE isoform selectivity.     

表达β-珠蛋白基因的安全性慢病毒载体的优化

目的:慢病毒载体(lentiviral vector,LVV)是一种有效的基因治疗导入系统。拟用已研发的携带人的β-珠蛋白基因自删除慢病毒载体,优化其表达有效性和提高其病毒颗粒数。方法:比较三款不同的启动子预测软件的分析结果,分别构建三种不同长度启动子的表达β-珠蛋白基因(β-globin)的LVV,并对其Ⅱ号内含子进行部分删减;用经优化的LVV转导β-地中海贫血(β-地贫)的小鼠诱导性多能性干细胞(induced pluripotent stem cells,iPSC)后,用此iPSC制备嵌合体小鼠模型;经RT-PCR、血涂片瑞氏吉姆萨染色等观察分析其功能性代偿的潜能。研究结果:经优化后的自删除慢病毒载体病毒对其病毒颗粒数的滴度影响不大(2.3×10~(11)LPs/ml),可在嵌合体小鼠模型体内检测到正常人β-珠蛋白基因的功能性表达。结论:优化了表达人β-珠蛋白基因的自删除LVV。     

AFP蛋白芯片技术的检测流程优化

目的:通过优化现有的蛋白芯片检测过程,在保证检测准确性的同时缩短甲胎蛋白(Alpha Fetal protein,AFP)的检测时间,提高检测效率,为原发性肝癌的筛查提供经济、便捷、省时、有效的检测方法。方法:本研究在传统蛋白芯片检测流程(1-1.5小时)的基础上,通过优化检测流程将检测时间缩短至18分钟,并且通过和传统方法进行比较,评价该优化方法的检测效能。结果:与传统蛋白芯片检测方法相比,本优化方法的检测时间缩短至18分钟。重复检测同一样本,传统方法 AFP水平为16.50±1.172ng/m L,优化方法 AFP水平为18.33±1.029 ng/m L,结果无明显统计学差异(P=0.251)。结论:本研究成功地优化了AFP的蛋白芯片检测流程,在缩短检测时间的同时,保证了检测的准确率,是一种经济省时易操作的AFP检测方法。