Tuning Plasmid Payload of DNA/polycation Nanoparticles and Validation of a Confined Impinging Jet Mixer for Flash Nanocomplexation Method

The pDNA/lPEI nanoparticles represent a major non-viral delivery vehicle for gene therapy. There have been poor understandings of property-function relationships for these nanoparticles to demonstrate how the vesicle characteristics would influence the in vitro gene delivery efficacy. In this thesis, a flash nanocomplexation (FNC) process is adopted to formulate nanoparticles to achieve well-defined nanoparticle size, composition, and surface characteristics. More importantly, the average plasmid payload in terms of the pDNA copy number per nanoparticle can be controlled within a range of 1.7 to 21.8 as characterized by the static light scattering technique. These formulations enabled the investigation of the effect of plasmid payload in the nanoparticles on their in vitro transfection efficiency, showing that average plasmid payload of 5–6 is required to achieve high level of transgene expression. In an effect to investigate the chamber volume of the confined impinging jet (CIJ) mixer device on nanoparticle production, a scale-down version of the device was designed to allow smaller dead volume. Its performance in nanoparticle production of pDNA/lPEI nanoparticles was validated by comparing with a standard device used in the field. The characteristics of the nanoparticles produced by this new device including the lyophilized nanoparticle formulation and its long-term stability (>9 months) was fully demonstrated. This study offers new insights into the FNC process for assembly of polyelectrolyte nanoparticles and extends its capability as a well-controlled nanoparticle production method

A Bee Evolutionary Algorithm for Multiobjective Vehicle Routing Problem with Simultaneous Pickup and Delivery

A new closed-loop supply chain logistics network of vehicle routing problem with simultaneous pickups and deliveries (VRPSPD) dominated by remanufacturer is constructed, in which the customers are originally divided into three types: distributors, recyclers, and suppliers. Furthermore, the fuel consumption is originally added to the optimization objectives of the proposed VRPSPD. In addition, a bee evolutionary algorithm guiding nondominated sorting genetic algorithm II (BEG-NSGA-II) with a two-stage optimization mechanism is originally designed to solve the proposed VRPSPD model with three optimization objectives: minimum fuel consumption, minimum waiting time, and the shortest delivery distance. The proposed BEG-NSGA-II could conquer the disadvantages of traditional nondominated sorting genetic algorithm II (NSGA-II) and algorithms with a two-stage optimization mechanism. Finally, the validity and feasibility of the proposed model and algorithm are verified by simulating an engineering machinery remanufacturing company’s reverse logistics and another three test examples

Comparison of the Long-Term Outcomes of Endoscopic Papillary Large Balloon Dilation Alone versus Endoscopic Sphincterotomy for Removal of Bile Duct Stones

Background and Aims. Endoscopic papillary large balloon dilation (EPLBD) alone is an alternative to endoscopic sphincterotomy (EST) for treatment of common bile duct (CBD) stones. However, limited data exists regarding comparison of the long-term outcomes for these techniques. In this study, we compared the long-term outcomes after EST with those after EPLBD alone for removal of CBD stones. Methods. The records of patients with EST or EPLBD alone referred for CBD stones retrieval between June 2008 and July 2015 were retrospectively reviewed. Complete stone clearance, ERCP-related adverse events, and late biliary complications during long-term follow-up were analyzed. Results. Basic patient characteristics were similar between the groups that underwent EST (n=60) and EPLBD alone (n=161). EPLBD compared with EST resulted in similar outcomes in terms of complete stone clearance (99.4% versus 100%, P=0.54) and ERCP-related adverse events (6.8% versus 6.7%, P=1.00). The mean duration of the follow-up was 74.5 months and 71.6 months who underwent EST and EPLBD alone, respectively (P=0.42). Late biliary complications were occurred frequently in the EST group than in the EPLBD alone group (11 [18.6%] versus 16 [10.2%]), although the difference did not reach statistical significance (P=0.11). Multivariate analysis showed that mechanical lithotripsy ([OR], 2.815; 95% CI, 1.148–6.902; P=0.024) was significantly associated with late biliary complications. Conclusion. As an alternative to EST, EPLBD has similar efficacy and safety for managing CBD stones. During long-term follow-up, patients who underwent EPLBD alone may have fewer late biliary complications compared with those after EST. In addition, mechanical lithotripsy may be an independent risk factor for late biliary complications

A Bee Evolutionary Guiding Nondominated Sorting Genetic Algorithm II for Multiobjective Flexible Job-Shop Scheduling

Flexible job-shop scheduling problem (FJSP) is an NP-hard puzzle which inherits the job-shop scheduling problem (JSP) characteristics. This paper presents a bee evolutionary guiding nondominated sorting genetic algorithm II (BEG-NSGA-II) for multiobjective FJSP (MO-FJSP) with the objectives to minimize the maximal completion time, the workload of the most loaded machine, and the total workload of all machines. It adopts a two-stage optimization mechanism during the optimizing process. In the first stage, the NSGA-II algorithm with T iteration times is first used to obtain the initial population N, in which a bee evolutionary guiding scheme is presented to exploit the solution space extensively. In the second stage, the NSGA-II algorithm with GEN iteration times is used again to obtain the Pareto-optimal solutions. In order to enhance the searching ability and avoid the premature convergence, an updating mechanism is employed in this stage. More specifically, its population consists of three parts, and each of them changes with the iteration times. What is more, numerical simulations are carried out which are based on some published benchmark instances. Finally, the effectiveness of the proposed BEG-NSGA-II algorithm is shown by comparing the experimental results and the results of some well-known algorithms already existed

Data Augmentation for Electricity Theft Detection Using Conditional Variational Auto-Encoder

Due to the strong concealment of electricity theft and the limitation of inspection resources, the number of power theft samples mastered by the power department is insufficient, which limits the accuracy of power theft detection. Therefore, a data augmentation method for electricity theft detection based on the conditional variational auto-encoder (CVAE) is proposed. Firstly, the stealing power curves are mapped into low dimensional latent variables by using the encoder composed of convolutional layers, and the new stealing power curves are reconstructed by the decoder composed of deconvolutional layers. Then, five typical attack models are proposed, and the convolutional neural network is constructed as a classifier according to the data characteristics of stealing power curves. Finally, the effectiveness and adaptability of the proposed method is verified by a smart meters’ data set from London. The simulation results show that the CVAE can take into account the shapes and distribution characteristics of samples at the same time, and the generated stealing power curves have the best effect on the performance improvement of the classifier than the traditional augmentation methods such as the random oversampling method, synthetic minority over-sampling technique, and conditional generative adversarial network. Moreover, it is suitable for different classifiers

Energy-efficient flexible flow shop scheduling with worker flexibility

The classical flexible flow shop scheduling problem (FFSP) only considers machine flexibility. Thus far, the relevant literature has not studied FFSPs with worker flexibility, which is widely seen in practical manufacturing systems. Worker flexibility may greatly affect production efficiency and productivity. Furthermore, with the increase of environmental pollution and energy consumption, manufacturers require innovative methods to improve energy efficiency. In this paper, we propose an energy-efficient FFSP with worker flexibility (EFFSPW), in which the flexibility of machines and workers as well as the processing time, energy consumption and worker cost related factors are considered simultaneously. A hybrid evolutionary algorithm (HEA) is then presented to solve the proposed EFFSPW, where some effective operators and a new variable neighborhood search approach are designed. Comprehensive experiments including 54 benchmark instances of the EFFSPW are carried out, and Taguchi analysis is used to determine the best combination of key parameters for the HEA. Experimental results show that the proposed HEA can obtain better solutions for most of these benchmark instances compared to two other well-known algorithms, demonstrating its superior performance in terms of both solution quality and computational efficiency

Effects of Aging Treatments on the Age Hardening Behavior and Microstructures in an Al-Mg-Si-Cu Alloy

In this study, we investigated the effects of modified aging treatments on the microstructures and hardness in a commercial 6016 Al alloy through hardness tests and transmission electron microscopy (TEM) observations. The results demonstrate that many fine needle-like β″ phases contribute to the high hardness of peak-aged (T6) alloys. Over-aging treatments lead to the precipitation of lath-like β′, β″/disordered, or B′/disordered composite phases. Moderate over-aging treatment results in the coarsening of grain boundary precipitates (GBPs) and widening of the precipitate-free zone (PFZ), while heavy over-aging treatment triggers the re-precipitation of Cu-containing GBPs and increases the number density of GBPs. A retrogression and re-aging (RRA) treatment precipitates β″, lath-like β′, and disordered phases, while a two-step aging (T78) treatment precipitates β″, B′, and disordered phases. Both the T78 and the RRA treatments lead to the coarsening of GBPs and the widening of PFZs. The decreased hardness during over-aging treatments is attributed to a combination of coarsening intragranular precipitates and/or wider PFZs. The T78 and RRA tempers achieve 95.5% and 94% of the hardness values of the T6 treatment, respectively. The hardness values of the RRA and T78 treated alloys are related to the finer nano-sized precipitates formed during the high temperature process. These precipitates can compensate for the loss of hardness caused by the increase in the widths of the PFZs and the coarsening of the matrix precipitates. The relationship between the hardness and microstructures such as PFZs and precipitates in the matrix during various heat treatments is elucidated

Recent advances in the effect of ultrasound on the binding of protein−polyphenol complexes in foodstuff

Abstract Foodstuff is a complex system that consists of a variety of nutrients. Protein is the basis of human life and health, which is made up of amino acids combined in different proportional orders. Polyphenols are a class of small molecule active substances with strong pro‐life health effects. It has been found that protein and polyphenols can be combined by covalent and non‐covalent interactions to form complex delivery carriers. The interaction between the two can effectively improve the physiological activities of proteins and enhance the bio‐accessibility of polyphenols. With the maturation of ultrasound technology, several studies have shown that ultrasound can promote the production of protein−polyphenol complexes. To promote the study of protein–polyphenol interactions in foodstuff by ultrasound technology, the preparation methods of protein−polyphenol complexes, the effects of ultrasound on complex generation, and analytical methods were systematically summarized based on an extensive literature review, and further research directions were proposed. It provides the reference for the ultrasound study of protein−polyphenol complexes