EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is overexpressed in solid tumors and regarded as a putative cancer stem cell marker. Here, we report that employing EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) dual approach, for the targeted delivery of siRNA to EpCAM positive cancer cells, efficiently inhibits cancer cell proliferation. RESULTS: Targeted delivery of siRNA using polyethyleneimine is one of the efficient methods for gene delivery, and thus, we developed a novel aptamer-PEI-siRNA nanocomplex for EpCAM targeting. PEI nanocomplex synthesized with EpCAM aptamer (EpApt) and EpCAM siRNA (SiEp) showed 198 nm diameter sized particles by dynamic light scattering, spherical shaped particles, of 151 ± 11 nm size by TEM. The surface charge of the nanoparticles was -30.0 mV using zeta potential measurements. Gel retardation assay confirmed the PEI-EpApt-SiEp nanoparticles formation. The difference in size observed by DLS and TEM could be due to coating of aptamer and siRNA on PEI nanocore. Flow cytometry analysis revealed that PEI-EpApt-SiEp has superior binding to cancer cells compared to EpApt or scramble aptamer (ScrApt) or PEI-ScrApt-SiEp. PEI-EpApt-SiEp downregulated EpCAM and inhibited selectively the cell proliferation of MCF-7 and WERI-Rb1 cells. CONCLUSIONS: The PEI nanocomplex fabricated with EpApt and siEp was able to target EpCAM tumor cells, deliver the siRNA and silence the target gene. This nanocomplex exhibited decreased cell proliferation than the scrambled aptamer loaded nanocomplex in the EpCAM expressing cancer cells and may have potential for EpCAM targeting in vivo.

Characterization of the extracellular polymeric substances and microbial community of aerobic granulation sludge exposed to cefalexin

This study characterizes the extracellular polymeric substances and bacterial community composition of aerobic granules exposed to cefalexin (CLX). The presence of CLX potentially decreases granular stabilities, resulting in a lowered granule diameter. Chemical oxygen demand and NH4+-N removal efficiencies were slightly decreased and the denitrification process was inhibited with CLX addition. Extracellular polymeric substance contents were significantly increased in aerobic granules exposed to CLX. The shifts of fluorescence intensities and peak locations in 3D-EEM fluorescence spectra indicated changes of EPS components. High-throughput sequencing analysis showed aerobic granules with CLX addition in synthetic wastewater had superior diversity of microbial species, and this was the reason that the level and components of EPS changed. The species richness for bacteria was increased from 341 to 352, which was revealed by Chao1. The Shannon index of diversity rose slightly from 3.59 to 3.73 with CLX addition. The abundance of Proteobacteria significantly decreased, while the abundance of Bacteroidetes and Chloroflexi underwent a highly significant increase in aerobic granules exposed to CLX.

Reinforcement and deformation behaviors of polyvinyl alcohol/graphene/montmorillonite clay composites

We report the synergistic reinforcement and deformation of polyvinyl alcohol (PVA)/graphene/montmorillonite clay (MMT) composites with the tensile properties being improved greatly. Particularly, the tensile strength and modulus of PVA composite with 0.9 wt% graphene and 0.3 wt% of MMT were improved by more than 58% and 43% when compared to the neat PVA, respectively, and were at least 10% higher than the enhanced sum of dual PVA composites with 0.9 wt% graphene and 0.3 wt% MMT. This reinforcement was resulted from the good dispersion and effective interfacial interactions as confirmed from morphology investigation, increased glass transition temperature and the shift of O-H stretching. When there were no fillers i.e. in situ reduced graphene (IRG) or MMT or their loading was low, high alignment of PVA could be observed, with increased crystallinity, melting point, lamellae thickness but narrowed crystallite size distribution. The synergistic reinforcement of PVA achieved from combined incorporation of IRG and MMT will pave the way for the development of stronger PVA composites in various applications.

Popularity of reinforcement-based and belief-based learning models: an evolutionary approach

In an evolutionary model, players from a given population meet randomly in pairs each instant to play a coordination game. At each instant, the learning model used is determined via some replicator dynamics that respects payoff fitness. We allow for two such models: a belief-based best-response model that uses a costly predictor, and a costless reinforcement-based one. This generates dynamics over the choice of learning models and the consequent choices of endogenous variables. We report conditions under which the long run outcomes are efficient (or inefficient) and they support the exclusive use of either of the models (or their co-existence).

Development of a novel soft parallel robot equipped with polymeric artificial muscles

This paper presents the design, analysis and fabrication of a novel low-cost soft parallel robot for biomedical applications, including bio-micromanipulation devices. The robot consists of two active flexible polymer actuator-based links, which are connected to two rigid links by means of flexible joints. A mathematical model is established between the input voltage to the polymer actuators and the robot's end effector position. The robot has two degrees-of-freedom, making it suitable for handling planar micromanipulation tasks. Moreover, a number of robots can be configured to operate in a cooperative manner for increasing micromanipulation dexterity. Finally, the experimental results demonstrate two main motion modes of the robot.

An integration of attachment theory and reinforcement sensitivity theory as a conceptual framework for understanding trauma

 The research examined the associations between Reinforcement Sensitivity Theory, Attachment Theory, and trauma symptoms among victims of interpersonal violence. Findings demonstrated a link between attachment, threat sensitivity, and trauma symptoms, indicating that RST and Attachment Theory provides a useful theoretical framework to understand how interpersonal violence contributes to psychological trauma.

Fabrication of polymeric microchannels with focused and defocused CO2 lasers

 The control of energy distribution or energy intensity inside a laser spot using a defocusing method enables the formation of high-quality microchannels of multiple cross-sections in polycarbonate. Moreover, a thermal mathematical model of the process was developed to aid understanding of the process and to allow channel topology prediction.

Parametric investigation of batch adsorption of proteins onto polymeric particles

Background: Effective bimolecular adsorption of proteins onto solid matrices is characterized by in-depth understanding of the biophysical features essential to optimize the adsorption performance. Results: The adsorption of bovine serum albumin (BSA) onto anion-exchange Q-sepharose solid particulate support was investigated in batch adsorption experiments. Adsorption kinetics and isotherms were developed as a function of key industrially relevant parameters such as polymer loading, stirring speed, buffer pH, protein concentration and the state of protein dispersion (solid/aqueous) in order to optimize binding performance and adsorption capacity. Experimental results showed that the first order rate constant is higher at higher stirring speed, higher polymer loading, and under alkaline conditions, with a corresponding increase in equilibrium adsorption capacity. Increasing the stirring speed and using aqueous dispersion protein system increased the adsorption rate, but the maximum protein adsorption was unaffected. Regardless of the stirring speed, the adsorption capacity of the polymer was 2.8 mg/ml. However, doubling the polymer loading increased the adsorption capacity to 9.4 mg/ml. Conclusions: The result demonstrates that there exists a minimum amount of polymer loading required to achieve maximum protein adsorption capacity under specific process conditions.

Knitted strain sensor textiles of highly conductive all-polymeric fibers

A scaled-up fiber wet-spinning production of electrically conductive and highly stretchable PU/PEDOT:PSS fibers is demonstrated for the first time. The PU/PEDOT:PSS fibers possess the mechanical properties appropriate for knitting various textile structures. The knitted textiles exhibit strain sensing properties that were dependent upon the number of PU/PEDOT:PSS fibers used in knitting. The knitted textiles show sensitivity (as measured by the gauge factor) that increases with the number of PU/PEDOT:PSS fibers deployed. A highly stable sensor response was observed when four PU/PEDOT:PSS fibers were co-knitted with a commercial Spandex yarn. The knitted textile sensor can distinguish different magnitudes of applied strain with cyclically repeatable sensor responses at applied strains of up to 160%. When used in conjunction with a commercial wireless transmitter, the knitted textile responded well to the magnitude of bending deformations, demonstrating potential for remote strain sensing applications. The feasibility of an all-polymeric knitted textile wearable strain sensor was demonstrated in a knee sleeve prototype with application in personal training and rehabilitation following injury.

A new reinforcement learning-based memetic particle swarm optimizer

Developing an effective memetic algorithm that integrates the Particle Swarm Optimization (PSO) algorithm and a local search method is a difficult task. The challenging issues include when the local search method should be called, the frequency of calling the local search method, as well as which particle should undergo the local search operations. Motivated by this challenge, we introduce a new Reinforcement Learning-based Memetic Particle Swarm Optimization (RLMPSO) model. Each particle is subject to five operations under the control of the Reinforcement Learning (RL) algorithm, i.e. exploration, convergence, high-jump, low-jump, and fine-tuning. These operations are executed by the particle according to the action generated by the RL algorithm. The proposed RLMPSO model is evaluated using four uni-modal and multi-modal benchmark problems, six composite benchmark problems, five shifted and rotated benchmark problems, as well as two benchmark application problems. The experimental results show that RLMPSO is useful, and it outperforms a number of state-of-the-art PSO-based algorithms.

Preformed and sprayable polymeric mulch film to improve agricultural water use efficiency

Plastic mulch films are widely used in agriculture to enhance crop production by suppressing weeds, conserving soil water and increasing soil temperature. The majority of plastic mulch films are however not biodegradable and are typically removed after each growing season. Recovery of these plastics from the soil is difficult and can affect successive crop yields while causing substantive cost to the environment and farmers. Due to increasingly stringent regulations regarding use of non-degradable plastic in agriculture they are likely to be phased out in the near future. In the past 10 years several classes of 'biodegradable' materials have been studied but most of these films are reported to be relatively weak in mechanical properties, not efficiently degradable and cost prohibitive.More recently, researchers have turned their attention to sprayable biodegradable polymer coatings for use on soils due to their easy application and versatility. The ability to mix natural additives, plasticizers and fillers to control and improve the mechanical and biodegradation properties of the core polymeric mulch film has been the driving force behind the development of these next generation sprayable polymeric mulch films.There have been many excellent review articles and papers written about polymeric mulch film, but the developing sprayable polymer systems have not been reviewed to the same extent. This paper focusses on the research progress in the area of biodegradable and sprayable polymer mulch film with emphasis on polymer formulations, properties and application. It also discusses current research to highlight the importance, potential benefits and future challenges in developing a cost effective biodegradable sprayable film for use in production agriculture.

Development of nanostructured polymeric materials using polymerizable lyotropic liquid crystals.

This thesis was focused on the development of nanostructured polymers for CO2 capture and energy storage applications, using polymerizable lyotropic liquid crystal. A combination of polarized optical microscopy, differential scanning calorimetry and Small-angle x-ray scattering has been used to characterize and understand the structure retention of these systems during photo-polymerization.

Control-oriented modeling of a polymeric soft robot

This article describes an efficient control-oriented model of a soft robot made of electroactive polymers. The proposed soft robot is constructed from two flexible links and has a multiphysics dynamic model consisting of both an electrochemical and electromechanical model. The electrochemical model is based on a distributed RC line approach, and the electromechanical model, considering the continuum vibration of the robot, is derived based on Hamilton's principle. The governing equation of the soft robot is solved by means of the Rayleigh-Ritz-Meirovitch substructure synthesis method, and the Laplace operator is used to obtain the transfer function of the soft robot as a 2 by 2 multiple-input multiple-output system.

Applying bi-directional evolutionary structural optimisation method for tunnel reinforcement design considering nonlinear material behaviour

In the empirical methods for reinforcement design of underground excavations, an even distribution of rock bolts is generally recommended. This work proves that this design is not necessarily optimal and shows how the state-of-the-art reinforcement design could be improved through topology optimisation techniques. The Bidirectional Evolutionary Structural Optimisation (BESO) method has been extended to consider nonlinear material behaviour. An elastic perfectly-plastic Mohr-Coulomb model is utilised for both original rock and reinforced rock. External work along the tunnel wall is considered as the objective function. Various in situ stress conditions with different horizontal stress ratios and different geostatic stress magnitudes are investigated through several examples. The outcomes show that the proposed approach is capable of improving tunnel reinforcement design. Also, significant difference in optimal reinforcement distribution for the cases of linear and nonlinear analysis results proves the importance of the influence of realistic nonlinear material properties on the final outcome.