Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay.

Human papillomaviruses (HPVs) are oncogenic viruses that cause numerous different cancers as well as benign lesions in the epithelia. To date, there is no effective cure for an ongoing HPV infection. Here, we describe the generation process of a platform for the development of anti-HPV drugs. This system consists of engineered full-length HPV genomes that express reporter genes for evaluation of the viral copy number in all three HPV replication stages. We demonstrate the usefulness of this system by conducting high-throughput screens to identify novel high-risk HPV-specific inhibitors. At least five of the inhibitors block the function of Tdp1 and PARP1, which have been identified as essential cellular proteins for HPV replication and promising candidates for the development of antivirals against HPV and possibly against HPV-related cancers.

An Integrated Data-Driven Strategy for Safe-by-Design Nanoparticles: The FP7 MODERN Project.

The development and implementation of safe-by-design strategies is key for the safe development of future generations of nanotechnology enabled products. The safety testing of the huge variety of nanomaterials that can be synthetized is unfeasible due to time and cost constraints. Computational modeling facilitates the implementation of alternative testing strategies in a time and cost effective way. The development of predictive nanotoxicology models requires the use of high quality experimental data on the structure, physicochemical properties and bioactivity of nanomaterials. The FP7 Project MODERN has developed and evaluated the main components of a computational framework for the evaluation of the environmental and health impacts of nanoparticles. This chapter describes each of the elements of the framework including aspects related to data generation, management and integration; development of nanodescriptors; establishment of nanostructure-activity relationships; identification of nanoparticle categories; hazard ranking and risk assessment.

Enhanced Low-Density Silicone Foams Blown by Water-Hydroxyl Blends.

Water, alcohols, diols, and glycerol are low-cost blowing agents that can be used to create the desired silicone foam structures. Although their combined use can be beneficial, it remains unclear how it affects the physical properties of the resulting materials. We conducted a comparative study of these hydroxyl-bearing blowing agents in fumed silica- and mica-filled polymer composite systems for simultaneous blowing and crosslinking to obtain a low-density, uniform porosity and superior mechanical properties. The foams were optimized for a uniform open-pore structure with densities ranging from 75 to 150 kg‧m-3. Varying the diol chain length (Cn) from one to seven carbons can alter the foam density and structure, thereby enhancing the foam tensile strength while maintaining a low density. Replacing 10 mol% of water with 1,4-butanediol decreased the density by 26%, while increasing the specific strength by 5%. By combining glycerol and water blowing, the resulting foams exhibited a 30% lower apparent density than their water-blown analogs. The results further showed that Cn > 4 alkane chain diols had an odd-even effect on the apparent density and cell wall thickness. All foamable compositions had viscosities of approximately 7000 cSt and curing times below 2 min, allowing for quick dispensing and sufficient time for the foam to cure in semi-industrial volumes.

Microbial growth and adhesion of Escherichia coli in elastomeric silicone foams with commonly used additives.

Silicone is often used in environments where water repellency is an advantage. Contact with water promotes the adhesion of microorganisms and biofilm formation. Depending on the application, this may increase the possibility of food poisoning and infections, the material's degrading appearance, and the likelihood of manufacturing defects. The prevention of microbial adhesion and biofilm formation is also essential for silicone-based elastomeric foams, which are used in direct contact with human bodies but are often difficult to clean. In this study, the microbial attachment in and the retention from the pores of silicone foams of different compositions is described and compared to those of commonly used polyurethane foams. The growth of the gram-negative Escherichia coli in the pores and their leaching during wash cycles is characterised by bacterial growth/inhibition, adhesion assay, and SEM imaging. The structural and surface properties of the materials are compared. Despite using common antibacterial additives, we have found that non-soluble particles stay isolated in the silicone elastomer layer, thus affecting surface microroughness. Water-soluble tannic acid dissolves into the medium and seems to aid in inhibiting planktonic bacterial growth, with a clear indication of the availability of tannic acid on the surfaces of SIFs.

Dip-coating electromechanically active polymer actuators with SIBS from midblock-selective solvents to achieve full encapsulation for biomedical applications.

Soft and compliant ionic electromechanically active polymer actuators (IEAPs) are a promising class of smart materials for biomedical and soft robotics applications. These materials change their shape in response to external stimuli like the electrical signal. This shape-change results solely from the ion flux inside the composite and hence the material can be miniaturized below the centimeter and millimeter levels-something that still poses a challenge for many other conventional actuation mechanisms in soft robotics (e.g., pneumatic, hydraulic, or tendon-based systems). However, the components used to prepare IEAPs are typically not safe for the biological environment, nor is the environment safe for the actuator. Safety concerns and unreliable operation in foreign liquid environments have been some of the main obstacles for the widespread adoption of IEAPs in many areas, e.g., in biomedical applications. Here we show a novel approach to fully encapsulate IEAP actuators with the biocompatible block copolymer SIBS (poly(styrene-block-isobutylene-block-styrene)) dissolved in block-selective solvents. Reduction in the bending amplitude due to the added passive layers, a common negative side-effect of encapsulating IEAPs, was not observed in this work. In conclusion, the encapsulated actuator is steered through a tortuous vasculature mock-up filled with a viscous buffer solution mimicking biological fluids.

Application of the QSPR approach to the boiling points of azeotropes.

CODESSA Pro derivative descriptors were calculated for a data set of 426 azeotropic mixtures by the centroid approximation and the weighted-contribution-factor approximation. The two approximations produced almost identical four-descriptor QSPR models relating the structural characteristic of the individual components of azeotropes to the azeotropic boiling points. These models were supported by internal and external validations. The descriptors contributing to the QSPR models are directly related to the three components of the enthalpy (heat) of vaporization.

Wider Potential Windows of Cellulose Multiwall Carbon Nanotube Fibers Leading to Qualitative Multifunctional Changes in an Organic Electrolyte.

The trend across the whole of society is to focus on natural and/or biodegradable materials such as cellulose (Cell) over synthetic polymers. Among other usage scenarios, Cell can be combined with electroactive components such as multiwall carbon nanotubes (CNT) to form composites, such as Cell-CNT fibers, for applications in actuators, sensors, and energy storage devices. In this work, we aim to show that by changing the potential window, qualitative multifunctionality of the composites can be invoked, in both electromechanical response as well as energy storage capability. Cell-CNT fibers were investigated in different potential ranges (0.8 V to -0.3 V, 0.55 V to -0.8 V, 1 V to -0.8 V, and 1.5 V to -0.8 V), revealing the transfer from cation-active to anion-active as the potential window shifted towards more positive potentials. Moreover, increasing the driving frequency also shifts the mode from cation- to anion-active. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy were conducted to determine the ion species participating in charge compensation under different conditions.

Antagonist Concepts of Polypyrrole Actuators: Bending Hybrid Actuator and Mirrored Trilayer Linear Actuator.

Following the natural muscle antagonist actuation principle, different adaptations for "artificial muscles" are introduced in this work. Polypyrrole (PPy) films of different polymerization techniques (potentiostatic and galvanostatic) were analyzed and their established responses were combined in several ways, resulting in beneficial actuation modes. A consecutive "one-pot" electrosynthesis of two layers with the different deposition regimes resulted in an all-PPy bending hybrid actuator. While in most cases the mixed-ion activity of conductive polymers has been considered a problem or a drawback, here for the first time, the nearly equal expansions upon oxidation and reduction of carefully selected conditions further allowed to fabricate a "mirrored" trilayer laminate, which behaved as a linear actuator.

A New Direction in Microfluidics: Printed Porous Materials.

In this work, the feasibility of a novel direction for microfluidics is studied by demonstrating a set of new methods to fabricate microfluidic systems. Similarly to microfluidic paper-based analytical devices, porous materials are being used. However, alternative porous materials and different printing methods are used here to give the material the necessary pattern to act as a microfluidic system. In this work, microfluidic systems were produced by the following three separate methods: (1) by curing a porous monolithic polymer sheet into a necessary pattern with photolithography, (2) by screen printing silica gel particles with gypsum, and (3) by dispensing silica gel particles with polyvinyl acetate binder using a modified 3D printer. Different parameters of the printed chips were determined (strength of the printed material, printing accuracy, printed material height, wetting characteristics, repeatability) to evaluate whether the printed chips were suitable for use in microfluidics. All three approaches were found to be suitable, and therefore the novel approach to microfluidics was successfully demonstrated.

Ion Mobility in Thick and Thin Poly-3,4 Ethylenedioxythiophene Films-From EQCM to Actuation.

Conductive polymer actuators and sensors rely on controlled ion transport coupled to a potential/charge change. In order to understand and control such devices, it is of paramount importance to understand the factors that determine ion flux at various conditions, including the synthesis potential. In this work, the ion transport in thinner poly-3,4-ethylenedioxythiophene (PEDOT) films during charge/discharge driven by cyclic voltammetry is studied by consideration of the electrochemical quartz crystal microbalance (EQCM) and the results are compared to the actuation responses of thicker films that have been synthesized with the same conditions in the bending and linear expansion modes. The effects of polymerization potentials of 1.0 V, 1.2 V, and 1.5 V are studied to elucidate how polymerization potential contributes to actuation, as well the involvement of the EQCM. In this work, it is revealed that there is a shift from anion-dominated to mixed to cation-dominated activity with increased synthesis potential. Scanning electron microscopy shows a decrease in porosity for the PEDOT structure with increasing synthesis potential. EQCM analysis of processes taking place at various potentials allows the determination of appropriate potential windows for increased control over devices.