Hybrid Nanoparticles and Composite Hydrogel Systems for Delivery of Peptide Antibiotics

The growing number of drug-resistant pathogenic bacteria poses a global threat to human health. For this reason, the search for ways to enhance the antibacterial activity of existing antibiotics is now an urgent medical task. The aim of this study was to develop novel delivery systems for polymyxins to improve their antimicrobial properties against various infections. For this, hybrid core–shell nanoparticles, consisting of silver core and a poly(glutamic acid) shell capable of polymyxin binding, were developed and carefully investigated. Characterization of the hybrid nanoparticles revealed a hydrodynamic diameter of approximately 100 nm and a negative electrokinetic potential. The nanoparticles demonstrated a lack of cytotoxicity, a low uptake by macrophages, and their own antimicrobial activity. Drug loading and loading efficacy were determined for both polymyxin B and E, and the maximal loaded value with an appropriate size of the delivery systems was 450 µg/mg of nanoparticles. Composite materials based on agarose hydrogel were prepared, containing both the loaded hybrid systems and free antibiotics. The features of polymyxin release from the hybrid nanoparticles and the composite materials were studied, and the mechanisms of release were analyzed using different theoretical models. The antibacterial activity against Pseudomonas aeruginosa was evaluated for both the polymyxin hybrid and the composite delivery systems. All tested samples inhibited bacterial growth. The minimal inhibitory concentrations of the polymyxin B hybrid delivery system demonstrated a synergistic effect when compared with either the antibiotic or the silver nanoparticles alone.     

Protective properties of organic phosphate-pigmented coatings on phosphated steel substrates

Investigations have been carried out on properties of coatings, differing by their pigmentation and binder, and applied on different chemical pre-treatments of the steel surface. Paints based on alkyd and alkyd-melamine binders, pigmented with zinc phosphate and modified basic zinc phosphate were applied on amorphous and crystalline phosphated steel surface and, for the comparison purpose, on degreased steel surface. The effect of the binder, the pigment and the pre-treatment of the steel surface on the protective properties of the coatings were determined by measurements of adhesion, water absorption and water permeability and by results obtained in salt spray and Prohesion tests. Coatings based on alkyd binder show a lower damage degree and good retention of adhesion in corrosion conditions, in spite of a higher water absorption and water permeability and a lower initial adhesive strength. Protective properties of coatings have been found to be highly dependent upon the substrate pre-treatment. Chemical pre-treatment of the steel substrate increases the protective properties of the system, which is particularly evident in the case of crystalline phosphating and the coating pigmented with modified basic zinc phosphate. This phenomenon can be explained by the synergism between this phosphate pigment with crystalline phosphate layer.     

Synthesis and structural characterization of a liquid polyisoprene bearing amidoxime end groups

Azo-bis(isobutyroamidoxime) was synthesized and used as functionalized initiator to prepare a liquid isoprene bearing amidoxime end groups via radical polymerization. The polymer was characterized by FT-IR, Gel Permeation Chromatography and NMR. In particular, the structure of the polymer was investigated using 1D and 2D NMR techniques. The distribution of the different isoprene units (1,4-trans, 1,4-cis, 1,2 and 3,4), as well as the structure of the amidoxime end-groups was determined. It was found that the structure of the end groups was governed by the steric hindrance of the initiator. Only 1,4 and 4,1 functionalized end units were evidenced, with a majority of 4,1 end units.     

Time delay induced effects on control of linear systems under random excitation

Recursive formulas in terms of statistics of the response of linear systems with time delay under normal white noise input are developed. Two alternative methods are presented, in order to capture the time delay effects. The first is given in an approximate solution obtained by expanding the control force in a Taylor series. The second, available for the stationary solution (if it exists) gets the variance of the controlled system, with time delay in an analytical form. The efficacy loss in terms of statistics of the response is discussed in detail.     

Global energy efficiency governance in the context of climate politics

This paper argues that energy efficiency and conservation is a noncontroversial, critical, and equitable option for rich and poor alike. Although there is growing scientific and political consensus on its significance as an important option at global and national level, the political momentum for taking action is not commensurate with the potential in the sector or the urgency with which measures need to be taken to deal with climate change. The current global energy (efficiency) governance framework is diffuse. This paper submits that there are four substantive reasons why global governance should play a complementary role in promoting energy efficiency worldwide. Furthermore, given that market mechanisms are unable to rapidly mobilize energy efficiency projects and that there are no clear vested interests in this field which involves a large number of actors, there is need for a dedicated agency to promote energy efficiency and conservation. This paper provides an overview of energy efficiency options presented by IPCC, the current energy efficiency governance structure at global level, and efforts taken at supranational and national levels, and makes suggestions for a governance framework.     

Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration

Whole exome sequencing of invasive mammary carcinomas revealed the association of mutations in PTEN and ZFHX3 tumor suppressor genes (TSGs). We generated single and combined PTEN and ZFHX3 knock-outs (KOs) in the immortalized mammary epithelial cell line MCF10A to study the role of these genes and their potential synergy in migration regulation. Inactivation of PTEN, but not ZFHX3, induced the formation of large colonies in soft agar. ZFHX3 inactivation in PTEN KO, however, increased colony numbers and normalized their size. Cell migration was affected in different ways upon PTEN and ZFHX3 KO. Inactivation of PTEN enhanced coordinated cell motility and thus, the collective migration of epithelial islets and wound healing. In contrast, ZFHX3 knockout resulted in the acquisition of uncoordinated cell movement associated with the appearance of immature adhesive junctions (AJs) and the increased expression of the mesenchymal marker vimentin. Inactivation of the two TSGs thus induces different stages of partial epithelial-to-mesenchymal transitions (EMT). Upon double KO (DKO), cells displayed still another motile state, characterized by a decreased coordination in collective migration and high levels of vimentin but a restoration of mature linear AJs. This study illustrates the plasticity of migration modes of mammary cells transformed by a combination of cancer-associated genes.     

Predicting the lightness of chromatic object colors using CIELAB

A metric of perceive lightness of object colors, L**, is derived and evaluated. This metric, based on CIELAB parameters, is designed to predict the Helmhltz-Kohlrausch effect whereby chromatic object colors appear lighter than achromatic object of the some luminance factor. Models were fitted to published data and then tested with results from a new lightness-matching experiment that is described in this article. The L** metric predicts perceived lightness to within the interobserver variability and provides a simple, practical measure of this appearance attribute.