Recent Developments and Practical Feasibility of Polymer-Based Antifouling Coatings

While nature has optimized its antifouling strategies over millions of years, synthetic antifouling coatings have not yet reached technological maturity. For an antifouling coating to become technically feasible, it should fulfill many requirements: high effectiveness, long-term stability, durability, ecofriendliness, large-scale applicability, and more. It is therefore not surprising that the search for the perfect antifouling coating has been going on for decades. With the discovery of metal-based antifouling paints in the 1970s, fouling was thought to be a problem of the past, yet its untargeted toxicity led to serious ecological concern, and its use became prohibited. As a response, research shifted focus toward a biocompatible alternative: polymer-based antifouling coatings. This has resulted in numerous advanced and innovative antifouling strategies, including fouling-resistant, fouling-release, and fouling-degrading coatings. Here, these novel and exciting discoveries are highlighted while simultaneously assessing their antifouling performance and practical feasibility

On trapped modes in the LHC recombination chambers: numerical and experimental results

The recombination chamber in LHC (Large Hadron Collider) allows the separated proton beams to merge into a common vacuum chamber surrounding the interaction points. It has been subject of thorough studies concerning its interaction with the circulating beam. In this paper we present the numerical and experimental results of our investigation. We show that in the smooth transitions between pipes of different diameters a trapped mode may exist. The mode results to be not harmful for the LHC operation, both for the beam stability and power loss

Bacterial microevolution and the Pangenome

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history

VEGF and the Fab fragment of a humanized neutralizing antibody: crystal structure of the complex at 2.4 å resolution and mutational analysis of the interface

AbstractBackground: Vascular endothelial growth factor (VEGF) is a highly specific angiogenic growth factor; anti-angiogenic treatment through inhibition of receptor activation by VEGF might have important therapeutic applications in diseases such as diabetic retinopathy and cancer. A neutralizing anti-VEGF antibody shown to suppress tumor growth in an in vivo murine model has been used as the basis for production of a humanized version.Results: We present the crystal structure of the complex between VEGF and the Fab fragment of this humanized antibody, as well as a comprehensive alanine-scanning analysis of the contact residues on both sides of the interface. Although the VEGF residues critical for antibody binding are distinct from those important for high-affinity receptor binding, they occupy a common region on VEGF, demonstrating that the neutralizing effect of antibody binding results from steric blocking of VEGF–receptor interactions. Of the residues buried in the VEGF–Fab interface, only a small number are critical for high-affinity binding; the essential VEGF residues interact with those of the Fab fragment, generating a remarkable functional complementarity at the interface.Conclusions: Our findings suggest that the character of antigen–antibody interfaces is similar to that of other protein–protein interfaces, such as ligand–receptor interactions; in the case of VEGF, the principal difference is that the residues essential for binding to the Fab fragment are concentrated in one continuous segment of polypeptide chain, whereas those essential for binding to the receptor are distributed over four different segments and span across the dimer interface

Injectable enzymatically cross linkable hydrogels:a minimally invasive cell free approach to regenerate chondral defects

Purpose: Focal cartilage defects as a consequence of trauma are a major risk factor for the development of early onset osteoarthritis. These defects still pose a largely unresolved problem for the treating physician. Previously, we have developed an injectable in situ gelating hydrogel that can be applied in an arthroscopic procedure to fill up cartilage defects by simple injection. These hydrogels consist of hyaluronic acid - tyramine and dextran - tyramine conjugates that cross link in in a cell-friendly enzymatic, peroxidase-based reaction, initiated by non-toxic concentrations of H2O2. During the cross linking reaction the hydrogels co-valently attach to the cartilage resulting in strong bonding and fixation of the hydrogel in the defect. These hydrogels possess chemoattractant properties facilitating the ingrowth of cells as demonstrated in an ex vivo chondral plug model opening the possibility for cell-free cartilage repair. The aim of this study is to test the use of these injectable hydrogels for cartilage repair in an orthotopic chondral defect rabbit model side-by-side compared with autologous chondrocyte implantation. In addition, we evaluated the concept in an equine model for focal cartilage defects. Methods: Three male rabbits were sacrificed to establish cultures of primary human chondrocytes for implantation purposes. In a pilot rabbit experiment skeletally mature female rabbits were operated under anesthesia and two 4mm wide chondral defects were created in each knee joint. The defects were left untreated, filled up with hydrogel only, or with hydrogel prior mixed with chondrocytes. The various combinations of hydrogel precursors were injected in a liquid state in the defect and left to settle in a mild enzymatically mediated cross linking reaction which took place within less than 20 seconds. Rabbits were sacrificed 4 weeks and 10 weeks after treatment and tissues were collected for histology. In a pilot experiment two horses were operated under general anaesthesia in a fully arthroscopic procedure. In each knee joint, 5mm wide chondral defects were created. These defects were in the same arthroscopic procedure completely filled with the hydrogel. Synovial fluid was collected after 1, 2, 3, 5, 7 and 14 days after surgery. After two weeks horses were humanely euthanisized and tissue was processed for histology. Results: In pilot experiments in rabbits, chondral defects were completely repaired using the injectable hydrogels after 10 weeks of surgery. Cell-free hydrogels appeared as efficient as cell-containing hydrogels. The data are now confirmed in a larger study group in which treatment with hydrogels is compared to microfracture. In the equine model we demonstrated that the injectable hydrogels could be used to fill up focal chondral defects in an completely arthroscopic procedure. Synovial fluid sampling demonstrated a clinically not relevant small increase in white blood cell count and protein count in the first 2 days after surgery which returned to base-line after 3 to 5 days. Clinical examination and follow up of the operated joints demonstrated normal response to arthroscopic surgery: no adverse effects were noted demonstrating the safety of the procedure. The horses were able to make functional use of their treated legs within a few days and walked normally 2-weeks after surgery. At this time point visual inspection demonstrated the presence of hydrogels in each of the defects. Histological examination demonstrated the presence of cell layers on top of the hydrogel and invasion of cells into the hydrogel both from the top and the bottom. The invading cells were organized in columns, like in normal cartilage, and stained positive for typical chondrocyte markers. They actively deposited glycosaminoglycans. Conclusions: This study demonstrates the feasibility of developing an arthroscopic and completely cell-free treatment of chondral defects. It also demonstrates the presence of populations of migratory cells in the traumatized joint. These cells can actively migrate to and invade an appropriate scaffolding material in vivo and start the deposition of cartilage matrix. In the future, this work may translate into a biomaterial based regenerative treatment of osteoarthritis by harnessing the regenerative potential of these migratory cells

Necrostatin-1 supplementation enhances young porcine islet maturation and in vitro function

BACKGROUND: Necroptosis has been demonstrated to be a primary mechanism of islet cell death. This study evaluated whether the supplementation of necrostatin-1 (Nec-1), a potent inhibitor of necroptosis, to islet culture media could improve the recovery, maturation, and function of pre-weaned porcine islets (PPIs). METHODS: PPIs were isolated from pre-weaned Yorkshire piglets (8-15 days old) and either cultured in control islet culture media (n = 6) or supplemented with Nec-1 (100 µM, n = 5). On days 3 and 7 of culture, islets were assessed for recovery, insulin content, viability, cellular composition, GLUT2 expression in beta cells, differentiation of pancreatic endocrine progenitor cells, function, and oxygen consumption rate. RESULTS: Nec-1 supplementation induced a 2-fold increase in the insulin content of PPIs on day 7 of culture. When compared to untreated islets, Nec-1 treatment doubled the beta- and alpha-cell composition and accelerated the development of delta cells. Additionally, beta cells of Nec-1-treated islets had a significant upregulation in GLUT2 expression. The enhanced development of major endocrine cells and GLUT2 expression after Nec-1 treatment subsequently led to a significant increase in the amount of insulin secreted in response to in vitro glucose challenge. Islet recovery, viability, and oxygen consumption rate were unaffected by Nec-1. CONCLUSION: This study underlines the importance of necroptosis in islet cell death after isolation and demonstrates the novel effects of Nec-1 to increase islet insulin content, enhance pancreatic endocrine cell development, facilitate GLUT2 upregulation in beta cells, and augment insulin secretion. Nec-1 supplementation to culture media significantly improves islet quality prior to xenotransplantation

A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16 × 16-cm-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter. We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring multilocus sequence type (MLST) clades to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino-acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination

Spontaneous emission rates of dipoles in photonic crystal membranes

We show theoretically that finite two-dimensional (2D) photonic crystals in thin semiconductor membranes strongly modify the spontaneous emission rate of embedded dipole emitters. Three-dimensional Finite-Difference Time-Domain calculations show over 7 times inhibition and 15 times enhancement of the emission rate compared to the vacuum emission rate for judiciously oriented and positioned dipoles. The vertical index confinement in membranes strongly enhances modifications of the emission rate as compared to vertically unconfined 2D photonic crystals. The emission rate modifications inside the membrane mimic the local electric field mode density in a simple 2D model. The inhibition of emission saturates exponentially as the crystal size around the source is increased, with a $1/e$ length that is inversely proportional to the bandwidth of the emission gap. We obtain inhibition of emission only close to the slab center. However, enhancement of emission persists even outside the membrane, with a distance dependence which dependence can be understood by analyzing the contributions to the spontaneous emission rate of the different vertically guided modes of the membrane. Finally we show that the emission changes can even be observed in experiments with ensembles of randomly oriented dipoles, despite the contribution of dipoles for which no gap exists

Angular redistribution of near-infrared emission from quantum dots in 3D photonic crystals

We study the angle-resolved spontaneous emission of near-infrared light sources in 3D photonic crystals over a wavelength range from 1200 to 1550 nm. To this end PbSe quantum dots are used as light sources inside titania inverse opal photonic crystals. Strong deviations from the Lambertian emission profile are observed. An attenuation of 60 % is observed in the angle dependent radiant flux emitted from the samples due to photonic stop bands. At angles that correspond to the edges of the stop band the emitted flux is increased by up to 34 %. This increase is explained by the redistribution of Bragg-diffracted light over the available escape angles. The results are quantitatively explained by an expanded escape-function model. This model is based on diffusion theory and adapted to photonic crystals using band structure calculations. Our results are the first angular redistributions and escape functions measured at near-infrared, including telecom, wavelengths. In addition, this is the first time for this model to be applied to describe emission from samples that are optically thick for the excitation light and relatively thin for the photoluminesence light.Comment: 24 pages, 8 figures (current format = single column, double spaced