MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy

Melanomas are aggressive tumors with a high metastatic potential and an increasing incidence rate. They are known for their heterogeneity and propensity to easily develop therapy-resistance. Nowadays they are one of the most common cancers diagnosed during pregnancy. Due to the difficulty in balancing maternal needs and foetal safety, melanoma is challenging to treat. The aim of this study was to provide a potential model system for the study of melanoma in pregnancy and to illustrate melanoma heterogeneity. For this purpose, a pigmented and a non-pigmented section of a lymph node metastasis from a pregnant patient were cultured under different conditions and characterized in detail. All four culture conditions exhibited different phenotypic, genotypic as well as tumorigenic properties, and resulted in four newly established melanoma cell lines. To address treatment issues, especially in pregnant patients, the effect of synthetic human lactoferricin-derived peptides was tested successfully. These new BRAF-mutated MUG Mel3 cell lines represent a valuable model in melanoma heterogeneity and melanoma pregnancy research. Furthermore, treatment with anti-tumor peptides offers an alternative to conventionally used therapeutic options—especially during pregnancy.     

Development and validation of a FISH-based method for the detection and quantification of E. coli and coliform bacteria in water samples

Monitoring of microbiological contaminants in water supplies requires fast and sensitive methods for the specific detection of indicator organisms or pathogens. We developed a protocol for the simultaneous detection of E. coli and coliform bacteria based on the Fluorescence in situ Hybridization (FISH) technology. This protocol consists of two approaches. The first allows the direct detection of single E. coli and coliform bacterial cells on the filter membranes. The second approach includes incubation of the filter membranes on a nutrient agar plate and subsequent detection of the grown micro-colonies. Both approaches were validated using drinking water samples spiked with pure cultures and naturally contaminated water samples. The effects of heat, chlorine and UV disinfection were also investigated. The micro-colony approach yielded very good results for all samples and conditions tested, and thus can be thoroughly recommended for usage as an alternative method to detect E. coli and coliform bacteria in water samples. However, during this study, some limitations became visible for the single cell approach. The method cannot be applied for water samples which have been disinfected by UV irradiation. In addition, our results indicated that green fluorescent dyes are not suitable to be used with chlorine disinfected samples.     

Optimization of enzymatic oligomerization reaction conditions for three milk protein products via ceteris-paribus approach

Via a ceteris-paribus approach, optimum reaction conditions for an oxidoreductase- (lactoperoxidase; laccase; glucose oxidase) induced oligomerization of milk proteins were assessed for three different milk protein products (sodium caseinate; whey protein isolate; skim milk powder).Optimum protein monomer modification conditions were enzyme- and substrate-specifically identified, yielding protein monomer modification levels of, e.g., 58% in case of lactoperoxidase-induced (w/w = 5% protein; 1.8 μmol hydrogen peroxide/mg protein; 4.8 U lactoperoxidase/mg protein; 50 °C; 1 h; pH 7.0), 92% in case of laccase-induced (w/w = 5% protein; 0.02 μmol chlorogenic acid/mg protein; 0.01 U laccase/mg protein; 40 °C; 1 h; pH 7.0) and 86% in case of glucose oxidase-induced (w/w = 1% protein; 0.5 U glucose oxidase/mg protein; 40 °C; 16 h; pH 7.0) modification of total milk proteins from skim milk powder.The study for the first time provides a comprehensive overview over reaction conditions facilitating high degrees of milk protein monomer modification upon oxidoreductase-induced oligomerization in regard to food protein tailoring via application of less substrate- and reaction-specific enzymes than transglutaminase.     

A sampling approach to biases in conditional probability judgments: Beyond base rate neglect and statistical format.

Conditional probability judgments of rare events are often inflated. Early accounts assumed a general deficit in using statistical base rates. More recent approaches predict improvement when problems are presented in frequency format or refer to natural categories. The present theory focuses on sampling processes. Experiment 1 showed that a seeming advantage of frequency over probability formats is due to a confounded factor, the need to mentally transform stimulus samples. An information search paradigm was used in Experiment 2. When sampling by the predictor, the probability to be estimated, p(criterion/predictor), was conserved in the samples and judgments were quite accurate. However, when sampling by the criterion, the low base-rate event was strongly overrepresented, accounting for the entire bias. Judgments were quite sensitive to the sampled data, but failed to take sampling constraints into account, as shown in Experiments 3 and 4. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dispersability of multiwalled carbon nanotubes in polycarbonate-chloroform solutions

The dispersion of commercial multiwalled carbon nanotubes (MWCNTs, Nanocyl™ NC7000) in chloroform and in polycarbonate (PC)-chloroform solutions was investigated by variation of the polymer concentration, MWCNT amount and sonication time and compared with PC/MWCNT composites, which were processed by melt mixing, subsequently dissolved in chloroform and dispersed via sonication under the same conditions. The sedimentation behaviour was characterised under centrifugal forces using a LUMiSizer^® separation analyser. The space and time resolved extinction profiles as a measure of the stability of the dispersion and the particle size distribution were evaluated. Sonication up to 5 min gradually increases the amount of dispersed particles in the solutions. A significant improvement of the MWCNT dispersion in chloroform was achieved by the addition of PC indicating the mechanism of polymer chain wrapping around the MWCNTs. In dispersions of melt mixed PC/MWCNT composites the dispersion of MWCNTs is significantly enhanced already at a low sonication time of only 0.5 min due to very efficient polymer wrapping during the melt mixing process. However, the best dispersion quality does not lead to the highest electrical conductivity of thin composite films made of these PC/MWCNT dispersions.     

Local Social Networks and Social Resources in Two Dutch Neighbourhoods

Much research in neighbour relations is inspired by two research questions. First, it is necessary to know to which degree social contacts are local and in particular whether local social contacts in disadvantaged neighbourhoods bear an instrumental disadvantage. Second, it is necessary to know whether policies aiming at mixing people from different social and ethnic backgrounds result in more diverse networks and therefore in better opportunities for low-income residents. To address these questions, this paper compares the role of local relationships and the social resources they provide in a low-income neighbourhood and a socio-economic mixed neighbourhood in the Netherlands. Contrary to assumptions in the research literature, residents in the low-income neighbourhood do not differ from their counterparts in the mixed neighbourhood in the degree to which they receive social support for dealing with everyday problems. However, networks of low-income residents provided fewer resources in terms of accessed prestige.     

Influence of different carbon nanotubes on the electrical and mechanical properties of melt mixed poly(ether sulfone)-multi walled carbon nanotube composites

Commercial Udel® poly(ether sulfone) (PSU) was filled with three different commercially available multiwalled carbon nanotubes (MWCNTs) by small scale melt mixing. The MWCNTs were as grown NC 7000 and two of its derivatives prepared by ball milling treatment. One of them was unmodified (NC 3150); the other was amino modified (NC 3152). The main difference beside the reactivity was the reduced aspect ratio of NC 3150 and NC 3152 caused by ball milling process. All PSU/MWCNT composites with similar filler content were prepared under fixed processing conditions and comparative analysis of their electrical and mechanical properties were performed and were correlated with their microstructure, characterized by optical microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A non-uniform MWCNT dispersion was observed in all composites. The MWCNTs were present in form of agglomerates in the size of 10–60 μm whereas the deagglomerated part was homogeneously distributed in the PSU matrix. The differences in the agglomeration states correlate with the variations of properties between different PSU/MWCNT composites. The lowest electrical percolation threshold of 0.25–0.5 wt.% was observed for the shortened non-functionalized MWCNT composites and the highest for amine-modified MWCNT composites (ca. 1.5 wt.%). The tensile behavior of the three composites was only slightly altered with CNT loading as compared to the pure PSU. However, the elongation at break showed a reduction with MWCNT loading and the reduction was least for composite with best MWCNT dispersion.     

The evaluation of liposome-water partitioning of 8-hydroxyquinolines and their copper complexes

Bioavailability and toxicity of mixtures are urgent research issues, but usually mixtures of exclusively organic chemicals or exclusively metals are investigated. In our study, we explored the role of combinations of hydrophobic ionogenic organic compounds (HIOCs) with copper (Cu2+)for uptake and bioavailability of metals and hydrophobic metal complexes in an in vitro membrane system. We investigated the influence of the interactions of copper and 8-hydroxyquinolines, both components used in formulations of pesticides, on their partitioning into liposomes, which are model systems for biological membranes and are composed of lipid bilayers made of phosphatidylcholine. The test set of compounds comprised the parent compound 8-hydroxyquinoline and 8-hydroxyquinolines with hydrophobic (e.g., 5-chloro-8-hydroxyquinoline, 5,7-dichloro-8-hydroxyquinoline, 5,7-dibromo-8-hydroxyquinoline) and with hydrophilic (e.g., 8-hydroxyquinoline-5-sulfonic acid) substituents. Hydrophobic 8-hydroxyquinolines facilitate the passive uptake of copper into phospholipid bilayers by complex formation. Not only the neutral species of the ligands and their neutral copper ligand complexes are significantly taken up into the membrane, but also the cationic and anionic species of the ligands and the cationic complexes. The neutral, anionic, and cationic species of 8-hydroxyquinoline and the hydrophobic substituted 8-hydroxyquinolines exhibit linear correlations between their logarithmic liposome-water partitioning coefficients (log Klipw) and the logarithmic octanol-water partitioning coefficients of their neutral species (log Kow, neutral). The neutral species show the strongest partitioning followed by the anionic and cationic species. The associated quantitative structure activity relationships describing the dependency of log Klipw of the various species from log Kow, neutral of the neutral ligand species have slopes between 0.9 and 1. In contrast, the partitioning of the neutral and cationic copper-8-hydroxyquinoline complexes is dependent on several factors including the hydrophobicity of the ligand, the effective molecular size, and the polarization of the complex itself. In consequence, there is no linear relationship between log Klipw of these complexes and log Kow of the neutral species of their ligands. The complexes with very bulky substituents showed a reduced uptake. The Klipw of the nominally neutral complexes, where Cu2+ is coordinated with two ligands, were a factor three to four higher than the Klipw of the positively charged complexes with only one ligand. Although liposome-water partitioning merely describes one element of the uptake process into biological membranes, it is a key process for bioavailability of hydrophobic compounds and, presumably, also plays a crucial role for biological uptake of the described metal organic complexes.     

Comparative analysis of thermally modified and native spruce loaded perpendicular to the grain

The aim of this work was to analyse the material behaviour of thermally modified and native spruce by load applied perpendicularly to the grain. Therefore, thermally modified and native samples were prepared for bending tests with the load in tangential direction. The bending strength in radial direction decreases significantly with the thermal treatment. The fracture surfaces in the tangential section of the bending samples after testing were analysed with a scanning electron microscope. For native samples, the typical failure was found in the intercellular area. For thermally modified samples, failure of the entire cell wall was observed. The material behaviour is more brittle, as demonstrated by the load-deflection curves, but also by anatomical studies of the fracture surfaces.