Surface induced selective delamination of amphiphilic ABA block copolymer thin films

This is the result of an ongoing collaboration with Dr. N. Sommerdijk’s Biomaterials group at the University of Eindhoven (the Netherlands) and illustrates the close collaboration that exists in pursuing the design and application of novel polymeric materials between the two groups. This details work on a physical phenomenon (selective delamination) and key materials (amphiphilic block copolymers) that have subsequently been applied in the design of novel biomaterials. These results have appeared in a larger body of work including Advanced Materials, Angewandtie Chemie International Edition and the Journal of Materials Chemistry

ABA triblock copolymers: from controlled synthesis to controlled function

The ABA amphiphilic block copolymers, poly(hydroxyethyl methacrylate-hlock-methylphenylsilane-block-hydroxyethyl methacrylate) (PHEMA-PMPS-PHEMA) and poly[oligo(ethylene glycol) methyl ether methacrylate-block-methylphenylsilane-block-oligo(ethylene glycol). methyl ether methacrylate] (POEGMA-PMPS-POEGMA) were successfully synthesised via atom transfer radical polymerisation (ATRP). Macroinitiators suitable for the ATRP of oligo(ethylene glycol) methyl ether methacrylate and 2-hydroxyethyl methacrylate were synthesised from the condensation reaction of alpha,omega-dihalopolymethylphenylsilane and 2'-hydroxyethyl 2-bromo-2-methylpropanoate. The copolymers were characterised using H-1 NMR and C-13 NMR spectroscopy and molecular weight characteristics were determined using size exclusion chromatography and H-1 NMR. The aggregation behaviour of some of the copolymers in water was studied using transmission and scanning electron microscopy and dynamic light scattering. These revealed the prevalent aggregate species to be micelles. Larger aggregates of 300-1000 nm diameter were also observed. The UV induced degradation of the aggregates was studied by UV-Vis spectroscopy. The thermal behaviour of selected copolymers was studied by differential scanning calorimetry and microphase separation of the two components was demonstrated

Sex specific associations in genome wide association analysis of renal cell carcinoma.

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC

ABA Amphiphilic block copolymers with comb-like segments from ATRP: Self-assembly in aqueous and electrolyte solutions

Amphiphilic block copolymers (BCs) can self-organize into various aggregates morphologies in solution where the solvent is selective for one of the blocks. The size and the shape of these various molecular assemblies depends on the balance of hydrophilic and hydrophobic regions of the block copolymer. Among these aggregates, vesicles, which have been considered as powerful nanocarriers, are especially interesting for their applications in the design of drug delivery systems. Here we report preliminary results of our studies into the self-assembly behaviour in aqueous dispersions of poly[olig(ethylene glycol methyl ether)]-block-polystyrene-block-[olig(ethylene glycol methyl ether)] (POEGMA-PS-POEGMA) prepared by atom transfer radical polymerisation techniques (ATRP) for different hydrophilic:hydrophobic weight ratios between the blocks. Size and morphology of the aggregates were analysed by TEM and dynamic light scattering. The effects of two salts, NaCl and CaBr2 on the aggregation behaviour were studied and fluorescence measurements were also carried out in order to determine the critical aggregation concentration (c.a.c.) and to exhibit the encapsulation of a fluorescent probe

The synthesis and self-assembly of ABA amphiphilic block copolymers containing styrene and oligo(ethylene glycol) methyl ether methacrylate in dilute aqueous solutions: Elevated cloud point temperatures for thermoresponsive micelles

A series of ABA amphiphilic triblock copolymers possessing polystyrene (PS) central hydrophobic blocks, one group with “short” PS blocks (DP = 54–86) and one with “long” PS blocks (DP = 183–204) were synthesized by atom transfer radical polymerization. The outer hydrophilic blocks were various lengths of poly(oligoethylene glycol methyl ether) methacrylate, a comb-like polymer. The critical aggregation concentrations were recorded for certain block copolymer samples and were found to be in the range circa 10?9 mol L?1 for short PS blocks and circa 10?12 mol L?1 for long PS blocks. Dilute aqueous solutions were analyzed by transmission electron microscopy (TEM) and demonstrated that the short PS block copolymers formed spherical micelles and the long PS block copolymers formed predominantly spherical micelles with smaller proportions of cylindrical and Y-branched cylindrical micelles. Dynamic light scattering analysis results agreed with the TEM observations demonstrating variations in micelle size with PS and POEGMA chain length: the hydrodynamic diameters (DH) of the shorter PS block copolymer micelles increased with increasing POEGMA block lengths while maintaining similar PS micellar core diameters (DC); in contrast the values of DH and DC for the longer PS block copolymer micelles decreased. Surface-pressure isotherms were recorded for two of the samples and these indicated close packing of a short PS block copolymer at the air–water interface. The aggregate solutions were demonstrated to be stable over a 38-day period with no change in aggregate size or noticeable precipitation. The cloud point temperatures of certain block copolymer aggregate solutions were measured and found to be in the range 76–93 °C; significantly these were ?11 °C higher in temperature than those of POEGMA homopolymer samples with similar chain lengths. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7739–7756, 200

The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution

Transcription of genes encoding cytochrome P 450 3A (CYP3A) monooxygenases is induced by a variety of xenobiotics and natural steroids. There are marked differences in the compds. that induce CYP3A gene expression between species. Recently, the mouse and human pregnane X receptor (PXR) were shown to be activated by compds. that induce CYP3A expression. However, most studies of CYP3A regulation have been performed using rabbit and rat hepatocytes. Here, the authors report the cloning and characterization of PXR from these two species. PXR is remarkably divergent between species, with the rabbit, rat, and human receptors sharing only approx. 80% amino acid identity in their ligand-binding domains. This sequence divergence is reflected by marked pharmacol. differences in PXR activation profiles. For example, the macrolide antibiotic rifampicin, the antidiabetic drug troglitazone, and the hypocholesterolemic drug SR12813 are efficacious activators of the human and rabbit PXR but have little activity on the rat and mouse PXR. Conversely, pregnane 16α-carbonitrile is a more potent activator of the rat and mouse PXR than the human and rabbit receptor. The activities of xenobiotics in PXR activation assays correlate well with their ability to induce CYP3A expression in primary hepatocytes. Through the use of a novel scintillation proximity binding assay, the authors demonstrate that many of the compds. that induce CYP3A expression bind directly to human PXR. These data establish PXR as a promiscuous xenobiotic receptor that has diverged during evolution

Challenges in Evaluating Psychosocial Interventions for autistic spectrum disorders

In 2002, the National Institutes of Health sponsored a meeting concerning methodological challenges of research in psychosocial interventions in Autism Spectrum Disorders. This paper provides a summary of the presentations and the discussions that occurred during this meeting. Recommendations to federal and private agencies included the need for randomized clinical trials of comprehensive interventions for autism as the highest, but not the sole priority. Ongoing working groups were proposed to address psychosocial interventions with a focus on relevant statistics, standardized documentation and methods of diagnosis, development of outcome measures, establishment of standards in research; and the need for innovative treatment designs, including application of designs from other research areas to the study of interventions in ASD. © 2005 Springer Science+Business Media, Inc