Sequence-Controlled Methacrylic Multiblock Copolymers: Expanding the Scope of Sulfur-Free RAFT

Sulfur-free reversible addition–fragmentation transfer polymerization (SF-RAFT) in emulsion allows access to the synthesis of sequence-controlled methacrylic multiblock copolymers. Herein, we expand the scope of SF-RAFT emulsion polymerization by utilizing four different macrochain transfer agents (mCTA) to mediate the synthesis of diblocks and sequence-controlled methacrylic multiblock copolymers. Poly­(methyl methacrylate) (pMMA), poly­(butyl methacrylate) (pBMA), poly­(ethyl methacrylate) (pEMA), and poly­(benzyl methacrylate) (pBzMA) of a similar <i>M</i>_n (∼4300 g mol^–1) were successfully synthesized via catalytic chain transfer polymerization (CCTP) in emulsion. The capability of these mCTAs to act as macroinitiators was investigated through the synthesis of “<i>in situ</i>” diblock copolymers and was then expanded to the synthesis of deca- and hexablock multiblock copolymers with varying degrees of polymerization (DP_n = 10–50 per block, <i>M</i>_n,total = 7000–55 000 g mol^–1), yielding well-defined copolymers with controlled molecular weights, quantitative conversions (>99%), and low dispersities (<i>Đ</i> ∼ 1.2) without employing sulfur or transition metal reagents

An evaluation of supported employment initiatives for disabled people

SIGLEAvailable from British Library Document Supply Centre-DSC:GPE/3338 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

A medieval farming glossary of Latin and English words Taken mainly from Essex records

SIGLEAvailable from British Library Document Supply Centre-DSC:3812.050(138) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Replication and Predictive Value of SNPs Associated with Melanoma and Pigmentation Traits in a Southern European Case-Control Study

<div><h3>Background</h3><p>Genetic association studies have revealed numerous polymorphisms conferring susceptibility to melanoma. We aimed to replicate previously discovered melanoma-associated single-nucleotide polymorphisms (SNPs) in a Greek case-control population, and examine their predictive value.</p> <h3>Methods</h3><p>Based on a field synopsis of genetic variants of melanoma (MelGene), we genotyped 284 patients and 284 controls at 34 melanoma-associated SNPs of which 19 derived from GWAS. We tested each one of the 33 SNPs passing quality control for association with melanoma both with and without accounting for the presence of well-established phenotypic risk factors. We compared the risk allele frequencies between the Greek population and the HapMap CEU sample. Finally, we evaluated the predictive ability of the replicated SNPs.</p> <h3>Results</h3><p>Risk allele frequencies were significantly lower compared to the HapMap CEU for eight SNPs (rs16891982 – <em>SLC45A2</em>, rs12203592 – <em>IRF4</em>, rs258322 – <em>CDK10</em>, rs1805007 – <em>MC1R</em>, rs1805008 - <em>MC1R</em>, rs910873 - <em>PIGU</em>, rs17305573- <em>PIGU</em>, and rs1885120 - <em>MTAP</em>) and higher for one SNP (rs6001027 – <em>PLA2G6</em>) indicating a different profile of genetic susceptibility in the studied population. Previously identified effect estimates modestly correlated with those found in our population (r = 0.72, P<0.0001). The strongest associations were observed for rs401681-T in <em>CLPTM1L</em> (odds ratio [OR] 1.60, 95% CI 1.22–2.10; P = 0.001), rs16891982-C in <em>SCL45A2</em> (OR 0.51, 95% CI 0.34–0.76; P = 0.001), and rs1805007-T in <em>MC1R</em> (OR 4.38, 95% CI 2.03–9.43; P = 2×10⁻⁵). Nominally statistically significant associations were seen also for another 5 variants (rs258322-T in <em>CDK10</em>, rs1805005-T in <em>MC1R</em>, rs1885120-C in <em>MYH7B</em>, rs2218220-T in <em>MTAP</em> and rs4911442-G in the <em>ASIP</em> region). The addition of all SNPs with nominal significance to a clinical non-genetic model did not substantially improve melanoma risk prediction (AUC for clinical model 83.3% versus 83.9%, p = 0.66).</p> <h3>Conclusion</h3><p>Overall, our study has validated genetic variants that are likely to contribute to melanoma susceptibility in the Greek population.</p> </div

Correlation of risk allele frequencies.

<p>Correlation of the risk allele frequencies found in the Greek population and the frequencies of the same alleles from the HapMap CEU sample. Not shown are: rs4636294 (excluded from analyses because of HWE deviation); rs1805009 and rs11547464 because all subjects were homozygous for the respective major alleles and OR and hence risk allele could not be identified.</p

Correlation of effect sizes.

<p>Correlation of the effect sizes found in the Greek population and those described in the original publication or MelGene..Not shown are: rs4636294 (excluded from analyses because of HWE deviation); rs1011970 because OR was not available in the original publication and/or MelGene; rs1805009 and rs11547464 because all subjects were homozygous for the major allleles.</p

Results of the univariable and multivariable analyses adjusting for hair color, skin color, eye color, phototype, sunburn and tanning and comparison with data from MelGene [23].

1<p>Association analysis on negative strand.</p><p>Abbreviations: NS, not significant.</p>2<p>MelGene status = Data from MelGene, an online database of reported genetic associations of melanoma including a systematic meta-analysis of melanoma-associated variants from published datasets and grading of these associations for strength of epidemiogical evidence <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055712#pone.0055712-Chatzinasiou1" target="_blank">[23]</a>. OR (95% CI) and p value correspond to nominal association with melanoma after meta-analysis of data for each variant.</p>3<p>For this variant no meta-analysis was performed in MelGene due to the lack of sufficient datasets. The data represent those derived from the initial GWAS reporting an association of this variant with melanoma <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055712#pone.0055712-Nan2" target="_blank">[50]</a>.</p

List of genotyped SNPs, risk alleles in the Greek sample, and risk allele frequency in the Greek sample and HapMap CEU.

<p>N/A: not applicable because all subjects were found homozygous for the major alleles.</p>1<p>Deviation from HWE, excluded from analyses.</p

Areas under the curve (AUC) for 3 predictive models.

<p>Receiver operating characteristic curves for the 3 models including respectively the non-genetic risk factors alone, the non-genetic risk factors with the 3 SNPs surviving Bonferoni correction, and the non-genetic risk factors with all 8 nominally significant SNPs.</p

Summary results for SNPs selected for replication in the present Greek case-control study.

1<p>Reference source = Melgene: nominal association with melanoma after meta-analysis of data for this variant derived from at least 3 datasets (MelGene is an online database of all reported genetic associations of melanoma which includes a systematic meta-analysis of melanoma-associated variants from published datasets and grading of this associations for strength of epidemiogical evidence) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055712#pone.0055712-Chatzinasiou1" target="_blank">[23]</a>, or data derived from original study (variants not meta-analyzed in Melgene).</p>2<p>Showed deviation from HWE, and was therefore not included in the analyses: N/A for MAF & OR in the Greek sample.</p>3<p>All individuals were homozygous for the major allele.</p><p>Abbreviations: MAF, minor allele frequency; CI, confidence interval; OR, odds ratio.</p