A computational investigation of the formation and structure of DNA intrastrand cross-links initiated by the uracil radical

xvi, 147 leaves : ill. (chiefly col.) ; 29 cm + 1 CD-ROMUsing computational methods, the formation pathways and structures of four experimentally-observed DNA intrastrand cross-links are determined. These lesions originate from the uracil radical and are of particular importance due to their potential role in the activity of the 5-halouracils as radiosensitizing agents in anti-tumour treatments. The formation pathways are studied with density functional theory under conditions relevant to both UV and ionizing radiation. Results reveal these intrastrand cross-links are likely to form under therapeutic conditions and provide an explanation for their observed formation preferences. The structures of the cross-links in DNA are determined with molecular dynamics simulations to reveal the distortions these lesions induce to the helix. This has provided information about the potential biological implications of these lesions, where results indicate intrastrand cross-links are likely both mutagenic and cytotoxic. Therefore, these lesions may contribute to tumour cell death in the therapeutic use of halouracils

Is the writing on the wall for tabletops?

We describe an ethnographic study that explores how low tech and new tech surfaces support participation and collaboration during a workshop breakout session. The low tech surfaces were post-it notes and large sheets of paper. The new tech surfaces were writeable walls and a multi-touch tabletop. Four groups used the different surfaces during three phases: i) brief presentation of position papers and discussion of themes, ii) the creation of a group presentation and iii) a report back session. Participation and collaboration varied depending on the physical, technological and social factors at play when using the different surfaces. We discuss why this is the case, noting how new shareable surfaces may need to be constrained to invite participation in ways that are simply taken for granted because of their familiarity when using low tech materials

Representational predicaments for employees: Their impact on perceptions of supervisors\u27 individualized consideration and on employee job satisfaction

A representational predicament for a subordinate vis-à-vis his or her immediate superior involves perceptual incongruence with the superior about the subordinate\u27s work or work context, with unfavourable implications for the employee. An instrument to measure the incidence of two types of representational predicament, being neglected and negative slanting, was developed and then validated through an initial survey of 327 employees. A subsequent substantive survey with a fresh sample of 330 employees largely supported a conceptual model linking being neglected and negative slanting to perceptions of low individualized consideration by superiors and to low overall job satisfaction. The respondents in both surveys were all Hong Kong Chinese. Two case examples drawn from qualitative interviews illustrate and support the conceptual model. Based on the research findings, we recommend some practical exercises to use in training interventions with leaders and subordinates. © 2013 Copyright Taylor and Francis Group, LLC

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd