The retinoblastoma (Rb) antioncogene encodes a nuclear phosphoprotein, p105-Rb, that forms protein complexes with the adenovirus E1A and SV40 large T oncoproteins. A novel, aberrant Rb protein detected in J82 bladder carcinoma cells was not able to form a complex with E1A and was less stable than p105-Rb. By means of a rapid method for the detection of mutations in Rb mRNA, this defective Rb protein was observed to result from a single point mutation within a splice acceptor sequence in J82 genomic DNA. This mutation eliminates a single exon and 35 amino acids from its encoded protein product.
We found deletions involving the retinoblastoma gene in 12 of49 tumors from patients with retinoblastoma or osteosarcoma. After mapping the deletion breakpoints, we found that no two breakpoints coincided. Thus, our data do not support the conclusions of others regarding the existence of a "hotspot" for deletion breakpoints in this gene. In 4 of the tumors, we sequenced 200 base pairs surrounding each deletion breakpoint. Three deletions had termini within pairs of short, direct repeats ranging in size from 4 to 7 base pairs. These results indicate that the "slipped mispairing" mechanism may predominate in the generation of deletions at this locus. Our review of deletion breakpoints at other genetic loci reveals that the nature of the sequences present at deletion breakpoints (short, direct repeats versus middle repetitive elements) varies according to the genetic locus under study.The retinoblastoma gene serves as a model for the study of recessive oncogenes. Mutations at the retinoblastoma locus play a role in the development of retinoblastoma, a malignant tumor arising in the eyes of young children, and possibly in the development of other human cancers, such as osteosarcoma (1-4), small cell lung carcinoma (5), and breast carcinoma (6, 7). The recent cloning (1, 2, 8) and restriction and exon mapping (9) of the retinoblastoma locus have allowed for a detailed analysis ofthe molecular basis of mutations that cause inactivation of the retinoblastoma gene and subsequent oncogenic transformation.Mutations of the retinoblastoma gene occur at a rate much higher than for most other human genes (10). Approximately 10-40o of the mutations are deletions detectable by Southern blotting (1)(2)(3)11). The data we present here address two questions concerning deletions that inactivate the retinoblastoma gene. We would like to know whether deletions occur preferentially at hotspots within the gene and whether specific DNA sequences within the gene predispose to them. To study these issues we mapped the deletion breakpoints in 12 tumors and sequenced the breakpoints in 4 of them. We present here the results of this study and discuss their relevance to the possible mechanisms for the generation of deletions of this gene.
These data demonstrate that this investigational assay used in conjunction with current screening algorithms may potentially add value to the biopsy decision making process.
High quality feedback is known to be essential for learning, yet in higher education it has been highlighted as a problem area in the UK by both the Quality Assurance Agency (QAA) and National Student Surveys. Furthermore, a recent study has shown that there is a fault-line between the highly structured guidance system that exists in schools/colleges and the culture of 'independent' learning that is promoted in higher education and suggests that this is a significant barrier to a successful transition. This article reports research to improve the transition for first year undergraduates by providing a structured set of guidance activities as a means of an extended induction into the assessment processes in higher education. The activities are based on the Dialogic Feedback Cycle which encompasses principles of feedback as dialogue, emphasising guidance at the start of, and during an assignment rather than summative written feedback. The intervention was evaluated by means of a questionnaire and supported by focus groups. The questionnaire was administered to a control group and an intervention group. Results showed statistically significant improvements (p<0.05) in students' perceptions of their understanding of assessment tasks, criteria, and confidence at completing assessment tasks and self-regulated learning. KeywordsFeedback, Feedforward, Dialogical Feedback Cycle DFC, Assessment, Self-regulated learning, transition, computing. IntroductionThe transition from school to higher education is increasingly recognised to constitute a crosscultural process 'with potential for substantial problems ' (Kirkpatrick and Mulligan, 2002, 75) and experienced as an 'alien environment' (Askham, 2008). There can be many reasons for such problems and Lawrence (2005) provides a detailed analysis of the complexities of the cultural transition in terms of socio-cultural competencies, university (learning) literacies and selfmanagement. However, a particularly important aspect concerns assessment practices and feedback. Beaumont, O'Doherty and Shannon (2011) identified the substantial difference between the approaches for assessment feedback at school and higher education as a significant barrier to successful transition. Their study of students' experiences in English schools and * Email:Chris.Beaumont@Edgehill.ac.uk Journal of Further and Higher Educationuniversities revealed that both students and teachers used the term 'spoon feeding' to describe the learning process in school, explaining that it aims to deliver high grades. Whilst this may be good for league tables, it leaves many students unprepared for university assessment, which is typically characterised as 'independent learning' (Leese, 2010). Bingham and O'Hara (2007) confirm the difficulty students have in becoming 'autonomous' learners.It is therefore important to explore the effectiveness of approaches that will help students make a successful transition between the two sectors; in short, to scaffold the development of self-regulated learning skills. Ind...
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