James F. Lee

MGMT methylation is associated primarily with the germline C>T SNP (rs16906252) in colorectal cancer and normal colonic mucosa

O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that restores mutagenic O6-methylguanine to guanine. MGMT methylation is frequently observed in sporadic colorectal cancer and was recently correlated with the C>T allele at SNP rs16906252, within the transcriptional enhancer element of the promoter. MGMT methylation has also been associated with KRAS mutations, particularly G>A transitions. We studied 1123 colorectal carcinoma to define the molecular and clinicopathological profiles associated with MGMT methylation. Furthermore, we assessed factors contributing to MGMT methylation in the development of colorectal cancer by studying the allelic pattern of MGMT methylation using SNP rs16906252, and the methylation status of neighbouring genes within 10q26 in selected tumours and matched normal colonic mucosa. MGMT methylation was detected by combined bisulphite restriction analysis in 28% of tumours and was associated with a number of characteristics, including CDKN2A methylation, absent lymphovascular space invasion and KRAS mutations (but not specifically with KRAS G>A transitions). In a multivariate analysis adjusted for age and sex, MGMT methylation was associated with the T allele of SNP rs16906252 (P<0.0001, OR 5.5, 95% CI 3.8–7.9). Low-level methylation was detected by quantitative methylation-specific PCR in the normal colonic mucosa of cases, particularly those with a correspondingly methylated tumour, as well as controls without neoplasia, and this was also associated with the C>T SNP. We show that the T allele at SNP rs16906252 is a key determinant in the onset of MGMT methylation in colorectal cancer, whereas the association of methylation at MGMT and CDKN2A suggests that these loci may be targets of a common mechanism of epigenetic dysregulation.

Second language acquisition/foreign language learning

Part 1 Some perspectives on SLA-FLL: theory and research in SLA and FLL - on producers and consumers what is foreign language research second and foreign language learning - same, different or none of the above models, processes, principles and strategies - second language acquisition in and out of the classroom. Part 2 Frameworks and approaches to research issues: Terence Odlin - word-order transfer, metalinguistics awareness and constraints on foreign language learning the acquisition of clitic pronouns in Spanish - two case studies, co-existing discourse worlds - the development of pragmatic competence in and outside the classroom foreign language learning - a social interaction and perspective on topic choice in oral proficiency assessment. Part 3 From research and theory to practice: second language acquisiton/foreign language learning, nothing is more practical than a good theory prefabricated speech for language learning a role for communicative competence and the acqusition/learning distinction in translator training can foreign language learning be like second language acquisition? - the curious case of immersion conservation of language resources.

Research and perspectives on processing instruction

This volume tracks the impact processing instruction has made since its conception. It provides an overview of new research trends on measuring the relative effects of processing instruction. Firstly, the authors explain processing instruction, both its main theoretical underpinnings as well as the guidelines for developing structured input practices. Secondly, they review the empirical research conducted, to date, so that readers have an overview of new research carried out on the effects of processing instruction. The authors finally reflect on the generalizability and limits of the research on processing instruction and offer future directions for processing instruction research.

The milestones in twenty years of processing instruction research

Abstract VanPatten and Cadierno (1993) published the first empirical investigation on the effects of processing instruction just over twenty years ago. This work inspired many, many more in subsequent years and continues to inspire research to this day, as evidenced by the studies gathered in this special edition. The purpose of this paper is to identify the milestones among the many processing instruction studies. Each study marks a significant development in the processing instruction research program.

Word Order and Linguistic Factors in the Second Language Processing of Spanish Passive Sentences

Abstract:The present study examines how second language learners (L2) assign the thematic roles of agent/patient in Spanish passive sentences with ser (often referred to as the true passive) when it is their initial exposure to this structure. The target sentences were preceded by a contextual sentence. After hearing the two sentences, participants were asked to identify the agent of the passive sentence. All the sentences were reversible, and other linguistic variables were manipulated. Variables that have been shown in other studies on other linguistic structures to promote correct thematic role assignment include: the number (singular/plural) of the agents and patients; the gender (masculine to feminine and feminine to masculine) of the agents and patients; and co-indexing of the grammatical subjects (1/2) in the context and target sentences. The quantitative analyses reveal that these native speakers of English, to varying degrees, assign thematic roles in passive sentences incorrectly. Furthermore, these learners show no sensitivity to number, gender, and co-referencing of grammatical subjects. None of the paired conditions promoted greater accuracy in assigning thematic roles. The results are discussed in terms of the First Noun Principle (VanPatten 2007) and the Canonical Alignment Hypothesis (Hyams et al. 2006).

Summary, conclusions, and recommendations for the practice of PI

This chapter summarises the findings of the empirical research presented in Chapters 3–5, and place it in the context of previous research on PI. Moreover, the pedagogical implications are extrapolated, focusing not only on delivering PI in classrooms and on computers, but on PI as part of a sequence of learning activities for grammar instruction that move learners from processing input to producing output.

Processing Instruction research: foci and findings

This chapter reviews the research conducted to date demonstrating a very consistent set of findings on the effects of PI and the elements of PI that cause those effects. In order to appreciate the breadth of the research base, the chapter begins with an account of the linguistic items that have been investigated.

The theory and practice of Processing Instruction

This chapter is formed of two parts: the theory and the practice of Processing Instruction. It has been pointed out that research in second language acquisition (SLA) has mainly been concerned with whether or not instruction has an effect on different aspects of language acquisition neglecting the fundamental questions of why and how instruction would make a difference in SLA.