Demonstratives play an important role in communication. Traditional analyses of demonstratives focused primarily on their morphology, semantics, syntax, and to some extent, on their diachrony and acquisition. Based on a 257,000-character conversational database, this dissertation examines how na ‘that’ can shift from marking spatial deixis to signaling the speaker’s stance in Mandarin Chinese conversation by linking discourse-pragmatic analysis with interactional actions. More specifically, it identifies 1) functions of na and the relative frequencies of its different usages; 2) contexts in which na typically appears and reasons speakers use na in those contexts; 3) interrelations among different usages; and 4) functional preference of na across positions within a turn.The results show that exophoric use is very much marginalized in natural conversation (2 tokens out of 1261 tokens, 0.2%). The predominant referential na is used as a discourse deictic (315 tokens out of 1261 tokens, 25.0%). Anaphoric na is relatively frequent (191 tokens out of 1261 tokens, 15.1%), with its most salient occurrence appearing in medial position of an utterance (75 tokens). The previous understudied recognitional use is by no means sparse (98 tokes out of 1261 tokens, 7.8%). I show that recognitional na is not restricted to contexts where a referent is identifiable based on specific knowledge or shared common ground between the speaker and the addressee. The speaker routinely makes use of recognitional na even when he/she knows that the referent is discourse new and hearer new. I argue that in contexts like this, the speaker employs recognitional na as an interpersonal strategy to establish a solidarity between himself/herself and the addressee and create an in-group perspective to better engage the addressee in the conversation. The non-referential na (655 tokens out of 1261 tokens, 51.9%) on the other hand, is routinely used by speakers to express contrastive meaning, encode attitudinal stances that are often disaffiliative, taking the form of disagreements, challenges, or criticisms. More specifically, I propose three functional categories of non-referential na: i) initiating a question (186 tokens out 1261 tokens, 14.8%); ii) indexing a disaffiliative stance (179 tokens out of 1261 tokens, 14.2%); and iii) projecting a question or a disaffiliative stance (130 tokens out of 1261 tokens, 10.3%). The analysis also indicates that these interactional functions of non-referential na are linked to the distal demonstrative’s deictic meanings in the sense that the na-prefaced turn indexes that the current turn is built from a prior turn but displays a shift in focus and often a contrastive or disaffiliative stance. With respect to functional preference of na across positions within a turn, the results demonstrate that na tends to serve to register a turn that embodies contrastive information or disaffiliative stance in response to a prior turn in turn-initial position. In medial position within an utterance, na functions to keep track of and orient the addressee’s attention to an element of the ongoing discourse. In medial position inside a turn, an utterance-initial na does not show a functional preference; it either is used to track a referent or to signal contrastive information/disaffiliative stance.

Background: Hypoxia inducible factor 1(HIF-1) and microRNAs (miRNAs) regulate transcriptional activities and contribute in several biological processes such as oxygen homeostasis, cell growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer etiology and outcomes. Nonetheless, there are few published studies of the relationship between HIF-1 and miRNA gene polymorphisms and susceptibility and survival of lung cancer or UADT cancers. Methods: 1,212 cancer patients (611 lung, 303 oral, 100 pharyngeal, 90 laryngeal, and 108 esophageal) and 1040 population controls were included and the cases were followed for a median duration of 11 years. We genotyped 18 single nucleotide polymorphisms (SNPs) using Fluidigm Dynamic 96.96 Array Assay--two from HIF-1, seven from the miRNA biogenesis pathway, two from hypoxia regulated miRNAs and seven from miRNA target genes--and investigated their associations with lung and UADT cancer risk with logistic regression and survival using Cox regression. We explored interactions between selected SNPs and established environmental risk factors. A semi-Bayesian shrinkage approach was used to reduce the potential false positive findings caused by multiple comparisons and small sample sizes. Results: The minor allele carriers CT+TT (vs. CC) of RAN rs14035 was associated with lung cancer development (posterior aOR=1.28, 95% posterior limits=1.00, 1.63), especially with non-small cell lung cancer (NSCLC); and associated with esophageal squamous carcinoma (SQC) susceptibility (posterior aOR=1.81, 95% posterior limits=1.07, 3.07). It was inversely associated with NSCLC death (posterior aHR=0.74, 95% posterior limits=0.59, 0.93). The minor allele carriers AC+CC (vs. AA) of XPO5 rs11077 presented inverse association with UADT cancer risk (posterior aOR=0.75, 95% posterior limits=0.58, 0.96), especially with UADT SQC and oral and oropharyngeal SQC; and its minor homozygote CC (vs. AA+AC) was inversely related to lung cancer mortality (posterior aHR=0.67, 95% posterior limits=0.51, 0.89), which was pronounced in NSCLC. The minor allele carriers CG+GG (vs. CC) of GEMIN4 rs2740348 were inversely related to UADT SQC susceptibility (posterior aOR=0.75, 95% posterior limits=0.57, 1.00) and associated with increased mortality of lung cancer (posterior aHR=1.28, 95% posterior limits =1.01, 1.62). In the Caucasian-only population, we repeatedly observed the inverse association between XPO5 rs11077 CC (vs. AA+AC) and lung cancer mortality; and the association between GEMIN4 rs2740348 CG+GG (vs. CC) and lung cancer death. Conclusion: Our findings suggested that single nucleotide polymorphisms (SNPs) of miRNA processing and maturation relevant genes played an important role in cancer development and progression; due to the population heterogeneity, their influence in the cancer pathophysiology need further investigations.

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