Exploring Response Tokens in Irish English - A Multidisciplinary Approach:Integrating Variational Pragmatics, Sociolinguistics and Corpus Linguistics?

Schneider &amp; Barron (2008) discuss the effect of macro-social factors such as region, ethnic background, age, social status and gender on intra-lingual pragmatic conventions, and state that, to date, they have received comparatively little attention in the study of pragmatics. This paper chooses two macro-social factors, age and gender, and focuses on how they impact on the use of response tokens in Irish English. Not only does the paper shed light on the use of variational pragmatics as a framework for corpus-based studies but it also brings together research on sociolinguistics and corpus linguistics, which has, to-date, been scarce (Baker 2010). The paper reveals the importance of avoiding the exploration of sociolinguistic variables in isolation and concludes by highlighting the importance of interdisciplinary research and the merits of fine-grained sociolinguistic investigations using small corpora.</jats:p

Exploring the construction of the Irish Mammy in ‘Mrs Brown’s Boys’:Making and breaking the stereotype

This paper explores how the cultural concept of the Irish Mammy is portrayed in the popular television comedy series \u27Mrs Brown\u27s Boys\u27. Considering the historicity and cultural aspects surrounding essential views of Irishness that have shaped the archetype of the stereotype, we draw on a corpus of (semi) scripted fictional interaction taken from the series. Using a Corpus Assisted Discourse Studies (CADS) approach to explore linguistic patterning surrounding the use of key lexical markers (e.g. Mammy), we investigate what they reveal about how the concept is represented, (de) constructed, and negotiated. The paper discusses the construction and deconstruction of the stereotype and the extent to which it draws on shared knowledge to reflect and navigate particular cultural values and concerns (Hall 1997; Hall et al. 2013). It views the deconstruction, in particular, as a way of challenging the traditional stereotype, in light of societal change, to provide a more layered, realistic and multi-faceted insight into the identities of the Irish Mammy figure within the fictional context of Mrs Brown\u27s Boys

Corpus types and uses

status: publishe

The Apoptosome Pathway to Caspase Activation in Primary Human Neutrophils Exhibits Dramatically Reduced Requirements for Cytochrome c

Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the “apoptosome” as a result of the cell stress–associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain. This prompted us to examine whether neutrophils retain an intact cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) pathway to caspase activation and apoptosis. We show that primary human neutrophils contain barely detectable levels of cytochrome c as well as other mitochondrial proteins. Surprisingly, neutrophil cell–free extracts readily supported Apaf-1–dependent caspase activation, suggesting that these cells may assemble cytochrome c–independent apoptosomes. However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1–dependent caspase activation in these cells. Thus, neutrophils have a lowered threshold requirement for cytochrome c in the Apaf-1–dependent cell death pathway. These observations suggest that neutrophils retain cytochrome c for the purpose of assembling functional apoptosomes rather than for oxidative phosphorylation

Predicting the cell death responsiveness and sensitization of glioma cells to TRAIL and temozolomide.

Genotoxic chemotherapy with temozolomide (TMZ) is a mainstay of treatment for glioblastoma (GBM); however, at best, TMZ provides only modest survival benefit to a subset of patients. Recent insight into the heterogeneous nature of GBM suggests a more personalized approach to treatment may be necessary to overcome cancer drug resistance and improve patient care. These include novel therapies that can be used both alone and with TMZ to selectively reactivate apoptosis within malignant cells. For this approach to work, reliable molecular signatures that can accurately predict treatment responsiveness need to be identified first. Here, we describe the first proof-of-principle study that merges quantitative protein-based analysis of apoptosis signaling networks with data- and knowledge-driven mathematical systems modeling to predict treatment responsiveness of GBM cell lines to various apoptosis-inducing stimuli. These include monotherapies with TMZ and TRAIL, which activate the intrinsic and extrinsic apoptosis pathways, respectively, as well as combination therapies of TMZ+TRAIL. We also successfully employed this approach to predict whether individual GBM cell lines could be sensitized to TMZ or TRAIL via the selective targeting of Bcl-2/Bcl-xL proteins with ABT-737. Our findings suggest that systems biology-based approaches could assist in personalizing treatment decisions in GBM to optimize cell death induction

Activation of executioner caspases is a predictor of progression-free survival in glioblastoma patients: a systems medicine approach.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. GBM cells are highly resistant to apoptosis induced by antitumor drugs and radiotherapy resulting in cancer progression. We assessed whether a systems medicine approach, analysing the ability of tumor cells to execute apoptosis could be utilized to predict the response of GBM patients to treatment. Concentrations of the key proapoptotic proteins procaspase-3, procaspase-9, Smac and Apaf-1 and the antiapopotic protein XIAP were determined in a panel of GBM cell lines and GBM patient tumor resections. These values were used as input for APOPTO-CELL, a systems biological based mathematical model built to predict cellular susceptibility to undergo caspase activation. The modeling was capable of accurately distinguishing between GBM cells that die or survive in response to treatment with temozolomide in 10 of the 11 lines analysed. Importantly the results obtained using GBM patient samples show that APOPTO-CELL was capable of stratifying patients according to their progression-free survival times and predicted the ability of tumor cells to support caspase activation in 16 of the 21 GBM patients analysed. Calculating the susceptibility to apoptosis execution may be a potent tool in predicting GBM patient therapy responsiveness and may allow for the use of APOPTO-CELL in a clinical setting

Investigations on apoptosis-associated caspase activation cascades

THESIS 7441Apoptosis is an important process in a wide variety of different biological systems such as the immune system, normal cell turnover and embryonic development (Stennicke et al., 2002). Apoptosis is characterized by a series of distinct morphological and biochemical alterations such as DNA fragmentation, chromatin condensation, cell shrinkage and membrane blebbing (Adrain and Martin, 2001). In mammalian systems, the core component of the death machinery responsible for these stereotypic changes is a family of proteases known as caspases (Earnshaw et al., 1999). The mammalian caspases may be divided into two broad subfamilies, the caspase-1 subfamily and the CED-3 subfamily. The CED-3 subfamily includes caspases -2, -3, -6, -7, -8, -9 and -10. These caspases are directly involved in apoptosis (Earnshaw et al., 1999; Lamkanfi et al., 2002). The research outlined in this thesis addresses these apoptotic caspases and in particular, the mechanisms governing the activation and regulation of these key proteases