145 research outputs found
How to solve a complex verbal task: Text structure, referential movement and the quaestio
Grammatical aspect influences motion event perception: Evidence from a cross-linguistic non-verbal recognition task
Using eye-tracking as a window on cognitive processing, this study investigates language effects on attention to motion events in a non-verbal task. We compare gaze allocation patterns by native speakers of German and Modern Standard Arabic (MSA), two languages that differ with regard to the grammaticalization of temporal concepts. Findings of the non-verbal task, in which speakers watch dynamic event scenes while performing an auditory distracter task, are compared to gaze allocation patterns which were obtained in an event description task, using the same stimuli. We investigate whether differences in the grammatical aspectual systems of German and MSA affect the extent to which endpoints of motion events are linguistically encoded and visually processed in the two tasks. In the linguistic task, we find clear language differences in endpoint encoding and in the eye-tracking data (attention to event endpoints) as well: German speakers attend to and linguistically encode endpoints more frequently than speakers of MSA. The fixation data in the non-verbal task show similar language effects, providing relevant insights with regard to the language-and-thought debate. The present study is one of the few studies that focus explicitly on language effects related to grammatical concepts, as opposed to lexical concepts
Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia
Pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) exhibit favorable survival rates. However, for AML and ALL patients carrying KMT2A gene translocations clinical outcome remains unsatisfactory. Key players in KMT2A-fusion-driven leukemogenesis include menin and DOT1L. Recently, menin inhibitors like revumenib have garnered attention for their potential therapeutic efficacy in treating KMT2A-rearranged acute leukemias. However, resistance to menin inhibition poses challenges, and identifying which patients would benefit from revumenib treatment is crucial. Here, we investigated the in vitro response to revumenib in KMT2A-rearranged ALL and AML. While ALL samples show rapid, dose-dependent induction of leukemic cell death, AML responses are much slower and promote myeloid differentiation. Furthermore, we reveal that acquired resistance to revumenib in KMT2A-rearranged ALL cells can occur either through the acquisition of MEN1 mutations or independently of mutations in MEN1. Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia.</p
Identity management strategies among HIV-positive Colombian gay men in London
This study set out to explore the social-psychological aspects of living with HIV among a group of HIV-positive Colombian gay men in London, and the strategies that they deployed to manage ensuing threats to their identities. Focus group and individual interview data were collected from 14 Colombian gay men living with HIV, and were analysed using qualitative thematic analysis and identity process theory. The following themes are discussed: (1) identity struggles and conflicts in Colombia, (2), managing multiple layers of social stigma in England, and (3) changing interpersonal and intergroup dynamics, which highlight the inter-connections between sexual prejudice, sexual risk-taking and HIV stigma. Identity may be chronically threatened due to the multiple layers of stigma, which can limit the coping strategies available to individuals. Findings strongly support the need for action and programmes to highlight and tackle both racism and HIV stigma on the gay scene and to fund more specific resources for sub-communities of gay, bisexual and other men who have sex with men, which employ appropriately trained and culturally competent staff
Cell-Free DNA as a Diagnostic and Prognostic Biomarker in Pediatric Rhabdomyosarcoma.
PURPOSE: Total cell-free DNA (cfDNA) and tumor-derived cfDNA (ctDNA) can be used to study tumor-derived genetic aberrations. We analyzed the diagnostic and prognostic potential of cfDNA and ctDNA, obtained from pediatric patients with rhabdomyosarcoma. METHODS: cfDNA was isolated from diagnostic plasma samples from 57 patients enrolled in the EpSSG RMS2005 study. To study the diagnostic potential, shallow whole genome sequencing (shWGS) and cell-free reduced representation bisulphite sequencing (cfRRBS) were performed in a subset of samples and all samples were tested using droplet digital polymerase chain reaction to detect methylated RASSF1A (RASSF1A-M). Correlation with outcome was studied by combining cfDNA RASSF1A-M detection with analysis of our rhabdomyosarcoma-specific RNA panel in paired cellular blood and bone marrow fractions and survival analysis in 56 patients. RESULTS: At diagnosis, ctDNA was detected in 16 of 30 and 24 of 26 patients using shallow whole genome sequencing and cfRRBS, respectively. Furthermore, 21 of 25 samples were correctly classified as embryonal by cfRRBS. RASSF1A-M was detected in 21 of 57 patients. The presence of RASSF1A-M was significantly correlated with poor outcome (the 5-year event-free survival [EFS] rate was 46.2% for 21 RASSF1A-M‒positive patients, compared with 84.9% for 36 RASSF1A-M‒negative patients [P < .001]). RASSF1A-M positivity had the highest prognostic effect among patients with metastatic disease. Patients both negative for RASSF1A-M and the rhabdomyosarcoma-specific RNA panel (28 of 56 patients) had excellent outcome (5-year EFS 92.9%), while double-positive patients (11/56) had poor outcome (5-year EFS 13.6%, P < .001). CONCLUSION: Analyzing ctDNA at diagnosis using various techniques is feasible in pediatric rhabdomyosarcoma and has potential for clinical use. Measuring RASSF1A-M in plasma at initial diagnosis correlated significantly with outcome, particularly when combined with paired analysis of blood and bone marrow using a rhabdomyosarcoma-specific RNA panel
An outline of an asymmetric two-component theory of aspect
The paper presents the bases of an asymmetric two-component model of aspect. The main theoretical conclusion of the study is that (grammatical) viewpoint aspect and situation aspect are not independent aspectual levels, since the former often modifies the input situation aspect of the phrase/sentence. As it is shown, besides the arguments and adjuncts of the predicate, viewpoint aspect is also an important factor in compositionally marking situation aspect. The aspectual framework put forward in the paper is verified and illustrated on the basis of the aspectual system of Hungarian and some examples taken from English linguistic data
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The role of statistical learning in the acquisition of motion event construal in a second language
Learning to talk about motion in a second language is very difficult because it involves restructuring deeply entrenched patterns from the first language (Slobin 1996). In this paper we argue that statistical learning (Saffran et al. 1997) can explain why L2 learners are only partially successful in restructuring their second language grammars. We explore to what extent L2 learners make use of two mechanisms of statistical learning, entrenchment and pre-emption (Boyd and Goldberg 2011) to acquire target-like expressions of motion and retreat from overgeneralisation in this domain. Paying attention to the frequency of existing patterns in the input can help learners to adjust the frequency with which they use path and manner verbs in French but is insufficient to acquire the boundary crossing constraint (Slobin and Hoiting 1994) and learn what not to say. We also look at the role of language proficiency and exposure to French in explaining the findings
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