| 1. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 2. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Förster, Frank, et al.
(författare)
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Working with troubles and failures in conversation between humans and robots: workshop report
- 2023
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Ingår i: Frontiers in Robotics and AI. - : Frontiers Media SA. - 2296-9144. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- This paper summarizes the structure and findings from the first Workshop on Troubles and Failures in Conversations between Humans and Robots. The workshop was organized to bring together a small, interdisciplinary group of researchers working on miscommunication from two complementary perspectives. One group of technology-oriented researchers was made up of roboticists, Human-Robot Interaction (HRI) researchers and dialogue system experts. The second group involved experts from conversation analysis, cognitive science, and linguistics. Uniting both groups of researchers is the belief that communication failures between humans and machines need to be taken seriously and that a systematic analysis of such failures may open fruitful avenues in research beyond current practices to improve such systems, including both speech-centric and multimodal interfaces. This workshop represents a starting point for this endeavour. The aim of the workshop was threefold: Firstly, to establish an interdisciplinary network of researchers that share a common interest in investigating communicative failures with a particular view towards robotic speech interfaces; secondly, to gain a partial overview of the “failure landscape” as experienced by roboticists and HRI researchers; and thirdly, to determine the potential for creating a robotic benchmark scenario for testing future speech interfaces with respect to the identified failures. The present article summarizes both the “failure landscape” surveyed during the workshop as well as the outcomes of the attempt to define a benchmark scenario.
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| 5. |
- Gregoromichelaki, Eleni, et al.
(författare)
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Completability vs (In)completeness
- 2020
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Ingår i: Acta Linguistica Hafniensia. - : Informa UK Limited. - 0374-0463 .- 1949-0763. ; 52:2, s. 260-284
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Linguistic Circle of Copenhagen. In everyday conversation, no notion of “complete sentence” is required for syntactic licensing. However, so-called “fragmentary”, “incomplete”, and abandoned utterances are problematic for standard formalisms. When contextualised, such data show that (a) non-sentential utterances are adequate to underpin agent coordination, while (b) all linguistic dependencies can be systematically distributed across participants and turns. Standard models have problems accounting for such data because their notions of ‘constituency’ and ‘syntactic domain’ are independent of performance considerations. Concomitantly, we argue that no notion of “full proposition” or encoded speech act is necessary for successful interaction: strings, contents, and joint actions emerge in conversation without any single participant having envisaged in advance the outcome of their own or their interlocutors’ actions. Nonetheless, morphosyntactic and semantic licensing mechanisms need to apply incrementally and subsententially. We argue that, while a representational level of abstract syntax, divorced from conceptual structure and physical action, impedes natural accounts of subsentential coordination phenomena, a view of grammar as a “skill” employing domain-general mechanisms, rather than fixed form-meaning mappings, is needed instead. We provide a sketch of a predictive and incremental architecture (Dynamic Syntax) within which underspecification and time-relative update of meanings and utterances constitute the sole concept of “syntax”.
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| 8. |
- Healey, Patrick G. T., et al.
(författare)
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When Words Fail: Collaborative Gestures During Clarification Dialogues
- 2015
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Ingår i: Turn-Taking and Coordination in Human-Machine Interaction. Papers from the 2015 AAAI Spring Symposium, March 23–25 2015, Palo Alto, USA. - 9781577357117 ; , s. 23-29
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Konferensbidrag (refereegranskat)abstract
- Research on co-speech gestures has primarily focussed on speakers. However, in conversation non-speaking addressees can also gesture. Often this is to provide concurrent feedback such as backchannels but sometimes it involves gestures that relate to the specific content of the speaker's turn. We hypothesise that non-speakers should contribute most actively during clarification sequences i.e. at the moments when mutual-understanding is threatened. We test this hypothesis using a corpus of story-telling dialogues, captured using video and motion capture. The results show that during clarification sequences speaker and non-speaker behaviours tend to merge. Non-speakers in particular move their hands faster and produce more than twice as many content-specific specific gestures in overlap with speaker turns. These results underline the collaborative nature of conversation, the strategic importance of non-verbal resources for sustaining mutual-understanding and the critical role of clarification and repair in successful communication.
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| 16. |
- Lavelle, Mary, et al.
(författare)
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Are we having a laugh? Conversational laughter in schizophrenia
- 2018
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Ingår i: Proceedings of the Workshop on Dialogue and Perception, Gothenburg, 14–15 June 2018.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Social exclusion and social dysfunction are persistent and debilitating aspects of schizophrenia. The interactional impact of patients’ social deficits during actual dialogue is poorly understood. Through analysis of a corpus of patients’ triadic interactions we explored laughter as a marker of discomfort or coalition in patients’ interactions. Patient interactions did not differ from controls in terms of laughter production. However, patients who were more symptomatic laughed less frequently, while their partners showed a trend for displaying more shared laughter, potentially indicating coalition formation.
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| 17. |
- Lavelle, Mary, et al.
(författare)
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Token Gestures: Self-repair and Gesture in Schizophrenia
- 2015
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Ingår i: Language in context: An ecological guide to embodied language. Institute for Multimodal Communication, 10-11 January 2015, London, UK.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Lavia, Lisa, et al.
(författare)
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Non-participant observation methods for soundscape design and urban planning
- 2018
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Ingår i: Handbook of Research on Perception-Driven Approaches to Urban Assessment and Design / Aletta, Francesco, and Jieling Xiao (eds.). - Hershey, PA : IGI Global. - 9781522536376
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Bokkapitel (refereegranskat)abstract
- More accurate non-participatory parameters and psychoacoustics to assess human perceptual responses to the acoustic environment are critical to inform effective urban sound planning and applied soundscape practice. Non-participatory observation methods are widely used by experts to capture animal behavior. In 2012, Lavia and Witchel applied these principles and methodologies for the first time to capturing and assessing human behavior “in the wild” to changes to the acoustic environment using added sound and music interventions in a clubbing district. Subsequent work was conducted with Aletta and Kang and Healey, Howes, Steffens, and Fiebig to begin characterizing the acoustic environment and human responses to align the perceptual and physical findings. Here, the authors report on new work and analysis and propose a preliminary predictive agile applied soundscape framework using non-participatory observation methods and psychoacoustics to be used with environmental assessment practice and evolving urban soundscape planning methods by researchers, practitioners, and policy makers.
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| 19. |
- Martrat, Griselda, et al.
(författare)
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Exploring the link between MORF4L1 and risk of breast cancer
- 2011
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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| 20. |
- Purver, Matthew, et al.
(författare)
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Split Utterances in Dialogue: A Corpus Study
- 2009
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Ingår i: Proceedings of the 10th Annual SIGDIAL Meeting on Discourse and Dialogue (SIGDIAL 2009 Conference). - London, UK : Association for Computational Linguistics. - 9781932432640 ; , s. 262-271
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Konferensbidrag (refereegranskat)
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