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LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration
Get PDFAbstract Cancer cells’ ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage.</jats:p
Exploring the Impact of Visual Aids on Engagement in Gamified Text Annotation
Get PDFNatural Language Processing (NLP) relies on large amounts of annotated data, traditionally gathered through small expert groups or paid crowdsourcing. Games With A Purpose (GWAPs) offer a more engaging alternative by embedding annotation tasks within playful environments. However, effectively motivating players and maintaining data quality in text-based GWAPs is challenging, especially when tasks can be laborious. This thesis investigates whether visual aids - ranging from animations in the onboarding phase to AI-generated images and emojis during gameplay - can enhance engagement in gamified text-annotation tasks. Comparisons of text-based and animated onboarding designs reveal that visual aids in introductions improve engagement without negatively affecting data quality. Meanwhile, presenting AI-generated images may be unnecessary in gamified NLP tasks (part-of-speech tagging and natural language inference), as they can overwhelm players. An alternative approach is to incorporate visuals during a puzzle break rather than during the annotation phase. A study on a word-sense disambiguation task demonstrated that emojis present during puzzle breaks benefit novice players, although expert annotators often find these features superfluous. Collectively, these findings highlight the value of carefully aligning visual elements with task complexity and user preferences, offering practical insights for designing engaging GWAPs for NLP
Key factors influencing post-diagnostic support and care planning for people with dementia from South Asian backgrounds: a systematic review of qualitative studies.
Get PDFBACKGROUND: Dementia in minority ethnic groups is on the rise. South Asian people represent 9.3% of the UK population and are the largest minority ethnic (ME) group. Most dementia care in South Asian communities is provided at home by family carers, yet there is low uptake of care planning and post-diagnostic support services. This review explored factors influencing care planning and post-diagnostic support for South Asian people with dementia. METHODS: Systematic review and thematic synthesis of qualitative studies exploring care planning and post-diagnostic support experiences and views of South Asian people with dementia, family carers, and health and social care professionals (HSCPs). There were no limits on country or date of publication. Six databases were searched (inception - June 2024) and two reviewers independently screened and quality-appraised studies. Reflexive thematic analysis was used to generate themes, which were then mapped to the Socioecological Model. The review protocol was registered on PROSPERO [Registration number: CRD42023404125]. RESULTS: From 3165 studies found, 2069 were screened (after de-duplication) and 24 studies were included for thematic synthesis. Key influential factors were mapped to one of four levels of a modified version of the Socio-ecological Model (SEM): (1) Individual and community level factors - cultural duty for home care, stigma and misinformation, support networks; (2) Interpersonal level factors - language barriers and person- and family-centred care; (3) Organisational and systems level factors - lack of integrated support, cultural competence, system pressures and institutional discrimination; (4) Structural level factors - socioeconomic and policy considerations. CONCLUSIONS: Recommendations to improve dementia care planning and post-diagnostic support for South Asian communities include (1) Reframing narratives around dementia and help-seeking through culturally-tailored community interventions; (2) Culturally competent, person- and family-centred care; (3) Holistic and integrated support beyond clinical care; (4) Equitable partnership working with South Asian communities to co-produce dementia services
Cathodoluminescence spectroscopy of triplet excitons in organic emitters
Get PDFAbstract Singlet and triplet excited-state energies are fundamental to a variety of processes and applications of organic semiconductors, such as singlet fission, triplet-triplet annihilation, and thermally activated delayed fluorescence. Measuring the triplet energy via traditional optical methods is often challenging though, due to spin selection rules governing these excited states following optical excitation. Here we examine cathodoluminescence (CL) spectroscopy in an electron microscope as a candidate to circumvent these challenges. Both singlet and triplet luminescence bands are observed in a single continuous wave CL spectrum, as the electron beam directly excites singlets alongside plasmons that decay into electron-hole pairs forming triplets. This process removes the need for intersystem crossing to generate triplet excitons in the emitter itself. It is estimated that on average 10 4 plasmon decay events are required to form a single exciton. The mechanism is in principle similar to electroluminescence as in OLED devices, with CL also allowing the target material to be investigated in its native state (or dilute in insulating media) without electrical biasing or adjacent transport layers. We propose that CL is potentially a powerful technique for organic semiconductor characterisation, although not yet capable of resolving triplet emission from more challenging emitters. Care must also be taken to minimise electron beam damage, since the luminescence from singlets is preferentially quenched, due to a longer diffusion length compared to triplets at room temperature.</jats:p
