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\"Gesture in Multiparty Interaction confronts the competing views that exist regarding gesture's relationship to language. In this work, Emily Shaw examines embodied discourses in American Sign Language and spoken English and seeks to establish connections between sign language and co-speech gesture. By bringing the two modalities together, Shaw illuminates the similarities between certain phenomena and presents a unified analysis of embodied discourse that more clearly captures gesture's connection to language as a whole. Shaw filmed Deaf and hearing participants playing a gesture-based game as part of a social game night. Their interactions were then studied using discourse analysis to see whether and how Deaf and hearing people craft discourses through the use of their bodies. This volume examines gesture, not just for its iconic, imagistic qualities, but also as an interactive resource in signed and spoken discourse. In addition, Shaw addresses the key theoretical barriers that prevent a full accounting of gesture's interface with signed and spoken language. Her study pushes further the notion that language is fundamentally embodied\"-- Provided by publisher.

Ocean acidification leads to changes in marine carbonate chemistry that are predicted to cause a decline in future coral reef calcification. Several laboratory and mesocosm experiments have described calcification responses of species and communities to increasing CO2. The few in situ studies on natural coral reefs that have been carried out to date have shown a direct relationship between aragonite saturation state (Ωarag) and net community calcification (Gnet). However, these studies have been performed over a limited range of Ωarag values, where extrapolation outside the observational range is required to predict future changes in coral reef calcification. We measured extreme diurnal variability in carbonate chemistry within a reef flat in the southern Great Barrier Reef, Australia. Ωarag varied between 1.1 and 6.5, thus exceeding the magnitude of change expected this century in open ocean subtropical/tropical waters. The observed variability comes about through biological activity on the reef, where changes to the carbonate chemistry are enhanced at low tide when reef flat waters are isolated from open ocean water. We define a relationship between net community calcification and Ωarag, using our in situ measurements. We find net community calcification to be linearly related to Ωarag, while temperature and nutrients had no significant effect on Gnet. Using our relationship between Gnet and Ωarag, we predict that net community calcification will decline by 55% of its preindustrial value by the end of the century. It is not known at this stage whether exposure to large variability in carbonate chemistry will make reef flat organisms more or less vulnerable to the non‐calcifying physiological effects of increasing ocean CO2 and future laboratory studies will need to incorporate this natural variability to address this question. Key Points Coral reef community calcification is related to seawater carbonate chemistry We show this using in situ data, giving insight into ocean acidification impacts We predict end‐century calcification will be 55% lower than the preindustrial value

\"Utilizing 1,150 sign illustrations and historical texts, this reference presents the detailed account of the origins of more than 500 ASL signs, including regional variations\"-- Provided by publisher.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD). Trajectory inference identifies three phases of control tissue fibroblast activation, leading to myofibroblast enrichment in tumour samples: initial upregulation of inflammatory cytokines, followed by stress-response signalling and ultimately increased expression of fibrillar collagens. Myofibroblasts correlate with poor overall survival rates in LUAD, associated with loss of epithelial differentiation, TP53 mutations, proximal molecular subtypes and myeloid cell recruitment. In squamous carcinomas myofibroblasts were not prognostic despite being transcriptomically equivalent. These findings have important implications for developing fibroblast-targeting strategies for cancer therapy. Fibroblast heterogeneity is a prominent but poorly understood feature of solid tumours. Here three major fibroblast subpopulations in non-small cell lung cancer are identified and characterised through single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry.

Understanding how social media platforms facilitate information exchange and influence behavior during health crises can enhance public health responses during times of uncertainty. While some risk factors for COVID-19 susceptibility and severity (eg, old age) were clear, whether e-cigarette use increased risk was not clear. People who used e-cigarettes had to navigate both the COVID-19 infodemic and a conflicting, politicized, and changing information environment about the interaction between COVID-19 and e-cigarette use. This study aims to characterize and contextualize e-cigarette-related behavior changes during the early COVID-19 pandemic and illuminate the role that social media played in decision-making. We conducted a qualitative analysis of COVID-19-related e-cigarette discussions on 3 Reddit forums about e-cigarettes. We collected 189 relevant discussion threads made in the first 6 months of the pandemic (collected from June 27, 2020, to July 3, 2020). Threads included 3155 total comments (mean 17 comments) from approximately 1200 unique Redditors. We developed and applied emergent codes related to e-cigarette perceptions and behaviors (eg, the role of nicotine in COVID-19 and do-it-yourself narratives) and web-based community interactions (eg, advice), identified thematic patterns across codes, and developed a model to synthesize the socioecological context of e-cigarette behaviors. e-Cigarette subreddits provided a platform for Redditors to discuss perceptions and experiences with e-cigarettes, make sense of information, and provide emotional support. Discussions reflected an array of e-cigarette-related behavioral responses, including increases and decreases in use intensity, changes in purchasing practices (eg, stockpiling), and changes in vaping practices (eg, reusing disposable pods). This study presented a theoretically and empirically informed model of how circumstances created by the pandemic (eg, changes in activity space and product shortages) compelled behavior changes. Redditors drew from their existing perceptions, intentions, and experiences with nicotine and tobacco products; their personal pandemic experiences; and their participation on Reddit to decide whether and how to change their e-cigarette behaviors during the early pandemic. Forums reflected uncertainty, stress, and debate about the rapidly evolving and complicated public health information. Consumption and discussion of media (eg, news articles and peer-reviewed publications) on Reddit informed e-cigarette perceptions and behaviors. Decisions were complicated by distrust of the media. Variations in individual traits and environmental circumstances during the early COVID-19 pandemic provide context for why there was no unified direction of e-cigarette behavior change during this period. Information and discussion on Reddit also informed risk perceptions and decisions during the pandemic. Social media is an effective and important place to communicate public health information, particularly during crisis or disaster situations. Moving forward, transparent, accurate, and specific message development should consider the stress, struggles, and stigma of people who use e-cigarettes and address the roles mistrust and misinformation play in decisions.

This study dives into the interactive functions of the palm-up across four language ecologies drawing on comparable corpus data from American Sign Language (ASL)-American English and French Belgian Sign Language (LSFB)-Belgian French. While researchers have examined palm-up in many different spoken and signed language contexts, they have primarily focused on the canonical forms and its epistemic variants. Work that directly compares palm-up across modalities and language ecologies remains scarce. This study addresses such gaps by documenting all instances of the palm approaching supination in four language ecologies to analyze its interactive functions cross-linguistically and cross-modally. Capitalizing on an existing typology of interactive gestures, palm-up annotations were conducted using ELAN on a total sample of 48 participants interacting face-to-face in dyads. Findings highlight the multifunctional nature of palm-up in terms of conversational dynamics with cross-modal differences in the specific interactive use of palm-up between spoken and signed language contexts. These findings underscore the versatility of the palm-up and reinforce its role in conversational dynamics as not merely supplementary but integral to human interaction.

BackgroundCurrent immunotherapies still have limited successful rates among cancers. It is now recognized that T cell functional state in the tumor microenvironment (TME) is a key determinant for effective antitumor immunity and immunotherapy. In addition to exhaustion, cellular senescence in tumor-infiltrating T cells (TILs) has recently been identified as an important T cell dysfunctional state induced by various malignant tumors. Therefore, a better understanding of the molecular mechanism responsible for T cell senescence in the TME and development of novel strategies to prevent effector T cell senescence are urgently needed for cancer immunotherapy.MethodsSenescent T cell populations in the TMEs in mouse lung cancer, breast cancer, and melanoma tumor models were evaluated. Furthermore, T cell senescence induced by mouse tumor and regulatory T (Treg) cells in vitro was determined with multiple markers and assays, including real-time PCR, flow cytometry, and histochemistry staining. Loss-of-function strategies with pharmacological inhibitors and the knockout mouse model were used to identify the potential molecules and pathways involved in T cell senescence. In addition, melanoma mouse tumor immunotherapy models were performed to explore the synergistical efficacy of antitumor immunity via prevention of tumor-specific T cell senescence combined with anti-programmed death-ligand 1 (anti-PD-L1) checkpoint blockade therapy.ResultsWe report that both mouse malignant tumor cells and Treg cells can induce responder T cell senescence, similar as shown in human Treg and tumor cells. Accumulated senescent T cells also exist in the TME in tumor models of lung cancer, breast cancer and melanoma. Induction of ataxia-telangiectasia mutated protein (ATM)-associated DNA damage is the cause for T cell senescence induced by both mouse tumor cells and Treg cells, which is also regulated by mitogen-activated protein kinase (MAPK) signaling. Furthermore, blockages of ATM-associated DNA damage and/or MAPK signaling pathways in T cells can prevent T cell senescence mediated by tumor cells and Treg cells in vitro and enhance antitumor immunity and immunotherapy in vivo in adoptive transfer T cell therapy melanoma models. Importantly, prevention of tumor-specific T cell senescence via ATM and/or MAPK signaling inhibition combined with anti-PD-L1 checkpoint blockade can synergistically enhance antitumor immunity and immunotherapy in vivo.ConclusionsThese studies prove the novel concept that targeting both effector T cell senescence and exhaustion is an effective strategy and can synergistically enhance cancer immunotherapy.

Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.

The Expanded Student Engagement Project (ESE) has developed three comprehensive inventories which aim to increase student knowledge of sustainability-related course content and increase student engagement in on- and off-campus, curricular, and non-curricular sustainability projects at the University of Toronto (U of T). The first is a sustainability course inventory (SCI) generated using keyword search based on the UN Sustainable Development Goals (SDGs). This is the first SCI that has been based on the SDGs. The inventory identified 2022 unique sustainability courses and found that SDG 13 had the greatest representation and SDG 6 had the least. The second inventory is a community-engaged learning (CEL) sustainability inventory which found 154 sustainability-focused CEL courses and identified 86 faculty members who teach sustainability CEL. Finally, an inventory of sustainability co-curricular and extracurricular opportunities revealed that U of T has 67 sustainability-focused student groups and identified 263 sustainability-focused opportunities. These inventories are an important foundation for future initiatives to increase student engagement in sustainability on campus and in the community. The ESE will integrate this data into U of T’s course management system and use the inventories to develop a new sustainability pathways program.

The MGH–USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH–USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU–Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH–Harvard–USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH–USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography. •Ultra high b-value diffusion MRI data were acquired on the MGH–USC CONNECTOM scanner.•We provided information about data access and the data sharing repositories.•We described the imaging protocols and data pre-processing steps in details.•We demonstrated diffusion data quality using q-ball ODF and streamline tractography.