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\"By documenting how voice synthesis developed over the course of the 20th century, as well as the cultural imagination that emerged around new talking machines as they were introduced, this book shows how synthetic voices index the complicated and sometimes paradoxical relationships that people have with increasingly lifelike digital technologies\"-- Provided by publisher.

We have seen longstanding research interest in diverse nature-society relations, including contentious debates regarding what nature is, the role of humans within or apart from it, and how varied types of non-human nature shape different societies and individuals within society. Within this work, relatively little attention has been paid to an important aspect of nature experienced everyday: people's \"weatherworlds.\" These encompass the qualities of sensory experience that are shaped by fluxes in the medium - the air - in which we routinely live and breathe. Such currents, forces and pressure gradients underwrite our capacities to act and interact with both the animate and inanimate materials and beings we encounter as we negotiate our everyday lives. We focus on these weather worlds here, drawing on the findings of an in-depth qualitative study exploring how people with varying forms and severities of sight impairment describe their nature experiences, with the weather emerging as an immediate and often highly visceral form of everyday nature encounter among all participants. We reflect on the ephemeral qualities of people's weatherworlds, highlighting their potential to comfort, invigorate and connect, but also to disorientate, threaten and isolate, at times supporting moments of well-being or exacerbating experiences of impairment and disability. In doing so, we highlight how attending to the weather is essential if we are to fully understand people's emplaced experiences of well-being, impairment and disability with(in) diverse forms of multi-elemental, assembled nature.

\"The government is a vast, complex system that Americans pay for, rebel against, rely upon, dismiss, and celebrate. It's also our shared resource for addressing the biggest problems of society. And it's made up of people, mostly unrecognized and uncelebrated, doing work that can be deeply consequential and beneficial to everyone. Michael Lewis invited his favorite writers to find someone doing an interesting job for the government and write about them in a special in-depth series for the Washington Post. The stories they found are unexpected, riveting, and inspiring, including a former coal miner devoted to making mine roofs less likely to collapse, saving thousands of lives; an IRS agent straight out of a crime thriller; and the manager who made the National Cemetery Administration the best-run organization, public or private, in the entire country. Each essay shines a spotlight on the essential behind-the-scenes work of exemplary federal employees. Whether they're digitizing archives, chasing down cybercriminals, or discovering new planets, these public servants are committed to their work and universally reluctant to take credit. Expanding on the Washington Post series, the vivid profiles in Who Is Government? blow up the stereotype of the irrelevant bureaucrat. They show how the essential business of government makes our lives possible, and how much it matters\"-- Provided by publisher.

The germinal centre (GC) is required for the generation of high affinity antibodies and immunological memory. Here we show that the RNA binding protein HuR has an essential function in GC B cells to sustain the GC response. In its absence, the GC reaction and production of high-affinity antibody is severely impaired. Mechanistically, HuR affects the transcriptome qualitatively and quantitatively. The expression and splicing patterns of hundreds of genes are altered in the absence of HuR. Among these genes, HuR is required for the expression of Myc and a Myc-dependent transcriptional program that controls GC B cell proliferation and Ig somatic hypermutation. Additionally, HuR regulates the splicing and abundance of mRNAs required for entry into and transition through the S phase of the cell cycle, and it modulates a gene signature associated with DNA deamination protecting GC B cells from DNA damage and cell death. Germinal centre (GC) responses may require RNA binding proteins (RBP) for post-transcriptional gene regulation. Here the authors show the RBP HuR supports GCs by promoting Myc and Myc-dependent transcription to enhance antigen-specific GC B cell selection and production of high affinity antibodies.

A growing evidence base highlights \"green\" and \"blue\" spaces as examples of \"therapeutic landscapes\" incorporated into people's lives to maintain a sense of well-being. A commonly overlooked dimension within this corpus of work concerns the dynamic nature of people's therapeutic place assemblages over time. This article provides these novel temporal perspectives, drawing on the findings of an innovative three-stage interpretive geonarrative study conducted in southwest England from May to November 2013, designed to explore the complex spatial-temporal ordering of people's lives. Activity maps produced using accelerometer and Global Positioning system (GPS) data were used to guide in-depth geonarrative interviews with thirty-three participants, followed by a subset of go-along interviews in therapeutic places deemed important by participants. Concepts of fleeting time, restorative time, and biographical time are used, alongside notions of individual agency, to examine participants' green and blue space experiences in the context of the temporal structures characterizing their everyday lives and the biographical experiences contributing to the perceived importance of such settings over time. In a culture that by and large prioritizes speed, dominated by social ideals of, for example, the productive worker and the good parent, participants conveyed a desire to shift from fleeting time to restorative time, seeking a balance between embodied stillness and therapeutic mobility. This was deemed particularly important during more stressful life transitions, such as parenthood, employment shifts, and the onset of illness or impairment, when participants worked hard to tailor their therapeutic geographies to shifting well-being needs and priorities.

[...] policies must be adopted to reduce carbon emissions and to increase carbon biosequestration, and thereby slow down global warming and eventually stabilise temperatures. [...] appropriate public health systems should be put into place to deal with adverse outcomes.

RNA binding proteins (RBP) of the ZFP36 family limit the differentiation and effector functions of CD4 and CD8 T cells, but little is known of their expression or function in regulatory T (Treg) cells. By using Treg cell-restricted deletion of Zfp36 family members we identify the role of Zfp36l1 and Zfp36l2 in Treg cells to maintain immune homeostasis. Mice with Treg cells deficient in these RBP display an inflammatory phenotype with an expansion in the numbers of type-2 conventional dendritic cells, T effector cells, T follicular helper and germinal center B cells and elevated serum cytokines and immunoglobulins. In the absence of Zfp36l1 and Zfp36l2 , the pool of cycling CTLA-4 in naïve Treg cells is reduced, Treg cells are less sensitive to IL-2 and IL-7 but are more sensitive to IFNγ. In mice lacking both RBP in Treg cells, the deletion of a single allele of Ifng is sufficient to ameliorate the pathology. Our results indicate that ZFP36L1 and ZFP36L2 regulate the availability of IFNγ and are required for the maintenance of Treg cell stability. Thus, ZFP36L1 and ZFP36L2 regulate multiple pathways that enable Treg cells to enforce immune homeostasis. RNA binding proteins have been shown to alter the function of various immune cells. Here the authors show that ZFP36-family RNA binding proteins play an important role in regulatory T cells to maintain immune cell homeostasis in mice by controlling DC, B and T cells.

Background In England, the national Government was responsible for balancing the risks of COVID-19 infection, transmission and illness against the known risks of school closures. The Department for Education (DfE) issued guidance to schools, however, there is limited empirical evidence on the experiences of staff and pupils affected by the guidance and accompanying COVID-19 mitigation measures. Methods This qualitative study explored secondary school staff and pupils’ views and experiences of COVID-19 guidance and mitigation measures. There were two main objectives: (i) to examine implementation effectiveness, and (ii) to explore their effectiveness at promoting safety. Participants were purposively sampled from English schools serving diverse communities participating in the CoMMinS (COVID-19 Mapping and Mitigation in Schools) study. Semi-structured interviews were conducted remotely, and data were analysed thematically. Results Interviews took place between January and August 2021 with participants from five secondary schools (20 staff and 25 pupils); staff represented a range of roles within the school and pupil demographics varied. Main themes were: (i) negative views of the DfE guidance; (ii) negative experiences of the DfE guidance; (iii) ineffectiveness of the DfE guidance and school mitigation measures at promoting safety and reducing risk; (iv) ineffective implementation of the mitigation measures due to poor adherence and acceptability (with sub-themes for Lateral Flow Testing (LFT), face coverings, physical distancing and ventilation); and (v) positive perceptions (with sub-themes for hygiene measures, and approaches that facilitated implementation and safety which included staff enforcing compliance, having an ethos of co-operation, addressing inconsistencies, and minimising change). Conclusions Insights from this research will help understand effectiveness of the measures in the ‘real-world school setting’. Understanding the experiences of staff and pupils will help to support policymakers and school leaders in future pandemic decision-making. This research identified challenges with the guidance and measures, minimal impact on perceived safety, and a negative impact on wellbeing. These challenges should be considered when assessing the benefit of the measures in keeping schools safe.

CD8 + T cell differentiation into effector cells is initiated early after antigen encounter by signals from the T cell antigen receptor and costimulatory molecules. The molecular mechanisms that establish the timing and rate of differentiation however are not defined. Here we show that the RNA binding proteins (RBP) ZFP36 and ZFP36L1 limit the rate of differentiation of activated naïve CD8 + T cells and the potency of the resulting cytotoxic lymphocytes. The RBP function in an early and short temporal window to enforce dependency on costimulation via CD28 for full T cell activation and effector differentiation by directly binding mRNA of NF-κB , Irf8 and Notch1 transcription factors and cytokines, including Il2 . Their absence in T cells, or the adoptive transfer of small numbers of CD8 + T cells lacking the RBP, promotes resilience to influenza A virus infection without immunopathology. These findings highlight ZFP36 and ZFP36L1 as nodes for the integration of the early T cell activation signals controlling the speed and quality of the CD8 + T cell response. RNA binding proteins (RBP) have a function in T cell activation and differentiation. Here the authors show that in the absence of two RBPs, ZFP36 and ZFP36L1, T cells acquire more rapidly superior effector capabilities, showing a limiting function for RBP in T cell activation and differentiation.

Teachers are at heightened risk of poor mental health and well-being, which is likely to impact on the support they provide to students, and student outcomes. We conducted a cluster randomised controlled trial, to test whether an intervention to improve mental health support and training for high school teachers led to improved mental health and well-being for teachers and students, compared to usual practice. We also conducted a cost evaluation of the intervention. The intervention comprised (i) Mental Health First Aid training for teachers to support students; (ii) a mental health awareness session; and (iii) a confidential staff peer support service. In total 25 mainstream, non-fee-paying secondary schools stratified by geographical area and free school meal entitlement were randomly allocated to intervention (n = 12) or control group (n = 13) after collection of baseline measures. We analysed data using mixed-effects repeated measures models in the intention-to-treat population, adjusted for stratification variables, sex, and years of experience. The primary outcome was teacher well-being (Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were teacher depression, absence, and presenteeism, and student well-being, mental health difficulties, attendance, and attainment. Follow-up was at months 12 (T1) and 24 (T2). We collected process data to test the logic model underpinning the intervention, to aid interpretation of the findings. A total of 1,722 teachers were included in the primary analysis. Teacher well-being did not differ between groups at T2 (intervention mean well-being score 47.5, control group mean well-being score 48.4, adjusted mean difference -0.90, 95% CI -2.07 to 0.27, p = 0.130). The only effect on secondary outcomes was higher teacher-reported absence among the intervention group at T2 (intervention group median number of days absent 0, control group median number of days absent 0, ratio of geometric means 1.04, 95% CI 1.00 to 1.09, p = 0.042). Process measures indicated little change in perceived mental health support, quality of relationships, and work-related stress. The average cost of the intervention was £9,103 per school. The study's main limitations were a lack of blinding of research participants and the self-report nature of the outcome measures. In this study, we observed no improvements to teacher or student mental health following the intervention, possibly due to a lack of impact on key drivers of poor mental health within the school environment. Future research should focus on structural and cultural changes to the school environment, which may be more effective at improving teacher and student mental health and well-being. www.isrctn.com ISRCTN95909211.