Notes

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We validated this association between autonomous signaling and enhanced function in several CAR constructs and, on the basis of these observations, designed a new short-linker CD22 single-chain variable fragment for clinical evaluation. Our findings both suggest that tonic 4-1BB-based signaling is beneficial to CAR function and demonstrate the utility of bedside-to-bench-to-bedside translation in the design and implementation of CAR T cell therapies.Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161+CD4+ T cells and interferon-γ production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4+ T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.Thin-film architectures are a staple in a wide range of technologies, such as semiconductor devices, optical coatings, magnetic recording, solar cells and batteries. Despite the industrial success of thin-film technology, mostly due to the easy fabrication and low cost, a fundamental drawback remains it is challenging to alter the features of the film once fabricated. Angiogenesis inhibitor Here we report a methodology to modify the thickness and sequence of the innermost solid-state thin-film layers. We start with a thin-film stack of amorphous iron oxide and silver. By applying a suitable voltage bias and then reversing it, we can float the silver layer above or below the oxide layer by virtue of the migration of silver atoms. Scanning transmission electron microscopy reveals various sequences and thicknesses of the silver and oxide layers achieved with different experimental conditions. As a proof-of-principle, we show a dynamic change of structural colours of the stack derived from this process. Our results may offer opportunities to dynamically reconfigure thin-film-based functional nanodevices in situ.Unhealthy food choice is an important driver of obesity, but research examining the relationship of food choices and social influence has been limited. We sought to assess associations in the healthfulness of workplace food choices among a large population of diverse employees whose food-related social connections were identified using passively collected data in a validated model. Data were drawn from 3 million encounters where pairs of employees made purchases together in 2015-2016. The healthfulness of food items was defined by 'traffic light' labels. Cross-sectional simultaneously autoregressive models revealed that proportions of both healthy and unhealthy items purchased were positively associated between connected employees. Longitudinal generalized estimating equation models also found positive associations between an employee's current food purchase and the most recent previous food purchase a coworker made together with the employee. These data indicate that workplace interventions to promote healthy eating and reduce obesity should test peer-based strategies.Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.Soil microorganisms shape ecosystem function, yet it remains an open question whether we can predict the composition of the soil microbiome in places before observing it. Furthermore, it is unclear whether the predictability of microbial life exhibits taxonomic- and spatial-scale dependence, as it does for macrobiological communities. Here, we leverage multiple large-scale soil microbiome surveys to develop predictive models of bacterial and fungal community composition in soil, then test these models against independent soil microbial community surveys from across the continental United States. We find remarkable scale dependence in community predictability. The predictability of bacterial and fungal communities increases with the spatial scale of observation, and fungal predictability increases with taxonomic scale. These patterns suggest that there is an increasing importance of deterministic versus stochastic processes with scale, consistent with findings in plant and animal communities, suggesting a general scaling relationship across biology. Biogeochemical functional groups and high-level taxonomic groups of microorganisms were equally predictable, indicating that traits and taxonomy are both powerful lenses for understanding soil communities. By focusing on out-of-sample prediction, these findings suggest an emerging generality in our understanding of the soil microbiome, and that this understanding is fundamentally scale dependent.
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