Structural effects and the spin reorientation in Au/Co/Au films

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Francisella tularensis Elicits IL-10 via a PGE2-Inducible Factor, to Drive Macrophage MARCH1 Expression and Class II Down-Regulation

Francisella tularensis is a bacterial pathogen that uses host-derived PGE2 to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE2 acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE2 can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensis macrophage supernatant), which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 “resistant” class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE2 can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE2 drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE2, these results suggest that a yet-to-be-identified PGE2-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens

Extended self-knowledge

We aim to move the externalism and self-knowledge debate forward by exploring two novel sceptical challenges to the prospects of self-knowledge of a paradigmatic sort, both of which result from ways in which our thought content, cognitive processes and cognitive successes depend crucially on our external environments. In particular, it is shown how arguments from extended cognition (e.g., Clark A, Chalmers D. Analysis 58:7–19 (1998); Clark A. Supersizing the mind: Embodiment, action, and cognitive extension. Oxford: Oxford University Press (2008)) and situationism (e.g., Alfano M. The Philosophical Quarterly 62:223–249 (2012), Alfano M. Expanding the situationist challenge to reliabilism about inference. In Fairweather A (ed) Virtue epistemology naturalized, Springer, Dordrecht, pp 103–122 (2014); Doris JM. Noûs 32:504–530 (1998), Doris JM. Lack of character: Personality and moral behavior. Cambridge University Press, Cambridge (2002); Harman G. Proceedings of the Aristotelian Society. 99:315–331 (1999), Harman G. Proceedings of the Aristotelian Society 100:223–226 (2000)) pose hitherto unexplored challenges to the prospects of self-knowledge as it is traditionally conceived. It is shown, however, that, suitably understood, these apparent challenges in fact only demonstrate two ways in which our cognitive lives can be dependent on our environment. As such, rather than undermining our prospects for attaining self-knowledge, they instead illustrate how self-knowledge can be extended and expanded

From icon of empire to national emblem: new evidence for the fallow deer of Barbuda

Barbuda and Antigua's national animal is the fallow deer, Dama dama dama, a species native to the eastern Mediterranean that has been transported around the world by people during the last 8,000 years. The timing and circumstances by which fallow deer came to be established on Barbuda are currently uncertain but, by examining documentary, osteological and genetic evidence, this paper will consider the validity of existing theories. It will review the dynamics of human-Dama relationships from the 1500s AD to the present day and consider how the meaning attached to this species has changed through time: from a symbol of colonial authority and dominance, to a 'walking larder' after the slave emancipation of 1834, and now an important part of the island's economy and cultural heritage that requires careful management

Submicrometer Pattern Fabrication by Intensification of Instability in Ultrathin Polymer Films under a Water-Solvent Mix

Dewetting of ultrathin (< 100 nm) polymer films, by heating above the glass transition, produces droplets of sizes of the order of microns and mean separations between droplets of the order of tens of microns. These relatively large length scales are because of the weak destabilizing van der Waals forces and the high surface energy penalty required for deformations on small scales. We show a simple, one-step versatile method to fabricate sub-micron (>~100 nm) droplets and their ordered arrays by room temperature dewetting of ultrathin polystyrene (PS) films by minimizing these limitations. This is achieved by controlled room temperature dewetting under an optimal mixture of water, acetone and methyl-ethyl ketone (MEK). Diffusion of organic solvents in the film greatly reduces its glass transition temperature and the interfacial tension, but enhances the destabilizing field by introduction of electrostatic force. The latter is reflected in a change in the exponent, n of the instability length scale, {\lambda} ~h^n, where h is the film thickness and n = 1.51 \pm 0.06 in the case of water-solvent mix, as opposed to its value of 2.19 \pm 0.07 for dewetting in air. The net outcome is more than one order of magnitude reduction in the droplet size as well as their mean separation and also a much faster dynamics of dewetting. We also demonstrate the use of this technique for controlled dewetting on topographically patterned substrates with submicrometer features where dewetting in air is either arrested, incomplete or unable to produce ordered patterns

Long-Distance Three-Color Neuronal Tracing in Fixed Tissue Using NeuroVue Dyes

Dissecting development of neuronal connections is critical for understanding neuronal function in both normal and diseased states. Charting the development of the multitude of connections is a monumental task, since a given neuron typically receives hundreds of convergent inputs from other neurons and provides divergent outputs for hundreds of other neurons. Although progress is being made utilizing various mutants and/or genetic constructs expressing fluorescent proteins like GFP, substantial work remains before a database documenting the development and final location of the neuronal pathways in an adult animal is completed. The vast majority of developing neurons cannot be specifically labeled with antibodies and making specific GFP-expressing constructs to tag each of them is an overwhelming task. Fortunately, fluorescent lipophilic dyes have emerged as very useful tools to systematically compare changes in neuronal networks between wild-type and mutant mice. These dyes diffuse laterally along nerve cell membranes in fixed preparations, allowing tracing of the position of a given neuron within the neuronal network in murine mutants fixed at various stages of development. Until recently, however, most evaluations have been limited to one, or at most, two color analyses. We have previously reported three color neuronal profiling using the novel lipophilic dyes NeuroVue (NV) Green, Red and Maroon (Fritzsch et al., Brain. Res. Bull. 66:249–258, 2005). Unfortunately such three color experiments have been limited by the fact that NV Green and its brighter successor, NV Emerald, both exhibit substantially decreased signal intensities when times greater than 48 hours at 37°C are required to achieve neuronal profile filling (unpublished observations). Here we describe a standardized test system developed to allow comparison of candidate dyes and its use to evaluate a series of 488 nm-excited green-emitting lipophilic dyes. The best of these, NV Jade, has spectral properties well matched to NV Red and NV Maroon, better solubility in DMF than DiO or DiA, improved thermostability compared with NV Emerald, and the ability to fill neuronal profiles at rates of 1 mm per day for periods of at least 5 days. Use of NV Jade in combination with NV Red and NV Maroon substantially improves the efficiency of connectional analysis in complex mutants and transgenic models where limited numbers of specimens are available

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges