Dunmore\u27s new world: Political culture in the British Empire, 1745--1796

Despite his participation in the Jacobite Rebellion of 1745, John Murray, fourth earl of Dunmore, eventually became royal governor of New York (1770-1771), Virginia (17711783), and the Bahama Islands (1787-1796). His life in the British Empire exposed him to an extraordinary range of political experience, including border disputes, land speculation, frontier warfare and diplomacy, sexual scandal, slave emancipation, naval combat, loyalist advocacy, Amerindian slavery, and trans-imperial filibusters, to say nothing of his proximity to the Haitian Revolution or his role in the defense of the British West Indies during the French Revolutionary Wars. Quick to break with convention on behalf of the system that ensured his privilege, Dunmore was an usually transgressive imperialist whose career can be used to explore the boundaries of what was possible in the political cultures of the Anglo-Atlantic world at the end of the eighteenth century.;Remarkably, Lord Dunmore has not been the subject of a book-length study in more than seventy years. With a few exceptions (the work of African American historians notable among them), modern scholars have dismissed him as a greedy incompetent. While challenging this characterization, the dissertation makes several arguments about the weakness of royal authority in pre-Revolutionary New York and Virginia, the prominent and problematic role of the land grant as a mechanism of political consent, the importance of Dunmore\u27s proclamation of emancipation, and the endurance of British ambition in North America after 1783. It seeks to make a methodological contribution as well. By positioning Dunmore as the epicenter of a web of interrelations, one reflected in a variety of historical texts and involving people at all levels of the imperial social structure, the dissertation suffuses a host of elements and actors within a single biographical narrative. This integrated approach can serve to counter the excessive compartmentalization that has marked some academic history in recent decades

Biochemical Determinants of Tissue Regeneration Conversion of one cell type into another: implications for understanding organ development, pathogenesis of cancer and generating cells for therapy

Abstract Metaplasia is the irreversible conversion of one differentiated cell or tissue type into another. Metaplasia usually occurs in tissues that undergo regeneration, and may, in a pathological context, predispose to an increased risk of disease. Studying the conditions leading to the development of metaplasia is therefore of significant clinical interest. In contrast, transdifferentiation (or cellular reprogramming) is a subset of metaplasia that describes the permanent conversion of one differentiated cell type into another, and generally occurs between cells that arise from neighbouring regions of the same germ layer. Transdifferentiation, although rare, has been shown to occur in Nature. New insights into the signalling pathways involved in normal tissue development may be obtained by investigating the cellular and molecular mechanisms in metaplasia and transdifferentiation, and additional identification of key molecular regulators in transdifferentiation and metaplasia could provide new targets for therapeutic treatment of diseases such as cancer, as well as generating cells for transplantation into patients with degenerative disorders. In the present review, we focus on the transdifferentiation of pancreatic cells into hepatocytelike cells, the development of Barrett's metaplasia in the oesophagus, and the cellular and molecular mechanisms underlying both processes

Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells

Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3–500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM). Like native antigens, this antigen preparation induces MR1 refolding and upregulates surface expression of human MR1, forms MR1 tetramers that detect MAIT cells in human PBMCs, and stimulates cytokine expression (IFNγ, TNF) by human MAIT cells. These antigens also induce MAIT cell accumulation in mouse lungs after administration with a co-stimulant. These chemical and immunological findings provide new insights into antigen properties and MAIT cell activation

Microtransfer printing high-efficiency GaAs photovoltaic cells onto silicon for wireless power applications

Here, the development of high‐efficiency microscale gallium arsenide (GaAs) laser power converters, and their successful transfer printing onto silicon substrates is reported, presenting a unique, high power, low‐cost, and integrated power supply solution for implantable electronics, autonomous systems, and Internet of Things (IoT) applications. 300 µm diameter single‐junction GaAs laser power converters are presented and the transfer printing of these devices to silicon is successfully demonstrated using a polydimethylsiloxane stamp, achieving optical power conversion efficiencies of 49% and 48% under 35 and 71 W cm−2 808 nm laser illumination respectively. The transferred devices are coated with indium tin oxide (ITO) to increase current spreading and are shown to be capable of handling very high short‐circuit current densities up to 70 A cm−2 under 141 W cm−2 illumination intensity (≈1400 Suns), while their open circuit voltage reaches 1235 mV, exceeding the values of pretransfer devices indicating the presence of photon recycling. These optical power sources could deliver Watts of power to sensors and systems in locations where wired power is not an option, while using a massively parallel, scalable, and low‐cost fabrication method for the integration of dissimilar materials and devices

Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18–dependent activation

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes known to elicit potent immunity to a broad range of bacteria, mainly via the rapid production of inflammatory cytokines. Whether MAIT cells contribute to antiviral immunity is less clear. Here we asked whether MAIT cells produce cytokines/chemokines during severe human influenza virus infection. Our analysis in patients hospitalized with avian H7N9 influenza pneumonia showed that individuals who recovered had higher numbers of CD161+Vα7.2+ MAIT cells in peripheral blood compared with those who succumbed, suggesting a possible protective role for this lymphocyte population. To understand the mechanism underlying MAIT cell activation during influenza, we cocultured influenza A virus (IAV)-infected human lung epithelial cells (A549) and human peripheral blood mononuclear cells in vitro, then assayed them by intracellular cytokine staining. Comparison of influenza-induced MAIT cell activation with the profile for natural killer cells (CD56+CD3−) showed robust up-regulation of IFNγ for both cell populations and granzyme B in MAIT cells, although the individual responses varied among healthy donors. However, in contrast to the requirement for cell-associated factors to promote NK cell activation, the induction of MAIT cell cytokine production was dependent on IL-18 (but not IL-12) production by IAV-exposed CD14+ monocytes. Overall, this evidence for IAV activation via an indirect, IL-18–dependent mechanism indicates that MAIT cells are protective in influenza, and also possibly in any human disease process in which inflammation and IL-18 production occur

Edge-Coupling of O-Band InP Etched-Facet Lasers to Polymer Waveguides on SOI by Micro-Transfer-Printing

O-band InP etched facets lasers were heterogeneously integrated by micro-transfer-printing into a 1.54~\mu \text{m} deep recess created in the 3~\mu \text{m} thick oxide layer of a 220 nm SOI wafer. A 7\times 1.5\,\,\mu \text{m}^{2} cross-section, 2 mm long multimode polymer waveguide was aligned to the ridge post-integration by e-beam lithography with \u3c 0.7~\mu \text{m} lateral misalignment and incorporated a tapered silicon waveguide. A 170 nm thick metal layer positioned at the bottom of the recess adjusts the vertical alignment of the laser and serves as a thermal via to sink the heat to the Si substrate. This strategy shows a roadmap for active polymer waveguide-based photonic integrated circuits