American Naval History, 1607-1865

For its first eighty-five years, the United States was only a minor naval power. Its fledgling fleet had been virtually annihilated during the War of Independence and was mostly trapped in port by the end of the War of 1812. How this meager presence became the major naval power it remains to this day is the subject of American Naval History, 1607–1865: Overcoming the Colonial Legacy. A wide-ranging yet concise survey of the U.S. Navy from the colonial era through the Civil War, the book draws on American, British, and French history to reveal how navies reflect diplomatic, political, economic, and social developments and to show how the foundation of America’s future naval greatness was laid during the Civil War. Award-winning author Jonathan R. Dull documents the remarkable transformation of the U.S. Navy between 1861 and 1865, thanks largely to brilliant naval officers like David Farragut, David D. Porter, and Andrew Foote; visionary politicians like Abraham Lincoln and Gideon Welles; and progressive industrialists like James Eads and John Ericsson. But only by understanding the failings of the antebellum navy can the accomplishments of Lincoln’s navy be fully appreciated. Exploring such topics as delays in American naval development, differences between the U.S. and European fleets, and the effect that the country’s colonial past had on its naval policies, Dull offers a new perspective on both American naval history and the history of the developing republic

CD1b-restricted GEM T cell responses are modulated by Mycobacterium tuberculosis mycolic acid meromycolate chains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in tuberculosis granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells

HIV Promoter Integration Site Primarily Modulates Transcriptional Burst Size Rather Than Frequency

Mammalian gene expression patterns, and their variability across populations of cells, are regulated by factors specific to each gene in concert with its surrounding cellular and genomic environment. Lentiviruses such as HIV integrate their genomes into semi-random genomic locations in the cells they infect, and the resulting viral gene expression provides a natural system to dissect the contributions of genomic environment to transcriptional regulation. Previously, we showed that expression heterogeneity and its modulation by specific host factors at HIV integration sites are key determinants of infected-cell fate and a possible source of latent infections. Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression. In contrast, burst frequencies are scattered about a typical value of several per cell-division time and demonstrate little correlation with the clonal means. This pattern of modulation generates consistently noisy distributions over the sampled integration positions, with large expression variability relative to the mean maintained even for the most productive integrations, and could contribute to specifying heterogeneous, integration-site-dependent viral production patterns in HIV-infected cells. Genomic environment thus emerges as a significant control parameter for gene expression variation that may contribute to structuring mammalian genomes, as well as be exploited for survival by integrating viruses

Benjamin Franklin and the American Revolution

The inventor, the ladies’ man, the affable diplomat, and the purveyor of pithy homespun wisdom: we all know the charming, resourceful Benjamin Franklin. What is less appreciated is the importance of Franklin’s part in the American Revolution: except for Washington he was its most irreplaceable leader. Although aged and in ill health, Franklin served the cause with unsurpassed zeal and dedication. Jonathan R. Dull, whose decades of work on The Papers of Benjamin Franklin have given him rare insight into his subject, explains Franklin’s role in the Revolution, what prepared him for that role, and what motivated him. The Franklin presented here, a man immersed in the violence, danger, and suffering of the Revolution, is a tougher person than the Franklin of legend. Dull’s portrait captures Franklin’s confidence and self-righteousness about himself and the American cause. It shows his fanatical zeal, his hatred of King George III and George’s American supporters (particularly Franklin’s own son), and his disdain for hardship and danger. It also shows a side of Franklin that he tried to hide: his vanity, pride, and ambition. Though not as lovable and avuncular as the person of legend, this Franklin is more interesting, more complex, and in many ways more impressive

The Age of the Ship of the Line: The British and French Navies, 1650-1815

For nearly two hundred years huge wooden warships called “ships of the line” dominated war at sea and were thus instrumental in the European struggle for power and the spread of imperialism. Foremost among the great naval powers were Great Britain and France, whose advanced economies could support large numbers of these expensive ships. This book, the first joint history of these great navies, offers a uniquely impartial and comprehensive picture of the two forces —their shipbuilding programs, naval campaigns, and battles, and their wartime strategies and diplomacy. Jonathan R. Dull is the author of two award-winning histories of the French navy. Bringing to bear years of study of war and diplomacy, his book conveys the fine details and the high drama of the age of grand and decisive naval conflict. Dull delves into the seven wars that Great Britain and France, often in alliance with lesser naval powers such as Spain and the Netherlands, fought between 1688 and 1815. Viewing war as most statesmen of the time saw it—as a contest of endurance—he also treats the tragic side of the Franco-British wars, which shattered the greater security and prosperity the two powers enjoyed during their brief period as allies