34 research outputs found

    Blockading The American Confederacy, 1861-1865:a Geo-strategic Analysis

    Get PDF
    A paper to be included in a volume devoted to the comparison to the comparative history of blockages, edited by Professor Jean-David Avenal. INTRODUCTION Blockade, as a formal and systematic weapon in modern naval warfare, distinct from battle and maneuver, developed during the Napoleonic wars and was further refined by the Royal Navy in its decades-long campaign after 1815 to suppress the African slave trade (1). In spite of this extensive history, it was not until the Treaty of Paris ending the Crimean War that a Declaration Respecting Maritime Law, dated April 16, 1856, formally established the general principles of international law that would define blockade and abolish privateering, blockade\u27s traditional response. Blockades were described in four short articles..

    The Visualization Of Cartographic Information: A Review Essay Of Six Civil War Atlases

    Get PDF
    The Visualization of Cartographic Information: A Review Essay of Six Civil War Atlasesby Hardy, Jr. James D. and Hochberg, Leonard J. Issue: Winter 2006Acknowledgement: This essay would not have been possible had the authors not worked with Professor Edward Whiting Fox, historian, c...

    Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c.

    Get PDF
    Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and PAR4 reactivity and were inversely correlated with PCTP mRNA levels, PC-TP protein levels and PAR4 reactivity. miR-376c regulated the expression of PC-TP in human megakaryocytes. A disproportionately high number of microRNAs that were differentially expressed by race and PAR4 reactivity, including miR-376c, are encoded in the DLK1-DIO3 locus and were expressed at lower levels in platelets from black subjects. These results suggest that PC-TP contributes to the racial difference in PAR4-mediated platelet activation, indicate a genomic contribution to platelet function that differs by race and emphasize a need to consider the effects of race when developing anti-thrombotic drugs

    Evolution inspired engineering of megasynthetases

    No full text
    Many clinically used drugs are derived from or inspired by bacterial natural products that often are biosynthesised via non-ribosomal peptide synthetases (NRPS), giant megasynthases that activate and join individual amino acids in an assembly line fashion. Since NRPS are not limited to the incorporation of the 20 proteinogenic amino acids, their efficient manipulation would allow the biotechnological generation of complex peptides including linear, cyclic and further modified natural product analogues, e.g. to optimise natural product leads. Here we describe a detailed phylogenetic analysis of several bacterial NRPS that led to the identification of a new recombination breakpoint within the thiolation (T) domain that is important for natural NRPS evolution. From this, an evolution-inspired eXchange Unit between T domains (XUT) approach was developed which allows the assembly of NRPS fragments over a broad range of GC contents, protein similarities, and extender unit specificities, as demonstrated for the specific production of a proteasome inhibitor designed and assembled from five different NRPS fragments

    Analysis of the association between chondrocalcinosis and osteoarthritis: a community based study.

    Get PDF
    OBJECTIVES--To analyse the association between chondrocalcinosis and osteoarthritis (OA) of the hands and knees in an unselected elderly rural population. METHODS--A community based cross sectional study was performed in individuals randomly selected from a previous epidemiological survey on the prevalence of chondrocalcinosis in people older than 60 years from Osona county, Catalonia, northeastern Spain. Radiological OA (grade 2 or more of Kellgren's classification) was evaluated in 26 individuals with chondrocalcinosis and in 104 controls. A total of 18 articular areas of both knees (medial and lateral tibiofemoral compartments) and hands (first, second and third metacarpophalangeal (MCP), first carpometacarpal, trapezium-scaphoid, radiocarpal and distal radioulnar joints) were studied. RESULTS--Radiological changes of OA in the knees were more common in subjects with chondrocalcinosis than in those without it, with an odds ratio adjusted for age and gender (aOR) of 4.3 (95% confidence interval (CI) 1.6 to 11.8, p = 0.005). OA was also more frequent in almost all areas of the hands in individuals with chondrocalcinosis, though the difference reached statistical significance only in the MCP joints (aOR 3.1; 95% CI 1.1 to 8.8; p = 0.033). However, taking into account the side and the different joint compartments analysed, the association between chondrocalcinosis and OA was significant only in the lateral tibiofemoral compartment and the left MCP joints. CONCLUSIONS--In an elderly population unselected for their rheumatic complaints, there was a real association between OA and chondrocalcinosis. This association was particularly relevant in the lateral tibiofemoral compartment of the knee and in the first three left MCP joints
    corecore