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

Addendum: "The Dynamics of M15: Observations of the Velocity Dispersion Profile and Fokker-Planck Models" (ApJ, 481, 267 [1997])

It has recently come to our attention that there are axis scale errors in three of the figures of Dull et al. (1997, hereafter D97). D97 presented Fokker-Planck models for the collapsed-core globular cluster M15 that include a dense, centrally concentrated population of neutron stars and massive white dwarfs, but do not include a central black hole. In this Addendum, we present corrected versions of Figures 9, 10, and 12, and an expanded version of Figure 6. This latter figure, which shows the full run of the velocity dispersion profile, indicates that the D97 model predictions are in good agreement with the moderately rising HST-STIS velocity dispersion profile for M15 reported by Gerssen et al. (2002, astro-ph/0209315). Thus, a central black hole is not required to fit the new STIS velocity measurements, provided that there is a sufficient population of neutron stars and massive white dwarfs. This conclusion is consistent with the findings of Gerssen et al. (2002, astro-ph/0210158), based on a reapplication of their Jeans equation analysis using the corrected mass-to-light profile (Figure 12) for the D97 models.Comment: 4 pages, 4 figures, submitted to Ap

Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase

BACKGROUND Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. METHODS NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. RESULTS Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). CONCLUSIONS At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasi

Monte Carlo Simulations of Star Clusters - IV. Calibration of the Monte Carlo Code and Comparison with Observations for the Open Cluster M67

We outline the steps needed in order to incorporate the evolution of single and binary stars into a particular Monte Carlo code for the dynamical evolution of a star cluster. We calibrate the results against N-body simulations, and present models for the evolution of the old open cluster M67 (which has been studied thoroughly in the literature with N-body techniques). The calibration is done by choosing appropriate free code parameters. We describe in particular the evolution of the binary, white dwarf and blue straggler populations, though not all channels for blue straggler formation are represented yet in our simulations. Calibrated Monte Carlo runs show good agreement with results of N-body simulations not only for global cluster parameters, but also for e.g. binary fraction, luminosity function and surface brightness. Comparison of Monte Carlo simulations with observational data for M67 shows that is possible to get reasonably good agreement between them. Unfortunately, because of the large statistical fluctuations of the numerical data and uncertainties in the observational data the inferred conclusions about the cluster initial conditions are not firm.Comment: 15 pages, 24 figure

Targeting lentiviral vectors to antigen-specific immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell Populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral Surface. This engineered vector could specifically bind to cells expressing Surface immunoglobulin recognizing CD20 (αCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing αCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect. Such targeting lentivectors also Could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology

An overview of the Michigan Positron Microscope Program

An overview of the Michigan Positron Microscope Program is presented with particular emphasis on the second generation microscope that is presently near completion. The design and intended applications of this microscope will be summarized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87602/2/391_1.pd

A Rapid and Economic In-House DNA Purification Method Using Glass Syringe Filters

Background Purity, yield, speed and cost are important considerations in plasmid purification, but it is difficult to achieve all of these at the same time. Currently, there are many protocols and kits for DNA purification, however none maximize all four considerations. Methodology/Principal Findings We now describe a fast, efficient and economic in-house protocol for plasmid preparation using glass syringe filters. Plasmid yield and quality as determined by enzyme digestion and transfection efficiency were equivalent to the expensive commercial kits. Importantly, the time required for purification was much less than that required using a commercial kit. Conclusions/Significance This method provides DNA yield and quality similar to that obtained with commercial kits, but is more rapid and less costly.This research was supported by Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Using Endogenous MicroRNA Expression Patterns to Visualize Neural Differentiation of Human Pluripotent Stem Cells

Many existing protocols for neuronal differentiation of human pluripotent cells result in heterogeneous cell populations and unsynchronized differentiation, necessitating the development of methods for labeling specific cell populations. Here we describe how microRNA-regulated lentiviral vectors can be used to visualize specific cell populations by exploiting endogenous microRNA expression patterns. This strategy provides a useful tool for visualization and identification of neural progeny derived from human pluripotent stem cells. We provide detailed protocols for lentiviral transduction, neural differentiation, and subsequent analysis of human embryonic stem cells