Premier John Jay: The Most Important Man in America

When John Jay returned from France in 1784, the Confederation Congress asked him to become Secretary for Foreign Affairs. After negotiating favorable terms for the department of foreign affairs and getting Congress to move the seat of government to New York City, Jay accepted the position. For the next five years Jay served as the de facto prime minister of the United States. His 500 reports to Congress on all diplomatic matters and many domestic concerns provided much needed guidance for Congress. He, in fact, was the glue that held the loose alliance of states together during the difficult postwar depression years. Many of his policies were adopted by his successor, Thomas Jefferson, who served as America's first secretary of state in the Washington administration

Massachusetts Historical Society, “The Adams Family Papers: An Electronic Archive”- Review of \u3ci\u3eMy Dearest Friend: Letters of Abigail and John Adams. Edited by Margaret A. Hogan and C. James Taylor\u3c/i\u3e

My Dearest Friend contains 289 letters “selected from the entire corpus” of the Adams letters from 1762 to 1801 and “is meant to show both the consistency of their relationship and the evolution of the family through the entire founding era.” A three-page epilogue on the death of Abigail consists of a short headnote and two letters exchanged between John and John Quincy Adams. All but three of the letters in My Dearest Friend are in the Adams Family manuscript collection given by the Adams family to the Massachusetts Historical Society (MHS) in 1956. The letters were all microfilmed on 608 reels by the MHS in the 1950s and sold to research libraries throughout the world. The Abigail and John letters appear on the MHS Web site (www.masshist.org) at “The Adams Family Papers: An Electronic Archive.” (See below.) Abigail and John’s letters also appear among the volumes of The Adams Family Correspondence published by The Bel - knap Press of Harvard University Press. Nine volumes have been published to date, covering the years through 1793. All of the published Adams volumes appear on the MHS Web site and are also digitally available on Rotunda, University of Virginia Press

Suppressive Oligodeoxynucleotides Inhibit Cytosolic DNA Sensing Pathways: A Dissertation

The innate immune system provides an essential first line of defense against infection. Innate immune cells detect pathogens through several classes of Pattern Recognition Receptors (PRR) allowing rapid response to a broad spectrum of infectious agents. Activated receptors initiate signaling cascades that lead to the production of cytokines, chemokines and type I interferons all of which are vital for controlling pathogen load and coordinating the adaptive immune response. Detection of nucleic acids by the innate immune system has emerged as a mechanism by which infection is recognized. Recognition of DNA is complex, influenced by sequence, structure, covalent modification and subcellular localization. Interestingly certain synthetic oligodeoxynucleotides comprised of the TTAGGG motif inhibit proinflammatory responses in a variety of disease models. These suppressive oligodeoxynucleotides (sup ODN) have been shown to directly block TLR9 signaling as well as prevent STAT1 and STAT4 phosphorylation. Recently AIM2 has been shown to engage ASC and assemble an inflammasome complex leading to the caspase-1-dependent maturation of IL-1β and IL-18. The AIM2 inflammasome is activated in response to cytosolic dsDNA and plays an important role in controlling replication of murine cytomegalovirus (MCMV). In the second chapter of this thesis, a novel role for the sup ODN A151 in inhibiting cytosolic nucleic acid sensing pathways is described. Treatment of dendritic cells and macrophages with the A151 abrogated type I IFN, TNF-α and ISG induction in response to cytosolic dsDNA. A151 also reduced INF-β and TNF-α induction in BMDC and BMDM responding to the herpesviruses HSV-1 and MCMV but had no effect on the responses to LPS or Sendai virus. In addition, A151 abrogated caspase-1-dependent IL-1β and IL-18 maturation in dendritic cells stimulated with dsDNA and MCMV. Although inhibition of interferon-inducing pathways and inflammasome assembly was dependent on backbone composition, sequence differentially affected these pathways. While A151 more potently suppressed the AIM2 inflammasome, a related construct C151, proved to be a more potent inhibitor of interferon induction. A151 suppressed inflammasome signaling by binding to AIM2 and competing with immune-stimulatory DNA. The interaction of A151 and AIM2 prevented recruitment of the adapter ASC and assembly of the macromolecular inflammasome complex. Collectively, these findings reveal a new route by which suppressive ODNs modulate the immune system and unveil novel applications for suppressive ODNs in the treatment of infectious and autoimmune diseases. The innate immune response to HSV-1 infection is critical for controlling early viral replication and coordinating the adaptive immune response. The cytokines IL-1β and IL-18 are important effector molecules in the innate response to HSV-1 in vivo. However, the PRRs responsible for the production and maturation of these cytokines have not been fully defined. In the third chapter of this thesis, The TLR2-MyD88 pathway is shown to be essential for the induction of pro-IL-1β transcription in dendritic cells and macrophages responding to HSV-1. The HSV-1 immediate-early protein ICP0 has previously been shown to block TLR2 responses and in keeping with this finding, ICP0 blocked pro-IL-1β expression. Following translation, pro-IL-1β exists as an inactive precursor that must be proteolytically cleaved by a multiprotein complex known as the inflammasome to yield its active form. Inflammasomes are composed of cytoplasmic receptors such as NLRP3 or AIM2, the adapter molecule ASC, and pro-caspase-1. In the present study we found that the NLRP3 inflammasome is important for maturation of IL-1β in macrophages and dendritic cells responding to HSV-1. In contrast the related NLRP12 protein controls IL-1β production in neutrophils. These data indicate that sensing of HSV-1 by TLR2 drives pro-IL-1β transcription and infection activates the inflammasome to mature this cytokine. Moreover, these studies reveal cell type-specific roles for NLRP3 and NLRP12 in inflammasome assembly

Tracking the Impact of Your Web-Based Content

Google™ Analytics is an easy-to-use Web analytics program that gives you insight into Web site traffic. Many Extension programs use the Web to distribute information. Extension program impact has traditionally been assessed through surveys or by the number of publications sold or requested, whereas tracking Web impact has been more difficult. Although site visits and page views could be tracked with previous Web analytics technology, Google™ Analytics allows for tracking of additional useful information. This article highlights a few useful features of Google™ Analytics and demonstrates how to track the impact of Web-based content

Tracking the Impact of Your Web-Based Content

Google™ Analytics is an easy-to-use Web analytics program that gives you insight into Web site traffic. Many Extension programs use the Web to distribute information. Extension program impact has traditionally been assessed through surveys or by the number of publications sold or requested, whereas tracking Web impact has been more difficult. Although site visits and page views could be tracked with previous Web analytics technology, Google™ Analytics allows for tracking of additional useful information. This article highlights a few useful features of Google™ Analytics and demonstrates how to track the impact of Web-based content

Biology of Ophiosphaerella agrostis, epidemiology of dead spot, and a molecular description of the pathogen

Ophiosphaerella agrostis is a newly described pathogen that incites dead spot disease of creeping bentgrass (Agrostis stolonifera) putting greens throughout the eastern United States. The objectives of this research project were to: 1) monitor environmental conditions and develop a predictive model for disease progress and pathogen dispersal under field conditions; 2) determine the effect of various fertilizers on dead spot recovery in bentgrass; and 3) develop molecular methods to diagnoses the disease and determine genetic variation among O. agrostis isolates. Field studies showed that the appearance of dead spot infection centers was influenced predominantly by air (greater than or equal to 18 degrees Centigrade) and soil (greater than or equal to 20 degrees Centigrade) temperature, but other factors including low relative humidity (less than or equal to 80%), shortened periods of leaf wetness (less than or equal to 14 hours), and high levels of solar radiation (greater than or equal to 230 W m to the minus 2) were associated with the development of dead spot epidemics. Patch diameter of O. agrostis infection centers and pseudothecia production generally increased at a linear rate between mid-June and early to mid-August. In a growth chamber study, ascospores were released from pseudothecia following a sharp decrease in relative humidity. Field studies revealed that ascospore release occurred primarily at dawn and dusk or during precipitation events. During precipitation events, ascospores may be forcefully discharged during the entire event, but most ascospores are released within the first 10 hours after precipitation begins. O. agrostis successfully over-wintered in bentgrass leaf sheaths, crowns, roots, and stolons, but little or no reactivation of the disease occurred in the second year. Plots treated with ammonium sulfate and isobutylidene diurea were among the fastest and slowest to recover from dead spot, respectively. In the second year (2003), dead spot recurred in plots treated since 2002 with KNO3, Ca(NO3)2, urea, and a complete fertilizer (20-20-20), but disease symptoms did not recur in plots receiving ammonium sulfate. Species-specific primers capable of detecting O. agrostis at very low concentrations (5 pg DNA) were developed and can be used to assist in diagnosing dead spot. Amplified fragment length polymorphism (AFLP) DNA fingerprinting resulted in placement of isolates (n=77) into three distinct clades that were greater than or equal to 69% similar

Differential Regulation of Mouse B Cell Development by Transforming Growth Factor β1

Transforming growth factor β (TGFβ) can inhibit the in vitro proliferation, survival and differentiation of B cell progenitors, mature B lymphocytes and plasma cells. Here we demonstrate unexpected, age-dependent reductions in the bone marrow (BM) B cell progenitors and immature B cells in TGFβ1-/- mice. To evaluate TGFβ responsiveness during normal B lineage development, cells were cultured in interleukin 7 (IL7)±TGFβ. Picomolar doses of TGFβ1 reduced pro-B cell recoveries at every timepoint. By contrast, the pre-B cells were initially reduced in number, but subsequently increased compared to IL7 alone, resulting in a 4-fold increase in the growth rate for the pre-B cell population. Analysis of purified BM sub-populations indicated that pro-B cells and the earliest BP1- pre-B cells were sensitive to the inhibitory effects of TGFβ1. However, the large BP1+ pre-B cells, although initially reduced, were increased in number at days 5 and 7 of culture. These results indicate that TGFβ1 is important for normal B cell development in vivo, and that B cell progenitors are differentially affected by the cytokine according to their stage of differentiation

Parkersburg Area Economic Outlook 2019-2024

The Parkersburg Area economy has generally struggled over the past several years. The five-county region avoided the economic downturn that plagued several regions in West Virginia between 2012 and 2015, as payrolls increased nearly 2,000 during this period of time. In more recent years, however, the Parkersburg Area economy has struggled significantly, with payrolls falling by more than 3,700 by mid-2018. The region’s economy does appear to have stabilized thanks to some recent growth in natural gas output and pipeline infrastructure as well as continued development of the Hino manufacturing facility, economic recovery remains tenuous due to structural issues that have hurt several service-providing sectors on both a regional and national scale

Pesticide Application Research Demonstrated at a Field Day Event

single fungicide was applied through four nozzle-types and four water-carrier volumes targeting a common foliar disease in turfgrass. Most golf course superintendents surveyed use the same nozzle-type for all pesticide applications, but this field study indicated better disease control from the fungicide applied through certain nozzle-types and water-carrier volumes. As a result, most superintendents intended to make improvements to their pesticide application programs, and many had a highly favorable view of including this type of research at future field day events