Inventing Eden: primitivism, millennialism, and the making of New England

Seventeenth-century exegetes described Eden as a three-fold paradise because they believed that Adam and Eve lived in an external garden of delight, possessed incorrupt physiologies, and enjoyed intellectual, spiritual, and social perfections before the Fall. Accordingly, the dissertation is organized thematically, treating the ways in which New England colonists sought to mold their lands, bodies, minds, language, souls, and social spheres after the pattern provided in Eden. Chapter one traces the transition of terms used to describe the New England landscape from the present paradise of John Smith to the hideous and desolate wilderness of William Bradford and the prospective Paradise of Cotton Mather. Chapter two outlines programs of physiological reform, as colonists like Anne Bradstreet disciplined their physical bodies and ministers like Edward Taylor regulated the ecclesiastical body's consumption of communion in order to achieve humoral temperance--the somatic and spiritual state of Adam and Eve in Eden. Chapters three and four document Francis Bacon's influence on educational and linguistic aspirations in New England. I argue that because the encyclopedic knowledge and divinely denotative language of Adam were believed to be inseparably linked, Leonard Hoar's plans to turn Harvard into the world's first experimental laboratory in chemistry situated at a university and John Cotton's attempt to model the language of the Bay Psalm Book after the lingua humana of Eden should be understood as related endeavors, companion contributions from New England to the Baconian project for the instauration of prelapsarian intellectual perfections. Chapter five examines the ways in which ministers of the Great Awakening presented Adam and Eve to their congregants as types of Christian conversion, and chapter six details the process by which theories of natural law distilled from Genesis became the basis for colonial rebellion and republican government through the influence of Oceana, James Harrington's vision of an idealized, edenic republic. Spanning two centuries and surveying the works of major British and American authors from George Herbert and John Milton to Jonathan Edwards and Benjamin Franklin, Inventing Eden is the history of an idea that irrevocably altered the theology, literature, and culture of early modern New England

Healthy Parks Healthy People: Evaluating and Improving Park Service Efforts to Promote Tourists Health and Well-being Introduction

Both Parks Victoria, AUS and the United States National Park Service (USNPS) focus on promoting human health and well-being while sustaining environmental well-being. This has been fostered by the agencies through the “Healthy Parks Healthy People” program, in which Parks Victoria and the USNPS are global leaders as well as agency collaborators. Given global concerns regarding health and well-being (human and environmental) this movement is crucial. However, in order for parks and associated tourism providers to implement effective health strategies, we must understand what a “healthy park” is, how evidence is being promoted to existing and potential tourists, and what lessons can be learned from these agencies to facilitate these benefits globally in other settings. This research examines these questions across both agencies through content analyses, interviews, and assessments of tourism use trends. Results inform global park tourism planning and promotion efforts to improve social and ecological

PhillydotMap: The Shape of Philadelphia

This book is the outgrowth of a working group entitled, “Modeling Urban Environmental Impacts on Health, Development, and Behavior sponsored by the University of Pennsylvania Institute for Urban Research. The purpose of the working gropu was to engage faculty from across campus and to encourage their collaborative use of GIS technology in the modeling of urban form and function. These ten chapters represent a wide range of GIS applications, from community-based social services to public history to social science research

Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses

Nucleoside modified mRNA combined with Acuitas Therapeutics\u27 lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs\u27 ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge. In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Offline Coupling of Asymmetrical Flow Field-Flow Fractionation and Capillary Electrophoresis for Separation of Extracellular Vesicles.

Extracellular vesicles (EVs) play important roles in cell-to-cell communications and carry high potential as markers targeted in disease diagnosis, prognosis, and therapeutic development. The main obstacles to EV study are their high heterogeneity; low amounts present in samples; and physical similarity to the abundant, interfering matrix components. Multiple rounds of separation and purification are often needed prior to EV characterization and function assessment. Herein, we report the offline coupling of asymmetrical flow field-flow fractionation (AF4) and capillary electrophoresis (CE) for EV analysis. While AF4 provides gentle and fast EV separation by size, CE resolves EVs from contaminants with similar sizes but different surface charges. Employing Western Blotting, ELISA, and SEM, we confirmed that intact EVs were eluted within a stable time window under the optimal AF4 and CE conditions. We also proved that EVs could be resolved from free proteins and high-density lipoproteins by AF4 and be further separated from the low-density lipoproteins co-eluted in AF4. The effectiveness of the coupled AF4-CE system in EV analysis was demonstrated by monitoring the changes in EV secretion from cells and by direct injection of human serum and detection of serum EVs. We believe that coupling AF4 and CE can provide rapid EV quantification in biological samples with much reduced matrix interference and be valuable for the study of total EVs and EV subpopulations produced by cells or present in clinical samples

Maritime operations centers with integrated and isolated planning teams

The Maritime Operations Center (MOC) was designed to effectively utilize the planning elements of Future Operations (FOPS) to provide more rapid, accurate resource allocations consistent with the vision of the Commander. MOC staff simultaneously participate in the planning effort, while executing the current operation, and supporting headquarters during planning and execution. Frequently, an operational planning team (OPT) – a task-organized team formed to conduct integrated planning for a specific mission – is formed by the MOC because it offers the advantage of a focused group of subject matter experts approaching the problem in an integrated manner. However, performance problems may be realized with the OPT being isolated in situations that require the OPT to coordinate closely with the rest of the MOC. An experiment was conducted in which the MOC planned with either an integrated or an isolated planning team where the (1) FOPS team was supported by a decision aid/planning tool that fosters coordination or (2) FOPS team used a planning tool with a reduced coordination capability. In line with the theme of this year’s symposium – The Evolution of C2 – this paper describes an experiment conducted to gain insight into advantages and disadvantages associated with formng an OPT