The composition of Saturn's rings

The origin and evolution of Saturn's rings is critical to understanding the Saturnian system as a whole. Here, we discuss the physical and chemical composition of the rings, as a foundation for evolutionary models described in subsequent chapters. We review the physical characteristics of the main rings, and summarize current constraints on their chemical composition. Radial trends are observed in temperature and to a limited extent in particle size distribution, with the C ring exhibiting higher temperatures and a larger population of small particles. The C ring also shows evidence for the greatest abundance of silicate material, perhaps indicative of formation from a rocky body. The C ring and Cassini Division have lower optical depths than the A and B rings, which contributes to the higher abundance of the exogenous neutral absorber in these regions. Overall, the main ring composition is strongly dominated by water ice, with minor silicate, UV absorber, and neutral absorber components. Sampling of the innermost D ring during Cassini's Grand Finale provides a new set of in situ constraints on the ring composition, and we explore ongoing work to understand the linkages between the main rings and the D ring. The D ring material is organic- and silicate-rich and water-poor relative to the main rings, with a large population of small grains. This composition may be explained in part by volatile losses in the D ring, and current constraints suggest some degree of fractionation rather than sampling of the bulk D ring material.Comment: Submitted to SSR for publication in the collection "New Vision of the Saturnian System in the Context of a Highly Dissipative Saturn

The Saturn Ring Skimmer Mission Concept: The next step to explore Saturn's rings, atmosphere, interior, and inner magnetosphere

The innovative Saturn Ring Skimmer mission concept enables a wide range of investigations that address fundamental questions about Saturn and its rings, as well as giant planets and astrophysical disk systems in general. This mission would provide new insights into the dynamical processes that operate in astrophysical disk systems by observing individual particles in Saturn's rings for the first time. The Ring Skimmer would also constrain the origin, history, and fate of Saturn's rings by determining their compositional evolution and material transport rates. In addition, the Ring Skimmer would reveal how the rings, magnetosphere, and planet operate as an inter-connected system by making direct measurements of the ring's atmosphere, Saturn's inner magnetosphere and the material owing from the rings into the planet. At the same time, this mission would clarify the dynamical processes operating in the planet's visible atmosphere and deep interior by making extensive high-resolution observations of cloud features and repeated measurements of the planet's extremely dynamic gravitational field. Given the scientific potential of this basic mission concept, we advocate that it be studied in depth as a potential option for the New Frontiers program.Comment: White paper submitted to the Planetary Science and Astrobiology Decadal Survey (submission #420

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

The Saturn Ring Skimmer Mission Concept: The next step to explore Saturn's rings, atmosphere, interior and inner magnetosphere

The innovative Saturn Ring Skimmer mission concept enables a wide range of investigations that address fundamental questions about Saturn and its rings, as well as giant planets and astrophysical disk systems in general. This mission would provide new insights into the dynamical processes that operate in astrophysical disk systems by observing individual particles in Saturn's rings for the first time. The Ring Skimmer would also constrain the origin, history, and fate of Saturn's rings by determining their compositional evolution and material transport rates. In addition, the Ring Skimmer would reveal how the rings, magnetosphere, and planet operate as an inter-connected system by making direct measurements of the ring's atmosphere, Saturn's inner magnetosphere and the material owing from the rings into the planet. At the same time, this mission would clarify the dynamical processes operating in the planet's visible atmosphere and deep interior by making extensive high-resolution observations of cloud features and repeated measurements of the planet's extremely dynamic gravitational field. Given the scientific potential of this basic mission concept, we advocate that it be studied in depth as a potential option for the New Frontiers program

Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis

Chaste : Cancer, Heart and Soft Tissue Environment

Funding: UK Engineering and Physical Sciences Research Council [grant number EP/N509711/1 (J.K.)].Chaste (Cancer, Heart And Soft Tissue Environment) is an open source simulation package for the numerical solution of mathematical models arising in physiology and biology. To date, Chaste development has been driven primarily by applications that include continuum modelling of cardiac electrophysiology (‘Cardiac Chaste’), discrete cell-based modelling of soft tissues (‘Cell-based Chaste’), and modelling of ventilation in lungs (‘Lung Chaste’). Cardiac Chaste addresses the need for a high-performance, generic, and verified simulation framewor kfor cardiac electrophysiology that is freely available to the scientific community. Cardiac chaste provides a software package capable of realistic heart simulations that is efficient, rigorously tested, and runs on HPC platforms. Cell-based Chaste addresses the need for efficient and verified implementations of cell-based modelling frameworks, providing a set of extensible tools for simulating biological tissues. Computational modelling, along with live imaging techniques, plays an important role in understanding the processes of tissue growth and repair. A wide range of cell-based modelling frameworks have been developed that have each been successfully applied in a range of biological applications. Cell-based Chaste includes implementations of the cellular automaton model, the cellular Potts model, cell-centre models with cell representations as overlapping spheres or Voronoi tessellations, and the vertex model. Lung Chaste addresses the need for a novel, generic and efficient lung modelling software package that is both tested and verified. It aims to couple biophysically-detailed models of airway mechanics with organ-scale ventilation models in a package that is freely available to the scientific community.Publisher PDFPeer reviewe

Identification of Anti-Malarial Compounds as Novel Antagonists to Chemokine Receptor CXCR4 in Pancreatic Cancer Cells

Despite recent advances in targeted therapies, patients with pancreatic adenocarcinoma continue to have poor survival highlighting the urgency to identify novel therapeutic targets. Our previous investigations have implicated chemokine receptor CXCR4 and its selective ligand CXCL12 in the pathogenesis and progression of pancreatic intraepithelial neoplasia and invasive pancreatic cancer; hence, CXCR4 is a promising target for suppression of pancreatic cancer growth. Here, we combined in silico structural modeling of CXCR4 to screen for candidate anti-CXCR4 compounds with in vitro cell line assays and identified NSC56612 from the National Cancer Institute's (NCI) Open Chemical Repository Collection as an inhibitor of activated CXCR4. Next, we identified that NSC56612 is structurally similar to the established anti-malarial drugs chloroquine and hydroxychloroquine. We evaluated these compounds in pancreatic cancer cells in vitro and observed specific antagonism of CXCR4-mediated signaling and cell proliferation. Recent in vivo therapeutic applications of chloroquine in pancreatic cancer mouse models have demonstrated decreased tumor growth and improved survival. Our results thus provide a molecular target and basis for further evaluation of chloroquine and hydroxychloroquine in pancreatic cancer. Historically safe in humans, chloroquine and hydroxychloroquine appear to be promising agents to safely and effectively target CXCR4 in patients with pancreatic cancer

Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals