6,633 research outputs found

    Treasury bill versus private money market yield curves

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    An abstract for this article is not availableMoney market ; Treasury bills ; Interest rates

    Oncogenic K-Ras suppresses IP<sub>3</sub>-dependent Ca<sup>2+</sup> release through remodeling of IP<sub>3</sub>Rs isoform composition and ER luminal Ca<sup>2+</sup> levels in colorectal cancer cell lines

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    The GTPase Ras is a molecular switch engaged downstream of G-protein coupled receptors and receptor tyrosine inases that controls multiple cell fate-determining signalling athways. Ras signalling is frequently deregulated in cancer underlying associated changes in cell phenotype. Although Ca2+ signalling pathways control some overlapping functions with Ras, and altered Ca2+ signalling pathways are emerging as important players in oncogenic transformation, how Ca2+ signalling is remodelled during transformation and whether it has a causal role remains unclear. We have investigated Ca2+ signalling in two human colorectal cancer cell lines and their isogenic derivatives in which the mutated K-Ras allele (G13D) has been deleted by homologous recombination. We show that agonist-induced Ca2+ release from intracellular stores is enhanced by loss of K-RasG13D through an increase in the ER store content and a modification of IP3R subtype abundance. Consistently, uptake of Ca2+ into mitochondria and sensitivity to apoptosis was enhanced as a result of KRasG13D loss. These results suggest that suppression of Ca2+ signalling is a common response to naturally occurring levels of K-RasG13D that contributes to a survival advantage during oncogenic transformation

    Water Table Level as Influenced by Tiling Method

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    Sections of the research farm were tiled in the fall of 1979. The primary reason for the tiling was to provide a good soil environment for large tillage trial plots that had been previously established. This was also used as an opportunity to install a comparison of tile installation with a conventional (at that time) trenching machine and a relatively new system of installing the tile with a trenchless “tile plow” machine. The tile plow inserted plastic tile using a mole approach, which opened the soil and inserted the tile without leaving an open trench, that would later require backfilling. The heaving of the soil by the tile plow did require packing and some soil manipulation to allow cropping. The primary reason for using this type of installation was cost. At the time of this installation, the cost of tiling could be reduced substantially (in some cases by over 50%) by using the plow method rather than the trench

    Can a combination of the conformal thin-sandwich and puncture methods yield binary black hole solutions in quasi-equilibrium?

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    We consider combining two important methods for constructing quasi-equilibrium initial data for binary black holes: the conformal thin-sandwich formalism and the puncture method. The former seeks to enforce stationarity in the conformal three-metric and the latter attempts to avoid internal boundaries, like minimal surfaces or apparent horizons. We show that these two methods make partially conflicting requirements on the boundary conditions that determine the time slices. In particular, it does not seem possible to construct slices that are quasi-stationary and avoid physical singularities and simultaneously are connected by an everywhere positive lapse function, a condition which must obtain if internal boundaries are to be avoided. Some relaxation of these conflicting requirements may yield a soluble system, but some of the advantages that were sought in combining these approaches will be lost.Comment: 8 pages, LaTeX2e, 2 postscript figure

    A new type of Na+-driven ATP synthase membrane rotor with a two-carboxylate ion-coupling motif

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    Abstract: The anaerobic bacterium Fusobacterium nucleatum uses glutamate decarboxylation to generate a transmembrane gradient of Na+. Here, we demonstrate that this ion-motive force is directly coupled to ATP synthesis, via an F1Fo-ATP synthase with a novel Na+ recognition motif, shared by other human pathogens. Molecular modeling and free-energy simulations of the rotary element of the enzyme, the c-ring, indicate Na+ specificity in physiological settings. Consistently, activity measurements showed Na+ stimulation of the enzyme, either membrane-embedded or isolated, and ATP synthesis was sensitive to the Na+ ionophore monensin. Furthermore, Na+ has a protective effect against inhibitors targeting the ion-binding sites, both in the complete ATP synthase and the isolated c-ring. Definitive evidence of Na+ coupling is provided by two identical crystal structures of the c11 ring, solved by X-ray crystallography at 2.2 and 2.6 Ă… resolution, at pH 5.3 and 8.7, respectively. Na+ ions occupy all binding sites, each coordinated by four amino acids and a water molecule. Intriguingly, two carboxylates instead of one mediate ion binding. Simulations and experiments demonstrate that this motif implies that a proton is concurrently bound to all sites, although Na+ alone drives the rotary mechanism. The structure thus reveals a new mode of ion coupling in ATP synthases and provides a basis for drug-design efforts against this opportunistic pathogen. Author Summary: Essential cellular processes such as biosynthesis, transport, and motility are sustained by the energy released in the hydrolysis of ATP, the universal energy carrier in living cells. Most ATP in the cell is produced by a membrane-bound enzyme, the ATP synthase, through a rotary mechanism that is coupled to the translocation of ions across the membrane. The majority of ATP synthases are energized by transmembrane electrochemical gradients of protons (proton-motive force), but a number of organisms, including some important human pathogens, use gradients of sodium ions instead (sodium-motive force). The ion specificity of ATP synthases is determined by a membrane-embedded sub-complex, the c-ring, which is the smallest known biological rotor. The functional mechanism of the rotor ring and its variations among different organisms are of wide interest, because of this enzyme's impact on metabolism and disease, and because of its potential for nanotechnology applications. Here, we characterize a previously unrecognized type of Na+-driven ATP synthase from the opportunistic human pathogen Fusobacterium nucleatum, which is implicated in periodontal diseases. We analyzed this ATP synthase and its rotor ring through a multi-disciplinary approach, combining cell-growth and biochemical assays, X-ray crystallography and computer-simulation methods. Two crystal structures of the membrane rotor were solved, at low and high pH, revealing an atypical ion-recognition motif mediated by two carboxylate side-chains. This motif is shared by other human pathogens, such as Mycobacterium tuberculosis or Streptococcus pneumonia, whose ATP synthases are targets of novel antibiotic drugs. The implications of this ion-recognition mode on the mechanism of the ATP synthase and the cellular bioenergetics of F. nucleatum were thus examined. Our results provide the basis for future pharmacological efforts against this important pathogen

    Landsat Science: 40 Years of Innovation and Opportunity

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    Landsat satellites have provided unparalleled Earth-observing data for nearly 40 years, allowing scientists to describe, monitor and model the global environment during a period of time that has seen dramatic changes in population growth, land use, and climate. The success of the Landsat program can be attributed to well-designed instrument specifications, astute engineering, comprehensive global acquisition and calibration strategies, and innovative scientists who have developed analytical techniques and applications to address a wide range of needs at local to global scales (e.g., crop production, water resource management, human health and environmental quality, urbanization, deforestation and biodiversity). Early Landsat contributions included inventories of natural resources and land cover classification maps, which were initially prepared by a visual interpretation of Landsat imagery. Over time, advances in computer technology facilitated the development of sophisticated image processing algorithms and complex ecosystem modeling, enabling scientists to create accurate, reproducible, and more realistic simulations of biogeochemical processes (e.g., plant production and ecosystem dynamics). Today, the Landsat data archive is freely available for download through the USGS, creating new opportunities for scientists to generate global image datasets, develop new change detection algorithms, and provide products in support of operational programs such as Reducing Emissions from Deforestation and Forest Degradation in Developing Countries (REDD). In particular, the use of dense (approximately annual) time series to characterize both rapid and progressive landscape change has yielded new insights into how the land environment is responding to anthropogenic and natural pressures. The launch of the Landsat Data Continuity Mission (LDCM) satellite in 2012 will continue to propel innovative Landsat science

    Preparing Priests to Lead Parish Schools: Concerns and Recommendations

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    Canon law recognizes the pastor as the chief educational officer (CEO) of the parish school. However, recent studies demonstrate that seminaries do not prepare seminarians for work in or leadership of Catholic schools, and recent scholarship also demonstrates that an increasing number of seminarians lack the desire to lead a parish school. Our research study examined the post-seminary preparation of priests for leadership of parish schools. We also explored alternative governance models for Catholic schools. We conducted structured interviews with 10 national leaders to explore these two areas of interest. Our findings demonstrate that preparation of newly ordained and veteran priests for parish school leadership is woefully inadequate. Interviewees suggested that the pastor/principal relationship and school finance are two important topics that should be addressed in best practice preparation programs for school leaders. All 10 interviewees had difficulty imagining alternative governance models for schools in which the pastor would not serve as the CEO, but at the same time, some of the participants could see potential benefits of alternative governance models. Based on the findings of our study, we recommend that: (1) seminary programs include an initial introduction to the importance of Catholic schools for evangelization; (2) a new national model for preparing young and veteran priests for school leadership be developed and implemented; (3) existing best practices for alternative governance models be collated and promulgated; and (4) church leaders and stakeholders determine the best governance models for their schools and then prepare the appropriate people for leadership roles accordingly

    The Innermost Stable Circular Orbit of Binary Black Holes

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    We introduce a new method to construct solutions to the constraint equations of general relativity describing binary black holes in quasicircular orbit. Black hole pairs with arbitrary momenta can be constructed with a simple method recently suggested by Brandt and Bruegmann, and quasicircular orbits can then be found by locating a minimum in the binding energy along sequences of constant horizon area. This approach produces binary black holes in a "three-sheeted" manifold structure, as opposed to the "two-sheeted" structure in the conformal-imaging approach adopted earlier by Cook. We focus on locating the innermost stable circular orbit and compare with earlier calculations. Our results confirm those of Cook and imply that the underlying manifold structure has a very small effect on the location of the innermost stable circular orbit.Comment: 8 pages, 3 figures, RevTex, submitted to PR
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