Treasury bill versus private money market yield curves

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

Oncogenic K-Ras suppresses IP₃-dependent Ca²⁺ release through remodeling of IP₃Rs isoform composition and ER luminal Ca²⁺ levels in colorectal cancer cell lines

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

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

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 Å 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

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

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

Landsat Science: 40 Years of Innovation and Opportunity

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

Stability and collapse of rapidly rotating, supramassive neutron stars: 3D simulations in general relativity

We perform 3D numerical simulations in full general relativity to study the stability of rapidly rotating, supramassive neutron stars at the mass-shedding limit to dynamical collapse. We adopt an adiabatic equation of state with $\Gamma = 2$ and focus on uniformly rotating stars. We find that the onset of dynamical instability along mass-shedding sequences nearly coincides with the onset of secular instability. Unstable stars collapse to rotating black holes within about one rotation period. We also study the collapse of stable stars which have been destabilized by pressure depletion (e.g. via a phase transition) or mass accretion. In no case do we find evidence for the formation of massive disks or any ejecta around the newly formed Kerr black holes, even though the progenitors are rapidly rotating.Comment: 16 pages, to appear in Phys. Rev.

Computing the Complete Gravitational Wavetrain from Relativistic Binary Inspiral

We present a new method for generating the nonlinear gravitational wavetrain from the late inspiral (pre-coalescence) phase of a binary neutron star system by means of a numerical evolution calculation in full general relativity. In a prototype calculation, we produce 214 wave cycles from corotating polytropes, representing the final part of the inspiral phase prior to reaching the ISCO. Our method is based on the inequality that the orbital decay timescale due to gravitational radiation is much longer than an orbital period and the approximation that gravitational radiation has little effect on the structure of the stars. We employ quasi-equilibrium sequences of binaries in circular orbit for the matter source in our field evolution code. We compute the gravity-wave energy flux, and, from this, the inspiral rate, at a discrete set of binary separations. From these data, we construct the gravitational waveform as a continuous wavetrain. Finally, we discuss the limitations of our current calculation, planned improvements, and potential applications of our method to other inspiral scenarios.Comment: 4 pages, 4 figure

The Innermost Stable Circular Orbit of Binary Black Holes

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

The Search for Supernova-produced Radionuclides in Terrestrial Deep-sea Archives

An enhanced concentration of 60Fe was found in a deep ocean's crust in 2004 in a layer corresponding to an age of ~2 Myr. The confirmation of this signal in terrestrial archives as supernova-induced and detection of other supernova-produced radionuclides is of great interest. We have identified two suitable marine sediment cores from the South Australian Basin and estimated the intensity of a possible signal of the supernova-produced radionuclides 26Al, 53Mn, 60Fe and the pure r-process element 244Pu in these cores. A finding of these radionuclides in a sediment core might allow to improve the time resolution of the signal and thus to link the signal to a supernova event in the solar vicinity ~2 Myr ago. Furthermore, it gives an insight on nucleosynthesis scenarios in massive stars, the condensation into dust grains and transport mechanisms from the supernova shell into the solar system