Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

Methods for geophysical model assessment, in particuale thecomputation of model parameter resolution, indicate the value and thelimitations of time-lapse data in estimating reservoir flow properties. Atrajectory-based method for computing sensitivities provides an effectivemeans to compute model parameter resolutions. We examine the commonsituation in which water encroaches into a resrvoir from below, as due tothe upward movement of an oil-water contact. Using straight-forwardtechniques we find that, by inclusing reflections off the top and bottomof a reservoir tens of meters thick, we can infer reservoir permeabilitybased upon time-lapse data. We find that, for the caseof water influxfrom below, using multiple time-lapse 'snapshots' does not necessarilyimprove the resolution of reservoir permeability. An application totime-lapse data from the Norne field illustrates that we can resolve thepermeability near a producing well using reflections from threeinterfaces associated with the reservoir.

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We present a variation of an adaptive projection method forcomputing solutions to the incompressible Navier-Stokes equations withsuspended particles. To compute the divergence-free component of themomentum forcing due to the particle drag, we employ an approach whichexploits the locality and smoothness of the Laplacian of the projectionoperator applied to the discretized particle drag force. We presentconvergence and performance results to demonstrate the effectiveness ofthis approach.

A semiclassical IVR formulation using the Van-Vleck propagator has been used to calculate the flux correlation function and thereby reaction rate constants. This Van-Vleck formulation of the flux-flux correlation function is computationally as simple as the classical Wigner model. However unlike the latter, it has the ability to capture quantum interference/coherence effects. Classical trajectories are evolved starting from the dividing surface that separates reactants and products, and are evolved negatively in time. This formulation has been tested on model problems ranging from the Eckart barrier, double well to the collinear H + H{sub 2}.

Ferritic stainless steels have been identified as potential candidates for interconnects in planar-type solid oxide fuel cells (SOFC) operating below 800ºC. Crofer 22 APU was selected for this study. It was studied under simulated SOFC-interconnect dual environment conditions with humidified air on one side of the sample and humidified hydrogen on the other side at 750ºC. The surfaces of the oxidized samples were studied by scanning electron microscopy (SEM) equipped with microanalytical capabilities. X-ray diffraction (XRD) analysis was also used in this study.

The formation and evolution of massive red galaxies form a crucial test of theories of galaxy formation based on hierarchical assembly. In this Letter we use observations of the clustering of luminous red galaxies from the Boötes field and N-body simulations to argue that about of the most luminous satellite galaxies appear to undergo merging or disruption within massive halos between and 0.5.

The IMPACT (Integrated Map and Particle Accelerator Tracking) code was first developed under Computational Grand Challenge project in the mid 1990s [1]. It started as a three-dimensional (3D) data parallel particle-in-cell (PIC) code written in High Performance Fortran. The code used a split-operator based method to solve the Hamiltonian equations of motion. It contained linear transfer maps for drifts, quadrupole magnets and rf cavities. The space-charge forces were calculated using an FFT-based method with 3D open boundary conditions and longitudinal periodic boundary conditions. This code was completely rewritten in the late 1990s based on a message passing parallel programming paradigm using Fortran 90 and MPI following an object-oriented software design. This improved the code's scalability on large parallel computer systems and also gave the code better software maintainability and extensibility [2]. In the following years, under the SciDAC-1 accelerator project, the code was extended to include more accelerating and focusing elements such as DTL, CCL, superconducting linac, solenoid, dipole, multipoles, and others. Besides the original split-operator based integrator, a direct integration of Lorentz equations of motion using a leap-frog algorithm was also added to the IMPACT code to handle arbitrary external nonlinear fields. This integrator can read in 3D electromagnetic …

We carry out a comprehensive theoretical and experimentalstudy of charge injection in poly(3-hexylthiophene) (P3HT) to determinethe most likely scenario for metal-insulator transition in this system.Wecalculate the optical-absorption frequencies corresponding to a polaronand a bipolaron lattice in P3HT. We also analyze the electronicexcitations for three possible scenarios under which a first- or asecond-order metal-insulator transition can occur in doped P3HT. Thesetheoretical scenarios are compared with data from infrared absorptionspectroscopy on P3HT thin-film field-effect transistors (FETs). Ourmeasurements and theoretical predictions suggest that charge-inducedlocalized states in P3HT FETs are bipolarons and that the highest dopinglevel achieved in our experiments approaches that required for afirst-order metal-insulator transition.

The lateral order of poly(styrene-block-isoprene) copolymer(PS-b-PI) thin films is characterized by the emerging technique ofresonant soft X-ray scattering (RSOXS) at the carbon K edge and comparedto ordering in bulk samples of the same materials measured usingconventional small-angle X-ray scattering. We show resonance using theoryand experiment that the loss of scattering intensity expected with adecrease in sample volume in the case of thin films can be overcome bytuning X-rays to the pi* resonance of PS or PI. Using RSOXS, we study themicrophase ordering of cylinder- and phere-forming PS-b-PI thin films andcompare these results to position space data obtained by atomic forcemicroscopy. Our ability to examine large sample areas (~;9000 mu m2) byRSOXS enables unambiguous identification of the lateral lattice structurein the thin films. In the case of the sphere-forming copolymer thin film,where the spheres are hexagonally arranged, the average sphere-to-spherespacing is between the bulk (body-centered cubic) nearest neighbor andbulk unit cell spacings. In the case of the cylinder-forming copolymerthin film, the cylinder-to-cylinder spacing is within experimental errorof that obtained in the bulk.

Telomeres are maintained by three DNA binding proteins, TRF1, TRF2 and POT1, and several associated factors. One factor, TIN2, binds TRF1 and TRF2 directly and POT1 indirectly. These and two other proteins form a soluble complex that may be the core telomere-maintenance complex. It is not clear whether subcomplexes exist or function in vivo. Here, we provide evidence for two TIN2 subcomplexes with distinct functions in human cells. TIN2 ablation by RNA interference caused telomere uncapping and p53-independent cell death in all cells tested. However, we isolated two TIN2 complexes from cell lysates, each selectively sensitive to a TIN2 mutant (TIN2-13, TIN2-15C). In cells with wild-type p53 function, TIN2-15C was more potent than TIN2-13 in causing telomere uncapping and eventual growth arrest. In cells lacking p53 function, TIN215C more than TIN2-13 caused genomic instability and cell death. Thus, TIN2 subcomplexes likely have distinct functions in telomere maintenance, and may provide selective targets for eliminating cells with mutant p53.

Left unprotected, both transmissive and reflective final optics in a laser inertial fusion power plant would quickly fail from melting, pulsed thermal stresses, or degradation of optical properties as a result of ion implantation. One potential option for mitigating this threat is to magnetically deflect the ions such that they are directed into a robust energy dump. In this paper we detail integrated studies that have been carried out to asses the viability of this approach for protecting final optics.

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We present the first direct study of charge density wave(CDW) formation in quasi-2D single layer LaTe2 using high-resolutionangle resolved photoemission spectroscopy (ARPES) and low energy electrondiffraction (LEED). CDW formation is driven by Fermi surface (FS)nesting, however characterized by a surprisingly smaller gap (~;50 meV)than seen in the double layer RTe3 compounds, extending over the entireFS. This establishes LaTe2 as the first reported semiconducting 2D CDWsystem where the CDW phase is FS nesting driven. In addition, the layerdependence of this phase in the tellurides and the possible transitionfrom a stripe to a checkerboard phase is discussed.

In this study we compare the use of kinetic and equilibriumreaction models in the simulation of gas (methane) hydrate behavior inporous media. Our objective is to evaluate through numerical simulationthe importance of employing kinetic versus equilibrium reaction modelsfor predicting the response of hydrate-bearing systems to externalstimuli, such as changes in pressure and temperature. Specifically, we(1) analyze and compare the responses simulated using both reactionmodels for natural gas production from hydrates in various settings andfor the case of depressurization in a hydrate-bearing core duringextraction; and (2) examine the sensitivity to factors such as initialhydrate saturation, hydrate reaction surface area, and numericaldiscretization. We find that for large-scale systems undergoing thermalstimulation and depressurization, the calculated responses for bothreaction models are remarkably similar, though some differences areobserved at early times. However, for modeling short-term processes, suchas the rapid recovery of a hydrate-bearing core, kinetic limitations canbe important, and neglecting them may lead to significantunder-prediction of recoverable hydrate. The use of the equilibriumreaction model often appears to be justified and preferred for simulatingthe behavior of gas hydrates, given that the computational demands forthe kinetic reaction model far exceed those for the equilibrium reactionmodel.

All too often we rely on Monte Carlo simulations withoutworrying too much about basic physics. It is possible to start with avery simple calorimeter (a big cylinder) and learn the functional form ofpi e by aninduction argument. Monte Carlo simulations provide sanitychecks and constants. A power-law functional form describes test beamresults surprisingly well. The prediction that calorimeters responddifferently to protons and pions of the same energy was unexpected. Theeffect was later demonstrated by the CMS forward calorimeter group, usingthe most noncompensating calorimeter ever built. Calorimeter resolutionis dominated by fluctuations in piz production and the energy deposit byneutrons. The DREAM collaboration has recently used a dual readoutcalorimeter to eliminate the first of these. Ultimate resolution dependson measuring neutrons on an event-by-event basis as well.

The conversion efficiency of ultra short-pulse laser radiation to K-{alpha} x-rays has been measured for various chlorine-containing targets to be used as x-ray scattering probes of dense plasmas. The spectral and temporal properties of these sources will allow spectrally-resolved x-ray scattering probing with picosecond temporal resolution required for measuring the plasma conditions in inertial confinement fusion experiments. Simulations of x-ray scattering spectra from these plasmas show that fuel capsule density, capsule ablator density, and shock timing information may be inferred.

This presentation will highlight the U.S. Department of Energy's FutureGen Initiative. The nearly $1 billion government-industry project is a stepping-stone toward future coal-fired power plants that will produce hydrogen and electricity with zero-emissions, including carbon dioxide. The 275-megawatt FutureGen plant will initiate operations around 2012 and employ advanced coal gasification technology integrated with combined cycle electricity generation, hydrogen production, and carbon capture and sequestration. The initiative is a response to a presidential directive to develop a hydrogen economy by drawing upon the best scientific research to address the issue of global climate change. The FutureGen plant will be based on cutting-edge power generation technology as well as advanced carbon capture and sequestration systems. The centerpiece of the project will be coal gasification technology that can eliminate common air pollutants such as sulfur dioxide and nitrogen oxides and convert them to useable by-products. Gasification will convert coal into a highly enriched hydrogen gas, which can be burned much more cleanly than directly burning the coal itself. Alternatively, the hydrogen can be used in a fuel cell to produce ultra-clean electricity, or fed to a refinery to help upgrade petroleum products. Carbon sequestration will also be a key feature that will set …

Hundred-joule, kilowatt-class lasers based on diode-pumped solid-state technologies, are being developed worldwide for laser-plasma interactions and as prototypes for fusion energy drivers. The goal of the Mercury Laser Project is to develop key technologies within an architectural framework that demonstrates basic building blocks for scaling to larger multi-kilojoule systems for inertial fusion energy (IFE) applications. Mercury has requirements that include: scalability to IFE beamlines, 10 Hz repetition rate, high efficiency, and 10{sup 9} shot reliability. The Mercury laser has operated continuously for several hours at 55 J and 10 Hz with fourteen 4 x 6 cm{sup 2} ytterbium doped strontium fluoroapatite (Yb:S-FAP) amplifier slabs pumped by eight 100 kW diode arrays. The 1047 nm fundamental wavelength was converted to 523 nm at 160 W average power with 73% conversion efficiency using yttrium calcium oxy-borate (YCOB).

With the current interest in the rare-earth tellurides ashigh temperature charge density wave materials, a greater understandingof the physics of these systems is needed, particularly in the case ofthe ditellurides. We report a detailed study of the band structure ofLaTe_2 in the charge density wave state using high-resolution angleresolved photoemission spectroscopy (ARPES). From thiswork we hope toprovide insights into the successes and weaknesses of past theoreticalstudy as well as helping to clear up prior ambiguities by providing anexperimental basis for future work inthe tellurides.

Bromide and resting-cell bacteria tracer tests carried out in a sand and gravel aquifer at the USGS Cape Cod site in 1987 were reinterpreted using a three-dimensional stochastic approach and Lagrangian particle tracking numerical methods. Bacteria transport was strongly coupled to colloid filtration through functional dependence of local-scale colloid transport parameters on hydraulic conductivity and seepage velocity in a stochastic advection-dispersion/attachment-detachment model. Information on geostatistical characterization of the hydraulic conductivity (K) field from a nearby plot was utilized as input that was unavailable when the original analysis was carried out. A finite difference model for groundwater flow and a particle-tracking model of conservative solute transport was calibrated to the bromide-tracer breakthrough data using the aforementioned geostatistical parameters. An optimization routine was utilized to adjust the mean and variance of the lnK field over 100 realizations such that a best fit of a simulated, average bromide breakthrough curve is achieved. Once the optimal bromide fit was accomplished (based on adjusting the lnK statistical parameters in unconditional simulations), a stochastic particle-tracking model for the bacteria was run without adjustments to the local-scale colloid transport parameters. Good predictions of the mean bacteria breakthrough data were achieved using several approaches for modeling components of …

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Uniaxial compression experiments on copper single crystals, oriented to maximize the shear for one slip system, show some unexpected results. In addition to the expected activity on the primary slip system, the results show appreciable activity perpendicular to the primary system. The magnitude of the activity orthogonal to the primary varies from being equal to the primary for the as-fabricated samples to 1/5 of the primary in the samples annealed after fabrication.

The 'Computational Crystallography Toolbox' (cctbx, http://cctbx.sourceforge.net/) is the open-source component of the Phenix project (http://www.phenix-online.org/). Most recent cctbx developments are geared towards supporting new features of the phenix.refine application. Thus, the open-source mmtbx (macromolecular toolbox) module is currently being most rapidly developed. In this article we give an overview of some of the recent developments. However, the main theme of this article is the presentation of a light-weight example command-line application that was specifically developed for this newsletter: sequence alignment and superposition of two molecules read from files in PDB format. This involves parameter input based on the Phil module presented in Newsletter No. 5, fast reading of the PDB files with the new iotbx.pdb.input class, simple sequence alignment using the new mmtbx.alignment module, and use of the Kearsley (1989) superposition algorithm to find the least-squares solution for superposing C-alpha positions. The major steps are introduced individually, followed by a presentation of the complete application. The example application is deliberately limited in functionality to make it concise enough for this article. The main goal is to show how the open-source components are typically combined into an application. Even though the example is quite specific to macromolecular crystallography, we believe it …