Specific inhibitors of MEK have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We employed a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understand molecular mechanisms conferring resistance to such compounds. Basal-type breast cancer cells were found to be particularly susceptible to growth-inhibition by small-molecule MEK inhibitors. Activation of the PI3 kinase pathway in response to MEK inhibition through a negative MEK-EGFR-PI3 kinase feedback loop was found to limit efficacy. Interruption of this feedback mechanism by targeting MEK and PI3 kinase produced synergistic effects, including induction of apoptosis and, in some cell lines, cell cycle arrest and protection from apoptosis induced by proapoptotic agents. These findings enhance our understanding of the interconnectivity of oncogenic signal transduction circuits and have implications for the design of future clinical trials of MEK inhibitors in breast cancer by guiding patient selection and suggesting rational combination therapies.

The resummation of soft gluon exchange for QCD hard scattering requires a matrix of anomalous dimensions, which has been computed through two loops. The two-loop matrix is proportional to the one-loop matrix. Recently there have been proposals that this proportionality extends to higher loops. One can test such proposals by computing the dependence of this matrix on the matter content in a generic gauge theory. It is shown that for the matter-dependent part the proportionality extends to three loops for arbitrary massless processes.

During the summers of 2004 and 2006, extinction and scattering coefficients of particle emissions inside a San Francisco Bay Area roadway tunnel were measured using a combined cavity ring-down and nephelometer instrument. Particle size distributions and humidification were also measured, as well as several gas phase species. Vehicles in the tunnel traveled up a 4% grade at a speed of approximately 60 km h{sup -1}. The traffic situation in the tunnel allows the apportionment of emission factors between light duty gasoline vehicles and diesel trucks. Cross-section emission factors for optical properties were determined for the apportioned vehicles to be consistent with gas phase and particulate matter emission factors. The absorption emission factor (the absorption cross-section per mass of fuel burned) for diesel trucks (4.4 {+-} 0.79 m{sup 2} kg{sup -1}) was 22 times larger than for light-duty gasoline vehicles (0.20 {+-} 0.05 m{sup 2} kg{sup -1}). The single scattering albedo of particles - which represents the fraction of incident light that is scattered as opposed to absorbed - was 0.2 for diesel trucks and 0.3 for light duty gasoline vehicles. These facts indicate that particulate matter from motor vehicles exerts a positive (i.e., warming) radiative climate forcing. Average particulate mass …

It is a challenge to generate full charge electrons from the electron sources without compromising polarization for the proposed ILC and CLIC. It is essential to advance polarized photocathodes to meet the requirements. SLAC has worldwide unique dedicated test facilities, Cathode Test System and dc-Gun Test Laboratory, to fully characterize polarized photocathodes. Recent systematic measurements on a strained-well InAlGaAs/AlGaAs cathode at the facilities show that 87% polarization and 0.3% QE are achieved. The QE can be increased to {approx}1.0% with atomic hydrogen cleaning. The surface charge limit at a very low current intensity and the clear dependence of the polarization on the surface charge limit are observed for the first time. On-going programs to develop photocathodes for the ILC and CLIC are briefly introduced.

The XRD-31 is a fast, windowless X-ray vacuum photodiode developed by EG&G. It is currently the primary fast X-ray detector used to diagnose the X-rays on NIF and OMEGA on the multichannel DANTE spectrometer. The XRD-31 has a dynamic range of less than 1e-12 amps to more than 10 amps. A technique is described to measure the impulse response of the diodes to a 150 fs pulse of 200 nm laser light and a method to calculate the “risetime” for a square pulse and compare it with the computed electron transit time from the photocathode to the anode. Measured response time for 5 XRD-31s assembled in early 2004 was 149.7 ps +-2.75 ps.

An evaluation of a large number of air sample filters was undertaken using a commercial alpha and beta spectroscopy system employing a passive implanted planar silicon (PIPS) detector. Samples were only measured after air flow through the filters had ceased. Use of a commercial radon stripping algorithm was implemented to discriminate anthropogenic alpha and beta activity on the filters from the radon progeny. When uncontaminated air filters were evaluated, the results showed that there was a time-dependent bias in both average estimates and measurement dispersion with the relative bias being small compared to the dispersion. By also measuring environmental air sample filters simultaneously with electroplated alpha and beta sources, use of the radon stripping algorithm demonstrated a number of substantial unexpected deviations. Use of the current algorithm is therefore not recommended for assay applications and so use of the PIPS detector should only be utilized for gross counting without appropriate modifications to the curve fitting algorithm. As a screening method, the radon stripping algorithm might be expected to see elevated alpha and beta activities on air sample filters (not due to radon progeny) around the 200 dpm level.

Recent developments in the theory of strong interactions are discussed in the framework of the AdS/CFT duality between string theories of gravity in a higher dimension Anti-de Sitter space and conformal quantum field theories in physical space-time. This novel theoretical approach, combined with 'light-front holography', leads to new insights into the quark and gluon structure of hadrons and a viable first approximation to quantum chromodynamics, the fundamental theory of the strong and nuclear interactions.

Using an extreme-ultraviolet (EUV) microscope to produce high-quality images of EUV reticles, we have developed a new wavelength tuning method to acquire through-focus data series with a higher level of stability and repeatability than was previously possible. We utilize the chromatic focal-length dependence of a diffractive Fresnel zoneplate objective lens, and while holding the mask sample mechanically still, we tune the wavelength through a narrow range, in small steps. In this paper, we demonstrate the method and discuss the relative advantages that this data collection technique affords.

Aerial images for isolated defects and the interactions of defects with features are compared between the Actinic Inspection Tool (AIT) at Lawrence Berkeley National Laboratory (LBNL) and the fast EUV simulation program RADICAL. Comparisons between AIT images from August 2007 and RADICAL simulations are used to extract aberrations. At this time astigmatism was the dominant aberration with a value of 0.55 waves RMS. Significant improvements in the imaging performance of the AIT were made between August 2007 and December 2008. A good match will be shown between the most recent AIT images and RADICAL simulations without aberrations. These comparisons will demonstrate that a large defect, in this case 7nm tall on the surface, is still printable even if it is centered under the absorber line. These comparisons also suggest that the minimum defect size is between 1.5nm and 0.8nm surface height because a 1.5nm defect was printable but a 0.8nm was not. Finally, the image of a buried defect near an absorber line through focus will demonstrate an inversion in the effect of the defect from a protrusion of the dark line into the space to a protrusion of the space into the line.

Geologic carbon sequestration is the injection of anthropogenic CO{sub 2} into deep geologic formations where the CO{sub 2} is intended to remain indefinitely. If successfully implemented, geologic carbon sequestration will have little or no impact on terrestrial ecosystems aside from the mitigation of climate change. However, failure of a geologic carbon sequestration site, such as large-scale leakage of CO{sub 2} into a potable groundwater aquifer, could cause impacts that would require costly remediation measures. Governments are attempting to develop regulations for permitting geologic carbon sequestration sites to ensure their safety and effectiveness. At present, these regulations focus largely on decreasing the probability of failure. In this paper we propose that regulations for the siting of early geologic carbon sequestration projects should emphasize limiting the consequences of failure because consequences are easier to quantify than failure probability.

The authors present a Dalitz-plot analysis of charmless B{sup {+-}} decays to the final state {pi}{sup {+-}}{pi}{sup {+-}}{pi}{sup {-+}} using a sample of (465 {+-} 5) x 10{sup 6} B{bar B} pairs collected by the BABAR experiment at {radical}s = 10.58 GeV. They measure the branching fractions {Beta}(B{sup {+-}} {yields} {pi}{sup {+-}}{pi}{sup {+-}}{pi}{sup {-+}}) = (15.2 {+-} 0.6 {+-} 1.2 {+-} 0.4) x 10{sup -6}, {Beta}(B{sup {+-}} {yields} {rho}{sup 0}(770){pi}{sup {+-}}) = (8.1 {+-} 0.7 {+-} 1.2{sub -1.1}{sup +0.4}) x 10{sup -6}, {Beta}(B{sup {+-}} {yields} f{sub 2}(1270){pi}{sup {+-}}) = (1.57 {+-} 0.42 {+-} 0.16{sub -0.19}{sup +0.53}) x 10{sup -6}, and {Beta}(B{sup {+-}} {yields} {pi}{sup {+-}}{pi}{sup {+-}}{pi}{sup {-+}} nonresonant) = (5.3 {+-} 0.7 {+-} 0.6{sub -0.5}{sup +1.1}) x 10{sup -6}, where the uncertainties are statistical, systematic, and model-dependent, respectively. Measurements of branching fractions for the modes B{sup {+-}} {yields} {rho}{sup 0}(1450){pi}{sup {+-}} and B{sup {+-}} {yields} f{sub 0}(1370){pi}{sup {+-}} are also presented. They observe no significant direct CP asymmetries for the above modes, and there is no evidence for the decays B{sup {+-}} {yields} f{sub 0}(980){pi}{sup {+-}}, B{sup {+-}} {yields} {chi}{sub c0}{pi}{sup {+-}}, or B{sup {+-}} {yields} {chi}{sub c2}{pi}{sup {+-}}.

We examine size dependent deliquescence/efflorescence phase transformation for particles down to several nanometers in size. A thin layer criterion (TLC) is introduced to define a deliquescence relative humidity (DRH) for small particles. The usual bulk deliquescence conditions are recovered in the limit of large dry particle size. Nano-size particles are shown to deliquesce to metastable states via a nucleation process at relative humidity just below the DRH. The nucleation barrier is located at a critical solution layer thickness and vanishes at the DRH defined by the TLC. Methods from nucleation theory form the basis for the analysis and yield new insights into the theory, facilitate the interpretation of measurements, and point to unification of deliquescence and efflorescence processes for particles in the nano regime. Methods include thermodynamic area constructions, Legendre transforms relating the binary free-energy surfaces for deliquescence and efflorescence processes, and application of nucleation theorems.

We consider the Bekenstein-Hawking entropy-area formula in four dimensional extended ungauged supergravity and its electric-magnetic duality property. Symmetries of both"large" and"small" extremal black holes are considered, as well as the ADM mass formula for N=4 and N=8 supergravity, preserving different fraction of supersymmetry. The interplay between BPS conditions and duality properties is an important aspect of this investigation.

We present results on a table-top microscope that uses an EUV stepper geometry to capture full-field images with a halfpitch spatial resolution of 55 nm. This microscope uses a 13.2 nm wavelength table-top laser for illumination and acquires images of reflective masks with exposures of 20 seconds. These experiments open the path to the realization of high resolution table-top imaging systems for actinic defect characterization.

Sum frequency generation vibrational spectroscopy (SFG) and quartz crystal microbalance with dissipation monitoring (QCM-D) are employed to study the interfacial structure and adsorbed amount of the amino acids l-lysine and l-proline and their corresponding homopeptides, poly-l-lysine and poly-l-proline, at two liquid-solid interfaces. SFG and QCM-D experiments of these molecules are carried out at the interface between phosphate buffered saline at pH 7.4 (PBS) and the hydrophobic deuterated polystyrene (d{sub 8}-PS) surface as well as the interface between PBS and hydrophilic fused silica (SiO{sub 2}). The SFG spectra of the amino acids studied here are qualitatively similar to their corresponding homopeptides; however, the SFG signal from amino acids at the solid/PBS interface is smaller in magnitude relative to their more massive homopeptides at the concentrations studied here. Substantial differences are observed in SFG spectra for each species between the hydrophobic d{sub 8}-PS and the hydrophilic SiO{sub 2} liquid-solid interfaces, suggesting surface-dependent interfacial ordering of the biomolecules. Over the range of concentrations used in this study, QCM-D measurements also indicate that on both surfaces poly-l-lysine adsorbs to a greater extent than its constituent amino acid l-lysine. The opposite trend is demonstrated by poly-l-proline which sticks to both surfaces less extensively than its …

The authors present measurements of the semileptonic decays B{sup -} {yields} D{sup 0} {tau}{sup -} {bar {nu}}{sub {tau}}, B{sup -} {yields} D*{sup 0} {tau}{sup -}{bar {nu}}{sub {tau}}, {bar B}{sup 0} {yields} D{sup +} {tau}{sup -} {bar {nu}}{sub {tau}}, and {bar B}{sup 0} {yields} D*{sup +} {tau}{sup -}{bar {nu}}{sub {tau}}, which are sensitive to non-Standard Model amplitudes in certain scenarios. The data sample consists of 232 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEP-II e{sup +}e{sup -} collider. They select events with a D or D* meson and a light lepton ({ell} = e or {mu}) recoiling against a fully reconstructed B meson. They perform a fit to the joint distribution of lepton momentum and missing mass squared to distinguish signal B {yields} D{sup (*)}{tau}{sup -} {bar {nu}}{sub {tau}} ({tau}{sup -} {yields} {ell}{sup -} {bar {nu}}{sub {ell}}{nu}{sub {tau}}) events from the backgrounds, predominantly B {yields} D{sup (*)} {ell}{sup -}{bar {nu}}{sub {ell}}. They measure the branching-fraction ratios R(D) {triple_bond} {Beta}(B {yields} D{tau}{sup -} {bar {nu}}{sub {tau}})/{Beta}(B {yields} D{ell}{sup -} {bar {nu}}{sub {ell}}) and R(D*) {triple_bond} {Beta}(B {yields} D*{tau}{sup -} {bar {nu}}{sub {tau}})/{Beta}(B {yields} D* {ell}{sup -} {bar {nu}}{sub {ell}}) and, from a combined fit …

Metastable vacua in supersymmetric QCD in the presence of single and multitrace deformations of the superpotential are explored, with the aim of obtaining an acceptable phenomenology. The metastable vacua appear at one loop, have a broken R-symmetry, and a magnetic gauge group that is completely Higgsed. With only a single trace deformation, the adjoint fermions from the meson superfield are approximately massless at one loop, even though they are massive at tree level and R-symmetry is broken. Consequently, if charged under the standard model, they are unacceptably light. A multitrace quadratic deformation generates fermion masses proportional to the deformation parameter. Phenomenologically viable models of direct gauge mediation can then be obtained, and some of their features are discussed.

For the commercialization of extreme ultraviolet lithography (EUVL), discharge or laser produced, pulsed plasma light sources are being considered. These sources are known to emit into a broad range of wavelengths that are collectively referred to as the out-of-band (OOB) radiation by lithographers. Multilayer EUV optics reflect OOB radiation emitted by the EUV sources onto the wafer plane resulting in unwanted background exposure of the resist (flare) and reduced image contrast. The reflectivity of multilayer optics at the target wavelength of 13.5 nm is comparable to that of their reflectivity in the deep ultraviolet (DUV) and UV regions from 100-350 nm. The aromatic molecular backbones of many of the resists used for EUV are equally absorptive at specific DUV wavelengths as well. In order to study the effect of these wavelengths on imaging performance in a real system, we are in the process of integrating a DUV source into the SEMATECH Berkeley 0.3-NA Microfield Exposure Tool (MET). The MET plays an active role in advanced research in resist and mask development for EUVL and as such, we will utilize this system to systematically evaluate the imaging impact of DUV wavelengths in a EUV system. In this paper, we present the …

We report on the first next-to-leading order QCD computation of W + 3-jet production in hadronic collisions including all partonic subprocesses. We compare the results with CDF data from the Tevatron, and find excellent agreement. The renormalization and factorization scale dependence is reduced substantially compared to leading-order calculations. The required one-loop matrix elements are computed using on-shell methods, implemented in a numerical program, BlackHat. We use the SHERPA package to generate the real-emission contributions and to integrate the various contributions over phase space. We use a leading-color (large-N{sub c}) approximation for the virtual part, which we confirm in W + 1,2-jet production to be valid to within three percent. The present calculation demonstrates the utility of on-shell methods for computing next-to-leading-order corrections to processes important to physics analyses at the Large Hadron Collider.

The authors search for charmless decays of charged B mesons to the three-body final state K{sub S}{sup 0}K{sub S}{sup 0}{pi}{sup +}. Using a data sample of 423.7 fb{sup -1} collected at the {Upsilon}(4S) resonance with the BABAR detector, corresponding to (465.1 {+-} 5.1) x 10{sup 6} B{bar B} pairs, they find no significant signal and determine a 90% confidence level upper limit on the branching fraction of 5.1 x 10{sup -7}.

Simulated calorimeter performance in the SiD detector is examined. The software calibration procedures are described, as well as the perfect pattern recognition PFA reconstruction. Performance of the SiD calorimeters is summarized with jet energy resolutions from calorimetry only, perfect pattern recognition and the SiD PFA algorithm. Presented at LCWS08[1]. Our objective is to simulate the calorimeter performance of the SiD detector, with and without a Particle Flow Algorithm (PFA). Full Geant4 simulations using SLIC[2] and the SiD simplified detector geometry (SiD02) are used. In this geometry, the calorimeters are represented as layered cylinders. The EM calorimeter is Si/W, with 20 layers of 2.5mm W and 10 layers of 5mm W, segmented in 3.5 x 3.5mm{sup 2} cells. The HAD calorimeter is RPC/Fe, with 40 layers of 20mm Fe and a digital readout, segmented in 10 x 10mm{sup 2} cells. The barrel detectors are layered in radius, while the endcap detectors are layered in z(along the beam axis).

The Savannah River Site (SRS) Burial Ground had a container labeled as Box 33 for which they had no reliable solid waste stream designation. The container consisted of an outer box of dimensions 48-inch x 46-inch x 66-inch and an inner box that contained high density and high radiation dose material. From the outer box Radiation Control measured an extremity dose rate of 22 mrem/h. With the lid removed from the outer box, the maximum dose rate measured from the inner box was 100 mrem/h extremity and 80 mrem/h whole body. From the outer box the material was sufficiently high in density that the Solid Waste Management operators were unable to obtain a Co-60 radiograph of the contents. Solid Waste Management requested that the Analytical Development Section of Savannah River National Laboratory perform a {gamma}-ray assay of the item to evaluate the radioactive content and possibly to designate a solid waste stream. This paper contains the results of three models used to analyze the measured {gamma}-ray data acquired in an unusual configuration.

Magnetization reversal in patterned ferromagnetic nanowires usually occurs via domain wall (DW) nucleation and propagation from one end (or both ends) of the wire which can be significantly reduced by a large, magnetically soft pad on one of the wire ends. These 'nucleation pads' reverse at lower fields than an isolated nanowire and introduce a DW to the wire from the wire end attached to the pad. Once a critical 'injection' field is reached, the DW sweeps through the wire, reversing its magnetization. Nucleation pads are frequently used as part of nanowire devices and experimental structures. Magnetic-field-driven shift register memory can include an injection pad to write data while those attached to nanowire spiral turn sensors act as both a source and sink of domain walls. Both of these devices use two-dimensional wire circuits and therefore require the use of orthogonal in-plane magnetic fields to drive domain walls through wires of different orientations. These bi-axial fields can significantly alter the fields at which DW injection occurs and control the number of different injection modes. We have used magnetic transmission soft X-ray microscopy (M-TXM) [6] providing 25nm spatial resolution to image the evolution of magnetization configurations in patterned 24nm thick Ni{sub …

Article discussing linear free energy relationship correlations for room temperature ionic liquids and revised cation-specific and anion-specific equation coefficients for predictive applications covering a much larger area of chemical space.