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.

This report examines compulsory DNA collection by law enforcement and its implications in regards to 4th amendment protections by examining legal precedents and considering the contemporary scientific understanding of DNA.

This report discusses the passing of the American Recovery and Reinvestment Act of 2009, which included tax cut and spending provisions totaling at a cost of $787 billion in an attempt to mitigate the economic fallout of the housing and financial crises on the general economy. The report examines issues surrounding fiscal stimulus such as timeliness, the magnitude of stimulus, long-term effects and previously adopted policies.

This annual report provides details on the research conducted at EMSL--the Environmental Molecular Sciences Laboratory in Fiscal Year 2008.

This report discusses the history of the Federal Protective Service, which is responsible for protecting federal government property, personnel, visitors, and customers, including property leased by the General Services Administration (GSA). FPS currently employs over 15,000 contract security guards to protect federal property.

Daily publication of the U.S. Office of the Federal Register contains rules and regulations, proposed legislation and rule changes, and other notices, including "Presidential proclamations and Executive Orders, Federal agency documents having general applicability and legal effect, documents required to be published by act of Congress, and other Federal agency documents of public interest" (p. ii). Table of Contents starts on page iii.

A letter report issued by the Government Accountability Office with an abstract that begins "U.S. Citizenship and Immigration Services (USCIS) announced an increase to its immigration and naturalization application fees by an average of 86 percent, effective July 2007, contributing to a surge in application volume that challenged the agency's pre-adjudicative operations. In July 2007, the incoming application volume increased an unprecedented 100 percent over the prior month and the processing of 1.47 million applications was delayed. GAO was asked to review USCIS's current fee design and compare it to the principles in GAO's user-fee design guide and USCIS's management of operations affected by the new fees, specifically in projecting application volumes and contracting for application processing services. To do so, GAO reviewed legislation and agency documentation; compared the fee design to GAO's principles of effective user-fee design (equity, efficiency, revenue adequacy, and administrative burden); visited processing centers; and interviewed agency officials at these locations and in headquarters."

This report discusses the Voluntary Voting System Guidelines (VVSG), which are a set of technical standards for voting systems that use computers to assist in recording or counting votes. Systems covered include most used in the United States—not only DREs (direct recording electronic systems) such as touchscreen voting machines, but also optical scan and punch card systems. Hand-counted paper-ballot and lever-machine systems, which do not involve computers, are not covered. However, they are used by a small and decreasing number of election jurisdictions.

A letter report issued by the Government Accountability Office with an abstract that begins "The Department of Homeland Security's (DHS) U.S. Citizenship and Immigration Services (USCIS) is responsible for granting or denying immigration benefits to individuals. USCIS charges fees for the millions of immigration applications it receives each year to fund the cost of processing and adjudicating them. In February 2007, USCIS completed a study to determine the full costs of its operations and the level at which application fees should be set to recover those costs. USCIS's new fee schedule increased application fees by a weighted average of 86 percent. Almost 96 percent of USCIS's fiscal year 2008 budget of $2.6 billion was expected to have come from fees. GAO was asked to review the methodology USCIS used in its fee review and controls in place over collection and use of fees. In this report, GAO addresses the consistency of the methodology with federal accounting standards and principles and other guidance, including whether key assumptions and methods were sufficiently justified and documented. The report also addresses internal controls USCIS has in place over the collection and use of fees."

This report discusses the primary civil, criminal, and immigration-related penalties associated with immigration-related document fraud. In order to enter or remain in the United States and be eligible for various immigration-related benefits, non-citizens (aliens) must comply with a number of document requirements under the Immigration and Nationality Act (INA).

This report discusses provisions of the Detainee Treatment Act concerning standards for the interrogation and treatment of detainees.

Failure occurs when one or more of the intended functions of a product are no longer fulfilled to the customer's satisfaction. The most critical product failures are those that escape design reviews and in-house quality inspection and are found by the customer. The product may work for a while until its performance degrades to an unacceptable level or it may have not worked even before customer took possession of the product. The end results of failures which may lead to unsafe conditions or major losses of the main function are rated high in severity. Failure Modes and Effects Analysis (FMEA) is a tool widely used in the automotive, aerospace, and electronics industries to identify, prioritize, and eliminate known potential failures, problems, and errors from systems under design, before the product is released (Stamatis, 1997). Several industrial FMEA standards such as those published by the Society of Automotive Engineers, US Department of Defense, and the Automotive Industry Action Group employ the Risk Priority Number (RPN) to measure risk and severity of failures. The Risk Priority Number (RPN) is a product of 3 indices: Occurrence (O), Severity (S), and Detection (D). In a traditional FMEA process design engineers typically analyze the 'root …

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.

This report discusses the mission of the North Atlantic Treaty Organization (NATO) in Afghanistan, the purpose of which is to stabilize and reconstruct Afghanistan by combating emerging threats such as terrorism and the proliferation of weapons of mass destruction. This report also discusses how the Obama Administration has made the Afghanistan conflict a policy priority, and what this stance could mean for potential future endeavors.

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.

This multi-investigator project was concerned with the development and application of new methods and computer codes that would allow realistic modeling of nanosystems. Carter's part in this team effort involved two method/algorithm/code development projects during the first 14 months of this grant. Carter's group has been advancing theory and applications of the orbital-free density functional theory (OF-DFT), the only DFT method that exhibits linear scaling for metals. Such a method offers the possibility of simulating large numbers of atoms with quantum mechanics, such that properties of metallic nanostructures (e.g. nanowires of realistic dimensions) could be investigated. In addition, her group has been developing and applying an embedded correlated wavefunction theory for treating localized excited states in condensed matter (including metals). The application of interest here is spin manipulation at the nanoscale, i.e., spintronics, in which local electron excitations interact with the surrounding material. Her embedded correlation method is ideal for studying such problems.

This report outlines some of the current supply issues facing biofuels industries, including implications for agricultural feedstocks, infrastructure concerns, energy supply for biofuels production, and fuel price uncertainties.

This document summarizes the performance of the groundwater restoration systems installed by the Commodity Credit Corporation of the U.S. Department of Agriculture (CCC/USDA) at the former CCC/USDA grain storage facility in Utica, Nebraska, during the fourth year of system operation, from December 1, 2007, until November 30, 2008. Performance in earlier years was reported previously (Argonne 2005, 2006, 2008). In the project at Utica, the CCC/USDA is cooperating with multiple state and federal agencies to remove carbon tetrachloride contamination from a shallow aquifer underlying the town and to provide supplemental treated groundwater for use in the restoration of a nearby wetlands area. Argonne National Laboratory assisted the CCC/USDA by providing technical oversight for the aquifer restoration effort and facilities during this review period. This document presents overviews of the aquifer restoration facilities (Section 2) and system operations (Section 3). The report then describes groundwater production results (Section 4); groundwater treatment results (Section 5); and associated maintenance, system modifications, and costs during the review period (Section 6). Section 7 summarizes the present year of operation.

A paper about how the United States Environmental Protection Agency accepts applications from federally recognized Tribal governments and Tribal consortia with specific focus on the availability of funds and solicits applications from eligible entities to receive financial assistance through the Sustainability for the 7th Generation Initiative (SGI).

A weekly publication, the Texas Register serves as the journal of state agency rulemaking for Texas. Information published in the Texas Register includes proposed, adopted, withdrawn and emergency rule actions, notices of state agency review of agency rules, governor's appointments, attorney general opinions, and miscellaneous documents such as requests for proposals. After adoption, these rulemaking actions are codified into the Texas Administrative Code.

This report frames potential policy questions concerning the U.S. Secret Service's (USSS's) mission and organization through an examination of the USSS history and its statutory authorities, mission, and present activities within the Department of Homeland Security (DHS).

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.