Advanced Waveform Simulation for Seismic Monitoring Events (open access)

Advanced Waveform Simulation for Seismic Monitoring Events

Abstract We conduct a detailed test of a recently developed technique, CAPloc, in recovering source parameters from a few stations against results from a large broadband network in Southern California. The method uses a library of 1D Green’s functions which are broken into segments and matched to waveform observations with adjustable timing shifts. These shifts can be established by calibration against a distribution of well-located earthquakes and assembled in tomographic images for predicting various phase-delays. Synthetics generated from 2D cross-sections through these models indicates that 1D synthetic waveforms are sufficient in modeling but simply shifted in time for most hard-rock sites. This simplification allows the source inversion for both mechanism and location to easily obtain by grid search. We test one-station mechanisms for 160 events against the array for both PAS and GSC which have data since 1960. While individual solutions work well (about 90%), joint solutions produce more reliable and defensible results. Inverting for both mechanism and location also works well except for certain complex paths across deep basins and along mountain ridges.
Date: January 27, 2009
Creator: Helmberger, Donald V.; Tromp, Jeroen & Rodgers, Arthur J.
Object Type: Report
System: The UNT Digital Library
California Wintertime Precipitation in Regional and Global Climate Models (open access)

California Wintertime Precipitation in Regional and Global Climate Models

In this paper, wintertime precipitation from a variety of observational datasets, regional climate models (RCMs), and general circulation models (GCMs) is averaged over the state of California (CA) and compared. Several averaging methodologies are considered and all are found to give similar values when model grid spacing is less than 3{sup o}. This suggests that CA is a reasonable size for regional intercomparisons using modern GCMs. Results show that reanalysis-forced RCMs tend to significantly overpredict CA precipitation. This appears to be due mainly to overprediction of extreme events; RCM precipitation frequency is generally underpredicted. Overprediction is also reflected in wintertime precipitation variability, which tends to be too high for RCMs on both daily and interannual scales. Wintertime precipitation in most (but not all) GCMs is underestimated. This is in contrast to previous studies based on global blended gauge/satellite observations which are shown here to underestimate precipitation relative to higher-resolution gauge-only datasets. Several GCMs provide reasonable daily precipitation distributions, a trait which doesn't seem tied to model resolution. GCM daily and interannual variability is generally underpredicted.
Date: April 27, 2009
Creator: Caldwell, P M
Object Type: Article
System: The UNT Digital Library
CCN Spectral Measurements (open access)

CCN Spectral Measurements

Detailed aircraft measurements were made of cloud condensation nuclei (CCN) spectra associated with extensive cloud systems off the central California coast in the July 2005 MASE project. These measurements include the wide supersaturation (S) range (2-0.01%) that is important for these polluted stratus clouds. Concentrations were usually characteristic of continental/anthropogenic air masses. The most notable feature was the consistently higher concentrations above the clouds than below. CCN measurements are so important because they provide a link between atmospheric chemistry and cloud-climate effects, which are the largest climate uncertainty. Extensive comparisons throughout the eleven flights between two CCN spectrometers operated at different but overlapping S ranges displayed the precision and accuracy of these difficult spectral determinations. There are enough channels of resolution in these instruments to provide differential spectra, which produce more rigorous and precise comparisons than traditional cumulative presentations of CCN concentrations. Differential spectra are also more revealing than cumulative spectra. Only one of the eleven flights exhibited typical maritime concentrations. Average below cloud concentrations over the two hours furthest from the coast for the 8 flights with low polluted stratus was 614?233 at 1% S, 149?60 at 0.1% S and 57?33 at 0.04% S cm-3. Immediately above cloud average …
Date: February 27, 2009
Creator: Hudson, James G.
Object Type: Report
System: The UNT Digital Library
CH Packaging Operations Manual (open access)

CH Packaging Operations Manual

This document provides the user with instructions for assembling a payload. All the steps in Subsections 1.2, Preparing 55-Gallon Drum Payload Assembly; 1.3, Preparing "Short" 85-Gallon Drum Payload Assembly (TRUPACT-II and HalfPACT); 1.4, Preparing "Tall" 85-Gallon Drum Payload Assembly (HalfPACT only); 1.5, Preparing 100-Gallon Drum Payload Assembly; 1.6, Preparing Shielded Container Payload Assembly; 1.7, Preparing SWB Payload Assembly; and 1.8, Preparing TDOP Payload Assembly, must be completed, but may be performed in any order as long as radiological control steps are not bypassed. Transport trailer operations, package loading and unloading from transport trailers, hoisting and rigging activities such as ACGLF operations, equipment checkout and shutdown, and component inspection activities must be performed, but may be performed in any order and in parallel with other activities as long as radiological control steps are not bypassed. Steps involving OCA/ICV lid removal/installation and payload removal/loading may be performed in parallel if there are multiple operators working on the same packaging. Steps involving removal/installation of OCV/ICV upper and lower main O-rings must be performed in sequence, except as noted.
Date: May 27, 2009
Creator: None, None
Object Type: Report
System: The UNT Digital Library
Comments on the Joint Proposed Rulemaking to Establish Light-Duty Vehicle Greenhouse Gas Emission Standards and Corporate Average Fuel Economy Standards (open access)

Comments on the Joint Proposed Rulemaking to Establish Light-Duty Vehicle Greenhouse Gas Emission Standards and Corporate Average Fuel Economy Standards

I appreciate the opportunity to provide comments on the joint rulemaking to establish greenhouse gas emission and fuel economy standards for light-duty vehicles. My comments are directed at the choice of vehicle footprint as the attribute by which to vary fuel economy and greenhouse gas emission standards, in the interest of protecting vehicle occupants from death or serious injury. I have made several of these points before when commenting on previous NHTSA rulemakings regarding CAFE standards and safety. The comments today are mine alone, and do not necessarily represent the views of the US Department of Energy, Lawrence Berkeley National Laboratory, or the University of California. My comments can be summarized as follows: (1) My updated analysis of casualty risk finds that, after accounting for drivers and crash location, there is a wide range in casualty risk for vehicles with the same weight or footprint. This suggests that reducing vehicle weight or footprint will not necessarily result in increased fatalities or serious injuries. (2) Indeed, the recent safety record of crossover SUVs indicates that weight reduction in this class of vehicles resulted in a reduction in fatality risks. (3) Computer crash simulations can pinpoint the effect of specific design changes …
Date: October 27, 2009
Creator: Wenzel, Thomas P
Object Type: Report
System: The UNT Digital Library
Conductivity maximum in a charged colloidal suspension (open access)

Conductivity maximum in a charged colloidal suspension

Molecular dynamics simulations of a charged colloidal suspension in the salt-free regime show that the system exhibits an electrical conductivity maximum as a function of colloid charge. We attribute this behavior to two main competing effects: colloid effective charge saturation due to counterion 'condensation' and diffusion slowdown due to the relaxation effect. In agreement with previous observations, we also find that the effective transported charge is larger than the one determined by the Stern layer and suggest that it corresponds to the boundary fluid layer at the surface of the colloidal particles.
Date: January 27, 2009
Creator: Bastea, S
Object Type: Article
System: The UNT Digital Library
Cryogenic Field Measurement of Pr2Fe14B Undulator and Performance Enhancement Options at the NSLS-II (open access)

Cryogenic Field Measurement of Pr2Fe14B Undulator and Performance Enhancement Options at the NSLS-II

Short period (14.5mm) hybrid undulator arrays composed of Praseodymium Iron Boron (Pr{sub 2}Fe{sub 14}B) magnets (CR53, NEOMAX, Inc.) and vanadium permendur poles have been fabricated at Brookhaven National Laboratory. Unlike Neodymium Iron Boron (Nd{sub 2}Fe{sub 14}B) magnets which exhibit spin reorientation at temperatures below 150K, PrFeB arrays monotonically increase performance with lower operating temperature. It opens up the posibility for use in operating a cryo-permanent magnet undulator (CPMU) in the range of 40K to 60K where very efficient cryocoolers are available. Magnetic flux density profiles were measured at various temperature ranges from room temperature down to liquid helium (LHe) using the Vertical Testing Facility (VTF) at the National Snchrotron Light Source-II (NSLS-II). Temperature variations of phase error have been characterized. In addition, we examined the use of textured Dysprosium (Dy) poles to replace permendur poles to obtain further improvement in performance.
Date: September 27, 2009
Creator: Tanabe, T.; Chubar, O.; Harder, David A.; Lehecka, Michael; Rank, James; Rakowsky, George et al.
Object Type: Article
System: The UNT Digital Library
Determining the Porosity and Saturated Hydraulic Conductivity of Binary Mixtures (open access)

Determining the Porosity and Saturated Hydraulic Conductivity of Binary Mixtures

Gravels and coarse sands make up significant portions of some environmentally important sediments, while the hydraulic properties of the sediments are typically obtained in the laboratory using only the fine fraction (e.g., <2 mm or 4.75 mm). Researchers have found that the content of gravel has significant impacts on the hydraulic properties of the bulk soils. Laboratory experiments were conducted to measure the porosity and the saturated hydraulic conductivity of binary mixtures with different fractions of coarse and fine components. We proposed a mixing-coefficient model to estimate the porosity and a power-averaging method to determine the effective particle diameter and further to predict the saturated hydraulic conductivity of binary mixtures. The proposed methods could well estimate the porosity and saturated hydraulic conductivity of the binary mixtures for the full range of gravel contents and was successfully applied to two data sets in the literature.
Date: September 27, 2009
Creator: Zhang, Z. F.; Ward, Anderson L. & Keller, Jason M.
Object Type: Report
System: The UNT Digital Library
Development of a Couette-Taylor flow device with active minimization of secondary circulation (open access)

Development of a Couette-Taylor flow device with active minimization of secondary circulation

A novel Taylor-Couette experiment has been developed to produce rotating shear ows for the study of hydrodynamic and magnetohydrodynamic instabilities which are believed to drive angular momentum transport in astrophysical accretion disks. High speed, concentric, corotating cylinders generate the flow where the height of the cylinders is twice the radial gap width. Ekman pumping is controlled and minimized by splitting the vertical boundaries into pairs of nested, differentially rotating rings. The end rings and cylinders comprise four independently driven rotating components which provide exibility in developing flow profiles. The working fluids of the experiment are water, a water-glycerol mix, or a liquid gallium alloy. The mechanical complexity of the apparatus and large dynamic pressures generated by high speed operation with the gallium alloy presented unique challenges. The mechanical implementation of the experiment and some representative results obtained with Laser Doppler Velocimetry in water are discussed.
Date: January 27, 2009
Creator: Schartman, Ethan
Object Type: Report
System: The UNT Digital Library
EERC Center for Biomass Utilization 2006 (open access)

EERC Center for Biomass Utilization 2006

The Center for Biomass Utilization (CBU®) 2006 project at the Energy & Environmental Research Center (EERC) consisted of three tasks related to applied fundamental research focused on converting biomass feedstocks to energy, liquid transportation fuels, and chemicals. Task 1, entitled Thermochemical Conversion of Biomass to Syngas and Chemical Feedstocks, involved three activities. Task 2, entitled Crop Oil Biorefinery Process Development, involved four activities. Task 3, entitled Management, Education, and Outreach, focused on overall project management and providing educational outreach related to biomass technologies through workshops and conferences.
Date: May 27, 2009
Creator: Zygarlicke, Christopher J.; Hurley, John P.; Aulich, Ted R.; Folkedahl, Bruce C.; Strege, Joshua R.; Patel, Nikhil et al.
Object Type: Report
System: The UNT Digital Library
Environment, Safety, and Health Self-Assessment Report, Fiscal Year 2008 (open access)

Environment, Safety, and Health Self-Assessment Report, Fiscal Year 2008

Lawrence Berkeley National Laboratory's Environment, Safety, and Health (ES&amp;H) Self-Assessment Program ensures that Integrated Safety Management (ISM) is implemented institutionally and by all divisions. The Self-Assessment Program, managed by the Office of Contract Assurance (OCA), provides for an internal evaluation of all ES&amp;H programs and systems at LBNL. The functions of the program are to ensure that work is conducted safely, and with minimal negative impact to workers, the public, and the environment. The Self-Assessment Program is also the mechanism used to institute continuous improvements to the Laboratory's ES&amp;H programs. The program is described in LBNL/PUB 5344, Environment, Safety, and Health Self-Assessment Program and is composed of four distinct assessments: the Division Self-Assessment, the Management of Environment, Safety, and Health (MESH) review, ES&amp;H Technical Assurance, and the Appendix B Self-Assessment. The Division Self-Assessment uses the five core functions and seven guiding principles of ISM as the basis of evaluation. Metrics are created to measure performance in fulfilling ISM core functions and guiding principles, as well as promoting compliance with applicable regulations. The five core functions of ISM are as follows: (1) Define the Scope of Work; (2) Identify and Analyze Hazards; (3) Control the Hazards; (4) Perform the Work; and …
Date: February 27, 2009
Creator: Chernowski, John
Object Type: Report
System: The UNT Digital Library
Experimental and Analytical Research on Fracture Processes in Rock (open access)

Experimental and Analytical Research on Fracture Processes in Rock

Experimental studies on fracture propagation and coalescence were conducted which together with previous tests by this group on gypsum and marble, provide information on fracturing. Specifically, different fracture geometries wsere tested, which together with the different material properties will provide the basis for analytical/numerical modeling. INitial steps on the models were made as were initial investigations on the effect of pressurized water on fracture coalescence.
Date: February 27, 2009
Creator: Einstein, Herbert H.; Miller, Jay & Silva, Bruno
Object Type: Report
System: The UNT Digital Library
FINAL REPORT (DE-FG02-97ER62338): Single-column modeling, GCM parameterizations, and ARM data (open access)

FINAL REPORT (DE-FG02-97ER62338): Single-column modeling, GCM parameterizations, and ARM data

Our overall goal is the development of new and improved parameterizations of cloud-radiation effects and related processes, using ARM data at all three ARM sites, and the implementation and testing of these parameterizations in global models. To test recently developed prognostic parameterizations based on detailed cloud microphysics, we have compared SCM (single-column model) output with ARM observations at the SGP, NSA and TWP sites. We focus on the predicted cloud amounts and on a suite of radiative quantities strongly dependent on clouds, such as downwelling surface shortwave radiation. Our results demonstrate the superiority of parameterizations based on comprehensive treatments of cloud microphysics and cloud-radiative interactions. At the SGP and NSA sites, the SCM results simulate the ARM measurements well and are demonstrably more realistic than typical parameterizations found in conventional operational forecasting models. At the TWP site, the model performance depends strongly on details of the scheme, and the results of our diagnostic tests suggest ways to develop improved parameterizations better suited to simulating cloud-radiation interactions in the tropics generally. These advances have made it possible to take the next step and build on this progress, by incorporating our parameterization schemes in state-of-the-art three-dimensional atmospheric models, and diagnosing and evaluating …
Date: February 27, 2009
Creator: Somerville, Richard C. J.
Object Type: Report
System: The UNT Digital Library
FINAL REPORT DOE Grant: DE-FG02-89ER45391 (open access)

FINAL REPORT DOE Grant: DE-FG02-89ER45391

The work reported here took place at the University of Minnesota from 07/01/1989 to 06/30/2006. Most of this work focused on computational materials applied to oxides during the first part of this funding period and to nanoscale materials toward the end of the funding period. This funding resulted in three monographs, 36 invited articles or book chapters, 160 articles in refereed journals and 89 invited talks. The funding helped train 13 PhD students and one masters student. The PI received two national research awards for this work. A list of these contributions are presented.
Date: February 27, 2009
Creator: Chelikowsky, James R.
Object Type: Report
System: The UNT Digital Library
Final Technical Report (open access)

Final Technical Report

Bioremediation of radionuclides and metals in the subsurface necessitate an understanding of the metabolic capacities and interactions of the anaerobic microorganisms that are found there, including members of the sulfate-reducing bacteria (SRB). Genetic investigation into the pathway of reductant flow to U(VI) in the SRB belonging to the genus Desulfovibrio has been the focus of this project. In Dv. desulfuricans strain G20, we confirmed the importance of the tetraheme cytochrome c3 by disruption of the gene encoding that cytochrome, cycA, and demonstrated a decrease in the ability of the mutant (I2) to reduce U(VI). We found that the cytochrome c3 was necessary for electrons from pyruvate to reach sulfate or fumarate as terminal electron acceptors. It was not needed for electrons from lactate to reach sulfate, from which we infer that a different pathway is used for the electrons from these two substrates. Cyrstal structure of the tetraheme cytochrome c3 was obtained and site-directed mutations of the protein indicated a binding site for metals at heme 4 of the structure. Kinetic studies for oxidation of reduced cytochrome c3 with U(VI) or molybdate revealed a preference for U(VI) as a substrate. Evidence for a role for sodium gradients in the energetic …
Date: February 27, 2009
Creator: Wall, Judy D.
Object Type: Report
System: The UNT Digital Library
Final Technical Report (open access)

Final Technical Report

During the 1-year duration of this project a new Shortwave Spectrometer (SWS) was designed and developed for deployment at the Southern Great Plains Central Facility to measure zenith solar spectral radiance. The SWS is comprised of two Zeiss miniature monolithic spectrometers (MMS-1 and MMS-NIR) for visible and near-infrared detection in the wavelength range between 350 and 2250 nm. Spectral resolution is 8 nm for the MMS-1 and 12 nm for the MMS-NIR. The light collector is a narrow field of view (±1.5 º) collimator at the front end of a high-grade custom-made fiber optic bundle. The data acquisition and control system is a 933 MHz Pentium based PC in a PC104 format with a USB interface between the computer and the spectrometers. Spectral sampling rate is approximately 1 Hz. A prototype SWS was deployed at SGP in November and December 2004 and it collected zenith-sky solar spectra at 1 Hz continuously over a 29 day period. Prior to deployment it was calibrated and characterized at the NASA Ames Airborne Sensor Facility (ASF) using a 30 inch Integrating Sphere. The SWS was also calibrated using a portable 12 inch integrating sphere at the Central Facility. The testing and calibration procedures were …
Date: May 27, 2009
Creator: Pilewskie, Peter
Object Type: Report
System: The UNT Digital Library
Formation of inner-shell autoionizing CO+ states below the CO++ threshold (open access)

Formation of inner-shell autoionizing CO+ states below the CO++ threshold

We report a kinematically complete experiment on the production of CO{sup +} autoionizing states following photoionization of carbon monoxide below its vertical double ionization threshold. Momentum imaging spectroscopy is used to measure the energies and body-frame angular distributions of both photo- and autoionization electrons, as well as the kinetic energy release (KER) of the atomic ions. This data, in combination with ab initio theoretical calculations, provides insight into the nature of the cation states produced and their subsequent dissociation into autoionizing atomic (O*) fragments.
Date: December 27, 2009
Creator: Osipov, Timur; Weber, Thorsten; Rescigno, Thomas N; Lee, Sun; Orel, Ann; Schoffler, Markus et al.
Object Type: Article
System: The UNT Digital Library
Functions, Evolution, and Application of the Supramolecular Machines of Hg Detoxification (open access)

Functions, Evolution, and Application of the Supramolecular Machines of Hg Detoxification

The bacterial mercury resistance (mer) operon functions in Hg biogeochemistry and bioremediation by converting reactive inorganic [Hg(II)] and organic [RHg(I)] mercurials to relatively inert monoatomic mercury vapor, Hg(0). Its genes regulate expression (MerR, MerD, MerOP), import Hg(II) (MerT, MerP, and MerC), and demethylate (MerB) and reduce (MerA) mercurials. We focus on how these components interact with each other and with the host cell to allow cells to survive and detoxify Hg compounds. Understanding how this ubiquitous detoxification system fits into the biology and ecology of its bacterial host is essential to guide interventions that support and enhance Hg remediation. At a more basic level, studies of interactions between the metal ion trafficking proteins in this pathway provide insights into general mechanisms used by proteins in pathways involved in trafficking of other metal ions in cells of all types of organisms, including pathways for essential metal ions such as Cu and Zn and other toxic metal ions such as Cd. In this project we focused on investigations of proteins from mer operons found in gamma-proteobacteria with specific objectives to use biophysical and biochemical approaches to detect and define (1) interactions between the structural components of the key detoxifying mer operon enzyme, …
Date: November 27, 2009
Creator: Miller, Susan M.
Object Type: Report
System: The UNT Digital Library
Fundamental Mechanistic Investigations of Silane and Chlorocarbon Addition to Low Valent Palladium Species and their Application to Catalysis (open access)

Fundamental Mechanistic Investigations of Silane and Chlorocarbon Addition to Low Valent Palladium Species and their Application to Catalysis

The collaboration between Mark Fink (Tulane University) and R. Morris Bullock (Brookhaven National Laboratory, currently at PNL) is an effort to understand some of the fundamental processes involved in catalytic bond activations with low coordinate palladium species. The project involves the photochemical generation of reactive low-valent palladium species as transients using nanosecond laser flash photolysis and the subsequent investigation of their reactions with chloroarenes and hydrosilanes. In the case of Si-H activation of hydrosilanes, relatively long-lived sigma complexes are implicated. These complexes may be important models for C-H activation in hydrocarbons. The information obtained from these studies will help in the understanding of fundamental processes involved in a number of important catalytic reactions in the petrochemical and environmental areas.
Date: January 27, 2009
Creator: Fink, Mark J.
Object Type: Report
System: The UNT Digital Library
FY08 LDRD Final Report LOCAL: Locality-Optimizing Caching Algorithms and Layouts (open access)

FY08 LDRD Final Report LOCAL: Locality-Optimizing Caching Algorithms and Layouts

This project investigated layout and compression techniques for large, unstructured simulation data to reduce bandwidth requirements and latency in simulation I/O and subsequent post-processing, e.g. data analysis and visualization. The main goal was to eliminate the data-transfer bottleneck - for example, from disk to memory and from central processing unit to graphics processing unit - through coherent data access and by trading underutilized compute power for effective bandwidth and storage. This was accomplished by (1) designing algorithms that both enforce and exploit compactness and locality in unstructured data, and (2) adapting offline computations to a novel stream processing framework that supports pipelining and low-latency sequential access to compressed data. This report summarizes the techniques developed and results achieved, and includes references to publications that elaborate on the technical details of these methods.
Date: February 27, 2009
Creator: Lindstrom, P
Object Type: Report
System: The UNT Digital Library
Glass Formulation for the Hanford Tank Waste Treatment and Immobilization Plant (Wtp) (open access)

Glass Formulation for the Hanford Tank Waste Treatment and Immobilization Plant (Wtp)

A computational method for formulating Hanford HLW glasses was developed that is based on empirical glass composition-property models, accounts for all associated uncertainties, and can be solved in Excel{sup R} in minutes. Calculations for all waste form processing and compliance requirements included. Limited experimental validation performed.
Date: May 27, 2009
Creator: Kruger, A. A.; Vienna, J. D.; Kim, D. S. & Jain, V.
Object Type: Article
System: The UNT Digital Library
Gnome-Coach, New Mexico Site Fact Sheet (open access)

Gnome-Coach, New Mexico Site Fact Sheet

The Gnome-Coach Site is located in southern Eddy County, New Mexico, 11 miles east of the Pecos River and 25 miles southeast of the city of Carlsbad. The site is approximately 680 acres. The land is currently withdrawn from all forms of disposition under the public land laws, including U.S. mining laws and leasing under mineral leasing laws. On December 10, 1961, a 3-kiloton-yield nuclear device was detonated at a depth of 1,183 feet belowground surface in a thick, bedded salt deposit within the Salado Formation.
Date: April 27, 2009
Creator: unknown
Object Type: Text
System: The UNT Digital Library
Heinz Heinemann.  The Berkeley Years  (1978-1993) (open access)

Heinz Heinemann. The Berkeley Years (1978-1993)

Heinz Heineman came to Berkeley in 1978 and stayed there for 15 years. This was the time of the energy crisis and we did not have anybody like him who had such a tremendous industrial experience with oil and coal conversion technology and science. He was interested in the conversion of coal to gaseous molecules and our studies with model catalysts appealed to him and attracted him. In a way, Heinz Heineman was bigger than life, since he played such a seminal role in the history of American catalysis science.
Date: August 27, 2009
Creator: Coble, Inger M.
Object Type: Article
System: The UNT Digital Library
HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment (open access)

HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment

Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared 2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of {beta}1 integrin, a major cell-ECM receptor subunit, significantly increased the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment. Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch between PI3K-AKT- and RAS-MAPKpathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are …
Date: July 27, 2009
Creator: Weigelt, Britta; Lo, Alvin T; Park, Catherine C; Gray, Joe W & Bissell, Mina J
Object Type: Article
System: The UNT Digital Library