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Understanding of interactions between single-walled carbon nanotubes and other materials is critical for developing a new technology of self-assembling carbon nanotubes into electronics or drug delivery systems. We demonstrate for the first time the use of nanotube electrodes to manipulate nanoparticles in solution using dielectrophoresis. On the other hand, to understand a non-electrical assisted interaction, we investigate the binding affinity of carbon nanotubes and peptides via combinatorial phage display technique. We find a tryptophan rich binding motif to nanotubes on solid silicon substrates. The motif resembles an alpha helix with tryptophan concentrated along one side that binds non-covalently via interactions to the walls of the nanotube., Sponsored in part by ONR and DARPA.

Learning disabilities severely deteriorate the life of many NF1 children by limiting their academic achievement, higher education and career choice. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available. This study was proposed to identify genes that are dysregulated in the hippocampus of the Nf1+/- mouse model by DNA microarray analysis. Characterization of these NF1-affected genes will dramatically improve our understanding of the molecular pathogenesis underlying NF1-associated learning deficits.

The long-terms goal is to further the understanding of air-sea interaction processes including momentum, heat, water vapor, surface and boundary layer dynamics under various meteorological and oceanographic conditions., code 1 only. The original document contains color images.

The long-terms goals of our research are to understand and parameterize the physics of air-sea interaction and the marine boundary layer over a wide spectrum of surface forcing ocean conditions and cloud coverage., Code 1 only. The original document contains color images.

The long-terms goal is to further the understanding of air-sea interactions processes including momentum, heat, water vapor and trace gas exchange under various meteorological and oceanographic conditions., The original document contains color images.

We investigate the connectivity of fading wireless ad-hoc networks with a pair of novel connectivity metrics. Our first metric looks at the problem of connectivity relying on the outage capacity of MIMO channels. Our second metric relies on a probabilistic treatment of the symbol error rates for such channels. We relate both capacity and symbol error rates to the characteristics of the underlying communication system such as antenna configuration, modulation, coding, and signal strength measured in terms of Signal-to-Interference-Noise-Ratio (SINR). For each metric of connectivity, we also provide a simplified treatment in the case of ergodic fading channels. In each case, we assume a pair of nodes are connected if their bi-directional measure of connectivity is better than a given threshold. Our analysis relies on the central limit theorem to approximate the distribution of the combined undesired signal affecting each link of an ad-hoc network as Gaussian. Our analysis shows that employing multiple antenna mobile nodes improves the connectivity of fading ad-hoc networks., The original document contains color images. Submitted to IEEE/KICS Journal of Communications and Networks.

This paper is on quantized beamforming in wireless amplify-and-forward relay networks. We use the Generalized Lloyd Algorithm (GLA) to design the quantizer of feedback information and specifically to optimize the bit error rate (BER) of the system. Achievable bounds for different performance measures are derived. First, we analytically show that a simple feedbask scheme based on relay selection can achieve full-diversity. Unlike the previous diversity analysis on the relay selection scheme, our analysis is not aided by the approximations and modified forwarding schemes. Then, for high-rate feedback, we find an upper bound on the average signal-to-noise ratio (SNR) loss and show that it decays at least exponentially with the number of feedback bits, B. Using this result, we also demonstrate that the capacity loss also decays exponentially with B. We also derive approximate upper and lower bounds on the BER, which can be calculated numerically. With R relays, our designs achieve full-diversity when B is greater than or equal to log(R). Moreover, simulations show that our BER approximations are reliable estimations of the simulation results, even for moderate values of B. This paper is on quantized beamforming in wireless amplify-and-forward relay networks. We use the Generalized Lloyd Algorithm (GLA) to design the quantizer of feedback information and specifically to optimize the bit error rate (BER) of the system. Achievable bounds for different performance measures are derived. First, we analytically show that a simple feedbask scheme based on relay selection can achieve full-diversity. Unlike the previous diversity analysis on the relay selection scheme, our analysis is not aided by the approximations and modified forwarding schemes. Then, for high-rate feedback, we find an upper bound on the average signal-to-noise ratio (SNR) loss and show that it decays at least exponentially with the number of feedback bits, B. Using this result, we also demonstrate that the ca, Submitted to IEEE Journal on Selected Areas in Communications

This report covers a Center grant comprised of nine project areas focused on developing advanced photonic systems for acute care and trauma medicine. All nine projects share common objectives in developing either diagnostic, therapeutic, and/or analytical photonic tools that are of interest to military and civilian medicine and that help solve complex problems of emerging national need. The projects outlined in the report include: Development of High Speed Functional OCT Airway Injury, Part I: An In Vitro Model of Toxic Gas Exposure Airway Injury, Part II: High Resolution Fiberoptic F-OCT Imaging in Acute Inhalation Injury. Airway Injury, Part III: High Resolution F-OCT and MPM/SHG Imaging of the Oral-Nasal Cavity Diffuse Optical Spectroscopy in Critical Patient Medicine, Optical Therapeutics in Cartilage for the Treatment of Traumatic Injuries and Degenerative Disease, Advanced Optical Technologies for Orthopedic Applications.

In the past five or so years, it has become clear that the US Air Force, Army, and Navy have all committed to a strategy of acquiring software-intensive systems that require or utilize an open architecture (OA) and open technology (OT) that may incorporate OSS technology or OSS development processes. There are many perceived benefits and anticipated cost savings associated with an OA strategy. However, the challenge for acquisition program managers is how to realize the savings and benefits through requirements that can be brought into system development practice. As such, the central problem we examine in this paper is to identify principles of software architecture and OSS copyright licenses that facilitate or inhibit the success of an OA strategy when OSS and open APIs are required or otherwise employed. By examining and analyzing this problem, we can begin to identify additional requirements that may be needed to fulfill an OA strategy during program acquisition., Presented at the Annual Acquisition Research Symposium (5th): Creating Synergy for Informed Change, held in Monterey, CA, on 14-15, 2008. Published in the proceedings of the symposium, p230-245, 2008. Document includes briefing charts in addition to text. The original document contains color images.

Open source software development (OSSD) is a community-oriented, network-centric approach to building complex software systems. OSSD projects are typically organized as edge organizations that lack an explicit management regime to control and coordinate decentralized project work. However, a growing number of OSSD projects are developing, delivering, and supporting large-scale software systems that are displacing proprietary software alternatives. The U.S. Department of Defense is now committed to the adoption and deployment of software-intensive systems with open architectures and OSS components for application areas including command and control systems. Recent empirical studies of OSSD projects reveal that OSS developers often self-organize into organizational forms we characterize as evolving socio-technical interaction networks (STINs). These STINs emerge in ways that effectively control semi-autonomous OSS developers and coordinate project activities to produce reliable and adaptive software systems. In this paper, we examine how practices and processes enable and govern edge organizations like OSSD projects when coalesced and configured as contingent, sociotechnical interaction networks. In so doing, we draw on results from two ongoing case studies of governance activities and elements in a small and a large OSSD project., Sponsored in part by National Science Foundation Grant no. 0534771.Presented at the International Command and Control Research and Technology Symposia (13th), ICCRTS 2008, Seattle, WA on 17-19 Jun 2008. The original document contains color images.

One of the major challenges in breast cancer research is to develop new chemotherapeutic and chemopreventive agents particularly for non-estrogen dependent and drug-resistant estrogen dependent breast cancers. SXR activators were able to cause cell cycle arrest and apoptosis in ER and ER breast cancer cell lines in culture. Different SXR activators caused accumulation of p53 in ER breast cancer cells leading to increase in its target genes involved in apoptosis and cell cycle. Confirmation of these results in at least two ER breast cancer cell lines suggests validity of this model in estrogen dependent breast cancer. Establishment of loss of function studies in these cell lines confirmed the significance and requirement of SXR in these compounds led apoptosis. Moreover loss of function studies and microarray studies on estroger receptor negative cells lines in next year of funding will be able to establish the role of SXR as apoptosis inducer in estrogen receptor independent cells and its mechanism of action in these cell lines. This will provide opportunities for rational drug design and improvement of the efficacy of existing drugs that act through SXR.

The Josephson junction (JJ) qubit is a leading candidate in the design of a quantum computer. A significant advantage of this approach is scalability, as these qubits may be readily fabricated in large numbers using integrated-circuit technology. A major obstacle to the realization of quantum computers with Josephson junction qubits is decoherence. The goal of our research was to elucidate the microscopic sources of this decoherence and to suggest ways to eliminate or reduce these culprits. We focused on the decoherence produced by two level systems in the insulating barrier of a Josephson junction as well as in the insulating dielectric material (e.g., SiO2) typically used to fabricate integrated circuit (IC) chips. Two level systems consist of an atom or group of atoms that can sit in one of two places. We worked with John Martinis' group (UCSB/NIST) which found that two level states are a dominant source of decoherence in superconducting qubits. One reason for this is that two level systems can resonantly absorb microwaves that are used to probe and manipulate the qubit. Once there are enough microwaves to saturate the two level systems, the rest of the microwaves can go through resulting in attenuation that decreases with increasing microwave power. Another mechanism for qubit decoherence is due to two level systems in the junction barrier which couple to the qubit. We explored two models in which a two level system couples to a qubit.

This research effort developed a computational theory for the control of human attention in two-dimensional visual tasks. Theory and experiments focused on the role of the spatial modulation transfer function for human vision, and on the characteristics and limitations of cortical receptive field processes.

The conference Frontiers in Human Information Processing (held 28-29 July 2007) goal was to synthesize the state of cognitive theory with focus on the formal, computational, and mathematical approaches that unify the areas of vision, attention, and memory. The conference also highlights several key applications of these approaches in medicine, engineering, and education.

The long-terms goal is to further the understanding of air-sea interactions processes including momentum, heat, water vapor and trace gas exchange under various meteorological and oceanographic conditions., code 1 only. The original document contains color images.

The long-terms goals of the research are to understand and parameterize the physics of air-sea interaction and the marine boundary layer over a wide spectrum of weather and ocean conditions., code 1 only.

In normal cells, proliferation and differentiation are regulated and coordinated in a way that activation of differentiation in normal cells is typically associated with cessation of proliferation. However, the balance between the two is usually disrupted in tumorigenesis, ultimately leading to a complex cellular phenotype typical of cancer cells. In attempts to identify the differentiation-inducing factors in conditioned medium, conditioned medium was fractioned and applied to breast cancer cell, MCF7, cultured in Matrigel. Unexpectedly, a cytotoxic activity was observed on MCF7 cells treated with the fraction of molecular weight between 10- 50kDa after seven days. In the past year, I first confirmed the cytotoxicity on various breast cancer cell lines with different genetic backgrounds, including MD-AMB-468 and SKBR3. From mass spectrometric analysis on this 10-50kDa fraction of the conditioned medium, six factors such as interleukins (ILs), bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs) and other cytokines, which are known to be involved in cell proliferation and death, have been selected as proteins of interests and their cytotoxic activities were confirmed by immunodepletion. Chinese hamster ovary (CHO) cells overexpressing each of the six factors have been established for future reconstitution experiments and animal studies.

In this position paper, we address some current limitations and challenges as well as emerging directions in three related areas of secure communication: (1) security in Wireless Sensor Networks - WSNs, (2) security in Mobile Ad Hoc Networks - MANETs, and, (3) security in Cellular Phone Networks., Presented at the 2007 ARO Planning Workshop on Embedded Systems and Network Security, held in Raleigh, NC on 22-23 Feb 2007 and published in proceedings of the same. The original document contains color images. This article is from ADA485570 Proceedings of the ARO Planning Workshop on Embedded Systems and Network Security Held in Raleigh, North Carolina on February 22-23, 2007

Principles of quantum computing using molecular vibronic states and time-frequency resolved coherent anti-stokes Raman scattering (TFRCARS) were demonstrated through, and the execution of standard algorithms were elaborated along with measures of fidelity. These proof-of-principle implementations are on ensembles of molecules in the gas phase, unlikely to be a realistic architecture in practical implementations. We have therefore focused on solid-state implementations of the same, where now the understanding and control of decoherence of systems in intimate contact with their surrounding environment is the key scientific challenge. Very significant progress in this regard has been made in, (a) developing the tools to probe quantum coherence and decoherence of vibronic states in phase space, (b) developing semi-classical methods for the analysis of the mechanics of decoherence, (c) demonstrating mesoscopic coherence ("cat"-states) and complete arrest of decoherence in stationary non-eigenstates prepared by environmentally induced coherence. Also, significant progress has been made in approaching the single molecule limit in TFRCARS implementations - a crucial step in considering scalable quantum computing using the molecular Hilbert space and nonlinear optics.

Alternative pre-mRNA splicing generates thousands of different mRNA isoforms in metazoan organisms. It is unknown if breast-cancer associated alternative splicing is regulated like tissue-specific splicing, or whether it is caused by changes in the splicing accuracy. To test the hypothesis that the accuracy of the spliceosome is compromised in breast tumor cells, we have designed a quantitative real-time PCR assay to determine the number of incorrectly spliced mRNA products made from pre-mRNA transcripts that produce only a single mRNA product in all eukaryotic genomes. Analysis of all possible alternative exon exclusion patterns for these genes demonstrates that in some cases a splicing mistake is made only once in 25,000 intron removal events. These results demonstrate that the error rate of the spliceosome is extremely low. Using this assay we examined splicing error rates in breast cancer cell lines. Using matched cancer and normal cell lines we demonstrated that breast cancer cell lines exhibit an up to 3-fold decrease in the number of splicing errors. We conclude that perturbed pre-mRNA splicing in breast cancer is mediated in part through alterations of the intrinsic fidelity of the spliceosome., The original document contains color images.

LMO4 is highly expressed in breast epithelial cells and is related to cell proliferation and/or invasion in vivo. Because these cellular features are associated with breast carcinogenesis and since LMO4 is overexpressed in more than 50% of breast cancer cases, we hypothesize that LMO4 may play roles in oncogenesis of breast epithelial cells by regulating proliferation, invasion and/or other cellular features. Using LMO4 over-expression or shRNA expression system in vitro, I found that LMO4 play crucial roles in the regulation of cell proliferation and apoptosis of normal mammary gland epithelial cells or breast cancer cells. Furthermore, I have also observed that deletion of LMO4 impaired the function and development of mammary gland in LMO4 conditional knockout mice, indicating that LMO4 protein is necessary for maintaining the normal development of mice mammary gland. In addition, I demonstrated that the LMO4 can modulate TGF signaling and regulated the proliferative response of epithelial cells to TGF signaling, and thereby linked LMO4 to a conserved signaling pathway that plays important roles in epithelial homeostasis. Under the support of grant, I received excellent training in bioinformatics. By combining previously described functional methods with bioinformatics approaches, we used DNA microarrays to discover LMO4-responsive genes, and identified BMP7 as a key down-stream gene of LMO4. In addition, we also found a significant correlation between LMO4 and BMP7 transcript levels in a large dataset of human breast cancers, providing additional support that BMP7 is a bona fide target gene of LMO4. Finally, we demonstrated that LMO4 binds to HDAC2 and that they are recruited together to the BMP7 promoter. We also suggested a novel mechanism for LMOs; LMO4, Clim2 and HDAC2 are part of a transcriptional complex, and alterations in LMO4 levels can disrupt the complex, leading to decreased HDAC2 recruitment and increased promoter activity., The original document contains color images.

BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex upregulates ANG1,which stabilizes endothelial cells forming capillary-like network structure. Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization and overexpressed ANG1. These results suggest, besides its role in maintaining genomic stability, BRCA1 directly regulates the expression of angiogenic factors to modulate the tumor microenvironment., The original document contains color images.

This study proposes to modify and improve an existing MR-compatible optical tomography system that is used for non-invasive tumor characterization and provides higher sensitivity and specificity for cancer imaging. The proposed research will conduct animal studies to evaluate the system's performance in distinguishing malignant from benign tumors in vivo. Additional experiments will be designed to assess the method's sensitivity to quantifying oxygenation gain factor in breast tumors. This investigation will have important implications for studies identifying tumor's hypoxic regions. Tumor hypoxia is believed to be strongly associated with tumor progression, prognosis, and resistance to therapy. In the first year of this multidisciplinary postdoctoral training grant, the principal investigator acquires training in breast cancer and dynamic contrast enhanced MRI. The major focus is on optical imaging system development/improvement and performance evaluation through phantom studies. We managed to increase the data acquisition speed by a factor of 10, which enabled us to perform dynamic contrast enhanced diffuse optical tomography on phantoms for the first time., The original document contains color images.

It is possible to detect locations of lesions accurately in breast cancer using techniques such as x-ray mammogram accurately; however, the specificity of current techniques is low. Since the conductivity values of malignant, benign, and normal tissues are significantly different, this information can be used in classification. Current conductivity imaging techniques can only provide low-resolution images and fail in extreme cases. Magnetic resonance-electrical impedance tomography (MREIT) is a new modality that can reconstruct high-resolution conductivity images. In this study, we propose the use of MREIT for improving accuracy of breast cancer classification. In this project, MREIT system for 3D data acquisition was implemented. Mesh generation and image reconstruction algorithms in 3D were developed. 3D phantom studies were carried out successfully. Preliminary animal experiments that demonstrate conductivity contrast for R3230 tumor models were carried out. Data acquisition system was generalized for imaging at different field strengths. Preliminary images were acquired using fast imaging sequences that is crucial in in vivo imaging. During this period, PI acquired training in tumor biology and different imaging modalities in tumor imaging., Research supported by DoD DAMD17-02-1-0326. The original document contains color images.

Secretory prostatic epithelial cells undergo apoptosis in response to androgen deprivation. Similarly,metastatic prostate cancers, which resemble secretory epithelium, also undergo apoptosis following androgen deprivation. Recent evidence suggests that death receptor signaling is required for prostate epithelial cell death following androgen withdrawal. We sought to extend this observation by investigating the role of death receptor signaling components in models of prostate epithelial cell death. Preliminary experiments suggest that FLIP can inhibit apoptosis of prostate epithelial cells. FLIP is an enzymatically inactive version of pro-caspase-8 which negatively regulates cell death, apparently via a dominant- negative mechanism. Based on our preliminary data, we hypothesize that FLIP is a key regulator of prostate apoptosis in response to androgen withdrawal. To address our hypothesis we propose a systematic approach involving, sequentially, correlative (aim 1), functional (aim 2) and mechanistic (aims 3 and 4) experiments. The specific aims are: i) correlate the pattern of FLIP expression with prostate epithelial cell death; ii) assess the functional consequences of forced FLIP expression on prostate epithelial apoptosis; iii) determine which death receptor pathway is involved in prostate epithelial cell death and iv) determine if androgens regulate the level of FLIP expression at the level of gene transcription.

Anti-estrogens such as tamoxifen are important therapeutic agents in the treatment and chemoprevention of breast cancers. Other compounds such as phytoestrogens, fatty acid amides such as anandamide and retinoid X receptor agonists are also effective against breast cancer in cell lines and in animal models. Because these compounds are structurally unrelated, it has not been appreciated that they might act through a common mechanism. All of these compounds share the ability to activate a heterodimer of the steroid and xenobiotic receptor (SXR) and retinoid X receptor (RXR). Our hypothesis is that SXR serves as a common molecular target for some of the anti-proliferative effects of these compounds and that activation of SXR is itself anti-proliferative. To this end, we have found that activation of SXR leads to apoptosis and G1 cell cycle arrest through a p53 dependent pathway in estrogen receptor positive MCF7 breast cancer cells. In this period of study, we have confirmed our initial results in another ER+ breast cancer cell line ZR-75-1. We have also been able to provide further support for our hypothesis by showing that activation of SXR not only causes increase in p53 mRNA, but also causes stabilization and accumulation of p53 protein in MCF7 cells. So far, we have been able to significantly knock down SXR in MCF-7 cells by using siRNA and we are currently performing the loss of function studies in these cells and optimizing the siRNA transfection conditions in ER- breast cancer cell lines., The original document contains color images.

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available. This study was proposed to identify genes that are dysregulated in the hippocampus of the Nf1+/- mouse model by DNA microarray analysis. Characterization of these NF1-affected genes will dramatically improve our understanding of the molecular pathogenesis underlying NF1-associated learning deficits. During the third year of the project, we have focused on determining the biological functions of NF1-affected genes. In addition, we also characterized the effect of lovastatin treatment on genomic expression of the NF1 hippocampus., The original document contains color images.

To understand chemistry is to be able to control it. The fulfillment of this long sought after goal ultimately hinges on a detailed knowledge at the atomic and molecular level. Control of chemistry not only provides insights into known materials and phenomena but also leads to chemicals with novel compositions, structures, and functions. The primary objective of this project is to use a homemade, variable low temperature scanning tunneling microscope (STM) to carry out atomic and molecular manipulation of chemical interactions for the discovery of novel nanostructures and properties. In effect, the goal is to carry out chemical changes by manipulating individual atoms and molecules to induce different bonding geometry and to create new interactions with their environment. These studies provide the scientific basis for the advancement of technology in catalysis, molecular electronics, optics, chemical and biological sensing, and magnetic storage., The original document contains color images.

Prostate cancer results from complex interactions among genetic, endocrine, and environmental factors. Understanding genetic risk factors that contribute to the occurrence of prostate cancer is crucial to design both preventative and therapeutic strategies and to identify at-risk individuals. Plausible candidates for susceptibility genes for prostate cancer risk include genes involved in insulin-like growth factor signaling, androgen signaling, and in immune response. We hypothesized that genetic variation in genes in these pathways was associated with prostate cancer risk. We studied 199 incident prostate cancer cases and 263 age-matched controls. Genotyping was performed for 59 polymorphisms in 18 genes and statistical analyses performed to look at their associations with prostate cancer risk and aggressiveness. As previously reported, the IRS1 G972R GR/RR genotypes (rs1801278) were associated with a significant 2.7-fold increased risk for prostate cancer (95% CI 1.5-4.9, p=0.0007). Other significant results were SNP rs2139924 in IGF1R with a 2.6-fold increased risk (95% CI 1.1-6.5) and rs361072 in PI3KCB with a 1.6 fold increased risk (95% CI 1.03-1.66). These results support a role of the insulin-like growth factor pathway in the etiology of prostate cancer. These results need to be replicated in multiple, larger studies.

The long-terms goals of the research are to understand and parameterize the physics of air-sea interaction and the marine boundary layer over a wide spectrum of weather and ocean conditions. The main objectives of this effort are to study the air-sea interaction under different conditions: cold air outbreaks in the Japan/East Sea experiment, trade winds off the east coast of Oahu, Hawaii during the Rough Evaporation Duct experiment (RED), stratocumulus marine layer off the central coast of California during the Cloud-Aerosol Research in the Marine Atmosphere I,II & III (CARMA I, CARMA II & CARMA III ) and the summertime mostly stable boundary-layer south of Martha s Vineyard, Massachusetts during the Coupled Boundary Layers/Air-Sea Transfer (CBLAST Low winds) We are primarily interested in the characterization of boundary-layer structure, the measurement of momentum, heat and water vapor (latent heat) air-sea fluxes, the determination of their spatial variability as well as their parameterization.

This research presents the development of a three-dimensional theoretical and computational procedures, for contact, impact, and penetration mechanics, based on the Meshless Local Petrov-Galerkin (MLPG) approach. In the current implementation, both velocities and velocity-gradients are interpolated independently, and their compatibility is enforced only at nodal points, The original document contains color images.

This paper is on beamforming in wireless relay networks with perfect channel information at relays, the receiver, and the transmitter if there is a direct link between the transmitter and receiver. It is assumed that every node in the network has its own power constraint. A two-step amplify-and-forward protocol is used, in which the transmitter and relays not only use match filters to form a beam at the receiver but also adaptively adjust their transmit powers according to the channel strength information. For a network with any number of relays and no direct link, the optimal power control is solved analytically. The complexity of finding the exact solution is linear in the number of relays. Our results show that the transmitter should always use its maximal power and the optimal power used at a relay is not a binary function. It can take any value between zero and its maximum transmit power. Also, surprisingly, this value depends on the quality of all other channels in addition to the relay's own channels. Despite this coupling fact, distributive strategies are proposed in which, with the aid of a low-rate broadcast from the receiver, a relay needs only its own channel information to implement the optimal power control. Simulated performance shows that network beamforming achieves the maximal diversity and outperforms other existing schemes. Then, beamforming in networks with a direct link are considered. We show that when the direct link exists during the first step only, the optimal power control at the transmitter and relays is the same as that of networks with no direct link. For networks with a direct link during the second step only and both steps, recursive numerical algorithms are proposed to solve the power control problem. Simulation shows that by adjusting the transmitter and relays' powers adaptively, network performance is significantly improved., Submitted for publication in IEEE Transactions on Information Theory. Final version printed in v55 n6 p2499-2517, 2009.

A theoretical and computational study of the break-up of injected liquid streams at high pressure by stress-induced cavitation is the research subject. The breakup criteria by stresses differs greatly from the traditional criterion in which a fluid cavitates at places and times at which the local pressure falls below the vapor pressure. Rather, cavitation occurs where the tensile stress exceeds the liquid breaking strength. The hydrodynamic stability and subsequent breakup of these liquid streams will be examined using viscous-potential-flow analysis and the direct numerical simulation of the viscous-fluid motions. The deformation of free surfaces and the fields of principal stresses are monitored to determine places and times at which the liquid is at risk to breakup., Presented at the ARO/AFOSR Contractors' Meeting in Chemical Propulsion held in Arlington, Virginia on 12-14 Jun 2006. This article is from ADA474195 Army Research Office and Air Force Office of Scientific Research Contractors' Meeting in Chemical Propulsion Held in Arlington, Virginia on June 12-14, 2006

The proposed theoretical/computational and experimental study addresses the vital two-way coupling between combustion processes and fluid dynamic phenomena associated with schemes for burning liquid fuels in high-speed, accelerating and turning transonic turbulent flows. A major motivation for this type of combustion configuration results from the demonstrated potential for immense improvements in the performance of gas turbine engines via combustion in the turbine passages. This program will address various fundamental issues concerning liquid-fuel combustion in an axially and centrifugally accelerating flow. The major combustion challenge involves ignition and flame-holding of the spray flame in the high-acceleration flow and associated optimization of the injection of the liquid fuel and some secondary air into a protected recirculation zone provided by a cavity., Presented at the ARO/AFOSR Contractors' Meeting in Chemical Propulsion held in Arlington, Virginia on 12-14 Jun 2006. This article is from ADA474195 Army Research Office and Air Force Office of Scientific Research Contractors' Meeting in Chemical Propulsion Held in Arlington, Virginia on June 12-14, 2006

The development of mammary gland is governed by multiple genetic pathways although how these pathways are regulated and how they interact with each other is not yet fully understood. Previous studies have implicated the involvement of the canonical Wnt signaling pathway which includes several key components that act together to activate other genes that are directly involved in controlling cell division or differentiation in both normal and abnormal mammary gland development. The timing and overall activity of the pathway is key as its disruption leads to aberrant mammary development and its over stimulation leads to breast cancer. We proposed genetic experiments to examine the role of a novel component of the Wnt pathway in mammary gland development and tumorigenesis. Specifically we proposed to target genetic manipulations to a subset of the mammary epithelial cells that have stem cell characteristics. The mutant mice generated in this study should provide novel animal models to study the ontogeny and progression of mammary tumors. Furthermore results from our studies should provide some insight into the role of epithelial stem cells in normal and diseased development. Finally our studies might implicate possible drug target for treating breast cancer in the future., The original document contains color images.

Secretory prostatic epithelial cells undergo apoptosis in response to androgen deprivation. Similarly, metastatic prostate cancers, which resemble secretory epithelium, also undergo apoptosis following androgen deprivation. Recent evidence suggests that death receptor signaling is required for prostate epithelial cell death following androgen withdrawal. We sought to extend this observation by investigating the role of death receptor signaling components in models of prostate epithelial cell death. Preliminary experiments suggest that FLIP can inhibit apoptosis of prostate epithelial cells. FLIP is an enzymatically inactive version of pro-caspase-8 which negatively regulates cell death, apparently via a dominant-negative mechanism. Based on our preliminary data, we hypothesize that FLIP is a key regulator of prostate apoptosis in response to androgen withdrawal. To address our hypothesis we propose a systematic approach involving, sequentially, correlative (aim 1), functional (aim 2) and mechanistic (aims 3 and 4) experiments. The specific aims are: 1) correlate the pattern of FLIP expression with prostate epithelial cell death; 2) assess the functional consequences of forced FLIP expression on prostate epithelial apoptosis; 3) determine which death receptor pathway is involved in prostate epithelial cell death and 4) determine if androgens regulate the level of FLIP expression at the level of gene transcription., The original document contains color images.

We examined if BRCA1 is involved in MEC differentiation and how its dysfunction pertains to breast tumor pathogenesis. We demonstrated that BRCA1 mediates acinar differentiation of MEC using 3-D culture. Reduction of BRCA1 by RNAi impairs acinus formation but enhances proliferation. Such aberrations can be rescued by expression of wild-type BRCA1 as well as a mutant in the central domain but not in the C-terminal BRCT domain, suggesting that the BRCT domain has a critical role in this process. Consistently, depletion of BRCA1 up-regulates the gene expression for proliferation but down-regulates that for differentiation. Moreover, application of the medium conditioned by differentiating normal MEC can reverse the phenotype of differentiation-defective breast cancer cells bearing reduced BRCA1 functions. This result implies BRCA1 is involved in secretion of certain paracrine/autocrine factors that induce MEC differentiation in response to extracellular matrix signals., The original document contains color images.

Prostate Cancer (PCa) accounts for nearly 30% of all newly diagnosed cancers among American men. Epidemiologic studies suggest that dietary factors may be important in the etiology of this disease. The objective of our research is to determine how nutritional compounds genistein, betasitosterol (SIT), and omega-6 fatty acids (FA) function as modulators of PCa. In the third and final year of this fellowship, the fellow joined the National Cancer Institute's Cancer Prevention Fellowship Program and has continued working on the DOD-PCRP Postdoctoral Fellowship project and 30% effort (with knowledge and approval from the DOd-PCRP). During this year, we finished printing our custom microarray as well as optimized the hybridization protocol. We are currently performing expression analysis using the microarrays for both the in vitro and in vivo experiments using well established cell lines. Finally, we have initiated xenograft in vivo experiments with a novel PCa model that was developed recently in a collaborating laboratory.

We continued to develop microfluidic chambers to study breast cancer cell chemotaxis as it relates to metastasis. As part of this effort, we developed 3D culture devices that can generate concentration gradients of soluble factors in 3D gels, allowing cancer cell migration to be investigated in physiologically relevant conditions. We first developed devices capable of generating linear and non-linear gradients in 3D collagen gels. We then implemented these devices and developed a co-culture model to study the interaction between breast cancer cells and macrophages, each cultured in a distinct extracellular matrix that better simulates tissue composition. We studied the migration of these different cell types in these 3D devices. These studies suggested an intriguing synergy between tumor cells and immune cells, and pave the way for complex studies of cancer cell behavior in in vitro models that can better mimic tumor and tissue microenvironments., The original document contains color images.

The long-terms goals of the research are to understand and parameterize the physics of air-sea interaction and the marine boundary layer over a wide spectrum of weather and ocean conditions., The original document contains color images.

ELECTRONIC FILE CHARACTERISTICS: 914 files; Adobe Acrobat (.PDF) and software. PHYSICAL DESCRIPTION: 2 CD-ROMs; 4 3/4 in. ea.; 697 KB and 29.4 MB. SYSTEMS DETAIL NOTE: ABSTRACT: Given the acknowledged importance of mobile code, current distribution models are surprisingly primitive. For example, Java's model assumes that the constituent parts that make up a mobile program will all be downloaded to a single location, and then verified, linked, possibly dynamically compiled, and finally executed at that very location. This research project made three important contributions: First, it demonstrated that it can be beneficial to perform verification, dynamic compilation, and execution at different physical locations. A prototype was built that performs code verification and just-in-time compilation at a "code generating router" inside the network itself. If the end-points of the network are resource-limited devices such as wirelessly-connected personal digital assistants (PDA's), off-loading dynamic code generation to the stationary network can result in substantial benefits. As a second contribution, the project identified a novel attack on mobile code systems, based on the complexity of the code verification algorithm itself. The third contribution is a new mobile-code verification algorithm that not only lacks this vulnerability, but that is also more efficient.

The objective of the present program of research is to study physiological processes that may mediate the links between psychological states and cancer. Specifically, the present study is designed to conduct an investigation of the cross-sectional associations between indices of stress reactivity and psychological coping styles in women with breast cancer and matched healthy controls. The aims of the project are: (1) To quantify parameters of biological reactivity to a behavioral stress paradigm in women with and without breast cancer; (2) To examine effects of menopause and familial risk on biological stress reactivity and emotional expression; and (3) To develop the methodology and obtain preliminary data which could justify subsequent, prospective research with high-risk populations. Data collection ended May 2005. Results of data analyses indicated significant differences in several cardiovascular indicators of stress-reactivity, as well as significant differences in changes in cortisol levels between the breast cancer and control group. While specific coping styles were shown to relate differently to cardiovascular stress responses and negative emotional responses among participants, coping styles were not associated with changes in cortisol levels. This suggests that the HPA-stress hormone link may not be mediated by perception of stress. Among reproductive and familial risk factors assessed, oral contraceptive use and length of use were associated with a dyregulated biological stress response profile (i.e., respond quicker and not recover as quickly).

Anti-estrogens such as tamoxifen are important therapeutics for treatment and chemoprevention of breast cancers. Other compounds such as phytoestrogens and fatty acid amides are also effective against breast cancer proliferation. These compounds share the ability to activate the steroid and xenobiotic receptor (SXR). Our hypothesis is that SXR serves as a common molecular target for the anti-proliferative effects of these compounds and activation of SXR is itself anti-proliferative. We have detected SXR protein in breast cancer cell lines, and have shown that either SXR activators or a constitutively active form of SXR are able to slow the proliferation of breast cancer cells. We found that SXR activators share the ability to increase the expression of inducible nitric oxide synthase in MCF-7 cells leading to an increased production of reactive nitrogen species. In SXR activator treated cells, we found that p53 expression as well as the p53 target genes p2l and BAX were increased. Apoptosis occurred in cells treated with SXR activators and is likely the reason for the observed decrease in cell proliferation. Activated/stabilized p53 due to cellular stress from increased reactive nitrogen species provides a mechanism explaining the apoptotic response and decreased proliferation in the presence of SXR activators.

We identified a novel transcription factor, LMO4, which is highly expressed in breast epithelial cells during mid- pregnancy when these cells are proliferating and invading the stroma. Since previous members of the LIM only (LMO) gene family are oncogenes, we hypothesized that LMO4 may play roles in mammary gland development and cancer. We have now shown that expression of LMO4 correlates with proliferation, and in transgenic mice we shrewd that dominant- negative LMO4 inhibits lobuloalveolar development, demonstrating that LMO4 plays roles in proliferation and/or invasion of breast epithelial cells. Because these cellular features are associated with breast carcinogenesis and because LMO4 is overexpressed in a subset of breast cancers, our studies implicate LMO4 as a possible oncogene in breast cancer. In addition, we found that the LMO4 gene is activated by the Her2/Neu receptor in breast cancer cells, providing further linkage to breast cancer. In biochemical assays we showed that LMO4 may act by associating with the GATA3 transcription factor, also expressed in mammary epithelial cells. We have also created stable breast cancer cell lines in which we can induce expression of LMO4 and Clim2. With this method, we have identified several target genes of LMO4, one of which is Bone Morphogenic Protein 7 (BMP-7), which can affect survival of breast cancer cells by regulating apoptosis. In summary, we have defined a role for a new gene, LMO4, in mammary epithelial cell proliferation in normal development and in breast cancer cells

LMO4 is a transcription factor which belongs to the LIM-only (LMO) gene family of oncogenes. We have now shown that expression of LMO4 is associated with undifferentiated cellular stage of breast epithelial cells, such as that found during lobuloalveolar development in pregnancy and in breast cancer. Yet, LMO4 is not induced by estrogen, suggesting that it may participate in an estrogen-independent pathway. Consistent with this idea, we found that LMO4 expression is induced by the Neu/ller2 oncogene in breast cancer cells, suggesting that LMO4 plays a role in this important oncogenic pathway. We created a transgenic mouse model to demonstrate that interfering with LMO4 results in significant inhibition of lobuloalveolar development, indicating that LMO4 plays roles in proliferation and/or invasion of breast epithelial cells. Because these cellular features are associated with breast carcinogenesis, and because LMO4 is overexpressed in a subset of breast cancers, our studies implicate LMO4 as a possible oncogene in breast cancer. On a molecular level, we found that LMO4 functions by interacting with Clim transcriptional co-factors and is likely recruited to DNA in breast cancer cells by the DNA-binding protein GATA3. Expression profiling studies show that LMO4 and Clim regulate several genes involved in breast cancer carcinogenesis. In summary, our studies identify LMO4 as an important regulator of cell growth in normal mammary epithelial cells and in breast cancer cells.

In mammography, dense breast regions persistently suffer from reduced contrast-to-noise ratio (CNR) because of degraded contrast from large scatter intensities and relatively high noise. Area x-ray beam equalization can improve image quality by increasing the x-ray exposure to under-penetrated regions without increasing the exposure to other breast regions. Optimal equalization parameters with respect to image quality and patient dose were determined through computer simulations and validated with experimental observations on a step phantom and an anthropomorphic breast phantom. The parameters important in equalization digital mammography were considered: attenuator material (Z=13 to 92), beam energy (22 to 34 kVp), and equalization level. A Mo/Mo digital mammography system was used for image acquisition. A prototype 16x 16 piston driven equalization system was used for preparing patient-specific equalization masks. Simulation studies showed that a molybdenum attenuator, a tube voltage of approximately 26-2g kVp, and an equalization level of 20 were optimal for improving contrast, CNR, and figure of merit (FOM=CNR exp 2/exposure). Experimental measurements using these parameters showed significant improvements in contrast, CNR, and FOM. Moreover, equalized images of a breast phantom showed improved image quality. These results indicate that area beam equalization can improve image quality in digital mammography.

This project focuses on the development of microfluidic chambers for the study of breast cancer cell chemotaxis. In the first phase of the project, we designed, fabricated, and tested the microfluidic chemotaxis chamber, ensuring its compatibility with breast cancer cell culture and observation using fluorescence and DIC microscopy. We began the next phase of the project, investigating the migration of breast cancer cells in epidermal growth factor (EGF). We showed that the concentration gradients of EGF induce the chemotaxis of breast cancer cells in a manner that is dependent on the shape of the concentration gradient profile. As we continue our work in this project, we will use the microfluidic chemotaxis chamber to study, in depth, the chemotaxis of breast cancer cells in superimposed gradients of multiple growth factors.

In screening of breast cancer, once abnormalities or lesions are discovered by the X-ray mammogram, generally, other imaging techniques are needed as an adjunct to diagnose the lesion as benign or malignant. It has been shown that cancer cells exhibit altered local electrical impedance. However, existing technology to measure the impedance of the breast has poor spatial resolution. We proposed to map the tissue impedance distribution with high spatial resolution, in conjunction with MH to improve diagnostic accuracy of screening. During the second year of this project, we improved the quality of conductivity images and conducted in vivo experiments. Several issues such as non-linearity in conductivity image reconstruction, out of slice effects were investigated. Improved reconstruction methods were studied. Multi-slice capability is added to the pulse sequence and various approaches were tested. Although it was not originally in the project proposal, we started collecting Contrast Enhanced MRI images to localize the tumor better. A serious malfunction in the MRI receiver unit caused a delay of more than six months. A no-cost extension was requested to collect more conductivity images from animals and complete this project successfully. Another conference manuscript was prepared and presented and a journal article was submitted., The original document contains color images. All DTIC reproductions will be in black and white.

The ability to detect, localize, quantity and monitor the expression of specific genes in living cells in real-time will offer unprecedented opportunities for advancement in molecular biology, disease pathophysiology, drug discovery, and medical diagnostics. However, current methods for quantifying gene expression employ either selective amplification (as in PCR) or saturation binding followed by removal of the excess probes (as in microarrays and in situ hybridization) to achieve specificity. Neither approach is applicable when detecting gene transcripts within living cells. Here we review the recent development in engineering nanostructured molecular probes for gene detection in vivo, describe probe design approaches and its structure-function relations, and discuss the critical issues and challenges in performing living cell gene detection with high specificity, sensitivity and signal-to-background ratio. The underlying biological and biochemical aspects are illustrated.

This project was proposed to study therapeutic indicators for anti-angiogenic therapy. Two different animal tumor models were studied, R323O AC adenocarcinoma and carcinogen ENU induced tumors. Longitudinal MRI studies were performed before and during therapy to monitor the changes occurring over the entire treatment period. Immunohistochemical analysis was performed to measure 4 molecular markers p53, TSP-l, VEGF and factor VIII microvessel density in pre-treatment and post-treatment specimens. ENU induced tumors came with different types, thus could simulate the wide variation of human breast cancer. However, the tumor also showed a very complicated response pattern. All MRI markers and IHC markers were correlated with final treatment outcome. Unlike in humans, the early volumetric changes did not predict outcome. The contrast enhancement kinetics measured using the blood pool agent Gadomer-l7 may provide an indication for therapy response. The vascular volume measured by Gadomer-l7 decreased in responder, and increased in non-responders. Also the baseline vascularity measured by Gadomer-l7 was associated with future response, possibly due to a higher blood supply thus more delivery of therapeutic agents. The developed methodology is currently applied in human studies, and that is expected to yield more interesting results in understanding chemotherapy induced changes., The original document contains color images.