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Works: 275 works in 356 publications in 1 language and 358 library holdings
Publication Timeline
Most widely held works by CALIFORNIA UNIV SAN DIEGO LA JOLLA
Ret Receptor: Functional Consequences of Oncogenic Rearrangements ( file )
6 editions published between 1995 and 1998 in English and held by 6 libraries worldwide
Ret/ptc2 is a soluble, constitutively active oncogenic protein whose gene was cloned from human papillary thyroid carcinomas. Ret/ptc2 is a chimeric protein resulting from a reciprocal chromosomal rearrangement translocation event between the cAMP-dependent protein kinase regulatory subunit type Ialpha (RIalpha) and the tyrosine kinase domain of the Ret receptor. Earlier microinjection studies showed the RIalpha dimerization domain is critical for eliciting a mitogenic response in mouse 1OT 1/2 fibroblasts. By combining results obtained from microinjection studies of Ret/ptc2 point mutants and mapping proteins identified from a yeast two-hybrid screen to a computer generated model of the Ret/ptc2 kinase core, we have previously identified specific tyrosine residues to which the SH2 domains of Grb10 and PLCgamma, the second C-terminal LIM domain of Enigma, and the PTB domain of Shc interact. From our recent characterization of the Enigma-Shc dual association with Ret/ptc2 in mouse 1OT 1/2 fibroblasts, we propose the mitogenic response elicited by Ret/ptc2 requires Enigma for proper cellular localization and utilizes the Ras pathway via the recruitment and phosphorylation of Shc. In addition to these studies, we have overexpressed and purified His6-Ret/ptc2 from the methylotrophic yeast, Pichia pastoris, to initiate extensive in vitro biochemical and biophysical characterization
Characterization of Novel Seven Transmembrane Helix, GS-Coupled Receptors and Pou Domain Proteins in Cancer of the Mammary Epithelium ( file )
6 editions published between 1995 and 1998 in English and held by 6 libraries worldwide
Understanding the molecular basis of breast carcinoma is central to designing rational and effective therapy for this prevalent disease. We have proposed to investigate several regulatory proteins that we hypothesized may underlie at least a subset of human breast carcinomas. In investigating transcription factors of the POU domain class and their synergistic interactions with nuclear receptors, we have discovered a novel protein, expressed in the breast, that acts as a specific repressor of retinoic acid and thyroid hormone receptors. This 270 kDa protein, postulated to mediate retinoic acid and thyroid hormone receptor actions as a repressor of specific gene expression, is recruited to estrogen receptor by antagonists and its regulation appears to underlie resistance in ER positive tumors
Remote Sensing of Inner Heliospheric Plasmas ( file )
5 editions published between 1991 and 1997 in English and held by 5 libraries worldwide
Solar disturbances produce major effects on the corona, the solar wind, the interplanetary medium, and the Earth along with its magnetosphere. We have developed new techniques for studying plasma disturbances in the inner heliosphere by remotely sensing them. These techniques use data from the HELIOS spacecraft zodiacal light photometers, the ISEE-3 spacecraft kilometer radio- wave experiment, and a variety of other spacecraft and ground-based instruments. The zodiacal light photometers on board the two HELIOS spacecraft (data coverage from 1974 to 1986) provide the first good information about the heliospheric masses and shapes of propagating disturbances. Metric and kilometric type II and type III radiation caused by shock waves and fast moving electrons respectively are another way to remotely sense the structures which propagate outward from the Sun. The best kilometric radio wave sensing of inner heliospheric plasma is available from the ISEE-3 spacecraft. The investigations into the physics of the disturbances sensed by these techniques and the ability to forecast their occurrences are well underway
Theories of Turbulent Combustion in High Speed Flows ( file )
5 editions published between 1991 and 1995 in English and held by 5 libraries worldwide
This research involves theoretical studies of the chemical and fluid- mechanical phenomena which make turbulent combustion in high-speed flows different from such combustion in low-speed flows. Finite-rate chemistry plays a significant role in high-speed flows because of the small ratios of flow times to chemical times. The studies address ignition and extinction phenomena in nonpremixed turbulent combustion of hydrogen-air systems by both numerical and asymptotic methods. Attention also is paid to effects of compressibility in high-speed turbulent combustion, with consideration given to interdispersal configurations of shocklets and flamelets. Efforts are made to provide a firmer foundation for the modeling of high-speed turbulent reacting flows, to aid in the development of a formulation which gives results that can be compared with experiments on turbulent combustion
Cholinesterase Structure: Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis ( file )
5 editions published between 1996 and 1999 in English and held by 5 libraries worldwide
During the project period we have initiated a completed studies in the following areas: (1) The crystal structure of a mouse acetylcholinesterase-fasciculin 2 complex has provided an essential template for structure-function studies; progress has been made in crystallizing acetylcholinesterasein the absence of fasciculin. (2) Studies of a series of enantiomeric organophosphates reacting with acetylcholinesterase have been completed; they have yielded vital information on their binding orientation in the ground and transition states. Residues on the enzyme governing enantiomer specificity and leaving group orientation have been defined through site-specific mutagenesis. (3) The interactions of fasciculin 2 with acetylcholinesterase have been studied by kinetic and site-specific mutagenesis methods. The fasciculin 2-acetylcholinesterase complex has enabled us to study entry of ligands to the active center gorge. (4) Studies in oxime reactivation of cholinesterase inhibited by the enantiomeric phosphates were undeataken using 2-PAM and HI-6 with wild-type and mutant acetylcholinesterases
Vascular Endothelial Growth Factor and Receptors in Breast Cancer ( Book )
4 editions published between 1997 and 1998 in English and held by 4 libraries worldwide
Experiments completed in the past year were designed to characterize the role of Vascular Endothelial Growth Factor (VEGF) and its receptors (VEGFr) in the progression of breast cancer. VEGF and VEGFr are known to be involved in tumor angiogenesis and many other vascular proliferative disorders. Since VEGF and VEGFr are intimately involved in generating the vascular invasion in tumors, they are likely to be important prognostic indicators. VEGF mRNA is alternatively spliced into 4 isoforms, while there are 2 high affinity receptors for VEGF. The relative roles and involvements of each isoform and receptor in cancer is unknown. Since VEGF can be regulated by estrogen, we have grown tumors (human MDA-MB-231 and murine MXT-OVEX) in ovariectomized mice implanted with either estradiol or placebo pellets. We proposed to study the effect of estrogen on the expression of the VEGF isoforms and receptors in the normal mammary gland and in breast cancers in ovariectomized animals
Measuring Sleep by Wrist Actigraph ( Book )
4 editions published between 1979 and 1981 in English and held by 4 libraries worldwide
Using a piezo-electric transducer, wrist activity was recorded simultaneously with EEG, EOG, and EMG to obtain 102 recordings -- 39 from hospital patients and 63 from non-patients -- during both Sleep and Wakefulness. On a minute-to-minute basis, wrist activity alone was used to estimate Sleep Time. Blind independent scoring of the EEG-EOG-EMG records was also done for Sleep and Wakefulness. Results from the two Sleep/Wake estimations agreed 94.5% of the minutes. Correlations between the two methods were determined for Total Sleep Period (r=0.90), Total Sleep Time (r=0.89), Total Wake Within Sleep (r=0.70), and number of Mid-Sleep Awakenings (r=0.25). Correlation coefficients were even higher when the 39 patients were excluded from the computations. On the average, the actigraphic method overestimated Sleep Time by 10 minutes. Continuous wrist activity recordings provide simple, inexpensive, but very accurate estimates of Sleep Time. (Author)
Design and Packaging of Fault Tolerant Optoelectronic Multiprocessor Computing System ( file )
4 editions published between 1991 and 1993 in English and held by 4 libraries worldwide
During this quarter, we continued our efforts on (1) studying alignment schemes for packaging and fabricating components for CMTM(Correlation Matrix Tensor Multiplier) packaging, (2) creating generalized e-beam fringe writing algorithms for automatically generating different types of HOEs for optical interconnects, and (3) design of switching elements in twin butterfly networks with parallel testing features built-in. The results are summarized below
Mechanism of Action of Substituted Indanones in Multidrug Resistant Breast Cancer ( file )
3 editions published between 2000 and 2002 in English and held by 3 libraries worldwide
Our laboratory has recently synthesized a series of novel substituted indanones that are selectively toxic to multidrug resistant cancer cells, including breast cancer cell lines. In this application we proposed to characterize the mechanism of action of indanocine and to assess the in vivo anti-tumor activity of indanocine. During the second year we: - published the second report on the biological activity of indanocine (Cancer Res 2001 Oct 1 61(1 9):7248-54) - analyzed the indanocine-resistant stable cell line - identified the potential indanocine-binding site on tubulin - continued the animal testing of indanocine - studies the pro-apoptotic mechanism of action in non-dividing tumor cells The results shown in this annual summary demonstrate that indanocine is a very promising new anti-cancer agent, with selective activity in slowly-dividing or quiescent tumor cells. The positive early animal models suggest that indanocine could be soon ready for clinical trials
Silicide Formation and Schottky Barrier of Rare-Earth Metals on SI ( Book )
3 editions published in 1983 in English and held by 3 libraries worldwide
During this period, our activities included the following: Design and construct mechanical masks for Er (and other thin film) depositions; Completion of the construction of a vacuum annealing furnace. The vacuum chamber is pumped by a turbo-molecular pump and is capable of annealing eight 88) different samples sequentially in one pump-down. The normal operating pressures is <2 x 1- to the -7 torr and the chamber is relatively free from carbon and oxygen contamination; Investigation of annealing Er layers deposited on Si in our new vacuum furnace, and the electronic properties of ErSi2 diodes using mechanical masks, and Acceptance of publication by Applied Physics Letters of our paper entitled Surface Morphology of Erbium Silicides (See Appendix A). (Author)
The Primary Sequence of Acetylcholinesterase and Selective Antibodies for the Detection of Organophosphate Toxicity ( Book )
3 editions published between 1987 and 1991 in English and held by 3 libraries worldwide
Acetylcholinesterase polymorphism is a consequence of alternative MRNA processing which gives rise to two distinct molecular species of acetylcholinesterase. The work summarized in the progress report characterized the protein structure of acetylcholinesterase from Torpedo and correlated it with the organization of the gene. A divergence is found at the carboxyl terminus of the molecule giving rise to a hydrophilic, oligomeric and a glycophospholipid linked species. Antibodies which react uniquely with each form of the enzyme have been prepared which revealed each enzyme species to be localized at distinct positions with the synapse. Other antibodies defined a unique carbohydrate epitope on the glycophospholipid linked form and revealed that the active center of the enzyme is occluded from the surface. Distinct epitopes within the active center of the enzyme were also delineated. Lastly, we have developed an expression system using a Spodoptera- baculovirus system which has enabled us to express recombinant derived enzymes in large quantity
Skeletal Muscle Ischemia and Heat Shock Proteins ( file )
3 editions published between 1994 and 1996 in English and held by 3 libraries worldwide
Blood loss resulting in decreased organ perfusion and subsequent ischemic injury of cardiac and skeletal muscle presents a significant problem for the soldier in combat. Recent findings have indicated that different forms of noxious stress including exposure to increased temperature, noxious chemical agents, and ischemia lead to increased expression of heat shock proteins (HSP) which have a protective effect against injury induced by noxious stimuli. We will determine in this proposal if a rat skeletal muscle derived permanent cell line, L6 cells, expressing increased amounts of HSP70 will show protection against damaged induced by simulated ischemia. To generate L6 cells which permanently overexpress the inducible HSP70 proteins, cells will be transfected with a neomycin resistance gene and the inducible HSP70 gene. Stable lines will be selected by growing L6 cells in the presence of neomycin. Cells which have the neomycin resistance gene and the HSP70 gene incorporated into their DNA will survive. Such stably transfected L6 cell lines will then be exposed to simulated ischemia consisting of hypoxia, absence of glucose, low tonicity, and resultant ischemic damage will be determined by quantitating cell viability measured in colony formation assays, the inhibition of protein synthesis and the release of cytoplasmic enzymes like creatine kinase. These studies will determine if inducible HSP70 exerts a protective effect against ischemia mediated muscle injury. Demonstrating a protective effect of HSP70 protein will make it a useful agent to reduce ischemic muscle damage in soldiers exposed to muscle injury in combat
Feasibility of Dual Optics/Ultrasound Imaging and Contrast Media for the Detection and Characterization of Prostate Cancer ( file )
3 editions published between 2008 and 2010 in English and held by 3 libraries worldwide
This research project focuses on prostate cancer, a devastating socioeconomic disease, whose detection is plagued with inadequate sensitivity and specificity. Hypoxia is the hallmark of malignancy because aggressive cancers outgrow their blood supply. We ultimately aim to build an instrument that combines OPtics and UltraSound (OPUS) to quantify hypoxia via optical imaging but with the improved spatial resolution of US imaging. Specifically, the acoustooptic effect will be used to only modulate light (at the ultrasound frequency) which propagates through a small ultrasound focal zone. This DOD Idea Development Award is concerned with the development of a novel acousto-optic detection method and using microbubble-based contrast agents to significantly increase the light modulation and, moreover, the use of fluorescent microbubbles to provide additional enhancement. During the first year of the research project we demonstrated the detection of ultrasound-modulated incoherent photons followed by novel quadrature detection of ultrasound-modulated photons and fluorescence photons with a gain-modulated image intensified CCD camera approach. During the second year of the research project we demonstrated significant signal enhancement with ultrasound microbubbles and generation of higher harmonic modulation. We also demonstrated acoustooptic detection with a novel SPAD detector. During the third year of this research project we developed a novel acousto-optic light scattering system to robustly characterize ultrasound-induced oscillation of individual microbubbles and also observed microbubble collapse and implosion at higher ultrasound pressures. In the fourth and final year of this project we plan to use this system to measure ultrasound-modulated fluorescence, fluorescence with microbubbles, and fluorescent microbubbles
Molecular Mechanisms of Glial Abnormalitites in Neurofibromatosis ( file )
3 editions published between 1998 and 2000 in English and held by 3 libraries worldwide
Neurofibromatosis is a genetic disease in which the major pathology is due to abnormal proliferation of Schwann cells. One of the two tumor suppressor genes mutated in this disease is the neurofibromatosis 1 gene (NF1). The product of this gene, neurofibromin, inhibits ras function. Based on several unique features of control of growth in Schwann cells, we believe that specific factors associated with CREB, and the CREB-binding protein, CBP, serve to specifically modulate cAMP and ras -dependent growth events in glia, and underly the NF1 mutation-induced Schwann cell proliferation. Our identification of CBP as an integral component of the activation complex for cAMP and Growth factors, and evidence that competition for limiting amounts of CBP can result in AP-1 inhibiting events, has led us to provide evidence for a molecular mechanism which integrates diverse signaling pathways, dictating differentiation and proliferation events. We hypothesize that this regulatory system can be exploited to discover novel approaches to the treatment of neurofibromatosis. We have proposed to generate various genetic models exhibiting altered cAMP and ras -dependent signaling pathways and utilize these model systems to identify and characterize factors which are responsible for the etiology of neurofibromatosis type 1
Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation ( file )
3 editions published between 2003 and 2005 in English and held by 3 libraries worldwide
Studies on the structural of acetyicholinesterase (AChE) as a target of organophosphate toxicity continue and have yielded several leads of significance and practical outcomes. First, studies on oxime reactivation reveal the importance of achieving a suitable angle of attack for the oxime within the confines of the active center gorge. Through the use of mutant AChE-oxime combinations, oxime assisted catalytic turnover of organophosphates can be achieved such that mutant AChE can be employed with oximes as a catalytic scavenger. Second, through cysteine substitution mutagenesis and acrylodan labeling we have developed a fluorescent enzyme whose emission spectrmn changes upon conjugation with organophosphate. These enzymes are now being immobilized and developed as a remote sensor for acetylcholinesterase. Third, we have developed mass spectrometry methods to detect directly the organophosphate conjugates with AChE. Lastly, we have developed several transgenic animal strains that enable us to study the roles cholinesterase inhibition centrally and in the periphery play in organophosphate toxicity and whether the antidotal actions of oximes arise solely through reactivation
Optimized NSAIDs for Breast Cancer Prevention ( file )
3 editions published between 2005 and 2007 in English and held by 3 libraries worldwide
Population studies have shown that women who use non-steroidal anti-inflammatory drugs (NSAIDs) developbreast cancer less frequently. However, these drugs have side effects toward the stomach, liver and kidneys, particularly at the high doses potentially required to prevent breast cancer. Also, how these agents prevent breastcancer is not understood. This project will develop an optimized NSAID for breast cancer prevention that can betaken safely at high doses, and will determine its mechanisms of action. The side effects of NSAlDs are mainly dueto inhibition of cyclo-oxygenase (COX) enzymes. Based on preliminary experiments, we hypothesize that thepreventative action of NSAlDs in breast cancer is not solely due to COX inhibition, but rather to alterations of otherbiochemical pathways in breast cells that control their proliferation. We have isolated modified NSAIDs that do notinhibit the COX enzyme, but still retain chemopreventative activity. Testing this COX independent NSAlD in arobust model of breast cancer, the MMTV-wnt1 transgenic mouse, has revealed a trend towards tumor preventionand a significant reduction in gene expression of wnt regulated targets. These data have already encouragedearly, biomarker based, clinical trials in women with breast cancer
Estrogen Nuclear Receptor Coactivators in Pathogenesis of Breast Cancer ( file )
3 editions published between 1998 and 1999 in English and held by 3 libraries worldwide
This project focuses on the role of nuclear receptor coactivators in steroid dependent regulation of cell growth in pathogenesis of breast cancer. A novel nuclear receptor coactivator of transcription, p300 and CBP associated factor (p/CAF) has been shown to be required for estrogen, thyroid hormone, and retinoic acid-dependent gene expression. The histone acetyltransferase activity of p/CAF was demonstrated to play essential role in nuclear receptor dependent gene expression and it appeared to be transcription factor specific. The ligand-dependent association of p/CAF with nuclear receptor depends upon nuclear receptor corepressor (NCoR) dismissal. These data suggest that p/CAF complex plays a central role in nuclear receptor dependent gene regulation, a key element in steroid dependent cancer development
Tagging of Breast Tumors for Excision and Specimen Radiography and of Sentinel Nodes for Ultrasound-Guided Localization Using Novel Particulate Agents ( file )
3 editions published between 1999 and 2001 in English and held by 3 libraries worldwide
During the first year, we identified a radiopaque tumor-marking agent and optimized the dose. During the second year we worked on coloring the agent and worked on the second agent for sentinel node detection to improve upon the water-soluble dye. Scope: We could not color the radiopaque perfluorocarbon (PFC) emulsion but successfully suspended India Ink within it. The optimum dose of the mixture was injected in tumors. We followed the black tract to locate and remove the tumor at 72 hours. The resected specimen was then radiographed. We began the work to accomplish the 3rd goal, the identification of the sentinel node
Final Technical Report for Defense University Research Instrumentation Program(96): Photonic Imaging Network ( Book )
2 editions published in 1998 in English and held by 2 libraries worldwide
The acquired DURIP (96) equipment was used to complement the Focused Research Initiative research project of BMDO/AFOSR on
Nonlinear Spatio-Temporal Processing of Femtosecond Pulses for Ultrahigh Bandwidth Communication ( file )
2 editions published between 1999 and 2000 in English and held by 2 libraries worldwide
We emphasize developing high speed and high efficiency parallel to serial multiplexers and serial to parallel demultiplexers, the two most critical challenges for current technology to meet the needs of ultra high bandwidth communication applications. In the following we describe research on nonlinear spatio temporal processors using cascaded second order nonlinearity to perform (1) Spatial temporal wave mixing for space to time conversion, and (2) Instantaneous time reversal and phase conjugation of ultrafast waveforms. In addition, we will also report our study on a (3) Femtosecond single shot pulse imaging system that uses transverse time delay pulse cross correlation
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