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Works: 270 works in 356 publications in 1 language and 359 library holdings
Publication Timeline
Most widely held works by CALIFORNIA UNIV SAN DIEGO LA JOLLA
Measuring Sleep by Wrist Actigraph ( Book )
4 editions published between 1979 and 1981 in English and held by 3 libraries worldwide
Results from the first year of our contract (1978-79) indicated that sleep can be identified from recordings of wrist activity, eliminating the need for costly EEG or unreliable observational sleep recognition procedures. In the current contract year we have explored alternative activity transducers, transducer placements, and orientations. Results indicate that a crystal transducer is superior to alternative activity transducers, and it responds adequately in any orientation. We have also demonstrated that wrist activity measures are superior to head or ankle measures. We have investigated methods of artifact rejection and digital preprocessing in converting analog activity data to a digital activity score. A simple digital filtering technique was effective in cancelling 60 Hz electrical noise, a persistent artifact in our analog data. A method of enhancing as well as compressing activity data by summing changes in activity over a 2-second data epoch yields the best discrimination between sleep and wake. A computer program to recognize sleep from the digital activity score is being refined. Once an optimal algorithm for retrospective sleep recognition has been derived, its success in prospectively recognizing sleep from wrist activity will be evaluated. A portable model of a wearable prototype digital actigraphic recorder has also been manufactured. (Author)
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)
Characterization of Novel Seven Transmembrane Helix, GS-Coupled Receptors and Pou Domain Proteins in Cancer of the Mammary Epithelium ( Book )
6 editions published between 1995 and 1998 in English and held by 2 libraries worldwide
Understanding the molecular basis of breast carcinoma is central to designing rational and effective therapy for this prevalent disease
Remote Sensing of Inner Heliospheric Plasmas ( Book )
5 editions published between 1991 and 1997 in English and held by 2 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
Relationship Between Scavenger Receptors and uPA:PAI-l and uPA Receptors in Breast Cancer ( Book )
3 editions published between 1997 and 1999 in English and held by 2 libraries worldwide
The overall goal of this research is to gather detailed information about the cellular distribution and activities of components of the uPA-system in relation to scavenger receptors and RAP in normal and breast cancer cells. We have especially noted a number of differences between the cell lines in either expression levels of these proteins or their localization. Scavenger receptors show higher expression levels in estrogen-insensitive compared to estrogen-sensitive and normal cells. Expression of both receptors seems to correspond with the malignant phenotype of these breast cancer cell lines. Immunocytochemical and immunochemical studies documented similar distribution pattern and expression levels for RAP in all cell lines
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 2 libraries worldwide
Studies are directed to the chemical structure of acetylcholinesterase, with particular reference to the positions and identification of amino acid residues involved in catalysis, inhibitor binding, secretion and linkage to structural subunits. This work is dependent on the known primary structure of acetylcholinesterase and involves the use of site-directed covalent inhibitors of the active site and peripheral amionic site, selective antibodies and peptide isolation. The work has been developed to complement ongoing molecular biological studies of enzyme structure and site-specific mutagenesis. (To date, our studies have shown that the catalytic subunits from the asymmetric and glycophospholipid forms of the enzyme diverge at residue 534 in the C-terminus of the molecule. Epitopes to the antibodies 2C-9 and 4E-7 have been tentatively assigned. Using these and other antibodies we have determined the localization of the asymmetric and glycophospholipid containing forms of the enzyme in the synapse.) Keywords: Acetylcholinesterase sequence, Acetylcholinesterase structure, Acetylcholinesterase Antibodies. (JES)
Ret Receptor: Functional Consequences of Oncogenic Rearrangements ( Book )
6 editions published between 1995 and 1998 in English and held by 2 libraries worldwide
The ret/ptc2 gene was cloned from human papillary thyroid carcinomas, and is the product of a reciprocal chromosomal rearrangement, translocation event between the cAMP dependent protein kinase regulatory subunit I alpha (RI alpha) and the tyrosine kinase domain of the Ret receptor. Ret/ptc2 is a dimer which is autophosphorylated, soluble, and constitutively active. We generated a computer model of the Ret/ptc2 kinase domain, expressed and purified Ret/ptc2, developed a kinase assay to test a variety of peptide substrates and a microinjection assay to compare the structure function relationship of Ret/ptc2 mutants. A number of tyrosine residues within the Ret/ptc2 kinase domain as well as the RI alpha dimerization domain are critical for eliciting a mitogenic response
Vascular Endothelial Growth Factor and Receptors in Breast Cancer ( Book )
4 editions published between 1997 and 1998 in English and held by 2 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
Feasibility of Dual Optics/Ultrasound Imaging and Contrast Media for the Detection and Characterization of Prostate Cancer ( Book )
3 editions published between 2008 and 2010 in English and held by 1 library 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 acousto-optic 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 idea based on quadrature measurements with a gain-modulated image intensified CCD camera. Furthermore, we proposed the novel idea of 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 have demonstrated the detection of ultrasound-modulated incoherent photons followed by the novel quadrature detection of ultrasound-modulated photons and fluorescence photons with the gain-modulated image intensified CCD camera approach. This research demonstrates the potential to perform acousto-optic molecular imaging of prostate cancer with incoherent and fluorescence photons using endogenous contrast, e.g. hypoxia, and also fluorescent probes
Cholinesterase Structure Identification of Residues and Domains Affecting Organophosphate Inhibition and Catalysis ( Book )
5 editions published between 1996 and 1999 in English and held by 1 library worldwide
In the second year of the grant, we have made excellent progress in several arenas: 1) The crystal structure of a mouse acetylcholinesterase-fasciculin 2 complex has provided an essential template for structure-function studies. 2) Studies with a series of enantiomeric organophosphates have been completed; they have yielded vital information on their binding orientation in the ground and transition states. Residues governing enantiomer specificity and leaving group orientation have been defined. 3) Studies in oxime reactivation of cholinesterase inhibited by the enantiomeric phosphates show two faces of attack between the oxime and the conjugated phosphonate. 4) The interactions of fasciculin 2 with acetylcholinesterase have been studied by kinetic and site-specific mutagenesis methods. The fasciculin2-acetylcholinesterase complex has enabled us to study entry of ligands to the active center gorge
Estrogen Nuclear Receptor Coactivators in Pathogenesis of Breast Cancer ( Book )
4 editions published between 1998 and 2000 in English and held by 1 library 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
Final Technical Report for Defense University Research Instrumentation Program(96): Photonic Imaging Network ( Book )
2 editions published in 1998 in English and held by 1 library worldwide
The acquired DURIP (96) equipment was used to complement the Focused Research Initiative research project of BMDO/AFOSR on Photonic Imaging Networks." The DURIP(96) equipment was used to carry out the research in three projects: 1. Nonlinear Space-Time Optical Signal Processing with Femtosecond Pulses 2. Robust Quantum and Classical Crytograph for Security and Privacy in Photonic Imaging Network 3. Artificial dielectrics and diffractive optics with multifunctionality and their applications
Tagging of Breast Tumors for Excision and Specimen Radiography and of Sentinel Nodes for Ultrasound-Guided Localization Using Novel Particulate Agents ( Book )
3 editions published between 1999 and 2001 in English and held by 1 library worldwide
Year 1, we identified a radiopaque tumor-marking agent and optimized the dose. This year we worked on coloring that agent and sentinel node detection. We could not color the radiopaque perfluorocarbon (PFC) emulsion, but successfully suspended India Ink within it. The optimum dose was then injected in tumors. We followed the black tract to locate/remove the tumor at 72-hours. The resected specimen was then radiographed. We worked on sentinel node detection with another agent. The black color identified the tumor in all rabbits. The radiopaque agent was visible within the tumor at 72-hours. Since it is difficult to color PFC emulsions, we abandoned the non-radiopaque PFC emulsion approach to locate the sentinel node. We identified a lipid emulsion where Sudan Black is dissolved within the vesicles. We have marked both the tumor with a radiopaque agent for specimen radiography and the tract to guide the surgeon to the tumor. We have identified a blue lipid emulsion that should have a longer dwell time in the lymphatics and a greater ability to localize in the sentinel node. The final year we will test the blue emulsion and compare its pharmacokinetics and sentinel node enhancement ability relative to the water-soluble blue dye
VR/Multimedia Synthesis, Phase II ( Book )
3 editions published between 1997 and 2000 in English and held by 1 library worldwide
ELECTRONIC FILE CHARACTERISTICS: VHS-format video. PHYSICAL DESCRIPTION: 2 videotapes; 1/2 in. ea.; 35 mins. and 6.45 mins. SYSTEMS DETAIL NOTE: Requires VHS video player and monitor. ABSTRACT: The Learning Resources Center (LRC), the hub of technology-based educational research at the University of California, San Diego (UCSD) School Of Medicine, has a strong track record for developing and distributing cutting-edge curricular resources. Under grants from DARPA (N000l4-93-l-l278 and DAMD l7-94-j-4487) and ONR (N00014-97-l-0356), the LRC has spent five years developing "VisualizeR (C)", a virtual environment for the teaching and learning of complex three-dimensional (3D) structures in conjunction with large quantities of diverse pedagogic materials. "Anatomic VisualizeR (C)" combines 3D models (based on the National Library of Medicine's Visible Human (TM) Dataset) with supporting 2D media (e.g., diagnostic imagery, surgical videos) to create compelling lessons in anatomy. The multimodal approach ("Virtual Reality - Multimedia Synthesis") is realized as a virtual dissection room where students can directly interact with 3D models and concurrently access supporting curricular materials. Anatomic Visualize (R) learning modules (e.g., skull, ear, abdomen, and skeleton) have been piloted with high school students at Southwest High School (a health sciences magnet school in San Diego county), medical students at UCSD, and graduate nursing students at the Unformed Services University of the Health Sciences in Bethesda, Maryland
Skeletal Muscle Ischemia and Heat Shock Proteins ( file )
3 editions published between 1994 and 1996 in English and held by 0 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
Theories of turbulent combustion in high speed flows by Paul A Libby( file )
6 editions published between 1991 and 1997 in English and held by 0 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 ... Turbulent flames, Diffusion flames, Supersonic combustion
Design and Packaging of Fault Tolerant Optoelectronic Multiprocessor Computing System ( file )
4 editions published between 1991 and 1993 in English and held by 0 libraries worldwide
During this quarter, we continued our research efforts on fabricating and testing packaged Correlation Matrix Tensor Multiplier module, developing a Computer Aided Design tool for solving PE placement problems in Oe-MCMs, and designing fault masking and reconfiguration of the twin butterfly interconnection network
Optimized NSAIDs for Breast Cancer Prevention ( file )
3 editions published between 2005 and 2007 in English and held by 0 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
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 0 libraries worldwide
Studies on the structure of acetylcholinesterase (AChE) as a target for organophosphate toxicity continue and have resulted in several leads of significance. First, we have completed the first phase of studies of the structural determinants on the enzyme responsible for inactivation and oxime reactivation. The oxime reactivation studies reveal mutations whereby reactivation can be accelerated some 100-fold, and the combination oxime-mutant AChE shows promise as a prophylactic agent or antidote. Second, through cysteine-substitution mutagenesis and labeling, we have developed steady-state and anisotrophy decay fluorescence methods to examine segmental motion in the protein. This has yielded valuable information on the flexibility of the active center gorge, and the practical outcome of a potentially high sensitivity detection method for organophosphate exposure using the enzyme target as a detector. Third, we have developed an analytical means of measuring organophosphate exposure by MALDI-TOF mass spectrometry that actually measures the product rather than drawing inferences from inhibition of activity. Lastly, several other studies related to our overall objectives are underway. The first is the production of gene knockouts for all of the cholinesterase splice variants
Mechanism of Action of Substituted Indanones in Multidrug Resistant Breast Cancer ( file )
3 editions published between 2000 and 2002 in English and held by 0 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
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