331 results on '"Michael J Thomas"'
Search Results
302. Allene epoxidation. Isolation of a 1,4-dioxaspiro[2.2]pentane derivative
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J.K. Crandall, Warren H. Machleder, and Michael J. Thomas
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Pentane ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,chemistry ,Stereochemistry ,Allene ,Organic chemistry ,General Chemistry ,Biochemistry ,Catalysis ,Derivative (chemistry) - Published
- 1968
303. The Game-as-Art Form: Historic Roots and Recent Trends
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Michael J. Thomas
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Painting ,Visual Arts and Performing Arts ,media_common.quotation_subject ,Context (language use) ,Art ,Set (psychology) ,Engineering (miscellaneous) ,Music ,Social relation ,Computer Science Applications ,First world war ,media_common ,Visual arts - Abstract
Among the many new art forms realized in the 1970s, one largely unacknowledged form is the game as art. Reviewing art since World War I, the author finds not only important works proliferating in this form recently but also a definite history to be traced. The form first appears in the work of Marcel Duchamp, who was the first major artist to place the game of chess in an artistic context. Oyvind Fahlstrom made moveable paintings and some of the first original game-as-art works. Later, a large number of artists from diverse artistic backgrounds explored the game-as-art form. Some of these artists made innovations in traditional games, others used the form for a specific impact and still others created works to encourage social interaction. What is lacking is a set of criteria for judging the aesthetic qualities of a game-as-art work. The game-as-art form holds an aesthetic challenge to today’s artists and promises to be an important art form of the future.
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- 1988
304. Letter to the editor
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Michael J. Thomas
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chemistry.chemical_compound ,Chemistry ,Physiology (medical) ,Hydroxyl radical ,Biochemistry ,Medicinal chemistry - Published
- 1989
305. Short Notes
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Norman D. Van Swelm, Molly Benson, David James, and Michael J. Thomas
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Ecology, Evolution, Behavior and Systematics ,Nature and Landscape Conservation - Published
- 1975
306. International Marketing Management
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Michael J. Thomas and A. Coskun Samli
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Marketing ,Business ,Business and International Management ,International marketing - Published
- 1970
307. Book Review:Marketing Management: Analysis, Planning and Control. Philip Kotler
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Michael J. Thomas
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Economics and Econometrics ,Marketing management ,Control (management) ,Business ,Statistics, Probability and Uncertainty ,Business and International Management ,Management - Published
- 1967
308. EVOLUTION OF GENOME SIZE IN PINES (PINUS) AND ITS LIFE-HISTORY CORRELATES: SUPERTREE ANALYSES
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Grotkopp, Rejmánek, Sanderson, Rost, Eva, Marcel, Michael J., Thomas L., Grotkopp and Soltis, P.
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- 2004
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309. The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes
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Amber B. Ouweneel, Michael J. Thomas, and Mary G. Sorci-Thomas
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microdomains ,cholesterol trafficking ,extracellular vesicles ,exosomes ,Biochemistry ,QD415-436 - Abstract
Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.
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- 2020
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310. Deactivation of 12(S)-HETE through (ω-1)-hydroxylation and β-oxidation in alternatively activated macrophages
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Tamas Kriska, Michael J. Thomas, John R. Falck, and William B. Campbell
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12(S)-HETE metabolism ,angiotensin II ,12/15-lipoxygenase ,cytochrome P450 ,Biochemistry ,QD415-436 - Abstract
Polarization of macrophages to proinflammatory M1 and to antiinflammatory alternatively activated M2 states has physiological implications in the development of experimental hypertension and other pathological conditions. 12/15-Lipoxygenase (12/15-LO) and its enzymatic products 12(S)- and 15(S)-hydroxyeicosatetraenoic acid (HETE) are essential in the process since disruption of the gene encoding 12/15-LO renders the mice unsusceptible to hypertension. The objective was to test the hypothesis that M2 macrophages catabolize 12(S)-HETE into products that are incapable of promoting vasoconstriction. Cultured M2 macrophages metabolized externally added [14C]12(S)-HETE into more polar metabolites, while M1 macrophages had little effect on the catabolism. The major metabolites were identified by mass spectrometry as (ω-1)-hydroxylation and β-oxidation products. The conversion was inhibited by both peroxisomal β-oxidation inhibitor, thioridazine, and cytochrome P450 inhibitors. Quantitative PCR analysis confirmed that several cytochrome P450 enzymes (CYP2E1 and CYP1B1) and peroxisomal β-oxidation markers were upregulated upon M2 polarization. The identified 12,19-dihydroxy-5,8,10,14-eicosatetraenoic acid and 8-hydroxy-6,10-hexadecadienoic acid metabolites were tested on abdominal aortic rings for biological activity. While 12(S)-HETE enhanced vasoconstrictions to angiotensin II from 15% to 25%, the metabolites did not. These results indicate that M2, but not M1, macrophages degrade 12(S)-HETE into products that no longer enhance the angiotensin II-induced vascular constriction, supporting a possible antihypertensive role of M2 macrophages.
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- 2018
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311. Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis
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Dalia E. Gaddis, Lindsey E. Padgett, Runpei Wu, Chantel McSkimming, Veronica Romines, Angela M. Taylor, Coleen A. McNamara, Mitchell Kronenberg, Shane Crotty, Michael J. Thomas, Mary G. Sorci-Thomas, and Catherine C. Hedrick
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Science - Abstract
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here Gaddis et al. show that Apolipoprotein AI prevents the conversion of Treg cells into pro-atherogenic T follicular helper cells, and thus regulates the immune response during atherogenesis.
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- 2018
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312. Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin-1β
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Taiki Miyazawa, Kiyotaka Nakagawa, Sharon H. Kim, Michael J. Thomas, Ligi Paul, Jean-Marc Zingg, Gregory G. Dolnikowski, Susan B. Roberts, Fumiko Kimura, Teruo Miyazawa, Angelo Azzi, and Mohsen Meydani
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Caloric restriction ,Curcumin ,Glucuronide ,High fat diet ,Inflammation ,Meso scale discovery ,Nutrition. Foods and food supply ,TX341-641 ,Nutritional diseases. Deficiency diseases ,RC620-627 - Abstract
Abstract Background Dietary bioactive compounds capable of improving metabolic profiles would be of great value, especially for overweight individuals undergoing a caloric restriction (CR) regimen. Curcumin (Cur), a possible anti-obesity compound, and piperine (Pip), a plausible enhancer of Cur’s bioavailability and efficacy, may be candidate agents for controlling body fat, metabolism and low grade inflammation. Methods 47 eight-week-old male C57BL/6 mice were fed a high fat diet (HFD) for 23 weeks to induce obesity. Then, mice were divided into 5 groups. Group 1 continued on HFD ad libitum. The other 4 groups underwent CR (reduced 10% HFD intake for 10 weeks, 20% for 20 weeks) with Cur, Pip, Cur + Pip or none of these. Percent body fat, plasma inflammatory markers associated with obesity (interferon (IFN)-γ, interleukin (IL)-10, IL-12 p70, IL-1β, IL-6 and KC/GRO), plasma Cur metabolites and liver telomere length were measured. Results Compared to the other groups, obese mice who underwent CR and received Cur + Pip in their diet lost more fat and had significantly lower IL-1β and KC/GRO. Tandem mass spectrometry analysis of plasma from obese mice under CR showed no difference in Cur metabolite levels between groups supplemented with Cur alone or combined with Pip. However, plasma IL-1β levels were inversely correlated with curcumin glucuronide. Minor modulation of telomere length were observed. Conclusions It is plausible that supplementing the high fat diet of CR mice with Cur + Pip may increase loss of body fat and suppresses HFD induced inflammation. Combination of Cur and Pip has potential to enhance CR effects for the prevention of metabolic syndrome.
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- 2018
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313. Development and Evaluation of a Chinook Salmon Smolt Swimming Behavior Model
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Edward S. Gross, Rusty C. Holleman, Michael J. Thomas, Nann A. Fangue, and Andrew L. Rypel
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San Francisco estuary ,Sacramento–San Joaquin Delta ,salmonid ,route selection ,hydrodynamic model ,movement ecology ,Hydraulic engineering ,TC1-978 ,Water supply for domestic and industrial purposes ,TD201-500 - Abstract
Hydrologic currents and swimming behavior influence routing and survival of emigrating Chinook salmon in branched migratory corridors. Behavioral particle-tracking models (PTM) of Chinook salmon can estimate migration paths of salmon using the combination of hydrodynamic velocity and swimming behavior. To test our hypotheses of the importance of management, models can simulate historical conditions and alternative management scenarios such as flow manipulation and modification of channel geometry. Swimming behaviors in these models are often specified to match aggregated observed properties such as transit time estimated from acoustic telemetry data. In our study, we estimate swimming behaviors at 5 s intervals directly from acoustic telemetry data and concurrent high-resolution three-dimensional hydrodynamic model results at the junction of the San Joaquin River and Old River in the Sacramento-San Joaquin Delta, California. We use the swimming speed dataset to specify a stochastic swimming behavior consistent with observations of instantaneous swimming. We then evaluate the effect of individual components of the swimming formulation on predicted route selection and the consistency with observed route selection. The PTM predicted route selection fractions are similar among passive and active swimming behaviors for most tags, but the observed route selection for some tags would be unlikely under passive behavior leading to the conclusion that active swimming behavior influenced the route selection of several tagged smolts.
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- 2021
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314. Real-time nodes permit adaptive management of endangered species of fishes
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A. Peter Klimley, Thomas V. Agosta, Arnold J. Ammann, Ryan D. Battleson, Matthew D. Pagel, and Michael J. Thomas
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Real-time nodes ,Telemetry ,Adaptive management ,Chinook salmon ,Oncorhynchus ,Ecology ,QH540-549.5 ,Animal biochemistry ,QP501-801 - Abstract
Abstract Background Currently acoustic tag-detecting autonomous receivers must be visited periodically to download the files of tag detections. Hence, the information about the whereabouts of tagged fishes is not available to make prompt regulatory decisions to reduce entrainment. In contrast, real-time receivers can detect the signal from a transmitter on a passing fish and immediately transmit its identity and time of detection to a website, where they can be viewed on either a computer or cellular telephone. Real-time nodes can aid regulatory biologists in making important decisions. This is a powerful new tool for resource managers and conservation biologists. Results We describe a network of real-time, fish-tracking nodes on the Sacramento River, California. Two case studies illustrate the value of the nodes. The first entails detecting the arrival of migrating winter-run Chinook salmon near a water diversion and alerting regulatory biologists to keep the diversion closed to increase the migratory success. The second study involves the detection of green sturgeon at potential stranding sites, alerting biologists of the need to transport them from that site to the main channel of the river so they can continue their upstream migration to their spawning sites.
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- 2017
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315. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization
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Mi-Hye Lee, Kathryn M. Appleton, Hesham M. El-Shewy, Mary G. Sorci-Thomas, Michael J. Thomas, Maria F. Lopes-Virella, Louis M. Luttrell, Samar M. Hammad, and Richard L. Klein
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high density lipoprotein ,sphingosine 1-phosphate ,protein-fragment complementation assay ,scavenger receptor BI ,S1P receptors ,Biochemistry ,QD415-436 - Abstract
HDL normally transports about 50–70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.
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- 2017
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316. Lipid‐Free Apolipoprotein A‐I Reduces Progression of Atherosclerosis by Mobilizing Microdomain Cholesterol and Attenuating the Number of CD131 Expressing Cells: Monitoring Cholesterol Homeostasis Using the Cellular Ester to Total Cholesterol Ratio
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Sushma Kaul, Hao Xu, Manal Zabalawi, Elisa Maruko, Brian E. Fulp, Theresa Bluemn, Kristina L. Brzoza‐Lewis, Mark Gerelus, Ranjuna Weerasekera, Rachel Kallinger, Roland James, Yi (Sherry) Zhang, Michael J. Thomas, and Mary G. Sorci‐Thomas
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apolipoprotein ,apolipoprotein A‐I ,cholesterol ,chronic inflammation ,high‐density lipoprotein ,inflammation ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundAtherosclerosis is a chronic inflammatory disorder whose development is inversely correlated with high‐density lipoprotein concentration. Current therapies involve pharmaceuticals that significantly elevate plasma high‐density lipoprotein cholesterol concentrations. Our studies were conducted to investigate the effects of low‐dose lipid‐free apolipoprotein A‐I (apoA‐I) on chronic inflammation. The aims of these studies were to determine how subcutaneously injected lipid‐free apoA‐I reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without sustained elevations in plasma high‐density lipoprotein cholesterol concentrations. Methods and ResultsLdlr−/− and Ldlr−/− apoA‐I−/− mice were fed a Western diet for a total of 12 weeks. After 6 weeks, a subset of mice from each group received subcutaneous injections of 200 μg of lipid‐free human apoA‐I 3 times a week, while the other subset received 200 μg of albumin, as a control. Mice treated with lipid‐free apoA‐I showed a decrease in cholesterol deposition and immune cell retention in the aortic root compared with albumin‐treated mice, regardless of genotype. This reduction in atherosclerosis appeared to be directly related to a decrease in the number of CD131 expressing cells and the esterified cholesterol to total cholesterol content in several immune cell compartments. In addition, apoA‐I treatment altered microdomain cholesterol composition that shifted CD131, the common β subunit of the interleukin 3 receptor, from lipid raft to nonraft fractions of the plasma membrane. ConclusionsApoA‐I treatment reduced lipid and immune cell accumulation within the aortic root by systemically reducing microdomain cholesterol content in immune cells. These data suggest that lipid‐free apoA‐I mediates beneficial effects through attenuation of immune cell lipid raft cholesterol content, which affects numerous types of signal transduction pathways that rely on microdomain integrity for assembly and activation.
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- 2016
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317. Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers[S]
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Mary G. Sorci-Thomas, John S. Owen, Brian Fulp, Shaila Bhat, Xuewei Zhu, John S. Parks, Dharika Shah, W. Gray Jerome, Mark Gerelus, Manal Zabalawi, and Michael J. Thomas
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ATP binding cassette transporter A1 ,nascent HDL ,cholesterol ,apolipoprotein A-I ,mass spectrometry ,Biochemistry ,QD415-436 - Abstract
This report details the lipid composition of nascent HDL (nHDL) particles formed by the action of the ATP binding cassette transporter A1 (ABCA1) on apolipoprotein A-I (apoA-I). nHDL particles of different size (average diameters of ∼12, 10, 7.5, and
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- 2012
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318. The NLRP3 Inflammasome Promotes Age-Related Thymic Demise and Immunosenescence
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Yun-Hee Youm, Thirumala-Devi Kanneganti, Bolormaa Vandanmagsar, Xuewei Zhu, Anthony Ravussin, Ayinuer Adijiang, John S. Owen, Michael J. Thomas, Joseph Francis, John S. Parks, and Vishwa Deep Dixit
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Biology (General) ,QH301-705.5 - Abstract
The collapse of thymic stromal cell microenvironment with age and resultant inability of the thymus to produce naive T cells contributes to lower immune-surveillance in the elderly. Here we show that age-related increase in ‘lipotoxic danger signals’ such as free cholesterol (FC) and ceramides, leads to thymic caspase-1 activation via the Nlrp3 inflammasome. Elimination of Nlrp3 and Asc, a critical adaptor required for inflammasome assembly, reduces age-related thymic atrophy and results in an increase in cortical thymic epithelial cells, T cell progenitors and maintenance of T cell repertoire diversity. Using a mouse model of irradiation and hematopoietic stem cell transplantation (HSCT), we show that deletion of the Nlrp3 inflammasome accelerates T cell reconstitution and immune recovery in middle-aged animals. Collectively, these data demonstrate that lowering inflammasome-dependent caspase-1 activation increases thymic lymphopoiesis and suggest that Nlrp3 inflammasome inhibitors may aid the re-establishment of a diverse T cell repertoire in middle-aged or elderly patients undergoing HSCT.
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- 2012
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319. Sturgeon in the Sacramento–San Joaquin Watershed: New Insights to Support Conservation and Management
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A. Peter Klimley, Eric D. Chapman, Joseph J. Cech, Jr., Dennis E. Cocherell, Nann A. Fangue, Marty Gingras, Zachary Jackson, Emily A. Miller, Ethan A. Mora, Jamilynn B. Poletto, Andrea M. Schreier, Alicia Seesholtz, Kenneth J. Sulak, Michael J. Thomas, David Woodbury, and Megan T. Wyman
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green sturgeon ,Acipenser medirostris ,white sturgeon ,Acipenser transmontanus ,conservation biology ,Environmental sciences ,GE1-350 - Abstract
doi: http://dx.doi.org/10.15447/sfews.2015v13iss4art1The goal of a day-long symposium on March 3, 2015, Sturgeon in the Sacramento–San Joaquin Watershed: New Insights to Support Conservation and Management, was to present new information about the physiology, behavior, and ecology of the green (Acipenser medirostris) and white sturgeon (Acipenser transmontanus) to help guide enhanced management and conservation efforts within the Sacramento–San Joaquin watershed. This symposium identified current unknowns and highlighted new electronic tracking technologies and physiological techniques to address these knowledge gaps. A number of presentations, each reviewing ongoing research on the two species, was followed by a round-table discussion, in which each of the participants was asked to share recom-mendations for future research on sturgeon in the watershed. This article presents an in-depth review of the scientific information presented at the sympo-sium with a summary of recommendations for future research.
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- 2015
320. Anti-inflammatory liaisons: T regulatory cells and HDL1
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Mary G. Sorci-Thomas and Michael J. Thomas
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Biochemistry ,QD415-436 - Published
- 2017
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321. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol[S]
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Xuewei Zhu, John S. Owen, Martha D. Wilson, Haitao Li, Gary L. Griffiths, Michael J. Thomas, Elizabeth M. Hiltbold, Michael B. Fessler, and John S. Parks
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free cholesterol ,cytokines ,immunology ,lipid droplets ,lymphocytes ,retinoids ,Biochemistry ,QD415-436 - Abstract
We previously showed that macrophages from macrophage-specific ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1-M/-M) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In the present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of macrophages to LPS in WT mice. Abca1-M/-M macrophages were also hyper-responsive to specific agonists to TLR2, TLR7, and TLR9, but not TLR3, compared with WT macrophages. We hypothesized that ABCA1 regulates macrophage responsiveness to TLR agonists by modulation of lipid raft cholesterol and TLR mobilization to lipid rafts. We demonstrated that Abca1-M/-M vs. WT macrophages contained 23% more FC in isolated lipid rafts. Further, mass spectrometric analysis suggested raft phospholipid composition was unchanged. Although cell surface expression of TLR4 was similar between Abca1-M/-M and WT macrophages, significantly more TLR4 was distributed in membrane lipid rafts in Abca1-M/-M macrophages. Abca1-M/-M macrophages also exhibited increased trafficking of the predominantly intracellular TLR9 into lipid rafts in response to TLR9-specific agonist (CpG). Collectively, our data suggest that macrophage ABCA1 dampens inflammation by reducing MyD88-dependent TLRs trafficking to lipid rafts by selective reduction of FC content in lipid rafts.
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- 2010
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322. Three-dimensional models of HDL apoA-I: implications for its assembly and function
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Michael J. Thomas, Shaila Bhat, and Mary G. Sorci-Thomas
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cholesterol ,mass spectrometry ,hydrogen-deuterium exchange ,molecular dynamic modeling ,chemical cross-linking ,apolipoprotein A-I ,Biochemistry ,QD415-436 - Abstract
The purpose of this review is to highlight recent advances toward the refinement of a three-dimensional structure for lipid-bound apolipoprotein A-I (apoA-I) on recombinant HDL. Recently, X-ray crystallography has yielded a new structure for full-length, lipid-free apoA-I. Although this approach has not yet been successful in solving the three-dimensional structure of lipid-bound apoA-I, analysis of the X-ray structures has been of immense help in the interpretation of structural data obtained from other methods that yield structural information. Recent studies emphasize the use of mass spectrometry to unambiguously identify cross-linked peptides or to quantify solvent accessibility using hydrogen-deuterium exchange. The combination of mass spectrometry, molecular modeling, molecular dynamic analysis, and small-angle X-ray diffraction has provided additional structural information on apoA-I folding that complements previous approaches.
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- 2008
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323. Inflammation and skin cholesterol in LDLr−/−, apoA-I−/− mice: link between cholesterol homeostasis and self-tolerance?
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Manal Zabalawi, Manish Bharadwaj, Heather Horton, Mark Cline, Mark Willingham, Michael J. Thomas, and Mary G. Sorci-Thomas
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apolipoprotein A-I ,high density lipoprotein ,inflammation ,low density lipoprotein receptor-deficient/apolipoprotein A-I-deficient mice ,whole body cholesterol ,skin ,Biochemistry ,QD415-436 - Abstract
Diet-fed low density lipoprotein receptor-deficient/apolipoprotein A-I-deficient (LDLr−/−, apoA-I−/−) mice accumulate a 10-fold greater mass of cholesterol in their skin despite a 1.5- to 2-fold lower plasma cholesterol concentration compared with diet-fed LDLr−/− mice. The accumulation of cholesterol predominantly in the skin has been shown to occur in a growing number of other hypercholesterolemic double knockout mouse models sharing deficits in genes regulating cellular cholesterol homeostasis. Exploring the relationship between cholesterol balance and inflammation, we have examined the time course of cholesterol accumulation in a number of extrahepatic tissues and correlated with the onset of inflammation in diet-fed LDLr−/−, apoA-I−/− mice. After 4 weeks of diet, LDLr−/−, apoA-I−/− mice showed a significant increase in skin cholesterol mass compared with LDLr−/− mice. In addition, after 4 weeks on the diet, cholesterol accumulation in the skin was also found to be associated with macrophage infiltration and accompanied by increases in tumor necrosis factor-α, cyclooxygenase-2, and langerin mRNA, which were not seen in the liver. Overall, these data suggest that as early as 4 weeks after starting the diet, the accumulation of skin cholesterol and the onset of inflammation occur concurrently. In summary, the use of hypercholesterolemic LDLr−/−, apoA-I−/− mice may provide a useful tool to investigate the role that apoA-I plays in maintaining cholesterol homeostasis and its relationship to inflammation.
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- 2007
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324. Ratio determination of plasma wild-type and L159R apoA-I using mass spectrometry: tools for studying apoA-IFin
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John S. Owen, Manish S. Bharadwaj, Michael J. Thomas, Shaila Bhat, Michael P. Samuel, and Mary G. Sorci-Thomas
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apolipoprotein A-I ,protein expression ,inclusion bodies ,apolipoprotein A-I mutant ,high-performance liquid chromatography-electrospray mass spectrometry ,high-performance liquid chromatography-electrospray tandem mass spectrometry ,Biochemistry ,QD415-436 - Abstract
In this report, methods are described to isolate milligram quantities of a mutant apolipoprotein A-I (apoA-I) protein for use in structure-function studies. Expression of the L159R apoA-I mutation in humans reduces the concentration of plasma wild-type apoA-I, thus displaying a dominant negative phenotype in vivo. Earlier attempts to express and isolate this mutant protein resulted in extensive degradation and protein misfolding. Using an Escherichia coli expression system used predominantly for the isolation of soluble apoA-I mutant proteins, we describe the expression and purification of L159R apoA-I (apoA-IFin) from inclusion bodies. In addition, we describe a mass spectrometric method for measuring the L159R-to-wild-type apoA-I ratio in a 1 μl plasma sample. These new methods will facilitate further studies into the mechanism behind the dominant negative phenotype associated with the expression of the L159R apoA-I protein in humans.
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- 2007
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325. An improved assay for platelet-activating factor using HPLC-tandem mass spectrometry
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John S. Owen, Robert L. Wykle, Michael P. Samuel, and Michael J. Thomas
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high-performance liquid chromatography tandem mass spectrometry ,trace analysis ,neutrophil ,Biochemistry ,QD415-436 - Abstract
We describe an improved assay for platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) using HPLC-tandem mass spectrometry (LC-MS/MS). The present method can readily detect as little as 1 pg (1.9 fmol) of PAF, a significant improvement over previously described LC-MS/MS methods, and gives a linear response up to 1,000 pg of PAF. Our method also overcomes the artifacts from isobaric lipids that have limited the usefulness of certain existing LC-MS/MS assays for PAF. In the course of these studies, we detected three novel lipid species in human neutrophils. One of the novel lipids appears to be a new molecular species of PAF, and the other two have chromatographic and mass spectrometric properties consistent with stearoyl-formyl-glycerophosphocholine and oleoyl-formyl-glycerophosphocholine.These observations identify previously unknown potential interferences in the measurement of PAF by LC-MS/MS. Moreover, our data suggest that the previously described palmitoyl-formyl-glycerophosphocholine is not unique but rather is a member of a new and poorly understood family of formylated lipids.
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- 2005
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326. Quality control in the apoA-I secretory pathway
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Shaila Bhat, Manal Zabalawi, Mark C. Willingham, Gregory S. Shelness, Michael J. Thomas, and Mary G. Sorci-Thomas
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apolipoprotein A-I ,high density lipoprotein ,mutant apolipoprotein A-I ,protein secretion ,quality control pathway ,aggresomes ,Biochemistry ,QD415-436 - Abstract
From a total of 47 known apolipoprotein A-I (apoA-I) mutations, only 18 are linked to low plasma HDL apoA-I concentrations, and 78% of these map to apoA-I helices 6 and 7 (residues 143–186). Gene transfer and transgenic mouse studies have shown that several helix 6 apoA-I mutations have reduced hepatic HDL production. Our objective was to examine the impact of helix 6 modifications on intracellular biosynthetic processing and secretion of apoA-I. Cells were transfected with wild-type or mutant apoA-I, radiolabeled with [35S]Met/Cys, and then placed in unlabeled medium for up to 4 h. Results show that >90% of newly synthesized wild-type apoA-I was secreted by 60 min. Over the same length of time, only 20% of helix 6 deletion mutant (Δ6 apoA-I) was secreted, whereas 80% remained cell associated. Microscopic and biochemical studies revealed that cell-associated Δ6 apoA-I was located predominantly within the cytoplasm as lipid-protein inclusions, whereas wild-type apoA-I was localized in the endoplasmic reticulum/Golgi. Results using other helix deletions or helix 6 substitution mutations indicated that only complete removal of helix 6 resulted in massive cytoplasmic accumulation.These data suggest that alterations in native apoA-I conformation can lead to aberrant trafficking and accumulation of apolipoprotein-phospholipid structures. Thus, conformation-dependent alterations in intracellular trafficking and turnover may underlie the reduced plasma HDL concentrations observed in individuals harboring deletion mutations within helix 6.
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- 2004
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327. Preβ high density lipoprotein has two metabolic fates in human apolipoprotein A-I transgenic mice
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Ji-Young Lee, Lorraine Lanningham-Foster, Elena Y. Boudyguina, Thomas L. Smith, Ellen R. Young, Perry L. Colvin, Michael J. Thomas, and John S. Parks
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high density lipoprotein metabolism ,in vivo ,lipid-free apolipoprotein A-I ,fractional catabolic rate ,turnover ,die-away ,Biochemistry ,QD415-436 - Abstract
We compared the in vivo metabolism of preβ HDL particles isolated by anti-human apolipoprotein A-I (apoA-I) immunoaffinity chromatography (LpA-I) in human apoA-I transgenic (hA-I Tg) mice with that of lipid-free apoA-I (LFA-I) and small LpA-I. After injection, preβ LpA-I were removed from plasma more rapidly than were LFA-I and small LpA-I. Preβ LpA-I and LFA-I were preferentially degraded by kidney compared with liver; small LpA-I were preferentially degraded by the liver. Five minutes after tracer injection, 99% of LFA-I in plasma was found to be associated with medium-sized (8.6 nm) HDL, whereas only 37% of preβ tracer remodeled to medium-sized HDL. Injection of preβ LpA-I doses into C57Bl/6 recipients resulted in a slower plasma decay compared with hA-I Tg recipients and a greater proportion (>60%) of the preβ radiolabel that was associated with medium-sized HDL. Preβ LpA-I contained one to four molecules of phosphatidylcholine per molecule of apoA-I, whereas LFA-I contained less than one.We conclude that preβ LpA-I has two metabolic fates in vivo, rapid removal from plasma and catabolism by kidney or remodeling to medium-sized HDL, which we hypothesize is determined by the amount of lipid associated with the preβ particle and the particle’s ability to bind to medium-sized HDL.
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- 2004
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328. α-Tocopherol protects against diet induced atherosclerosis in New Zealand white rabbits
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Dawn C. Schwenke, Lawrence L. Rudel, Mary G. Sorci-Thomas, and Michael J. Thomas
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α-tocopherol ,fatty acid ,polyunsaturated fatty acid ,saturated fatty acid ,monounsaturated fatty acid ,high density lipoprotein ,Biochemistry ,QD415-436 - Abstract
In this study, we asked the question “does α-tocopherol supplementation prevent an increase in total plasma cholesterol (TPC) concentration and reduce the deposition of cholesterol in arterial plaques of rabbits fed atherogenic diets?” Isocaloric diets containing 0.1% cholesterol to induce atherosclerosis were enriched in one of three fats: saturated fats (SAT), monounsaturated fats (MONO), or n-6 polyunsaturated fats (POLY). Half of each of the three diets were supplemented with 2,500 IU α-tocopherol/kg-diet. Unsupplemented diets contained 25 IU α-tocopherol/kg-diet. Rabbits supplemented with α-tocopherol had plasma α-tocopherol concentrations 10-fold higher and an average TPC concentration 31% lower, P = 0.017, than rabbits fed unsupplemented diets. Among the three fat-fed groups, the difference was greatest for the POLY fat fed group (54%, P = 0.041). POLY fat-fed rabbits without α-tocopherol supplementation had plasma HDL cholesterol concentrations that were less than half that of rabbits fed other fats, P ⩽ 0.0001. In general, differences in mean esterified artery cholesterol concentrations among the three fat-fed groups, with and without α-tocopherol supplementation, paralleled differences in TPC concentration among the groups.This study suggests that for rabbits fed high pharmacological doses of α-tocopherol, atherosclerosis can be diminished in situations where the plasma cholesterol concentrations are also significantly lower.
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- 2002
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329. Molecular species composition of rat liver phospholipids by ESI-MS/MS: the effect of chromatography
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Cynthia J. DeLong, Paul R.S. Baker, Michael Samuel, Zheng Cui, and Michael J. Thomas
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glycerophospholipids ,electrospray mass spectrometry ,lipids ,choline glycerophosphates ,ethanolamine glycerophosphates ,tandem mass spectrometry ,Biochemistry ,QD415-436 - Abstract
Using electrospray ionization tandem mass spectrometry (ESI-MS/MS) this study shows that the loss of glycerophospholipid (GPL) after chromatography was unevenly distributed across the GPL molecular species. Both TLC and HPLC caused a preferential loss of GPL with 0 to 3 double bonds: 20% and 7.2% for choline glycerophosphates (PC) and 19.7% and 7.5% for ethanolamine glycerophosphates (PE), respectively. A consequence of these losses was that GPLs containing fatty acids with four or more double bonds had a greater contribution to the total after chromatography. ESI-MS/MS analysis also showed that PC molecular species with four or more double bonds migrated at the front of the TLC band of PCs. GPLs extracted from TLC plates occasionally contained PCs that were smaller than those in the original extract. These low molecular mass PCs were easily reduced to alcohols and formed derivatives with 2,4-dinitrophenylhydrazine, suggesting that aldehydes were generated by the oxidation of unsaturated fatty acids. Directly analyzing lipid extracts by ESI-MS/MS without preliminary chromatographic separation gives an accurate distribution of GPL molecular species in lipid mixtures. However, the ionization of the phospholipids in the electrospray jet maximized at relatively low concentrations of GPL. There was a linear response between phospholipid mass and ion intensity for concentrations around 1–2 nmol/ml for both PC and PE. The total ion intensity continued to increase with concentrations above 1–2 nmol/ml, but the response was non-linear.—DeLong, C. J., P. R. S. Baker, M. Samuel, Z. Cui, and M. J. Thomas. Molecular species composition of rat liver phospholipids by ESI-MS/MS: the effect of chromatography. J. Lipid Res. 2001. 42: 1959–1968.
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- 2001
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330. Preparation and incorporation of probe-labeled apoA-I for fluorescence resonance energy transfer studies of rHDL
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Hui-hua Li, Michael J. Thomas, Wei Pan, Eric Alexander, Michael Samuel, and Mary G. Sorci-Thomas
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recombinant apoA-I ,protein expression of mature apoA-I ,fluorescent probes ,Eschericha coli expression ,intein ,LCAT activity ,Biochemistry ,QD415-436 - Abstract
Apolipoprotein A-I (apoA-I), the major constituent of HDL, plays an essential role in regulating cholesterol metabolism, acting as the physiological activator of lecithin: cholesterol acyltransferase, which converts cholesterol to cholesterol ester. Thiol-reactive fluorescent probes attached to cysteine-containing apoA-I mutants are currently being used to investigate the “LCAT active” conformation of lipid-bound apoA-I. Herein, we report new methodologies allowing rapid expression, fluorescent labeling, and recombinant HDL (rHDL) preparation for use in apoA-I in fluorescence resonance energy transfer (FRET) studies. Cysteine-containing mutant forms of human apoA-I were cloned into the pTYB12 vector containing a T7 promoter, a modified self-splicing protein element (intein), and a small affinity tag [chitin binding domain (CBD)]. The fusion proteins were expressed in Escherichia coli, isolated from cell lysates, and bound to a chitin-affinity column. Release of mature human apoA-I was initiated by the addition of DTT, which induced self-cleavage at the COOH terminus of the intein-CBD fusion protein. ApoA-I was further purified by Q-sepharose and then used for fluorescent probe labeling. Discoidal rHDL were then prepared with donor and/or acceptor labeled apoA-I and characterized with respect to their size, composition and ability to activate LCAT.—Li, H-h., M. J. Thomas, W. Pan, E. Alexander, M. Samuel, and M. G. Sorci-Thomas. Preparation and incorporation of probe-labeled apoA-I for fluorescence resonance energy transfer studies of rHDL. J. Lipid Res. 2001. 42: 2084–2091.
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- 2001
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331. Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association.
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James C. Sisson, John Freitas, Iain Ross McDougall, Lawrence T. Dauer, James R. Hurley, James D. Brierley, Charlotte H. Edinboro, David Rosenthal, Michael J. Thomas, Jason A Wexler, Ernest Asamoah, Anca M. Avram, Mira Milas, and Carol Greenlee
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RADIATION protection , *THYROID diseases , *IODINE isotopes , *HYPOTHYROIDISM , *THYROID cancer , *HEALTH outcome assessment - Abstract
Background:Radiation safety is an essential component in the treatment of patients with thyroid diseases by 131I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines.Methods:Reviews of Nuclear Regulatory Commission regulations formed the basic structure of recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines.Results:The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with 131I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician''s advice to patients and caregivers on precautions to be adopted within and outside the home.Conclusion:Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with 131I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with 131I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine. [ABSTRACT FROM AUTHOR]
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- 2011
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