Science.gov

Sample records for labeled cytidine analog

  1. The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2

    PubMed Central

    Smid, Kees; de Klerk, Daniël; van Kuilenburg, André B. P.; Meinsma, Rutger; Lee, Young B.; Kim, Deog J.; Peters, Godefridus J.

    2016-01-01

    Fluorocyclopentenylcytosine (RX-3117) is an orally available cytidine analog, currently in Phase I clinical trial. RX-3117 has promising antitumor activity in various human tumor xenografts including gemcitabine resistant tumors. RX-3117 is activated by uridine-cytidine kinase (UCK). Since UCK exists in two forms, UCK1 and UCK2, we investigated which form is responsible for RX-3117 phosphorylation. For that purpose we transfected A549 and SW1573 cell lines with UCK-siRNAs. Transfection of UCK1-siRNA efficiently downregulated UCK1-mRNA, but not UCK2-mRNA expression, and did not affect sensitivity to RX-3117. However, transfection of UCK2-siRNA completely downregulated UCK2-mRNA and protein and protected both A549 and SW1573 against RX-3117. UCK enzyme activity in two panels of tumor cell lines and xenograft cells correlated only with UCK2-mRNA expression (r = 0.803 and 0.915, respectively), but not with UCK1-mRNA. Moreover, accumulation of RX-3117 nucleotides correlated with UCK2 expression. In conclusion, RX-3117 is activated by UCK2 which may be used to select patients potentially sensitive to RX-3117. PMID:27612203

  2. The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2.

    PubMed

    Sarkisjan, Dzjemma; Julsing, Joris R; Smid, Kees; de Klerk, Daniël; van Kuilenburg, André B P; Meinsma, Rutger; Lee, Young B; Kim, Deog J; Peters, Godefridus J

    2016-01-01

    Fluorocyclopentenylcytosine (RX-3117) is an orally available cytidine analog, currently in Phase I clinical trial. RX-3117 has promising antitumor activity in various human tumor xenografts including gemcitabine resistant tumors. RX-3117 is activated by uridine-cytidine kinase (UCK). Since UCK exists in two forms, UCK1 and UCK2, we investigated which form is responsible for RX-3117 phosphorylation. For that purpose we transfected A549 and SW1573 cell lines with UCK-siRNAs. Transfection of UCK1-siRNA efficiently downregulated UCK1-mRNA, but not UCK2-mRNA expression, and did not affect sensitivity to RX-3117. However, transfection of UCK2-siRNA completely downregulated UCK2-mRNA and protein and protected both A549 and SW1573 against RX-3117. UCK enzyme activity in two panels of tumor cell lines and xenograft cells correlated only with UCK2-mRNA expression (r = 0.803 and 0.915, respectively), but not with UCK1-mRNA. Moreover, accumulation of RX-3117 nucleotides correlated with UCK2 expression. In conclusion, RX-3117 is activated by UCK2 which may be used to select patients potentially sensitive to RX-3117. PMID:27612203

  3. Labeled Cocaine Analogs

    SciTech Connect

    Goodman, Mark M.; Shi, Bing Zhi; Keil, Robert N.

    1999-03-30

    Novel methods for positron emission tomography or single photon emission spectroscopy using tracer compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)napthyl Y in .beta. configuration is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, The compounds bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.

  4. Labeled Cocaine Analogs

    SciTech Connect

    Goodman, Mark M.; Shi, Bing Zhi; Keil, Robert N.

    1999-01-26

    Novel compounds having the structure: ##STR1## where X in .beta. configuration is phenyl, naphthyl; 2,3 or 4-iodophenyl; 2,3 or 4-(trimethylsilyl)phenyl; 3,4,5 or 6-iodonaphthyl; 3,4,5 or 6-(trimethylsilyl)naphthyl; 2,3 or 4-(trialkylstannyl)phenyl; or 3,4,5 or 6-(trialkylstannyl)naphthyl Y in .beta. configuration is Y.sub.1 or Y.sub.2, where Y.sub.1 is 2-fluoroethoxy, 3-fluoropropoxy, 4-fluorobutoxy, 2-fluorocyclopropoxy, 2 or 3-fluorocyclobutoxy, R,S 1'-fluoroisopropoxy, R 1'-fluoroisopropoxy, S 1'-fluoroisopropoxy, 1',3'-difluoroisopropoxy, R,S 1'-fluoroisobutoxy, R 1'-fluoroisobutoxy, S 1'-fluoroisobutoxy, R,S 4'-fluoroisobutoxy, R 4'-fluoroisobutoxy, S 4'-fluoroisobutoxy, or 1',1'-di(fluoromethyl)isobutoxy, and Y.sub.2 is 2-methanesulfonyloxy ethoxy, 3-methanesulfonyloxy propoxy, 4-methanesulfonyloxy butoxy, 2-methanesulfonyloxy cyclopropoxy, 2 or 3-methanesulfonyloxy cyclobutoxy, 1'methanesulfonyloxy isopropoxy, 1'-fluoro, 3'-methanesulfonyloxy isopropoxy, 1'-methanesulfonyloxy, 3'-fluoro isopropoxy, 1'-methanesulfonyloxy isobutoxy, or 4'-methanesulfonyloxy isobutoxy bind dopamine transporter protein and can be labeled with .sup.18 F or .sup.123 I for imaging.

  5. Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis[OPEN

    PubMed Central

    Liu, Chun-Hsin; Finke, Andreas; Díaz, Mariana; Rozhon, Wilfried; Poppenberger, Brigitte; Baubec, Tuncay; Pecinka, Ales

    2015-01-01

    DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway. PMID:26023162

  6. 3'-end labeling of RNA with [5'-32P]Cytidine 3',5'-bis(phosphate) and T4 RNA ligase 1.

    PubMed

    Nilsen, Timothy W

    2014-04-01

    This protocol is used to radiolabel the 3' ends of RNAs, either synthesized by in vitro transcription or purified from cells or tissues, by ligation of [5'-(32)P]cytidine 3',5'-bis(phosphate) (pCp). [5'-(32)P]pCp can be obtained commercially or prepared in the laboratory using polynucleotide kinase to phosphorylate cytidine-3'-monophosphate (Cp) with [γ-(32)P]ATP. "Homemade" [5'-(32)P]pCp is considerably cheaper and has a higher final concentration than that obtained from commercial sources. The labeling protocol uses T4 RNA ligase 1, which covalently joins [5'-(32)P]pCp to the free 3' hydroxyl of RNA. For best labeling, [5'-(32)P]pCp should be at least equimolar or higher to available 3'-hydroxyl ends. The reaction requires overnight incubation at low temperature. At the end of the procedure, the reaction is desalted by gel filtration to remove any unincorporated [5'-(32)P]pCp.

  7. Synthesis of γ-Phosphate-Labeled and Doubly Labeled Adenosine Triphosphate Analogs.

    PubMed

    Hacker, Stephan M; Welter, Moritz; Marx, Andreas

    2015-03-09

    This unit describes the synthesis of γ-phosphate-labeled and doubly labeled adenosine triphosphate (ATP) analogs and their characterization using the phosphodiesterase I from Crotalus adamanteus (snake venom phosphodiesterase; SVPD). In the key step of the synthesis, ATP or an ATP analog, bearing a linker containing a trifluoroacetamide group attached to the nucleoside, are modified with an azide-containing linker at the terminal phosphate using an alkylation reaction. Subsequently, different labels are introduced to the linkers by transformation of one functional group to an amine and coupling to an N-hydroxysuccinimide ester. Specifically, the Staudinger reaction of the azide is employed as a straightforward means to obtain an amine in the presence of various labels. Furthermore, the fluorescence characteristics of a fluorogenic, doubly labeled ATP analog are investigated following enzymatic cleavage by SVPD.

  8. Synthesis of tritium-labeled vitamin A and its analogs

    SciTech Connect

    Rhee, S.W.; Bubb, J.E.

    1985-11-01

    Metabolic and pharmacologic studies of Vitamin A and its analogs related to the prevention of lung cancer and other epithelial cancers required tritium-labeled Vitamin A analogs and ..beta..-carotene at high specific activity. Syntheses of some of the isomers were therefore developed in the laboratory, as described in the paper. The advantages of the scheme shown are that : 1. Tritiums are introduced into the molecule by catalytic hydrogenation, thus affording high specific activity. 2. It uses an allylic rearrangement of tritiated vinyl-..beta..-ionol to C/sub 15/-phosphonium salt, which is condensed with C/sub 5/-nitrile to give C/sub 20/-skeleton of retinonitrile. 3. It permits the development of milder methods to convert tritium-labeled retinaldehyde, as a common intermediate, to the other retinoids (i.e., retinoic acid, retinol, and retinyl acetate). Furthermore, tritium-labeled all-trans-..beta..-carotene, an important carotenoid, has been obtained from the retinaldehyde.

  9. Enhancement by cytidine of membrane phospholipid synthesis

    NASA Technical Reports Server (NTRS)

    G-Coviella, I. L.; Wurtman, R. J.

    1992-01-01

    Cytidine, as cytidine 5'-diphosphate choline, is a major precursor in the synthesis of phosphatidylcholine in cell membranes. In the present study, we examined the relationships between extracellular levels of cytidine, the conversion of [14C]choline to [14C]phosphatidylcholine, and the net syntheses of phosphatidylcholine and phosphatidylethanolamine by PC12 cells. The rate at which cytidine (as [3H]cytidine) was incorporated into the PC12 cells followed normal Michaelis-Menten kinetics (Km = 5 microM; Vmax = 12 x 10(-3) mmol/mg of protein/min) when the cytidine concentrations in the medium were below 50 microM; at higher concentrations, intracellular [3H]cytidine nucleotide levels increased linearly. Once inside the cell, cytidine was converted mainly into cytidine triphosphate. In pulse-chase experiments, addition of cytidine to the medium caused a time- and dose-dependent increase (by up to 30%) in the incorporation of [14C]choline into membrane [14C]-phosphatidylcholine. When the PC12 cells were supplemented with both cytidine and choline for 14 h, small but significant elevations (p less than 0.05) were observed in their absolute contents of membrane phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, all increasing by 10-15% relative to their levels in cells incubated with choline alone. Exogenous cytidine, acting via cytidine triphosphate, can thus affect the synthesis and levels of cell membrane phospholipids.

  10. A (18)F-labeled glucose analog: synthesis using a click labeling method and in vitro evaluation.

    PubMed

    Kim, Dong Hyun; Choe, Yearn Seong; Jung, Kyung-Ho; Lee, Kyung-Han; Choi, Joon Young; Choi, Yong; Kim, Byung-Tae

    2008-05-01

    A (18)F-labeled glucose analog, 4-[(2-[(18)F]fluoroethyl)-1-(beta-D: -glucopyranosyl)]-1H-1,2,3-triazole ([(18)F]1), was synthesized using a click labeling method and evaluated in vitro for its cellular transportation via glucose transporter (Glut-1) and its potential as a hexokinase substrate. The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mumol vs. 23.5 GBq/mumol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [(18)F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional groups, although a triazole moiety at C1 of [(18)F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1. PMID:18481013

  11. Separation of aracytidine and cytidine by capillary electrophoretic techniques.

    PubMed

    Krivánková, L; Kostálová, A; Vargas, G; Havel, J; Bocek, P

    1996-12-01

    Aracytidine (cytarabine, 1-beta-D-arabinofuranosylcytosine) is a synthetic analog of cytidine in which ribose is substituted by arabinose; it is used as a drug for the treatment of leukemia. A fast and reliable capillary electrophoretic method for the analysis of cytarabine and cytidine is described. The procedure utilizes the interactions with sodium dodecyl sulfate (SDS) micelles and borate, present in the background electrolyte, for the mobilization and selective separation of the analytes. The detection is carried out by UV absorbance at 275 nm. The method was applied both to pharmaceutical preparations and human serum. Analysis of an untreated serum requires 15 min; the detection limit is 0.8 microgram/mL and the relative standard deviation (RSD) is 5.3%.

  12. A clickable UTP analog for the posttranscriptional chemical labeling and imaging of RNA.

    PubMed

    Sawant, Anupam A; Mukherjee, Progya P; Jangid, Rahul K; Galande, Sanjeev; Srivatsan, Seergazhi G

    2016-06-28

    The development of robust tools and practical RNA labeling strategies that would facilitate the biophysical analysis of RNA in both cell-free and cellular systems will have profound implications in the discovery of new RNA diagnostic tools and therapeutic strategies. In this context, we describe the development of a new alkyne-modified UTP analog, 5-(1,7-octadinyl)uridine triphosphate (ODUTP), which serves as an efficient substrate for the introduction of a clickable alkyne label into RNA transcripts by bacteriophage T7 RNA polymerase and mammalian cellular RNA polymerases. The ODU-labeled RNA is effectively used by reverse transcriptase to produce cDNA, a property which could be utilized in expanding the chemical space of a RNA library in the aptamer selection scheme. Further, the alkyne label on RNA provides a convenient tool for the posttranscriptional chemical functionalization with a variety of biophysical tags (fluorescent, affinity, amino acid and sugar) by using alkyne-azide cycloaddition reaction. Importantly, the ability of endogenous RNA polymerases to specifically incorporate ODUTP into cellular RNA transcripts enabled the visualization of newly transcribing RNA in cells by microscopy using click reactions. In addition to a clickable alkyne group, ODU contains a Raman scattering label (internal disubstituted alkyne), which exhibits characteristic Raman shifts that fall in the Raman-silent region of cells. Our results indicate that an ODU label could potentially facilitate two-channel visualization of RNA in cells by using click chemistry and Raman spectroscopy. Taken together, ODU represents a multipurpose ribonucleoside tool, which is expected to provide new avenues to study RNA in cell-free and cellular systems. PMID:27173127

  13. Follow the Carbon: Laboratory Studies of 13C-Labeled Early Earth Haze Analogs

    NASA Astrophysics Data System (ADS)

    Hicks, R. K.; Day, D. A.; Mojzsis, S. J.; Jimenez, J. L.; Tolbert, M. A.

    2013-12-01

    While the Sun was still young and faint before the rise of molecular oxygen 2.4 Ga, early Earth might have been kept warm by an atmosphere containing the greenhouse gases methane and carbon dioxide in abundances greater than what is found on Earth today. It has been suggested that an atmosphere containing approximately 1000 ppmv methane and carbon dioxide could provided the needed greenhouse warming for liquid water to exist at the surface. Laboratory and modeling studies suggest that an atmosphere containing methane and carbon dioxide could lead to the formation of significant amounts of organic haze due to photochemical reactions initiated by Lyman-α (121.6 nm) excitation. Chemical mechanisms proposed to explain the chemistry rely on methane as the source of carbon in these hazes and treat carbon dioxide as a source of oxygen only. In the present work, we use isotopically labelled precursor gases to examine the source of carbon in photochemical haze formed in a CH4/CO2/N2 atmosphere. We generate haze analogs in the laboratory by far-UV irradiation of analog atmospheres containing permutations of 1,000 ppmv unlabeled and 13C-labeled methane and carbon. Products in the particle phase were analyzed by both unit mass resolution and high-resolution (m/Δm=5,000) aerosol mass spectrometry. Results indicate that carbon from carbon dioxide accounts for 20% (×5%) of the total carbon contained in the hazes. These results have implications for the geochemical interpretations of inclusions found in Archaean rocks on Earth, and for the astrobiological potential of other planetary atmospheres.

  14. Copper-62 labeled ReCCMSH peptide analogs for melanoma PET imaging.

    PubMed

    Zhang, Xiuli; Yue, Zhiwei; Lu, Bao-Yuan; Vazquez-Flores, Gerson J; Yuen, Johnny; Figueroa, Said Daibes; Gallazzi, Fabio; Cutler, Cathy; Quinn, Thomas P; Lacy, Jeffrey L

    2012-10-01

    High-specific activity radiolabeled melanocortin peptide preparations are necessary for optimal melanoma imaging due to the relatively low number of melanocortin-1 receptors (MC1-Rs) per tumor cell. In this study, a one-step synthesis of 62Cu-labeled MC1-R targeting peptide Re(Arg11)CCMSH was developed, which yielded high specific activity radiolabeled peptide preparations that required no post-labeling purification. DOTA and NOTA conjugated Re(Arg11)CCMSH peptides were synthesized and examined for 62Cu radiolabeling and cell binding properties. Biodistribution and PET imaging studies were performed to assess the in vivo tumor targeting and imaging characteristics of the optimal radiolabeled peptide. Melanoma cell binding affinities for NOTA-, NOTA-GGG-, and NOTA-GSG- conjugated Re(Arg11)CCMSH were determined to be 1.3×10-9 M, 1.9×10-9 M and 6.0×10-9 M. The 62Cu radiolabeling efficiencies of DOTA- and NOTA- conjugated Re(Arg11)CCMSH analogs were 30% and > 98% after 2 min at 24° C, while 0.5 μg of NOTA-GGG-peptide could be labeled to > 95% with a maximum specific activity of 138 Ci/μmol. Tumor uptake of 62Cu- NOTA-GGG-Re(Arg11)CCMSH in B16/F1 melanoma bearing mice was 4.65±0.48% ID/g and 9.43±2.69% ID/g at 20 and 40 min post injection and was visualized by PET imaging. High specific activity 62Cu-NOTA-GGG-Re(Arg11)CCMSH was prepared in a one-step procedure at 24°C in 6 min. 62Cu-NOTA-GGG-Re(Arg11)CCMSH exhibited MC1-R selective binding and rapid tumor uptake in B16/F1 melanoma bearing mice that was confirmed by PET imaging studies. High specific activity 62Cu from a 62Zn/62Cu generator coupled with simple one step radiolabeling procedures makes 62Cu an attractive radionuclide for PET imaging of low-density receptor targets.

  15. Affinity Labeling of Hepatitis C Virus Replicase with a Nucleotide Analog: Identification of binding site

    PubMed Central

    Manvar, Dinesh; Singh, Kamlendra; Pandey, Virendra N.

    2013-01-01

    We have used an ATP analog, 5′-[p-(fluorosulfonyl)benzoyl]adenosine (FSBA), to modify HCV replicase in order to identify ATP binding site in the enzyme. FSBA inactivates HCV replicase activity in a concentration dependent manner with a binding stoichiometry of 2 moles of FSBA per mole of enzyme. The enzyme activity is protected from FSBA in the presence of rNTP substrates or double stranded RNA template primers that do not support ATP as the incoming nucleotide but not in the presence of polyrU.rA26. The HPLC analysis of tryptic peptides of FSBA-modified enzyme revealed the presence of two distinct peptides eluted at 23 min and 36 min; these were absent in the control. Further we noted that both the peptides were protected from FSBA modification in the presence of Mg.ATP. The LC/MS/MS analysis of the affinity-labeled tryptic peptides purified from HPLC, identified two major modification sites at positions 382 (Tyr), and 491 (Lys) and a minor site at position 38 (Tyr). To validate the functional significance of Tyr38, Tyr382 and Lys491 in catalysis, we individually substituted these residues by alanine and examined their ability to catalyze RdRp activity. We found that both Y382A and K491A mutants were significantly affected in their ability to catalyze RdRp activity while Y38A remained unaffected. We further observed that both Y382A and K491A mutants were not affected in their ability to bind template primer but significantly affected in their ability to photo-crosslink ATP in the absence or presence of template primer. PMID:23268692

  16. 76 FR 2268 - Viruses, Serums, Toxins, and Analogous Products; Packaging and Labeling

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-13

    ... storage temperature recommended in labeling for veterinary biologics; require vaccination and... adequate instructions for the proper use of the product, including vaccination schedules, warnings, and...)(5) to clarify that ``full instructions for the proper use of the product'' refers to...

  17. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog

    SciTech Connect

    Akiyama, S.; Cornwell, M.M.; Kuwano, M.; Pastan, I.; Gottesman, M.M.

    1988-02-01

    Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-(3-/sup 125/I)salicyl)-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N-solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P-glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts.

  18. Communication: Orientational self-ordering of spin-labeled cholesterol analogs in lipid bilayers in diluted conditions

    SciTech Connect

    Kardash, Maria E.; Dzuba, Sergei A.

    2014-12-07

    Lipid-cholesterol interactions are responsible for different properties of biological membranes including those determining formation in the membrane of spatial inhomogeneities (lipid rafts). To get new information on these interactions, electron spin echo (ESE) spectroscopy, which is a pulsed version of electron paramagnetic resonance (EPR), was applied to study 3β-doxyl-5α-cholestane (DCh), a spin-labeled analog of cholesterol, in phospholipid bilayer consisted of equimolecular mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phosphocholine. DCh concentration in the bilayer was between 0.1 mol.% and 4 mol.%. For comparison, a reference system containing a spin-labeled 5-doxyl-stearic acid (5-DSA) instead of DCh was studied as well. The effects of “instantaneous diffusion” in ESE decay and in echo-detected (ED) EPR spectra were explored for both systems. The reference system showed good agreement with the theoretical prediction for the model of spin labels of randomly distributed orientations, but the DCh system demonstrated remarkably smaller effects. The results were explained by assuming that neighboring DCh molecules are oriented in a correlative way. However, this correlation does not imply the formation of clusters of cholesterol molecules, because conventional continuous wave EPR spectra did not show the typical broadening due to aggregation of spin labels and the observed ESE decay was not faster than in the reference system. So the obtained data evidence that cholesterol molecules at low concentrations in biological membranes can interact via large distances of several nanometers which results in their orientational self-ordering.

  19. Communication: Orientational self-ordering of spin-labeled cholesterol analogs in lipid bilayers in diluted conditions

    NASA Astrophysics Data System (ADS)

    Kardash, Maria E.; Dzuba, Sergei A.

    2014-12-01

    Lipid-cholesterol interactions are responsible for different properties of biological membranes including those determining formation in the membrane of spatial inhomogeneities (lipid rafts). To get new information on these interactions, electron spin echo (ESE) spectroscopy, which is a pulsed version of electron paramagnetic resonance (EPR), was applied to study 3β-doxyl-5α-cholestane (DCh), a spin-labeled analog of cholesterol, in phospholipid bilayer consisted of equimolecular mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phosphocholine. DCh concentration in the bilayer was between 0.1 mol.% and 4 mol.%. For comparison, a reference system containing a spin-labeled 5-doxyl-stearic acid (5-DSA) instead of DCh was studied as well. The effects of "instantaneous diffusion" in ESE decay and in echo-detected (ED) EPR spectra were explored for both systems. The reference system showed good agreement with the theoretical prediction for the model of spin labels of randomly distributed orientations, but the DCh system demonstrated remarkably smaller effects. The results were explained by assuming that neighboring DCh molecules are oriented in a correlative way. However, this correlation does not imply the formation of clusters of cholesterol molecules, because conventional continuous wave EPR spectra did not show the typical broadening due to aggregation of spin labels and the observed ESE decay was not faster than in the reference system. So the obtained data evidence that cholesterol molecules at low concentrations in biological membranes can interact via large distances of several nanometers which results in their orientational self-ordering.

  20. Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.

    PubMed

    Chiotellis, Aristeidis; Mu, Linjing; Müller, Adrienne; Selivanova, Svetlana V; Keller, Claudia; Schibli, Roger; Krämer, Stefanie D; Ametamey, Simon M

    2013-01-01

    In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.

  1. Direct comparison of the generalized Visual Analog Scale (gVAS) and general Labeled Magnitude Scale (gLMS).

    PubMed

    Hayes, John E; Allen, Alissa L; Bennett, Samantha M

    2013-04-01

    Hundreds of studies have used the generalized Labeled Magnitude Scale (gLMS) to collect intensity data. Recent work on generalized affective scales like the Labeled Affective Magnitude (LAM) scale and Labeled Hedonic Scale (LHS) suggest a substantial proportion of participants fail to use the entire range of generalized scales, marking only at the adjective labels. This categorical behavior (i.e., clustering) is not limited to affective ratings, as it is well known anecdotally among users of the gLMS. One way to stop this behavior would be to retain a generalized top anchor and cross modal orientation procedure while stripping away the internal adjectives. Several published studies have already used this variant, the generalized Visual Analog Scale (gVAS). Because there are no reports directly comparing the gVAS and gLMS head to head, we did so in two experiments. In Experiment 1, participants (n=87) were randomized to 1 of 3 conditions to test effects of scaling instructions and scale structure. In Experiment 2, participants (n=58) assessed perceived ease of use and resolving power for each scale in a two-session crossover design. gLMS data showed evidence of categorical behavior, while gVAS data did not. Explicitly instructing participants to rate between adjectives did not reduce this behavior. The gLMS was easier to use according to participants, but resulted in non-normal data due to clustering near the adjective labels. gVAS data did not show categorical behavior, as there are no adjectives to cluster around, but the gVAS sacrifices semantic information about the magnitude of response. Regardless of scale type, participants felt the cross-modal orientation procedure helped them understand how to use the scale. Both scales were able to discriminate between sucrose samples in a concentration series. Relative tradeoffs between the two methods suggest the choice of one scale over the other depends on the specific goals and context of the project. PMID:23175601

  2. Binding of labeled thyroxin analog to serum proteins evaluated after radioimmunoassay of free thyroxin

    SciTech Connect

    Arevalo, G.

    1989-03-01

    In ambulatory patients, assay of free thyroxin (FT4) in serum correlates well with thyroid status and with results obtained by equilibrium dialysis. The validity of FT4 results has been questioned mainly in euthyroid patients with altered concentrations of thyroid hormone-binding proteins, as in nonthyroidal illness, hereditary analbuminemia, familial dysalbuminemic hyperthyroxinemia (FDH), and the presence of iodothyronine-binding antibodies. I present here a study of the binding of (/sup 125/I)T4-derivative to serum proteins in the supernate, which is ordinarily discarded after determination of FT4 by one-step radioimmunoassay with dextran-coated charcoal used to separate the free and bound fractions. The results are expressed as a ratio, with results for a normal serum pool as reference. The average ratio was high in hyperthyroid subjects, 1.26 (SD 0.12, n = 25), and in hypoalbuminemia, 1.20 (SD 0.10, n = 15), and low in FDH, 0.62 (SD 0.11, n = 9), and hypothyroid subjects, 0.90 (SD 0.06, n = 20). In normal individuals it was 0.98 (SD 0.05, n = 30). Determination of the analog-binding rate complements the FT4 result and allows for the recognition of cases with abnormal binding by serum proteins, without recourse to other tests recommended for thyroid-function studies.

  3. Divergent role of (68)Ga-labeled somatostatin analogs in the workup of patients with NETs: AIIMS experience.

    PubMed

    Naswa, Niraj; Bal, C S

    2013-01-01

    Neuroendocrine tumors (NETs) encompass a wide range of rare and heterogeneous neoplasms arising from the neural crest. Diagnosis of NETs is conventionally done by a combination of common clinical symptoms and biochemical evidence of hormonal excess, which these tumors are known to secrete. After a diagnosis of NET is established, a search for its localization is carried out using common morphologic imaging methods such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). The main problem with structural imaging is, however, its inability to distinguish between endocrine and exocrine lesions. Functional imaging of NETs started with use of iodine-131-meta-iodobenzylguanidine ((131)I-MIBG) and has come a long way since. From accurate demonstration of functioning tumors to detection of small and occult lesions, functional imaging has penetrated almost every aspect of NET management. Procedures such as (131/123)I-MIBG, (111)In-Octreoscan and others are rapidly giving way to use of PET/CT based on the superior resolution of the system and the availability of target-specific positron-emitting radiotracers. The availability of (68)Ga from generator-based radionuclide systems, namely (68)Ge/(68)Ga generators, opened up a new era of molecular imaging for NETs. A multitude of somatostatin analogs can be easily radioliganded with (68)Ga using heterocyclic macromolecular bifunctional chelating systems for targeted diagnosis of somatostatin receptor-expressing tumors, used most effectively to date for detection of NETs. This chapter focuses on our experience at the All India Institute of Medical Sciences, New Delhi regarding the divergent roles of (68)Ga-labeled somatostatin analogs in the workup of patients with NETs.

  4. Action of troxacitabine on cells transduced with human cytidine deaminase cDNA.

    PubMed

    Boivin, Anne-Julie; Gourdeau, Henriette; Momparler, Richard L

    2004-01-01

    Troxacitabine (beta-L-Dioxolane-cytidine; Troxatyl) is a beta-L-nucleoside analog, which has shown preclinical antitumor activity in human xenograft tumor models and antileukemic response in patients with relapsed myeloid leukemia. Troxacitabine is activated by cellular kinases and incorporated into DNA, inhibiting its replication. In contrast to other cytosine nucleoside analogs, troxacitabine is resistant to inactivation by cytidine deaminase (CD). In this study we have investigated the effects of increased intracellular levels of CD on the antineoplastic action of troxacitabine and the related antileukemic drug, cytosine arabinoside (ARA-C). Retroviral transduction of the human CD gene in A549 lung carcinoma cells (A549-CD cells) markedly increased the expression of this gene. The A549-CD cells were more resistant to the cytotoxic action of ARA-C than the wild type A549 cells as determined by clonogenic assays. In contrast, the CD-transduced cells were as or more sensitive to the cytotoxic action of troxacitabine than the wild type cells. These results suggest that troxacitabine may be an effective antineoplastic agent against tumors with high levels of CD that show drug resistance to cytosine nucleoside analogs.

  5. EPR Studies of Functionally Active, Nitroxide Spin-Labeled Peptide Analogs of the C-terminus of a G-Protein Alpha Subunit

    PubMed Central

    Van Eps, Ned; Anderson, Lori L.; Kisselev, Oleg G.; Baranski, Thomas J.; Hubbell, Wayne L.; Marshall, Garland R.

    2010-01-01

    The C-terminal tail of the transducin alpha subunit, Gtα(340–350), is known to bind and stabilize the active conformation of rhodopsin upon photoactivation (R*). Five spin-labeled analogs of Gtα(340–350) demonstrated native-like activity in their ability to bind and stabilize R*. The spin label 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) was employed at interior sites within the peptide, whereas a Proxyl (3-carboxyl-2,2,5,5-tetramethyl-pyrrolidinyloxy) spin label was employed at the amino terminus of the peptide. Upon binding to R*, the electron paramagnetic resonance spectrum of TOAC343-Gtα(340–350) revealed greater immobilization of the nitroxide when compared to that of the N-terminal modified Proxyl-Gtα(340–350) analog. A double-labeled Proxyl/TOAC348-Gtα(340–350) was examined by DEER spectroscopy to determine the distribution of distances between the two nitroxides in the peptides when in solution and when bound to R*. TOAC and Proxyl spin labels in this GPCR-G-protein α-peptide system provide unique biophysical probes that can be used to explore the structure and conformational changes at the rhodopsin-G-protein interface. PMID:20695526

  6. Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

    PubMed Central

    Rublack, Nico

    2014-01-01

    Summary Over the past 20 years, the generation of functional RNAs by in vitro selection has become a standard technique. Apart from aptamers for simple binding of defined ligands, also RNAs for catalysis of chemical reactions have been selected. In the latter case, a key step often is the conjugation of one of the two reactants to the library, requiring suitable strategies for terminal or internal RNA functionalization. With the aim of selecting a ribozyme for deamination of cytidine, we have set up a selection scheme involving the attachment of the cytidine acting as deamination substrate to the 3'-terminus of the RNAs in the library, and library immobilization. Here, we report the synthesis of a bifunctional cytidine derivative suitable for conjugation to RNA and linkage of the conjugated library to a streptavidine-coated surface. Successful conjugation of the cytidine derivative to the 3'-terminus of a model RNA is demonstrated. PMID:25246949

  7. Uridine and cytidine in the brain: their transport and utilization.

    PubMed

    Cansev, Mehmet

    2006-09-01

    The pyrimidines cytidine (as CTP) and uridine (which is converted to UTP and then CTP) contribute to brain phosphatidylcholine and phosphatidylethanolamine synthesis via the Kennedy pathway. Their uptake into brain from the circulation is initiated by nucleoside transporters located at the blood-brain barrier (BBB), and the rate at which uptake occurs is a major factor determining phosphatide synthesis. Two such transporters have been described: a low-affinity equilibrative system and a high-affinity concentrative system. It is unlikely that the low-affinity transporter contributes to brain uridine or cytidine uptake except when plasma concentrations of these compounds are increased several-fold experimentally. CNT2 proteins, the high-affinity transporters for purines like adenosine as well as for uridine, have been found in cells comprising the BBB of rats. However, to date, no comparable high-affinity carrier protein for cytidine, such as CNT1, has been detected at this location. Thus, uridine may be more available to brain than cytidine and may be the major precursor in brain for both the salvage pathway of pyrimidine nucleotides and the Kennedy pathway of phosphatide synthesis. This recognition may bear on the effects of cytidine or uridine sources in neurodegenerative diseases.

  8. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  9. Selection of the best blood compartment to measure cytidine deaminase activity to stratify for optimal gemcitabine or cytarabine treatment.

    PubMed

    Peters, Godefridus J; Honeywell, Richard J; Maulandi, Marie; Giovannetti, Elisa; Losekoot, Nienke; Etienne-Grimaldi, Marie-Christine; Milano, Gerard; Serdjebi, Cindy; Ciccolini, Joseph

    2014-01-01

    Cytidine deaminase (CDA) plays a crucial role in the degradation of cytidine analogs, such as gemcitabine and cytarabine. Several studies showed that a low CDA activity is associated with more toxicity but a higher efficacy, while a high activity will lead to a lower efficacy but less toxicity. A stratified dosing strategy based on the relative CDA activity would increase efficiency. In order to predict these events, a reliable measurement of CDA with a validated method is crucial. We aimed to determine which phenotype assay would be most suitable; a spectrophotometric assay using cytidine as a substrate, or an HPLC assay using gemcitabine as a substrate. In serum and whole blood of 26 volunteers, both assays showed an excellent correlation (R>0.999), but not in plasma nor in red blood cells. Moreover, there was no difference between males and females. In conclusion, the spectrophotometric assay seems the most simple and cost-effective test. It should be performed in serum, while it should be normalized on protein content as measured by the Bicinchoninic Acid. PMID:24940698

  10. Functional analysis of protein N-myristoylation: Metabolic labeling studies using three oxygen-substituted analogs of myristic acid and cultured mammalian cells provide evidence for protein-sequence-specific incorporation and analog-specific redistribution

    SciTech Connect

    Johnson, D.R.; Heuckeroth, R.O.; Gordon, J.I. ); Cox, A.D.; Solski, P.A.; Buss, J.E. ); Devadas, B.; Adams, S.P.; Leimgruber, R.M. )

    1990-11-01

    Covalent attachment of myristic acid (C14:0) to the NH{sub 2}-terminal glycine residue of a number of cellular, viral, and oncogene-encoded proteins is essential for full expression of their biological function. Substitution of oxygen for methylene groups in this fatty acid does not produce a significant change in chain length or stereochemistry but does result in a reduction in hydrophobicity. These heteroatom-containing analogs serve as alternative substrates for mammalian myristoyl-CoA: protein N-myristoyltransferase and offer the opportunity to explore structure/function relationships of myristate in N-myristoyltransferase proteins. The authors have synthesized three tritiated analogs of myristate with oxygen substituted for methylene groups at C6, C11, and C13. Metabolic labeling studies were performed with these compounds and (i) a murine myocyte cell line (BC{sub 3}H1), (ii) a rat fibroblast cell that produces p60{sup v-src} (3Xsrc), or (iii) NIH 3T3 cells that have been engineered to express a fusion protein consisting of an 11-residue myristoylation signal from the Rasheed sarcoma virus (RaSV) gag protein linked to c-Ha-ras with a Cys {yields} Ser-186 mutation. Two-dimensional gel electrophoresis of membrane and soluble fractions prepared from cell lysates revealed different patterns of incorporation of the analogs into cellular N-myristoyl proteins. The demonstration that these analogs differ in the extent to which they are incorporated and in their ability to cause redistribution of any single protein suggests that they may also have sufficient selectivity to be of potential therapeutic value.

  11. An Enzymatic Assay for High-Throughput Screening of Cytidine-Producing Microbial Strains

    PubMed Central

    Dong, Huina; Liu, Yongfei; Zu, Xin; Li, Ning; Li, Feiran; Zhang, Dawei

    2015-01-01

    Cytidine is an industrially useful precursor for the production of antiviral compounds and a variety of industrial compounds. Interest in the microbial production of cytidine has grown recently and high-throughput screening of cytidine over-producers is an important approach in large-scale industrial production using microorganisms. An enzymatic assay for cytidine was developed combining cytidine deaminase (CDA) and indophenol method. CDA catalyzes the cleavage of cytidine to uridine and NH3, the latter of which can be accurately determined using the indophenol method. The assay was performed in 96-well plates and had a linear detection range of cytidine of 0.058 - 10 mM. This assay was used to determine the amount of cytidine in fermentation flasks and the results were compared with that of High Perfomance Liquid Chromatography (HPLC) method. The detection range of the CDA method is not as wide as that of the HPLC, furthermore the correlation factor of CDA method is not as high as that of HPLC. However, it was suitable for the detection of large numbers of crude samples and was applied to high-throughput screening for high cytidine-producing strains using 96-well deep-hole culture plates. This assay was proved to be simple, accurate, specific and suitable for cytidine detection and high-throughput screening of cytidine-producing strains in large numbers of samples (96 well or more). PMID:25816248

  12. Affinity labeling of (2'-5')-oligoadenylate-activated endonuclease with (/sup 32/P)-2', 5'A and its analogs

    SciTech Connect

    Saarma, M.Y.; Gordon, J.; Minks, M.A.

    1985-09-01

    This paper examines the role interferons play in the origin of the antiviral state of cells and in the inhibition of virus reproduction. Treatment of cells with interferon induces the synthesis of a whole series of proteins. For affinity labeling of 2', 5'A-dependent endoribonuclease, the authors synthesized P-32 labeled 2; 5'A by two methods. Results of the investigation show that the most probable candidate for 2', 5'A-dependent endoribonuclease is the protein with molecular weight 80,000. The role of the other two proteins is still unknown.

  13. Stable isotope-labeled vitamin D, metabolites and chemical analogs: Synthesis and use in mass spectrometric studies

    SciTech Connect

    Coldwell, R.D.; Trafford, D.J.; Varley, M.J.; Kirk, D.N.; Makin, H.L. )

    1990-10-01

    Methods for the measurement of vitamin D and its metabolites using stable isotope-labeled internal standards and mass spectrometry are reviewed. The synthesis of both labeled and unlabeled standards is illustrated, and details of the synthesis of (26,26,27,27,27(-2)H5)-25,26-dihydroxyvitamin D3 and (28,28,28(-2)H3)-24,25-dihydroxyvitamin D2 are given. The use of in vitro biologic systems for the production of further metabolites of deuterated 25-hydroxyvitamin D3 is discussed. Use of deuterated 25-hydroxydihydrotachysterol3 as a substrate in the isolated perfused rat kidney has provided valuable data for the assignment of structure to a number of metabolites of 25-hydroxydihydrotachysterol3 formed in this system. 51 refs.

  14. Building a stable RNA U-turn with a protonated cytidine.

    PubMed

    Gottstein-Schmidtke, Sina R; Duchardt-Ferner, Elke; Groher, Florian; Weigand, Julia E; Gottstein, Daniel; Suess, Beatrix; Wöhnert, Jens

    2014-08-01

    The U-turn is a classical three-dimensional RNA folding motif first identified in the anticodon and T-loops of tRNAs. It also occurs frequently as a building block in other functional RNA structures in many different sequence and structural contexts. U-turns induce sharp changes in the direction of the RNA backbone and often conform to the 3-nt consensus sequence 5'-UNR-3' (N = any nucleotide, R = purine). The canonical U-turn motif is stabilized by a hydrogen bond between the N3 imino group of the U residue and the 3' phosphate group of the R residue as well as a hydrogen bond between the 2'-hydroxyl group of the uridine and the N7 nitrogen of the R residue. Here, we demonstrate that a protonated cytidine can functionally and structurally replace the uridine at the first position of the canonical U-turn motif in the apical loop of the neomycin riboswitch. Using NMR spectroscopy, we directly show that the N3 imino group of the protonated cytidine forms a hydrogen bond with the backbone phosphate 3' from the third nucleotide of the U-turn analogously to the imino group of the uridine in the canonical motif. In addition, we compare the stability of the hydrogen bonds in the mutant U-turn motif to the wild type and describe the NMR signature of the C+-phosphate interaction. Our results have implications for the prediction of RNA structural motifs and suggest simple approaches for the experimental identification of hydrogen bonds between protonated C-imino groups and the phosphate backbone.

  15. Radiopharmacological characterization of ⁶⁴Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma.

    PubMed

    Gao, Feng; Sihver, Wiebke; Jurischka, Christoph; Bergmann, Ralf; Haase-Kohn, Cathleen; Mosch, Birgit; Steinbach, Jörg; Carta, Davide; Bolzati, Cristina; Calderan, Andrea; Pietzsch, Jens; Pietzsch, Hans-Jürgen

    2016-03-01

    The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. α-Melanocyte stimulating hormone (α-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear α-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with εAhx-β-Ala linker, and a cyclic α-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with εAhx-β-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-εAhx-β-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear α-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging.

  16. Synthesis, uptake mechanism characterization and biological evaluation of 18F labeled fluoroalkyl phenylalanine analogs as potential PET imaging agents

    PubMed Central

    Wang, Limin; Qu, Wenchao; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2010-01-01

    Introduction Amino acids based tracers represent a promising class of tumor metabolic imaging agents with successful clinical applications. Two new phenylalanine derivatives, p-(2-[18F]fluoroethyl)-L-phenylalanine (FEP, [18F]2) and p-(3-[18F]fluoropropyl)-L-phenylalanine (FPP, [18F]3) were synthesized and evaluated in comparison to clinically utilized O-(2-[18F]fluoroethyl)-L-tyrosine (FET, [18F]1). Methods FEP ([18F]2) and FPP ([18F]3) were successfully synthesized by a rapid and efficient two-step nucleophilic fluorination of tosylate precursors and deprotection reaction. In vitro cell uptake studies were carried out in 9L glioma cells. In vivo studies, 9L tumor xenografts were implanted in Fisher 344 rats. Results FEP ([18F]2) and FPP ([18F]3) could be efficiently labeled within 90 min with good enantiomeric purity (>95%), good yield (11–37%) and high specific activity (21–69 GBq/μmol). Cell uptake studies showed FEP had higher uptake than FPP as well as reference ligand FET ([18F]1). Uptake mechanism studies suggested that FEP is a selective substrate for system L and prefers its subtype LAT1. In vivo biodistribution studies demonstrated FEP had specific accumulation in tumor cells and tumor to background ratio reached 1.45 at 60 min. Small animal PET imaging studies showed FEP was comparable to FET for imaging rats bearing 9L tumor model. FEP had high uptake in 9L tumor compared to surrounding tissue and was quickly excreted through urinary tract. Conclusion Biological evaluations indicate that FEP ([18F]2) is a potential useful tracer for tumor imaging with PET. PMID:21220129

  17. Biological function of activation-induced cytidine deaminase (AID).

    PubMed

    Kumar, Ritu; DiMenna, Lauren J; Chaudhuri, Jayanta; Evans, Todd

    2014-01-01

    Activation-induced Cytidine Deaminase (AID) is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  18. Cytidine derivatives as IspF inhibitors of Burkolderia pseudomallei

    PubMed Central

    Zhang, Zheng; Jakkaraju, Sriram; Blain, Joy; Gogol, Kenneth; Zhao, Lei; Hartley, Robert C.; Karlsson, Courtney A.; Staker, Bart L.; Stewart, Lance J.; Myler, Peter J.; Clare, Michael; Begley, Darren W.; Horn, James R.; Hagen, Timothy J

    2013-01-01

    Published biological data suggest that the methyl erythritol phosphate (MEP) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. One highly conserved enzyme in the MEP pathway is 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF). Fragment-bound complexes of IspF from Burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fragment binders. Testing by surface plasmon resonance (SPR) found one molecule in the series to possess binding affinity equal to that of cytidine diphosphate, despite lacking any metal-coordinating phosphate groups. Close inspection of the SPR data suggest different binding stoichiometries between IspF and test compounds. Crystallographic analysis shows important variations between the binding mode of one synthesized compound and the pose of the bound fragment from which it was designed. The binding modes of these molecules add to our structural knowledge base for IspF and suggest future refinements in this compound series. PMID:24157367

  19. Specific labeling and permanent activation of the retinal rod cGMP-activated channel by the photoaffinity analog 8-p-azidophenacylthio-cGMP.

    PubMed Central

    Brown, R L; Gerber, W V; Karpen, J W

    1993-01-01

    Cyclic nucleotide-gated ion channels play a key role in visual excitation and a variety of other signaling pathways. The photoaffinity probe 8-p-azidophenacylthio-cGMP (APT-cGMP) has been developed for structural and functional studies of the cGMP-activated channel of retinal rod outer segments. Using this analog, we have demonstrated both specific labeling of the channel in a partially purified biochemical preparation from bovine rod outer segments and permanent activation of the channel current in excised membrane patches from salamander outer segments. After UV illumination, a 32P-labeled version of APT-cGMP was shown by SDS/PAGE and autoradiography to be covalently attached to the 63-kDa channel subunit. This incorporation was significantly reduced by 8-Br-cGMP but was not reduced by 5'-GMP. In patch-clamp experiments APT-cGMP was a potent activator of the channel; APT-cGMP typically opened half of the channels in a patch at a 10-fold lower concentration than cGMP. Exposure of membrane patches to UV light in the presence of APT-cGMP resulted in a persistent current observed in the absence of bath-applied nucleotide. This current increased with repeated exposure of the patch to both UV light and fresh APT-cGMP, approaching the maximum current originally evoked by saturating (500 microM) cGMP. At this point, addition of 500 microM cGMP caused a negligible increase in current. The persistent current had several other properties expected of current through cGMP-activated channels: it was outwardly rectifying; outward current was blocked > 90% by 2 mM internal Mg2+, whereas inward current was blocked much less efficiently; a low concentration of cGMP caused a larger increase in current atop a half-maximal persistent current than it did originally. We conclude that the persistent current was caused by the covalent tethering of cGMP moieties to channel binding sites, resulting in irreversible channel activation. APT-cGMP should prove useful for further studies of

  20. Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

    PubMed Central

    Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

    2014-01-01

    The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

  1. A single-label phenylpyrrolocytidine provides a molecular beacon-like response reporting HIV-1 RT RNase H activity.

    PubMed

    Wahba, Alexander S; Esmaeili, Abbasali; Damha, Masad J; Hudson, Robert H E

    2010-01-01

    6-Phenylpyrrolocytidine (PhpC), a structurally conservative and highly fluorescent cytidine analog, was incorporated into oligoribonucleotides. The PhpC-containing RNA formed native-like duplex structures with complementary DNA or RNA. The PhpC-modification was found to act as a sensitive reporter group being non-disruptive to structure and the enzymatic activity of RNase H. A RNA/DNA hybrid possessing a single PhpC insert was an excellent substrate for HIV-1 RT Ribonuclease H and rapidly reported cleavage of the RNA strand with a 14-fold increase in fluorescence intensity. The PhpC-based assay for RNase H was superior to the traditional molecular beacon approach in terms of responsiveness, rapidity and ease (single label versus dual). Furthermore, the PhpC-based assay is amenable to high-throughput microplate assay format and may form the basis for a new screen for inhibitors of HIV-RT RNase H.

  2. Ubiquitination and filamentous structure of cytidine triphosphate synthase

    PubMed Central

    Pai, Li-Mei; Wang, Pei-Yu; Lin, Wei-Cheng; Chakraborty, Archan; Yeh, Chau-Ting; Lin, Yu-Hung

    2016-01-01

    ABSTRACT Living organisms respond to nutrient availability by regulating the activity of metabolic enzymes. Therefore, the reversible post-translational modification of an enzyme is a common regulatory mechanism for energy conservation. Recently, cytidine-5′-triphosphate (CTP) synthase was discovered to form a filamentous structure that is evolutionarily conserved from flies to humans. Interestingly, induction of the formation of CTP synthase filament is responsive to starvation or glutamine depletion. However, the biological roles of this structure remain elusive. We have recently shown that ubiquitination regulates CTP synthase activity by promoting filament formation in Drosophila ovaries during endocycles. Intriguingly, although the ubiquitination process was required for filament formation induced by glutamine depletion, CTP synthase ubiquitination was found to be inversely correlated with filament formation in Drosophila and human cell lines. In this article, we discuss the putative dual roles of ubiquitination, as well as its physiological implications, in the regulation of CTP synthase structure. PMID:27116391

  3. Photoaffinity Labeling of Developing Jojoba Seed Microsomal Membranes with a Photoreactive Analog of Acyl-Coenzyme A (Acyl-CoA) (Identification of a Putative Acyl-CoA:Fatty Alcohol Acyltransferase.

    PubMed Central

    Shockey, J. M.; Rajasekharan, R.; Kemp, J. D.

    1995-01-01

    Jojoba (Simmondsia chinensis, Link) is the only plant known that synthesizes liquid wax. The final step in liquid wax biosynthesis is catalyzed by an integral membrane enzyme, fatty acyl-coenzyme A (CoA):fatty alcohol acyltransferase, which transfers an acyl chain from acyl-CoA to a fatty alcohol to form the wax ester. To purify the acyltransferase, we have labeled the enzyme with a radioiodinated, photoreactive analog of acyl-CoA, 12-[N-(4-azidosalicyl)amino] dodecanoyl-CoA (ASD-CoA). This molecule acts as an inhibitor of acyltransferase activity in the dark and as an irreversible inhibitor upon exposure to ultraviolet light. Oleoyl-CoA protects enzymatic activity in a concentration-dependent manner. Photolysis of microsomal membranes with labeled ASD-CoA resulted in strong labeling of two polypeptides of 57 and 52 kD. Increasing concentrations of oleoyl-CoA reduced the labeling of the 57-kD polypeptide dramatically, whereas the labeling of the 52-kD polypeptide was much less responsive to oleoyl-CoA. Also, unlike the other polypeptide, the labeling of the 57-kD polypeptide was enhanced considerably when photolyzed in the presence of dodecanol. These results suggest that a 57-kD polypeptide from jojoba microsomes may be the acyl-CoA:fatty alcohol acyltransferase. PMID:12228351

  4. Photoaffinity Labeling of Developing Jojoba Seed Microsomal Membranes with a Photoreactive Analog of Acyl-Coenzyme A (Acyl-CoA) (Identification of a Putative Acyl-CoA:Fatty Alcohol Acyltransferase.

    PubMed

    Shockey, J. M.; Rajasekharan, R.; Kemp, J. D.

    1995-01-01

    Jojoba (Simmondsia chinensis, Link) is the only plant known that synthesizes liquid wax. The final step in liquid wax biosynthesis is catalyzed by an integral membrane enzyme, fatty acyl-coenzyme A (CoA):fatty alcohol acyltransferase, which transfers an acyl chain from acyl-CoA to a fatty alcohol to form the wax ester. To purify the acyltransferase, we have labeled the enzyme with a radioiodinated, photoreactive analog of acyl-CoA, 12-[N-(4-azidosalicyl)amino] dodecanoyl-CoA (ASD-CoA). This molecule acts as an inhibitor of acyltransferase activity in the dark and as an irreversible inhibitor upon exposure to ultraviolet light. Oleoyl-CoA protects enzymatic activity in a concentration-dependent manner. Photolysis of microsomal membranes with labeled ASD-CoA resulted in strong labeling of two polypeptides of 57 and 52 kD. Increasing concentrations of oleoyl-CoA reduced the labeling of the 57-kD polypeptide dramatically, whereas the labeling of the 52-kD polypeptide was much less responsive to oleoyl-CoA. Also, unlike the other polypeptide, the labeling of the 57-kD polypeptide was enhanced considerably when photolyzed in the presence of dodecanol. These results suggest that a 57-kD polypeptide from jojoba microsomes may be the acyl-CoA:fatty alcohol acyltransferase.

  5. A Cytidine Deaminase Edits C to U in Transfer RNAs in Archaea

    PubMed Central

    Randau, Lennart; Stanley, Bradford J.; Kohlway, Andrew; Mechta, Sarah; Xiong, Yong; Söll, Dieter

    2010-01-01

    All canonical transfer RNAs (tRNAs) have a uridine at position 8, involved in maintaining tRNA tertiary structure. However, the hyperthermophilic archaeon Methanopyrus kandleri harbors 30 (out of 34) tRNA genes with cytidine at position 8. Here, we demonstrate C-to-U editing at this location in the tRNA’s tertiary core, and present the crystal structure of a tRNA-specific cytidine deaminase, CDAT8, which has the cytidine deaminase domain linked to a tRNA-binding THUMP domain. CDAT8 is specific for C deamination at position 8, requires only the acceptor stem hairpin for activity, and belongs to a unique family within the “cytidine deaminase–like” superfamily. The presence of this C-to-U editing enzyme guarantees the proper folding and functionality of all M. kandleri tRNAs. PMID:19407206

  6. The Effect of Cytidine on the Structure and Function of an RNA Ligase Ribozyme

    NASA Technical Reports Server (NTRS)

    Rogers, Jeff; Joyce, Gerald F.

    2001-01-01

    A cytidine-free ribozyme with RNA ligase activity was obtained by in vitro evolution, starting from a pool of random- sequence RNAs that contained only guanosine, adenosine, and uridine. This ribozyme contains 74 nt and catalyzes formation of a 3',5' -phosphodiester linkage with a catalytic rate of 0.016/min. The RNA adopts a simple secondary structure based on a three-way junction motif, with ligation occurring at the end of a stem region located several nucleotides away from the junction. Cytidine was introduced to the cytidine-free ribozyme in a combinatorial fashion and additional rounds of in vitro evolution were carried out to allow the molecule to adapt to this added component. The resulting cytidine-containing ribozyme formed a 3',5' linkage with a catalytic rate of 0.32/min. The improved rate of the cytidine-containing ribozyme was the result of 12 mutations, including seven added cytidines, that remodeled the internal bulge loops located adjacent to the three-way junction and stabilized the peripheral stem regions.

  7. Cytidine deaminase activity in synovial fluid of patients with rheumatoid arthritis: relation to lactoferrin, acidosis, and cartilage proteoglycan release.

    PubMed Central

    Månsson, B; Geborek, P; Saxne, T; Björnsson, S

    1990-01-01

    It is claimed that cytidine deaminase activity reflects local granulocyte turnover or activity in the synovial fluid of patients with rheumatoid arthritis, but cytidine deaminase is not a granulocyte specific enzyme. Lactoferrin is a granulocyte specific protein that is released from the secondary granulae during activation. We measured cytidine deaminase activity and lactoferrin concentrations in 33 rheumatic synovial fluid samples. Cytidine deaminase activity and lactoferrin concentrations correlated closely, indicating that both analyses reflect similar events in the joint-that is, result in their release from granulocytes. Cytidine deaminase activity and granulocyte concentrations correlated less closely, suggesting that there are additional factors besides the cell number which contribute to this release. Joint acidosis may be one such factor, as pH and cytidine deaminase activity correlated inversely. There was no association with synovial fluid proteoglycan concentrations, a marker of cartilage degradation. PMID:2396864

  8. The ONIOM molecular dynamics method for biochemical applications: cytidine deaminase

    SciTech Connect

    Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

    2007-03-22

    Abstract We derived and implemented the ONIOM-molecular dynamics (MD) method for biochemical applications. The implementation allows the characterization of the functions of the real enzymes taking account of their thermal motion. In this method, the direct MD is performed by calculating the ONIOM energy and gradients of the system on the fly. We describe the first application of this ONOM-MD method to cytidine deaminase. The environmental effects on the substrate in the active site are examined. The ONIOM-MD simulations show that the product uridine is strongly perturbed by the thermal motion of the environment and dissociates easily from the active site. TM and MA were supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. MD was supported by the Division of Chemical Sciences, Office of Basic Energy Sciences, and by the Office of Biological and Environmental Research of the U.S. Department of Energy DOE. Battelle operates Pacific Northwest National Laboratory for DOE.

  9. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  10. Site-specific fluorescence labelling of RNA using bio-orthogonal reaction of trans-cyclooctene and tetrazine.

    PubMed

    Asare-Okai, P N; Agustin, E; Fabris, D; Royzen, M

    2014-07-25

    This communication describes a general approach for site-specific fluorescence labelling of RNA using a cytidine triphosphate (CTP) analogue derivatized with a trans-cyclooctene group. The analogue was efficiently incorporated into a model RNA strand using in vitro transcription. Bio-orthogonal reaction with fluorescein-labelled tetrazine was utilized to fluorescently tag the synthetic RNA strand.

  11. [NIR-SERS Spectra Detection of Cytidine on Nano-Silver Films].

    PubMed

    Zhang, De-qing; Liu, Ren-ming; Zhang, Guo-qiang; Zhang, Yan; Xiong, Yang; Zhang, Chuan-yun; Li, Lun; Si, Min-zhen

    2016-03-01

    The polyvinyl alcohol (PVA) protected silver glass-like nanostructure (PVA-Ag-GNS) with high surface-enhanced Raman scattering (SERS) activity was prepared and employed to detect the near-infrared surface enhanced Raman scattering (NIR-SERS) spectra of cytidine aqueous solution (10(-2)-10(-8) mol x L(-1)). In the work, the near-infrared laser beam (785 nm) was used as the excitation light source. The experiment results show that high-quality NIR-SERS spectra were obtained in the ranges of 300 to 2 000 cm(-1) and the detection limit of cytidine aqueous solution was down to 10(-7) mol x L(-1). Meanwhile, the PVA-Ag-GNS shows a high enhancement factor (EF) of -10(8). In order to test the optical reproducibility of PVA-Ag-GNS, ten samples of cytidine aqueous solution (10(-2)-10(-5) mol x L(-1)) had been dropped onto the surface of PVA-Ag-GNS respectively. Meanwhile, these samples were measured by the portable Raman spectrometer. As a result, the PVA-Ag-GNS demonstrated good optical reproducibility in the detection of cytidine aqueous solution. In addition, to explain the reason of enhancement effect, the ultraviolet-visible (UV-Vis) extinction spectrum and scanning electron microscope (SEM) of cytidine molecules adsorbed on the surface of PVA-Ag-GNS were measured. There is plasmon resonance band at 800 nm in the UV-Vis extinction Spectrum of the compound system. Therefore, when the near-infrared laser beam (785 nm) was used as excitation light source, the compound system may produce strongly surface plasmon resonance (SPR). According to the SEM of PVA-Ag-GNS, there are much interstitial between the silver nanoparticles. So NIR-SERS is mainly attributed to electromagnetic (EM) fields associated with strong surface plasmon resonance. At last, the geometry optimization and pre-Raman spectrum of cytidine for the ground states were performed with DFT, B3LYP functional and the 6-311G basis set, and the near-infrared laser with wavelength of 785 nm was employed in the pre

  12. [NIR-SERS Spectra Detection of Cytidine on Nano-Silver Films].

    PubMed

    Zhang, De-qing; Liu, Ren-ming; Zhang, Guo-qiang; Zhang, Yan; Xiong, Yang; Zhang, Chuan-yun; Li, Lun; Si, Min-zhen

    2016-03-01

    The polyvinyl alcohol (PVA) protected silver glass-like nanostructure (PVA-Ag-GNS) with high surface-enhanced Raman scattering (SERS) activity was prepared and employed to detect the near-infrared surface enhanced Raman scattering (NIR-SERS) spectra of cytidine aqueous solution (10(-2)-10(-8) mol x L(-1)). In the work, the near-infrared laser beam (785 nm) was used as the excitation light source. The experiment results show that high-quality NIR-SERS spectra were obtained in the ranges of 300 to 2 000 cm(-1) and the detection limit of cytidine aqueous solution was down to 10(-7) mol x L(-1). Meanwhile, the PVA-Ag-GNS shows a high enhancement factor (EF) of -10(8). In order to test the optical reproducibility of PVA-Ag-GNS, ten samples of cytidine aqueous solution (10(-2)-10(-5) mol x L(-1)) had been dropped onto the surface of PVA-Ag-GNS respectively. Meanwhile, these samples were measured by the portable Raman spectrometer. As a result, the PVA-Ag-GNS demonstrated good optical reproducibility in the detection of cytidine aqueous solution. In addition, to explain the reason of enhancement effect, the ultraviolet-visible (UV-Vis) extinction spectrum and scanning electron microscope (SEM) of cytidine molecules adsorbed on the surface of PVA-Ag-GNS were measured. There is plasmon resonance band at 800 nm in the UV-Vis extinction Spectrum of the compound system. Therefore, when the near-infrared laser beam (785 nm) was used as excitation light source, the compound system may produce strongly surface plasmon resonance (SPR). According to the SEM of PVA-Ag-GNS, there are much interstitial between the silver nanoparticles. So NIR-SERS is mainly attributed to electromagnetic (EM) fields associated with strong surface plasmon resonance. At last, the geometry optimization and pre-Raman spectrum of cytidine for the ground states were performed with DFT, B3LYP functional and the 6-311G basis set, and the near-infrared laser with wavelength of 785 nm was employed in the pre

  13. Photoactivable analogs for labeling 25-hydroxyvitamin D3 serum binding protein and for 1,25-dihydroxyvitamin D3 intestinal receptor protein

    NASA Technical Reports Server (NTRS)

    Kutner, A.; Link, R. P.; Schnoes, H. K.; DeLuca, H. F.

    1986-01-01

    3-Azidobenzoates and 3-azidonitrobenzoates of 25-hydroxyvitamin D3 as well as 3-deoxy-3-azido-25-hydroxyvitamin D3 and 3-deoxy-3-azido-1,25-dihydroxyvitamin D3 were prepared as photoaffinity labels for vitamin D serum binding protein and 1,25-dihydroxyvitamin D3 intestinal receptor protein. The compounds prepared were easily activated by short- or long-wavelength uv light, as monitored by uv and ir spectrometry. The efficacy of the compounds to compete with 25-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 for the binding site of serum binding protein and receptor, respectively, was studied to evaluate the vitamin D label with the highest affinity for the protein. The presence of an azidobenzoate or azidonitrobenzoate substituent at the C-3 position of 25-OH-D3 significantly decreased (10(4)- to 10(6)-fold) the binding activity. However, the labels containing the azido substituent attached directly to the vitamin D skeleton at the C-3 position showed a high affinity, only 20- to 150-fold lower than that of the parent compounds with their respective proteins. Therefore, 3-deoxy-3-azidovitamins present potential ligands for photolabeling of vitamin D proteins and for studying the structures of the protein active sites.

  14. Structural and biological function of NYD-SP15 as a new member of cytidine deaminases.

    PubMed

    Xu, Yidan; Li, Lei; Li, Jianmin; Liu, Qinghuai

    2016-05-25

    Recent studies were mainly focus on the cytidine deaminase family genes, which contained a lot of members that varied on the function of catalytic deamination in RNA or DNA and were involved in the process of growth maintenance, host immunity, retroviral infection, tumorigenesis, and drug resistance with a feature of C-U deamination. In this study, we identified a new member of cytidine deaminase family, NYD-SP15. Previous work showed that the deduced structure of the protein contained two dCMP_cyt_deam domains, which were involved in zinc ion binding. NYD-SP15 was expressed variably in a wide range of tissues, indicating its worthy biological function and creative significances. Sequence analysis, RT-PCR, western blot, flow cytometry, direct-site mutation and GST pull-down assay were performed to analyze the construction and function of NYD-SP15. The results in our studies showed that NYD-SP15 was closely related to deoxycytidylate deaminase and cytidine deaminase, with authentic cytidine deaminase activity in vivo and vitro as well as homo dimerization effects. NYD-SP15 contained nuclear localization sequence (NLS) and nuclear export-signal (NES) and could dynamically shuttle between the nucleus and cytoplasm. Furthermore, NYD-SP15 gene over-expression reduced the cells growth and blocked G1 to S phase, which implied a potential inhibition effect on cell growth. PMID:26945630

  15. A terbium(III)-organic framework for highly selective sensing of cytidine triphosphate.

    PubMed

    Zhao, Xi Juan; He, Rong Xing; Li, Yuan Fang

    2012-11-21

    Highly selective sensing of cytidine triphosphate (CTP) against other triphosphate nucleosides including ATP, GTP and UTP is successfully achieved with a luminescent terbium(III)-organic framework (TbOF) of [Tb(2)(2,3-pzdc)(2)(ox)(H(2)O)(2)](n) (2,3-pzdc(2-) = 2,3-pyrazinedicarboxylate, ox(2-) = oxalate).

  16. Effect of 15 N Labeled Riparian Fertilization And Salmon Carcass Analog Addition On Food Web Dynamics And Productivity In Four Idaho Streams

    NASA Astrophysics Data System (ADS)

    Rugenski, A. T.; Kohler, A.; Minshall, G. W.; Danehy, R. J.; Taki, D.

    2005-05-01

    Nutrient budgets of stream/riparian ecosystems in the Intermountain West have been depleted through declining salmon populations and certain anthropogenic disturbances (e.g. forestry practices). We measured stream food web responses to a riparian fertilization and an in-stream carcass analog addition in 4 Idaho streams with a 15 N tracer. Aerial application of fertilizer pellets to light (224 kg/ha) and heavy (448 kg/ha) treatment sections of 2 streams and carcass analog additions to 2 others were completed in autumn. Periphyton response was measured through chlorophyll a, nutrient diffusing substrata, and stable isotope analyses. Macroinvertebrates were analyzed for abundance, biomass, community structure, and stable isotope composition. Also, willow (Salix) breakdown rates were determined. Pre-treatment chlorophyll a values showed no significant difference between treatment and reference reaches. Post-treatment results showed significantly higher chlorophyll a and δ 15 N values in treatment reaches compared to reference reaches. Macroinvertebrate abundance, richness, biomass, and δ 15 N values also increased in treated reaches. No significant differences were detected in leaf breakdown rates between reaches. Riparian fertilization effects were longer lasting than the in-stream treatment. These results suggest that nutrient addition to streams and riparian areas can be used as a management tool to increase stream productivity where nutrients are limiting.

  17. Convenient preparation of deuterium-labeled analogs of peptides containing N-substituted glycines for a stable isotope dilution LC-MS quantitative analysis.

    PubMed

    Bąchor, Remigiusz; Dębowski, Dawid; Łęgowska, Anna; Stefanowicz, Piotr; Rolka, Krzysztof; Szewczuk, Zbigniew

    2015-11-01

    N-substituted glycines constitute mimics of natural amino acids that are of great interest in the peptide-based drug development. Peptoids-oligo(N-substituted glycines) have been recently demonstrated to be highly active peptidomimetics in biological systems, resistant to proteolytic degradation. We developed a method of the deuterium labeling of peptidomimetics containing N-substituted glycine residues via H/D exchange of their α-carbon hydrogen atoms. The labeling was shown to be easy, inexpensive, and without the use of derivatization reagents or the need for a further purification. The deuterons introduced at the α-carbon atoms do not undergo a back exchange under acidic conditions during liquid chromatography mass spectrometry (LC-MS) analysis. The LC-MS analysis of a mixture of isotopologues revealed a co-elution of deuterated and nondeuterated forms of the peptidomimetics, which may be useful in the quantitative isotope dilution analysis of peptoids and other derivatives of N-substituted glycines. PMID:26415697

  18. Synthesis and biological evaluation of fluorine-18 labeled RS-15385-197 analogs: Potent and selective alpha-2 adrenergic receptor radioligands for PET

    SciTech Connect

    Enas, J.D.; VanBrocklin, H.F.; Budinger, T.F.; Clark, R.D.

    1997-12-31

    Aberrations in the {alpha}{sub 2}-adrenergic receptor system have been implicated in a number of disease states including hypertension, drug abuse, depression, and neurodegenerative disorders such as Alzheimer`s Disease. RS-15385-FP (1) and RS-15385-FPh (2) are analogs of the {alpha}{sub 2}-adrenergic receptor antagonist RS- 15385-197 which display a high receptor binding affinity (K{sub i} = 0.2 and 0.5 nM, respectively) as well as a high degree of {alpha}{sub 2}/{alpha}{sub 1} selectivity (7000:1 and 2000:1, respectively). We synthesized [F-18]-2 was synthesized by fluoro-for-nitro exchange on the corresponding nitrophenyl derivative which was produced in two steps from the hydroxypropyl sulfonamide. In vivo distribution studies in rats and PET studies in monkeys demonstrate uptake in {alpha}{sub 2}-adrenergic receptor rich regions of the brain, particularly the locus coeruleus.

  19. Comparison of the Pharmacokinetics of Different Analogs of 11C-Labeled TZTP for Imaging Muscarinic M2 Receptors with PET

    PubMed Central

    Reid, Alicia E.; Ding, Yu-Shin; Eckelman, William C.; Logan, Jean; Alexoff, David; Shea, Colleen; Xu, Youwen; Fowler, Joanna S.

    2011-01-01

    Introduction The only radiotracer available for the selective imaging of muscarinic M2 receptors in vivo is 3-(3-{3-[18F]fluoropropyl)thio}-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine) ([18F]FP-TZTP). We have prepared and labeled FP-TZTP and two other TZTP derivatives with 11C at the methylpyridine moiety to explore the potential of using C-11 labeled FP-TZTP for PET imaging of M2 receptors and to compare the effect of small structural changes on tracer pharmacokinetics (PK) in brain and peripheral organs. Methods 11C radiolabeled [FP-TZTP, 3], 3-(3-propyl)-TZTP [P-TZTP, 6], 3,3,3-(3-(3-trifluoropropyl)-TZTP [F3P-TZTP, 10] were prepared and log D, plasma protein binding (PPB), affinity constants, time-activity curves (TACs), area under the curve (AUC) for arterial plasma, distribution volumes (DV) and pharmacological blockade in baboons were compared. Results Values for log D, PPB and affinity constants were similar for 3, 6 and 10. The fraction of parent radiotracer in the plasma was higher and the AUC lower for 10 than for 3 and 6. TACs for brain regions were similar for 3 and 6, which showed PK similar to the F-18 tracer, while 10 showed slower uptake and little clearance over 90 min. DV’s for 3 and 6 were similar to the F-18 tracer but higher for 10. Uptake of the three tracers was significantly reduced by coinjection of unlabeled 3 and 6. Conclusion Small structural variations on the TZTP structure greatly altered the PK in brain and behavior in blood with little change in the log D, PPB or affinity. The study suggests that 11C radiolabeled 3 will be a suitable alternative to [18F]FP-TZTP for translational studies in humans. PMID:18355684

  20. Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET

    PubMed Central

    Kim, Sung Won; Hooker, Jacob M.; Otto, Nicola; Win, Khaing; Muench, Lisa; Shea, Colleen; Carter, Pauline; King, Payton; Reid, Alicia E.; Volkow, Nora D.; Fowler, Joanna S.

    2013-01-01

    The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profile. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using 11CO2 and the appropriate Grignard reagents. [11C]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity was the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low (<0.006%ID/cc, BA>VPA>PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [11C]BA showed relatively high uptake in spleen and pancreas whereas [11C]PBA showed high uptake in liver and heart. Notably, [11C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of relevance in understanding their therapeutic and side effect profile including their teratogenic effects. PMID:23906667

  1. Lipid Chain-Length Dependence for Incorporation of Alamethicin in Membranes: Electron Paramagnetic Resonance Studies on TOAC-Spin Labeled Analogs

    PubMed Central

    Marsh, Derek; Jost, Micha; Peggion, Cristina; Toniolo, Claudio

    2007-01-01

    Alamethicin is a 19-residue hydrophobic peptide, which is extended by a C-terminal phenylalaninol but lacks residues that might anchor the ends of the peptide at the lipid-water interface. Voltage-dependent ion channels formed by alamethicin depend strongly in their characteristics on chain length of the host lipid membranes. EPR spectroscopy is used to investigate the dependence on lipid chain length of the incorporation of spin-labeled alamethicin in phosphatidylcholine bilayer membranes. The spin-label amino acid TOAC is substituted at residue positions n = 1, 8, or 16 in the sequence of alamethicin F50/5 [TOACn, Glu(OMe)7,18,19]. Polarity-dependent isotropic hyperfine couplings of the three TOAC derivatives indicate that alamethicin assumes approximately the same location, relative to the membrane midplane, in fluid diCNPtdCho bilayers with chain lengths ranging from N = 10–18. Residue TOAC8 is situated closest to the bilayer midplane, whereas TOAC16 is located farther from the midplane in the hydrophobic core of the opposing lipid leaflet, and TOAC1 remains in the lipid polar headgroup region. Orientational order parameters indicate that the tilt of alamethicin relative to the membrane normal is relatively small, even at high temperatures in the fluid phase, and increases rather slowly with decreasing chain length (from 13° to 23° for N = 18 and 10, respectively, at 75°C). This is insufficient for alamethicin to achieve hydrophobic matching. Alamethicin differs in its mode of incorporation from other helical peptides for which transmembrane orientation has been determined as a function of lipid chain length. PMID:17351010

  2. Lipid chain-length dependence for incorporation of alamethicin in membranes: electron paramagnetic resonance studies on TOAC-spin labeled analogs.

    PubMed

    Marsh, Derek; Jost, Micha; Peggion, Cristina; Toniolo, Claudio

    2007-06-01

    Alamethicin is a 19-residue hydrophobic peptide, which is extended by a C-terminal phenylalaninol but lacks residues that might anchor the ends of the peptide at the lipid-water interface. Voltage-dependent ion channels formed by alamethicin depend strongly in their characteristics on chain length of the host lipid membranes. EPR spectroscopy is used to investigate the dependence on lipid chain length of the incorporation of spin-labeled alamethicin in phosphatidylcholine bilayer membranes. The spin-label amino acid TOAC is substituted at residue positions n = 1, 8, or 16 in the sequence of alamethicin F50/5 [TOAC(n), Glu(OMe)(7,18,19)]. Polarity-dependent isotropic hyperfine couplings of the three TOAC derivatives indicate that alamethicin assumes approximately the same location, relative to the membrane midplane, in fluid diC(N)PtdCho bilayers with chain lengths ranging from N = 10-18. Residue TOAC(8) is situated closest to the bilayer midplane, whereas TOAC(16) is located farther from the midplane in the hydrophobic core of the opposing lipid leaflet, and TOAC(1) remains in the lipid polar headgroup region. Orientational order parameters indicate that the tilt of alamethicin relative to the membrane normal is relatively small, even at high temperatures in the fluid phase, and increases rather slowly with decreasing chain length (from 13 degrees to 23 degrees for N = 18 and 10, respectively, at 75 degrees C). This is insufficient for alamethicin to achieve hydrophobic matching. Alamethicin differs in its mode of incorporation from other helical peptides for which transmembrane orientation has been determined as a function of lipid chain length. PMID:17351010

  3. Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma.

    PubMed

    Yang, Yi-Shan; Zhang, Xianzhong; Xiong, Zhengming; Chen, Xiaoyuan

    2006-04-01

    Bombesin (BBN), an analog of human gastrin-releasing peptide (GRP), binds to the GRP receptor (GRPR) with high affinity and specificity. Overexpression of GRPR has been discovered in mostly androgen-independent human prostate tissues and, thus, provides a potential target for prostate cancer diagnosis and therapy. We have previously demonstrated the feasibility of the positron emission tomography (PET) imaging using 64Cu-1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA)-[Lys3]BBN to detect GRPR-positive prostate cancer. In this study, we compared the receptor affinity, metabolic stability, tumor-targeting efficacy, and pharmacokinetics of a truncated BBN analog 64Cu-DOTA-Aca-BBN(7-14) with 64Cu-DOTA-[Lys3]BBN. Binding of each DOTA conjugate to GRPR on PC-3 and 22Rv1 prostate cancer cells was evaluated with competitive binding assay using 125I-[Tyr4]BBN as radioligand. In vivo pharmacokinetics was determined on male nude mice subcutaneously implanted with PC-3 cells. Dynamic microPET imaging was performed to evaluate the systemic distribution of the tracers. Metabolic stability of the tracers in blood, urine, tumor, liver and kidney was studied using high-performance liquid chromatography. The results showed that 125I-[Tyr4]BBN has a K(d) of 14.8+/-0.4 nM against PC-3 cells, and the receptor concentration on PC-3 cell surface is approximately 2.7+/-0.1 x 10(6) receptors per cell. The 50% inhibitory concentration value for DOTA-Aca-BBN(7-14) is 18.4 +/- 0.2 nM, and that for DOTA-[Lys3]BBN is 2.2 +/- 0.5 nM. DOTA-[Lys3]BBN shows a better tumor contrast and absolute tumor activity accumulation compared to DOTA-Aca-BBN(7-14). Studies on metabolic stability for both tracers on organ homogenates showed that 64Cu-DOTA-[Lys3]BBN is relatively stable. This study demonstrated that both tracers are suitable for targeted PET imaging to detect the expression of GRPR in prostate cancer, while 64Cu-DOTA-[Lys3]BBN may have a better potential for clinical translation.

  4. Therapeutic Efficacy of a {sup 188}Re-Labeled {alpha}-Melanocyte-Stimulating Hormone Peptide Analog in Murine and Human Melanoma-Bearing Mouse Models

    SciTech Connect

    Miao, Yubin; Owen, Nellie K.; Fisher, Darrell R.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to examine the therapeutic efficacy of {sup 188}Re-(Arg{sup 11})CCMSH in the B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. Method: (Arg11)CCMSH was synthesized and labeled with {sup 188}Re to form {sup 188}Re-(Agr{sup 11})CCMSH. B16/F1 melanoma tumor bearing mice were administrated with 200 Ci, 600 Ci and 2x400 Ci of {sup 188}Re-(Arg{sup 11})CCMSH via the tail vein, respectively. TXM13 melanoma tumor hearing mice were separately injected with 600 Ci, 2x400 Ci and 1000 Ci of 100Re-(Arg{sup 11})CCMSH through the tail vein. Two groups of 10 mice bearing either B16/F1 or TXM13 tumors were injected with saline as untreated controls. Results: In contrast to the untreated control group, {sup 188}Re(Arg11)CCMSH yielded rapid and lasting therapeutic effects in the treatment groups with either B16/F1 or TXM13 tumors. The tumor growth rate was reduced and the survival rate was prolonged in the treatment groups. Treatment with 2x400 Ci of {sup 188}Re-Arg{sup 11}CCMSH significantly extended the mean life of B16/F1 tumor mice (p<0.05), while the mean life of TXm13 tumor mice was significantly prolonged after treatment with 600 Ci and 1000 Ci doses of {sup 188}Re-(Arg{sup 11})CCMSH (p<0.05 High-dose {sup 188}Re-(Arg{sup 11}))CCMSH produced no observed normal-tissue toxicity. Conclusions: The therapy study results revealed that {sup 188}Re-Arg11 CCMSH yielded significant therapeutic effects in both B16/F1 murine melanoma and TXM13 human melanoma bearing mouse models. {sup 188}Re-(Arg{sup 11})CCMSH appears to be a promising radiolabeled peptide for targeted radionuclide therapy of melanoma.

  5. Epigenetic Function of Activation-Induced Cytidine Deaminase and Its Link to Lymphomagenesis

    PubMed Central

    Dominguez, Pilar M.; Shaknovich, Rita

    2014-01-01

    Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of immunoglobulin (Ig) genes during B cell maturation and immune response. Expression of AID is tightly regulated due to its mutagenic and recombinogenic potential, which is known to target not only Ig genes, but also non-Ig genes, contributing to lymphomagenesis. In recent years, a new epigenetic function of AID and its link to DNA demethylation came to light in several developmental systems. In this review, we summarize existing evidence linking deamination of unmodified and modified cytidine by AID to base-excision repair and mismatch repair machinery resulting in passive or active removal of DNA methylation mark, with the focus on B cell biology. We also discuss potential contribution of AID-dependent DNA hypomethylation to lymphomagenesis. PMID:25566255

  6. APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages

    PubMed Central

    Sharma, Shraddha; Patnaik, Santosh K.; Thomas Taggart, R.; Kannisto, Eric D.; Enriquez, Sally M.; Gollnick, Paul; Baysal, Bora E.

    2015-01-01

    The extent, regulation and enzymatic basis of RNA editing by cytidine deamination are incompletely understood. Here we show that transcripts of hundreds of genes undergo site-specific C>U RNA editing in macrophages during M1 polarization and in monocytes in response to hypoxia and interferons. This editing alters the amino acid sequences for scores of proteins, including many that are involved in pathogenesis of viral diseases. APOBEC3A, which is known to deaminate cytidines of single-stranded DNA and to inhibit viruses and retrotransposons, mediates this RNA editing. Amino acid residues of APOBEC3A that are known to be required for its DNA deamination and anti-retrotransposition activities were also found to affect its RNA deamination activity. Our study demonstrates the cellular RNA editing activity of a member of the APOBEC3 family of innate restriction factors and expands the understanding of C>U RNA editing in mammals. PMID:25898173

  7. Characterization of a membrane-associated cytidine diphosphate-diacylglycerol-dependent phosphatidylserine synthase in bacilli.

    PubMed Central

    Dutt, A; Dowhan, W

    1981-01-01

    The synthesis of phosphatidylserine in two gram-positive aerobic bacteria has been partially characterized. We have located a cytidine 5'-diphospho-diacylglycerol:L-serine O-phosphatidyltransferase (phosphatidylserine synthase) activity in the membrane fraction of Bacillus licheniformis and Bacillus subtilis. The activity was demonstrated to be membrane associated by differential centrifugation, sucrose gradient centrifugation, and detergent solubilization. The direct involvement of cytidine 5'-diphospho-diacylglycerol in the reaction was demonstrated by the conversion of the liponucleotide phosphatidyl moiety to phosphatidylserine. This activity is dependent on divalent metal ion (manganese being optimal) and is stimulated by nonionic detergent and its product phosphatidylserine. Based on studies with various combinations of products and substrates, the reaction appears to follow a sequential BiBi kinetic mechanism. PMID:6267011

  8. Combining molecular dynamics and docking simulations of the cytidine deaminase from Mycobacterium tuberculosis H37Rv.

    PubMed

    Timmers, Luís Fernando Saraiva Macedo; Ducati, Rodrigo Gay; Sánchez-Quitian, Zilpa Adriana; Basso, Luiz Augusto; Santos, Diógenes Santiago; de Azevedo, Walter Filgueira

    2012-02-01

    Cytidine Deaminase (CD) is an evolutionarily conserved enzyme that participates in the pyrimidine salvage pathway recycling cytidine and deoxycytidine into uridine and deoxyuridine, respectively. Here, our goal is to apply computational techniques in the pursuit of potential inhibitors of Mycobacterium tuberculosis CD (MtCDA) enzyme activity. Molecular docking simulation was applied to find the possible hit compounds. Molecular dynamics simulations were also carried out to investigate the physically relevant motions involved in the protein-ligand recognition process, aiming at providing estimates for free energy of binding. The proposed approach was capable of identifying a potential inhibitor, which was experimentally confirmed by IC(50) evaluation. Our findings open up the possibility to extend this protocol to different databases in order to find new potential inhibitors for promising targets based on a rational drug design process.

  9. Interleukin-1 and tumor necrosis factor-α trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID).

    PubMed

    Watashi, Koichi; Liang, Guoxin; Iwamoto, Masashi; Marusawa, Hiroyuki; Uchida, Nanako; Daito, Takuji; Kitamura, Kouichi; Muramatsu, Masamichi; Ohashi, Hirofumi; Kiyohara, Tomoko; Suzuki, Ryosuke; Li, Jisu; Tong, Shuping; Tanaka, Yasuhito; Murata, Kazumoto; Aizaki, Hideki; Wakita, Takaji

    2013-11-01

    Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection.

  10. Interleukin-1 and Tumor Necrosis Factor-α Trigger Restriction of Hepatitis B Virus Infection via a Cytidine Deaminase Activation-induced Cytidine Deaminase (AID)*

    PubMed Central

    Watashi, Koichi; Liang, Guoxin; Iwamoto, Masashi; Marusawa, Hiroyuki; Uchida, Nanako; Daito, Takuji; Kitamura, Kouichi; Muramatsu, Masamichi; Ohashi, Hirofumi; Kiyohara, Tomoko; Suzuki, Ryosuke; Li, Jisu; Tong, Shuping; Tanaka, Yasuhito; Murata, Kazumoto; Aizaki, Hideki; Wakita, Takaji

    2013-01-01

    Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection. PMID:24025329

  11. Ab Initio ONIOM-Molecular Dynamics (MD) Study on the Deamination Reaction by Cytidine Deaminase

    SciTech Connect

    Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

    2007-08-23

    We applied the ONIOM-molecular dynamics (MD) method to the hydrolytic deamination of cytidine by cytidine deaminase, which is an essential step of the activation process of the anticancer drug inside the human body. The direct MD simulations were performed for the realistic model of cytidine deaminase calculating the energy and its gradient by the ab initio ONIOM method on the fly. The ONIOM-MD calculations including the thermal motion show that the neighboring amino acid residue is an important factor of the environmental effects and significantly affects not only the geometry and energy of the substrate trapped in the pocket of the active site but also the elementary step of the catalytic reaction. We successfully simulate the second half of the catalytic cycle, which has been considered to involve the rate-determining step, and reveal that the rate-determing step is the release of the NH3 molecule. TM and MA were supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. MD was supported by the Division of Chemical Sciences, Office of Basic Energy Sciences, and by the Office of Biological and Environmental Research of the U.S. Department of Energy DOE. Battelle operates Pacific Northwest National Laboratory for DOE.

  12. Beyond SHM and CSR: AID and related cytidine deaminases in the host response to viral infection.

    PubMed

    Rosenberg, Brad R; Papavasiliou, F Nina

    2007-01-01

    As the primary effector of immunoglobulin somatic hypermutation (SHM) and class switch recombination (CSR), activation-induced cytidine deaminase (AID) serves an important function in the adaptive immune response. Recent advances have demonstrated that AID and a group of closely related cytidine deaminases, the APOBEC3 proteins, also act in the innate host response to viral infection. Antiviral activity was first attributed to APOBEC3G as a potent inhibitor of HIV. It is now apparent that the targets of the APOBEC3 proteins extend beyond HIV, with family members acting against a wide variety of viruses as well as host-encoded retrotransposable genetic elements. Although it appears to function through a different mechanism, AID also possesses antiviral properties. Independent of its antibody diversification functions, AID protects against transformation by Abelson murine leukemia virus (Ab-MLV), an oncogenic retrovirus. Additionally, AID has been implicated in the host response to other pathogenic viruses. These emerging roles for the AID/APOBEC cytidine deaminases in viral infection suggest an intriguing evolutionary connection of innate and adaptive immune mechanisms.

  13. Pyrimidine biosynthetic enzymes of Salmonella typhimurium, repressed specifically by growth in the presence of cytidine.

    PubMed Central

    Kelln, R A; Kinahan, J J; Foltermann, K F; O'Donovan, G A

    1975-01-01

    The repressive effects of exogenous cytidine on growing cells was examined in a specially constructed strain in which the pool sizes of endogenous uridine 5'-diphosphate and uridine 5'-triphosphate cannot be varied by the addition of uracil and/or uridine to the medium. Five enzymes of the pyrimidine biosynthetic pathway and one enzyme of the arginine biosynthetic pathway were assayed from cells grown under a variety of conditions. Cytidine repressed the synthesis of dihydroorotase (encoded by pyrC), dihydroorotate dehydrogenase (encoded by pyrD), and ornithine transcarbamylase (encoded by argI). Moreover, aspartate transcarbamylase (encoded by pyrB) became further derepressed upon cytidine addition, whereas no change occurred in the levels of the last two enzymes (encoded by pyrE and pyrF) of the pyrimidine pathway. Quantitative nucleotide pool determinations have provided evidence that any individual ribo- or deoxyribonucleoside mono-, di-, or triphosphate of cytosine or uracil is not a repressing metabolite for the pyrimidine biosynthetic enzymes. Other nucleotide derivatives or ratios must be considered. PMID:1102530

  14. Radioimmunoassays of plasma thymidine, uridine, deoxyuridine, and cytidine/deoxycytidine

    SciTech Connect

    Dudman, N.P.B.; Deveski, W.B.; Tattersall, M.H.N.

    1981-08-01

    Radioimmunoassay techniques have been developed for the assay of thymidine, uridine, deoxyuridine, and deoxycytidine. Plasma levels of the first three nucleosides have been measured, and an upper limit has been determined for the plasma concentration of deoxycytidine. The assays involve displacement of a (3H)pyrimidine nucleoside from the appropriate labeled rabbit immunoglobulin. By assaying a mixture of uridine and deoxyuridine in the presence and absence of borax, the concentrations of both nucleosides have been measured. In seven healthy adults, plasma levels of uridine were 21.1 +/- 8.4 ..mu..M (mean +/- SD) and of deoxyuridine were 0.62 +/- 0.39 ..mu..M. In cancer patients, thymidine levels were 7.5 +/- 2.7 x 10/sup -7/M. The upper limit for plasma deoxycytidine levels in six healthy adults was 0.71 +/- 0.1 ..mu..M.

  15. Analog earthquakes

    SciTech Connect

    Hofmann, R.B.

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  16. Rotanone analogs: method of preparation and use

    DOEpatents

    VanBrocklin, Henry F; O& #x27; Neil, James P; Gibbs, Andrew R; Erathodiyil, Nandanan

    2013-10-08

    The present invention provides rotenone analogs and methods of making and using them. Labeled with single photon and positron emitting isotopes, the rotenone analogs of the present invention are useful in, for example, clinical imaging applications as tracers to measure cardiac blood flow and detect regions of ischemia.

  17. Cytidine-stabilized gold nanocluster as a fluorescence turn-on and turn-off probe for dual functional detection of Ag(+) and Hg(2+).

    PubMed

    Zhang, Yuanyuan; Jiang, Hui; Wang, Xuemei

    2015-04-22

    In this study, we have developed a label-free, dual functional detection strategy for highly selective and sensitive determination of aqueous Ag(+) and Hg(2+) by using cytidine stabilized Au NCs and AuAg NCs as fluorescent turn-on and turn off probes, respectively. The Au NCs and AuAg NCs showed a remarkably rapid response and high selectivity for Ag(+) and Hg(2+) over other metal ions, and relevant detection limit of Ag(+) and Hg(2+) is ca. 10 nM and 30 nM, respectively. Importantly, the fluorescence enhanced Au NCs by doping Ag(+) can be conveniently reusable for the detection of Hg(2+) based on the corresponding fluorescence quenching. The sensing mechanism was based on the high-affinity metallophilic Hg(2+)-Ag(+) interaction, which effectively quenched the fluorescence of AuAg NCs. Furthermore, these fluorescent nanoprobes could be readily applied to Ag(+) and Hg(2+) detection in environmental water samples, indicating their possibility to be utilized as a convenient, dual functional, rapid response, and label-free fluorescence sensor for related environmental and health monitoring.

  18. Triptycene analogs

    NASA Technical Reports Server (NTRS)

    Hua, Duy (Inventor); Perchellet, Jean-Pierre (Inventor)

    2004-01-01

    This invention provides analogs of triptycene which are useful as anticancer drugs, as well as for other uses. The potency of these compounds is in a similar magnitude as daunomycin, a currently used anticancer drug. Each compound of the invention produces one or more desired effects (blocking nucleoside transport, inhibiting nucleic acid or protein syntheses, decreasing the proliferation and viability of cancer cells, inducing DNA fragmentation or retaining their effectiveness against multidrug-resistant tumor cells).

  19. The association constant of 5′,8-cyclo-2′-deoxyguanosine with cytidine

    PubMed Central

    Capobianco, Amedeo; Caruso, Tonino; Fusco, Sandra; Terzidis, Michael A.; Masi, Annalisa; Chatgilialoglu, Chryssostomos; Peluso, Andrea

    2015-01-01

    The association of 5′,8-cyclo-2′-deoxyguanosine (cdG), a DNA tandem lesion, with its complementary base cytosine has been studied by voltammetry and NMR in chloroform, using properly silylated derivatives of the two nucleobases for increasing their solubilities. Both voltammetric data and NMR titrations indicated that the Watson-Crick complex of cytidine with cdG is weaker than that with guanosine, the difference being approximately of one order of magnitude between the two association constants. PMID:25870853

  20. Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines.

    PubMed

    Klier, Lydia; Aranzamendi, Eider; Ziegler, Dorothée; Nickel, Johannes; Karaghiosoff, Konstantin; Carell, Thomas; Knochel, Paul

    2016-03-01

    The Lewis acid MgCl2 allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl2, zincation using TMP2Zn·2LiCl·2MgCl2 occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP2Zn·2LiCl·2MgCl2 also allows to functionalize cytidine derivatives at the position C(6).

  1. Yin and yang of cytidine deaminase roles in clinical response to azacitidine in the elderly: a pharmacogenetics tale.

    PubMed

    Fanciullino, Raphaelle; Mercier, Cédric; Serdjebi, Cindy; Venton, Geoffroy; Colle, Julien; Fina, Frédéric; Ouafik, L'Houcine; Lacarelle, Bruno; Ciccolini, Joseph; Costello, Régis

    2015-11-01

    Azacitidine is a mainstay for treating hematological disorders. Azacitidine is metabolized by cytidine deaminase, coded by a highly polymorphic gene. Here, we present two elderly patients with opposite clinical outcomes after azacitidine treatment. First, an acute myeloid leukemia patient showed life-threatening toxicities, but outstanding complete remission, after a single round of azacitidine. Further investigations showed that this patient was cytidine deaminase 79A>C (rs2072671) homozygous with a marked deficient phenotype. Next, a chronic myelomonocytic leukemia patient displayed complete lack of response despite several cycles of azacitidine. This patient had a rapid-deaminator phenotype linked to the -31delC deletion (rs3215400). These polymorphisms lead to opposite clinical outcomes in patients with myelodysplastic syndromes treated with azacitidine, thus suggesting that determining cytidine deaminase status could help to forecast clinical outcome.

  2. Photo protection of RNA building blocks: Adenosine 5‧-monophosphate, cytidine 5‧-monophosphate and cytosine

    NASA Astrophysics Data System (ADS)

    Nielsen, Jakob Brun; Thøgersen, Jan; Jensen, Svend Knak; Keiding, Søren Rud

    2013-04-01

    Photoprotection of the RNA nucleotides adenosine 5'-monophosphate and cytidine 5'-monophosphate, and the nucleobase cytosine was studied using UV pump, IR probe femtosecond transient absorption spectroscopy. The excitation energy is contained in the aromatic ring system, protecting the RNA backbone. All three molecules dissipate the excitation energy by internal conversion and subsequent vibrational relaxation to the electronic ground state in less than 10 ps. In addition, a second deactivation channel is found in cytidine 5'-monophosphate, illustrated by a signal at 1563 cm-1 with a lifetime of 33 ps assigned to an nπ∗ state in agreement with observations in the UV region.

  3. Characterization of immunoglobulin gene somatic hypermutation in the absence of activation-induced cytidine deaminase

    PubMed Central

    Longo, Nancy S.; Satorius, Colleen L.; Plebani, Alessandro; Durandy, Anne; Lipsky, Peter E.

    2008-01-01

    Somatic hypermutation (SHM) of Ig genes depends upon the deamination of C nucleotides in WRCY (W=A/T, R=A/G, Y=C/T) motifs by activation-induced cytidine deaminase (AICDA). Despite this, a large number of mutations occur in WA motifs that can be accounted for by the activity of polymerase eta (POL η). To determine whether there are AICDA-independent mutations and to characterize the relationship between AICDA- and POL η-mediated mutations, 1,470 H chain and 1,313 kappa and lambda chain rearrangements from three AICDA−/− patients were analyzed. The Ig mutation frequency of all VH genes from AICDA−/− patients was 40-fold less than that of normal donors whereas the mutation frequency of mutated VH sequences from AICDA−/− patients was 6.8-fold less than normal donors. AICDA−/− B cells lack mutations in WRCY/RGYW motifs as well as replacement mutations and mutational targeting in complementarity determining regions. A significantly reduced mutation frequency in WA motifs compared to normal donors and an increased percentage of transitions, which may relate to reduced uracil DNA-glycosylase (UNG) activity, suggest a role for AICDA in regulating POL η and UNG activity. Similar results were observed in VL rearrangements. The residual mutations were predominantly G:C substitutions, indicating that AICDA-independent cytidine deamination was a likely, yet inefficient, mechanism for mutating Ig genes. PMID:18606684

  4. ESR study of irradiated single crystals of the cocrystalline complex of cytidine: Salicylic acid

    SciTech Connect

    Close, D.M.; Sagstuen, E.

    1983-12-01

    Irradiation at 77 K of single crystals of the 1:1 complex of cytidine and salicylic acid produces a phenoxyl radical formed by oxidation of the salicylic acid. Anisotropic hyperfine coupling tensors have been determined for this radical which are associated with the para and ortho hydrogens. No cytidine oxidation products (alkoxy or hydroxyalkyl radicals) were observed at 77 K. Following the decay of the phenoxyl radical at room temperature, four radicals were detected. These include the cytosine 5--yl and 6--yl radicals, formed by H addition to the cytosine ring, and an anisotropic doublet. By UV irradiation at room temperature, it is possible to convert a significant fraction of 6-yl radicals into 5-yl radicals. Hyperfine coupling and g tensors determined for the anisotropic doublet indicate that this radical is formed in the C/sub 1'/-C/sub 2'/ region of the sugar moiety. These results indicate a shift in radiation damage away from the salicylic acid upon warming, and show that the radiation chemistry of the cocrystalline complex is different from that of the isolated bases.

  5. Irmpd Action Spectroscopy and Computational Approaches to Elucidate Gas-Phase Structures and Energetics of 2'-DEOXYCYTIDINE and Cytidine Sodium Complexes

    NASA Astrophysics Data System (ADS)

    Zhu, Yanlong; Hamlow, Lucas; He, Chenchen; Gao, Juehan; Oomens, Jos; Rodgers, M. T.

    2016-06-01

    The local structures of DNA and RNA are influenced by protonation, deprotonation and noncovalent interactions with cations. In order to determine the effects of Na+ cationization on the gas-phase structures of 2'-deoxycytidine, [dCyd+Na]+, and cytidine, [Cyd+Na]+, infrared multiple photon dissociation (IRMPD) action spectra of these sodium cationized nucleosides are measured over the range extending from 500 to 1850 wn using the FELIX free electron laser. Complementary electronic structure calculations are performed to determine the stable low-energy conformations of these complexes. Geometry optimizations, frequency analyses, and IR spectra of these species are determined at the B3LYP/6-311+G(d,p) level of theory. Single-point energies are calculated at the B3LYP/6-311+G(2d,2p) level of theory to determine the relative stabilities of these conformations. Comparison of the measure IRMPD action spectra and computed linear IR spectra enable the conformations accessed in the experiments to be elucidated. For both cytosine nucleosides, tridentate binding of the Na+ cation to the O2, O4' and O5' atoms of the nucleobase and sugar is observed. Present results for the sodium cationized nucleosides are compared to results for the analogous protonated forms of these nucleosides to elucidate the effects of multiple chelating interactions with the sodium cation vs. hydrogen bonding interactions in the protonated systems on the structures and stabilities of these nucleosides.

  6. The pivotal role of uridine-cytidine kinases in pyrimidine metabolism and activation of cytotoxic nucleoside analogues in neuroblastoma.

    PubMed

    van Kuilenburg, André B P; Meinsma, Rutger

    2016-09-01

    Uridine-cytidine kinase (UCK) catalyzes the phosphorylation of uridine and cytidine as well as the pharmacological activation of several cytotoxic pyrimidine ribonucleoside analogues. In this study, we investigated the functional role of two isoforms of UCK in neuroblastoma cell lines. Analysis of mRNA coding for UCK1 and UCK2 showed that UCK2 is the most abundantly expressed UCK in a panel of neuroblastoma cell lines. Transient and stable overexpression of UCK2 in neuroblastoma cells increased the metabolism of uridine and cytidine as well as the cytotoxicity of 3-deazauridine. Knockdown of endogenous UCK2 as well as overexpression of UCK1 resulted in decreased metabolism of uridine and cytidine and protected the neuroblastoma cells from 3-deazauridine-induced toxicity. Subcellular localization studies showed that UCK1-GFP and UCK2-GFP were localized in the cell nucleus and cytosol, respectively. However, co-expression of UCK1 with UCK2 resulted in a nuclear localization of UCK2 instead of its normal cytosolic localization, thereby impairing its normal function. The physical association of UCK1 and UCK2 was further demonstrated through pull-down analysis using his-tagged UCK. The discovery that UCK2 is highly expressed in neuroblastoma opens the possibility for selectively targeting neuroblastoma cells using UCK2-dependent pyrimidine analogues, while sparing normal tissues. PMID:27239701

  7. Photoelectron and computational studies of the copper-nucleoside anionic complexes, Cu{sup -}(cytidine) and Cu{sup -}(uridine)

    SciTech Connect

    Li Xiang; Ko, Yeon-Jae; Wang Haopeng; Bowen, Kit H.; Guevara-Garcia, Alfredo; Martinez, Ana

    2011-02-07

    The copper-nucleoside anions, Cu{sup -}(cytidine) and Cu{sup -}(uridine), have been generated in the gas phase and studied by both experimental (anion photoelectron spectroscopy) and theoretical (density functional calculations) methods. The photoelectron spectra of both systems are dominated by single, intense, and relatively narrow peaks. These peaks are centered at 2.63 and 2.71 eV for Cu{sup -}(cytidine) and Cu{sup -}(uridine), respectively. According to our calculations, Cu{sup -}(cytidine) and Cu{sup -}(uridine) species with these peak center [vertical detachment energy (VDE)] values correspond to structures in which copper atomic anions are bound to the sugar portions of their corresponding nucleosides largely through electrostatic interactions; the observed species are anion-molecule complexes. The combination of experiment and theory also reveal the presence of a slightly higher energy, anion-molecule complex isomer in the case of the Cu{sup -}(cytidine). Furthermore, our calculations found that chemically bond isomers of these species are much more stable than their anion-molecule complex counterparts, but since their calculated VDE values are larger than the photon energy used in these experiments, they were not observed.

  8. Structural and functional analyses of Mycobacterium tuberculosis Rv3315c-encoded metal-dependent homotetrameric cytidine deaminase.

    PubMed

    Sánchez-Quitian, Zilpa A; Schneider, Cristopher Z; Ducati, Rodrigo G; de Azevedo, Walter F; Bloch, Carlos; Basso, Luiz A; Santos, Diógenes S

    2010-03-01

    The emergence of drug-resistant strains of Mycobacterium tuberculosis, the causative agent of tuberculosis, has exacerbated the treatment and control of this disease. Cytidine deaminase (CDA) is a pyrimidine salvage pathway enzyme that recycles cytidine and 2'-deoxycytidine for uridine and 2'-deoxyuridine synthesis, respectively. A probable M. tuberculosis CDA-coding sequence (cdd, Rv3315c) was cloned, sequenced, expressed in Escherichia coli BL21(DE3), and purified to homogeneity. Mass spectrometry, N-terminal amino acid sequencing, gel filtration chromatography, and metal analysis of M. tuberculosis CDA (MtCDA) were carried out. These results and multiple sequence alignment demonstrate that MtCDA is a homotetrameric Zn(2+)-dependent metalloenzyme. Steady-state kinetic measurements yielded the following parameters: K(m)=1004 microM and k(cat)=4.8s(-1) for cytidine, and K(m)=1059 microM and k(cat)=3.5s(-1) for 2'-deoxycytidine. The pH dependence of k(cat) and k(cat)/K(M) for cytidine indicate that protonation of a single ionizable group with apparent pK(a) value of 4.3 abolishes activity, and protonation of a group with pK(a) value of 4.7 reduces binding. MtCDA was crystallized and crystal diffracted at 2.0 A resolution. Analysis of the crystallographic structure indicated the presence of a Zn(2+) coordinated by three conserved cysteines and the structure exhibits the canonical cytidine deaminase fold.

  9. Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2'-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases.

    PubMed

    Jin, Zhinan; Tucker, Kathryn; Lin, Xiaoyan; Kao, C Cheng; Shaw, Ken; Tan, Hua; Symons, Julian; Behera, Ishani; Rajwanshi, Vivek K; Dyatkina, Natalia; Wang, Guangyi; Beigelman, Leo; Deval, Jerome

    2015-12-01

    Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2'-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC50s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2'-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities.

  10. Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2′-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases

    PubMed Central

    Tucker, Kathryn; Lin, Xiaoyan; Kao, C. Cheng; Shaw, Ken; Tan, Hua; Symons, Julian; Behera, Ishani; Rajwanshi, Vivek K.; Dyatkina, Natalia; Wang, Guangyi; Beigelman, Leo

    2015-01-01

    Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2′-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC50s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2′-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities. PMID:26392512

  11. Mycoplasma hyorhinis-encoded cytidine deaminase efficiently inactivates cytosine-based anticancer drugs

    PubMed Central

    Vande Voorde, Johan; Vervaeke, Peter; Liekens, Sandra; Balzarini, Jan

    2015-01-01

    Mycoplasmas may colonize tumor tissue in patients. The cytostatic activity of gemcitabine was dramatically decreased in Mycoplasma hyorhinis-infected tumor cell cultures compared with non-infected tumor cell cultures. This mycoplasma-driven drug deamination could be prevented by exogenous administration of the cytidine deaminase (CDA) inhibitor tetrahydrouridine, but also by the natural nucleosides or by a purine nucleoside phosphorylase inhibitor. The M. hyorhinis-encoded CDAHyor gene was cloned, expressed as a recombinant protein and purified. CDAHyor was found to be more catalytically active than its human equivalent and efficiently deaminates (inactivates) cytosine-based anticancer drugs. CDAHyor expression at the tumor site may result in selective drug inactivation and suboptimal therapeutic efficiency. PMID:26322268

  12. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes

    PubMed Central

    Kato, Lucia; Begum, Nasim A.; Burroughs, A. Maxwell; Doi, Tomomitsu; Kawai, Jun; Daub, Carsten O.; Kawaguchi, Takahisa; Matsuda, Fumihiko; Hayashizaki, Yoshihide; Honjo, Tasuku

    2012-01-01

    Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and class-switch recombination in activated B cells. AID is also known to target nonimmunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks by using two independent genome-wide approaches. Along with known AID targets, this screen identified a set of unique genes (SNHG3, MALAT1, BCL7A, and CUX1) and confirmed that these loci accumulated mutations as frequently as Ig locus after AID activation. Moreover, these genes share three important characteristics with the Ig gene: translocations in tumors, repetitive sequences, and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites. PMID:22308462

  13. Cytidine 5'-Diphosphocholine (Citicoline) in Glaucoma: Rationale of Its Use, Current Evidence and Future Perspectives.

    PubMed

    Roberti, Gloria; Tanga, Lucia; Michelessi, Manuele; Quaranta, Luciano; Parisi, Vincenzo; Manni, Gianluca; Oddone, Francesco

    2015-01-01

    Cytidine 5'-diphosphocholine or citicoline is an endogenous compound that acts in the biosynthetic pathway of phospholipids of cell membranes, particularly phosphatidylcholine, and it is able to increase neurotrasmitters levels in the central nervous system. Citicoline has shown positive effects in Parkinson's disease and Alzheimer's disease, as well as in amblyopia. Glaucoma is a neurodegenerative disease currently considered a disease involving ocular and visual brain structures. Neuroprotection has been proposed as a valid therapeutic option for those patients progressing despite a well-controlled intraocular pressure, the main risk factor for the progression of the disease. The aim of this review is to critically summarize the current evidence about the effect of citicoline in glaucoma. PMID:26633368

  14. APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer

    PubMed Central

    Periyasamy, Manikandan; Patel, Hetal; Lai, Chun-Fui; Nguyen, Van T.M.; Nevedomskaya, Ekaterina; Harrod, Alison; Russell, Roslin; Remenyi, Judit; Ochocka, Anna Maria; Thomas, Ross S.; Fuller-Pace, Frances; Győrffy, Balázs; Caldas, Carlos; Navaratnam, Naveenan; Carroll, Jason S.; Zwart, Wilbert; Coombes, R. Charles; Magnani, Luca; Buluwela, Laki; Ali, Simak

    2015-01-01

    Summary Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER) and to repair by non-homologous end-joining (NHEJ) pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action. PMID:26411678

  15. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes.

    PubMed

    Kato, Lucia; Begum, Nasim A; Burroughs, A Maxwell; Doi, Tomomitsu; Kawai, Jun; Daub, Carsten O; Kawaguchi, Takahisa; Matsuda, Fumihiko; Hayashizaki, Yoshihide; Honjo, Tasuku

    2012-02-14

    Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and class-switch recombination in activated B cells. AID is also known to target nonimmunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks by using two independent genome-wide approaches. Along with known AID targets, this screen identified a set of unique genes (SNHG3, MALAT1, BCL7A, and CUX1) and confirmed that these loci accumulated mutations as frequently as Ig locus after AID activation. Moreover, these genes share three important characteristics with the Ig gene: translocations in tumors, repetitive sequences, and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites.

  16. Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis.

    PubMed

    Sapoznik, Stav; Bahar-Shany, Keren; Brand, Hadar; Pinto, Yishay; Gabay, Orshay; Glick-Saar, Efrat; Dor, Chen; Zadok, Oranit; Barshack, Iris; Zundelevich, Adi; Gal-Yam, Einav Nili; Yung, Yuval; Hourvitz, Ariel; Korach, Jacob; Beiner, Mario; Jacob, Jasmine; Levanon, Erez Y; Barak, Michal; Aviel-Ronen, Sarit; Levanon, Keren

    2016-02-01

    In recent years, the notion that ovarian carcinoma results from ovulation-induced inflammation of the fallopian tube epithelial cells (FTECs) has gained evidence. However, the mechanistic pathway for this process has not been revealed yet. In the current study, we propose the mutator protein activation-induced cytidine deaminase (AID) as a link between ovulation-induced inflammation in FTECs and genotoxic damage leading to ovarian carcinogenesis. We show that AID, previously shown to be functional only in B lymphocytes, is expressed in FTECs under physiological conditions, and is induced in vitro upon ovulatory-like stimulation and in vivo in carcinoma-associated FTECs. We also report that AID activity results in epigenetic, genetic and genomic damage in FTECs. Overall, our data provides new insights into the etiology of ovarian carcinogenesis and may set the ground for innovative approaches aimed at prevention and early detection. PMID:26936395

  17. Production of cytidine 5'-diphosphorylcholine with high utilization of ATP by whole cells of Saccharomyces cerevisiae.

    PubMed

    Tang, Jiapeng; Chen, Yong; Chen, Xiaochun; Yao, Yuelan; Ying, Hanjie; Xiong, Jian; Bai, Jianxin

    2010-11-01

    Cytidine 5'-diphosphorylcholine (CDP-choline) was produced using a high efficiency ATP regeneration system and the Kennedy pathway in whole cells of Saccharomyces cerevisiae As 2.398. Out of eight variables, KH(2)PO(4), glycerol and (NH(4))(2)SO(4) were considered to be the most significant factors by response surface methodology including a Plackett-Burman design, path of steepest accent and central composite design. The optimum levels of the three variables were 20.13g/L KH(2)PO(4), 12.35g/L glycerol and 0.49g/L (NH(4))(2)SO(4), respectively. Energy utilization efficiency increased from 10.59% to 16.72% and choline chloride conversion yields increased from 12.35% to 42.78%. A high efficiency ATP regeneration system improves CDP-choline production.

  18. RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase.

    PubMed

    Liang, Guoxin; Kitamura, Kouichi; Wang, Zhe; Liu, Guangyan; Chowdhury, Sajeda; Fu, Weixin; Koura, Miki; Wakae, Kousho; Honjo, Tasuku; Muramatsu, Masamichi

    2013-02-01

    Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV.

  19. 9 CFR 116.3 - Label records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... Each label shall be identified as to: (1) Name and product code number as it appears on the product... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Label records. 116.3 Section 116.3..., SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS RECORDS AND REPORTS § 116.3 Label...

  20. 9 CFR 116.3 - Label records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... Each label shall be identified as to: (1) Name and product code number as it appears on the product... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Label records. 116.3 Section 116.3..., SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS RECORDS AND REPORTS § 116.3 Label...

  1. 9 CFR 116.3 - Label records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... Each label shall be identified as to: (1) Name and product code number as it appears on the product... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Label records. 116.3 Section 116.3..., SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS RECORDS AND REPORTS § 116.3 Label...

  2. 9 CFR 116.3 - Label records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... Each label shall be identified as to: (1) Name and product code number as it appears on the product... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Label records. 116.3 Section 116.3..., SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS RECORDS AND REPORTS § 116.3 Label...

  3. Molecular recognition of 7-(2-octadecyloxycarbonylethyl)guanine to cytidine at the air/water interface and LB film studied by Fourier transform infrared spectroscopy.

    PubMed

    Miao, Wangen; Luo, Xuzhong; Liang, Yingqiu

    2003-03-15

    Monolayer behavior of a nucleolipid amphiphile, 7-(2-octadecyloxycarbonylethyl)guanine (ODCG), on aqueous cytidine solution was investigated by means of surface-molecular area (pi-A) isotherms. It indicates that molecular recognition by hydrogen bonding is present between ODCG monolayer and the cytidine in subphase. The Fourier transform infrared (FTIR) transmission spectroscopic result indicates that the cytidine molecules in the subphase can be transferred onto solid substrates by Langmuir-Blodgett (LB) technique as a result of the formation of Watson-Crick base-pairing at the air/water interface. Investigation by rotating polarized FTIR transmission also suggests that the headgroup recognition of this amphiphile to the dissolved cytidine influence the orientation of the tailchains.

  4. Fourier transform infrared spectroscopy study on order-disorder transition in Langmuir-Blodgett films of 7-(2-octadecyloxycarbonylethyl)guanine before and after recognition to cytidine.

    PubMed

    Miao, Wangen; Luo, Xuzhong; Wu, Sanxie; Liang, Yingqiu

    2004-01-01

    Order-disorder transitions of 9-monolayer Langmuir-Blodgett (LB) films of 7-(2-octadecyloxycarbonylethyl)guanine (ODCG) before and after recognition to cytidine were investigated by Fourier transform infrared (FTIR) spectroscopy. The different order-disorder transitions suggest that molecular recognition between ODCG and cytidine influence these two LB films on the order-disorder process of alkyl tailchain. Cleavage of the multi-hydrogen bonds was also observed by the infrared spectroscopy at elevated temperature.

  5. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

    An improved subranging or comparator circuit is provided for an analog-to-digital converter. As a subranging circuit, the circuit produces a residual signal representing the difference between an analog input signal and an analog of a digital representation. This is achieved by subdividing the digital representation into two or more parts and subtracting from the analog input signal analogs of each of the individual digital portions. In another aspect of the present invention, the subranging circuit comprises two sets of differential input pairs in which the transconductance of one differential input pair is scaled relative to the transconductance of the other differential input pair. As a consequence, the same resistor string may be used for two different digital-to-analog converters of the subranging circuit.

  6. Relative stability of guanosine-cytidine diribonucleotide cores: a 1H NMR assessment.

    PubMed

    Sinclair, A; Alkema, D; Bell, R A; Coddington, J M; Hughes, D W; Neilson, T; Romaniuk, P J

    1984-06-01

    Proton NMR was used to study the secondary structure and melting behavior of six self-complementary oligoribonucleotide tetramers, each containing two guanosine and two cytidine residues (GGCC, CCGG, GCCG, CGGC, GCGC, and CGCG). GGCC and CCGG formed perfect duplexes containing four G.C base pairs with Tms of 54 and 47.8 degrees C, respectively; GCCG and CGGC formed staggered duplexes with two G.C base pairs and four 3' double-dangling bases, with Tms of 35.5 and 29.2 degrees C, respectively; GCGC formed a perfect duplex with a Tm of 49.9 degrees C, while CGCG formed a staggered duplex with a Tm of 36.9 degrees C. From these results, an order of stability of the cores containing two G.C base pairs was proposed: GC:GC is more stable than GG:CC which is more stable than CG:CG. The RY model for secondary structure stability prediction was applied to the above tetramers with reasonable success. Suggestions for refinements are discussed.

  7. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    SciTech Connect

    Hu, Yi Ericsson, Ida Doseth, Berit Liabakk, Nina B. Krokan, Hans E. Kavli, Bodil

    2014-03-10

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.

  8. Involvement of activation-induced cytidine deaminase in skin cancer development

    PubMed Central

    Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro

    2016-01-01

    Most skin cancers develop as the result of UV light–induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus–dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics. PMID:26974156

  9. LINE-1 retroelements complexed and inhibited by activation induced cytidine deaminase.

    PubMed

    Metzner, Mirjam; Jäck, Hans-Martin; Wabl, Matthias

    2012-01-01

    LINE-1 (abbreviated L1) is a major class of retroelements in humans and mice. If unrestricted, retroelements accumulate in the cytoplasm and insert their DNA into the host genome, with the potential to cause autoimmune disease and cancer. Retroviruses and other retroelements are inhibited by proteins of the APOBEC family, of which activation-induced cytidine deaminase (AID) is a member. Although AID is mainly known for being a DNA mutator shaping the antibody repertoire in B lymphocytes, we found that AID also restricts de novo L1 integrations in B- and non-B-cell lines. It does so by decreasing the protein level of open reading frame 1 (ORF1) of both exogenous and endogenous L1. In activated B lymphocytes, AID deficiency increased L1 mRNA 1.6-fold and murine leukemia virus (MLV) mRNA 2.7-fold. In cell lines and activated B lymphocytes, AID forms cytoplasmic high-molecular-mass complexes with L1 mRNA, which may contribute to L1 restriction. Because AID-deficient activated B lymphocytes do not express ORF1 protein, we suggest that ORF1 protein expression is inhibited by additional restriction factors in these cells. The greater increase in MLV compared to L1 mRNA in AID-deficient activated B lymphocytes may indicate less strict surveillance of retrovirus. PMID:23133680

  10. A Role for Host Activation-Induced Cytidine Deaminase in Innate Immune Defense against KSHV

    PubMed Central

    Bekerman, Elena; Jeon, Diana; Ardolino, Michele; Coscoy, Laurent

    2013-01-01

    Activation-induced cytidine deaminase (AID) is specifically induced in germinal center B cells to carry out somatic hypermutation and class-switch recombination, two processes responsible for antibody diversification. Because of its mutagenic potential, AID expression and activity are tightly regulated to minimize unwanted DNA damage. Surprisingly, AID expression has been observed ectopically during pathogenic infections. However, the function of AID outside of the germinal centers remains largely uncharacterized. In this study, we demonstrate that infection of human primary naïve B cells with Kaposi's sarcoma-associated herpesvirus (KSHV) rapidly induces AID expression in a cell intrinsic manner. We find that infected cells are marked for elimination by Natural Killer cells through upregulation of NKG2D ligands via the DNA damage pathway, a pathway triggered by AID. Moreover, without having a measurable effect on KSHV latency, AID impinges directly on the viral fitness by inhibiting lytic reactivation and reducing infectivity of KSHV virions. Importantly, we uncover two KSHV-encoded microRNAs that directly regulate AID abundance, further reinforcing the role for AID in the antiviral response. Together our findings reveal additional functions for AID in innate immune defense against KSHV with implications for a broader involvement in innate immunity to other pathogens. PMID:24244169

  11. Critical role of activation induced cytidine deaminase in experimental autoimmune encephalomyelitis.

    PubMed

    Sun, Yonglian; Peng, Ivan; Senger, Kate; Hamidzadeh, Kajal; Reichelt, Mike; Baca, Miriam; Yeh, Ronald; Lorenzo, Maria N; Sebrell, Andrew; Dela Cruz, Christopher; Tam, Lucinda; Corpuz, Racquel; Wu, Jiansheng; Sai, Tao; Roose-Girma, Merone; Warming, Søren; Balazs, Mercedesz; Gonzalez, Lino C; Caplazi, Patrick; Martin, Flavius; Devoss, Jason; Zarrin, Ali A

    2013-03-01

    Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE. PMID:23167594

  12. Critical role of activation induced cytidine deaminase in Experimental Autoimmune Encephalomyelitis

    PubMed Central

    2013-01-01

    Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE. PMID:23167594

  13. Involvement of activation-induced cytidine deaminase in skin cancer development.

    PubMed

    Nonaka, Taichiro; Toda, Yoshinobu; Hiai, Hiroshi; Uemura, Munehiro; Nakamura, Motonobu; Yamamoto, Norio; Asato, Ryo; Hattori, Yukari; Bessho, Kazuhisa; Minato, Nagahiro; Kinoshita, Kazuo

    2016-04-01

    Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.

  14. Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID.

    PubMed

    Wakae, Koshou; Magor, Brad G; Saunders, Holly; Nagaoka, Hitoshi; Kawamura, Akemi; Kinoshita, Kazuo; Honjo, Tasuku; Muramatsu, Masamichi

    2006-01-01

    Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the only known B cell-specific protein required for inducing CSR and SHM in mammals. Lower vertebrates have an AID homologue, and there is some evidence of SHM in vivo. However there is no evidence of CSR in the cartilaginous or bony fishes, and this may be due in part to a lack of cis-elements in the IgH gene that are the normal targets of AID-mediated recombination. We have tested whether bony fish (zebrafish and catfish) AID can mediate CSR and SHM in mammalian cells. As expected, ectopic expression of fish AID in mouse fibroblasts resulted in mutations in an introduced SHM reporter gene, indicating that fish AID can mediate SHM. Unexpectedly, expression of fish AID in mouse AID-/- B cells induced surface IgG expression as well as switched transcripts from Ig gene loci, clearly indicating that the fish AID protein can mediate CSR, at least in mouse cells. These results suggest that the AID protein acquired the ability to mediate CSR before the IgH locus evolved the additional exon clusters and switch regions that are the targets of recombination. We discuss how pleiotropic functions of specific domains within the AID protein may have facilitated the early evolution of CSR in lower vertebrates.

  15. Broad-spectrum antiviral activity of carbodine, the carbocyclic analogue of cytidine.

    PubMed

    De Clercq, E; Bernaerts, R; Shealy, Y F; Montgomery, J A

    1990-01-15

    Carbocyclic cytidine (C-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [pox (vaccinia)], (+)RNA viruses [toga (Sindbis, Semliki forest), corona], (-)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), rhabdo (vesicular stomatitis)] and (+/-)RNA viruses (reo). The target enzyme of C-Cyd is supposed to be CTP synthetase that converts UTP to CTP. In keeping with this assumption are the observations that (i) C-Cyd effects a dose-dependent inhibition of RNA synthesis in both virus-infected and uninfected cells, and (ii) exogenous addition of either Urd or Cyd reverses both the antiviral and cytocidal activity of C-Cyd, whereas addition of dThd or dCyd fails to do so. The selectivity of C-Cyd against Sindbis, vesicular stomatitis and reo virus is markedly increased when C-Cyd is combined with Cyd (10 micrograms/mL). This combination may therefore be worth pursuing as a chemotherapeutic modality for the treatment of virus infections. PMID:1689159

  16. Effect of NH4+ and glycerol on cytidine 5'-diphosphocholine synthesis in Saccharomyces cerevisiae.

    PubMed

    Tang, Jiapeng; Yao, Yuelan; Ying, Hanjie; Xiong, Jian; Zhang, Lei; Li, Zhenjiang; Bai, Jianxin; Zhang, Yeyong; Ouyang, Pingkai

    2009-10-01

    Both stimulation of ammonium ion on the glycolytic flux and regulation by glycerol of enzymes in Kennedy pathway for cytidine diphosphate choline production in S. cerevisiae were studied. The conventional transformation course featured four stages. Firstly, CMP and choline chloride were phosphorylated and CDP-choline was formed rapidly; secondly, the rate of CDP-choline formation declined and CMP was not detected in the mixture; thirdly, CMP was released and the CDP-choline concentration reached a peak; Fourthly, the compound concentrations did not practically changes eventually. Using the central composite design, the concentration, yield, and utilization efficiency of energy reached 24.7 mmol/L, 82.3% and 10.6%, with 30 mmol/L of ammonium ion and 1% (V/V) of glycerol, respectively. Ammonium ion not only strengthened the glycolytic pathway, but also coordinated the reaction rate between the glycolytic pathway and the Kennedy pathway. Glycerol alleviated the activity decrease of the key enzymes in the mixture.

  17. 9 CFR 112.3 - Diluent labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.3 Diluent... organisms or viruses, the notice, “Burn this container and all unused contents,” except that, in the case...

  18. Synthesis of 5-nitro-2-(N-3-(4-azidophenyl)-propylamino)-benzoic acid: Photoaffinity labeling of human red blood cell ghosts with a 5-nitro-2-(3-phenylpropylamino)-benzoic acid analog

    SciTech Connect

    Branchini, B.R.; Murtiashaw, M.H.; Egan, L.A. )

    1991-04-15

    A photoaffinity analog of the potent epithelial chloride channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoic acid has been synthesized and characterized. In the dark, this reagent, 5-nitro-2-(N-3-(4-azidophenyl)-propylamino)-benzoic acid, and the parent compound reversibly inhibited chloride efflux in human red blood cell ghosts. Irradiation of ghost membranes with 350 microM arylazide analog reduced the rate of chloride efflux to 33% of the control value. The photoinactivation process was not reversed by exhaustive washing of ghost membranes. Covalent incorporation of the photoaffinity reagent was supported by difference ultraviolet spectroscopy, which indicated the attachment of the substituted 2-amino-5-nitrobenzoic acid chromophore to ghost membranes. The novel photolabeling agent described here should be a useful structural probe for chloride channels in erythrocyte membranes and epithelial cells.

  19. Of the Nine Cytidine Deaminase-Like Genes in Arabidopsis, Eight Are Pseudogenes and Only One Is Required to Maintain Pyrimidine Homeostasis in Vivo.

    PubMed

    Chen, Mingjia; Herde, Marco; Witte, Claus-Peter

    2016-06-01

    CYTIDINE DEAMINASE (CDA) catalyzes the deamination of cytidine to uridine and ammonia in the catabolic route of C nucleotides. The Arabidopsis (Arabidopsis thaliana) CDA gene family comprises nine members, one of which (AtCDA) was shown previously in vitro to encode an active CDA. A possible role in C-to-U RNA editing or in antiviral defense has been discussed for other members. A comprehensive bioinformatic analysis of plant CDA sequences, combined with biochemical functionality tests, strongly suggests that all Arabidopsis CDA family members except AtCDA are pseudogenes and that most plants only require a single CDA gene. Soybean (Glycine max) possesses three CDA genes, but only two encode functional enzymes and just one has very high catalytic efficiency. AtCDA and soybean CDAs are located in the cytosol. The functionality of AtCDA in vivo was demonstrated with loss-of-function mutants accumulating high amounts of cytidine but also CMP, cytosine, and some uridine in seeds. Cytidine hydrolysis in cda mutants is likely caused by NUCLEOSIDE HYDROLASE1 (NSH1) because cytosine accumulation is strongly reduced in a cda nsh1 double mutant. Altered responses of the cda mutants to fluorocytidine and fluorouridine indicate that a dual specific nucleoside kinase is involved in cytidine as well as uridine salvage. CDA mutants display a reduction in rosette size and have fewer leaves compared with the wild type, which is probably not caused by defective pyrimidine catabolism but by the accumulation of pyrimidine catabolism intermediates reaching toxic concentrations. PMID:27208239

  20. Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine Deaminases ▿

    PubMed Central

    Dörrschuck, Eva; Fischer, Nicole; Bravo, Ignacio G.; Hanschmann, Kay-Martin; Kuiper, Heidi; Spötter, Andreas; Möller, Ronny; Cichutek, Klaus; Münk, Carsten; Tönjes, Ralf R.

    2011-01-01

    Xenotransplantation of porcine cells, tissues, and organs shows promise to surmount the shortage of human donor materials. Among the barriers to pig-to-human xenotransplantation are porcine endogenous retroviruses (PERV) since functional representatives of the two polytropic classes, PERV-A and PERV-B, are able to infect human embryonic kidney cells in vitro, suggesting that a xenozoonosis in vivo could occur. To assess the capacity of human and porcine cells to counteract PERV infections, we analyzed human and porcine APOBEC3 (A3) proteins. This multigene family of cytidine deaminases contributes to the cellular intrinsic immunity and act as potent inhibitors of retroviruses and retrotransposons. Our data show that the porcine A3 gene locus on chromosome 5 consists of the two single-domain genes A3Z2 and A3Z3. The evolutionary relationships of the A3Z3 genes reflect the evolutionary history of mammals. The two A3 genes encode at least four different mRNAs: A3Z2, A3Z3, A3Z2-Z3, and A3Z2-Z3 splice variant A (SVA). Porcine and human A3s have been tested toward their antiretroviral activity against PERV and murine leukemia virus (MuLV) using novel single-round reporter viruses. The porcine A3Z2, A3Z3 and A3Z2-Z3 were packaged into PERV particles and inhibited PERV replication in a dose-dependent manner. The antiretroviral effect correlated with editing by the porcine A3s with a trinucleotide preference for 5′ TGC for A3Z2 and A3Z2-Z3 and 5′ CAC for A3Z3. These results strongly imply that human and porcine A3s could inhibit PERV replication in vivo, thereby reducing the risk of infection of human cells by PERV in the context of pig-to-human xenotransplantation. PMID:21307203

  1. The role of Drosophila cytidine monophosphate-sialic acid synthetase in the nervous system.

    PubMed

    Islam, Rafique; Nakamura, Michiko; Scott, Hilary; Repnikova, Elena; Carnahan, Mindy; Pandey, Dheeraj; Caster, Courtney; Khan, Saba; Zimmermann, Tina; Zoran, Mark J; Panin, Vladislav M

    2013-07-24

    While sialylation plays important functions in the nervous system, the complexity of glycosylation pathways and limitations of genetic approaches preclude the efficient analysis of these functions in mammalian organisms. Drosophila has recently emerged as a promising model for studying neural sialylation. Drosophila sialyltransferase, DSiaT, was shown to be involved in the regulation of neural transmission. However, the sialylation pathway was not investigated in Drosophila beyond the DSiaT-mediated step. Here we focused on the function of Drosophila cytidine monophosphate-sialic acid synthetase (CSAS), the enzyme providing a sugar donor for DSiaT. Our results revealed that the expression of CSAS is tightly regulated and restricted to the CNS throughout development and in adult flies. We generated CSAS mutants and analyzed their phenotypes using behavioral and physiological approaches. Our experiments demonstrated that mutant phenotypes of CSAS are similar to those of DSiaT, including decreased longevity, temperature-induced paralysis, locomotor abnormalities, and defects of neural transmission at neuromuscular junctions. Genetic interactions between CSAS, DSiaT, and voltage-gated channel genes paralytic and seizure were consistent with the hypothesis that CSAS and DSiaT function within the same pathway regulating neural excitability. Intriguingly, these interactions also suggested that CSAS and DSiaT have some additional, independent functions. Moreover, unlike its mammalian counterparts that work in the nucleus, Drosophila CSAS was found to be a glycoprotein-bearing N-glycans and predominantly localized in vivo to the Golgi compartment. Our work provides the first systematic analysis of in vivo functions of a eukaryotic CSAS gene and sheds light on evolutionary relationships among metazoan CSAS proteins.

  2. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations.

    PubMed

    Sawai, Yugo; Kodama, Yuzo; Shimizu, Takahiro; Ota, Yuji; Maruno, Takahisa; Eso, Yuji; Kurita, Akira; Shiokawa, Masahiro; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumoto, Yuko; Masui, Toshihiko; Uemoto, Shinji; Marusawa, Hiroyuki; Chiba, Tsutomu

    2015-08-15

    Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC.

  3. Adsorption of nucleotides on biomimetic apatite: The case of cytidine 5' monophosphate (CMP).

    PubMed

    Choimet, Maëla; Tourrette, Audrey; Drouet, Christophe

    2015-10-15

    The chemical interaction between DNA macromolecules and hard tissues in vertebrate is of foremost importance in paleogenetics, as bones and teeth represent a major substrate for the genetic material after cell death. Recently, the empirical hypothesis of DNA "protection" over time thanks to its adsorption on hard tissues was revisited from a physico-chemical viewpoint. In particular, the existence of a strong interaction between phosphate groups of DNA backbone and the surface of apatite nanocrystals (mimicking bone/dentin mineral) was evidenced on an experimental basis. In the field of nanomedicine, DNA or RNA can be used for gene transport into cells, and apatite nanocarriers then appear promising. In order to shed some more light on interactions between DNA molecules and apatite, the present study focuses on the adsorption of a "model" nucleotide, cytidine 5' monophosphate (CMP), on a carbonated biomimetic apatite sample. The follow-up of CMP kinetics of adsorption pointed out the rapidity of interaction with stabilization reached within few minutes. The adsorption isotherm could be realistically fitted to the Sips model (Langmuir-Freundlich) suggesting the influence of surface heterogeneities and adsorption cooperativity in the adsorption process. The desorption study pointed out the reversible character of CMP adsorption on biomimetic apatite. This contribution is intended to prove helpful in view of better apprehending the molecular interaction of DNA fragments and apatite compounds, independently of the application domain, such as bone diagenesis or nanomedicine. This study may also appear informative for researchers interested in the origins of life on Earth and the occurrence and behavior of primitive biomolecules.

  4. Adsorption of nucleotides on biomimetic apatite: The case of cytidine 5' monophosphate (CMP).

    PubMed

    Choimet, Maëla; Tourrette, Audrey; Drouet, Christophe

    2015-10-15

    The chemical interaction between DNA macromolecules and hard tissues in vertebrate is of foremost importance in paleogenetics, as bones and teeth represent a major substrate for the genetic material after cell death. Recently, the empirical hypothesis of DNA "protection" over time thanks to its adsorption on hard tissues was revisited from a physico-chemical viewpoint. In particular, the existence of a strong interaction between phosphate groups of DNA backbone and the surface of apatite nanocrystals (mimicking bone/dentin mineral) was evidenced on an experimental basis. In the field of nanomedicine, DNA or RNA can be used for gene transport into cells, and apatite nanocarriers then appear promising. In order to shed some more light on interactions between DNA molecules and apatite, the present study focuses on the adsorption of a "model" nucleotide, cytidine 5' monophosphate (CMP), on a carbonated biomimetic apatite sample. The follow-up of CMP kinetics of adsorption pointed out the rapidity of interaction with stabilization reached within few minutes. The adsorption isotherm could be realistically fitted to the Sips model (Langmuir-Freundlich) suggesting the influence of surface heterogeneities and adsorption cooperativity in the adsorption process. The desorption study pointed out the reversible character of CMP adsorption on biomimetic apatite. This contribution is intended to prove helpful in view of better apprehending the molecular interaction of DNA fragments and apatite compounds, independently of the application domain, such as bone diagenesis or nanomedicine. This study may also appear informative for researchers interested in the origins of life on Earth and the occurrence and behavior of primitive biomolecules. PMID:26117294

  5. Iron inhibits activation-induced cytidine deaminase enzymatic activity and modulates immunoglobulin class switch DNA recombination.

    PubMed

    Li, Guideng; Pone, Egest J; Tran, Daniel C; Patel, Pina J; Dao, Lisa; Xu, Zhenming; Casali, Paolo

    2012-06-15

    Immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM) are critical for the maturation of the antibody response. Activation-induced cytidine deaminase (AID) initiates CSR and SHM by deaminating deoxycytidines (dCs) in switch (S) and V(D)J region DNA, respectively, to generate deoxyuracils (dUs). Processing of dUs by uracil DNA glycosylase (UNG) yields abasic sites, which are excised by apurinic/apyrimidinic endonucleases, eventually generating double strand DNA breaks, the obligatory intermediates of CSR. Here, we found that the bivalent iron ion (Fe(2+), ferrous) suppressed CSR, leading to decreased number of switched B cells, decreased postrecombination Iμ-C(H) transcripts, and reduced titers of secreted class-switched IgG1, IgG3, and IgA antibodies, without alterations in critical CSR factors, such as AID, 14-3-3γ, or PTIP, or in general germline I(H)-S-C(H) transcription. Fe(2+) did not affect B cell proliferation or plasmacytoid differentiation. Rather, it inhibited AID-mediated dC deamination in a dose-dependent fashion. The inhibition of intrinsic AID enzymatic activity by Fe(2+) was specific, as shown by lack of inhibition of AID-mediated dC deamination by other bivalent metal ions, such as Zn(2+), Mn(2+), Mg(2+), or Ni(2+), and the inability of Fe(2+) to inhibit UNG-mediated dU excision. Overall, our findings have outlined a novel role of iron in modulating a B cell differentiation process that is critical to the generation of effective antibody responses to microbial pathogens and tumoral cells. They also suggest a possible role of iron in dampening AID-dependent autoimmunity and neoplastic transformation.

  6. Unusual C7- versus Normal 5'-O-Dimethoxytritylation of 6-Arylpyrrolocytidine Analogs.

    PubMed

    Suchý, Mojmír; Ettles, Christie; Wisner, James A; Matarazzo, Augusto; Hudson, Robert H E

    2016-09-16

    Fluorescent deoxynucleosides possessing the modified bases 6-(2-benzo[b]furyl)- and 6-(2-furyl)pyrrolocytosine (BFpC and FpC) have been synthesized along with the quencher nucleosides possessing 6-{4-[(4-dimethylamino)azo]phenyl}pyrrolocytosine (DABCYLpC) and 6-(p-nitrophenyl)pyrrolocytosine (p-NO2-PhpC) nucleobase analogs. Standard treatment of BFpC, FpC, DABCYLpC, and p-NO2-PhpC with dimethoxytrityl chloride (DMT-Cl) led to the unusual substitution on the C7 of the pyrrolocytosine skeleton. The desired 5'-O-DMT-protected nucleoside analogs were synthesized from suitably protected 5'-O-DMT cytidines. Subsequent phosphitylation smoothly afforded BFpC-, FpC-, DABCYLpC-, and p-NO2-PhpC-derived monomers suitable for standard oligonucleotide synthesis. PMID:27529362

  7. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  8. Reparameterization of RNA chi Torsion Parameters for the AMBER Force Field and Comparison to NMR Spectra for Cytidine and Uridine.

    PubMed

    Yildirim, Ilyas; Stern, Harry A; Kennedy, Scott D; Tubbs, Jason D; Turner, Douglas H

    2010-05-11

    A reparameterization of the torsional parameters for the glycosidic dihedral angle, chi, for the AMBER99 force field in RNA nucleosides is used to provide a modified force field, AMBER99chi. Molecular dynamics simulations of cytidine, uridine, adenosine, and guanosine in aqueous solution using the AMBER99 and AMBER99chi force fields are compared with NMR results. For each nucleoside and force field, 10 individual molecular dynamics simulations of 30 ns each were run. For cytidine with AMBER99chi force field, each molecular dynamics simulation time was extended to 120 ns for convergence purposes. Nuclear magnetic resonance (NMR) spectroscopy, including one-dimensional (1D) (1)H, steady-state 1D (1)H nuclear Overhauser effect (NOE), and transient 1D (1)H NOE, was used to determine the sugar puckering and preferred base orientation with respect to the ribose of cytidine and uridine. The AMBER99 force field overestimates the population of syn conformations of the base orientation and of C2'-endo sugar puckering of the pyrimidines, while the AMBER99chi force field's predictions are more consistent with NMR results. Moreover, the AMBER99 force field prefers high anti conformations with glycosidic dihedral angles around 310 degrees for the base orientation of purines. The AMBER99chi force field prefers anti conformations around 185 degrees , which is more consistent with the quantum mechanical calculations and known 3D structures of folded ribonucleic acids (RNAs). Evidently, the AMBER99chi force field predicts the structural characteristics of ribonucleosides better than the AMBER99 force field and should improve structural and thermodynamic predictions of RNA structures.

  9. HIV-1 Vif Versus the APOBEC3 Cytidine Deaminases: An Intracellular Duel Between Pathogen and Host Restriction Factors

    PubMed Central

    Wissing, Silke; Galloway, Nicole L. K.; Greene, Warner C.

    2010-01-01

    The Vif protein of HIV is essential for the effective propagation of this pathogenic retrovirus in vivo. Vif acts by preventing virion encapsidation of two potent antiviral factors, the APOBEC3G and APOBEC3F cytidine deaminases. Decreased encapsidation in part involves Vif-mediated recruitment of a ubiquitin E3 ligase complex that promotes polyubiquitylation and proteasome-mediated degradation of APOBEC3G/F. The resultant decline in intracellular levels of these enzymes leads to decreased encapsidation of APOBECG/F into budding virions. This review discusses recent advances in our understanding of the dynamic interplay of Vif with the antiviral APOBEC3 enzymes. PMID:20538015

  10. HIV-1 Vif versus the APOBEC3 cytidine deaminases: an intracellular duel between pathogen and host restriction factors.

    PubMed

    Wissing, Silke; Galloway, Nicole L K; Greene, Warner C

    2010-10-01

    The Vif protein of HIV is essential for the effective propagation of this pathogenic retrovirus in vivo. Vif acts by preventing virion encapsidation of two potent antiviral factors, the APOBEC3G and APOBEC3F cytidine deaminases. Decreased encapsidation in part involves Vif-mediated recruitment of a ubiquitin E3 ligase complex that promotes polyubiquitylation and proteasome-mediated degradation of APOBEC3G/F. The resultant decline in intracellular levels of these enzymes leads to decreased encapsidation of APOBECG/F into budding virions. This review discusses recent advances in our understanding of the dynamic interplay of Vif with the antiviral APOBEC3 enzymes. PMID:20538015

  11. Non-enzymatic synthesis of the coenzymes, uridine diphosphate glucose and cytidine diphosphate choline, and other phosphorylated metabolic intermediates

    NASA Technical Reports Server (NTRS)

    Mar, A.; Dworkin, J.; Oro, J.

    1987-01-01

    Using urea and cyanamide, the two condensing agents considered to have been present on the primitive earth, uridine diphosphate glucose (UDPG), cytidine diphosphate choline (CDP-choline), glucose-1-phosphate (G1P), and glucose-6-phosphate (G6P) were synthesized under simulated prebiotic conditions. The reaction products were separated and identified using paper chromatography, thin layer chromatography, enzymatic analyses, and ion-pair reverse-phase high performance liquid chromatography. The possibility of nonenzymatic synthesis of metabolic intermediates on the primitive earth from simple precursors was thus demonstrated.

  12. 9 CFR 112.3 - Diluent labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Diluent labels. 112.3 Section 112.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.3...

  13. 9 CFR 112.3 - Diluent labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Diluent labels. 112.3 Section 112.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.3...

  14. 9 CFR 116.3 - Label records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Label records. 116.3 Section 116.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS RECORDS AND REPORTS § 116.3 Label records. (a) Each licensee and permittee...

  15. Synthesis of isotopically labeled P-site substrates for the ribosomal peptidyl transferase reaction

    PubMed Central

    Zhong, Minghong

    2010-01-01

    Isotopomers of the ribosomal P-site substrate, the trinucleotide peptide conjugate CCA-pcb,1 have been designed and synthesized in 26–350020steps. These include individual isotopic substitution at the α-proton, carbonyl carbon, and carbonyl oxygen of the amino acid, the O2' and O3' of the adenosine, and a remote label in the N3 and N4 of both cytidines. These isotopomers were synthesized by coupling cytidylyl-(3'5')-cytidine phosphoramidite isotopomers, as the common synthetic intermediates, with isotopically substituted A-Phe-cap-biotin (A-pcb). The isotopic enrichment is higher than 99% for 1-13C (Phe), 2-2H (Phe), and 3,4-15N2 (cytidine), 93% for 2'/3'- 18O (adenosine), and 64% for 1-18O (Phe). A new synthesis of highly enriched [1-18O2] phenylalanine has been developed. The synthesis of [3'-18O] adenosine was improved by Lewis acid aided regioselective ring opening of the epoxide and by an economical SN2-SN2 method with high isotopic enrichment (93%). Such substrates are valuable for studies of the ribosomal peptidyl transferase reaction by complete kinetic isotope effect analysis and of other biological processes catalyzed by nucleic acid related enzymes, including polymerases, reverse transcriptases, ligases, nucleases, and ribozymes. PMID:18081346

  16. Nutrition Labeling

    NASA Astrophysics Data System (ADS)

    Metzger, Lloyd E.

    Nutrition labeling regulations differ in countries around the world. The focus of this chapter is on nutrition labeling regulations in the USA, as specified by the Food and Drug Administration (FDA) and the Food Safety and Inspection Service (FSIS) of the United States Department of Agriculture (USDA). A major reason for analyzing the chemical components of foods in the USA is nutrition labeling regulations. Nutrition label information is not only legally required in many countries, but also is of increasing importance to consumers as they focus more on health and wellness.

  17. Analog, still without fear

    NASA Astrophysics Data System (ADS)

    Delagrange, A. D.

    1984-09-01

    This report is an update of one issued in 1977 which predicted that the predicted death of analog circuitry (also called linear) would not occur; in fact, the patient appeared remarkably healthy. The report proved correct. We have the same situation again today: the same predictions and counter-prediction. Each year brings significant advances in the field of analog integrated circuitry. Many of the traditional arguments against analog circuitry are no longer valid. This report attempts to summarize what is available now, and what can (and cannot) be done with analog integrated circuits. It defines analog and makes some comparisons with digital. The most common types of analog integrated circuits are then listed and discussed. Lastly, some design and trouble-shooting hints are given, and the state-of-the-art is discussed.

  18. Pm-149 DOTA bombesin analogs for potential radiotherapy. in vivo comparison with Sm-153 and Lu-177 labeled DO3A-amide-betaAla-BBN(7-14)NH(2).

    PubMed

    Hu, Fang; Cutler, Cathy S; Hoffman, Timothy; Sieckman, Gary; Volkert, Wynn A; Jurisson, Silvia S

    2002-05-01

    Promethium-149 (149Pm) is one of only three radiolanthanides that can be prepared in no carrier added concentrations. This high specific activity radiolanthanide is thus suitable for targeting limited numbers of specific receptors found on many tumor cells. Promethium-149 is a moderate energy beta(-) emitter (1.07 MeV (95.9%)) with a half-life of 2.21 days. Pm-149 also emits a low abundance of an imageable gamma ray (286 keV (3%)) that may allow in vivo tracking of the therapeutic dose. The 149Pm and Sm complexes with the DO3A-amide chelator with zero and three carbon spacers to the bombesin peptide analog BBN(7-14)NH(2) were synthesized and characterized. The Sm complexes were synthesized for macroscopic characterization purposes (ESI-MS, in vitro cell binding) since no stable isotopes of Pm are known. The biological properties of the 149Pm, 153Sm and 177Lu-DO3A-amide-betaAla-BBN complexes were compared in normal mouse biodistribution studies.

  19. 9 CFR 112.10 - Special packaging and labeling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Special packaging and labeling. 112.10... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND LABELING § 112.10 Special packaging and labeling. A biological product, which requires special packaging...

  20. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

    A nonvolatile analog memory uses pairs of ferroelectric field effect transistors (FFETs). Each pair is defined by a first FFET and a second FFET. When an analog value is to be stored in one of the pairs, the first FFET has a saturation voltage applied thereto, and the second FFET has a storage voltage applied thereto that is indicative of the analog value. The saturation and storage voltages decay over time in accordance with a known decay function that is used to recover the original analog value when the pair of FFETs is read.

  1. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  2. Self-assembly of a chiral carbonate- and cytidine-containing dodecanuclear copper(II) complex: a multiarm-supplied globular capsule.

    PubMed

    Armentano, Donatella; Marino, Nadia; Mastropietro, Teresa F; Martínez-Lillo, José; Cano, Joan; Julve, Miguel; Lloret, Francesc; De Munno, Giovanni

    2008-11-17

    A dodecanuclear copper(II) globular-shaped structure has been obtained with the cytidine nucleoside and the templating carbonate anion. It shows receptor properties through anion-cation and multiple anion-pi interactions toward ClO 4 (-) as well as an overall antiferromagnetic coupling.

  3. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  4. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  5. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  6. Labeled nucleotide phosphate (NP) probes

    SciTech Connect

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2009-02-03

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  7. In Silico Discovery of Potential Uridine-Cytidine Kinase 2 Inhibitors from the Rhizome of Alpinia mutica.

    PubMed

    Malami, Ibrahim; Abdul, Ahmad Bustamam; Abdullah, Rasedee; Bt Kassim, Nur Kartinee; Waziri, Peter; Christopher Etti, Imaobong

    2016-01-01

    Uridine-cytidine kinase 2 is implicated in uncontrolled proliferation of abnormal cells and it is a hallmark of cancer, therefore, there is need for effective inhibitors of this key enzyme. In this study, we employed the used of in silico studies to find effective UCK2 inhibitors of natural origin using bioinformatics tools. An in vitro kinase assay was established by measuring the amount of ADP production in the presence of ATP and 5-fluorouridine as a substrate. Molecular docking studies revealed an interesting ligand interaction with the UCK2 protein for both flavokawain B and alpinetin. Both compounds were found to reduce ADP production, possibly by inhibiting UCK2 activity in vitro. In conclusion, we have identified flavokawain B and alpinetin as potential natural UCK2 inhibitors as determined by their interactions with UCK2 protein using in silico molecular docking studies. This can provide information to identify lead candidates for further drug design and development. PMID:27070566

  8. Cytidine 5′-Diphosphocholine (Citicoline) in Glaucoma: Rationale of Its Use, Current Evidence and Future Perspectives

    PubMed Central

    Roberti, Gloria; Tanga, Lucia; Michelessi, Manuele; Quaranta, Luciano; Parisi, Vincenzo; Manni, Gianluca; Oddone, Francesco

    2015-01-01

    Cytidine 5′-diphosphocholine or citicoline is an endogenous compound that acts in the biosynthetic pathway of phospholipids of cell membranes, particularly phosphatidylcholine, and it is able to increase neurotrasmitters levels in the central nervous system. Citicoline has shown positive effects in Parkinson’s disease and Alzheimer’s disease, as well as in amblyopia. Glaucoma is a neurodegenerative disease currently considered a disease involving ocular and visual brain structures. Neuroprotection has been proposed as a valid therapeutic option for those patients progressing despite a well-controlled intraocular pressure, the main risk factor for the progression of the disease. The aim of this review is to critically summarize the current evidence about the effect of citicoline in glaucoma. PMID:26633368

  9. Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in both cytidine deaminase domains of Apobec3G.

    PubMed

    Uyttendaele, Isabel; Lavens, Delphine; Catteeuw, Dominiek; Lemmens, Irma; Bovijn, Celia; Tavernier, Jan; Peelman, Frank

    2012-01-01

    The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultaneously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization. PMID:22970171

  10. Random Mutagenesis MAPPIT Analysis Identifies Binding Sites for Vif and Gag in Both Cytidine Deaminase Domains of Apobec3G

    PubMed Central

    Uyttendaele, Isabel; Lavens, Delphine; Catteeuw, Dominiek; Lemmens, Irma; Bovijn, Celia

    2012-01-01

    The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultanously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization. PMID:22970171

  11. Fate Mapping for Activation-Induced Cytidine Deaminase (AID) Marks Non-Lymphoid Cells During Mouse Development

    PubMed Central

    Rommel, Philipp C.; Bosque, David; Gitlin, Alexander D.; Croft, Gist F.; Heintz, Nathaniel; Casellas, Rafael; Nussenzweig, Michel C.; Kriaucionis, Skirmantas; Robbiani, Davide F.

    2013-01-01

    The Aicda gene encodes Activation-Induced cytidine Deaminase (AID), an enzyme essential for remodeling antibody genes in mature B lymphocytes. AID is also responsible for DNA damage at oncogenes, leading to their mutation and cancer-associated chromosome translocation in lymphoma. We used fate mapping and AIDGFP reporter mice to determine if AID expression in the mouse extends beyond lymphocytes. We discovered that AIDcre tags a small fraction of non-lymphoid cells starting at 10.5 days post conception (dpc), and that AIDGFP+ cells are detectable at dpc 11.5 and 12.5. Embryonic cells are tagged by AIDcre in the submandibular region, where conditional deletion of the tumor suppressor PTEN causes squamous papillomas. AIDcre also tags non-lymphoid cells in the embryonic central nervous system. Finally, in the adult mouse brain, AIDcre marks a small fraction of diverse neurons and distinct neuronal populations, including pyramidal cells in cortical layer IV. PMID:23861962

  12. Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance.

    PubMed

    Cantaert, Tineke; Schickel, Jean-Nicolas; Bannock, Jason M; Ng, Yen-Shing; Massad, Christopher; Oe, Tyler; Wu, Renee; Lavoie, Aubert; Walter, Jolan E; Notarangelo, Luigi D; Al-Herz, Waleed; Kilic, Sara Sebnem; Ochs, Hans D; Nonoyama, Shigeaki; Durandy, Anne; Meffre, Eric

    2015-11-17

    Activation-induced cytidine deaminase (AID), the enzyme-mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells.

  13. Cytidine deaminases from B. subtilis and E. coli: compensating effects of changing zinc coordination and quaternary structure.

    PubMed

    Carlow, D C; Carter, C W; Mejlhede, N; Neuhard, J; Wolfenden, R

    1999-09-21

    Cytidine deaminase from E. coli is a dimer of identical subunits (M(r) = 31 540), each containing a single zinc atom. Cytidine deaminase from B. subtilis is a tetramer of identical subunits (M(r) = 14 800). After purification from an overexpressing strain, the enzyme from B. subtilis is found to contain a single atom of zinc per enzyme subunit by flame atomic absorption spectroscopy. Fluorescence titration indicates that each of the four subunits contains a binding site for the transition state analogue inhibitor 5-fluoro-3,4-dihydrouridine. A region of amino acid sequence homology, containing residues that are involved in zinc coordination in the enzyme from E. coli, strongly suggests that in the enzyme from B. subtilis, zinc is coordinated by the thiolate side chains of three cysteine residues (Cys-53, Cys-86, and Cys-89) [Song, B. H., and Neuhard, J. (1989) Mol. Gen. Genet. 216, 462-468]. This pattern of zinc coordination appears to be novel for a hydrolytic enzyme, and might be expected to reduce the reactivity of the active site substantially compared with that of the enzyme from E. coli (His-102, Cys-129, and Cys-132). Instead, the B. subtilis and E. coli enzymes are found to be similar in their activities, and also in their relative binding affinities for a series of structurally related inhibitors with binding affinities that span a range of 6 orders of magnitude. In addition, the apparent pK(a) value of the active site is shifted upward by less than 1 unit. Sequence alignments, together with model building, suggest one possible mechanism of compensation.

  14. Reactions of an osmium-hexahydride complex with cytosine, deoxycytidine, and cytidine: the importance of the minor tautomers.

    PubMed

    Esteruelas, Miguel A; García-Raboso, Jorge; Oliván, Montserrat

    2012-09-01

    Complex OsH(6)(P(i)Pr(3))(2) (1) deprotonates cytosine to give molecular hydrogen and the d(4)-trihydride derivative OsH(3)(cytosinate)(P(i)Pr(3))(2) (2), which in solution exists as a mixture of isomers containing κ(2)-N1,O (2a) and κ(2)-N3,O (2b) amino-oxo and κ(2)-N3,N4 (2c) imino-oxo tautomers. The major isomer 2b associates with the minor one 2c through N-H···N and N-H···O hydrogen bonds to form [2b·2c](2) dimers, which crystallize from saturated pentane solutions of 2. Complex 1 is also able to perform the double deprotonation of cytosine (cytosinate') to afford the dinuclear derivative (P(i)Pr(3))(2)H(3)Os(cytosinate')OsH(3)(P(i)Pr(3))(2) (3), where the anion is coordinated κ(2)-N1,O and κ(2)-N3,N4 to two different OsH(3)(P(i)Pr(3))(2) metal fragments. The deprotonation of deoxycytidine and cytidine leads to OsH(3)(deoxycytidinate)(P(i)Pr(3))(2) (4) and OsH(3)(cytidinate)(P(i)Pr(3))(2) (5), respectively, containing the anion κ(2)-N3,N4 coordinated. Dimer [2b·2c](2) and dinuclear complex 3 have been characterized by X-ray diffraction analysis.

  15. Meat analog: a review.

    PubMed

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers.

  16. Challenges in Using Analogies

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-11-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features.1-7 One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  17. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  18. Gravito-electromagnetic analogies

    NASA Astrophysics Data System (ADS)

    Costa, L. Filipe O.; Natário, José

    2014-10-01

    We reexamine and further develop different gravito-electromagnetic (GEM) analogies found in the literature, and clarify the connection between them. Special emphasis is placed in two exact physical analogies: the analogy based on inertial fields from the so-called "1+3 formalism", and the analogy based on tidal tensors. Both are reformulated, extended and generalized. We write in both formalisms the Maxwell and the full exact Einstein field equations with sources, plus the algebraic Bianchi identities, which are cast as the source-free equations for the gravitational field. New results within each approach are unveiled. The well known analogy between linearized gravity and electromagnetism in Lorentz frames is obtained as a limiting case of the exact ones. The formal analogies between the Maxwell and Weyl tensors are also discussed, and, together with insight from the other approaches, used to physically interpret gravitational radiation. The precise conditions under which a similarity between gravity and electromagnetism occurs are discussed, and we conclude by summarizing the main outcome of each approach.

  19. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  20. Electrical analogous in viscoelasticity

    NASA Astrophysics Data System (ADS)

    Ala, Guido; Di Paola, Mario; Francomano, Elisa; Li, Yan; Pinnola, Francesco P.

    2014-07-01

    In this paper, electrical analogous models of fractional hereditary materials are introduced. Based on recent works by the authors, mechanical models of materials viscoelasticity behavior are firstly approached by using fractional mathematical operators. Viscoelastic models have elastic and viscous components which are obtained by combining springs and dashpots. Various arrangements of these elements can be used, and all of these viscoelastic models can be equivalently modeled as electrical circuits, where the spring and dashpot are analogous to the capacitance and resistance, respectively. The proposed models are validated by using modal analysis. Moreover, a comparison with numerical experiments based on finite difference time domain method shows that, for long time simulations, the correct time behavior can be obtained only with modal analysis. The use of electrical analogous in viscoelasticity can better reveal the real behavior of fractional hereditary materials.

  1. Analogical Reasoning in Geometry Education

    ERIC Educational Resources Information Center

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  2. Digital and analog communication systems

    NASA Technical Reports Server (NTRS)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  3. Analogy, explanation, and proof

    PubMed Central

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  4. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  5. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  6. Reasoning through Instructional Analogies

    ERIC Educational Resources Information Center

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  7. How Analogy Drives Physics

    SciTech Connect

    Hofstadter, Doug

    2004-05-05

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  8. Analog signal isolation techniques

    SciTech Connect

    Beadle, E.R.

    1992-12-31

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  9. Analog signal isolation techniques

    SciTech Connect

    Beadle, E.R.

    1992-01-01

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  10. Synthesis and biodistribution of radioiodinated nicotine analogs

    SciTech Connect

    Chan, S.M.; Basmadjian, G.P.; Marten, D.F.; Sadek, S.; Magarian, R.A.; Grunder, J.R.; Ice, R.D.

    1984-01-01

    The authors reported previously on the synthesis and biodistribution of radioiodinated 5-iodonicotine. In their continuous effort to search for a potential brain as well as adrenal medulla imaging agent, the authors synthesized four radioiodinated nicotine analogs. The labeled compounds were prepared by brominating nicotinic acid, and reacting the acylated product with the appropriate amines to give the respective amides which were then reduced with diborane to the amines. I-125 labeling was done by halogen exchange. Biodistribution studies performed in female Sprague-Dawley rats showed that all these compounds were taken up rapidly by the brain and the adrenal. The highest uptake of all these compounds in both organs occurred at 2 minutes after tail vein injections. The organ:blood ratios at 2 minutes and the T/sub 1/3/ (min.) of radioactivity in these organs were compared.

  11. A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching.

    PubMed

    Hu, Yi; Ericsson, Ida; Torseth, Kathrin; Methot, Stephen P; Sundheim, Ottar; Liabakk, Nina B; Slupphaug, Geir; Di Noia, Javier M; Krokan, Hans E; Kavli, Bodil

    2013-01-23

    Activation-induced cytidine deaminase (AID) is a DNA mutator enzyme essential for adaptive immunity. AID initiates somatic hypermutation and class switch recombination (CSR) by deaminating cytosine to uracil in specific immunoglobulin (Ig) gene regions. However, other loci, including cancer-related genes, are also targeted. Thus, tight regulation of AID is crucial to balance immunity versus disease such as cancer. AID is regulated by several mechanisms including nucleocytoplasmic shuttling. Here we have studied nuclear import kinetics and subnuclear trafficking of AID in live cells and characterized in detail its nuclear localization signal. Importantly, we find that the nuclear localization signal motif also directs AID to nucleoli where it colocalizes with its interaction partner, catenin-β-like 1 (CTNNBL1), and physically associates with nucleolin and nucleophosmin. Moreover, we demonstrate that release of AID from nucleoli is dependent on its C-terminal motif. Finally, we find that CSR efficiency correlates strongly with the arithmetic product of AID nuclear import rate and DNA deamination activity. Our findings suggest that directional nucleolar transit is important for the physiological function of AID and demonstrate that nuclear/nucleolar import and DNA cytosine deamination together define the biological activity of AID. This is the first study on subnuclear trafficking of AID and demonstrates a new level in its complex regulation. In addition, our results resolve the problem related to dissociation of deamination activity and CSR activity of AID mutants.

  12. Aberrant activation-induced cytidine deaminase expression in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.

    PubMed

    Shi, Yang; Zhao, Xiaoxian; Durkin, Lisa; Rogers, Heesun Joyce; Hsi, Eric D

    2016-06-01

    Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and plays a critical role in somatic hypermutation and class-switch recombination of immunoglobulin genes. Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carries a poor prognosis and is specifically treated with tyrosine kinase inhibitors. Interestingly, AID has been shown to be aberrantly expressed and functional in Ph+ ALL and is thought to contribute to genetic instability. We hypothesized that AID might be detectable in routinely processed bone marrow biopsies by immunohistochemistry (IHC) and assist in identifying Ph+ ALL. We found that AID was expressed in 26 (70%) of 37 cases of Ph+ ALL but only 1 (2.9%) of 38 cases of Ph- ALL cases. There was a significant difference in AID expression between these 2 ALL groups (P < .001, Fisher exact test). The expression of AID was confirmed by RT-PCR (reverse-transcriptase polymerase chain reaction) and correlated with IHC scoring. AID protein is expressed in a large proportion of Ph+ ALL cases at levels detectable by IHC in clinical samples and might be useful to rapidly identify cases likely to have a BCR/ABL1 fusion. PMID:26980048

  13. [Cloning and expression analysis of 4- (cytidine-5-diphospho) -2-C-methyl-D-erythritol kinase gene in Tripterygium wilfordii].

    PubMed

    Tong, Yu-ru; Su, Ping; Zhao, Yu-jun; Zhang, Meng; Wang, Xiu-juan; Hu, Tian-yuan; Gao, Wei; Huang, Lu-qi

    2015-11-01

    4-(Cytidine-5-diphospho) -2-C-methyl-D-erythritol kinase is a key enzyme in the biosynthesis pathway of terpenoids. According to the transcriptome database, the specific primers were designed and used in PCR. The bioinformatic analysis of the sequenced TwCMK gene was performed in several bioinformatics software. The Real-time fluorescence quantification polymerase chain reaction (RT-qPCR) were used to detect the expression levels of TwCMK from T. wilfordii after elicitor MeJA supplied. The results showed that the full length of TwCMK cDNA was 1 732 bp encoding 387 amino acids. The theoretical isoelectric point of the putative TwCMK protein was 5.79 and the molecular weight was about 42.85 kDa. MeJA stimulated the rising of TwCMK expression in suspension cell and signally impacted at 24 h. The research provides a basis for further study on the regulation of terpenoid secondary metabolism and biological synthesis. PMID:27071250

  14. Generation of α1,3-galactosyltransferase and cytidine monophospho-N-acetylneuraminic acid hydroxylase gene double-knockout pigs.

    PubMed

    Miyagawa, Shuji; Matsunari, Hitomi; Watanabe, Masahito; Nakano, Kazuaki; Umeyama, Kazuhiro; Sakai, Rieko; Takayanagi, Shuko; Takeishi, Toki; Fukuda, Tooru; Yashima, Sayaka; Maeda, Akira; Eguchi, Hiroshi; Okuyama, Hiroomi; Nagaya, Masaki; Nagashima, Hiroshi

    2015-01-01

    Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are new tools for producing gene knockout (KO) animals. The current study reports produced genetically modified pigs, in which two endogenous genes were knocked out. Porcine fibroblast cell lines were derived from homozygous α1,3-galactosyltransferase (GalT) KO pigs. These cells were subjected to an additional KO for the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene. A pair of ZFN-encoding mRNAs targeting exon 8 of the CMAH gene was used to generate the heterozygous CMAH KO cells, from which cloned pigs were produced by somatic cell nuclear transfer (SCNT). One of the cloned pigs obtained was re-cloned after additional KO of the remaining CMAH allele using the same ZFN-encoding mRNAs to generate GalT/CMAH-double homozygous KO pigs. On the other hand, the use of TALEN-encoding mRNAs targeting exon 7 of the CMAH gene resulted in efficient generation of homozygous CMAH KO cells. These cells were used for SCNT to produce cloned pigs homozygous for a double GalT/CMAH KO. These results demonstrate that the combination of TALEN-encoding mRNA, in vitro selection of the nuclear donor cells and SCNT provides a robust method for generating KO pigs. PMID:26227017

  15. Synthesis of the coenzymes adenosine diphosphate glucose, guanosine diphosphate glucose, and cytidine diphosphoethanolamine under primitive Earth conditions

    NASA Technical Reports Server (NTRS)

    Mar, A.; Oro, J.

    1991-01-01

    The nonenzymatic synthesis of the coenzymes adenosine diphosphate glucose (ADPG), guanosine diphosphate glucose (GDPG), and cytidine diphosphoethanolamine (CDP-ethanolamine) has been carried out under conditions considered to have been prevalent on the early Earth. The production of these compounds was performed by allowing simple precursor molecules to react under aqueous solutions, at moderate temperatures and short periods of time, with mediation by cyanamide or urea. These two condensing agents are considered to have been present in significant amounts on the primitive Earth and have been previously used in the nonenzymatic synthesis of several other important biochemical compounds. In our experiments, ADPG was obtained by heating glucose-1-phosphate (G1P) and ATP in the presence of cyanamide for 24 h at 70 degrees C. The reaction of G1P and GTP under the same conditions yielded GDPG. The cyanamide-mediated production of CDP-ethanolamine was carried out by reacting a mixture of ethanolamine phosphate and CTP for 24 h at 70 degrees C. The separation and identification of the reaction products was carried out by paper chromatography, thin-layer chromatography, high performance thin-layer chromatography, high performance liquid chromatography, both normal and reverse-phase, UV spectroscopy, enzymatic assays, and acid hydrolysis. Due to the mild conditions employed, and to the relative ease of these reactions, these studies offer a simple attractive system for the nonenzymatic synthesis of phosphorylated high-energy metabolic intermediates under conditions considered to have been prevalent on the ancient Earth.

  16. Target sequence accessibility limits activation-induced cytidine deaminase activity in primary mediastinal B-cell lymphoma.

    PubMed

    Popov, Sergey W; Moldenhauer, Gerhard; Wotschke, Beate; Brüderlein, Silke; Barth, Thomas F; Dorsch, Karola; Ritz, Olga; Möller, Peter; Leithäuser, Frank

    2007-07-15

    Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) in activated B lymphocytes and is potentially implicated in genomic instability of B-cell malignancies. For unknown reasons, B-cell neoplasms often lack SHM and CSR in spite of high AID expression. Here, we show that primary mediastinal B-cell lymphoma (PMBL), an immunoglobulin (Ig)-negative lymphoma that possesses hypermutated, class-switched Ig genes, expresses high levels of AID with an intact primary structure but does not do CSR in 14 of 16 cases analyzed. Absence of CSR coincided with low Ig germ-line transcription, whereas high level germ-line transcription was observed only in those two cases with active CSR. Interleukin-4/CD40L costimulation induced CSR and a marked up-regulation of germ-line transcription in the PMBL-derived cell line MedB-1. In the PMBL cell line Karpas 1106P, CSR was not inducible and germ-line transcription remained low on stimulation. However, Karpas 1106P, but not MedB-1, had ongoing SHM of the Ig gene and BCL6. These genes were transcribed in Karpas 1106P, whereas transcription was undetectable or low in MedB-1 cells. Thus, accessibility of the target sequences seems to be a major limiting factor for AID-dependent somatic gene diversification in PMBL. PMID:17638864

  17. Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig loci in activated B cells

    PubMed Central

    Staszewski, Ori; Baker, Richard E.; Ucher, Anna J.; Martier, Raygene; Stavnezer, Janet; Guikema, Jeroen E.J.

    2011-01-01

    After immunization or infection, activation-induced cytidine deaminase (AID) initiates diversification of immunoglobulin (Ig) genes in B cells, introducing mutations within the antigen binding V regions (somatic hypermutation, SHM) and double-strand DNA breaks (DSBs) into switch (S) regions, leading to antibody class switch recombination (CSR). We asked if during B cell activation, AID also induces DNA breaks at genes other than IgH genes. Using a non-biased genome-wide approach, we have identified hundreds of reproducible AID-dependent DSBs in mouse splenic B cells shortly after induction of CSR in culture. Most interestingly, AID induces DSBs at sites syntenic with sites of translocations, deletions, and amplifications found in human B cell lymphomas, including within the oncogene B cell lymphoma11a (bcl11a)/evi9. Unlike AID-induced DSBs in Ig genes, genome-wide AID-dependent DSBs are not restricted to transcribed regions, and frequently occur within repeated sequence elements, including CA-repeats and non-CA tandem repeats, and SINEs. PMID:21255732

  18. Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes

    PubMed Central

    Taylor, Benjamin JM; Wu, Yee Ling; Rada, Cristina

    2014-01-01

    Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral infection. Improper access to the genome leads to translocations and mutations in B cells and contributes to the mutation landscape in cancer, such as kataegis. It remains unclear how deaminases access double stranded genomes and whether off-target mutations favor certain loci, although transcription and opportunistic access during DNA repair are thought to play a role. In yeast, AID and the catalytic domain of APOBEC3G preferentially mutate transcriptionally active genes within narrow regions, 110 base pairs in width, fixed at RNA polymerase initiation sites. Unlike APOBEC3G, AID shows enhanced mutational preference for small RNA genes (tRNAs, snoRNAs and snRNAs) suggesting a putative role for RNA in its recruitment. We uncover the high affinity of the deaminases for the single stranded DNA exposed by initiating RNA polymerases (a DNA configuration reproduced at stalled polymerases) without a requirement for specific cofactors. DOI: http://dx.doi.org/10.7554/eLife.03553.001 PMID:25237741

  19. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5.

    PubMed

    Pavri, Rushad; Gazumyan, Anna; Jankovic, Mila; Di Virgilio, Michela; Klein, Isaac; Ansarah-Sobrinho, Camilo; Resch, Wolfgang; Yamane, Arito; Reina San-Martin, Bernardo; Barreto, Vasco; Nieland, Thomas J; Root, David E; Casellas, Rafael; Nussenzweig, Michel C

    2010-10-01

    Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class switch recombination (CSR) of antibody loci. We found that Spt5, a factor associated with stalled RNA polymerase II (Pol II) and single stranded DNA (ssDNA), is required for CSR. Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II. Further, Spt5 accumulation at sites of Pol II stalling is predictive of AID-induced mutation. We propose that AID is targeted to sites of Pol II stalling in part via its association with Spt5. PMID:20887897

  20. Estradiol induces gene proximity and MLL-MLLT3 fusion in an activation-induced cytidine deaminase-mediated pathway.

    PubMed

    Wright, Rebecca L; Slemmons, Katherine K; Vaughan, Andrew T M

    2015-05-01

    Epidemiological data have linked birth control formulations to an increased risk of infant acute leukemia involving MLL rearrangements. Reverse transcription polymerase chain reaction (RT-PCR) studies showed that 10 nM estradiol enhanced MLL transcription in addition to its common translocation partners, MLLT2 (AF4) and MLLT3 (AF9). The same concentration of estradiol triggered MLL and MLLT3 co-localization without affecting the interaction of genes located on the same chromosomes. Estradiol also stimulated the generation of MLL-MLLT3 fusion transcripts as seen by RT-PCR. RNAi knockdown of activation-induced cytidine deaminase (AICDA) suppressed the induction of MLL-MLLT3 fusion transcript formation observed with estradiol. Additionally, chromatin immunoprecipitation (ChIP) analysis showed estradiol dependent localization of AICDA in MLL intron 11, upstream of a hotspot for both DNA cleavage and rearrangement, but not downstream within intron 12. Combined, these studies show that levels of estradiol consistent with that observed during pregnancy have the potential to initiate MLL fusions through an AICDA-mediated mechanism.

  1. Involvement of the histaminergic system in cytidine 5'-diphosphocholine-induced reversal of critical haemorrhagic hypotension in rats.

    PubMed

    Jochem, J; Savci, V; Filiz, N; Rybus-Kalinowska, B; Fogel, W A; Yalcin, M

    2010-02-01

    Cytidine 5'-diphosphocholine (CDP-choline) is an endogenously synthesized mononucleotide which exerts a variety of physiological effects by altering central cholinergic transmission. Administered intracerebroventricularly (i.c.v.) or intravenously, it reverses haemorrhagic hypotension in rats, apparently by the activation of central cholinergic receptors. The study was undertaken to investigate the involvement of the central histaminergic system in CDP-choline-mediated reversal of haemorrhagic hypotension. Experiments were carried out in male ketamine/xylazine-anaesthetised Wistar rats subjected to haemorrhagic hypotension of 20-26 mmHg. CDP-choline (2 micromol; i.c.v.) administered at 5 min of critical hypotension produced a long-lasting pressor effect with increases in mean arterial pressure (MAP), heart rate (HR), and renal, hindquarters and mesenteric blood flows, resulting in a 100% survival at 2 h. The action was accompanied by approximately a 26% increase in extracellular histamine concentration at the posterior hypothalamus, as measured by microdialysis. Cardiovascular effects mediated by CDP-choline were almost completely blocked by pretreatment with H(1) receptor antagonist chlorpheniramine (50 nmol; i.c.v.), but not with H(2) receptor blocker ranitidine (25 nmol; icv) or H(3)/H(4) receptor antagonist thioperamide (50 nmol; i.c.v.). In conclusion, the present results show that he central histaminergic system, through the activation of H(1) histaminergic receptors, is involved in CDP-choline-induced resuscitating effect in haemorrhage-shocked rats.

  2. Chronic lung injury by constitutive expression of activation-induced cytidine deaminase leads to focal mucous cell metaplasia and cancer.

    PubMed

    Kitamura, Jiro; Uemura, Munehiro; Kurozumi, Mafumi; Sonobe, Makoto; Manabe, Toshiaki; Hiai, Hiroshi; Date, Hiroshi; Kinoshita, Kazuo

    2015-01-01

    Activation-induced cytidine deaminase (AID) is an enzyme required for antibody diversification, and it causes DNA mutations and strand breaks. Constitutive AID expression in mice invariably caused lung lesions morphologically similar to human atypical adenomatous hyperplasia (AAH), which can be a precursor of bronchioloalveolar carcinoma. Similar to AAH, mouse AAH-like lesion (MALL) exhibited signs of alveolar differentiation, judging from the expression of alveolar type II (AT2) cell marker surfactant protein C (SP-C). However, electron microscopy indicated that MALL, which possessed certain features of a mucous cell, is distinct from an AAH or AT2 cell. Although MALL developed in all individuals within 30 weeks after birth, lung tumors occurred in only 10%; this suggests that the vast majority of MALLs fail to grow into visible tumors. MALL expressed several recently described markers of lung alveolar regeneration such as p63, keratin 5, keratin 14, leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), and Lgr6. Increased cell death was observed in the lungs of AID transgenic mice compared with wild-type mice. Based on these observations, we speculate that MALL is a regenerating tissue compensating for cellular loss caused by AID cytotoxicity. AID expression in such regenerating tissue should predispose cells to malignant transformation via its mutagenic activity. PMID:25659078

  3. Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells.

    PubMed

    Staszewski, Ori; Baker, Richard E; Ucher, Anna J; Martier, Raygene; Stavnezer, Janet; Guikema, Jeroen E J

    2011-01-21

    After immunization or infection, activation-induced cytidine deaminase (AID) initiates diversification of immunoglobulin (Ig) genes in B cells, introducing mutations within the antigen-binding V regions (somatic hypermutation, SHM) and double-strand DNA breaks (DSBs) into switch (S) regions, leading to antibody class switch recombination (CSR). We asked if, during B cell activation, AID also induces DNA breaks at genes other than IgH genes. Using a nonbiased genome-wide approach, we have identified hundreds of reproducible, AID-dependent DSBs in mouse splenic B cells shortly after induction of CSR in culture. Most interestingly, AID induces DSBs at sites syntenic with sites of translocations, deletions, and amplifications found in human B cell lymphomas, including within the oncogene B cell lymphoma11a (bcl11a)/evi9. Unlike AID-induced DSBs in Ig genes, genome-wide AID-dependent DSBs are not restricted to transcribed regions and frequently occur within repeated sequence elements, including CA repeats, non-CA tandem repeats, and SINEs.

  4. Generation of α1,3-galactosyltransferase and cytidine monophospho-N-acetylneuraminic acid hydroxylase gene double-knockout pigs

    PubMed Central

    MIYAGAWA, Shuji; MATSUNARI, Hitomi; WATANABE, Masahito; NAKANO, Kazuaki; UMEYAMA, Kazuhiro; SAKAI, Rieko; TAKAYANAGI, Shuko; TAKEISHI, Toki; FUKUDA, Tooru; YASHIMA, Sayaka; MAEDA, Akira; EGUCHI, Hiroshi; OKUYAMA, Hiroomi; NAGAYA, Masaki; NAGASHIMA, Hiroshi

    2015-01-01

    Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are new tools for producing gene knockout (KO) animals. The current study reports produced genetically modified pigs, in which two endogenous genes were knocked out. Porcine fibroblast cell lines were derived from homozygous α1,3-galactosyltransferase (GalT) KO pigs. These cells were subjected to an additional KO for the cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene. A pair of ZFN-encoding mRNAs targeting exon 8 of the CMAH gene was used to generate the heterozygous CMAH KO cells, from which cloned pigs were produced by somatic cell nuclear transfer (SCNT). One of the cloned pigs obtained was re-cloned after additional KO of the remaining CMAH allele using the same ZFN-encoding mRNAs to generate GalT/CMAH-double homozygous KO pigs. On the other hand, the use of TALEN-encoding mRNAs targeting exon 7 of the CMAH gene resulted in efficient generation of homozygous CMAH KO cells. These cells were used for SCNT to produce cloned pigs homozygous for a double GalT/CMAH KO. These results demonstrate that the combination of TALEN-encoding mRNA, in vitro selection of the nuclear donor cells and SCNT provides a robust method for generating KO pigs. PMID:26227017

  5. Identification of DNA cleavage- and recombination-specific hnRNP cofactors for activation-induced cytidine deaminase.

    PubMed

    Hu, Wenjun; Begum, Nasim A; Mondal, Samiran; Stanlie, Andre; Honjo, Tasuku

    2015-05-01

    Activation-induced cytidine deaminase (AID) is essential for antibody class switch recombination (CSR) and somatic hypermutation (SHM). AID originally was postulated to function as an RNA-editing enzyme, based on its strong homology with apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 1 (APOBEC1), the enzyme that edits apolipoprotein B-100 mRNA in the presence of the APOBEC cofactor APOBEC1 complementation factor/APOBEC complementation factor (A1CF/ACF). Because A1CF is structurally similar to heterogeneous nuclear ribonucleoproteins (hnRNPs), we investigated the involvement of several well-known hnRNPs in AID function by using siRNA knockdown and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated disruption. We found that hnRNP K deficiency inhibited DNA cleavage and thereby induced both CSR and SHM, whereas hnRNP L deficiency inhibited only CSR and somewhat enhanced SHM. Interestingly, both hnRNPs exhibited RNA-dependent interactions with AID, and mutant forms of these proteins containing deletions in the RNA-recognition motif failed to rescue CSR. Thus, our study suggests that hnRNP K and hnRNP L may serve as A1CF-like cofactors in AID-mediated CSR and SHM.

  6. SU-C-303-01: Activation-Induced Cytidine Deaminase Confers Cancer Resistance to Radiation Therapy

    SciTech Connect

    Yi, S; La Count, S; Liu, J; Bai, X; Lu, L

    2015-06-15

    Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types.

  7. Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution.

    PubMed

    Kasar, S; Kim, J; Improgo, R; Tiao, G; Polak, P; Haradhvala, N; Lawrence, M S; Kiezun, A; Fernandes, S M; Bahl, S; Sougnez, C; Gabriel, S; Lander, E S; Kim, H T; Getz, G; Brown, J R

    2015-01-01

    Patients with chromosome 13q deletion or normal cytogenetics represent the majority of chronic lymphocytic leukaemia (CLL) cases, yet have relatively few driver mutations. To better understand their genomic landscape, here we perform whole-genome sequencing on a cohort of patients enriched with these cytogenetic characteristics. Mutations in known CLL drivers are seen in only 33% of this cohort, and associated with normal cytogenetics and unmutated IGHV. The most commonly mutated gene in our cohort, IGLL5, shows a mutational pattern suggestive of activation-induced cytidine deaminase (AID) activity. Unsupervised analysis of mutational signatures demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, and an ageing signature responsible for most mutations. Using mutation clonality to infer time of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour evolution. PMID:26638776

  8. 9 CFR 101.4 - Labeling terminology.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Labeling terminology. 101.4 Section 101.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS §...

  9. 19 CFR 12.22 - Labels; samples.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Labels; samples. 12.22 Section 12.22 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Viruses, Serums, Toxins, Antitoxins, and Analogous Products for...

  10. 9 CFR 101.4 - Labeling terminology.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Labeling terminology. 101.4 Section 101.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS §...

  11. 9 CFR 101.4 - Labeling terminology.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Labeling terminology. 101.4 Section 101.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS §...

  12. 9 CFR 101.4 - Labeling terminology.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Labeling terminology. 101.4 Section 101.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS §...

  13. 9 CFR 101.4 - Labeling terminology.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Labeling terminology. 101.4 Section 101.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS §...

  14. 19 CFR 12.22 - Labels; samples.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Labels; samples. 12.22 Section 12.22 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Viruses, Serums, Toxins, Antitoxins, and Analogous Products for...

  15. 19 CFR 12.22 - Labels; samples.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Labels; samples. 12.22 Section 12.22 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Viruses, Serums, Toxins, Antitoxins, and Analogous Products for...

  16. The “Speedy” Synthesis of Atom-Specific 15N Imino/Amido-Labeled RNA

    PubMed Central

    Kreutz, Christoph; Micura, Ronald

    2016-01-01

    Although numerous reports on the synthesis of atom-specific 15N-labeled nucleosides exist, fast and facile access to the corresponding phosphoramidites for RNA solid-phase synthesis is still lacking. This situation represents a severe bottleneck for NMR spectroscopic investigations on functional RNAs. Here, we present optimized procedures to speed up the synthesis of 15N(1) adenosine and 15N(1) guanosine amidites, which are the much needed counterparts of the more straightforward-to-achieve 15N(3) uridine and 15N(3) cytidine amidites in order to tap full potential of 1H/15N/15N-COSY experiments for directly monitoring individual Watson–Crick base pairs in RNA. Demonstrated for two preQ1 riboswitch systems, we exemplify a versatile concept for individual base-pair labeling in the analysis of conformationally flexible RNAs when competing structures and conformational dynamics are encountered. PMID:26237536

  17. Terrestrial Spaceflight Analogs: Antarctica

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  18. Analog storage integrated circuit

    DOEpatents

    Walker, J. T.; Larsen, R. S.; Shapiro, S. L.

    1989-01-01

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks.

  19. Antarctic analogs for Enceladus

    NASA Astrophysics Data System (ADS)

    Murray, A. E.; Andersen, D. T.; McKay, C. P.

    2014-12-01

    Enceladus is a new world for Astrobiology. The Cassini discovery of the icy plume emanating from the South Polar region indicates an active world, where detection of water, organics, sodium, and nano-particle silica in the plume strongly suggests that the source is a subsurface salty ocean reservoir. Recent gravity data from Cassini confirms the presence of a regional sea extending north to 50°S. An ocean habitat under a thick ice cover is perhaps a recurring theme in the Outer Solar System, but what makes Enceladus unique is that the plume jetting out into space is carrying samples of this ocean. Therefore, through the study of Enceladus' plumes we can gain new insights not only of a possible habitable world in the Solar Systems, but also about the formation and evolution of other icy-satellites. Cassini has been able to fly through this plume - effectively sampling the ocean. It is time to plan for future missions that do more detailed analyses, possibly return samples back to Earth and search for evidence of life. To help prepare for such missions, the need for earth-based analog environments is essential for logistical, methodological (life detection) and theoretical development. We have undertaken studies of two terrestrial environments that are close analogs to Enceladus' ocean: Lake Vida and Lake Untersee - two ice-sealed Antarctic lakes that represent physical, chemical and possibly biological analogs for Enceladus. By studying the diverse biology and physical and chemical constraints to life in these two unique lakes we will begin to understand the potential habitability of Enceladus and other icy moons, including possible sources of nutrients and energy, which together with liquid water are the key ingredients for life. Analog research such as this will also enable us to develop and test new strategies to search for evidence of life on Enceladus.

  20. Analog storage integrated circuit

    DOEpatents

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  1. The promise of analog computation

    NASA Astrophysics Data System (ADS)

    MacLennan, B. J.

    2014-10-01

    Future computing paradigms and technologies will have to be more like the physical processes by which they are realized, and because these processes are primarily continuous, post-Moore's law computing will involve an increased use of analog computation. Traditionally analog computers have computed ordinary differential equations of time, but analog field computation permits massively parallel temporal integration of partial differential equations. In principle many different physical media - not just electronics - can be exploited to implement the basic operations of analog computing, a small number of which are sufficient to approximate a wide variety of analog computations, thus providing a basis for universal analog computation and general-purpose analog computers. The contentious issue of the computational power of analog computers is addressed best on its own terms, rather by asking it within the context of Church-Turing computation, which distorts the relevant questions and their answers.

  2. Ribonucleoside labeling with Os(VI): a methodological approach to evaluation of RNA methylation by HPLC-ICP-MS.

    PubMed

    Wrobel, Katarzyna; Rodríguez Flores, Crescencio; Chan, Qilin; Wrobel, Kazimierz

    2010-02-01

    Covalent modifications of nucleobases are thought to play an important role in regulating the functions of DNA and various cellular RNA types. Perhaps the best characterized is DNA methylation on cytosine (methyl tag attached to carbon 5 position) and such modification has also been detected in stable and long-lived RNA molecules. In this work, we propose a novel procedure enabling very sensitive quantification of methylcytidine and other ribonucleosides, based on reversed phase liquid chromatography with inductively coupled plasma mass spectrometry (ICP-MS) detection. The procedure relies on labeling ribose residues with osmium, by formation of a ternary complex between cis-diol ribose groups, hexavalent osmium (K(2)OsO(2)(OH)(4)) and tetramethylethylenediamine (TEMED). The derivatization reaction was carried out with 50 : 1 molar excess of Os to ribonucleoside, pH 4, for 2 h at room temperature. The structures of Os-labeled cytidine and methylcytidine were confirmed by electrospray ionization mass spectrometry. The separation of Os-labeled cytidine (C), uridine (U), 5-methylcytidine (5mC) and guanosine (G) was achieved on C18 column (Gemini, 150 × 3 mm, 5 μm) with isocratic elution (0.05% triethylamine + 6 mmol L(-1) ammonium acetate, pH 4.4: methanol (85 : 15)) and a total flow rate 0.6 mL min(-1). The column effluent was on-line introduced to ICP-MS (a model 7500 ce, Agilent Technologies) for specific detection at (189)Os. Calibration was performed within the concentration range 0-200 nmol L(-1) of each ribonucleoside and the analytical figures of merit were evaluated. For 100 μL injection, the detection limits for C, U, 5mC, G were 24, 38, 21 and 28 pmol L(-1), respectively. While introducing Os(vi)-TEMED to the column, it eluted in the dead volume and the detection limit for osmium was 20 pmol L(-1). The results obtained in this work might be helpful in the analysis of RNA digests, providing quantitative data on the ribonucleoside composition and

  3. Transgenerational epigenetic effects of the Apobec1 cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability.

    PubMed

    Nelson, Vicki R; Heaney, Jason D; Tesar, Paul J; Davidson, Nicholas O; Nadeau, Joseph H

    2012-10-01

    Environmental agents and genetic variants can induce heritable epigenetic changes that affect phenotypic variation and disease risk in many species. These transgenerational effects challenge conventional understanding about the modes and mechanisms of inheritance, but their molecular basis is poorly understood. The Deadend1 (Dnd1) gene enhances susceptibility to testicular germ cell tumors (TGCTs) in mice, in part by interacting epigenetically with other TGCT modifier genes in previous generations. Sequence homology to A1cf, the RNA-binding subunit of the ApoB editing complex, raises the possibility that the function of Dnd1 is related to Apobec1 activity as a cytidine deaminase. We conducted a series of experiments with a genetically engineered deficiency of Apobec1 on the TGCT-susceptible 129/Sv inbred background to determine whether dosage of Apobec1 modifies susceptibility, either alone or in combination with Dnd1, and either in a conventional or a transgenerational manner. In the paternal germ-lineage, Apobec1 deficiency significantly increased susceptibility among heterozygous but not wild-type male offspring, without subsequent transgenerational effects, showing that increased TGCT risk resulting from partial loss of Apobec1 function is inherited in a conventional manner. By contrast, partial deficiency in the maternal germ-lineage led to suppression of TGCTs in both partially and fully deficient males and significantly reduced TGCT risk in a transgenerational manner among wild-type offspring. These heritable epigenetic changes persisted for multiple generations and were fully reversed after consecutive crosses through the alternative germ-lineage. These results suggest that Apobec1 plays a central role in controlling TGCT susceptibility in both a conventional and a transgenerational manner.

  4. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA

    PubMed Central

    Gemble, Simon; Ahuja, Akshay; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Dairou, Julien; Biard, Denis S. F.; Lambert, Sarah; Lopes, Massimo; Amor-Guéret, Mounira

    2015-01-01

    Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA) deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at “difficult-to-replicate” sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS), a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3’-5’ DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects. PMID:26181065

  5. Neural Analog Information Processing

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1982-07-01

    Neural Analog Information Processing (NAIP) is an effort to develop general purpose pattern classification architectures based upon biological information processing principles. This paper gives an overview of NAIP and its relationship to the previous work in neural modeling from which its fundamental principles are derived. It also presents a theorem concerning the stability of response of a slab (a two dimensional array of identical simple processing units) to time-invariant (spatial) patterns. An experiment (via computer emulation) demonstrating classification of a spatial pattern by a simple, but complete NAIP architecture is described. A concept for hardware implementation of NAIP architectures is briefly discussed.

  6. Antarctic Space Analog Program

    NASA Technical Reports Server (NTRS)

    Palinkas, Lawrence A; Gunderson, E. K. Eric; Johnson, Jeffrey C.; Holland, Albert W.

    1998-01-01

    The primary aim of this project was to examine group dynamics and individual performance in extreme, isolated environments and identify human factors requirements for long-duration space missions using data collected in an analog environment. Specifically, we wished to determine: 1) the characteristics of social relations in small groups of individuals living and working together in extreme, isolated environments, and 2) the environmental, social and psychological determinants of performance effectiveness in such groups. These two issues were examined in six interrelated studies using data collected in small, isolated research stations in Antarctica from 1963 to the present. Results from these six studies indicated that behavior and performance on long-duration space flights is likely to be seasonal or cyclical, situational, social, and salutogenic in nature. The project responded to two NASA program emphases for FY 1997 as described in the NRA: 1) the primary emphasis of the Behavior and Performance Program on determining long-term individual and group performance responses to space, identifying critical factors affecting those responses and understanding underlying mechanisms involved in behavior and performance, and developing and using ground-based models and analogs for studying space-related behavior and performance; and 2) the emphasis of the Data Analysis Program on extended data analysis. Results from the study were used to develop recommendations for the design and development of pre-flight crew training and in-flight psychological countermeasures for long-duration manned space missions.

  7. Reversible sialylation: synthesis of cytidine 5'-monophospho-N-acetylneuraminic acid from cytidine 5'-monophosphate with alpha2,3-sialyl O-glycan-, glycolipid-, and macromolecule-based donors yields diverse sialylated products.

    PubMed

    Chandrasekaran, E V; Xue, Jun; Xia, Jie; Locke, Robert D; Matta, Khushi L; Neelamegham, Sriram

    2008-01-01

    Sialyltransferases transfer sialic acid from cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to an acceptor molecule. Trans-sialidases of parasites transfer alpha2,3-linked sialic acid from one molecule to another without the involvement of CMP-NeuAc. Here we report another type of sialylation, termed reverse sialylation, catalyzed by mammalian sialyltransferase ST3Gal-II. This enzyme synthesizes CMP-NeuAc by transferring NeuAc from the NeuAcalpha2,3Galbeta1,3GalNAcalpha unit of O-glycans, 3-sialyl globo unit of glycolipids, and sialylated macromolecules to 5'-CMP. CMP-NeuAc produced in situ is utilized by the same enzyme to sialylate other O-glycans and by other sialyltransferases such as ST6Gal-I and ST6GalNAc-I, forming alpha2,6-sialylated compounds. ST3Gal-II also catalyzed the conversion of 5'-uridine monophosphate (UMP) to UMP-NeuAc, which was found to be an inactive sialyl donor. Reverse sialylation proceeded without the need for free sialic acid, divalent metal ions, or energy. Direct sialylation with CMP-NeuAc as well as the formation of CMP-NeuAc from 5'-CMP had a wide optimum range (pH 5.2-7.2 and 4.8-6.4, respectively), whereas the entire reaction comprising in situ production of CMP-NeuAc and sialylation of acceptor had a sharp optimum at pH 5.6 (activity level 50% at pH 5.2 and 6.8, 25% at pH 4.8 and 7.2). Several properties distinguish forward/conventional versus reverse sialylation: (i) sodium citrate inhibited forward sialylation but not reverse sialylation; (ii) 5'-CDP, a potent forward sialyltransferase inhibitor, did not inhibit the conversion of 5'-CMP to CMP-NeuAc; and (iii) the mucin core 2 compound 3-O-sulfoGalbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-benzyl, an efficient acceptor for ST3Gal-II, inhibited the conversion of 5'-CMP to CMP-NeuAc. A significant level of reverse sialylation activity is noted in human prostate cancer cell lines LNCaP and PC3. Overall, the study demonstrates that the sialyltransferase reaction is

  8. Vorticity in analog gravity

    NASA Astrophysics Data System (ADS)

    Cropp, Bethan; Liberati, Stefano; Turcati, Rodrigo

    2016-06-01

    In the analog gravity framework, the acoustic disturbances in a moving fluid can be described by an equation of motion identical to a relativistic scalar massless field propagating in curved space-time. This description is possible only when the fluid under consideration is barotropic, inviscid, and irrotational. In this case, the propagation of the perturbations is governed by an acoustic metric that depends algebrically on the local speed of sound, density, and the background flow velocity, the latter assumed to be vorticity-free. In this work we provide a straightforward extension in order to go beyond the irrotational constraint. Using a charged—relativistic and nonrelativistic—Bose-Einstein condensate as a physical system, we show that in the low-momentum limit and performing the eikonal approximation we can derive a d’Alembertian equation of motion for the charged phonons where the emergent acoustic metric depends on flow velocity in the presence of vorticity.

  9. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

    Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design.

  10. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

    Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design. PMID:11987303

  11. Cytidine 5′-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

    PubMed Central

    Emril, Dessy R; Wibowo, Samekto; Meliala, Lucas; Susilowati, Rina

    2016-01-01

    Background Cytidine 5′-diphosphocholine (citicoline) has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury. Methods Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold) were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT) tests were used to assess motoric function. Results The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17) compared with the crush/saline group (53.33%, n=15, P<0.005). The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001). However, the sciatic functional index analysis did not show significant differences between groups (P=0.35). The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18) and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume. Conclusion In situ administration of 0.4 mL of 100 µmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery, evaluated by EPT test, 4 weeks after sciatic nerve injury. PMID:27284264

  12. A study of the eigenvectors of low frequency vibrational modes in crystalline cytidine via high pressure infrared absorption and molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Starkey, Carl; Woods, Kristina; Lee, Scott

    High-pressure infrared absorption experiments and molecular dynamics simulations have been used to study the eigenvectors and eigenvalues of the vibrational modes of crystalline cytidine at 295 K by evaluating the logarithmic derivative of the vibrational frequency with respect to pressure: 1/ωdω/dP . Crystalline samples of molecular materials such as cytidine have vibrational modes that are localized within a molecular unit (``internal'' modes) as well as modes in which the molecular units vibrate against each other (``external'' modes). The value of the logarithmic derivative is a diagnostic probe of the nature of the eigenvector of the vibrational modes, making high pressure experiments a very useful probe for such studies. Internal stretching modes have low logarithmic derivatives while external as well as internal torsional and bending modes have higher logarithmic derivatives. Modes at about 503, 757, 795, 3093 and 3351 cm-1 are found to have negative logarithmic pressure derivatives, indicating a weakening of the effective force constants associated with those modes. The two modes above 3000 cm-1 are hydrogen-bond-stretching modes. The identity of all of these modes will be determined via molecular dynamical simuations.

  13. A novel pathway for the synthesis of inositol phospholipids uses cytidine diphosphate (CDP)-inositol as donor of the polar head group.

    PubMed

    Jorge, Carla D; Borges, Nuno; Santos, Helena

    2015-07-01

    We describe a novel biosynthetic pathway for glycerophosphoinositides in Rhodothermus marinus in which inositol is activated by cytidine triphosphate (CTP); this is unlike all known pathways that involve activation of the lipid group instead. This work was motivated by the detection in the R. marinus genome of a gene with high similarity to CTP:L-myo-inositol-1-phosphate cytidylyltransferase, the enzyme that synthesizes cytidine diphosphate (CDP)-inositol, a metabolite only known in the synthesis of di-myo-inositol phosphate. However, this solute is absent in R. marinus. The fate of radiolabelled CDP-inositol was investigated in cell extracts to reveal that radioactive inositol was incorporated into the chloroform-soluble fraction. Mass spectrometry showed that the major lipid product has a molecular mass of 810 Da and contains inositol phosphate and alkyl chains attached to glycerol by ether bonds. The occurrence of ether-linked lipids is rare in bacteria and has not been described previously in R. marinus. The relevant synthase was identified by functional expression of the candidate gene in Escherichia coli. The enzyme catalyses the transfer of L-myo-inositol-1-phosphate from CDP-inositol to dialkylether glycerol yielding dialkylether glycerophosphoinositol. Database searching showed homologous proteins in two bacterial classes, Sphingobacteria and Alphaproteobacteria. This is the first report of the involvement of CDP-inositol in phospholipid synthesis.

  14. Analog and digital signal processing

    NASA Astrophysics Data System (ADS)

    Baher, H.

    The techniques of signal processing in both the analog and digital domains are addressed in a fashion suitable for undergraduate courses in modern electrical engineering. The topics considered include: spectral analysis of continuous and discrete signals, analysis of continuous and discrete systems and networks using transform methods, design of analog and digital filters, digitization of analog signals, power spectrum estimation of stochastic signals, FFT algorithms, finite word-length effects in digital signal processes, linear estimation, and adaptive filtering.

  15. An auditory analog of the picture superiority effect.

    PubMed

    Crutcher, Robert J; Beer, Jenay M

    2011-01-01

    Previous research has found that pictures (e.g., a picture of an elephant) are remembered better than words (e.g., the word "elephant"), an empirical finding called the picture superiority effect (Paivio & Csapo. Cognitive Psychology 5(2):176-206, 1973). However, very little research has investigated such memory differences for other types of sensory stimuli (e.g. sounds or odors) and their verbal labels. Four experiments compared recall of environmental sounds (e.g., ringing) and spoken verbal labels of those sounds (e.g., "ringing"). In contrast to earlier studies that have shown no difference in recall of sounds and spoken verbal labels (Philipchalk & Rowe. Journal of Experimental Psychology 91(2):341-343, 1971; Paivio, Philipchalk, & Rowe. Memory & Cognition 3(6):586-590, 1975), the experiments reported here yielded clear evidence for an auditory analog of the picture superiority effect. Experiments 1 and 2 showed that sounds were recalled better than the verbal labels of those sounds. Experiment 2 also showed that verbal labels are recalled as well as sounds when participants imagine the sound that the word labels. Experiments 3 and 4 extended these findings to incidental-processing task paradigms and showed that the advantage of sounds over words is enhanced when participants are induced to label the sounds. PMID:21264626

  16. [Analogies and analogy research in technical biology and bionics].

    PubMed

    Nachtigall, Werner

    2010-01-01

    The procedural approaches of Technical Biology and Bionics are characterized, and analogy research is identified as their common basis. The actual creative aspect in bionical research lies in recognizing and exploiting technically oriented analogies underlying a specific biological prototype to indicate a specific technical application.

  17. FET comparator detects analog signal levels without loading analog device

    NASA Technical Reports Server (NTRS)

    Wallace, H. L.

    1966-01-01

    FET comparator circuit detects discrete analog computer output levels without excessively loading the output amplifier of the computer. An FET common source amplifier is coupled by a differential amplifier to a bistable transistor flip-flop. This circuit provides a digital output for analog voltages above or below a predetermined level.

  18. Producing and Recognizing Analogical Relations

    ERIC Educational Resources Information Center

    Lipkens, Regina; Hayes, Steven C.

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among…

  19. Drawing Analogies in Environmental Education

    ERIC Educational Resources Information Center

    Affifi, Ramsey

    2014-01-01

    Reconsidering the origin, process, and outcomes of analogy-making suggests practices for environmental educators who strive to disengage humans from the isolating illusions of dichotomizing frameworks. We can view analogies as outcomes of developmental processes within which human subjectivity is but an element, threading our sense of self back…

  20. Natural analog studies: Licensing perspective

    SciTech Connect

    Bradbury, J.W.

    1995-09-01

    This report describes the licensing perspective of the term {open_quotes}natural analog studies{close_quotes} as used in CFR Part 60. It describes the misunderstandings related to its definition which has become evident during discussions at the U.S Nuclear Regulatory Commission meetings and tries to clarify the appropriate applications of natural analog studies to aspects of repository site characterization.

  1. Sulfonimidamide analogs of oncolytic sulfonylureas.

    PubMed

    Toth, J E; Grindey, G B; Ehlhardt, W J; Ray, J E; Boder, G B; Bewley, J R; Klingerman, K K; Gates, S B; Rinzel, S M; Schultz, R M; Weir, L C; Worzalla, J F

    1997-03-14

    A series of sulfonimidamide analogs of the oncolytic diarylsulfonylureas was synthesized and evaluated for (1) in vitro cytotoxicity against CEM cells, (2) in vivo antitumor activity against subaxillary implanted 6C3HED lymphosarcoma, and (3) metabolic breakdown to the o-sulfate of p-chloroaniline. The separated enantiomers of one sulfonimidamide analog displayed very different activities in the in vivo screening model. In general, several analogs demonstrated excellent growth inhibitory activity in the 6C3HED model when dosed orally or intraperitoneally. A correlative structure-activity relationship to the oncolytic sulfonylureas was not apparent.

  2. Identification of cytidine 2',3'-cyclic monophosphate and uridine 2',3'-cyclic monophosphate in Pseudomonas fluorescens pfo-1 culture.

    PubMed

    Bordeleau, Emily; Oberc, Christopher; Ameen, Eve; da Silva, Amanda Mendes; Yan, Hongbin

    2014-09-15

    Cytidine 2',3'-cyclic monophosphate (2',3'-cCMP) and uridine 2',3'-cyclic monophosphate (2',3'-cUMP) were isolated from Pseudomonas fluorescens pfo-1 cell extracts by semi-preparative reverse phase HPLC. The structures of the two compounds were confirmed by NMR and mass spectroscopy against commercially available authentic samples. Concentrations of both intracellular and extracellular 2',3'-cCMP and 2',3'-cUMP were determined. Addition of 2',3'-cCMP and 2',3'-cUMP to P. fluorescens pfo-1 culture did not significantly affect the level of biofilm formation in static liquid cultures. PMID:25139571

  3. The splicing regulator PTBP2 interacts with the cytidine deaminase AID and promotes binding of AID to switch-region DNA.

    PubMed

    Nowak, Urszula; Matthews, Allysia J; Zheng, Simin; Chaudhuri, Jayanta

    2011-02-01

    During immunoglobulin class-switch recombination (CSR), the cytidine deaminase AID induces double-strand breaks into transcribed, repetitive DNA elements called switch sequences. The mechanism that promotes the binding of AID specifically to switch regions remains to be elucidated. Here we used a proteomic screen with in vivo biotinylation of AID to identify the splicing regulator PTBP2 as a protein that interacts with AID. Knockdown of PTBP2 mediated by short hairpin RNA in B cells led to a decrease in binding of AID to transcribed switch regions, which resulted in considerable impairment of CSR. PTBP2 is thus an effector of CSR that promotes the binding of AID to switch-region DNA.

  4. Sequence-specific binding of a hormonally regulated mRNA binding protein to cytidine-rich sequences in the lutropin receptor open reading frame.

    PubMed

    Kash, J C; Menon, K M

    1999-12-21

    In previous studies, a lutropin receptor mRNA binding protein implicated in the hormonal regulation of lutropin receptor mRNA stability was identified. This protein, termed LRBP-1, was shown by RNA gel electrophoretic mobility shift assay to specifically interact with lutropin receptor RNA sequences. The present studies have examined the specificity of lutropin receptor mRNA recognition by LRBP-1 and mapped the contact site by RNA footprinting and by site-directed mutagenesis. LRBP-1 was partially purified by cation-exchange chromatography, and the mRNA binding properties of the partially purified LRBP-1 were examined by RNA gel electrophoretic mobility shift assay and hydroxyl-radical RNA footprinting. These data showed that the LRBP-1 binding site is located between nucleotides 203 and 220 of the receptor open reading frame, and consists of the bipartite polypyrimidine sequence 5'-UCUC-X(7)-UCUCCCU-3'. Competition RNA gel electrophoretic mobility shift assays demonstrated that homoribopolymers of poly(rC) were effective RNA binding competitors, while poly(rA), poly(rG), and poly(rU) showed no effect. Mutagenesis of the cytidine residues contained within the LRBP-1 binding site demonstrated that all the cytidines in the bipartite sequence contribute to LRBP-1 binding specificity. Additionally, RNA gel electrophoretic mobility supershift analysis showed that LRBP-1 was not recognized by antibodies against two well-characterized poly(rC) RNA binding proteins, alphaCP-1 and alphaCP-2, implicated in the regulation of RNA stability of alpha-globin and tyrosine hydroxylase mRNAs. In summary, we show that partially purified LRBP-1 binds to a polypyrimidine sequence within nucleotides 203 and 220 of lutropin receptor mRNA with a high degree of specificity which is indicative of its role in posttranscriptional control of lutropin receptor expression.

  5. Evaluating countermeasures in spaceflight analogs.

    PubMed

    Ploutz-Snyder, Lori

    2016-04-15

    Countermeasures are defined as solutions to prevent the undesirable physiologic outcomes associated with spaceflight. Spaceflight analogs provide a valuable opportunity for the evaluation of countermeasures because they allow for the evaluation of more subjects, more experimental control, and are considerably less expensive than actual spaceflight. The various human analogs have differing strengths and weaknesses with respect to the development and evaluation of countermeasures. The human analogs are briefly reviewed with a focus on their suitability for countermeasure evaluation. Bed rest is the most commonly used analog for evaluating countermeasures. While countermeasures are typically developed to target one or maybe two particular physiologic issues, it is increasingly important to evaluate all of the organ systems to discern whether they might be unintended consequences on nontargeted tissues. In preparation for Mars exploration it will be necessary to fully integrate countermeasures to protect all organ systems. The synergistic and antagonistic effects of multiple countermeasures needs to be the focus of future work. PMID:26662054

  6. Introduction to Analog Field Testing

    NASA Video Gallery

    NASA tests systems and operational concepts in analog environments, which include locations underwater, in the arctic, on terrestrial impact craters, in the desert, and on the International Space S...

  7. Flight Analogs (Bed Rest Research)

    NASA Video Gallery

    Flight Analogs / Bed Rest Research Projects provide NASA with a ground based research platform to complement space research. By mimicking the conditions of weightlessness in the human body here on ...

  8. Incorporation of thymidine analogs for studying replication kinetics in fission yeast

    PubMed Central

    Rhind, Nicholas

    2016-01-01

    Labeling DNA during in vivo replication by the incorporation of exogenous thymidine and thymidine analogs has been a mainstay of DNA replication and repair studies for decades. Unfortunately, thymidine labeling does not work in fungi, because they lack the thymidine salvage pathway required for up take of exogenous thymidine. This obstacle to thymidine labeling has been overcome in yeast by engineering a minimal thymidine salvage pathway consisting of a nucleoside transporter to allow uptake of exogenous thymidine from the medium and a thymidine kinase to phosphorylate the thymidine into thymidine monophosphate, which can be used by the cell. This chapter describes the labeling of fission yeast, Schizosaccharomyces pombe, with the thymidine analog BrdU in order to identify sites and determine kinetics of DNA replication. PMID:25916707

  9. The Robustness of Acoustic Analogies

    NASA Technical Reports Server (NTRS)

    Freund, J. B.; Lele, S. K.; Wei, M.

    2004-01-01

    Acoustic analogies for the prediction of flow noise are exact rearrangements of the flow equations N(right arrow q) = 0 into a nominal sound source S(right arrow q) and sound propagation operator L such that L(right arrow q) = S(right arrow q). In practice, the sound source is typically modeled and the propagation operator inverted to make predictions. Since the rearrangement is exact, any sufficiently accurate model of the source will yield the correct sound, so other factors must determine the merits of any particular formulation. Using data from a two-dimensional mixing layer direct numerical simulation (DNS), we evaluate the robustness of two analogy formulations to different errors intentionally introduced into the source. The motivation is that since S can not be perfectly modeled, analogies that are less sensitive to errors in S are preferable. Our assessment is made within the framework of Goldstein's generalized acoustic analogy, in which different choices of a base flow used in constructing L give different sources S and thus different analogies. A uniform base flow yields a Lighthill-like analogy, which we evaluate against a formulation in which the base flow is the actual mean flow of the DNS. The more complex mean flow formulation is found to be significantly more robust to errors in the energetic turbulent fluctuations, but its advantage is less pronounced when errors are made in the smaller scales.

  10. Mental Labels and Tattoos

    ERIC Educational Resources Information Center

    Hyatt, I. Ralph

    1977-01-01

    Discusses the ease with which mental labels become imprinted in our system, six basic axioms for maintaining negative mental tattoos, and psychological processes for eliminating mental tattoos and labels. (RK)

  11. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  12. 9 CFR 112.10 - Special packaging and labeling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Special packaging and labeling. 112.10 Section 112.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  13. 9 CFR 112.10 - Special packaging and labeling.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Special packaging and labeling. 112.10 Section 112.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  14. 9 CFR 112.10 - Special packaging and labeling.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Special packaging and labeling. 112.10 Section 112.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  15. The Origin of the s, p, d, f Orbital Labels

    ERIC Educational Resources Information Center

    Jensen, William B.

    2007-01-01

    The theory of s, p, d and f dealing with the line spectra of the alkali metals during the period 1881 based on analogies with the harmonic ratios of sound is described. Friedrich Hund followed Bohr's practice of labelling the various shells and subshells by replacing the secondary quantum number with the series notations (s, p, d, and f), which…

  16. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  17. 9 CFR 112.10 - Special packaging and labeling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Special packaging and labeling. 112.10 Section 112.10 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  18. Metaphors as Second Labels: Difficult for Preschool Children?

    ERIC Educational Resources Information Center

    Rubio-Fernández, Paula; Grassmann, Susanne

    2016-01-01

    This study investigates the development of two cognitive abilities that are involved in metaphor comprehension: implicit analogical reasoning and assigning an unconventional label to a familiar entity (as in Romeo's "Juliet is the sun"). We presented 3- and 4-year-old children with literal object-requests in a pretense setting (e.g.,…

  19. 9 CFR 112.5 - Review and approval of labeling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Review and approval of labeling. 112.5 Section 112.5 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  20. All-optical analog comparator.

    PubMed

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  1. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training.

  2. All-optical analog comparator

    NASA Astrophysics Data System (ADS)

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  3. All-optical analog comparator

    PubMed Central

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

  4. All-optical analog comparator.

    PubMed

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

  5. Crows spontaneously exhibit analogical reasoning.

    PubMed

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. PMID:25532894

  6. Are polymers suitable rock analogs?

    NASA Astrophysics Data System (ADS)

    ten Grotenhuis, Saskia M.; Piazolo, Sandra; Pakula, T.; Passchier, Cees W.; Bons, Paul D.

    2002-05-01

    To evaluate if a polymer is suitable for analog modeling, it is essential to know the rheological properties of the material. Polymers used in analog modeling exhibit a complex rheological behavior; only part of which has been taken into account in most modeling studies. The mechanical behavior is strongly dependent on strain rate and temperature, and is characterized by specific dependencies of the storage and loss moduli, related to the elasticity and viscosity, on the deformation rate (frequency). We have measured the storage and loss moduli at a broad range of strain rates and strains, using an oscillatory parallel-disk rheometer. Investigated materials are polydimethylsiloxane (PDMS), mixtures of PDMS and BaSO 4 (filler), Rhodorsil Gomme and mixtures of Rhodorsil Gomme and plastilina, all commonly used in analog experiments. Our measurements show that the rheological properties of mixtures of plastilina and Rhodorsil Gomme depend on its deformation history. Therefore, these mixtures are problematic for analog modeling. For mixtures of PDMS and BaSO 4, the significance of the elastic component increases with increasing filler content, and accordingly, these mixtures have a limited application for modeling of viscous deformation. Pure PDMS and Rhodorsil Gomme exhibit Newtonian flow behavior at strain rates commonly used in analog modeling.

  7. Synthesis of 2'-deoxy-2'-[.sup.18F]fluoro-5-methyl-1-B-D-arabinofuranosyluracil (.sup.18F-FMAU)

    DOEpatents

    Li, Zibo; Cai, Hancheng; Conti, Peter S

    2014-12-16

    The present invention relates to methods of synthesizing .sup.18F-FMAU. In particular, .sup.18F-FMAU is synthesized using one-pot reaction conditions in the presence of Friedel-Crafts catalysts. The one-pot reaction conditions are incorporated into a fully automated cGMP-compliant radiosynthesis module, which results in a reduction in synthesis time and simplifies reaction conditions. The one-pot reaction conditions are also suitable for the production of 5-substituted thymidine or cytidine analogs. The products from the one-pot reaction (e.g. the labeled thymidine or cytidine analogs) can be used as probes for imaging tumor proliferative activity. More specifically, these [.sup.18F]-labeled thymidine or cytidine analogs can be used as a PET tracer for certain medical conditions, including, but not limited to, cancer disease, autoimmunity inflammation, and bone marrow transplant.

  8. Natural analogs for Yucca Mountain

    SciTech Connect

    Murphy, W.M.

    1995-11-01

    High-level radioactive waste in the US, spent fuels from commercial reactors and nuclear materials generated by defense activities, will remain potentially hazardous for thousands of years. Demonstrable long-term stability of certain geologic and geochemical systems motivates and sustains the concept that high-level waste can be safely isolated in geologic repositories for requisite periods of time. Each geologic repository is unique in its properties and performance with reguard to isolation of nuclear wastes. Studies of processes analogous to waste-form alteration and radioelement transport in environments analogous to Yucca Mountain are being conducted at two sites, described in this article to illustrate uses of natural analog data: the Nopal I uranium deposit in the Sierra Pena Blanca, Mexico, and the Akrotiri archaeological site on the island of Santorini, Greece.

  9. Test Wiseness and Analogy Test Performance

    ERIC Educational Resources Information Center

    Moore, James C.

    1971-01-01

    Subjects received self instruction on how to approach analogy questions. Instruction was directed toward knowledge of the general format of analogy questions in standarized tests and the 15 types of relationships commonly asked for in analogy questions. An analogies post-test showed a significant effect for the group. (Author)

  10. Analogies in Science and Science Teaching

    ERIC Educational Resources Information Center

    Brown, Simon; Salter, Susan

    2010-01-01

    Analogies are often used in science, but students may not appreciate their significance, and so the analogies can be misunderstood or discounted. For this reason, educationalists often express concern about the use of analogies in teaching. Given the important place of analogies in the discourse of science, it is necessary that students are…

  11. Multilateral Collaborations in Analog Research

    NASA Technical Reports Server (NTRS)

    Cromwell, R. l.

    2016-01-01

    International collaborations in studies utilizing ground-based space flight analogs are an effective means for answering research questions common to participating agencies. These collaborations bring together worldwide experts to solve important space research questions. By collaborating unnecessary duplication of science is reduced, and the efficiency of analog use is improved. These studies also share resources among agencies for cost effective solutions to study implementation. Recently, NASA has engaged in collaborations with international partners at a variety of analog sites. The NASA Human Exploration Research Analog (HERA) is currently hosting investigator studies from NASA and from the German Space Agency (DLR). These isolation studies will answer questions in the areas of team cohesion, sleep and circadian rhythms, and neurobehavioral correlates to function. Planning for the next HERA campaign is underway as proposal selections are being made from the International Life Sciences Research Announcement (ILSRA). Studies selected from the ILSRA will be conducted across 4 HERA missions in 2017. NASA is planning collaborative studies with DLR at the :envihab facility in Cologne, Germany. Investigations were recently selected to study the effects of 0.5% CO2 exposure over 30 days of bed rest. These studies will help to determine the fidelity of this ground-based analog for studying the visual impairment intracranial pressure syndrome. NASA is also planning a multilateral collaboration at :envihab with DLR and the European Space Agency (ESA) to examine artificial gravity as a countermeasure to mitigate the effects of 60 days of bed rest. NASA is also considering collaborations with the Russian Institute for Biomedical Problems (IBMP) in studies that will utilize their Ground-based Experimental Facility (NEK). The NEK is comprised of 4 interconnected modules and a Martian surface simulator. This isolation analog can support 3 -10 crew members for long duration

  12. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate

    PubMed Central

    Deval, Jerome; Hong, Jin; Wang, Guangyi; Taylor, Josh; Smith, Lucas K.; Fung, Amy; Stevens, Sarah K.; Liu, Hong; Jin, Zhinan; Dyatkina, Natalia; Prhavc, Marija; Stoycheva, Antitsa D.; Serebryany, Vladimir; Liu, Jyanwei; Smith, David B.; Tam, Yuen; Zhang, Qingling; Moore, Martin L.; Fearns, Rachel; Chanda, Sushmita M.; Blatt, Lawrence M.; Symons, Julian A.; Beigelman, Leo

    2015-01-01

    Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections, yet no vaccines or effective therapeutics are available. ALS-8176 is a first-in-class nucleoside analog prodrug effective in RSV-infected adult volunteers, and currently under evaluation in hospitalized infants. Here, we report the mechanism of inhibition and selectivity of ALS-8176 and its parent ALS-8112. ALS-8176 inhibited RSV replication in non-human primates, while ALS-8112 inhibited all strains of RSV in vitro and was specific for paramyxoviruses and rhabdoviruses. The antiviral effect of ALS-8112 was mediated by the intracellular formation of its 5'-triphosphate metabolite (ALS-8112-TP) inhibiting the viral RNA polymerase. ALS-8112 selected for resistance-associated mutations within the region of the L gene of RSV encoding the RNA polymerase. In biochemical assays, ALS-8112-TP was efficiently recognized by the recombinant RSV polymerase complex, causing chain termination of RNA synthesis. ALS-8112-TP did not inhibit polymerases from host or viruses unrelated to RSV such as hepatitis C virus (HCV), whereas structurally related molecules displayed dual RSV/HCV inhibition. The combination of molecular modeling and enzymatic analysis showed that both the 2'F and the 4'ClCH2 groups contributed to the selectivity of ALS-8112-TP. The lack of antiviral effect of ALS-8112-TP against HCV polymerase was caused by Asn291 that is well-conserved within positive-strand RNA viruses. This represents the first comparative study employing recombinant RSV and HCV polymerases to define the selectivity of clinically relevant nucleotide analogs. Understanding nucleotide selectivity towards distant viral RNA polymerases could not only be used to repurpose existing drugs against new viral infections, but also to design novel molecules. PMID:26098424

  13. Stable isotope-labeled RNA phosphoramidites to facilitate dynamics by NMR.

    PubMed

    Wunderlich, Christoph H; Juen, Michael A; LeBlanc, Regan M; Longhini, Andrew P; Dayie, T Kwaku; Kreutz, Christoph

    2015-01-01

    Given that Ribonucleic acids (RNAs) are a central hub of various cellular processes, methods to synthesize these RNAs for biophysical studies are much needed. Here, we showcase the applicability of 6-(13)C-pyrimidine phosphoramidites to introduce isolated (13)C-(1)H spin pairs into RNAs up to 40 nucleotides long. The method allows the incorporation of 6-(13)C-uridine and -cytidine residues at any desired position within a target RNA. By site-specific positioning of the (13)C-label using RNA solid phase synthesis, these stable isotope-labeling patterns are especially well suited to resolve resonance assignment ambiguities. Of even greater importance, the labeling pattern affords accurate quantification of important functional transitions of biologically relevant RNAs (e.g., riboswitch aptamer domains, viral RNAs, or ribozymes) in the μs- to ms time regime and beyond without complications of one bond carbon scalar couplings. We outline the chemical synthesis of the 6-(13)C-pyrimidine building blocks and their use in RNA solid phase synthesis and demonstrate their utility in Carr Purcell Meiboom Gill relaxation dispersion, ZZ exchange, and chemical exchange saturation transfer NMR experiments. PMID:26577742

  14. Sex pheromone receptor proteins. Visualization using a radiolabeled photoaffinity analog

    SciTech Connect

    Vogt, R.G.; Prestwich, G.D.; Riddiford, L.M.

    1988-03-15

    A tritium-labeled photoaffinity analog of a moth pheromone was used to covalently modify pheromone-selective binding proteins in the antennal sensillum lymph and sensory dendritic membranes of the male silk moth, Antheraea polyphemus. This analog, (E,Z)-6,11-(/sup 3/H)hexadecadienyl diazoacetate, allowed visualization of a 15-kilodalton soluble protein and a 69-kilodalton membrane protein in fluorescence autoradiograms of electrophoretically separated antennal proteins. Covalent modification of these proteins was specifically reduced when incubation and UV irradiation were conducted in the presence of excess unlabeled pheromone, (E,Z)-6,11-hexadecadienyl acetate. These experiments constitute the first direct evidence for a membrane protein of a chemosensory neuron interacting in a specific fashion with a biologically relevant odorant.

  15. Dynein ATPase pathway: ATP analogs and regulation by phosphorylation

    SciTech Connect

    Chilcote, T.J.

    1988-01-01

    Three biochemical aspects of 22S dynein from Tetrahymena cilia have been investigated: its ATP binding polypeptides and the manner in which they bind ATP, its AMPPNP-induced dissociation from microtubules, and its phosphorylation. We have attempted to identify the polypeptides of dynein that bind ATP, i.e., the active site polypeptides, with the photoaffinity ATP analog 8-N{sub 3}ATP. The 8-N{sub 3}ATP has been shown to bind to dyneins active sites and in a manner similar to that of ATP. Upon irradiation, (2-{sup 3}H)8-N{sub 3}ATP covalently labels the three heavy chains, i.e., heads, which is detected by autoradiography of SDS PAG's. Thus, the three heads are considered to be the three active sites of dynein. AMPPNP is a nonhydrolyzable ATP analog which we have assayed for the ability to induce dynein dissociation from microtubules.

  16. Understanding the mechanism of sweet taste: synthesis of ultrapotent guanidinoacetic acid photoaffinity labeling reagents.

    PubMed

    Nagarajan, S; Kellogg, M S; DuBois, G E; Hellekant, G

    1996-10-11

    Azido-functionalized analogs of potently sweet guanidinoacetic acids have been synthesized for use as sweetener receptor photoaffinity labeling reagents. These compounds have been synthesized using readily available starting materials. One of the azido-labeled guanidinoacetic acids has been evaluated in an electrophysiological model in the Rhesus monkey. We found that the photoaffinity-labeling reagent caused irreversible inhibition in electrophysiological response to sweeteners upon exposure of the monkey tongue to a combination of the reagent and UV light.

  17. Terrestrial analogs for space exploration habitation systems

    NASA Technical Reports Server (NTRS)

    Campbell, Paul D.; Brown, Jeri W.

    1992-01-01

    The Space Exploration Initiative (SEI) can use early earth-based analogs to simulate many aspects of space flight missions and system operation. These analogs can thus provide information supporting future missions to the moon and to Mars. A study was performed to investigate the potential of terrestrial analogs in simulating human space exploration missions. The study resulted in preliminary requirements and concepts for analog habitation systems, and further study in this area is necessary for SEI terrestrial analog development.

  18. Dissecting APOBEC3G Substrate Specificity by Nucleoside Analog Interference*S⃞

    PubMed Central

    Rausch, Jason W.; Chelico, Linda; Goodman, Myron F.; Le Grice, Stuart F. J.

    2009-01-01

    The apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminase genes encode a set of enzymes including APOBEC1 (A1), APOBEC2 (A2), APOBEC4 (A4), and APOBEC3A-H (A3A-H). Although each possesses one or more zinc binding motifs conserved among enzymes catalyzing C → U conversion, the functions and substrate specificities of these gene products vary considerably. For example, although two closely related enzymes, A3F and A3G, both restrict HIV-1 infection in strains deficient in virus infectivity factor (vif), A3F selectively deaminates cytosine within 5′-TTCA-3′ motifs in single stranded DNA, whereas A3G targets 5′-CCCA-3′ sequences. In the present study we have used nucleoside analog interference mapping to probe A3G-DNA interactions throughout the enzyme-substrate complex as well as to determine which DNA structural features determine substrate specificity. Our results indicate that multiple components of nucleosides within the consensus sequence are important for substrate recognition by A3G (with base moieties being most critical), whereas deamination interference by analog substitution outside this region is minimal. Furthermore, exocyclic groups in pyrimidines 1–2 nucleotides 5′ of the target cytosine were shown to dictate substrate recognition by A3G, with chemical composition at ring positions 3 and 4 found to be more important than at ring position 5. Taken together, these results provide insights into how the enzyme selects A3G hotspot motifs for deamination as well as which approaches might be best suited for forming a stable, catalytically competent cross-linked A3G-DNA complex for future structural studies. PMID:19136562

  19. Heat shock protein 70 (Hsp70)-stimulated deoxycytidine deaminases from a human lymphoma cell but not the activation-induced cytidine deaminase (AID) from Ramos 6.4 human Burkitt's lymphoma cells.

    PubMed

    Bases, Robert

    2011-01-01

    Deoxycytidine deaminase enzyme activity was reduced in lysates of human leukemic THP1 cells 24 h after transfection with siRNA designed to inhibit cell synthesis of heat shock protein 70 (Hsp70)1a and Hsp701b. The cytidine deaminase enzyme activity from the cell lysates was purified from an affinity column which contained bound single-stranded oligodeoxycytidylic acid. Deficient enzyme activity in certain elution fractions from the siRNA-transfected cells was restored by including recombinant HSP 70 in the assays. Enzyme activity in some other fractions was increased after siRNA transfection. Activation-induced cytidine deaminase (AID) is a central factor in the immune response. A more specific assay for AID was used to study the influence of Hsp70 on AID activity. Unlike Hsp70's ability to stimulate certain enzymes of DNA base excision repair and other cytidine deaminases, it had little effect on AID activity in vitro, or was weakly inhibitory.

  20. Analog Input Data Acquisition Software

    NASA Technical Reports Server (NTRS)

    Arens, Ellen

    2009-01-01

    DAQ Master Software allows users to easily set up a system to monitor up to five analog input channels and save the data after acquisition. This program was written in LabVIEW 8.0, and requires the LabVIEW runtime engine 8.0 to run the executable.

  1. Geometrical Analogies in Mathematics Lessons

    ERIC Educational Resources Information Center

    Eid, Wolfram

    2007-01-01

    A typical form of thinking to approach problem solutions humanly is thinking in analogous structures. Therefore school, especially mathematical lessons should help to form and to develop corresponding heuristic abilities of the pupils. In the contribution, a summary of possibilities of mathematics lessons regarding this shall particularly be…

  2. Analogy of the Cell Project

    ERIC Educational Resources Information Center

    Science Scope, 2005

    2005-01-01

    In this project, students compare the makeup of a cell to an everyday working unit or system. They create a three-dimensional object that represents their analogy. For example, students could create a car motor or manufacturing plant. (Of course, this is totally hand-created by them, so it can be a homemade re-creation of a system, not an actual…

  3. Analog Simulation of a Laser.

    ERIC Educational Resources Information Center

    Kessler, Gary

    1982-01-01

    Presents an analog simulation of laser properties (finding time evolution of the intensity of a ruby laser pulse) which serves as the basis of a three-four hour laboratory experiment. Includes programs for solution to rate equations of a three-level laser and production of a giant pulse in a ruby laser. (Author/SK)

  4. Algicidal Activity of Stilbene Analogs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As part of our continuing search for natural product and natural product-based compounds for the control of off-flavor in catfish, a total of twenty nine stilbene analogs were synthesized and evaluated for algicidal activity against the 2-methylisoborneol (MIB)-producing cyanobacterium Oscillatoria ...

  5. Paper Analogies Enhance Biology Teaching.

    ERIC Educational Resources Information Center

    Stencel, John E.

    1997-01-01

    Describes how to use paper analogies as models to illustrate various concepts in biology, human anatomy, and physiology classes. Models include biochemical paper models, protein papergrams, a paper model of early brain development, and a 3-D paper model of a eukaryotic cell. (AIM)

  6. Mathematical Analogy and Metaphorical Insight

    ERIC Educational Resources Information Center

    Zwicky, Jan

    2010-01-01

    How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

  7. Understanding & Teaching Genetics Using Analogies

    ERIC Educational Resources Information Center

    Woody, Scott; Himelblau, Ed

    2013-01-01

    We present a collection of analogies that are intended to help students better understand the foreign and often nuanced vocabulary of the genetics curriculum. Why is it called the "wild type"? What is the difference between a locus, a gene, and an allele? What is the functional (versus a rule-based) distinction between dominant and…

  8. International Alligator Rivers Analog Project

    SciTech Connect

    Bichard, G.F.

    1988-01-01

    The Australian Nuclear Science and Technology Organization (ANSTO), the Japan Atomic Energy Research Institute, the Swedish Nuclear Power Inspectorate, the U.K. Department of the Environment, the US Nuclear Regulatory Commission (NRC), and the Power Reactor and Nuclear Fuel Development Corporation of Japan are participating under the aegis of the Nuclear Energy Agency in the International Alligator Rivers Analog Project. The project has a duration of 3 yr, starting in 1988. The project has grown out of a research program on uranium ore bodies as analogs of high-level waste (HLW) repositories undertaken by ANSTO supported by the NRC. A primary objective of the project is to develop an approach to radionuclide transport model validation that may be used by the participants to support assessments of the safety of radioactive waste repositories. The approach involves integrating mathematical and physical modeling with hydrological and geochemical field and laboratory investigations of the analog site. The Koongarra uranium ore body has been chosen as the analog site because it has a secondary ore body that has formed over the past million years as a result of leaching by groundwater flowing through fractures in the primary ore body.

  9. Electrical analog to projectile motion

    NASA Astrophysics Data System (ADS)

    Vondracek, Mark

    1998-04-01

    This article describes an electrical analog to traditional projectile problems given in high school and introductory college classes. It also discusses the importance of stressing the understanding of physical laws and principles to students, and that the physics behind a problem is more important than being able to memorize and use various equations.

  10. Analogy between Thermodynamics and Mechanics.

    ERIC Educational Resources Information Center

    Peterson, Mark A.

    1979-01-01

    Establishes and illustrates a formal analogy between the motion of a particle and the "motion" of the equilibrium state of a homogeneous system in a quasistatic process. The purpose is to show that there is a much larger set of natural coordinate transformations in thermodynamics. (GA)

  11. Bayesian Analogy with Relational Transformations

    ERIC Educational Resources Information Center

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J.

    2012-01-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy…

  12. Bar Code Labels

    NASA Technical Reports Server (NTRS)

    1988-01-01

    American Bar Codes, Inc. developed special bar code labels for inventory control of space shuttle parts and other space system components. ABC labels are made in a company-developed anodizing aluminum process and consecutively marketed with bar code symbology and human readable numbers. They offer extreme abrasion resistance and indefinite resistance to ultraviolet radiation, capable of withstanding 700 degree temperatures without deterioration and up to 1400 degrees with special designs. They offer high resistance to salt spray, cleaning fluids and mild acids. ABC is now producing these bar code labels commercially or industrial customers who also need labels to resist harsh environments.

  13. Partitioning, diffusion, and ligand binding of raft lipid analogs in model and cellular plasma membranes.

    PubMed

    Sezgin, Erdinc; Levental, Ilya; Grzybek, Michal; Schwarzmann, Günter; Mueller, Veronika; Honigmann, Alf; Belov, Vladimir N; Eggeling, Christian; Coskun, Unal; Simons, Kai; Schwille, Petra

    2012-07-01

    Several simplified membrane models featuring coexisting liquid disordered (Ld) and ordered (Lo) lipid phases have been developed to mimic the heterogeneous organization of cellular membranes, and thus, aid our understanding of the nature and functional role of ordered lipid-protein nanodomains, termed "rafts". In spite of their greatly reduced complexity, quantitative characterization of local lipid environments using model membranes is not trivial, and the parallels that can be drawn to cellular membranes are not always evident. Similarly, various fluorescently labeled lipid analogs have been used to study membrane organization and function in vitro, although the biological activity of these probes in relation to their native counterparts often remains uncharacterized. This is particularly true for raft-preferring lipids ("raft lipids", e.g. sphingolipids and sterols), whose domain preference is a strict function of their molecular architecture, and is thus susceptible to disruption by fluorescence labeling. Here, we analyze the phase partitioning of a multitude of fluorescent raft lipid analogs in synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). We observe complex partitioning behavior dependent on label size, polarity, charge and position, lipid headgroup, and membrane composition. Several of the raft lipid analogs partitioned into the ordered phase in GPMVs, in contrast to fully synthetic GUVs, in which most raft lipid analogs mis-partitioned to the disordered phase. This behavior correlates with the greatly enhanced order difference between coexisting phases in the synthetic system. In addition, not only partitioning, but also ligand binding of the lipids is perturbed upon labeling: while cholera toxin B binds unlabeled GM1 in the Lo phase, it binds fluorescently labeled GMI exclusively in the Ld phase. Fluorescence correlation spectroscopy (FCS) by stimulated emission depletion (STED) nanoscopy on intact

  14. Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets.

    PubMed

    Endrizzi, James A; Kim, Hanseong; Anderson, Paul M; Baldwin, Enoch P

    2004-06-01

    Cytidine triphosphate synthetases (CTPSs) produce CTP from UTP and glutamine, and regulate intracellular CTP levels through interactions with the four ribonucleotide triphosphates. We solved the 2.3-A resolution crystal structure of Escherichia coli CTPS using Hg-MAD phasing. The structure reveals a nearly symmetric 222 tetramer, in which each bifunctional monomer contains a dethiobiotin synthetase-like amidoligase N-terminal domain and a Type 1 glutamine amidotransferase C-terminal domain. For each amidoligase active site, essential ATP- and UTP-binding surfaces are contributed by three monomers, suggesting that activity requires tetramer formation, and that a nucleotide-dependent dimer-tetramer equilibrium contributes to the observed positive cooperativity. A gated channel that spans 25 A between the glutamine hydrolysis and amidoligase active sites provides a path for ammonia diffusion. The channel is accessible to solvent at the base of a cleft adjoining the glutamine hydrolysis active site, providing an entry point for exogenous ammonia. Guanine nucleotide binding sites of structurally related GTPases superimpose on this cleft, providing insights into allosteric regulation by GTP. Mutations that confer nucleoside drug resistance and release CTP inhibition map to a pocket that neighbors the UTP-binding site and can accommodate a pyrimidine ring. Its location suggests that competitive feedback inhibition is affected via a distinct product/drug binding site that overlaps the substrate triphosphate binding site. Overall, the E. coli structure provides a framework for homology modeling of other CTPSs and structure-based design of anti-CTPS therapeutics. PMID:15157079

  15. Conformers and hydrogen bonds in cytidine 5‧-diphosphocholine sodium single crystals grown from a mixture of ethanol and water

    NASA Astrophysics Data System (ADS)

    Du, Zhenxing; Hu, Yanan; Wang, Pei; Zhou, Jingwei; Xiong, Jian; Ying, Hanjie; Bai, Jianxin

    2011-01-01

    The molecular structure of cytidine 5'-diphosphocholine sodium (CDPC) grown from a mixture of ethanol and water was determined by X-ray diffraction (XRD). CDPC was found to have an orthorhombic structure with confirmed lattice parameters of a = 6.978 Å, b = 12.406 Å and c = 29.326 Å. This nucleotide coenzyme was highly folded and net-like. Each crystallographic unit consisted of one sodium atom, one pyrophosphate group, one cytosine group, one coordinated water molecule, one pentose molecule, and three lattice water molecules. The interspaces of neighboring CDPC molecules were filled with water molecules and methyl groups. Although the coordinated water was connected to sodium atoms, the lattice water molecules formed chair-shaped water hexamers. The hydrogen bonds which played an important role in maintaining the structure included O sbnd H···O, N sbnd H···O and C sbnd H···O and ranged in length from 2.682 (17) to 3.349 (17) Å. Fourier transform infrared spectroscopy (FTIR) showed a broad absorption in the 400-2000 cm -1 region characteristic of short hydrogen bonds. So for industrial crystallization, methods which could eliminate the influence of hydrogen bonds should be taken, and it would be beneficial for the process of crystallization.

  16. Uracil DNA Glycosylase Is Dispensable for Human Immunodeficiency Virus Type 1 Replication and Does Not Contribute to the Antiviral Effects of the Cytidine Deaminase Apobec3G

    PubMed Central

    Kaiser, Shari M.; Emerman, Michael

    2006-01-01

    It is well established that many host factors are involved in the replication of human immunodeficiency virus (HIV) type 1. One host protein, uracil DNA glycosylase 2 (UNG2), binds to multiple viral proteins and is packaged into HIV type 1 virions. UNG initiates the removal of uracils from DNA, and this has been proposed to be important both for reverse transcription and as a mediator to the antiviral effect of virion-incorporated Apobec3G, a cytidine deaminase that generates numerous uracils in the viral DNA during virus replication. We used a natural human UNG−/− cell line as well as cells that express a potent catalytic active-site inhibitor of UNG to assess the effects of removing UNG activity on HIV infectivity. In both cases, we find UNG2 activity and protein to be completely dispensable for virus replication. Moreover, we find that virion-associated UNG2 does not affect the loss of infectivity caused by Apobec3G. PMID:16378989

  17. Role of Genetic Polymorphisms of Deoxycytidine Kinase and Cytidine Deaminase to Predict Risk of Death in Children with Acute Myeloid Leukemia

    PubMed Central

    Medina-Sanson, Aurora; Ramírez-Pacheco, Arturo; Moreno-Guerrero, Silvia Selene; Dorantes-Acosta, Elisa María; Sánchez-Preza, Metzeri; Reyes-López, Alfonso

    2015-01-01

    Cytarabine is one of the most effective antineoplastic agents among those used for the treatment of acute myeloid leukemia. However, some patients develop resistance and/or severe side effects to the drug, which may interfere with the efficacy of the treatment. The polymorphisms of some Ara-C metabolizing enzymes seem to affect outcome and toxicity in AML patients receiving cytarabine. We conducted this study in a cohort of Mexican pediatric patients with AML to investigate whether the polymorphisms of the deoxycytidine kinase and cytidine deaminase enzymes are implicated in clinical response and toxicity. Bone marrow and/or peripheral blood samples obtained at diagnosis from 27 previously untreated pediatric patients with de novo AML were processed for genotyping and in vitro chemosensitivity assay, and we analyzed the impact of genotypes and in vitro sensitivity on disease outcome and toxicity. In the multivariate Cox regression analysis, we found that age at diagnosis, wild-type genotype of the CDA A79C polymorphism, and wild-type genotype of the dCK C360G polymorphism were the most significant prognostic factors for predicting the risk of death. PMID:26090398

  18. Battery hydrometer with analog output

    SciTech Connect

    Patis, B.L.

    1982-09-21

    There is disclosed a battery hydrometer for providing an analog electrical signal having a magnitude related to the specific gravity of a battery electrolyte. The hydrometer includes a source of radiation for providing a detectable beam of radiation and a piston member arranged to be submerged within the electrolyte and to intercept and modulate the beam of radiation in response to the specific gravity of the electrolyte. The piston member is suspended within the electrolyte by a spring which exerts a compressive force upon the piston member against which the electrolyte must act. The hydrometer further includes a radiation detector aligned with the radiation source for providing an analog electrical signal having a magnitude responsive to the modulated beam of radiation.

  19. Analog Nonvolatile Computer Memory Circuits

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd

    2007-01-01

    In nonvolatile random-access memory (RAM) circuits of a proposed type, digital data would be stored in analog form in ferroelectric field-effect transistors (FFETs). This type of memory circuit would offer advantages over prior volatile and nonvolatile types: In a conventional complementary metal oxide/semiconductor static RAM, six transistors must be used to store one bit, and storage is volatile in that data are lost when power is turned off. In a conventional dynamic RAM, three transistors must be used to store one bit, and the stored bit must be refreshed every few milliseconds. In contrast, in a RAM according to the proposal, data would be retained when power was turned off, each memory cell would contain only two FFETs, and the cell could store multiple bits (the exact number of bits depending on the specific design). Conventional flash memory circuits afford nonvolatile storage, but they operate at reading and writing times of the order of thousands of conventional computer memory reading and writing times and, hence, are suitable for use only as off-line storage devices. In addition, flash memories cease to function after limited numbers of writing cycles. The proposed memory circuits would not be subject to either of these limitations. Prior developmental nonvolatile ferroelectric memories are limited to one bit per cell, whereas, as stated above, the proposed memories would not be so limited. The design of a memory circuit according to the proposal must reflect the fact that FFET storage is only partly nonvolatile, in that the signal stored in an FFET decays gradually over time. (Retention times of some advanced FFETs exceed ten years.) Instead of storing a single bit of data as either a positively or negatively saturated state in a ferroelectric device, each memory cell according to the proposal would store two values. The two FFETs in each cell would be denoted the storage FFET and the control FFET. The storage FFET would store an analog signal value

  20. Classical Analog to Entanglement Reversibility

    NASA Astrophysics Data System (ADS)

    Chitambar, Eric; Fortescue, Ben; Hsieh, Min-Hsiu

    2015-08-01

    In this Letter we study the problem of secrecy reversibility. This asks when two honest parties can distill secret bits from some tripartite distribution pX Y Z and transform secret bits back into pX Y Z at equal rates using local operation and public communication. This is the classical analog to the well-studied problem of reversibly concentrating and diluting entanglement in a quantum state. We identify the structure of distributions possessing reversible secrecy when one of the honest parties holds a binary distribution, and it is possible that all reversible distributions have this form. These distributions are more general than what is obtained by simply constructing a classical analog to the family of quantum states known to have reversible entanglement. An indispensable tool used in our analysis is a conditional form of the Gács-Körner common information.

  1. Spanish labeling guide.

    PubMed

    Juliá, A M; García, S V; Breckinridge, M F

    1983-01-01

    A systematic reference of English-Spanish prescription label translations is presented. The purpose of the reference list (which is the most comprehensive published to date) is to enable a pharmacist to write precise, accurate label directions in Spanish for any patient who cannot read English.

  2. Spin-labeled polyribonucleotides.

    PubMed Central

    Petrov, A I; Sukhorukov, B I

    1980-01-01

    Poly (U), poly (C) and poly (A) were spin labeled with N-(2,2,5,5-tetramethyl-3-carbonylpyrroline-1-oxyl)-imidazole. This spin label interacts selectively with 2' OH ribose groups of polynucleotides and does not modify the nucleic acid bases. The extent of spin labeling is not dependent upon the nature of the base and is entirely determined by rigidity of the secondary structure of the polynucleotide. The extent of modification for poly (U), poly (C) and poly (A) was 4.2, 1.7 and 1.5 per cent, respectively, the secondary structure of the polynucleotides being practically unchanged. Some physico-chemical properties of the spin-labeled polynucleotides were investigated by ESR spectroscopy. Rotational correlation times of the spin label and activation energy of its motion were calculated. PMID:6253911

  3. Label fusion strategy selection.

    PubMed

    Robitaille, Nicolas; Duchesne, Simon

    2012-01-01

    Label fusion is used in medical image segmentation to combine several different labels of the same entity into a single discrete label, potentially more accurate, with respect to the exact, sought segmentation, than the best input element. Using simulated data, we compared three existing label fusion techniques-STAPLE, Voting, and Shape-Based Averaging (SBA)-and observed that none could be considered superior depending on the dissimilarity between the input elements. We thus developed an empirical, hybrid technique called SVS, which selects the most appropriate technique to apply based on this dissimilarity. We evaluated the label fusion strategies on two- and three-dimensional simulated data and showed that SVS is superior to any of the three existing methods examined. On real data, we used SVS to perform fusions of 10 segmentations of the hippocampus and amygdala in 78 subjects from the ICBM dataset. SVS selected SBA in almost all cases, which was the most appropriate method overall. PMID:22518113

  4. Thermal analog device reduces machining errors

    NASA Technical Reports Server (NTRS)

    Mcclure, E. R.

    1972-01-01

    Thermal analog devices predict thermal expansion and contraction of machine structures subjected to various heat inputs. Analog devices correct positioning of machine tools to compensate for distortion of machine frame.

  5. Simple Electronic Analog of a Josephson Junction.

    ERIC Educational Resources Information Center

    Henry, R. W.; And Others

    1981-01-01

    Demonstrates that an electronic Josephson junction analog constructed from three integrated circuits plus an external reference oscillator can exhibit many of the circuit phenomena of a real Josephson junction. Includes computer and other applications of the analog. (Author/SK)

  6. Basic Electricity--a Novel Analogy.

    ERIC Educational Resources Information Center

    Grant, Richard

    1996-01-01

    Uses the analogy of water flow to introduce concepts in basic electricity. Presents a demonstration that uses this analogy to help students grasp the relationship between current, voltage, and resistance. (JRH)

  7. Hegel, Analogy, and Extraterrestrial Life

    NASA Astrophysics Data System (ADS)

    Ross, Joseph T.

    Georg Wilhelm Friedrich Hegel rejected the possibility of life outside of the Earth, according to several scholars of extraterrestrial life. Their position is that the solar system and specifically the planet Earth is the unique place in the cosmos where life, intelligence, and rationality can be. The present study offers a very different interpretation of Hegel's statements about the place of life on Earth by suggesting that, although Hegel did not believe that there were other solar systems where rationality is present, he did in fact suggest that planets in general, not the Earth exclusively, have life and possibly also intelligent inhabitants. Analogical syllogisms are superficial, according to Hegel, insofar as they try to conclude that there is life on the Moon even though there is no evidence of water or air on that body. Similar analogical arguments for life on the Sun made by Johann Elert Bode and William Herschel were considered by Hegel to be equally superficial. Analogical arguments were also used by astronomers and philosophers to suggest that life could be found on other planets in our solar system. Hegel offers no critique of analogical arguments for life on other planets, and in fact Hegel believed that life would be found on other planets. Planets, after all, have meteorological processes and therefore are "living" according to his philosophical account, unlike the Moon, Sun, and comets. Whereas William Herschel was already finding great similarities between the Sun and the stars and had extended these similarities to the property of having planets or being themselves inhabitable worlds, Hegel rejected this analogy. The Sun and stars have some properties in common, but for Hegel one cannot conclude from these similarities to the necessity that stars have planets. Hegel's arguments against the presence of life in the solar system were not directed against other planets, but rather against the Sun and Moon, both of which he said have a different

  8. Science Teachers' Analogical Reasoning

    ERIC Educational Resources Information Center

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-01-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to…

  9. How to Read Drug Labels

    MedlinePlus

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  10. Capacitive label reader

    DOEpatents

    Arlowe, H.D.

    1983-07-15

    A capacitive label reader includes an outer ring transmitting portion, an inner ring transmitting portion, and a plurality of insulated receiving portions. A label is the mirror-image of the reader except that identifying portions corresponding to the receiving portions are insulated from only one of two coupling elements. Positive and negative pulses applied, respectively, to the two transmitting rings biased a CMOS shift register positively to either a 1 or 0 condition. The output of the CMOS may be read as an indication of the label.

  11. Nucleic acid analysis using terminal-phosphate-labeled nucleotides

    DOEpatents

    Korlach, Jonas; Webb, Watt W.; Levene, Michael; Turner, Stephen; Craighead, Harold G.; Foquet, Mathieu

    2008-04-22

    The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.

  12. Visual homing in analog hardware.

    PubMed

    Möller, R

    1999-10-01

    Insects of several species rely on visual landmarks for returning to important locations in their environment. The "average landmark vector model" is a parsimonious model which reproduces some aspects of the visual homing behavior of bees and ants. To gain insights in the structure and complexity of the neural apparatus that might underly the navigational capabilities of these animals, the average landmark vector model was implemented in analog hardware and used to control a mobile robot. The experiments demonstrate that the apparently complex task of visual homing might be realized by simple and mostly peripheral neural circuits in insect brains.

  13. Classical analog of quantum phase

    SciTech Connect

    Ord, G.N.

    1992-07-01

    A modified version of the Feynman relativistic chessboard model (FCM) is investigated in which the paths involved are spirals in the space-time. Portions of the paths in which the particle`s proper time is reversed are interpreted in terms of antiparticles. With this intepretation the particle-antiparticle field produced by such trajectories provides a classical analog of the phase associated with particle paths in the unmodified FCM. It is shwon that in the nonrelativistic limit the resulting kernel is the correct Dirac propagator and that particle-antiparticle symmetry is in this case responsible for quantum interference. 7 refs., 3 figs.

  14. Programming of the macronucleus of Paramecium during asexual and sexual reproduction: A further study with cytidine analogues, dimethylsulfoxide, L-ethionine and N-butyric acid.

    PubMed

    Au, K Y; Yao, C M; Cowan, R; Ng, S F

    1990-08-31

    The control of the function of the macronucleus of Paramecium is studied, in connection with its role in the compensation for the asexual somatic function of the micronucleus. Following removal of the micronuclei, amicronucleate cell lines as a rule suffer a transient period of growth and developmental depression in the initial phase of asexual propagation. But they gradually recover to near-normal. Previous studies of treatment of amicronucleate cells with cytidine analogues have implicated the macronucleus in compensating for the somatic function of the micronucleus following the loss of the micronucleus, and the activation of this macronuclear function probably involves DNA-demethylation. The present study further tests this notion, by treating micronucleate cells with agents known to promote demethylation of 5-methylcytosine. After treatment, the cells were vegetatively propagated, and then enucleated to give rise to amicronucleate cell lines. Treatments with dimethylsulfoxide, L-ethionine, and 5-aza-2'-deoxycytidine promoted recovery in amicronucleate cell lines thus derived. Cells treated with 6-azacytidine did not produce such an effect. Hence, the compensatory mechanism, presumably residing in a repressed state in the macronucleus, can be activated or primed to activate by demethylating agents even before the loss of the micronucleus, and once established the new macronuclear programme perpetuates in succeeding asexual cell generations. This shows that during asexual propagation the macronuclear programme can be altered to 'pre-adapt' the cells for amicronuclearity. Treatment of micronucleate conjugants with 5-azacytidine, when the macronuclear anlagen develop, produced clones that had become similarly pre-adapted. There were also some indication of persistence of such effects of the analogue into the next clonal cycle following autogamy. The notion of macronuclear DNA-demethylation as a basis for the activation and maintenance of the compensatory mechanism

  15. C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion.

    PubMed

    Sabouri, Somayeh; Kobayashi, Maki; Begum, Nasim A; Xu, Jianliang; Hirota, Kouji; Honjo, Tasuku

    2014-02-11

    Activation-induced cytidine deaminase (AID) introduces single-strand breaks (SSBs) to initiate class switch recombination (CSR), gene conversion (GC), and somatic hypermutation (SHM). CSR is mediated by double-strand breaks (DSBs) at donor and acceptor switch (S) regions, followed by pairing of DSB ends in two S regions and their joining. Because AID mutations at its C-terminal region drastically impair CSR but retain its DNA cleavage and SHM activity, the C-terminal region of AID likely is required for the recombination step after the DNA cleavage. To test this hypothesis, we analyzed the recombination junctions generated by AID C-terminal mutants and found that 0- to 3-bp microhomology junctions are relatively less abundant, possibly reflecting the defects of the classical nonhomologous end joining (C-NHEJ). Consistently, the accumulation of C-NHEJ factors such as Ku80 and XRCC4 was decreased at the cleaved S region. In contrast, an SSB-binding protein, poly (ADP)-ribose polymerase1, was recruited more abundantly, suggesting a defect in conversion from SSB to DSB. In addition, recruitment of critical DNA synapse factors such as 53BP1, DNA PKcs, and UNG at the S region was reduced during CSR. Furthermore, the chromosome conformation capture assay revealed that DNA synapse formation is impaired drastically in the AID C-terminal mutants. Interestingly, these mutants showed relative reduction in GC compared with SHM in chicken DT40 cells. Collectively, our data indicate that the C-terminal region of AID is required for efficient generation of DSB in CSR and GC and thus for the subsequent pairing of cleaved DNA ends during recombination in CSR.

  16. The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation.

    PubMed

    Begum, Nasim A; Stanlie, Andre; Nakata, Mikiyo; Akiyama, Hideo; Honjo, Tasuku

    2012-09-21

    H3K4me3 plays a critical role in the activation-induced cytidine deaminase (AID)-induced DNA cleavage of switch (S) regions in the immunoglobulin heavy chain (IgH) locus during class-switch recombination (CSR). The histone chaperone complex facilitates chromatin transcription (FACT) is responsible for forming H3K4me3 at AID target loci. Here we show that the histone chaperone suppressor of Ty6 (Spt6) also participates in regulating H3K4me3 for CSR and for somatic hypermutation in AID target loci. We found that H3K4me3 loss was correlated with defects in AID-induced DNA breakage and reduced mutation frequencies in IgH loci in both S and variable regions and in non-IgH loci such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and small nucleolar RNA host gene 3 (SNHG3). Global gene expression analysis revealed that Spt6 can act as both a positive and negative transcriptional regulator in B cells, affecting ∼5% of the genes that includes suppressor of Ty4 (Spt4) and AID. Interestingly, Spt6 regulates CSR and AID expression through two distinct histone modification pathways, H3K4me3 and H3K36me3, respectively. Tandem SH2 domain of Spt6 plays a critical role in CSR and H3K4me3 regulation involving Set1 histone methyltransferase. We conclude that Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus.

  17. The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation.

    PubMed

    Begum, Nasim A; Stanlie, Andre; Nakata, Mikiyo; Akiyama, Hideo; Honjo, Tasuku

    2012-09-21

    H3K4me3 plays a critical role in the activation-induced cytidine deaminase (AID)-induced DNA cleavage of switch (S) regions in the immunoglobulin heavy chain (IgH) locus during class-switch recombination (CSR). The histone chaperone complex facilitates chromatin transcription (FACT) is responsible for forming H3K4me3 at AID target loci. Here we show that the histone chaperone suppressor of Ty6 (Spt6) also participates in regulating H3K4me3 for CSR and for somatic hypermutation in AID target loci. We found that H3K4me3 loss was correlated with defects in AID-induced DNA breakage and reduced mutation frequencies in IgH loci in both S and variable regions and in non-IgH loci such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and small nucleolar RNA host gene 3 (SNHG3). Global gene expression analysis revealed that Spt6 can act as both a positive and negative transcriptional regulator in B cells, affecting ∼5% of the genes that includes suppressor of Ty4 (Spt4) and AID. Interestingly, Spt6 regulates CSR and AID expression through two distinct histone modification pathways, H3K4me3 and H3K36me3, respectively. Tandem SH2 domain of Spt6 plays a critical role in CSR and H3K4me3 regulation involving Set1 histone methyltransferase. We conclude that Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus. PMID:22843687

  18. Programming of the macronucleus of Paramecium during asexual and sexual reproduction: A further study with cytidine analogues, dimethylsulfoxide, L-ethionine and N-butyric acid.

    PubMed

    Au, K Y; Yao, C M; Cowan, R; Ng, S F

    1990-08-31

    The control of the function of the macronucleus of Paramecium is studied, in connection with its role in the compensation for the asexual somatic function of the micronucleus. Following removal of the micronuclei, amicronucleate cell lines as a rule suffer a transient period of growth and developmental depression in the initial phase of asexual propagation. But they gradually recover to near-normal. Previous studies of treatment of amicronucleate cells with cytidine analogues have implicated the macronucleus in compensating for the somatic function of the micronucleus following the loss of the micronucleus, and the activation of this macronuclear function probably involves DNA-demethylation. The present study further tests this notion, by treating micronucleate cells with agents known to promote demethylation of 5-methylcytosine. After treatment, the cells were vegetatively propagated, and then enucleated to give rise to amicronucleate cell lines. Treatments with dimethylsulfoxide, L-ethionine, and 5-aza-2'-deoxycytidine promoted recovery in amicronucleate cell lines thus derived. Cells treated with 6-azacytidine did not produce such an effect. Hence, the compensatory mechanism, presumably residing in a repressed state in the macronucleus, can be activated or primed to activate by demethylating agents even before the loss of the micronucleus, and once established the new macronuclear programme perpetuates in succeeding asexual cell generations. This shows that during asexual propagation the macronuclear programme can be altered to 'pre-adapt' the cells for amicronuclearity. Treatment of micronucleate conjugants with 5-azacytidine, when the macronuclear anlagen develop, produced clones that had become similarly pre-adapted. There were also some indication of persistence of such effects of the analogue into the next clonal cycle following autogamy. The notion of macronuclear DNA-demethylation as a basis for the activation and maintenance of the compensatory mechanism

  19. Delta Inulin Adjuvant Enhances Plasmablast Generation, Expression of Activation-Induced Cytidine Deaminase and B-Cell Affinity Maturation in Human Subjects Receiving Seasonal Influenza Vaccine

    PubMed Central

    Li, Lei; Honda-Okubo, Yoshikazu; Li, Connie; Sajkov, Dimitar; Petrovsky, Nikolai

    2015-01-01

    There is a major need for new adjuvants to improve the efficacy of seasonal and pandemic influenza vaccines. Advax is a novel polysaccharide adjuvant based on delta inulin that has been shown to enhance the immunogenicity of influenza vaccine in animal models and human clinical trials. To better understand the mechanism for this enhancement, we sought to assess its effect on the plasmablast response in human subjects. This pilot study utilised cryopreserved 7 day post-vaccination (7dpv) peripheral blood mononuclear cell samples obtained from a subset of 25 adult subjects from the FLU006-12 trial who had been immunized intramuscularly with a standard dose of 2012 trivalent inactivated influenza vaccine (TIV) alone (n=9 subjects) or combined with 5mg (n=8) or 10mg (n=8) of Advax adjuvant. Subjects receiving Advax adjuvant had increased 7dpv plasmablasts, which in turn exhibited a 2-3 fold higher rate of non-silent mutations in the B-cell receptor CDR3 region associated with higher expression of activation-induced cytidine deaminase (AID), the major enzyme controlling BCR affinity maturation. Together, these data suggest that Advax adjuvant enhances influenza immunity in immunized subjects via multiple mechanisms including increased plasmablast generation, AID expression and CDR3 mutagenesis resulting in enhanced BCR affinity maturation and increased production of high avidity antibody. How Advax adjuvant achieves these beneficial effects on plasmablasts remains the subject of ongoing investigation. Trial Registration Australia New Zealand Clinical Trials Register ACTRN12612000709842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362709 PMID:26177480

  20. Crystal Structure of DNA Cytidine Deaminase ABOBEC3G Catalytic Deamination Domain Suggests a Binding Mode of Full-length Enzyme to Single-stranded DNA*

    PubMed Central

    Lu, Xiuxiu; Zhang, Tianlong; Xu, Zeng; Liu, Shanshan; Zhao, Bin; Lan, Wenxian; Wang, Chunxi; Ding, Jianping; Cao, Chunyang

    2015-01-01

    APOBEC3G (A3G) is a DNA cytidine deaminase (CD) that demonstrates antiviral activity against human immunodeficiency virus 1 (HIV-1) and other pathogenic virus. It has an inactive N-terminal CD1 virus infectivity factor (Vif) protein binding domain (A3G-CD1) and an actively catalytic C-terminal CD2 deamination domain (A3G-CD2). Although many studies on the structure of A3G-CD2 and enzymatic properties of full-length A3G have been reported, the mechanism of how A3G interacts with HIV-1 single-stranded DNA (ssDNA) is still not well characterized. Here, we reported a crystal structure of a novel A3G-CD2 head-to-tail dimer (in which the N terminus of the monomer H (head) interacts with the C terminus of monomer T (tail)), where a continuous DNA binding groove was observed. By constructing the A3G-CD1 structural model, we found that its overall fold was almost identical to that of A3G-CD2. We mutated the residues located in or along the groove in monomer H and the residues in A3G-CD1 that correspond to those seated in or along the groove in monomer T. Then, by performing enzymatic assays, we confirmed the reported key elements and the residues in A3G necessary to the catalytic deamination. Moreover, we identified more than 10 residues in A3G essential to DNA binding and deamination reaction. Therefore, this dimer structure may represent a structural model of full-length A3G, which indicates a possible binding mode of A3G to HIV-1 ssDNA. PMID:25542899

  1. Crystal structure of DNA cytidine deaminase ABOBEC3G catalytic deamination domain suggests a binding mode of full-length enzyme to single-stranded DNA.

    PubMed

    Lu, Xiuxiu; Zhang, Tianlong; Xu, Zeng; Liu, Shanshan; Zhao, Bin; Lan, Wenxian; Wang, Chunxi; Ding, Jianping; Cao, Chunyang

    2015-02-13

    APOBEC3G (A3G) is a DNA cytidine deaminase (CD) that demonstrates antiviral activity against human immunodeficiency virus 1 (HIV-1) and other pathogenic virus. It has an inactive N-terminal CD1 virus infectivity factor (Vif) protein binding domain (A3G-CD1) and an actively catalytic C-terminal CD2 deamination domain (A3G-CD2). Although many studies on the structure of A3G-CD2 and enzymatic properties of full-length A3G have been reported, the mechanism of how A3G interacts with HIV-1 single-stranded DNA (ssDNA) is still not well characterized. Here, we reported a crystal structure of a novel A3G-CD2 head-to-tail dimer (in which the N terminus of the monomer H (head) interacts with the C terminus of monomer T (tail)), where a continuous DNA binding groove was observed. By constructing the A3G-CD1 structural model, we found that its overall fold was almost identical to that of A3G-CD2. We mutated the residues located in or along the groove in monomer H and the residues in A3G-CD1 that correspond to those seated in or along the groove in monomer T. Then, by performing enzymatic assays, we confirmed the reported key elements and the residues in A3G necessary to the catalytic deamination. Moreover, we identified more than 10 residues in A3G essential to DNA binding and deamination reaction. Therefore, this dimer structure may represent a structural model of full-length A3G, which indicates a possible binding mode of A3G to HIV-1 ssDNA.

  2. Behind the Label "Alcoholic."

    ERIC Educational Resources Information Center

    Wright, Deborah M.

    1989-01-01

    Relates individual's personal story of her childhood influenced by her parent's alcoholism, her own alcoholism as a young adult, and her experiences with counseling. Asks others not to reject her because of the label "alcoholic." (ABL)

  3. Like your labels?

    PubMed

    Field, Michele

    2010-01-01

    The descriptive “conventions” used on food labels are always evolving. Today, however, the changes are so complicated (partly driven by legislation requiring disclosures about environmental impacts, health issues, and geographical provenance) that these labels more often baffle buyers than enlighten them. In a light-handed manner, the article points to how sometimes reading label language can be like deciphering runes—and how if we are familiar with the technical terms, we can find a literal meaning, but still not see the implications. The article could be ten times longer because food labels vary according to cultures—but all food-exporting cultures now take advantage of our short attention-span when faced with these texts. The question is whether less is more—and if so, in this contest for our attention, what “contestant” is voted off. PMID:21539053

  4. Incorporation of reporter-labeled nucleotides by DNA polymerases.

    PubMed

    Anderson, Jon P; Angerer, Bernhard; Loeb, Lawrence A

    2005-02-01

    The incorporation of fluorescently labeled nucleotides into DNA by DNA polymerases has been used extensively for tagging genes and for labeling DNA. However, we lack studies comparing polymerase efficiencies for incorporating different fluorescently labeled nucleotides. We analyzed the incorporation of fluorescent deoxynucleoside triphosphates by 10 different DNA polymerases, representing a cross-section of DNA polymerases from families A, B, and reverse transcriptase. The substitution of one or more different reporter-labeled nucleotides for the cognate nucleotides was initially investigated by using an in vitro polymerase extension filter-binding assay with natural DNA as a template. Further analysis on longer DNA fragments containing one or more nucleotide analogs was performed using a newly developed extension cut assay. The results indicate that incorporation of fluorescent nucleotides is dependent on the DNA polymerase, fluorophore, linker between the nucleotide and the fluorophore, and position for attachment of the linker and the cognate nucleotide. Of the polymerases tested, Taq and Vent exo DNA polymerases were most efficient at incorporating a variety of fluorescently labeled nucleotides. This study suggests that it should be feasible to copy DNA with reactions mixtures that contain all four fluorescently labeled nucleotides allowing for high-density labeling of DNA. PMID:15727132

  5. The nicotinic acetylcholine receptor: Binding of nitroxide analogs of a local anesthetic and a photoactivatable analog of phosphatidylserine

    SciTech Connect

    Blanton, M.P.

    1989-01-01

    Electron spin resonance was used to contrast the accessibility of tertiary and quaternary amine local anesthetics to their high affinity binding site in the desensitized Torpedo californica acetylcholine receptor (AchR). Preincubation of AchR-rich membranes with agonist resulted in a substantial reduction in the initial association of the quaternary amine local anesthetic C6SLMEI with the receptor. The time-dependent reduction in association follows a biphasic exponential function having rate constants of 0.19 min{sup {minus}1} and 0.03 min{sup {minus}1}. In contrast, agonist preincubation did not produce a comparable decrease in the association of C6SL, a tertiary amine analog, with the AchR. The results are modeled in two ways: (1) A charge gate near the channel mouth in the desensitized receptor limits access of the permanently charged cationic local anesthetic (C6SLMEI), but not for the uncharged form of the tertiary amine anesthetic C6SL. (2) A hydrophobic pathway, possibly through a corridor in the annular lipid surrounding receptor subunits, allows the uncharged form of C6SL to reach the high affinity binding site in the AchR. A photoactivatable analog of phosphatidylserine {sup 125}I 4-azido salicylic acid-phosphatidylserine ({sup 125}I ASA-PS) was use to label both Torpedo californica acetylcholine receptor-rich membranes and reconstituted AchR membranes. All four subunits of the AchR were found to incorporate label, with the {alpha} subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchR {alpha} subunit that incorporate {sup 125}I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. Eighty-one per cent of the incorporated label was localized to 11.7 and 10.1 kdal V8 cleavage fragments.

  6. Routing and Label Space Reduction in Label Switching Networks

    NASA Astrophysics Data System (ADS)

    Solano, Fernando; Caro, Luis Fernando; Stidsen, Thomas; Papadimitriou, Dimitri

    This chapter is devoted to the analysis and modeling of some problems related to the optimal usage of the label space in label switching networks. Label space problems concerning three different technologies and architectures - namely Multi-protocol Label Switching (MPLS), Ethernet VLAN-Label Switching (ELS) and All-Optical Label Switching (AOLS) - are discussed in this chapter. Each of these cases yields to different constraints of the general label space reduction problem. We propose a generic optimization model and, then, we describe some adaptations aiming at modeling each particular case. Simulation results are briefly discussed at the end of this chapter.

  7. Off-Label Drug Use

    MedlinePlus

    ... Your Local Offices Close + - Text Size Off-label Drug Use What is off-label drug use? In the United States new drugs are ... unapproved use of a drug. Is off-label drug use legal? The off-label use of FDA- ...

  8. Analog computing by Brewster effect.

    PubMed

    Youssefi, Amir; Zangeneh-Nejad, Farzad; Abdollahramezani, Sajjad; Khavasi, Amin

    2016-08-01

    Optical computing has emerged as a promising candidate for real-time and parallel continuous data processing. Motivated by recent progresses in metamaterial-based analog computing [Science343, 160 (2014)SCIEAS0036-807510.1126/science.1242818], we theoretically investigate the realization of two-dimensional complex mathematical operations using rotated configurations, recently reported in [Opt. Lett.39, 1278 (2014)OPLEDP0146-959210.1364/OL.39.001278]. Breaking the reflection symmetry, such configurations could realize both even and odd Green's functions associated with spatial operators. Based on such an appealing theory and by using the Brewster effect, we demonstrate realization of a first-order differentiator. Such an efficient wave-based computation method not only circumvents the major potential drawbacks of metamaterials, but also offers the most compact possible device compared to conventional bulky lens-based optical signal and data processors.

  9. QCD analogy for quantum gravity

    NASA Astrophysics Data System (ADS)

    Holdom, Bob; Ren, Jing

    2016-06-01

    Quadratic gravity presents us with a renormalizable, asymptotically free theory of quantum gravity. When its couplings grow strong at some scale, as in QCD, then this strong scale sets the Planck mass. QCD has a gluon that does not appear in the physical spectrum. Quadratic gravity has a spin-2 ghost that we conjecture does not appear in the physical spectrum. We discuss how the QCD analogy leads to this conjecture and to the possible emergence of general relativity. Certain aspects of the QCD path integral and its measure are also similar for quadratic gravity. With the addition of the Einstein-Hilbert term, quadratic gravity has a dimensionful parameter that seems to control a quantum phase transition and the size of a mass gap in the strong phase.

  10. Methods for tritium labeling

    DOEpatents

    Andres, Hendrik; Morimoto, Hiromi; Williams, Philip G.

    1993-01-01

    Reagents and processes for reductively introducing deuterium or tritium into organic molecules are described. The reagents are deuterium or tritium analogs of trialkyl boranes, borane or alkali metal aluminum hydrides. The process involves forming these reagents in situ from alkali metal tritides or deuterides.

  11. The Young Solar Analogs Project

    NASA Astrophysics Data System (ADS)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Seeds, M. F.; Morrison, S. S.

    2012-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using the Dark Sky Observatory (DSO -- Appalachian State University) 32-inch telescope and the G/M spectrograph. These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in our 5th year of obtaining Ca II K & H chromospheric flux measurements, and are beginning to see signs of long-term activity cycles in a number of our stars. In addition, rotational modulation of the chromospheric fluxes is detectable in our data, and we have determined rotational periods for many of our stars. Short timescale increases in the K & H fluxes have been observed in a number of our stars; these events may be related to stellar flares. VATTSpec, a new moderate-resolution spectrograph on the 1.8-m Vatican Telescope in Arizona, has recently become involved with the project. This spectrograph will increase our ability to detect short-term changes in stellar activity on timescales of hours to minutes. We have been monitoring the program stars for one year in a multi-band photometric system consisting of Stromgren-v, and Johnson B, V, and R filters. We will soon add a narrow-band H-alpha filter to the system. Photometry is being carried out with a small piggy-back telescope on the 32-inch, but a robotic photometric telescope is currently being installed at DSO for this purpose. This project is supported by the National Science Foundation.

  12. Children's use of analogy during collaborative reasoning.

    PubMed

    Lin, Tzu-Jung; Anderson, Richard C; Hummel, John E; Jadallah, May; Miller, Brian W; Nguyen-Jahiel, Kim; Morris, Joshua A; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age M=10.0, SD=0.6). Use of analogy was found to spread among the children in discussion groups and occur at an accelerating rate, primarily because of the increasing use of novel analogies. Relational analogies with shared surface features triggered purely relational analogies during the next 2 speaking turns, showing a trend of relational shift. These results provide distinctive new evidence for the importance of social interaction in an aspect of cognitive development. PMID:22670717

  13. An emergent approach to analogical inference

    NASA Astrophysics Data System (ADS)

    Thibodeau, Paul H.; Flusberg, Stephen J.; Glick, Jeremy J.; Sternberg, Daniel A.

    2013-03-01

    In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference.

  14. Classical Analogs of a Diatomic Chain

    SciTech Connect

    Gutierrez, L.; Diaz-de-Anda, A.; Mendez-Sanchez, R. A.; Morales, A.; Flores, J.; Monsivais, G.

    2010-12-21

    Using one dimensional rods with different configurations classical analogs of quantum mechanical systems frequently used in solid state physics can be obtained. Among this analogs we have recently discussed locally periodic rods which lead to band spectra; the effect of a topological defect, and the Wannier Stark ladders. In this paper, we present an elastic analog of the diatomic chain and show how the acoustical and optical bands emerge, as well of the nature of the wave amplitudes.

  15. A versatile toolbox for posttranscriptional chemical labeling and imaging of RNA.

    PubMed

    Sawant, Anupam A; Tanpure, Arun A; Mukherjee, Progya P; Athavale, Soumitra; Kelkar, Ashwin; Galande, Sanjeev; Srivatsan, Seergazhi G

    2016-01-29

    Cellular RNA labeling strategies based on bioorthogonal chemical reactions are much less developed in comparison to glycan, protein and DNA due to its inherent instability and lack of effective methods to introduce bioorthogonal reactive functionalities (e.g. azide) into RNA. Here we report the development of a simple and modular posttranscriptional chemical labeling and imaging technique for RNA by using a novel toolbox comprised of azide-modified UTP analogs. These analogs facilitate the enzymatic incorporation of azide groups into RNA, which can be posttranscriptionally labeled with a variety of probes by click and Staudinger reactions. Importantly, we show for the first time the specific incorporation of azide groups into cellular RNA by endogenous RNA polymerases, which enabled the imaging of newly transcribing RNA in fixed and in live cells by click reactions. This labeling method is practical and provides a new platform to study RNA in vitro and in cells. PMID:26384420

  16. Real World: Analog Testing in Extreme Environments

    NASA Video Gallery

    See how NASA uses analog testing to simulate space exploration. Explore extreme environments like the Aquarius underwater laboratory in Key Largo, Florida. Find out how scientists use mathematical ...

  17. B cell Rab7 mediates induction of activation-induced cytidine deaminase expression and class-switching in T-dependent and T-independent antibody responses.

    PubMed

    Pone, Egest J; Lam, Tonika; Lou, Zheng; Wang, Rui; Chen, Yuhui; Liu, Dongfang; Edinger, Aimee L; Xu, Zhenming; Casali, Paolo

    2015-04-01

    Class switch DNA recombination (CSR) is central to the maturation of the Ab response because it diversifies Ab effector functions. Like somatic hypermutation, CSR requires activation-induced cytidine deaminase (AID), whose expression is restricted to B cells, as induced by CD40 engagement or dual TLR-BCR engagement (primary CSR-inducing stimuli). By constructing conditional knockout Igh(+/C)γ(1-cre)Rab7(fl/fl) mice, we identified a B cell-intrinsic role for Rab7, a small GTPase involved in intracellular membrane functions, in mediating AID induction and CSR. Igh(+/C)γ(1-cre)Rab7(fl/fl) mice displayed normal B and T cell development and were deficient in Rab7 only in B cells undergoing Igh(C)γ(1-cre) Iγ1-Sγ1-Cγ1-cre transcription, as induced--like Igh germline Iγ1-Sγ1-Cγ1 and Iε-Sε-Cε transcription--by IL-4 in conjunction with a primary CSR-inducing stimulus. These mice could not mount T-independent or T-dependent class-switched IgG1 or IgE responses while maintaining normal IgM levels. Igh(+/C)γ(1-cre)Rab7(fl/fl) B cells showed, in vivo and in vitro, normal proliferation and survival, normal Blimp-1 expression and plasma cell differentiation, as well as intact activation of the noncanonical NF-κB, p38 kinase, and ERK1/2 kinase pathways. They, however, were defective in AID expression and CSR in vivo and in vitro, as induced by CD40 engagement or dual TLR1/2-, TLR4-, TLR7-, or TLR9-BCR engagement. In Igh(+/C)γ(1-cre)Rab7(fl/fl) B cells, CSR was rescued by enforced AID expression. These findings, together with our demonstration that Rab7-mediated canonical NF-κB activation, as critical to AID induction, outline a novel role of Rab7 in signaling pathways that lead to AID expression and CSR, likely by promoting assembly of signaling complexes along intracellular membranes.

  18. Expert analogy use in a naturalistic setting

    PubMed Central

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

    The use of analogy is an important component of human cognition. The type of analogy we produce and communicate depends heavily on a number of factors, such as the setting, the level of domain expertise present, and the speaker's goal or intent. In this observational study, we recorded economics experts during scientific discussion and examined the categorical distance and structural depth of the analogies they produced. We also sought to characterize the purpose of the analogies that were generated. Our results supported previous conclusions about the infrequency of superficial similarity in subject-generated analogs, but also showed that distance and depth characteristics were more evenly balanced than in previous observational studies. This finding was likely due to the nature of the goals of the participants, as well as the broader nature of their expertise. An analysis of analogical purpose indicated that the generation of concrete source examples of more general target concepts was most prevalent. We also noted frequent instances of analogies intended to form visual images of source concepts. Other common purposes for analogies were the addition of colorful speech, inclusion (i.e., subsumption) of a target into a source concept, or differentiation between source and target concepts. We found no association between depth and either of the other two characteristics, but our findings suggest a relationship between purpose and distance; i.e., that visual imagery typically entailed an outside-domain source whereas exemplification was most frequently accomplished using within-domain analogies. Overall, we observed a rich and diverse set of spontaneously produced analogical comparisons. The high degree of expertise within the observed group along with the richly comparative nature of the economics discipline likely contributed to this analogical abundance. PMID:25505437

  19. Novel Analog For Muscle Deconditioning

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd, Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Bloomberg, Jacob

    2010-01-01

    Existing models of muscle deconditioning are cumbersome and expensive (ex: bedrest). We propose a new model utilizing a weighted suit to manipulate strength, power or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre- and post-flight astronaut performance data using the same tasks. Spline regression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of: leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/ BW of 79 J/kg, knee extension (KE) isokinetic/BW of 6 Nm/Kg and KE torque/BW of 1.9 Nm/kg. Conclusions: Laboratory manipulation of strength / BW has promise as an appropriate analog for spaceflight-induced loss of muscle function for predicting occupational task performance and establishing operationally relevant exercise targets.

  20. Novel Analog For Muscle Deconditioning

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori; Ryder, Jeff; Buxton, Roxanne; Redd. Elizabeth; Scott-Pandorf, Melissa; Hackney, Kyle; Fiedler, James; Ploutz-Snyder, Robert; Bloomberg, Jacob

    2011-01-01

    Existing models (such as bed rest) of muscle deconditioning are cumbersome and expensive. We propose a new model utilizing a weighted suit to manipulate strength, power, or endurance (function) relative to body weight (BW). Methods: 20 subjects performed 7 occupational astronaut tasks while wearing a suit weighted with 0-120% of BW. Models of the full relationship between muscle function/BW and task completion time were developed using fractional polynomial regression and verified by the addition of pre-and postflightastronaut performance data for the same tasks. Splineregression was used to identify muscle function thresholds below which task performance was impaired. Results: Thresholds of performance decline were identified for each task. Seated egress & walk (most difficult task) showed thresholds of leg press (LP) isometric peak force/BW of 18 N/kg, LP power/BW of 18 W/kg, LP work/BW of 79 J/kg, isokineticknee extension (KE)/BW of 6 Nm/kg, and KE torque/BW of 1.9 Nm/kg.Conclusions: Laboratory manipulation of relative strength has promise as an appropriate analog for spaceflight-induced loss of muscle function, for predicting occupational task performance and establishing operationally relevant strength thresholds.

  1. Solar System Analog; WMO Statement

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    Scientists searching for extra-solar planets have discovered the closest known analog to our own Solar System. A planet with a mass about twice that of Jupiter is in a near-circular orbit of the star HD70642, a team of astronomers from Australia, the United Kingdom, and the United States announced on 3 July at a conference in Paris on extra-solar planets.The planet measures about three-fifths the size of Jupiter, circles its star about every six years, and is in an orbit equivalent to being about halfway between Mars and Jupiter if it were located in our Solar System, according to the astronomers. The star is about 90 light years away from Earth in the constellation Puppis.Public concern about a spate of well-publicized, extreme weather events around the world this year has prompted the World Meteorological Organization to issue a statement that, as global temperatures continues to rise due to climate change, the number and intensity of extreme events might increase. The July 2 statement is based on scientific assessments by the Intergovernmental Panel on Climate Change and others, rather than on any new studies, according to Ken Davidson, director orf WMO's World Climate Program Department. The statement cites record high termperatures so far this summer in southern France and in Switzerland, an abnormally high number of tornadoes in the U.S. in May, and particularly heavy rains from tropical cyclones in Sri Lanka.

  2. Diverse pathways of phosphatidylcholine biosynthesis in algae as estimated by labeling studies and genomic sequence analysis.

    PubMed

    Sato, Naoki; Mori, Natsumi; Hirashima, Takashi; Moriyama, Takashi

    2016-08-01

    Phosphatidylcholine (PC) is an almost ubiquitous phospholipid in eukaryotic algae and plants but is not found in a few species, for example Chlamydomonas reinhardtii. We recently found that some species of the genus Chlamydomonas possess PC. In the universal pathway, PC is synthesized de novo by methylation of phosphatidylethanolamine (PE) or transfer of phosphocholine from cytidine diphosphate (CDP)-choline to diacylglycerol. Phosphocholine, the direct precursor to CDP-choline, is synthesized either by methylation of phosphoethanolamine or phosphorylation of choline. Here we analyzed the mechanism of PC biosynthesis in two species of Chlamydomonas (asymmetrica and sphaeroides) as well as in a red alga, Cyanidioschyzon merolae. Comparative genomic analysis of enzymes involved in PC biosynthesis indicated that C. merolae possesses only the PE methylation pathway. Radioactive tracer experiments using [(32) P]phosphate showed delayed labeling of PC with respect to PE, which was consistent with the PE methylation pathway. In Chlamydomonas asymmetrica, labeling of PC was detected from the early time of incubation with [(32) P]phosphate, suggesting the operation of phosphoethanolamine methylation pathway. Genomic analysis indeed detected the genes for the phosphoethanolamine methylation pathway. In contrast, the labeling of PC in C. sphaeroides was slow, suggesting that the PE methylation pathway was at work. These results as well as biochemical and computational results uncover an unexpected diversity of the mechanisms for PC biosynthesis in algae. Based on these results, we will discuss plausible mechanisms for the scattered distribution of the ability to biosynthesize PC in the genus Chlamydomonas. PMID:27133435

  3. The Pennies-as-Electrons Analogy

    ERIC Educational Resources Information Center

    Ashmann, Scott

    2009-01-01

    Everyday experiences familiarize students with the ways in which electricity is used, but often the underlying concepts remain a mystery. Teachers often use analogies to help students relate the flow of electrons to other common systems, but many times these analogies are incomplete and lead to more student misconceptions. However, the "pass the…

  4. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

    Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

    2015-01-01

    Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

  5. Piperazine-based nucleic acid analogs

    DOEpatents

    Schmidt, Jurgen; Silks, Louis A.; Michalczyk, Ryszard

    2005-01-11

    A novel nucleoside analog is disclosed which comprises a piperazine ring in the place of the ring ribose or deoxyribose sugar. Monomers utilizing a broad variety of nucleobases are disclosed, as well as oligomers comprising the monomers disclosed herein linked by a variety of linkages, including amide, phosphonamide, and sulfonamide linkages. A method of synthesizing the nucleoside analogs is also disclosed.

  6. An Analog Computer for Electronic Engineering Education

    ERIC Educational Resources Information Center

    Fitch, A. L.; Iu, H. H. C.; Lu, D. D. C.

    2011-01-01

    This paper describes a compact analog computer and proposes its use in electronic engineering teaching laboratories to develop student understanding of applications in analog electronics, electronic components, engineering mathematics, control engineering, safe laboratory and workshop practices, circuit construction, testing, and maintenance. The…

  7. A Mechanical Analogy for the Photoelectric Effect

    ERIC Educational Resources Information Center

    Kovacevic, Milan S.; Djordjevich, Alexandar

    2006-01-01

    Analogy is a potent tool in the teacher's repertoire. It has been particularly well recognized in the teaching of science. However, careful planning is required for its effective application to prevent documented drawbacks when analogies are stretched too far. Befitting the occasion of the World Year of Physics commemorating Albert Einstein's 1905…

  8. Analogical Processes and College Developmental Reading

    ERIC Educational Resources Information Center

    Paulson, Eric J.

    2014-01-01

    Although a solid body of research concerning the role of analogies in reading processes has emerged at a variety of age groups and reading proficiencies, few of those studies have focused on analogy use by readers enrolled in college developmental reading courses. The current study explores whether 232 students enrolled in mandatory (by placement…

  9. Children's Use of Analogy during Collaborative Reasoning

    ERIC Educational Resources Information Center

    Lin, Tzu-Jung; Anderson, Richard C.; Hummel, John E.; Jadallah, May; Miller, Brian W.; Nguyen-Jahiel, Kim; Morris, Joshua A.; Kuo, Li-Jen; Kim, Il-Hee; Wu, Xiaoying; Dong, Ting

    2012-01-01

    This microgenetic study examined social influences on children's development of analogical reasoning during peer-led small-group discussions of stories about controversial issues. A total of 277 analogies were identified among 7,215 child turns for speaking during 54 discussions from 18 discussion groups in 6 fourth-grade classrooms (N = 120; age…

  10. Young Children's Analogical Reasoning in Science Domains

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

    This exploratory study in a classroom setting investigates first graders' (age 7-8 years, N = 25) ability to perform analogical reasoning and create their own analogies for two irreversible natural phenomena: mixing and heat transfer. We found that the children who contributed actively to a full-class discussion were consistently successful at…

  11. The Structure of Analogical Models in Science.

    ERIC Educational Resources Information Center

    Gentner, Dedre

    Analogical models can be powerful aids to reasoning, as when light is explained in terms of water waves; or they can be misleading, as when chemical processes are thought of in terms of life processes such as putrefaction. This paper proposes a structural characterization of good science analogy using a theoretical approach in which complex…

  12. Mathematical Analogs and the Teaching of Fractions.

    ERIC Educational Resources Information Center

    Charles, Kathy; Nason, Rod; Cooper, Tom

    The literature has noted that some mathematical analogs are more effective than others for the teaching of fractions. This study aimed to evaluate the efficacy of seven mathematical analogs commonly used in the teaching of the partitive quotient fraction construct. A sample of twelve purposively selected Year Three children were presented with…

  13. 38 CFR 4.20 - Analogous ratings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Analogous ratings. 4.20 Section 4.20 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS SCHEDULE FOR RATING DISABILITIES General Policy in Rating § 4.20 Analogous ratings. When an unlisted condition is encountered...

  14. Use of Analogy in Computer Language Acquisition.

    ERIC Educational Resources Information Center

    Pohl, Heidi L.; Nutter, Jane Terry

    1985-01-01

    Subjects in a study of analogic reasoning use in learning a computer language read text describing an invented LISP dialect and then solved problems and described language constructs. Five of six factors studied indicating use of analogy with a familiar computer language showed statistically significant results, supporting the hypothesis.…

  15. Energy Savings Assessment for Digital-to-Analog Converter Boxes

    SciTech Connect

    Cheung, Hoi Ying Iris; Meier, Alan; Brown, Richard

    2011-01-18

    The Digital Television (DTV) Converter Box Coupon Program was administered by the U.S. government to subsidize purchases of digital-to-analog converter boxes, with up to two $40 coupons for each eligible household. In order to qualify as Coupon Eligible Converter Boxes (CECBs), these devices had to meet a number of minimum performance specifications, including energy efficiency standards. The Energy Star Program also established voluntary energy efficiency specifications that are more stringent than the CECB requirements. In this study, we measured the power and energy consumptions for a sample of 12 CECBs (including 6 Energy Star labeled models) in-use in homes and estimated aggregate energy savings produced by the energy efficiency policies. Based on the 35 million coupons redeemed through the end of the program, our analysis indicates that between 2500 and 3700 GWh per year are saved as a result of the energy efficiency policies implemented on digital-to-analog converter boxes. The energy savings generated are equivalent to the annual electricity use of 280,000 average US homes.

  16. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  17. An Analog Earth Climate Model

    NASA Astrophysics Data System (ADS)

    Varekamp, J. C.

    2010-12-01

    The earth climate is broadly governed by the radiative power of the sun as well as the heat retention and convective cooling of the atmosphere. I have constructed an analog earth model for an undergraduate climate class that simulates mean climate using these three parameters. The ‘earth’ is a hollow, black, bronze sphere (4 cm diameter) mounted on a thin insulated rod, and illuminated by two opposite optic fibers, with light focused on the sphere by a set of lenses. The sphere is encased in a large double-walled aluminum cylinder (34 cm diameter by 26 cm high) with separate water cooling jackets at the top, bottom, and sides. The cylinder can be filled with a gas of choice at a variety of pressures or can be run in vacuum. The exterior is cladded with insulation, and the temperature of the sphere, atmosphere and walls is monitored with thermocouples. The temperature and waterflow of the three cooling jackets can be monitored to establish the energy output of the whole system; the energy input is the energy yield of the two optic fibers. A small IR transmissive lens at the top provides the opportunity to hook up the fiber of a hyper spectrometer to monitor the emission spectrum of the black ‘earth’ sphere. A pressure gauge and gas inlet-outlet system for flushing of the cell completes it. The heat yield of the cooling water at the top is the sum of the radiative and convective components, whereas the bottom jacket only carries off the radiative heat of the sphere. Undergraduate E&ES students at Wesleyan University have run experiments with dry air, pure CO2, N2 and Ar at 1 atmosphere, and a low vacuum run was accomplished to calibrate the energy input. For each experiment, the lights are flipped on, the temperature acquisition routine is activated, and the sphere starts to warm up until an equilibrium temperature has been reached. The lights are then flipped off and the cooling sequence towards ambient is registered. The energy input is constant for a given

  18. Investigation of Celestial Solid Analogs

    NASA Technical Reports Server (NTRS)

    Sievers, A. J.

    2003-01-01

    Our far infrared studies of both hydrophobic and hydrophilic aerogel grains have demonstrated that the mm and sub-mm wave absorption produced by the fundamental two level systems (TLS) mechanism represents a more significant contribution for these open grain structures than for bulk amorphous silicate grains. We found that the region with the anomalous temperature dependence of the spectral index due to the TLS excitations can extend in a fluffy material up to 80 per cm, which is well beyond its typical upper limit for bulk glasses. Currently there is no theoretical explanation for this surprising result. The effects of reduced dimensionality on the optical properties of carbonaceous grains have been studied with a systematic investigation of carbon aerogels. This spectroscopic approach has permitted a more reliable determination of the single grain mass normalized absorption coefficient based on the experimentally determined characteristics of the fluffy material rather than on first principles calculations involving the bulk properties of the substance. Our finding is that the electrical connectivity of the material is the main factor affecting its far infrared absorption coefficient. Another one of the main constituents of the interstellar dust, amorphous ice, has been investigated in the mm-wave region both in the high (HDA) and low (LDA) density amorphous phases and as a function of impurities. We found that doping either phase with ionic (LiCl) or molecular (methanol) impurities decreases the difference in the mm-wave absorption coefficient between the HDA and LDA ice phases so that the HDA spectrum can be used as an analog for impure ice absorption in the far infrared spectral region.

  19. [Cell analogs of viral proteins].

    PubMed

    Blinov, V M; Gaĭsler, V; Krasnov, G S; Shargunov, A V; Shurdov, M A; Zverev, V V

    2014-01-01

    Horizontal transfer of genes between viruses and their hosts played an important role in the evolution of various eukaryotes including contemporary mammals as well as the pathogens themselves. Elements of viruses of various types can be found in the genome of animals. Endogenous retroviral elements composing up to 8% of human genome length not only determine its high flexibility and rapid adaptation potential. Many of virus genes such as Fv1, Lv1, Lv2 being analogues of capsid and other proteins determine effective suppression of viral replication after cell penetration by the causative agent. Introduction of these elements into genome of a wide variety of animals from fish to primates could have taken place against the background of global natural cataclysms of viral origin. Integration of retrovirus genes coding surface glycoproteins with immunosuppressing domains into genetic apparatus of animals served as an impetus to the development of viviparity and spread ofplacental mammals. Their cell analogs syncytins perform a dual function: take direct part in the formation of syncytiotrophoblast layer of placenta and ensure tolerance of immune system of mother to embryo. The acquisition of cell genes by viruses also played an important role in their evolution: various interleukins and other modulators of immune response introduced into viral genome from cell genetic apparatus became one of the most important factors of pathogenicity of a wide variety of causative agents including poxviruses, cytomegalovirus, Epstein-Barr virus and many others. Evolutionary pathways of the virus and host are thus inseparable from each other, and character of one of these directions is largely dictated by the vector of another. PMID:25051706

  20. Labeling lake water with tritium

    USGS Publications Warehouse

    Frederick, B.J.

    1963-01-01

    A method of packaging tritiated water in a manner that facilitates safe handling in environmental labeling operations, and procedures followed in labeling a large body of water with a small volume of tritiated water are described. ?? 1963.

  1. 99m tc labeled liposomes

    SciTech Connect

    Phillips, W.T.; Klipper, R.W.; Timmons, J.H.; Rudolph, A.S.

    1992-10-27

    This patent describes a method of preparing stable gamma-emitting radionuclide-labeled alkyleneamine oxime, the incubating being for a period of time sufficient to form labeled liposome-encapsulated protein.

  2. Decode the Sodium Label Lingo

    MedlinePlus

    ... For Preschooler For Gradeschooler For Teen Decode the Sodium Label Lingo Published January 24, 2013 Print Email Reading food labels can help you slash sodium. Here's how to decipher them. "Sodium free" or " ...

  3. Fostering Multilateral Involvement in Analog Research

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2015-01-01

    International collaboration in space flight research is an effective means for conducting investigations and utilizing limited resources to the fullest extent. Through these multilateral collaborations mutual research questions can be investigated and resources contributed by each international partner to maximize the scientific benefits to all parties. Recently the international partners embraced this approach to initiate collaborations in ground-based space flight analog environments. In 2011, the International Analog Research Working Group was established, and later named the International Human Space Flight Analog Research Coordination Group (HANA). Among the goals of this working group are to 1) establish a framework to coordinate research campaigns, as appropriate, to minimize duplication of effort and enhance synergy; 2) define what analogs are best to use for collaborative interests; and 3) facilitate interaction between discipline experts in order to have the full benefit of international expertise. To accomplish these goals, HANA is currently engaged in developing international research campaigns in ground-based analogs. Plans are being made for an international solicitation for proposals to address research of common interest to all international partners. This solicitation with identify an analog environment that will best accommodate the types of investigations requested. Once selected, studies will be integrated into a campaign and implemented at the analog site. Through these combined efforts, research beneficial to all partners will be conducted efficiently to further address human risks of space exploration.

  4. Label-Free Sensing of Adenosine Based on Force Variations Induced by Molecular Recognition

    PubMed Central

    Li, Jingfeng; Li, Qing; Colombi Ciacchi, Lucio; Wei, Gang

    2015-01-01

    We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM) probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS). In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated. PMID:25808841

  5. Label-free sensing of adenosine based on force variations induced by molecular recognition.

    PubMed

    Li, Jingfeng; Li, Qing; Ciacchi, Lucio Colombi; Wei, Gang

    2015-03-01

    We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM) probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS). In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated.

  6. Analogies: Explanatory Tools in Web-Based Science Instruction

    ERIC Educational Resources Information Center

    Glynn, Shawn M.; Taasoobshirazi, Gita; Fowler, Shawn

    2007-01-01

    This article helps designers of Web-based science instruction construct analogies that are as effective as those used in classrooms by exemplary science teachers. First, the authors explain what analogies are, how analogies foster learning, and what form analogies should take. Second, they discuss science teachers' use of analogies. Third, they…

  7. Programmable Analog-To-Digital Converter

    NASA Technical Reports Server (NTRS)

    Kist, Edward H., Jr.

    1993-01-01

    High-speed analog-to-digital converter with programmable voltage steps that can be changed during operation. Allows concentration of converter resolution over specific portion of waveform. Particularly useful in digitizing wind-shear radar and lidar return signals, in digital oscilloscopes, and other applications in which desirable to increase digital resolution over specific area of waveform while accepting lower resolution over rest of waveform. Effective increase in dynamic range achieved without increase in number of analog-to-digital converter bits. Enabling faster analog-to-digital conversion.

  8. Analog detection for cavity lifetime spectroscopy

    DOEpatents

    Zare, Richard N.; Harb, Charles C.; Paldus, Barbara A.; Spence, Thomas G.

    2001-05-15

    An analog detection system for determining a ring-down rate or decay rate 1/.tau. of an exponentially decaying ring-down beam issuing from a lifetime or ring-down cavity during a ring-down phase. Alternatively, the analog detection system determines a build-up rate of an exponentially growing beam issuing from the cavity during a ring-up phase. The analog system can be employed in continuous wave cavity ring-down spectroscopy (CW CRDS) and pulsed CRDS (P CRDS) arrangements utilizing any type of ring-down cavity including ring-cavities and linear cavities.

  9. Analog detection for cavity lifetime spectroscopy

    DOEpatents

    Zare, Richard N.; Harb, Charles C.; Paldus, Barbara A.; Spence, Thomas G.

    2003-01-01

    An analog detection system for determining a ring-down rate or decay rate 1/.tau. of an exponentially decaying ring-down beam issuing from a lifetime or ring-down cavity during a ring-down phase. Alternatively, the analog detection system determines a build-up rate of an exponentially growing beam issuing from the cavity during a ring-up phase. The analog system can be employed in continuous wave cavity ring-down spectroscopy (CW CRDS) and pulsed CRDS (P CRDS) arrangements utilizing any type of ring-down cavity including ring-cavities and linear cavities.

  10. Comparative conformational analysis of peptide T analogs

    NASA Astrophysics Data System (ADS)

    Akverdieva, Gulnare; Godjayev, Niftali; Akyuz, Sevim

    2009-01-01

    A series of peptide T analogs were investigated within the molecular mechanics framework. In order to determine the role of the aminoacid residues in spatial formation of peptide T the conformational peculiarities of the glycine-substituted analogs were investigated. The conformational profiles of some biologically tested analogs of this peptide were determined independently. The received data permit to assess the active form of this peptide. It is characterized by β-turn at the C-terminal physiologically active pentapeptide fragment of peptide molecule. The received results are important for the investigation of the structure-activity relationship and may be used at design of a rigid-molecule drug against HIV.

  11. Learning with imperfectly labeled patterns

    NASA Technical Reports Server (NTRS)

    Chittineni, C. B.

    1979-01-01

    The problem of learning in pattern recognition using imperfectly labeled patterns is considered. The performance of the Bayes and nearest neighbor classifiers with imperfect labels is discussed using a probabilistic model for the mislabeling of the training patterns. Schemes for training the classifier using both parametric and non parametric techniques are presented. Methods for the correction of imperfect labels were developed. To gain an understanding of the learning process, expressions are derived for success probability as a function of training time for a one dimensional increment error correction classifier with imperfect labels. Feature selection with imperfectly labeled patterns is described.

  12. Metaphors as Second Labels: Difficult for Preschool Children?

    PubMed

    Rubio-Fernández, Paula; Grassmann, Susanne

    2016-08-01

    This study investigates the development of two cognitive abilities that are involved in metaphor comprehension: implicit analogical reasoning and assigning an unconventional label to a familiar entity (as in Romeo's 'Juliet is the sun'). We presented 3- and 4-year-old children with literal object-requests in a pretense setting (e.g., 'Give me the train with the hat'). Both age-groups succeeded in a baseline condition that used building blocks as props (e.g., placed either on the front or the rear of a train engine) and only required spatial analogical reasoning to interpret the referential expression. Both age-groups performed significantly worse in the critical condition, which used familiar objects as props (e.g., small dogs as pretend hats) and required both implicit analogical reasoning and assigning second labels. Only the 4-year olds succeeded in this condition. These results offer a new perspective on young children's difficulties with metaphor comprehension in the preschool years. PMID:26162307

  13. Analog Computer Laboratory with Biological Examples.

    ERIC Educational Resources Information Center

    Strebel, Donald E.

    1979-01-01

    The use of biological examples in teaching applications of the analog computer is discussed and several examples from mathematical ecology, enzyme kinetics, and tracer dynamics are described. (Author/GA)

  14. An Electrical Analog Computer for Poets

    ERIC Educational Resources Information Center

    Bruels, Mark C.

    1972-01-01

    Nonphysics majors are presented with a direct current experiment beyond Ohms law and series and parallel laws. This involves construction of an analog computer from common rheostats and student-assembled voltmeters. (Author/TS)

  15. Synthesis of sulfonate analogs of bile acids.

    PubMed

    Kihira, K; Mikami, T; Ikawa, S; Okamoto, A; Yoshii, M; Miki, S; Mosbach, E H; Hoshita, T

    1992-04-01

    Sulfonate analogs of C23 and C24 bile acids were synthesized from norcholic, norchenodeoxycholic, norursodeoxycholic, nordeoxycholic, norhyodeoxycholic, cholic, deoxycholic, hyodeoxycholic, and lithocholic acids. The principal reactions used were (1) reduction of the bile acids with NaBH4 to the corresponding bile alcohols, (2) selective tosylation of the terminal hydroxyl group, (3) iodination of the tosyl esters with NaI, and (4) treatment of the iodides with Na2SO3 to form the sulfonate analogs of the bile acids. The sulfonate analogs showed polarity similar to that of taurine-conjugated bile acids on thin-layer chromatography. The carbon 13 nuclear magnetic resonance spectral data for the sulfonate analogs were tabulated.

  16. NASA Now: Exploring Asteroids: An Analog Mission

    NASA Video Gallery

    NASA’s Extreme Environment Mission Operations, or NEEMO, project lead Bill Todd describes this analog mission and how aquanauts living and working in an undersea habitat are helping NASA prepare ...

  17. An Electronic Analog of the Diffraction Grating.

    ERIC Educational Resources Information Center

    MacLeod, A. M.

    1978-01-01

    Gives an outline description of electronic circuitry which is analogous to the optical diffraction grating or to crystals used in the Bragg reflection of X-rays or electron waves, and explains how to use it. (Author/GA)

  18. Computer Analogies: Teaching Molecular Biology and Ecology.

    ERIC Educational Resources Information Center

    Rice, Stanley; McArthur, John

    2002-01-01

    Suggests that computer science analogies can aid the understanding of gene expression, including the storage of genetic information on chromosomes. Presents a matrix of biology and computer science concepts. (DDR)

  19. The Analog (Computer) As a Physiology Adjunct.

    ERIC Educational Resources Information Center

    Stewart, Peter A.

    1979-01-01

    Defines and discusses the analog computer and its use in a physiology laboratory. Includes two examples: (1) The Respiratory Control Function and (2) CO-Two Control in the Respiratory System. Presents diagrams and mathematical models. (MA)

  20. Optical analog-to-digital converter

    DOEpatents

    Vawter, G. Allen; Raring, James; Skogen, Erik J.

    2009-07-21

    An optical analog-to-digital converter (ADC) is disclosed which converts an input optical analog signal to an output optical digital signal at a sampling rate defined by a sampling optical signal. Each bit of the digital representation is separately determined using an optical waveguide interferometer and an optical thresholding element. The interferometer uses the optical analog signal and the sampling optical signal to generate a sinusoidally-varying output signal using cross-phase-modulation (XPM) or a photocurrent generated from the optical analog signal. The sinusoidally-varying output signal is then digitized by the thresholding element, which includes a saturable absorber or at least one semiconductor optical amplifier, to form the optical digital signal which can be output either in parallel or serially.

  1. Imatinib Analogs as Potential Agents for PET Imaging of Bcr-Abl/c-KIT Expression at a Kinase Level

    PubMed Central

    Peng, Zhenghong; Maxwell, David S.; Sun, Duoli; Bhanu Prasad, Basvoju A.; Pal, Ashutosh; Wang, Shimei; Balatoni, Julius; Ghosh, Pradip; Lim, Seok T.; Volgin, Andrei; Shavrin, Aleksander; Alauddin, Mian M.; Gelovani, Juri G.; Bornmann, William G.

    2014-01-01

    We synthesized two series of imatinib mesylate (STI-571) analogs to develop a Bcr-Abl and c-KIT receptor-specific labeling agent for positron emission tomography (PET) imaging to measure Bcr-Abl and c-KIT expression levels in a mouse model. The methods of molecular modeling, synthesis of STI-571 and its analogs, in vitro kinase assays, and radiolabeling are described. Molecular modeling revealed that these analogs bind the same Bcr-Abl and c-KIT binding sites as those bound by STI-571. The analogs potently inhibit the tyrosine kinase activity of Bcr-Abl and c-KIT, similarly to STI-571. [18F]-labeled STI-571 was prepared with high specific activity (75 GBq/μmol) by nucleophilic displacement and an average radiochemical yield of 12%. [131I]-labeled STI-571 was prepared with high purity (>95%) and an average radiochemical yield of 23%. The uptake rates of [18F]-STI-571 in K562 cells expressing Abl and in U87WT cells overexpressing c-KIT were significantly higher than those in the U87 cell and could be inhibited by STI-71 (confirming the specificity of uptake). PET scans of K562 and U87WT tumor-bearing mice with [18F]-STI-571 as a contrast agent showed visible tumor uptake and tumor-to-non-target contrast. PMID:24280068

  2. AMiBA WIDEBAND ANALOG CORRELATOR

    SciTech Connect

    Li, Chao-Te; Kubo, Derek Y.; Lin, Kai-Yang; Chen, Ming-Tang; Ho, P. T. P.; Chen, Chung-Cheng; Han, Chih-Chiang; Oshiro, Peter; Martin-Cocher, Pierre; Chang, Chia-Hao; Chang, Shu-Hao; Altamirano, Pablo; Jiang, Homin; Wilson, Warwick; Chiueh, Tzi-Dar; Lien, Chun-Hsien; Wang, Huei; Wei, Ray-Ming; Yang, Chia-Hsiang; Peterson, Jeffrey B.

    2010-06-10

    A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband intermediate frequency distribution, back-end signal processing, and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.

  3. ANALOG-TO-DIGITAL DATA CONVERTER

    DOEpatents

    Rodgers, G.W.; Althouse, J.E.; Anderson, D.P.; Bussey, G.R.; Minnear, L.H.

    1960-09-01

    Electrical apparatus is described, particularly useful in telemetry work, for converting analog signals into electrical pulses and recording them. An electronic editor commands the taking of signal readings at a frequency which varies according to linearity of the analog signal being converted. Readings of information signals are recorded, along with time base readings and serial numbering, if desired, on magnetic tape and the latter may be used to operate a computer or the like. Magnetic tape data may be transferred to punched cards.

  4. Analog environments in space human factors

    NASA Technical Reports Server (NTRS)

    Connors, Mary M.

    1992-01-01

    An account is given of what has been learned from space analog environments, which mimic such significant features of space as isolation, confinement, risk, and deprivation; emphasis is placed on the especially successful environments constituted by extended submarine research, undersea habitats, and Antarctic station wintering. Attention is also given to the advantages and limitations of the use of analog environments for space human factors research, and possibilities for such research efforts' management.

  5. AMiBA Wideband Analog Correlator

    NASA Astrophysics Data System (ADS)

    Li, Chao-Te; Kubo, Derek Y.; Wilson, Warwick; Lin, Kai-Yang; Chen, Ming-Tang; Ho, P. T. P.; Chen, Chung-Cheng; Han, Chih-Chiang; Oshiro, Peter; Martin-Cocher, Pierre; Chang, Chia-Hao; Chang, Shu-Hao; Altamirano, Pablo; Jiang, Homin; Chiueh, Tzi-Dar; Lien, Chun-Hsien; Wang, Huei; Wei, Ray-Ming; Yang, Chia-Hsiang; Peterson, Jeffrey B.; Chang, Su-Wei; Huang, Yau-De; Hwang, Yuh-Jing; Kesteven, Michael; Koch, Patrick; Liu, Guo-Chin; Nishioka, Hiroaki; Umetsu, Keiichi; Wei, Tashun; Proty Wu, Jiun-Huei

    2010-06-01

    A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband intermediate frequency distribution, back-end signal processing, and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.

  6. Analog hardware for learning neural networks

    NASA Technical Reports Server (NTRS)

    Eberhardt, Silvio P. (Inventor)

    1991-01-01

    This is a recurrent or feedforward analog neural network processor having a multi-level neuron array and a synaptic matrix for storing weighted analog values of synaptic connection strengths which is characterized by temporarily changing one connection strength at a time to determine its effect on system output relative to the desired target. That connection strength is then adjusted based on the effect, whereby the processor is taught the correct response to training examples connection by connection.

  7. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  8. Analog modelling of obduction processes

    NASA Astrophysics Data System (ADS)

    Agard, P.; Zuo, X.; Funiciello, F.; Bellahsen, N.; Faccenna, C.; Savva, D.

    2012-04-01

    Obduction corresponds to one of plate tectonics oddities, whereby dense, oceanic rocks (ophiolites) are presumably 'thrust' on top of light, continental ones, as for the short-lived, almost synchronous Peri-Arabic obduction (which took place along thousands of km from Turkey to Oman in c. 5-10 Ma). Analog modelling experiments were performed to study the mechanisms of obduction initiation and test various triggering hypotheses (i.e., plate acceleration, slab hitting the 660 km discontinuity, ridge subduction; Agard et al., 2007). The experimental setup comprises (1) an upper mantle, modelled as a low-viscosity transparent Newtonian glucose syrup filling a rigid Plexiglas tank and (2) high-viscosity silicone plates (Rhodrosil Gomme with PDMS iron fillers to reproduce densities of continental or oceanic plates), located at the centre of the tank above the syrup to simulate the subducting and the overriding plates - and avoid friction on the sides of the tank. Convergence is simulated by pushing on a piston at one end of the model with velocities comparable to those of plate tectonics (i.e., in the range 1-10 cm/yr). The reference set-up includes, from one end to the other (~60 cm): (i) the piston, (ii) a continental margin containing a transition zone to the adjacent oceanic plate, (iii) a weakness zone with variable resistance and dip (W), (iv) an oceanic plate - with or without a spreading ridge, (v) a subduction zone (S) dipping away from the piston and (vi) an upper, active continental margin, below which the oceanic plate is being subducted at the start of the experiment (as is known to have been the case in Oman). Several configurations were tested and over thirty different parametric tests were performed. Special emphasis was placed on comparing different types of weakness zone (W) and the extent of mechanical coupling across them, particularly when plates were accelerated. Displacements, together with along-strike and across-strike internal deformation in all

  9. Development of analogical problem-solving skill.

    PubMed

    Holyoak, K J; Junn, E N; Billman, D O

    1984-12-01

    3 experiments were performed to assess children's ability to solve a problem by analogy to a superficially dissimilar situation. Preschoolers and fifth and sixth graders were asked to solve a problem that allowed multiple solutions. Some subjects were first read a story that included an analogous problem and its solution. When the mapping between the relations involved in the corresponding solutions was relatively simple, and the corresponding instruments were perceptually and functionally similar, even preschoolers were able to use the analogy to derive a solution to the transfer problem (Experiment 1). Furthermore, salient similarity of the instruments was neither sufficient (Experiment 2) nor necessary (Experiment 3) for success by preschool subjects. When the story analog mapped well onto the transfer problem, 4-year-olds were often able to generate a solution that required transformation of an object with little perceptual or semantic similarity to the instrument used in the base analog (Experiment 3). The older children used analogies in a manner qualitatively similar to that observed in comparable studies with adults (Experiment 1), whereas the younger children exhibited different limitations.

  10. Leukocyte labeling with isonitrile complexes of Tc-99m

    SciTech Connect

    Van den Abbeele, A.D.; Solorzano, C.; Jones, A.G.; Beardsley, D.S.; Treves, S.; Davison, A.

    1985-05-01

    Leukocyte labelling with Tc-99m may result in a useful method for the detection and localization of active inflammatory processes in patients, particularly in the pediatric population. Previous studies qin this laboratory have shown that hexakis(alkylisonitrile)technetium(I) complexes readily label V79 lung fibroblasts in vitro, and this work is now being extended to isolated human white blood cells (WBC). Two lipophilic water-soluble technetium cations, the t-butyl (Tc-99m(TBI)) and cyclohexyl (Tc-99m(CHI)) analogs, were prepared essentially ligand-free at no-carrier-added levels in aqueous media and introduced in 10% propylene glycol/90% normal saline solution to WBC at room temperature. The cells were isolated from whole blood via sedimentation, centrifugation, and hypotonic hemolysis of the red blood cells. The labeling yield was studied as a function of incubation time (10-45 min), amount of activity (0.35-8.0 mCi), and total WBC (2.5 x 10/sup 7/-1.3 x 10/sup 8/). After 10 min incubation using 10/sup 8/ cells, the initial uptake of Tc-99m(TBI) was 40%, of which 50% remained bound after one saline wash. By contrast, the labeling efficiency with Tc-99m(CHI) was 85%, with 90% of the label still bound after washing. The labeling yield was unrelated to activity levels of incubation time, but was proportional to the number of WBC present. The entire process could be complemented in approximately one hour. The labeling yields with Tc-99m-(CHI) are comparable to those now obtained with the clinically available In-111 oxine.

  11. Optical domain analog to digital conversion methods and apparatus

    DOEpatents

    Vawter, Gregory A

    2014-05-13

    Methods and apparatus for optical analog to digital conversion are disclosed. An optical signal is converted by mapping the optical analog signal onto a wavelength modulated optical beam, passing the mapped beam through interferometers to generate analog bit representation signals, and converting the analog bit representation signals into an optical digital signal. A photodiode receives an optical analog signal, a wavelength modulated laser coupled to the photodiode maps the optical analog signal to a wavelength modulated optical beam, interferometers produce an analog bit representation signal from the mapped wavelength modulated optical beam, and sample and threshold circuits corresponding to the interferometers produce a digital bit signal from the analog bit representation signal.

  12. The binding of host-selective toxin analogs to mitochondria from normal and ;texas' male sterile cytoplasm maize.

    PubMed

    Frantzen, K A; Daly, J M; Knoche, H W

    1987-04-01

    Tritium-labeled toxin analogs were prepared by reduction with NaB(3)H(4) of either the toxin from Helminthosporium maydis race T or a toxin component from Phyllosticta maydis. These reduced analogs had high radiochemical specific activities, high biological activities, and plant specificities identical to the native toxins. A filtration assay was developed to test the binding of these labeled analogs to isolated mitochondria. Binding was not energy dependent nor was there measurable matrical uptake. The analogs were shown to be lipophilic, a characteristic which gave rise to considerable nondisplaceable binding. Under conditions limiting nondisplaceable binding, the displaceable binding was shown to be linear with respect to toxin concentration and unsaturable. No significant differences were observed in the binding characteristics between the mitochondria from normal and male-sterile (Texas) cytoplasm maize. The findings suggest that, at physiologically relevant concentrations, these toxin analogs permeate the membranes of susceptible and resistant mitochondria alike. The lack of demonstrable specific binding does not rule out the involvement of a classical receptor site but does indicate that other kinds of molecular interactions may be involved in the mechanisms for toxicity and specificity. PMID:16665353

  13. Binding of host-selective toxin analogs to mitochondria from normal and Texas male sterile cytoplasm maize

    SciTech Connect

    Frantzen, K.A.; Daly, J.M.; Knoche, H.W.

    1987-04-01

    Tritium-labeled toxin analogs were prepared by reduction with NaB/sup 3/H/sub 4/ of either the toxin from Helminthosporium maydis race T or a toxin component from Phyllosticta maydis. These reduced analogs had high radiochemical specific activities, high biological activities, and plant specificities identical to the native toxins. A filtration assay was developed to test the binding of these labeled analogs to isolated mitochondria. Binding was not energy dependent nor was there measurable matrical uptake. The analogs were shown to be lipophilic, a characteristic which gave rise to considerable nondisplaceable binding. Under conditions limiting nondisplaceable binding, the displaceable binding was shown to be linear with respect to toxin concentration and unsaturable. No significant differences were observed in the binding characteristics between the mitochondria from normal and male-sterile (Texas) cytoplasm maize. The findings suggest that, at physiologically relevant concentrations, these toxin analogs permeate the membranes of susceptible and resistant mitochondria alike. The lack of demonstrable specific binding does not rule out the involvement of a classical receptor site but does indicate that other kinds of molecular interactions may be involved in the mechanisms for toxicity and specificity.

  14. Synthesis and applications of selectively {sup 13}C-labeled RNA

    SciTech Connect

    SantaLucia, J. Jr.; Shen, L.X.; Lewis, H.; Cai, Z.; Tinoci, I. Jr.

    1994-12-01

    Spectral overlap is a substantial problem in NMR studies of RNA molecules >30 nucleotides. To overcome this difficulty, we synthesized selectively {sup 13}C-labeled RNAs and adapted several isotope-edited two- and three-dimensional NMR experiments originally developed for protein studies. We optimized protocols for synthesis of multi-gram quantities of CTP, UTp, ATP, and GTP using a combination of synthetic organic and enzymatic methods. Uracil is prepared in 40 to 50% yield from {sup 13}C-cyanide in two steps. Using acetyl- tribenzoyl-ribose and standard chemistry uracil is then attached to the sugar (90% yield). The tribenzoyl-uridine intermediate is converted into uridine or cytidine quantitatively, depending on the deblocking protocol. Labeled purines are synthesized using simple pyrimidine precursors and reacting with {sup 13}C-formic acid (80% yield). Purine nucleosides are then synthesized using uridine phosphorylase and purine nucleoside phosphorylase. The nucleosides were converted to NMPs by treatment with POC1{sub 3} in triethylphosphate. We converted NMPs to NTPs by standard enzymatic methods. Selectively labeled RNAs were synthesized by run-off transcription using {sup 13}C-labeled NTPs. Several different strategies help solve over-lap problems in larger RNAs. Isotope-edited two-dimensional NMR experiments such as {omega}1-1/2 X-filtered NOESY simplify NMR spectra by dividing the normal NOESY spectrum into two subspectra-one involving NOEs from protons bound to {sup 12}C and one from protons bound to {sup 13}C. For example, we labeled A and U residues of a 34-nucleotide pseudoknot, and the {sup 12}C subspectrum of the 1/2 X-filtered NOESY contained NOEs only from G and C residues (along with adenine 2H); the {sup 13}C subspectrum contained NOEs only from A and U residues. Each subspectrum has less overlap than the NOESY of an unlabeled sample; the editing strategy allows each resonance to be identified by residue type (A, C, G, or U).

  15. Neuroendocrine tumor targeting: study of novel gallium-labeled somatostatin radiopeptides in a rat pancreatic tumor model.

    PubMed

    Froidevaux, Sylvie; Eberle, Alex N; Christe, Martine; Sumanovski, Lazar; Heppeler, Axel; Schmitt, Jörg S; Eisenwiener, Klaus; Beglinger, Christoph; Mäcke, Helmut R

    2002-04-20

    Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors.

  16. Label and Label-Free Detection Techniques for Protein Microarrays

    PubMed Central

    Syahir, Amir; Usui, Kenji; Tomizaki, Kin-ya; Kajikawa, Kotaro; Mihara, Hisakazu

    2015-01-01

    Protein microarray technology has gone through numerous innovative developments in recent decades. In this review, we focus on the development of protein detection methods embedded in the technology. Early microarrays utilized useful chromophores and versatile biochemical techniques dominated by high-throughput illumination. Recently, the realization of label-free techniques has been greatly advanced by the combination of knowledge in material sciences, computational design and nanofabrication. These rapidly advancing techniques aim to provide data without the intervention of label molecules. Here, we present a brief overview of this remarkable innovation from the perspectives of label and label-free techniques in transducing nano-biological events.

  17. Principles of protein labeling techniques.

    PubMed

    Obermaier, Christian; Griebel, Anja; Westermeier, Reiner

    2015-01-01

    Protein labeling methods prior to separation and analysis have become indispensable approaches for proteomic profiling. Basically, three different types of tags are employed: stable isotopes, mass tags, and fluorophores. While proteins labeled with stable isotopes and mass tags are measured and differentiated by mass spectrometry, fluorescent labels are detected with fluorescence imagers. The major purposes for protein labeling are monitoring of biological processes, reliable quantification of compounds and specific detection of protein modifications and isoforms in multiplexed samples, enhancement of detection sensitivity, and simplification of detection workflows. Proteins can be labeled during cell growth by incorporation of amino acids containing different isotopes, or in biological fluids, cells or tissue samples by attaching specific groups to the ε-amino group of lysine, the N-terminus, or the cysteine residues. The principles and the modifications of the different labeling approaches on the protein level are described; benefits and shortcomings of the methods are discussed.

  18. Cleavage of an RNA analog by Zn(II) macrocyclic catalysts appended with a methyl or an acridine group.

    PubMed

    Rossiter, Clifford S; Mathews, Ryan A; Morrow, Janet R

    2007-06-01

    Two macrocycles (1 and 2) are prepared that incorporate pendent groups in macrocycle 3 (3=1-oxa-4,7,10-triazacyclododecane) with the goal of studying the effect of these pendent groups on metal ion complexation, solution chemistry and catalysis. Zn(1) contains a macrocyclic ligand with a pendent acridine group and Zn(2) has an appended methyl group. Water ligand pK(a) values for Zn(1) (6.7) and Zn(2) (7.3) are lower than that of Zn(3) (7.7). Zn(II) complexes of 1 and 2 are studied as catalysts for the cleavage of 2-hydroxypropyl 4-nitrophenylphosphate (HpPNP), an RNA analog. Zn(2) has a lower catalytic activity over the pH range 7-10 for cleavage of HpPNP compared to the parent macrocyclic complex, Zn(3). In contrast, Zn(1) has a threefold larger rate constant at pH 7.0 compared to Zn(2), attributed to the presence of a catalytic species which has a protonated acridine amino group. The binding constant of 1.5mM at pH 8.0 for formation of the Zn(2)-uridine adduct is similar to that for Zn(3), suggesting that N-alkylation of the macrocyclic ligand does not interfere with binding of the Zn(II) complex to uridine groups. Binding of cytidine to Zn(2) was not detectable under similar conditions up to 25mM nucleoside. Binding experiments under similar conditions could not be carried out for adenosine or guanosine due to their low solubility.

  19. Analogy, higher order thinking, and education.

    PubMed

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships.

  20. An analog silicon retina with multichip configuration.

    PubMed

    Kameda, Seiji; Yagi, Tetsuya

    2006-01-01

    The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

  1. Analog forecasting with dynamics-adapted kernels

    NASA Astrophysics Data System (ADS)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  2. An analog integrated-circuit vocal tract.

    PubMed

    Keng Hoong Wee; Turicchia, L; Sarpeshkar, R

    2008-12-01

    We present the first experimental integrated-circuit vocal tract by mapping fluid volume velocity to current, fluid pressure to voltage, and linear and nonlinear mechanical impedances to linear and nonlinear electrical impedances. The 275 muW analog vocal tract chip includes a 16-stage cascade of two-port pi-elements that forms a tunable transmission line, electronically variable impedances, and a current source as the glottal source. A nonlinear resistor models laminar and turbulent flow in the vocal tract. The measured SNR at the output of the analog vocal tract is 64, 66, and 63 dB for the first three formant resonances of a vocal tract with uniform cross-sectional area. The analog vocal tract can be used with auditory processors in a feedback speech locked loop-analogous to a phase locked loop-to implement speech recognition that is potentially robust in noise. Our use of a physiological model of the human vocal tract enables the analog vocal tract chip to synthesize speech signals of interest, using articulatory parameters that are intrinsically compact and linearly interpolatable. PMID:23853134

  3. Analogy, higher order thinking, and education.

    PubMed

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. PMID:26263071

  4. NaturAnalogs for the Unsaturated Zone

    SciTech Connect

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  5. Identification by UV resonance Raman spectroscopy of an imino tautomer of 5-hydroxy-2′-deoxycytidine, a powerful base analog transition mutagen with a much higher unfavored tautomer frequency than that of the natural residue 2′-deoxycytidine

    PubMed Central

    Suen, Wu; Spiro, Thomas G.; Sowers, Lawrence C.; Fresco, Jacques R.

    1999-01-01

    UV resonance Raman spectroscopy was used to detect and estimate the frequency of the unfavored imino tautomer of the transition mutagen 5-hydroxy-2′-deoxycytidine (HO5dCyt) in its anionic form. In DNA, this 2′-deoxycytidine analog arises from the oxidation of 2′-deoxycytidine and induces C → T transitions with 102 greater frequency than such spontaneous transitions. An imino tautomer marker carbonyl band (≈1650 cm−1) is enhanced at ≈65°C against an otherwise stable spectrum of bands associated with the favored amino tautomer. This band is similarly present in the UV resonance Raman spectra of the imino cytidine analogs N3-methylcytidine at high pH and N4-methoxy-2′-deoxycytidine at pH 7 and displays features attributable to the imino form of C residues and their derivatives. The fact that the imino tautomer of HO5dCyt occurs at a frequency consistent with its high mutagenic enhancement lends strong support to the hypothesis that unfavored base tautomers play important roles in the mispair intermediates of replication leading to substitution mutations. PMID:10200291

  6. Appliance energy labeling takes effect

    SciTech Connect

    Not Available

    1980-06-01

    Consumers buying household appliances will be helped by energy-efficiency labels and minimum efficiency standards required for refrigerators and refrigerator/freezers, freezers, dishwashers, water heaters, clothes washers, room air conditioners, and furnaces. The ENERGYGUIDE labels must be displayed in the store and in catalogs. Two voluntary efficiency programs were combined in the Energy Policy and Conservation Act (EPCA) requiring labels by 1980. Shoppers may compare the efficiencies of appliances and compute the actual cost differential over the lifetime of the equipment. Manufacturers have responded with more-efficient models, but the impact of efficient appliances on energy consumption will be small. A sample label with the required information is illustrated. (DCK)

  7. Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage

    ERIC Educational Resources Information Center

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

  8. Students' Pre- and Post-Teaching Analogical Reasoning when They Draw Their Analogies

    ERIC Educational Resources Information Center

    Mozzer, Nilmara Braga; Justi, Rosaria

    2012-01-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in…

  9. 78 FR 66826 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... the Agency (76 FR 75809). FSIS also proposed to combine the regulations that provide for the approval... preamble (76 FR 75814), FSIS wrote: . . . statements on labels that are defined in FSIS's regulations or... ``Product Labeling: Definition of the Term ``Natural'' and related materials (71 FR 70503, Dec. 5, 2006)...

  10. Laser labeling, a safe technology to label produce

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Labeling of the produce has gained marked attention in recent years. Laser labeling technology involves the etching of required information on the surface using a low energy CO2 laser beam. The etching forms alphanumerical characters by pinhole dot matrix depressions. These openings can lead to wat...

  11. Laser labeling, a safe technology to label produce

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laser labeling of fruits and vegetables is an alternative means to label produce. Low energy CO2 laser beams etch the surface showing the contrasting underlying layer. These etched surfaces can promote water loss and potentially allow for entry of decay organisms. The long-term effects of laser labe...

  12. 76 FR 75809 - Prior Label Approval System: Generic Label Approval

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... poultry products will take effect January 1, 2012 (75 FR 82148, Dec. 29, 2010). These mandatory features... limited types of labels (e.g., labels for raw, single ingredient meat and poultry products) (48 FR 11410... Agency. On March 25, 1992, FSIS published an Advance Notice of Proposed Rulemaking (ANPRM) (57 FR...

  13. Gravitoelectromagnetic analogy based on tidal tensors

    SciTech Connect

    Costa, L. Filipe O.; Herdeiro, Carlos A. R.

    2008-07-15

    We propose a new approach to a physical analogy between general relativity and electromagnetism, based on tidal tensors of both theories. Using this approach we write a covariant form for the gravitational analogues of the Maxwell equations, which makes transparent both the similarities and key differences between the two interactions. The following realizations of the analogy are given. The first one matches linearized gravitational tidal tensors to exact electromagnetic tidal tensors in Minkowski spacetime. The second one matches exact magnetic gravitational tidal tensors for ultrastationary metrics to exact magnetic tidal tensors of electromagnetism in curved spaces. In the third we show that our approach leads to a two-step exact derivation of Papapetrou's equation describing the force exerted on a spinning test particle. Analogous scalar invariants built from tidal tensors of both theories are also discussed.

  14. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    ERIC Educational Resources Information Center

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  15. The Importance of Explicitly Mapping Instructional Analogies in Science Education

    ERIC Educational Resources Information Center

    Asay, Loretta Johnson

    2013-01-01

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With…

  16. Space flight nutrition research: platforms and analogs

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Uchakin, Peter N.; Tobin, Brian W.

    2002-01-01

    Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

  17. Analog graphic display method and apparatus

    DOEpatents

    Kronberg, J.W.

    1991-08-13

    Disclosed are an apparatus and method for using an output device such as an LED to show the approximate analog level of a variable electrical signal wherein a modulating AC waveform is superimposed either on the signal or a reference voltage, both of which are then fed to a comparator which drives the output device. Said device flashes at a constant perceptible rate with a duty cycle which varies in response to variations in the level of the input signal. The human eye perceives these variations in duty cycle as analogous to variations in the level of the input signal. 21 figures.

  18. Associative Pattern Recognition In Analog VLSI Circuits

    NASA Technical Reports Server (NTRS)

    Tawel, Raoul

    1995-01-01

    Winner-take-all circuit selects best-match stored pattern. Prototype cascadable very-large-scale integrated (VLSI) circuit chips built and tested to demonstrate concept of electronic associative pattern recognition. Based on low-power, sub-threshold analog complementary oxide/semiconductor (CMOS) VLSI circuitry, each chip can store 128 sets (vectors) of 16 analog values (vector components), vectors representing known patterns as diverse as spectra, histograms, graphs, or brightnesses of pixels in images. Chips exploit parallel nature of vector quantization architecture to implement highly parallel processing in relatively simple computational cells. Through collective action, cells classify input pattern in fraction of microsecond while consuming power of few microwatts.

  19. Parallel Analog-to-Digital Image Processor

    NASA Technical Reports Server (NTRS)

    Lokerson, D. C.

    1987-01-01

    Proposed integrated-circuit network of many identical units convert analog outputs of imaging arrays of x-ray or infrared detectors to digital outputs. Converter located near imaging detectors, within cryogenic detector package. Because converter output digital, lends itself well to multiplexing and to postprocessing for correction of gain and offset errors peculiar to each picture element and its sampling and conversion circuits. Analog-to-digital image processor is massively parallel system for processing data from array of photodetectors. System built as compact integrated circuit located near local plane. Buffer amplifier for each picture element has different offset.

  20. Solid-phase synthesis of prenylcysteine analogs

    PubMed Central

    Donelson, James L.; Hodges-Loaiza, Heather B.; Henriksen, Brian S.; Hrycyna, Christine A.

    2009-01-01

    Prenylcysteine derivatives are of interest for a variety of different biological reasons, including probing the CaaX protein processing pathway. A solid-phase synthesis protocol for the preparation of prenylcysteines using 2-chlorotrityl chloride resin as a solid support has been developed. A series of novel amide-modified farnesylcysteine analogs were synthesized in both high purity and yield under mild conditions. The farnesylcysteine analogs were evaluated using human isoprenylcysteine carboxyl methyltransferase (Icmt) as a biological target, and several new inhibitors, one with significantly enhanced potency, were identified. PMID:19320430

  1. Landauer bound for analog computing systems.

    PubMed

    Diamantini, M Cristina; Gammaitoni, Luca; Trugenberger, Carlo A

    2016-07-01

    By establishing a relation between information erasure and continuous phase transitions we generalize the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence, every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy. PMID:27575108

  2. Landauer bound for analog computing systems

    NASA Astrophysics Data System (ADS)

    Diamantini, M. Cristina; Gammaitoni, Luca; Trugenberger, Carlo A.

    2016-07-01

    By establishing a relation between information erasure and continuous phase transitions we generalize the Landauer bound to analog computing systems. The entropy production per degree of freedom during erasure of an analog variable (reset to standard value) is given by the logarithm of the configurational volume measured in units of its minimal quantum. As a consequence, every computation has to be carried on with a finite number of bits and infinite precision is forbidden by the fundamental laws of physics, since it would require an infinite amount of energy.

  3. Synthetic heparin-binding factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul O.; Lin, Xinhua; Glass, John D.

    2010-04-20

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain, and preferably two peptide chains branched from a dipeptide branch moiety composed of two trifunctional amino acid residues, which peptide chain or chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a linker, which may be a hydrophobic linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  4. Analog graphic display method and apparatus

    DOEpatents

    Kronberg, James W.

    1991-01-01

    An apparatus and method for using an output device such as an LED to show the approximate analog level of a variable electrical signal wherein a modulating AC waveform is superimposed either on the signal or a reference voltage, both of which are then fed to a comparator which drives the output device. Said device flashes at a constant perceptible rate with a duty cycle which varies in response to variations in the level of the input signal. The human eye perceives these variations in duty cycle as analogous to variations in the level of the input signal.

  5. Ground-water studies and analog models

    USGS Publications Warehouse

    Robinove, Charles Joseph

    1962-01-01

    Hydrologists make ground-water studies to aid managers and users of water resources in solving their problems in the development and management of ground water. Geologic and hydrologic information provides the basic knowledge for construction of electric analog models that portray the ground-water system in miniature. Analog models can be analyzed electrically, and the results of the analysis are presented in terms of the ground-water system so that the effects of alternative methods of water development can be assessed.

  6. Auxin transport sites are visualized in planta using fluorescent auxin analogs.

    PubMed

    Hayashi, Ken-ichiro; Nakamura, Shouichi; Fukunaga, Shiho; Nishimura, Takeshi; Jenness, Mark K; Murphy, Angus S; Motose, Hiroyasu; Nozaki, Hiroshi; Furutani, Masahiko; Aoyama, Takashi

    2014-08-01

    The plant hormone auxin is a key morphogenetic signal that controls many aspects of plant growth and development. Cellular auxin levels are coordinately regulated by multiple processes, including auxin biosynthesis and the polar transport and metabolic pathways. The auxin concentration gradient determines plant organ positioning and growth responses to environmental cues. Auxin transport systems play crucial roles in the spatiotemporal regulation of the auxin gradient. This auxin gradient has been analyzed using SCF-type E3 ubiquitin-ligase complex-based auxin biosensors in synthetic auxin-responsive reporter lines. However, the contributions of auxin biosynthesis and metabolism to the auxin gradient have been largely elusive. Additionally, the available information on subcellular auxin localization is still limited. Here we designed fluorescently labeled auxin analogs that remain active for auxin transport but are inactive for auxin signaling and metabolism. Fluorescent auxin analogs enable the selective visualization of the distribution of auxin by the auxin transport system. Together with auxin biosynthesis inhibitors and an auxin biosensor, these analogs indicated a substantial contribution of local auxin biosynthesis to the formation of auxin maxima at the root apex. Moreover, fluorescent auxin analogs mainly localized to the endoplasmic reticulum in cultured cells and roots, implying the presence of a subcellular auxin gradient in the cells. Our work not only provides a useful tool for the plant chemical biology field but also demonstrates a new strategy for imaging the distribution of small-molecule hormones.

  7. Study of the orientation of retinal in bovine rhodopsin: the use of a photoactivatable retinal analog

    SciTech Connect

    Nakayama, T.

    1987-05-01

    Rhodopsin is the major transmembrane protein in the photoreceptor cells of vertebrate and invertebrate retina. Bovine rhodopsin consists of a polypeptide chain of 348 amino acids of known sequence in which the chromophore, 11-cis-retinal, is linked to Lys-296 as a Schiff base. To investigate the orientation of retinal in the protein and to study the interactions between retinal and the protein, the authors have developed a crosslinking approach using a /sup 3/H-labeled photoactivatable analog of retinal. Bleached rhodopsin in rod outer segments was reconstituted with the analog to give a pigment with lambda/sub max/ at 460nm. Reduction of the Schiff base with borane dimenthylamine, followed by degradation with CNBr and sequencing of the radioactive fragment showed that the analog is attached to Lys-296, as in the native rhodopsin. Further, the reconstitute protein after photolysis was phosphorylated by rhodopsin kinase. Photolysis of the reconstituted pigment at -15/sup 0/C resulted in crosslinking of the analog to the opsin to the extent of 30% as analyzed by SDS electrophoresis. The site(s) of crosslinking in the protein are under investigation.

  8. Effect on days of lactation and methionine hydroxy analog on incorporation of plasma fatty acids into plasma triglycerides

    SciTech Connect

    Pullen, D.L.; Emergy, R.S. ); Palmquist, D.L. )

    1989-01-01

    Methionine hydroxy analog has been proposed to stimulate hepatic lipoprotein synthesis and incorporation of plasma fatty acids into plasma triglyceride. Seven cows were fed diets containing 0 to 30 g analog/d starting 14 d prepartum. At approximately 30 and 60 d postpartum, cows were continuously infused intravenously with 1-({sup 14}C)palmitic acid for 160 min to achieve steady-state labeling of plasma fatty acid and triglyceride. Turnover of fatty acid and transfer quotients for triglyceride and CO{sub 2} were 3.3 an 2.7 mmol min{sup {minus}1}; 13.0 and 10.0%; and 8.0 and 5.0%, for control and analog, respectively. Proportion of fatty acid turnover incorporated into triglyceride and CO{sub 2} were 14.0 and 15.0%; and 21.0 and 18.0, respectively, for control and analog. Analog increased {sup 14}C recovered in milk fat (52 vs. 36%). Plasma concentration of fatty acids, percent oxidized to CO{sub 2}, and percent of CO{sub 2} from fatty acids decreased with increasing lactation days. Milk fat percent and yield fatty acid turnover, and oxidation were positively correlated with concentration of plasma fatty acids, whereas fatty acid incorporated into plasma triglyceride was negatively correlated with fatty acid concentration. The data suggest that hepatic triglyceride secretion is not increased in early lactation; further, no effects of analog on lipid metabolism were detected.

  9. Synthesis of a suite of click-compatible sugar analogs for probing carbohydrate metabolism.

    PubMed

    Wang, Bo; McClosky, Daniel D; Anderson, Charles T; Chen, Gong

    2016-10-01

    Metabolic labeling based on the click chemistry between alkynyl and azido groups offers a powerful tool to study the function of carbohydrates in living systems, including plants. Herein, we describe the chemical synthesis of six alkynyl-modified sugars designed as analogs to D-glucose, D-mannose, L-rhamnose and sucrose present in plant cell walls. Among these new alkynyl probes, four of them are the 6-deoxy-alkynyl analogs of the corresponding sugars and do not possess any 6-OH groups. The other two are based on a new structural design, in which an ethynyl group is incorporated at the C-6 position of the sugar and the 6-OH group remains. The synthetic routes for both types of probes share common aldehyde intermediates, which are derived from the corresponding 6-OH precursor with other hydroxy groups protected. The overall synthesis sequence of these probes is efficient, concise, and scalable. PMID:27447057

  10. Nutrition Marketing on Food Labels

    ERIC Educational Resources Information Center

    Colby, Sarah E.; Johnson, LuAnn; Scheett, Angela; Hoverson, Bonita

    2010-01-01

    Objective: This research sought to determine how often nutrition marketing is used on labels of foods that are high in saturated fat, sodium, and/or sugar. Design and Setting: All items packaged with food labels (N = 56,900) in all 6 grocery stores in Grand Forks, ND were surveyed. Main Outcome Measure(s): Marketing strategy, nutrient label…

  11. Meat and Poultry Labeling Terms

    MedlinePlus

    ... Food Standards and Labels: The Facts Labeling and Marketing Information [ Top of Page ] OVEN PREPARED: Product is fully cooked and ready to eat. [ Top of Page ] YOUNG TURKEY: Turkeys of either sex that are less than 8 months of age according to present regulations. [ Top of Page ] Last ...

  12. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  13. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  14. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  15. 21 CFR 610.60 - Container label.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Container label. 610.60 Section 610.60 Food and... GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.60 Container label. (a) Full label. The following items shall appear on the label affixed to each container of a product capable of bearing a...

  16. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  17. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  18. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  19. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  20. 16 CFR 460.12 - Labels.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Labels. 460.12 Section 460.12 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.12 Labels. If you are a manufacturer, you must label all packages of your insulation. The labels...

  1. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Magnesium labeling. 201.71 Section 201.71 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.71 Magnesium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the magnesium...

  2. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Magnesium labeling. 201.71 Section 201.71 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.71 Magnesium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the magnesium...

  3. 21 CFR 201.71 - Magnesium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Magnesium labeling. 201.71 Section 201.71 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.71 Magnesium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the magnesium...

  4. 9 CFR 317.4 - Labeling approval.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... labeling of such final labeling has been submitted for approval to the Food Labeling Division, Regulatory... Secretary upon request. (b) The Food Labeling Division shall permit submission for approval of only sketch... Food Labeling Division, Regulatory Programs, Food Safety and Inspection Service, U.S. Department...

  5. 21 CFR 201.72 - Potassium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Potassium labeling. 201.72 Section 201.72 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.72 Potassium labeling. (a) The labeling of over-the-counter (OTC) drug products intended for oral ingestion shall contain the potassium...

  6. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  7. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  8. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  9. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  10. 21 CFR 201.64 - Sodium labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... contains sodium bicarbonate, sodium phosphate, or sodium biphosphate as an active ingredient for oral... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sodium labeling. 201.64 Section 201.64 Food and... LABELING Labeling Requirements for Over-the-Counter Drugs § 201.64 Sodium labeling. (a) The labeling...

  11. (-)-Botryodiplodin, A Unique Ribose Analog Toxin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many toxins owe their mechanisms of action to being structural analogs of essential metabolites, messengers or structural components. Examples range from tubo-curare to penicillin. Ribose plays a unique role in the metabolism of living organisms, whether prokaryotes or eukaryotes. It and its deri...

  12. The GMO-Nanotech (Dis)Analogy?

    ERIC Educational Resources Information Center

    Sandler, Ronald; Kay, W. D.

    2006-01-01

    The genetically-modified-organism (GMO) experience has been prominent in motivating science, industry, and regulatory communities to address the social and ethical dimensions of nanotechnology. However, there are some significant problems with the GMO-nanotech analogy. First, it overstates the likelihood of a GMO-like backlash against…

  13. Invention through Form and Function Analogy

    ERIC Educational Resources Information Center

    Rule, Audrey C.

    2015-01-01

    "Invention through Form and Function Analogy" is an invention book for teachers and other leaders working with youth who are involving students in the invention process. The book consists of an introduction and set of nine learning cycle formatted lessons for teaching the principles of invention through the science and engineering design…

  14. A Mechanical Analogy for Ohm's Law.

    ERIC Educational Resources Information Center

    do Couto Tavares, Milton; And Others

    1991-01-01

    A mechanical analogy between the microscopic motion of a charged carrier in an ordinary resistor and the macroscopic motion of a ball falling along a slanted board covered with a lattice of nails is introduced. The Drude model is also introduced to include the case of inelastic collisions. Computer simulation of the motion is described. (KR)

  15. Radiation Behavior of Analog Neural Network Chip

    NASA Technical Reports Server (NTRS)

    Langenbacher, H.; Zee, F.; Daud, T.; Thakoor, A.

    1996-01-01

    A neural network experiment conducted for the Space Technology Research Vehicle (STRV-1) 1-b launched in June 1994. Identical sets of analog feed-forward neural network chips was used to study and compare the effects of space and ground radiation on the chips. Three failure mechanisms are noted.

  16. An Analog Processor for Image Compression

    NASA Technical Reports Server (NTRS)

    Tawel, R.

    1992-01-01

    This paper describes a novel analog Vector Array Processor (VAP) that was designed for use in real-time and ultra-low power image compression applications. This custom CMOS processor is based architectually on the Vector Quantization (VQ) algorithm in image coding, and the hardware implementation fully exploits the inherent parallelism built-in the VQ algorithm.

  17. RF digital-to-analog converter

    DOEpatents

    Conway, P.H.; Yu, D.U.L.

    1995-02-28

    A digital-to-analog converter is disclosed for producing an RF output signal proportional to a digital input word of N bits from an RF reference input, N being an integer greater or equal to 2. The converter comprises a plurality of power splitters, power combiners and a plurality of mixers or RF switches connected in a predetermined configuration. 18 figs.

  18. Classical analog of electromagnetically induced transparency

    NASA Astrophysics Data System (ADS)

    Garrido Alzar, C. L.; Martinez, M. A. G.; Nussenzveig, P.

    2002-01-01

    We present a classical analog of electromagnetically induced transparency (EIT). In a system of just two coupled harmonic oscillators subject to a harmonic driving force, we reproduce the phenomenology observed in EIT. We also describe a simple experiment with two linearly coupled RLC circuits which can be incorporated into an undergraduate laboratory.

  19. Analog Acoustic Expression in Speech Communication

    ERIC Educational Resources Information Center

    Shintel, Hadas; Nusbaum, Howard C.; Okrent, Arika

    2006-01-01

    We present the first experimental evidence of a phenomenon in speech communication we call "analog acoustic expression." Speech is generally thought of as conveying information in two distinct ways: discrete linguistic-symbolic units such as words and sentences represent linguistic meaning, and continuous prosodic forms convey information about…

  20. Synthesis Of Labeled Metabolites

    DOEpatents

    Martinez, Rodolfo A.; Silks, III, Louis A.; Unkefer, Clifford J.; Atcher, Robert

    2004-03-23

    The present invention is directed to labeled compounds, for example, isotopically enriched mustard gas metabolites including: [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1-[[2-(methylsulfinyl)ethyl]sulfonyl]-2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylsulfinyl)]; and, 2,2'-sulfinylbis([1,2-.sup.13 C.sub.2 ]ethanol of the general formula ##STR1## where Q.sup.1 is selected from the group consisting of sulfide (--S--), sulfone (--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), at least one C* is .sup.13 C, X is selected from the group consisting of hydrogen and deuterium, and Z is selected from the group consisting of hydroxide (--OH), and --Q.sup.2 --R where Q.sup.2 is selected from the group consisting of sulfide (--S--), sulfone(--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), and R is selected from the group consisting of hydrogen, a C.sub.1 to C.sub.4 lower alkyl, and amino acid moieties, with the proviso that when Z is a hydroxide and Q.sup.1 is a sulfide, then at least one X is deuterium.

  1. Radioiodinated fatty acid analogs for myocardial imaging

    SciTech Connect

    Ruyan, M.K.

    1993-01-01

    Fatty acids are the preferred substrate for the normoxic heart. About sixty percent of the energy required by the myocardium is provided by fatty acid [beta]-oxidation. Many scientists have focused on the alterations in fatty acid metabolism in the ischemic heart for the development of radiolabelled fatty acids for functional imaging of the heart. Three main categories of compounds were synthesized: tetrazoles (1 and 2), glycidic and [alpha]-methylene acids (3-5), and analogs of oleic acid (6,7 and 7A). The tetrazole group has a similar pKa and size to that of a carboxyl group; however, such fatty acid analogs cannot undergo normal fatty acid metabolism. Glycidic and [alpha]-methylene analogs are potential irreversible inhibitors of fatty acid metabolism. Oleic acid analogs were investigated to assess the affect of stereochemical consequences on biodistribution. The key intermediates in the synthesis of the target compounds were [omega]-nitrophenyl alkylcarboxylic acids and alcohols, which were made using a variety of cross-coupling reactions. The Wittig reaction, which was used in the synthesis of tetrazole 1 and glycidic acid 3, gave low yields of the cross-coupled products. The remaining target compounds were synthesized by condensation of appropriate RCu (CN) ZnI and substituted benzyl bromides or by Pd[sup II] catalyzed cross-coupling of substituted arylhalides with suitable alkynes. The latter two reactions produced much higher yields of the desired products. All of the target compounds were radiolabeled with [sup 125]I by various Cu(I) catalyzed radioiodine exchange procedures and were then subjected to tissue biodistribution (TD) studies in rats. Except for the 15-(4-iodophenyl)-2-methylene-pentadecanoic acid (5), all of the fatty acid analogs failed to surpass clinically-used 15-(4-iodophenyl)pentadecanoic acid (IPPA) in their ability to be taken up and retained by the rat myocardium.

  2. Myocardial imaging with a radioiodinated norepinephrine storage analog

    SciTech Connect

    Wieland, D.M.; Brown, L.E.; Rogers, W.L.; Worthington, K.C.; Wu, J.L.; Clinthorne, N.H.; Otto, C.A.; Swanson, D.P.; Beierwaltes, W.H.

    1981-01-01

    Meta-iodobenzylguanidine (M-IBG), an iodinated aromatic analog of the hypotensive drug guanethidine, localizes in the heart of the rat, dog, and rhesus monkey. A comparative study of tissue distribution in the dog has been performed with five myocardiophilic agents: thallium-201, I-125 16-iodohexadecanoic acid, H-3 norepinephrine, C-14 guanethidine and I-125 M-IBG. The last two compounds give heart concentrations and heart-to-blood concentration ratios similar to those of thallium-201. Planar and tomographic images of the hearts of the dog and rhesus monkey were obtained using I-131 or I-123 labeled M-IBG. Blocking studies with reserpine suggest that a major component of myocardial retention of M-IBG is sequestration within the norepinephrine storage vesicles of the adrenergic nerves. The localization of M-IBG in other organs with rich sympathetic innervation and the relative insensitivity of myocardial uptake to a wide range of loading doses lend additional support for a neuronal mode of retention.

  3. CRC handbook of neurohypophyseal hormone analogs. Volume I

    SciTech Connect

    Jost, K.; Lebl, M.; Brtnik, F.

    1987-01-01

    This book is discussed in two parts. Part one discusses Introductory Remarks. Nomenclature. Natural Forms of Neurohypophyseal Hormones. Synthesis, Purification, and Stability of the Neurohypophyseal Hormone Analogs. Isotopically Modified Analogs. Studies of Analogs Using Physiocochemical and Theoretical Methods. Conformational properties of Neurohypophyseal Hormone Analogs in Solution as Determined bu NMR and Laser Raman Spectroscopies. Other Methods used in the Investigation of Neurohypophyseal Hormone Analog Conformations. Conformation Properties of Analogs in Solution as Revealed by Circular Dichroism Spectroscopy. Conformational Energy Calculations. Quantitative Structure Activity Relationships. References. Part 2 discusses The Use of Neurohypophyseal Hormone Analogs in the Study of Neurophysin-Hormone Interactions. Enzymatic Inactivation. Immunochemistry. Studies of Neurohypopophyseal Hormone Activities at the Cellular Level. Fundamental Biological Evaluation. Important Structural Modifications. Noncoded Amino Acids. Modification of ..cap alpha..-Amino Group; 1-Deamino and 1-Hydroxy Analogs. Modifications in the Issulfide Bridge (Carba-Analogs). Modification of Other Functional Groups. Changes in the Backbone. References. Index.

  4. One-electron oxidation of gemcitabine and analogs: mechanism of formation of C3' and C2' sugar radicals.

    PubMed

    Adhikary, Amitava; Kumar, Anil; Rayala, Ramanjaneyulu; Hindi, Ragda M; Adhikary, Ananya; Wnuk, Stanislaw F; Sevilla, Michael D

    2014-11-01

    Gemcitabine is a modified cytidine analog having two fluorine atoms at the 2'-position of the ribose ring. It has been proposed that gemcitabine inhibits RNR activity by producing a C3'• intermediate via direct H3'-atom abstraction followed by loss of HF to yield a C2'• with 3'-keto moiety. Direct detection of C3'• and C2'• during RNR inactivation by gemcitabine still remains elusive. To test the influence of 2'- substitution on radical site formation, electron spin resonance (ESR) studies are carried out on one-electron oxidized gemcitabine and other 2'-modified analogs, i.e., 2'-deoxy-2'-fluoro-2'-C-methylcytidine (MeFdC) and 2'-fluoro-2'-deoxycytidine (2'-FdC). ESR line components from two anisotropic β-2'-F-atom hyperfine couplings identify the C3'• formation in one-electron oxidized gemcitabine, but no further reaction to C2'• is found. One-electron oxidized 2'-FdC is unreactive toward C3'• or C2'• formation. In one-electron oxidized MeFdC, ESR studies show C2'• production presumably from a very unstable C3'• precursor. The experimentally observed hyperfine couplings for C2'• and C3'• match well with the theoretically predicted ones. C3'• to C2'• conversion in one-electron oxidized gemcitabine and MeFdC has theoretically been modeled by first considering the C3'• and H3O(+) formation via H3'-proton deprotonation and the subsequent C2'• formation via HF loss induced by this proximate H3O(+). Theoretical calculations show that in gemcitabine, C3'• to C2'• conversion in the presence of a proximate H3O(+) has a barrier in agreement with the experimentally observed lack of C3'• to C2'• conversion. In contrast, in MeFdC, the loss of HF from C3'• in the presence of a proximate H3O(+) is barrierless resulting in C2'• formation which agrees with the experimentally observed rapid C2'• formation.

  5. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING... and labeling. The symbol shall be prominently located on the label or the labeling of the...

  6. 21 CFR 1302.04 - Location and size of symbol on label and labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Location and size of symbol on label and labeling. 1302.04 Section 1302.04 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE LABELING... and labeling. The symbol shall be prominently located on the label or the labeling of the...

  7. Multilateral Research Opportunities in Ground Analogs

    NASA Technical Reports Server (NTRS)

    Corbin, Barbara J.

    2015-01-01

    The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. International collaboration provides an opportunity to leverage other nations' investments to meet common goals. The Humans In Space Community shares a common goal to enable safe, reliable, and productive human space exploration within and beyond Low Earth Orbit. Meeting this goal requires efficient use of limited resources and International capabilities. The International Space Station (ISS) is our primary platform to conduct microgravity research targeted at reducing human health and performance risks for exploration missions. Access to ISS resources, however, is becoming more and more constrained and will only be available through 2020 or 2024. NASA's Human Research Program (HRP) is actively pursuing methods to effectively utilize the ISS and appropriate ground analogs to understand and mitigate human health and performance risks prior to embarking on human exploration of deep space destinations. HRP developed a plan to use ground analogs of increasing fidelity to address questions related to exploration missions and is inviting International participation in these planned campaigns. Using established working groups and multilateral panels, the HRP is working with multiple Space Agencies to invite International participation in a series of 30- day missions that HRP will conduct in the US owned and operated Human Exploration Research Analog (HERA) during 2016. In addition, the HRP is negotiating access to Antarctic stations (both US and non-US), the German :envihab and Russian NEK facilities. These facilities provide unique capabilities to address critical research questions requiring longer duration simulation or isolation. We are negotiating release of international research opportunities to ensure a multilateral approach to future analog research campaigns, hoping to begin multilateral campaigns in the

  8. Not all analogies are created equal: Associative and categorical analogy processing following brain damage

    PubMed Central

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and categorical (dog-cat) relations. To test the hypothesis that analogical mapping of different types of relations would have different neural instantiations, we tested patients with left and right hemisphere lesions on their ability to understand two types of analogies, ones expressing an associative relationship and others expressing a categorical relationship. Voxel-based lesion-symptom mapping (VLSM) and behavioral analyses revealed that associative analogies relied on a large left-lateralized language network while categorical analogies relied on both left and right hemispheres. The verbal nature of the task could account for the left hemisphere findings. We argue that categorical relations additionally rely on the right hemisphere because they are more difficult, abstract, and fragile; and contain more distant relationships. PMID:22402184

  9. Not all analogies are created equal: Associative and categorical analogy processing following brain damage.

    PubMed

    Schmidt, Gwenda L; Cardillo, Eileen R; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-06-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and categorical (dog-cat) relations. To test the hypothesis that analogical mapping of different types of relations would have different neural instantiations, we tested patients with left and right hemisphere lesions on their ability to understand two types of analogies, ones expressing an associative relationship and others expressing a categorical relationship. Voxel-based lesion-symptom mapping (VLSM) and behavioral analyses revealed that associative analogies relied on a large left-lateralized language network while categorical analogies relied on both left and right hemispheres. The verbal nature of the task could account for the left hemisphere findings. We argue that categorical relations additionally rely on the right hemisphere because they are more difficult, abstract, and fragile, and contain more distant relationships.

  10. Homosexual Labeling by University Youths

    ERIC Educational Resources Information Center

    Nyberg, Kenneth L.; Alston, Jon P.

    1977-01-01

    Details the responses of young, urban, college-educated people on their attitudes toward homosexuals, specifically focusing on issues of public identification and negative labeling as it effects homosexual persons and their behaviors. (Author/RK)

  11. How to read food labels

    MedlinePlus

    ... 1 serving. You should also pay attention to trans fats on any food label. These fats raise "bad" ... foods and desserts. Many fast food restaurants use trans fats for frying. If a food has these fats, ...

  12. Dietary Supplement Label Database (DSLD)

    MedlinePlus

    ... Print Report Error T he Dietary Supplement Label Database (DSLD) is a joint project of the National ... participants in the latest survey in the DSLD database (NHANES): The search options: Quick Search, Browse Dietary ...

  13. Food Labels Tell the Story!

    MedlinePlus

    ... Environment Kids Health Topics Environment & Health Healthy Living Pollution Reduce, Reuse, Recycle Science – How It Works The ... Pay close attention to serving sizes. Products labeled "light" or "lite" must have 1/3 fewer calories ...

  14. Playing with a double-edged sword: Analogies in biochemistry

    NASA Astrophysics Data System (ADS)

    Orgill, Marykay

    Analogy pervades our everyday reasoning. No situation we encounter is exactly like a situation we have encountered previously, and our ability to learn and survive in the world is based on our ability to find similarities between past and present situations and use the knowledge we have gained from past situations to manage current situations. Analogies can be powerful teaching tools because they can make new material intelligible to students by comparing it to material that is already familiar. It is clear, though, that not all analogies are good and that not all good analogies are useful to all students. In this study, I have used textbook analysis, classroom observations, student interviews and instructor interviews to determine the role that analogies play in biochemistry learning. Analogies are an important teaching technique in biochemistry classes, being used more often in both biochemistry classes and textbooks than they are in high school chemistry classes and textbooks. Most biochemistry students like, pay particular attention to, and remember the analogies their instructors provide; and they use these analogies to understand, visualize, and recall information from class. Even though students like and use analogies, they do not understand what analogies are or the mechanism by which they improve learning. For the students, analogies are simply any teaching technique that eases understanding, visualization, or recall. Instructors, on the other hand, have a good understanding of what analogies are and of how they should be presented in class; but they do not use analogies as effectively as they should. They do not plan, explain or identify the limitations of the analogies they use in class. However, regardless of how effectively instructors present analogies in class, this study indicates that, in general, analogies are useful in promoting understanding, visualization, recall, and motivation in biochemistry students at all levels. They would be even more

  15. A new program on digitizing analog seismograms

    NASA Astrophysics Data System (ADS)

    Wang, Maofa; Jiang, Qigang; Liu, Qingjie; Huang, Meng

    2016-08-01

    Historical seismograms contain a great variety of useful information which can be used in the study of earthquakes. It is necessary for researchers to digitize analog records and extract the information just as modern computing analysis requires. Firstly, an algorithm based on color scene filed method is presented in order to digitize analog seismograms. Secondly, an interactive software program using C# has been developed to digitize seismogram traces from raster files quickly and accurately. The program can deal with gray-scale images stored in a suitable file format and it offers two different methods: manual digitization and automatic digitization. The test result of the program shows that the methods presented in this paper can lead to good performance.

  16. Terrestrial analogs of the hellespontus dunes, Mars

    USGS Publications Warehouse

    Breed, C.S.

    1977-01-01

    Geomorphic features in the Hellespontus region, Mars, were compared with dunes of the crescentic ridge type in numerous terrestrial sand seas quantitatively by dimensional analysis of dune lengths, widths, and wavelengths. Mean values for the Hellespontus dunes are close to mean values derived from measurements of all sampled terrestrial sand seas. Terrestrial analogs of form and areal distribution of the Hellespontus dunes are shown by comparison of scale ratios derived from the measurements. Dunes of similar form occur in South West Africa, in Pakistan, in the southeastern Arabian peninsula, in the Sahara, in eastern USSR and northern China, and in western North America. Terrestrial analogs closest to form and areal distribution of the Hellespontus dunes are in the Kara Kum Desert, Turkmen SSR, and in the Ala Shan (Gobi) Desert, China. ?? 1977.

  17. Optimal neural computations require analog processors

    SciTech Connect

    Beiu, V.

    1998-12-31

    This paper discusses some of the limitations of hardware implementations of neural networks. The authors start by presenting neural structures and their biological inspirations, while mentioning the simplifications leading to artificial neural networks. Further, the focus will be on hardware imposed constraints. They will present recent results for three different alternatives of parallel implementations of neural networks: digital circuits, threshold gate circuits, and analog circuits. The area and the delay will be related to the neurons` fan-in and to the precision of their synaptic weights. The main conclusion is that hardware-efficient solutions require analog computations, and suggests the following two alternatives: (i) cope with the limitations imposed by silicon, by speeding up the computation of the elementary silicon neurons; (2) investigate solutions which would allow the use of the third dimension (e.g. using optical interconnections).

  18. Analog Computation by DNA Strand Displacement Circuits.

    PubMed

    Song, Tianqi; Garg, Sudhanshu; Mokhtar, Reem; Bui, Hieu; Reif, John

    2016-08-19

    DNA circuits have been widely used to develop biological computing devices because of their high programmability and versatility. Here, we propose an architecture for the systematic construction of DNA circuits for analog computation based on DNA strand displacement. The elementary gates in our architecture include addition, subtraction, and multiplication gates. The input and output of these gates are analog, which means that they are directly represented by the concentrations of the input and output DNA strands, respectively, without requiring a threshold for converting to Boolean signals. We provide detailed domain designs and kinetic simulations of the gates to demonstrate their expected performance. On the basis of these gates, we describe how DNA circuits to compute polynomial functions of inputs can be built. Using Taylor Series and Newton Iteration methods, functions beyond the scope of polynomials can also be computed by DNA circuits built upon our architecture. PMID:27363950

  19. Understanding the Nature of PHL 1811 Analogs

    NASA Astrophysics Data System (ADS)

    Brandt, W. N.

    2012-09-01

    A central tenet of X-ray astronomy is that luminous X-ray emission is a universal property of efficiently accreting supermassive black holes. However, we have recently studied a population of type 1 quasars that challenge this idea: PHL 1811 analogs. These objects are all X-ray weak and have exceptional UV emission-line properties. We propose snapshot observations of 10 bright radio-quiet PHL 1811 analogs that will more than double the sample of these objects with sensitive X-ray coverage. The improved sample size will better characterize the X-ray weakness of this population and allow correlation tests with emission-line properties. The improved photon statistics will aid joint spectral analyses investigating hints of hard X-ray spectra and X-ray absorption.

  20. Parabolic flight as a spaceflight analog.

    PubMed

    Shelhamer, Mark

    2016-06-15

    Ground-based analog facilities have had wide use in mimicking some of the features of spaceflight in a more-controlled and less-expensive manner. One such analog is parabolic flight, in which an aircraft flies repeated parabolic trajectories that provide short-duration periods of free fall (0 g) alternating with high-g pullout or recovery phases. Parabolic flight is unique in being able to provide true 0 g in a ground-based facility. Accordingly, it lends itself well to the investigation of specific areas of human spaceflight that can benefit from this capability, which predominantly includes neurovestibular effects, but also others such as human factors, locomotion, and medical procedures. Applications to research in artificial gravity and to effects likely to occur in upcoming commercial suborbital flights are also possible.

  1. Analog data transmission via fiber optics

    SciTech Connect

    Cisneros, E.L.; Burgueno, G.F.

    1986-10-01

    In the SLAC Linear Collider Detector (SLD), as in most high-energy particle detectors, the electromagnetic noise environment is the limiting factor in electronic readout performance. Front-end electronics are particulary susceptible to electromagnetic interference (EMI), and great care has been taken to minimize its effects. The transfer of preprocessed analog signals from the detector environs, to the remote digital processing electronics, by conventional means (via metal conductors), may ultimately limit the performance of the system. Because it is highly impervious to EMI and ground loops, a fiber-optic medium has been chosen for the transmission of these signals. This paper describes several fiber-optic transmission schemes which satisfy the requirements of the SLD analog data transmission.

  2. Submarine Analogs to Venusian Pancake Domes

    NASA Technical Reports Server (NTRS)

    Bridges, Nathan T.

    1995-01-01

    The morphology and dimensions of the large diameter, steep-sided, flat-topped "pancake domes" on Venus make them unlike any type of terrestrial subaerial volcano. Comparisons between images of Hawaiian seamounts and pancake domes show similarities in shapes and secondary features. The morphometry of pancake domes is closer to that of Pacific seamounts than subaerial lava domes. Considering both morphology and morphometry, seamounts seem a better analog to the pancake domes. The control of volatile exsolution by pressure on Venus and the seafloor can cause lavas to have similar viscosities and densities, although the latter will be counteracted by high buoyancy underwater. However, analogous effects of the Venusian and seafloor alone are probably not sufficient to produce similar volcanoes. Rather, Venusian lavas of various compositions may behave like basalt on the seafloor if appropriate rates and modes of extrusion and planetary thermal structure are also considered.

  3. Nonintentional analogical inference in text comprehension.

    PubMed

    Day, Samuel B; Gentner, Dedre

    2007-01-01

    We present findings suggesting that analogical inference processes can play a role in fluent comprehension and interpretation. Participants were found to use information from a prior relationally similar example in understanding the content of a later example, but they reported that they were not aware of having done so. These inference processes were sensitive to structural mappings between the two instances, ruling out explanations based solely on more general kinds of activation, such as priming. Reading speed measures were consistent with the possibility that these inferences had taken place during encoding of the target rather than during the later recognition test. These findings suggest that analogical mapping, though often viewed as an explicit deliberative process, can sometimes operate without intent or even awareness.

  4. Observing spin optodynamical analog of cavity optomechanics

    NASA Astrophysics Data System (ADS)

    Gerber, Justin; Kohler, Jonathan; Spethmann, Nicolas; Schreppler, Sydney; Stamper-Kurn, Dan

    2016-05-01

    Cavity Optomechanics has been realized in many diverse systems and led to many interesting results such as ponderomotive squeezing of light, beyond-SQL measurement sensitivity, and squeezing of mechanical oscillators. Optical cavities also allow sensitive measurements of the spin of an atomic ensemble. It has been proposed to utilize this sensitivity to realize an analog of optomechanics by measuring the precession of small excitations of a spin-oscillator around a transverse magnetic field. I will present our recent work in which we realize optomechanical analogs in our system such as cavity-assisted cooling and amplification and optical spring shifts. In addition, the presence of a high-energy `ground state' of the spin oscillator allows the realization of an effective negative mass oscillator which is demonstrated by an inverted sideband asymmetry. In our ongoing work we attempt to realize coherent quantum noise cancelation by coupling spin oscillation with mechanical oscillation.

  5. Terrestrial analogs of the Hellespontus dunes, Mars

    NASA Technical Reports Server (NTRS)

    Breed, C. S.

    1977-01-01

    Geomorphic features in the Hellespontus region, Mars, were compared with dunes of the crescentic ridge type in numerous terrestrial sand seas quantitatively by dimensional analysis of dune lengths, widths, and wavelengths. Mean values for the Hellespontus dunes are close to mean values derived from measurements of all sampled terrestrial sand seas. Terrestrial analogs of form and areal distribution of the Hellespontus dunes are shown by comparison of scale ratios derived from the measurements. Dunes of similar form occur in South West Africa, in Pakistan, in the southeastern Arabian peninsula, in the Sahara, in eastern USSR and northern China, and in western North America. Terrestrial analogs closest to form and areal distribution of the Hellespontus dunes are in the Kara Kum Desert, Turkmen SSR, and in the Ala Shan (Gobi) Desert, China.

  6. Electrothermal branding for embryo labeling.

    PubMed

    Wang, L; Beebe, D J; Williams, A R; Easley, K D

    1997-11-01

    A novel embryo labeling technique based on electrothermal branding is developed. Two types of micro branding irons are fabricated and tested. One utilizes 25 microns tungsten wire as the heating element. The other utilizes surface micromachining techniques to fabricate polysilicon branding irons. The thermal behavior of the branding irons and the heat distributions in the embryos are analytically modeled. Micron-scale labels on unfertilized bovine embryos are achieved.

  7. Biomedical sensor design using analog compressed sensing

    NASA Astrophysics Data System (ADS)

    Balouchestani, Mohammadreza; Krishnan, Sridhar

    2015-05-01

    The main drawback of current healthcare systems is the location-specific nature of the system due to the use of fixed/wired biomedical sensors. Since biomedical sensors are usually driven by a battery, power consumption is the most important factor determining the life of a biomedical sensor. They are also restricted by size, cost, and transmission capacity. Therefore, it is important to reduce the load of sampling by merging the sampling and compression steps to reduce the storage usage, transmission times, and power consumption in order to expand the current healthcare systems to Wireless Healthcare Systems (WHSs). In this work, we present an implementation of a low-power biomedical sensor using analog Compressed Sensing (CS) framework for sparse biomedical signals that addresses both the energy and telemetry bandwidth constraints of wearable and wireless Body-Area Networks (BANs). This architecture enables continuous data acquisition and compression of biomedical signals that are suitable for a variety of diagnostic and treatment purposes. At the transmitter side, an analog-CS framework is applied at the sensing step before Analog to Digital Converter (ADC) in order to generate the compressed version of the input analog bio-signal. At the receiver side, a reconstruction algorithm based on Restricted Isometry Property (RIP) condition is applied in order to reconstruct the original bio-signals form the compressed bio-signals with high probability and enough accuracy. We examine the proposed algorithm with healthy and neuropathy surface Electromyography (sEMG) signals. The proposed algorithm achieves a good level for Average Recognition Rate (ARR) at 93% and reconstruction accuracy at 98.9%. In addition, The proposed architecture reduces total computation time from 32 to 11.5 seconds at sampling-rate=29 % of Nyquist rate, Percentage Residual Difference (PRD)=26 %, Root Mean Squared Error (RMSE)=3 %.

  8. Analog Processor To Solve Optimization Problems

    NASA Technical Reports Server (NTRS)

    Duong, Tuan A.; Eberhardt, Silvio P.; Thakoor, Anil P.

    1993-01-01

    Proposed analog processor solves "traveling-salesman" problem, considered paradigm of global-optimization problems involving routing or allocation of resources. Includes electronic neural network and auxiliary circuitry based partly on concepts described in "Neural-Network Processor Would Allocate Resources" (NPO-17781) and "Neural Network Solves 'Traveling-Salesman' Problem" (NPO-17807). Processor based on highly parallel computing solves problem in significantly less time.

  9. Analog optical computing primitives in silicon photonics.

    PubMed

    Jiang, Yunshan; DeVore, Peter T S; Jalali, Bahram

    2016-03-15

    Optical computing accelerators help alleviate bandwidth and power consumption bottlenecks in electronics. We show an approach to implementing logarithmic-type analog co-processors in silicon photonics and use it to perform the exponentiation operation and the recovery of a signal in the presence of multiplicative distortion. The function is realized by exploiting nonlinear-absorption-enhanced Raman amplification saturation in a silicon waveguide. PMID:26977687

  10. Survey of Evaluated Isobaric Analog States

    SciTech Connect

    MacCormick, M.

    2014-06-15

    Isobaric analog states (IAS) can be used to estimate the masses of members belonging to the same isospin multiplet. Experimental and estimated IAS have been used frequently within the Atomic Mass Evaluation (AME) in the past, but the associated set of evaluated masses have been published for the first time in AME2012 and NUBASE2012. In this paper the current trends of the isobaric multiplet mass equation (IMME) coefficients are shown. The T = 2 multiplet is used as a detailed illustration.

  11. Synthesis and biological evaluation of platensimycin analogs

    SciTech Connect

    Shen, Hong C.; Ding, Fa-Xiang; Singh, Sheo B.; Parthasarathy, Gopalakrishnan; Soisson, Stephen M.; Ha, Sookhee N.; Chen, Xun; Kodali, Srinivas; Wang, Jun; Dorso, Karen; Tata, James R.; Hammond, Milton L.; MacCoss, Malcolm; Colletti, Steven L.

    2009-07-23

    Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.

  12. The 2012 Moon and Mars Analog Mission

    NASA Technical Reports Server (NTRS)

    Graham, Lee

    2014-01-01

    The 2012 Moon and Mars Analog Mission Activities (MMAMA) scientific investigations were completed on Mauna Kea volcano in Hawaii in July 2012. The investigations were conducted on the southeast flank of the Mauna Kea volcano at an elevation of approximately 11,500 ft. This area is known as "Apollo Valley" and is in an adjacent valley to the Very Large Baseline Array dish antenna.

  13. Ophiolites as Analogs to Habitats on Mars

    NASA Technical Reports Server (NTRS)

    Schulte, M.; Blake, D. F.

    2003-01-01

    Ophiolite sequences that are located in northern and central California provide easily accessible areas that serve as good analogs for martian crustal rocks. The rock types found in a typical ophiolite sequence compare well with those found in the Mars meteorites, and those expected from spectrophotometric analysis. We have begun investigating and characterizing these sites in order to understand better the processes that may be responsible for the groundwater chemistry, mineralogy and biology of similar environments on Mars.

  14. Magnetic Analog Random-Access Memory

    NASA Technical Reports Server (NTRS)

    Katti, Romney R.; Wu, Jiin-Chuan; Stadler, Henry L.

    1991-01-01

    Proposed integrated, solid-state, analog random-access memory base on principle of magnetic writing and magnetoresistive reading. Current in writing conductor magnetizes storage layer. Remanent magnetization in storage layer penetrates readout layer and detected by magnetoresistive effect or Hall effect. Memory cells are part of integrated circuit including associated reading and writing transistors. Intended to provide high storage density and rapid access, nonvolatile, consumes little power, and relatively invulnerable to ionizing radiation.

  15. Multi-focus cluster labeling.

    PubMed

    Eikvil, Line; Jenssen, Tor-Kristian; Holden, Marit

    2015-06-01

    Document collections resulting from searches in the biomedical literature, for instance, in PubMed, are often so large that some organization of the returned information is necessary. Clustering is an efficient tool for organizing search results. To help the user to decide how to continue the search for relevant documents, the content of each cluster can be characterized by a set of representative keywords or cluster labels. As different users may have different interests, it can be desirable with solutions that make it possible to produce labels from a selection of different topical categories. We therefore introduce the concept of multi-focus cluster labeling to give users the possibility to get an overview of the contents through labels from multiple viewpoints. The concept for multi-focus cluster labeling has been established and has been demonstrated on three different document collections. We illustrate that multi-focus visualizations can give an overview of clusters along axes that general labels are not able to convey. The approach is generic and should be applicable to any biomedical (or other) domain with any selection of foci where appropriate focus vocabularies can be established. A user evaluation also indicates that such a multi-focus concept is useful.

  16. Synthetic analog computation in living cells.

    PubMed

    Daniel, Ramiz; Rubens, Jacob R; Sarpeshkar, Rahul; Lu, Timothy K

    2013-05-30

    A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.

  17. Neurotoxicity of artemisinin analogs in vitro.

    PubMed Central

    Wesche, D L; DeCoster, M A; Tortella, F C; Brewer, T G

    1994-01-01

    The sesquiterpene endoperoxide antimalarial agents arteether and artemether have been reported to cause neurotoxicity with a discrete distribution in the brain stems of rats and dogs after multiple doses. The nature and distribution of the brain lesions suggest a specific neuronal target, the identity of which is unknown. In order to further investigate artemisinin analog-induced neurotoxicity, we evaluated several in vitro models: fetal rat primary neuronal cultures, fetal rat secondary astrocyte cultures, and transformed neuronal cultures (rat-derived neuroblastoma NG108-15 and mouse-derived neuroblastoma Neuro-2a). Results indicate that toxicity was specific for neuronal cell types but not glial cells. Neurotoxicity, as indexed by liberation of lactate dehydrogenase and/or inhibition of radiolabelled-leucine uptake, was seen in all three neuronal culture types, implicating a common target. In vitro neurotoxicity was dose and time dependent. Acute exposure to drug results in delayed, but not immediate, manifestations of cell toxicity. Structure-activity comparisons indicate that substitutions at positions 9 and 10 and stereoisomerism at position 10 of the artemisinin backbone influence the degree of toxicity. The endoperoxide is necessary but not sufficient for toxicity. Sodium artesunate and dihydroartemisinin, a metabolite common to all artemisinin analogs currently being developed for clinical use, are the most potent of all analogs tested. These results are consistent with a specific neuronal target, but the identity of the target(s) remains unknown. PMID:7986012

  18. Clinical utility of insulin and insulin analogs

    PubMed Central

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  19. Backtracking quantum trajectories with analog feedback

    NASA Astrophysics Data System (ADS)

    de Lange*, G.; Ristè*, D.; Tiggelman, M. J.; Eichler, C.; Tornberg, L.; Johansson, G.; Wallraff, A.; Schouten, R. N.; Dicarlo, L.

    2014-03-01

    Circuit quantum electrodynamics offers a nearly ideal platform for the fundamental study of continuous quantum measurement. A nondemolition measurement of a superconducting qubit can be performed via homodyne detection of microwave transmission through a dispersively coupled cavity. By boosting the homodyne signal with a nearly noiseless phase-sensitive parametric amplifier, we experimentally show that a form of measurement backaction, consisting of stochastic quantum phase kicks on the measured qubit, is highly correlated with the fluctuations in the continuous homodyne record. We demonstrate a real-time analog feedback scheme that counteracts these phase kicks and thereby reduces measurement-induced dephasing. We develop a numerical optimization technique to overcome the bandwidth limitations of the amplification chain and provide a theoretical model for the optimization result. A quantum efficiency of 50% is extracted for the complete analog feedback loop. Finally, we discuss the integration of this analog feedback technique to improve performance in our recent demonstration of entanglement by dispersive parity measurement. *equal contribution. Research funded by NWO and the EU projects SOLID and SCALEQIT.

  20. Sensing Methods for Detecting Analog Television Signals

    NASA Astrophysics Data System (ADS)

    Rahman, Mohammad Azizur; Song, Chunyi; Harada, Hiroshi

    This paper introduces a unified method of spectrum sensing for all existing analog television (TV) signals including NTSC, PAL and SECAM. We propose a correlation based method (CBM) with a single reference signal for sensing any analog TV signals. In addition we also propose an improved energy detection method. The CBM approach has been implemented in a hardware prototype specially designed for participating in Singapore TV white space (WS) test trial conducted by Infocomm Development Authority (IDA) of the Singapore government. Analytical and simulation results of the CBM method will be presented in the paper, as well as hardware testing results for sensing various analog TV signals. Both AWGN and fading channels will be considered. It is shown that the theoretical results closely match with those from simulations. Sensing performance of the hardware prototype will also be presented in fading environment by using a fading simulator. We present performance of the proposed techniques in terms of probability of false alarm, probability of detection, sensing time etc. We also present a comparative study of the various techniques.

  1. Automated D/3 to Visio Analog Diagrams

    2000-08-10

    ADVAD1 reads an ASCII file containing the D/3 DCS MDL input for analog points for a D/3 continuous database. It uses the information in the files to create a series of Visio files representing the structure of each analog chain, one drawing per Visio file. The actual drawing function is performed by Visio (requires Visio version 4.5+). The user can configure the program to select which fields in the database are shown on the diagrammore » and how the information is to be presented. This gives a visual representation of the structure of the analog chains, showing selected fields in a consistent manner. Updating documentation can be done easily and the automated approach eliminates human error in the cadding process. The program can also create the drawings far faster than a human operator is capable, able to create approximately 270 typical diagrams in about 8 minutes on a Pentium II 400 MHz PC. The program allows for multiple option sets to be saved to provide different settings (i.e., different fields, different field presentations, and /or different diagram layouts) for various scenarios or facilities on one workstation. Option sets may be exported from the Windows registry to allow duplication of settings on another workstation.« less

  2. Targeting thyroid diseases with TSH receptor analogs.

    PubMed

    Galofré, Juan C; Chacón, Ana M; Latif, Rauf

    2013-12-01

    The thyroid-stimulating hormone (TSH) receptor (TSHR) is a major regulator of thyroid function and growth, and is the key antigen in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Various effective treatment strategies are currently available for many of these clinical conditions such as antithyroid drugs or radioiodine therapy, but they are not devoid of side effects. In addition, treatment of complications of Graves' disease such as Graves' ophthalmopathy is often difficult and unsatisfactory using current methods. Recent advances in basic research on both in vitro and in vivo models have suggested that TSH analogs could be used for diagnosis and treatment of some of the thyroid diseases. The advent of high-throughput screening methods has resulted in a group of TSH analogs called small molecules, which have the potential to be developed as promising drugs. Small molecules are low molecular weight compounds with agonist, antagonist and, in some cases, inverse agonist activity on TSHR. This short review will focus on current advances in development of TSH analogs and their potential clinical applications. Rapid advances in this field may lead to the conduct of clinical trials of small molecules related to TSHR for the management of Graves' disease, thyroid cancer, and thyroid-related osteoporosis in the coming years.

  3. Periglacial and glacial analogs for Martian landforms

    NASA Technical Reports Server (NTRS)

    Rossbacher, Lisa A.

    1992-01-01

    The list of useful terrestrial analogs for Martian landforms has been expanded to include: features developed by desiccation processes; catastrophic flood features associated with boulder-sized materials; and sorted ground developed at a density boundary. Quantitative analytical techniques developed for physical geography have been adapted and applied to planetary studies, including: quantification of the patterns of polygonally fractured ground to describe pattern randomness independent of pattern size, with possible correlation to the mechanism of origin and quantification of the relative area of a geomorphic feature or region in comparison to planetary scale. Information about Martian geomorphology studied in this project was presented at professional meetings world-wide, at seven colleges and universities, in two interactive televised courses, and as part of two books. Overall, this project has expanded the understanding of the range of terrestrial analogs for Martian landforms, including identifying several new analogs. The processes that created these terrestrial features are characterized by both cold temperatures and low humidity, and therefore both freeze-thaw and desiccation processes are important. All these results support the conclusion that water has played a significant role in the geomorphic history of Mars.

  4. 1,N6-etheno deoxy and ribo adenosine and 3,N4-etheno deoxy and ribo cytidine phosphoramidites. Strongly fluorescent structures for selective introduction in defined sequence DNA and RNA molecules.

    PubMed Central

    Srivastava, S C; Raza, S K; Misra, R

    1994-01-01

    Synthesis of 1,N6-etheno-2'-deoxyadenosine, 3,N4-etheno-2'-deoxycytidine, and further chemistry on both deoxy and ribo series etheno nucleosides produces the corresponding phosphoramidites. These novel phosphoramidites are introduced selectively, quantitatively, and at specific positions at single or multiple sites into DNA or RNA sequences. The purification and chemistry involved in the synthesis of these products has been optimized to achieve the purity in excess of 99%. The resulting phosphoramidites were tested for their ability to couple and produce poly deoxy and ribonucleotides by solid phase chemistry. The coupling efficiency achieved was greater than 99% per step. Due to the instability of these etheno compounds in acidic and basic medium, various criteria to obtain pure oligomers have been established. The selective introduction of these fluorescent nucleosides into defined sequence DNA and RNA molecule will greatly facilitate the structure-function studies of various RNAs, protein-RNA structures, and DNA-RNA based diagnostics applications. The characteristic and high fluorescent intensity (detection below 1 x 10(-9) M for adenosine sites and below 1 x 10(-7) M for cytidine sites) is particularly suited for the biochemical and biological research and product development applications. The usefulness of these etheno containing modified sequences as sequencing and amplification primers is demonstrated by their full participation in polymerase chain reaction experiments. Images PMID:7513082

  5. Simultaneous Quantification of Methylated Cytidine and Adenosine in Cellular and Tissue RNA by Nano-Flow Liquid Chromatography-Tandem Mass Spectrometry Coupled with the Stable Isotope-dilution Method

    PubMed Central

    Fu, Lijuan; Amato, Nicolas J.; Wang, Pengcheng; McGowan, Sara J.; Niedernhofer, Laura J.; Wang, Yinsheng

    2016-01-01

    The rising interest in understanding the functions, regulation and maintenance of the epitranscriptome calls for robust and accurate analytical methods for the identification and quantification of post-transcriptionally modified nucleosides in RNA. Mono-methylations of cytidine and adenosine are common post-transcriptional modifications in RNA. Herein, we developed an LC-MS/MS/MS coupled with the stable isotope-dilution method for the sensitive and accurate quantifications of 5-methylcytidine (m5C), 2′-O-methylcytidine (Cm), N6-methyladenosine (m6A) and 2′-O-methyladenosine (Am) in RNA isolated from mammalian cells and tissues. Our results showed that the distributions of the four methylated nucleosides are tissue-specific. In addition, the 2′-O-methylated ribonucleosides (Cm and Am) are present at higher levels than the corresponding methylated nucleobase products (m5C and m6A) in total RNA isolated from mouse brain, pancreas and spleen, but not mouse heart. We also found that the levels of m5C, Cm and Am are significantly lower (by 6.5-43 fold) in mRNA than in total RNA isolated from HEK293T cells, whereas the level of m6A was slightly higher (by 1.6 fold) in mRNA than in total RNA. The availability of this analytical method, in combination with genetic manipulation, may facilitate the future discovery of proteins involved in the maintenance and regulation of these RNA modifications. PMID:26158405

  6. Enhanced dendritic cell maturation by TNF-alpha or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo.

    PubMed

    Brunner, C; Seiderer, J; Schlamp, A; Bidlingmaier, M; Eigler, A; Haimerl, W; Lehr, H A; Krieg, A M; Hartmann, G; Endres, S

    2000-12-01

    Dendritic cells (DC) manipulated ex vivo can induce tumor immunity in experimental murine tumor models. To improve DC-based tumor vaccination, we studied whether DC maturation affects the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4 alone or by further addition of TNF-alpha or a cytidine-phosphate-guanosine (CpG)-containing oligonucleotide (ODN-1826), which mimics the immunostimulatory effect of bacterial DNA. Flow cytometric analysis of costimulatory molecules and MHC class II showed that DC maturation was stimulated most by ODN-1826, whereas TNF-alpha had an intermediate effect. The extent of maturation correlated with the secretion of IL-12 and the induction of alloreactive T cell proliferation. In BALB/c mice, s.c. injection of colon carcinoma cells resulted in rapidly growing tumors. In this model, CpG-ODN-stimulated DC cocultured with irradiated tumor cells also induced prophylactic protection most effectively and were therapeutically effective when administered 3 days after tumor challenge. Thus, CpG-ODN-enhanced DC maturation may represent an efficient means to improve clinical tumor vaccination.

  7. Toward synthesis of third-generation spin-labeled podophyllotoxin derivatives using isocyanide multicomponent reactions.

    PubMed

    Kou, Liang; Wang, Mei-Juan; Wang, Li-Ting; Zhao, Xiao-Bo; Nan, Xiang; Yang, Liu; Liu, Ying-Qian; Morris-Natschke, Susan L; Lee, Kuo-Hsiung

    2014-03-21

    Spin-labeled podophyllotoxins have elicited widespread interest due to their far superior antitumor activity compared to podophyllotoxin. To extend our prior studies in this research area, we synthesized a new generation of spin-labeled podophyllotoxin analogs via isocyanide multicomponent reactions and evaluated their cytotoxicity against four human cancer cell lines (A-549, DU-145, KB and KBvin). Most of the compounds exhibited potent cytotoxic activity against all four cell lines, notably against the drug resistant KBvin cancer cell line. Among the new analogs, compounds 12e (IC50: 0.60-0.75 μM) and 12h (IC50: 1.12-2.03 μM) showed superior potency to etoposide (IC50: 2.03 to >20 μM), a clinically available anticancer drug. With a concise efficient synthesis and potent cytotoxic profiles, compounds 12e and 12h merit further development as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidates. PMID:24553146

  8. Scientific Analogies and Their Use in Teaching Science

    NASA Astrophysics Data System (ADS)

    Kipnis, Nahum

    Analogy in science knew its successes and failures, as illustrated by examples from the eighteenth-century physics. At times, some scientists abstained from using a certain analogy on the ground that it had not yet been demonstrated. Several false discoveries in the 18th and early 19th centuries appeared to support their caution. It is now clear that such a position reflected a methodological confusion that resulted from a failure to distinguish between particular and general analogies. Considering analogy as a hierarchical structure provides a new insight into "testing an analogy". While warning science teachers of dangers associated with use of analogy, historical cases and their analysis provided here may encourage them to use analogy more extensively while avoiding misconceptions. An argument is made that the history of science may be a better guide than philosophy of science and cognitive psychology when it concerns the role of analogy in science and in teaching science for understanding.

  9. [Relationship between chemical structure and sweetness. XIV. Analogs of aspartame].

    PubMed

    De Nardo, M

    1977-07-01

    Several analogs structurally related to aspartame were prepared in order to establish if chemical modifications of the molecule might improve sweetness. None of these analogs exhibited any sweet taste; on the contrary in most cases they were bitter.

  10. Drug binding to the acetylcholine receptor: Nitroxide analogs of phencyclidine and a local anesthetic

    SciTech Connect

    Palma, A.L.

    1988-01-01

    The interaction of noncompetitive inhibitors (NCIs) with Torpedo californica native nicotinic acetylcholine receptor (nAChR) membranes was examined primarily by the technique of electron paramagnetic resonance (EPR) spectroscopy. The goal of this work being to define some of the physical characteristics for the site(s) of association between an NCI and the nAChR membrane. A nitroxide labeled analog of a quaternary amine local anesthetic, 2-(N,N-dimethyl-N-4-(2,2,6,6-tetramethylpiperidinoxyl)amino)-ethyl 4-hexyloxybenzoate iodide (C6SLMeI), displays a strongly immobilized EPR component when added to nAChR membranes in the presence of carbamylcholine (carb). To further this work, a nitroxide labeled analog of phencyclidine (PCP), a potent NCI, was synthesized. 4-phenyl-4-(1-piperidinyl)-2,2,6,6-tetramethylpiperidinoxyl (PPT) exhibited one-third the potency of PCP in inhibiting nAChR mediated ion flux, and from competition binding studies with ({sup 3}H)PCP displayed a K{sub D} of 0.21 {mu}M towards a carb desensitized nAChR and a K{sub 0.5} of 18 {mu}M for a resting {alpha}-bungarotoxin treated nAChR.

  11. Smectites versus palagonites in Mars soil: Evidence from simulations of Viking biology labeled release experiments

    NASA Technical Reports Server (NTRS)

    Banin, A.; Margulies, L.

    1983-01-01

    The results of an experimental comparison between palagonites and a smectite (montmorillonite) in the simulation of the Viking Biology Labeled Release (LR) experiment and conclusions regarding their suitability as MarSAMs are reproved. It was found that palagonites do not cause formate decomposition and C-14 release in their natural form or after acidification and thus cannot be a completely satisfactory analog to the Mars soil studied by Viking.

  12. Interactive Optical Disc Systems: Part 1: Analog Storage.

    ERIC Educational Resources Information Center

    Hessler, David W.

    1984-01-01

    Details distinction between digital and analog data, advantages of analog storage, and optical disc use to store analog data. Configuration and potential of three levels of laser disc systems are explained. Selection of display devices for use with laser disc systems and accessing audio data are addressed. (Continued in next issue.) (EJS)

  13. Using Analogies as an Experiential Learning Technique in Multicultural Education

    ERIC Educational Resources Information Center

    Suthakaran, V.; Filsinger, Keri; White, Brittany

    2013-01-01

    In this article the authors specifically address the use of narratives in the form of analogies as an experiential learning activity. The use of analogies as an experiential learning tool in multicultural education can be helpful in a number of ways. Analogies provide an alternative tool for processing multicultural topics with students who have…

  14. Modern Communication: Exploring Physiological Transmission through Tech-Savvy Analogies

    ERIC Educational Resources Information Center

    Hollabaugh, Christopher R.; Milanick, Mark A.

    2014-01-01

    Analogies are often helpful for students to grasp key physiological concepts; sometimes the technical jargon makes the concept seem more complex than it actually is. In this article the authors provide several analogies for information transfer processes that sometimes confuse students. For an analogy to be useful, of course, it needs to be…

  15. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming

    ERIC Educational Resources Information Center

    Pena, Gil Patrus; Andrade-Filho, Jose de Souza

    2010-01-01

    Analogies are important tools in human reasoning and learning, for resolving problems and providing arguments, and are extensively used in medicine. Analogy and similarity involve a structural alignment or mapping between domains. This cognitive mechanism can be used to make inferences and learn new abstractions. Through analogies, we try to…

  16. Investigating and Theorizing Discourse during Analogy Writing in Chemistry

    ERIC Educational Resources Information Center

    Bellocchi, Alberto; Ritchie, Stephen M.

    2011-01-01

    Explanations of the role of analogies in learning science at a cognitive level are made in terms of creating bridges between new information and students' prior knowledge. In this empirical study of learning with analogies in an 11th grade chemistry class, we explore an alternative explanation at the "social" level where analogy shapes classroom…

  17. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    PubMed

    Talaat, Roba; El-Sayed, Waheba; Agwa, Hussein S; Gamal-Eldeen, Amira M; Moawia, Shaden; Zahran, Magdy A H

    2015-08-01

    Thalidomide has anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It has been used to treat a variety of cancers and autoimmune diseases. This study aimed to characterize anti-inflammatory activities of novel thalidomide analogs by exploring their effects on splenocytes proliferation and macrophage functions and their antioxidant activity. MTT assay was used to assess the cytotoxic effect of thalidomide analogs against splenocytes. Tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB-P65) were determined by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was estimated by colorimetric assay. Antioxidant activity was examined by ORAC assay. Our results demonstrated that thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 produced a slight increase in splenocyte proliferation compared with thalidomide. Thalidomide dithiocarbamate analog 1 is a potent inhibitor of TNF-α production, whereas thalidomide dithiocarbamate analog 5 is a potent inhibitor of both TNF-α and NO. Analog 2 has a pronounced inhibitory effect on NF-κB-P65 production level. All thalidomide analogs showed prooxidant activity against hydroxyl (OH) radical. Analog 1 and thalidomide dithioate analog 3 have prooxidant activity against peroxyl (ROO) radical in relation to thalidomide. On the other hand, analog 4 has a potent scavenging capacity against peroxyl (ROO) radical compared with thalidomide. Taken together, the results of this study suggest that thalidomide analogs might have valuable anti-inflammatory activities with more pronounced effect than thalidomide itself.

  18. Can Pupils Use Taught Analogies for Electric Current?

    ERIC Educational Resources Information Center

    Black, David; Solomon, Joan

    1987-01-01

    Discusses the use of analogies and models for teaching about electric current. Reports on a study in which one group of students used analogies to learn about electric current and one did not. Results indicate that, in this case, analogies did not play a significant role in student understanding. (TW)

  19. Functional DNA: Teaching Infinite Series through Genetic Analogy

    ERIC Educational Resources Information Center

    Kowalski, R. Travis

    2011-01-01

    This article presents an extended analogy that connects infinite sequences and series to the science of genetics, by identifying power series as "DNA for a function." This analogy allows standard topics such as convergence tests or Taylor approximations to be recast in a "forensic" light as mathematical analogs of genetic concepts such as DNA…

  20. Analogical Instruction in Statistics: Implications for Social Work Educators

    ERIC Educational Resources Information Center

    Thomas, Leela

    2008-01-01

    This paper examines the use of analogies in statistics instruction. Much has been written about the difficulty social work students have with statistics. To address this concern, Glisson and Fischer (1987) called for the use of analogies. Understanding of analogical problem solving has surged in the last few decades with the integration of…