WorldWideScience

Sample records for 6-deoxy analogs synthesis

  1. Synthesis of all eight stereoisomeric 6-deoxy-l-hexopyranosyl donors - trends in using stereoselective reductions or mitsunobu epimerizations

    DEFF Research Database (Denmark)

    Frihed, Tobias; Pedersen, Christian Marcus; Bols, Mikael

    2014-01-01

    The synthesis of all eight rare but biologically important 6deoxy-L-hexoses as their thioglycoside glycosyl donors starting from the commercially available L-rhamnose or L-fucose is reported. The synthesis of all eight 6-deoxy-L-hexoses was accomplished using a variety of epimerization methods...

  2. Regioselective synthesis of cationic 6-deoxy-6-(N,N,N-trialkylammonio)curdlan derivatives.

    Science.gov (United States)

    Zhang, Ruoran; Liu, Shu; Edgar, Kevin J

    2016-01-20

    Curdlan, a bioactive β-1,3-glucan, is of intense interest for pharmaceutical and biomedical applications. Cationic derivatives of curdlan and other polysaccharides are especially attractive for their potential to interact in controlled fashion with proteins, among many other possible applications, but relatively few methods exist for their synthesis. Herein we report a regioselective method for preparation of cationic, water-soluble 6-(N,N,N-trialkylammonio)-6-deoxycurdlan salts by reaction of 6-bromo-6-deoxycurdlan and its 2,4-O-diesters with trialkylamines. Dimethyl sulfoxide was identified as the optimal solvent for this nucleophilic displacement to produce cationic curdlan derivatives (80 °C, 24h), providing maximum degree of triethylammonium substitution (DS) of 0.89, exclusively at the C-6 position. 6-Bromo-6-deoxycurdlan was also reacted with heterocyclic amines such as pyridine and imidazole, providing ammonium-substituted curdlan derivatives with substantial DS (0.66 and 0.86, respectively). The new combination of regioselective Furuhata bromination and bromine displacement under optimized conditions with tertiary amines provides access to quaternized curdlan derivatives that possess high, permanent positive charge and are readily water-soluble, properties that indicate potential application promise including for mucoadhesion, permeation enhancement, and delivery of genes and anionic drugs. Regioselectivity and DS of those curdlan ammonium derivatives were quantified by means of (1)H NMR, (13)C NMR and FTIR spectroscopic methods and by elemental analysis. PMID:26572378

  3. Synthesis and Anti-Influenza A Virus Activity of 6'-amino-6'-deoxy-glucoglycerolipids Analogs.

    Science.gov (United States)

    Ren, Li; Zhang, Jun; Ma, Haizhen; Sun, Linlin; Zhang, Xiaoshuang; Yu, Guangli; Guan, Huashi; Wang, Wei; Li, Chunxia

    2016-01-01

    A series of aminoglucoglycerolipids derivatives had been synthesized, including 6'-acylamido-glucoglycerolipids 1a-1f and corresponding 2'-acylamido-glucoglycerolipids 2a-2c bearing different fatty acids, glucosyl diglycerides 3a-3e bearing different functional groups at C-6' and ether-linked glucoglycerolipids 4a-4c with double-tailed alkyl alcohol. The anti-influenza A virus (IAV) activity was evaluated by the cytopathic effects (CPE) inhibition assay. The results indicated that the integral structure of the aminoglycoglycerolipid was essential for the inhibition of IAV in MDCK cells. Furthermore, oral administration of compound 1d was able to significantly improve survival and decrease pulmonary viral titers in IAV-infected mice, which suggested that compound 1d merited further investigation as a novel anti-IAV candidate in the future. PMID:27322292

  4. A two-step strategy for the preparation of 6-deoxy-l-sorbose.

    Science.gov (United States)

    Wen, Liuqing; Huang, Kenneth; Zheng, Yuan; Liu, Yunpeng; Zhu, He; Wang, Peng George

    2016-09-01

    A two-step enzymatic strategy for the efficient and convenient synthesis of 6-deoxy-l-sorbose was reported herein. In the first reaction step, the isomerization of l-fucose (6-deoxy-l-galactose) to l-fuculose (6-deoxy-l-tagatose) catalyzed by l-fucose isomerase (FucI), and the epimerization of l-fuculose to 6-deoxy-l-sorbose catalyzed by d-tagatose 3-epimerase (DTE) were coupled with the targeted phosphorylation of 6-deoxy-l-sorbose by fructose kinase from human (HK) in a one-pot reaction. The resultant 6-deoxy-l-sorbose 1-phosphate was purified by silver nitrate precipitation method. In the second reaction step, the phosphate group of the 6-deoxy-l-sorbose 1-phosphate was hydrolyzed with acid phosphatase (AphA) to produce 6-deoxy-l-sorbose in 81% yield with regard to l-fucose. PMID:27485385

  5. A two-step strategy for the preparation of 6-deoxy-l-sorbose.

    Science.gov (United States)

    Wen, Liuqing; Huang, Kenneth; Zheng, Yuan; Liu, Yunpeng; Zhu, He; Wang, Peng George

    2016-09-01

    A two-step enzymatic strategy for the efficient and convenient synthesis of 6-deoxy-l-sorbose was reported herein. In the first reaction step, the isomerization of l-fucose (6-deoxy-l-galactose) to l-fuculose (6-deoxy-l-tagatose) catalyzed by l-fucose isomerase (FucI), and the epimerization of l-fuculose to 6-deoxy-l-sorbose catalyzed by d-tagatose 3-epimerase (DTE) were coupled with the targeted phosphorylation of 6-deoxy-l-sorbose by fructose kinase from human (HK) in a one-pot reaction. The resultant 6-deoxy-l-sorbose 1-phosphate was purified by silver nitrate precipitation method. In the second reaction step, the phosphate group of the 6-deoxy-l-sorbose 1-phosphate was hydrolyzed with acid phosphatase (AphA) to produce 6-deoxy-l-sorbose in 81% yield with regard to l-fucose.

  6. Synthesis of Paclitaxel Analogs

    OpenAIRE

    Xu, Zhibing

    2010-01-01

    Paclitaxel is one of the most successful anti-cancer drugs, particularly in the treatment of breast cancer and ovarian cancer. For the investigation of the interaction between paclitaxel and MD-2 protein, and development of new antagonists for lipopolysaccharide, several C10 A-nor-paclitaxel analogs have been synthesized and their biological activities have been evaluated. In order to reduce the myelosuppression effect of the paclitaxel, several C3â ² and C4 paclitaxel analogs have been synth...

  7. SYNTHESIS OF MONO 6-DEOXY-TOSYL-β-CYCLODEXTRIN IN ALKALI SOLUTION%碱液中单6-对甲苯磺酰酯-β-环糊精的制备

    Institute of Scientific and Technical Information of China (English)

    韩清华; 黄明贤; 张艳伟; 白银鸽; 蒋登高

    2012-01-01

    以β-环糊精(β-CD)与对甲苯磺酰氯(p-TsCl)为原料,在不加入有机溶剂的条件下,采用分批加料的方式,在氢氧化钠溶液中制备了单6-对甲苯磺酰酯-β-环糊精(6-OTs-β-CD).通过单因素法考察了反应条件对目标产物收率的影响,得到的较佳工艺条件为:反应温度为0℃,反应时间为5h,碱液浓度为0.45 mol/L,n(p-TsCl):n(β-CD)=4,碱液用量为240 mL(β-CD的加入量为8 g时).在较佳工艺条件下,6-OTs-β-CD的收率可达46.2%.%Adopting batch feeding, 6-deoxy-tosyl-β-Cyclodextrin(6-Ots-β-CD) was prepared by batch-wise feeding of β-cyclodextrin(β-CD) and p-toluene sulfonyl chloride (p-TsCl) in sodium hydroxide a-queous solution without the introduction of organic reagents. By examining effects of reaction conditions on the yield with single-factor method, the optimum technological conditions were found as follows: reaction temperature 0 ℃ , total reaction time 5 h, alkali solubility 0.45 mol/L, n(p-TsCl) :n (β-CD) = 4, the amount of alkali solution 240 mL(when the amount of β-CD is 8 g ). Under these conditions, the yield of 6-Ots-β-CD is up to 46. 2%.

  8. Synthesis and Biological Activity of Philanthotoxin Analogs

    Institute of Scientific and Technical Information of China (English)

    Yong An ZHANG; Ke Zhong LIU; Deng Yuan WANG; Yu Zhu WANG; Liang Jian QU; Chang Jin ZHU

    2006-01-01

    The synthesis of four analogs of philanthotoxin is described. The preliminary bioassay showed that these compounds all had good insecticidal activities, and the compound 6a had the best killing effect.

  9. Novel process for producing 6-deoxy monosaccharides from l-fucose by coupling and sequential enzymatic method.

    Science.gov (United States)

    Shompoosang, Sirinan; Yoshihara, Akihide; Uechi, Keiko; Asada, Yasuhiko; Morimoto, Kenji

    2016-01-01

    We biosynthesized 6-deoxy-L-talose, 6-deoxy-L-sorbose, 6-deoxy-L-gulose, and 6-deoxy-L-idose, which rarely exist in nature, from L-fucose by coupling and sequential enzymatic reactions. The first product, 6-deoxy-L-talose, was directly produced from L-fucose by the coupling reactions of immobilized D-arabinose isomerase and immobilized L-rhamnose isomerase. In one-pot reactions, the equilibrium ratio of L-fucose, L-fuculose, and 6-deoxy-L-talose was 80:9:11. In contrast, 6-deoxy-L-sorbose, 6-deoxy-L-gulose, and 6-deoxy-L-idose were produced from L-fucose by sequential enzymatic reactions. D-Arabinose isomerase converted L-fucose into L-fuculose with a ratio of 88:12. Purified L-fuculose was further epimerized into 6-deoxy-L-sorbose by D-allulose 3-epimerase with a ratio of 40:60. Finally, purified 6-deoxy-L-sorbose was isomerized into both 6-deoxy-L-gulose with an equilibrium ratio of 40:60 by L-ribose isomerase, and 6-deoxy-L-idose with an equilibrium ratio of 73:27 by D-glucose isomerase. Based on the amount of L-fucose used, the production yields of 6-deoxy-L-talose, 6-deoxy-L-sorbose, 6-deoxy-L-gulose, and 6-deoxy-L-idose were 7.1%, 14%, 2%, and 2.4%, respectively.

  10. Zinc-mediated fragmentation of methyl 6-deoxy-6-iodo-hexopyranosides

    DEFF Research Database (Denmark)

    Skaanderup, Philip Robert; Hyldtoft, Lene; Madsen, Robert

    2002-01-01

    An improved procedure was developed for the zinc-mediated fragmentation of protected and unprotected methyl 6-deoxy-6-iodo-hexopyranosides. The method employs sonication of the iodoglycoside with zinc dust in a THF/H2O mixture.......An improved procedure was developed for the zinc-mediated fragmentation of protected and unprotected methyl 6-deoxy-6-iodo-hexopyranosides. The method employs sonication of the iodoglycoside with zinc dust in a THF/H2O mixture....

  11. Analog Electronic Filters Theory, Design and Synthesis

    CERN Document Server

    Dimopoulos, Hercules G

    2012-01-01

    Filters are essential subsystems in a huge variety of electronic systems. Filter applications are innumerable; they are used for noise reduction, demodulation, signal detection, multiplexing, sampling, sound and speech processing, transmission line equalization and image processing, to name just a few. In practice, no electronic system can exist without filters. They can be found in everything from power supplies to mobile phones and hard disk drives and from loudspeakers and MP3 players to home cinema systems and broadband Internet connections. This textbook introduces basic concepts and methods and the associated mathematical and computational tools employed in electronic filter theory, synthesis and design.  This book can be used as an integral part of undergraduate courses on analog electronic filters. Includes numerous, solved examples, applied examples and exercises for each chapter. Includes detailed coverage of active and passive filters in an independent but correlated manner. Emphasizes real filter...

  12. Remarkably stable inclusion complexes with heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-beta-cyclodextrin.

    Science.gov (United States)

    Gómez-Biagi, Rodolfo F; Jagt, Richard B C; Nitz, Mark

    2008-12-21

    Complexes of heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-beta-cyclodextrin (1) and a series of common cyclodextrin guests were studied by NMR, fluorescence spectroscopy, and ITC experiments. NMR conformational analysis shows that the thioethers of 1 are positioned over the hydrophobic cavity of the cyclodextrin, increasing potential hydrophobic interactions with guest molecules. The combination of the increased hydrophobic character, the electrostatic complementarity and a hypothesized conformational change in 1 lead to a complex with the dye 2,6-ANS (5) that is over 2000 times more stable than with the native beta-cyclodextrin. One of the most stable host-guest complexes between a cyclodextrin and a small molecule measured to date was revealed between 1 and lithocholic acid (4) with an association constant of 5.5 x 10(7) M(-1).

  13. Synthesis and Antifeeding Activity of Acetylene-Containing Tonghaosu Analogs

    Institute of Scientific and Technical Information of China (English)

    CHEN,Li; HU,Tai-Shan; XU,Han-Hong; YIN,Biao-Lin; XIAO,Chun; WU,Yu-Lin

    2004-01-01

    @@ During our continuous efforts towards the search for environmental benign insect antifeedant, we established a concise method for the synthesis of Tonghaosu, a naturally occurring antifeedant.[1] Herein, we report the synthesis and antifeeding activity of 22 new tonghaosu analogs, which contain varied B ring as well as one or two acetylene functionalities. Preliminary bioassay indicates that two acetylene groups containing tonghaosu analogs have better antifeedant activity against large white butterfly (Pieris brassicae L.) than those with one acetylene group. More interestingly,Z-isomers are much more active than their corresponding E-isomers.

  14. Synthesis and Evaluation of Desmethyl Azumamide Analogs

    DEFF Research Database (Denmark)

    Maolanon, Alex

    the azumamide analogs; however, removal of the methyl group had a significant impact relative to the natural products. To understand this effect, the NMR structure was solved with the assistance from Casper Hoeck and Charlotte H. Gotfredsen and docked conformations were obtained from Niels J. Christensen...... and Peter Fristrup. Compared to the natural compounds, the 3Dstructure of the scaffold in the azumamide analogs were similar. Although a conclusion was not found, the preliminary docking results indicated favorable lipophilic interaction with the methyl group in the azumamides. Largazole is another...... macrocylic natural product with HDAC inhibitory activity. The compound has a thioester functionality in the side chain, which is hydrolyzed before interaction with the enzymes. In the attempt to mimic the prodrug nature of largazole, compounds containing a thiol group were designed, as it was hypothesized...

  15. Synthesis and Biological Evaluation of Paclitaxel Analogs

    OpenAIRE

    Baloglu, Erkan

    2001-01-01

    The complex natural product paclitaxel (Taxol®), first isolated from Taxus brevifolia, is a member of a large family of taxane diterpenoids. Paclitaxel is extensively used for the treatment of solid tumors, particularly those of the breasts and ovaries. In order to obtain additional information about the mechanism of action of paclitaxel and the environment of the paclitaxel-binding site, several fluorescent analogs of paclitaxel were synthesized, and thei...

  16. Expedient total synthesis of pyrrothine natural products and analogs

    DEFF Research Database (Denmark)

    Hjelmgaard, Thomas; Givskov, Michael Christian; Nielsen, John

    2007-01-01

    This paper describes an expedient and straightforward total synthesis of the two pyrrothine natural products holomycin (7 steps, 11% overall) and xenorhabdin I (7 steps, 11% overall) and analogs thereof via a common late-stage intermediate. The pathway proceeds via the pyrrothine hydrochloride...

  17. 40 CFR 721.2076 - D-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium...

    Science.gov (United States)

    2010-07-01

    ...-deoxy-L-mannose and D-glucose, acetate, calcium magnesium potassium sodium salt. 721.2076 Section 721...-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium potassium sodium... identified as D-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium...

  18. Synthesis and antimicrobial activity of 6-triazolo-6-deoxy eugenol glucosides.

    Science.gov (United States)

    de Souza, Thiago Belarmino; Raimundo, Paulo Otávio Botelho; Andrade, Saulo Fernandes; Hipólito, Taciane Maira Magalhães; Silva, Naiara Chaves; Dias, Amanda Latercia Tranches; Ikegaki, Masaharu; Rocha, Raissa Prado; Coelho, Luiz Felipe Leomil; Veloso, Marcia Paranho; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira

    2015-06-17

    A new series of 1,2,3-triazole eugenol glucosides were synthesized. The new compound structures were confirmed by MS, (1)H NMR and (13)C NMR. All of the synthesized compounds were screened for antimicrobial and cytotoxic activity. Five compounds exerted significant activity against the Gram-negative bacteria Salmonella typhimurium with low IC50 values (49.73-68.53 μΜ), and seven compounds were active against the Gram-positive bacteria Micrococcus luteus (42.89-210.94 μM). In vitro cytotoxicity on mouse spleen cells was also evaluated. One compound bearing a phenyl substituent at the triazole ring showed good activity against Salmonella typhimurium (49.73 μM) and low toxicity to normal cells (CC50=157.83 μM). Thus, the compounds herein can be considered for further modification for improving their antibacterial activity or obtaining novel antibacterial drug candidates.

  19. Synthesis and biological activity of Wuweizisu C and analogs.

    Science.gov (United States)

    Chang, J B; Wang, Q; Li, Y F

    2009-01-01

    Lignans are widely distributed in nature. The earliest recorded medicinal use of lignans dated back to over 1000 years ago. Lignan-rich plant products were also active ingredients in Chinese and Japanese folk medicines for the treatment of various diseases. The dried root and stem of this plant are listed in the Chinese pharmacopoeia for the treatment of rheumatoid arthritis, gastric, duodenal ulcers and many other diseases. This review highlights synthetic strategies for the Wuweizisu C analogs and the important pharmacological activities as well as therapeutic findings related to the treatment of HBV and other diseases. Notably a significant and ongoing project on Wuweizisu C and its analogs has led to the discovery and development of two potent derivatives alpha-DDB and BICYCLOL which are currently in clinical trials against HBV, especially in lowering elevated SGPT levels. Further design, synthesis, and evaluation of Wuweizisu C analogs are discussed.

  20. Synthesis and biological activity of Wuweizisu C and analogs.

    Science.gov (United States)

    Chang, J B; Wang, Q; Li, Y F

    2009-01-01

    Lignans are widely distributed in nature. The earliest recorded medicinal use of lignans dated back to over 1000 years ago. Lignan-rich plant products were also active ingredients in Chinese and Japanese folk medicines for the treatment of various diseases. The dried root and stem of this plant are listed in the Chinese pharmacopoeia for the treatment of rheumatoid arthritis, gastric, duodenal ulcers and many other diseases. This review highlights synthetic strategies for the Wuweizisu C analogs and the important pharmacological activities as well as therapeutic findings related to the treatment of HBV and other diseases. Notably a significant and ongoing project on Wuweizisu C and its analogs has led to the discovery and development of two potent derivatives alpha-DDB and BICYCLOL which are currently in clinical trials against HBV, especially in lowering elevated SGPT levels. Further design, synthesis, and evaluation of Wuweizisu C analogs are discussed. PMID:19903156

  1. Synthesis and biological evaluation of biaryl analogs of antitubulin compounds

    Energy Technology Data Exchange (ETDEWEB)

    Tozatti, Camila Santos Suniga; Khodyuk, Rejane Goncalves Diniz; Silva, Adriano Olimpio da; Santos, Edson dos Anjos dos; Amaral, Marcos Serrou do; Lima, Denis Pires de, E-mail: denis.lima@ufms.br [Centro de Ciencias Exatas e Tecnologia, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS (Brazil); Hamel, Ernest [Screening Technologies Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, MD (United States)

    2012-07-01

    This paper reports the synthesis of methanones and esters bearing different substitution patterns as spacer groups between aromatic rings. This series of compounds can be considered phenstatin analogs. Two of the newly synthesized compounds, 5a and 5c, strongly inhibited tubulin polymerization and the binding of [{sup 3}H] colchicine to tubulin, suggesting that, akin to phenstatin and combretastatin A-4, they can bind to tubulin at the colchicine site. (author)

  2. Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs

    OpenAIRE

    Adams, Drew J.; Dai, Mingji; Pellegrino, Giovanni; Wagner, Bridget K.; Stern, Andrew M.; Shamji, Alykhan F.; Schreiber, Stuart L.

    2012-01-01

    Piperlongumine is a naturally occurring small molecule recently identified to be toxic selectively to cancer cells in vitro and in vivo. This compound was found to elevate cellular levels of reactive oxygen species (ROS) selectively in cancer cell lines. The synthesis of 80 piperlongumine analogs has revealed structural modifications that retain, enhance, and ablate key piperlongumine-associated effects on cells, including elevation of ROS, cancer cell death, and selectivity for cancer cells ...

  3. Synthesis and biological evaluation of biaryl analogs of antitubulin compounds

    Directory of Open Access Journals (Sweden)

    Camila Santos Suniga Tozatti

    2012-01-01

    Full Text Available This paper reports the synthesis of methanones and esters bearing different substitution patterns as spacer groups between aromatic rings. This series of compounds can be considered phenstatin analogs. Two of the newly synthesized compounds, 5a and 5c, strongly inhibited tubulin polymerization and the binding of [³H] colchicine to tubulin, suggesting that, akin to phenstatin and combretastatin A-4, they can bind to tubulin at the colchicine site.

  4. SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF DICHOTOMIN A ANALOGS

    OpenAIRE

    Himaja Malipeddi; Malipeddi Venkataramana; Sahoo Atish Kumar; Anand Ranjitha; Karigar Asif

    2010-01-01

    A solution phase peptide synthesis was employed to synthesize Dichotomin A analogs. The N, O-dimethylation on Tyrosine and configurational change of L- to D- on Valine was made on Dichotomin A to derive the compounds 1) Cyclo-L-[Gly-Thr-Phe-Leu-(N-CH3, O-CH3) Tyr-Val] and 2) Cyclo-L-[Gly-Thr-Phe-Leu-(N-CH3,O-CH3)Tyr-D-Val]. The structure of these compounds was confirmed by IR, 1H NMR, and FABMASS. The synthesized compounds were tested for their biological activities against bacterial and fung...

  5. SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF DICHOTOMIN A ANALOGS

    Directory of Open Access Journals (Sweden)

    Himaja Malipeddi

    2010-09-01

    Full Text Available A solution phase peptide synthesis was employed to synthesize Dichotomin A analogs. The N, O-dimethylation on Tyrosine and configurational change of L- to D- on Valine was made on Dichotomin A to derive the compounds 1 Cyclo-L-[Gly-Thr-Phe-Leu-(N-CH3, O-CH3 Tyr-Val] and 2 Cyclo-L-[Gly-Thr-Phe-Leu-(N-CH3,O-CH3Tyr-D-Val]. The structure of these compounds was confirmed by IR, 1H NMR, and FABMASS. The synthesized compounds were tested for their biological activities against bacterial and fungal organisms and were found to be active. Compound (2 carrying D-valine unit have shown more antimicrobial activity than the compound carrying L-valine unit.

  6. A convenient synthesis of ezetimibe analogs as cholesterol ab sorption inhibitors

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A convenient method for the synthesis of ezetimibe analogs as cholesterol absorption inhibitors was described.The key step in the synthesis was the intramolecular ring formation through Mitsunobu reaction.Furthermore,a new series of analogs was designed and synthesized.

  7. Design, synthesis and antimicrobial evaluation of novel carbendazim dithioate analogs

    DEFF Research Database (Denmark)

    Zahran, Magdy A H; Osman, Amany M A; Wahed, Rania A.;

    2015-01-01

    A novel series of carbendazim dithioate analogs was synthesized by the reaction of 2-aminobenzimdazole with CS2 and different alkyl halide in one pot reaction. All the chemical structure of carbendazim analogs were elucidated with all the spectroscopical tools IR, 1H, 13C NMR and mass...... against soil dehydrogenase activity. Among the carbendazim dithioates, some analogs were the most effective analogs against all the Gram-negative and positive-bacteria. While the most of them showed slight activities against Fusarium solani and Fusarium oxysporum. One of these analogs seemed to be more...... suppressive for dehydrogenase activity of soil microorganisms compared to all carbendazim sulfur analogs....

  8. Studies on the Synthesis of a Natural Product-Piceatannol and its Analogs

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Piceatannol, (E)-3, 3(, 4, 5(-tetrahydroxy stilbene, a natural polyhydroxy stilbene, possesses many biological activities, its synthesis has been reported. We designed another route of its synthesis, which can be controlled more easily. The synthetic product was characterized by elemental analysis, IR, MS and 1H-NMR. Its analogs were synthesized by the similar method.

  9. Synthesis and biological activity of nifuroxazide and analogs. II.

    Science.gov (United States)

    Tavares, L C; Chisté, J J; Santos, M G; Penna, T C

    1999-09-01

    Nifuroxazyde and six analogs were synthesized by varying the substitute from the para-position of the benzenic ring and the heteroatom of the heterocyclic ring. The MIC of seven resultant compounds was determined by serial dilutions, testing the ATCC 25923 strain of Staphylococcus aureus. A significant increase in the anti-microbial activity of thyophenic analogs, as compared with furanic and pyrrholic analogs, was observed. In addition, unlike the cyano and hydroxyl groups, the acetyl group promoted anti-microbial activity. PMID:10622109

  10. Fluorinated Analogs of Malachite Green: Synthesis and Toxicity

    Directory of Open Access Journals (Sweden)

    Bahram Parvin

    2008-04-01

    Full Text Available A series of fluorinated analogs of malachite green (MG have been synthesizedand their toxicity to Saccharomyces cerevisiae and a human ovarian epithelial cell lineexamined. The toxicity profiles were found to be different for these two species. Twoanalogs, one with 2,4-difluoro substitution and the other with 2-fluoro substitution seem tobe the most promising analogs because they showed the lowest toxicity to the human cells.

  11. Synthesis and bioactivity of 2',3'-benzoabscisic acid analogs.

    Science.gov (United States)

    Han, Xiaoqiang; Wan, Chuan; Li, Xiuyun; Li, Hong; Yang, Dongyan; Du, Shijie; Xiao, Yumei; Qin, Zhaohai

    2015-06-01

    2',3'-Benzoabscisic acid 4a is significantly more active than (±)-ABA and can be potentially used as a plant growth regulator for agriculture. In this study, six 4a analogs were designed and synthesized. Bioassay showed that 4a displayed greater activity than (±)-ABA and the six analogs produced less inhibition than 4a itself. Specially, some analogs displayed markedly different activities to different physiological and biochemical process, which were largely different from ABA and 4a. Compared to (±)-ABA, 4b and 4c were more effective germination inhibitors for lettuce, but less effective inhibitors for rice elongation. Five-membered analog 5 was higher or slightly weaker in inhibiting Arabidopsis seed germination and rice elongation, respectively, but at least 10 times less effective than (±)-ABA in lettuce seed germination. Dual acid 6 and alkyne acid 20 nearly produced no inhibitory activity for Arabidopsis seed germination, but displayed excellent activity in inhibiting rice seedling growth. The preference of the analogs to different physiology process indicated that they might provide a strategy to develop novel ABA agonists or antagonist and be used as probe to investigate the function of different ABA receptors. PMID:25913114

  12. The synthesis of spermine analogs of the shark aminosterol squalamine.

    Science.gov (United States)

    Shu, Youheng; Jones, Stephen R; Kinney, William A; Selinsky, Barry S

    2002-03-01

    Aminosterols isolated from the dogfish shark Squalus acanthias are promising therapeutic agents in the treatment of infection and cancer. One of these, MSI-1436, has been shown to possess antimicrobial activity slightly better than squalamine. In this study, a series of analogs of MSI-1436 have been synthesized from stigmasterol. The 7 alpha-hydroxy substituent of MSI-1436 was either omitted or the stereochemistry modified to the 7 beta position. Also, analogs of MSI-1436 with 24-sulfate, 24-amino, and 24-hydroxy substituents were synthesized in order to assess the importance of the side chain functional group on antimicrobial activity. All of the analogs possess significant antimicrobial activity, suggesting that substitution at C7 and C24 of the aminosterols plays a minor role in their antimicrobial potency. PMID:11856553

  13. On automatic synthesis of analog/digital circuits

    Energy Technology Data Exchange (ETDEWEB)

    Beiu, V.

    1998-12-31

    The paper builds on a recent explicit numerical algorithm for Kolmogorov`s superpositions, and will show that in order to synthesize minimum size (i.e., size-optimal) circuits for implementing any Boolean function, the nonlinear activation function of the gates has to be the identity function. Because classical and--or implementations, as well as threshold gate implementations require exponential size, it follows that size-optimal solutions for implementing arbitrary Boolean functions can be obtained using analog (or mixed analog/digital) circuits. Conclusions and several comments are ending the paper.

  14. Synthesis of N-acetyl Glucosamine Analogs as Inhibitors for Hyaluronan Biosynthesis

    OpenAIRE

    Wasonga, Gilbert; Tatara, Yota; Kakizaki, Ikuko; Huang, Xuefei

    2013-01-01

    Elevated hyaluronan expression is a hallmark of many types of cancer. Therefore, inhibition of hyaluronan biosynthesis can potentially slow the growth of tumor cells. Herein, we explore a chain termination strategy to reduce hyaluronan synthesis by tumor cells. Several analogs of glucosamine were prepared, which contained modifications at the C-3 positions. These analogs can possibly cap the nonreducing end of a growing hyaluronan chain, thus lowering the amount of hyaluronan synthesized. Upo...

  15. Synthesis and biological activity of nifuroxazide and analogs.

    Science.gov (United States)

    Tavares, L C; Penna, T C; Amaral, A T

    1997-03-01

    Nifuroxazide and thirteen analogs were synthesized from substituted benzoic acids and minimal inhibitory concentrations were determined using the serial dilution tests, in three sequential steps. Nifuroxazide and chloramphenicol were used as reference standards. The tests were performed in TSB against the standard bacterial strain of Staphylococcus aureus ATCC 25923. PMID:9164164

  16. Synthesis of tetracycline analogs and their bone affinities

    Institute of Scientific and Technical Information of China (English)

    Wen Cai Huang; Hu Zheng; Ling Ling Weng

    2008-01-01

    Tetracycline analogs were designed and synthesized and their bone affinities were tested on hydroxyapatite. The results showedthat the carbonyl-amide-enol structure in A ring and phenol-ketone structure in BCD ring may be responsible for tetracycline's highbone affinity and either A ring or BCD ring has a planar conformation is essential.

  17. Design, synthesis and antibacterial activity of novel 1-oxacephem analogs

    Institute of Scientific and Technical Information of China (English)

    Yi He; Jian Bo Wu; Fan Lei; Pei Chen; Li Hai; Yong Wu

    2012-01-01

    A series of 1-oxacephem analogs were synthesized and their antibacterial properties against five strains of Gram-positive and Gram-negative bacteria were evaluated in vitro while ceftazidine was selected as control.Some of the tested compounds,compound 12c in particular,showed more active against three selected strains than the standard.

  18. Synthesis, bioanalysis and pharmacology of nucleoside and nucleotide analogs

    NARCIS (Netherlands)

    Jansen, R.S.

    2009-01-01

    Nucleoside analogs are an important class of drugs in anticancer and antiviral therapy. The compounds are, however, only active after intracellular conversion to their mono-, di- and triphosphate nucleotide form. In this thesis the development of sensitive liquid chromatography coupled to tandem mas

  19. Synthesis of New Anthihelmintic Analogs of Marine Natural Products

    OpenAIRE

    Gloria Serra; Graciela Mahler; Sandra Gordon; Marcelo Incerti; Eduardo Manta

    2000-01-01

    The synthesis of new anthelmintic compounds derived from 2-amine-4-hydroxy-δ-valerolactams and 2,4-dialkylthiazoles is described. The synthetic procedures and biological activity data for these compounds will be presented.

  20. Plumbagin analogs-synthesis, characterization, and antitubercular activity

    OpenAIRE

    Nishi Nayak; Meenakshi Bajpai; Balkishen Razdan

    2014-01-01

    Considering the emerging problem of drug resistance in tuberculosis, there is an urgent need of development of new analogs that are useful in curing drug resistant tuberculosis. In India, tuberculosis continues to remain one of the most pressing health problems. India is the highest tuberculosis burden country in the world, accounting one fifth of global incidence - estimated 2.0-2.5 million cases annually. In 2011, approximately 8.7 million new cases of tuberculosis and 1.4 million people di...

  1. Synthesis of computational structures for analog signal processing

    CERN Document Server

    Popa, Cosmin Radu

    2011-01-01

    Presents the most important classes of computational structures for analog signal processing, including differential or multiplier structures, squaring or square-rooting circuits, exponential or Euclidean distance structures and active resistor circuitsIntroduces the original concept of the multifunctional circuit, an active structure that is able to implement, starting from the same circuit core, a multitude of continuous mathematical functionsCovers mathematical analysis, design and implementation of a multitude of function generator structures

  2. Plumbagin analogs-synthesis, characterization, and antitubercular activity

    Directory of Open Access Journals (Sweden)

    Nishi Nayak

    2014-01-01

    Full Text Available Considering the emerging problem of drug resistance in tuberculosis, there is an urgent need of development of new analogs that are useful in curing drug resistant tuberculosis. In India, tuberculosis continues to remain one of the most pressing health problems. India is the highest tuberculosis burden country in the world, accounting one fifth of global incidence - estimated 2.0-2.5 million cases annually. In 2011, approximately 8.7 million new cases of tuberculosis and 1.4 million people die from tuberculosis each year worldwide. Current antitubercular therapies are successful against normal tuberculosis but it is not suitable for drug resistant tuberculosis. In this study Plumbagin analogs, obtained from Plumbago zeylanica (Family-Plumbaginaceae, have been synthesized. Out of the various synthesized analogs, the antitubercular activity of compound a and b was evaluated using standard H 37 Rv and S, H, R, and E sensitive M tuberculosis strains using LRF assay method. Compound a showed strong activity against both standard H 37 Rv and S, H, R and E sensitive M. tuberculosis strains as compared to standard Rifampicin. The other compounds are proved to be more active against standard H 37 Rv and S, H, R and E sensitive M. tuberculosis strain as compared to Rifampicin.

  3. Synthesis and radiolabeling of a somatostatin analog for multimodal imaging

    Science.gov (United States)

    Edwards, W. Barry; Liang, Kexian; Xu, Baogang; Anderson, Carolyn J.; Achilefu, Samuel

    2006-02-01

    A new multimodal imaging agent for imaging the somatostatin receptor has been synthesized and evaluated in vitro and in vivo. A somatostatin analog, conjugated to both 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid (DOTA) and cypate (BS-296), was synthesized entirely on the solid phase (Fmoc) and purified by RP-HPLC. DOTA was added as a ligand for radiometals such as 64Cu or 177Lu for either radio-imaging or radiotherapy respectively. Cytate, a cypatesomatostatin analog conjugate, has previously demonstrated the ability to visualize somatostatin receptor rich tumor xenografts and natural organs by optical imaging techniques. BS-296 exhibited low nanomolar inhibitory capacity toward the binding of radiolabeled somatostatin analogs in cell membranes enriched in the somatostatin receptor, demonstrating the high affinity of this multimodal imaging peptide and indicating its potential as a molecular imaging agent. 64Cu, an isotope for diagnostic imaging and radiotherapy, was selected as the isotope for radiolabeling BS-296. BS-296 was radiolabeled with 64Cu in high specific activity (200 μCi/μg) in 90% radiochemical yield. Addition of 2,5-dihydroxybenzoic acid (gentisic acid) prevented radiolysis of the sample, allowing for study of the 64Cu -BS-296 the day following radiolabeling. Furthermore, inclusion of DMSO at a level of 20% was found not to interfere with radiolabeling yields and prevented the adherence of 64Cu -BS-296 to the walls of the reaction vessel.

  4. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

    OpenAIRE

    Alessandra Mirtes Marques Neves Gonçalves; Aline Brito de Lima; Maria Cristina da Silva Barbosa; Luiz Fernando de Camargos; Júlia Teixeira Oliveira; Camila de Souza Barbosa; José Augusto Ferreira Perez Villar; André Carvalho Costa; Isabella Viana Gomes da Silva; Luciana Maria Silva; Fernando de Pilla Varotti; Fabio Vieira dos Santos; Gustavo Henrique Ribeiro Viana

    2014-01-01

    Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA) analogs in four steps and with good yields. The key step for the synthesis of these compounds is a ...

  5. A facile and efficient synthesis of (+)- and (-)-allo-muscarine and analogs

    DEFF Research Database (Denmark)

    Norrild, Jens Chr.; Pedersen, Christian

    1997-01-01

    Treatment of easily obtainable 1-alkylamino-1,3,6-trideoxyhexitols with hydrogen fluoride in the presence of formic acid gives the corresponding C-5 inverted 2,5-anhydrides in high yields. The synthesis of allo-muscarine and its N-benzyl analog from galactono-1,4-lactone is reported in 30 and 41%...

  6. A convenient synthesis of pseudoceratidine and three analogs for biological evaluation

    DEFF Research Database (Denmark)

    Behrens, C.; Christoffersen, M.W.; Gram, Lone;

    1997-01-01

    be adopted to the preparation of other derivatives. This was demonstrated by the synthesis of a 5,5'-didebromo derivative (2) and two analogs (3-4). The compounds 1-4 have been tested for antibacterial activity and the results compared to a previous study. Also activity against the marine brine...... shrimp Artemia salina is reported....

  7. Deoxyadenosine family: improved synthesis, DNA damage and repair, analogs as drugs.

    Science.gov (United States)

    Biswas, Himadri; Kar, Indrani; Chattopadhyaya, Rajagopal

    2013-08-01

    Improved synthesis of 2'-deoxyadenosine using Escherichia coli overexpressing some enzymes and gram-scale chemical synthesis of 2'-deoxynucleoside 5'-triphosphates reported recently are described in this review. Other topics include DNA damage induced by chromium(VI), Fenton chemistry, photoinduction with lumazine, or by ultrasound in neutral solution; 8,5'-cyclo-2'-deoxyadenosine isomers as potential biomarkers; and a recapitulation of purine 5',8-cyclonucleoside studies. The mutagenicities of some products generated by oxidizing 2'-deoxyadenosine 5'-triphosphate, nucleotide pool sanitization, and translesion synthesis are also reviewed. Characterizing cross-linking between nucleosides in opposite strands of DNA and endonuclease V-mediated deoxyinosine excision repair are discussed. The use of purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias is reviewed. Some analogs at the C8 position induced delayed polymerization arrest during HIV-1 reverse transcription. The susceptibility of clinically metronidazole-resistant Trichomonas vaginalis to two analogs, toyocamycin and 2-fluoro-2'-deoxyadenosine, were tested in vitro. GS-9148, a dAMP analog, was translocated to the priming site in a complex with reverse transcriptase and double-stranded DNA to gain insight into the mechanism of reverse transcriptase inhibition. PMID:25436589

  8. Synthesis and antimicrobial properties of 1,3,4-oxadiazole analogs containing dibenzosuberone moiety

    Energy Technology Data Exchange (ETDEWEB)

    Moger, Manjunath [Mangalore University, Karnataka (India). Department of Chemistry; Satam, Vijay; Paniraj, A.S.; Gopinath, Vadiraj S.; Hindupur, Rama Mohan; Pati, Hari N., E-mail: hari.pati@advinus.com [Advinus Therapeutics Ltd., 21 and 22, Phase II, Peenya Industrial Area, Karnataka (India); Govindaraju, Darshan Raj C. [Department of Bio-Medicinal Research, Vidya Herbs Pvt. Ltd., Karnataka (India)

    2014-01-15

    A series of ten novel 1,3,4-oxadiazole analogs containing dibenzosuberone moiety were synthesized using linear as well as convergent synthesis approach. All the compounds were characterized by mass spectrometry, infrared (IR), {sup 1}H and {sup 13}C nuclear magnetic resonance ({sup 1}H NMR and {sup 13}C NMR) spectroscopies and elemental analysis. These compounds were evaluated for antibacterial and antifungal activities. Among ten analogs, four compounds, namely, 8a, 8d, 8e and 8j were found to be highly active antibacterial and antifungal agents (author)

  9. Asymmetric synthesis of -aminophosphonates: The bio-isosteric analogs of -aminobutyric acid

    Indian Academy of Sciences (India)

    Kalisankar Bera; Dwayaja Nadkarni; Iirishi N N Namboothiri

    2013-05-01

    The properties of aminophosphonates as transition state analogs of amino acids, and as antibacterial, antifungal and antiHIV agents attracted considerable attention in recent years. Although many reviews appeared in the literature covering - and -aminophosphonates, -aminophosphonates did not receive sufficient attention despite the fact that parent -aminophosphonic acid and its derivatives are bio-isosteric analogs of GABA (-amino butyric acid). This review provides a critical summary of the significance of -aminophosphonates and various approaches to their synthesis, with particular emphasis to asymmetric versions.

  10. Carbon-11 labelled analogs of alanine by the Strecker synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Prenant, C.; Theobald, A.; Siegel, T.; Joachim, J.; Weber, K.; Haberkorn, U.; Oberdorfer, F. [Deutsches Krebsforschungszentrum, Heidelberg (Germany)

    1995-06-01

    Derivatives of alanine, {alpha}-[2-sup(11)C]aminoisobutyric acid 1a and {alpha}-(N-methyl)-[2-{sup 11} C]aminoisobutyric acid 1b were prepared for the in-vivo study of amino acid transport phenomena by positron-emission-tomography (PET). Compounds 1a and 1b were obtained by a Zelinski-Stadnikoff variant of the Strecker {alpha}-amino acid synthesis from in-situ formed [{sup 11} C]acetone in presence of sodium cyanide and either ammonium sulfate (for 1a) or methylamine hydrochloride (for 1b). The complete preparation required 50 min from the end of [{sup 11}C]CO{sub 2} production, and delivered 1.2 - 2 GBq of labelled product for application (2.4 -4%); not corrected for decay; related to trapped [{sup C}]CO{sub 2}. The specific activity of the labelled products was 16 to 20 GBq{center_dot}{mu}mol{sup -1}. The radiochemical and chemical purity of the preparations was greater than 98%. (Author).

  11. Total synthesis and biochemical evaluation of azumamides A–E and analogs

    DEFF Research Database (Denmark)

    Villadsen, Jesper

    structures. The key step in this route is a diastereoselective Mannich reaction, which enabled us to prepare two site-specifically edited epimeric azumamide analogs, where the stereochemistry in the unique -amino acid was inverted. The two epimeric homologs were screened together with azumamide A−E against...... the entire panel of recombinant HDAC isoforms. Thus, providing the first full profiling of the azumamides. The epimers were inactive against the full panel of HDAC enzymes and show that the -amino acid scaffold is highly sensitive to modifications in the stereochemistry. The profiling of the natural products...... analogs. Having observed the importance of the aromatic amino acid in the azumamides, a tryptophan-series was also prepared. The synthesis of these compounds underline the broad perspective and flexibility of the developed Mannich strategy. The dimethylated analogs were found to be poor HDAC inhibitors...

  12. A Proposed Model of Self-Generated Analogical Reasoning for the Concept of Translation in Protein Synthesis

    Science.gov (United States)

    Salih, Maria

    2008-01-01

    This paper explored and described the analogical reasoning occurring in the minds of different science achievement groups for the concept of translation in protein synthesis. "What is the process of self-generated analogical reasoning?", "What types of matching was involved?" and "What are the consequences of the matching processes?" were some of…

  13. Potent oxazoline analog of apratoxin C: Synthesis, biological evaluation, and conformational analysis.

    Science.gov (United States)

    Yoshida, Masahito; Onda, Yuichi; Masuda, Yuichi; Doi, Takayuki

    2016-11-01

    In this research, the synthesis, biological evaluation, and conformational analysis of an apratoxin C oxazoline analog (3) have been demonstrated. The preparation of synthetic key intermediate 9 was achieved using an improved strategy that involves commercially available 3-methylglutaric anhydride (12), an enzymatic enantioselective alcoholysis, and a diastereoselective reduction. The Pro-Dtrina (3,7-dihydroxy-2,5,8-trimethylnonanoic acid) moiety 8 was successfully synthesized in a similar manner as our previously reported synthesis of apratoxin C (1). The cyclization precursor 5 was formed after the coupling of Pro-Dtrina 8 with a known tetrapeptide 7 to afford a linear peptide 6, the formation of an oxazoline, and the removal of the protecting groups. Finally, the macrolactamization of 5 with O-(7-aza-1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)/N,N-diisopropylethylamine (DIEA) furnished an apratoxin C oxazoline analog (3), which exhibited a potent cytotoxicity against HeLa cells (IC50 value of 22 nM) that was comparable with the cytotoxicity of apratoxin C (1) (IC50 value of 4.2 nM). Conformational analyses of 1 and 3 through NMR experiments showed that oxazoline analog 3 formed a tertiary structure that was similar to the apratoxin C (1) structure in CD3 CN, which provided a probable explanation for their comparable cytotoxicities. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 404-414, 2016. PMID:26584466

  14. Total synthesis, structural, and biological evaluation of stylissatin A and related analogs.

    Science.gov (United States)

    Shaheen, Farzana; Jabeen, Almas; Ashraf, Samreen; Nadeem-Ul-Haque, Muhammad; Shah, Zafar Ali; Ziaee, Muhammad Asad; Dastagir, Nida; Ganesan, A

    2016-09-01

    The natural product cyclic peptide stylissatin A (1a) was reported to inhibit nitric oxide production in LPS-stimulated murine macrophage RAW 264.7 cells. In the current study, solid-phase total synthesis of stylissatin A was performed by using a safety-catch linker and yielded the peptide with a trans-Phe(7) -Pro(6) linkage, whereas the natural product is the cis rotamer at this position as evidenced by a marked difference in NMR chemical shifts. In order to preclude the possibility of 1b being an epimer of the natural product, we repeated the synthesis using d-allo-Ile in place of l-Ile and a different site for macrocyclization. The resulting product (d-allo-Ile(2) )-stylissatin A (1c) was also found to have the trans-Phe(7) -Pro(6) peptide conformations like rotamer 1b. Applying the second route to the synthesis of stylissatin A itself, we obtained stylissatin A natural rotamer 1a accompanied by rotamer 1b as the major product. Rotamers 1a, 1b, and the epimer 1c were separable by HPLC, and 1a was found to match the natural product in structure and biological activity. Six related analogs 2-7 of stylissatin A were synthesized on Wang resin and characterized by spectral analysis. The natural product (1a), the rotamer (1b), and (d-allo-Ile(2) )-stylissatin A (1c) exhibited significant inhibition of NO(.) . Further investigations were focused on 1b, which also inhibited proliferation of T-cells and inflammatory cytokine IL-2 production. The analogs 2-7 weakly inhibited NO(.) production, but strongly inhibited IL-2 cytokine production compared with synthetic peptide 1b. All analogs inhibited the proliferation of T-cells, with analog 7 having the strongest effect. In the analogs, the Pro(6) residue was replaced by Glu/Ala, and the SAR indicates that the nature of this residue plays a role in the biological function of these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27526945

  15. Synthesis of D-Desosamine and Analogs by Rapid Assembly of 3-Amino Sugars.

    Science.gov (United States)

    Zhang, Ziyang; Fukuzaki, Takehiro; Myers, Andrew G

    2016-01-11

    D-Desosamine is synthesized in 4 steps from methyl vinyl ketone and sodium nitrite. The key step in this chromatography-free synthesis is the coupling of (R)-4-nitro-2-butanol and glyoxal (trimeric form) mediated by cesium carbonate, which affords in crystalline form 3-nitro-3,4,6-trideoxy-α-D-glucose, a nitro sugar stereochemically homologous to D-desosamine. This strategy has enabled the syntheses of an array of analogous 3-nitro sugars. In each case the 3-nitro sugars are obtained in pure form by crystallization.

  16. Second generation benzofuranone ring substituted noscapine analogs: synthesis and biological evaluation.

    Science.gov (United States)

    Mishra, Ram Chandra; Karna, Prasanthi; Gundala, Sushma Reddy; Pannu, Vaishali; Stanton, Richard A; Gupta, Kamlesh Kumar; Robinson, M Hope; Lopus, Manu; Wilson, Leslie; Henary, Maged; Aneja, Ritu

    2011-07-15

    Microtubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems. Noscapinoids represent an emerging class of microtubule-modulating anticancer agents based upon the parent molecule noscapine, a naturally occurring non-toxic cough-suppressant opium alkaloid. Here we report in silico molecular modeling, chemical synthesis and biological evaluation of novel analogs derived by modification at position-7 of the benzofuranone ring system of noscapine. The synthesized analogs were evaluated for their tubulin polymerization activity and their biological activity was examined by their antiproliferative potential using representative cancer cell lines from varying tissue-origin [A549 (lung), CEM (lymphoma), MIA PaCa-2 (pancreatic), MCF-7 (breast) and PC-3 (prostate)]. Cell-cycle studies were performed to explore their ability to halt the cell-cycle and induce subsequent apoptosis. The varying biological activity of these analogs that differ in the nature and bulk of substituent at position-7 was rationalized utilizing predictive in silico molecular modeling. PMID:21501599

  17. A Better Understanding of Protein Structure and Function by the Synthesis and Incorporation of Selenium- and Tellurium Containing Tryptophan Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Helmey, Sherif Samir [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Rice, Ambrose Eugene [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Hatch, Duane Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Belmont Univ., Nashville, TN (United States). Dept. of Chemistry and Physics; Silks, Louis A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division; Marti-Arbona, Ricardo [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division

    2016-08-17

    Unnatural heavy metal-containing amino acid analogs have shown to be very important in the analysis of protein structure, using methods such as X-ray crystallography, mass spectroscopy, and NMR spectroscopy. Synthesis and incorporation of selenium-containing methionine analogs has already been shown in the literature however with some drawbacks due to toxicity to host organisms. Thus synthesis of heavy metal tryptophan analogs should prove to be more effective since the amino acid tryptophan is naturally less abundant in many proteins. For example, bioincorporation of β-seleno[3,2-b]pyrrolyl-L-alanine ([4,5]SeTrp) and β-selenolo[2,3-b]pyrrolyl-L-alanine ([6,7]SeTrp) has been shown in the following proteins without structural or catalytic perturbations: human annexin V, barstar, and dihydrofolate reductase. The reported synthesis of these Se-containing analogs is currently not efficient for commercial purposes. Thus a more efficient, concise, high-yield synthesis of selenotryptophan, as well as the corresponding, tellurotryptophan, will be necessary for wide spread use of these unnatural amino acid analogs. This research will highlight our progress towards a synthetic route of both [6,7]SeTrp and [6,7]TeTrp, which ultimately will be used to study the effect on the catalytic activity of Lignin Peroxidase (LiP).

  18. Chemistry of isoflavone heterocyclic analogs. 10. Synthesis of pyrimidines by recyclization of isoflavones and their heterocyclic analogs

    Energy Technology Data Exchange (ETDEWEB)

    Khilya, V.P.; Kornilov, M.Yu.; Gorbulenko, N.V.; Golubushina, G.M.; Kovtun, E.N.; Kolotusha, N.V.; Panasenko, G.V.

    1986-05-01

    Isoflavones and their thiazole and pyrazole analogs are recyclized into the corresponding 4-(2-hydroxyphenyl)-pyrimidine derivatives under the effect of amidines. Their PMR spectra were studied. The effects related to the formation and strength of the intramolecular hydrogen bond were examined.

  19. Synthesis and Biological Evaluation of Novel 3-Alkylpyridine Marine Alkaloid Analogs with Promising Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Alessandra Mirtes Marques Neves Gonçalves

    2014-07-01

    Full Text Available Cancer continues to be one of the most important health problems worldwide, and the identification of novel drugs and treatments to address this disease is urgent. During recent years, marine organisms have proven to be a promising source of new compounds with action against tumoral cell lines. Here, we describe the synthesis and anticancer activity of eight new 3-alkylpyridine alkaloid (3-APA analogs in four steps and with good yields. The key step for the synthesis of these compounds is a Williamson etherification under phase-transfer conditions. We investigated the influence of the length of the alkyl chain attached to position 3 of the pyridine ring on the cytotoxicity of these compounds. Biological assays demonstrated that compounds with an alkyl chain of ten carbon atoms (4c and 5c were the most active against two tumoral cell lines: RKO-AS-45-1 and HeLa. Micronucleus and TUNEL assays showed that both compounds are mutagenic and induce apoptosis. In addition, Compound 5c altered the cellular actin cytoskeleton in RKO-AS-45-1 cells. The results suggest that Compounds 4c and 5c may be novel prototype anticancer agents.

  20. Stereoselective synthesis of an iodinated resveratrol analog: Preliminary bioevaluation studies of the radioiodinated species

    Energy Technology Data Exchange (ETDEWEB)

    Dhyani, Manish V.; Kameswaran, Mythili; Korde, Aruna G.; Pandey, Usha [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Chattopadhyay, Subrata [Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Banerjee, Sharmila, E-mail: sharmila@barc.gov.i [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2011-07-15

    Stereoselective synthesis of an E-hydroxystilbene has been carried out using the McMurry reaction. Synthesis of a monoiodinated hydroxystilbene has been carried out by a McMurry cross-coupling reaction. For the purpose of biological evaluation, the facile electrophilic substitution route has been attempted to radioiodinate it with {sup 125}I. The HPLC pattern of the radioiodinated hydroxystilbene, which could be obtained in >90% radiochemical purity, was found to be identical to that of its non-radioactive analog that has been independently prepared using the McMurry cross-coupling route. In vitro cell uptake studies were carried out in breast cancer cells MCF7, overexpressing estrogen receptors. In vivo biodistribution studies in female Swiss mice show a uterine uptake of 0.85{+-}0.4% ID/g at 3 h.p.i. with a uterus to muscle ratio of 2.83. Uptake in the thyroid was insignificant indicating good in vivo stability of the radioiodinated hydroxystilbene.

  1. Chemoenzymatic synthesis of the bacterial polysaccharide repeating unit undecaprenyl pyrophosphate and its analogs.

    Science.gov (United States)

    Li, Lei; Woodward, Robert L; Han, Weiqing; Qu, Jingyao; Song, Jing; Ma, Cheng; Wang, Peng G

    2016-07-01

    Polysaccharides are essential and immunologically relevant components of bacterial cell walls. These biomolecules can be found covalently attached to lipids (e.g., O-polysaccharide (PS) contains undecaprenyl and lipopolysaccharide (LPS) contains lipid A) or noncovalently associated with cell wells (e.g., capsular PS (CPS)). Although extensive genetic studies have indicated that the Wzy-dependent biosynthetic pathway is primarily responsible for producing such polysaccharides, in vitro biochemical studies are needed to determine, for example, which gene product is responsible for catalyzing each step in the pathway, and to reveal molecular details about the Wzx translocase, Wzy polymerase and O-PS chain-length determinant. Many of these biochemical studies require access to a structurally well-defined PS repeating unit undecaprenyl pyrophosphate (RU-PP-Und), the key building block in this pathway. We describe herein the chemoenzymatic synthesis of Escherichia coli (serotype O157) RU-PP-Und. This involves (i) chemical synthesis of precursor N-acetyl-D-galactosamine (GalNAc)-PP-Und (2 weeks) and (ii) enzymatic extension of the precursor to produce RU-PP-Und (2 weeks). Undecaprenyl phosphate and peracetylated GalNAc-1-phosphate are prepared from commercially available undecaprenol and peracetylated GalNAc. The chemical coupling of these two products, followed by structural confirmation (mass spectrometry and NMR) and deprotection, generates GalNAc-PP-Und. This compound is then sequentially modified by enzymes in the E. coli serotype O157 (E. coli O157) O-PS biosynthetic pathway. Three glycosyltransferases (GTs) are involved (WbdN, WbdO and WbdP) and they transfer glucose (Glc), L-fucose (L-Fuc) and N-acetylperosamine (PerNAc) onto GalNAc-PP-Und to form the intact RU-PP-Und in a stepwise manner. Final compounds and intermediates are confirmed by mass spectrometry. The procedure can be adapted to the synthesis of analogs with different PS or lipid moieties. PMID:27336706

  2. Synthesis and evaluation of fluorine-18 labeled glyburide analogs as {beta}-cell imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, A.; Shiue, C.-Y. E-mail: Shiue@rad.upenn.edu; Feng, Q.; Shiue, G.G.; Deng, S.; Pourdehnad, M.T.; Schirrmacher, R.; Vatamaniuk, M.; Doliba, N.; Matschinsky, F.; Wolf, B.; Roesch, F.; Naji, A.; Alavi, A.A

    2004-05-01

    Glyburide is a prescribed hypoglycemic drug for the treatment of type 2 diabetic patients. We have synthesized two of its analogs, namely N-{l_brace}4-[{beta}-(2-(2'-fluoroethoxy)-5-chlorobenzenecarboxamido)ethyl] benzenesulfonyl{r_brace}-N'-cyclohexylurea (2-fluoroethoxyglyburide, 8b) and N-{l_brace}4-[{beta}-(2-(2'-fluoroethoxy)-5-iodobenzenecarboxamido)ethyl]benzenesulfonyl {r_brace}-N'-cyclohexylurea (2-fluoroethoxy-5-deschloro-5-iodoglyburide, 8a), and their fluorine-18 labeled analogs as {beta}-cell imaging agents. Both F-18 labeled compound 8a and compound 8b were synthesized by alkylation of the corresponding multistep synthesized hydroxy precursor 4a and 4b with 2-[{sup 18}F]fluoroethyl tosylate in DMSO at 120 degree sign C for 20 minutes followed by HPLC purification in an overall radiochemical yield of 5-10% with a synthesis time of 100 minutes from EOB. The octanol/water partition coefficients of compounds 8a and 8b were 141.21 {+-} 27.77 (n = 8) and 124.33 {+-} 21.61 (n = 8), respectively. Insulin secretion experiments of compounds 8a and 8b on rat islets showed that both compounds have a similar stimulating effect on insulin secretion as that of glyburide. In vitro binding studies showed that {approx}2% of compounds 8a and 8b bound to {beta}TC3 and Min6 cells and that the binding was saturable. Preliminary biodistribution studies in mice showed that the uptake of both compounds 8a and 8b in liver and small intestine were high, whereas the uptake in other organs studied including pancreas were low. Additionally, the uptake of compound 8b in vivo was nonsaturable. These results tend to suggest that compounds 8a and 8b may not be the ideal {beta}-cell imaging agents.

  3. [Interpretative method as a synthesis of explicative, teleologic and analogic models].

    Science.gov (United States)

    Yáñez Cortés, R

    1980-06-01

    To establish the basis of the interpretative method is congruous with finding a solid basis--epistemologically speaking--to the analytic theory. This basis would be the means to transform this theory into a real science with its necessary adecuation among method, act and object of knowledge. It is only from a scientific stand that the psychoanalytic theory will be able to face successfully the reductionisms that menace it, be it the biologist-naturalism with its explanations of the psychic phenomena by means of mechanisms and biologic models or be it the speculative ideologies with their nucleus of technical praxis which make it impossible for the social-factic sciences to become real sciences. We propose as interpretative method the union of two models: the teleologic one which makes possible the appearance of intelligible, contingent and variable explanations between an antecedent and a consequent on one side, and on the other, the analogic model with its two moments: the comparative and the symbolic one. These moments makes possible the comparison and the union between antecedent and consequent baring in mind the "natural" ambiguity of the subject-object in question. The principal objective of the method--as a regulative idea in the Kantian sense--would be the search of univocity as regards the choice of one and only one sense from all the possible senses that "explain" the motive relationship or motive-end relationship in order to make the interpretation scientific. This status of scientificity should obey the rules of explanation: that the interpretations be derived effectively from the presupposed theory, that they really explain what they claim to explain, that they are not contradictory or contrary in the same ontologic level. We postulate that the synthesis of the two mentioned models, the teleologic-explanative and the analogic one allows us to find a possibility to make clear the "dark" sense of the noun interpretation and in this way the factibility of

  4. The chemical synthesis of α-conotoxins and structurally modified analogs with enhanced biological stability.

    Science.gov (United States)

    Banerjee, Jayati; Gyanda, Reena; Chang, Yi-Pin; Armishaw, Christopher J

    2013-01-01

    α-Conotoxins are peptide neurotoxins isolated from the venom ducts of carnivorous marine cone snails that exhibit exquisite pharmacological potency and selectivity for various nicotinic acetylcholine receptor subtypes. As such, they are important research tools and drug leads for treating various diseases of the central nervous system, including pain and tobacco addiction. Despite their therapeutic potential, the chemical synthesis of α-conotoxins for use in structure-activity relationship studies is complicated by the possibility of three disulfide bond isomers, where inefficient folding methods can lead to a poor recovery of the pharmacologically active isomer. In order to achieve higher yields of the native isomer, especially in high-throughput syntheses it is necessary to select appropriate oxidative folding conditions. Moreover, the poor biochemical stability exhibited by α-conotoxins limits their general therapeutic applicability in vivo. Numerous strategies to enhance their stability including the substitution of disulfide bond with diselenide bond and N-to-C cyclization via an oligopeptide spacer have successfully overcome these limitations. This chapter describes methods for performing both selective and nonselective disulfide bond oxidation strategies for controlling the yields and formation of α-conotoxin disulfide bond isomers, as well as methods for the production of highly stable diselenide-containing and N-to-C cyclized conotoxin analogs. PMID:24014431

  5. Analogies in the Teaching of Chemical Equilibrium: A Synthesis/Analysis of the Literature

    Science.gov (United States)

    Raviolo, Andres; Garritz, Andoni

    2009-01-01

    This paper presents a thorough literature review of the analogies used to teach chemical equilibrium. The main objective is to compile all the analogies that have been found to be of service to the teacher and the student. Additionally, we categorize and analyze analogies in relation to the following aspects: representation of the dynamic nature…

  6. Synthesis and biological evaluation of branched and conformationally restricted analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd)

    DEFF Research Database (Denmark)

    Hrdlicka, Patrick J; Andersen, Nicolai K; Jepsen, Jan S;

    2005-01-01

    The synthesis of branched and conformationally restricted analogs of the anticancer nucleosides 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd) is presented. Molecular modeling and (1)H NMR coupling constant analysis revealed that the furanose rings of all analogs except the LNA analog...... are conformationally biased towards South conformation, and are thus mimicking the structure of ECyd. All target nucleosides were devoid of anti-HIV or anticancer activity....

  7. Synthesis and Antiproliferative Activity of C3' and B-ring Modified Paclitaxel Analogs

    OpenAIRE

    Hodge, Mathis

    2007-01-01

    The natural product, paclitaxel, has made tremendous contributions in supplying the arsenal of anticancer therapeutics, and was FDA approved for clinical use in 1992. In order to design simplified analogs, the conformation that paclitaxel adopts when binding to tubulin has been the subject of ongoing studies. Much evidence has led to a T-taxol proposal and a C3' constrained analog has been designed and synthesized as a test of this conformation. In the search for more active analogs, a number...

  8. Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation

    OpenAIRE

    Zhao, Jielu; Bane, Susan; Snyder, James P.; Hu, Haipeng; Mukherjee, Kamalika; Slebodnick, Carla; Kingston, David G I

    2011-01-01

    A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed ...

  9. Synthesis of Distamycin Analogs and Their Interactions withCalf Thymus DNA

    Institute of Scientific and Technical Information of China (English)

    肖军华; 袁谷; 黄伟强; 杜卫红; 王保怀; 李芝芬

    2001-01-01

    Two distamycin analogs (PyPyPy-γ-Dp and PyPyPyPy-γ- Dp)were synthesized by a halform reaction and the DCC/HOBT coupling reaction in a simple and fast way without amino protection.By using calf thymus DNA,the interaction between the analogs and DNA duplex was studied by CD, and ITC.

  10. Synthesis of carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases

    Science.gov (United States)

    Cho, Jong hyun; Coats, Steven J.; Schinazi, Raymond F.

    2015-01-01

    New carbocyclic nucleoside analogs with five-membered heterocyclic nucleobases were synthesized and evaluated as potential anti-HIV and anti-HCV agents. Among the synthesized carbocyclic nucleoside analogs, the pyrazole amide 15f exhibited modest selective anti-HIV-1 activity (EC50 = 24 µM). PMID:26028788

  11. Design, synthesis and aphicidal activity of N-terminal modified insect kinin analogs.

    Science.gov (United States)

    Zhang, Chuanliang; Qu, Yanyan; Wu, Xiaoqing; Song, Dunlun; Ling, Yun; Yang, Xinling

    2015-06-01

    The insect kinins are a class of multifunctional insect neuropeptides present in a diverse variety of insects. Insect kinin analogs showed multiple bioactivities, especially, the aphicidal activity. To find a biostable and bioactive insecticide candidate with simplified structure, a series of N-terminal modified insect kinin analogs was designed and synthesized based on the lead compound [Aib]-Phe-Phe-[Aib]-Trp-Gly-NH2. Their aphicidal activity against the soybean aphid Aphis glycines was evaluated. The results showed that all the analogs maintained the aphicidal activity. In particular, the aphicidal activity of the pentapeptide analog X Phe-Phe-[Aib]-Trp-Gly-NH2 (LC50=0.045mmol/L) was similar to the lead compound (LC50=0.048mmol/L). This indicated that the N-terminal protective group may not play an important role in the activity and the analogs structure could be simplified to pentapeptide analogs while retaining good aphicidal activity. The core pentapeptide analog X can be used as the lead compound for further chemical modifications to discover potential insecticides. PMID:25116632

  12. Synthesis and Biological Evaluation of a Valinomycin Analog Bearing a Pentafluorophenyl Active Ester Moiety.

    Science.gov (United States)

    D'Accolti, Lucia; Denora, Nunzio; La Piana, Gianluigi; Marzulli, Domenico; Siwy, Zuzanna S; Fusco, Caterina; Annese, Cosimo

    2015-12-18

    A valuable analog of the K(+)-ionophore valinomycin (1), bearing a pentafluorophenyl ester moiety, has been obtained by selective reaction between the tertiary hydroxyl moiety of analog 2 (available from valinomycin hydroxylation) and the isocyanate group of pentafluorophenyl N-carbonyl glycinate (3) catalyzed by bis(N,N-dimethylformamide)dichlorodioxomolybdenum(VI). LC-HRMS studies show that analog 4 undergoes easy derivatization under mild conditions by reaction with OH- and NH2-containing compounds. Mitochondrial depolarization assays suggest that 4 acts as a K(+)-ionophore, provided that the glycine carboxyl group is appropriately masked. PMID:26566090

  13. Total Synthesis of the Natural Product-Pinosylvin and its Analog

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    We synthesised a natural product (10) , isolated from G.parvifolium , and its analog. The synthetic product was characterized by elemental analysis and 1H-NMR in comparision with the corresponding natural product.

  14. First Synthesis of 2α-Thiol Ether Analog of Docetaxel

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A 2α-phenylthio ether analog 1c of docetaxel was synthesized for the first time from 10-deacetylbaccatin Ⅲ 3 via double inversion of C-2 configuration. This compound showed very weak cytotoxicity toward several tumor cell lines.

  15. Synthesis of Analogs of Amathamide A and Their Preliminary Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    G. Aguirre

    2005-01-01

    Full Text Available Syntheses of three non-brominated analogs of amathamide A (1, a natural alkaloid isolated from the Tasmanian marine bryozoan Amathia wilsoni, are described. Antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, and Candida albicans was tested. Test results for amathamide A (1 showed a weak activity against C. albicans and E. coli. The three non-natural analogs 2-4 proved to be inactive compounds.

  16. Synthesis of Analogs of Amathamide A and Their Preliminary Antimicrobial Activity

    OpenAIRE

    Aguirre, G.; R. Somanathan; Molins, E.; L. Hernández; D. Chávez; M. Ramírez-Osuna

    2005-01-01

    Syntheses of three non-brominated analogs of amathamide A (1), a natural alkaloid isolated from the Tasmanian marine bryozoan Amathia wilsoni, are described. Antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, and Candida albicans was tested. Test results for amathamide A (1) showed a weak activity against C. albicans and E. coli. The three non-natural analogs 2-4 proved to be inactive compounds.

  17. Synthesis and evaluation of novel lipidated neuromedin U analogs with increased stability and effects on food intake.

    Science.gov (United States)

    Dalbøge, Louise S; Pedersen, Søren L; van Witteloostuijn, Søren B; Rasmussen, Jakob E; Rigbolt, Kristoffer T G; Jensen, Knud J; Holst, Birgitte; Vrang, Niels; Jelsing, Jacob

    2015-02-01

    Neuromedin U (NMU) is a 25 amino acid peptide expressed and secreted in the brain and gastrointestinal tract. Data have shown that peripheral administration of human NMU decreases food intake and body weight and improves glucose tolerance in mice, suggesting that NMU receptors constitute a possible anti-diabetic and anti-obesity drug target. However, the clinical use of native NMU is hampered by a poor pharmacokinetic profile. In the current study, we report in vitro and in vivo data from a series of novel lipidated NMU analogs. In vitro plasma stability studies of native NMU were performed to investigate the proteolytic stability and cleavage sites using LC-MS. Native NMU was found to be rapidly cleaved at the C-terminus between Arg(24) and Asn(25) , followed by cleavage between Arg(16) and Gly(17) . Lipidated NMU analogs were generated using solid-phase peptide synthesis, and in vitro potency was investigated using a human embryonic kidney 293-based inositol phosphate accumulation assay. All lipidated analogs had preserved in vitro activity on both NMU receptors with potency improving as the lipidation site was moved away from the receptor-interacting C-terminal octapeptide segment. In vivo efficacy was assessed in lean mice as reduction in food intake after acute subcutaneous administration of 1, 0.3, 0.1, and 0.03 µmol/kg. These lipidated NMU analogs prolonged the anorectic effect of NMU in a dose-dependent manner. This was likely an effect of improved pharmacokinetic properties because of improved vitro plasma stability. Accordingly, the data demonstrate that lipidated NMU analogs may represent drug candidates for the treatment of obesity. PMID:25521062

  18. A Laboratory Preparation of Aspartame Analogs Using Simultaneous Multiple Parallel Synthesis Methodology

    Science.gov (United States)

    Qvit, Nir; Barda, Yaniv; Gilon, Chaim; Shalev, Deborah E.

    2007-01-01

    This laboratory experiment provides a unique opportunity for students to synthesize three analogues of aspartame, a commonly used artificial sweetener. The students are introduced to the powerful and useful method of parallel synthesis while synthesizing three dipeptides in parallel using solid-phase peptide synthesis (SPPS) and simultaneous…

  19. Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs.

    Science.gov (United States)

    Carocci, Alessia; Catalano, Alessia; Bruno, Claudio; Lentini, Giovanni; Franchini, Carlo; De Bellis, Michela; De Luca, Annamaria; Conte Camerino, Diana

    2010-03-01

    New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use-dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use-dependent block than mexiletine. The most potent analog, (S)-3-(2,6-dimethylphenoxy)-1-phenylpropan-1-amine (S)-(5), was six-fold more potent than (R)-Mex in producing a tonic block. As observed with mexiletine, the newly synthesized compounds exhibit modest enantioselective behavior, that is more evident in 3-(2,6-dimethylphenoxy)butan-1-amine (3). PMID:19544349

  20. Synthesis and antifungal activity of halogenated aromatic bis-γ-lactones analogous to avenaciolide

    International Nuclear Information System (INIS)

    Here we describe the total syntheses and characterization by elemental analyses, infrared and NMR spectroscopy of three new compounds analogous to avenaciolide, a bis-g-lactone isolated from Aspergillus avenaceus that possesses antifungal activity, where the octyl group of the natural product was replaced by aromatic groups containing chlorine and fluorine atoms. The effects of the avenaciolide, the novel compounds and their synthetic precursors on mycelia development and conidia germination of Colletotrichum gloeosporioides and Fusarium solani were evaluated in vitro. The title compounds were almost as active as avenaciolide. The absolute structures of the chlorinated analogs were determined by X-ray diffraction analysis. (author)

  1. Synthesis and Biological Activity of Tonghaosu Analogs Containing Phenoxy-phenyl Moiety

    Institute of Scientific and Technical Information of China (English)

    CHEN Li陈立; XU Han-Hong徐汉虹; YIN Biao-Lin尹标林; XIAO Chun肖春; HU Tai-Shan胡泰山; WU Yu-Lin吴毓林

    2004-01-01

    A new series of phenoxy-phenyl moieties containing tonghaosu analogs with varied B-ring 9 were synthesized and characterized by spectral studies. Their insect antifeedant activity against Pieris brassicae and insecticidal activity against Culex quinquefasciatus were investigated. Compound 9e exhibited excellent antifeeding activity.

  2. Optimization of cocoa butter analog synthesis variables using neural networks and genetic algorithm.

    Science.gov (United States)

    Shekarchizadeh, Hajar; Tikani, Reza; Kadivar, Mahdi

    2014-09-01

    Cocoa butter analog was prepared from camel hump fat and tristearin by enzymatic interesterification in supercritical carbon dioxide (SC-CO2) using immobilized Thermomyces lanuginosus lipase (Lipozyme TL IM) as a biocatalyst. Optimal process conditions were determined using neural networks and genetic algorithm optimization. Response surfaces methodology was used to design the experiments to collect data for the neural network modelling. A general regression neural network model was developed to predict the response of triacylglycerol (TAG) distribution of cocoa butter analog from the process pressure, temperature, tristearin/camel hump fat ratio, water content, and incubation time. A genetic algorithm was used to search for a combination of the process variables for production of most similar cocoa butter analog to the corresponding cocoa butter. The combinations of the process variables during genetic algorithm optimization were evaluated using the neural network model. The pressure of 10 MPa; temperature of 40 °C; SSS/CHF ratio of 0.6:1; water content of 13 % (w/w); and incubation time of 4.5 h were found to be the optimum conditions to achieve the most similar cocoa butter analog to the corresponding cocoa butter.

  3. The Petasis Reaction: Microscale Synthesis of a Tertiary Amine Antifungal Analog

    Science.gov (United States)

    Koroluk, Katherine J.; Jackson, Derek A.; Dicks, Andrew P.

    2012-01-01

    Students prepare a tertiary amine antifungal analog in an upper-level undergraduate organic laboratory. A microscale Petasis reaction is performed to generate a liquid compound readily characterized via IR and proton NMR spectroscopy. The biological relevance of the product is highlighted, with the tertiary amine scaffold being an important…

  4. Synthesis and Evaluation of Macrocyclic Diarylether Heptanoid Natural Products and their Analogs

    OpenAIRE

    Bryant, Vashti C.; Kishore Kumar, G. D.; Nyong, Abijah M; Natarajan, Amarnath

    2011-01-01

    The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-κB. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growt...

  5. Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.

    Science.gov (United States)

    Steele, Andrew D; Keohane, Colleen E; Knouse, Kyle W; Rossiter, Sean E; Williams, Sierra J; Wuest, William M

    2016-05-11

    Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere.

  6. Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

    Science.gov (United States)

    Sun, Man; Yang, Hui-Hui; Tian, Lei; Li, Jian-Qiang; Zhao, Wei-Guang

    2015-12-15

    The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9μM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew.

  7. Utilizing Symbolic Programming in Analog Circuit Synthesis of Arbitrary Rational Transfer Functions

    Directory of Open Access Journals (Sweden)

    Amjad Fuad Hajjar

    2014-11-01

    Full Text Available The employment of symbolic programming in analog circuit design for system interfaces is proposed. Given a rational transfer function with a set of specifications and constraints, one may autonomously synthesize it into an analog circuit. First, a classification of the target transfer function polynomials into 14 classes is performed. The classes include both stable and unstable functions as required. A symbolic exhaustive search algorithm based on a circuit configuration under investigation is then conducted where a polynomial in hand is to be identified. For illustration purposes, a set of complete design equations for the primary rational transfer functions is obtained targeting all classes of second order polynomials based on a proposed general circuit configuration. The design consists of a single active element and four different circuit structures. Finally, an illustrative example with full analysis and simulation is presented.

  8. Synthesis and anthelmintic activity of osthol analogs against Dactylogyrus intermedius in goldfish.

    Science.gov (United States)

    Liu, Guang-Lu; Hao, Bing; Liu, Shao-Peng; Wang, Gao-Xue

    2012-08-01

    In an attempt to develop novel anthelmintic agents, our previously isolated osthol was used as lead structures for further optimization. In our research, a series of coumarin analogs, prepared from 7-hydroxy coumarin or 7-hydroxy-4-methyl coumarin, have been evaluated for their anthelmintic activities. In all of the compounds, 6 and 7 were first synthesized, and their structures were identified based on NMR and MS values. Among the candidates, 8-allyl-7-allyloxycoumarin showed better anthelmintic activity than other compounds against Dactylogyrus infestation with EC(50) value of 1.81 mg/L. The quantitative structure-activity relationship (QSAR) of 16 osthol analogs with anthelmintic activity expressed as pEC(50) and toxicity to goldfish expressed pLC(50), such results can offer useful theoretical references for future experimental works. PMID:22749191

  9. Efficient microwave irradiation enhanced stereoselective synthesis and antitumor activity of indolylchalcones and their pyrazoline analogs

    Indian Academy of Sciences (India)

    Magdy A H Zahran; Hanan F Salama; Yasmin G Abdin; Amira M Gamal-Eldeen

    2010-07-01

    2-Aryl-1-indole-3-carbaldehyde derivatives underwent Claisen-Schmidt condensation with acetophenone derivatives under microwave irradiation condition compared with the conventional heating to afford excellent yields of trans substituted indolylchalcones which subjected to condensation reaction with phenylhydrazine to afford their indolylpyrazoline analogs. The antitumor activity of the synthesized compounds was examined and evaluated against human hepatocellular carcinoma cell line (Hep-G2) as well as the half maximal inhibitory concentration (IC50). Most of them showed high potent antitumor activity.

  10. Synthesis and antibacterial activity of 4“-O-carbamoyl analogs of clarithromycin

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of novel 4"-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.

  11. Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents

    Directory of Open Access Journals (Sweden)

    Qiang Yu

    2008-12-01

    Full Text Available Enantioselective syntheses from dimethyl tartrate of 1,3,5-triazine homo-N-nucleoside analogs, containing a 1,4-dioxane moiety replacing the sugar unit in natural nucleosides, were accomplished. The triazine heterocycle in the nucleoside analogs was further substituted with combinations of NH2, OH and Cl in the 2,4-triazine positions.

  12. Algicidal and antifungal compounds from the roots of Ruta graveolens and synthesis of their analogs.

    Science.gov (United States)

    Meepagala, Kumudini M; Schrader, Kevin K; Wedge, David E; Duke, Stephen O

    2005-11-01

    Bioassay-guided fractionation of the ethyl acetate extract of Ruta graveolens roots yielded rutacridone epoxide with potent selective algicidal activity towards the 2-methyl-isoborneol (MIB)-producing blue-green alga Oscillatoria perornata, with relatively little effect on the green alga Selenastrum capricornutum. The diol-analog of rutacridone epoxide, gravacridondiol, which was also present in the same extract, had significantly less activity towards O. perornata. Rutacridone epoxide also showed significantly higher activity than commercial fungicides captan and benomyl in our micro-bioassay against the agriculturally important pathogenic fungi Colletotrichum fragariae, C. gloeosporioides, C. acutatum, and Botrytis cineara and Fusarium oxysporium. Rutacridone epoxide is reported as a direct-acting mutagen, precluding its use as an agrochemical. In order to understand the structure-activity relationships and to develop new potential biocides without toxicity and mutagenicity, some analogs containing the (2-methyloxiranyl)-dihydrobenzofuran moiety with an epoxide were synthesized and tested. None of the synthetic analogs showed comparable activities to rutacridone epoxide. The absolute stereochemistry of rutacridone was determined to be 2'(R) and that of rutacridone epoxide to be 2'(R), 3'(R) by CD and NMR analysis.

  13. Chemical synthesis of echistatin, a potent inhibitor of platelet aggregation from Echis carinatus: synthesis and biological activity of selected analogs.

    Science.gov (United States)

    Garsky, V M; Lumma, P K; Freidinger, R M; Pitzenberger, S M; Randall, W C; Veber, D F; Gould, R J; Friedman, P A

    1989-06-01

    Echistatin, a polypeptide from the venom of the saw-scaled viper, Echis carinatus, containing 49 amino acids and 4 cystine bridges was synthesized by solid-phase methodology in 4% yield. In the final step, air oxidation of the octahydroderivative was found to be optimal at pH 8. The synthetic product was shown to be physically and biologically indistinguishable from native material. It inhibits fibrinogen-dependent platelet aggregation stimulated by ADP with IC50 = 3.3 x 10(-8) M and also prevents aggregation initiated by thrombin, epinephrine, collagen, or platelet-activating factor. Reduction of purified synthetic echistatin to octahydroechistatin with dithiothreitol followed by air oxidation regenerated homogeneous echistatin in quantitative yield. This highly specific refolding strongly suggests that the linear sequence of octahydroechistatin contains all of the information that is required for the proper folding of the peptide. The sequence Arg24-Gly-Asp of echistatin occurs also in adhesive glycoproteins that bind to the platelet fibrinogen receptor--a heterodimeric complex composed of glycoproteins IIb and IIIa. In an effort to evaluate the role of this putative binding site we have synthesized analogs of echistatin with substitution of Arg-24. Replacement with ornithine-24 (Orn-24) resulted in an analog having a platelet aggregation inhibitory activity with IC50 = 1.05 x 10(-7) M. Substitution with Ala-24 gave IC50 = 6.1 x 10(-7) M. The inhibitory activity of the corresponding short sequence analogs Arg-Gly-Asp-Phe (IC50 = 6 x 10(-6) M), Orn-Gly-Asp-Phe (IC50 = 1.3 x 10(-4) M), and Ala-Gly-Asp-Phe (IC50 = 5.0 x 10(-4) M) was also determined. These results suggest that arginine plays a more important role in the binding of the tetrapeptide than in that of echistatin. PMID:2726764

  14. Synthesis and Docking Studies of 2,4,6-Trihydroxy-3-Geranylacetophenone Analogs as Potential Lipoxygenase Inhibitor

    Directory of Open Access Journals (Sweden)

    Chean Hui Ng

    2014-08-01

    Full Text Available The natural product molecule 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA isolated from the medicinal plant Melicope ptelefolia was shown to exhibit potent lipoxygenase (LOX inhibitory activity. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of unsaturated fatty acids, such as linoleic acid to form hydroperoxides. The search for selective LOX inhibitors may provide new therapeutic approach for inflammatory diseases. Herein, we report the synthesis of tHGA analogs using simple Friedel-Craft acylation and alkylation reactions with the aim of obtaining a better insight into the structure-activity relationships of the compounds. All the synthesized analogs showed potent soybean 15-LOX inhibitory activity in a dose-dependent manner (IC50 = 10.31–27.61 μM where compound 3e was two-fold more active than tHGA. Molecular docking was then applied to reveal the important binding interactions of compound 3e in soybean 15-LOX binding site. The findings suggest that the presence of longer acyl bearing aliphatic chain (5Cs and aromatic groups could significantly affect the enzymatic activity.

  15. Strigolactone Analogs as Molecular Probes in Chasing the (SLs) Receptor/s: Design and Synthesis of Fluorescent Labeled Molecules

    Institute of Scientific and Technical Information of China (English)

    Cristina Prandi; Helèna Rosso; Beatrice Lace; Ernesto G. Occhiato; Alberto Oppedisano; Silvia Tabasso; Gabriele Alberto

    2013-01-01

    Originally identified as allelochemicals involved in plant-parasite interactions,more recently,Strigolactones (SLs) have been shown to play multiple key roles in the rhizosphere communication between plants and mycorrhizal fungi.Even more recent is the hormonal role ascribed to SLs which broadens the biological impact of these relatively simple molecules.In spite of the crucial and multifaceted biological role of SLs,there are no data on the receptor(s) which bind(s) such active molecules,neither in the producing plants nor in parasitic weeds or AM fungi.Information about the putative receptor of SLs can be gathered by means of structural,molecular,and genetic approaches.Our contribution on this topic is the design and synthesis of fluorescent labeled SL analogs to be used as probes for the detection in vivo of the receptor(s).Knowledge of the putative receptor structure will boost the research on analogs of the natural substrates as required for agricultural applications.

  16. SYNTHESIS AND BIOLOGICAL STUDIES OF CHERIMOLACYCLOPEPTIDE E AND ITS N- METHYLATED ANALOG

    Directory of Open Access Journals (Sweden)

    Himaja M

    2011-12-01

    Full Text Available The N-methyl derivative of Cherimolacyclopeptide E cyclo[Phe-(DimethylTyr-Pro-Gly-Leu-Gly] was synthesized using solution phase peptide synthesis. The synthesized compound was characterized by spectral data and was evaluated for anthelmintic and insecticidal activities. The compound exhibited potent anthelmintic activity as compared to the standard drug mebendazole.

  17. Synthesis and pharmacological evaluation of DHβE analogs as neuronal nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Jepsen, Tue H.; Jensen, Anders A.; Lund, Mads Henrik;

    2014-01-01

    Dihydro-β-erythroidine (DHβE) is a member of the Erythrina family of alkaloids and a potent competitive antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors (nAChRs). Guided by an X-ray structure of DHβE in complex with an ACh binding protein, we detail the design, synthesis...

  18. Aircraft interior noise prediction using a structural-acoustic analogy in NASTRAN modal synthesis

    Science.gov (United States)

    Grosveld, Ferdinand W.; Sullivan, Brenda M.; Marulo, Francesco

    1988-01-01

    The noise induced inside a cylindrical fuselage model by shaker excitation is investigated theoretically and experimentally. The NASTRAN modal-synthesis program is used in the theoretical analysis, and the predictions are compared with experimental measurements in extensive graphs. Good general agreement is obtained, but the need for further refinements to account for acoustic-cavity damping and structural-acoustic interaction is indicated.

  19. Synthesis and Antimicrobial Screening of New Pyrazolines Derived From Chalcones of Vanillin Analog

    Directory of Open Access Journals (Sweden)

    Krushnkumar Karangiya

    2016-03-01

    Full Text Available In present study the new series of 3-(Aryl-5-[4-(2, 4-Dichlorophenylmethoxy-3-methoxyphenyl]-4, 5-dihydro pyrazoline (2a-k and 3-(Aryl-5-[4-(2, 4-Dichlorophenylmethoxy-3-methoxyphenyl]-4, 5-dihydroacetyl pyrazoline (3a-k derivatives were synthesized from various substituted 3-Methoxy-4-(2, 4-Dichlorophenyl methoxy chalcones (1a-k. The new chalcones were synthesized using various acetophenones with newly synthesized aldehyde of vanillin analog by Claisen-Schmidt condensation. Characterization of pyrazoline derivatives have been established on the basis of IR, NMR, Mass and elemental analyses. The derivatives were screened for their in vitro antimicrobial Screening.

  20. Synthesis and Bio-activities of Pyrazolyl or Pyridinyl Substituted Tonghaosu Analogs

    Institute of Scientific and Technical Information of China (English)

    YIN,Biao-Lin; CHEN,Li; XU,Han-Hong; ZHANG,Jian-Cun; WU,Yu-Lin

    2007-01-01

    11 pyrazolyl or pyridinyl substituted tonghaosu analogs were synthesized. Structures of all the new compounds were confirmed by 1H NMR, IR, MS, HREIMS or elemental analysis. Their antifeedant activity against larvae of large white butterfly (Pieris brassicae L.), larvicidal activity toward mosquito (Culex quinquefasciatus Say) and growth control activity toward larvae of Spodoptera litura Fab were examined. Some of them exhibited antifeeding activities comparable to or stronger than tonghaosu Z-1. Based on the activity data, the preliminary structure-activity relationship was also discussed, which might be instructive for finding out lead compounds with better bioactivities in the future.

  1. Synthesis and antifungal activity of new bis-γ-lactones analogous to avenaciolide

    International Nuclear Information System (INIS)

    In a study of the antifungal activity of selected compounds as potentials agrochemicals, we have prepared and characterized by elemental analyses, infrared and NMR spectroscopies three new bis-γ-lactones analogous to avenaciolide, where the octyl group of this natural product was replaced by heptyl, hexyl and pentyl groups. The effects on the mycelia development and conidia germination of Colletotrichum gloesporioides of these compounds and their synthetic precursors were evaluated in vitro. The title compounds were active in the tested conditions, while all the synthetic precursors were inactive. The preparation and characterization of 15 new synthetic intermediates are also described. (author)

  2. Synthesis and antifungal activity of new bis-{gamma}-lactones analogous to avenaciolide

    Energy Technology Data Exchange (ETDEWEB)

    Magaton, Andreia da Silva; Rubinger, Mayura M. M.; Macedo Junior, Fernando C. de [Vicosa Univ., MG (Brazil). Dept. de Quimica]. E-mail: mayura@ufv.br; Zambolim, Laercio [Vicosa Univ., MG (Brazil). Dept. de Fitopatologia

    2007-03-15

    In a study of the antifungal activity of selected compounds as potentials agrochemicals, we have prepared and characterized by elemental analyses, infrared and NMR spectroscopies three new bis-{gamma}-lactones analogous to avenaciolide, where the octyl group of this natural product was replaced by heptyl, hexyl and pentyl groups. The effects on the mycelia development and conidia germination of Colletotrichum gloesporioides of these compounds and their synthetic precursors were evaluated in vitro. The title compounds were active in the tested conditions, while all the synthetic precursors were inactive. The preparation and characterization of 15 new synthetic intermediates are also described. (author)

  3. Technetium-99m labeled somatostatin and analogs: synthesis, characterization and in vivo evaluation

    International Nuclear Information System (INIS)

    Technetium-99m complexes of somatostatin and analogs were synthesized following the introduction of sulfhydryl groups with 2-iminothiolane (Traut's Reagent). In rats the complex was taken up by the liver, kidneys, adrenals, lungs and the pancreas. Analysis of urine samples of treated rats showed that the radiochemicals have reasonably good in vivo stability. This implies that the complexes may be potentially useful for biochemical characterization of somatostatin receptors and also in scintigraphic detection of somatostatin receptor positive tumors, especially for metastatic deposits in patients on somatostatin therapy. (Author)

  4. Technetium-99m labeled somatostatin and analogs: synthesis, characterization and in vivo evaluation

    International Nuclear Information System (INIS)

    Technetium-99m complexes of somatostatin and analogs were synthesized following the introduction of sulfhydryl groups with 2-iminothiolane (Traut's Reagent). In rats the complex was taken up by the liver, kidneys, adrenals, lungs and the pancreas. Analysis of urine samples of treated rats showed that the radiochemicals have reasonably good in vivo stability. This implies that the complexes may be potentially useful for biochemical characterization of somatostatin receptors and also in scintigraphic detection of somatostatin receptor positive tumors, especially for metastatic deposits in patients on somatostatin therapy. (author)

  5. Synthesis, Cytotoxic and Antimalarial Activities of Benzoyl Thiosemicarbazone Analogs of Isoquinoline and Related Compounds

    Directory of Open Access Journals (Sweden)

    Somsak Ruchirawat

    2010-02-01

    Full Text Available Thiosemicarbazone analogs of papaveraldine and related compounds 1–6 were synthesized and evaluated for cytotoxic and antimalarial activities. The cytotoxic activity was tested against HuCCA-1, HepG2, A549 and MOLT-3 human cancer cell lines. Thiosemicarbazones 1–5 displayed cytotoxicity toward all the tested cell lines, while compounds 2–5 selectively showed potent activity against the MOLT-3 cell lines. Significantly, N(4-phenyl-2-benzoylpyridine thiosemicarbazone 4 exhibited the most potent activity against HuCCA-1, HepG2, A549 and MOLT-3 cell lines with IC50 values of 0.03, 4.75, 0.04 and 0.004 µg/mL, respectively. In addition, 2-benzoylpyridine thio-semicarbazones 3 and 4 showed antimalarial activity against Plasmodium falciparum with IC50 of 10-7 to < 10-6 M. The study demonstrates the quite promising activity of analog 4 as a lead molecule for further development.

  6. Chemoenzymatic synthesis and antileukemic activity of novel C9- and C14-functionalized parthenolide analogs.

    Science.gov (United States)

    Tyagi, Vikas; Alwaseem, Hanan; O'Dwyer, Kristen M; Ponder, Jessica; Li, Qi Ying; Jordan, Craig T; Fasan, Rudi

    2016-09-01

    Parthenolide is a naturally occurring terpene with promising anticancer properties, particularly in the context of acute myeloid leukemia (AML). Optimization of this natural product has been challenged by limited opportunities for the late-stage functionalization of this molecule without affecting the pharmacologically important α-methylene-γ-lactone moiety. Here, we report the further development and application of a chemoenzymatic strategy to afford a series of new analogs of parthenolide functionalized at the aliphatic positions C9 and C14. Several of these compounds were determined to be able to kill leukemia cells and patient-derived primary AML specimens with improved activity compared to parthenolide, exhibiting LC50 values in the low micromolar range. These studies demonstrate that different O-H functionalization chemistries can be applied to elaborate the parthenolide scaffold and that modifications at the C9 or C14 position can effectively enhance the antileukemic properties of this natural product. The C9-functionalized analogs 22a and 25b were identified as the most interesting compounds in terms of antileukemic potency and selectivity toward AML versus healthy blood cells. PMID:27396927

  7. Synthesis and biological evaluation of fluconazole analogs with triazole-modified scaffold as potent antifungal agents.

    Science.gov (United States)

    Hashemi, Seyedeh Mahdieh; Badali, Hamid; Irannejad, Hamid; Shokrzadeh, Mohammad; Emami, Saeed

    2015-04-01

    In order to find new azole antifungals, we have recently designed a series of triazole alcohols in which one of the 1,2,4-triazol-1-yl group in fluconazole structure has been replaced with 4-amino-5-aryl-3-mercapto-1,2,4-triazole motif. In this paper, we focused on the structural refinement of the primary lead, by removing the amino group from the structure to achieve 5-aryl-3-mercapto-1,2,4-triazole derivatives 10a-i and 11a-i. The in vitro antifungal susceptibility testing of title compounds demonstrated that most compounds had potent inhibitory activity against Candida species. Among them, 5-(2,4-dichlorophenyl)triazole analogs 10h and 11h with MIC values of fluconazole against Candida species.

  8. DNA Nucleobase Synthesis at Titan Atmosphere Analog by Soft X-rays

    CERN Document Server

    Pilling, S; Neto, Alvaro C; Rittner, R; de Brito, A Naves; 10.1021/jp902824v

    2009-01-01

    Titan, the largest satellite of Saturn, has an atmosphere chiefly made up of N2 and CH4 and includes traces of many simple organic compounds. This atmosphere also partly consists of haze and aerosol particles which during the last 4.5 gigayears have been processed by electric discharges, ions, and ionizing photons, being slowly deposited over the Titan surface. In this work, we investigate the possible effects produced by soft X-rays (and secondary electrons) on Titan aerosol analogs in an attempt to simulate some prebiotic photochemistry. The experiments have been performed inside a high vacuum chamber coupled to the soft X-ray spectroscopy beamline at the Brazilian Synchrotron Light Source, Campinas, Brazil. In-situ sample analyses were performed by a Fourier transform infrared spectrometer. The infrared spectra have presented several organic molecules, including nitriles and aromatic CN compounds. After the irradiation, the brownish-orange organic residue (tholin) was analyzed ex-situ by gas chromatographi...

  9. Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors.

    Science.gov (United States)

    An, Ying; Lee, Eun; Yu, Yeongji; Yun, Jieun; Lee, Myeong Youl; Kang, Jong Soon; Kim, Woo-Young; Jeon, Raok

    2016-07-01

    A novel series of benzoxazole analogs was designed and synthesized, and their inhibitory activities against Aurora kinases were evaluated. Some of the tested compounds exhibited a promising activity with respect to the inhibition of Aurora B kinase. A structure-activity relationship study indicated that linker length, regiochemistry, and halogen substitution play important roles in kinase inhibitory potency. The binding modes between representative compounds and Aurora kinases were interpreted through a molecular docking study to explain the inhibitory activity and selectivity for Aurora A and B kinases. Compounds 13l and 13q also show an antiproliferative effect on the human tumor cell lines in a dose-dependent manner. The most potent 13q demonstrated good efficacy in the prostate cancer PC-3 tumor xenograft model.

  10. Expediting analog design retargeting by design knowledge re-use and circuit synthesis: a practical example on a Delta-Sigma modulator

    Science.gov (United States)

    Webb, Matthew; Tang, Hua

    2016-08-01

    In the past decade or two, due to constant and rapid technology changes, analog design re-use or design retargeting to newer technologies has been brought to the table in order to expedite the design process and improve time-to-market. If properly conducted, analog design retargeting could significantly cut down design cycle compared to designs starting from the scratch. In this article, we present an empirical and general method for efficient analog design retargeting by design knowledge re-use and circuit synthesis (CS). The method first identifies circuit blocks that compose the source system and extracts the performance parameter specifications of each circuit block. Then, for each circuit block, it scales the values of design variables (DV) from the source design to derive an initial design in the target technology. Depending on the performance of this initial target design, a design space is defined for synthesis. Subsequently, each circuit block is automatically synthesised using state-of-art analog synthesis tools based on a combination of global and local optimisation techniques to achieve comparable performance specifications to those extracted from the source system. Finally, the overall system is composed of those synthesised circuit blocks in the target technology. We illustrate the method using a practical example of a complex Delta-Sigma modulator (DSM) circuit.

  11. Synthesis of fluorescent analogs of relaxin family peptides and their preliminary in vitro and in vivo characterization.

    Science.gov (United States)

    Chan, Linda J; Smith, Craig M; Chua, Berenice E; Lin, Feng; Bathgate, Ross A D; Separovic, Frances; Gundlach, Andrew L; Hossain, Mohammed Akhter; Wade, John D

    2013-01-01

    Relaxin, a heterodimeric polypeptide hormone, is a key regulator of collagen metabolism and multiple vascular control pathways in humans and rodents. Its actions are mediated via its cognate G-protein-coupled receptor, RXFP1 although it also "pharmacologically" activates RXFP2, the receptor for the related, insulin-like peptide 3 (INSL3), which has specific actions on reproduction and bone metabolism. Therefore, experimental tools to facilitate insights into the distinct biological actions of relaxin and INSL3 are required, particularly for studies of tissues containing both RXFP1 and RXFP2. Here, we chemically functionalized human (H2) relaxin, the RXFP1-selective relaxin analog H2:A(4-24)(F23A), and INSL3 to accommodate a fluorophore without marked reduction in binding or activation propensity. Chemical synthesis of the two chains for each peptide was followed by sequential regioselective formation of their three disulfide bonds. Click chemistry conjugation of Cy5.5 at the B-chain N-terminus, with conservation of the disulfide bonds, yielded analogs displaying appropriate selective binding affinity and ability to activate RXFP1 and/or RXFP2 in vitro. The in vivo biological activity of Cy5.5-H2 relaxin and Cy5.5-H2:A(4-24)(F23A) was confirmed in mice, as acute intracerebroventricular (icv) infusion of these peptides (but not Cy5.5-INSL3) stimulated water drinking, an established behavioral response elicited by central RXFP1 activation. The central distribution of Cy5.5-conjugated peptides was examined in mice killed 30 min after infusion, revealing higher fluorescence within brain tissue near-adjacent to the cerebral ventricle walls relative to deeper brain areas. Production of fluorophore-conjugated relaxin family peptides will facilitate future pharmacological studies to probe the function of H2 relaxin/RXFP1 and INSL3/RXFP2 signaling in vivo while tracking their distribution following central or peripheral administration. PMID:24790958

  12. Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings.

    Science.gov (United States)

    Li, Yuhao; Zhu, Hongjun; Chen, Kai; Liu, Rui; Khallaf, Abdalla; Zhang, Xiangning; Ni, Jueping

    2013-06-28

    A series of anthranilic diamides analogs (3–11, 16–24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by (1)H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (18, CCDC-) was determined by X-ray diffraction crystallography. The insecticidal activities against Plutella xylostella and Spodoptera exigua were evaluated. The results showed that most of title compounds displayed good larvicidal activities against P. xylostella, especially compound 3-bromo-N-(4-chloro-2-methyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (6), which displayed 71.43% activity against P. xylostella at 0.4 μg mL(-1) and 33.33% against S. exigua at 1 μg mL(-1). The structure-activity relationship showed that compounds decorated with a 1,3,4-oxadiazole were more potent than compounds decorated with a 1,2,4-oxadiazole, and different substituents attached to the oxadiazole ring also affected the insecticidal activity. This work provides some hints for further structure modification and the enhancement of insecticidal activity.

  13. Synthesis and evaluation of L-glutamic acid analogs as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Viswanathan C

    2008-01-01

    Full Text Available Four N-(benzenesulfonyl-L-glutamic acid bis(p-substituted phenylhydrazides were synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3 prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog with the nitro group substitution exhibited potent activity (% Inhibition 84.7 and 72.0 in DU-145 and PC-3 respectively at 80 mg/ml concentration. Another series of substituted 1-(benzenesulfonyl-5-oxopyrrolidine 2-carboxamides (11a-f were synthesized and evaluated for anticancer activity in vitro in colon (COLO-205, breast (Zr-75-1 and prostate (PC-3 cancer cell lines by MTT assay using adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition 61.2 to 79.2 at 20 mg/ml and 67.2 to 87.2 at 40 mg/ml in PC-3 cell line which is superior to the activity of Adriamycin. In comparison compounds 11d-f were less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to 54.9 at 10 mg/ml concentration while in COLO-205 cell line 11a-f showed poor activity.

  14. Synthesis and Insecticidal Activity of Novel Camptothecin Derivatives Containing Analogs of Chrysanthemic Acid Moieties

    Institute of Scientific and Technical Information of China (English)

    DENG Li; ZHANG Lan; CAO Li-dong; XIE Ru-liang; ZHANG Yan-ning; HE Wei-zhi; JIANG Hong-yun

    2014-01-01

    Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin (CPT) and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin (1) and 10-hydroxycamptothecin (2) derivatives (1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e) were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua Hübner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.

  15. Synthesis and anti-HBV activity of α-stereoisomer of aristeromycin based analogs.

    Science.gov (United States)

    Kasula, Mohan; Toyama, Masaaki; Samunuri, Ramakrishnamraju; Rozy, Farhana; Yadav, Monika; Bal, Chandralata; Jha, Ashok Kumar; Baba, Masanori; Sharon, Ashoke

    2016-08-15

    The potential antiviral activity of aristeromycin type of derivatives (I) is limited by associated toxicity due to its possible 5'-O-phosphorylation and S-adenosyl-l-homocysteine hydrolase (SAHase) inhibitory activity. Aristeromycin structure has major pharmacophoric motif as 5'-OH and adenosine base, which may have significant role in enzyme binding followed by activity and or toxicity. Thus, the structural optimization to alter this major motif by replacing with its bioisostere and changing the 5'-O conformation through stereochemistry reversal was of interest. Thus, the inverted stereochemistry at 4'-position coupled with bioisostere of adenosine base in the target compounds (6-7) to access antiviral potential. The stereoselective formation of a key stereoisomer (2a) was achieved exclusively from neplanocin sugar (1a) by reduction in a single step. The novel target molecules (6-7) were synthesized in 4 steps with 55-62% yield. Compound 6 was analyzed by single crystal X-ray diffraction, which confirms the stereoselective formation of α-analogs with highly puckered cyclopentane ring and 2'-endo conformation. The compound 6 shown significant anti-hepatitis B virus activity of 6.5μM with CC50>100μM and yielded a promising lead with novel structural feature. PMID:27426303

  16. Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings.

    Science.gov (United States)

    Li, Yuhao; Zhu, Hongjun; Chen, Kai; Liu, Rui; Khallaf, Abdalla; Zhang, Xiangning; Ni, Jueping

    2013-06-28

    A series of anthranilic diamides analogs (3–11, 16–24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by (1)H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (18, CCDC-) was determined by X-ray diffraction crystallography. The insecticidal activities against Plutella xylostella and Spodoptera exigua were evaluated. The results showed that most of title compounds displayed good larvicidal activities against P. xylostella, especially compound 3-bromo-N-(4-chloro-2-methyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (6), which displayed 71.43% activity against P. xylostella at 0.4 μg mL(-1) and 33.33% against S. exigua at 1 μg mL(-1). The structure-activity relationship showed that compounds decorated with a 1,3,4-oxadiazole were more potent than compounds decorated with a 1,2,4-oxadiazole, and different substituents attached to the oxadiazole ring also affected the insecticidal activity. This work provides some hints for further structure modification and the enhancement of insecticidal activity. PMID:23657615

  17. Synthesis and preliminary biological evaluation of a technetium-99m labeled thymidine analog

    Institute of Scientific and Technical Information of China (English)

    Chun Xiong Lu; Zheng Wu Wang; Quan Fu Jiang; Jie Tang; Cheng Tan; Jian Kang Zhang

    2011-01-01

    The synthesis and labeling of 99mTc-N3-{N'-[2-sulfanyl-ethylamino)acetyl]-2-aminoethyl-sulfanyl-l-hexanamide}thymidine (99mTc-NHT) were studied. In the presence of sodium glucoheptonate (GH) and ethylene diamine tetraacetic acid (EDTA), 99mTc-NHT was obtained by using bisaminoethanethiol (N2S2) as a bifunctional coupling agent. The radiochemical purity of the 99mTc-NHT was over 95%. Biodistribution of 99mTc-NHT was performed in hepatoma HepA tumor-bearing mice. At 2 h p.i., the ratios of tumor-to-muscle, tumor-to-bone and tumor-to-blood were 4.41 ± 0.32, 2.45 ± 0.24 and 1.51 ±0.18, respectively.

  18. Synthesis and biological activity of sulfur compounds showing structural analogy with combretastatin A-4

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Edson dos A. dos; Prado, Paulo C.; Carvalho, Wanderley R. de; Lima, Ricardo V. de; Beatriz, Adilson; Lima, Denis P. de, E-mail: denis.lima@ufms.br [Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Departamento de Quimica; Hamel, Ernest [Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD (United States); Dyba, Marzena A. [Basic Science Program , SAIC-Frederick, Inc., Structural Biophysics Laboratory National Cancer Institute, Frederick, MD (United States); Albuquerque, Sergio [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Ciencias Farmaceuticas

    2013-09-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904),and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15). (author)

  19. Synthesis and evaluation of 18F-labeled benzylguanidine analogs for targeting the human norepinephrine transporter

    International Nuclear Information System (INIS)

    Both 131I- and 123I-labeled meta-iodobenzylguanidine (MIBG) have been widely used in the clinic for targeted imaging of the norepinephrine transporter (NET). The human NET (hNET) gene has been imaged successfully with 124I-MIBG positron emission tomography (PET) at time points of >24 h post-injection (p.i.). 18F-labeled MIBG analogs may be ideal to image hNET expression at time points of 18F]MFBG and [18F]PFBG and evaluated them in hNET reporter gene-transduced C6 rat glioma cells and xenografts. [18F]MFBG and [18F]PFBG were synthesized manually using a three-step synthetic scheme. Wild-type and hNET reporter gene-transduced C6 rat glioma cells and xenografts were used to comparatively evaluate the 18F-labeled analogs with [123I]/[124I]MIBG. The fluorination efficacy on benzonitrile was predominantly determined by the position of the trimethylammonium group. The para-isomer afforded higher yields (75 ± 7 %) than meta-isomer (21 ± 5 %). The reaction of [18F]fluorobenzylamine with 1H-pyrazole-1-carboximidamide was more efficient than with 2-methyl-2-thiopseudourea. The overall radiochemical yields (decay-corrected) were 11 ± 2 % (n = 12) for [18F]MFBG and 41 ± 12 % (n = 5) for [18F]PFBG, respectively. The specific uptakes of [18F]MFBG and [18F]PFBG were similar in C6-hNET cells, but 4-fold less than that of [123I]/[124I]MIBG. However, in vivo [18F]MFBG accumulation in C6-hNET tumors was 1.6-fold higher than that of [18F]PFBG at 1 h p.i., whereas their uptakes were similar at 4 h. Despite [18F]MFBG having a 2.8-fold lower affinity to hNET and approximately 4-fold lower cell uptake in vitro compared to [123I]/[124I]MIBG, PET imaging demonstrated that [18F]MFBG was able to visualize C6-hNET xenografts better than [124I]MIBG. Biodistribution studies showed [18F]MFBG and 123I-MIBG had a similar tumor accumulation, which was lower than that of no-carrier-added [124I]MIBG, but [18F]MFBG showed a significantly more rapid body clearance and lower uptake in most non

  20. Protonation effects on the inclusion complexation of 6-deoxy-6-diethylamino-beta-cyclodextrin with 2-anthracenesulfonate, 2-naphthalenesulfonate, 2,6-naphthalenedisulfonate, and 2,7-naphthalenedisulfonate in aqueous solutions.

    Science.gov (United States)

    Hamai, S; Ishikawa, S

    2001-01-01

    At pH values 5.5 and 10.3, 6-deoxy-6-diethylamino-beta-cyclodextrin (DD-beta-CD) as well as beta-CD forms 1:1 inclusion complexes with 2-anthracenesulfonate (2AS), 2-naphthalenesulfonate (2NS), 2,6-naphthalenedisulfonate (2,6NDS), and 2,7-naphthalenedisulfonate (2,7NDS). The equilibrium constants (K) for the formation of the 1:1 inclusion complexes have been evaluated from the absorbance and/or fluorescence intensity changes. With respect to the beta-CD inclusion complexes of 2AS, 2NS, 2,6NDS, and 2,7NDS, the K values at pH 5.5 are nearly the same as the corresponding ones at pH 10.3. In the case of the DD-beta-CD inclusion complexes, the K values of 2AS and 2NS similarly do not depend on the pH value. However, the K values of 2,6NDS and 2,7NDS for DD-beta-CD at pH 5.5 have been found to be more than two times greater than the corresponding ones at pH 10.3, suggesting the electrostatic attraction between the protonated diethylamino group of DD-beta-CD and the sulfonato group of the NDSs.

  1. Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.

    Science.gov (United States)

    Wang, Hao-Meng; Zhang, Li; Liu, Jiang; Yang, Zhao-Liang; Zhao, Hong-Ye; Yang, Yao; Shen, Di; Lu, Kui; Fan, Zhen-Chuan; Yao, Qing-Wei; Zhang, Yong-Min; Teng, Yu-Ou; Peng, Yu

    2015-03-01

    Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing apoptosis. PMID:25590864

  2. 6-Deoxy-6-fluoro-d-galactose

    Directory of Open Access Journals (Sweden)

    Sarah F. Jenkinson

    2010-06-01

    Full Text Available The crystal structure unequivocally confirms the relative stereochemistry of the title compound, C6H11FO5. The absolute stereochemistry was determined by the use of d-galactose as the starting material. The compound exists as a three-dimensional O—H...O hydrogen-bonded network with each molecule acting as a donor and acceptor for four hydrogen bonds.

  3. Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway.

    Directory of Open Access Journals (Sweden)

    Judith A Enyeart

    Full Text Available Adrenal zona fasciculata (AZF cells express a cAMP-activated guanine nucleotide exchange protein (Epac2 that may function in ACTH-stimulated cortisol synthesis. Experiments were done to determine whether cAMP analogs that selectively activate Epacs could induce cortisol synthesis and the expression of genes coding for steroidogenic proteins in bovine AZF cells. Treatment of AZF cells with the Epac-selective cAMP analog (ESCA 8CPT-2'-OMe-cAMP induced large (>100 fold, concentration-dependent, delayed increases in cortisol synthesis and the expression of mRNAs coding for the steroid hydroxylases CYP11a1, CYP17, CYP21, and the steroid acute regulatory protein (StAR. However, a non-hydrolyzable analog of this ESCA, Sp-8CPT-2'-OMe-cAMP, failed to stimulate cortisol production even at concentrations that activated Rap1, a downstream effector of Epac2. Accordingly, putative metabolites of 8CPT-2'-OMe-cAMP, including 8CPT-2'-OMe-5'AMP, 8CPT-2'-OMe-adenosine, and 8CPT-adenine all induced cortisol synthesis and steroid hydroxylase mRNA expression with a temporal pattern, potency, and effectiveness similar to the parent compound. At concentrations that markedly stimulated cortisol production, none of these metabolites significantly activated cAMP-dependent protein kinase (PKA. These results show that one or more metabolites of the ESCA 8CPT-2'-OMe-cAMP induce cortico-steroidogenesis by activating a panel of genes that code for steroidogenic proteins. The remarkable increases in cortisol synthesis observed in this study appear to be mediated by a novel cAMP-, Epac- and PKA-independent signaling pathway.

  4. Synthesis and evaluation of {sup 18}F-labeled benzylguanidine analogs for targeting the human norepinephrine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hanwen; Huang, Ruimin; Pillarsetty, NagaVaraKishore; Thorek, Daniel L.J. [Memorial Sloan-Kettering Cancer Center (MSKCC), Department of Radiology, New York, NY (United States); Vaidyanathan, Ganesan [Duke University School of Medicine, Department of Radiology, Durham, NC (United States); Serganova, Inna [Memorial Sloan-Kettering Cancer Center (MSKCC), Department of Neurology, New York, NY (United States); Blasberg, Ronald G. [Memorial Sloan-Kettering Cancer Center (MSKCC), Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center (MSKCC), Department of Neurology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center (MSKCC), Molecular Pharmacology and Chemistry Program, New York, NY (United States); Lewis, Jason S. [Memorial Sloan-Kettering Cancer Center (MSKCC), Department of Radiology, New York, NY (United States); Memorial Sloan-Kettering Cancer Center (MSKCC), Molecular Pharmacology and Chemistry Program, New York, NY (United States); Molecular Pharmacology and Chemistry Program, SKI, Memorial Sloan-Kettering Cancer Center, Radiochemistry and Imaging Sciences Service, Department of Radiology, New York, NY (United States)

    2014-02-15

    Both {sup 131}I- and {sup 123}I-labeled meta-iodobenzylguanidine (MIBG) have been widely used in the clinic for targeted imaging of the norepinephrine transporter (NET). The human NET (hNET) gene has been imaged successfully with {sup 124}I-MIBG positron emission tomography (PET) at time points of >24 h post-injection (p.i.). {sup 18}F-labeled MIBG analogs may be ideal to image hNET expression at time points of <8 h p.i. We developed improved methods for the synthesis of known MIBG analogs, [{sup 18}F]MFBG and [{sup 18}F]PFBG and evaluated them in hNET reporter gene-transduced C6 rat glioma cells and xenografts. [{sup 18}F]MFBG and [{sup 18}F]PFBG were synthesized manually using a three-step synthetic scheme. Wild-type and hNET reporter gene-transduced C6 rat glioma cells and xenografts were used to comparatively evaluate the {sup 18}F-labeled analogs with [{sup 123}I]/[{sup 124}I]MIBG. The fluorination efficacy on benzonitrile was predominantly determined by the position of the trimethylammonium group. The para-isomer afforded higher yields (75 ± 7 %) than meta-isomer (21 ± 5 %). The reaction of [{sup 18}F]fluorobenzylamine with 1H-pyrazole-1-carboximidamide was more efficient than with 2-methyl-2-thiopseudourea. The overall radiochemical yields (decay-corrected) were 11 ± 2 % (n = 12) for [{sup 18}F]MFBG and 41 ± 12 % (n = 5) for [{sup 18}F]PFBG, respectively. The specific uptakes of [{sup 18}F]MFBG and [{sup 18}F]PFBG were similar in C6-hNET cells, but 4-fold less than that of [{sup 123}I]/[{sup 124}I]MIBG. However, in vivo [{sup 18}F]MFBG accumulation in C6-hNET tumors was 1.6-fold higher than that of [{sup 18}F]PFBG at 1 h p.i., whereas their uptakes were similar at 4 h. Despite [{sup 18}F]MFBG having a 2.8-fold lower affinity to hNET and approximately 4-fold lower cell uptake in vitro compared to [{sup 123}I]/[{sup 124}I]MIBG, PET imaging demonstrated that [{sup 18}F]MFBG was able to visualize C6-hNET xenografts better than [{sup 124}I

  5. Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

    Science.gov (United States)

    Horník, Štěpán; Červenková Šťastná, Lucie; Cuřínová, Petra; Sýkora, Jan; Káňová, Kateřina; Hrstka, Roman; Císařová, Ivana; Dračínský, Martin

    2016-01-01

    Summary Background: Derivatives of D-glucosamine and D-galactosamine represent an important family of the cell surface glycan components and their fluorinated analogs found use as metabolic inhibitors of complex glycan biosynthesis, or as probes for the study of protein–carbohydrate interactions. This work is focused on the synthesis of acetylated 3-deoxy-3-fluoro, 4-deoxy-4-fluoro and 3,4-dideoxy-3,4-difluoro analogs of D-glucosamine and D-galactosamine via 1,6-anhydrohexopyranose chemistry. Moreover, the cytotoxicity of the target compounds towards selected cancer cells is determined. Results: Introduction of fluorine at C-3 was achieved by the reaction of 1,6-anhydro-2-azido-2-deoxy-4-O-benzyl-β-D-glucopyranose or its 4-fluoro analog with DAST. The retention of configuration in this reaction is discussed. Fluorine at C-4 was installed by the reaction of 1,6:2,3-dianhydro-β-D-talopyranose with DAST, or by fluoridolysis of 1,6:3,4-dianhydro-2-azido-β-D-galactopyranose with KHF2. The amino group was introduced and masked as an azide in the synthesis. The 1-O-deacetylated 3-fluoro and 4-fluoro analogs of acetylated D-galactosamine inhibited proliferation of the human prostate cancer cell line PC-3 more than cisplatin and 5-fluorouracil (IC50 28 ± 3 μM and 54 ± 5 μM, respectively). Conclusion: A complete series of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine is now accessible by 1,6-anhydrohexopyranose chemistry. Intermediate fluorinated 1,6-anhydro-2-azido-hexopyranoses have potential as synthons in oligosaccharide assembly. PMID:27340467

  6. 1 alpha,25-dihydroxyvitamin D3 analogs featuring aromatic and heteroaromatic rings: design, synthesis, and preliminary biological testing.

    Science.gov (United States)

    Posner, G H; Li, Z; White, M C; Vinader, V; Takeuchi, K; Guggino, S E; Dolan, P; Kensler, T W

    1995-10-27

    Aromatic compounds 2a-c, analogs of 1 alpha, 25-dihydroxyvitamin (calcitriol, 1), and heteroaromatic compounds 4a-c and 5a-c, analogs of 19-nor-1 alpha, 25-dihydroxyvitamin D3 (3), were designed to simulate the topology of their biologically potent parent compounds while avoiding previtamin D equilibrium. Convergent and facile total syntheses of the analogs (+)-2b, (+)-2c, (-)-4b, and (-)-5b were achieved via carbonyl addition of regiospecifically formed organolithium nucleophiles to the enantiomerically pure C,D-ring ketone (+)-17, characteristic of natural calcitriol (1). Likewise, hybrid analogs 20a-c were prepared to determine whether incorporation of a known potentiating side chain would lead to increased biological activity. Preliminary in vitro biological testing showed that aromatic analogs (+)-2b, (+)-2c, and 20a-c as well as heteroaromatic analogs (-)-4b and (-)-5b have very low affinities for the calf thymus vitamin D receptor but considerable antiproliferative activities in murine keratinocytes at micromolar concentration. No biological advantage was observed in this keratinocyte assay for the doubly modified hybrid analogs 20a-c over the singly modified parent (+)-2b. Analog (+)-2b, but surprisingly not the corresponding analog 20b differing from (+)-2b only in the side chain, showed considerable activity in nongenomic opening of calcium channels in rat osteosarcoma cells. PMID:7473581

  7. Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake.

    Science.gov (United States)

    Ding, Derong; Nickell, Justin R; Deaciuc, Agripina G; Penthala, Narsimha Reddy; Dwoskin, Linda P; Crooks, Peter A

    2013-11-01

    Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a-15c and 22a-22c) potently inhibited [(3)H]dopamine (DA) uptake into isolated synaptic vesicles (Ki⩽66nM). The cis-4-methoxy analog 22b was the most potent inhibitor (Ki=24nM), and was twofold more potent that either lobelane (2a, Ki=45nM) or norlobelane (2b, Ki=43nM). The trans-methylenedioxy analog, 15c (Ki=31nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis- and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse.

  8. Analog circuits cookbook

    CERN Document Server

    Hickman, Ian

    2013-01-01

    Analog Circuits Cookbook presents articles about advanced circuit techniques, components and concepts, useful IC for analog signal processing in the audio range, direct digital synthesis, and ingenious video op-amp. The book also includes articles about amplitude measurements on RF signals, linear optical imager, power supplies and devices, and RF circuits and techniques. Professionals and students of electrical engineering will find the book informative and useful.

  9. Pyrrolidine analogs of GZ-793A: synthesis and evaluation as inhibitors of the vesicular monoamine transporter-2 (VMAT2).

    Science.gov (United States)

    Penthala, Narsimha Reddy; Ponugoti, Purushothama Rao; Nickell, Justin R; Deaciuc, Agripina G; Dwoskin, Linda P; Crooks, Peter A

    2013-06-01

    Central heterocyclic ring size reduction from piperidinyl to pyrrolidinyl in the vesicular monoamine transporter-2 (VMAT2) inhibitor GZ-793A and its analogs resulted in novel N-propane-1,2(R)-diol analogs 11a-i. These compounds were evaluated for their affinity for the dihydrotetrabenazine (DTBZ) binding site on VMAT2 and for their ability to inhibit vesicular dopamine (DA) uptake. The 4-difluoromethoxyphenethyl analog 11f was the most potent inhibitor of [(3)H]-DTBZ binding (Ki=560 nM), with 15-fold greater affinity for this site than GZ-793A (Ki=8.29 μM). Analog 11f also showed similar potency of inhibition of [(3)H]-DA uptake into vesicles (Ki=45 nM) compared to that for GZ-793A (Ki=29 nM). Thus, 11f represents a new water-soluble inhibitor of VMAT function.

  10. Differential half-maximal effects of human insulin and its analogs for in situ glucose transport and protein synthesis in rat soleus muscle

    Science.gov (United States)

    Weinstein, Randi B.; Eleid, Noura; LeCesne, Catherine; Durando, Bianca; Crawford, Julie T.; Heffner, Michelle; Layton, Christle; O'Keefe, Matthew; Robinson, Jennifer; Rudinsky, Suzy; Henriksen, Erik J.; Tischler, Marc E.

    2002-01-01

    Analogs of human insulin have been used to discriminate between responses of metabolic and mitogenic (growth-related) pathways. This study compared the stimulatory effects of human insulin (HI) and 2 analogs (X2, B-Asp(9), B-Glu(27) and H2, A-His(8),B-His(4),B-Glu(10), B-His(27)) on glucose uptake and protein synthesis in rat soleus muscle in situ. Glucose uptake, estimated by intramuscular (IM) injection of 2-deoxy[1,2-3H]glucose with or without insulin, was maximally increased at 10(-6) mol/L for HI and X2 and 10(-7) mol/L for H2. HI had a larger effect (318%) than either X2 (156%) or H2 (124%). The half-maximal effect (ED(50)) values for HI, X2, and H2 were 3.3 x10(-8) mol/L, 1.7 x 10(-7) mol/L, and 1.6 x 10(-9) mol/L, respectively. Protein synthesis, estimated by protein incorporation of [(3)H]phenylalanine injected into muscles with or without insulin, was maximally increased at 10(-5) mol/L for HI and 10(-6) for X2 and H2. HI had a larger effect in stimulating protein synthesis (34%) than either X2 (25%) or H2 (19.8%). The ED(50) values for HI, X2, and H2 were 3.0 x 10(-7) mol/L, 3.2 x 10(-7) mol/L, and 1.0 x 10(-9) mol/L, respectively. The biological potency of each analog (ED(50)insulin/ED(50)analog) showed X2 to be less potent than HI for both glucose uptake (0.2) and protein synthesis (0.9), whereas H2 is more potent than HI with ratios of 20 and 300, respectively. These data suggest that this approach for studying insulin responsiveness in a single muscle in situ may be a useful tool for investigating insulin signaling in muscle in vivo. Copyright 2002, Elsevier Science (USA). All rights reserved.

  11. Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: synthesis and biological activity of fluorinated tebufenpyrad analogs.

    Science.gov (United States)

    Fustero, Santos; Román, Raquel; Sanz-Cervera, Juan F; Simón-Fuentes, Antonio; Cuñat, Ana C; Villanova, Salvador; Murguía, Marcelo

    2008-05-01

    The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity.

  12. Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2'-hydroxyphenyl)benzoxazole analogs of UK-1.

    Science.gov (United States)

    McKee, Mireya L; Kerwin, Sean M

    2008-02-15

    UK-1 is a bis(benzoxazole) natural product displaying activity against a wide range of human cancer cell lines. A simplified analog of UK-1, 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, was previously found to be almost as active as UK-1 against cancer cell lines, and similar to the natural product, formed complexes with a variety of metal ions such as Mg2+ and Zn2+. A series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazole analogs of this 'minimal pharmacophore' of UK-1 were prepared. The anti-cancer activity of these analogs was examined in breast and lung cancer cell lines. Spectrophotometric titrations in methanol were carried out in order to assess the ability of UK-1 and these analogs to coordinate with Mg2+ and Cu2+ ions. Although none of the new analogs were more cytotoxic than 4-carbomethoxy-2-(2'-hydroxyphenyl)benzoxazole, some analogs were identified that display similar cytotoxicity to this simplified UK-1 analog with improved water solubility. UK-1 and all of these new analogs bind Cu2+ ions better than Mg2+ ions, and the nature of the 4-substituent is important for the Mg2+ ion binding ability of these 2-(2'-hydroxyphenyl)benzoxazoles. Previous studies of a limited number of UK-1 analogs demonstrated a correlation between Mg2+ ion binding ability and cytotoxicity; however, within this series of 4-substituted-2-(2'-hydroxyphenyl)benzoxazoles the variations in cytotoxicity do not correlate with either Mg2+ or Cu2+ ion binding ability. These results, together with recent ESI-MS studies of Cu2+-mediated DNA binding by UK-1 and analogs, indicate that UK-1 and analogs may exert their cytotoxic effects by interaction with Cu2+ or other transition metal ions, rather than Mg2+, and that metal ion-mediated DNA binding, rather than metal ion binding affinity, is important for the cytotoxic effect of these compounds. The potential role of Cu2+ ions in the cytotoxic action of UK-1 is further supported by the observation that UK-1 in the presence of Cu2

  13. Design, synthesis, and biological activities of conformationally restricted analogs of primaquine with a 1,10-phenanthroline framework

    OpenAIRE

    Sall, C.; Yapi, A. D.; Desbois, N.; Chevalley, Séverine; Chezal, J.M.; Tan, K.; Teulade, J. C.; Valentin, A; Y. Blache

    2008-01-01

    A series of primaquine analogs was prepared, according to a conformationally restricted conformation of primaquine. In vitro antiplasmodial activities were evaluated and showed that all compounds were active on different strains of Plasmodium falciparum. In particular compounds 5 and 15 possessing a methoxy group were more active than was primaquine. Furthermore, analog 5 displayed good in vitro gametocytocidal activity. In addition selectivity indexes were calculated in respect with cytotoxi...

  14. Isomeric iodinated analogs of nimesulide: Synthesis, physicochemical characterization, cyclooxygenase-2 inhibitory activity, and transport across Caco-2 cells.

    Science.gov (United States)

    Yamamoto, Yumi; Arai, Jun; Hisa, Takuya; Saito, Yohei; Mukai, Takahiro; Ohshima, Takashi; Maeda, Minoru; Yamamoto, Fumihiko

    2016-08-15

    Isomeric iodinated derivatives of nimesulide, with an iodine substituent on the phenoxy ring, were prepared with the aim of identifying potential candidate compounds for the development of imaging agents targeting cyclooxygenase-2 (COX-2) in the brain. Both the experimental logP7.4 and pKa values for these iodinated analogs were in the acceptable range for passive brain penetration. The para-iodo-substituted analog was a more potent and selective COX-2 inhibitor than nimesulide, with a potency that was comparable to the reference drug, celecoxib. Iodination at the ortho- or meta-position of the phenoxy ring was associated with a substantial loss of COX-2 inhibitory activity. Transport studies across Caco-2 cell monolayers in the presence and absence of a P-glycoprotein (P-gp) inhibitor, verapamil, indicated that the para-iodo-substituted analog was not a P-gp transport substrate; this feature is a prerequisite for potential in vivo brain imaging compounds. The para-iodo-substituted analog of nimesulide appears to be an attractive candidate for the development of radioiodine-labeled tracers for in vivo brain imaging of COX-2 levels. PMID:27325447

  15. Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.

    Science.gov (United States)

    Perlikowska, Renata; Piekielna, Justyna; Gentilucci, Luca; De Marco, Rossella; Cerlesi, Maria Camilla; Calo, Girolamo; Artali, Roberto; Tömböly, Csaba; Kluczyk, Alicja; Janecka, Anna

    2016-02-15

    Cyclic pentapeptide Tyr-c[D-Lys-Phe-Phe-Asp]NH2, based on the structure of endomorphin-2 (EM-2), which shows high affinity to the μ-opioid receptor (MOR) and a very strong antinociceptive activity in mice was used as a parent compound for the structure-activity relationship studies. In this report we synthesized analogs of a general sequence Dmt-c[D-Lys-Xaa-Yaa-Asp]NH2, with D-1- or D-2-naphthyl-3-alanine (D-1-Nal or D-2-Nal) in positions 3 or 4. In our earlier papers we have indicated that replacing a phenylalanine residue by the more extended aromatic system of naphthylalanines may result in increased bioactivities of linear analogs. The data obtained here showed that only cyclopeptides modified in position 4 retained the sub-nanomolar MOR and nanomolar κ-opioid receptor (KOR) affinity, similar but not better than that of a parent cyclopeptide. In the in vivo mouse hot-plate test, the most potent analog, Dmt-c[D-Lys-Phe-D-1-Nal-Asp]NH2, exhibited higher than EM-2 but slightly lower than the cyclic parent peptide antinociceptive activity after peripheral (ip) and also central administration (icv). Conformational analyses in a biomimetic environment and molecular docking studies disclosed the structural determinants responsible for the different pharmacological profiles of position 3- versus position 4-modified analogs. PMID:26785295

  16. Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer.

    Science.gov (United States)

    Agarwal, Hitesh K; Khalil, Ahmed; Ishita, Keisuke; Yang, Weilian; Nakkula, Robin J; Wu, Lai-Chu; Ali, Tehane; Tiwari, Rohit; Byun, Youngjoo; Barth, Rolf F; Tjarks, Werner

    2015-07-15

    A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogs and will profoundly impact future design strategies for these agents. PMID:26087030

  17. Synthesis and Anti-HIV-1 Evaluation of Some Novel MC-1220 Analogs as Non-Nucleoside Reverse Transcriptase Inhibitors

    DEFF Research Database (Denmark)

    Loksha, Yasser M; Pedersen, Erik B; Loddo, Roberta;

    2016-01-01

    Some novel MC-1220 analogs were synthesized by condensation of 4,6-dichloro-N-methylpyrimidin-2-amine derivatives (1a,b and 15) and/or 4-chloro-6-methoxy-N,N,5-trimethylpyrimidin-2-amine (2a) with the sodium salt of 2,6-difluorophenylacetonitrile followed by treatment with aqueous sodium hydroxide...

  18. Synthesis and evaluation of novel lipidated neuromedin U analogs with increased stability and effects on food intake

    DEFF Research Database (Denmark)

    Dalbøge, Louise S.; Pedersen, Søren L.; van Witteloostuijn, Søren Blok;

    2015-01-01

    Neuromedin U (NMU) is a 25 amino acid peptide expressed and secreted in the brain and gastrointestinal tract. Data have shown that peripheral administration of human NMU decreases food intake and body weight and improves glucose tolerance in mice, suggesting that NMU receptors constitute a possible...... was investigated using a human embryonic kidney 293-based inositol phosphate accumulation assay. All lipidated analogs had preserved in vitro activity on both NMU receptors with potency improving as the lipidation site was moved away from the receptor-interacting C-terminal octapeptide segment. In vivo efficacy...... was assessed in lean mice as reduction in food intake after acute subcutaneous administration of 1, 0.3, 0.1, and 0.03μmol/kg. These lipidated NMU analogs prolonged the anorectic effect of NMU in a dose-dependent manner. This was likely an effect of improved pharmacokinetic properties because of improved vitro...

  19. Synthesis, biological evaluation and molecular modeling studies of psammaplin A and its analogs as potent histone deacetylases inhibitors and cytotoxic agents.

    Science.gov (United States)

    Wen, Jiachen; Bao, Yu; Niu, Qun; Liu, Jiang; Yang, Jinyu; Wang, Wanqiao; Jiang, Tao; Fan, Yinbo; Li, Kun; Wang, Jian; Zhao, Linxiang; Liu, Dan

    2016-09-01

    In this study, a concise synthetic method of psammaplin A was achieved from 3-bromo-4-hydroxybenzaldahyde and hydantoin through a four-step synthesis via Knoevenagel condensation, hydrolysis, oximation and amidation in 37% overall yield. A collection of novel psammaplin A analogs focused on the variations of substituents at the benzene ring and modifications at the oxime moiety were synthesized. Among all the synthesized compounds, 5d and 5e showed better HDAC inhibition than psammaplin A and comparable cytotoxicity against four cancer cell lines (PC-3, MCF-7, A549 and HL-60). Molecular docking and dynamics simulation revealed that (i) hydrogen atom of the oxime group interacts with Asp99 of HDAC1 through a water bridged hydrogen bond and (ii) a hydroxyl group is optimal attached on the para-position of benzene, interacting with Glu203 at the entrance to the active site tunnel.

  20. Analog computing

    CERN Document Server

    Ulmann, Bernd

    2013-01-01

    This book is a comprehensive introduction to analog computing. As most textbooks about this powerful computing paradigm date back to the 1960s and 1970s, it fills a void and forges a bridge from the early days of analog computing to future applications. The idea of analog computing is not new. In fact, this computing paradigm is nearly forgotten, although it offers a path to both high-speed and low-power computing, which are in even more demand now than they were back in the heyday of electronic analog computers.

  1. Human neutrophil elastase peptide sensors conjugated to cellulosic and nanocellulosic materials: part I, synthesis and characterization of fluorescent analogs

    Science.gov (United States)

    Here we describe the synthesis and characterization of peptide conjugated cellulose and nanocellulose materials as sensors for fluorescent detection of human neutrophil elastase (HNE). The cellulose sensor surfaces selected are filter paper (FP) and print cloth (PC) fabric, which are composed of pro...

  2. Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists.

    Science.gov (United States)

    Gim, Hyo Jin; Cheon, Ye-Jin; Ryu, Jae-Ha; Jeon, Raok

    2011-05-15

    A series of benzoxazole or benzothiazole containing indole analogs, 6-alkoxyindole-2-carboxylic acids and 5-alkoxy-3-indolylacetic acids, were synthesized as novel candidates of PPARγ/δ dual agonists and their ligand activities for PPAR subtypes (α, γ, and δ) were investigated. In transient transactivation assay, several compounds activated PPARγ and δ with little activity of PPARα. Putative binding mode of the compounds 1a and 2a in the active site of PPARγ was similar with that of rosiglitazone and the molecular modeling provides molecular insight to the observed activity.

  3. Interferon Analogs

    NARCIS (Netherlands)

    Poelstra, Klaas; Prakash, Jai; Beljaars, Eleonora; Bansal, Ruchi

    2015-01-01

    The invention relates to the field of medicine. Among others, it relates to biologically active analogs of interferons (IFNs) which show less unwanted side-effects and to the therapeutic uses thereof. Provided is an IFN analog, wherein the moiety mediating binding to its natural receptor is at least

  4. Interferon Analogs

    NARCIS (Netherlands)

    Poelstra, Klaas; Prakash, Jai; Beljaars, Leonie; Bansal, Ruchi

    2010-01-01

    The invention relates to the field of medicine. Among others, it relates to biologically active analogs of interferons (IFNs) which show less unwanted side-effects and to the therapeutic uses thereof. Provided is an IFN analog, wherein the moiety mediating binding to its natural receptor is at least

  5. Synthesis of a fluorescence resonance energy transfer-based probe containing a tricyclic nucleoside analog for single nucleotide polymorphism typing.

    Science.gov (United States)

    Hayai, Aya; Maeda, Yusuke; Ueno, Yoshihito

    2016-08-01

    Here, we report the synthesis of a fluorescence resonance energy transfer (FRET)-based probe for single nucleotide polymorphism (SNP) typing. The probe contains a fluorescent tricyclic base, 8-amino-3-(2,3-dihydroxypropyl)imidazo[4',5':5,6]pyrido[2,3-d]pyrimidine, as a donor molecule and 7-diethylaminocoumarin-3-carboxylic acid as an acceptor molecule. FRET was observed between the donor and acceptor molecules on the probe. The identity of the target bases on DNA and RNA strands could be determined using the probe. PMID:27329795

  6. Imidase catalyzing desymmetric imide hydrolysis forming optically active 3-substituted glutaric acid monoamides for the synthesis of gamma-aminobutyric acid (GABA) analogs.

    Science.gov (United States)

    Nojiri, Masutoshi; Hibi, Makoto; Shizawa, Hiroaki; Horinouchi, Nobuyuki; Yasohara, Yoshihiko; Takahashi, Satomi; Ogawa, Jun

    2015-12-01

    The recent use of optically active 3-substituted gamma-aminobutyric acid (GABA) analogs in human therapeutics has identified a need for an efficient, stereoselective method of their synthesis. Here, bacterial strains were screened for enzymes capable of stereospecific hydrolysis of 3-substituted glutarimides to generate (R)-3-substituted glutaric acid monoamides. The bacteria Alcaligenes faecalis NBRC13111 and Burkholderia phytofirmans DSM17436 were discovered to hydrolyze 3-(4-chlorophenyl) glutarimide (CGI) to (R)-3-(4-chlorophenyl) glutaric acid monoamide (CGM) with 98.1% enantiomeric excess (e.e.) and 97.5% e.e., respectively. B. phytofirmans DSM17436 could also hydrolyze 3-isobutyl glutarimide (IBI) to produce (R)-3-isobutyl glutaric acid monoamide (IBM) with 94.9% e.e. BpIH, an imidase, was purified from B. phytofirmans DSM17436 and found to generate (R)-CGM from CGI with specific activity of 0.95 U/mg. The amino acid sequence of BpIH had a 75% sequence identity to that of allantoinase from A. faecalis NBRC13111 (AfIH). The purified recombinant BpIH and AfIH catalyzed (R)-selective hydrolysis of CGI and IBI. In addition, a preliminary investigation of the enzymatic properties of BpIH and AfIH revealed that both enzymes were stable in the range of pH 6-10, with an optimal pH of 9.0, stable at temperatures below 40 °C, and were not metalloproteins. These results indicate that the use of this class of hydrolase to generate optically active 3-substituted glutaric acid monoamide could simplify the production of specific chiral GABA analogs for drug therapeutics.

  7. Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza A agents.

    Science.gov (United States)

    Lin, Cai; Sun, Chenghai; Liu, Xiao; Zhou, Yiqian; Hussain, Muzammal; Wan, Junting; Li, Minke; Li, Xue; Jin, Ruiliang; Tu, Zhengchao; Zhang, Jiancun

    2016-05-01

    Among many subtypes of influenza A viruses, influenza A(H1N1) and A(H3N2) subtypes are currently circulating among humans (WHO report 2014-15). Therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. To this regard, the design and synthesis of nucleoside analog inhibitors as potential anti-influenza A agents is a very active field of research nowadays. In this study, we designed and synthesized a series of hitherto unknown 6-methyl-7-substituted-7-deaza purine nucleoside analogs, and evaluated for their biological activities against influenza A virus strains, H1N1 and H3N2. From the viral inhibition assay, we identified some effective compounds, among which, compounds 5x (IC50 = 5.88 μM and 6.95 μM for H1N1 and H3N2, respectively) and 5z (IC50 = 3.95 μM and 3.61 μM for H1N1 and H3N2, respectively) demonstrated potent anti-influenza A activity. On the basis of selectivity index, we conceive that compound 5x may serve as a chemical probe of interest for further lead optimization studies with a general aim of developing novel and effective anti-influenza A virus agents. PMID:26802557

  8. Analog earthquakes

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, R.B. [Center for Nuclear Waste Regulatory Analyses, San Antonio, TX (United States)

    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.

  9. Synthesis of analogs of juvenile hormone on the basis of the telomerization reaction of piperylene with sulfones

    Energy Technology Data Exchange (ETDEWEB)

    Tolstikov, G.A.; Rozentsvet, O.A.; Pantukh, B.I.; Khalilov, L.M.

    1986-10-20

    In continuing the work on the study of the telomerization of 1,3-dienes with sulfones containing an active H atom, and also with the aim of synthesizing analogs of juvenile hormone (JH) based on the telomers obtained, they studied the catalytic telomerization of 1,3-pentadiene (piperylene) with ..beta..-substituted sulfonates. It was established that trans-piperlyene participates in the telomerization reaction with sulfones in the presence of the catalytic system PdCl/sub 2/(Ph/sub 3/P)/sub 2/-PhONa. Methyl 2-phenylsulfonyl-3,7-dimethyl-4(E), 9-decadienecarboxylate (II) is formed in a yield of 65% by the reaction of methyl phenylsulfonylacetate (I) with piperylene in the course of 20 h at 85/sup 0/C. The presence of absorption bands at 920 (CH/sub 2/=C) and 980 cm/sup -1/ (E-CH=CH) in the IR spectrum of compound (II) and the presence of a group of multiplet signals at delta 4.8-5.3 ppm in the PMR spectrum, corresponding to five protons of double bonds, indicate the addition of two molecules of piperylene to the molecule of the sulfone (I). The oxidation with oxygen on a Pd/Cu-catalyst proceeds smoothly to the methyl ketone (III); this clearly confirms the presence of the terminal C=C bond in the telomer (II). In the PMR spectrum of (II), notice is taken of the group of signals in the region of 3.30-3.53 ppm corresponding to three methoxy protons. There are three pairs of doublets (J = 7 Hz) in the region of 0.1-1.3 ppm which correspond to the methyl group. The complexity of the PMR spectrum is probably explained by the fact that the reaction leads to the formation of a complex mixture of diastereoisomers. As was to be expected, methyl 3,7-dimethyl-4,9-decadienoate (IV) is formed as the sole product with a yield of 70% in the desulfonation of the telomer (II) using Na/Hg in methanol according to the method of (5); the structure of (IV) was established with the aid of /sup 13/C NMR spectroscopy.

  10. Synthesis, structure-activity relationship and molecular docking of cyclohexenone based analogous as potent non-nucleoside reverse-transcriptase inhibitors

    Science.gov (United States)

    Nazar, Muhammad Faizan; Abdullah, Muhammad Imran; Badshah, Amir; Mahmood, Asif; Rana, Usman Ali; Khan, Salah Ud-Din

    2015-04-01

    The chalcones core in compounds is advantageously chosen effective synthons, which offer exciting perspectives in biological and pharmacological research. The present study reports the successful development of eight new cyclohexenone based anti-reverse transcriptase analogous using rational drug design synthesis principles. These new cyclohexenone derivatives (CDs) were synthesized by following a convenient route of Robinson annulation, and the molecular structure of these CDs were later confirmed by various analytical techniques such as 1H NMR, 13C NMR, FT-IR, UV-Vis spectroscopy and mass spectrometry. All the synthesized compounds were screened theoretically and experimentally against reverse transcriptase (RT) and found potentially active reverse transcriptase (RT) inhibitors. Of the compounds studied, the compound 2FC4 showed high interaction with RT at non-nucleoside binding site, contributing high free binding energy (ΔG -8.01 Kcal) and IC50 (0.207 μg/ml), respectively. Further results revealed that the compounds bearing more halogen groups, with additional hydrophobic character, offered superior anti-reverse transcriptase activity as compared to rest of compounds. It is anticipate that the present study would be very useful for the selection of potential reverse transcriptase inhibitors featuring inclusive pharmacological profiles.

  11. Synthesis of some glycoside analogs and related compounds from 9-amino-6-(methylthio)-9H-purine.

    Science.gov (United States)

    Temple, C; Kussner, C L; Montgomery, J A

    1975-12-01

    Additional information on the anticancer activity of 9-amino-9H-purine-6(1H)-thione and its derivatives was sought by the synthesis of some 9-(substituted amino)-6-(methylthio)-9H-purines in which the 9-substituent contained functional groups capable of either reversible or irreversible binding with an enzymatic site. Condensation of 9-amino-6-(methylthio)-9H-purine (1) with some carbonyl compounds followed by hydride reduction of the azomethine linkage in the intermediates leads to the 2-pyrrolylmethyl (8), 2,3,4-trihydroxybutyl (10), and the 1,5-dihydroxy-2- and 3-pentyl (11 and 12) compounds. A 4-hydroxybutyl derivative (13) was obtained by alkylation of 18, the 9-acetyl derivative of 1, with 4-chlorobutyl acetate followed by saponification. The cyclization of 13 and 11 with a sulfonyl chloride gave the 9-pyrrolidin-1-yl (27) and the 9-[2-(tosyloxymethyl)pyrrolidin-1-yl] (28), respectively. Acylation of 1 with ethyl L-2-pyrrolidine-5-carboxylate and ethyl 1-methyl-5-pyrrolidone-3-carboxylate, respectively, in Me2SO containing NaH gave the corresponding amides 15 and 17. Alkylation of 18 with 1-bromo-2-chloroethane and epichlorohydrin gave the N-(2-chloroethyl) and N-(1,2-epoxy-3-propyl) derivatives 19 and 20. The chloro group of the chlorobutyl derivative of 18 was displaced with KSCN and NaN3, respectively, to give the thiocyanate and azido derivatives 23 and 24. Hydrogenation of the latter gave the amine (25), which was acylated with ethyl chloroformate to give the (ethoxycarbonyl)amino compound 26. None of these compounds showed activity against L1210 leukemia cells implanted ip in mice on a single-dose schedule, suggesting that the activity observed in the simpler 9-aminopurines resulted from cleavage of the hydrazino linkage to give pH-purine-6(1H)-thione. PMID:1195279

  12. Synthesis and biological evaluation of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd)

    DEFF Research Database (Denmark)

    Hrdlicka, Patrick J; Jepsen, Jan S; Wengel, Jesper;

    2005-01-01

    A series of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd) and its uracil analog (EUrd) have been synthesized. While none of the conformationally restricted analogs displayed anticancer activity, 5-iodo-EUrd and 5-bromo-EUrd disp...

  13. 6-Methylpurine derived sugar modified nucleosides: Synthesis and in vivo antitumor activity in D54 tumor expressing M64V-Escherichia coli purine nucleoside phosphorylase.

    Science.gov (United States)

    Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Parker, William B; Allan, Paula W; Secrist, John A

    2016-01-27

    Impressive antitumor activity has been observed with fludarabine phosphate against tumors that express Escherichia coli purine nucleoside phosphorylase (PNP) due to the liberation of 2-fluoroadenine in the tumor tissue. 6-Methylpurine (MeP) is another cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving E. coli PNP. The prototype MeP releasing prodrug 9-(2-deoxy-β-d-ribofuranosyl)-6-methylpurine (1) [MeP-dR] has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify a combination of non-toxic MeP prodrugs and non-human adenosine glycosidic bond cleaving enzymes. The two best MeP-based substrates with M64V-E coli PNP, a mutant which was engineered to tolerate modification at the 5'-position of adenosine and its analogs, were 9-(6-deoxy-α-l-talofuranosyl)-6-methylpurine (3) [methyl(talo)-MeP-R] and 9-(α-l-lyxofuranosyl)6-methylpurine (4) [lyxo-MeP-R]. The detailed synthesis methyl(talo)-MeP-R and lyxo-MeP-R, and the evaluation of their substrate activity with 4 enzymes not normally associated with cancer patients is described. In addition, we have determined the intraperitoneal pharmacokinetic (ip-PK) properties of methyl(talo)-MeP-R and have determined its in vivo bystander activity in mice bearing D54 tumors that express M64V PNP. The observed good in vivo bystander activity of [methyl(talo)-MeP-R/M64V-E coli PNP combination suggests that these agents could be useful for the treatment of cancer.

  14. Aplysinopsin Analogs: Synthesis and Anti-proliferative Activity of Substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones

    OpenAIRE

    Reddy, Y. Thirupathi; Reddy, P. Narsimha; Koduru, Srinivas; Damodaran, Chendil; Crooks, Peter A.

    2010-01-01

    A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC50 ...

  15. Synthesis of a novel 4H-pyran analog as minor groove binder to DNA using ethidium bromide as fluorescence probe

    Science.gov (United States)

    Ramana, M. M. V.; Betkar, Rahul; Nimkar, Amey; Ranade, Prasanna; Mundhe, Balaji; Pardeshi, Sachin

    2016-01-01

    In the present work, isopropyl-6-amino-4-(3,5-bis(trifluoromethyl)phenyl)-5-cyano-2-methyl-4H-pyran-3-carboxylate (4H-pyran analog) has been synthesized by a three component reaction catalyzed by CsOH/γ-Al2O3 and characterized. The interaction of 4H-pyran analog with herring sperm DNA (hs DNA) under physiological conditions (phosphate buffer of pH 7.2) was investigated by UV absorption, FT-IR, fluorescence, 31P NMR and circular dichroism (CD) spectroscopy. Fluorescence quenching results reveal that static quenching mechanism is involved in binding between 4H-pyran analog and hs DNA. The calculated thermodynamic parameters (ΔH° and ΔS°) indicate that hydrogen bonding plays a major role in binding between them. UV absorption and fluorescence shows the binding mode of 4H-pyran analog with hs DNA as non-intercalative. According to the IR spectroscopy, 4H-pyran analog binds to guanine, thymine, adenine bases of hs DNA but not to phosphate backbone of hs DNA which is also in good agreement with 31P NMR results. CD and competitive binding experiment results confirms the minor groove binding of 4H-pyran analog to hs DNA.

  16. Synthesis of naturally occurring iminosugars from D-fructose by the use of a zinc-mediated fragmentation reaction

    DEFF Research Database (Denmark)

    Lauritsen, Anne; Madsen, Robert

    2006-01-01

    A short synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) and a formal synthesis of australine are described. In both cases, D-fructose is employed as the starting material and converted into a protected methyl 6-deoxy-6-iodo-furanoside. Zinc-mediated fragmentation produces an unsaturated...... ketone which serves as a key building block for both syntheses. Ozonolysis, reductive amination with benzylamine and deprotection affordfs 1,4-dideoxy-1,4-imino-D-arabinitol in only 7 steps and 11% overall yield from D-fructose. Alternatively, reductive amination with homoallylamine, ring...

  17. Synthesis and in vitro evaluation of water-soluble 1,4-diphenethylpiperazine analogs as novel inhibitors of the vesicular monoamine transporter-2.

    Science.gov (United States)

    Nickell, Justin R; Culver, John P; Janganati, Venumadhav; Zheng, Guangrong; Dwoskin, Linda P; Crooks, Peter A

    2016-09-15

    A small library of 1,4-diphenethylpiperazine analogs was synthesized and evaluated for inhibition of [(3)H]dihydrotetrabenazine binding and [(3)H]dopamine uptake at the vesicular monoamine transporter-2 (VMAT2). Results from these studies identified three novel molecules, 6b, 6e and 9a (Ki=35nM, 48nM and 37nM, respectively) that exhibit similar potency for inhibition of VMAT2 function compared with lobelane (Ki=45nM), and importantly, have enhanced water-solubility when compared to the previously reported 1,4-diphenethylpiperidine analogs. These 1,4-diphenethylpiperazine analogs constitute promising new leads in the discovery of potential pharmacotherapeutics for treatment of methamphetamine use disorders.

  18. Synthesis and tritium labeling of the highly potent mast cell-degranulating substance P analog H-Arg-Pro-Lys-Pro-NH-C sub 12 H sub 25

    Energy Technology Data Exchange (ETDEWEB)

    Bienert, M.; Oehlke, J.; Niedrich, H. (Academy of Sciences of GDR, Berlin (Germany, F.R.). Inst. of Drug Research); Mittag, E. (Zentralinstitut fuer Kernforschung, Rossendorf (Germany, F.R.))

    1990-12-01

    Tritium labeling of the mast cell degranulating substance P analog H-Arg-Pro-Lys(3,4-{sup 3}H-Pro)-NH-C{sub 12}H{sub 25} by catalytic saturation of the dehydroproline (Dhp{sup 1}) double bond is described. Catalytic tritiation in water afforded the radioactive analog with a specific activity of 1.07 TBq/mmol. Tenfold enhancement of the catalyst-to-substrate ratio resulted in a reduced specific activity of 0.74 TBq/mmol. (author).

  19. Synthesis and biological evaluation of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd)

    DEFF Research Database (Denmark)

    Hrdlicka, Patrick J; Jepsen, Jan S; Nielsen, Claus;

    2005-01-01

    A series of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd) were designed to overcome the strict substrate specificity of the activating uridine-cytidine kinase. EUrd, ECyd and target nucleosides were obtained using a short...

  20. Synthesis and Anti-HIV Activity of Trisubstituted (3'R, 4'R)-3',4'- Di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) Analogs

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To further explore the potential of DCK analogs as anti-HIV drug candidates, ten new tri-substituted (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives (4-13)were designed, synthesized, and evaluated against HIV replication in MT4 cells and H9 lymphocytes.

  1. Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3',5'difluorophenyl)-alanine.

    Science.gov (United States)

    Martín-Gago, Pablo; Rol, Álvaro; Todorovski, Toni; Aragón, Eric; Martin-Malpartida, Pau; Verdaguer, Xavier; Vallès Miret, Mariona; Fernández-Carneado, Jimena; Ponsati, Berta; Macias, Maria J; Riera, Antoni

    2016-01-01

    Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1-5). We have designed six new Somatostatin analogs with L-3-(3',5'-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor aromatic ring in the network of aromatic interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aqueous solution by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a π-π interaction with the Phe present at 11 or 6, respectively. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin. PMID:27271737

  2. Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3-(3′,5′difluorophenyl)-alanine

    Science.gov (United States)

    Martín-Gago, Pablo; Rol, Álvaro; Todorovski, Toni; Aragón, Eric; Martin-Malpartida, Pau; Verdaguer, Xavier; Vallès Miret, Mariona; Fernández-Carneado, Jimena; Ponsati, Berta; Macias, Maria J.; Riera, Antoni

    2016-01-01

    Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1–5). We have designed six new Somatostatin analogs with L-3-(3′,5′-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor aromatic ring in the network of aromatic interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aqueous solution by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a π-π interaction with the Phe present at 11 or 6, respectively. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin. PMID:27271737

  3. Diversity-oriented synthesis of medicinally important 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives and higher analogs.

    Science.gov (United States)

    Kotha, Sambasivarao; Deodhar, Deepak; Khedkar, Priti

    2014-12-01

    1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid (Tic) is a constrained analog of phenylalanine (Phe). The Tic unit has been identified as a core structural element present in several peptide-based drugs and forms an integral part of various biologically active compounds. This report covers the biological significance of the Tic core and provides a detailed account of various synthetic approaches available for the construction of Tic derivatives. Along with the traditional methods such as the Pictet-Spengler and Bischler-Nepieralski reactions, we cover various recent approaches such as enyne metathesis, [2 + 2 + 2] cycloaddition and the Diels-Alder reaction to generate Tic derivatives. In addition, syntheses of higher analogs of Tic are also discussed. PMID:25299735

  4. The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6 beta-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid.

    Science.gov (United States)

    Jones, S R; Kinney, W A; Zhang, X; Jones, L M; Selinsky, B S

    1996-10-01

    Analogs of the aminosterol antimicrobial agent squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from cis to trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3 alpha and 3 beta addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics. PMID:8910969

  5. Synthesis and membrane behavior of a new class of unnatural phospholipid analogs useful as phospholipase A2 degradable liposomal drug carriers

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jørgensen, Kent

    2005-01-01

    A new and unnatural type of lipid analogs with the phosphocholine and phosphoglycerol head groups linked to the C-2 position of the glycerol moiety have been synthesized and the thermodynamic lipid membrane behavior has been investigated using differential scanning calorimetry. From the heat capa...... results also suggest new approaches to rationally design liposomal drug carries that can undergo a triggered activation in diseased tissue by overexpressed PLA2....

  6. A simplified synthesis of novel dictyostatin analogs with in vitro activity against epothilone B resistant cells and antiangiogenic activity in zebrafish embryos

    OpenAIRE

    Vollmer, Laura L.; Jiménez, Maria; Camarco, Daniel P.; Wei ZHU; Daghestani, Hikmat N.; Balachandran, Raghavan; Reese, Celeste E.; Lazo, John S.; Hukriede, Neil A.; Curran, Dennis P.; Day, Billy W; Vogt, Andreas

    2011-01-01

    The natural product (−)-dictyostatin is a microtubule stabilizing agent that potently inhibits the growth of human cancer cells including paclitaxel-resistant clones. Extensive structure-activity relationship studies have revealed several regions of the molecule that could be altered without loss of activity. The most potent synthetic dictyostatin analog described to date, 6-epi-dictyostatin, has in vivo antitumor activity against human breast cancer xenografts superior to paclitaxel. Despite...

  7. Analog and VLSI circuits

    CERN Document Server

    Chen, Wai-Kai

    2009-01-01

    Featuring hundreds of illustrations and references, this book provides the information on analog and VLSI circuits. It focuses on analog integrated circuits, presenting the knowledge on monolithic device models, analog circuit cells, high performance analog circuits, RF communication circuits, and PLL circuits.

  8. Analogical Reasoning in the Engineering Design Process and Technology Education Applications

    OpenAIRE

    Daugherty, Jenny; Mentzer, Nathan

    2008-01-01

    This synthesis paper discusses the research exploring analogical reasoning, the role of analogies in the engineering design process, and educational applications for analogical reasoning. Researchers have discovered that analogical reasoning is often a fundamental cognitive tool in design problem solving. Regarding the possible role of analogical reasoning in the context of technology education; analogies may be a useful tool to develop student’s design skills, teach abstract or complex conce...

  9. Science Teachers' Analogical Reasoning

    Science.gov (United States)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-08-01

    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 introduce analogies in their lessons. Both aspects have been discussed in the literature in the last few decades. However, almost nothing is known about how teachers draw their own analogies for instructional purposes or, in other words, about how they reason analogically when planning and conducting teaching. This is the focus of this paper. Six secondary teachers were individually interviewed; the aim was to characterize how they perform each of the analogical reasoning subprocesses, as well as to identify their views on analogies and their use in science teaching. The results were analyzed by considering elements of both theories about analogical reasoning: the structural mapping proposed by Gentner and the analogical mechanism described by Vosniadou. A comprehensive discussion of our results makes it evident that teachers' content knowledge on scientific topics and on analogies as well as their pedagogical content knowledge on the use of analogies influence all their analogical reasoning subprocesses. Our results also point to the need for improving teachers' knowledge about analogies and their ability to perform analogical reasoning.

  10. Synthesis and biological evaluation of a novel class of curcumin analogs as anti-inflammatory agents for prevention and treatment of sepsis in mouse model

    Directory of Open Access Journals (Sweden)

    Zhao C

    2015-03-01

    Full Text Available Chengguang Zhao,1,2,* Yali Zhang,1,2,* Peng Zou,1 Jian Wang,3 Wenfei He,2 Dengjian Shi,2 Huameng Li,2 Guang Liang,2 Shulin Yang1 1School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, 2Chemical Biology Research Center, School of Pharmaceutical Sciences, 3Department of Orthopedics, The 1st Affiliated Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A novel class of asymmetric mono-carbonyl analogs of curcumin (AMACs were synthesized and screened for anti-inflammatory activity. These analogs are chemically stable as characterized by UV absorption spectra. In vitro, compounds 3f, 3m, 4b, and 4d markedly inhibited lipopolysaccharide (LPS-induced expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in a dose-dependent manner, with IC50 values in low micromolar range. In vivo, compound 3f demonstrated potent preventive and therapeutic effects on LPS-induced sepsis in mouse model. Compound 3f downregulated the phosphorylation of extracellular signal-regulated kinase (ERK1/2 MAPK and suppressed IκBα degradation, which suggests that the possible anti-inflammatory mechanism of compound 3f may be through downregulating nuclear factor kappa binding (NF-κB and ERK pathways. Also, we solved the crystal structure of compound 3e to confirm the asymmetrical structure. The quantitative structure–activity relationship analysis reveals that the electron-withdrawing substituents on aromatic ring of lead structures could improve activity. These active AMACs represent a new class of anti-inflammatory agents with improved stability, bioavailability, and potency compared to curcumin. Our results suggest that 3f may be further developed as a potential agent for prevention and treatment of sepsis or other inflammation-related diseases. Keywords: asymmetric mono-carbonyl analogs of curcumin (AMACs

  11. Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors.

    Science.gov (United States)

    Bruel, Amélie; Bénéteau, Romain; Chabanne, Mylène; Lozach, Olivier; Le Guevel, Rémy; Ravache, Myriam; Bénédetti, Hélène; Meijer, Laurent; Logé, Cédric; Robert, Jean-Michel

    2014-11-01

    New pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs were synthesized and their inhibitory activities against DYRK1A, CDK5/p25, GSK3α/β and p110-α isoform of PI3K evaluated using harmine as reference. Both furan-2-yl 10 and pyridin-4-yl 19 from the two different series, exhibited submicromolar IC50 against DYRK1A with no activities against the three other kinases. In addition, compound 10 exhibited antiproliferative activities in the Huh-7, Caco2 and MDA-MB-231 cell lines. PMID:25248682

  12. Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity.

    Science.gov (United States)

    Xu, Yun-Yun; Cao, Yi; Ma, Hailkuo; Li, Huan-Qiu; Ao, Gui-Zhen

    2013-01-15

    A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed the most potent EGFR inhibitory activity (IC(50) = 0.43 μM and 1.54 μM, respectively). Molecular docking of I(12) into EGFR TK active site was also performed. This inhibitor nicely fitting the active site might well explain its excellent inhibitory activity.

  13. Design, synthesis, and in vitro evaluation of cytotoxic analogs of bombesin-like peptides containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin

    OpenAIRE

    Nagy Attila; Armatis, Patricia; Cai, Ren-Zhi; Szepesházi Károly; Schally, Andrew V.; Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)

    1997-01-01

    Five peptide fragments, based on the C-terminal sequence of bombesin (BN)-(6-14) or BN-(7-14), were selected as carriers for radicals doxorubicin (DOX) and 2-pyrrolino-DOX to create hybrid cytotoxic analogs. All these compounds had a reduced peptide bond (CH2-NH or CH2-N) between positions 13 (Phe or Leu) and 14 (Phe, Leu, or Tac) (Tac = thiazolidine-4-carboxylic acid). Three pseudononapeptide carriers contained N-terminal d-Phe or d-Tpi at position 6 (Tpi = 2,3,4,9-tetrahydro-1H-pyrido[3,4-b...

  14. Analogical Reasoning in the Engineering Design Process and Technology Education Applications

    Science.gov (United States)

    Daugherty, Jenny; Mentzer, Nathan

    2008-01-01

    This synthesis paper discusses the research exploring analogical reasoning, the role of analogies in the engineering design process, and educational applications for analogical reasoning. Researchers have discovered that analogical reasoning is often a fundamental cognitive tool in design problem solving. Regarding the possible role of analogical…

  15. Intuitive analog circuit design

    CERN Document Server

    Thompson, Marc

    2013-01-01

    Intuitive Analog Circuit Design outlines ways of thinking about analog circuits and systems that let you develop a feel for what a good, working analog circuit design should be. This book reflects author Marc Thompson's 30 years of experience designing analog and power electronics circuits and teaching graduate-level analog circuit design, and is the ideal reference for anyone who needs a straightforward introduction to the subject. In this book, Dr. Thompson describes intuitive and ""back-of-the-envelope"" techniques for designing and analyzing analog circuits, including transistor amplifi

  16. Synthesis of nisin AB dicarba analogs using ring-closing metathesis: influence of sp(3) versus sp(2) hybridization of the α-carbon atom of residues dehydrobutyrine-2 and dehydroalanine-5 on the lipid II binding affinity.

    Science.gov (United States)

    Slootweg, Jack C; van Herwerden, Eric F; van Doremalen, Mark F M; Breukink, Eefjan; Liskamp, Rob M J; Rijkers, Dirk T S

    2015-06-01

    Herein the synthesis of two nisin AB dicarba analogs is described, focusing on amino acid modifications at positions 2 and 5. The nisin mimics were synthesized by a combination of solid phase synthesis of the linear peptides, followed by macrocyclization via ring-closing metathesis and fragment assembly by means of solution phase chemistry. The two N-terminal nisin AB-fragment mimics contain either the native dehydrobutyrine (Dhb)/dehydroalanine (Dha) amino acid residues or alanine at position 2 and 5, respectively. The native dehydrobutyrine at position 2 and dehydroalanine at position 5 were introduced as their precursors, namely threonine and serine, respectively, and subsequent dehydration was carried out by EDCI/CuCl as the condensing agent. Both AB-fragment mimics were analyzed in a lipid II binding assay and it was found that the Ala2/Ala5 AB-mimic (2) showed a reduced activity, while the Dhb2/Dha5 AB-mimic (3) was as active as the native AB-fragment (1).

  17. Synthesis of 1-Substituted Carbazolyl-1,2,3,4-tetrahydro- and Carbazolyl-3,4-dihydro-β-carboline Analogs as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Ji-Wang Chern

    2011-02-01

    Full Text Available A series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-b-carboline analogs have been synthesized and evaluated for antitumor activity against human tumor cells including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines. Among these, compounds 2, 6, 7, and 9 exhibited the most potent and selective activity against the tested tumor cells. As for inhibition of topoisomerase II, compounds 1–14 and 18 showed better activity than etoposide. Among them, compounds 3, 4, 7, 9, and 10 exhibited potent activity. The structure and activity relationship (SAR study revealed correlation between carbon numbers of the side chain and biological activities. The molecular complex with DNA for compound 2 was proposed.

  18. Synthesis and Antibacterial Activity of Analogs of 5-Arylidene-3-(4-methylcoumarin-7-yloxyacetylamino-2-thioxo-1,3-thiazoli-din-4-one

    Directory of Open Access Journals (Sweden)

    Nguyen Tien Cong

    2014-09-01

    Full Text Available In an effort to develop new antimicrobial agents, 3-(4-methylcoumarin-7-yloxyacetylamino-2-thioxo-1,3-thiazolidin-4-one (4 was synthesized by reaction of thiocarbonylbisthioglycolic acid with ethyl (4-methyl-2-oxo-2H-chromen-7-yloxyaceto- hydrazide (3, which was prepared in turn from 7-hydroxy-4-methylcoumarin (1. The condensation of compound 4 with different aromatic aldehydes afforded a series of 5-(arylidene-3-(4-methylcoumarin-7-yloxyacetyl-amino-2-thioxo-1,3-thiozolidin-4-one analogs 5a–h. The structures of these synthetic compounds were elucidated on the basis of IR, 1H-NMR and 13C-NMR spectral data and ESI-MS spectrometric analysis. Compounds 5a–h were examined for their antibacterial activity against several strains of Gram-positive and Gram-negative bacteria.

  19. Rh2 (S-1,2-NTTL)4 : A novel Rh2 (S-PTTL)4 analog with lower ligand symmetry for asymmetric synthesis of chiral cyclopropylphosphonates.

    Science.gov (United States)

    Adly, Frady G; Maddalena, Johncarlo; Ghanem, Ashraf

    2014-11-01

    A new series of dirhodium(II) tetracarboxylate was derived from N-1,2-naphthaloyl-(S)-amino acid ligands. In terms of enantioselectivity, Rh2 (S-1,2-NTTL)4 () derived from N-1,2-naphthaloyl-(S)-tert-leucine, was the best-performing catalyst among the new series in the enantioselective synthesis of cyclopropylphosphonate derivatives (up to >99% enantiomeric excess). A predictive model was proposed to justify the observed high enantiomeric induction exhibited by Rh2 (S-1,2-NTTL)4 with donor-acceptor phosphonate carbenoids.

  20. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  1. ( sup 18 F)fluoro-. beta. -fluormethylene-m-tyrosine analogs, potential PET agents for presynaptic dopamine terminals: synthesis and spectroscopic characterization

    Energy Technology Data Exchange (ETDEWEB)

    Murali, D.; Dejesus, O.T.; Sunderland, J.J.; Nickles, R.J. (Wisconsin Univ., Madison, WI (United States). Dept. of Medical Physics)

    1992-08-01

    {sup 18}F-labeled (E)-{beta}-fluoromethylene-DL-m-tyrosine (FMMT) was prepared by the direct reaction of FMMT with ({sup 18}F)acetylhypofluorite (AcOF) resulting in three product isomers. Extensive {sup 1}H, {sup 13}C and {sup 19}F-NMR spectroscopic analysis identified these products to be 2-fluoro, 6-fluoro-FMMT and 2,6-difluoro-FMMT. The HPLC isolated radiochemical EOB yields of these products were 22, 25 and 14%, respectively, based on starting ({sup 18}F)AcOF. The specific activity at the end of a synthesis time of an hour was ca 200 mCi/mmol. With the possible advantage of ''metabolic trapping'' in dopamine nerve terminals via covalent binding to MAO and reduced metabolite formation, ({sup 18}F)F-FMMT may potentially be the optimal PET tracer for CNS dopamine nerve terminals. (author).

  2. Synthesis and antitumor activity in vitro of curcumin analogs%姜黄素类似物合成与体外抗肿瘤活性研究

    Institute of Scientific and Technical Information of China (English)

    刘洋; 许建华; 黄秀旺; 刘锋; 吴梅花

    2011-01-01

    Nineteen curcumin analogs were designed and synthesized front aromatic aldehydes and 4-piperidone by claisen-schmidt condensation. Their structures were characterized by 1H-NMR and MS. Their antitumor activities in vitro were evaluated against K562 and SW1116 tumor cell lines by MTT assay. The results showed that compounds 1,2,3,4,5,9,14,18 had significantly better activity against K562 cells than EF-24(IC50 = l. 58 μmol·L-1). Compounds 7,10,11 were stronger than EF-24(IC50 = 11.7μmol ·L-1)on SW1116.%以芳香醛、4-哌啶酮为原料,Claisen-Schimidt缩合制备3,5-(E)-二亚苄基哌啶-4-酮类化合物.采用MTT法测试目标化合物对人类慢性粒细胞白血病急变细胞K562,人结肠癌细胞SW1 116增殖的抑制活性.化合物1-19的结构经核磁和质谱确证,化合物7、10、11对SW1 116的抑制活性比EF-24强,化合物1-5、9、14、18对K562的抑制活性均比EF-24强.

  3. 5'-azido-N-1-naphthylphthalamic acid, a photolabile analog of the auxin transport inhibitor, N-1-naphthylphthalamic acid: synthesis and binding properties

    Energy Technology Data Exchange (ETDEWEB)

    Voet, J.G.; Howley, K.; Shumsky, J.S.

    1987-05-01

    The polar transport of the plant growth regulator, auxin (indole-3-acetic acid, IAAH), is thought to involve the participation of several proteins in the plasma membrane, including a specific, saturable, voltage independent H/sup +//IAA/sup -/ efflux carrier located preferentially at the basal end of each cell. Auxin transport is specifically inhibited by the herbicide, N-1-naphthylphthalamic acid (NPA), which binds specifically to a protein in the plasma membrane, thought to be either the IAA/sup -/ efflux carrier or an allosteric effector protein. They have synthesized and characterized a photolabile analog of NPA, 5'-azido-N-1-naphthylphthalamic acid (Az-NPA). This potential photoaffinity label for the NPA binding protein competes with /sup 3/H-NPA for binding sites on Curcurbita pepo L. (zucchini) stem cell membranes with K/sub j/ = 1.5 x 10/sup -7/ M. The K/sub i/ for NPA under these conditions is 2 x 10/sup -8/M, indicating that the affinity of Az-NPA for the membranes is only 7.5 fold lower than NPA. While the binding of 4.6 x 10/sup -6/ M Az-NPA to NPA binding sites is reversible in the dark, exposure to light results in a 30% loss in /sup 3/H-NPA binding ability. Pretreatment with 10/sup -4/ M NPA protects the membranes against photodestruction of /sup 3/H-NPA binding sites by Az-NPA, supporting the conclusion that Az-NPA destroys these sites by specific covalent attachment.

  4. Insulin analogs and cancer

    Directory of Open Access Journals (Sweden)

    Laura eSciacca

    2012-02-01

    Full Text Available Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R, prevalent activation of the ERK rather than the AKT intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to IR but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin

  5. Analog circuit design

    CERN Document Server

    Dobkin, Bob

    2012-01-01

    Analog circuit and system design today is more essential than ever before. With the growth of digital systems, wireless communications, complex industrial and automotive systems, designers are being challenged to develop sophisticated analog solutions. This comprehensive source book of circuit design solutions aids engineers with elegant and practical design techniques that focus on common analog challenges. The book's in-depth application examples provide insight into circuit design and application solutions that you can apply in today's demanding designs. <

  6. Anti-parallel triplexes: Synthesis of 8-aza-7-deazaadenine nucleosides with a 3-aminopropynyl side-chain and its corresponding LNA analog.

    Science.gov (United States)

    Kosbar, Tamer R; Sofan, Mamdouh A; Waly, Mohamed A; Pedersen, Erik B

    2015-05-15

    The phosphoramidites of DNA monomers of 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine (Y) and 7-(3-aminopropyn-1-yl)-8-aza-7-deazaadenine LNA (Z) are synthesized, and the thermal stability at pH 7.2 and 8.2 of anti-parallel triplexes modified with these two monomers is determined. When, the anti-parallel TFO strand was modified with Y with one or two insertions at the end of the TFO strand, the thermal stability was increased 1.2°C and 3°C at pH 7.2, respectively, whereas one insertion in the middle of the TFO strand decreased the thermal stability 1.4°C compared to the wild type oligonucleotide. In order to be sure that the 3-aminopropyn-1-yl chain was contributing to the stability of the triplex, the nucleobase X without the aminopropynyl group was inserted in the same positions. In all cases the thermal stability was lower than the corresponding oligonucleotides carrying the 3-aminopropyn-1-yl chain, especially at the end of the TFO strand. On the other hand, the thermal stability of the anti-parallel triplex was dramatically decreased when the TFO strand was modified with the LNA monomer analog Z in the middle of the TFO strand (ΔTm=-9.1°C). Also the thermal stability decreased about 6.1°C when the TFO strand was modified with Z and the Watson-Crick strand with adenine-LNA (A(L)). The molecular modeling results showed that, in case of nucleobases Y and Z a hydrogen bond (1.69 and 1.72Ǻ, respectively) was formed between the protonated 3-aminopropyn-1-yl chain and one of the phosphate groups in Watson-Crick strand. Also, it was shown that the nucleobase Y made a good stacking and binding with the other nucleobases in the TFO and Watson-Crick duplex, respectively. In contrast, the nucleobase Z with LNA moiety was forced to twist out of plane of Watson-Crick base pair which is weakening the stacking interactions with the TFO nucleobases and the binding with the duplex part. PMID:25868748

  7. Analog synthetic biology.

    Science.gov (United States)

    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

  8. Analog circuit design for communication SOC

    CERN Document Server

    Tu, Steve Hung-Lung

    2012-01-01

    This e-book provides several state-of-the-art analog circuit design techniques. It presents both empirical and theoretical materials for system-on-a-chip (SOC) circuit design. Fundamental communication concepts are used to explain a variety of topics including data conversion (ADC, DAC, S-? oversampling data converters), clock data recovery, phase-locked loops for system timing synthesis, supply voltage regulation, power amplifier design, and mixer design. This is an excellent reference book for both circuit designers and researchers who are interested in the field of design of analog communic

  9. Analog pulse processor

    Science.gov (United States)

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

    A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

  10. Hydraulic Capacitor Analogy

    Science.gov (United States)

    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…

  11. Digital to Analog Converter

    NARCIS (Netherlands)

    Westra, Jan R.; Annema, Anne J.; Boom, van den Jeroen M.; Dijkmans, Eise C.

    2002-01-01

    A digital to analog converter (DAC) for converting a digital signal (DS) having a maximum voltage range which corresponds to a first supply voltage (UL) into an analog signal (UOUT) having a maximum voltage range which corresponds to a second supply voltage (UH). The first supply voltage (UL) is off

  12. Digital to Analog Converter

    NARCIS (Netherlands)

    Westra, Jan R.; Annema, Anne J.; Boom, van den Jeroen M.; Dijkmans, Eise C.

    2006-01-01

    A digital to analog converter (DAC) for converting a digital signal (DS) having a maximum voltage range which corresponds to a first supply voltage (UL) into an analog signal (UOUT) having a maximum voltage range which corresponds to a second supply voltage (UH). The first supply voltage (UL) is off

  13. Meat analog: a review.

    Science.gov (United States)

    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. PMID:24915320

  14. Troubleshooting analog circuits

    CERN Document Server

    Pease, Robert A

    1991-01-01

    Troubleshooting Analog Circuits is a guidebook for solving product or process related problems in analog circuits. The book also provides advice in selecting equipment, preventing problems, and general tips. The coverage of the book includes the philosophy of troubleshooting; the modes of failure of various components; and preventive measures. The text also deals with the active components of analog circuits, including diodes and rectifiers, optically coupled devices, solar cells, and batteries. The book will be of great use to both students and practitioners of electronics engineering. Other

  15. Analog Module Placement Design Using Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    This paper presents a novel genetic algorithm for analog module placement based on ageneralization of the two-dimensional bin packing problem. The genetic encoding and operators assure that allproblem constraints are always satisfied. Thus the potential problems of adding penalty terms to the costfunction are eliminated so that the search configuration space is drastically decreased. The dedicated costfunction is based on the special requirements of analog integrated circuits. A fractional factorial experimentwas conducted using an orthogonal array to study the algorithm parameters. A meta GA was applied todetermine the optimal parameter values. The algorithm was tested with several local benchmark circuits. Theexperimental results show that the algorithm has better performance than the simulated annealing approachwith satisfactory results comparable to manual placement. This study demonstrates the effectiveness of thegenetic algorithm in the analog module placement problem. The algorithm has been successfully used in alayout synthesis tool.

  16. Challenges in Analogical Reasoning

    CERN Document Server

    Lin, Shih-Yin

    2016-01-01

    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 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

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY); Takahashi, Kazuyuki (Germantown, MD)

    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. Electrical Circuits and Water Analogies

    Science.gov (United States)

    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)

  19. Organic Synthesis in Simulated Interstellar Ice Analogs

    Science.gov (United States)

    Dworkin, Jason P.; Bernstein, Max P.; Sandford, Scott A.; Allamandola, Louis J.; Deamer, David W.; Elsila, Jamie; Zare, Richard N.

    2001-01-01

    Comets and carbonaceous micrometeorites may have been significant sources of organic compounds on the early Earth. Ices on grains in interstellar dense molecular clouds contain a variety of simple molecules as well as aromatic molecules of various sizes. While in these clouds the icy grains are processed by ultraviolet light and cosmic radiation which produces more complex organic molecules. We have run laboratory simulations to identify the types of molecules which could have been generated photolytically in pre-cometary ices. Experiments were conducted by forming various realistic interstellar mixed-molecular ices with and without polycyclic aromatic hydrocarbons (PAHs) at approx. 10 K under high vacuum irradiated with UV light from a hydrogen plasma lamp. The residue that remained after warming to room temperature was analyzed by HPLC, and by laser desorption mass spectrometry. The residue contains several classes of compounds which may be of prebiotic significance.

  20. Analogical Reasoning in Geometry Education

    Science.gov (United States)

    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…

  1. Digital and analog communication systems

    Science.gov (United States)

    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.

  2. Quantum Analog Computing

    Science.gov (United States)

    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.

  3. C-Glycosyl Analogs of Oligosaccharides

    Science.gov (United States)

    Vauzeilles, Boris; Urban, Dominique; Doisneau, Gilles; Beau, Jean-Marie

    This chapter covers the synthesis of a large collection of "C-oligosaccharides ", synthetic analogs of naturally occurring oligosaccharides in which a carbon atom replaces the anomeric, interglycosidic oxygen atom. These non-natural constructs are stable to chemical and enzymatic degradation, and are primarily devised to probe carbohydrate-based biological processes. These mainly target carbohydrate-protein interactions such as the modulation of glycoenzyme (glycosylhydrolases and transferases) activities or the design of ligands for lectin Carbohydrate Recognition Domains. The discussion is based on the key carbon-carbon bond assembling steps on carbohydrate templates: ionic (anionic and cationic chemistries, sigmatropic rearrangements) or radical assemblage, and olefin metathesis. Synthetic schemes in which at least one of the monosaccharide units is constructed by total synthesis or by cyclization of acyclic chiral chains are presented separately in a "partial de novo synthesis" section. The review also provides comments, when they are known, on the conformational and binding properties of these synthetic analogs, as well as their biological behavior when tested.

  4. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    OpenAIRE

    Nádia Rezende Barbosa Raposo; Adilson David da Silva; Raquel da Silva Teixeira; Gustavo Senra Gonçalves de Carvalho; Paula Rafaela Rocha; Danielle Cristina Zimmermann Franco

    2012-01-01

    Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory ac...

  5. Terrestrial Spaceflight Analogs: Antarctica

    Science.gov (United States)

    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.

  6. USW area analogs

    OpenAIRE

    Everett, Keith R.

    2005-01-01

    The purpose of this project is to investigate the feasibility of and methodology for the development of a set of environmental analogs of operational Undersea Warfare (USW) areas within fleet training areas. It is primarily a discussion of the identification of parameters that characterize the tactical USW environment, prioritization of these parameters, identification of existing databases that contain these parameters and an outline of the processes required to extract the desired data fro...

  7. Analogy, Explanation, and Proof

    Directory of Open Access Journals (Sweden)

    John eHummel

    2014-11-01

    Full Text Available 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 (inductive inference that the milk is sour have in common with the (deductive 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 small-seeming difference poses a challenge to the task of marshaling our understanding of analogical reasoning in the service of 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.

  8. A Transiting Jupiter Analog

    CERN Document Server

    Kipping, David M; Henze, Chris; Teachey, Alex; Isaacson, Howard T; Petigura, Erik A; Marcy, Geoffrey W; Buchhave, Lars A; Chen, Jingjing; Bryson, Steve T; Sandford, Emily

    2016-01-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\\pm0.02)$ $R_{\\mathrm{Jup}}$, a low orbital eccentricity ($0.06_{-0.04}^{+0.10}$) and an equilibrium temperature of $(131\\pm3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric ...

  9. The Age of Analog Networks

    OpenAIRE

    Mattiussi, Claudio; Swiss Federal Institute of Technology in Lausanne (EPFL); Marbach, Daniel; Swiss Federal Institute of Technology in Lausanne (EPFL); Dürr, Peter; Swiss Federal Institute of Technology in Lausanne (EPFL); Floreano, Dario; Swiss Federal Institute of Technology in Lausanne (EPFL)

    2008-01-01

    A large class of systems of biological and technological relevance can be described as analog networks, that is, collections of dynamical devices interconnected by links of varying strength. Some examples of analog networks are genetic regulatory networks, metabolic networks, neural networks, analog electronic circuits, and control systems. Analog networks are typically complex systems which include nonlinear feedback loops and possess temporal dynamics at different timescales. When tackled b...

  10. Some non-anomerically C-C-linked carbohydrate amino acids related to leucine-synthesis and structure determination.

    Science.gov (United States)

    Steiner, Bohumil; Micová, Júlia; Koós, Miroslav; Langer, Vratislav; Gyepesová, Dalma

    2003-06-23

    (5'R)-5'-Isobutyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-L-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione was synthesised starting from methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside via methyl 6-deoxy-6-isopropyl-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose applying the Bucherer-Bergs reaction. Its 5'-R configuration was confirmed by X-ray crystallography. Corresponding alpha-amino acid-methyl (5R)-5-amino-5-C-carboxy-5,6-dideoxy-6-isopropyl-alpha-D-lyxo-hexofuranoside (alternative name: 2-[methyl (4R)-beta-L-erythrofuranosid-4-C-yl]-D-leucine) was obtained from the above hydantoin by acid hydrolysis of the isopropylidene group followed by basic hydrolysis of the hydantoin ring. Analogous derivatives with 5S configuration, formed in a minority, were also isolated and characterised. PMID:12801708

  11. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    Directory of Open Access Journals (Sweden)

    Nádia Rezende Barbosa Raposo

    2012-10-01

    Full Text Available Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL, two times more active than resveratrol (IC50 = 57.05 µg/mL, followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

  12. ESD analog circuits and design

    CERN Document Server

    Voldman, Steven H

    2014-01-01

    A comprehensive and in-depth review of analog circuit layout, schematic architecture, device, power network and ESD design This book will provide a balanced overview of analog circuit design layout, analog circuit schematic development, architecture of chips, and ESD design.  It will start at an introductory level and will bring the reader right up to the state-of-the-art. Two critical design aspects for analog and power integrated circuits are combined. The first design aspect covers analog circuit design techniques to achieve the desired circuit performance. The second and main aspect pres

  13. Discrete Calculus by Analogy

    CERN Document Server

    Izadi, F A; Bagirov, G

    2009-01-01

    With its origins stretching back several centuries, discrete calculus is now an increasingly central methodology for many problems related to discrete systems and algorithms. The topics covered here usually arise in many branches of science and technology, especially in discrete mathematics, numerical analysis, statistics and probability theory as well as in electrical engineering, but our viewpoint here is that these topics belong to a much more general realm of mathematics; namely calculus and differential equations because of the remarkable analogy of the subject to this branch of mathemati

  14. Feedback in analog circuits

    CERN Document Server

    Ochoa, Agustin

    2016-01-01

    This book describes a consistent and direct methodology to the analysis and design of analog circuits with particular application to circuits containing feedback. The analysis and design of circuits containing feedback is generally presented by either following a series of examples where each circuit is simplified through the use of insight or experience (someone else’s), or a complete nodal-matrix analysis generating lots of algebra. Neither of these approaches leads to gaining insight into the design process easily. The author develops a systematic approach to circuit analysis, the Driving Point Impedance and Signal Flow Graphs (DPI/SFG) method that does not require a-priori insight to the circuit being considered and results in factored analysis supporting the design function. This approach enables designers to account fully for loading and the bi-directional nature of elements both in the feedback path and in the amplifier itself, properties many times assumed negligible and ignored. Feedback circuits a...

  15. Vorticity in analog gravity

    Science.gov (United States)

    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.

  16. Beginning analog electronics through projects

    CERN Document Server

    Singmin, Andrew

    2001-01-01

    Analog electronics is the simplest way to start a fun, informative, learning program. Beginning Analog Electronics Through Projects, Second Edition was written with the needs of beginning hobbyists and students in mind. This revision of Andrew Singmin's popular Beginning Electronics Through Projects provides practical exercises, building techniques, and ideas for useful electronics projects. Additionally, it features new material on analog and digital electronics, and new projects for troubleshooting test equipment.Published in the tradition of Beginning Electronics Through Projects an

  17. Analog and digital signal processing

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

    Science.gov (United States)

    Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

    2009-01-01

    Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs

  1. Natural analog studies: Licensing perspective

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, J.W. [Nuclear Regulatory Commission, Washington, DC (United States)

    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.

  2. Drawing Analogies in Environmental Education

    Science.gov (United States)

    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…

  3. SU11274衍生物的合成及受体酪氨酸激酶抑制活性评价%Synthesis and Biochemical Evaluation of Receptor Tyrosine Kinase Inhibitory Activity of SUl1274 Analogs

    Institute of Scientific and Technical Information of China (English)

    徐培培; 颜海燕; 张首国; 刘靖; 温晓雪; 彭涛; 徐琪寿; 王林

    2011-01-01

    目的 合成SU11274衍生物并对其进行受体PTK抑制活性评价.方法 合成了用乙二胺、1,3-丙二胺、1,2-丙二胺、1,6-己二胺替代SU11274哌嗪基团的4个SU11274新衍生物,结构经1H-NMR和ESI-MS验证.采用ELISA方法对这4个化合物进行了受体PTK抑制活性评价.结果 合成的4个SU11274衍生物(5a,5b,5c,5d)均为新化合物.生物学评价结果显示化合物5b的受体PTK抑制活性要显著优于SU11274,化合物5c有非常显著的受体PTK抑制活性,而5a和5d则较弱.结论 SU11274的哌嗪基团被不同二胺取代会影响化合物的受体PTK抑制活性.%Objective To synthesize and evaluate the inhibition of SUl1274 analogs on the receptor tyrosine kinase. Methods Four new SUI 1274 analogs with 1,2-diaminoethane, 1,3-diaminopropane, 1,2-diaminopropane and 1,6-diaminohexane substituting the SUl1274 piperazine group were synthesized. Their structur es were verified by 1H-NMR and ESI-MS. The receptor tyrosine kinase inhibitiory activity was studied by ELISA assay. Results Four SU11274 analogs were new compounds. Biochemicalevaluations demonstrate that receptor tyrosine kinase inhibitory activity of 5 b was significantly better than that of SU 11274, but that of compound 5 c was the most significant. The inhibitory activities of 5 a and 5 b was very low. Conclusion Substitution of the piperazine of SU 11274 with different side chains affects the inhibitory activity of receptor tyrosine kinase of SU11274 analogs.

  4. The Synthesis and Evaluation of Novel Hydroxyl Substituted Chalcone Analogs with in Vitro Anti-Free Radicals Pharmacological Activity and in Vivo Anti-Oxidation Activity in a Free Radical-Injury Alzheimer’s Model

    OpenAIRE

    Ying Pan; Yicun Chen; Qingnan Li; Xiaoyu Yu; Jinzhi Wang; Jinhong Zheng

    2013-01-01

    Alzheimer’s disease (AD) pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which possessed anti-free radical activity, and screened their effects on scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH free radicals in vitro. Compound C7, 4,2'-dihydroxy-3,5-dimethoxychalcone was found to have potent activity in these anti-free radica...

  5. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-09-15

    In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 microM to 0.14 microM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 microM; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 microM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. PMID:20728367

  6. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2′,2′-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-01-01

    In a continued study, 23 3′R,4′R-di-O-(−)-camphanoyl-2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5–27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 μM to 0.14 μM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 μM; TI 310 and 200, respectively), and were two-fold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 μM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5–10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. PMID:20728367

  7. Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.

    Science.gov (United States)

    Zhou, Ting; Shi, Qian; Chen, Chin-Ho; Zhu, Hao; Huang, Li; Ho, Phong; Lee, Kuo-Hsiung

    2010-09-15

    In a continued study, 23 3'R,4'R-di-O-(-)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) derivatives (5-27) were synthesized, and screened for anti-HIV activity against both a non-drug-resistant NL4-3 strain and multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR-1) strain, using 2-EDCP (4) and 2-MDCP (35) as controls. New DCP analogs 5, 9, 14, and 22 exhibited potent anti-HIV activity against HIVNL4-3 with EC50 and therapeutic index (TI) values ranging from 0.036 microM to 0.14 microM and from 110 to 420, respectively. Compounds 5 and 9 also exhibited good activity against RTMDR-1 (EC50 0.049 and 0.054 microM; TI 310 and 200, respectively), and were twofold more potent than the leads 4 and 35 (EC50 0.11 and 0.19 microM; TI 60 and 58, respectively). Evaluation of water solubility showed that 5 and 22 were 5-10 times more water soluble than 4. Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates.

  8. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J M

    2010-01-01

    The design of an analog-to-digital converter or digital-to-analog converter is one of the most fascinating tasks in micro-electronics. In a converter the analog world with all its intricacies meets the realm of the formal digital abstraction. Both disciplines must be understood for an optimum conversion solution. In a converter also system challenges meet technology opportunities. Modern systems rely on analog-to-digital converters as an essential part of the complex chain to access the physical world. And processors need the ultimate performance of digital-to-analog converters to present the results of their complex algorithms. The same progress in CMOS technology that enables these VLSI digital systems creates new challenges for analog-to-digital converters: lower signal swings, less power and variability issues. Last but not least, the analog-to-digital converter must follow the cost reduction trend. These changing boundary conditions require micro-electronics engineers to consider their design choices for...

  9. Melon: A carbon-nitride analog to graphene

    Science.gov (United States)

    Therrien, Joel; Li, Yancen; Schmidt, Daniel

    2012-02-01

    Although graphene remains the premier 2-D material, many others have been shown to exist. A close analog to graphene would be a two-dimensional sheet composed of carbon and nitrogen, known as melon. Bulk melon, also known as graphitic carbon-nitride, has been successfully synthesized and shown to be an organic semiconductor with a band-gap around 2.7 eV. We report on the successful synthesis of single layer and few layer melon. The physical and electrical characteristics of this close cousin to graphene will be presented along with the synthesis method.

  10. Integrated Circuits for Analog Signal Processing

    CERN Document Server

    2013-01-01

      This book presents theory, design methods and novel applications for integrated circuits for analog signal processing.  The discussion covers a wide variety of active devices, active elements and amplifiers, working in voltage mode, current mode and mixed mode.  This includes voltage operational amplifiers, current operational amplifiers, operational transconductance amplifiers, operational transresistance amplifiers, current conveyors, current differencing transconductance amplifiers, etc.  Design methods and challenges posed by nanometer technology are discussed and applications described, including signal amplification, filtering, data acquisition systems such as neural recording, sensor conditioning such as biomedical implants, actuator conditioning, noise generators, oscillators, mixers, etc.   Presents analysis and synthesis methods to generate all circuit topologies from which the designer can select the best one for the desired application; Includes design guidelines for active devices/elements...

  11. Analog Systems for Gravity Duals

    OpenAIRE

    Hossenfelder, S.

    2014-01-01

    We show that analog gravity systems exist for charged, planar black holes in asymptotic Anti-de Sitter space. These black holes have been employed to describe, via the gauge-gravity duality, strongly coupled condensed matter systems on the boundary of AdS-space. The analog gravity system is a different condensed matter system that, in a suitable limit, describes the same bulk physics as the theory on the AdS boundary. This combination of the gauge-gravity duality and analog gravity therefore ...

  12. Molecular modeling of fentanyl analogs

    Directory of Open Access Journals (Sweden)

    LJILJANA DOSEN-MICOVIC

    2004-11-01

    Full Text Available Fentanyl is a highly potent and clinically widely used narcotic analgesic. A large number of its analogs have been synthesized, some of which (sufentanil and alfentanyl are also in clinical use. Theoretical studies, in recent years, afforded a better understanding of the structure-activity relationships of this class of opiates and allowed insight into the molecular mechanism of the interactions of fentanyl analogs with their receptors. An overview of the current computational techniques for modeling fentanyl analogs, their receptors and ligand-receptor interactions is presented in this paper.

  13. Sulfonimidamide analogs of oncolytic sulfonylureas.

    Science.gov (United States)

    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.

  14. Therapy with radiolabelled somatostatin analogs in neuroendocrine tumors

    International Nuclear Information System (INIS)

    In the 80's the discovery of somatostatin receptors expression on NET cells enabled the application of somatostatin analogues in diagnosis and therapy. Initially, 'cold' somatostatin analogs were used for therapeutical purpose, with overall good clinical response, but with minimal anti-proliferation effect. Furthermore, radiolabelled receptor-binding peptides have been shown to be an important class of radiopharmaceuticals for tumor diagnosis and therapy with minimal side-effects. Specific binding between receptor on tumor cell and peptide with beta emitting radionuclide act not only on tumor related symptoms but also on tumor cell via radiotoxic effect of beta radiation. Discoveries of next receptor combinations, allow the work over synthesis and applications of next receptors' analogs both in diagnosis and in therapy. Due to complex characteristics of NET's, the use therapeutic 'cocktail' containing the variety analogs may be of great importance. (author)

  15. The Synthesis and Evaluation of Novel Hydroxyl Substituted Chalcone Analogs with in Vitro Anti-Free Radicals Pharmacological Activity and in Vivo Anti-Oxidation Activity in a Free Radical-Injury Alzheimer’s Model

    Directory of Open Access Journals (Sweden)

    Ying Pan

    2013-01-01

    Full Text Available Alzheimer’s disease (AD pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which possessed anti-free radical activity, and screened their effects on scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH and OH free radicals in vitro. Compound C7, 4,2'-dihydroxy-3,5-dimethoxychalcone was found to have potent activity in these anti-free radical activity tests. Further research revealed that C7 could elevate glutathione peroxidase (GSH-PX and super oxide dismutase (SOD levels and lower malonaldehyde (MDA level in vivo in the Alzheimer’s model. The indication of C7’s effect on AD needs further study.

  16. Analog filters in nanometer CMOS

    CERN Document Server

    Uhrmann, Heimo; Zimmermann, Horst

    2014-01-01

    Starting from the basics of analog filters and the poor transistor characteristics in nanometer CMOS 10 high-performance analog filters developed by the authors in 120 nm and 65 nm CMOS are described extensively. Among them are gm-C filters, current-mode filters, and active filters for system-on-chip realization for Bluetooth, WCDMA, UWB, DVB-H, and LTE applications. For the active filters several operational amplifier designs are described. The book, furthermore, contains a review of the newest state of research on low-voltage low-power analog filters. To cover the topic of the book comprehensively, linearization issues and measurement methods for the characterization of advanced analog filters are introduced in addition. Numerous elaborate illustrations promote an easy comprehension. This book will be of value to engineers and researchers in industry as well as scientists and Ph.D students at universities. The book is also recommendable to graduate students specializing on nanoelectronics, microelectronics ...

  17. An Optimized Device Sizing of Analog Circuits using Particle Swarm Optimization

    Directory of Open Access Journals (Sweden)

    K. Duraiswamy

    2012-01-01

    Full Text Available Problem statement: Day by day more and more products rely on analog circuits to improve the speed and reduce the power consumption(Products rely on analog circuits to improve the speed and reduce the power consumption day by day more and more.. For the VLSI implementation analog circuit design plays an important role. This analog circuit synthesis might be the most challenging and time-consumed task, because it does not only consist of topology and layout synthesis but also of component sizing. Approach: A Particle Swarm Optimization (PSO technique for the optimal design of analog circuits. Analog signal processing finds many applications and widely uses OpAmp based amplifiers, mixers, comparators. and filters. Results: A two-stage opamp (Miller Operational Trans-conductance Amplifier (OTA is considered for the synthesis that satisfies certain design specifications. Performance has been evaluated with the Simulation Program with Integrated Circuit Emphasis (SPICE circuit simulator until optimal sizes of the transistors are found. Conclusion: The output of the simulation for the two-stage opamp shows that the PSO technique is an accurate and promising approach in determining the device sizes in an analog circuit.

  18. Microwave assisted synthesis of bis and tris(ω -bromoacetophenones): versatile precursors for novel bis(imidazo[1,2- a]pyridines), bis(imidazo[1,2- a]pyrimidines) and their tris-analogs

    OpenAIRE

    Shaaban, Mohamed R.

    2013-01-01

    Background α-Bromination of the side chain of aromatic ketones using NBS in the presence of p-toluenesulfonic acid (p-TsOH) in acetonitrile is very common. However, regioselective bromination of bis and tris(ω -bromoacetophenones) with NBS in the presence of p-TsOH in acetonitrile under microwave irradiation is quite novel. The bis- and tris(ω -bromoacetophenones) are used in synthesis of bis and tris(heterocycles). bis(heterocycles) have received a great deal of attention, because many biolo...

  19. Synthesis, crystal structures and spectral characterization of imidazo[1,2-a]pyrimidin-2-yl-acetic acid and related analog with imidazo[2,1-b]thiazole ring

    Science.gov (United States)

    Dylong, Agnieszka; Goldeman, Waldemar; Sowa, Michał; Ślepokura, Katarzyna; Drożdżewski, Piotr; Matczak-Jon, Ewa

    2016-08-01

    Imidazo[1,2-a]pyrimidin-2-yl-acetic acid (HIPM-2-ac) and its analog with imidazo[2,1-b]thiazole ring (HITZ-6-ac) were synthesized and structurally characterized by single-crystal X-ray diffraction corroborated with calculations of Hirshfeld surfaces, which provided detailed insight into intermolecular interactions constituting both crystals. The IR and Raman spectra of HIPM-2-ac and HITZ-6-ac were recorded and interpreted in details with the aid of Density Functional Theory (DFT) calculations and Potential Energy Distribution (PED) analysis of computed normal vibrations. Special attention was paid on hydroxyl and methylene groups involved in hydrogen bonds, which vibrations were monitored by H/D substitution. Recrystallization of parent compounds from deuterium oxide (D2O) solutions resulted in deuteration of their carboxylic OH groups and almost complete deuteration of HIPM-2-ac methylene group. The latter phenomenon is clearly reflected in the vibrational spectra and confirmed by 1H NMR experiments in solution.

  20. All-optical analog comparator

    Science.gov (United States)

    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.

  1. Analog electronics for radiation detection

    CERN Document Server

    2016-01-01

    Analog Electronics for Radiation Detection showcases the latest advances in readout electronics for particle, or radiation, detectors. Featuring chapters written by international experts in their respective fields, this authoritative text: Defines the main design parameters of front-end circuitry developed in microelectronics technologies Explains the basis for the use of complementary metal oxide semiconductor (CMOS) image sensors for the detection of charged particles and other non-consumer applications Delivers an in-depth review of analog-to-digital converters (ADCs), evaluating the pros and cons of ADCs integrated at the pixel, column, and per-chip levels Describes incremental sigma delta ADCs, time-to-digital converter (TDC) architectures, and digital pulse-processing techniques complementary to analog processing Examines the fundamental parameters and front-end types associated with silicon photomultipliers used for single visible-light photon detection Discusses pixel sensors ...

  2. Test Wiseness and Analogy Test Performance

    Science.gov (United States)

    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)

  3. Conversion of Substrate Analogs Suggests a Michael Cyclization in Iridoid Biosynthesis

    OpenAIRE

    Lindner, Stephanie; Geu-Flores, Fernando; Bräse, Stefan; Sherden, Nathaniel H.; O’Connor, Sarah E.

    2014-01-01

    Summary The core structure of the iridoid monoterpenes is formed by a unique cyclization reaction. The enzyme that catalyzes this reaction, iridoid synthase, is mechanistically distinct from other terpene cyclases. Here we describe the synthesis of two substrate analogs to probe the mechanism of iridoid synthase. Enzymatic assay of these substrate analogs along with clues from the product profile of the native substrate strongly suggest that iridoid synthase utilizes a Michael reaction to ach...

  4. Multilateral Collaborations in Analog Research

    Science.gov (United States)

    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

  5. Synthesis and characterization of novel N3O3-Schiff base complexes of 99gTc, and in vivo imaging studies with analogous 99mTc complexes.

    Science.gov (United States)

    Marmion, M E; Woulfe, S R; Newmann, W L; Pilcher, G; Nosco, D L

    1996-07-01

    Sixteen novel derivatives of 1,1,1-tris (salicylaldiminomethyl)ethane have been synthesized for the purpose of encapsulating 99mTc(IV) ions and generating new 99mTc radiopharmaceuticals. Two methods for the preparation of the 99gTc(IV) analog complexes are presented; one utilizes SnCl2 reduction on 99gTcO4- and the other a direct substitution route starting with [99gTcCl6]2-. Free ligands (H3L) are characterized by melting points, 1H NMR, 13C NMR, mass spectroscopy, TLC, and/or elemental analyses. [99gTcL]+ complexes are characterized by FAB-ms, UV-VIS, IR and/or CV. An X-ray structural analysis was performed on a crystal of [M(6,6'-[[2-[[((4-Methoxy-2-hydroxyphenyl) methylene)-amino]methyl]-2-methyl- 1,3-propanediyl]bis(nitrilomethylidyne)]-bis-3-methoxyphenol )] tetraphenylborate, where M represents a 1/3 isomorphous mixture of 99gTc/Sn as determined by SEM. The metal coordination site is 6-coordinate, composed of N3O3 donor atoms, and intermediate between octahedral and trigonal prismatic geometry. The [99mTcL]+ complexes were prepared in a stannous environment; equivalence of the 99mTc and 99gTc complexes is demonstrated by HPLC techniques. The [SnL]+ complex was prepared for comparison purposes. An unusual ligand oxidation occurs for one series of ligands in which in situ amine-->imine conversion is observed during the complexation reaction in reducing media. Guinea pig, rat, dog, and human metabolism studies are reported for selected [99mTcL]+ complexes, the myocardial uptake of which approaches 2% of the injected dose. PMID:8905821

  6. Synthesis of variants of Marfey's reagent having d-amino acids as chiral auxiliaries and liquid-chromatographic enantioseparation of (RS)-Mexiletine in spiked plasma: assessment and comparison with L-amino acid analogs.

    Science.gov (United States)

    Bhushan, Ravi; Vashistha, Vinod Kumar

    2015-01-30

    Five d-amino acids have been used for the first time to synthesize chiral derivatizing reagents (as variants of Marfey's reagent) by nucleophilic displacement of one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene as against the literature reports on application of only l-amino acids or their amides as chiral auxiliaries in dinitrobenzene (DNB) moiety. Five other DNB based reagents were also prepared by nucleophilic substitution of fluorine atom with the set of the same amino acids in l-configuration, as chiral auxiliaries. These reagents were characterized and used for synthesis of diastereomers of (RS)-Mexiletine spiked in human plasma. Diastereomers were synthesized employing microwave irradiation and were separated on reversed-phase C18 column. Performance of the two types of chiral derivatizing reagents was compared. The reagents containing d-amino acids provided enhanced separation of diastereomers than those containing l-amino acids. The best resolution was obtained using mobile phase consisting of acetonitrile and 0.1% trifluoroacetic acid in gradient mode. The detection was carried out at 340nm. The method so developed was validated for linearity, accuracy and precision. The limit of quantitation was found to be approximately 25.2ngmL(-1) in human plasma. PMID:25576038

  7. Three-chain insulin analogs demonstrate the importance of insulin secondary structure to bioactivity.

    Science.gov (United States)

    Wu, Fangzhou; Chabenne, Joseph R; Gelfanov, Vasily M; Mayer, John P; DiMarchi, Richard D

    2015-03-01

    This report describes the chemical synthesis and biological characterization of novel three-chain insulin analogs with a destabilized secondary structure. The analogs, obtained by chemical synthesis via a single-chain precursor and selective enzymatic digestion, were used to investigate the role of the highly conserved 'insulin fold'. Biological characterization through in vitro biochemical signaling showed extremely low activity at each insulin receptor when compared with native insulin. We conclude that the 'insulin fold' is a structural foundation that supports insulin biological action.

  8. 49205 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1997-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course 49205 Analog and Digital Filters...

  9. Analog Input Data Acquisition Software

    Science.gov (United States)

    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.

  10. Multichannel analog temperature sensing system

    Science.gov (United States)

    Gribble, R.

    1985-08-01

    A multichannel system that protects the numerous and costly water-cooled magnet coils on the translation section of the FRX-C/T magnetic fusion experiment is described. The system comprises a thermistor for each coil, a constant current circuit for each thermistor, and a multichannel analog-to-digital converter interfaced to the computer.

  11. International Alligator Rivers Analog Project

    International Nuclear Information System (INIS)

    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

  12. Analogy between Thermodynamics and Mechanics.

    Science.gov (United States)

    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)

  13. Multichannel analog temperature sensing system

    International Nuclear Information System (INIS)

    A multichannel system that protects the numerous and costly water-cooled magnet coils on the translation section of the FRX-C/T magnetic fusion experiment is described. The system comprises a thermistor for each coil, a constant current circuit for each thermistor, and a multichannel analog-to-digital converter interfaced to the computer

  14. Analog circuit design art, science and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    This book is far more than just another tutorial or reference guide - it's a tour through the world of analog design, combining theory and applications with the philosophies behind the design process. Readers will learn how leading analog circuit designers approach problems and how they think about solutions to those problems. They'll also learn about the `analog way' - a broad, flexible method of thinking about analog design tasks.A comprehensive and useful guide to analog theory and applications. Covers visualizing the operation of analog circuits. Looks at how to rap

  15. Bottomed analog of Z+(4433)

    International Nuclear Information System (INIS)

    The newly observed Z+(4433) resonance by BELLE is believed to be a tetraquark bound state made up of (cu)(cd). We propose the bottomed analog of this bound state, namely, by replacing one of the charm quarks by a bottom quark, thus forming Zbc0,±,±±. One of the Zbc is doubly charged. The predicted mass of Zbc is around 7.6 GeV. This doubly charged bound state can be detected by its decay into Bc±π±. Similarly, we can also replace both charm quark and antiquark of the Z+(4433) by bottom quark and antiquark, respectively, thus forming Zbb the bottomonium analog of Z+(4433). The predicted mass of Zbb is about 10.7 GeV

  16. Mechanical Analogies of Fractional Elements

    Institute of Scientific and Technical Information of China (English)

    HU Kai-Xin; ZHU Ke-Qin

    2009-01-01

    A Fractional element model describes a special kind of viscoelastic material.Its stress is proportional to the fractional-order derivative of strain. Physically the mechanical analogies of fractional elements can be represented by spring-dashpot fractal networks. We introduce a constitutive operator in the constitutive equations of viscoelastic materials.To derive constitutive operators for spring-dashpot fractal networks, we use Heaviside operational calculus, which provides explicit answers not otherwise obtainable simply.Then the series-parallel formulas for the constitutive operator are derived. Using these formulas, a constitutive equation of fractional element with 1/2-order derivative is obtained.Finally we find the way to derive the constitutive equations with other fractional-order derivatives and their mechanical analogies.

  17. Analog Nonvolatile Computer Memory Circuits

    Science.gov (United States)

    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

  18. Splitting Compounds by Semantic Analogy

    OpenAIRE

    Daiber, Joachim; Quiroz, Lautaro; Wechsler, Roger; Frank, Stella

    2015-01-01

    Compounding is a highly productive word-formation process in some languages that is often problematic for natural language processing applications. In this paper, we investigate whether distributional semantics in the form of word embeddings can enable a deeper, i.e., more knowledge-rich, processing of compounds than the standard string-based methods. We present an unsupervised approach that exploits regularities in the semantic vector space (based on analogies such as "bookshop is to shop as...

  19. A Global Analog of Cheshire Charge

    OpenAIRE

    McGraw, Patrick

    1994-01-01

    It is shown that a model with a spontaneously broken global symmetry can support defects analogous to Alice strings, and a process analogous to Cheshire charge exchange can take place. A possible realization in superfluid He-3 is pointed out.

  20. Hegel, Analogy, and Extraterrestrial Life

    Science.gov (United States)

    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

  1. Analog circuit design art, science, and personalities

    CERN Document Server

    Williams, Jim

    1991-01-01

    Analog Circuit Design: Art, Science, and Personalities discusses the many approaches and styles in the practice of analog circuit design. The book is written in an informal yet informative manner, making it easily understandable to those new in the field. The selection covers the definition, history, current practice, and future direction of analog design; the practice proper; and the styles in analog circuit design. The book also includes the problems usually encountered in analog circuit design; approach to feedback loop design; and other different techniques and applications. The text is

  2. Analog and mixed-signal electronics

    CERN Document Server

    Stephan, Karl

    2015-01-01

    A practical guide to analog and mixed-signal electronics, with an emphasis on design problems and applications This book provides an in-depth coverage of essential analog and mixed-signal topics such as power amplifiers, active filters, noise and dynamic range, analog-to-digital and digital-to-analog conversion techniques, phase-locked loops, and switching power supplies. Readers will learn the basics of linear systems, types of nonlinearities and their effects, op-amp circuits, the high-gain analog filter-amplifier, and signal generation. The author uses system design examples to motivate

  3. Practical analog electronics for technicians

    CERN Document Server

    Kimber, W A

    2013-01-01

    'Practical Analog Electronics for Technicians' not only provides an accessible introduction to electronics, but also supplies all the problems and practical activities needed to gain hands-on knowledge and experience. This emphasis on practice is surprisingly unusual in electronics texts, and has already gained Will Kimber popularity through the companion volume, 'Practical Digital Electronics for Technicians'. Written to cover the Advanced GNVQ optional unit in electronics, this book is also ideal for BTEC National, A-level electronics and City & Guilds courses. Together with 'Practical Digit

  4. Classical analogy of Fano resonances

    International Nuclear Information System (INIS)

    We present an analogy of Fano resonances in quantum interference to classical resonances in the harmonic oscillator system. It has a manifestation as a coupled behaviour of two effective oscillators associated with propagating and evanescent waves. We illustrate this point by considering a classical system of two coupled oscillators and interfering electron waves in a quasi-one-dimensional narrow constriction with a quantum dot. Our approach provides a novel insight into Fano resonance physics and provides a helpful view in teaching Fano resonances

  5. Analog-to-digital conversion

    CERN Document Server

    Pelgrom, Marcel J. M

    2013-01-01

    This textbook is appropriate for use in graduate-level curricula in analog to digital conversion, as well as for practicing engineers in need of a state-of-the-art reference on data converters.  It discusses various analog-to-digital conversion principles, including sampling, quantization, reference generation, nyquist architectures and sigma-delta modulation.  This book presents an overview of the state-of-the-art in this field and focuses on issues of optimizing accuracy and speed, while reducing the power level. This new, second edition emphasizes novel calibration concepts, the specific requirements of new systems, the consequences of 45-nm technology and the need for a more statistical approach to accuracy.  Pedagogical enhancements to this edition include more than twice the exercises available in the first edition, solved examples to introduce all key, new concepts and warnings, remarks and hints, from a practitioner’s perspective, wherever appropriate.  Considerable background information and pr...

  6. Approaches to synthetic platelet analogs.

    Science.gov (United States)

    Modery-Pawlowski, Christa L; Tian, Lewis L; Pan, Victor; McCrae, Keith R; Mitragotri, Samir; Sen Gupta, Anirban

    2013-01-01

    Platelet transfusion is routinely used for treating bleeding complications in patients with hematologic or oncologic clotting disorders, chemo/radiotherapy-induced myelosuppression, trauma and surgery. Currently, these transfusions mostly use allogeneic platelet concentrates, while products like lyophilized platelets, cold-stored platelets and infusible platelet membranes are under investigation. These natural platelet-based products pose considerable risks of contamination, resulting in short shelf-life (3-5 days). Recent advances in pathogen reduction technologies have increased shelf-life to ~7 days. Furthermore, natural platelets are short in supply and also cause several biological side effects. Hence, there is significant clinical interest in platelet-mimetic synthetic analogs that can allow long storage-life and minimum side effects. Accordingly, several designs have been studied which decorate synthetic particles with motifs that promote platelet-mimetic adhesion or aggregation. Recent refinement in this design involves combining the adhesion and aggregation functionalities on a single particle platform. Further refinement is being focused on constructing particles that also mimic natural platelet's shape, size and elasticity, to influence margination and wall-interaction. The optimum design of a synthetic platelet analog would require efficient integration of platelet's physico-mechanical properties and biological functionalities. We present a comprehensive review of these approaches and provide our opinion regarding the future directions of this research. PMID:23092864

  7. Synthesis and Antifungal Activity of Musa Phytoalexins and Structural Analogs

    OpenAIRE

    Adriana Gallego; Gloria Cardona; Victor Arango; Yoni Rosero; Fernando Torres; Fernando Echeverri; Gustavo Escobar; Winston Quiñones

    2000-01-01

    Several perinaphthenone/phenylphenalenone compounds were synthesized to establish a relationship between structure and antifungal activity against Mycosphaerella fijiensis. Substitutions on the unsaturated carbonyl system or addition of a phenyl group reduced antibiotic activity.

  8. Synthesis and Antifungal Activity of Musa Phytoalexins and Structural Analogs

    Directory of Open Access Journals (Sweden)

    Adriana Gallego

    2000-07-01

    Full Text Available Several perinaphthenone/phenylphenalenone compounds were synthesized to establish a relationship between structure and antifungal activity against Mycosphaerella fijiensis. Substitutions on the unsaturated carbonyl system or addition of a phenyl group reduced antibiotic activity.

  9. Convenient Microscale Synthesis of a Coumarin Laser Dye Analog

    Science.gov (United States)

    Aktoudianakis, Evangelos; Dicks, Andrew P.

    2006-01-01

    Coumarin (2H-1-benzopyran-2-one) and its derivatives constitute a fascinating class of organic substances that are utilized industrially in areas such as cosmetics, food preservatives, insecticides and fluorescent laser dyes. The product can be synthesized, purified, and characterized within two hours with benefits of microscale reactivity being…

  10. QCD analogy for quantum gravity

    Science.gov (United States)

    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.

  11. Analog computing by Brewster effect.

    Science.gov (United States)

    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.

  12. Priming analogical reasoning with false memories.

    Science.gov (United States)

    Howe, Mark L; Garner, Sarah R; Threadgold, Emma; Ball, Linden J

    2015-08-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false memory priming of complex analogical reasoning tasks in the absence of simple semantic associations. In Experiment 1, we demonstrated the robustness of false memory priming in analogical reasoning when backward associative strength among the problem terms was eliminated. In Experiments 2a and 2b, we extended these findings by demonstrating priming on newly created homonym analogies that can only be solved by inhibiting semantic associations within the analogy. Overall, the findings of the present experiments provide evidence that the efficacy of false memory priming extends to complex analogical reasoning problems. PMID:25784574

  13. Xampling: Compressed Sensing of Analog Signals

    OpenAIRE

    Mishali, Moshe; Eldar, Yonina C.

    2011-01-01

    Xampling generalizes compressed sensing (CS) to reduced-rate sampling of analog signals. A unified framework is introduced for low rate sampling and processing of signals lying in a union of subspaces. Xampling consists of two main blocks: Analog compression that narrows down the input bandwidth prior to sampling with commercial devices followed by a nonlinear algorithm that detects the input subspace prior to conventional signal processing. A variety of analog CS applications are reviewed wi...

  14. Analog to Digital Conversion in Physical Measurements

    OpenAIRE

    Kapitaniak, T.; Zyczkowski, K.; Feudel, U.; Grebogi, C.

    1999-01-01

    There exist measuring devices where an analog input is converted into a digital output. Such converters can have a nonlinear internal dynamics. We show how measurements with such converting devices can be understood using concepts from symbolic dynamics. Our approach is based on a nonlinear one-to-one mapping between the analog input and the digital output of the device. We analyze the Bernoulli shift and the tent map which are realized in specific analog/digital converters. Furthermore, we d...

  15. Robust hyperchaotic synchronization via analog transmission line

    Science.gov (United States)

    Sadoudi, S.; Tanougast, C.

    2016-02-01

    In this paper, a novel experimental chaotic synchronization technique via analog transmission is discussed. We demonstrate through Field-Programmable Gate Array (FPGA) implementation design the robust synchronization of two embedded hyperchaotic Lorenz generators interconnected with an analog transmission line. The basic idea of this work consists in combining a numerical generation of chaos and transmitting it with an analog signal. The numerical chaos allows to overcome the callback parameter mismatch problem and the analog transmission offers robust data security. As application, this technique can be applied to all families of chaotic systems including time-delayed chaotic systems.

  16. Acetylated and Methylated β-Cyclodextrins as Viable Soluble Supports for the Synthesis of Short 2′-Oligodeoxyribo-nucleotides in Solution

    Directory of Open Access Journals (Sweden)

    Harri Lönnberg

    2012-10-01

    Full Text Available Novel soluble supports for oligonucleotide synthesis 11a–c have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoylthymidine (6 or 7 to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I-promoted 1,3-dipolar cycloaddition. The applicability of the supports to oligonucleotide synthesis by the phosphoramidite strategy has been demonstrated by assembling a 3′-TTT-5′ trimer from commercially available 5′-O-(4,4′-dimethoxytritylthymidine 3′-phosphoramidite. To simplify the coupling cycle, the 5′-O-(4,4′-dimethoxytrityl protecting group has been replaced with an acetal that upon acidolytic removal yields volatile products. For this purpose, 5′-O-(1-methoxy-1-methylethyl-protected 3′-(2-cyanoethyl-N,N-diisopropyl-phosphoramidites of thymidine (5a, N4-benzoyl-2′-deoxycytidine (5b and N6-benzoyl-2′-deoxyadenosine (5c have been synthesized and utilized in synthesis of a pentameric oligonucleotide 3′-TTCAT-5′ on the permethylated cyclodextrin support 11c.

  17. Novel glycosylated endomorphin-2 analog produces potent centrally-mediated antinociception in mice after peripheral administration.

    Science.gov (United States)

    Fichna, Jakub; Mazur, Marzena; Grzywacz, Daria; Kamysz, Wojciech; Perlikowska, Renata; Piekielna, Justyna; Sobczak, Marta; Sałaga, Maciej; Toth, Geza; Janecka, Anna; Chen, Chunqiu; Olczak, Jacek

    2013-12-15

    We report the synthesis and pharmacological characterization of a novel glycosylated analog of a potent and selective endogenous μ-opioid receptor (MOP) agonist, endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2), obtained by the introduction in position 3 of the tyrosine residue possessing the glucose moiety attached to the phenolic function via a β-glycosidic bond. The improved blood-brain barrier permeability and enhanced antinociceptive effect of the novel glycosylated analog suggest that it may be a promising template for design of potent analgesics. Furthermore, the described methodology may be useful for increasing the bioavailability and delivery of opioid peptides to the CNS. PMID:24220171

  18. In vitro and In vivo Evaluation of Select Kahalalide F Analogs with Antitumor and Antifungal Activities

    OpenAIRE

    Shilabin, Abbas Gholipour; Hamann, Mark T

    2011-01-01

    Kahalalide F (KF) and the regioisomer isoKF are novel anticancer drugs of marine origin and currently under clinical investigation. Here we report the synthesis of two new KF analogs with significant in vitro and in vivo antifungal and antitumor activities. The primary amine hydrogen of ornithine in KF has been replaced with 4-fluoro-3-methylbenzyl and morpholin-4-yl-benzyl via reductive N-alkylation. The TGI of these analogs using the NCI-60 cell line screening revealed promising results whe...

  19. Novel Analog For Muscle Deconditioning

    Science.gov (United States)

    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.

  20. An optical analog signal transmitter

    Energy Technology Data Exchange (ETDEWEB)

    Fudzita, K.; Itida, T.; Tanaka, Kh.

    1984-01-11

    An optical laser analog signal transmitter employing an amplitude modulated subcarrier is patented; this transmitter performs stable and high quality transmission of information signals over great distances. A feature of the proposed transmitter is a special transmitter operational mode in which the light emission reflected off the connection point to the fiber optic conduit is sent back to the laser diode in a transient period. As a result, the critical mode of the generated emission is not influenced by the reflected signal. The transmitter consists of a laser diode with biasing near the cutoff point, an amplitude modulator with a subcarrier frequency oscillator, a section of flexible fiber-optic cable of length L, which connects the laser diode to the primary optical fiber conduit, and the connector itself. The subcarrier frequency may vary over wide ranges to establish the necessary correlation between the length of the light conduit section L and the return propagation time of the reflected light signal from the connection point to the laser diode. The difference between the lasing time of the light signal and the return time to the laser diode of the signal reflected off the connector is determined by the relation tau equals 2nL/c - mtauc, where L is the length of the connecting section; n is the refractivity of the optical fiber; c is the velocity of light; tauc is the period of the high frequency subcarrier signal; and m is an integer.

  1. A Mechanical Analogy for the Photoelectric Effect

    Science.gov (United States)

    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…

  2. A physical analogy to fuzzy clustering

    DEFF Research Database (Denmark)

    Jantzen, Jan

    2004-01-01

    This tutorial paper provides an interpretation of the membership assignment in the fuzzy clustering algorithm fuzzy c-means. The membership of a data point to several clusters is shown to be analogous to the gravitational forces between bodies of mass. This provides an alternative way to explain...... the algorithm to students. The analogy suggests a possible extension of the fuzzy membership assignment equation....

  3. An Analog Computer for Electronic Engineering Education

    Science.gov (United States)

    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…

  4. Analogies in high school Brazilian chemistry textbooks

    Directory of Open Access Journals (Sweden)

    Rosária Justi

    2000-05-01

    Full Text Available This paper presents and discusses an analysis of the analogies presented by Brazilian chemistry textbooks for the medium level. The main aim of the analysis is to discuss whether such analogies can be said good teaching models. From the results, some aspects concerning with teachers' role are discussed. Finally, some new research questions are emphasised.

  5. Several Forms of Fuzzy Analogical Reasoning

    OpenAIRE

    Bouchon-Meunier, B; Delechamp, J.; Marsala, C.; Rifqi, M.

    1997-01-01

    We present a general framework representing analogy, on the basis of a link between variables and measures of comparison between values of variables. This analogical scheme is proven to represent a common description of several forms of reasoning used in fuzzy control or in the management of knowledge-based systems, such as deductive reasoning, inductive reasoning or prototypical reasoning, gradual reasoning.

  6. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    Directory of Open Access Journals (Sweden)

    Bhavitavya Nijampatnam

    2014-09-01

    Full Text Available 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.

  7. Analogical Processes and College Developmental Reading

    Science.gov (United States)

    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…

  8. Analogies in biology textbooks in zoology teaching

    Directory of Open Access Journals (Sweden)

    Saulo Cézar Seiffert Santos

    2011-05-01

    Full Text Available The biologic structures of living creatures are of difficult understanding for students, because they are usually unknown by those, in needs of strategic didactics in order to facilitate the student understanding. There are several strategies and methods for teaching, such as, analogies, metaphors, descriptions, among others. In this article we aim to identify, assess and classify the analogies used in the Higher School Biology textbooks, commonly used in Public State Schools of Manaus – AM, related to the zoology theme. The methodological procedure includes: a analysis of the whole zoological content of the most used textbooks in the public state network of Amazonas throughout the year; b three didactic textbooks have been specifically analyzed in order to specify the class taxon of “Fish” for the comparison of possible variations of types and quantities of analogies. The adopted classification of analogies was of Curtis & Reigeluth (1984 and the model of enriching analysis was according to the TWA Glynn model (Harrison & Treagust, 1993. It has been concluded that the use of analogies is greater in the content of invertebrates than that of vertebrates. Most Analogies are presented in a simple and direct manner, comparing structures, concrete to concrete, and of verbal mediation, almost nothing is presented in a diverse and heuristic manner of Zoology content on the LD. The development of limits of comparison and reflexion about the analogies was rare, only the presentation of the analogue and the target of analogy occurred.

  9. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  10. Synthesis and Properties of Novel Hemicyanine Dye-β-Cyclodextrin

    Institute of Scientific and Technical Information of China (English)

    WANG,Lan-Ying; LI,Feng-Mei; HUANG,Yi; MEI,Man-Yu; ZHANG,Zu-Xun

    2007-01-01

    A series of novel hemicyanine dye-β-cyclodextrin compounds: mono-6-deoxy-β-cyclodextrin-6-[p-(p-substituted styryl)pyridium] p-totylfulfonates were synthesized by the condensation of mono-6-deoxy-β- cyclodextrin-6-(p-methyl pyridinium) p-toluenesulfonate with (un)substituted benzaldehydes. Their structures were established by 1H NMR, IR, UV-Vis and elemental analysis. The absorption and fluorescence properties of the novel compounds were measured in solution and the photostability of a selected hemicyanine dye-β-cyclodextrin compound was also investigated.

  11. An Analog Earth Climate Model

    Science.gov (United States)

    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

  12. Analog regulation of metabolic demand

    Directory of Open Access Journals (Sweden)

    Muskhelishvili Georgi

    2011-03-01

    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  13. Mechatronics by Analogy and Application to Legged Locomotion

    Science.gov (United States)

    Ragusila, Victor

    A new design methodology for mechatronic systems, dubbed as Mechatronics by Analogy (MbA), is introduced and applied to designing a leg mechanism. The new methodology argues that by establishing a similarity relation between a complex system and a number of simpler models it is possible to design the former using the analysis and synthesis means developed for the latter. The methodology provides a framework for concurrent engineering of complex systems while maintaining the transparency of the system behaviour through making formal analogies between the system and those with more tractable dynamics. The application of the MbA methodology to the design of a monopod robot leg, called the Linkage Leg, is also studied. A series of simulations show that the dynamic behaviour of the Linkage Leg is similar to that of a combination of a double pendulum and a spring-loaded inverted pendulum, based on which the system kinematic, dynamic, and control parameters can be designed concurrently. The first stage of Mechatronics by Analogy is a method of extracting significant features of system dynamics through simpler models. The goal is to determine a set of simpler mechanisms with similar dynamic behaviour to that of the original system in various phases of its motion. A modular bond-graph representation of the system is determined, and subsequently simplified using two simplification algorithms. The first algorithm determines the relevant dynamic elements of the system for each phase of motion, and the second algorithm finds the simple mechanism described by the remaining dynamic elements. In addition to greatly simplifying the controller for the system, using simpler mechanisms with similar behaviour provides a greater insight into the dynamics of the system. This is seen in the second stage of the new methodology, which concurrently optimizes the simpler mechanisms together with a control system based on their dynamics. Once the optimal configuration of the simpler system is

  14. Advances in Analog Circuit Design 2015

    CERN Document Server

    Baschirotto, Andrea; Harpe, Pieter

    2016-01-01

    This book is based on the 18 tutorials presented during the 24th workshop on Advances in Analog Circuit Design. Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, including low-power and energy-efficient analog electronics, with specific contributions focusing on the design of efficient sensor interfaces and low-power RF systems. This book serves as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development. ·         Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; ·         Presents material in a tutorial-based format; ·         Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing.

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

    Science.gov (United States)

    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…

  16. A computational model of analogical reasoning

    Institute of Scientific and Technical Information of China (English)

    李波; 赵沁平

    1997-01-01

    A computational model of analogical reasoning is presented, which divides analogical reasoning process into four subprocesses, i.e. reminding, elaboration, matching and transfer. For each subprocess, its role and the principles it follows are given. The model is discussed in detail, including salient feature-based reminding, relevance-directed elaboration, an improved matching model and a transfer model. And the advantages of this model are summarized based on the results of BHARS, which is an analogical reasoning system implemented by this model.

  17. Analog to Digital Conversion in Physical Measurements

    CERN Document Server

    Kapitaniak, T; Feudel, U; Grebogi, C

    1999-01-01

    There exist measuring devices where an analog input is converted into a digital output. Such converters can have a nonlinear internal dynamics. We show how measurements with such converting devices can be understood using concepts from symbolic dynamics. Our approach is based on a nonlinear one-to-one mapping between the analog input and the digital output of the device. We analyze the Bernoulli shift and the tent map which are realized in specific analog/digital converters. Furthermore, we discuss the sources of errors that are inevitable in physical realizations of such systems and suggest methods for error reduction.

  18. Photonic analog computing with integrated silicon waveguides

    CERN Document Server

    Dong, Jianji; Zheng, Aoleng; Zhang, Xinliang

    2014-01-01

    The spectra of silicon integrated waveguides are tailored to process analog computing (i.e.,differential and integral) in optical domain with huge bandwidth.With the theory of signal and system, we design some silicon integrated devices to implement photonic differentiator and optical differential equation solver. The basic principle is to tailor the spectra of silicon integrated waveguides to meet the requirements of analog computing circuits. These analog photonic integrated circuits are very promising in future computing systems with high speed, low cost, and compact size. We also plan to employ these basic computing units in more complex computing modules.

  19. Antischistosomal activity of N,N'-arylurea analogs against Schistosoma japonicum.

    Science.gov (United States)

    Yao, Houzong; Liu, Fengyou; Chen, Jinglei; Li, Yan; Cui, Jinhao; Qiao, Chunhua

    2016-03-01

    Although the antischistosomal activities of N,N'-arylurea analogs were reported, systematic structure-activity relationships have not been conducted. In this Letter, we reported the design, synthesis and evaluation of 45 N,N'-arylurea analogs. Among these prepared compounds, 13 compounds were urea linker modified and 32 were N,N'-arylurea derivatives. The activity evaluation revealed 12 analogs exhibited IC50 values lower than 22.6μM, and 7 of them had IC50 less than 10μM against the juvenile Schistosoma japonicum in vitro. Their worm killing potency was even higher against adult worm. Unfortunately, low to moderate worm burden reduction of 0-33.4% was recorded after administration of a single oral dose of 200mg/kg or 400mg/kg to mice harboring S. japonicum.

  20. Military Importance of Natural Toxins and Their Analogs.

    Science.gov (United States)

    Pitschmann, Vladimír; Hon, Zdeněk

    2016-01-01

    Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots); it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks. PMID:27136512

  1. Military Importance of Natural Toxins and Their Analogs

    Directory of Open Access Journals (Sweden)

    Vladimír Pitschmann

    2016-04-01

    Full Text Available Toxin weapon research, development, production and the ban on its uses is an integral part of international law, with particular attention paid to the protection against these weapons. In spite of this, hazards associated with toxins cannot be completely excluded. Some of these hazards are also pointed out in the present review. The article deals with the characteristics and properties of natural toxins and synthetic analogs potentially constituting the basis of toxin weapons. It briefly describes the history of military research and the use of toxins from distant history up to the present age. With respect to effective disarmament conventions, it mentions certain contemporary concepts of possible toxin applications for military purposes and the protection of public order (suppression of riots; it also briefly refers to the question of terrorism. In addition, it deals with certain traditional as well as modern technologies of the research, synthesis, and use of toxins, which can affect the continuing development of toxin weapons. These are, for example, cases of new toxins from natural sources, their chemical synthesis, production of synthetic analogs, the possibility of using methods of genetic engineering and modern biotechnologies or the possible applications of nanotechnology and certain pharmaceutical methods for the effective transfer of toxins into the organism. The authors evaluate the military importance of toxins based on their comparison with traditional chemical warfare agents. They appeal to the ethics of the scientific work as a principal condition for the prevention of toxin abuse in wars, military conflicts, as well as in non-military attacks.

  2. Enantioselectivity Induced by Oxazaborolidine Supported on Mesoporous Silica or by Its Analog in Homogeneous Phase

    Directory of Open Access Journals (Sweden)

    Jeremy H. Yune

    2010-05-01

    Full Text Available The impact of immobilization of oxazaborolidines supported on silica via different substituents on the boron and nitrogen atoms is evaluated in the enantioselective reduction of acetophenone. The performances of the homogeneous analog oxazaborolidines and silica supported-ones are compared by varying different parameters. This article deals with the synthesis, characterization and catalytic evaluation of silica-supported oxazaborolidines, their recycling capabilities and regeneration limitations.

  3. Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs

    OpenAIRE

    Yang, Chao

    2008-01-01

    Paclitaxel was isolated from the bark of Taxus brevifolia in the late 1960s. It exerts its biological effect by promoting tubulin polymerization and stabilizing the resulting microtubules. Paclitaxel has become one of the most important current drugs for the treatment of breast and ovarian cancers. Studies aimed at understanding the biologically active conformation of paclitaxel bound on ï ¢â tubulin are described. In this work, the synthesis of isotopically labeled taxol analogs is desc...

  4. Photoresistance analog multiplier has wide range

    Science.gov (United States)

    Hartenstein, R. G.

    1965-01-01

    Photoactivated bridge facilitates equal performance of analog multipliers over a wide frequency range. The multiplier operates from direct current to an upper frequency limited by either the light source or the closed-loop amplifier.

  5. An Electrical Analog Computer for Poets

    Science.gov (United States)

    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)

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

    Science.gov (United States)

    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)

  7. Synthetic heparin-binding growth factor analogs

    Science.gov (United States)

    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. Implementing neural architectures using analog VLSI circuits

    OpenAIRE

    Maher, Mary Ann C.; DeWeerth, Stephen P.; Mahowald, Misha A.; Mead, Carver A.

    1989-01-01

    Analog very large-scale integrated (VLSI) technology can be used not only to study and simulate biological systems, but also to emulate them in designing artificial sensory systems. A methodology for building these systems in CMOS VLSI technology has been developed using analog micropower circuit elements that can be hierarchically combined. Using this methodology, experimental VLSI chips of visual and motor subsystems have been designed and fabricated. These chips exhibit behavior similar to...

  9. Analogical Learning and Automated Rule Constructions

    Institute of Scientific and Technical Information of China (English)

    周哈阳

    1991-01-01

    This paper describes some experiments of analogical learning and automated rule construction.The present investigation focuses on knowledge acquisition,learning by analyogy,and knowledge retention.The developed system initially learns from scratch,gradually acquires knowledge from its environment through trial-and-error interaction,incrementally augments its knowledge base,and analogically solves new tasks in a more efficient and direct manner.

  10. A review of EBMT using proportional analogies

    OpenAIRE

    Somers, Harold; Dandapat, Sandipan; Naskar, Sudip Kumar

    2009-01-01

    Some years ago a number of papers reported an experimental implementation of Example Based Machine Translation (EBMT) using Proportional Analogy. This approach, a type of analogical learning, was attractive because of its simplicity; and the papers reported considerable success with the method. This paper reviews what we believe to be the totality of research reported using this method, as an introduction to our own experiments in this framework, reported in a companion paper. We report first...

  11. AMiBA Wideband Analog Correlator

    CERN Document Server

    Li, Chao-Te; 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; Wu, Jiun-Huei Proty

    2010-01-01

    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 IF distribution, backend 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.

  12. AMiBA Wideband Analog Correlator

    OpenAIRE

    Li, Chao-Te; Kubo, Derek Y.; Wilson, Warwick; Lin, Kai-Yang; Chen, Ming-Tang; P. T. P. Ho; Chen, Chung-Cheng; Han, Chih-Chiang; Oshiro, Peter; Martin-Cocher, Pierre; Chang, Chia-Hao; Chang, Shu-Hao; Altamirano, Pablo; Jiang, Homin; Chiueh, Tzi-Dar

    2010-01-01

    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 IF distribution, backend 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 c...

  13. AMiBA Wideband Analog Correlator

    Science.gov (United States)

    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.

  14. Analog modelling of obduction processes

    Science.gov (United States)

    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

  15. Development of analogical problem-solving skill.

    Science.gov (United States)

    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.

  16. Cyclic side-chain-linked opioid analogs utilizing cis- and trans-4-aminocyclohexyl-D-alanine.

    Science.gov (United States)

    Piekielna, Justyna; Gentilucci, Luca; De Marco, Rossella; Perlikowska, Renata; Adamska, Anna; Olczak, Jacek; Mazur, Marzena; Artali, Roberto; Modranka, Jakub; Janecki, Tomasz; Tömböly, Csaba; Janecka, Anna

    2014-12-01

    Cyclization of linear sequences is a well recognized tool in opioid peptide chemistry for generating analogs with improved bioactivities. Cyclization can be achieved through various bridging bonds between peptide ends or side-chains. In our earlier paper we have reported the synthesis and biological activity of a cyclic peptide, Tyr-c[D-Lys-Phe-Phe-Asp]NH2 (1), which can be viewed as an analog of endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH2). Cyclization was achieved through an amide bond between side-chains of D-Lys and Asp residues. Here, to increase rigidity of the cyclic structure, we replaced d-Lys with cis- or trans-4-aminocyclohexyl-D-alanine (D-ACAla). Two sets of analogs incorporating either Tyr or Dmt (2',6'-dimethyltyrosine) residues in position 1 were synthesized. In the binding studies the analog incorporating Dmt and trans-D-ACAla showed high affinity for both, μ- and δ-opioid receptors (MOR and DOR, respectively) and moderate affinity for the κ-opioid receptor (KOR), while analog with Dmt and cis-D-ACAla was exceptionally MOR-selective. Conformational analyses by NMR and molecular docking studies have been performed to investigate the molecular structural features responsible for the noteworthy MOR selectivity. PMID:25456075

  17. Conformational analysis of Infectious bursal disease virus (IBDV derived cell penetrating peptide (CPP analogs

    Directory of Open Access Journals (Sweden)

    Vinay G. Joshi

    2013-12-01

    Full Text Available Aim: This study was designed to develop peptide analogs of Infectious Bursal Disease (IBD virus VP5 protein segment having cell penetrating ability to improve their interaction with cargo molecule (Nucleic acid without affecting the backbone conformation. Materials and Methods: IBDV VP5 protein segment designated as RATH peptide were synthesized using solid phase peptide synthesis and their solution conformation was elucidated using CD spectroscopy in polar (water and apolar (TFE solvents. Cell penetrating ability of RATH-CONH2 was observed using FITC labeled peptide internalization in to HeLa cells under fluorescent microscopy. The efficacy of RATH analog interactions with nucleic acids was evaluated using FITC labeled oligonucleotides by fluorescence spectroscopy and plasmid constructs in gel retardation assay. Results: CD spectra of RATH analogs in water and apolar trifluroethanol (TFE helped to compare their secondary structures which were almost similar with dominant beta conformations suggesting successful induction of positive charge in the analogs without affecting back bone conformation of CPP designed. Cell penetrating ability of RATH CONH2 in HeLa cell was more than 90%. The fluorescence spectroscopy and plasmid constructs in gel retardation assay demonstrated successful interaction of amide analogs with nucleic acid. Conclusion: Intentional changes made in IBDV derived peptide RATH COOH to RATH CONH2 did not showed major changes in backbone conformation and such modifications may help to improve the cationic charge in most CPPs to interact with nucleic acid. [Vet World 2013; 6(6.000: 307-312

  18. Antinociceptive and antidepressant-like action of endomorphin-2 analogs with proline surrogates in position 2.

    Science.gov (United States)

    Perlikowska, Renata; Piekielna, Justyna; Mazur, Marzena; Koralewski, Robert; Olczak, Jacek; do Rego, Jean-Claude; Fichna, Jakub; Modranka, Jakub; Janecki, Tomasz; Janecka, Anna

    2014-09-01

    In our efforts to develop new candidate drugs with antinociceptive and/or antidepressant-like activity, two novel endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH2) analogs, containing proline surrogates in position 2 were synthesized using commercially available racemic trans-4-phenylpyrrolidine-3-carboxylic acid (4-Ph-β-Pro). The obtained mixture of two diastereoisomeric peptides (2a and 2b) was separated by HPLC and both enantiopure analogs were used in the in vitro and in vivo studies. To assign the absolute configuration to the 4-Ph-β-Pro residues in both peptides, the stereoselective synthesis of (3R,4S)-4-phenylpyrrolidine-3-carboxylic acid was performed and this enantiomer was introduced into position 2 of EM-2 sequence. Based on the HPLC retention times we were able to assign the absolute configuration of 4-Ph-β-Pro residues in both peptide analogs. Analog 2a incorporating (3R,4S)-4-Ph-β-Pro residue produced strong analgesia in mice after intracerebroventricular (icv) administration which was antagonized by the μ-opioid receptor (MOR) antagonist, β-funaltrexamine (β-FNA). This analog also influenced an emotion-related behavior of mice, decreasing immobility time in the forced swimming and tail suspension tests, without affecting locomotor activity. The antidepressant-like effect was reversed by the δ-selective antagonist, naltrindole (NLT) and κ-selective nor-binaltorphimine (nor-BNI). Thus, the experiments with selective opioid receptor antagonists revealed that analgesic action of analog 2a was mediated through the MOR, while the δ- and κ-receptors (DOR and KOR, respectively) were engaged in the antidepressant-like activity. Analog 2b with (3S,4R)-4-Ph-β-Pro in position 2 showed no antinociceptive or antidepressant-like activity in animal studies. PMID:25047937

  19. First total synthesis and stereochemical revision of laxaphycin B and its extension to lyngbyacyclamide A.

    Science.gov (United States)

    Boyaud, France; Mahiout, Zahia; Lenoir, Christine; Tang, Shoubin; Wdzieczak-Bakala, Joanna; Witczak, Anne; Bonnard, Isabelle; Banaigs, Bernard; Ye, Tao; Inguimbert, Nicolas

    2013-08-01

    The first total synthesis of laxaphycin B was accomplished through stepwise automated Solid Phase Peptide Synthesis (SPPS), leading to the structural revision of its stereochemistry especially with regard to the configuration of one of the two 3-hydroxyleucines of this cyclic dodecapeptide of marine origin. The analogous Lyngbyacyclamide A was obtained by an extension of this synthesis.

  20. The future of vitamin D analogs

    Directory of Open Access Journals (Sweden)

    Carlien eLeyssens

    2014-04-01

    Full Text Available The active form of vitamin D3, 1,25-dihydroxyvitamin D3, is a major regulator of bone and calcium homeostasis. In addition, this hormone also inhibits the proliferation and stimulates the differentiation of normal as well as malignant cells. Supraphysiological doses of 1,25-dihydroxyvitamin D3 are required to reduce cancer cell proliferation. However, these doses will lead in vivo to calcemic side effects such as hypercalcemia and hypercalciuria. During the last 25 years, many structural analogs of 1,25-dihydroxyvitamin D3 have been synthesized by the introduction of chemical modifications in the A-ring, central CD-ring region or side chain of 1,25-dihydroxyvitamin D3 in the hope to find molecules with a clear dissociation between the beneficial antiproliferative effects and adverse calcemic side effects. One example of such an analog with a good dissociation ratio is calcipotriol (DaivonexR, which is clinically used to treat the hyperproliferative skin disease psoriasis. Other vitamin D analogs were clinically approved for the treatment of osteoporosis or secondary hyperparathyroidism. No vitamin D analog is currently used in the clinic for the treatment of cancer although several analogs have been shown to be potent drugs in animal models of cancer. Omics studies as well as in vitro cell biological experiments unraveled basic mechanisms involved in the antineoplastic effects of vitamin D and its analogs. 1,25-dihydroxyvitamin D3 and analogs act in a cell type- and tissue-specific manner. Moreover, a blockade in the transition of the G0/1 towards S phase of the cell cycle, induction of apoptosis, inhibition of migration and invasion of tumor cells together with effects on angiogenesis and inflammation have been implicated in the pleiotropic effects of 1,25-dihydroxyvitamin D3 and its analogs. In this review we will give an overview of the action of vitamin D analogs in tumor cells and look forward how these compounds could be introduced in the

  1. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon

    2004-12-01

    Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the

  2. Magnetic activity of seismic solar analogs

    CERN Document Server

    Salabert, D

    2016-01-01

    We present our latest results on the solar-stellar connection by studying 18 solar analogs that we identified among the Kepler seismic sample (Salabert et al., 2016a). We measured their magnetic activity properties using observations collected by the Kepler satellite and the ground-based, high-resolution Hermes spectrograph. The photospheric (Sph) and chromospheric (S) magnetic activity proxies of these seismic solar analogs are compared in relation to solar activity. We show that the activity of the Sun is actually comparable to the activity of the seismic solar analogs. Furthermore, we report on the discovery of temporal variability in the acoustic frequencies of the young (1 Gyr-old) solar analog KIC10644253 with a modulation of about 1.5 years, which agrees with the derived photospheric activity (Salabert et al., 2016b). It could actually be the signature of the short-period modulation, or quasi-biennal oscillation, of its magnetic activity as observed in the Sun and the 1-Gyr-old solar analog HD30495. In...

  3. NaturAnalogs for the Unsaturated Zone

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Natural Analogs for the Unsaturated Zone

    International Nuclear Information System (INIS)

    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. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    Directory of Open Access Journals (Sweden)

    Troco K. Mihali

    2010-07-01

    Full Text Available Saxitoxin (STX and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs. PSTs are the causative agents of paralytic shellfish poisoning (PSP and are mostly associated with marine dinoflagellates (eukaryotes and freshwater cyanobacteria (prokaryotes, which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

  6. Analog forecasting with dynamics-adapted kernels

    Science.gov (United States)

    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.

  7. Not All Analogies Are Created Equal: Associative and Categorical Analogy Processing following Brain Damage

    Science.gov (United States)

    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. Automated synthesis of 8-output voltage distributor using incremental evolution

    OpenAIRE

    Sapargaliyev, Y; Kalganova, TG

    2010-01-01

    The automated synthesis of the analog electronic circuit, including both the topology and the numerical values for each of the circuit’s component, is recognized as a difficult problem. This problem is aggregating considerably when the size of a circuit and the number of its input/output pins increases. In this paper for the first time the method of automated synthesis of the analog electronic circuit by mean of evolution is applied to the synthesis of a multi-output circuit, namely 8-output ...

  9. Analog Forecasting with Dynamics-Adapted Kernels

    CERN Document Server

    Zhao, Zhizhen

    2014-01-01

    Analog forecasting is a non-parametric 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 state-space reconstruction for dynamical systems and kernel methods developed in harmonic analysis and machine learning. The first improvement is to augment the dimension of the initial data using Takens' delay-coordinate maps to recover information in the initial data lost through partial observations. Then, instead of using Euclidean distances between the states, weighted ensembles of analogs are constructed according to similarity kernels in delay-coordinate space, featuring an explicit dependence on the dynamical vector field generating the data. The eigenvalues and eigenfunctions ...

  10. Electronic devices for analog signal processing

    CERN Document Server

    Rybin, Yu K

    2012-01-01

    Electronic Devices for Analog Signal Processing is intended for engineers and post graduates and considers electronic devices applied to process analog signals in instrument making, automation, measurements, and other branches of technology. They perform various transformations of electrical signals: scaling, integration, logarithming, etc. The need in their deeper study is caused, on the one hand, by the extension of the forms of the input signal and increasing accuracy and performance of such devices, and on the other hand, new devices constantly emerge and are already widely used in practice, but no information about them are written in books on electronics. The basic approach of presenting the material in Electronic Devices for Analog Signal Processing can be formulated as follows: the study with help from self-education. While divided into seven chapters, each chapter contains theoretical material, examples of practical problems, questions and tests. The most difficult questions are marked by a diamon...

  11. On Lovelock analogs of the Riemann tensor

    Energy Technology Data Exchange (ETDEWEB)

    Camanho, Xian O. [Albert-Einstein-Institut, Max-Planck-Institut fuer Gravitationsphysik, Golm (Germany); Dadhich, Naresh [Jamia Millia Islamia, Centre for Theoretical Physics, New Delhi (India); Inter-University Centre for Astronomy and Astrophysics, Pune (India)

    2016-03-15

    It is possible to define an analog of the Riemann tensor for Nth order Lovelock gravity, its characterizing property being that the trace of its Bianchi derivative yields the corresponding analog of the Einstein tensor. Interestingly there exist two parallel but distinct such analogs and the main purpose of this note is to reconcile both formulations. In addition we will introduce a simple tensor identity and use it to show that any pure Lovelock vacuum in odd d = 2N + 1 dimensions is Lovelock flat, i.e. any vacuum solution of the theory has vanishing Lovelock-Riemann tensor. Further, in the presence of cosmological constant it is the Lovelock-Weyl tensor that vanishes. (orig.)

  12. Formal analogies in physics teacher education

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Ricardo, Elio

    2012-01-01

    Reasoning by similarities, especially the ones associated with formal aspects, is one of the most valuable sources for the development of physical theories. The essential role of formal analogies in science can be highlighted by the fact that several equations for different physical situations have...... the exact same appearance. Coulomb’s law’s similarity with Newton’s, Maxwell’s application of fluid theory to electromagnetism and Hamilton’s optical mechanical analogy are some among many other examples. These cases illustrate the power of mathematics in providing unifying structures for physics. Despite...... the relevance of the subject, formal analogies are rarely systematically approached in physics education. In order to discuss this issue with pre-service physics teachers, we planned a lecture and designed a questionnaire with the goal of encouraging them to think about some “coincidences” in well known...

  13. Analogy-Enhanced Instruction: Effects on Reasoning Skills in Science

    Science.gov (United States)

    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…

  14. Analogies between a Meniscus and a Cantilever

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-Lin

    2009-01-01

    Systematic and quantitative analyses of exact analogies between a meniscus and an elastica are performed. It is shown that the two governing equations take the same style after coordinate translation and scale transformation. The morphologies of the liquid bridge and the cantilever are calculated in terms of elliptic integrations, which can be reduced to the same shape,after converting the boundary conditions. The present analyses can make us grasp the nature of this physical phenomenon deeply and show some inspiration for designing the analogy experiments. Moreover, the calculated results are helpful to engineering applications, such as design and fabrication of MEMS, and micro-manipulations in micro/nano- technology.

  15. Synthetic heparin-binding factor analogs

    Science.gov (United States)

    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.

  16. Associative Pattern Recognition In Analog VLSI Circuits

    Science.gov (United States)

    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.

  17. An Optical Analog of a Black Holes

    CERN Document Server

    Royston, A; Royston, Andrew; Gass, Richard

    2002-01-01

    Using media with extremely low group velocities one can create an optical analog of a curved space-time. Leonhardt and Piwnicki have proposed that a vortex flow will act as an optical black hole. We show that although the Leonhardt - Piwnicki flow has an orbit of no return and an infinite red-shift surface, it is not a true black hole since it lacks a null hypersurface. However a radial flow will produce a true optical black hole that has a Hawking temperature and obeys the first law of black hole mechanics. By combining the Leonhardt - Piwnicki flow with a radial flow we obtain the analog of the Kerr black hole.

  18. HAPS, a Handy Analog Programming System

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1975-01-01

    HAPS (Hybrid Analog Programming System) is an analog compiler that can be run on a minicomputer in an interactive mode. Essentially HAPS is written in FORTRAN. The equations to be programmed for an ana log computer are read in by using a FORTRAN-like notation. The input must contain maximum...... and minimum values for the variables. The output file includes potentiometer coefficients and static-test 'measuring values.' The file format is fitted to an automatic potentiometer-setting and static-test program. Patch instructions are printed by HAPS. The article describes the principles of HAPS...

  19. Landauer bound for analog computing systems.

    Science.gov (United States)

    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

  20. Landauer bound for analog computing systems

    Science.gov (United States)

    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.

  1. Landauer Bound for Analog Computing Systems

    CERN Document Server

    Diamantini, M Cristina; Trugenberger, Carlo A

    2016-01-01

    By establishing a relation between information erasure and continuous phase transitions we generalise 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.

  2. Simultaneous synthesis of work exchange networks with heat integration

    OpenAIRE

    Onishi, Viviani C.; Ravagnani, Mauro A.S.S.; Caballero Suárez, José Antonio

    2014-01-01

    The optimal integration of work and its interaction with heat can represent large energy savings in industrial plants. This paper introduces a new optimization model for the simultaneous synthesis of work exchange networks (WENs), with heat integration for the optimal pressure recovery of process gaseous streams. The proposed approach for the WEN synthesis is analogous to the well-known problem of synthesis of heat exchanger networks (HENs). Thus, there is work exchange between high-pressure ...

  3. High-speed and high-resolution analog-to-digital and digital-to-analog converters

    NARCIS (Netherlands)

    van de Plassche, R.J.

    1989-01-01

    Analog-to-digital and digital-to-analog converters are important building blocks connecting the analog world of transducers with the digital world of computing, signal processing and data acquisition systems. In chapter two the converter as part of a system is described. Requirements of analog filte

  4. Radiation Behavior of Analog Neural Network Chip

    Science.gov (United States)

    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.

  5. Analog Acoustic Expression in Speech Communication

    Science.gov (United States)

    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…

  6. The GMO-Nanotech (Dis)Analogy?

    Science.gov (United States)

    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…

  7. Analog circuit design designing waveform processing circuits

    CERN Document Server

    Feucht, Dennis

    2010-01-01

    The fourth volume in the set Designing Waveform-Processing Circuits builds on the previous 3 volumes and presents a variety of analog non-amplifier circuits, including voltage references, current sources, filters, hysteresis switches and oscilloscope trigger and sweep circuitry, function generation, absolute-value circuits, and peak detectors.

  8. C4913 ANALOGE OG DIGITALE FILTRE

    DEFF Research Database (Denmark)

    Gaunholt, Hans

    1996-01-01

    Theese lecture notes treats the fundamental theory and the most commonly used design methods for passive- active and digital filters with special emphasis on microelectronic realizations. The lecture notes covers 75% of the material taught in the course C4913 Analog and Digital Filters...

  9. CMOS circuits for analog signal processing

    NARCIS (Netherlands)

    Wallinga, Hans

    1988-01-01

    Design choices in CMOS analog signal processing circuits are presented. Special attention is focussed on continuous-time filter technologies. The basics of MOSFET-C continuous-time filters and CMOS Square Law Circuits are explained at the hand of a graphical MOST characteristics representation.

  10. Biological Analogs for Language Contact Situations

    Science.gov (United States)

    Seliger, Herbert W.

    1977-01-01

    This article proposes that language contact can be best understood if the entire range of such situations from second language learning to evolution of dialects and creoles is studied within a framework analogical to the symbiosis of living organisms. Language contact is viewed in terms of dynamic evolutionary stages. (CHK)

  11. A high-speed analog neural processor

    NARCIS (Netherlands)

    Masa, Peter; Hoen, Klaas; Wallinga, Hans

    1994-01-01

    Targeted at high-energy physics research applications, our special-purpose analog neural processor can classify up to 70 dimensional vectors within 50 nanoseconds. The decision-making process of the implemented feedforward neural network enables this type of computation to tolerate weight discretiza

  12. Bootstrapped Low-Voltage Analog Switches

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jesper

    1999-01-01

    Novel low-voltage constant-impedance analog switch circuits are proposed. The switch element is a single MOSFET, and constant-impedance operation is obtained using simple circuits to adjust the gate and bulk voltages relative to the switched signal. Low-voltage (1-volt) operation is made feasible...

  13. Generating Analog IC Layouts with LAYGEN II

    CERN Document Server

    Martins, Ricardo M F; Horta, Nuno C G

    2013-01-01

    This book presents an innovative methodology for the automatic generation of analog integrated circuits (ICs) layout, based on template descriptions and on evolutionary computational techniques. A design automation tool, LAYGEN II, was implemented to validate the proposed approach giving special emphasis to reusability of expert design knowledge and to efficiency on retargeting operations.

  14. Analog Optical Computing Primitives in Silicon Photonics

    CERN Document Server

    Jiang, Yunshan; Jalali, Bahram

    2015-01-01

    Optical computing accelerators may 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. The function is realized by exploiting nonlinear-absorption-enhanced Raman amplification saturation in a silicon waveguide.

  15. Analog optical computing primitives in silicon photonics

    Science.gov (United States)

    Jiang, Yunshan; DeVore, Peter T. S.; Jalali, Bahram

    2016-03-01

    Optical computing accelerators may 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. The function is realized by exploiting nonlinear-absorption-enhanced Raman amplification saturation in a silicon waveguide.

  16. A Mechanical Analogy for Ohm's Law.

    Science.gov (United States)

    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)

  17. Classical Analog of Electromagnetically Induced Transparency

    CERN Document Server

    Alzar, C L G; Nussenzveig, P

    2002-01-01

    We present a classical analog for Electromagnetically Induced Transparency (EIT). In a system of just two coupled harmonic oscillators subject to a harmonic driving force we can reproduce the phenomenology observed in EIT. We describe a simple experiment performed with two linearly coupled RLC circuits which can be taught in an undergraduate laboratory class.

  18. Analogy between thermal convective and magnetohydrodynamic instabilities

    Energy Technology Data Exchange (ETDEWEB)

    Valdmanis, Ya.Ya.; Kukainis, O.A.

    1977-01-01

    An examination is made of the analogy between thermo-convective instability and instability produced by various electromagnetic forces both in steady and alternating thermal and electromagnetic fields. An example is given for calculating an assumed bubble instability which could occur in an alternating magnetic field. 17 references.

  19. Plasma analog of particle-pair production

    International Nuclear Information System (INIS)

    It is shown that the plasma axial shear flow instability satisfies the Klein-Gordon equation. The plasma instability is then shown to be analogous to spontaneous particle-pair production when a potential energy is present that is greater than twice the particle rest mass energy. Stability criteria can be inferred based on field theoretical conservation laws. (UK)

  20. Double point modified analogs of vitamin d as potent activators of vitamin D receptor.

    Science.gov (United States)

    Nadkarni, Sharmin; Chodynski, Michal; Corcoran, Aoife; Marcinkowska, Ewa; Brown, Geoffrey; Kutner, Andrzej

    2015-01-01

    Rational design, chemical synthesis, structural analysis, molecular modeling and biological evaluation are reviewed for all the double point modified vitamin D analogs that have been developed as potential therapeutics over the last several years. The idea of double modifications was based on the 3D structure of the ligand binding domain of the model of the vitamin D receptor. It was recently proved that structural modifications in the two remote parts of the vitamin D molecule might have additive biological effects resulting in an increased functional activity and lowered calcemic side effect. Recent in vivo experiments clearly demonstrated the potential use of these analogs in new therapeutic areas such as autoimmune and hyper-proliferative diseases, including cancer and the systemic treatment of psoriasis. Although some of these analogs are already approaching clinical trials, the molecular mechanism of action and their improved efficiency still remain to be fully understood. In this review the key steps of the convergent synthetic strategies that combine the modified A-ring and the CD-ring fragment carrying the altered side-chain are presented. The advantages of using the natural alicyclic and acyclic precursors are demonstrated as well as all the modern synthetic methodologies used for combining structural fragments. The results of molecular mechanics modeling are critically examined as well as the advantages and limitations of the use of the models of vitamin D proteins for the docking experiments and the design of new analogs. The potential use of advanced structural approaches, including high resolution X-ray crystallography, is discussed as to the prospect of providing a better understanding of the observed activity of modified analogs. Biological profiles in vitro and in vivo for groups of analogs are presented in a new tabular form to illustrate structure activity relationships. PMID:25483861

  1. Synthesis and Anti-Fungal Activity of Seven Oleanolic Acid Glycosides

    Directory of Open Access Journals (Sweden)

    Daoquan Wang

    2011-01-01

    Full Text Available In order to develop potential anti-fungal agents, seven glycoconjugates composed of a-L-rhamnose, 6-deoxy-a-L-talose, b-D-galactose, a-D-mannose, b-D-xylose-(1®4-6-deoxy-a-L-talose, b-D-galactose-(1®4-a-L-rhamnose, b-D-galactose-(1®3-b-D-xylose-(1®4-6-deoxy-a-L-talose as the glycone and oleanolic acid as the aglycone were synthesized in an efficient and practical way using glycosyl trichloroacetimidates as donors. The structures of the new compounds were confirmed by MS, 1H-NMR and 13C- NMR. Preliminary studies based on means of mycelium growth rate, indicated that all the compounds possess certain fungicidal activity against Sclerotinia sclerotiorum (Lib. de Bary, Rhizoctonia solani Kuhn, Botrytis cinerea Pers and Phytophthora parasitica Dast.

  2. Microwave-assisted radiosynthesis of [{sup 18}F]fluorinated fatty acid analogs

    Energy Technology Data Exchange (ETDEWEB)

    Belanger, Anthony P.; Pandey, Mukesh K.; DeGrado, Timothy R., E-mail: tdegrado@partners.or

    2011-04-15

    Microwave reactors remain largely underutilized in the field of positron emission tomography (PET) chemistry. This is particularly unfortunate since microwave synthesis elegantly addresses two of the most critical issues of PET radiochemistry with short-lived radionuclides: reaction rate and side-product formation. In this study, we investigate the efficiency of synthesis of terminally [{sup 18}F]fluorinated fatty acid analogs using a commercial microwave reactor in comparison with conventional heating (CH). Methods: The labeling precursors were methyl esters of terminally substituted alkyl bromides and iodides. Duration and temperatures of the [{sup 18}F]fluorination reaction were varied. Chemical and radiochemical purities, and radiochemical yields were investigated for conventional (CH) and microwave-assisted (MW) radiosyntheses. Results: The results demonstrate that microwave heating enhanced [{sup 18}F]fluoride incorporation to >95% (up to 55% improvement), while reducing reaction times to 2 min ({approx}10-fold reduction) or temperatures to 55-60{sup o}C (20{sup o}C reduction). Overall decay-corrected radiochemical yields of purified [{sup 18}F]fluoro fatty acids were higher (MW=49.0{+-}4.5%, CH=23.6{+-}3.5%, P<.05) with microwave heating and side-products were notably fewer. Conclusion: For routine synthesis of [{sup 18}F]fluoro fatty acid analogs, microwave heating is faster, milder, cleaner, less variable and higher yielding than CH and therefore the preferred reaction method.

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

    Science.gov (United States)

    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

  4. Glucagon-Like Peptide 1 Analogs and their Effects on Pancreatic Islets.

    Science.gov (United States)

    Tudurí, Eva; López, Miguel; Diéguez, Carlos; Nadal, Angel; Nogueiras, Rubén

    2016-05-01

    Glucagon-like peptide 1 (GLP-1) exerts many actions that improve glycemic control. GLP-1 stimulates glucose-stimulated insulin secretion and protects β cells, while its extrapancreatic effects include cardioprotection, reduction of hepatic glucose production, and regulation of satiety. Although an appealing antidiabetic drug candidate, the rapid degradation of GLP-1 by dipeptidyl peptidase 4 (DPP-4) means that its therapeutic use is unfeasible, and this prompted the development of two main GLP-1 therapies: long-acting GLP-1 analogs and DPP-4 inhibitors. In this review, we focus on the pancreatic effects exerted by current GLP-1 derivatives used to treat diabetes. Based on the results from in vitro and in vivo studies in humans and animal models, we describe the specific actions of GLP-1 analogs on the synthesis, processing, and secretion of insulin, islet morphology, and β cell proliferation and apoptosis. PMID:27062006

  5. Probing functions of the ribosomal peptidyl transferase center by nucleotide analog interference.

    Science.gov (United States)

    Erlacher, Matthias D; Polacek, Norbert

    2012-01-01

    The ribosome is a huge ribonucleoprotein complex in charge of protein synthesis in every living cell. The catalytic center of this dynamic molecular machine is entirely built up of 23S ribosomal RNA and therefore the ribosome can be referred to as the largest natural ribozyme known so far. The in vitro reconstitution approach of large ribosomal subunits described herein allows nucleotide analog interference studies to be performed. The approach is based on the site-specific introduction of nonnatural nucleotide analogs into the peptidyl transferase center, the active site located on the interface side of the large ribosomal subunit. This method combined with standard tests of ribosomal functions broadens the biochemical repertoire to investigate the mechanism of diverse aspects of translation considerably and adds another layer of molecular information on top of structural and mutational studies of the ribosome. PMID:22315072

  6. Playing with a double-edged sword: Analogies in biochemistry

    Science.gov (United States)

    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

  7. Analog Computation by DNA Strand Displacement Circuits.

    Science.gov (United States)

    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

  8. A new program on digitizing analog seismograms

    Science.gov (United States)

    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.

  9. Optimal neural computations require analog processors

    Energy Technology Data Exchange (ETDEWEB)

    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).

  10. An analogy strategy for transformation optics

    International Nuclear Information System (INIS)

    We introduce an analogy strategy to design transformation optical devices. Based on the similarities between field lines in different physical systems, the trajectories of light can be intuitively determined to curve in a gentle manner, and the resulting materials are isotropic and nonmagnetic. Furthermore, the physical meaning of the analogue problems plays a key role in the removal of dielectric singularities. We illustrate this approach by creating two designs of carpet cloak and a collimating lens as representative examples in two- and three-dimensional spaces, respectively. The analogy strategy not only reveals the intimate connections between different physical disciplines, such as optics, fluid mechanics and electrostatics, but also provides a heuristic pathway to designing advanced photonic systems

  11. Observing spin optodynamical analog of cavity optomechanics

    Science.gov (United States)

    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.

  12. Parabolic flight as a spaceflight analog.

    Science.gov (United States)

    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.

  13. Analog fault diagnosis by inverse problem technique

    KAUST Repository

    Ahmed, Rania F.

    2011-12-01

    A novel algorithm for detecting soft faults in linear analog circuits based on the inverse problem concept is proposed. The proposed approach utilizes optimization techniques with the aid of sensitivity analysis. The main contribution of this work is to apply the inverse problem technique to estimate the actual parameter values of the tested circuit and so, to detect and diagnose single fault in analog circuits. The validation of the algorithm is illustrated through applying it to Sallen-Key second order band pass filter and the results show that the detecting percentage efficiency was 100% and also, the maximum error percentage of estimating the parameter values is 0.7%. This technique can be applied to any other linear circuit and it also can be extended to be applied to non-linear circuits. © 2011 IEEE.

  14. ON THE FREQUENCY OF JUPITER ANALOGS

    International Nuclear Information System (INIS)

    The Anglo-Australian Planet Search has now accumulated 12 years of radial-velocity data with long-term instrumental precision better than 3 m s-1. In this paper, we expand on earlier simulation work, to probe the frequency of near-circular, long-period gas-giant planets residing at orbital distances of 3-6 AU-the so-called Jupiter analogs. We present the first comprehensive analysis of the frequency of these objects based on radial-velocity data. We find that 3.3% of stars in our sample host Jupiter analogs; detailed, star-by-star simulations show that no more than 37% of stars host a giant planet between 3 and 6 AU.

  15. Analog data transmission via fiber optics

    International Nuclear Information System (INIS)

    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

  16. Analog controllers using digital stochastic logic

    OpenAIRE

    Quero Reboul, José Manuel; S. L. Toral; García Ortega, Juan de la Cruz; García Franquelo, Leopoldo

    1999-01-01

    Stochastic logic is based on digital processing of a random pulse stream, where the information is codified as the probability of a high level in a finite sequence. The probability of the pulse stream codifies a continuous time variable. Subsequently, this pulse stream can be digitally processed to perform analog operations. In this paper we propose a stochastic approach to the digital implementation of complex controllers. This is approach allows for the realization of the controllers, and A...

  17. Priming Analogical Reasoning with False Memories

    OpenAIRE

    Howe, M. L.; Garner, S. R.; Threadgold, E.; Ball, L. J.

    2015-01-01

    Like true memories, false memories are capable of priming answers to insight-based problems. Recent research has attempted to extend this paradigm to more advanced problem-solving tasks, including those involving verbal analogical reasoning. However, these experiments are constrained inasmuch as problem solutions could be generated via spreading activation mechanisms (much like false memories themselves) rather than using complex reasoning processes. In three experiments we examined false mem...

  18. Developing Fluorescent Hyaluronan Analogs for Hyaluronan Studies

    OpenAIRE

    Shi Ke; Arlin G. Cameron; Wei Wang

    2012-01-01

    Two kinds of fluorescent hyaluronan (HA) analogs, one serving as normal imaging agent and the other used as a biosensitive contrast agent, were developed for the investigation of HA uptake and degradation. Our approach of developing HA imaging agents depends on labeling HA with varying molar percentages of a near-infrared (NIR) dye. At low labeling ratios, the hyaluronan uptake can be directly imaged while at high labeling ratios, the fluorescent signal is quenched and signal generation occur...

  19. Analog optical computing primitives in silicon photonics.

    Science.gov (United States)

    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

  20. The 2012 Moon and Mars Analog Mission

    Science.gov (United States)

    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.

  1. An introduction to analog and digital communications

    CERN Document Server

    Haykin, Simon

    2012-01-01

    The second edition of this accessible book provides readers with an introductory treatment of communication theory as applied to the transmission of information-bearing signals. While it covers analog communications, the emphasis is placed on digital technology. It begins by presenting the functional blocks that constitute the transmitter and receiver of a communication system. Readers will next learn about electrical noise and then progress to multiplexing and multiple access techniques.

  2. Electrical Analogy to an Atomic Force Microscope

    Directory of Open Access Journals (Sweden)

    O. Kucera

    2010-04-01

    Full Text Available Several applications of the atomic force microscopy (AFM, such as measurement of soft samples, manipulation with molecules, etc., require mechanical analysis of the AFM probe behavior. In this article we suggest the electrical circuit analogy to AFM cantilever tip motion. Well developed circuit theories in connection with fairly accessible software for circuit analysis make this alternative method easy to use for a wide community of AFM users.

  3. Survey of Evaluated Isobaric Analog States

    Energy Technology Data Exchange (ETDEWEB)

    MacCormick, M., E-mail: maccorm@ipno.in2p3.fr [Institut de Physique Nucléaire, CNRS/IN2P3, Université Paris-Sud, 91406 Orsay CEDEX (France); Audi, G. [Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse, CNRS/IN2P3, Université Paris-Sud, Bât. 108, F-91405 Orsay Campus (France)

    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.

  4. The exoplanets analogy to the Multiverse

    OpenAIRE

    Kinouchi, Osame

    2015-01-01

    The idea of a Mutiverse is controversial, although it is a natural possible solution to particle physics and cosmological fine-tuning problems (FTPs). Here I explore the analogy between the Multiverse proposal and the proposal that there exist an infinite number of stellar systems with planets in a flat Universe, the Multiplanetverse. Although the measure problem is present in this scenario, the idea of a Multiplanetverse has predictive power, even in the absence of direct evidence for exopla...

  5. Backtracking quantum trajectories with analog feedback

    Science.gov (United States)

    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.

  6. Theory of analogous force on number sets

    International Nuclear Information System (INIS)

    A general statistical thermodynamic theory that considers given sequences of x-integers to play the role of particles of known type in an isolated elastic system is proposed. By also considering some explicit discrete probability distributions px for natural numbers, we claim that they lead to a better understanding of probabilistic laws associated with number theory. Sequences of numbers are treated as the size measure of finite sets. By considering px to describe complex phenomena, the theory leads to derive a distinct analogous force fx on number sets proportional to (∂px/∂x)T at an analogous system temperature T. In particular, this yields to an understanding of the uneven distribution of integers of random sets in terms of analogous scale invariance and a screened inverse square force acting on the significant digits. The theory also allows to establish recursion relations to predict sequences of Fibonacci numbers and to give an answer to the interesting theoretical question of the appearance of the Benford's law in Fibonacci numbers. A possible relevance to prime numbers is also analyzed. (author)

  7. ANALOG SIGNAL PROCESSING SOLUTION FOR IMAGE ALIGNMENT

    Directory of Open Access Journals (Sweden)

    Nihar Athreyas

    2014-11-01

    Full Text Available Imaging and Image sensors is a field that is continuously evolving. There are new products coming into the market every day. Some of these have very severe Size, Weight and Power constraints whereas other devices have to handle very high computational loads. Some require both these conditions to be met simultaneously. Current imaging architectures and digital image processing solutions will not be able to meet these ever increasing demands. There is a need to develop novel imaging architectures and image processing solutions to address these requirements. In this work we propose analog signal processing as a solution to this problem. The analog processor is not suggested as a replacement to a digital processor but it will be used as an augmentation device which works in parallel with the digital processor, making the system faster and more efficient. In order to show the merits of analog processing the highly computational Normalized Cross Correlation algorithm is implemented. We propose two novel modifications to the algorithm and a new imaging architecture which, significantly reduces the computation time.

  8. Radiolabeled somatostatin analogs: Biodistribution and pharmacokinetics

    International Nuclear Information System (INIS)

    Different somatostatin analogs labeled with iodine-123 or indium-111 are currently used for the scintigraphic in vivo detection of somatostatin receptor expression by neuroendocrine tumors. The general features of the biodistribution of iodine-123-Tyr3-octreotide are the rapid clearance from the circulation and the predominantly hepatobiliary excretion. This pathway of excretion leads to a considerable amount of activity in the bowels and thus may compromise the diagnostic reliability of somatostatin receptor scintigraphy in gastroentereopancreatic tumors. In contrast, up to 85% of the applied dose of indium-111 labeled pentreotide is cleared from the circulation via the kidneys. High receptor density and affinity as well as the small molecular size of the labeled somatostatin analogs are most likely responsible for the observed rapid tumor visualization within a few hours after intravenous application of the radiopharmaceuticals. Continuous treatment with somatostatin analogs changes the biodistribution of indium-111 pentetreotide, but the diagnostic reliability of somatostatin receptor scintigraphy is not necessarily compromised under these therapeutic conditions. (orig./MG)

  9. Progress in Synthesis and Antagonistic Activities towards PAFR and GlyR of Ginkgolide Derivatives and Analogs%银杏内酯衍生物和类似物的合成及PAFR和GlyR拮抗活性研究进展

    Institute of Scientific and Technical Information of China (English)

    惠爱玲; 吴泽宇; 袁媛; 周安; 潘见

    2013-01-01

    Ginkgolides are diterpene trilactones with a cage-like skeleton consisting of six five-membered rings and a unique t-Bu group from Ginkgo biloba tree.Many studies have demonstrated that they are highly potent and selective antagonists of platelet activating factor receptor (PAFR) and glycine receptor (GlyR).Ginkgolide skeleton modifications may conduce to physiological activities variation.Therefore,many ginkgolide derivatives and analogs have been synthesized for the optimal antagonistic activities towards PAFR or GlyR.This review covers the structure-activity relationship studies of ginkgolide derivatives and analogs.%银杏内酯是从银杏树中分离的二萜内酯成分,它的结构是由6个五元环形成的笼状骨架并嵌有一个独特的叔丁基.研究已证实银杏内酯是血小板活化因子受体(PAFR)和甘氨酸受体(GlyR)的强有力拮抗剂,它的结构变化将引起生物活性的改变.因此,为了寻找更优的PAFR和GlyR拮抗剂,人们合成了许多银杏内酯衍生物及类似物.重点综述了近年来银杏内酯类化合物的构效关系研究.

  10. Analogies in Medicine: Valuable for Learning, Reasoning, Remembering and Naming

    Science.gov (United States)

    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…

  11. Functional DNA: Teaching Infinite Series through Genetic Analogy

    Science.gov (United States)

    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…

  12. Anti-inflammatory effect of thalidomide dithiocarbamate and dithioate analogs.

    Science.gov (United States)

    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.

  13. 6-Deoxyhexoses from l-Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

    DEFF Research Database (Denmark)

    Liu, Zilei; Yoshihara, Akihide; Kelly, Ciarán;

    2016-01-01

    In the search for alternative non-metabolizable inducers in the l-rhamnose promoter system, the synthesis of fifteen 6-deoxyhexoses from l-rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3-acetonide of rhamnonolactone allows inversion...... of configuration at C4 and/or C5 of rhamnose to give 6-deoxy-d-allose, 6-deoxy-d-gulose and 6-deoxy-l-talose. Highly crystalline 3,5-benzylidene rhamnonolactone gives easy access to l-quinovose (6-deoxy-l-glucose), l-olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic...... fluorination of rhamnal gives a mixture of 2-deoxy-2-fluoro-l-rhamnose and 2-deoxy-2-fluoro-l-quinovose. Biotechnology provides access to 6-deoxy-l-altrose and 1-deoxy-l-fructose....

  14. SSERVI Analog Regolith Simulant Testbed Facility

    Science.gov (United States)

    Minafra, Joseph; Schmidt, Gregory; Bailey, Brad; Gibbs, Kristina

    2016-10-01

    The Solar System Exploration Research Virtual Institute (SSERVI) at NASA's Ames Research Center in California's Silicon Valley was founded in 2013 to act as a virtual institute that provides interdisciplinary research centered on the goals of its supporting directorates: NASA Science Mission Directorate (SMD) and the Human Exploration & Operations Mission Directorate (HEOMD).Primary research goals of the Institute revolve around the integration of science and exploration to gain knowledge required for the future of human space exploration beyond low Earth orbit. SSERVI intends to leverage existing JSC1A regolith simulant resources into the creation of a regolith simulant testbed facility. The purpose of this testbed concept is to provide the planetary exploration community with a readily available capability to test hardware and conduct research in a large simulant environment.SSERVI's goals include supporting planetary researchers within NASA, other government agencies; private sector and hardware developers; competitors in focused prize design competitions; and academic sector researchers.SSERVI provides opportunities for research scientists and engineers to study the effects of regolith analog testbed research in the planetary exploration field. This capability is essential to help to understand the basic effects of continued long-term exposure to a simulated analog test environment.The current facility houses approximately eight tons of JSC-1A lunar regolith simulant in a test bin consisting of a 4 meter by 4 meter area, including dust mitigation and safety oversight.Facility hardware and environment testing scenarios could include, Lunar surface mobility, Dust exposure and mitigation, Regolith handling and excavation, Solar-like illumination, Lunar surface compaction profile, Lofted dust, Mechanical properties of lunar regolith, Surface features (i.e. grades and rocks)Numerous benefits vary from easy access to a controlled analog regolith simulant testbed, and

  15. Novel Gemini vitamin D3 analogs

    DEFF Research Database (Denmark)

    Okamoto, Ryoko; Gery, Sigal; Kuwayama, Yoshio;

    2014-01-01

    anticancer potency, but similar toxicity causing hypercalcemia. We focused on the effect of these compounds on the stimulation of expression of human cathelicidin antimicrobial peptide (CAMP) whose gene has a vitamin D response element in its promoter. Expression of CAMP mRNA and protein increased in a dose......-response fashion after exposure of acute myeloid leukemia (AML) cells to the Gemini analog, BXL-01-126, in vitro. A xenograft model of AML was developed using U937 AML cells injected into NSG-immunodeficient mice. Administration of vitamin D3 compounds to these mice resulted in substantial levels of CAMP...

  16. Integrated Analogic Filter Tuning System Design

    Directory of Open Access Journals (Sweden)

    Karolis Kiela

    2016-06-01

    Full Text Available Parameters of integrated analog filters can vary due to temperatu-re change, IC process variation and therefore they should have dedicated tuning circuits that compensate these imperfections. A method is proposed that speeds up switched resistor bank design while taking into account the required tuning range and step size. A novel counter structure is used in the tuning circuit that is ba-sed on successive approximation approach. The proposed swit-ched resistor design method and tuning circuit are designed in 0.18 μm CMOS technology and verified. Results are compared to existing tuning circuit designs.

  17. Analogic China map constructed by DNA

    Institute of Scientific and Technical Information of China (English)

    QIAN Lulu; HE Lin; WANG Ying; ZHANG Zhao; ZHAO Jian; PAN Dun; ZHANG Yi; LIU Qiang; FAN Chunhai; HU Jun

    2006-01-01

    In this research, a nanoscale DNA structure of analogic China map is created. The nanostructure of roughly 150 nm in diameter with a spatial resolution of 6 nm is purely constructed by folding DNA. The picture observed by atomic force microscopy (AFM) is almost identical with the designed shape. The DNA origami technology invented by Rothemund in 2006 is employed in the construction of this shape, which has proved the capability of constructing almost any complicated shape enabled by DNA origami, and provides new bottom-up method for constructing nanostructures.

  18. High fluid intelligence and analogical reasoning

    OpenAIRE

    Preusse, Franziska

    2011-01-01

    Hitherto, previous studies on the cerebral correlates of fluid intelligence (fluIQ) used tasks that did not exclusively demand fluIQ, or were restricted to participants of average fluIQ (ave-fluIQ) solving intelligence test items of varying difficulty, thus not allowing assumptions on interindividual differences in fluIQ. Geometric analogical reasoning (GAR) demands fluIQ very purely and thus is an eligible approach for research on interindividual differences in fluIQ. In a first study, we ...

  19. Design of analog circuits through symbolic analysis

    CERN Document Server

    Fakhfakh, Mourad; V Fernández, Francisco

    2012-01-01

    Symbolic analyzers have the potential to offer knowledge to sophomores as well as practitioners of analog circuit design. Actually, they are an essential complement to numerical simulators, since they provide insight into circuit behavior which numerical analyzers do not provide. Symbolic analysis of electronic circuits addresses the generation of symbolic expressions for the parameters that describe the performance of linear and nonlinear circuits in three domains: DC, AC and time; some or all the circuit parameters can be kept as symbols. Due to the fact that these expressions remain va

  20. Microstore: the Stanford analog memory unit

    Energy Technology Data Exchange (ETDEWEB)

    Walker, J.T.; Chae, S.I.; Shapiro, S.; Larsen, R.S.

    1984-11-01

    An NMOS device has been developed which provides high speed analog signal storage and readout for time expansion of transient signals. This device takes advantage of HMOS-1 VLSI technology to implement an array of 256 storage cells. Sequential samples of an input waveform can be taken every 5 ns while providing an effective sampling aperture time of less than 1 ns. The design signal-to-noise ratio is 1 part in 2000. Digital control circuitry is provided on the chip for controlling the read-in and read-out processes. A reference circuit is incorporated in the chip for first order compensation of leakage drifts, sampling pedestals, and temperature effects.

  1. An optical analog of quantum optomechanics

    CERN Document Server

    Rodríguez-Lara, B M

    2014-01-01

    We present a two-dimensional array of nearest-neighbor coupled waveguides that is the optical analog of a quantum optomechanical system. We show that the quantum model predicts the appearance of effective column isolation, diagonal-coupling and other non-trivial couplings in the two-dimensional photonic lattice under a standard approximation from ion-trap cavity electrodynamics. We provide an approximate impulse function for the case of effective column isolation and compare it with exact numerical propagation in the photonic lattice.

  2. Analogy perception applied to seven tests of word comprehension

    CERN Document Server

    Turney, Peter D

    2011-01-01

    It has been argued that analogy is the core of cognition. In AI research, algorithms for analogy are often limited by the need for hand-coded high-level representations as input. An alternative approach is to use high-level perception, in which high-level representations are automatically generated from raw data. Analogy perception is the process of recognizing analogies using high-level perception. We present PairClass, an algorithm for analogy perception that recognizes lexical proportional analogies using representations that are automatically generated from a large corpus of raw textual data. A proportional analogy is an analogy of the form A:B::C:D, meaning "A is to B as C is to D". A lexical proportional analogy is a proportional analogy with words, such as carpenter:wood::mason:stone. PairClass represents the semantic relations between two words using a high-dimensional feature vector, in which the elements are based on frequencies of patterns in the corpus. PairClass recognizes analogies by applying s...

  3. Analogies as categorization phenomena: Studies from scientific discourse

    Science.gov (United States)

    Atkins, Leslie Jill

    Studies on the role of analogies in science classrooms have tended to focus on analogies that come from the teacher or curriculum, and not the analogies that students generate. Such studies are derivative of an educational system that values content knowledge over scientific creativity, and derivative of a model of teaching in which the teacher's role is to convey content knowledge. This dissertation begins with the contention that science classrooms should encourage scientific thinking and one role of the teacher is to model that behavior and identify and encourage it in her students. One element of scientific thinking is analogy. This dissertation focuses on student-generated analogies in science, and offers a model for understanding these. I provide evidence that generated analogies are assertions of categorization, and the base of an analogy is the constructed prototype of an ad hoc category. Drawing from research on categorization, I argue that generated analogies are based in schemas and cognitive models. This model allows for a clear distinction between analogy and literal similarity; prior to this research analogy has been considered to exist on a spectrum of similarity, differing from literal similarity to the degree that structural relations hold but features do not. I argue for a definition in which generated analogies are an assertion of an unexpected categorization: that is, they are asserted as contradictions to an expected schema.

  4. Palytoxin and Analogs: Biological and Ecological Effects

    Directory of Open Access Journals (Sweden)

    Vítor Ramos

    2010-06-01

    Full Text Available Palytoxin (PTX is a potent marine toxin that was originally found in soft corals from tropical areas of the Pacific Ocean. Soon after, its occurrence was observed in numerous other marine organisms from the same ecological region. More recently, several analogs of PTX were discovered, remarkably all from species of the dinoflagellate genus Ostreopsis. Since these dinoflagellates are also found in other tropical and even in temperate regions, the formerly unsuspected broad distribution of these toxins was revealed. Toxicological studies with these compounds shows repeatedly low LD50 values in different mammals, revealing an acute toxic effect on several organs, as demonstrated by different routes of exposure. Bioassays tested for some marine invertebrates and evidences from environmental populations exposed to the toxins also give indications of the high impact that these compounds may have on natural food webs. The recognition of its wide distribution coupled with the poisoning effects that these toxins can have on animals and especially on humans have concerned the scientific community. In this paper, we review the current knowledge on the effects of PTX and its analogs on different organisms, exposing the impact that these toxins may have in coastal ecosystems.

  5. Isolation and characterization of soybean NBS analogs

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Isolation of plant resistance genes is greatly helpful to crop resistance breeding and the insight of resistance mechanism. The cloned plant resistance genes are classified into four classes according to their putative structural domain, of which the majority possesses nucleotide-binding site (NBS) domain that consists of P-loop, kinase2a and kinase3a. The conservation of this domain affords the potential possibility of cloning the plant resistance genes, which is homology-based cloning technique. In the present study, the degenerate oligonucleotide primers were designed according to the tobacco N and Arabidopsis RPS2, and 358 clones were isolated from the genomic DNA of resistance soybean cultivar Kefeng1, resistant to soybean mosaic virus, and 4 open-reading NBS analogs were finally characterized and designated as KNBS1, KNBS2, KNBS3 and KNBS4. Southern hybridization suggested that they were present with multicopy in the soybean genome; KNBS4 was mapped to F linkage group and KNBS2 co-located J linkage group with the SCAR marker of Rsa resistant to soybean mosaic virus by RFLP analysis. Northern analysis suggested that KNBS2- related sequence was low and constitutively expressed in the root, stem and leaves of soybean. The detailed characterization of NBS analogs is very helpful to ultimately cloning the soybean resistance gene.

  6. Antarctic Analog for Dilational Bands on Europa

    Science.gov (United States)

    Hurford, T. A.; Brunt, K. M.

    2014-01-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  7. The exoplanets analogy to the Multiverse

    CERN Document Server

    Kinouchi, Osame

    2015-01-01

    The idea of a Mutiverse is controversial, although it is a natural possible solution to particle physics and cosmological fine-tuning problems (FTPs). Here I explore the analogy between the Multiverse proposal and the proposal that there exist an infinite number of stellar systems with planets in a flat Universe, the Multiplanetverse. Although the measure problem is present in this scenario, the idea of a Multiplanetverse has predictive power, even in the absence of direct evidence for exoplanets that appeared since the 90s. We argue that the fine-tuning of Earth to life (and not only the fine-tuning of life to Earth) could predict with certainty the existence of exoplanets decades or even centuries before that direct evidence. Several other predictions can be made by studying only the Earth and the Sun, without any information about stars. The analogy also shows that theories that defend that the Earth is the unique existing planet and that, at the same time, is fine-tuned to life by pure chance (or pure phy...

  8. Efficient Analog Circuits for Boolean Satisfiability

    CERN Document Server

    Yin, Xunzhao; Varga, Melinda; Ercsey-Ravasz, Maria; Toroczkai, Zoltan; Hu, Xiaobo Sharon

    2016-01-01

    Efficient solutions to NP-complete problems would significantly benefit both science and industry. However, such problems are intractable on digital computers based on the von Neumann architecture, thus creating the need for alternative solutions to tackle such problems. Recently, a deterministic, continuous-time dynamical system (CTDS) was proposed (Nature Physics, 7(12), 966 (2011)) to solve a representative NP-complete problem, Boolean Satisfiability (SAT). This solver shows polynomial analog time-complexity on even the hardest benchmark $k$-SAT ($k \\geq 3$) formulas, but at an energy cost through exponentially driven auxiliary variables. With some modifications to the CTDS equations, here we present a novel analog hardware SAT solver, AC-SAT, implementing the CTDS. AC-SAT is intended to be used as a co-processor, and with its modular design can be readily extended to different problem sizes. The circuit is designed and simulated based on a 32nm CMOS technology. SPICE simulation results show speedup factor...

  9. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    Science.gov (United States)

    Costa, Ricardo; Bacchi, Carlos E.; Almeida Filho, Paulo

    2013-01-01

    Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU). PMID:24455330

  10. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    Directory of Open Access Journals (Sweden)

    Ricardo Costa

    2013-01-01

    Full Text Available Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT scans, magnetic resonance imaging (MRI, and positron emission tomography (PET/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU.

  11. Four channel analog router for spectroscopy applications

    International Nuclear Information System (INIS)

    A four input analog multiplexer/router has been developed in order to acquire spectral data from four different detector systems on first-come-first-sort basis. The circuit is incorporated in a single width NIM module and is fully compatible with the HPD 4K MCA developed in the Health Physics Division. The analog router accepts output from upto 4 detectors after these are passed through individual preamplifiers and linear amplifiers. The router generates signal for the channel whose input crosses set LLD limits first and simultaneously disables other inputs. The selected input is then passed to the ADC for further processing. The processed signal generates a channel dependent two bit address along with normal digital outputs of the ADC. The channel dependent two bit address is directly used to store the event in one of the four 1k segment of the HPD 4K MCA. The multiplexer is re-enabled to accept next input on priority basis. One such unit has already been commissioned to acquire data from four solid state detectors used for spectrometry. The paper discusses hardware of the router, its linearity resolution cross-talk between the channels and other performance characteristics. (author). 3 figs

  12. Developing Fluorescent Hyaluronan Analogs for Hyaluronan Studies

    Directory of Open Access Journals (Sweden)

    Shi Ke

    2012-02-01

    Full Text Available Two kinds of fluorescent hyaluronan (HA analogs, one serving as normal imaging agent and the other used as a biosensitive contrast agent, were developed for the investigation of HA uptake and degradation. Our approach of developing HA imaging agents depends on labeling HA with varying molar percentages of a near-infrared (NIR dye. At low labeling ratios, the hyaluronan uptake can be directly imaged while at high labeling ratios, the fluorescent signal is quenched and signal generation occurs only after degradation. It is found that the conjugate containing 1%–2% NIR dye can be used as a normal optical imaging agent, while bioactivable imaging agents are formed at 6% to 17% dye loading. It was determined that the conjugation of dye to HA with different loading percentages does not impact HA biodegradation by hyaluronidase (Hyal. The feasibility of using these two NIR fluorescent hyaluronan analogs for HA investigation was evaluated in vivo with optical imaging. The data demonstrates that the 1% dye loaded fluorescent HA can be used to monitor the behavior of HA and its fragments, whereas bioactivatable HA imaging agent (17% dye in HA is more suitable for detecting HA fragments.

  13. Comparison between analog and digital filters

    Directory of Open Access Journals (Sweden)

    Zoltan Erdei

    2010-12-01

    Full Text Available Digital signal processing(DSP is one of the most powerful technologies and will model science and engineering in the 21st century. Revolutionary changes have already been made in different areas of research such as communications, medical imaging, radar and sonar technology, high fidelity audio signal reproducing etc. Each of these fields developed a different signal processing technology with its own algorithms, mathematics and technology, Digital filters are used in two general directions: to separate mixed signals and to restore signals that were compromised in different modes. The objective of this paper is to compare some basic digital filters versus analog filters such as low-pass, high-pass, band-pass filters. Scientists and engineers comprehend that, in comparison with analog filters, digital filters can process the same signal in real-time with broader flexibility. This understanding is considered important to instill incentive for engineers to become interested in the field of DSP. The analysis of the results will be made using dedicated libraries in MATLAB and Simulink software, such as the Signal Processing Toolbox.

  14. Analog IC reliability in nanometer CMOS

    CERN Document Server

    Maricau, Elie

    2013-01-01

    This book focuses on modeling, simulation and analysis of analog circuit aging. First, all important nanometer CMOS physical effects resulting in circuit unreliability are reviewed. Then, transistor aging compact models for circuit simulation are discussed and several methods for efficient circuit reliability simulation are explained and compared. Ultimately, the impact of transistor aging on analog circuits is studied. Aging-resilient and aging-immune circuits are identified and the impact of technology scaling is discussed.   The models and simulation techniques described in the book are intended as an aid for device engineers, circuit designers and the EDA community to understand and to mitigate the impact of aging effects on nanometer CMOS ICs.   ·         Enables readers to understand long-term reliability of an integrated circuit; ·         Reviews CMOS unreliability effects, with focus on those that will emerge in future CMOS nodes; ·         Provides overview of models for...

  15. Analog models of computations \\& Effective Church Turing Thesis: Efficient simulation of Turing machines by the General Purpose Analog Computer

    CERN Document Server

    Pouly, Amaury; Graça, Daniel S

    2012-01-01

    \\emph{Are analog models of computations more powerful than classical models of computations?} From a series of recent papers, it is now clear that many realistic analog models of computations are provably equivalent to classical digital models of computations from a \\emph{computability} point of view. Take, for example, the probably most realistic model of analog computation, the General Purpose Analog Computer (GPAC) model from Claude Shannon, a model for Differential Analyzers, which are analog machines used from 1930s to early 1960s to solve various problems. It is now known that functions computable by Turing machines are provably exactly those that are computable by GPAC. This paper is about next step: understanding if this equivalence also holds at the \\emph{complexity} level. In this paper we show that the realistic models of analog computation -- namely the General Purpose Analog Computer (GPAC) -- can simulate Turing machines in a computationally efficient manner. More concretely we show that, modulo...

  16. An expanded set of amino acid analogs for the ribosomal translation of unnatural peptides.

    Directory of Open Access Journals (Sweden)

    Matthew C T Hartman

    Full Text Available BACKGROUND: The application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA. METHODOLOGY/PRINCIPAL FINDINGS: We have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few alpha,alpha disubstituted, N-methyl and alpha-hydroxy derivatives, but no beta-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides.

  17. Production of tranilast [N-(3',4'-dimethoxycinnamoyl)-anthranilic acid] and its analogs in yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Eudes, Aymerick; Baidoo, Edward E K; Yang, Fan; Burd, Helcio; Hadi, Masood Z; Collins, F William; Keasling, Jay D; Loqué, Dominique

    2011-02-01

    Biological synthesis of therapeutic drugs beneficial for human health using microbes offers an alternative production strategy to the methods that are commonly employed such as direct extraction from source organisms or chemical synthesis. In this study, we evaluated the potential for yeast (Saccharomyces cerevisiae) to be used as a catalyst for the synthesis of tranilast and various tranilast analogs (cinnamoyl anthranilates). Several studies have demonstrated that these phenolic amides have antioxidant properties and potential therapeutic benefits including antiinflammatory, antiproliferative, and antigenotoxic effects. The few cinnamoyl anthranilates naturally produced in plants such as oats and carnations result from the coupling of various hydroxycinnamoyl-CoAs to anthranilic acid. In order to achieve the microbial production of tranilast and several of its analogs, we engineered a yeast strain to co-express a 4-coumarate/CoA ligase (4CL, EC 6.2.1.12) from Arabidopsis thaliana and a hydroxycinnamoyl/benzoyl-CoA/anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT, EC 2.3.1.144) from Dianthus caryophyllus. This modified yeast strain allowed us to produce tranilast and 26 different cinnamoyl anthranilate molecules within a few hours after exogenous supply of various combinations of cinnamic acids and anthranilate derivatives. Our data demonstrate the feasibility of rapidly producing a wide range of defined cinnamoyl anthranilates in yeast and underline a potential for the biological designed synthesis of naturally and non-naturally occurring molecules.

  18. Identification of Synthesis Routes of "Ecstasy" by GC-MS Coupled Soft Independent Modeling of Class Analogies%气相色谱-质谱联用结合软独立建模分类法识别摇头丸的合成途径

    Institute of Scientific and Technical Information of China (English)

    吴国萍; 蔡锡兰; 相秉仁

    2005-01-01

    @@ 摇头丸的合成原料以及合成途径很多,对缴获的摇头丸进行检测时发现,几乎每一粒片剂中都存在与合成途径相关的各种杂质,且不同合成途径产生的杂质体系大致相同.根据杂质情况推断其合成途径有较大的模糊性.本文应用模式识别中软独立建模分类法(soft independent modeling of class analogies,SIMCA)对杂质与合成途径的关系进行了研究,建立了一种较为理想的用于推断摇头丸合成途径的方法,为实战缉毒工作提供了依据.

  19. Synthesis, in vitro and in vivo pharmacology of a C-11 labeled analog of CP-101,606, ({+-})threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[{sup 11}C]methoxyphenyl) peridino]-1-propanol, as a PET tracer for NR2B subunit-containing NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Haradahira, Terushi E-mail: terushi@nirs.go.jp; Maeda, Jun; Okauchi, Takashi; Zhang, Ming-Rong; Hojo, Junko; Kida, Takayo; Arai, Takuya; Yamamoto, Fumihiko; Sasaki, Shigeki; Maeda, Minoru; Suzuki, Kazutoshi; Suhara, Tetsuya

    2002-07-01

    A carbon-11 labeled methoxyl analog of CP-101,606, ({+-})threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[{sup 11}C]methoxyphenyl) piperidino]-1-propanol [({+-})[{sup 11}C]1], was synthesized as a new subtype-selective PET radioligand for NMDA receptors. The in vitro binding studies using rat brain slices demonstrated that ({+-})[{sup 11}C]1 shows an extremely high-specific binding to the NR2B subunit of NMDA receptors. In contrast to the in vitro binding, the in vivo binding to mouse and monkey brains showed no apparent specific localization of the radioactivity in any of the brain regions. Metabolism and physicochemical properties such as the lipophilicity of ({+-})[{sup 11}C]1 seemed unlikely to affect the in vivo ({+-})[{sup 11}C]1 binding. Among the various endogenous ligands acting at the NMDA receptors, polyamines (spermine and spermidine) and divalent cations (Mg{sup 2+,} Zn{sup 2+,} and Ca{sup 2+}) strongly inhibited the in vitro ({+-})[{sup 11}C]1 binding. Thus, the present studies point to the possibility that the polyamines and cations behave as endogenous inhibitors for ({+-})[{sup 11}C]1 binding, leading to the loss of the specific binding in vivo.

  20. Analog computing using reflective plasmonic metasurfaces

    CERN Document Server

    Pors, Anders; Bozhevolnyi, Sergey I

    2016-01-01

    Motivated by the recent renewed interest in compact analog computing using light and metasurfaces (Silva, A. et al., Science 2014, 343, 160-163), we suggest a practical approach to its realization that involves reflective metasurfaces consisting of arrayed gold nanobricks atop a subwavelength-thin dielectric spacer and optically-thick gold film, a configuration that supports gap-surface plasmon resonances. Using well established numerical routines, we demonstrate that these metasurfaces enable independent control of the light phase and amplitude, and design differentiator and integrator metasurfaces featuring realistic system parameters. Proof-of-principle experiments are reported along with the successful realization of a high-quality poor-man's integrator metasurface operating at the wavelength of 800 nm.

  1. Z~+(4430) and Analogous Heavy Flavor States

    Institute of Scientific and Technical Information of China (English)

    DING Gui-jun

    2009-01-01

    We have studied Z~+ (4430)as a D~* D_1 molecule from the quark model,state mixing effect is considered by solving the coupled channel Schr(o)dinger equation numerically.More precise measurements of Z~+ (4430)mass and width,partial wave analysis are helpful to understand its structure.If it lies below the D~* D_1 threshold,molecule interpretation with J~P=1~- is favored,and JP =0~- can not be ruled out.Otherwise Z~+ (4430)may be a virtual state with J~P=2~-.The analogous heavy flavor mesons Z~+_(bb) and Z~(++)_(bc) are considered as well,and the masses predicted in our model are in agreement with the predictions from the potential model and QCD sum rule.

  2. Ultra Low-Power Analog Median Filters

    Directory of Open Access Journals (Sweden)

    A. Diaz-Sanchez

    2013-09-01

    Full Text Available The design and implementation of three analog median filter topologies, whose transistors operate in the deep weak-inversion region, is described. The first topology is a differential pairs array, in which drain currents are driven into two nodes in a differential fashion, while the second topology is based on a wide range OTA, which is used to maximize the dynamic range. Finally, the third topology uses three range-extended OTAs. The proposed weak-inversion filters were designed and fabricated in ON Semiconductor 0.5 micrometer technology through MOSIS. Experimental results of three-input fabricated prototypes for all three topologies are show, where power consumptions of 90nW in the first case, and 270nW in the other two cases can be noticed. A dual power supply +/-1.5 Volts were used.

  3. Four-gate transistor analog multiplier circuit

    Science.gov (United States)

    Mojarradi, Mohammad M. (Inventor); Blalock, Benjamin (Inventor); Cristoloveanu, Sorin (Inventor); Chen, Suheng (Inventor); Akarvardar, Kerem (Inventor)

    2011-01-01

    A differential output analog multiplier circuit utilizing four G.sup.4-FETs, each source connected to a current source. The four G.sup.4-FETs may be grouped into two pairs of two G.sup.4-FETs each, where one pair has its drains connected to a load, and the other par has its drains connected to another load. The differential output voltage is taken at the two loads. In one embodiment, for each G.sup.4-FET, the first and second junction gates are each connected together, where a first input voltage is applied to the front gates of each pair, and a second input voltage is applied to the first junction gates of each pair. Other embodiments are described and claimed.

  4. Analog circuit for controlling acoustic transducer arrays

    Energy Technology Data Exchange (ETDEWEB)

    Drumheller, Douglas S. (Cedar Crest, NM)

    1991-01-01

    A simplified ananlog circuit is presented for controlling electromechanical transducer pairs in an acoustic telemetry system. The analog circuit of this invention comprises a single electrical resistor which replaces all of the digital components in a known digital circuit. In accordance with this invention, a first transducer in a transducer pair of array is driven in series with the resistor. The voltage drop across this resistor is then amplified and used to drive the second transducer. The voltage drop across the resistor is proportional and in phase with the current to the transducer. This current is approximately 90 degrees out of phase with the driving voltage to the transducer. This phase shift replaces the digital delay required by the digital control circuit of the prior art.

  5. Test signal generation for analog circuits

    Science.gov (United States)

    Burdiek, B.; Mathis, W.

    2003-05-01

    In this paper a new test signal generation approach for general analog circuits based on the variational calculus and modern control theory methods is presented. The computed transient test signals also called test stimuli are optimal with respect to the detection of a given fault set by means of a predefined merit functional representing a fault detection criterion. The test signal generation problem of finding optimal test stimuli detecting all faults form the fault set is formulated as an optimal control problem. The solution of the optimal control problem representing the test stimuli is computed using an optimization procedure. The optimization procedure is based on the necessary conditions for optimality like the maximum principle of Pontryagin and adjoint circuit equations.

  6. Test signal generation for analog circuits

    Directory of Open Access Journals (Sweden)

    B. Burdiek

    2003-01-01

    Full Text Available In this paper a new test signal generation approach for general analog circuits based on the variational calculus and modern control theory methods is presented. The computed transient test signals also called test stimuli are optimal with respect to the detection of a given fault set by means of a predefined merit functional representing a fault detection criterion. The test signal generation problem of finding optimal test stimuli detecting all faults form the fault set is formulated as an optimal control problem. The solution of the optimal control problem representing the test stimuli is computed using an optimization procedure. The optimization procedure is based on the necessary conditions for optimality like the maximum principle of Pontryagin and adjoint circuit equations.

  7. X-Rays from Green Pea Analogs

    Science.gov (United States)

    Brorby, Matthew

    2014-09-01

    X-rays may have contributed to the heating and reionization of the IGM in the early universe. High mass X-ray binaries (HMXB) within small, low-metallicity galaxies are expected to be the main source of X-rays at this time. Since studying these high-redshift galaxies is currently impossible, we turn to local analogs that have the same properties the galaxies in the early are expected to have. A number of recent studies have shown an enhanced number of HMXBs in nearby low metallicity galaxies. We propose to observe a sample of metal-deficient luminous compact galaxies (LCG) in order to determine if the X-ray luminosity is enhanced relative to SFR, thereby providing further evidence to the importance of X-rays in the early universe.

  8. A Probabilistic Approach to Pronunciation by Analogy

    CERN Document Server

    Kujala, Janne V

    2011-01-01

    The relationship between written and spoken words is convoluted in languages with a deep orthography such as English and therefore it is difficult to devise explicit rules for generating the pronunciations for unseen words. Pronunciation by analogy (PbA) is a data-driven method of constructing pronunciations for novel words from concatenated segments of known words and their pronunciations. PbA performs relatively well with English and outperforms several other proposed methods. However, the best published word accuracy of 65.5% (for the 20,000 word NETtalk corpus) suggests there is much room for improvement in it. Previous PbA algorithms have used several different scoring strategies such as the product of the frequencies of the component pronunciations of the segments, or the number of different segmentations that yield the same pronunciation, and different combinations of these methods, to evaluate the candidate pronunciations. In this article, we instead propose to use a probabilistically justified scorin...

  9. 23rd workshop on Advances in Analog Circuit Design

    CERN Document Server

    Baschirotto, Andrea; Makinwa, Kofi

    2015-01-01

    This book is based on the 18 tutorials presented during the 23rd workshop on Advances in Analog Circuit Design.  Expert designers present readers with information about a variety of topics at the frontier of analog circuit design, serving as a valuable reference to the state-of-the-art, for anyone involved in analog circuit research and development.    • Includes coverage of high-performance analog-to-digital and digital to analog converters, integrated circuit design in scaled technologies, and time-domain signal processing; • Provides a state-of-the-art reference in analog circuit design, written by experts from industry and academia; • Presents material in a tutorial-based format.

  10. Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

    OpenAIRE

    Lisa F. Becker; Schwarz, Dennis H; Gerhard Wenz

    2014-01-01

    Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially the β-cyclodextrin derivatives exhibit very high binding potentials...

  11. An asynchronous spike event coding scheme for programmable analog arrays

    OpenAIRE

    Gouveia, L.C.; Koickal, T.; Hamilton, A.

    2008-01-01

    This paper presents a spike event coding scheme for the communication of analog signals in programmable analog arrays. In the scheme presented here no events are transmitted when the signals are constant leading to low power dissipation and traffic reduction in analog arrays. The design process and the implementation of the scheme in a programmable array context are explained. The validation of the presented scheme is performed using a speech signal. Finally, we demonstrate how the event code...

  12. A Novel cooked extruded lentils analog: physical and chemical properties

    OpenAIRE

    Abu-Ghoush, Mahmoud; Alavi, Sajid; Al-Shathri, Abdulaziz

    2014-01-01

    Developing an extruded lentil analog is our aim. Lentil analog with six formulations were produced using a pilot-scale single (SS) and twin screw (TS) extruders. Texture analysis of lentil analogs prepared for consumption revealed that the products formulated with 60:40 and 70:30 soy: wheat ratios exhibited a significantly higher hardness, adhesiveness and lower springiness as compared to all other treatments. Differential Scanning Calorimeter (DSC) results indicated that all starches in dry ...

  13. Configurable analog-digital conversion using the neural engineering framework

    OpenAIRE

    Christian G Mayr; Partzsch, Johannes; Noack, Marko; Schüffny, Rene

    2014-01-01

    Efficient Analog-Digital Converters (ADC) are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e., to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and...

  14. Analog circuit design a tutorial guide to applications and solutions

    CERN Document Server

    Williams, Jim

    2011-01-01

    * Covers the fundamentals of linear/analog circuit and system design to guide engineers with their design challenges. * Based on the Application Notes of Linear Technology, the foremost designer of high performance analog products, readers will gain practical insights into design techniques and practice. * Broad range of topics, including power management tutorials, switching regulator design, linear regulator design, data conversion, signal conditioning, and high frequency/RF design. * Contributors include the leading lights in analog design, Robert Dobkin, Jim Willia

  15. Ring size in cyclic endomorphin-2 analogs modulates receptor binding affinity and selectivity.

    Science.gov (United States)

    Piekielna, Justyna; Kluczyk, Alicja; Gentilucci, Luca; Cerlesi, Maria Camilla; Calo', Girolamo; Tomböly, Csaba; Łapiński, Krzysztof; Janecki, Tomasz; Janecka, Anna

    2015-06-01

    The study reports the solid-phase synthesis and biological evaluation of a series of new side chain-to-side chain cyclized opioid peptide analogs of the general structure Tyr-[D-Xaa-Phe-Phe-Asp]NH2, where Xaa = Lys (1), Orn (2), Dab (3), or Dap (4) (Dab = 2,4-diaminobutyric acid, Dap = 2,3-diaminopropionic acid), containing 17- to 14-membered rings. The influence of the ring size on binding to the MOP, DOP and KOP opioid receptors was studied. In general, the reduction of the size of the macrocyclic ring increased the selectivity for the MOP receptor. The cyclopeptide incorporating Xaa = Lys displayed subnanomolar MOP affinity but modest selectivity over the KOP receptor, while the analog with the Orn residue showed increased affinity and selectivity for MOP. The analog with Dab was a weak MOP agonist and did not bind to the other two opioid receptors. Finally, the peptide with Xaa = Dap was completely MOP receptor-selective with subnanomolar affinity. Interestingly, the deletion of one Phe residue from 1 led to the 14-membered Tyr-c[D-Lys-Phe-Asp]NH2 (5), a potent and selective MOP receptor ligand. The in vitro potencies of the new analogs were determined in a calcium mobilization assay performed in Chinese Hamster Ovary (CHO) cells expressing human recombinant opioid receptors and chimeric G proteins. A good correlation between binding and the functional test results was observed. The influence of the ring size, solid support and the N-terminal protecting group on the formation of cyclodimers was studied. PMID:25948019

  16. CRC handbook of neurohypophyseal hormone analogs. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    Jost, K.; Lebl, M.; Brtnik, F.

    1987-01-01

    This book is discussed in two parts. The Part 1 discusses the: Prohormones and Hormonogens of Neuro-hypophyseal Hormones, Analogs with Inhibitory properties. Analogs with Dissociated and/or High activities. Introduction. Uterotonic Activity. Galactogogic Activity. Pressor Activity. Antidiuretic Activity. References. Part 2 discusses the Other Important Activities. CNS Activities. Corticotropin- and ..beta..-Entriuretic Action. Natriferic Action. References. Practical Use in Human and Veterinary Medicine. Introduction. Methyloxytocin. Deamino-Oxytocin. Cargutocin. Glypressin. Octapressin. Desmopressin. Analogs Clinically Tried But Not Introduced into Production and Routine Clinical Practice. References. Tables of Analogs and Index.

  17. Practical approach to programmable analog circuits with memristors

    CERN Document Server

    Pershin, Yuriy V

    2009-01-01

    We suggest an approach to use memristors (resistors with memory) in programmable analog circuits. Our idea consists in a circuit design in which low voltages are applied to memristors during their operation as analog circuit elements and high voltages are used to program the memristor's states. This way, as it was demonstrated in recent experiments, the state of memristors does not essentially change during analog mode operation. As an example of our approach, we have built several programmable analog circuits demonstrating memristor-based programming of threshold, gain and frequency.

  18. Analog solar system model relates celestial bodies spatially

    Science.gov (United States)

    Baerg, H. R.

    1966-01-01

    Portable analog planetarium indicates the relative time and space angular locations of the sun and planets. Distance measuring scales, angular direction indicators, and typical probe trajectories are included.

  19. Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

    OpenAIRE

    Reith, Maarten E.A.; Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

    2012-01-01

    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast...

  20. Reynolds analogy for the Rayleigh problem at various flow modes.

    Science.gov (United States)

    Abramov, A A; Butkovskii, A V

    2016-07-01

    The Reynolds analogy and the extended Reynolds analogy for the Rayleigh problem are considered. For a viscous incompressible fluid we derive the Reynolds analogy as a function of the Prandtl number and the Eckert number. We show that for any positive Eckert number, the Reynolds analogy as a function of the Prandtl number has a maximum. For a monatomic gas in the transitional flow regime, using the direct simulation Monte Carlo method, we investigate the extended Reynolds analogy, i.e., the relation between the shear stress and the energy flux transferred to the boundary surface, at different velocities and temperatures. We find that the extended Reynolds analogy for a rarefied monatomic gas flow with the temperature of the undisturbed gas equal to the surface temperature depends weakly on time and is close to 0.5. We show that at any fixed dimensionless time the extended Reynolds analogy depends on the plate velocity and temperature and undisturbed gas temperature mainly via the Eckert number. For Eckert numbers of the order of unity or less we generalize an extended Reynolds analogy. The generalized Reynolds analogy depends mainly only on dimensionless time for all considered Eckert numbers of the order of unity or less. PMID:27575220

  1. Non-analog Monte Carlo estimators for radiation momentum deposition

    Energy Technology Data Exchange (ETDEWEB)

    Densmore, Jeffery D [Los Alamos National Laboratory; Hykes, Joshua M [Los Alamos National Laboratory

    2008-01-01

    The standard method for calculating radiation momentum deposition in Monte Carlo simulations is the analog estimator, which tallies the change in a particle's momentum at each interaction with the matter. Unfortunately, the analog estimator can suffer from large amounts of statistical error. In this paper, we present three new non-analog techniques for estimating momentum deposition. Specifically, we use absorption, collision, and track-length estimators to evaluate a simple integral expression for momentum deposition that does not contain terms that can cause large amounts of statistical error in the analog scheme. We compare our new non-analog estimators to the analog estimator with a set of test problems that encompass a wide range of material properties and both isotropic and anisotropic scattering. In nearly all cases, the new non-analog estimators outperform the analog estimator. The track-length estimator consistently yields the highest performance gains, improving upon the analog-estimator figure of merit by factors of up to two orders of magnitude.

  2. Analog-digital converters for industrial applications including an introduction to digital-analog converters

    CERN Document Server

    Ohnhäuser, Frank

    2015-01-01

    This book offers students and those new to the topic of analog-to-digital converters (ADCs) a broad introduction, before going into details of the state-of-the-art design techniques for SAR and DS converters, including the latest research topics, which are valuable for IC design engineers as well as users of ADCs in applications. The book then addresses important topics, such as correct connectivity of ADCs in an application, the verification, characterization and testing of ADCs that ensure high-quality end products. Analog-to-digital converters are the central element in any data processing system and regulation loops such as modems or electrical motor drives. They significantly affect the performance and resolution of a system or end product. System development engineers need to be familiar with the performance parameters of the converters and understand the advantages and disadvantages of the various architectures. Integrated circuit development engineers have to overcome the problem of achieving high per...

  3. The first synthesis of an epidiselenodiketopiperazine.

    Science.gov (United States)

    McMahon, Travis C; Stanley, Sarah; Kazyanskaya, Edward; Hung, Deborah; Wood, John L

    2012-09-01

    Epidithiodiketopiperazines (ETPs) are natural products (e.g., gliotoxin) with varied and important biological activity, which often is attributed to the redox properties of the disulfide moiety. As such, analogs with altered redox properties and similar structural characteristics would be of value to biological investigations. The use of an ETP as the point of departure in the first synthesis of an epidiselenodiketopiperazine (ESeP) and its activity against Mycobacterium tuberculosis (MTB) is reported. PMID:22913407

  4. High-speed and high-resolution analog-to-digital and digital-to-analog converters

    OpenAIRE

    van de Plassche, R.J.

    1992-01-01

    Analog-to-digital and digital-to-analog converters are important building blocks connecting the analog world of transducers with the digital world of computing, signal processing and data acquisition systems. In chapter two the converter as part of a system is described. Requirements of analog filtering of input signals before they are applied to an A/D converter are defined. In the case of a D/A converter the amount of filtering of the repetitive signal bands around multiples of the sampling...

  5. How strategists really think. Tapping the power of analogy.

    Science.gov (United States)

    Gavetti, Giovanni; Rivkin, Jan W

    2005-04-01

    Leaders tend to be so immersed in the specifics of strategy that they rarely stop to think how much of their reasoning is done by analogy. As a result, they miss useful insights that psychologists and other scientists have generated about analogies' pitfalls. Managers who pay attention to their own analogical thinking will make better strategic decisions and fewer mistakes. Charles Lazarus was inspired by the supermarket when he founded Toys R Us; Intel promoted its low-end chips to avoid becoming like U.S. Steel; and Circuit City created CarMax because it saw the used-car market as analogous to the consumer-electronics market. Each example displays the core elements of analogical reasoning: a novel problem or a new opportunity, a specific prior context that managers deem to be similar in its essentials, and a solution that managers can transfer from its original setting to the new one. Analogical reasoning is a powerful tool for sparking breakthrough ideas. But dangers arise when analogies are built on surface similarities (headlong diversification based on loose analogies played a role in Enron's collapse, for instance). Psychologists have discovered that it's all too easy to overlook the superficiality of analogies. The situation is further complicated by people's tendency to hang on to beliefs even after contrary evidence comes along (a phenomenon known as anchoring) and their tendency to seek only the data that confirm their beliefs (an effect known as the confirmation bias). Four straightforward steps can improve a management team's odds of using an analogy well: Recognize the analogy and identify its purpose; thoroughly understand its source; determine whether the resemblance is more than superficial; and decide whether the original strategy, properly translated, will work in the target industry. PMID:15807039

  6. Synthesis and Chiral Separation of Dinucleotide(TpAZT) Phosphoramidates

    Institute of Scientific and Technical Information of China (English)

    Chang Xue LIN; Hua FU; Guang Zhong TU; Yu Fen ZHAO

    2003-01-01

    Dinucleotide (TpAZT) phosphoramidates were synthesized by Todd reaction of dinucleoside H-phosphonates and amino acid methyl esters, and their diastereomers (Rp and Sp) were separated by crystallization, and the results showed that natural and cheap methyl esters of alanine and phenylalanine can be used for large-scale synthesis of dinucleotide analogs.

  7. SYNTHESIS OF 17-(ISOCYANOTOSYLMETHYLENE) STEROIDS - PRECURSORS TO PREGNANE DERIVATIVES

    NARCIS (Netherlands)

    VANLEUSEN, D; VANLEUSEN, AM

    1991-01-01

    The synthesis is described of a series of twenty 17-(isocyanotosylmethylene) steroids 5 from 17-oxo steroids and 4-tolysulfonylmethyl isocyanide (TosMIC). Furthermore, nine analogous 17-(isocyanosulfonylmethylene) steroids (15-21a) have been prepared using sulfonylmethyl isocyanides other than TosMI

  8. One-Pot Synthesis of N-Phosphoryl Amino Acids

    Institute of Scientific and Technical Information of China (English)

    GUO Xin; FU Hua; LIN Chang-Xue; ZHAO Yu-Fen

    2003-01-01

    @@ Phosphoramidates have been considered as an important class of rationally designed therapeutics especially asoligonucleotide analogs employed as antisene and antigene agents. [1] N-Phosphoryl amino acids are of biological andpharmaceutical interest, [2] and can be used as the building blocks in synthesis of polypeptides. [3

  9. Radiolabeled somatostatin analogs in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, M.L.; Kolan, H.; Li, J.; Wiaderkiewicz, R.; Pallela, V.R.; Duggaraju, R.; Schally, A.V

    1997-01-01

    Vapreotide (RC-160), a somatostatin analog, was labeled with {sup 99m}Tc by a direct method and also by using CPTA [1,4,8,11-tetraazacyclotetradecane] as a bifunctional chelating agent. The labeled compounds were evaluated in nude mice bearing experimental human prostate cancers. In these studies, {sup 111}In-DTPA-D-Phe-Octreotide ({sup 111}In-DTPA-octreotide) served as a standard and {sup 99m}Tc-oxytocin as a receptor-non-specific control. {sup 99m}Tc-octreotide was also used. The 24 htumor uptake of {sup 99m}Tc-RC-160 was nearly 400% higher, (p < 0.05), than that of {sup 111}In-DTPA-octreotide and diminished upon receptor blocking. In all tissues except the kidneys, the uptake of {sup 99m}Tc-RC-160 was also higher than that of {sup 111}In-DTPA-octreotide. The uptake of {sup 99m}Tc-RC-160 was influenced by the amount of peptide injected and the best tumor/muscle and tumor/blood ratios were obtained when only one {mu}g of the peptide (200 Ci/mmol) was administered.

  10. Amino acid analogs for tumor imaging

    Science.gov (United States)

    Goodman, M.M.; Shoup, T.

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  11. Applying analog integrated circuits for HERO protection

    Science.gov (United States)

    Willis, Kenneth E.; Blachowski, Thomas J.

    1994-01-01

    One of the most efficient methods for protecting electro-explosive devices (EED's) from HERO and ESD is to shield the EED in a conducting shell (Faraday cage). Electrical energy is transferred to the bridge by means of a magnetic coupling which passes through a portion of the conducting shell that is made from a magnetically permeable but electrically conducting material. This technique was perfected by ML Aviation, a U.K. company, in the early 80's, and was called a Radio Frequency Attenuation Connector (RFAC). It is now in wide use in the U.K. Previously, the disadvantage of RFAC over more conventional methods was its relatively high cost, largely driven by a thick film hybrid circuit used to switch the primary of the transformer. Recently, through a licensing agreement, this technology has been transferred to the U.S. and significant cost reductions and performance improvements have been achieved by the introduction of analog integrated circuits. An integrated circuit performs the following functions: (1) Chops the DC input to a signal suitable for driving the primary of the transformer; (2) Verifies the input voltage is above a threshold; (3) Verifies the input voltage is valid for a pre set time before enabling the device; (4) Provides thermal protection of the circuit; and (5) Provides an external input for independent logic level enabling of the power transfer mechanism. This paper describes the new RFAC product and its applications.

  12. Natural Analog Studies at Pena Blanca, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    A.M. Simmons

    2005-07-11

    The significance of the Pena Blanca uranium deposits in the State of Chihuahua, Mexico as potential natural analogs for a nuclear waste repository in unsaturated welded tuff was first recognized in the 1980s. In the 1970s, the Pena Blanca region was a major target of uranium exploration and exploitation by the Mexican government. Since then the Nopal I uranium deposit has been studied extensively by researchers in the U.S., Mexico, and Europe. The Nopal I deposit represents an environment similar to that of the proposed high-level radioactive waste repository at Yucca Mountain in many ways. Both are located in semi-arid regions. Both are located in Tertiary rhyolitic tuffs overlying carbonate rocks that have been subjected to basin and range-style tectonic deformation. Both are located in a chemically oxidizing, unsaturated zone 200 m or more above the water table. The alteration of uraninite to secondary minerals at Nopal I may be similar to the alteration of uranium fuel rods in this type of setting. Investigations at Nopal I and in the surrounding Sierra Pena Blanca have included detailed outcrop mapping, hydrologic and isotopic studies of flow and transport, studies of mineral alteration, modeling, and performance assessment.

  13. Natural Analog Studies at Pena Blanca, Mexico

    International Nuclear Information System (INIS)

    The significance of the Pena Blanca uranium deposits in the State of Chihuahua, Mexico as potential natural analogs for a nuclear waste repository in unsaturated welded tuff was first recognized in the 1980s. In the 1970s, the Pena Blanca region was a major target of uranium exploration and exploitation by the Mexican government. Since then the Nopal I uranium deposit has been studied extensively by researchers in the U.S., Mexico, and Europe. The Nopal I deposit represents an environment similar to that of the proposed high-level radioactive waste repository at Yucca Mountain in many ways. Both are located in semi-arid regions. Both are located in Tertiary rhyolitic tuffs overlying carbonate rocks that have been subjected to basin and range-style tectonic deformation. Both are located in a chemically oxidizing, unsaturated zone 200 m or more above the water table. The alteration of uraninite to secondary minerals at Nopal I may be similar to the alteration of uranium fuel rods in this type of setting. Investigations at Nopal I and in the surrounding Sierra Pena Blanca have included detailed outcrop mapping, hydrologic and isotopic studies of flow and transport, studies of mineral alteration, modeling, and performance assessment

  14. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Mark M. (Atlanta, GA); Shoup, Timothy (Decatur, GA)

    1998-09-15

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  15. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Mark M. (Atlanta, GA); Shoup, Timothy (Decatur, GA)

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is ›.sup.18 F!-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an .alpha.-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of .alpha.-aminoisobutyric acid.

  16. Amino acid analogs for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, M.M.; Shoup, T.

    1998-10-06

    The invention provides novel amino acid compounds of use in detecting and evaluating brain and body tumors. These compounds combine the advantageous properties of 1-amino-cycloalkyl-1-carboxylic acids, namely, their rapid uptake and prolonged retention in tumors with the properties of halogen substituents, including certain useful halogen isotopes including fluorine-18, iodine-123, iodine-125, iodine-131, bromine-75, bromine-76, bromine-77 and bromine-82. In one aspect, the invention features amino acid compounds that have a high specificity for target sites when administered to a subject in vivo. Preferred amino acid compounds show a target to non-target ratio of at least 5:1, are stable in vivo and substantially localized to target within 1 hour after administration. An especially preferred amino acid compound is [{sup 18}F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC). In another aspect, the invention features pharmaceutical compositions comprised of an {alpha}-amino acid moiety attached to either a four, five, or a six member carbon-chain ring. In addition, the invention features analogs of {alpha}-aminoisobutyric acid.

  17. Somatostatin analog treatment of acromegaly: new aspects.

    Science.gov (United States)

    Lamberts, S W; del Pozo, E

    1988-01-01

    Ten acromegalics received daily doses of 200-300 micrograms of a long-acting somatostatin analog, SMS 201-995 (Sandostatin, SMS), for an average of 64 weeks. Basal mean GH values of 44 +/- (SE) 7.8 ng/ml had fallen into the normal range at the end of the observation period (mean 64 weeks). This effect was accompanied by a substantial drop in somatomedin-C values. Reduction of pituitary tumor size could be documented in 3 of 6 patients. Whereas SMS did not affect high plasma PRL in 4 microprolactinoma patients, lactotrophs turned sensitive to this agent in mixed GH/PRL tumors. In a comparative study between SMS and bromocriptine, the former normalized circulating GH in 10 of 17 acromegalics in an acute trial, whereas bromocriptine was effective in only 5. A combination of both substances was effective in 2 of 3 patients who were insensitive to single drug administration. Cultures of GH-secreting tumor cells showed a statistically significant hormone decrease in the medium when exposed to SMS. However, in some instances, a diminution of the GH contents of the tumor cells was also observed, presumably as the basis for intracellular breakdown and clinical tumor shrinkage.

  18. Vitamin E Analogs as Radiation Response Modifiers

    Directory of Open Access Journals (Sweden)

    Pankaj K. Singh

    2015-01-01

    Full Text Available The potentially life-threatening effects of total body ionizing radiation exposure have been known for more than a century. Despite considerable advances in our understanding of the effects of radiation over the past six decades, efforts to identify effective radiation countermeasures for use in case of a radiological/nuclear emergency have been largely unsuccessful. Vitamin E is known to have antioxidant properties capable of scavenging free radicals, which have critical roles in radiation injuries. Tocopherols and tocotrienols, vitamin E analogs together known as tocols, have shown promise as radioprotectors. Although the pivotal mechanisms of action of tocols have long been thought to be their antioxidant properties and free radical scavenging activities, other alternative mechanisms have been proposed to drive their activity as radioprotectors. Here we provide a brief overview of the effects of ionizing radiation, the mechanistic mediators of radiation-induced damage, and the need for radiation countermeasures. We further outline the role for, efficacy of, and mechanisms of action of tocols as radioprotectors, and we compare and contrast their efficacy and mode of action with that of another well-studied chemical radioprotector, amifostine.

  19. The MARS2013 Mars analog mission.

    Science.gov (United States)

    Groemer, Gernot; Soucek, Alexander; Frischauf, Norbert; Stumptner, Willibald; Ragonig, Christoph; Sams, Sebastian; Bartenstein, Thomas; Häuplik-Meusburger, Sandra; Petrova, Polina; Evetts, Simon; Sivenesan, Chan; Bothe, Claudia; Boyd, Andrea; Dinkelaker, Aline; Dissertori, Markus; Fasching, David; Fischer, Monika; Föger, Daniel; Foresta, Luca; Fritsch, Lukas; Fuchs, Harald; Gautsch, Christoph; Gerard, Stephan; Goetzloff, Linda; Gołebiowska, Izabella; Gorur, Paavan; Groemer, Gerhard; Groll, Petra; Haider, Christian; Haider, Olivia; Hauth, Eva; Hauth, Stefan; Hettrich, Sebastian; Jais, Wolfgang; Jones, Natalie; Taj-Eddine, Kamal; Karl, Alexander; Kauerhoff, Tilo; Khan, Muhammad Shadab; Kjeldsen, Andreas; Klauck, Jan; Losiak, Anna; Luger, Markus; Luger, Thomas; Luger, Ulrich; McArthur, Jane; Moser, Linda; Neuner, Julia; Orgel, Csilla; Ori, Gian Gabriele; Paternesi, Roberta; Peschier, Jarno; Pfeil, Isabella; Prock, Silvia; Radinger, Josef; Ramirez, Barbara; Ramo, Wissam; Rampey, Mike; Sams, Arnold; Sams, Elisabeth; Sandu, Oana; Sans, Alejandra; Sansone, Petra; Scheer, Daniela; Schildhammer, Daniel; Scornet, Quentin; Sejkora, Nina; Stadler, Andrea; Stummer, Florian; Taraba, Michael; Tlustos, Reinhard; Toferer, Ernst; Turetschek, Thomas; Winter, Egon; Zanella-Kux, Katja

    2014-05-01

    We report on the MARS2013 mission, a 4-week Mars analog field test in the northern Sahara. Nineteen experiments were conducted by a field crew in Morocco under simulated martian surface exploration conditions, supervised by a Mission Support Center in Innsbruck, Austria. A Remote Science Support team analyzed field data in near real time, providing planning input for the management of a complex system of field assets; two advanced space suit simulators, four robotic vehicles, an emergency shelter, and a stationary sensor platform in a realistic work flow were coordinated by a Flight Control Team. A dedicated flight planning group, external control centers for rover tele-operations, and a biomedical monitoring team supported the field operations. A 10 min satellite communication delay and other limitations pertinent to human planetary surface activities were introduced. The fields of research for the experiments were geology, human factors, astrobiology, robotics, tele-science, exploration, and operations research. This paper provides an overview of the geological context and environmental conditions of the test site and the mission architecture, in particular the communication infrastructure emulating the signal travel time between Earth and Mars. We report on the operational work flows and the experiments conducted, including a deployable shelter prototype for multiple-day extravehicular activities and contingency situations.

  20. Symmetry Energy II: Isobaric Analog States

    CERN Document Server

    Danielewicz, Pawel

    2014-01-01

    Using excitation energies to isobaric analog states (IAS) and charge invariance, we extract nuclear symmetry coefficients, from a mass formula, on a nucleus-by-nucleus basis. Consistently with charge invariance, the coefficients vary weakly across an isobaric chain. However, they change strongly with nuclear mass and range from a_a~10 MeV at mass A~10 to a_a~22 MeV at A~240. Following the considerations of a Hohenberg-Kohn functional for nuclear systems, we determine how to find in practice the symmetry coefficient using neutron and proton densities, even when those densities are simultaneously affected by significant symmetry-energy and Coulomb effects. These results facilitate extracting the symmetry coefficients from Skyrme-Hartree-Fock (SHF) calculations, that we carry out using a variety of Skyrme parametrizations in the literature. For the parametrizations, we catalog novel short-wavelength instabilities. In comparing the SHF and IAS results for the symmetry coefficients, we arrive at narrow (+-2.4 MeV)...

  1. Biosynthesis of sphinganine-analog mycotoxins.

    Science.gov (United States)

    Du, L; Zhu, X; Gerber, R; Huffman, J; Lou, L; Jorgenson, J; Yu, F; Zaleta-Rivera, K; Wang, Q

    2008-06-01

    Sphinganine-analog mycotoxins (SAMT) are polyketide-derived natural products produced by a number of plant pathogenic fungi and are among the most economically important mycotoxins. The toxins are structurally similar to sphinganine, a key intermediate in the biosynthesis of ceramides and sphingolipids, and competitive inhibitors for ceramide synthase. The inhibition of ceramide and sphingolipid biosynthesis is associated with several fatal diseases in domestic animals and esophageal cancer and neural tube defects in humans. SAMT contains a highly reduced, acyclic polyketide carbon backbone, which is assembled by a single module polyketide synthase. The biosynthesis of SAMT involves a unique polyketide chain-releasing mechanism, in which a pyridoxal 5'-phosphate-dependent enzyme catalyzes the termination, offloading and elongation of the polyketide chain. This leads to the introduction of a new carbon-carbon bond and an amino group to the polyketide chain. The mechanism is fundamentally different from the thioesterase/cyclase-catalyzed polyketide chain releasing found in bacterial and other fungal polyketide biosynthesis. Genetic data suggest that the ketosynthase domain of the polyketide synthase and the chain-releasing enzyme are important for controlling the final product structure. In addition, several post-polyketide modifications have to take place before SAMT become mature toxins.

  2. Serial Pixel Analog-to-Digital Converter

    Energy Technology Data Exchange (ETDEWEB)

    Larson, E D

    2010-02-01

    This method reduces the data path from the counter to the pixel register of the analog-to-digital converter (ADC) from as many as 10 bits to a single bit. The reduction in data path width is accomplished by using a coded serial data stream similar to a pseudo random number (PRN) generator. The resulting encoded pixel data is then decoded into a standard hexadecimal format before storage. The high-speed serial pixel ADC concept is based on the single-slope integrating pixel ADC architecture. Previous work has described a massively parallel pixel readout of a similar architecture. The serial ADC connection is similar to the state-of-the art method with the exception that the pixel ADC register is a shift register and the data path is a single bit. A state-of-the-art individual-pixel ADC uses a single-slope charge integration converter architecture with integral registers and “one-hot” counters. This implies that parallel data bits are routed among the counter and the individual on-chip pixel ADC registers. The data path bit-width to the pixel is therefore equivalent to the pixel ADC bit resolution.

  3. Natural CO2 Analogs for Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Scott H. Stevens; B. Scott Tye

    2005-07-31

    The report summarizes research conducted at three naturally occurring geologic CO{sub 2} fields in the US. The fields are natural analogs useful for the design of engineered long-term storage of anthropogenic CO{sub 2} in geologic formations. Geologic, engineering, and operational databases were developed for McElmo Dome in Colorado; St. Johns Dome in Arizona and New Mexico; and Jackson Dome in Mississippi. The three study sites stored a total of 2.4 billion t (46 Tcf) of CO{sub 2} equivalent to 1.5 years of power plant emissions in the US and comparable in size with the largest proposed sequestration projects. The three CO{sub 2} fields offer a scientifically useful range of contrasting geologic settings (carbonate vs. sandstone reservoir; supercritical vs. free gas state; normally pressured vs. overpressured), as well as different stages of commercial development (mostly undeveloped to mature). The current study relied mainly on existing data provided by the CO{sub 2} field operator partners, augmented with new geochemical data. Additional study at these unique natural CO{sub 2} accumulations could further help guide the development of safe and cost-effective design and operation methods for engineered CO{sub 2} storage sites.

  4. Molecular interactions between (--epigallocatechin gallate analogs and pancreatic lipase.

    Directory of Open Access Journals (Sweden)

    Shihui Wang

    Full Text Available The molecular interactions between pancreatic lipase (PL and four tea polyphenols (EGCG analogs, like (--epigallocatechin gallate (EGCG, (--gallocatechin gallate (GCG, (--epicatechin gallate (ECG, and (--epigallocatechin (EC, were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent.

  5. Resistance to somatostatin analogs in acromegaly: an evolving concept?

    Science.gov (United States)

    Gola, M; Bonadonna, S; Mazziotti, G; Amato, G; Giustina, A

    2006-01-01

    The aim of acromegaly treatment is to control the disease by suppressing GH hyperactivity and reducing the size or impeding the growth of the pituitary GH secreting mass. Over recent years, many studies have emphasized the role of SS analogs in the treatment of acromegaly. In fact, SS analogs have been demonstrated to be an effective tool not only in the control of GH hypersecretion but also more recently in the control of tumor growth, in a relevant number of acromegalic patients both as primary or adjunctive treatment. In this context, the therapeutic failure of medical treatment with SS analogs needs to be accurately defined particularly when they are used as primary treatment but also when they are given to patients previously operated upon, since other effective therapeutic options are nowadays available. Current definition of resistance to SS analogs is based on their efficacy to control GH and IGF-I. However, due to the emerging significance of the shrinkage effect of SS analogs on pituitary adenomas as well as to the apparent dissociation between this effect and the biochemical effects of treatment with these analogs, an evolution in the concept of SS resistance is likely to be occurring. In this review, we will discuss the biological basis of the discordance between biochemical and volumetric effects of SS analogs, and we will address the intriguing clinical and therapeutic aspects related to a possible redefinition of the resistance to SS analogs. PMID:16553040

  6. Analog circuit design techniques at 0.5V

    CERN Document Server

    Chatterjee, Shouri; Stanic, Nebojša

    2010-01-01

    This book tackles challenges for the design of analog integrated circuits that operate from ultra-low power supply voltages (down to 0.5V). Coverage demonstrates the signal processing circuit and circuit biasing approaches through the design of operational transconductance amplifiers (OTAs). These amplifiers are then used to build analog system functions including continuous time filter and a sample and hold amplifier.

  7. Novel analog switching circuit for van der Pauw measurements

    OpenAIRE

    David, T.; Molchadsky, I.; Somechi, A.; Rosenbaum, R.

    2005-01-01

    A simple electronic circuit is described using four common and very inexpensive analog multiplexer/demultiplexer chips. These analog switches are used to select eight different wiring configurations to a van der Pauw sample. Several interfacing schemes to a PC are suggested. The van der Pauw resistivity and Hall voltage expressions are also summarized.

  8. Analog modeling of transient moisture flow in unsaturated soil

    NARCIS (Netherlands)

    Wind, G.P.

    1979-01-01

    Hydraulic and electronic analog models are developed for the simulation of moisture flow and accumulation in unsaturated soil. The analog models are compared with numerical models and checked with field observations. Application of soil physical knowledge on a soil technological problem by means of

  9. Introducing Analog Drawing into a Prison Art Education Setting.

    Science.gov (United States)

    Yesh, Patrick

    A qualitative research study documents the progress of an adult male art student enrolled in a grade nine art class of adult males in a federal, maximum security penitentiary. Analog drawings were used as part of the curriculum. An analog drawing is a symbolic drawing expressing one's emotions, ideas, and feelings, often used to identify and help…

  10. Using Analogies to Prevent Misconceptions about Chemical Equilibrium

    Science.gov (United States)

    Sahin Pekmez, Esin

    2010-01-01

    The main purpose of this study was to find the effectiveness of using analogies to prevent misconceptions about chemical equilibrium. Nineteen analogies, which were based on dynamic aspects of chemical equilibrium and application of Le Chatelier's principle, were developed. The participations of this study consisted of 11th grade students (n: 151)…

  11. Magic Bullets, Slate, and Stradivarius: Analogies, Research, and Policy Making.

    Science.gov (United States)

    Baker, Keith

    1998-01-01

    Considering how important analogies are to human thinking, it is surprising how little attention educators and educational researchers give them. Valid research results can lead to false conclusions if viewed through the mental filter of a faulty analogy. This article examines two policy problems (prison literacy/recidivism rates and vanishing…

  12. Recombinant DNA technology in the treatment of diabetes: insulin analogs.

    Science.gov (United States)

    Vajo, Z; Fawcett, J; Duckworth, W C

    2001-10-01

    After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogs were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analog, lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States, and several other analogs are being intensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct significance to both patients and their physicians. The introduction of new short-acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed. PMID:11588149

  13. The interplay of conflict and analogy in multidisciplinary teams.

    Science.gov (United States)

    Paletz, Susannah B F; Schunn, Christian D; Kim, Kevin H

    2013-01-01

    Creative teamwork in multidisciplinary teams is a topic of interest to cognitive psychologists on the one hand, and to both social and organizational psychologists on the other. However, the interconnections between cognitive and social layers have been rarely explored. Drawing on mental models and dissonance theories, the current study takes a central variable studied by cognitive psychologists-analogy-and examines its relationship to a central variable examined by social psychologists-conflict. In an observational, field study, over 11h of audio-video data from conversations of the Mars Exploration Rover scientists were coded for different types of analogy and micro-conflicts that reveal the character of underlying psychological mechanisms. Two different types of time-lagged logistic models applied to these data revealed asymmetric patterns of associations between analogy and conflict. Within-domain analogies, but not within-discipline or outside-discipline analogies, preceded science and work process conflicts, suggesting that in multidisciplinary teams, representational gaps in very close domains will be more likely to spark conflict. But analogies also occurred in reaction to conflict: Process and negative conflicts, but not task conflicts, preceded within-discipline analogies, but not to within-domain or outside-discipline analogies. This study demonstrates ways in which cognition can be bidirectionally tied to social processes and discourse.

  14. Analogy as a means of theoretical adoption of pedagogical disciplines

    Directory of Open Access Journals (Sweden)

    Solovcova Irina A.

    2006-01-01

    Full Text Available The paper considers an application of analogy in the initial-teacher training as a tool of approaching pedagogical disciplines. The author proposes a classification of pedagogical analogies which provides choices of the most efficient model for a specific didactic situation. The article clarifies the model of the theoretical approach to pedagogical disciplines through active use of analogy, which contributes to a higher efficiency in a teacher and student interaction. The model consists of three stages: training (the stage of acquiring analogy model, the analytical stage (acquisition of pedagogical concepts, phenomena and systems through the application of analogy, and the stage of self-realization (the application of analogy method in students’ scientific-research activities considering external and internal didactic conditions which transform analogy from a teaching method into a tool for the acquisition of pedagogical disciplines. The author demonstrates that the application of analogy has a positive effect not only on the acquisition of pedagogical knowledge (especially methodic and the development of heuristic skills in students, but also on motivation for the study of pedagogical disciplines (cognitive aspect and professional pedagogical activity (formation of an individual-pedagogical attitude. .

  15. Physical properties and structure of enzymatically synthesized amylopectin analogs

    NARCIS (Netherlands)

    Ciric, Jelena; Woortman, Albert J. J.; Gordiichuk, Pavlo; Stuart, Marc C. A.; Loos, Katja

    2013-01-01

    The mechanism of the enzymatic polymerization of amylopectin analogs with phosphorylase b and glycogen branching enzyme is very intriguing. Recently, size exclusion chromatography with multi-detection of enzymatically synthesized amylopectin analogs in combination with MALDI-ToF MS analysis of enzym

  16. Analogical Reasoning in the Classroom: Insights from Cognitive Science

    Science.gov (United States)

    Vendetti, Michael S.; Matlen, Bryan J.; Richland, Lindsey E.; Bunge, Silvia A.

    2015-01-01

    Applying knowledge from one context to another is a notoriously difficult problem, both for children and adults, but lies at the heart of educational endeavors. Analogical reasoning is a cognitive underpinning of the ability to notice and draw similarities across contexts. Reasoning by analogy is especially challenging for students, who must…

  17. Nonpeptide somatostatin analogs: recent advances in its application and research

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Along with its wide anatomical distribution, somatostatin (SST) acts on multiple targets via a family of 5 receptors to produce a broad spectrum of biological effects. Therefore, a variety of peptide analogs have been produced and are widely used in clinical treatment. However, because of their flaws in the structure of peptide, the clinical efficacy is limited. In this review, we summarize the structure, pharmacological effects and the potential clinical value of non-peptide SST analogs. We focus on the research and development of non-peptide SST analogs since 1998, and discuss the problems and potential prospects for non-peptide SST analogs. We believe that as more non-peptide somatostatin analogs are successfully developed, the extensive clinical application of SSTs will contribute a great deal to medical science.

  18. NASA HRP Immunology Discipline - Use of Terrestrial Analogs

    Science.gov (United States)

    Crucian, Brian

    2014-01-01

    Due to the cost and operational constraints, as well as technical implementation limitations, it is desirous to perform relevant space physiology investigations first in terrestrial 'space analogs'. This is particularly true for initial investigations, which may then provide appropriate focus for subsequent flight investigations, or for mechanistic investigations that simply cannot be performed during spaceflight. Appropriate analog choice is extremely important. There are a wide variety of terrestrial space analogs, each relevant to a particular physiological discipline (or disciplines) and each with a particular fidelity (or lack thereof) to spaceflight, and each with unique operational constraints. The HRP Immunology Discipline is tasked with managing the HRP Risk concerning clinical risk for Astronaut crews related to spaceflight-associated immune dysregulation. Such dysregulation has been documented to occur during spaceflight, and found to persist for the duration of a 6-month ISS mission. Studies continue to characterize the onorbit phenomenon, but it generally consists of diminished immunocyte function, dysregulated cytokine profiles, and persistent herpesvirus reactivation. Causes are thought to synergistically include microgravity, psychological or physiological stress, radiation, and/or circadian misalignment. An appropriate terrestrial analog for immune dysregulation would replicate as many of these influences as possible. Such analogs may include clinostat or bioreactor cell culture (microgravity), hindlimb suspension (stress, fluid shifts, hypokinesis), or human deployment to remote or extreme environments (isolation, stress, circadian). Also, the laboratory setting may be used as an analog, or to augment analogs, such as sleep deprivation/misalignment or human centrifugation to replicate gravitational stress. As an appropriate example of a NASA Disciplines use of Terrestrial space analogs, this talk will discuss spaceflight associated immune

  19. Rhodium-105 Bombesin Analogs for Prostate Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Silvia S. Jurisson, PhD

    2005-12-31

    Over the period of this grant (11/01/2001 to 12/31/2005), the consistent and reproducible production of Rh-105, synthesis and evaluation of three new chelate systems based on hydroxymethyl phosphines, development of a new non-hydroxymethyl phosphine N{sub 2}P{sub 2} chelate system, conjugation of two of the chelates to the bombesin peptide analog BBN[7-14]NH{sub 2}, evaluation of the bombesin conjugates and their Rh-105 complexes for stability, cell binding affinity, and in vivo biodistribution in normal mice has been developed. The BBN analogs bind to GRP receptors that are overexpressed on PC-3 prostate tumor cells. A dedicated glove box is used for the separation and isolation of {sup 105}Rh from the target ({sup 104}Ru). All tubing/connections/valves from the point of the Cl{sub 2} tank are made of Teflon to minimize/eliminate the introduction of any metal into the process (e.g., iron from stainless steel corrosion). The separation of {sup 105}Rh produced from the enriched {sup 104}Ru target involves oxidation of the enriched {sup 104}Ru metal target to ruthenium tetroxide with chlorine gas and sodium hydroxide solution to generate hypochlorite in situ. The RuO4 is removed by distillation and the {sup 105}Rh remaining in the reaction vial is converted into {sup 105}Rh-chloride by acidification with hydrochloric acid and heating. The {sup 105}Rh production process has become reproducible over the past year to consistently make 10-30 mCi of {sup 105}Rh from 1-3 mg of an enriched (99.21%) {sup 104}Ru target. The process itself involves irradiation of the enriched {sup 104}Ru target in the core of the reactor (University of Missouri Research Reactor (MURR)) for one week to yield 16-40 mCi of {sup 105}Rh. The irradiated target is processed to separate the Rh-105 in high specific activity from the {sup 104}Ru target. The irradiated target is dissolved in NaOH (2M, 3 mL) by bubbling Cl{sub 2} gas through the solution (generating NaOCl in situ) to generate RuO{sub 4

  20. Resistance to somatostatin analogs in acromegaly.

    Science.gov (United States)

    Colao, Annamaria; Auriemma, Renata S; Lombardi, Gaetano; Pivonello, Rosario

    2011-04-01

    Somatostatin analogs (SA) are widely used in acromegaly, either as first-line or adjuvant treatment after surgery. First-line treatment with these drugs is generally used in the patients with macroadenomas or in those with clinical conditions so severe as to prevent unsafe reactions during anesthesia. Generally, the response to SA takes into account both control of GH and IGF-I excess, with consequent improvement of clinical symptoms directly related to GH and IGF-I excess, and tumor shrinkage. This latter effect is more prominent in the patients treated first-line and bearing large macroadenomas, but it is also observed in patients with microadenomas, even with little clinical implication. Predictors of response are patients' gender, age, initial GH and IGF-I levels, and tumor mass, as well as adequate expression of somatostatin receptor types 2 and 5, those with the highest affinity for octreotide and lanreotide. Only sporadic cases of somatostatin receptor gene mutation or impaired signaling pathways have been described in GH-secreting tumors so far. The response to SA also depends on treatment duration and dosage of the drug used, so that a definition of resistance based on short-term treatments using low doses of long-acting SA is limited. Current data suggest that response to these drugs is better analyzed taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA. PMID:21123741

  1. BOOK REVIEW: An Analog Electronics Companion

    Science.gov (United States)

    Hamilton, Scott

    2003-09-01

    The expression 'Analog electronics' here means the sum of a vast quantity of scientific and technical knowledge and topics. By the same token, the electronic analogue and circuit designer should also have a vast cultural and scientific know-how. The aim of this book is to be a guide for neophytes as well as a useful 'travelling companion' for the mature designer confronted with such a vast world. In my opinion it successfully meets these intentions. The subjects are treated in a concise, clear and self-contained fashion, always helped by a broad exhaustive bibliography, and cover all the necessary aspects for electronic design, such as: the essential elements of mathematical analysis, trigonometry and logarithms to reach Fourier and Laplace transforms and differential equations; physics phenomena and laws from electrostatics and electrodynamics up to Maxwell equations and electronic noise; the fundamental elements of electronic circuit theory and their methods of analysis up to the theory of feedback and control systems; an analysis of the electrical characteristics of the main passive and active electronic components. The above mentioned points take up about half of the text. The remaining topics deal with circuit applications often faced by the electronic designer. In the second part, circuit analysis is treated analytically as well as by the use of CAD, and Pspice software is provided on a CD which illustrates examples. The list of topics treated is long and ranges from operational amplifier circuits to rectifier circuits as well as current feedback amplifiers and high frequency transformers. The book closes by mentioning chaos theory. Daniele Marioli

  2. Remote Sensing and Quantization of Analog Sensors

    Science.gov (United States)

    Strauss, Karl F.

    2011-01-01

    This method enables sensing and quantization of analog strain gauges. By manufacturing a piezoelectric sensor stack in parallel (physical) with a piezoelectric actuator stack, the capacitance of the sensor stack varies in exact proportion to the exertion applied by the actuator stack. This, in turn, varies the output frequency of the local sensor oscillator. The output, F(sub out), is fed to a phase detector, which is driven by a stable reference, F(sub ref). The output of the phase detector is a square waveform, D(sub out), whose duty cycle, t(sub W), varies in exact proportion according to whether F(sub out) is higher or lower than F(sub ref). In this design, should F(sub out) be precisely equal to F(sub ref), then the waveform has an exact 50/50 duty cycle. The waveform, D(sub out), is of generally very low frequency suitable for safe transmission over long distances without corruption. The active portion of the waveform, t(sub W), gates a remotely located counter, which is driven by a stable oscillator (source) of such frequency as to give sufficient digitization of t(sub W) to the resolution required by the application. The advantage to this scheme is that it negates the most-common, present method of sending either very low level signals (viz. direct output from the sensors) across great distances (anything over one-half meter) or the need to transmit widely varying higher frequencies over significant distances thereby eliminating interference [both in terms of beat frequency generation and in-situ EMI (electromagnetic interference)] caused by ineffective shielding. It also results in a significant reduction in shielding mass.

  3. Differentiation of Keratinocytes Modulates Skin HPA Analog.

    Science.gov (United States)

    Wierzbicka, Justyna M; Żmijewski, Michał A; Antoniewicz, Jakub; Sobjanek, Michal; Slominski, Andrzej T

    2017-01-01

    It is well established, that epidermal keratinocytes express functional equivalent of hypothalamus-pituitary-adrenal axis (HPA) in order to respond to changing environment and maintain internal homeostasis. We are presenting data indicating that differentiation of primary neonatal human keratinocytes (HPEKp), induced by prolonged incubation or calcium is accompanied by significant changes in the expression of the elements of skin analog of HPA (sHPA). Expression of CRF, UCN1-3, POMC, ACTH, CRFR1, CRFR2, MC1R, MC2R, and GR (coded by NR3C1 gene) were observed on gene/protein levels along differentiation of keratinocytes in culture with similar pattern seen by immunohistochemistry on full thickness skin biopsies. Expression of CRF was more pronounced in less differentiated keratinocytes, which corresponded to the detection of CRF immunoreactivity preferentially in the stratum basale. POMC expression was enhanced in more differentiated keratinocytes, which corresponded to detection of ACTH immunoreactivity, predominantly in the stratum spinosum and stratum granulosum. Expression of urocortins was also affected by induction of HPEKp differentiation. Immunohistochemical studies showed high prevalence of CRFR1 in well differentiated keratinocytes, while smaller keratinocytes showed predominantly CRFR2 immunoreactivity. MC2R mRNA levels were elevated from days 4 to 8 of in vitro incubation, while MC2R immunoreactivity was the highest in the upper layers of epidermis. Similar changes in mRNA/protein levels of sHPA elements were observed in HPEKp keratinocytes treated with calcium. Summarizing, preferential expression of CRF and POMC (ACTH) by populations of keratinocytes on different stage of differentiation resembles organization of central HPA axis suggesting their distinct role in physiology and pathology of the epidermis. J. Cell. Physiol. 232: 154-166, 2017. © 2016 Wiley Periodicals, Inc.

  4. De Analogía a Digitalia

    Directory of Open Access Journals (Sweden)

    Dr. Xaime Fandiño Alonso

    2001-01-01

    ía, creatividad y contenidos.ABSTRACTThe transition towards binary-based technology has unleashed dramatic changes that in the last decade have affected the different stages involved in an audiovisual production: from scripting and creating a project, through the various technological procedures of the actual production process to its final distribution.The remains of the analogical era are finally sinking under a seemingly unstoppable wave of constantly evolving new digital environments.The new hardware devices used in this field are mainly prototypes. An ever evolving market, the constant arising of new competitors, newborn joint-ventures and a myriad of related facts force technology providers to keep a pace of constant updating in a mad race of fierce competition.The old system which implied one machine for each process is increasingly becoming a memory of the past. Today new devices are being launched at such a speed that the old technological approach which dealt with mechanical appliances like magnetoscopes, closed platforms and linear recording are already bound for extinction.It’s only natural then that the sacred cows of the industry fear for their position. Big and small are elusive concepts in this new audiovisual frenzy. Its almost daily routine to read about big audiovisual corporations announcing mergers, buy-outs or the acquisition of a stake in new and small creativity and development firms built from scratch by young entrepreneurs out of the blue.The digital era is drawing a heavy curtain that luckily leaves behind an analogical era in which the ownership of the costly means of production was the most important card in the game. The artist could only exercise its art if access to the professional team and technical equipment required for an audiovisual work was granted by its proprietors.Today, digital means new systems with far more productive environments which besides are user-friendly and cost only a small fraction of the old hardware.Right now, with

  5. Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences.

    Science.gov (United States)

    Coin, Irene; Beyermann, Michael; Bienert, Michael

    2007-01-01

    This protocol for solid-phase peptide synthesis (SPPS) is based on the widely used Fmoc/tBu strategy, activation of the carboxyl groups by aminium-derived coupling reagents and use of PEG-modified polystyrene resins. A standard protocol is described, which was successfully applied in our lab for the synthesis of the corticotropin-releasing factor (CRF), >400 CRF analogs and a countless number of other peptides. The 41-mer peptide CRF is obtained within approximately 80 working hours. To achieve the so-called difficult sequences, special techniques have to be applied in order to reduce aggregation of the growing peptide chain, which is the main cause of failure for peptide chemosynthesis. Exemplary application of depsipeptide and pseudoproline units is shown for synthesizing an extremely difficult sequence, the Asn(15) analog of the WW domain FBP28, which is impossible to obtain using the standard protocol.

  6. Novel alpha-MSH peptide analogs for melanoma targeting

    Science.gov (United States)

    Flook, Adam Michael

    Skin cancer is the one of the most diagnosed cancers in the United States with increasing incidence over the past two decades. There are three major forms of skin cancer but melanoma is the deadliest. It is estimated that 76,690 new diagnoses of melanoma and 9,480 deaths will occur in 2013. Melanoma accounts for approximately 1.6% of all cancer related deaths and is the 5 th leading diagnosed cancer in the United States. The mean survival rate of patients diagnosed with metastatic melanoma is six months, with five year survival rates of less than 5%. In this project, we describe the design and characterization of novel melanoma-targeting peptide analogs for use in diagnostic imaging of both primary and metastatic melanoma lesions. Novel alpha-MSH peptide conjugates were designed to target the melanocortin-1 receptor present and over-expressed on melanoma cells. These peptides were synthesized and their in-vitro melanocortin-1 receptor binding affinities were established in murine melanoma cells. Once binding affinities were determined, the peptides were radiolabeled with 99mTc utilizing a novel direct radiolabeling technique developed in our laboratory. The peptides were purified via reverse-phase high performance liquid chromatography and in-vivo melanoma targeting and pharmacokinetic properties were determined in B16/F1 melanoma-bearing female C57BL/6 mice. Biodistribution and SPECT/CT imaging studies were performed with the promising 99m Tc-labeled peptide conjugates. All alpha-MSH peptide conjugates tested showed low nanomolar binding affinity for the melanocortin-1 receptor. All peptides were readily radiolabeld with 99mTc with greater than 95% radiochemical purity. All 99mTc-labeled peptides displayed high specific in-vivo melanoma tumor uptake while maintaining low normal organ accumulation, and were excreted through the urinary system in a timely fashion. In addition, all tested 99mTc-labeld alpha-MSH peptides demonstrated clear visualization of in

  7. Use Pronunciation by Analogy for text to speech system in Persian language

    CERN Document Server

    Jowharpour, Ali; Yektaee, Mohammad hosein

    2011-01-01

    The interest in text to speech synthesis increased in the world .text to speech have been developed formany popular languages such as English, Spanish and French and many researches and developmentshave been applied to those languages. Persian on the other hand, has been given little attentioncompared to other languages of similar importance and the research in Persian is still in its infancy.Persian language possess many difficulty and exceptions that increase complexity of text to speechsystems. For example: short vowels is absent in written text or existence of homograph words. in thispaper we propose a new method for persian text to phonetic that base on pronunciations by analogy inwords, semantic relations and grammatical rules for finding proper phonetic. Keywords:PbA, text to speech, Persian language, FPbA

  8. Braneworld physics from the analog-gravity perspective

    CERN Document Server

    Barcelo, C; Barcelo, Carlos; Campos, Antonio

    2003-01-01

    We study Randall-Sundrum brane models from the viewpoint of condensed matter/quantum optics. Following the idea of analog gravity we obtain effective metrics in fluid and Bose-Einstein-condensate systems mimicking those in the brane framework. We see that the effect of warp factors in the bulk geometry translates into finite-size of the analog systems. We stress that many open questions in braneworld physics can benefit from the understanding of critical phenomena of surfaces in finite analog systems.

  9. Airframe Noise Prediction by Acoustic Analogy: Revisited

    Science.gov (United States)

    Farassat, F.; Casper, Jay H.; Tinetti, A.; Dunn, M. H.

    2006-01-01

    The present work follows a recent survey of airframe noise prediction methodologies. In that survey, Lighthill s acoustic analogy was identified as the most prominent analytical basis for current approaches to airframe noise research. Within this approach, a problem is typically modeled with the Ffowcs Williams and Hawkings (FW-H) equation, for which a geometry-independent solution is obtained by means of the use of the free-space Green function (FSGF). Nonetheless, the aeroacoustic literature would suggest some interest in the use of tailored or exact Green s function (EGF) for aerodynamic noise problems involving solid boundaries, in particular, for trailing edge (TE) noise. A study of possible applications of EGF for prediction of broadband noise from turbulent flow over an airfoil surface and the TE is, therefore, the primary topic of the present work. Typically, the applications of EGF in the literature have been limited to TE noise prediction at low Mach numbers assuming that the normal derivative of the pressure vanishes on the airfoil surface. To extend the application of EGF to higher Mach numbers, the uniqueness of the solution of the wave equation when either the Dirichlet or the Neumann boundary condition (BC) is specified on a deformable surface in motion. The solution of Lighthill s equation with either the Dirichlet or the Neumann BC is given for such a surface using EGFs. These solutions involve both surface and volume integrals just like the solution of FW-H equation using FSGF. Insight drawn from this analysis is evoked to discuss the potential application of EGF to broadband noise prediction. It appears that the use of a EGF offers distinct advantages for predicting TE noise of an airfoil when the normal pressure gradient vanishes on the airfoil surface. It is argued that such an approach may also apply to an airfoil in motion. However, for the prediction of broadband noise not directly associated with a trailing edge, the use of EGF does not

  10. RAM, an RGDS analog, exerts potent anti-melanoma effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Maria Simona Aguzzi

    Full Text Available Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum-induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a mouse metastatic melanoma in vivo model, increasing doses of RAM significantly reduce up to about 80% lung metastases development, while comparable doses of RGDS are less potent. In conclusion these data show that RAM is a potent inhibitor of melanoma growth in vitro, strongly reduces melanoma metastases development in vivo and represents a novel candidate for further in vivo investigations in the cancer treatment field.

  11. Small Molecule AngIV-based Analogs to Treat Alzheimers Disease

    Directory of Open Access Journals (Sweden)

    John W Wright

    2016-06-01

    Full Text Available Alzheimer’s disease (AD patients are presently without adequate treatment thus new therapeutic approaches are needed to slow and hopefully reverse disease progression. Neurotrophic agents such as nerve growth factor and brain-derived neurotrophic factor have received research attention concerning their potential to treat AD but have not progressed to clinical trials due to their large size, inability to penetrate the blood-brain barrier (BBB, and the high cost of synthesis. This review focuses on one over looked neurotrophin, hepatocyte growth factor (HGF that acts via the Type 1 tyrosine kinase receptor Met to mediate stem cell differentiation, synaptogenesis, neurogenesis, and protect against tissue insults in a wide range of cell types including neurons. We have determined that the brain angiotensin and HGF/c-Met systems interact in such a way that angiotensin IV (AngIV-based analogs including Nle1-AngIV, Norleual-AngIV, Dihexa, and others influence HGF dimerization which is a prerequisite to binding at the Met receptor. Several of these analogs have shown the ability to facilitate the formation of new functional synaptic connections in hippocampal slices, promote neurogenesis, and augment memory consolidation and retrieval in animal models of AD. This family of compounds represents a new class of drugs with lead candidates that are orally active, penetrate the BBB sufficiently to reach therapeutic concentrations, and reverse memory deficits seen in animal models of dementia.

  12. LAT-1 activity of meta-substituted phenylalanine and tyrosine analogs.

    Science.gov (United States)

    Augustyn, Evan; Finke, Karissa; Zur, Arik A; Hansen, Logan; Heeren, Nathan; Chien, Huan-Chieh; Lin, Lawrence; Giacomini, Kathleen M; Colas, Claire; Schlessinger, Avner; Thomas, Allen A

    2016-06-01

    The transporter protein Large-neutral Amino Acid Transporter 1 (LAT-1, SLC7A5) is responsible for transporting amino acids such as tyrosine and phenylalanine as well as thyroid hormones, and it has been exploited as a drug delivery mechanism. Recently its role in cancer has become increasingly appreciated, as it has been found to be up-regulated in many different tumor types, and its expression levels have been correlated with prognosis. Substitution at the meta position of aromatic amino acids has been reported to increase affinity for LAT-1; however, the SAR for this position has not previously been explored. Guided by newly refined computational models of the binding site, we hypothesized that groups capable of filling a hydrophobic pocket would increase binding to LAT-1, resulting in improved substrates relative to parent amino acid. Tyrosine and phenylalanine analogs substituted at the meta position with halogens, alkyl and aryl groups were synthesized and tested in cis-inhibition and trans-stimulation cell assays to determine activity. Contrary to our initial hypothesis we found that lipophilicity was correlated with diminished substrate activity and increased inhibition of the transporter. The synthesis and SAR of meta-substituted phenylalanine and tyrosine analogs is described.

  13. [New synthesis empathogenic agents].

    Science.gov (United States)

    Velea, D; Hautefeuille, M; Vazeille, G; Lantran-Davoux, C

    1999-01-01

    The use of synthesis drugs is the object of numerous written articles and TV programs in the last, decade. These synthesis drugs or "designer drugs", are well known for their ability to enhance, reinforce or appease social difficulties and relationships. In the research for empathetic and entactogenic relations one discover an obvious lack of communication and "warmth" in personal or professional relationship. An image of chemical "well being" has become a frequent stereotype of a society with an atrophying of performance and values while supposedly dedicating itself to individual performance. The youths are the first victims of these new drugs, the economical and social environment are the main reinforcing factors of this behaviour. The main characteristic of these drugs, is the non-recognition of their danger, some users go so far as to describe this category of substances as "drugs which are not drugs". As a characteristic, the use of a these synthesis drugs is almost recreative, during the week-end and holiday. The drug addiction is different than that of opiates or cocaine. One can observe some cases of real dependence--corresponding to the DSW IV criterion--when the personality of the users is the main characteristic (narcissic failure, immature personality, family and school problems). Many adverse effects--hypertension, kidney failure, psychoses--were declared. The mass-media has presented many articles concerning Ecstasy (MDMA). This is the most used drug during the rave parties. Its adverse effects are well known and proven. The authors would like to present other more recent synthesis drugs, also known as "analogs". These drugs, a kind of mixture between amphetamine-like (MDMA, MBDB, MDA) and misused medicines (ketamine, gamma OH, atropine) represent a real danger. GHB, 2 CB, HMB, are some of these recent substances. The possibility to procure them on the Web, or to produce them by oneself, add to their danger because of the lack of controls on toxicity

  14. Bridging Converts a Noncytotoxic nor-Paclitaxel Derivative to a Cytotoxic Analog by Constraining it to the T-Taxol Conformation

    OpenAIRE

    Tang, Shoubin; Yang, Chao; Brodie, Peggy; Bane, Susan; Ravindra, Rudravajhala; Sharma, Shubhada; Jiang, Yi; Snyder, James P.; Kingston, David G I

    2006-01-01

    The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially non-cytotoxic, the bridged analog 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.

  15. Protection by antioxidants against toxicity and apoptosis induced by the sulphur mustard analog 2-chloroethylethyl sulphide (CEES) in Jurkat T cells and normal human lymphocytes

    OpenAIRE

    Han, Suhua; Espinoza, Luis A; Liao, Hongling; Boulares, A Hamid; Smulson, Mark E.

    2004-01-01

    The mechanism of toxicity of sulphur mustard was investigated by examining the biochemical effects of the analog 2-chloroethylethyl sulphide (CEES) in both human Jurkat cells as well as normal human lymphocytes.Exposure of both types of cells to CEES resulted in a marked decrease in the intracellular concentration of the reduced form of glutathione (GSH), and CEES-induced cell death was potentiated by L-buthionine sulphoximine, an inhibitor of GSH synthesis.CEES increased the endogenous produ...

  16. Project Birdseye Aerial Photograph Collection: Digital and Analog Materials

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This collection consists of both analog and digital aerial photographs from Arctic areas in and around Baffin Bay, the Labrador Sea, the Arctic Ocean, the Beaufort...

  17. Digitoxin and its analogs as novel cancer therapeutics

    Directory of Open Access Journals (Sweden)

    Elbaz Hosam A

    2012-04-01

    Full Text Available Abstract A growing body of evidence indicates that digitoxin cardiac glycoside is a promising anticancer agent when used at therapeutic concentrations. Digitoxin has a prolonged half-life and a well-established clinical profile. New scientific avenues have shown that manipulating the chemical structure of the saccharide moiety of digitoxin leads to synthetic analogs with increased cytotoxic activity. However, the anticancer mechanism of digitoxin or synthetic analogs is still subject to study while concerns about digitoxin's cardiotoxicity preclude its clinical application in cancer therapeutics. This review focuses on digitoxin and its analogs, and their cytotoxicity against cancer cells. Moreover, a new perspective on the pharmacological aspects of digitoxin and its analogs is provided to emphasize new research directions for developing potent chemotherapeutic drugs.

  18. FXR agonist activity of conformationally constrained analogs of GW 4064

    Energy Technology Data Exchange (ETDEWEB)

    Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y.; Caldwell, Richard D.; Caravella, Justin A.; Chen, Lihong; Creech, Katrina L.; Deaton, David N.; Madauss, Kevin P.; Marr, Harry B.; McFadyen, Robert B.; Miller, Aaron B.; Navas, III, Frank; Parks, Derek J.; Spearing, Paul K.; Todd, Dan; Williams, Shawn P.; Wisely, G. Bruce; (GSKNC)

    2010-09-27

    Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

  19. Energy Harvesting Using an Analog Circuit under Multimodal Vibration

    Directory of Open Access Journals (Sweden)

    Shigeru Shimose

    2013-01-01

    Full Text Available The efficiency of harvesting energy from a vibrating structure using a piezoelectric transducer and a simple analog circuit is investigated experimentally. This analog circuit was originally invented for a synchronized switch damping on inductor (SSDI technique, which enhances the damping of mechanical vibration. In this study, the circuit is used to implement a synchronized switch harvesting on inductor (SSHI technique. A multiple degree of freedom (MDOF structure is excited by single sinusoidal forces at its resonant frequencies and by random forces. The piezoelectric transducer converts this mechanical energy into electrical energy which is harvested using a standard rectifier bridge circuit with and without our analog circuit. Experimental results show that our analog circuit makes it possible to harvest twice as much energy under both single sinusoidal and random vibration excitations.

  20. A Uniform Approach to Analogies, Synonyms, Antonyms, and Associations

    CERN Document Server

    Turney, Peter D

    2008-01-01

    Recognizing analogies, synonyms, antonyms, and associations appear to be four distinct tasks, requiring distinct NLP algorithms. In the past, the four tasks have been treated independently, using a wide variety of algorithms. These four semantic classes, however, are a tiny sample of the full range of semantic phenomena, and we cannot afford to create ad hoc algorithms for each semantic phenomenon; we need to seek a unified approach. We propose to subsume a broad range of phenomena under analogies. To limit the scope of this paper, we restrict our attention to the subsumption of synonyms, antonyms, and associations. We introduce a supervised corpus-based machine learning algorithm for classifying analogous word pairs, and we show that it can solve multiple-choice SAT analogy questions, TOEFL synonym questions, ESL synonym-antonym questions, and similar-associated-both questions from cognitive psychology.