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Sample records for derived methoxylated analog

  1. First total synthesis of (5Z,9Z)-(±)-2-methoxy-5,9-octadecadienoic acid, a marine derived methoxylated analog of taxoleic acid

    PubMed Central

    Carballeira, Néstor M.; O’Neill, Rosann; Silva, Diana

    2008-01-01

    The first total synthesis for the sponge derived (5Z,9Z)-(±)-2-methoxy-5,9-octadecadienoic acid, an analog of taxoleic acid, was accomplished in seven steps and in a 10% overall yield. It was again corroborated that the best strategy to prepare these cis,cis dimethylene interrupted double bonds is the double-alkyne bromide coupling reaction of 1,5-hexadiyne, which provides the advantage of achieving a 100% cis stereochemical purity for both double bonds after hydrogenation under Lindlar conditions. The α-methoxy functionality was best prepared via the Mukaiyama reaction of (4Z,8Z)-heptadecadienal with trimethylsilyl cyanide and triethylamine followed by acid hydrolysis. Selective methylation of the hydroxyl group of (5Z,9Z)-(±)-2-hydroxy-5,9-octadecadienoic acid was achieved with sodium hydride/methyl iodide when tetrahydrofuran was used as solvent. Complete spectral data is presented, for the first time, for this unusual marine α-methoxylated fatty acid. PMID:18761005

  2. Stability of apigeninidin and its methoxylated derivatives in the presence of sulfites.

    PubMed

    Ojwang, Leonnard O; Awika, Joseph M

    2010-08-25

    3-Deoxyanthocyanin pigments are more stable than anthocyanins and show promising bioactive properties. However, little is known about their stability in the presence of food additives such as sulfites. This work investigates the stability of apigeninidin and its derivatives in the presence of sulfites. Pigment (apigeninidin, 5-mono-, and 5,7-dimethoxyapigeninidin) stability at pH 1.8, 3.0, and 5.0, in the presence of sodium metabisulfite (molar ratio ∼ 1:40, pigment/SO2) was monitored over 21 days at room temperature. The structure of sulfite complexation products was monitored using HPLC-MS and NMR spectroscopy. All pigments were significantly bleached within 30 min in the presence of sulfites; the bleaching effect was more severe at pH 5.0 and 3.0 compared to pH 1.8. Apigeninidin was more resistant to bleaching than its methoxylated derivatives. However, all pigments regained some or all of the bleached color within 14-21 days at pH 3.0 and 1.8 in the presence of sulfites, indicating equilibrium favored flavylium cation at these pH values. Formation of colorless sulfonates via bisulfite ion addition at C-4 was responsible for the bleaching effect. Both structure and pH significantly affected stability of 3-deoxyanthocyanidins in the presence of sulfites. The pigments may have potential applications in low pH systems containing sulfites.

  3. “One-shot” analysis of polybrominated diphenyl ethers and their hydroxylated and methoxylated analogs in human breast milk and serum using gas chromatography-tandem mass spectrometry

    PubMed Central

    Butryn, Deena; Gross, Michael; Chi, Lai-Har; Schecter, Arnold; Olson, James; Aga, Diana

    2015-01-01

    The presence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-BDE) and methoxylated (MeO-BDE) analogs in humans is an area of high interest to public health due to their neurotoxic and endocrine disrupting effects. Consequently, there is a rise involving the investigation of these three classes of compounds together in order to understand their bioaccumulation patterns in environmental matrices and in humans. Analysis of PBDEs, OH-BDEs, and MeO-BDEs using liquid chromatography-mass spectrometry (LC-MS) can be accomplished simultaneously, but detection limits for PBDEs and MeO-BDEs in LC-MS is insufficient for trace level quantification. Therefore, fractionation steps of the phenolic (OH-BDEs) and neutral (PBDEs and MeO-BDEs) compounds during sample preparation are typically performed so different detection techniques can be used to achieve the needed sensitivities. However, this approach involves multiple injections, ultimately increasing analysis time. In this study, an analytical method was developed for a “one-shot” analysis of 12 PBDEs, 12 OH-BDEs, and 13 MeO-BDEs using gas chromatography tandem mass spectrometry (GC-MS/MS). This overall method includes simultaneous extraction of all analytes via pressurized liquid extraction followed by lipid removal steps to reduce matrix interferences. The OH-BDEs were derivatized using N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide, producing OH-TMDS derivatives that can be analyzed with PBDEs and MeO-BDEs by GC-MS/MS in “one shot” within a 25-min run. The overall recoveries were generally greater than 65%, and the limits of detection ranged from 2–14 pg in both breast milk and serum. The applicability of the method was successfully validated on four paired human breast milk and serum samples. The mean concentrations of total PBDEs, OH-BDEs, and MeO-BDEs in breast milk were 59, 2.2, and 0.57 ng g−1 lipid, respectively. In serum, the mean total concentrations were 79, 38, and 0.96 ng g

  4. "One-shot" analysis of polybrominated diphenyl ethers and their hydroxylated and methoxylated analogs in human breast milk and serum using gas chromatography-tandem mass spectrometry.

    PubMed

    Butryn, Deena M; Gross, Michael S; Chi, Lai-Har; Schecter, Arnold; Olson, James R; Aga, Diana S

    2015-09-10

    The presence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (OH-BDE) and methoxylated (MeO-BDE) analogs in humans is an area of high interest to scientists and the public due to their neurotoxic and endocrine disrupting effects. Consequently, there is a rise in the investigation of the occurrence of these three classes of compounds together in environmental matrices and in humans in order to understand their bioaccumulation patterns. Analysis of PBDEs, OH-BDEs, and MeO-BDEs using liquid chromatography-mass spectrometry (LC-MS) can be accomplished simultaneously, but detection limits for PBDEs and MeO-BDEs in LC-MS is insufficient for trace level quantification. Therefore, fractionation steps of the phenolic (OH-BDEs) and neutral (PBDEs and MeO-BDEs) compounds during sample preparation are typically performed so that different analytical techniques can be used to achieve the needed sensitivities. However, this approach involves multiple injections, ultimately increasing analysis time. In this study, an analytical method was developed for a "one-shot" analysis of 12 PBDEs, 12 OH-BDEs, and 13 MeO-BDEs using gas chromatography with tandem mass spectrometry (GC-MS/MS). This overall method includes simultaneous extraction of all analytes via pressurized liquid extraction followed by lipid removal steps to reduce matrix interferences. The OH-BDEs were derivatized using N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide (TBDMS-MTFA), producing OH-TBDMS derivatives that can be analyzed together with PBDEs and MeO-BDEs by GC-MS/MS in "one shot" within a 25-min run time. The overall recoveries were generally higher than 65%, and the limits of detection ranged from 2 to 14 pg in both breast milk and serum matrices. The applicability of the method was successfully validated on four paired human breast milk and serum samples. The mean concentrations of total PBDEs, OH-BDEs, and MeO-BDEs in breast milk were 59, 2.2, and 0.57 ng g(-1) lipid, respectively. In

  5. Mean annual temperatures of mid-latitude regions derived from δ(2)H values of wood lignin methoxyl groups and its implications for paleoclimate studies.

    PubMed

    Anhäuser, Tobias; Greule, Markus; Polag, Daniela; Bowen, Gabriel J; Keppler, Frank

    2017-01-01

    Tree-rings are widely used climate archives providing annual resolutions on centennial to millennial timescales. Stable isotope ratios of tree-rings have been applied to assist with the delineation of climate parameters such as temperature and precipitation. Here, we investigated stable hydrogen isotope ratios (expressed as δ(2)H values) of lignin methoxyl groups of wood from various tree species collected along a ~3500km north-south transect across Europe with mean annual temperatures (MAT) ranging from -4 to +17°C. We found a strong linear relationship between MATs and δ(2)H values of wood lignin methoxyl groups. We used this relationship to predict MATs from randomly collected wood samples and found general agreement between predicted and observed MATs for the mid-latitudes on a global scale. Our results are discussed in context of their paleoclimate relevance and suggest that δ(2)H values of lignin methoxyl groups might have the potential to reconstruct MATs when applied on mid-latitudinal tree-ring chronologies of the Late Holocene.

  6. 3,5,4'-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial-mesenchymal transition.

    PubMed

    Tsai, Jie-Heng; Hsu, Li-Sung; Lin, Chih-Li; Hong, Hui-Mei; Pan, Min-Hsiung; Way, Tzong-Der; Chen, Wei-Jen

    2013-11-01

    The molecular basis of epithelial-mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4'-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of β-catenin, accompanied with the downregulation of β-catenin target genes and the increment of membrane-bound β-catenin. These results suggest the involvement of Wnt/β-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3β activity by inhibiting the phosphorylation of Akt, the event required for β-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, β-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells.

  7. 3,5,4′-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/β-catenin signaling cascades and reversal of epithelial–mesenchymal transition

    SciTech Connect

    Tsai, Jie-Heng; Hsu, Li-Sung; Lin, Chih-Li; Hong, Hui-Mei; Pan, Min-Hsiung; Way, Tzong-Der; Chen, Wei-Jen

    2013-11-01

    The molecular basis of epithelial–mesenchymal transition (EMT) functions as a potential therapeutic target for breast cancer because EMT may endow breast tumor-initiating cells with stem-like characteristics and enable the dissemination of breast cancer cells. We have recently verified the antitumor activity of 3,5,4′-trimethoxystilbene (MR-3), a naturally methoxylated derivative of resveratrol, in colorectal cancer xenografts via an induction of apoptosis. The effect of MR-3 on EMT and the invasiveness of human MCF-7 breast adenocarcinoma cell line were also explored. We found that MR-3 significantly increased epithelial marker E-cadherin expression and triggered a cobblestone-like morphology of MCF-7 cells, while reciprocally decreasing the expression of mesenchymal markers, such as snail, slug, and vimentin. In parallel with EMT reversal, MR-3 downregulated the invasion and migration of MCF-7 cells. Exploring the action mechanism of MR-3 on the suppression of EMT and invasion indicates that MR-3 markedly reduced the expression and nuclear translocation of β-catenin, accompanied with the downregulation of β-catenin target genes and the increment of membrane-bound β-catenin. These results suggest the involvement of Wnt/β-catenin signaling in the MR-3-induced EMT reversion of MCF-7 cells. Notably, MR-3 restored glycogen synthase kinase-3β activity by inhibiting the phosphorylation of Akt, the event required for β-catenin destruction via a proteasome-mediated system. Overall, these findings indicate that the anti-invasive activity of MR-3 on MCF-7 cells may result from the suppression of EMT via down-regulating phosphatidylinositol 3-kinase (PI3K)/AKT signaling, and consequently, β-catenin nuclear translocation. These occurrences ultimately lead to the blockage of EMT and the invasion of breast cancer cells. - Highlights: • MR-3 blocked MCF-7 cell invasion by inducing a reversal of EMT. • Wnt/β-catenin signaling is involved in MR-3-induced EMT

  8. Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide.

    PubMed

    Iwai, Yuma; Takahashi, Hitoshi; Hatakeyama, Dai; Motoshima, Kazunori; Ishikawa, Minoru; Sugita, Kazuyuki; Hashimoto, Yuichi; Harada, Yuichi; Itamura, Shigeyuki; Odagiri, Takato; Tashiro, Masato; Sei, Yoshihisa; Yamaguchi, Kentaro; Kuzuhara, Takashi

    2010-07-15

    Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.

  9. Natural neo acids and neo alkanes: their analogs and derivatives.

    PubMed

    Dembitsky, Valery M

    2006-04-01

    This review presents more than 260 naturally occurring (as well as 47 synthesized) neo fatty (carboxylic) acids, neo alkanes, and their analogs and derivatives, isolated and identified from plants, algae, fungi, marine invertebrates, and microorganisms, that demonstrate different biological activities. These natural metabolites are good prospects for future chemical preparations as antioxidants, and also as anticancer, antimicrobial, and antibacterial agents. Described also are some synthetic bioactive compounds containing a tertiary butyl group(s) that have shown high anticancer, antifungal, and other activities. Applications of some neo fatty (carboxylic) acid derivatives in cosmetic, agronomic, and pharmaceutical industries also are considered. This is the first review to consider naturally occurring neo fatty (carboxylic) acids, neo alkanes, and other metabolites containing a tertiary butyl group(s) [or tert-butyl unit(s)].

  10. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    ERIC Educational Resources Information Center

    Ruiz, Francisco J.; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among…

  11. Derivational Analogy: A Theory of Reconstructive Problem Solving and Expertise Acquisition.,

    DTIC Science & Technology

    2014-09-26

    Enrichment of Case-Based Memory 16 4.2.2. Generalized Plans 1 4.2.3. Strategy Acquisition 16 4.2.4. Fractioning Derivations into Rules 18 5. Concluding...analogy process: The derivational traces of similar past 8 problems are replayed , and where necessary modified, to reconstruct a solution to a similar...term memory of past problem solving episodes. There are two distinct approaches to analogical problem solving. The first approach, called

  12. Identification of pyridine analogs as new predator-derived kairomones

    PubMed Central

    Brechbühl, Julien; Moine, Fabian; Tosato, Monique Nenniger; Sporkert, Frank; Broillet, Marie-Christine

    2015-01-01

    In the wild, animals have developed survival strategies relying on their senses. The individual ability to identify threatening situations is crucial and leads to increase in the overall fitness of the species. Rodents, for example have developed in their nasal cavities specialized olfactory neurons implicated in the detection of volatile cues encoding for impending danger such as predator scents or alarm pheromones. In particular, the neurons of the Grueneberg ganglion (GG), an olfactory subsystem, are implicated in the detection of danger cues sharing a similar chemical signature, a heterocyclic sulfur- or nitrogen-containing motif. Here we used a “from the wild to the lab” approach to identify new molecules that are involuntarily emitted by predators and that initiate fear-related responses in the recipient animal, the putative prey. We collected urines from carnivores as sources of predator scents and first verified their impact on the blood pressure of the mice. With this approach, the urine of the mountain lion emerged as the most potent source of chemical stress. We then identified in this biological fluid, new volatile cues with characteristic GG-related fingerprints, in particular the methylated pyridine structures, 2,4-lutidine and its analogs. We finally verified their encoded danger quality and demonstrated their ability to mimic the effects of the predator urine on GG neurons, on mice blood pressure and in behavioral experiments. In summary, we were able to identify here, with the use of an integrative approach, new relevant molecules, the pyridine analogs, implicated in interspecies danger communication. PMID:26283896

  13. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    PubMed Central

    Ruiz, Francisco J; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning. PMID:21547072

  14. Cross-domain analogies as relating derived relations among two separate relational networks.

    PubMed

    Ruiz, Francisco J; Luciano, Carmen

    2011-05-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning.

  15. Relating Derived Relations as a Model of Analogical Reasoning: Reaction Times and Event-Related Potentials

    ERIC Educational Resources Information Center

    Barnes-Holmes, Dermot; Regan, Donal; Barnes-Holmes, Yvonne; Commins, Sean; Walsh, Derek; Stewart, Ian; Smeets, Paul M.; Whelan, Robert; Dymond, Simon

    2005-01-01

    The current study aimed to test a Relational Frame Theory (RFT) model of analogical reasoning based on the relating of derived same and derived difference relations. Experiment 1 recorded reaction time measures of similar-similar (e.g., "apple is to orange as dog is to cat") versus different-different (e.g., "he is to his brother as…

  16. Relating Derived Relations as a Model of Analogical Reasoning: Reaction Times and Event-Related Potentials

    ERIC Educational Resources Information Center

    Barnes-Holmes, Dermot; Regan, Donal; Barnes-Holmes, Yvonne; Commins, Sean; Walsh, Derek; Stewart, Ian; Smeets, Paul M.; Whelan, Robert; Dymond, Simon

    2005-01-01

    The current study aimed to test a Relational Frame Theory (RFT) model of analogical reasoning based on the relating of derived same and derived difference relations. Experiment 1 recorded reaction time measures of similar-similar (e.g., "apple is to orange as dog is to cat") versus different-different (e.g., "he is to his brother as…

  17. Analogs, formulations and derivatives of imatinib: a patent review.

    PubMed

    Musumeci, Francesca; Schenone, Silvia; Grossi, Giancarlo; Brullo, Chiara; Sanna, Monica

    2015-01-01

    The Bcr-Abl inhibitor imatinib was approved in 2001 for chronic myeloid leukemia therapy, and dramatically changed the lives of patients affected by this disease. Since it also inhibits platelet derived growth factor receptor (PDGFR) and c-Kit, imatinib is used for various other tumors caused by abnormalities of one or both these two enzymes. This review presents an overview on imatinib formulations and derivatives, synthetic methodologies and therapeutic uses that have appeared in the patent literature since 2008. Innovative imatinib formulations, such as nanoparticles containing the drug, will improve its bioavailability. Moreover, oral solutions or high imatinib content tablets or capsules will improve patient compliance. Some solid formulations and innovative syntheses that have appeared in the last few years will reduce the cost of the drug, offering big advantages for poor countries. Some recently patented efficacious imatinib derivatives are in preclinical studies and could enter clinical trials in the next few years. Overall, Bcr-Abl inhibitors constitute a very appealing research field that can be expected to expand further.

  18. Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds.

    PubMed

    Borsari, Chiara; Santarem, Nuno; Torrado, Juan; Olías, Ana Isabel; Corral, María Jesús; Baptista, Catarina; Gul, Sheraz; Wolf, Markus; Kuzikov, Maria; Ellinger, Bernhard; Witt, Gesa; Gribbon, Philip; Reinshagen, Jeanette; Linciano, Pasquale; Tait, Annalisa; Costantino, Luca; Freitas-Junior, Lucio H; Moraes, Carolina B; Bruno Dos Santos, Pascoalino; Alcântara, Laura Maria; Franco, Caio Haddad; Bertolacini, Claudia Danielli; Fontana, Vanessa; Tejera Nevado, Paloma; Clos, Joachim; Alunda, José María; Cordeiro-da-Silva, Anabela; Ferrari, Stefania; Costi, Maria Paola

    2017-01-27

    Chalcones display a broad spectrum of pharmacological activities. Herein, a series of 2'-hydroxy methoxylated chalcones was synthesized and evaluated towards Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Among the synthesized library, compounds 1, 3, 4, 7 and 8 were the most potent and selective anti-T. brucei compounds (EC50 = 1.3-4.2 μM, selectivity index >10-fold). Compound 4 showed the best early-tox and antiparasitic profile. The pharmacokinetic studies of compound 4 in BALB/c mice using hydroxypropil-β-cyclodextrins formulation showed a 7.5 times increase in oral bioavailability. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Current prospects of synthetic curcumin analogs and chalcone derivatives against mycobacterium tuberculosis.

    PubMed

    Bukhari, Syed Nasir Abbas; Franzblau, Scott G; Jantan, Ibrahim; Jasamai, Malina

    2013-11-01

    Tuberculosis, caused by Mycobacterium tuberculosis, is amongst the foremost infectious diseases. Treatment of tuberculosis is a complex process due to various factors including a patient's inability to persevere with a combined treatment regimen, the difficulty in eradicating the infection in immune-suppressed patients, and multidrug resistance (MDR). Extensive research circumscribing molecules to counteract this disease has led to the identification of many inhibitory small molecules. Among these are chalcone derivatives along with curcumin analogs. In this review article, we summarize the reported literature regarding anti tubercular activity of chalcone derivatives and synthetic curcumin analogs. Our goal is to provide an analysis of research to date in order to facilitate the synthesis of superior antitubercular chalcone derivatives and curcumin analogs.

  20. Diels-Alder cycloaddition in the synthesis of 1-azafagomine, analogs, and derivatives as glycosidase inhibitors.

    PubMed

    Salgueiro, Daniela A L; Sousa, Cristina E A; Fortes, A Gil; Alves, M José

    2012-12-01

    This comprehensive review deals with the synthesis of 1-azafagomine, analogs, and derivatives having the Diels-Alder cycloaddition as the key step. Most of the compounds referred are racemic or have been resolved by lipase transesterification. There are two asymmetric cycloadditions leading to 1-azafagomine or to an analog. In one case both enantiomers of 1-azafagomine were prepared together with a pair of derivatives. The study comprises glycosidase inhibition studies of the target compounds to a set of glycosidic enzymes, and evidenced molecular features that enhance or diminish their activity as glycosidase inhibitors.

  1. Dramatic 13C-depletion in the plant methoxyl pool and its global biogeochemical implications

    NASA Astrophysics Data System (ADS)

    Keppler, F.; Kalin, R. M.; Harper, D. B.; McRoberts, C. W.; Hamilton, J. T.

    2004-12-01

    Stable isotope analysis has become a powerful tool for environmental scientists, plant biologists, ecologists and geochemists studying global elemental cycles or past climatic conditions. Thus most plant species have been photosynthetically characterised as Calvin cycle (C3), Slack-Hatch cycle (C4) and Crassulacean acid metabolism (CAM) categories using carbon isotope signatures. Moreover variations in the carbon isotope composition (d13C) of compounds, produced and destroyed in the global carbon cycle, are often used to investigate biogeochemical cycles and global source-sink relationships, as well as the underlying mechanisms. Stable isotope techniques are increasingly applied to the study of atmospheric budgets of volatile organic compounds (VOCs). We report evidence that methoxyl groups in terrestrial plants (in esters and aromatic ethers) have a unique carbon isotope signature exceptionally depleted in 13C. Plant-derived C1 volatile organic compounds (VOCs) are also highly depleted in 13C compared with Cn+1 VOCs. Our observations suggest that the plant methoxyl pool is the predominant source of C1 compounds of plant origin in the biosphere such as methanol, chloromethane, bromomethane, iodomethane, and cyanomethane. Moreover this pool, which comprises approximately 2.5% of carbon in plant biomass and represents an important substrate for methanogenesis, is likely to be a significant source of highly depleted methane entering the atmosphere. The distinct 13C depletion of methoxyl groups in plants which is reflected in isotope signatures of C1 VOCs may provide a helpful tool in constraining complex environmental processes. These isotope anomalies have a tremendous potential to improve our understanding of the global cycles of atmospheric trace gases and the biochemical pathways involved. Furthermore methoxyl groups could act as markers for biological activity in organic matter of terrestrial and extraterrestrial origin.

  2. Recent advances in gossypol derivatives and analogs: a chemistry and biology view.

    PubMed

    Lu, Yuzhi; Li, Jun; Dong, Chun-E; Huang, Jian; Zhou, Hai-Bing; Wang, Wei

    2017-07-01

    Gossypol as a natural occurring polyphenol has been studied in a wide range of therapeutic contexts for a long time. The chemical modifications on gossypol were limited due to the unique chemical properties of polyphenols. The design and synthesis of gossypol derivatives and the exploration of their biological activities are the interest of the synthetic chemists, medicinal chemists and pharmacologists. Thus, the progress of diverse gossypol derivatives and analogs' synthesis, biological activities, mechanism elucidation and drug discovery based on gossypol scaffold is summarized.

  3. δ²H, δ¹³C and δ¹⁸O from whole wood, α-cellulose and lignin methoxyl groups in Pinus sylvestris: a multi-parameter approach.

    PubMed

    Mischel, Maria; Esper, Jan; Keppler, Frank; Greule, Markus; Werner, Willy

    2015-01-01

    Novel tree ring parameters - δ(13)C and δ(2)H from methoxyl groups - have been developed to reconstruct palaeoclimate. Tests with δ(13)C and δ(18)O derived from whole wood and cellulose samples, however, indicated differences in the isotopic composition and climate signal, depending on the extracted wood component. We assess this signal dependency by analysing (i) δ(13)C and δ(18)O from whole wood and cellulose and (ii) δ(13)C and δ(2)H from methoxyl groups, using Pinus sylvestris L. growing near Altenkirchen (Germany). Results indicate significant correlations among the time series derived from whole wood, cellulose, and lignin methoxyl groups. Compared with the whole wood samples, δ(13)C from methoxyl groups showed a different and overall lower response to climate parameters. On the other hand, δ(2)H from methoxyl groups showed high correlations with temperature and was also correlated with ring width, indicating its potential as a temperature proxy. Isotope time series with the highest correlation with climatic parameter were: (i) whole wood and cellulose δ(13)C with growing season precipitation and summer temperature; (ii) methoxyl groups with spring precipitation; (iii) whole wood and cellulose δ(18)O correlates with annual evapotranspiration and water balance; and (iv) methoxyl group δ(2)H with spring temperatures. These findings reveal that multiple climate elements can be reconstructed from different wood components and that whole wood proxies perform comparably to cellulose time series.

  4. Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol and their biological evaluation.

    PubMed

    Ohyoshi, Takayuki; Tamura, Yuki; Hayakawa, Ichiro; Hirai, Go; Miyazawa, Yamato; Funakubo, Shota; Sodeoka, Mikiko; Kigoshi, Hideo

    2016-12-28

    We have established an efficient synthetic methodology for the 13-oxyingenol natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring-closing olefin metathesis reaction for the "direct" construction of a highly strained inside-outside framework and a Mislow-Evans-type [2,3]-sigmatropic rearrangement for the stereoselective introduction of the hydroxy group at C5. We also synthesized artificial analogs of 13-oxyingenol and ingenol by using our synthetic strategy. In vitro activation assays of protein kinase C (PKC) α and δ revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had a significant role in PKCδ activation. The PKCα- or PKCδ-activating 13-oxyingenol and ingenol analogs induced both distinct morphological changes and increases of CD11b expression in HL-60 cells, which would be typical signs of HL-60 cell differentiation to macrophage-like cells, as expected by previous reports. Intriguingly, however, similar differentiation phenotypes were observed with the use of 13-oxyingenol natural derivatives and 13-oxyingenol-13-dodecanoate showing a remarkably less potent PKCα or PKCδ activation ability, which the PKC inhibitor Gö6983 diminished. This indicated the involvement of other PKC isozymes or related kinase activities. 13-Oxyingenol analogs, which induced HL-60 cell differentiation, also induced HL-60 cell death, similar to the action of a phorbol ester, a strong PKC activator.

  5. Biomonitoring of human exposures to chlorinated derivatives and structural analogs of bisphenol A.

    PubMed

    Andra, Syam S; Charisiadis, Pantelis; Arora, Manish; van Vliet-Ostaptchouk, Jana V; Makris, Konstantinos C

    2015-12-01

    The high reactivity of bisphenol A (BPA) with disinfectant chlorine is evident in the instantaneous formation of chlorinated BPA derivatives (ClxBPA) in various environmental media that show increased estrogen-activity when compared with that of BPA. The documented health risks associated with BPA exposures have led to the gradual market entry of BPA structural analogs, such as bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), etc. A suite of exposure sources to ClxBPA and BPA analogs in the domestic environment is anticipated to drive the nature and range of halogenated BPA derivatives that can form when residual BPA comes in contact with disinfectant in tap water and/or consumer products. The primary objective of this review was to survey all available studies reporting biomonitoring protocols of ClxBPA and structural BPA analogs (BPS, BPF, BPB, etc.) in human matrices. Focus was paid on describing the analytical methodologies practiced for the analysis of ClxBPA and BPA analogs using hyphenated chromatography and mass spectrometry techniques, because current methodologies for human matrices are complex. During the last decade, an increasing number of ecotoxicological, cell-culture and animal-based and human studies dealing with ClxBPA exposure sources and routes of exposure, metabolism and toxicity have been published. Up to date findings indicated the association of ClxBPA with metabolic conditions, such as obesity, lipid accumulation, and type 2 diabetes mellitus, particularly in in-vitro and in-vivo studies. We critically discuss the limitations, research needs and future opportunities linked with the inclusion of ClxBPA and BPA analogs into exposure assessment protocols of relevant epidemiological studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Nonlinear analysis and analog simulation of a piezoelectric buckled beam with fractional derivative

    NASA Astrophysics Data System (ADS)

    Mokem Fokou, I. S.; Buckjohn, C. Nono Dueyou; Siewe Siewe, M.; Tchawoua, C.

    2017-08-01

    In this article, an analog circuit for implementing fractional-order derivative and a harmonic balance method for a vibration energy harvesting system under pure sinusoidal vibration source is proposed in order to predict the system response. The objective of this paper is to discuss the performance of the system with fractional derivative and nonlinear damping (μb). Bifurcation diagram, phase portrait and power spectral density (PSD) are provided to deeply characterize the dynamics of the system. These results are corroborated by the 0-1 test. The appearance of the chaotic vibrations reduces the instantaneous voltage. The pre-experimental investigation is carried out through appropriate software electronic circuit (Multisim). The corresponding electronic circuit is designed, exhibiting periodic and chaotic behavior, in accord with numerical simulations. The impact of fractional derivative and nonlinear damping is presented with detail on the output voltage and power of the system. The agreement between numerical and analytical results justifies the efficiency of the analytical technique used. In addition, by combining the harmonic excitation with the random force, the stochastic resonance phenomenon occurs and improves the harvested energy. It emerges from these results that the order of fractional derivative μ and nonlinear damping μb play an important role in the response of the system.

  7. Effects of Hydrostatic Loading on a Self-Aggregating, Suspension Culture–Derived Cartilage Tissue Analog

    PubMed Central

    Kraft, Jeffrey J.; Jeong, Changhoon; Novotny, John E.; Seacrist, Thomas; Chan, Gilbert; Domzalski, Marcin; Turka, Christina M.; Richardson, Dean W.; Dodge, George R.

    2011-01-01

    Objective: Many approaches are being taken to generate cartilage replacement materials. The goal of this study was to use a self-aggregating suspension culture model of chondrocytes with mechanical preconditioning. Design: Our model differs from others in that it is based on a scaffold-less, self-aggregating culture model that produces a cartilage tissue analog that has been shown to share many similarities with the natural cartilage phenotype. Owing to the known loaded environment under which chondrocytes function in vivo, we hypothesized that applying force to the suspension culture–derived chondrocyte biomass would improve its cartilage-like characteristics and provide a new model for engineering cartilage tissue analogs. Results: In this study, we used a specialized hydrostatic pressure bioreactor system to apply mechanical forces during the growth phase to improve biochemical and biophysical properties of the biomaterial formed. We demonstrated that using this high-density suspension culture, a biomaterial more consistent with the hyaline cartilage phenotype was produced without any foreign material added. Unpassaged chondrocytes responded to a physiologically relevant hydrostatic load by significantly increasing gene expression of critical cartilage molecule collagen and aggrecan along with other cartilage relevant genes, CD44, perlecan, decorin, COMP, and iNOS. Conclusions: This study describes a self-aggregating bioreactor model without foreign material or scaffold in which chondrocytes form a cartilage tissue analog with many features similar to native cartilage. This study represents a promising scaffold-less, methodological advancement in cartilage tissue engineering with potential translational applications to cartilage repair. PMID:26069584

  8. High performance liquid chromatography enantioseparation of the novel designed mexiletine derivatives and its analogs.

    PubMed

    Zheng, Chengzhen; Zhang, Datong; Wu, Qi; Lin, Xianfu

    2011-02-01

    A series of novel designed mexiletine derivatives and its analogs were prepared, the structures were confirmed by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and Electrospray Ionization-Mass Spectrometry (ESI-MS), and the enantioseparations were performed on polysaccharide-based chiral stationary phase (CSP), Chiralcel OD-H, and Chiralcel OJ-H, under normal-phase mode. The effects of the concentration of isopropanol in the mobile phase were studied, seven of the eight enantiomers got baseline separation on Chiralcel OD-H, and five of the eight enantiomers got successfully separation on Chiralcel OJ-H. The effects of structural features were also discussed. Copyright © 2010 Wiley-Liss, Inc.

  9. Methoxylated polybrominated diphenyl ethers (MeO-PBDE) in human milk from Bizerte, Tunisia.

    PubMed

    Ben Hassine, Sihem; Ben Ameur, Walid; Eljarrat, Ethel; Barceló, Damià; Touil, Soufiane; Driss, Mohamed Ridha

    2015-04-01

    Methoxylated polybrominated diphenyl ethers (MeO-PBDEs) were determined in 36 human milk samples collected in 2010 from healthy mothers living in Bizerte region from Tunisia. Gas chromatography coupled to mass spectrometry working with negative ion chemical ionization (GC-NCI-MS) was used to identify and quantify residue levels on a lipid basis of organo-brominated compounds. Among the 8 examined MeO-PBDE congeners 6-MeO-BDE-47, 2'-MeO-BDE-68, 4'-MeO-BDE-49 and 5'-MeO-BDE-100 were detected in human milk at different levels and frequencies. This is the first study reporting 5'-MeO-BDE-100 and 4'-MeO-BDE-49 levels in human milk samples. Levels of ∑MeO-PBDEs ranged from 0.23 to 4.70ngg(-)(1) lipid weight (lw) in the samples, with a mean and median value of 1.52 and 1.11ngg(-1)lw respectively. Concentrations of ∑MeO-PBDEs in human milk were negatively correlated with age of primapara mothers (p<0.05) and no age-dependency was observed for multipara mothers. Primapara mothers had higher levels of MeO-PBDEs than multipara mothers however no statistical significance was observed. A weak correlation between ∑PBDEs and ∑MeO-PBDEs was found but not between BDE-47 and its methoxylated analog 6-MeO-BDE-47, suggesting differences in exposure pathways for these contaminants in humans and further supporting the hypothesis that MeO-PBDEs were likely not only originated from PBDE precursors. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Effects of valproate derivatives I. Antiepileptic efficacy of amides, structural analogs and esters.

    PubMed

    Redecker, C; Altrup, U; Hoppe, D; Düsing, R; Speckmann, E J

    2000-01-04

    Derivatives of the antiepileptic drug valproate (VPA, 2-propylpentanoic acid) have been synthesized and tested in order to improve the intracellular availability of VPA. The buccal ganglia of Helix pomatia were used as a test nervous system and antiepileptic efficacies were reconfirmed using rat cortex in vivo. Epileptiform activities consisted of typical paroxysmal depolarization shifts (PDS) which appeared in the identified neuron B3 with application of pentylenetetrazol. Epileptiform activities were found to be accelerated, unaffected or blocked. (i) The Amide-derivatives 2-propylpentanamide and N,N-dipropyl-2-propylpentanamide, and short chain ester derivatives 1-O-(2-propylpentanoyl)-2,3-propandiol, 2,2-di(hydroxymethyl)-1-O-(2-propylpentanoyl)-1,3-propanediol and 2,2-di(hydroxymethyl)-1,3-di-O-(2-propylpentanoyl)-1,3-propanediol accelerated epileptiform activities. Membrane potential often shifted to a permanent depolarization which corresponded to the PDS-inactivation level. (ii) The structural analogs 1-cycloheptene-1-carboxylic acid and cyclooctanecarboxylic acid accelerated epileptiform activities only slightly or were without effects. (iii) The small VPA-ester, 2-propylpentanoic acid ethyl ester, decreased the epileptiform activities in a way that is comparable to the effects of VPA well known from previous studies. It thus could be thought as a VPA-pro-drug. (iv) The mannitol-esters 1-O-(2-propylpentanoyl)-D-mannitol and 3,4;5,6-Di-O-isopropylidene-1-O-(2-propylpentanoyl)-D-mannitol blocked the PDS in a way which is different from the known effects of VPA. These substances are interpreted not to exert their effects after being metabolized to VPA and thus they are thought to be new antiepileptic substances.

  11. Characterization of the global structure of low methoxyl pectin in solution

    USDA-ARS?s Scientific Manuscript database

    Low methoxyl citrus pectin (LMP) and amidated low methoxyl pectin (LMAP) were characterized by high performance size exclusion chromatography (HPSEC) with online light scattering (LS), intrinsic viscosity ('w), differential refractive index (dRI) and ultra violet detection (UV), by amino acid anal...

  12. The antibody-enzyme analogy. Characterization of antibodies to phosphopyridoxyltyrosine derivatives.

    PubMed

    Raso, V; Stollar, B D

    1975-02-11

    Stable analogs of the crucial Schiff base intermediate of enzymatic and nonenzymatic pyridoxal phosphate catalysis have been used as haptens for induction of specific antibodies. N-(5-phosphopyridoxyl)-3'-amino-L-tyrosine and its conformationally distinct cyclized derivative resemble the Schiff base formed upon mixing tyrosine with pyridoxal phosphate. These compounds were covalently coupled to a protein carrier via the 3'-amino group so as to confer a prescribed orientation, with the coenzyme region farthest removed from the carrier. A third antigen, with the phosphopyridoxyl group alone as the hapten, was prepared by linkage of pyridoxal phosphate directly to free amino groups on the carrier protein. Antibodies elicited for each determinant were purified by means of appropriate affinity columns. Antibody heterogeneity was observed in that different species could be separated from a given serum by sequential elution from the affinity columns with 1 M sodium phosphate buffers of pH 7.6, 5.2, 2.6 and 1.5. In assays of quantitative precipitation, inhibition of precipitation, equilibrium dialysis, and fluorescence quenching, antibodies to the phosphopyridoxyltyrosine haptens showed specificity for the phosphorylated form of the coenzyme and binding activity for both the coenzyme and tyrosine portions of the hapten. Antibodies to the phosphopyridoxyl groups alone did not display a similar reactivity toward the tyrosine portion of the complex haptens. The cyclic and noncyclic conformations of the hapten were serologically distinct, as antibody to each reacted preferentially with the homologous form.

  13. Synthesis of radioiodinated 1-deoxy-nojirimycin derivatives: novel glucose analogs.

    PubMed

    Xu, Y; Choi, S R; Kung, M P; Kung, H F

    1999-10-01

    Novel lipophilic and neutral glucose analogs, which are potentially useful for tumor imaging, have been developed. They are designed to circumvent Glut-facilitated transport mechanism, and direct the localization by either hexokinase binding or enzyme reactions (phosphorylation) as potential metabolic markers of tumor cells. Syntheses of tetraacetylated N-(3'-iodo-2'-propenyl)-1-deoxy-nojirimycin (11) and N-(3'-iodo-benzyl)-1-deoxy-nojirimycin (14) were achieved by reacting 1-deoxy-nojirimycin with appropriate alkylating agents. The corresponding tri-butyltin derivatives were also prepared as the starting materials for preparation of I-125-labeled compounds for biodistribution study in rats. Biodistribution in rats showed that [123I]14 exhibited a modest initial brain uptake and retention at a later time (0.59, 0.38, 0.30, and 0.30% dose/organ at 2, 30, 60, and 120 min after an intravenous [i.v.] injection, respectively), whereas [125I]11 displayed a lower brain uptake (0.35, 0.27, 0.20, and 0.18% dose/organ at 2, 30, 60, and 120 min). In addition, compounds with free hydroxyl groups (12 and 13) were also obtained. As expected, after an i.v. injection, these free hydroxyl compounds showed a dramatic decrease in brain uptake in rats. It appears that both of the acetylated agents (11 and 14), which display higher lipophilicity (partition coefficient [P.C.] = 57.9 and 1,462, respectively), can penetrate the blood-brain barrier (BBB) by a simple diffusion mechanism whereas the free hydroxy compounds (12 and 13), with lower lipophilicity (P.C. = 0.43 and 6.8), showed no brain uptake. A similar pair of glucose derivatives, fluorodeoxyglucose (FDG) and tetraacetylated FDG (AFDG), displayed a dramatic difference in brain uptake in rats. While the lipophilic AFDG (P.C. = 3.79) may penetrate the intact BBB, due to its relatively low P.C. value, the first pass extraction due to simple diffusion mechanism may be low (brain uptake at 2 min was 0.68% dose/organ). The FDG itself

  14. New Fluorescent Macrolide Derivatives for Studying Interactions of Antibiotics and Their Analogs with the Ribosomal Exit Tunnel.

    PubMed

    Tereshchenkov, A G; Shishkina, A V; Karpenko, V V; Chertkov, V A; Konevega, A L; Kasatsky, P S; Bogdanov, A A; Sumbatyan, N V

    2016-10-01

    Novel fluorescent derivatives of macrolide antibiotics related to tylosin bearing rhodamine, fluorescein, Alexa Fluor 488, BODIPY FL, and nitrobenzoxadiazole (NBD) residues were synthesized. The formation of complexes of these compounds with 70S E. coli ribosomes was studied by measuring the fluorescence polarization depending on the ribosome amount at constant concentration of the fluorescent substance. With the synthesized fluorescent tylosin derivatives, the dissociation constants for ribosome complexes with several known antibiotics and macrolide analogs previously obtained were determined. It was found that the fluorescent tylosin derivatives containing BODIPY FL and NBD groups could be used to screen the binding of novel antibiotics to bacterial ribosomes in the macrolide-binding site.

  15. Interactions of soy protein fractions with high-methoxyl pectin.

    PubMed

    Lam, Monica; Paulsen, Paul; Corredig, Milena

    2008-06-25

    A protein-binding technique was employed to visualize, using scanning electron microscopy, the soy protein as well as the association between HMP and soy protein fractions. Image analysis indicated that at pH 7.5 and 3.5 soy protein isolate showed a bimodal distribution of sizes with an average [ d(0.5)] of about 0.05 microm, but at pH 3.8 the proteins formed larger aggregates than at high pH. Addition of HMP at pH 3.8 changed the surface charge of the particles from +20 to -15 mV. A small addition of HMP caused bridging of the pectin between soy protein aggregates and destabilization. With sufficient HMP, the suspensions showed improved stability to precipitation. The microscopy images are the first direct evidence of the interactions between soy proteins with high-methoxyl pectin (HMP).

  16. Lignin methoxyl hydrogen isotope ratios in a coastal ecosystem

    NASA Astrophysics Data System (ADS)

    Feakins, Sarah J.; Ellsworth, Patricia V.; Sternberg, Leonel da Silveira Lobo

    2013-11-01

    Stable hydrogen isotope ratios of plant lignin methoxyl groups have recently been shown to record the hydrogen isotopic composition of meteoric water. Here we extend this technique towards tracing water source variations across a saltwater to freshwater gradient in a coastal, subtropical forest ecosystem. We measure the hydrogen isotopic composition of xylem water (δDxw) and methoxyl hydrogen (δDmethoxyl) to calculate fractionations for coastal mangrove, buttonwood and hammock tree species in Sugarloaf Key, as well as buttonwoods from Miami, both in Florida, USA. Prior studies of the isotopic composition of cellulose and plant leaf waxes in coastal ecosystems have yielded only a weak correlation to source waters, attributed to leaf water effects. Here we find δDmethoxyl values range from -230‰ to -130‰, across a 40‰ range in δDxw with a regression equation of δDmethoxyl ‰ = 1.8 * δDxw - 178‰ (R2 = 0.48, p < 0.0001, n = 74). This is comparable within error to the earlier published relationship for terrestrial trees which was defined across a much larger 125‰ isotopic range in precipitation. Analytical precision for measurements of δD values of pure CH3I by gas chromatography-pyrolysis-isotope ratio mass spectrometry (GC-P-IRMS) is σ = 6‰ (n = 31), which is considerably better than for CH3I liberated through cleavage with HI from lignin with σ = 18‰ (n = 26). Our results establish that δDmethoxyl can record water sources and salinity incursion in coastal ecosystems, where variations sufficiently exceed method uncertainties (i.e., applications with δD excursions >50‰). For the first time, we also report yields of propyl iodide, which may indicate lignin synthesis of propoxyl groups under salt-stress.

  17. Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs implicated by a viral entry blocking mechanism.

    PubMed

    Yang, Jian; Chen, Gang; Li, Long Long; Pan, Wei; Zhang, Fang; Yang, Jingxiang; Wu, Shuwen; Tien, Po

    2013-05-01

    A series of chiral gossypol derivatives and its analogs were synthesized and tested in vitro for their anti-H5N1 activity. Interestingly, (+)-gossypol derivatives and its analogs were more active against H5N1 than the corresponding (-)-gossypol derivatives and its analogs. Through a simple chemical modification with amino acids, less active chiral gossypol could be converted into more active derivatives, and most of chiral gossypol derivatives were more potent against H5N1 than 1-adamantylamine. With regard to the mechanism of action, chiral gossypol derivatives and its analogs might impair the virus entry step of cell infection, likely targeting to HA2 protein. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Characterization of acylated flavonoid-O-glycosides and methoxylated flavonoids from Tagetes maxima by liquid chromatography coupled to electrospray ionization tandem mass spectrometry.

    PubMed

    Parejo, Irene; Jáuregui, Olga; Viladomat, Francesc; Bastida, Jaume; Codina, Carles

    2004-01-01

    Liquid chromatography coupled to negative electrospray ionization (ESI) tandem mass spectrometry (MS/MS) employing a triple quadrupole mass spectrometer was used in the structural determination of acylated flavonoid-O-glycosides and methoxylated flavonoids occurring in Tagetes maxima. The compounds were identified by experiments in full scan mode (MS), and tandem mass experiments (MS/MS) of precursor ion scan, product ion scan, and neutral loss scan modes. In order to characterize the aglycones of the flavonoid glycosides, in-source fragmentation of the deprotonated molecule [M-H]- followed by product ion scan of the resulting aglycone [A-H]- were performed. This combined approach allowed the identification of 51 phenolic compounds, including flavonoid-O-glycosides acylated with galloyl, protocatechuoyl, coumaroyl or caffeoyl groups, methoxylated flavonoids, and hydroxycinnamic acid and phenolic acid derivatives, none of them previously reported in Tagetes maxima.

  19. Matching Derived Functionally-Same Stimulus Relations: Equivalence-Equivalence and Classical Analogies

    ERIC Educational Resources Information Center

    Carpentier, Franck; Smeets, Paul M.; Barnes-Holmes, Dermot; Stewart, Ian

    2004-01-01

    Previous studies have shown that, after being trained on A-B and A-C matching tasks, subjects match not only functionally-same B and C stimuli (stimulus equivalence), but also BC compounds with same-class elements and BC compounds with different-class elements (equivalence-equivalence). Similar performances are required in classical analogies (a :…

  20. Matching Derived Functionally-Same Stimulus Relations: Equivalence-Equivalence and Classical Analogies

    ERIC Educational Resources Information Center

    Carpentier, Franck; Smeets, Paul M.; Barnes-Holmes, Dermot; Stewart, Ian

    2004-01-01

    Previous studies have shown that, after being trained on A-B and A-C matching tasks, subjects match not only functionally-same B and C stimuli (stimulus equivalence), but also BC compounds with same-class elements and BC compounds with different-class elements (equivalence-equivalence). Similar performances are required in classical analogies (a :…

  1. Effects of solute methoxylation on glass-forming ability and stability of vitrification solutions

    PubMed

    Wowk; Darwin; Harris; Russell; Rasch

    1999-11-01

    The effects of replacing hydroxyl groups with methoxyl (OCH(3)) groups in the polyols ethylene glycol (EG), propylene glycol (PG), glycerol, and threitol were studied by differential scanning calorimetry (DSC) during cooling of aqueous solutions to -150 degrees C and subsequent rewarming. For 35% (w/w) PG, 40% EG, and 45% glycerol, a single substitution of a terminal hydroxyl group with a methoxyl group reduced the critical cooling rate necessary to avoid ice on cooling (vitrify) from approximately 500 to 50 degrees C/min. This reduction was approximately equivalent to increasing the parent polyol concentration by 5% (w/w). The critical warming rate calculated to avoid formation of ice on rewarming (devitrification) was also reduced by methoxyl substitution, typically by a factor of 10(4) for dilute solutions. Double methoxylation (replacement of both terminal hydroxyls) tended to result in hydrate formation, making these compounds less interesting. An exception was threitol, for which substituting both terminal hydroxyls by methoxyls reduced the critical rewarming rate of a 50% solution by a factor of 10(7) without any hydrate formation. These glass-forming and stability properties of methoxylated compounds, combined with their low viscosity, enhanced permeability, and high glass transition temperatures, make them interesting candidate cryoprotective agents for cryopreservation by vitrification or freezing. Copyright 1999 Academic Press.

  2. Cystocyte and lymphocyte derived fusomes/spectrosomes: analogies and differences: a mini-review.

    PubMed

    Dubielecka, Patrycja M; Stebelska, Katarzyna; Jaźwiec, Bozena; Sikorski, Aleksander F

    2003-01-01

    Structures analogous to Drosophila spectrosomes were found in mammalian lymphocytes. Repasky and colleagues discovered an intracellular spectrin-rich structure in lymphoid cells, which had far-reaching parallels with the fusome/spectrosome of D. melanogaster germ cells. This fact implies that spectrosomes may be characteristic not only of insect germ cells, but also that an analogous structure may play an important role in other cell types. The term "spectrosome" was first used by Lin and Spradling in 1995 to describe a large sphere of fusomal material in D. melanogaster germline stem cells and their differentiated daughter cells - cytoblasts. In the D. melanogaster ovary, membrane skeletal proteins such as ankyrin, alpha/beta spectrin as well as adducin-like Hts protein(s) were found in this specific organelle - spectrosome/fusome. These orgalelles are involved in the creation of mitotic spindles and D. melanogaster cyst formation and oocyte differentiation, but the role of analogous spectrin-based aggregates found in nucleated cells still remains unclear.

  3. Obligate sulfide-dependent degradation of methoxylated aromatic compounds and formation of methanethiol and dimethyl sulfide by a freshwater sediment isolate, Parasporobacterium paucivorans gen. nov., sp. nov.

    PubMed

    Lomans, B P; Leijdekkers, P; Wesselink, J J; Bakkes, P; Pol, A; van der Drift, C; den Camp, H J

    2001-09-01

    Methanethiol (MT) and dimethyl sulfide (DMS) have been shown to be the dominant volatile organic sulfur compounds in freshwater sediments. Previous research demonstrated that in these habitats MT and DMS are derived mainly from the methylation of sulfide. In order to identify the microorganisms that are responsible for this type of MT and DMS formation, several sulfide-rich freshwater sediments were amended with two potential methyl group-donating compounds, syringate and 3,4,5-trimethoxybenzoate (0.5 mM). The addition of these methoxylated aromatic compounds resulted in excess accumulation of MT and DMS in all sediment slurries even though methanogenic consumption of MT and DMS occurred. From one of the sediment slurries tested, a novel anaerobic bacterium was isolated with syringate as the sole carbon source. The strain, designated Parasporobacterium paucivorans, produced MT and DMS from the methoxy groups of syringate. The hydroxylated aromatic residue (gallate) was converted to acetate and butyrate. Like Sporobacterium olearium, another methoxylated aromatic compound-degrading bacterium, the isolate is a member of the XIVa cluster of the low-GC-content Clostridiales group. However, the new isolate differs from all other known methoxylated aromatic compound-degrading bacteria because it was able to degrade syringate in significant amounts only in the presence of sulfide.

  4. FeCl3-promoted and ultrasound-assisted synthesis of resveratrol O-derived glycoside analogs.

    PubMed

    Marzag, Hamid; Robert, Guillaume; Dufies, Maeva; Bougrin, Khalid; Auberger, Patrick; Benhida, Rachid

    2015-01-01

    Phenol derived O-glycosides were synthesized using a direct and convenient O-glycosidation, starting from acetylated sugars in the presence of FeCl3, an inexpensive, mild and benign Lewis acid catalyst. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with conventional conditions leading to the corresponding β-O-glycosides as the major anomer. Post-synthetic transformations of iodophenol intermediates led to new resveratrol O-glycoside analogs in good overall yields. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Bioavailabilty of beta-amino acid and C-terminally derived PK/PBAN analogs

    USDA-ARS?s Scientific Manuscript database

    The ability of linear beta amino-acid-substituted peptides (PK-betaA-1: Ac-YFT[beta3-P]RLa; PK-betaA-2: Ac-Y[beta2-homoF]TPRLa; PK-betaA-3: Ac-Y[beta3-F]TPRLa and PK-betaA-4: Ac-[beta3-F]FT[beta3-P]RLa) and unsubstituted analogs (Ac-YFTPRLa and YFTPRLa) of the pyrokinin(PK)/pheromone biosynthesis-ac...

  6. Computational protein design to reengineer stromal cell-derived factor-1α generates an effective and translatable angiogenic polypeptide analog.

    PubMed

    Hiesinger, William; Perez-Aguilar, Jose Manuel; Atluri, Pavan; Marotta, Nicole A; Frederick, John R; Fitzpatrick, J Raymond; McCormick, Ryan C; Muenzer, Jeffrey R; Yang, Elaine C; Levit, Rebecca D; Yuan, Li-Jun; Macarthur, John W; Saven, Jeffery G; Woo, Y Joseph

    2011-09-13

    Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.

  7. Glucosamine and Glucosamine-6-phosphate Derivatives: Catalytic Cofactor Analogs for the glmS Ribozyme

    PubMed Central

    Posakony, Jeffrey J.; Ferré-D'Amaré, Adrian R.

    2013-01-01

    Two analogues of glucosamine-6-phosphate (GlcN6P, 1) and five of glucosamine (GlcN, 2) were prepared for evaluation as catalytic cofactor of the glmS ribozyme, a bacterial gene-regulatory RNA that controls cell wall biosynthesis. Glucosamine and allosamine with 3-azido substitutions were prepared by SN2 reactions of the respective 1,2,4,6-protected sugars; final acidic hydrolysis afforded the fully deprotected compounds as their TFA salts. A 6-phospho-2-aminoglucolactam (31) was prepared from glucosamine in a 13-step synthesis, which included a late-stage POCl3-phosphorylation. A simple and widely applicable 2-step procedure with the triethylsilyl (TES) protecting group was developed to selectively expose the 6-OH group in N-protected glucosamine analogs, which provided another route to chemical phosphorylation. Mitsunobu chemistry afforded 6-cyano (35) and 6-azido (36) analogues of GlcN-(Cbz) and the selectivity for the 6-position was confirmed by NMR (COSY, HMBC, HMQC) experiments. Compound 36 was converted to the fully deprotected 6-azido-GlcN (37) and 2,6-diaminoglucose (38) analogs. A 2-hydroxylamino glucose (42) analogue was prepared via an oxaziridine (41). Enzymatic phosphorylation of 42 and chemical phosphorylation of its 6-OH precursor (43) were possible, but 42 and the 6-phospho product (44) were unstable under neutral or basic conditions. Chemical phosphorylation of the previously described 2-guanidinyl-glucose (46) afforded its 6-phospho analogue (49) after final deprotection. PMID:23578404

  8. Tracing the geographical origin of early potato tubers using stable hydrogen isotope ratios of methoxyl groups.

    PubMed

    Keppler, Frank; Hamilton, John T G

    2008-12-01

    The application of stable isotope ratio measurements has become an extremely useful tool for tracing the provenance of food products, thus ensuring that consumers receive products which comply with their labelled specifications. Recently, it has been shown that relative stable hydrogen isotope abundances (delta(2)H values) of wood lignin methoxyl groups have a distinct range that reflects the delta(2)H values of their meteoric source water. Furthermore, it has been suggested that the isotope information stored in methoxyl groups in plant matter generally might assist with determining the place of origin of plant material. We now have measured delta(2)H values of methoxyl groups from natural compounds in tubers of early potatoes (Solanum tuberosum) grown in different geographical locations. Tubers of early potatoes were collected from across Europe and regions close to the Mediterranean Sea between April and July 2004. The methoxyl groups from the potatoes were found to be highly depleted in (2)H, relative to both their meteoric water and bulk biomass, and a systematic shift of the delta(2)H values between methoxyl groups and meteoric water was observed. A constant fractionation of-161+/-11 per thousand. between methoxyl groups and modelled meteoric water is shown over a transaction covering the delta(2)H values of meteoric water from-95 per thousand in Northern Sweden to+25 per thousand in Egypt. From this information, early potato tubers from Middle Europe can be clearly distinguished from those of Mediterranean regions and from Northern Europe. Thus, we suggest that delta(2)H values of methoxyl groups have the potential to become an effective tool in assisting with the constraint of the geographical origin of potato tubers and other food stuffs.

  9. Phospholipid derivatives of nucleoside analogs as prodrugs with enhanced catabolic stability

    SciTech Connect

    Matsushita, T.; Ryu, E.K.; Hong, C.I.; MacCoss, M.

    1981-07-01

    The nucleoside 5'-diphosphate-L-1,2-dipalmitin derivatives of 1-..beta..-D-arabinofuranosylcytosine (ara-D), 9-..beta..-D-arabinofuranosyladenine (ara-A), and tubercidin have been synthesized, and their cytotoxicity has been evaluated against a mouse myeloma cell line (MPC-11) in vitro and against L1210 lymphoid leukemia both in vitro and in vivo. Sonication methods were utilized to solubilize these lipophilic derivatives in aqueous solution in order to facilitate such biological evaluation; the ara-A derivative resisted solubilization by several techniques. (JMT)

  10. Covalent binding to DNA in vitro of 2',3'-oxides derived from allylbenzene analogs.

    PubMed

    Luo, G; Guenthner, T M

    1996-09-01

    Epoxidation at the allylic side chain is a major metabolic pathway for allylbenzene and its naturally occurring analogs safrole, estragole, and eugenol. We demonstrate herein that the epoxide metabolites of allylbenzene, estragole, and safrole can form covalent adducts with DNA in vitro, binding primarily to guanine, but also to the other three DNA bases. Epoxide hydrolases can prevent the binding of allylbenzene 2',3'-oxide to DNA in vitro. Four distinct adducts were detected by analytical TLC after the reaction of 2'-deoxyguanosine with allylbenzene 2',3'-oxide. One unstable adduct was formed rapidly, but gradually disappeared, whereas the other three adducts were formed more slowly but persisted. The major persistent adduct, which was isolated by preparative chromatography, was examined by MS and NMR. The structure of this adduct is 3'-N1-deoxyguanosyl-(2'-hydroxypropylbenzene). In addition, a generally applicable paradigm for the identification of deoxyguanosine or guanosine adducts by 13C and 1H NMR spectroscopy is presented.

  11. Enhancing Physicochemical Properties through Synthesis and Formulation of Piclamilast- and Lapatinib-Derived Analogs

    NASA Astrophysics Data System (ADS)

    Woodring, Jennifer L.

    Human African trypanosomiasis (HAT) is a neglected tropical disease of significant morbidity and mortality in sub-Saharan Africa. Current chemotherapeutics targeting the causative agent Trypanosoma brucei lack oral bioavailability, efficacy, and safety. New small molecule drugs are desperately needed for HAT. Target repurposing represents one method for rapidly discovering new anti-trypanosomal compounds. This concept has been applied to repurposing small molecule inhibitors of human phosphodiesterases (PDEs) and protein tyrosine kinases (PTKs) for HAT, while improving physicochemical properties. The first project in this dissertation begins with the human PDE4 inhibitor piclamilast, which has an IC50 value of 4.7 microM against T. brucei PDEB1. Based upon this scaffold, new analogs were designed, synthesized, and screened for their biological activity against TbrPDEB1. Secondly, previous optimization of the human tyrosine kinase inhibitor lapatinib led to the discovery of the 4-anilino-quinazoline NEU-617, a potent (EC 50 = 42 nM) antitrypanosomal agent. Since alkynyl thienopyrimidines are well-known scaffolds for tyrosine kinase inhibitors, we assessed this scaffold as an alternative to the quinazoline of NEU-617. In addition, analogs of the NEU-617 were designed and synthesized to improve their physicochemical properties, such as lipophilicity and predicted central nervous system penetration. Lastly, nanoformulations have been shown to improve the oral bioavailability and circulation half-life of their encapsulated drug components. Because of this, nanoemulsions, liposomes, and polymeric nanoparticles were explored for their potential parasitic inhibitory effects and their ability to improve the physicochemical properties of NEU-617.

  12. Pyrrolopyrimidine derivatives and purine analogs as novel activators of Multidrug Resistance-associated Protein 1 (MRP1, ABCC1).

    PubMed

    Schmitt, Sven Marcel; Stefan, Katja; Wiese, Michael

    2017-01-01

    Multidrug resistance (MDR) is the main cause of diminished success in cancer chemotherapy. ABC transport proteins are considered to be one important factor of MDR. Besides P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2), Multidrug Resistance-associated Protein 1 (MRP1, ABCC1) is associated with non-response to chemotherapy in different cancers. While considerable effort was spent in overcoming MDR during the last two decades, almost nothing is known with respect to activators of transport proteins. In this work we present certain pyrrolo[3,2-d]pyrimidine derivatives with variations at positions 4 and 5 and purine analogs with variations at position 6 as novel activators of MRP1-mediated transport of the MRP1 substrate calcein AM and the anticancer drug daunorubicin in low nanomolar concentration range. Two different MRP1 overexpressing cell lines were used, the doxorubicin-selected human lung cancer cell line H69 AR and the transfected Madin-Darby Canine Kidney cell line MDCK II MRP1. No effect was observed in the sensitive counterparts H69 and MDCK II wild type (wt). Derivatives with higher molecular weight possessed also inhibitory properties at low micromolar concentrations, although most compounds were rather poor MRP1 inhibitors. Purine analogs derived from potent MRP1 inhibitors of the pyrrolopyrimidine class showed equal activating, but no inhibiting effects at all. All tested compounds were non-toxic and had only minor impact on P-gp or BCRP, showing no inhibition or activation. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. NMR studies on turn mimetic analogs derived from melanocyte-stimulating hormones.

    PubMed

    Cho, Min-Kyu; Kim, Sung-Soo; Lee, Myung-Ryul; Shin, Joon; Lee, Jiyong; Lim, Sung-Kil; Baik, Ja-Hyun; Yoon, Chang-Ju; Shin, Injae; Lee, Weontae

    2003-11-30

    Oligomers with alpha-aminooxy acids are reported to form very stable turn and helix structures, and they are supposed to be useful peptidomimetics for drug design. A recent report suggested that homochiral oxa-peptides form a strong eight-member-ring structure by a hydrogen bond between adjacent aminooxy-acid residues in a CDCl3 solution. In order to design an alpha-MSH analog with a stable turn conformation, we synthesized four tetramers and one pentamer, based on alpha-MSH sequence, and determined the solution structures of the molecules by two-dimensional NMR spectroscopy and simulated annealing calculations. The solution conformations of the three peptidomimetic molecules (TLV, TDV, and TLL) in DMSO-d6 contain a stable 7-membered-ring structure that is similar to a gamma-turn in normal peptides. Newly-designed tetramer TDF and pentamer PDF have a ball-type rigid structure that is induced by strong hydrogen bonds between adjacent amide protons and carbonyl oxygens. In conclusion, the aminooxy acids, easily prepared from natural or unnatural amino acids, can be employed to prepare peptidomimetic analogues with well-defined turn structures for pharmaceutical interest.

  14. Methoxyl groups of lignin are essential carbon donors in C1 metabolism of Sphingobium sp. SYK-6.

    PubMed

    Sonoki, Tomonori; Masai, Eiji; Sato, Kanna; Kajita, Shinya; Katayama, Yoshihiro

    2009-09-01

    Sphingobium sp. SYK-6 can utilize lignin biphenyl compounds, such as 2,2'-dihydroxy-3,3'-dimethoxy-5,5'-dicarboxybiphenyl (DDVA). In the metabolism of DDVA, this microorganism exploits two O -demethylation systems with different substrate specificities, namely, a DDVA-specific oxygenative O -demethylation system and a vanillate-specific (VA-specific) tetrahydrofolate-dependent (THF-dependent) methyltransferase system. We examined the way in which these two systems interact in the metabolism of lignin in Sphingobium sp. SYK-6. Our results indicate that THF accepts methyl groups derived not only from the THF-dependent O -demethylation of VA but also from the oxygenative O -demethylation of DDVA. Thus, the methoxyl groups of lignin model compounds are an essential source of carbon in Sphingobium sp. SYK-6. ((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

  15. Caffeic acid derivatives, analogs and applications: a patent review (2009-2013).

    PubMed

    Silva, Tiago; Oliveira, Catarina; Borges, Fernanda

    2014-11-01

    Caffeic acid (CA) is broadly distributed in several species of the plant kingdom and is widely consumed in human diet. CA and derivatives have been extensively studied in the past years, which unveiled a broad spectrum of biological activities and potential therapeutic applications. As a result, there has been an upsurge in the development of new chemical entities based on the CA scaffold. The scope of this review is to revisit the therapeutic potential of CA and derivatives. It provides an overview of patented processes and applications thereof between 2009 and 2013. The phenylpropanoid framework is currently considered a valid structure for drug discovery programs. Actually, CA has been widely used as a template for the development of new chemical entities with potential therapeutic interest in human diseases associated with oxidative stress. Additionally, the applicability of CA derivatives expands to the realms of cosmetic industry due to its stabilizing properties. The synthesis of esters, amides and hybrids with currently marketed drugs is a trending strategy for the development of derivatives with therapeutic application. It is our opinion that the innovative artwork currently being developed involving this chemical scaffold will yield new and effective therapeutic agents in a foreseeable future.

  16. Preparation and biological evaluation of novel leucomycin analogs derived from nitroso Diels–Alder reactions†

    PubMed Central

    Yang, Baiyuan; Zollner, Tina; Gebhardt, Peter; Mollmann, Ute; Miller, Marvin J.

    2014-01-01

    A series of 10,13-disubstituted 16-membered macrolides was synthesized using nitroso Diels–Alder reactions of leucomycin A7. Despite the extensive constituent functionalities in leucomycin, the hetero cycloaddition reactions proceeded in a highly regio- and stereoselective fashion. Subsequent chemical modifications of the nitroso cycloadducts, including N–O bond reduction, were also conducted. Most leucomycin derivatives retained antibiotic profiles similar to leucomycin A7, and, in contrast to leucomycin itself, several exhibited moderate antiproliferative and cytotoxic activity. PMID:20090988

  17. Benzamide derivatives and their constrained analogs as histamine H3 receptor antagonists.

    PubMed

    Nirogi, Ramakrishna; Shinde, Anil; Tiriveedhi, Vinaykumar; Kota, Laxman; Saraf, Sangram Keshari; Badange, Rajesh Kumar; Mohammed, Abdul Rasheed; Subramanian, Ramkumar; Muddana, Nageshwararao; Bhyrapuneni, Gopinadh; Abraham, Renny

    2016-01-27

    A series of 4-(1-substituted piperidin-4-yloxy) benzamides and 6-(1-substituted piperidin-4-yloxy)-3,4-dihydro-2H-isoquinolin-1-one derivatives have been synthesized and tested for their binding affinity towards H3 receptor. Most of these synthesized compounds have displayed potent binding affinity for H3 receptor when tested in in vitro binding assay. Preliminary SAR studies, functional activity, pharmacokinetic profile and efficacy profile constitute the subject matter of this communication.

  18. Sugar and Sugar Derivatives in Residues Produced from the UV Irradiation of Astrophysical Ice Analogs

    NASA Technical Reports Server (NTRS)

    Nuevo, M.; Sandford, S. A.; Cooper, G.

    2016-01-01

    A large variety and number of organic compounds of prebiotic interest are known to be present in carbonaceous chondrites. Among them, one sugar (dihydroxyacetone) as well as several sugar acids, sugar alcohols, and other sugar derivatives have been reported in the Murchison and Murray meteorites. Their presence, along with amino acids, amphiphiles, and nucleobases strongly suggests that molecules essential to life can form abiotically under astrophysical conditions. This hypothesis is supported by laboratory studies on the formation of complex organic molecules from the ultraviolet (UV) irradiation of simulated astrophysical ice mixtures consisting of H2O, CO, CO2, CH3OH, CH4, NH3, etc., at low temperature. In the past 15 years, these studies have shown that the organic residues recovered at room temperature contain amino acids, amphiphiles, nucleobases, as well as other complex organics. However, no systematic search for the presence of sugars and sugar derivatives in laboratory residues have been reported to date, despite the fact that those compounds are of primary prebiotic significance. Indeed, only small (up to 3 carbon atoms) sugar derivatives including glycerol and glyceric acid have been detected in residues so far.

  19. Sugars and Sugar Derivatives in Residues Produced from the UV Irradiation of Astrophysical Ice Analogs

    NASA Technical Reports Server (NTRS)

    Nuevo, M.; Sandford, S. A.; Cooper, G.

    2017-01-01

    Carbonaceous chondrites contain a large variety of organic compounds of prebiotic interest, which include amino acids, amphiphiles, nucleobases, and sugar derivatives. The presence of these compounds strongly suggests that molecules essential to life can form abiotically under astrophysical conditions. Among the sugar derivatives reported in the Murchison and Murray meteorites, only one sugar (dihydroxyacetone) was found, together with a variety of sugar alcohols and sugar acids containing up to 6 carbon atoms, including sugar acid derivatives of the biological sugars ribose and glucose. On the other hand, laboratory studies on the formation of complex organic molecules from the ultraviolet (UV) irradiation of simulated astrophysical ice mixtures consisting of H2O, CO, CO2, CH3OH, CH4, NH3, etc., at low temperature have been routinely carried out in the past 15 years. These studies have shown that the organic residues recovered at room temperature contain amino acids, amphiphiles, nucleobases, as well as other complex organics, supporting a scenario in which molecules of prebiotic interest can form in extra-terrestrial environments.

  20. Maximizing dermal targeting and minimizing transdermal penetration by magnolol/honokiol methoxylation.

    PubMed

    Lin, Chwan-Fwu; Hwang, Tsong-Long; Al-Suwayeh, Saleh A; Huang, Yu-Ling; Hung, Yi-Yun; Fang, Jia-You

    2013-03-10

    Magnolol and honokiol, predominant active compounds in the family Magnoliaceae, are known to exhibit strong anti-inflammatory activities against dermal disorders. We attempted to modify the structures of magnolol and honokiol by methoxylation to optimize the skin delivery ability. Absorption of these permeants into and through the skin was performed at both an infinite dose and saturated solubility. Superoxide anion and elastase released from human neutrophils were the biomarkers used to examine anti-inflammatory potencies of these permeants. The safety of the permeants was evaluated by keratinocyte viability and in vivo bioengineering techniques. Topical magnolol and honokiol at an infinite dose (7.5 mM) showed skin accumulations of 0.22 and 0.16 nmol/mg, respectively. Methoxylation significantly enhanced their skin absorption. Deposition amounts of dimethylmagnolol and dimethylhonokiol were respectively 15- and 7-fold greater than those of magnolol and honokiol. Contrary to the skin accumulation results, the transdermal penetration across skin decreased following methoxylation. No transdermal delivery occurred for dimethylhonokiol. Skin uptake of 4'-O-methylhonokiol was 2-fold higher than that of 2-O-methylhonokiol, although they are isomers. Methoxylated permeants demonstrated selective absorption into follicles, which showed 3-5-fold higher follicular amounts compared to magnolol and honokiol. The relative order of anti-inflammatory activities was honokiol>2-O-methylmagnolol>dimethylhonokiol>magnolol. The other compounds exhibited negligible or negative responses in activated neutrophils. Magnolol and honokiol induced slight but significant keratinocyte cytotoxicity and stratum corneum disruption. Daily administration of methoxylated permeants, especially dimethylhonokiol, produced no skin irritation for up to 7 days. Methoxylated magnolol and honokiol can be efficient and safe candidates for treating inflammatory skin disorders. Copyright © 2013 Elsevier B

  1. Yellow passion fruit rind--a potential source of low-methoxyl pectin.

    PubMed

    Yapo, Beda Marcel; Koffi, Kouassi Leonard

    2006-04-05

    Yellow passion fruit (Passiflora edulis f. flavicarpa Degener) rind pectic substances were fractionated with water, ammonium oxalate, and dilute acid solutions. The extracted pectins were rich in anhydrogalacturonic acid and had a low degree of methyl esterification. Moreover, their acetyl groups and neutral sugar contents were relatively low. Furthermore, a low amount of proteinaceous material was also found within them. Their gelling ability and viscoelastic properties as evaluated by the SAG and small amplitude oscillatory shear tests, respectively, were comparable to those of a commercial citrus low-methoxyl pectin. Hence, yellow passion fruit rind occurs as a potentially good source of naturally low-methoxyl pectin.

  2. Pharmacological aspects of cytotoxic polyamine analogs and derivatives for cancer therapy.

    PubMed

    Seiler, Nikolaus

    2005-07-01

    During the past 20 years, numerous derivatives and analogues of spermidine (Spd) and spermine (Spm) were synthesized with the aim to generate a new type of anticancer drug. The common denominator of most cytotoxic polyamine analogues is their lipophilicity, which is superior to that of the parent amines. The natural polyamines bind to polyanions and to proteins with anionic binding sites. Their hydrophilicity/hydrophobicity is balanced, allowing them to perform physiological functions by interacting with some of these anionic structures, without impairing the functionality of others. Because the attachment of lipophilic substituents to the polyamine backbone increases the binding energy, lipophilic polyamine derivatives affect secondary and tertiary structures of a larger number of macromolecules than do their natural counterparts. In addition, lipophilicity improves the blood-brain barrier transport and thus enhances CNS toxicity. Close structural analogues of spermidine and spermine mimic the natural polyamines in regulatory functions. The cytotoxic mechanisms of analogues with a less close structural resemblance to spermidine or spermine have not been completely clarified. The displacement of spermidine from functional binding sites and the consequent prevention of its physiological roles is a likely mechanism, but many others may play a role as well. Up to now, polyamine analogues were conceived without specific growth-related targets in mind. To develop therapeutically useful drugs, it will be imperative to identify specific targets and to design compounds that interact selectively with the target molecules. It will also be necessary to include, at an early state of the work, pharmacological and toxicological considerations, to avoid unproductive directions.

  3. Biological and structural effects of the conjugation of an antimicrobial decapeptide with saturated, unsaturated, methoxylated and branched fatty acids.

    PubMed

    Húmpola, María Verónica; Rey, María Carolina; Carballeira, Nestor M; Simonetta, Arturo Carlos; Tonarelli, Georgina Guadalupe

    2017-01-01

    The increasing bacterial resistance against conventional antibiotics has led to the search for new antimicrobial drugs with different modes of action. Cationic antimicrobial peptides (AMPs) and lipopeptides are promising candidates to treat infections because they act on bacterial membranes causing rapid destruction of sensitive bacteria. In this study, a decapeptide named A2 (IKQVKKLFKK) was conjugated at the N-terminus with saturated, unsaturated, methoxylated and methyl -branched fatty acids of different chain lengths (C8 - C20), the antimicrobial and structural properties of the lipopeptides being then investigated. The attachment of the fatty acid chain significantly improved the antimicrobial activity of A2 against bacteria, and so, endowed it with moderated antifungal activity against yeast strains belonging to genus Candida. Lipopeptides containing hydrocarbon chain lengths between C8 and C14 were the best antibacterial compounds (MIC = 0.7 to 5.8 μM), while the most active compounds against yeast were A2 conjugated with methoxylated and enoic fatty acids (11.1 to 83.3 μM). The improvement in antimicrobial activity was mainly related to the amphipathic secondary structure adopted by A2 lipopeptides in the presence of vesicles that mimic bacterial membranes. Peptide conjugation with long hydrocarbon chains (C12 or more), regardless of their structure, significantly increased toxicity towards eukaryotic cells, resulting in a loss of selectivity. These findings suggest that A2-derived lipopeptides are potential good candidates for the treatment of infectious diseases caused by bacteria and opportunistic pathogenic yeast belonging to genus Candida. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  4. Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs.

    PubMed Central

    Parant, M A; Audibert, F M; Chedid, L A; Level, M R; Lefrancier, P L; Choay, J P; Lederer, E

    1980-01-01

    The immunostimulant properties of a new muramyl dipeptide (MDP) derivative bearing a lipophilic moiety on the C-terminal end of the peptide chain are described. It is shown, in particular, that 1,O-(acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate had increased immunostimulant activity in comparison with MDP. It induced hypersensitivity even when administered with an antigen in saline, and it gave higher protection against bacterial infections than did MDP. A quite unexpected finding was obtained with the corresponding desmuramyl compound 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate, which had no activity in producing humoral antibodies but was just as active as the muramic acid-containing compound in stimulating nonspecific resistance to bacterial infections. It was not pyrogenic. Modifications of the peptide moiety or the lipid moiety of this peptidolipid led to decrease, or even loss, of activity. These results show the importance of the N-acetylmuramyl moiety in MDP for humoral antibody production. The peptidolipid 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate is the first member of a new category of nonspecific immunostimulants. PMID:7380554

  5. Psychopharmacological effects of tianeptine analogous hetero[2,1] benzothiazepine derivatives.

    PubMed

    Sánchez-Mateo, Candelaria C; Darias, Victoriano; Albertos, Luz M; Expósito-Orta, María A

    2003-01-01

    The psychopharmacological effects of a number of thieno and pyrazolo[2,1] benzothiazepine derivatives as well as several synthetic intermediate compounds were investigated in mice. Previously published studies in mice have shown that some of these compounds were effective in the tetrabenazine and Porsolt tests. In the present study, 7 of the 15 compounds under study clearly antagonized the apomorphine (16 mg/kg s.c.)-induced hypothermia, but no significant potentiation of the 5-hydroxytryptophan (5-HTP) and amphetamine actions was found. Five of them inhibited the syndrome induced by 5-HTP (250 mg/kg i.p.). Moreover, some of them were effective in the plus-maze test and antagonized the apomorphine (3 mg/kg s.c.)-induced effects. On the other hand, these compounds produced a moderate inhibition of exploratory behaviour in the hole-board test, but they had no significant muscle relaxant and anticonvulsant activities. The results indicate that some of the compounds under study combine a spectrum of antidepressant, anxiolytic and neuroleptic properties in mice with a lack of muscle relaxant and anticonvulsant activities.

  6. Chloroethyinitrosourea-derived ethano cytosine and adenine adducts are substrates for escherichia coli glycosylases excising analogous etheno adducts

    SciTech Connect

    Guliaev, Anton B.; Singer, B.; Hang, Bo

    2004-05-05

    Exocyclic ethano DNA adducts are saturated etheno ring derivatives formed mainly by therapeutic chloroethylnitrosoureas (CNUs), which are also mutagenic and carcinogenic. In this work, we report that two of the ethano adducts, 3,N{sup 4}-ethanocytosine (EC) and 1,N{sup 6}-ethanoadenine (EA), are novel substrates for the Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug) and 3-methyladenine DNA glycosylase II (AlkA), respectively. It has been shown previously that Mug excises 3,N{sup 4}-ethenocytosine ({var_epsilon}C) and AlkA releases 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using synthetic oligonucleotides containing a single ethano or etheno adduct, we found that both glycosylases had a {approx}20-fold lower excision activity toward EC or EA than that toward their structurally analogous {var_epsilon}C or {var_epsilon}A adduct. Both enzymes were capable of excising the ethano base paired with any of the four natural bases, but with varying efficiencies. The Mug activity toward EC could be stimulated by E. coli endonuclease IV and, more efficiently, by exonuclease III. Molecular dynamics (MD) simulations showed similar structural features of the etheno and ethano derivatives when present in DNA duplexes. However, also as shown by MD, the stacking interaction between the EC base and Phe 30 in the Mug active site is reduced as compared to the {var_epsilon}C base, which could account for the lower EC activity observed in this study.

  7. Antiproliferative effects of 1alpha,25-dihydroxyvitamin D(3) and vitamin D analogs on tumor-derived endothelial cells.

    PubMed

    Bernardi, Ronald J; Johnson, Candace S; Modzelewski, Ruth A; Trump, Donald L

    2002-07-01

    Although there is abundant evidence that 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] inhibits the growth of several cancer cell types, inhibition of angiogenesis may also play a role in mediating the antitumor effects of 1,25-(OH)(2)D(3.) We examined the ability of 1,25-(OH)(2)D(3) to inhibit the growth of tumor-derived endothelial cells (TDECs) and normal endothelial cells and to modulate angiogenic signaling. 1,25-(OH)(2)D(3) inhibited the growth of TDECs from two tumor models at nanomolar concentrations, but was less potent against normal aortic or yolk sac endothelial cells. The vitamin D analogs Ro-25-6760, EB1089, and ILX23-7553 were also potent inhibitors of TDEC proliferation. Furthermore, the combination of 1,25-(OH)(2)D(3) and dexamethasone had greater activity than either agent alone. 1,25-(OH)(2)D(3) increased vitamin D receptor and p27(Kip1) protein levels in TDECs, whereas phospho-ERK1/2 and phospho-Akt levels were reduced. These changes were not observed in normal aortic endothelial cells. In squamous cell carcinoma and radiation-induced fibrosarcoma-1 cells, 1,25-(OH)(2)D(3) treatment caused a reduction in the angiogenic signaling molecule, angiopoietin-2. In conclusion, 1,25-(OH)(2)D(3) and its analogs directly inhibit TDEC proliferation at concentrations comparable to those required to inhibit tumor cells. Further, 1,25-(OH)(2)D(3) modulates cell cycle and survival signaling in TDECs and affects angiogenic signaling in cancer cells. Thus, our work supports the hypothesis that angiogenesis inhibition plays a role in the antitumor effects of 1,25-(OH)(2)D(3).

  8. Dualism of carbonium ion and carbenoid reactivity of surface methoxyl groups on zeolite catalysts

    SciTech Connect

    Chuvylkin, N.D.; Korsunov, V.A.; Kazanskii, V.B.

    1987-05-01

    The dualism of the carbonium ion and carbenoid reactivity of the surface methoxyl groups on zeolite catalysts was analyzed within the framework of the cluster method of boundary pseudoions, using uncharged and moderately charged ionic models and the unified quantum chemical procedure CINDORU.

  9. The structure of high-methoxyl sugar acid gels of citrus pectin as determined by AFM

    USDA-ARS?s Scientific Manuscript database

    Images of native high methoxyl sugar acid gels (HMSAG) were obtained by atomic force microscopy (AFM) in the Tapping ModeTM. Electronic thinning of the pectin strands to one pixel wide allowed the pectin network to be viewed in the absence of variable strand widths related to preferentially solvate...

  10. Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria

    PubMed Central

    Frantz, Marie-Céline; Skoda, Erin M.; Sacher, Joshua R.; Epperly, Michael W.; Goff, Julie P.; Greenberger, Joel S.

    2013-01-01

    JP4-039 is a lead structure in a series of nitroxide conjugates that are capable of accumulating in mitochondria and scavenging reactive oxygen species (ROS). To explore structure-activity relationships (SAR), new analogs with variable nitroxide moieties were prepared. Furthermore, fluorophore-tagged analogs were synthesized and provided the opportunity for visualization in mitochondria. All analogs were tested for radioprotective and radiomitigative effects in 32Dcl3 cells. PMID:23715589

  11. DOTA-Derivatives of Octreotide Dicarba-Analogs with High Affinity for Somatostatin sst2,5 Receptors.

    PubMed

    Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

    2017-01-01

    In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumors and their metastases. In fact, peptide ligands of somatostatin receptors (sst's) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogs, which show interesting binding profiles at sst's. In this context, it was mandatory to explore the possibility that our analogs could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogs of octreotide. Interestingly, two conjugated analogs exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes.

  12. Biosynthesis and urinary excretion of methyl sulfonium derivatives of the sulfur mustard analog, 2-chloroethyl ethyl sulfide, and other thioethers

    SciTech Connect

    Mozier, N.M.; Hoffman, J.L. )

    1990-12-01

    Thioether methyltransferase was previously shown to catalyze the S-adenosylmethionine-dependent methylation of diemthyl selenide, dimethyl telluride, and various thioethers to produce the corresponding methyl onium ions. In this paper we show that the following thioethers are also substrates for this enzyme in vitro: 2-hydroxyethyl ethyl sulfide, 2-chloroethyl ethyl sulfide, thiodiglycol, t-butyl sulfide, and isopropyl sulfide. To demonstrate thioether methylation in vivo, mice were injected with (methyl-{sup 3}H)methionine plus different thioethers, and extracts of lungs, livers, kidneys, and urine were analyzed by high-performance liquid chromatography for the presence of ({sup 3}H)methyl sulfonium ions. The following thioethers were tested, and all were found to be methylated in vivo: dimethyl sulfide, diethyl sulfide, methyl n-propyl sulfide, tetrahydrothiophene, 2-(methylthio)ethylamine, 2-hydroxyethyl ethyl sulfide, and 2-chloroethyl ethyl sulfide. This supports our hypothesis that the physiological role of thioether methyltransferase is to methylate seleno-, telluro-, and thioethers to more water-soluble onium ions suitable for urinary excretion. Conversion of the mustard gas analog, 2-chloroethyl ethyl sulfide, to the methyl sulfonium derivative represents a newly discovered mechanism for biochemical detoxification of sulfur mustards, as this conversion blocks formation of the reactive episulfonium ion that is the ultimate alkylating agent for this class of compounds.

  13. Stable hydrogen isotope ratios of methoxyl groups in Eifel (Germany) maar deposits: a potential palaeotemperature proxy

    NASA Astrophysics Data System (ADS)

    Anhäuser, Tobias; Sirocko, Frank; Greule, Markus; Esper, Jan; Keppler, Frank

    2014-05-01

    Stable hydrogen isotope ratios (δD values) of methoxyl groups in a variety of plant types from different locations have been shown to record δD values of precipitation, with a mean uniform isotopic fractionation. Since δD in precipitation is mainly influenced by climatic conditions, including temperature, evaporation and precipitation amount, methoxyl groups of organic matter have been proposed as a potential palaeoclimate proxy. We measured the δD values of the methoxyl groups in bulk sediment and oospores (algal spores from charophytes) from Eifel maar sediment core samples. The sediment cores cover the entire Holocene and part of the Late Glacial (9640 BC to ~12,000 BC). The methodology employed was precise with mean standard deviations of δD values of 3.3‰ (n = 12) and 1.3‰ (n = 3) for methoxyl groups of bulk sediment and oospore samples, respectively. Based on our measurements palaeoclimatic interpretations were made. Along a North-South transect of Europe δD values of precipitation and lake water are both strikingly correlated with the mean annual air temperature (R² = 0.99 and R² = 0.93, respectively), leading to a temperature gradient of 4-6‰ per 1° C. We used this gradient to calculate changes in temperature over the past ~14,000 years as indicated by changes in the δD values of the bulk sediment and oospores. Whereas the mean temperature variation within the Holocene was found to be consistently less than 2° C, the covered Late Glacial period indicates colder temperatures, by as much as 5° C, both with respect to the average Holocene temperature. The observed long term temperature trend is broadly in line with that reported from the NGRIP ice core for the same time period. δD values of methoxyl groups of bulk sediment are also consistent with those obtained from oospores. We suggest that the δD values of methoxyl groups from well-characterized organic material, especially in the case of oospores, have great potential to assist

  14. Novel sirtuin inhibitory warheads derived from the N(ε)-acetyl-lysine analog L-2-amino-7-carboxamidoheptanoic acid.

    PubMed

    He, Yanhua; Yan, Lingling; Zang, Wenwen; Zheng, Weiping

    2015-11-14

    Built upon the catalytic mechanism-based pan-SIRT1/2/3 inhibitory warhead L-2-amino-7-carboxamidoheptanoic acid (L-ACAH, a close structural analog of N(ε)-acetyl-lysine) that our laboratory discovered recently, in the current study, its carboxamide NH2-ethylated analog was found to be a ∼2.4-6.6-fold stronger SIRT1/2/3 inhibitory warhead than L-ACAH. Carboxamide NH2-dodecylated and carboxymethylated analogs of L-ACAH were also identified as potent SIRT6 and SIRT5 inhibitory warheads, respectively.

  15. Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid.

    PubMed

    Pessah, Neta; Yagen, Boris; Hen, Naama; Shimshoni, Jakob A; Wlodarczyk, Bogdan; Finnell, Richard H; Bialer, Meir

    2011-11-01

    A series of glycinamide conjugates and N-methoxy amide derivatives of valproic acid (VPA) analogs and constitutional isomers were synthesized and evaluated for anticonvulsant activity. Of all compounds synthesized and tested, only N-methoxy-valnoctamide (N-methoxy-VCD) possessed better activity than VPA in the following anticonvulsant tests: maximal electroshock, subcutaneous metrazol, and 6-Hz (32-mA) seizure tests. In mice, the ED(50) values of N-methoxy-VCD were 142 mg/kg (maximal electroshock test), 70 mg/kg (subcutaneous metrazol test), and 35 mg/kg (6-Hz test), and its neurotoxicity TD(50) was 118 mg/kg. In rats, the ED(50) of N-methoxy-VCD in the subcutaneous metrazol test was 36 mg/kg and its protective index (PI=TD(50)/ED(50)) was >5.5. In the rat pilocarpine-induced status epilepticus model, N-methoxy-VCD demonstrated full protection at 200mg/kg, without any neurotoxicity. N-Methoxy-VCD was tested for its ability to induce teratogenicity in a mouse strain susceptible to VPA-induced teratogenicity and was found to be nonteratogenic, although it caused some resorptions. Nevertheless, a safety margin was still maintained between the ED(50) values of N-methoxy-VCD in the mouse subcutaneous metrazol test and the doses that caused the resorptions. On the basis of these results, N-methoxy-VCD is a good candidate for further evaluation as a new anticonvulsant and central nervous system drug. Copyright © 2011. Published by Elsevier Inc.

  16. Effects of semirigid methoxamine analogs on vascular smooth muscle: studies of methoxy-2-aminotetralin and 2-aminoindane derivatives.

    PubMed

    Arnerić, S P; Roetker, A; Long, J P; Mott, J; Barfknecht, C F

    1982-06-01

    The effects of semirigid methoxy analogs of 2-aminotetralin (2-AT) and 2-aminoindane (2-AI) were studied on superfused dog metatarsal veins to investigate postjunctional interactions produced by these agents on sympathetically innervated vascular smooth muscle. The following compounds were tested: norepinephrine (NE); serotonin (5-HT); amphetamine (AMP); methoxamine (MTH); 2-di-n-propylamino-4,7-dimethoxyindane (RDS-127); 2-di-n-propylamino-5,6,-dimethoxyindane (JPC-211); 2-di-n-propylaminoindane (JPC-6036); 2-methylamino-5,8-dimethoxytetralin (DR-31); 2-methylamino-4,7-dimethoxyindane (RDS-31). The results of this study indicate that contractions produced by these compounds have the following ranked ordered potencies: 5-HT greater than NE much greater than MTH greater than or equal to RDS-127 = DR-31; JPC-6036, RDS-31, JPC-211 and AMP were inactive. The contractions produced by NE, MTH, RDS-127 or DR-31, but not 5-HT, probably occur through alpha1-adrenergic receptors since these contractions were blocked with prazosin. 5-HT and RDS-127, but not NE, MTH or DR-31 activate serotonin receptors since methysergide blocked the response produced by 5-HT or RDS-127. NE-induced contractions were augmented and tyramine-induced contractions were attenuated with cocaine. The responses of MTH, RDS-127 or DR-31 probably do not displace NE through a tyramine-like action since cocaine had no effect on contractions induced by these compounds. These data suggest that semirigid paramethoxylated derivatives of 2-AT and 2-AI are potent postjunctional receptor agonists which probably initiate venoconstriction via direct receptor interactions. The structure-activity relationships of these compounds are discussed.

  17. Antibacterial activity and dual mechanisms of peptide analog derived from cell-penetrating peptide against Salmonella typhimurium and Streptococcus pyogenes.

    PubMed

    Li, Lirong; Shi, Yonghui; Cheserek, Maureen Jepkorir; Su, Guanfang; Le, Guowei

    2013-02-01

    A number of research have proven that antimicrobial peptides are of greatest potential as a new class of antibiotics. Antimicrobial peptides and cell-penetrating peptides share some similar structure characteristics. In our study, a new peptide analog, APP (GLARALTRLLRQLTRQLTRA) from the cell-penetrating peptide ppTG20 (GLFRALLRLLRSLWRLLLRA), was identified simultaneously with the antibacterial mechanism of APP against Salmonella typhimurium and Streptococcus pyogenes. APP displayed potent antibacterial activity against Gram-negative and Gram-positive strains. The minimum inhibitory concentration was in the range of 2 to 4 μM. APP displayed higher cell selectivity (about 42-fold increase) as compared to the parent peptide for it decreased hemolytic activity and increased antimicrobial activity. The calcein leakage from egg yolk L-α-phosphatidylcholine (EYPC)/egg yolk L-α-phosphatidyl-DL-glycerol and EYPC/cholesterol vesicles demonstrated that APP exhibited high selectivity. The antibacterial mechanism analysis indicated that APP induced membrane permeabilization in a kinetic manner for membrane lesions allowing O-nitrophenyl-β-D-galactoside uptake into cells and potassium release from APP-treated cells. Flow cytometry analysis demonstrated that APP induced bacterial live cell membrane damage. Circular dichroism, fluorescence spectra, and gel retardation analysis confirmed that APP interacted with DNA and intercalated into the DNA base pairs after penetrating the cell membrane. Cell cycle assay showed that APP affected DNA synthesis in the cell. Our results suggested that peptides derived from the cell-penetrating peptide have the potential for antimicrobial agent development, and APP exerts its antibacterial activity by damaging bacterial cell membranes and binding to bacterial DNA to inhibit cellular functions, ultimately leading to cell death.

  18. Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction

    PubMed Central

    Hiesinger, William; Frederick, John R.; Atluri, Pavan; McCormick, Ryan C.; Marotta, Nicole; Muenzer, Jeffrey R.; Woo, Y. Joseph

    2011-01-01

    Objectives Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. Methods EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n=48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. Results EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. Conclusions A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α. PMID:20951261

  19. Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction.

    PubMed

    Hiesinger, William; Frederick, John R; Atluri, Pavan; McCormick, Ryan C; Marotta, Nicole; Muenzer, Jeffrey R; Woo, Y Joseph

    2010-11-01

    Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n = 48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α. Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  20. DOTA-Derivatives of Octreotide Dicarba-Analogs with High Affinity for Somatostatin sst2,5 Receptors

    PubMed Central

    Pratesi, Alessandro; Ginanneschi, Mauro; Lumini, Marco; Papini, Anna M.; Novellino, Ettore; Brancaccio, Diego; Carotenuto, Alfonso

    2017-01-01

    In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumors and their metastases. In fact, peptide ligands of somatostatin receptors (sst's) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogs, which show interesting binding profiles at sst's. In this context, it was mandatory to explore the possibility that our analogs could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogs of octreotide. Interestingly, two conjugated analogs exhibited nanomolar affinities on sst2 and sst5 somatostatin receptor subtypes. PMID:28286746

  1. Improved protein kinase C affinity through final step diversification of a simplified salicylate-derived bryostatin analog scaffold.

    PubMed

    Wender, Paul A; Staveness, Daryl

    2014-10-03

    Bryostatin 1, in clinical trials or preclinical development for cancer, Alzheimer's disease, and a first-of-its-kind strategy for HIV/AIDS eradication, is neither readily available nor optimally suited for clinical use. In preceding work, we disclosed a new class of simplified bryostatin analogs designed for ease of access and tunable activity. Here we describe a final step diversification strategy that provides, in only 25 synthetic steps, simplified and tunable analogs with bryostatin-like PKC modulatory activities.

  2. Effect of low and high methoxyl citrus pectin on the properties of polypyrrole based electroactive hydrogels.

    PubMed

    Lopes, Laís C; Simas-Tosin, Fernanda F; Cipriani, Thales R; Marchesi, Luís F; Vidotti, Marcio; Riegel-Vidotti, Izabel C

    2017-01-02

    Electroactive hydrogels were prepared using commercial citric pectin, either raw (PC) or purified through dialysis (dPC), and chemically synthesized polypyrrole (PPy). (1)H NMR analyses showed that PC is a low methoxyl pectin (degree of methoxylation, DM=46%) and dPC is a high methoxyl pectin (DM=77%). The pyrrole polymerization was monitored through UV-vis spectroscopy and both samples were observed to be good stabilizers for PPy in aqueous medium. The dispersions were used to prepare the hydrogels h-PC-PPy and h-dPC-PPy. The hydrogel h-dPC-PPy has a higher swelling index (SI≈25%) at pH 1.2 than the hydrogel h-PC-PPy (SI≈7%). Contrastingly, at pH 6.8 both hydrogels lost their mechanical integrity. Raman spectroscopy revealed that PPy is more oxidized in h-PC-PPy. Nevertheless, both hydrogels are electroactive and therefore can be considered for applications in which the control of the degree of swelling is desired. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Mathematically engineered stromal cell-derived factor-1α stem cell cytokine analog enhances mechanical properties of infarcted myocardium.

    PubMed

    MacArthur, John W; Trubelja, Alen; Shudo, Yasuhiro; Hsiao, Philip; Fairman, Alexander S; Yang, Elaine; Hiesinger, William; Sarver, Joseph J; Atluri, Pavan; Woo, Y Joseph

    2013-01-01

    The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction. Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB. Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle. Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  4. What climate information is recorded in stable isotope ratios of wood lignin methoxyl groups?

    NASA Astrophysics Data System (ADS)

    Greule, Markus; Keppler, Frank

    2010-05-01

    The stable isotope composition of the bioelements C, O, H and N in plant organic matter is known to be a very powerful for various environmental impacts. Particularly tree rings are suitable for this analysis because they exhibit a "climate archive" with a yearly or even biannual resolution. One of the most determined wood compounds is cellulose which amongst others is used to reconstruct the temperature due to measurement of stable hydrogen and oxygen isotopes. Therefore cellulose is converted into cellulose nitrate to eliminate the exchangeable hydroxyl hydrogen or equilibration methods are used. However, a general problem associated with the determination of the stable hydrogen values of marker compounds for the study of climate and environmental conditions is the isolation of the pure compound for analysis by isotope ratio mass spectrometry. Exploitation of components of wood as markers, in particular, has been restricted by the very labour intensive and time consuming preparation of samples (e.g. cellulose nitrate). An alternative way to record climate information from tree rings was recently proposed by Keppler et al. (2007) who measured the stable hydrogen values of methoxyl groups in wood. Lignin methoxyl groups are considered to be stable, i.e. the hydrogen atoms of the methoxyl moiety do not exchange with those of plant water during ongoing metabolic reactions in the plant. Thus the initial deuterium content of the methoxyl groups of lignin in woody tissue at formation is retained throughout the lifetime of the tree and in preserved tissue. The methoxyl content of lignin in wood is usually determined by the Zeisel method (Zeisel, 1885) - the reaction between methyl ethers and hydroiodic acid to form methyl iodide. Exploiting this reaction for the measurement of stable hydrogen values of lignin methoxyl groups ensures that during the entire analytical procedure the isotope signal is preserved since no isotopic exchange occurs between the methyl groups and

  5. PYRIDOXAMINE ANALOGS SCAVENGE LIPID-DERIVED γ-KETOALDEHYDES AND PROTECT AGAINST H2O2-MEDIATED CYTOTOXICITY†

    PubMed Central

    Davies, Sean S.; Brantley, Eric J.; Voziyan, Paul A.; Amarnath, Venkataraman; Zagol-Ikapitte, Irene; Boutaud, Olivier; Hudson, Billy G.; Oates, John A.; Jackson Roberts, L.

    2008-01-01

    Isoketals and levuglandins are highly reactive γ-ketoaldehydes formed by oxygenation of arachidonic acid in settings of oxidative injury and cyclooxygenase activation, respectively. These compounds rapidly adduct to proteins via lysyl residues, which can alter protein structure/function. We examined whether pyridoxamine, which has been shown to scavenge α-ketoaldehydes formed by carbohydrate or lipid peroxidation, could also effectively protect proteins from the more reactive γ-ketoaldehydes. Pyridoxamine prevented adduction of ovalbumin and also prevented inhibition of RNase A and glutathione reductase activity by the synthetic γ-ketoaldehyde, 15-E2-isoketal. We identified the major products of the reaction of pyridoxamine with the 15-E2-isoketal, including a stable lactam adduct. Two lipophilic analogs of pyridoxamine, salicylamine and 5’O-pentylpyridoxamine, also formed lactam adducts when reacted with 15-E2-isoketal. When we oxidized arachidonic acid in the presence of pyridoxamine or its analogs, pyridoxamine-isoketal adducts were found in significantly greater abundance than the pyridoxamine-N-acyl adducts formed by α-ketoaldehyde scavenging. Therefore, pyridoxamine and its analogs appear to preferentially scavenge γ-ketoaldehydes. Both pyridoxamine and its lipophilic analogs inhibited the formation of lysyl-levuglandin adducts in platelets activated ex vivo with arachidonic acid. The two lipophilic pyridoxamine analogs provided significant protection against H2O2-mediated cytotoxicity in HepG2 cells. These results demonstrate the utility of pyridoxamine and lipophilic pyridoxamine analogs to assess the potential contributions of isoketals and levuglandins in oxidant injury and inflammation and suggest their potential utility as pharmaceutical agents in these conditions. PMID:17176098

  6. Synthesis of peptide nucleic acids containing pyridazine derivatives as cytosine and thymine analogs, and their duplexes with complementary oligodeoxynucleotides.

    PubMed

    Tomori, Takahito; Miyatake, Yuya; Sato, Yuta; Kanamori, Takashi; Masaki, Yoshiaki; Ohkubo, Akihiro; Sekine, Mitsuo; Seio, Kohji

    2015-03-20

    Synthesis of peptide nucleic acids (PNAs) is reported with new pyridazine-type nucleobases: 3-aminopyridazine (aPz) and 1-aminophthalazine (aPh) as cytosine analogs, and pyridazin-3-one (Pz(O)) and phthalazin-1-one (Ph(O)) as thymine analogs. The PNAs having an aPz or a Pz(O) formed duplexes with each complementary oligodeoxynucleotide forming a base pair with G or A, respectively, as evaluated by using UV melting analyses and circular dichroism (CD) spectra.

  7. N(6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside induces sedative and hypnotic effects via GAD enzyme activation in mice.

    PubMed

    Shi, Y; Dong, J W; Tang, L N; Kang, R X; Shi, J G; Zhang, J J

    2014-11-01

    N(6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is an analog of N(6)-(4-hydroxybenzyl) adenine riboside (NHBA), which was originally isolated from Gastrodia elata Blume. Our laboratory has previously demonstrated that B2 can produce strong sedative and hypnotic effects, but the mechanism remains to be determined. There is evidence that gamma-aminobutyric acid (GABA) acts as an inhibitory neurotransmitter in the brain, plays a major role in sleep regulation, and participates in the sedative and hypnotic effects of B2. Therefore, we studied the interactions between B2 and several GABAergic neurochemical parameters based on the sedative and hypnotic effects of B2. The GABA and glutamic acid (Glu) in the mouse brain were derivatized with o-phthalaldehyde (OPA) and measured by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The GAD and GABA-T enzyme activities were determined by measuring GABA and NADH production, respectively. The sleep structure analyses were performed by EEG studies in mice. B2 increased the GABA levels and GAD enzyme activity in the mouse hypothalamus and cortex. The EEG results confirmed that B2 significantly shortened the sleep latency and increased the amount of NREM sleep. The GAD enzyme inhibitor semicarbazide (SCZ) blocked the sedative and hypnotic effects of B2. These findings suggest that the GAD enzyme plays a significant role in the sedative and hypnotic effects of B2. Therefore B2 may be a promising candidate for further clinical studies and the appropriate use of GAD agonist may be a promising approach for sleep disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Antiangiogenic properties of substituted (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol/one analogs and their derivatives

    PubMed Central

    Venkateswaran, Amudhan; Reddy, Y. Thirupathi; Sonar, Vijaykumar N.; Muthusamy, Venkatraj; Crooks, Peter A.; Freeman, Michael L.; Sekhar, Konjeti R.

    2010-01-01

    In the past half century research efforts have defined a critical role for angiogenesis in tumor growth and metastasis. We previously reported that inhibition of a novel target, ENOX1, by a (Z)-2-benzylindol-3-ylmethylene) quinuclidin-3-ol, suppressed tumor angiogenesis. The present study was undertaken in order to establish structure-activity relationships for quinuclidine analogs. The angiogenesis inhibiting activity of a series of substituted (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ols (1a–1k), (Z)-2-benzylindol-3-ylmethylene)quinuclidin-3-ones (2a–2h), (Z)-(±)-2-(1H/N-methyl-indol-3-ylmethylene)quinuclidin-3-ols (3a–3b), and substituted (Z)-(±)-2-(N-benzenesulfonylindol-3-yl-methylene)quinuclidin-3-ols and their derivatives (4a–4d) that incorporate a variety of substituents in both the indole and N-benzyl moieties was evaluated using Human Umbilical Vein Endothelial Cells (HUVECs) subjected to in vitro cell migration scratch assays, tubule formation in Matrigel, cell viability and proliferation assays. In total, 25 different analogs were evaluated. Based on in vitro cell migration scratch assays, eight analogs were identified as potent angiogenesis inhibitors at 10 µM, a concentration that was determined to be nontoxic by colony formation assay. In addition, this approach identified a potent antiangiogenic ENOX1 inhibitor, analog 4b. PMID:21055930

  9. Intracerebroventricular injection of L-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks.

    PubMed

    Asechi, Mari; Tomonaga, Shozo; Tachibana, Tetsuya; Han, Li; Hayamizu, Kohsuke; Denbow, D Michael; Furuse, Mitsuhiro

    2006-06-03

    Four experiments were conducted to clarify the central functions of L-serine and its analogs on an acute stressful condition. Intracerebroventricular (i.c.v.) injection of L-serine (0.21, 0.42 and 0.84 micromol) attenuated stress responses in a dose-dependent fashion, as well as induced sleep, in Experiment 1. The effects of L- and D-serine in Experiment 2, those of L-serine, phosphoserine, acetylserine and L-cysteine in Experiment 3 and those of L-serine, glycine and lysophosphatidylserine in Experiment 4 were compared at an equimolar basis (0.84 micromol). D-Serine, proposed as an endogenous agonist of N-methyl-D-aspatate (NMDA) receptor, did not have sedative and hypnotic effects as observed with L-serine. In contrast, all the analogs and derivatives of L-serine had a sedative effect, although with a different manner in several behavioral markers of stress such as spontaneous activity and distress vocalizations. No significant changes in plasma corticosterone concentration were observed in any experiment. Taken together, the i.c.v. injection of L-serine analogs and its derivatives have sedative and hypnotic effects under an acute stressful condition, which does not involve the hypothalamic-pituitary-adrenal axis. In conclusion, L-serine may be effective in improving anxiety or sleep disorders induced by psychological stressor.

  10. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

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

  11. Structure-activity relationship in the mutagenicity and cytotoxicity of putative metabolites and related analogs of benzene derived from the valence tautomers benzene oxide and oxepin

    SciTech Connect

    Stark, A.A.; Rastetter, W.H.

    1996-12-31

    A series of putative metabolites and related analogs of benzene, derived from the valence tautomers benzene oxide and oxepin, was tested for mutagenicity (reversions to histidine prototrophy and forward mutations to resistance to 8-azaguanine) and for cytotoxicity by the Ames Salmonella mutagenicity test. Benzene was not mutagenic in either assay. The benzene oxide-oxepin system and benzene dihydrodial induced point mutations but not frameshifts. 4,5-sym-Oxepin oxide, which is a putative metabolite of the oxepin valence tautomer; 3,6-diazo-cyclohexane-1,6-3,4-dioxide, a synthetic precursor of sym-oxepin oxide; and transoid-4,11-dioxatricyclo(5.1 0)undeca-1,6-diene, a stable bridgehead diene analog of sym-oxepin oxide, were toxic but not mutagenic in both assays. 4H-Pyran-4-=carboxaldehyde, a stable acid catalyzed rearrangement product of sym-oxepin oxide, was not mutagenic and much less cytotoxic than sym-oxepin oxide. Stable analogs of the valence tautomer benzene oxide, namely syn-indan-3a,7a-oxide and syn-2-hydroxyindan-3a,7a-oxide, were mutagenic and induced point mutations. All compounds were cytotoxic to Salmonella. Firstly, the apparent decay times of these chemicals, especially that of sym-oxepin oxide, were surprisingly longer than expected, as judged by quantitative plate diffusion assays. Secondly, it is concluded that if benzene oxide is further metabolized in its oxepin tautomeric form, toxic but not mutagenic products are formed. Thirdly, the relatively weak mutagenicity of benzene oxide may be mainly due to its instability and corresponding low probability to reach intracellular polynucleotide targets, whereas stable analogs of benzene oxide are relatively more potent mutagens. 48 refs., 4 figs., 3 tabs.

  12. Inhibitory and antimicrobial activities of OGTI and HV-BBI peptides, fragments and analogs derived from amphibian skin.

    PubMed

    Dębowski, Dawid; Łukajtis, Rafał; Łęgowska, Anna; Karna, Natalia; Pikuła, Michał; Wysocka, Magdalena; Maliszewska, Irena; Sieńczyk, Marcin; Lesner, Adam; Rolka, Krzysztof

    2012-06-01

    A series of linear and cyclic fragments and analogs of two peptides (OGTI and HV-BBI) isolated from skin secretions of frogs were synthesized by the solid-phase method. Their inhibitory activity against several serine proteinases: bovine β-trypsin, bovine α-chymotypsin, human leukocyte elastase and cathepsin G from human neutrophils, was investigated together with evaluation of their antimicrobial activities against Gram-negative bacteria (Escherichia coli) and Gram-positive species isolated from patients (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus sp., Streptococcus sp.). The cytotoxicity of the selected peptides toward an immortal human skin fibroblast cell line was also determined. Three peptides: HV-BBI, its truncated fragment HV-BBI(3-18) and its analog [Phe(8)]HV-BBI can be considered as bifunctional compounds with inhibitory as well as antibacterial properties. OGTI, although it did not display trypsin inhibitory activity as previously reported in the literature, exerted antimicrobial activity toward S. epidermidis. In addition, under our experimental conditions, this peptide did not show cytotoxicity.

  13. Stable hydrogen isotope ratios of lignin methoxyl groups as a paleoclimate proxy and constraint of the geographical origin of wood.

    PubMed

    Keppler, Frank; Harper, David B; Kalin, Robert M; Meier-Augenstein, Wolfram; Farmer, Nicola; Davis, Simon; Schmidt, Hanns-Ludwig; Brown, David M; Hamilton, John T G

    2007-01-01

    Stable isotope ratios of organic compounds are valuable tools for determining the geographical origin, identity, authenticity or history of samples from a vast range of sources such as sediments, plants and animals, including humans. Hydrogen isotope ratios (delta(2)H values) of methoxyl groups in lignin from wood of trees grown in different geographical areas were measured using compound-specific pyrolysis isotope ratio mass spectrometry analysis. Lignin methoxyl groups were depleted in (2)H relative to both meteoric water and whole wood. A high correlation (r(2) = 0.91) was observed between the delta(2)H values of the methoxyl groups and meteoric water, with a relatively uniform fractionation of -216 +/- 19 per thousand recorded with respect to meteoric water over a range of delta(2)H values from -110 in northern Norway to +20 per thousand in Yemen. Thus, woods from northern latitudes can be clearly distinguished from those from tropical regions. By contrast, the delta(2)H values of bulk wood were only relatively poorly correlated (r(2) = 0.47) with those of meteoric water. Measurement of the delta(2)H values of lignin methoxyl groups is potentially a powerful tool that could be of use not only in the constraint of the geographical origin of lignified material but also in paleoclimate, food authenticity and forensic investigations.

  14. New glycoside derivatives of carnosine and analogs resistant to carnosinase hydrolysis: synthesis and characterization of their copper(II) complexes.

    PubMed

    Lanza, Valeria; Bellia, Francesco; D'Agata, Roberta; Grasso, Giuseppe; Rizzarelli, Enrico; Vecchio, Graziella

    2011-02-01

    Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide widely and abundantly distributed in muscle and nervous tissues of several animal species. Many functions have been proposed for this compound, such as antioxidant and metal ion-chelator properties. However, the main limitation on therapeutic use of carnosine on pathologies related to increased oxidative stress and/or metal ion dishomeostasis is associated with the hydrolysis by the specific dipeptidase carnosinase. Several attempts have been made to overcome this limitation. On this basis, we functionalized carnosine and its amide derivative with small sugars such as glucose and lactose. The resistance of these derivatives to the carnosinase hydrolysis was tested and compared with that of carnosine. We found that the glycoconjugation protects the dipeptide moiety from carnosinase hydrolysis, thus potentially improving the availability of carnosine. The copper(II) binding properties of all the new synthesized compounds were investigated by spectroscopic (UV-Visible and circular dichroism) and ESI-MS studies. Particularly, the new family of amide derivatives that are not significantly hydrolyzed by carnosinase is a very promising class of carnosine derivatives. The sugar moiety can act as a recognition element. These new derivatives are potentially able to act as chelating agents in the development of clinical approaches for the regulation of metal homeostasis in the field of medicinal inorganic chemistry. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Vegetation-derived insights on the mobilization and potential transport of radionuclides from the Nopal I natural analog site, Mexico

    SciTech Connect

    Leslie, B.W.; Pickett, D.A.; Pearcy, E.C.

    1999-07-01

    The Nopal I uranium (U) deposit, Pena Blanca, Mexico is a source term and contaminant transport natural analog to the proposed high-level nuclear waste repository at Yucca Mountain, Nevada. In an attempt to characterize the mobilization and potential transport of radionuclides in the unsaturated zone at the Nopal I deposit, vegetation growing on ore piles was analyzed for {sup 238}U, {sup 235}U, and {sup 232}Th decay-series isotopes. Specimens of Phacelia robusta growing on high-grade piles of U ore were collected and analyzed by alpha autoradiography, and by alpha and gamma spectrometry. Activities for U, thorium (Th), and radium (Ra) isotopes (Bq/kg dried plant) were 300, 1,000, and 7,000 for {sup 238}U, {sup 230}Th, and {sup 226}Ra, respectively. The {sup 226}Ra activities in these specimens are among the highest ever measured for plants; furthermore, the plant-to-soil {sup 226}Ra concentration ratio is higher than expected. These results demonstrate the large mobility and bio-availability of Ra in the Nopal I environment, and support previous indications of recent loss of {sup 226}Ra from the ore body. Comparison between the activities of {sup 238}U and {sup 232}Th decay-chain Th isotopes in the plants and in the ore substrate indicate that relative mobilization into pore solutions of {sup 228}Th > {sup 230}Th > {sup 232}Th, in a ratio of about 50--25:4:1, respectively. The similarity of the plant's {sup 234}U/{sup 238}U activity ratio ({approximately}1.2) to that of a caliche deposit that formed adjacent to the Nopal ore body around 54 ka suggests the {sup 234}U/{sup 238}U activity ratio of U released from the ore is approximately 1.2. The U and {sup 226}Ra isotope activities of the plants and ore substrate, and solubility considerations, are used to assess a source term model of the potential Yucca Mountain repository. These results suggest the use of a natural analog source term model in performance assessments may be non-conservative.

  16. Analog-to-digital conversion as a source of drifts in displacements derived from digital recordings of ground acceleration

    USGS Publications Warehouse

    Boore, D.M.

    2003-01-01

    Displacements obtained from double integration of digitally recorded ground accelerations often show drifts much larger than those expected for the true ground displacements. These drifts might be due to many things, including dynamic elastic ground tilt, inelastic ground deformation, hysteresis in the instruments, and cross feed due to misalignment of nominally orthogonal sensors. This article shows that even if those effects were not present, the analog-to-digital conversion (ADC) process can produce apparent "pulses" and offsets in the acceleration baseline if the ground motion is slowly varying compared with the quantization level of the digitization. Such slowly varying signals can be produced by constant offsets that do not coincide with a quantization level and by near- and intermediate-field terms in the wave field radiated from earthquakes. Double integration of these apparent pulses and offsets leads to drifts in the displacements similar to those found in processing real recordings. These effects decrease in importance as the resolution of the ADC process increases.

  17. Methoxylated polybrominated diphenyl ethers (MeO-PBDEs) are major contributors to the persistent organobromine load in sub-Arctic and Arctic marine mammals, 1986-2009.

    PubMed

    Rotander, Anna; van Bavel, Bert; Rigét, Frank; Auðunsson, Guðjón Atli; Polder, Anuschka; Gabrielsen, Geir Wing; Víkingsson, Gísli; Mikkelsen, Bjarni; Dam, Maria

    2012-02-01

    A selection of MeO-BDE and BDE congeners were analyzed in pooled blubber samples of pilot whale (Globicephala melas), ringed seal (Phoca hispida), minke whale (Balaenoptera acutorostrata), fin whale (Balaenoptera physalus), harbor porpoise (Phocoena phocoena), hooded seal (Cystophora cristata), and Atlantic white-sided dolphin (Lagenorhynchus acutus), covering a time period of more than 20 years (1986-2009). The analytes were extracted and cleaned-up using open column extraction and multi-layer silica gel column chromatography. The analysis was performed using both low resolution and high resolution GC-MS. MeO-PBDE concentrations relative to total PBDE concentrations varied greatly between sampling periods and species. The highest MeO-PBDE levels were found in the toothed whale species pilot whale and white-sided dolphin, often exceeding the concentration of the most abundant PBDE, BDE-47. The lowest MeO-PBDE levels were found in fin whales and ringed seals. The main MeO-BDE congeners were 6-MeO-BDE47 and 2'-MeO-BDE68. A weak correlation only between BDE47 and its methoxylated analog 6-MeO-BDE47 was found and is indicative of a natural source for MeO-PBDEs.

  18. Synthesis and characterization of an in situ forming hydrogel using tyramine conjugated high methoxyl gum tragacanth.

    PubMed

    Tavakol, Moslem; Vasheghani-Farahani, Ebrahim; Mohammadifar, Mohammad Amin; Soleimani, Masoud; Hashemi-Najafabadi, Sameereh

    2016-02-01

    In this study, an enzyme catalyzed in situ forming hydrogel based on tyramine conjugated high methoxyl content gum tragacanth (TA-HMGT) was prepared and characterized. TA-HMGT was synthesized via heterogeneous ammonolysis of methyl ester groups of HMGT. Then, the hydrogel was prepared via horseradish peroxidase catalyzed coupling reaction in the presence of hydrogen peroxide. Hydrogel properties, such as gelation time, swelling/degradation behavior and rheological properties could be adjusted by tuning the gelation parameters and extent of tyramine conjugation. This system was a soft elastic hydrogel with appropriate biocompatibility. The fast gelation of the hydrogel is desirable for clinical applications. Also, in vitro bovine serum albumin release from the synthesized hydrogel showed good release profile with limited burst release.

  19. Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs.

    PubMed

    Fujii, Shinya; Kano, Atsushi; Masuno, Hiroyuki; Songkram, Chalermkiat; Kawachi, Emiko; Hirano, Tomoya; Tanatani, Aya; Kagechika, Hiroyuki

    2014-09-15

    Vitamin D receptor (VDR), a nuclear receptor for 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3, 1), is a promising target for multiple clinical applications. We recently developed non-secosteroidal VDR ligands based on a carbon-containing boron cluster, 1,12-dicarba-closo-dodecaborane (p-carborane), and examined the binding of one of them to VDR by means of crystallographic analysis. Here, we utilized that X-ray structure to design novel p-carborane-based tetraol-type vitamin D analogs, and we examined the biological activities of the synthesized compounds. Structure-activity relationship study revealed that introduction of an ω-hydroxyalkoxy functionality enhanced the biological activity, and the configuration of the substituent significantly influenced the potency. Among the synthesized compounds, 4-hydroxybutoxy derivative 9a exhibited the most potent activity, which was equal to that of the secosteroidal vitamin D analog, 19-nor-1α,25-dihydroxyvitamin D3 (2). Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Glycosaminoglycan backbone is not required for the modulation of hemostasis: effect of different heparin derivatives and non-glycosaminoglycan analogs.

    PubMed

    Bouças, Rodrigo I; Jarrouge-Bouças, Thais R; Lima, Marcelo A; Trindade, Edvaldo S; Moraes, Fabio A; Cavalheiro, Renan P; Tersariol, Ivarne L S; Hoppenstead, Debra; Fareed, Jawed; Nader, Helena B

    2012-06-01

    Heparin and its derivatives are known to regulate a variety of pathophysiological events related to vascular biology. In the present manuscript we examine a variety of heparinomimetics biochemically (electrophoretic behavior and enzymatic degradation) and pharmacologically (in vitro anticoagulant activity and in vivo hemorrhagic and antithrombotic tests) as well as their interactions with cells from the vessel wall using a time resolved fluorometric method and confocal microscopy. Data were determined for unfractionated heparin (UFH), enoxaparin, synthetic heparin pentasaccharide, C3 heparin derived oligosaccharides and phosphosulfomannan (PI-88). While being structurally distinct from UFH, all compounds exhibited anticoagulant, antithrombotic and hemorrhagic activities. In addition, besides the pentasaccharide, they all stimulated the synthesis of an antithrombotic heparan sulfate present at the cell surface and secreted by endothelial cells. Also, like UFH, they interacted with both endothelial and smooth muscle cells and dislodged UFH from its binding sites in a dose dependent manner but, with distinct saturable curves showing that the binding of polymeric structures to extracellular matrix (ECM) proteins does not depend on a glycosaminoglycan backbone. The data also suggest a common pathway, which does not depend on the presence of the conventionally accepted antithrombin binding pentasaccharide, for ECM dependent activity of the heparinomimetic stimulated synthesis of antithrombotic heparan sulfate. Notably, although of similar molecular weight as well as polymeric backbone, the synthetic heparin pentasaccharide showed significant hemorrhagic action and negligible antithrombotic activity in a venous thrombosis model, contrasting with C3, that displayed negligible hemorrhagic effect and potent antithrombotic action. These results provide evidence that structurally unrelated polymers can elicit similar hemostatic activities and show that polymeric sequence is

  1. Derivation of the Statistical Distribution of the Mass Peak Centroids of Mass Spectrometers Employing Analog-to-Digital Converters and Electron Multipliers

    DOE PAGES

    Ipsen, Andreas

    2017-02-03

    Here, the mass peak centroid is a quantity that is at the core of mass spectrometry (MS). However, despite its central status in the field, models of its statistical distribution are often chosen quite arbitrarily and without attempts at establishing a proper theoretical justification for their use. Recent work has demonstrated that for mass spectrometers employing analog-to-digital converters (ADCs) and electron multipliers, the statistical distribution of the mass peak intensity can be described via a relatively simple model derived essentially from first principles. Building on this result, the following article derives the corresponding statistical distribution for the mass peak centroidsmore » of such instruments. It is found that for increasing signal strength, the centroid distribution converges to a Gaussian distribution whose mean and variance are determined by physically meaningful parameters and which in turn determine bias and variability of the m/z measurements of the instrument. Through the introduction of the concept of “pulse-peak correlation”, the model also elucidates the complicated relationship between the shape of the voltage pulses produced by the preamplifier and the mean and variance of the centroid distribution. The predictions of the model are validated with empirical data and with Monte Carlo simulations.« less

  2. Protective effect of p-methoxyl-diphenyl diselenide in lethal acute liver failure induced by lipopolysaccharide and D-galactosamine in mice.

    PubMed

    Wilhelm, E A; Jesse, C R; Nogueira, C W

    2009-12-01

    Organoselenium compounds display important antioxidant activity and many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the hepatoprotective effect of p-methoxyl-diphenyl diselenide, a disubstituted diaryl diselenide, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. The animals received p-methoxyl-diphenyl diselenide (10, 50 and 100 mg/kg; per oral, p.o.) and 1 h after d-GalN (500 mg/kg) and LPS (50 microg/kg) were administered by intraperitoneal route (i.p.). Twenty-four hours after LPS/d-GalN exposure the animals were euthanized to the biochemical and histological analysis. Pretreatment with p-methoxyl-diphenyl diselenide (50 and 100 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by LPS/d-GalN exposure in mice. p-Methoxyl-diphenyl diselenide at the doses of 50 and 100 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by LPS/D-GalN exposure. In this study, no alteration in ascorbic acid levels was observed in livers of mice exposed to LPS/D-GalN. Glutathione-S-transferase (GST) activity was stimulated by LPS/D-GalN exposure and p-methoxyl-diphenyl diselenide, at all doses, protected against this alteration. p-Methoxyl-diphenyl diselenide was effective in ameliorating inhibition of catalase activity induced by LPS/d-GalN exposure. Histological data showed that sections of livers from LPS/D-GalN-treated mice presented massive hemorrhage, inflammatory cells and necrosis. p-Methoxyl-diphenyl diselenide significantly attenuated LPS/D-GalN-induced hepatic histopathological alterations. Based on the results, we suggest the hepatoprotective effect of p-methoxyl-diphenyl diselenide on acute liver injury induced by LPS/d-GalN exposure in mice.

  3. Cytocompatibility of novel extracellular matrix protein analogs of biodegradable polyester polymers derived from α-hydroxy amino acids.

    PubMed

    Lecht, Shimon; Cohen-Arazi, Naomi; Cohen, Gadi; Ettinger, Keren; Momic, Tatjana; Kolitz, Michal; Naamneh, Majdi; Katzhendler, Jehoshua; Domb, Abraham J; Lazarovici, Philip; Lelkes, Peter I

    2014-01-01

    One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, (1)H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering.

  4. Methoxylated Flavones from Salvia Mirzayanii Rech. f. and Esfand with Immunosuppressive Properties

    PubMed Central

    Ayatollahi, Abdul Majid; Ghanadian, Mustafa; Att-ur-Rahman, Rahman; Mesaik, M. Ahmed; Khalid, Ahmad Shukralla; Adeli, Fateme

    2015-01-01

    Aerial parts of Salvia Mirzayanii was extracted with methanol. Methanol extract was suspended in water and defatted with petroleum ether. The defatted part was then partitioned between ethyl acetate and water. The ethyl acetate partition was chromatographed on a silica gel column to afford several fractions. Lymphocyte proliferation inhibitory assay of the resulted fractions was compared in-vitro and the fraction with more immunosuppressive activity was subjected to more purification to yield three methoxylated flavones: 5,7-dihydroxy,6,4’– dimethoxyflavone(1), 5-hydroxy,6,7,3’,4’–tetramethoxyflavone(2) and 5,3’-dihydroxy,6,7,4’– trimethoxyflavone (3). Compounds 2 and 3 potently suppressed the proliferation of human blood lymphocytes with IC50 values of 1.3 ± 0.04 μg/mL and 1.3 ± 0.21 μg/mL in comparison with prednisolone as one of the lymphocyte suppressor drugs (IC50=1.45 ± 0.6 μg/mL). In phagocyte chemiluminescence assay, compounds 1 and 3 in peripheral mononuclear cells (PMNCs) exerted suppressive moderate activity against ROS with IC50 of 55.3 ± 0.4 and 36.2 ± 0.7 μg/mL, respectively, while compound 2 showed weak activity with IC50 values more than 100 μg/mL. In conclusion, compounds 2 and 3 have a similar suppressive effect more than compound 1 on PHA-activated lymphocyte proliferation, which might be because of their C-3’ oxidation pattern of ring B. It is indicated that the presence of 3’-OH or 3’-OMe in flavone ring B, caused more anti-proliferation activity than 3’-H. Oxidative burst assay showed more activity for compound 1 which is less methoxylated than others. It also showed more activity for compounds 3 than 2, which differ only in 3’-OH instead of 3’-OMe. PMID:26330886

  5. Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure.

    PubMed

    Moghaddam, Ghazaal; Ebrahimi, Soltan Ahmad; Rahbar-Roshandel, Nahid; Foroumadi, Alireza

    2012-07-01

    Dracocephalum kotschyi Boiss. has been used as part of an ethnobotanical remedy against many forms of human cancer in Iran. It has been demonstrated that a flavonoid named xanthomicrol from D. kotschyi contributes to its preferential antiproliferative activity against malignant cells. In the present study, the antiproliferative activity of its flavonoid fraction was further characterized. Using liquid-liquid extraction and a semi-preparative reversed-phase HPLC method, eight flavonoid aglycones were isolated from the aerial parts of the plant and their identities were confirmed through MS and NMR analyses as luteolin, naringenin, apigenin, isokaempferide, cirsimaritin, penduletin, xanthomicrol and calycopterin. The in vitro antiproliferative activity of each compound was evaluated against a panel of established normal and malignant cell lines using the MTT assay and some structure-activity relationships were observed. The hydroxyflavones (luteolin, apigenin and isokaempferide) exerted comparable antiproliferative activities against malignant and normal cells, while the methoxylated hydroxyflavones (cirsimaritin, penduletin, xanthomicrol and calycopterin) showed preferential activities against tumor cells. This activity may be of value in treating tumors as it would exert few side effects in normal tissues. Xanthomicrol selectively inhibited the growth of human gastric adenocarcinoma, while calycopterin selectively prevented human acute promyelocytic leukemia and human colon carcinoma cells proliferation.

  6. Antiproliferative activity of three methoxylated flavonoids isolated from Zeyheria montana Mart. (Bignoniaceae) leaves.

    PubMed

    Seito, Leonardo Noboru; Ruiz, Ana Lucia Tasca Goiz; Vendramini-Costa, Debora; Tinti, Sirlene Valério; de Carvalho, João Ernesto; Bastos, Jairo Kenupp; Di Stasi, Luiz Claudio

    2011-10-01

    The present study isolated three major active flavonoids, two flavones named 4',5,7-trimethoxy-luteolin (1) and 6-hydroxy-5,7-dimethoxyflavone (2) and the flavanone 5-hydroxy-6,7-dimethoxyflavanone (3) from Zeyheria montana dichloromethane leaf extract. Isolation and purification were conducted with the application of column chromatography and structures were assigned by spectral analysis. All compounds were evaluated for cytotoxic activities against human tumor cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-ADR/RES (breast expressing phenotype multiple drug resistance), 786-0 (renal), NCI-H460 (lung, non-small cells), PC-3 (prostate), OVCAR-3 (ovarian), HT-29 (colon) and K562 (leukemia) in vitro. All compounds were active in different degrees on several tumor cell lines and flavanone 3 showed cytotoxicity against almost all cell lines, particularly against human NCI-ADR/RES and K562 cell lines. In conclusion, three antiproliferative compounds were isolated for the first time from Zeyheria montana and its leaves were characterized as an important source of methoxylated flavones and flavanone as potential antitumor compounds. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Determination and prediction of octanol-air partition coefficients of hydroxylated and methoxylated polybrominated diphenyl ethers.

    PubMed

    Zhao, Hongxia; Xie, Qing; Tan, Feng; Chen, Jingwen; Quan, Xie; Qu, Baocheng; Zhang, Xin; Li, Xiaona

    2010-07-01

    The octanol-air partition coefficient (K(OA)) of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and 10 methoxylated polybrominated diphenyl ethers (MeO-PBDEs) were measured as a function of temperature using a gas chromatographic retention time technique. At room temperature (298.15K), log K(OA) ranged from 8.30 for monobrominated OH/MeO-PBDEs to 13.29 for hexabrominated OH/MeO-PBDEs. The internal energies of phase change from octanol to air (Delta(OA)U) for 29 OH/MeO-PBDE congeners ranged from 72 to 126 kJ mol(-1). Using partial least-squares (PLS) analysis, a statistically quantitative structure-property relationship (QSPR) model for logK(OA) of OH/MeO-PBDE congeners was developed based on the 16 fundamental quantum chemical descriptors computed by PM3 Hamiltonian, for which the Q(cum)(2) was about 0.937. The molecular weight (Mw) and energy of the lowest unoccupied molecular orbital (E(LUMO)) were found to be main factors governing the log K(OA).

  8. Climatic interpretation of tree-ring methoxyl d2H time-series from a central alpine larch forest

    NASA Astrophysics Data System (ADS)

    Riechelmann, Dana F. C.; Greule, Markus; Siegwolf, Rolf T. W.; Esper, Jan; Keppler, Frank

    2017-04-01

    We measured stable hydrogen isotope ratios of lignin methoxyl groups (d2HLM) in high elevation larch trees (Larix decidua Mill.) from the Simplon Valley in southern Switzerland. Thirty-seven larch trees were sampled and five individuals analysed for their d2HLM values at annual (1971-2009) and pentadal resolution (1746-2009). Testing the climate response of the d2HLM series, the annually resolved series show a positive correlation of r = 0.60 with June/July precipitation and weaker but negative correlation with June/July temperature. In addition, a negative correlation with June-August d2H in precipitation of the nearby GNIP station in Locarno is observed. The pentadally resolved d2HLM series show no significant correlation to climate parameters. The positive correlation of the annually resolved data to summer precipitation is uncommon to d2H measurements from tree-rings (Feakins et al., 2013; Helle and Schleser, 2004; McCarroll and Loader, 2004; Mischel et al., 2015; White et al., 1994). However, we explain the positive association with warm season hydroclimate as follows: methoxyl groups of lignin are directly formed from tissues in the xylem water. More precipitation during June and July, which are on average relatively dry month, results in higher d2H values of the xylem water and therefore, higher d2H value in the lignin methoxyl groups. Therefore, we suggest that d2HLM values of high elevation larch trees might likely serve as a summer precipitation proxy. References: Feakins, S.J., Ellsworth, P.V., Sternberg, L.d.S.L., 2013. Lignin methoxyl hydrogen isotope rations in a coastal ecosystem. Geochimica et Cosmochimica Acta, 121: 54-66. Helle, G., Schleser, G.H., 2004. Interpreting Climate Proxies from Tree-rings. In: Fischer, H., Floeser, G., Kumke, T., Lohmann, G., Miller, H., Negendank, J.F.W., et al., editors. The Climate in Historical Times. Springer Berlin Heidelberg, pp. 129-148. McCarroll, D., Loader, N.J., 2004. Stable isotopes in tree rings. Quaternary

  9. Comparison of the growth promoting activities and toxicities of various auxin analogs on cells derived from wild type and a nonrooting mutant of tobacco

    SciTech Connect

    Caboche, M.; Muller, J.F. ); Chanut, F. ); Aranda, G.; Cirakoglu, S. )

    1987-01-01

    A naphthaleneacetic acid tolerant mutant isolated from a mutagenized culture of tobacco mesophyll protoplasts and impaired in root morphogenesis has been previously characterized by genetic analysis. To understand the biochemical basis for naphthaleneacetic acid resistance, cells derived from this mutant and from wild-type tobacco were compared for their ability to respond to various growth regulators. The growth promoting abilities and cytotoxicities of auxin analogs were different for mutant and wild-type cells. These different activities were not correlated with increased rate of conjugation or breakdown of the auxins by mutant cells. These observations, as well as previous studies on the interaction of the mutant with Agrobacterium, suggest that mutant resistance to auxins is not a result of a specific modification of the process by which auxins induce cell killing, but to a more general alteration of the cellular response to auxin. A screening of auxin-related molecules which induce cell death in wild-type cells but not mutant cells without promoting growth in either was performed. p-Bromophenyleacetic acid was found to display these characteristics.

  10. Immunosuppressive Effects of Natural α,β-Unsaturated Carbonyl-Based Compounds, and Their Analogs and Derivatives, on Immune Cells: A Review

    PubMed Central

    Arshad, Laiba; Jantan, Ibrahim; Bukhari, Syed Nasir Abbas; Haque, Md. Areeful

    2017-01-01

    The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over activity or abnormally low activity of the immune cells resulting in autoimmune or immune deficiency diseases. Compounds containing α,β-unsaturated carbonyl-based moieties are often reactive. The reactivity of these groups is responsible for their diverse pharmacological activities, and the most important and widely studied include the natural compounds curcumin, chalcone, and zerumbone. Numerous studies have revealed the mainly immunosuppressive and anti-inflammatory activities of the aforesaid compounds. This review highlights the specific immunosuppressive effects of these natural α,β-unsaturated carbonyl-based compounds, and their analogs and derivatives on different types of immune cells of the innate (granulocytes, monocytes, macrophages, and dendritic cells) and adaptive (T cells, B cells, and natural killer cells) immune systems. The inhibitory effects of these compounds have been comprehensively studied on neutrophils, monocytes and macrophages but their effects on T cells, B cells, natural killer cells, and dendritic cells have not been well investigated. It is of paramount importance to continue generating experimental data on the mechanisms of action of α,β-unsaturated carbonyl-based compounds on immune cells to provide useful information for ensuing research to discover new immunomodulating agents. PMID:28194110

  11. Immunosuppressive Effects of Natural α,β-Unsaturated Carbonyl-Based Compounds, and Their Analogs and Derivatives, on Immune Cells: A Review.

    PubMed

    Arshad, Laiba; Jantan, Ibrahim; Bukhari, Syed Nasir Abbas; Haque, Md Areeful

    2017-01-01

    The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over activity or abnormally low activity of the immune cells resulting in autoimmune or immune deficiency diseases. Compounds containing α,β-unsaturated carbonyl-based moieties are often reactive. The reactivity of these groups is responsible for their diverse pharmacological activities, and the most important and widely studied include the natural compounds curcumin, chalcone, and zerumbone. Numerous studies have revealed the mainly immunosuppressive and anti-inflammatory activities of the aforesaid compounds. This review highlights the specific immunosuppressive effects of these natural α,β-unsaturated carbonyl-based compounds, and their analogs and derivatives on different types of immune cells of the innate (granulocytes, monocytes, macrophages, and dendritic cells) and adaptive (T cells, B cells, and natural killer cells) immune systems. The inhibitory effects of these compounds have been comprehensively studied on neutrophils, monocytes and macrophages but their effects on T cells, B cells, natural killer cells, and dendritic cells have not been well investigated. It is of paramount importance to continue generating experimental data on the mechanisms of action of α,β-unsaturated carbonyl-based compounds on immune cells to provide useful information for ensuing research to discover new immunomodulating agents.

  12. Comparison of the Growth Promoting Activities and Toxicities of Various Auxin Analogs on Cells Derived from Wild Type and a Nonrooting Mutant of Tobacco 1

    PubMed Central

    Caboche, Michel; Muller, Jean-François; Chanut, Françoise; Aranda, Gérard; C̷irakoǵlu, Sheyda

    1987-01-01

    A naphthaleneacetic acid tolerant mutant isolated from a mutagenized culture of tobacco mesophyll protoplasts and impaired in root morphogenesis has been previously characterized by genetic analysis. To understand the biochemical basis for naphthaleneacetic acid resistance, cells derived from this mutant and from wild-type tobacco were compared for their ability to respond to various growth regulators. The growth promoting abilities and cytotoxicities of auxin analogs were different for mutant and wild-type cells. These different activities were not correlated with increased rate of conjugation or breakdown of the auxins by mutant cells. These observations, as well as previous studies on the interaction of the mutant with Agrobacterium, suggest that mutant resistance to auxins is not a result of a specific modification of the process by which auxins induce cell killing, but to a more general alteration of the cellular response to auxin. A screening of auxin-related molecules which induce cell death in wild-type cells but not mutant cells without promoting growth in either was performed. p-Bromophenyleacetic acid was found to display these characteristics. Images Fig. 1 Fig. 4 PMID:16665341

  13. Synthesis and biological activities of the amide derivative of aplog-1, a simplified analog of aplysiatoxin with anti-proliferative and cytotoxic activities.

    PubMed

    Hanaki, Yusuke; Yanagita, Ryo C; Sugahara, Takahiro; Aida, Misako; Tokuda, Harukuni; Suzuki, Nobutaka; Irie, Kazuhiro

    2015-01-01

    Aplog-1 is a simplified analog of the tumor-promoting aplysiatoxin with anti-proliferative and cytotoxic activities against several cancer cell lines. Our recent findings have suggested that protein kinase Cδ (PKCδ) could be one of the target proteins of aplog-1. In this study, we synthesized amide-aplog-1 (3), in which the C-1 ester group was replaced with an amide group, to improve chemical stability in vivo. Unfortunately, 3 exhibited seventy-fold weaker binding affinity to the C1B domain of PKCδ than that of aplog-1, and negligible anti-proliferative and cytotoxic activities even at 10(-4) M. A conformational analysis and density functional theory calculations indicated that the stable conformation of 3 differed from that of aplog-1. Since 27-methyl and 27-methoxy derivatives (1, 2) without the ability to bind to PKC isozymes exhibited marked anti-proliferative and cytotoxic activities at 10(-4) M, 3 may be an inactive control to identify the target proteins of aplogs.

  14. Analog earthquakes

    SciTech Connect

    Hofmann, R.B.

    1995-09-01

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

  15. Theoretical and Analog Studies of the Effects of Nonlinear Stability Derivatives on the Longitudinal Motions of an Aircraft in Response to Step Control Deflections and to the Influence of Proportional Automatic Control

    NASA Technical Reports Server (NTRS)

    Curfman, Howard J , Jr

    1955-01-01

    Through theoretical and analog results the effects of two nonlinear stability derivatives on the longitudinal motions of an aircraft have been investigated. Nonlinear functions of pitching-moment and lift coefficients with angle of attack were considered. Analog results of aircraft motions in response to step elevator deflections and to the action of the proportional control systems are presented. The occurrence of continuous hunting oscillations was predicted and demonstrated for the attitude stabilization system with proportional control for certain nonlinear pitching-moment variations and autopilot adjustments.

  16. Polar amplification of the early Eocene indicated by δ2H values of lignin methoxyl groups of mummified wood

    NASA Astrophysics Data System (ADS)

    Anhäuser, Tobias; Hook, Benjamin; Halfar, Jochen; Greule, Markus; Keppler, Frank

    2017-04-01

    A number of well-preserved mummified wood samples have been excavated during diamond mining operations in early Eocene (55-50 Ma) kimberlite deposits located near the Arctic Circle (64° N, 110° W) in the Canadian Northwest Territories. The preserved wood, containing multi-decadal length tree-ring information, therefore allows the reconstruction of an unprecedented snapshot of terrestrial high-latitude climate during the early Eocene. Here we used wood-derived stable hydrogen isotopes (δ2H) as proxy for paleoclimatic interpretations. While cellulose extractions are commonly used for the analysis of modern wood-derived δ2H values, the mummified wood samples had been affected by selective degradation leading to a strong or even complete loss of cellulose while leaving a lignin-rich material behind. We have therefore analyzed δ2H values of the lignin methoxyl groups that have previously been shown to reflect the δ2H values of the local precipitation and can thus be used to infer paleoclimate information such as temperature changes. We applied this proxy to specimens found in three adjacent kimberlite pipes (30 km apart) which represent a range of early Eocene ages (Rb/Sr dating: 55.5 ± 0.7, 55.2 ± 0.3 and 53.3 ± 0.6 Ma [2σ standard deviation]). The δ2H values were measured at annual resolution for the three mummified wood series (length of individual time series: 82, 62 and 40 years) and the mean δ2H value of precipitation for the three decadal-scale time slices was reconstructed. Finally, we used existing relationships between early Eocene temperatures and stable isotopes in precipitation to quantify temperature changes. Warming phases such as the one covered here (culminating in the Early Eocene Climatic Optimum [52 to 50 Ma]) are commonly accompanied by a stronger increase in arctic/subarctic surface air temperatures in comparison to the global average (the ratio of these temperature differences is referred to as the polar amplification). Our estimation

  17. PBDEs, hydroxylated PBDEs and methoxylated PBDEs in bivalves from Beijing markets.

    PubMed

    Liu, Xitao; Jiao, Ying; Lin, Chunye; Sun, Ke; Zhao, Ye

    2014-09-01

    The structural analogues of polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs) and methoxylated PBDEs (MeO-PBDEs) have been attracting increasing concern in recent years. Five bivalve species (blue mussel, short-necked clam, surf clam, ark shell and razor clam) were collected from Beijing markets, and the concentrations of seven PBDEs, four OH-PBDEs and fourteen MeO-PBDEs in the bivalves were measured. The seasonal variations of these three types of polybrominated compound in blue mussels were also monitored. The results indicate that the levels of ΣPBDEs in this study were comparable to those in short-necked clams from Liaodong Bay, China, with BDE47 as the dominant congener. For the ortho-MeO-PBDEs, 6-MeO-BDE47 was found at higher concentrations than the others, while for the meta- and para-MeO-PBDEs, 4'-MeO-BDE17 was found at higher concentrations. 6-OH-BDE-47 was the most abundant congener among the 4 measured OH-PBDEs, followed by 6-OH-BDE-137 and 6-OH-BDE-85. The levels of OH-PBDEs and MeO-PBDEs in bivalves from Beijing markets were much lower than the corresponding compounds in blue mussels from the Baltic Sea. In the blue mussels collected in April, June and September of 2012, apparent seasonal variations were observed for these three types of polybrominated compounds, but the acidic components displayed different trends from the neutral components, with PBDEs and MeO-PBDEs showing the highest concentrations in June, while OH-PBDEs had the lowest concentrations in June. This difference in seasonal variations between the neutral components and the acidic components may be explained by their different sources and transformation/elimination mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A Gas-Liquid Chromatographic Examination of Stilbene Derivatives

    Treesearch

    Richard W. Hemingway; W. E. Hillis; K Burerton

    1970-01-01

    Trimethylsilyl ether derivatives of twenty hydroxystilbenes were separated by gas-liquid chromatography on Apiezon-L, OV-1, OV-17, and SE-54. Relative retention times were highly dependent upon the degree of hydroxylation and methoxylation, the positions of these groups and on cis-trans...

  19. Triptycene analogs

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  20. Synthesis and structure-activity relationships of novel lincomycin derivatives. Part 4: synthesis of novel lincomycin analogs modified at the 6- and 7-positions and their potent antibacterial activities.

    PubMed

    Wakiyama, Yoshinari; Kumura, Ko; Umemura, Eijiro; Ueda, Kazutaka; Watanabe, Takashi; Yamada, Keiko; Okutomi, Takafumi; Ajito, Keiichi

    2017-07-01

    To modify lincomycin (LCM) at the C-6 and the C-7 positions, we firstly prepared various substituted proline intermediates (7, 11-15 and 17). These proline intermediates were coupled with methyl 1-thio-α-lincosamide and tetrakis-O-trimethylsilylation followed by selective deprotection of the TMS group at the 7-position gave a wide variety of key intermediates (23-27, 47 and 50). Then, we synthesized a variety of novel LCM analogs modified at the 7-position in application of the Mitsunobu reaction, an SN2 reaction, and a Pd-catalyzed cross-coupling reaction. Compounds 34 and 35 (1'-NH derivatives) exhibited enhanced antibacterial activities against resistant pathogens with erm gene compared with the corresponding 1'-N-methyl derivatives (3 and 37). On the basis of reported SAR, we modified the 4'-position of LCM derivatives possessing a 5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl group at the C-7 position. Compound 56 showed significantly potent antibacterial activities against S. pneumoniae and S. pyogenes with erm gene, and its activities against S. pneumoniae with erm gene were improved compared with those of 34 and 57. Although we synthesized novel analogs by transformation of a C-7 substituent focusing on the 1'-demethyl framework to prepare very potent analogs 73 and 75, it was impossible to generate novel derivatives exhibiting stronger antibacterial activities against S. pneumoniae with erm gene compared with 56.

  1. 99mTc-HYNIC-TNF analogs (WH701) derived from phage display peptide libraries for imaging TNF-receptor-positive ovarian carcinoma: preclinical evaluation

    NASA Astrophysics Data System (ADS)

    Xiang, Yan; Xia, Jinsong; Wu, H.; Li, H. F.

    2002-04-01

    Radiolabeled bioactive peptides which bind specifically to surface receptors over expressed in tumor cells are considered as alternatives for tumor detection with ECT. In this investigation, 99mTc-hydrazinonicotinyl - TNF analogs (WH701) was labeled using ethylenediaminediacetic acid (EDDA) as coligand (a number of TNF analogs had been selected and synthesized using random phage-display peptides library in our lab) and Pharmacokinetics and feasibility studies were performed.

  2. 5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

    PubMed Central

    Wu, Lei; Li, Xueqin; Wu, Haifeng; Long, Wei; Jiang, Xiaojian; Shen, Ting; Qiang, Qian; Si, Chuanling; Wang, Xinfeng; Jiang, Yunyao; Hu, Weicheng

    2016-01-01

    For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases. PMID:26938526

  3. The use of J-coupling as a sole criterion to assign the total absolute stereochemistry of new pyrrolidinone class synthetic analogs, derived from S-pyroglutamic acid

    NASA Astrophysics Data System (ADS)

    Kellici, Tahsin F.; Ntountaniotis, Dimitrios; Vanioti, Marianna; Golic Grdadolnik, Simona; Simcic, Mihael; Michas, Georgios; Moutevelis-Minakakis, Panagiota; Mavromoustakos, Thomas

    2017-02-01

    During the synthesis of new pyrrolidinone analogs possessing biological activity it is intriguing to assign their absolute stereochemistry as it is well known that drug potency is influenced by the stereochemistry. The combination of J-coupling information with theoretical results was used in order to establish their total stereochemistry when the chiral center of the starting material has known absolute stereochemistry. The J-coupling can be used as a sole criterion for novel synthetic analogs to identify the right stereochemistry. This approach is extremely useful especially in the case of analogs whose 2D NOESY spectra cannot provide this information. Few synthetic examples are given to prove the significance of this approach.

  4. Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives.

    PubMed

    Leong, Sze Wei; Mohd Faudzi, Siti Munirah; Abas, Faridah; Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Lam, Kok Wai; Abdul Bahari, Mohd Nazri; Ahmad, Syahida; Tham, Chau Ling; Shaari, Khozirah; Lajis, Nordin H

    2015-08-15

    A series of twenty-four 2-benzoyl-6-benzylidenecyclohexanone analogs were synthesized and evaluated for their nitric oxide inhibition and antioxidant activity. Six compounds (3, 8, 10, 17, 18 and 19) were found to exhibit significant NO inhibitory activity in LPS/IFN-induced RAW 264.7 macrophages, of which compound 10 demonstrated the highest activity with the IC50 value of 4.2 ± 0.2 μM. Furthermore, two compounds (10 and 17) displayed antioxidant activity upon both the DPPH scavenging and FRAP analyses. However, none of the 2-benzoyl-6-benzylidenecyclohexanone analogs significantly scavenged NO radical. Structure-activity comparison suggested that 3,4-dihydroxylphenyl ring is crucial for bioactivities of the 2-benzoyl-6-benzylidenecyclohexanone analogs. The results from this study and the reports from previous studies indicated that compound 10 could be a candidate for further investigation on its potential as a new anti-inflammatory agent.

  5. Transformation of hydroxylated and methoxylated 2,2',4,4',5-brominated diphenyl ether (BDE-99) in plants.

    PubMed

    Pan, Lili; Sun, Jianteng; Wu, Xiaodan; Wei, Zi; Zhu, Lizhong

    2016-11-01

    The occurrence and fate of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) have received significant attention. However, there is limited information on the metabolism relationship between OH-pentaBDEs and MeO-pentaBDEs that were frequently detected with relatively high concentrations in the environment. In this study, the biotransformation between OH-BDE-99 and MeO-BDE-99 was investigated in rice, wheat, and soybean plants. All the three plants can metabolize OH-BDE-99 to corresponding homologous methoxylated metabolites, while the transformation from MeO-BDE-99 to OH-BDE-99 could only be found in soybean. The conversion of parent compounds was the highest in soybean, followed by wheat and rice. Transformation products were found mainly in the roots, with few metabolites being translocated to the shoots and solution after exposure. The results of this study provide valuable information for a better understanding of the accumulation and transformation of OH-PBDEs and MeO-PBDEs in different plants. Copyright © 2016. Published by Elsevier B.V.

  6. Analogy, explanation, and proof

    PubMed Central

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

    2014-01-01

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

  7. Analogy, explanation, and proof.

    PubMed

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

    2014-01-01

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

  8. Cannabinoid properties of methylfluorophosphonate analogs.

    PubMed

    Martin, B R; Beletskaya, I; Patrick, G; Jefferson, R; Winckler, R; Deutsch, D G; Di Marzo, V; Dasse, O; Mahadevan, A; Razdan, R K

    2000-09-01

    Methylarachidonylfluorophosphonate (MAFP) and related analogs have been shown to inhibit fatty acid amidohydrolase activity (FAAH), the enzyme responsible for hydrolysis of the endogenous cannabinoid ligand anandamide. To fully characterize this class of compounds, methylfluorophosphonate compounds with saturated alkyl chains ranging from C8 to C20 along with C20 unsaturated derivatives were synthesized and evaluated for their ability to interact with the CB1 receptor, inhibit FAAH, and produce in vivo pharmacological effects. These analogs demonstrated widely varying affinities for the CB1 receptor. Of the saturated compounds, C8:0 was incapable of displacing [(3)H]CP 55,940 binding, whereas C12:0 exhibited high affinity (2.5 nM). The C20:0 saturated analog had low affinity (900 nM), but the introduction of unsaturation into the C20 analogs restored receptor affinity. However, none of the analogs were capable of fully displacing [(3)H]CP 55,940 binding. On the other hand, all compounds were able to completely inhibit FAAH enzyme activity, with the C20:0 analog being the least potent. The most potent FAAH inhibitor was the short-chained saturated C12:0, whereas the other analogs were 15- to 30-fold less potent. In vivo, the C8:0 and C12:0 analogs were highly potent and fully efficacious in producing tetrahydrocannabinol (THC)-like effects, whereas the other analogs were either inactive or acted as partial agonists. None was capable of attenuating the agonist effects of THC. Conversely, the C20:0 analog potentiated the effects of anandamide but not those of 2-arachidonoyl-glycerol and THC. The high in vivo potency of the novel short-chain saturated MAFP derivatives (C8:0 and C12:0) underscores the complexity of manipulating the endogenous cannabinoid system.

  9. A chemical analog of curcumin as an improved inhibitor of amyloid Abeta oligomerization.

    PubMed

    Orlando, Robert A; Gonzales, Amanda M; Royer, Robert E; Deck, Lorraine M; Vander Jagt, David L

    2012-01-01

    Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6

  10. Climate signal in d13C of wood lignin methoxyl groups from high-elevation alpine larch trees

    NASA Astrophysics Data System (ADS)

    Reichelmann, Dana; Greule, Markus; Treydte, Kerstin; Keppler, Frank; Esper, Jan

    2015-04-01

    Tree-rings of high alpine larch trees (Larix decidua) were investigated by a recently established method that measures d13C values of the wood lignin methoxyl groups (Greule et al. 2009). The resulting d13C time series were tested for their potential as a climate proxy. For this 37 larch trees were sampled at the tree line near Simplon Village (Southern Switzerland). They were analysed for their tree-ring width (TRW) and from five individuals d13C of the wood lignin methoxyl groups (d13Cmethoxyl) were measured at annual resolution from 1971-2009 and at pentadal resolution from 1747-2009. The d13Cmethoxyl chronologies were corrected for the anthropogenic change in atmospheric CO2 concentration and its decreasing d13C value. Further, the physiological response of the trees to these atmospheric changes was corrected using the flexible correction factor approach of Treydte et al. (2009), which minimise the residuals with the target climate data. This approach results in the highest so far reported correction factors of 0.032 - 0.036‰/ppmv CO2, which are explained by a low water-use efficiency of deciduous larch. The climate response of the new d13Cmethoxyl proxy shows a significant correlation of 0.75 for the annually and 0.87 for the pentadally resolved data with June to August temperatures. TRW shows also significant correlations with June to August temperatures, but they are lower than the correlations observed for the d13Cmethoxyl chronologies. These results indicate the potential of d13Cmethoxyl chronologies as a summer temperature proxy from high-elevation alpine trees with an even stronger signal than reported from earlier published tree-ring width and maximum latewood density temperature reconstructions. References: Greule, M., Mosandl, A., Hamilton, J.T.G., Keppler, F., 2009. A simple rapid method to precisely determine 13C/12C ratios of plant methoxyl groups. Rapid Communications in Mass Spectrometry, 23(11): 1710-1714. Treydte, K.S., Frank, D.C., Saurer, M

  11. Biotoxicity of Mars soils: 2. Survival of Bacillus subtilis and Enterococcus faecalis in aqueous extracts derived from six Mars analog soils

    NASA Astrophysics Data System (ADS)

    Schuerger, Andrew C.; Ming, Doug W.; Golden, D. C.

    2017-07-01

    The search for an extant microbiota on Mars depends on exploring sites that contain transient or permanent liquid water near the surface. Examples of possible sites for liquid water may be active recurring slope lineae (RSL) and fluid inclusions in ice or salt deposits. The presence of saline fluids on Mars will act to depress the freezing points of liquid water to as low as ‒60 °C, potentially permitting the metabolism and growth of halophilic microorganisms to temperatures significantly below the freezing point of pure water at 0 °C. In order to predict the potential risks of forward contamination by Earth microorganisms to subsurface sites on Mars with liquid brines, experiments were designed to characterize the short-term survival of two bacteria in aqueous soil solutions from six analog soils. The term ''soil'' is used here to denote any loose, unconsolidated matrix with no implications for the presence or absence of organics or biology. The analog soils were previously described (Schuerger et al., 2012, Planetary Space Sci., 72, 91-101), and represented crushed Basalt (benign control), Salt, Acid, Alkaline, Aeolian, and Phoenix analogs on Mars. The survival rates of spores of Bacillus subtilis and vegetative cells of Enterococcus faecalis were tested in soil solutions from each analog at 24, 0, or ‒70 °C for time periods up to 28 d. Survival of dormant spores of B. subtilis were mostly unaffected by incubation in the aqueous extracts of all six Mars analogs. In contrast, survival rates of E. faecalis cells were suppressed by all soil solutions when incubated at 24 °C but improved at 0 and ‒70 °C, except for assays in the Salt and Acid soil solutions in which most cells were killed. Results suggest that Earth microorganisms that form spores may persist in liquid brines on Mars better than non-spore forming species, and thus, spore-forming species may pose a potential forward contamination risk to sites with liquid brines.

  12. Producing and Recognizing Analogical Relations

    PubMed Central

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  13. Neural Analog Information Processing

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1982-07-01

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

  14. Pyrimidine non-nucleoside analogs: A direct synthesis of a novel class of N-substituted amino and N-sulfonamide derivatives of pyrimidines.

    PubMed

    Elgemeie, Galal H; Salah, Ali M; Abbas, Nermeen S; Hussein, Hoda A; Mohamed, Reham A

    2017-03-04

    A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides. The scope and limitation of the method are demonstrated. The antibacterial and antifungal activities of the synthesized compounds were also evaluated.

  15. The potential toxicological insights about the anti-HIV drug azidothymidine-derived monoselenides in human leukocytes: Toxicological insights of new selenium-azidothymidine analogs.

    PubMed

    Mariano, Doc; de Souza, D; Meinerz, D F; Allebrandt, J; de Bem, A F; Hassan, W; Rodrigues, Oed; da Rocha, Jbt

    2017-09-01

    Acquired immunodeficiency syndrome (AIDS) is a worldwide disease characterized by impairments of immune function. AIDS can be associated with oxidative stress (OS) that can be linked to selenium (Se) deficiency. Se is fundamental for the synthesis of selenoproteins, such as glutathione peroxidase and thioredoxin reductase. These enzymes catalyze the decomposition of reactive oxygen species and contribute to maintain equilibrium in cell redox status. Literature data indicate that organoselenium compounds, such as ebselen and diphenyl diselenide, have antioxidant properties in vitro and in vivo models associated with OS. Nevertheless, selenocompounds can also react and oxidize thiols groups, inducing toxicity in mammals. Here, we tested the potential cytotoxic and genotoxic properties of six analogs of the prototypal anti-HIV drug azidothymidine (AZT) containing Se (5'-Se-(phenyl)zidovudine; 5'-Se-(1,3,5-trimethylphenyl)zidovudine; 5'-Se-(1-naphtyl)zidovudine; 5'-Se-(4-chlorophenyl)zidovudine) (C4); 5'-Se-(4-methylphenyl)zidovudine (C5); and 5'-(4-methylbenzoselenoate)zidovudine). C5 increased the rate of dithiothreitol oxidation (thiol oxidase activity) and C2-C4 and C6 (at 100 µM) increased DNA damage index (DI) in human leukocytes. Moreover, C5 (200 µM) decreased human leukocyte viability to about 50%. Taken together, these results indicated the low in vitro toxicity in human leukocytes of some Se-containing analogs of AZT.

  16. A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products.

    PubMed

    Uchiyama, Nahoko; Shimokawa, Yoshihiko; Kikura-Hanajiri, Ruri; Demizu, Yosuke; Goda, Yukihiro; Hakamatsuka, Takashi

    Six new psychoactive substances were identified together with two other substances (compounds 1-8) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4-fluorobenzyl)-N-(naphthalen-1-yl)-1H-indole-3-carboxamide, 2], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 (1). Two 2H-indazole isomers of synthetic cannabinoids, AB-CHMINACA 2H-indazole analog (3) and NNEI 2H-indazole analog (4), were newly identified with 1H-indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N-(naphthalen-1-yl) carbamate (5) and isobutyl 1-pentyl-1H-indazole-3-carboxylate (6) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1H-indazole. A phenethylamine derivative, N-OH-EDMA [N-hydroxy-3,4-ethylenedioxy-N-methylamphetamine, 7], and a cathinone derivative, dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively.

  17. Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

    PubMed Central

    Hiesinger, William; Perez-Aguilar, Jose Manuel; Atluri, Pavan; Marotta, Nicole A.; Frederick, John R.; Fitzpatrick, J. Raymond; McCormick, Ryan C.; Muenzer, Jeffrey R.; Yang, Elaine C.; Levit, Rebecca D.; Yuan, Li-Jun; MacArthur, John W.; Saven, Jeffery G.; Woo, Y. Joseph

    2014-01-01

    BACKGROUND After ischemic injury, cardiac secretion of the potent endothelial progenitor stem cell (EPC) chemokine SDF stimulates endogenous neovascularization and myocardial repair, a process insufficiently robust to repair major infarcts. Experimentally, exogenous administration of recombinant SDF enhances neovasculogenesis and cardiac function after MI. However, SDF has a short half-life, is bulky, and very expensive. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS and RESULTS Protein structure model was used to engineer an SDF polypeptide analog (ESA) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. EPCs in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared to both SDF and control gradients (ESA 567±74 cells/HPF vs SDF 438±46 p=0.037; vs Control 156±45 p=0.001). EPC receptor activation was evaluated by quantifying phosphorylated AKT. ESA had significantly greater pAKT levels than SDF and control (1.64±0.24 vs 1.26±0.187, p=0.01; vs. 0.95±0.08, p<0.001). Angiogenic growth factor assays revealed a distinct increase in Angiopoietin-1 expression in the ESA and SDF treated hearts. Also, CD-1 mice (n=30) underwent LAD ligation and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in EF, CO, SV, and Fractional Area Change (FAC) in mice treated with ESA when compared to controls and significant improvement in FAC when compared to SDF treated

  18. 17(R),18(S)-Epoxyeicosatetraenoic Acid, A Potent Eicosapentaenoic Acid (EPA)-Derived Regulator of Cardiomyocyte Contraction: Structure-Activity Relationships and Stable Analogs

    PubMed Central

    Falck, John R.; Wallukat, Gerd; Puli, Narender; Goli, Mohan; Arnold, Cosima; Konkel, Anne; Rothe, Michael; Fischer, Robert; Müller, Dominik N.; Schunck, Wolf-Hagen

    2011-01-01

    17(R),18(S)-Epoxyeicosatetraenoic acid [17(R),18(S)-EETeTr], a cytochrome P450 epoxygenase metabolite of eicosapentaenoic acid (EPA), exerts negative chronotropic effects and protects neonatal rat cardiomyocytes against Ca2+-overload with an EC50 ~1–2 nM. Structure-activity studies revealed a cis-Δ11,12- or Δ14,15-olefin and a 17(R),18(S)-epoxide are minimal structural elements for anti-arrhythmic activity whereas antagonist activity was often associated with the combination of a Δ14,15-olefin and a 17(S),18(R)-epoxide. Compared with natural material, the agonist and antagonist analogs are chemically and metabolically more robust and several show promise as templates for future development of clinical candidates. PMID:21591683

  19. Induction of apoptosis and inhibition of prostate and breast cancer growth by BGP-15, a new calcipotriene-derived vitamin D3 analog.

    PubMed

    Berkovich, Liron; Ben-Shabat, Shimon; Sintov, Amnon C

    2010-07-01

    The role of vitamin D3 in cancer prevention and its potential as an anticancer therapeutic agent have been researched and are well established. However, the clinical use of the natural vitamin D3 metabolite, 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol] is limited by a possible cause of hypercalcemia and hypercalciuria. A new 24-chloro calcipotriene-based vitamin D3 analog (BGP-15) was synthesized and examined for antiproliferative activity in the androgen-dependent cell lines of prostate cancer (LNCaP) and breast cancer (MCF-7). The new analog led to significant decrease in cell viability in cultured LNCaP and MCF-7 cell lines compared with calcipotriene and 1,25(OH)2D3. We observed elevated vitamin D receptor protein levels in both LNCaP and MCF-7 cells, which were treated with 5 micromol/l of 1,25(OH)2D3, calcipotriene or BGP-15 for 20 h, indicating vitamin D receptor-binding ability. Treatments of LNCaP and MCF-7 cells with 5 micromol/l BGP-15 and calcipotriene for 20 h generated procaspase-3 cleavage and therefore, apoptosis. Interestingly, BGP-15, and to a lesser extent calcipotriene, but not 1,25(OH)2D3, activated caspase-3 in MCF-7 cells, a cell line that normally lacks this specific caspase (and procaspase). It is presumed that management of MCF-7 with BGP-15 modulates procaspase-3 expression and cleavage, and a subsequent activation of caspase-3. Similar treatments of LNCaP cells induced procaspase-9 cleavage and therefore caspase-9 activation, whereas similar treatments of MCF-7 cells failed to induce caspase-9 activation. Cytochrome c release was, however, detected in both cell lines, LNCaP and MCF-7. In-vivo results suggested that BGP-15 (similar to its parent drug) did not cause calcium-related toxic side effects after chronic treatment.

  20. Graphene-encapsulated silica as matrix solid-phase dispersion extraction sorbents for the analysis of poly-methoxylated flavonoids in the leaves of Murraya panaculata (L.) Jack.

    PubMed

    Sun, Ting; Li, Xuwen; Yang, Jie; Li, Lanjie; Jin, Yongri; Shi, Xiaolei

    2015-06-01

    In this study, graphene-encapsulated silica was synthesized by a hydrothermal reduction strategy. The presence of silica in graphene was identified by Fourier-transform infrared spectrometry, X-ray diffraction and scanning electron microscopy. The graphene-encapsulated silica subsequently was used as adsorbent for matrix solid-phase dispersion extraction of poly-methoxylated flavonoids from the dried leaves of Murraya panaculata (L.) Jack. Compared with the other adsorbents (graphene, silica gel, C18 silica, neutral alumina, diatomaceous earth) and without any adsorbents, better results were obtained. Then a method for analysis of poly-methoxylated flavonoids was established by coupling matrix solid-phase dispersion extraction with ultra high performance liquid chromatography and UV detection. Compared with reflux extraction and ultrasonic extraction, the proposed method is quicker, more efficient and more environmental protection. Less than 10 min is needed from extraction to detection.

  1. When Gesture Becomes Analogy.

    PubMed

    Cooperrider, Kensy; Goldin-Meadow, Susan

    2017-07-01

    Analogy researchers do not often examine gesture, and gesture researchers do not often borrow ideas from the study of analogy. One borrowable idea from the world of analogy is the importance of distinguishing between attributes and relations. Gentner (, ) observed that some metaphors highlight attributes and others highlight relations, and called the latter analogies. Mirroring this logic, we observe that some metaphoric gestures represent attributes and others represent relations, and propose to call the latter analogical gestures. We provide examples of such analogical gestures and show how they relate to the categories of iconic and metaphoric gestures described previously. Analogical gestures represent different types of relations and different degrees of relational complexity, and sometimes cohere into larger analogical models. Treating analogical gestures as a distinct phenomenon prompts new questions and predictions, and illustrates one way that the study of gesture and the study of analogy can be mutually informative. Copyright © 2017 Cognitive Science Society, Inc.

  2. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

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

  3. Synthesis and Antifungal Activity against Fusarium oxysporum of Some Brassinin Analogs Derived from l-tryptophan: A DFT/B3LYP Study on the Reaction Mechanism.

    PubMed

    Quiroga, Diego; Becerra, Lili Dahiana; Sadat-Bernal, John; Vargas, Nathalia; Coy-Barrera, Ericsson

    2016-10-11

    An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from l-tryptophan 2, N,N'-dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino}propanoate 6 type compounds were obtained as main products in different ratios depending on the reaction conditions via a tandem dithiocarbamate formation and Michael addition reaction. In order to understand the dependence of the reaction conditions on the mechanism pathway, a DFT/B3LYP study was performed. The results suggested the existence of competitive mechanistic routes which involve the presence of an ionic dithiocarbamate intermediate 9. Antifungal activities of all products were then evaluated against Fusarium oxysporum through mycelial growth inhibition using a microscale amended-medium assay. IC50 values were thus determined for each compound. These results showed that 6-related compounds can be considered as promissory antifungal agents.

  4. Enhanced Antimicrobial Activity of AamAP1-Lysine, a Novel Synthetic Peptide Analog Derived from the Scorpion Venom Peptide AamAP1

    PubMed Central

    Almaaytah, Ammar; Tarazi, Shadi; Abu-Alhaijaa, Ahmad; Altall, Yara; Alshar’i, Nizar; Bodoor, Khaldon; Al-Balas, Qosay

    2014-01-01

    There is great interest in the development of antimicrobial peptides as a potentially novel class of antimicrobial agents. Several structural determinants are responsible for the antimicrobial and cytolytic activity of antimicrobial peptides. In our study, a new synthetic peptide analog, AamAP1-Lysine from the naturally occurring scorpion venom antimicrobial peptide AamAP1, was designed by modifying the parent peptide in order to increase the positive charge and optimize other physico-chemical parameters involved in antimicrobial activity. AamAP1-Lysine displayed potent antibacterial activity against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration was in the range of 5 to 15 µM with a 10 fold increase in potency over the parent peptide. The hemolytic and antiproliferative activity of AamAP1-Lysine against eukaryotic mammalian cells was minimal at the concentration range needed to inhibit bacterial growth. The antibacterial mechanism analysis indicated that AamAP1-Lysine is probably inducing bacterial cell death through membrane damage and permeabilization determined by the release of β-galactosidase enzyme from peptide treated E. coli cells. DNA binding studies revealed that AamAP1-Lysine caused complete retardation of DNA migration and could display intracellular activities in addition to the membrane permeabilization mode of action reported earlier. In conclusion, AamAP1-Lysine could prove to be a potential candidate for antimicrobial drug development in future studies. PMID:24776889

  5. Analog enhancement of radiographic images

    NASA Technical Reports Server (NTRS)

    Baily, N. A.; Nachazel, R. J.

    1976-01-01

    The paper shows how analog methods for edge sharpening, contrast enhancement, and expansion of the range of gray levels of particular interest are effective for easy on-line application to video viewing of X-ray roentgenograms or to fluoroscopy. The technique for analog enhancement of radiographic images is a modified version of the system designed by Fuchs et al. (1972), whereby an all directional second derivative signal called detail signal is used to produce both vertical and horizontal enhancement of the image. Particular attention is given to noise filtration and contrast enhancement. Numerous radiographs supplement the text.

  6. Comparative Study of the Effect of Baicalin and Its Natural Analogs on Neurons with Oxygen and Glucose Deprivation Involving Innate Immune Reaction of TLR2/TNFα

    PubMed Central

    Li, Hui-Ying; Hu, Jun; Zhao, Shuang; Yuan, Zhi-Yi; Wan, Hong-Jiao; Lei, Fan; Ding, Yi; Xing, Dong-Ming; Du, Li-Jun

    2012-01-01

    This work is to study the baicalin and its three analogs, baicalin, wogonoside, and wogonin, on the protective effect of neuron from oxygen-glucose deprivation (OGD) and toll-like receptor 2 (TLR2) expression in OGD damage. The results showed that baicalin and its three analogs did protect neurons from OGD damage and downregulated protein level of TLR2. D-Glucopyranosiduronic acid on site 7 in the structure played a core of cytotoxicity of these flavonoid analogs. The methoxyl group on carbon 8 of the structure had the relation with TLR2 protein expression, as well as the anti-inflammation. In addition, we detected caspase3 and antioxidation capability, to investigate the effect of four analogs on cell apoptosis and total antioxidation competence in OGD model. PMID:22536016

  7. Properties of compressible elastica from relativistic analogy.

    PubMed

    Oshri, Oz; Diamant, Haim

    2016-01-21

    Kirchhoff's kinetic analogy relates the deformation of an incompressible elastic rod to the classical dynamics of rigid body rotation. We extend the analogy to compressible filaments and find that the extension is similar to the introduction of relativistic effects into the dynamical system. The extended analogy reveals a surprising symmetry in the deformations of compressible elastica. In addition, we use known results for the buckling of compressible elastica to derive the explicit solution for the motion of a relativistic nonlinear pendulum. We discuss cases where the extended Kirchhoff analogy may be useful for the study of other soft matter systems.

  8. 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.

    PubMed

    Yang, Shyh-Ming; Tang, Yuting; Zhang, Rui; Lu, Huajun; Kuo, Gee-Hong; Gaul, Michael D; Li, Yaxin; Ho, George; Conway, James G; Liang, Yin; Lenhard, James M; Demarest, Keith T; Murray, William V

    2013-12-15

    A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Novel methoxylated polybrominated diphenoxybenzene congeners and possible sources in herring gull eggs from the Laurentian Great Lakes of North America.

    PubMed

    Chen, Da; Letcher, Robert J; Gauthier, Lewis T; Chu, Shaogang; McCrindle, Robert; Potter, Dave

    2011-11-15

    An increasing number of brominated flame retardants and other brominated substances are being reported in herring gull eggs from the Laurentian Great Lakes basin. Yet, in extracts from gulls' eggs, numerous bromide anion response peaks in electron capture negative ion (ECNI) mass chromatograms remain unidentified. Using archived herring gull egg homogenates, we characterize the structures of three major and three minor, new and unique brominated substances. After extensive cleanup and separation to isolate these substances from the extracts, high-quality ECNI and electron impact (EI) mass spectra revealed fragmentation patterns consistent with congeners of methoxylated polybrominated diphenoxybenzene (MeO-PBDPB), where four congeners contained five bromines and the other two contain four and six bromines, respectively. Optimized, semiquantitative analysis revealed sum concentrations of the MeO-PBDBP congeners ranged from <0.2 to 36.8 ng/g ww in pooled egg homogenates (collected in 2009) from fourteen herring gull colony sites across the Great Lakes, with the highest concentration being for Channel-Shelter Island in Saginaw Bay (Lake Huron). To our knowledge, there are no published reports on the environmental presence and sources of MeO-PBDPBs. We hypothesize that these MeO-PBDPBs are degradation products of the polybrominated diphenoxybenzenes, for example, tetradecabromodiphenoxybenzene (currently marketed as SAYTEX 120) or polybromo 3P2E. MeO-PBDPBs in Great Lakes herring gull eggs indicates their bioaccumulation potential, and raises concerns about their origin, environmental behavior and influences on wildlife and environmental health.

  10. Detection of methoxylated and hydroxylated polychlorinated biphenyls in sewage sludge in China with evidence for their microbial transformation

    PubMed Central

    Sun, Jianteng; Zhu, Lizhong; Pan, Lili; Wei, Zi; Song, Yao; Zhang, Yuduo; Qu, Liping; Zhan, Yu

    2016-01-01

    The concentrations of methoxylated polychlorinated biphenyls (MeO-PCBs) and hydroxylated polychlorinated biphenyls (OH-PCBs) were measured in the sewage sludge samples collected from twelve wastewater treatment plants in China. Two MeO-PCB congeners, including 3′-MeO-CB-65 and 4′-MeO-CB-101, were detected in three sludge with mean concentrations of 0.58 and 0.52 ng/g dry weight, respectively. OH-PCBs were detected in eight sludge samples, with an average total concentration of 4.2 ng/g dry weight. Furthermore, laboratory exposure was conducted to determine the possible source of OH-PCBs and MeO-PCBs in the sewage sludge, and their metabolism by the microbes. Both 4′-OH-CB-101 and 4′-MeO-CB-101 were detected as metabolites of CB-101 at a limited conversion rate after 5 days. Importantly, microbial interconversion between OH-PCBs and MeO-PCBs was observed in sewage sludge. Demethylation of MeO-PCBs was favored over methylation of OH-PCBs. The abundant and diverse microbes in sludge play a key role in the transformation processes of the PCB analogues. To our knowledge, this is the first report on MeO-PCBs in environmental matrices and on OH-PCBs in sewage sludge. The findings are important to understand the environmental fate of PCBs. PMID:27417462

  11. Detection of methoxylated and hydroxylated polychlorinated biphenyls in sewage sludge in China with evidence for their microbial transformation.

    PubMed

    Sun, Jianteng; Zhu, Lizhong; Pan, Lili; Wei, Zi; Song, Yao; Zhang, Yuduo; Qu, Liping; Zhan, Yu

    2016-07-15

    The concentrations of methoxylated polychlorinated biphenyls (MeO-PCBs) and hydroxylated polychlorinated biphenyls (OH-PCBs) were measured in the sewage sludge samples collected from twelve wastewater treatment plants in China. Two MeO-PCB congeners, including 3'-MeO-CB-65 and 4'-MeO-CB-101, were detected in three sludge with mean concentrations of 0.58 and 0.52 ng/g dry weight, respectively. OH-PCBs were detected in eight sludge samples, with an average total concentration of 4.2 ng/g dry weight. Furthermore, laboratory exposure was conducted to determine the possible source of OH-PCBs and MeO-PCBs in the sewage sludge, and their metabolism by the microbes. Both 4'-OH-CB-101 and 4'-MeO-CB-101 were detected as metabolites of CB-101 at a limited conversion rate after 5 days. Importantly, microbial interconversion between OH-PCBs and MeO-PCBs was observed in sewage sludge. Demethylation of MeO-PCBs was favored over methylation of OH-PCBs. The abundant and diverse microbes in sludge play a key role in the transformation processes of the PCB analogues. To our knowledge, this is the first report on MeO-PCBs in environmental matrices and on OH-PCBs in sewage sludge. The findings are important to understand the environmental fate of PCBs.

  12. Detection of methoxylated and hydroxylated polychlorinated biphenyls in sewage sludge in China with evidence for their microbial transformation

    NASA Astrophysics Data System (ADS)

    Sun, Jianteng; Zhu, Lizhong; Pan, Lili; Wei, Zi; Song, Yao; Zhang, Yuduo; Qu, Liping; Zhan, Yu

    2016-07-01

    The concentrations of methoxylated polychlorinated biphenyls (MeO-PCBs) and hydroxylated polychlorinated biphenyls (OH-PCBs) were measured in the sewage sludge samples collected from twelve wastewater treatment plants in China. Two MeO-PCB congeners, including 3‧-MeO-CB-65 and 4‧-MeO-CB-101, were detected in three sludge with mean concentrations of 0.58 and 0.52 ng/g dry weight, respectively. OH-PCBs were detected in eight sludge samples, with an average total concentration of 4.2 ng/g dry weight. Furthermore, laboratory exposure was conducted to determine the possible source of OH-PCBs and MeO-PCBs in the sewage sludge, and their metabolism by the microbes. Both 4‧-OH-CB-101 and 4‧-MeO-CB-101 were detected as metabolites of CB-101 at a limited conversion rate after 5 days. Importantly, microbial interconversion between OH-PCBs and MeO-PCBs was observed in sewage sludge. Demethylation of MeO-PCBs was favored over methylation of OH-PCBs. The abundant and diverse microbes in sludge play a key role in the transformation processes of the PCB analogues. To our knowledge, this is the first report on MeO-PCBs in environmental matrices and on OH-PCBs in sewage sludge. The findings are important to understand the environmental fate of PCBs.

  13. Learning by Analogy: Discriminating between Potential Analogs

    ERIC Educational Resources Information Center

    Richland, Lindsey E.; McDonough, Ian M.

    2010-01-01

    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

  14. Synthesis and structure-activity relationships of novel lincomycin derivatives part 3: discovery of the 4-(pyrimidin-5-yl)phenyl group in synthesis of 7(S)-thiolincomycin analogs.

    PubMed

    Wakiyama, Yoshinari; Kumura, Ko; Umemura, Eijiro; Masaki, Satomi; Ueda, Kazutaka; Sato, Yasuo; Watanabe, Takashi; Hirai, Yoko; Ajito, Keiichi

    2017-01-01

    Novel lincomycin derivatives possessing an aryl phenyl group or a heteroaryl phenyl group at the C-7 position via sulfur atom were synthesized by Pd-catalyzed cross-coupling reactions of 7(S)-7-deoxy-7-thiolincomycin (5) with various aryl halides. This reaction is the most useful method to synthesize a variety of 7(S)-7-deoxy-7-thiolincomycin derivatives. On the basis of analysis of structure-activity relationships of these novel lincomycin derivatives, we found that (a) the location of basicity in the C-7 side chain was an important factor to enhance antibacterial activities, and (b) compounds 22, 36, 42, 43 and 44 had potent antibacterial activities against a variety of Streptococcus pneumoniae with erm gene, which cause severe respiratory infections, even compared with our C-7-modified lincomycin analogs (1-4) reported previously. Furthermore, 7(S)-configuration was found to be necessary for enhancing antibacterial activities from comparison of configurations at the 7-position of 36 (S-configuration) and 41 (R-configuration).

  15. Novel Receptor-Derived Cyclopeptides to Treat Heart Failure Caused by Anti-β1-Adrenoceptor Antibodies in a Human-Analogous Rat Model

    PubMed Central

    Boivin, Valérie; Beyersdorf, Niklas; Palm, Dieter; Nikolaev, Viacheslav O.; Schlipp, Angela; Müller, Justus; Schmidt, Doris; Kocoski, Vladimir; Kerkau, Thomas; Hünig, Thomas; Ertl, Georg; Lohse, Martin J.; Jahns, Roland

    2015-01-01

    Despite recent therapeutic advances the prognosis of heart failure remains poor. Recent research suggests that heart failure is a heterogeneous syndrome and that many patients have stimulating auto-antibodies directed against the second extracellular loop of the β1 adrenergic receptor (β1EC2). In a human-analogous rat model such antibodies cause myocyte damage and heart failure. Here we used this model to test a novel antibody-directed strategy aiming to prevent and/or treat antibody-induced cardiomyopathy. To generate heart failure, we immunised n = 76/114 rats with a fusion protein containing the human β1EC2 (amino-acids 195–225) every 4 weeks; n = 38/114 rats were control-injected with 0.9% NaCl. Intravenous application of a novel cyclic peptide mimicking β1EC2 (β1EC2-CP, 1.0 mg/kg every 4 weeks) or administration of the β1-blocker bisoprolol (15 mg/kg/day orally) was initiated either 6 weeks (cardiac function still normal, prevention-study, n = 24 (16 treated vs. 8 untreated)) or 8.5 months after the 1st immunisation (onset of cardiomyopathy, therapy-study, n = 52 (40 treated vs. 12 untreated)); n = 8/52 rats from the therapy-study received β1EC2-CP/bisoprolol co-treatment. We found that β1EC2-CP prevented and (alone or as add-on drug) treated antibody-induced cardiac damage in the rat, and that its efficacy was superior to mono-treatment with bisoprolol, a standard drug in heart failure. While bisoprolol mono-therapy was able to stop disease-progression, β1EC2-CP mono-therapy -or as an add-on to bisoprolol- almost fully reversed antibody-induced cardiac damage. The cyclo¬peptide acted both by scavenging free anti-β1EC2-antibodies and by targeting β1EC2-specific memory B-cells involved in antibody-production. Our model provides the basis for the clinical translation of a novel double-acting therapeutic strategy that scavenges harmful anti-β1EC2-antibodies and also selectively depletes memory B-cells involved in the production of such antibodies

  16. Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

    USDA-ARS?s Scientific Manuscript database

    Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

  17. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

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

  18. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

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

  19. The Analogical Mind.

    ERIC Educational Resources Information Center

    Holyoak, Keith J.; Thagard, Paul

    1997-01-01

    The use of analogy in human thinking is examined from the perspective of a multiconstraint theory that postulates similarity, structure, and purpose as three kinds of constraints. The theory has been implemented in computational simulations of the analogical human mind using the Analogical Mapping by Constraint Satisfaction (ACME) model. (SLD)

  20. Structural insight into the active site of mushroom tyrosinase using phenylbenzoic acid derivatives.

    PubMed

    Oyama, Takahiro; Yoshimori, Atsushi; Takahashi, Satoshi; Yamamoto, Tetsuya; Sato, Akira; Kamiya, Takanori; Abe, Hideaki; Abe, Takehiko; Tanuma, Sei-Ichi

    2017-07-01

    So far, many inhibitors of tyrosinase have been discovered for cosmetic and clinical agents. However, the molecular mechanisms underlying the inhibition in the active site of tyrosinase have not been well understood. To explore this problem, we examined here the inhibitory effects of 4'-hydroxylation and methoxylation of phenylbenzoic acid (PBA) isomers, which have a unique scaffold to inhibit mushroom tyrosinase. The inhibitory effect of 3-PBA, which has the most potent inhibitory activity among the isomers, was slightly decreased by 4'-hydroxylation and further decreased by 4'-methoxylation against mushroom tyrosinase. Surprisingly, 4'-hydroxylation but not methoxylation of 2-PBA appeared inhibitory activity. On the other hand, both 4'-hydroxylation and methoxylation of 4-PBA increased the inhibitory activity against mushroom tyrosinase. In silico docking analyses using the crystallographic structure of mushroom tyrosinase indicated that the carboxylic acid or 4'-hydroxyl group of PBA derivatives could chelate with cupric ions in the active site of mushroom tyrosinase, and that the interactions of Asn260 and Phe264 in the active site with the adequate-angled biphenyl group are involved in the inhibitory activities of the modified PBAs, by parallel and T-shaped π-π interactions, respectively. Furthermore, Arg268 could fix the angle of the aromatic ring of Phe264, and Val248 is supposed to interact with the inhibitors as a hydrophobic manner. These results may enhance the structural insight into mushroom tyrosinase for the creation of novel tyrosinase inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. C ring may be dispensable for β-carboline: Design, synthesis, and bioactivities evaluation of tryptophan analog derivatives based on the biosynthesis of β-carboline alkaloids.

    PubMed

    Huang, Yuanqiong; Liu, Yongxian; Liu, Yuxiu; Song, Hongjian; Wang, Qingmin

    2016-02-01

    According to our previous work and the latest research on the biosynthesis of β-carboline, and using the reverse thinking strategy, tryptophan, the biosynthesis precursor of β-carboline alkaloids, and their derivatives were synthesized, and their biological activities and structure-activity relationships were studied. This bioassay showed that these compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV); especially (S)-2-amino-3-(1H-indol-3-yl)-N-octylpropanamide (4) (63.3±2.1%, 67.1±1.9%, 68.7±1.3%, and 64.5±3.1%, 500μg/mL) exhibited the best antiviral activity both in vitro and in vivo. Compound 4 was chosen for the field trials and the acute oral toxicity test, the results showed that the compound exhibited good anti-TMV activity in the field and low acute oral toxicity. We also found that these compounds showed antifungal activities and insecticidal activities. Copyright © 2016. Published by Elsevier Ltd.

  2. p,p'-Methoxyl-diphenyl diselenideincorporation into polymeric nanocapsules improves its antinociceptive action: Physicochemical and behavioral studies.

    PubMed

    Sari, Marcel Henrique Marcondes; Ferreira, Luana Mota; AngonesiZborowski, Vanessa; Araujo, Paulo Cesar Oliveira; Nadal, Jessica Mendes; Farago, Paulo Vitor; Cruz, Letícia; Nogueira, Cristina Wayne

    2017-09-01

    The p,p'-methoxyl-diphenyl diselenide [(OMePhSe)2] is an, organoselenium compound that elicits antinociceptive action in different, animal models of pain. However, the compound has physicochemical, Limitations that delay its clinical studies. Herein, (OMePhSe)2, nanocapsules were developed and their physicochemical properties were, analyzed using different techniques (Scanning electron microscopy with, field emissionguns, wide-angle X-ray diffractometry, fourier-transform, infrared spectroscopy, thermogravimetric analysis and differential, scanning calorimetry). The antinociceptive action of (OMePhSe)2 free or, nanoencapsulated was evaluated in an animal model of thermal nociception., The (OMePhSe)2 nanocapsules or the free compound (25mg/kg, 10ml/kg), were administered to Swiss mice by the intragastric (i.g.), intraperitoneal (i.p.) or subcutaneous (s.c.) route in a single or, repeated administration regimen. The (OMePhSe)2 nanocapsules had, spherical shape, no chemical interaction among the formulation components, and high thermal stability. Treatment with (OMePhSe)2 elicited an, antinociceptive action independent of the administration route and, regimen schedule. The (OMePhSe)2 incorporation into nanocapsules, prolonged and improved the compound antinociceptive action. The, (OMePhSe)2 antinociceptive action was influenced by the route of, administration (intragastric>intraperitoneal>subcutaneous) and by the, vehicle used (NCs>canola oil). Altogether, the current study, demonstrated that the (OMePhSe)2 nanoencapsulation increased the compound, thermal stability and the antinociceptive action in mice, suggesting that, the polymeric nanocapsules provided advantages in comparison to the free, compound form. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Evaluation of lophine derivatives as L-012 (luminol analog)-dependent chemiluminescence enhancers for measuring horseradish peroxidase and H2O2.

    PubMed

    Ichibangase, T; Ohba, Y; Kishikawa, N; Nakashima, K; Kuroda, N

    2014-03-01

    8-Amino-5-chloro-7-phenylpyrido[3,4-d]pyridazine-1,4(2H,3H)dione (L-012) was recently synthesized as a new chemiluminescence (CL) probe; the light intensity and the sensitivity of L-012 are higher than those of other CL probes such as luminol. Previously, our group developed four lophine-based CL enhancers of the horseradish peroxidase (HRP)-catalyzed CL oxidation of luminol, namely 2-(4-hydroxyphenyl)-4,5-diphenylimidazole (HDI), 2-(4-hydroxyphenyl)-4,5-di(2-pyridyl)imidazole (HPI), 4-(4,5-diphenyl-1H-imidazol-2-yl)phenylboronic acid (DPA), and 4-[4,5-di(2-pyridyl)-1H-imidazol-2-yl]phenylboronic acid (DPPA), and showed that DPPA was suitable for the photographic detection of HRP. In this study, we replaced luminol with L-012 and evaluated these as L-012-dependent CL enhancers. In addition, to detect HRP and/or H2O2 with higher sensitivity, each detection condition for the L-012-HRP-H2O2 enhanced CL was optimized. All the derivatives enhanced the L-012-dependent CL as well as luminol CL; HPI generated the highest enhanced luminescence. Under optimized conditions for HRP detection, the detection limit of HRP was 0.08 fmol. By contrast, the detection limit of HRP with the enhanced L-012-dependent CL using 4-iodophenol, which is a common enhancer of luminol CL, was 1.1 fmol. With regard to H2O2 detection, the detection limits for enhanced CL with HPI and 4-iodophenol were 0.29 and 1.5 pmol, respectively. Therefore, it is demonstrated that HPI is the most superior L-012-dependent CL enhancer. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Proton-coupled electron transfer versus hydrogen atom transfer in benzyl/toluene, methoxyl/methanol, and phenoxyl/phenol self-exchange reactions.

    PubMed

    Mayer, James M; Hrovat, David A; Thomas, Jennie L; Borden, Weston Thatcher

    2002-09-18

    Degenerate hydrogen atom exchange reactions have been studied using calculations, based on density functional theory (DFT), for (i) benzyl radical plus toluene, (ii) phenoxyl radical plus phenol, and (iii) methoxyl radical plus methanol. The first and third reactions occur via hydrogen atom transfer (HAT) mechanisms. The transition structure (TS) for benzyl/toluene hydrogen exchange has C(2)(h)() symmetry and corresponds to the approach of the 2p-pi orbital on the benzylic carbon of the radical to a benzylic hydrogen of toluene. In this TS, and in the similar C(2) TS for methoxyl/methanol hydrogen exchange, the SOMO has significant density in atomic orbitals that lie along the C-H vectors in the former reaction and nearly along the O-H vectors in the latter. In contrast, the SOMO at the phenoxyl/phenol TS is a pi symmetry orbital within each of the C(6)H(5)O units, involving 2p atomic orbitals on the oxygen atoms that are essentially orthogonal to the O.H.O vector. The transferring hydrogen in this reaction is a proton that is part of a typical hydrogen bond, involving a sigma lone pair on the oxygen of the phenoxyl radical and the O-H bond of phenol. Because the proton is transferred between oxygen sigma orbitals, and the electron is transferred between oxygen pi orbitals, this reaction should be described as a proton-coupled electron transfer (PCET). The PCET mechanism requires the formation of a hydrogen bond, and so is not available for benzyl/toluene exchange. The preference for phenoxyl/phenol to occur by PCET while methoxyl/methanol exchange occurs by HAT is traced to the greater pi donating ability of phenyl over methyl. This results in greater electron density on the oxygens in the PCET transition structure for phenoxyl/phenol, as compared to the PCET hilltop for methoxyl/methanol, and the greater electron density on the oxygens selectively stabilizes the phenoxyl/phenol TS by providing a larger binding energy of the transferring proton.

  5. Analog Frame Store Memory.

    DTIC Science & Technology

    1980-01-15

    information in analog form for periods up to ten (i0)seconds. The storage element is a state-of-the-art monolithic charge coupled device (CCD) which...Analog Field Storage Device The Analog Field Storage Device is a solid state monolithic array operating on the "charge coupled" principle. It consists...the implementation of the corrective action. A three-month slip in delivery of the full system will result with integration test taking place in June

  6. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

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

  7. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

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

  8. Analog without fear

    NASA Technical Reports Server (NTRS)

    Delagrange, A. D.

    1977-01-01

    Analog circuitry, also referred to as Linear, has been nearly run over by the digital/computer bandwagon. This is unfortunate because tremendous advances are being made in the field of analog integrated circuitry. Each year's progress raises the state-of-the-art, bringing achievements not possible even the year before. Many of the traditional prejudices against analog circuitry are no longer valid. This report attempts to summarize what is available now and what can (and can't) be done with analog integrated circuitry.

  9. The analogy between stereo depth and brightness.

    PubMed

    Brookes, A; Stevens, K A

    1989-01-01

    Apparent depth in stereograms exhibits various simultaneous-contrast and induction effects analogous to those reported in the luminance domain. This behavior suggests that stereo depth, like brightness, is reconstructed, ie recovered from higher-order spatial derivatives or differences of the original signal. The extent to which depth is analogous to brightness is examined. There are similarities in terms of contrast effects but dissimilarities in terms of the lateral inhibition effects traditionally attributed to underlying spatial-differentiation operators.

  10. Stable hydrogen isotope values of lignin methoxyl groups of four tree species across Germany and their implication for temperature reconstruction.

    PubMed

    Anhäuser, Tobias; Greule, Markus; Keppler, Frank

    2017-02-01

    Stable hydrogen isotope ratios of lignin methoxyl groups (δ(2)HLM values) in wood have been shown to mirror the δ(2)H signatures of precipitation (δ(2)Hprecip values). Thus, δ(2)HLM values were suggested to serve as a potential paleotemperature proxy since δ(2)Hprecip values are dominantly controlled by air temperature in the mid-latitudes. A recent study where a significant δ(2)HLM-temperature relationship was found for a European transect with mean annual temperatures ranging from -4 to 17°C strengthened this assumption. However, using δ(2)HLM values as a paleotemperature proxy requires quantification of noise from site-, species- and biosynthetic-specific influences to determine the significance of recording smaller temperature changes. Here, we measured δ(2)HLM values of tree-ring sections covering 1981-1990 and 1991-2011 of four different tree species (European beech, English oak, Scots pine, Norway spruce) at 15 sampling sites across Germany. The maximum difference in mean annual temperature between sample sites was 5°C and all sites showed small temperature increases from 1981 to 1990 to 1991-2011 (mean Δ=0.7°C). For all species investigated, the maximum difference of δ(2)HLM within the tree was <10mUr or ‰ (median values) and between trees at a single site was ≤28mUr (median values). The general pattern of the spatial δ(2)HLM-temperature relationship found for the European transect was confirmed here although a significant correlation was lacking. This can be explained by the lower spatial δ(2)Hprecip-temperature correlation (R(2)=0.39) found for sampling sites in this study and the δ(2)HLM differences between trees. Nevertheless, the temporal changes in δ(2)HLM values of European beech trees correctly reflected within ±2°C the temperature change at every sampling site. Therefore, we suggest that δ(2)HLM values of European beech trees have considerable potential for reconstructing temperature changes when applied on tree

  11. Matrix solid-phase dispersion of polybrominated diphenyl ethers and their hydroxylated and methoxylated analogues in lettuce, carrot and soil.

    PubMed

    Iparraguirre, A; Rodil, R; Quintana, J B; Bizkarguenaga, E; Prieto, A; Zuloaga, O; Cela, R; Fernández, L A

    2014-09-19

    In the present work, a novel analytical method for the simultaneous determination of ten polybrominated diphenyl ethers (PBDEs), eight methoxylated PBDEs (MeO-PBDEs) and seven hydroxylated PBDEs (OH-PBDEs) in soil, lettuce and carrot samples was developed. The procedure was based on matrix solid-phase dispersion (MSPD) followed by gas chromatography coupled to negative chemical ionization-mass spectrometry (GC-NCI-MS). Under optimum conditions, 0.5g of sample (freeze-dried in the case of lettuce and carrot samples) was dispersed with 0.5g of octadecyl-functionalized silica (C18) and 1.75g of acidified silica (10% H2SO4, w/w) was used as clean-up sorbent. A two-step fractionated elution was carried out. First, PBDEs and MeO-PBDEs were eluted in 75:25% (v/v) n-hexane/dichloromethane mixture and, then, the retained OH-PBDEs were eluted in pure dichloromethane. Both extracts were analyzed by GC-NCI-MS separately, in the case of OH-PBDEs after derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide. The developed method was validated in terms of accuracy for soil, lettuce and carrot matrices, spiked at two fortification levels (5 and 25ngg(-1)). After correction with the corresponding surrogate, apparent recovery values (defined as the recovery obtained after correction with the corresponding surrogate) were in the 80-129% range. Precision (as relative standard deviation) in the 1-21% range and method detection limits (MDLs) in the 0.003 and 0.3ngg(-1) range for soil and in the 0.003-0.4ngg(-1) range (dry weight) for lettuce and carrot samples were obtained. For PBDEs the method was also validated with a standard reference material (SRM-2585) of house dust. Finally, the method was applied for the determination of target analytes in soil, lettuce and carrot. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Analogies for Avogadro's Number.

    ERIC Educational Resources Information Center

    Poskozim, Paul S.; And Others

    1986-01-01

    Reviews analogies used to try to capture the concept of the magnitude of Avogadro's number, including analogies related to small/tiny objects, counting, people, water, and money. Also presents several new ones which are based on modern computers and printers. (JN)

  13. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

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

  14. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

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

  15. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

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

  16. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

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

  17. Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Alexander, Patricia A.; And Others

    1987-01-01

    Experiments involving a componential approach to analogy training were conducted with 36 fourth, 34 eighth, and 96 tenth graders. Results indicate a significant positive effect on all students' verbal analogy skills and no significant effect on fourth graders' inferential skills. In-class training and reading/language arts instruction implications…

  18. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

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

  19. Analog pulse processor

    DOEpatents

    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.

  20. Hydroxyproline-containing collagen analogs trigger the release and activation of collagen-sequestered proMMP-2 by competition with prodomain-derived peptide P33-42

    PubMed Central

    2011-01-01

    Background Fibrolytic and profibrotic activities of the matrix metalloproteinases (MMPs)-2 and -9 play a central role in liver fibrosis. Since binding to the extracellular matrix influences the activity of both gelatinases, here the role of fibrillar collagens as the most abundant matrix components in fibrotic tissue was investigated. Results In situ zymography and immunohistology showed association of enzymatically inactive prodomain-containing proMMP-2 and proMMP-9 but not of their activated forms to fibrillar collagen structures, which are not substrates of these gelatinases. In solid-phase binding studies with human collagens and collagen fragments, up to 45% of [125I]-labeled proMMP-2 and proMMP-9 but not of active (act)MMP-2 and actMMP-9 were retained by natural collagenous molecules and by synthetic analogs containing repeated Gly-Pro-Hyp triplets (GPO). Surface plasmon resonance yielded binding constants for the interaction of collagen type I (CI) with proMMP-2 and proMMP-9 in a nanomolar range. Values for actMMP-2 and actMMP-9 were 30-40 times higher. Tenfold molar excesses of (GPO)10 reduced the interaction of CI with pro- and actMMP-2 by 22- or 380-fold and resulted in prodomain release accompanied by high enzymatic activation and activity. Pointing to gelatine substrate displacement, higher (GPO)10 concentrations blocked the enzymatic activity. The MMP-2 prodomain-derived collagen-binding domain peptide (P33-42) binds to the collagen-binding domain of MMP-2, thereby preserving enzymatic inactivity. Synthetic P33-42 peptide competed with proMMP-2 binding to CI and prevented (GPO)10-mediated proMMP-2 activation. In contrast to (GPO)10, P33-42 did not activate proMMP-2, making triple helical and hydroxyproline-containing (GPO)10 unique in modulating gelatinase availability and activity. Conclusions These findings suggest novel strategies using collagen analogs for the resolution of liver fibrosis via fibrotic matrix-sequestered gelatinases. PMID:21211003

  1. Hydroxyproline-containing collagen analogs trigger the release and activation of collagen-sequestered proMMP-2 by competition with prodomain-derived peptide P33-42.

    PubMed

    Ruehl, Martin; Muche, Marion; Freise, Christian; Erben, Ulrike; Neumann, Ulf; Schuppan, Detlef; Popov, Yury; Dieterich, Walburga; Zeitz, Martin; Farndale, Richard W; Somasundaram, Rajan

    2011-01-06

    Fibrolytic and profibrotic activities of the matrix metalloproteinases (MMPs)-2 and -9 play a central role in liver fibrosis. Since binding to the extracellular matrix influences the activity of both gelatinases, here the role of fibrillar collagens as the most abundant matrix components in fibrotic tissue was investigated. In situ zymography and immunohistology showed association of enzymatically inactive prodomain-containing proMMP-2 and proMMP-9 but not of their activated forms to fibrillar collagen structures, which are not substrates of these gelatinases. In solid-phase binding studies with human collagens and collagen fragments, up to 45% of [125I]-labeled proMMP-2 and proMMP-9 but not of active (act)MMP-2 and actMMP-9 were retained by natural collagenous molecules and by synthetic analogs containing repeated Gly-Pro-Hyp triplets (GPO). Surface plasmon resonance yielded binding constants for the interaction of collagen type I (CI) with proMMP-2 and proMMP-9 in a nanomolar range. Values for actMMP-2 and actMMP-9 were 30-40 times higher. Tenfold molar excesses of (GPO)10 reduced the interaction of CI with pro- and actMMP-2 by 22- or 380-fold and resulted in prodomain release accompanied by high enzymatic activation and activity. Pointing to gelatine substrate displacement, higher (GPO)10 concentrations blocked the enzymatic activity. The MMP-2 prodomain-derived collagen-binding domain peptide (P33-42) binds to the collagen-binding domain of MMP-2, thereby preserving enzymatic inactivity. Synthetic P33-42 peptide competed with proMMP-2 binding to CI and prevented (GPO)10-mediated proMMP-2 activation. In contrast to (GPO)10, P33-42 did not activate proMMP-2, making triple helical and hydroxyproline-containing (GPO)10 unique in modulating gelatinase availability and activity. These findings suggest novel strategies using collagen analogs for the resolution of liver fibrosis via fibrotic matrix-sequestered gelatinases.

  2. Meat analog: a review.

    PubMed

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

    2015-01-01

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

  3. Health as an analogical concept.

    PubMed

    Mordacci, R

    1995-10-01

    This article examines the normative structure of the concept of health and tries to suggest an account of it in a phenomenological-hermeneutic framework. It is argued that the concept of health has a logical priority to illness, though the latter has an experiential priority. The fundamental feature of the concept of health as discussed in the literature is initially recognized in the notion of 'norm', in both the bio-statistical and normative-ideal sense. An analysis of this body of literature reveals some weaknesses in bio-statistical definitions of health as well as in those normative ones which endorse a value-relativity thesis. An approach based on the analogical structure of language is then advanced. In this framework, the notion of biological normativeness proposed by G. Canguilhem is connected with an analysis of the language of health through etymologies. It is argued that health can be characterized as an analogy of 'plenitude', which is the common ideal reference of the various health-concepts. The analogical structuring of language allows the recognition of different levels of meaning, and therefore of different kinds of normativeness (biological, mental, social, moral). Some hints of a theory of health deriving from this framework are then given.

  4. Analogies as categorization phenomena: Studies from scientific discourse

    NASA Astrophysics Data System (ADS)

    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.

  5. Challenges in Using Analogies

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-11-01

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

  6. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

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

  7. FGF growth factor analogs

    DOEpatents

    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.

  8. Synthesis and antibacterial activity of novel 15-membered macrolide derivatives: 4''-carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin.

    PubMed

    Ma, Shutao; Ma, Ruixin; Liu, Zhaopeng; Ma, Chenchen; Shen, Xuecui

    2009-10-01

    4''-Carbamate, 11,12-cyclic carbonate-4''-carbamate and 11,4''-di-O-arylcarbamoyl analogs of azithromycin were designed, synthesized and evaluated. The 4''-carbamate analogs retained excellent activity against erythromycin-susceptible Staphylococcus pneumoniae and showed improved activity against erythromycin-resistant Staphylococcus pneumoniae. Compared with 4''-carbamate analogs, 11,12-cyclic carbonate-4''-carbamate analogs exhibited improved activity against erythromycin-resistant Staphylococcus pneumoniae encoded by the mef gene or the erm and mef genes, and 11,4''-di-O-arylalkylcarbamoyl analogs showed greatly improved activity (0.25-0.5 microg/mL) against erythromycin-resistant Staphylococcus pneumoniae encoded by the erm gene. Among them, the novel series of 11,4''-di-O-arylalkylcarbamoyl analogs 7a-k exhibited potent and balanced activity against susceptible and resistant bacteria. In particular, compounds 7f and 7k were the most effective against susceptible bacteria and resistant bacteria encoded by the erm gene or the mef gene.

  9. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

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

  10. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

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

  11. A Strategy for Simultaneous Isolation of Less Polar Ginsenosides, Including a Pair of New 20-Methoxyl Isomers, from Flower Buds of Panax ginseng.

    PubMed

    Li, Sha-Sha; Li, Ke-Ke; Xu, Fei; Tao, Li; Yang, Li; Chen, Shu-Xiao; Gong, Xiao-Jie

    2017-03-10

    The present study was designed to simultaneously isolate the less polar ginsenosides from the flower buds of Panax ginseng (FBPG). Five ginsenosides, including a pair of new 20-methoxyl isomers, were extracted from FBPG and purified through a five-step integrated strategy, by combining ultrasonic extraction, Diaion Hp-20 macroporous resin column enrichment, solid phase extraction (SPE), reversed-phase high-performance liquid chromatography (RP-HPLC) analysis and preparation, and nuclear magnetic resonance (NMR) analysis. The quantification of the five ginsenosides was also discussed by a developed method with validations within acceptable limits. Ginsenoside Rg5 showed content of about 1% in FBPG. The results indicated that FBPG might have many different ginsenosides with diverse chemical structures, and the less polar ginsenosides were also important to the quality control and standardization of FBPG.

  12. LL-37-derived short antimicrobial peptide KR-12-a5 and its d-amino acid substituted analogs with cell selectivity, anti-biofilm activity, synergistic effect with conventional antibiotics, and anti-inflammatory activity.

    PubMed

    Kim, Eun Young; Rajasekaran, Ganesan; Shin, Song Yub

    2017-08-18

    KR-12-a5 is a 12-meric α-helical antimicrobial peptide (AMP) with dual antimicrobial and anti-inflammatory activities designed from human cathelicidin LL-37. We designed and synthesized a series of d-amino acid-substituted analogs of KR-12-a5 with the aim of developing novel α-helical AMPs that possess higher cell selectivity than KR-12-a5, while maintaining the anti-inflammatory activity. d-amino acid incorporation into KR-12-a5 induced a significant improvement in the cell selectivity by 2.6- to 13.6-fold as compared to KR-12-a5, while maintaining the anti-inflammatory activity. Among the three analogs, KR-12-a5 (6-(D)L) with d-amino acid in the polar-nonpolar interface (Leu(6)) showed the highest cell selectivity (therapeutic index: 61.2). Similar to LL-37, KR-12-a5 and its analogs significantly inhibited the expression and secretion of NO, TNF-α, IL-6 and MCP-1 from LPS-stimulated RAW264.7 cells. KR-12-a5 and its analogs showed a more potent antimicrobial activity against antibiotic-resistant bacteria, including clinically isolated MRSA, MDRPA, and VREF than LL-37 and melittin. Furthermore, compared to LL-37, KR-12-a5 and its analogs showed greater synergistic effects with conventional antibiotics, such as chloramphenicol, ciprofloxacin, and oxacillin against MDRPA; KR-12-a5 and its analogs had a FICI range between 0.25 and 0.5, and LL-37 had a range between 0.75 and 1.5. KR-12-a5 and its analogs were found to be more effective anti-biofilm agents against MDRPA than LL-37. In addition, KR-12-a5 and its analogs maintained antimicrobial activity in physiological salts and human serum. SYTOX Green uptake and membrane depolarization studies revealed that KR-12-a5 and its analogs kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Taken together, our results suggest that KR-12-a5 and its analogs can be developed further as novel antimicrobial/anti-inflammatory agents to treat antibiotic-resistant infections. Copyright

  13. Carbon, hydrogen and oxygen stable isotope ratios of whole wood, cellulose and lignin methoxyl groups of Picea abies as climate proxies.

    PubMed

    Gori, Y; Wehrens, R; Greule, M; Keppler, F; Ziller, L; La Porta, N; Camin, F

    2013-01-15

    Carbon, hydrogen and oxygen (C, H and O) stable isotope ratios of whole wood and components are commonly used as paleoclimate proxies. In this work we consider eight different proxies in order to discover the most suitable wood component and stable isotope ratio to provide the strongest climate signal in Picea abies in a southeastern Alpine region (Trentino, Italy). δ(13)C, δ(18)O and δ(2)H values in whole wood and cellulose, and δ(13)C and δ(2)H values in lignin methoxyl groups were measured. Analysis was performed using an Isotopic Ratio Mass Spectrometer coupled with an Elemental Analyser for measuring (13)C/(12)C and a Pyrolyser for measuring (2)H/(1)H and (18)O/(16)O. The data were evaluated by Principal Component Analysis, and a simple Pearson's correlation between isotope chronologies and climatic features, and multiple linear regression were performed to evaluate the data. Each stable isotope ratio in cellulose and lignin methoxyl differs significantly from the same stable isotope ratio in whole wood, the values begin higher in cellulose and lignin except for the lignin δ(2)H values. Significant correlations were found between the whole wood and the cellulose fractions for each isotope ratio. Overall, the highest correlations with temperature were found with the δ(18)O and δ(2)H values in whole wood, whereas no significant correlations were found between isotope proxies and precipitation. δ(18)O and δ(2)H values in whole wood provide the best temperature signals in Picea abies in the northern Italian study area. Extraction of cellulose and lignin and analysis of other isotopic ratios do not seem to be necessary. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Warm season precipitation signal in δ(2) H values of wood lignin methoxyl groups from high elevation larch trees in Switzerland.

    PubMed

    Riechelmann, Dana F C; Greule, Markus; Siegwolf, Rolf T W; Anhäuser, Tobias; Esper, Jan; Keppler, Frank

    2017-10-15

    In this study, we tested stable hydrogen isotope ratios of wood lignin methoxyl groups (δ(2) Hmethoxyl values) as a palaeoclimate proxy in dendrochronology. This is a quite new method in the field of dendrochronology and the sample preparation is much simpler than the methods used before to measure δ(2) H values from wood. We measured δ(2) Hmethoxyl values in high elevation larch trees (Larix decidua Mill.) from Simplon Valley (southern Switzerland). Thirty-seven larch trees were sampled and five individuals analysed for their δ(2) Hmethoxyl values at annual (1971-2009) and pentadal resolution (1746-2009). The δ(2) Hmethoxyl values were measured as CH3 I released upon treatment of the dried wood samples with hydroiodic acid. 10-90 μL from the head-space were injected into the gas chromatography/high-temperature conversion/isotope ratio mass spectrometry (GC/HTC-IRMS) system. Testing the climate response of the δ(2) Hmethoxyl values, the annually resolved series show a positive correlation of r = 0.60 with June/July precipitation. The pentadally resolved δ(2) Hmethoxyl series do not show any significant correlation to climate parameters. Increased precipitation during June and July, which are on average warm and relatively dry months, results in higher δ(2) H values of the xylem water and, therefore, higher δ(2) H values in the lignin methoxyl groups. Therefore, we suggest that δ(2) Hmethoxyl values of high elevation larch trees might serve as a summer precipitation proxy. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Weyl quantization of fractional derivatives

    SciTech Connect

    Tarasov, Vasily E.

    2008-10-15

    The quantum analogs of the derivatives with respect to coordinates q{sub k} and momenta p{sub k} are commutators with operators P{sub k} and Q{sub k}. We consider quantum analogs of fractional Riemann-Liouville and Liouville derivatives. To obtain the quantum analogs of fractional Riemann-Liouville derivatives, which are defined on a finite interval of the real axis, we use a representation of these derivatives for analytic functions. To define a quantum analog of the fractional Liouville derivative, which is defined on the real axis, we can use the representation of the Weyl quantization by the Fourier transformation.

  16. Novel stilbene-based Fischer base analog of leuco-TAM - (2E,2'Z)-{2-(4-(E)-styrylphenyl)propane-1,3-diylidene}bis(1,3,3-trimethylindoline) - derivatives: synthesis and structural consideration by 1D NMR and 2D NMR spectroscopy.

    PubMed

    Keum, Sam-Rok; Lim, Hyun-Woo

    2016-02-01

    We report the synthesis of a series of novel stilbene-based (St) Fischer base analogs of leuco-triarylmethane (LTAM) dyes by treating Fischer base with (E)-4-styrylbenzaldehyde derivatives. All St-LTAM molecules examined herein are characterized by 1D and 2D NMR. They were found to exhibit ZE configuration and isomerize to their diastereomers EE and ZZ in 2-3 h. They exhibit type I behavior of diastereomeric isomerization.

  17. Analog measurement of scattered optical fluctuations

    NASA Astrophysics Data System (ADS)

    Smith, P. R.; Green, D. A.

    1995-12-01

    A statistical model that describes the analog measurement of a fluctuating light intensity that arises from a non-Gaussian scattering process is developed. The higher-order statistical moments are derived for a p-i-n diode receiver model and gamma-distributed intensity fluctuations. Criteria for the accurate measurement of the scattering fluctuations are found, and these are used to analyze data derived from an on-line scatterometer system. Implications for future on-line measurement technology are discussed.

  18. Effect of distal sugars and interglycosidic linkage on the N-glycoprotein linkage region conformation: synthesis and X-ray crystallographic investigation of β-1-N-alkanamide derivatives of cellobiose and maltose as disaccharide analogs of the conserved chitobiosylasparagine linkage.

    PubMed

    Mathiselvam, Manoharan; Ramkumar, Venkatachalam; Loganathan, Duraikkannu; Pérez, Serge

    2014-01-01

    The linkage region constituents, 2-deoxy-2-acetamido-β-D-glucopyranose (GlcNAc) and L-asparagine (Asn) are conserved in the N-glycoproteins of all eukaryotes. Elucidation of the structure and conformation of the linkage region of glycoproteins is important to understand the presentation and dynamics of the carbohydrate chain at the protein/cell surface. Earlier crystallographic studies using monosaccharide models and analogs of N-glycoprotein linkage region have shown that the N-glycosidic torsion, ϕN, is more influenced by the structural variation in the sugar part than that of the aglycon moiety. To access the influence of distal sugar as well as interglycosidic linkage (α or β) on the N-glycosidic torsion angles, cellobiosyl and maltosyl alkanamides have been synthesized and structural features of seven of these analogs have been characterized by X-ray crystallography. Comparative analysis of the seven disaccharide analogs with the reported monosaccharide analogs showed that the ϕN value of cellobiosyl analogs deviate ~9° with respect to GlcβNHAc. In the case of maltosyl analogs, deviation is more than 18°. These deviations indicate that the N-glycosidic torsion is influenced by addition of distal sugar as well as with respect to inter glycosidic linkage (α or β); it is less influenced by changes occurring at the aglycon. The χ₂ value of alkanamide derived from glucose, cellobiose and maltose exhibit a large range of variations (from 1.6° to -109.9°). This large span of χ₂ value suggests the greater degree of rotational freedom around C1'-C2' bond which is restricted in GlcNAc alkanamides. The present finding explicitly proved the importance of molecular architecture in the N-glycoproteins linkage region to maintain the linearity, planarity and rigidity. These factors are necessary for N-glycan to serve role in inter- as well as intramolecular carbohydrate-protein interactions.

  19. Digital and analog communication systems

    NASA Technical Reports Server (NTRS)

    Shanmugam, K. S.

    1979-01-01

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

  20. Analogical Reasoning in Geometry Education

    ERIC Educational Resources Information Center

    Magdas, Ioana

    2015-01-01

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

  1. Electrical analogous in viscoelasticity

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  2. Analog Optical Links

    NASA Astrophysics Data System (ADS)

    Cox, Charles H., III

    2004-05-01

    Unlike books that focus on the devices used in links, such as lasers and photodiodes, among others, this text focuses on the next level. It covers the collection of devices that form a link, how the individual device performance affects the link performance, or the reverse. Analog links are used for the distribution of cable TV signals, and in conveying the signals to and from antennas (so called antenna remoting). The design of analog links differs significantly from digital links which are primarily used in telecommunications.

  3. Caffeine analogs: biomedical impact.

    PubMed

    Daly, J W

    2007-08-01

    Caffeine, widely consumed in beverages, and many xanthine analogs have had a major impact on biomedical research. Caffeine and various analogs, the latter designed to enhance potency and selectivity toward specific biological targets, have played key roles in defining the nature and role of adenosine receptors, phosphodiesterases, and calcium release channels in physiological processes. Such xanthines and other caffeine-inspired heterocycles now provide important research tools and potential therapeutic agents for intervention in Alzheimer's disease, asthma, cancer, diabetes, and Parkinson's disease. Such compounds also have activity as analgesics, antiinflammatories, antitussives, behavioral stimulants, diuretics/natriuretics, and lipolytics. Adverse effects can include anxiety, hypertension, certain drug interactions, and withdrawal symptoms.

  4. Analogies in medicine: valuable for learning, reasoning, remembering and naming.

    PubMed

    Pena, Gil Patrus; Andrade-Filho, José de Souza

    2010-10-01

    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 explain a knowledge to be achieved (the target), with pieces of information already familiar to the learner (the source), keeping in mind the constraints of similarity, structure and purpose. The purpose of this essay is to examine the use of analogies in medicine. We provide a brief review of the theoretical basis of analogical reasoning. This theoretical background is discussed in the light of actual examples of analogies retrieved from medical literature. In medicine, analogies have long been used to explain several physiologic and pathologic processes. Besides deeper structural relations, superficial attribute similarity is extensively used in many medical specialties. These attribute similarities are important in naming, categorizing and classifying, and play a role as learning and memorizing tools. Analogies also serve as basis for medical nomenclature. The choice of the source of analogies is highly dependent on cultural background, and may derive from ancient or diverse cultures. Learning by analogies may thus require research on culture diversity in order to establish an adequate justification and to comprehend the purpose of an analogy.

  5. Antiviral nucleoside analogs phosphorylation by nucleoside diphosphate kinase.

    PubMed

    Gallois-Montbrun, S; Veron, M; Deville-Bonne, D

    2004-05-01

    The reaction of NDP kinase was studied in vitro with several antiviral derivatives, using kinetic steady state and presteady state analysis. The enzyme is highly efficient with natural nucleotides but most of the analogs are slow substrates. The catalytic efficiency, also related to the affinity of the analog, is mainly dependent on the presence of a 3'-OH group on the ribose moiety.

  6. The effect of resveratrol, its naturally occurring derivatives and tannic acid on the induction of cell cycle arrest and apoptosis in rat C6 and human T98G glioma cell lines.

    PubMed

    Zielińska-Przyjemska, Małgorzata; Kaczmarek, Mariusz; Krajka-Kuźniak, Violetta; Łuczak, Michał; Baer-Dubowska, Wanda

    2017-09-01

    Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a potent chemopreventive and potentially cancer therapeutic agent. Since rapid metabolism limits resveratrol bioavailability, derivatives less prone to metabolic transformation are being sought and tested. We evaluated the effect of resveratrol, and its analogs (pterostilbene and 3,5,4'-trimethoxystilbene) along with tannic acid, on cell cycle and apoptosis in rat C6 and human T98G glioma cells. At concentration ranges both lower and higher than IC50 calculated based on MTT assay, all these polyphenols affected the cell cycle distribution. However, resveratrol and pterostilbene increased the percentage of the cells in S phase, while trimethoxystilbene (TMS) caused a massive accumulation of cells at the G2/M phase of the cell cycle. Tannic acid had no effect on cell cycle distribution in C6 cells, but increased the number of dead cells in both glioma cell lines. The ability to induce apoptosis by tannic acid and stilbenes was confirmed by phosphatidylserine externalization, the loss of mitochondrial membrane potential and the level of cleaved caspase-3. The apoptosis rate was most significantly increased by TMS and this was related to p53 induction. These results indicate that methoxylated stilbenes are efficient inhibitors of glioma cell proliferation and apoptosis inducers and might be considered adjuvants in glioma therapy. Copyright © 2017. Published by Elsevier Ltd.

  7. Analogies between elastic and capillary interfaces*

    NASA Astrophysics Data System (ADS)

    Snoeijer, Jacco H.

    2016-10-01

    In this paper we exploit some analogies between flows near capillary interfaces and near elastic interfaces. We first consider the elastohydrodynamics of a ball bearing and the motion of a gas bubble inside a thin channel. It is shown that there is a strong analogy between these two lubrication problems, and the respective scaling laws are derived side by side. Subsequently, the paper focuses on the limit where the involved elastic interfaces become extremely soft. It is shown that soft gels and elastomers, like liquids, can be shaped by their surface tension. We highlight some recent advances on this class of elastocapillary phenomena.

  8. Are Scientific Analogies Metaphors?

    DTIC Science & Technology

    1981-02-01

    psychospiritual processes. A more modern example of unclarified analogy is Freud’s (1973; reprinted from 1955) discussion of anal- eroticism , in which...299-304. Freud, S. On transformations of instinct as exemplified in anal eroticism . In J. Strachey (Ed.), The standard 37 edition of the complete

  9. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

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

  10. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

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

  11. An Interesting Analogy

    ERIC Educational Resources Information Center

    Pacheco, Jose M.; Fernandez, Isabel

    2002-01-01

    The aim of this note is to give some insight into the formal unity of a very applicable area of mathematics by showing an interesting analogy between the weak part of the Rouche-Frobenius theorem and the existence result for the initial value problem for the general first-order linear two-dimensional PDE.

  12. Reasoning through Instructional Analogies

    ERIC Educational Resources Information Center

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

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

  13. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

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

    1980-01-01

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

  14. How Analogy Drives Physics

    SciTech Connect

    Hofstadter, Doug

    2004-05-05

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

  15. Terrestrial analogs to Mars

    NASA Technical Reports Server (NTRS)

    Farr, T. G.; Arcone, S.; Arvidson, R.; Baker, V.; Barlow, N.; Beaty, D.; Bell, M.; Blankenship, D.; Bridges, N.; Briggs, G.; hide

    2002-01-01

    It is well recognized that interpretations of Mars must begin with the Earth as a reference. The most successful comparisons have focused on understanding geologic processes on the Earth well enough to extrapolate to Mars' environment. Several facets of terrestrial analog studies have been pursued and are continuing.

  16. Inhibition of cancer growth and induction of apoptosis by BGP-13 and BGP-15, new calcipotriene-derived vitamin D3 analogs, in-vitro and in-vivo studies.

    PubMed

    Berkovich, Liron; Sintov, Amnon C; Ben-Shabat, Shimon

    2013-04-01

    One of the most innovative approaches to the treatment of cancer entails the use of 1α,25-dihydroxyvitamin D3 (calcitriol) analogs to inhibit cancer cell growth. We demonstrate here that BGP-13, a new calcipotriene-based 1α,25-dihydroxyvitamin D3 analog that we synthesized in our laboratory, inhibits the growth of prostate cancer (LNCaP), breast cancer (MCF-7), and colon cancer (HT-29) cell lines. Moreover, we also show that BGP-13 causes cells both to accumulate in G0-G1 and to activate caspase-3 and undergo apoptosis. In addition, we observed elevated vitamin D receptor (VDR) mRNA and protein levels in both LNCaP and MCF-7 cells following the exposure of the two cell lines to BGP-13. Importantly, we found that both the new analog BGP-13 and also BGP-15, another calcipotriene-based analog we synthesized previously and about which we published recently, inhibit the growth of HT-29 tumor xenografts in nude mice.

  17. A precondition prover for analogy.

    PubMed

    Bledsoe, W W

    1995-01-01

    We describe here a prover PC (precondition) that normally acts as an ordinary theorem prover, but which returns a 'precondition' when it is unable to prove the given formula. If F is the formula attempted to be proved and PC returns the precondition Q, then (Q-->F) is a theorem (that PC can prove). This prover, PC, uses a proof-plan. In its simplest mode, when there is no proof-plan, it acts like ordinary abduction. We show here how this method can be used to derive certain proofs by analogy. To do this, it uses a proof-plan from a given guiding proof to help construct the proof of a similar theorem, by 'debugging' (automatically) that proof-plan. We show here the analogy proofs of a few simple example theorems and one hard pair, Ex4 and Ex4L. The given proof-plan for Ex4 is used by the system to prove automatically Ex4; and that same proof-plan is then used to prove Ex4L, during which the proof-plan is 'debugged' (automatically). These two examples are similar to two other, more difficult, theorems from the theory of resolution, namely GCR (the ground completeness of resolution) and GCLR (the ground completeness of lock resolution). GCR and GCLR have also been handled, in essence, by this system but not completed in all their details.

  18. Prostacyclin analogs inhibit fibroblast migration.

    PubMed

    Kohyama, Tadashi; Liu, Xiangde; Kim, Hui Jung; Kobayashi, Tetsu; Ertl, Ronald F; Wen, Fu-Qiang; Takizawa, Hajime; Rennard, Stephen I

    2002-08-01

    The controlled accumulation of fibroblasts to sites of inflammation is crucial to effective tissue repair after injury. Either inadequate or excessive accumulation of fibroblasts could result in abnormal tissue function. Prostacyclin (PGI(2)) is a potent mediator in the coagulation and inflammatory processes. The aim of this study was to investigate the effect of PGI(2) on chemotaxis of human fetal lung fibroblasts (HFL-1). Using the blind well chamber technique, we found that the PGI(2) analog carbaprostacyclin (10(-6) M) inhibited HFL-1 chemotaxis to human plasma fibronectin (20 microg/ml) 58.0 +/- 13.2% (P < 0.05) and to platelet-derived growth factor (PDGF)-BB (10 ng/ml) 48.7 +/- 4.6% (P < 0.05). Checkerboard analysis demonstrated that carbaprostacyclin inhibits both directed and undirected migration. The inhibitory effect of the carbaprostacyclin was concentration dependent and blocked by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, suggesting that a cAMP-PKA pathway may be involved in the process. Two other PGI(2) analogs, ciprostene and dehydro-15-cyclohexyl carbaprostacyclin (both 10(-6) M), significantly inhibited fibroblast migration to fibronectin. In summary, PGI(2) appears to inhibit fibroblast chemotaxis to fibronectin and PDGF-BB. Such an effect may contribute to the regulation of fibroblasts in wound healing and could contribute to the pathogenesis of diseases characterized by abnormal tissue repair remodeling.

  19. Gravitoelectromagnetic analogy based on tidal tensors

    SciTech Connect

    Costa, L. Filipe O.; Herdeiro, Carlos A. R.

    2008-07-15

    We propose a new approach to a physical analogy between general relativity and electromagnetism, based on tidal tensors of both theories. Using this approach we write a covariant form for the gravitational analogues of the Maxwell equations, which makes transparent both the similarities and key differences between the two interactions. The following realizations of the analogy are given. The first one matches linearized gravitational tidal tensors to exact electromagnetic tidal tensors in Minkowski spacetime. The second one matches exact magnetic gravitational tidal tensors for ultrastationary metrics to exact magnetic tidal tensors of electromagnetism in curved spaces. In the third we show that our approach leads to a two-step exact derivation of Papapetrou's equation describing the force exerted on a spinning test particle. Analogous scalar invariants built from tidal tensors of both theories are also discussed.

  20. Interaction of Chloramphenicol Tripeptide Analogs with Ribosomes.

    PubMed

    Tereshchenkov, A G; Shishkina, A V; Tashlitsky, V N; Korshunova, G A; Bogdanov, A A; Sumbatyan, N V

    2016-04-01

    Chloramphenicol amine peptide derivatives containing tripeptide fragments of regulatory "stop peptides" - MRL, IRA, IWP - were synthesized. The ability of the compounds to form ribosomal complexes was studied by displacement of the fluorescent erythromycin analog from its complex with E. coli ribosomes. It was found that peptide chloramphenicol analogs are able to bind to bacterial ribosomes. The dissociation constants were 4.3-10 µM, which is 100-fold lower than the corresponding values for chloramphenicol amine-ribosome complex. Interaction of the chloramphenicol peptide analogs with ribosomes was simulated by molecular docking, and the most probable contacts of "stop peptide" motifs with the elements of nascent peptide exit tunnel were identified.

  1. Four analogies between biological and cultural/linguistic evolution.

    PubMed

    Sereno, M I

    1991-08-21

    The intricate phenomena of biology on the one hand, and language and culture on the other, have inspired many writers to draw analogies between these two evolutionary systems. These analogies can be divided into four principal types: species/language, organism/concept, genes/culture, and cell/person. Here, it is argued that the last analogy--between cells and persons--is the most profound in several respects, and, more importantly, can be used to generate a number of empirical predictions. In the first half of the paper, the four analogies are each evaluated after briefly describing criteria for a good predictive analogy. In the second half of the paper, the cell/person analogy and predictions deriving from it are explored in detail.

  2. A Systematic Evaluation of Analogs for the Read-across ...

    EPA Pesticide Factsheets

    Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a target data-poor chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified based on structural similarity. Although much guidance has been published for read-across, practical guiding principles for the identification and evaluation of the scientific validity of source analogs, which is a critical step in deriving a robust read-across prediction, remains largely lacking.This case study explores the extent to which 3 structure descriptor sets (Pubchem, Chemotyper and MoSS) and their combinations are able to identify valid analogs for reading across Estrogen Receptor (ER) activity for a specific class of chemicals: hindered phenols. For each target chemical, two sets of analogs (hindered and non-hindered phenols) were selected using each descriptor set with two cut-offs: (1). Minimum Tanimoto similarity (range 0.1 - 0.9), and (2). Closest N analogs (range 1 - 10). Each target-analog pair was then evaluated for its agreement with measured ER binding and agonism. Subsequently, the analogs were filtered using physchem properties (LogKow & Molecular Volume) and the resultant agreement between each target-analog pair was evaluated. The data set comprised 462 hindered phenols and 296 non-hindered phenols. The results demonstrate that: (1). The concordance in ER activity r

  3. Magnetic activity of seismic solar analogs

    NASA Astrophysics Data System (ADS)

    Salabert, D.; García, R. A.; Beck, P. G.

    2016-12-01

    We present our latest results on the solar-stellar connection by studying 18 solar analogs that we identified among the Kepler seismic sample tep{salabert16a}. We measured their magnetic activity properties using observations collected by the Kepler satellite and the ground-based, high-resolution HERMES spectrograph. The photospheric (S{_ph}) 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 KIC 10644253 with a modulation of about 1.5 years, which agrees with the derived photospheric activity tep{salabert16b}. 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 HD 30495. In addition, the lithium abundance and the chromospheric activity estimated from HERMES confirms that KIC 10644253 is a young and more active star than the Sun.

  4. Reactivity and acid-base behavior of ring-methoxylated arylalkanoic acid radical cations and radical zwitterions in aqueous solution. Influence of structural effects and pH on the benzylic C-H deprotonation pathway.

    PubMed

    Bietti, Massimo; Capone, Alberto

    2006-07-07

    A product and time-resolved kinetic study of the one-electron oxidation of ring-methoxylated phenylpropanoic and phenylbutanoic acids (Ar(CH2)nCO2H, n = 2, 3) has been carried out at different pH values. Oxidation leads to the formation of aromatic radical cations (Ar.+(CH2)nCO2H) or radical zwitterions (Ar.+(CH2)nCO2-) depending on pH, and pKa values for the corresponding acid-base equilibria have been measured. In the radical cation, the acidity of the carboxylic proton decreases by increasing the number of methoxy ring substituents and by increasing the distance between the carboxylic group and the aromatic ring. At pH 1.7 or 6.7, the radical cations or radical zwitterions undergo benzylic C-H deprotonation as the exclusive side-chain fragmentation pathway, as clearly shown by product analysis results. At pH 1.7, the first-order deprotonation rate constants measured for the ring-methoxylated arylalkanoic acid radical cations are similar to those measured previously in acidic aqueous solution for the alpha-C-H deprotonation of structurally related ring-methoxylated alkylaromatic radical cations. In basic solution, the second-order rate constants for reaction of the radical zwitterions with (-)OH (k-OH)) have been obtained. These values are similar to those obtained previously for the (-)OH-induced alpha-C-H deprotonation of structurally related ring-methoxylated alkylaromatic radical cations, indicating that under these conditions the radical zwitterions undergo benzylic C-H deprotonation. Very interestingly, with 3,4-dimethoxyphenylethanoic acid radical zwitterion, that was previously observed to undergo exclusive decarboxylation up to pH 10, competition between decarboxylation and benzylic C-H deprotonation is observed above pH 11.

  5. New analogs of trimethoprim.

    PubMed

    Then, R L; Böhni, E; Angehrn, P; Plozza-Nottebrock, H; Stoeckel, K

    1982-01-01

    Possible goals and recent developments in the field of antimicrobial 2,4-diamino-5-benzylpyrimidines are discussed. Three analogs of trimethoprim--all bearing different substituents at position 4 of the benzyl moiety and one also having the methoxy groups replaced by ethoxy substituents--are characterized in some detail. These analogs exhibit physicochemical properties different from those of trimethoprim and are potent inhibitors of several dihydrofolate reductases. Because they differ from trimethoprim in lipophilicity, their in vitro activity, spectrum of activity, and pharmacokinetic properties also differ from those of trimethoprim. These differences are judged to be the reason for enhanced in vivo efficacy against several experimental infections. Distinct pharmacokinetic differences observed in dogs include a longer elimination half-life and a larger volume of distribution. These favorable properties indicate the potential value of further studies in humans.

  6. Terrestrial Spaceflight Analogs: Antarctica

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2013-01-01

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

  7. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  8. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  9. VIIP Bedrest Analog Roadmap

    NASA Technical Reports Server (NTRS)

    Villarreal, Jennifer D.

    2014-01-01

    The objective is to define successive bed rest campaigns leading to a potential VIIP (Vision Impairment and Intracranial Pressure) countermeasure. To determine if the analog is successful, changes need to occur in the following outcome measures (dependent variables): Intracranial pressure; Retinal nerve fiber layer; Choroidal engorgement; Globe flattening; Axial biometry; Optic nerve sheath diameter distention; Cycloplegic refraction; Visual acuity. Study parameters (independent variables) to include: CO2; Sodium; Exercise (resistive & aerobic); Strict tilt angle.

  10. Analog storage integrated circuit

    DOEpatents

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

    1989-01-01

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

  11. Antarctic analogs for Enceladus

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  12. Analog storage integrated circuit

    DOEpatents

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

    1989-03-07

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

  13. A Transiting Jupiter Analog

    NASA Astrophysics Data System (ADS)

    Kipping, D. M.; Torres, G.; Henze, C.; Teachey, A.; Isaacson, H.; Petigura, E.; Marcy, G. W.; Buchhave, L. A.; Chen, J.; Bryson, S. T.; Sandford, E.

    2016-04-01

    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+/- 0.02) {R}{{J}}, a low orbital eccentricity ({0.06}-0.04+0.10), and an equilibrium temperature of (131+/- 3) 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 coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target.

  14. Combined chemical-enzymic synthesis of deoxygenated oligosaccharide analogs: transfer of deoxygenated D-GlcpNAc residues from their UDP-GlcpNAc derivatives using N-acetylglucosaminyltransferase I.

    PubMed

    Srivastava, G; Alton, G; Hindsgaul, O

    1990-10-25

    The 3''-, 4''-, and 6''-deoxy analogs of UDP-GlcpNAc have been synthesized chemically and found to act as donor-substrates for N-acetylglucosaminyltransferase-I (GnT-I) from human milk. Incubation of UDP-GlcpNAc and these deoxy analogs with GnT-I in the presence of alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-beta-D-Manp -O(CH2)8COOMe gave beta-D-GlcpNAc-(1----2)-alpha-D-Manp-(1----3)-[alpha-D-Manp- (1----6)]- beta-D-Manp-O(CH2)8COOMe (6), and the deoxy analogs 12-14 where HO-3, HO-4, and HO-6, respectively, of the beta-D-GlcNAc residue were replaced by hydrogen. The tetrasaccharide glycosides 6 and 12-14 were characterized by 1H-n.m.r. spectroscopy and evaluated as acceptors for GnT-II, the next enzyme in the pathway of biosynthesis of Asn-linked oligosaccharides. Deoxygenation of the 3-position of the beta-D-GlcNAc residue of 6 completely abolished its acceptor activity, whereas removal of HO-4 or HO-6 caused only modest decreases in activity.

  15. Polybrominated diphenyl ethers (PBDEs) and their methoxylated derivatives in pike from Swedish waters with emphasis on temporal trends, 1967-2000.

    PubMed

    Kierkegaard, A; Bignert, A; Sellström, U; Olsson, M; Asplund, L; Jansson, B; De Wit, C A

    2004-07-01

    Temporal trends of five tetra- to hexabromodiphenyl ethers [BDE47, BDE99, BDE100, BDE153 and BDE154) and two methoxy-tetraBDEs [6-methoxy-2,2',4,4'- tetraBDE (6-MeO-BDE47) and 2'-methoxy-2,3',4,5'- tetraBDE (2'-MeO-BDE68)] in pike from Lake Bolmen for the years 1967-2000, are presented. All BDE congeners show increasing trends up to the mid-1980s (Sigma5PBDE from 60 to 1600 pg/g wet weight in 1989, i.e. a more than 25-fold increase), and then decrease or level off. The decreasing trends of PBDEs after the 1980s were considerably slower in the present study than was found in a study of an environmental matrix from the Baltic Proper covering the same time period. This difference suggests local sources near Lake Bolmen. The MeO-BDEs show initially decreasing concentrations, which for 6-MeO-BDE47 continues until the early 1990s. The concentrations of 6-MeO-BDE47 in herring from five locations along the Swedish coast increased from south to north in the Baltic Sea. No correlation between the concentrations of the BDE congeners and the MeO-BDEs was observed, indicating sources other than PBDEs for these compounds. The presence of MeO-BDEs in fish from lakes with different characteristics suggests a natural production not favoured by eutrophication, or dependent on sampling season and geographical location.

  16. The Analogy Theme in Geography.

    ERIC Educational Resources Information Center

    Andrews, Alice C.

    1987-01-01

    Describes ten types of analogies and the role they play in thinking and learning. Devotes specific attention to the use of analogies in geography instruction. Claims that the use of analogies in teaching physical, cultural, and regional geography helps students absorb knowledge quickly and integrate it into their existing frameworks. (JDH)

  17. Terrestrial analogs of the hellespontus dunes, Mars

    USGS Publications Warehouse

    Breed, C.S.

    1977-01-01

    Geomorphic features in the Hellespontus region, Mars, were compared with dunes of the crescentic ridge type in numerous terrestrial sand seas quantitatively by dimensional analysis of dune lengths, widths, and wavelengths. Mean values for the Hellespontus dunes are close to mean values derived from measurements of all sampled terrestrial sand seas. Terrestrial analogs of form and areal distribution of the Hellespontus dunes are shown by comparison of scale ratios derived from the measurements. Dunes of similar form occur in South West Africa, in Pakistan, in the southeastern Arabian peninsula, in the Sahara, in eastern USSR and northern China, and in western North America. Terrestrial analogs closest to form and areal distribution of the Hellespontus dunes are in the Kara Kum Desert, Turkmen SSR, and in the Ala Shan (Gobi) Desert, China. ?? 1977.

  18. Analogical scaffolding: Making meaning in physics through representation and analogy

    NASA Astrophysics Data System (ADS)

    Podolefsky, Noah Solomon

    This work reviews the literature on analogy, introduces a new model of analogy, and presents a series of experiments that test and confirm the utility of this model to describe and predict student learning in physics with analogy. Pilot studies demonstrate that representations (e.g., diagrams) can play a key role in students' use of analogy. A new model of analogy, Analogical Scaffolding, is developed to explain these initial empirical results. This model will be described in detail, and then applied to describe and predict the outcomes of further experiments. Two large-scale (N>100) studies will demonstrate that: (1) students taught with analogies, according to the Analogical Scaffolding model, outperform students taught without analogies on pre-post assessments focused on electromagnetic waves; (2) the representational forms used to teach with analogy can play a significant role in student learning, with students in one treatment group outperforming students in other treatment groups by factors of two or three. It will be demonstrated that Analogical Scaffolding can be used to predict these results, as well as finer-grained results such as the types of distracters students choose in different treatment groups, and to describe and analyze student reasoning in interviews. Abstraction in physics is reconsidered using Analogical Scaffolding. An operational definition of abstraction is developed within the Analogical Scaffolding framework and employed to explain (a) why physicists consider some ideas more abstract than others in physics, and (b) how students conceptions of these ideas can be modeled. This new approach to abstraction suggests novel approaches to curriculum design in physics using Analogical Scaffolding.

  19. Biophysical characterization of hyper-branched polyethylenimine-graft-polycaprolactone-block-mono-methoxyl-poly(ethylene glycol) copolymers (hy-PEI-PCL-mPEG) for siRNA delivery.

    PubMed

    Liu, Yu; Samsonova, Olga; Sproat, Brian; Merkel, Olivia; Kissel, Thomas

    2011-08-10

    A library of mono-methoxyl-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) modified hyperbranched PEI copolymers (hy-PEI-PCL-mPEG) was synthesized to establish structure function relationships for siRNA delivery. These amphiphilic block-copolymers were thought to provide improved colloidal stability and endosomal escape of polyplexes containing siRNA. The influence of the mPEG chain length, PCL segment length, hy-PEI molecular weight and the graft density on their biophysical properties was investigated. In particular, buffer capacity, complex formation constants, gene condensation, polyplex stability, polyplex size and zeta-potential were measured. It was found that longer mPEG chains, longer PCL segments and higher graft density beneficially affected the stability and formation of polyplexes and reduced the zeta-potential of siRNA polyplexes. Significant siRNA mediated knockdown was observed for hy-PEI25k-(PCL900-mPEG2k)(1) at N/P 20 and 30, implying that the PCL hydrophobic segment played a very important role in siRNA transfection. These gene delivery systems merit further investigation under in vivo conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Biomagnification of naturally-produced methoxylated polybrominated diphenyl ethers (MeO-PBDEs) in harbour seals and harbour porpoises from the southern North Sea.

    PubMed

    Weijs, Liesbeth; Losada, Sara; Das, Krishna; Roosens, Laurence; Reijnders, Peter J H; Santos, Javier F; Neels, Hugo; Blust, Ronny; Covaci, Adrian

    2009-08-01

    Harbour seals and harbour porpoises are top predator species from the North Sea, have long life spans and hence, are known to accumulate high levels of anthropogenic contaminants. To gain knowledge about the behaviour of naturally-produced compounds in these marine mammals, the biomagnification of naturally-produced methoxylated polybrominated diphenyl ethers (MeO-PBDEs) was assessed. The biomagnification of MeO-PBDEs (2'-MeO-BDE 68 and 6-MeO-BDE 47) was lower in harbour seals (all biomagnification factors (BMFs)<1) compared to the same age-gender groups of the harbour porpoises (all BMFs>1). This may indicate a better metabolic breakdown of MeO-PBDEs in harbour seals, as was previously suggested for polybrominated diphenyl ethers (PBDEs). In both predators, 6-MeO-BDE 47 had the highest concentrations (range: 45-483 ng/g lw and 2-38 ng/g lw for harbour porpoises and seals, respectively) compared to 2'-MeO-BDE 68 (range: 2-28 ng/g lw and 1-6 ng/g lw for harbour porpoises and seals, respectively). In general, the highest concentrations were found in juveniles, suggesting an increased biotransformation capacity with age or the influence of dilution by growth for both species. Here we show that naturally-produced brominated organic compounds can biomagnify and accumulate in North Sea top predators, although to a lesser extent than anthropogenic lipophilic contaminants, such as polychlorinated biphenyls (PCBs) or PBDEs.

  1. Differential estimation of isomeric 2- and 4-methoxylated estrogens in serum by matrix-assisted laser desorption ionization-tandem mass spectrometry.

    PubMed

    Moon, Ju-Yeon; Kim, Sun Ju; Moon, Myeong Hee; Chung, Bong Chul; Choi, Man Ho

    2013-01-01

    As a simple and rapid method for small-molecule analysis, matrix-assisted laser desorption ionization coupled with linear ion-trap tandem mass spectrometry (MALDI-LTQ-MS/MS) was used to differentially quantify 2- and 4-methoxyestrogens in spiked serum samples. Both 2- and 4-methoxyestrogens were consistently identified using distinct analyte-matrix adduct [M+H+CHCA](+) precursor ions when a mixture of 10 mg mL(-1) α-cyano-4-hydroxycinnamic acid (CHCA) in 0.2% trifluoroacetic acid/70% acetonitrile was used as the MALDI matrix. Especially, unusual isomeric product ions from each precursor ion were characterized during MALDI-MS/MS analysis, which permitted differential estimations of isomeric 2- and 4-methoxylated estrone and 17β-estradiol. The calibration linearity was higher than 0.99 in the dynamic range, while the inter-day precision and accuracy ranged from 6.8 to 30.6%, and from 91.4 to 108.5%, respectively. The present technique could be used as a screening assay for 2- and 4-methoxyestrogens without the need for prior chromatographic separation, opening up possible applications in large-scale pharmacokinetic studies.

  2. Levels and distribution of methoxylated and hydroxylated polybrominated diphenyl ethers in plant and soil samples surrounding a seafood processing factory and a seafood market.

    PubMed

    Sun, Jianteng; Liu, Jiyan; Liu, Yanwei; Jiang, Guibin

    2013-05-01

    Polybrominated diphenyl ethers (PBDEs) along with hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) were found in plant and soil samples collected surrounding a seafood processing factory and a seafood market in China. The profiles of MeO-PBDE congeners were different between seafood processing factory and seafood market. The detection frequency and concentration of 6-OH-BDE-47 were lower than that of MeO-PBDEs. Near seafood processing factory, a decreasing trend of analyte concentrations in plants was found downstream the river where factory wastewater was discharged. Concentrations of ΣMeO-PBDEs in plant and soil samples showed difference as root > soil > leaf. However, at seafood market, the concentrations of ΣMeO-PBDEs were much higher in leaves than those in soil. The concentration of ΣMeO-PBDEs in leaves showed a remarkable difference between Calystegia soldanella (Linn.) R. Br. and Setaira viridis (L.) Beauv. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Improved 3D-QSPR analysis of the predictive octanol-air partition coefficients of hydroxylated and methoxylated polybrominated diphenyl ethers

    NASA Astrophysics Data System (ADS)

    Liu, Hongxia; Shi, Jiaqi; Liu, Hui; Wang, Zunyao

    2013-10-01

    The octanol/air partition coefficient (KOA) is a key physicochemical parameter for describing the partition of organic pollutants between air and environment organic phase. The development of appropriate method to estimate KOA is of great importance. In the present study, the steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor descriptors were computed by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). On the basis of these parameters, the statistically quantitative structure-property relationship (QSPR) models for logKOA of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) congeners were developed using partial least-squares (PLS) analysis, of which the R2 is about 0.980, 0.952 respectively. The electrostatic field was found to be main factors governing the logKOA. The results of validation indicate the models of this study exhibit optimum stability, and thus it is feasible to predict logKOA.

  4. Characterization of polybrominated diphenyl ethers (PBDEs) and hydroxylated and methoxylated PBDEs in soils and plants from an e-waste area, China.

    PubMed

    Wang, Sen; Zhang, Shuzhen; Huang, Honglin; Niu, Zhenchuan; Han, Wei

    2014-01-01

    In order to characterize polybrominated diphenyl ethers (PBDEs), and hydroxylated and methoxylated PBDEs (OH-PBDEs and MeO-PBDEs) in the soil-plant system, soil and plant samples were collected from an e-waste recycling area in China. Forty one PBDEs, twelve OH-PBDEs and MeO-PBDEs were detected in the soil and plant samples. Concentrations of PBDEs in roots were significantly correlated to their concentrations in the soils, but the percentages of lower brominated congeners in the plants were higher than those in the soils. Significant positive linear relationships exist between concentrations of ∑OH-PBDEs and ∑MeO-PBDEs with higher levels of ∑MeO-PBDEs than those of ∑OH-PBDEs in the soils, plant roots and leaves. A majority of the OH-/MeO-PBDEs had the hydroxyl or methoxy group at the ortho-positions to the biphenyl bond for most of the plant species. However the occurrence of meta- and para- substituted OH-/MeO-PBDEs in soils and plants were also confirmed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. 2-amino-nonyl-6-methoxyl-tetralin muriate activity against Candida albicans augments endogenous reactive oxygen species production --a microarray analysis study.

    PubMed

    Liang, Rong Mei; Yong, Xiao Lan; Jiang, Yun Ping; Tan, Yong Hong; Dai, Bao Di; Wang, Shi Hua; Hu, Ting Ting; Chen, Xi; Li, Nan; Dong, Zhao Hui; Huang, Xiao Chun; Chen, Jun; Cao, Yong Bing; Jiang, Yuan Ying

    2011-04-01

    Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections.

  6. Effects of Accelerated Storage on the Quality of Kenaf Seed Oil in Chitosan-Coated High Methoxyl Pectin-Alginate Microcapsules.

    PubMed

    Leong, Mei-Huan; Tan, Chin-Ping; Nyam, Kar-Lin

    2016-10-01

    The objective of this research was to study the oxidative stability and antioxidant properties of microencapsulated kenaf (Hibiscus cannabinus L.) seed oil (MKSO) produced by co-extrusion technology upon accelerated storage. The combination of sodium alginate, high methoxyl pectin, and chitosan were used as shell materials. The oxidative stability of the kenaf seed oil was determined by iodine value, peroxide value, p-Anisidine value, total oxidation (TOTOX), thiobarbituric acid reactive substances assay, and free fatty acid content. Total phenolic content, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) cation radical-scavenging assay and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay were used to examine the antioxidant properties of oils. Oxidative stability tests showed that bulk kenaf seed oil (BKSO) was oxidized significantly higher (P < 0.05) than MKSO. The total increment of TOTOX value of BKSO was 165.93% significantly higher (P < 0.05) than MKSO. Co-extrusion technology has shown to be able to protect kenaf seed oil against lipid oxidation and delay the degradation of natural antioxidants that present in oil during storage.

  7. Antarctic Space Analog Program

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  8. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

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

  9. Female analogies to perversion.

    PubMed

    Beier, K M

    2000-01-01

    Unlike the intrapsychic mechanism for self-esteem regulation in males as a basic component of perversion--extrapsychically (compensationally) culminating in an output of sexual impulses--a functional stabilization of the female self-concept seems more likely if conflict drives were to be focused on reproductional aspects and not on sexuality. It therefore seems more suitable to use a new expression in linguistic analogy to perversion: "reproversion." The case history gives an example of a clinical manifestation of "reproverse" symptom formation. The general survey describes the main points of view in regard to clinically oriented differentiation, i.e., intensity, ego-proximity in the personality structure, and one's own self-acceptance within "reproverse" symptom formation. Underlying personality disturbances are also discussed. The significance of reproversion is relevant to many different specialized medical fields. This is explained in conclusion, using the examples of denied pregnancy and infanticide at birth based on initial empirical results.

  10. Hydroxylated and methoxylated polybrominated diphenyl ethers and polybrominated dibenzo-p-dioxins in red alga and cyanobacteria living in the Baltic Sea.

    PubMed

    Malmvärn, Anna; Zebühr, Yngve; Kautsky, Lena; Bergman, Ke; Asplund, Lillemor

    2008-06-01

    Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and methoxylated polybrominated diphenyl ethers (MeO-PBDEs) are present in the ecosystem of the Baltic Sea. OH-PBDEs are known to be both natural products from marine environments and metabolites of the anthropogenic polybrominated diphenyl ethers (PBDEs), whereas, MeO-PBDEs appear to be solely natural in origin. Polybrominated dibenzo-p-dioxins (PBDDs) are by-products formed in connection with the combustion of brominated flame retardants (BFRs), but are also indicated as natural products in a red alga (Ceramium tenuicorne) and blue mussels living in the Baltic Sea. The aims of the present investigation were to quantify the OH-PBDEs and MeO-PBDEs present in C. tenuicorne; to verify the identities of PBDDs detected previously in this species of red alga and to investigate whether cyanobacteria living in this same region of the Baltic Sea contain OH-PBDEs, MeO-PBDEs and/or PBDDs. The red alga was confirmed to contain tribromodibenzo-p-dioxins (triBDDs), by accurate mass determination and additional PBDD congeners were also detected in this sample. This is the first time that PBDDs have been identified in a red alga. The SigmaOH-PBDEs and SigmaMeO-PBDEs concentrations, present in C. tenuicorne were 150 and 4.6 ng g(-1) dry weight, respectively. In the cyanobacteria 6 OH-PBDEs, 6 MeO-PBDEs and 4 PBDDs were detected by mass spectrometry (electron capture negative ionization (ECNI)). The PBDDs and OH-PBDEs and MeO-PBDEs detected in the red alga and cyanobacteria are most likely of natural origin.

  11. p,p'-Methoxyl-diphenyl diselenide-loaded polymeric nanocapsules as a novel approach to inflammatory pain treatment: Behavioral, biochemistry and molecular evidence.

    PubMed

    Marcondes Sari, Marcel Henrique; Zborowski, Vanessa Angonesi; Ferreira, Luana Mota; Jardim, Natália Silva; Barbieri, Allanna Valentini; Cruz, Letícia; Nogueira, Cristina Wayne

    2017-09-22

    The current study investigated the effect of organoselenium compound p,p'-methoxyl-diphenyl diselenide [(OMePhSe)2], free or incorporated into nanocapsules, on behavioral, biochemical and molecular alterations in an inflammatory pain model induced by complete Freund's adjuvant (CFA). Male Swiss mice received an intraplantar injection of CFA in the hindpaw and 24 h later they were treated via the intragastric route with a single (OMePhSe)2 administration, in its free form (dissolved in canola oil) or (OMePhSe)2 NC. The anti-hypernociceptive time- and dose-response curves were carried out using the von Frey hair test. Biochemical and histological parameters were determined in samples of injected paws and those of cerebral contralateral cortex were collected to determine immuno content of inflammatory proteins. Both (OMePhSe)2 forms reduced the hypernociception induced by CFA as well as attenuated the altered parameters of the inflammatory process in the paw (paw edema, myeloperoxidase and histological). However, the (OMePhSe)2 NC had a more prolonged anti-hypernociceptive action (7h) at a lower dose (10mg/kg) and superior effects on the paw alterations than the free compound form (4h and 25mg/kg). Furthermore, independent of the (OMePhSe)2 form, its administration decreased the MAPKs pathway activation (JNK;ERK1,2; p38) as well as iNOS, COX-2, Nf-κB and IL-1β protein contents in the cerebral contralateral cortex that were increased by paw CFA injection. Therefore, (OMePhSe)2 NC had superior anti-inflammatory action, which possibly occurs by the inflammatory protein content modulation and also attenuates paw biochemical and histological inflammatory alterations induced by CFA injection. Copyright © 2017. Published by Elsevier B.V.

  12. High internal phase emulsions stabilized solely by whey protein isolate-low methoxyl pectin complexes: effect of pH and polymer concentration.

    PubMed

    Wijaya, Wahyu; Van der Meeren, Paul; Wijaya, Christofora Hanny; Patel, Ashok R

    2017-02-22

    In recent years, there has been significant progress in edible emulsion technology especially with respect to creating and stabilizing surfactant-free emulsion systems for food applications. In this paper, we demonstrate the fabrication of high internal phase emulsions (HIPE) (φoil = 0.82) stabilized using colloidal complexes of non-gelling biopolymers (at concentrations as low as 0.3 wt%). The colloidal complexes were pre-formed by combining whey protein isolate (WPI) and low-methoxyl pectin (LMP) at three different pH values (i.e. pH 3.5, 4.5, 5.5) and used further for fabricating stable HIPEs. In addition to the effect of pH, the influence of total biopolymer concentration on the formation and properties of HIPEs was also evaluated. Depending on the total concentration of biopolymers used, the WPI-LMP complexes (formed at pH 4.5) showed a Z-average diameter in the range of 250-350 nm. It was found that the formation of HIPEs was strongly influenced by the pH of the colloidal complexes. At a pH close to the isoelectric point of WPI (≈pH 4.8) and WPI-LMP complexes (≈pH 3.4), severe aggregation of colloidal particles occurred, resulting in poor formation and stability of HIPEs. On comparing the stabilization behaviour of the complexes with the uncomplexed protein, it was noticed that the former provided comparatively better stabilization to the HIPEs against coalescence at pH 4.5 and 5.5. Based on the rheological data (low amplitude oscillatory shear rheology and flow measurements), all HIPE samples showed viscoelastic and shear-thinning behaviour. We believe that such viscoelastic gel-like systems could find potential commercial applications in the development of label-friendly novel food products with interesting textures.

  13. Nuclear Hormone Receptor Activity of Polybrominated Diphenyl Ethers and Their Hydroxylated and Methoxylated Metabolites in Transactivation Assays Using Chinese Hamster Ovary Cells

    PubMed Central

    Kojima, Hiroyuki; Takeuchi, Shinji; Uramaru, Naoto; Sugihara, Kazumi; Yoshida, Takahiko; Kitamura, Shigeyuki

    2009-01-01

    Background An increasing number of studies are reporting the existence of polybrominated diphenyl ethers (PBDEs) and their hydroxylated (HO) and methoxylated (MeO) metabolites in the environment and in tissues from wildlife and humans. Objective Our aim was to characterize and compare the agonistic and antagonistic activities of principle PBDE congeners and their HO and MeO metabolites against human nuclear hormone receptors. Methods We tested the hormone receptor activities of estrogen receptor α (ERα), ERβ, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor α1 (TRα1), and TRβ1 against PBDE congeners BDEs 15, 28, 47, 85, 99, 100, 153, and 209, four para-HO-PBDEs, and four para-MeO-PBDEs by highly sensitive reporter gene assays using Chinese hamster ovary cells. Results Of the 16 compounds tested, 6 and 2 showed agonistic activities in the ERα and ERβ assays, respectively, and 6 and 6 showed antagonistic activities in these assays. 4′-HO-BDE-17 showed the most potent estrogenic activity via ERα/β, and 4′-HO-BDE-49 showed the most potent anti estrogenic activity via ERα/β. In the AR assay, 13 compounds showed antagonistic activity, with 4′-HO-BDE-17 in particular inhibiting AR-mediated transcriptional activity at low concentrations in the order of 10−8 M. In the GR assay, seven compounds, including two HO-PBDEs and two MeO-PBDEs, showed weak antagonistic activity. In the TRα1 and TRβ1 assays, only 4-HO-BDE-90 showed weak antagonistic activity. Conclusions Taken together, these results suggest that PBDEs and their metabolites might have multiple endocrine-disrupting effects via nuclear hormone receptors, and para-HO-PBDEs, in particular, possess more potent receptor activities compared with those of the parent PBDEs and corresponding para-MeO-PBDEs. PMID:19672399

  14. Mathematical problem solving by analogy.

    PubMed

    Novick, L R; Holyoak, K J

    1991-05-01

    We report the results of 2 experiments and a verbal protocol study examining the component processes of solving mathematical word problems by analogy. College students first studied a problem and its solution, which provided a potential source for analogical transfer. Then they attempted to solve several analogous problems. For some problems, subjects received one of a variety of hints designed to reduce or eliminate the difficulty of some of the major processes hypothesized to be involved in analogical transfer. Our studies yielded 4 major findings. First, the process of mapping the features of the source and target problems and the process of adapting the source solution procedure for use in solving the target problem were clearly distinguished: (a) Successful mapping was found to be insufficient for successful transfer and (b) adaptation was found to be a major source of transfer difficulty. Second, we obtained direct evidence that schema induction is a natural consequence of analogical transfer. The schema was found to co-exist with the problems from which it was induced, and both the schema and the individual problems facilitated later transfer. Third, for our multiple-solution problems, the relation between analogical transfer and solution accuracy was mediated by the degree of time pressure exerted for the test problems. Finally, mathematical expertise was a significant predictor of analogical transfer, but general analogical reasoning ability was not. The implications of the results for models of analogical transfer and for instruction were considered.

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

    PubMed

    Nachtigall, Werner

    2010-01-01

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

  16. Synthesis of tetracycline ring A analogs.

    PubMed

    Moskalyk, R E; Mak, A L; Chatten, L G; Locock, R A

    1981-05-01

    Studies directed at the synthesis of tetracycline ring A analogs are described. 4-Carbethoxycyclohexane-1,3-dione was converted to the ethyl urethan dispiro[1,3-dioxolane-2,2'-cyclohexane-4',2"(1,3)-dioxolane]-1'-carbamic acid ethyl ester via the dispiro[1,3-dioxolane-2,2'-cyclohexane-4'-2"(1,3)-dioxolane]-1'-carboxylic acid hydrazide. An improved synthesis of another cyclohexenone from methyl vinyl ketone and ethyl nitroacetate is reported. Reaction of N-(3-hydroxy-1-oxo-2-cyclohexen-4-yl)benzamide with alpha-chloroacetyl isocyanate afforded a 4(5H)-oxazolone derivative, as did the identical reaction on 5,5-dimethyl-1,3-cyclohexanedione (dimedone). This reaction provides a novel approach to these oxazolones with potential therapeutic importance. Other ring A analogs were synthesized also.

  17. Digital and analog chemical evolution.

    PubMed

    Goodwin, Jay T; Mehta, Anil K; Lynn, David G

    2012-12-18

    Living matter is the most elaborate, elegant, and complex hierarchical material known and is consequently the natural target for an ever-expanding scientific and technological effort to unlock and deconvolute its marvelous forms and functions. Our current understanding suggests that biological materials are derived from a bottom-up process, a spontaneous emergence of molecular networks in the course of chemical evolution. Polymer cooperation, so beautifully manifested in the ribosome, appeared in these dynamic networks, and the special physicochemical properties of the nucleic and amino acid polymers made possible the critical threshold for the emergence of extant cellular life. These properties include the precise and geometrically discrete hydrogen bonding patterns that dominate the complementary interactions of nucleic acid base-pairing that guide replication and ensure replication fidelity. In contrast, complex and highly context-dependent sets of intra- and intermolecular interactions guide protein folding. These diverse interactions allow the more analog environmental chemical potential fluctuations to dictate conformational template-directed propagation. When these two different strategies converged in the remarkable synergistic ribonucleoprotein that is the ribosome, this resulting molecular digital-to-analog converter achieved the capacity for both persistent information storage and adaptive responses to an ever-changing environment. The ancestral chemical networks that preceded the Central Dogma of Earth's biology must reflect the dynamic chemical evolutionary landscapes that allowed for selection, propagation, and diversification and ultimately the demarcation and specialization of function that modern biopolymers manifest. Not only should modern biopolymers contain molecular fossils of this earlier age, but it should be possible to use this information to reinvent these dynamic functional networks. In this Account, we review the first dynamic network

  18. Natural analog studies: Licensing perspective

    SciTech Connect

    Bradbury, J.W.

    1995-09-01

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

  19. Drawing Analogies in Environmental Education

    ERIC Educational Resources Information Center

    Affifi, Ramsey

    2014-01-01

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

  20. Analogy, Dialectics and Lifelong Learning.

    ERIC Educational Resources Information Center

    Bailey, Ted

    2003-01-01

    Compares analogies and dialectics, discussing limitations of the Hegelian/Marxian dialectical form in adult education. Proposes the more holistic approach of Vico, a double dialectic that connects social and individual relationships, knowledge, and experience. Demonstrates a dialectical learning exchange that uses an analogy trigger. (SK)

  1. Drawing Analogies in Environmental Education

    ERIC Educational Resources Information Center

    Affifi, Ramsey

    2014-01-01

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

  2. Conjecturing via Reconceived Classical Analogy

    ERIC Educational Resources Information Center

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  3. Conjecturing via Reconceived Classical Analogy

    ERIC Educational Resources Information Center

    Lee, Kyeong-Hwa; Sriraman, Bharath

    2011-01-01

    Analogical reasoning is believed to be an efficient means of problem solving and construction of knowledge during the search for and the analysis of new mathematical objects. However, there is growing concern that despite everyday usage, learners are unable to transfer analogical reasoning to learning situations. This study aims at facilitating…

  4. Analog pixel array detectors.

    PubMed

    Ercan, A; Tate, M W; Gruner, S M

    2006-03-01

    X-ray pixel array detectors (PADs) are generally thought of as either digital photon counters (DPADs) or X-ray analog-integrating pixel array detectors (APADs). Experiences with APADs, which are especially well suited for X-ray imaging experiments where transient or high instantaneous flux events must be recorded, are reported. The design, characterization and experimental applications of several APAD designs developed at Cornell University are discussed. The simplest design is a ;flash' architecture, wherein successive integrated X-ray images, as short as several hundred nanoseconds in duration, are stored in the detector chips for later off-chip digitization. Radiography experiments using a prototype flash APAD are summarized. Another design has been implemented that combines flash capability with the ability to continuously stream X-ray images at slower (e.g. milliseconds) rates. Progress is described towards radiation-hardened APADs that can be tiled to cover a large area. A mixed-mode PAD, design by combining many of the attractive features of both APADs and DPADs, is also described.

  5. Enzymic glycosphingolipid synthesis on polymer supports. III. Synthesis of GM3, its analog [NeuNAcalpha(2-3)Galbeta(1-4)Glcbeta(1-3)Cer] and their lyso-derivatives.

    PubMed

    Zehavi, U; Tuchinsky, A

    1998-07-01

    Two water-soluble polymers, carrying 0.24 meq g(-1) of lactosyl-beta(1-1)-sphingosine (7) and 0.13 meq g(-1) of lactosyl-beta(1-3)-sphingosine (8) were prepared. The polymers served as acceptors in the alpha-(2-3)-sialyltransferase reaction (up to 55.3 and 38.5% transfer yields, respectively). Subsequent photolysis, released compounds 11 (lyso-GM3) and 12 (lyso-GM3 analog), respectively; acylation and chromatography afforded (5-acetamido-3,5-dideoxy-D-glycero-alpha-galacto-2-nonulopyranosyloni c acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-1)-(2 S, 3R, 4E)-2-octadecanoylamino-4-octadecene-1,3-diol (13, GM3) and (5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylo nic acid)-(2-3)-beta-D-galactopyranosyl-(1-4)-beta-D-glucopyranosyl-(1-3)-(2 S, 3R, 4E)-2-octadecanoylamino-4-octadecene-1,3-diol (14, GM3 analogue), respectively, thus presenting a route to glycosphingolipids possessing the unusual glycosyl-beta(1-3)-spingosine linkage.

  6. Orthographic analogies and developmental dyslexia.

    PubMed

    Hanley, J R; Reynolds, C J; Thornton, A

    1997-08-01

    Goswami (1986, 1988) has demonstrated that children can use orthographic analogies (particularly at the onset-rime level) between the spelling patterns in words to help to decode new words (e.g. using 'beak' to read 'peak'). This strategy has been shown in children as young as six years old. Since it is known that children with developmental dyslexia find it particularly difficult to read words that they have not been specifically taught (Lovett, Warren-Chaplin, Ransby & Borden, 1990), the present study investigated whether dyslexic children might be unable to use analogies. Employing a design similar to that used by Goswami (1988), it was hypothesized that dyslexics would find it difficult to transfer spontaneously knowledge of a 'clue' word to decode new words that could be read by analogy with the clue word. The results of Expt 1 indicated that the dyslexic readers read significantly fewer of the analogous words than a reading age-matched comparison group of younger children. Furthermore, none of the nine dyslexic children read as many of the analogous words as the lowest scoring control child. In a second experiment, a design similar to that of Muter, Snowling & Taylor (1994) was used with a new and larger sample of dyslexic children. In this experiment, all the children were brought to criterion in reading the clue words before the analogous words were presented. Once again, the dyslexic children read significantly fewer words that were analogous with the clue words than did a reading age-matched comparison group. The number of analogous words that the dyslexic children read was significantly correlated with their performance on a test that is sensitive to the ability to detect rhyme. It is argued that a failure to make analogies may be one of the main causes of the reading impairment experienced by children with developmental dyslexia.

  7. Theory of analogous force on number sets

    NASA Astrophysics Data System (ADS)

    Canessa, Enrique

    2003-10-01

    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 leads 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.

  8. Resonance Enhanced Multi-Photon Ionization and Uv-Uv Hole-Burning Spectroscopic Studies of Jet-Cooled Acetanilide Derivatives

    NASA Astrophysics Data System (ADS)

    Moon, Ceol Joo; Min, Ahreum; Ahn, Ahreum; Lee, Seung Jun; Choi, Myong Yong; Kim, Seong Keun

    2013-06-01

    Conformational investigations and photochemistry of jet-cooled methacetine (MA) and phenacetine (PA) using one color resonant two-photon ionization (REMPI), UV-UV hole-burning and IR-dip spectroscopy are presented. MA and PA are derivatives of acetanilide, substituted by methoxyl, ethoxyl group in the para position of acetanilide, respectively. Moreover, we have investigated conformational information of the acetanilide derivatives (AAP, MA and PA)-water. In this work, we will present and discuss the solvent effects of the hydroxyl group of acetanilide derivatives in the excited state.

  9. Factors Affecting the Difficulty of Verbal Analogies.

    ERIC Educational Resources Information Center

    Roccas, Sonia; Moshinsky, Avital

    2003-01-01

    Examined factors affecting the difficulty of verbal analogies in a psychometric examination by characterizing 104 analogies using 5 defined attributes. Both knowledge and process attributes were found to contribute to the difficulty of verbal analogies assessed by 10 judges. (SLD)

  10. Analog actuator-piston memory

    NASA Technical Reports Server (NTRS)

    Sable, B. A.

    1980-01-01

    Simple analog control system of digitally controlled acuator uses 'stopped' position of actuator as 'memory' and potentiometer as sensing element during power failure to reload drive circuit to value equal to its last position preceding power loss.

  11. Flight Analogs (Bed Rest Research)

    NASA Image and Video Library

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

  12. Analog device simulates physiological waveforms

    NASA Technical Reports Server (NTRS)

    Hickman, D. M.

    1964-01-01

    An analog physiological simulator generates representative waveforms for a wide range of physiological conditions. Direct comparison of these waveforms with those from telemetric inputs permits quick detection of signal parameter degradation.

  13. Introduction to Analog Field Testing

    NASA Image and Video Library

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

  14. Solving a problem by analogy

    NASA Astrophysics Data System (ADS)

    Easton, Don

    1999-03-01

    This note is a description of a student solution to a problem. I found the solution exciting because it exemplifies the kind of solution by analogy that Feynman describes in The Feynman Lectures on Physics.

  15. Verbal Analogies in the ITPA

    ERIC Educational Resources Information Center

    Levinson, Philip J.; Kunze, Luvern H.

    1973-01-01

    This study examined the extent to which the Auditory Association subtest of the revised Illinois Test of Psycholinguistic Abilities (ITPA) measures the ability of children to complete verbal analogies. (Author)

  16. Improving nucleoside diphosphate kinase for antiviral nucleotide analogs activation.

    PubMed

    Gallois-Montbrun, Sarah; Schneider, Benoit; Chen, Yuxing; Giacomoni-Fernandes, Veronique; Mulard, Laurence; Morera, Solange; Janin, Joel; Deville-Bonne, Dominique; Veron, Michel

    2002-10-18

    Antiviral nucleoside analog therapies rely on their incorporation by viral DNA polymerases/reverse transcriptase leading to chain termination. The analogs (3'-deoxy-3'-azidothymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (d4T), and other dideoxynucleosides) are sequentially converted into triphosphate by cellular kinases of the nucleoside salvage pathway and are often poor substrates of these enzymes. Nucleoside diphosphate (NDP) kinase phosphorylates the diphosphate derivatives of the analogs with an efficiency some 10(4) lower than for its natural substrates. Kinetic and structural studies of Dictyostelium and human NDP kinases show that the sugar 3'-OH, absent from all antiviral analogs, is required for catalysis. To improve the catalytic efficiency of NDP kinase on the analogs, we engineered several mutants with a protein OH group replacing the sugar 3'-OH. The substitution of Asn-115 in Ser and Leu-55 in His results in an NDP kinase mutant with an enhanced ability to phosphorylate antiviral derivatives. Transfection of the mutant enzyme in Escherichia coli results in an increased sensitivity to AZT. An x-ray structure at 2.15-A resolution of the Dictyostelium enzyme bearing the serine substitution in complex with the R(p)-alpha-borano-triphosphate derivative of AZT shows that the enhanced activity reflects an improved geometry of binding and a favorable interaction of the 3'-azido group with the engineered serine.

  17. Methanogenic degradation of lignin-derived monoaromatic compounds by microbial enrichments from rice paddy field soil.

    PubMed

    Kato, Souichiro; Chino, Kanako; Kamimura, Naofumi; Masai, Eiji; Yumoto, Isao; Kamagata, Yoichi

    2015-09-24

    Anaerobic degradation of lignin-derived aromatics is an important metabolism for carbon and nutrient cycles in soil environments. Although there are some studies on degradation of lignin-derived aromatics by nitrate- and sulfate-reducing bacteria, knowledge on their degradation under methanogenic conditions are quite limited. In this study, methanogenic microbial communities were enriched from rice paddy field soil with lignin-derived methoxylated monoaromatics (vanillate and syringate) and their degradation intermediates (protocatechuate, catechol, and gallate) as the sole carbon and energy sources. Archaeal community analysis disclosed that both aceticlastic (Methanosarcina sp.) and hydrogenotrophic (Methanoculleus sp. and Methanocella sp.) methanogens dominated in all of the enrichments. Bacterial community analysis revealed the dominance of acetogenic bacteria (Sporomusa spp.) only in the enrichments on the methoxylated aromatics, suggesting that Sporomusa spp. initially convert vanillate and syringate into protocatechuate and gallate, respectively, with acetogenesis via O-demethylation. As the putative ring-cleavage microbes, bacteria within the phylum Firmicutes were dominantly detected from all of the enrichments, while the dominant phylotypes were not identical between enrichments on vanillate/protocatechuate/catechol (family Peptococcaceae bacteria) and on syringate/gallate (family Ruminococcaceae bacteria). This study demonstrates the importance of cooperation among acetogens, ring-cleaving fermenters/syntrophs and aceticlastic/hydrogenotrophic methanogens for degradation of lignin-derived aromatics under methanogenic conditions.

  18. Methanogenic degradation of lignin-derived monoaromatic compounds by microbial enrichments from rice paddy field soil

    PubMed Central

    Kato, Souichiro; Chino, Kanako; Kamimura, Naofumi; Masai, Eiji; Yumoto, Isao; Kamagata, Yoichi

    2015-01-01

    Anaerobic degradation of lignin-derived aromatics is an important metabolism for carbon and nutrient cycles in soil environments. Although there are some studies on degradation of lignin-derived aromatics by nitrate- and sulfate-reducing bacteria, knowledge on their degradation under methanogenic conditions are quite limited. In this study, methanogenic microbial communities were enriched from rice paddy field soil with lignin-derived methoxylated monoaromatics (vanillate and syringate) and their degradation intermediates (protocatechuate, catechol, and gallate) as the sole carbon and energy sources. Archaeal community analysis disclosed that both aceticlastic (Methanosarcina sp.) and hydrogenotrophic (Methanoculleus sp. and Methanocella sp.) methanogens dominated in all of the enrichments. Bacterial community analysis revealed the dominance of acetogenic bacteria (Sporomusa spp.) only in the enrichments on the methoxylated aromatics, suggesting that Sporomusa spp. initially convert vanillate and syringate into protocatechuate and gallate, respectively, with acetogenesis via O-demethylation. As the putative ring-cleavage microbes, bacteria within the phylum Firmicutes were dominantly detected from all of the enrichments, while the dominant phylotypes were not identical between enrichments on vanillate/protocatechuate/catechol (family Peptococcaceae bacteria) and on syringate/gallate (family Ruminococcaceae bacteria). This study demonstrates the importance of cooperation among acetogens, ring-cleaving fermenters/syntrophs and aceticlastic/hydrogenotrophic methanogens for degradation of lignin-derived aromatics under methanogenic conditions. PMID:26399549

  19. The Robustness of Acoustic Analogies

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  20. Polymorphism of ceramide 3. Part 2: a vibrational spectroscopic and X-ray powder diffraction investigation of N-octadecanoyl phytosphingosine and the analogous specifically deuterated d(35) derivative.

    PubMed

    Raudenkolb, Steve; Wartewig, Siegfried; Neubert, Reinhard H H

    2003-07-01

    In order to characterize the arrangements of the hydrocarbon chains of ceramide 3, the thermotropic phase behaviour of the ceramides N-octadecanoylphytosphingosine (CER3) and its chain deuterated derivative N-(d(35)-octadecanoyl)phytosphingosine (d(35)CER3) was studied by means of X-ray powder diffraction, FT-IR and Raman spectroscopy. CER3 and d(35)CER3 exhibit an identical thermotropic polymorphism involving three different crystalline phases. The selective deuteration of the fatty acid chain enables to distinguish the sphingoid part from the fatty acid part by means of FT-IR and Raman spectroscopy. It could be shown that both hydrocarbon chains are arranged in different subcells. Temperature dependent Raman measurements elucidate simultaneously the changes in the trans/gauche ratios and the packing of both the hydrocarbon chains of the fatty acid and of the sphingoid part. The phase behaviour of CER3 and d(35)CER3, both dry and hydrated, was investigated.

  1. Soil-to-plant transfer factors of radioactive Ca, Sm and Pd isotopes: critical assessment of the use of analogies to derive best-estimates from existing non-specific data.

    PubMed

    Henner, Pascale; Hurtevent, Pierre; Thiry, Yves

    2014-10-01

    (45)Ca, (151)Sm and (107)Pd are three radionuclides present in low to intermediate in activity radioactive wastes for which no soil-to-plant Transfer Factors (TF) values are available to be used in biosphere models for Ecological Risk Assessment. In the absence of specific radioecological studies, this work reviews and analyzes the existing literature for stable isotopes of Pd, Sm and Ca in order to derive best estimates for TF values that could be used as Transfer Factors. Alternative methods of extrapolation are also critically assessed. The values have been classified according to climatic zone, plant class and soil type for each element. The overall geometric mean TF values (for all plants and conditions) was calculated as 8.4E-02 for Pd, for which the value of radioRu in TRS-472 is also available. The mean TF for Sm was 4.2E-04. This value was lower than the TF values for radioactive Ce that are proposed as alternative values for Sm in TRS-472. The former may be relevant for long term assessments and the latter could possibly used to describe the short term (151)Sm post-release behaviour. The mean value for Ca is 2.3E-01 but varies considerably among plants of a given class due to the variety of plant Ca uptake behaviors. Alternatively, to limit this variability, Ca data content for dry plant matter, as analyzed using the phylogenetic method, could be used to derive TF values if the conservation of isotopic ratio of (45)Ca to stable Ca in soils and in plants hypothesis is taken into account. The TF for Ca in sub-tropical zones is 10-fold lower than in temperate zones. There is a lot of data available about exchangeable Ca in soil, which mean that we could calculate an available TF. The analysis shows that Ca bioavailability is also a key factor within transfer.

  2. Analog approach to mixed analog-digital circuit simulation

    NASA Astrophysics Data System (ADS)

    Ogrodzki, Jan

    2013-10-01

    Logic simulation of digital circuits is a well explored research area. Most up-to-date CAD tools for digital circuits simulation use an event driven, selective trace algorithm and Hardware Description Languages (HDL), e.g. the VHDL. This techniques enable simulation of mixed circuits, as well, where an analog part is connected to the digital one through D/A and A/D converters. The event-driven mixed simulation applies a unified, digital-circuits dedicated method to both digital and analog subsystems. In recent years HDL techniques have been also applied to mixed domains, as e.g. in the VHDL-AMS. This paper presents an approach dual to the event-driven one, where an analog part together with a digital one and with converters is treated as the analog subsystem and is simulated by means of circuit simulation techniques. In our problem an analog solver used yields some numerical problems caused by nonlinearities of digital elements. Efficient methods for overriding these difficulties have been proposed.

  3. Linearity optimization in a class of analog phase modulators

    NASA Technical Reports Server (NTRS)

    Hearn, C. P.

    1985-01-01

    This paper examines the ultimate modulating linearity attainable with a phase modulation technique based on the linear addition of quadrature phase carrier signals which have been multiplied by precisely defined nonlinear transformations of the modulating signal. Optimum gain coefficients are derived and plotted to permit implementation of analog phase modulators capable of exceptionally good linearity of phase deviations as large as 5 radians.

  4. All-optical analog comparator

    PubMed Central

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

    2016-01-01

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

  5. Biomimetic Analogs for Collagen Biomineralization

    PubMed Central

    Gu, L.; Kim, Y.K.; Liu, Y.; Ryou, H.; Wimmer, C.E.; Dai, L.; Arola, D.D.; Looney, S.W.; Pashley, D.H.; Tay, F.R.

    2011-01-01

    Inability of chemical phosphorylation of sodium trimetaphosphate to induce intrafibrillar mineralization of type I collagen may be due to the failure to incorporate a biomimetic analog to stabilize amorphous calcium phosphates (ACP) as nanoprecursors. This study investigated adsorption/desorption characteristics of hydrolyzed and pH-adjusted sodium trimetaphosphate (HPA-Na3P3O9) to collagen. Based on those results, a 5-minute treatment time with 2.8 wt% HPA-Na3P3O9 was used in a single-layer reconstituted collagen model to confirm that both the ACP-stabilization analog and matrix phosphoprotein analog must be present for intrafibrillar mineralization. The results of that model were further validated by complete remineralization of phosphoric-acid-etched dentin treated with the matrix phosphoprotein analog and lined with a remineralizing lining composite, and with the ACP-stabilization analog supplied in simulated body fluid. An understanding of the basic processes involved in intrafibrillar mineralization of reconstituted collagen fibrils facilitates the design of novel tissue engineering materials for hard tissue repair and regeneration. PMID:20940362

  6. All-optical analog comparator.

    PubMed

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

    2016-08-23

    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.

  7. All-optical analog comparator

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  8. Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice.

    PubMed

    Astudillo, Luis; Rodriguez, Jaime A; Schmeda-Hirschmann, Guillermo

    2002-04-01

    The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on gastric ulceration in rats. The effect of a single oral dose of OA was evaluated at 50, 100 and 200 mg kg(-1) in the following models: pylorus ligature (Shay), and aspirin- and ethanol-induced gastric ulcers. A single oral administration of OA at doses of 50, 100 and 200 mg kg-' inhibited the appearance of gastric lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature and aspirin models, the effect of OA at the selected concentrations was comparable with that of ranitidine at 50 mg kg(-1). In the ethanol-induced gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg kg(-1) was as active as omeprazole at 20 mg kg(-1). The effect of OA, its acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were assessed on HCI/ethanol-induced ulcers in mice at 200 mg kg(-1). OA and its methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in this animal model. The semisynthetic derivatives OAM and OAAM had the greatest gastroprotective activity, but their effect was not significantly greater than OA. In an acute toxicity test on mice, intraperitoneal administration of OA showed no toxicity at doses up to 600 mg kg(-1).

  9. Relationship of superficial scald development and alpha-farnesene oxidation to reactions of diphenylamine and diphenylamine derivatives in Cv. Granny Smith apple peel.

    PubMed

    Rudell, David R; Mattheis, James P; Fellman, John K

    2005-10-19

    Cv. Granny Smith apple fruit, treated at harvest with aqueous emulsions containing diphenylamine (DPA) and DPA derivatives, were evaluated for the peel disorder superficial scald (scald) after 6 months of cold storage at 1 degrees C plus 0 or 7 days at 20 degrees C. Metabolism of these derivatives and alpha-farnesene oxidation were also evaluated after 6 months. Derivatives substituted at the para position prevented scald, but scald developed on fruit treated with derivatives substituted in the amino, ortho, or meta positions. The extent of scald control was also dependent on the chemical nature of the functional group used to derivatize DPA. Hydroxylation of DPA and DPA derivatives during storage was not associated with scald control. Methoxylated DPA derivatives produced during storage resulted from O-methylation of C-hydroxylated derivatives rather than C-methoxylation of DPA. N-Nitrosodiphenylamine provided partial scald control, possibly resulting from its degradation to DPA, indicating that the amino hydrogen of DPA may be crucial for scald control. Results suggest that functional group position and chemical properties both contribute to the efficacy of DPA derivatives for scald control.

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

    SciTech Connect

    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.

  11. Analogies in Science and Science Teaching

    ERIC Educational Resources Information Center

    Brown, Simon; Salter, Susan

    2010-01-01

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

  12. Analogies in Science and Science Teaching

    ERIC Educational Resources Information Center

    Brown, Simon; Salter, Susan

    2010-01-01

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

  13. Teaching Scientific Analogies: A Proposed Model.

    ERIC Educational Resources Information Center

    Zeitoun, Hassan Hussein

    Cognitive psychologists have recently alluded to the role analogies might play in learning unfamiliar topics. However, since the use of analogies in science teaching has not been adequately addressed, analogies mean different things to different people. Therefore, a model for the teaching of scientific analogies is proposed. A theoretical…

  14. Natural analogs for Yucca Mountain

    SciTech Connect

    Murphy, W.M.

    1995-11-01

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

  15. Structure- and isoform-specific glucuronidation of six curcumin analogs.

    PubMed

    Lu, Danyi; Liu, Hui; Ye, Wencai; Wang, Ying; Wu, Baojian

    2017-04-01

    1. In the present study, we aimed to characterize the glucuronidation of six curcumin analogs (i.e. RAO-3, RAO-8, RAO-9, RAO-18, RAO-19, and RAO-23) derived from galangal using human liver microsomes (HLM) and twelve expressed UGT enzymes. 2. Formation of glucuronide was confirmed using high-resolution mass spectrometry. Single glucuronide metabolite was generated from each of six curcumin analogs. The fragmentation patterns were analyzed and were found to differ significantly between alcoholic and phenolic glucuronides. 3. All six curcumin analogs except one (RAO-23) underwent significant glucuronidation in HLM and expressed UGT enzymes. In general, the methoxy group (close to the phenolic hydroxyl group) enhanced the glucuronidation liability of the curcumin analogs. 4. UGT1A9 and UGT2B7 were primarily responsible for the glucuronidation of two alcoholic analogs (RAO-3 and RAO-18). By contrast, UGT1A9 and four UGT2Bs (UGT2B4, 2B7, 2B15 and 2B17) played important roles in conjugating three phenolic analogs (RAO-8, RAO-9, and RAO-19). Interestingly, the conjugated double bonds system (in the aliphatic chain) was crucial to the substrate selectivity of gastrointestinal UGTs (i.e. UGT1A7, 1A8 and 1A10). 5. In conclusion, glucuronidation of six curcumin analogs from galangal were structure- and isoform-specific. The knowledge should be useful in identifying a curcumin analog with improved metabolic property.

  16. Analog circuits for relaxation networks.

    PubMed

    Card, H

    1993-12-01

    Selected examples are presented of recent advances, primarily from the U.S. and Canada, in analog circuits for relaxation networks. Relaxation networks having feedback connections exhibit potentially greater computational power per neuron than feedforward networks. They are also more poorly understood especially with respect to learning algorithms. Examples are described of analog circuits for (i) supervised learning in deterministic Boltzmann machines, (ii) unsupervised competitive learning and feature maps and (iii) networks with resistive grids for vision and audition tasks. We also discuss recent progress on in-circuit learning and synaptic weight storage mechanisms.

  17. A Functional-Analytic Model of Analogy Using the Relational Evaluation Procedure

    ERIC Educational Resources Information Center

    Stewart, Ian; Barnes-Holmes, Dermot; Roche, Bryan

    2004-01-01

    Analogical reasoning is conceptualized by Relational Frame Theory as responding in accordance with an equivalence relation between equivalence or other types of derived stimulus relations. The purpose of this study was to provide an empirical demonstration of analogy using the Relational Evaluation Procedure (REP), a recently developed technique…

  18. A Functional-Analytic Model of Analogy Using the Relational Evaluation Procedure

    ERIC Educational Resources Information Center

    Stewart, Ian; Barnes-Holmes, Dermot; Roche, Bryan

    2004-01-01

    Analogical reasoning is conceptualized by Relational Frame Theory as responding in accordance with an equivalence relation between equivalence or other types of derived stimulus relations. The purpose of this study was to provide an empirical demonstration of analogy using the Relational Evaluation Procedure (REP), a recently developed technique…

  19. Terrestrial analogs for space exploration habitation systems

    NASA Technical Reports Server (NTRS)

    Campbell, Paul D.; Brown, Jeri W.

    1992-01-01

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

  20. Infrared spectra of lunar soil analogs. [spectral reflectance of minerals

    NASA Technical Reports Server (NTRS)

    Aronson, J. R.

    1977-01-01

    The infrared spectra of analogs of lunar soils were investigated to further the development of methodology for interpretation of remotely measured infrared spectra of the lunar surface. The optical constants of dunite, bytownite, augite, ilmenite, and a mare glass analog were obtained. The infrared emittance spectra of powdered minerals were measured and compared with spectra calculated by the reflectance theory using a catalog of optical constants. The results indicate that the predictions of the theory closely simulate the experimental measurements if the optical constants are properly derived.

  1. Synthesis and characterization of poly(methoxyl ethylene glycol-caprolactone-co-methacrylic acid-co-poly(ethylene glycol) methyl ether methacrylate) pH-sensitive hydrogel for delivery of dexamethasone.

    PubMed

    Wang, Ke; Xu, Xu; Wang, YuJun; Yan, Xi; Guo, Gang; Huang, MeiJuan; Luo, Feng; Zhao, Xia; Wei, YuQuan; Qian, ZhiYong

    2010-04-15

    In this work, a novel pH-sensitive hydrogels based on macromonomer of methoxyl poly(ethylene glycol)-poly(caprolactone)-acryloyl chloride (MPEG-PCL-AC, PCE-AC), poly(ethylene glycol) methyl ether methacrylate (MPEGMA), and methacrylic acid (MAA) were successfully synthesized by heat-initiated free radical polymerization method. The obtained macromonomers and hydrogels were characterized by (1)H NMR and FT-IR, respectively. Morphology study, swelling behavior, in vitro drug release behavior, acute oral toxicity of hydrogels, and cytotoxicity of PCE-AC macromonomer were also investigated in this paper. Finally, the hydrogels demonstrated that the sharp change in different pH value, thus believing to be promising the suitability of the candidate for oral drug-delivery systems.

  2. Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs.

    PubMed

    Gallois-Montbrun, Sarah; Faraj, Abdesslem; Seclaman, Edward; Sommadossi, Jean-Pierre; Deville-Bonne, Dominique; Véron, Michel

    2004-11-01

    Nucleoside analogs used in antiviral therapies need to be phosphorylated to their tri-phospho counterparts in order to be active on their cellular target. Human phosphoglycerate kinase (hPGK) was recently reported to participate in the last step of phosphorylation of cytidine L-nucleotide derivatives [Krishnan PGE, Lam W, Dutschman GE, Grill SP, Cheng YC. Novel role of 3-phosphoglycerate kinase, a glycolytic enzyme, in the activation of L-nucleoside analogs, a new class of anticancer and antiviral agents. J Biol Chem 2003;278:36726-32]. In the present work, we extended the enzymatic study of human PGK specificity to purine and pyrimidine nucleotide derivatives in both D- and L-configuration. Human PGK demonstrated catalytic efficiencies in the 10(4)-10(5)M(-1)s(-1) range for purine ribo-, deoxyribo- and dideoxyribonucleotide derivatives, either in D- or L-configuration. In contrast, it was poorly active with natural pyrimidine D-nucleotides (less than 10(3)M(-1)s(-1)). Pyrimidine L-enantiomers, which are promising therapeutic analogs against B hepatitis, were 2-25 times better substrates than their D-counterparts. The broad specificity of substrate of human PGK suggests that this enzyme may be involved in the cellular activation of several antiviral nucleoside analogs including dideoxyinosine, acyclovir, L-2'-deoxycytosine and L-2'-deoxythymidine.

  3. Analogies and "Modeling Analogies" in Teaching: Some Examples in Basic Electricity.

    ERIC Educational Resources Information Center

    Dupin, J. J.; Johsua, S.

    1989-01-01

    Investigates the effect of modeling analogy on learning of the concepts of electricity in grade 6, 8, and 10. Describes 2 analogies (train analogy and thermal analogy) with diagrams and examples. Discusses the accessibility, transferability, and difficulty of each analogy. Reports treatment effect and some further implications. (YP)

  4. Algicidal Activity of Stilbene Analogs

    USDA-ARS?s Scientific Manuscript database

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

  5. Paper Analogies Enhance Biology Teaching.

    ERIC Educational Resources Information Center

    Stencel, John E.

    1997-01-01

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

  6. Understanding & Teaching Genetics Using Analogies

    ERIC Educational Resources Information Center

    Woody, Scott; Himelblau, Ed

    2013-01-01

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

  7. Electrical analog to projectile motion

    NASA Astrophysics Data System (ADS)

    Vondracek, Mark

    1998-04-01

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

  8. Analog Input Data Acquisition Software

    NASA Technical Reports Server (NTRS)

    Arens, Ellen

    2009-01-01

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

  9. Analogy of the Cell Project

    ERIC Educational Resources Information Center

    Science Scope, 2005

    2005-01-01

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

  10. Analogy of the Cell Project

    ERIC Educational Resources Information Center

    Science Scope, 2005

    2005-01-01

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

  11. Analog Simulation of a Laser.

    ERIC Educational Resources Information Center

    Kessler, Gary

    1982-01-01

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

  12. Bayesian Analogy with Relational Transformations

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  13. Geometrical Analogies in Mathematics Lessons

    ERIC Educational Resources Information Center

    Eid, Wolfram

    2007-01-01

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

  14. Mathematical Analogy and Metaphorical Insight

    ERIC Educational Resources Information Center

    Zwicky, Jan

    2010-01-01

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

  15. Analogy between Thermodynamics and Mechanics.

    ERIC Educational Resources Information Center

    Peterson, Mark A.

    1979-01-01

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

  16. Understanding & Teaching Genetics Using Analogies

    ERIC Educational Resources Information Center

    Woody, Scott; Himelblau, Ed

    2013-01-01

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

  17. Analog Simulation of a Laser.

    ERIC Educational Resources Information Center

    Kessler, Gary

    1982-01-01

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

  18. Schema Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Robins, Shani; Mayer, Richard E.

    1993-01-01

    In 3 experiments, 93, 97, and 86 college students, respectively, learned how to solve 20 verbal analogy problems and took transfer and memory tests. Results are inconsistent with active responding theory and further indicate that schema induction is maximized when the schemas are made salient and the cognitive system is not overloaded. (SLD)

  19. Processes in Verbal Analogy Solution.

    ERIC Educational Resources Information Center

    Grudin, Jonathan

    1980-01-01

    Verbal analogy solution is more flexible than is suggested by either the standard process theory or Sternberg's theory. It was determined that subjects initially examine terms A and B; if this strategy is not successful, they examine the relationship between A and C. (Author/CP)

  20. Bayesian Analogy with Relational Transformations

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  1. International Alligator Rivers Analog Project

    SciTech Connect

    Bichard, G.F.

    1988-01-01

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

  2. Schema Training in Analogical Reasoning.

    ERIC Educational Resources Information Center

    Robins, Shani; Mayer, Richard E.

    1993-01-01

    In 3 experiments, 93, 97, and 86 college students, respectively, learned how to solve 20 verbal analogy problems and took transfer and memory tests. Results are inconsistent with active responding theory and further indicate that schema induction is maximized when the schemas are made salient and the cognitive system is not overloaded. (SLD)

  3. Mathematical Analogy and Metaphorical Insight

    ERIC Educational Resources Information Center

    Zwicky, Jan

    2010-01-01

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

  4. Laminate analogy for composites enhanced concrete structures

    SciTech Connect

    Chamis, C.C.; Gotsis, P.K.

    1997-10-01

    A new and effective method is described to design composites to repair damage or enhance the overload strength of concrete infrastructures. The method is based on laminate analogy which is derivable from composite mechanics and available in computer codes. It is used to simulate structural sections made from reinforced concrete which are typical in infrastructures as well as select reinforced concrete structures. The structural sections are represented by a number of layers through the thickness where different layers are used for the concrete, for the reinforcing steel in concrete, and for the composite. The reinforced concrete structures are represented with finite elements where the element stiffness parameters are from the structural sections which are represented by the laminate analogy. The load carrying capability of the structure is determined by progressive structural fracture. Results show up to 40 percent improvements for damage and for overload enhancement with relatively small laminate thickness for the structural sections and up to three times for the composite enhanced select structures (arch and dome).

  5. Crows spontaneously exhibit analogical reasoning.

    PubMed

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

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Bayesian analogy with relational transformations.

    PubMed

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

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  7. ANALOG: a program for estimating paleoclimate parameters using the method of modern analogs

    USGS Publications Warehouse

    Schweitzer, Peter N.

    1994-01-01

    Beginning in the 1970s with CLIMAP, paleoclimatologists have been trying to derive quantitative estimates of climatic parameters from the sedimentary record. In general the procedure is to observe the modern distribution of some component of surface sediment that depends on climate, find an empirical relationship between climate and the character of sediments, then extrapolate past climate by studying older sediments in the same way. Initially the empirical relationship between climate and components of the sediment was determined using a multiple regression technique (Imbrie and Kipp, 1971). In these studies sea-floor sediments were examined to determine the percentage of various species of planktonic foraminifera present in them. Supposing that the distribution of foraminiferal assemblages depended strongly on the extremes of annual sea-surface temperature (SST), the foraminiferal assemblages (refined through use of varimax factor analysis) were regressed against the average SST during the coolest and warmest months of the year. The result was a set of transfer functions, equations that could be used to estimate cool and warm SST from the faunal composition of a sediment sample. Assuming that the ecological preference of the species had remained constant throughout the last several hundred thousand years, these transfer functions could be used to estimate SSTs during much of the late Pleistocene. Hutson (1980) and Overpeck, Webb, and Prentice (1985) proposed an alternative approach to estimating paleoclimatic parameters. Their 'method of modern analogs' revolved not around the existence of a few climatically-sensitive faunal assemblages but rather on the expectation that similar climatic regimes should foster similar faunal and floral assemblages. From a large pool of modern samples, those few are selected whose faunal compositions are most similar to a given fossil sample. Paleoclimate estimates are derived using the climatic character of only the most similar

  8. Mechanisms of transthyretin cardiomyocyte toxicity inhibition by resveratrol analogs.

    PubMed

    Bourgault, Steve; Choi, Sungwook; Buxbaum, Joel N; Kelly, Jeffery W; Price, Joshua L; Reixach, Natàlia

    2011-07-15

    The transthyretin amyloidoses are a subset of protein misfolding diseases characterized by the extracellular deposition of aggregates derived from the plasma homotetrameric protein transthyretin (TTR) in peripheral nerves and the heart. We have established a robust disease-relevant human cardiac tissue culture system to explore the cytotoxic effects of amyloidogenic TTR variants. We have employed this cardiac amyloidosis tissue culture model to screen 23 resveratrol analogs as inhibitors of amyloidogenic TTR-induced cytotoxicity and to investigate their mechanisms of protection. Resveratrol and its analogs kinetically stabilize the native tetramer preventing the formation of cytotoxic species. In addition, we demonstrate that resveratrol can accelerate the formation of soluble non-toxic aggregates and that the resveratrol analogs tested can bring together monomeric TTR subunits to form non-toxic native tetrameric TTR. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Analog to digital workflow improvement: a quantitative study.

    PubMed

    Wideman, Catherine; Gallet, Jacqueline

    2006-01-01

    This study tracked a radiology department's conversion from utilization of a Kodak Amber analog system to a Kodak DirectView DR 5100 digital system. Through the use of ProModel Optimization Suite, a workflow simulation software package, significant quantitative information was derived from workflow process data measured before and after the change to a digital system. Once the digital room was fully operational and the radiology staff comfortable with the new system, average patient examination time was reduced from 9.24 to 5.28 min, indicating that a higher patient throughput could be achieved. Compared to the analog system, chest examination time for modality specific activities was reduced by 43%. The percentage of repeat examinations experienced with the digital system also decreased to 8% vs. the level of 9.5% experienced with the analog system. The study indicated that it is possible to quantitatively study clinical workflow and productivity by using commercially available software.

  10. A CMOS field-programmable analog array

    NASA Astrophysics Data System (ADS)

    Lee, Edward K. F.; Gulak, P. G.

    1991-12-01

    The design details and test results of a field-programmable analog array (FPAA) prototype chip in 1.2-micron CMOS are presented. The analog array is based on subthreshold circuit techniques and consists of a collection of a homogeneous configurable analog blocks (CABs) and an interconnection network. Interconnections between CABs and the analog functions to be implemented in each block are defined by a set of configuration bits loaded serially into an onboard shift register by the user. Macromodels are developed for the analog functions in order to simulate various neural network applications on the field-programmable analog array.

  11. Antimutagenic effects of dehydrozingerone and its analogs on UV-induced mutagenesis in Escherichia coli.

    PubMed

    Motohashi, N; Ashihara, Y; Yamagami, C; Saito, Y

    1997-06-09

    Antimutagenic activities of dehydrozingerone, benzalacetone and its analogs substituted with the hydroxyl, methoxyl or methyl group on the benzene ring were investigated by the post-treatment for UV-induced mutagenesis in Escherichia coli WP2s (uvrA). In this assay, dehydrozingerone was a poor antimutagen. Among the test compounds except for 2-hydroxybenzalacetone, benzalacetone was the most strong antimutagen, showing that the ring substitutions decrease the antimutagenic activities. 2-Hydroxybenzalacetone was, however, more effective than benzalacetone. The antimutagenicity of 2-hydroxybenzalacetone might be dependent on the property that is known to associate inter-molecularly by hydrogen bonding between the hydroxyl group and the carbonyl group. The effects of the side chain, single, double or triple bond and its adjacent carbonyl group, were further investigated using benzylacetone with saturated carbonyl chain, benzalacetone with double-bonded carbonyl chain, 4-phenyl-3-butyn-2-one with triple-bonded carbonyl chain and trans-beta-methyl styrene with only double bond. Benzalacetone and 4-phenyl-3-butyn-2-one suppressed the UV-induced mutagenesis, but benzylacetone and trans-beta-methyl styrene scarcely inhibited the mutagenesis: an alpha, beta-double or triple-bonded carbonyl system was necessary for the antimutagenic activity. 4-Phenyl-3-butyn-2-one showed the potent antimutagenicity at one order lower concentrations than that of benzalacetone. Benzalacetone, 2-hydroxybenzalacetone and 4-phenyl-3-butyn-2-one that were effective on the UV-induced mutagenesis also decreased the gamma-induced mutagenesis in Salmonella typhimurium TA2638.

  12. Analog to digital converter for two-dimensional radiant energy array computers

    NASA Technical Reports Server (NTRS)

    Shaefer, D. H.; Strong, J. P., III (Inventor)

    1977-01-01

    The analog to digital converter stage derives a bit array of digital radiant energy signals representative of the amplitudes of an input radiant energy analog signal array and derives an output radiant energy analog signal array to serve as an input to succeeding stages. The converter stage includes a digital radiant energy array device which contains radiant energy array positions so that the analog array is less than a predetermined threshold level. A scaling device amplifies the radiant signal levels of the input array and the digital array so that the radiant energy signal level carried by the digital array corresponds to the threshold level. An adder device adds the signals of the scaled input and digital arrays at corresponding array positions to form the output analog array.

  13. Battery hydrometer with analog output

    SciTech Connect

    Patis, B.L.

    1982-09-21

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

  14. Synaptic dynamics in analog VLSI.

    PubMed

    Bartolozzi, Chiara; Indiveri, Giacomo

    2007-10-01

    Synapses are crucial elements for computation and information transfer in both real and artificial neural systems. Recent experimental findings and theoretical models of pulse-based neural networks suggest that synaptic dynamics can play a crucial role for learning neural codes and encoding spatiotemporal spike patterns. Within the context of hardware implementations of pulse-based neural networks, several analog VLSI circuits modeling synaptic functionality have been proposed. We present an overview of previously proposed circuits and describe a novel analog VLSI synaptic circuit suitable for integration in large VLSI spike-based neural systems. The circuit proposed is based on a computational model that fits the real postsynaptic currents with exponentials. We present experimental data showing how the circuit exhibits realistic dynamics and show how it can be connected to additional modules for implementing a wide range of synaptic properties.

  15. Analog Nonvolatile Computer Memory Circuits

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd

    2007-01-01

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

  16. Classical Analog to Entanglement Reversibility

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  17. Superconducting Analog to Digital Converters

    DTIC Science & Technology

    1991-09-01

    superconductivity, Josephson junctions, and superconducting quantum interference devices ( SQUIDs ) are briefly described. Various techniques to perform analog-to...deployment in the 1990s may require a dynamic range in excess of 90 dB (15- bit precision) [3]. However, at the present time, A/D conversion with 16-bit...Interference Devices ( SQUIDs ). JOSEPHSON EFFECTS AND JUNCTIONS Consider a very thin, non-superconducting region separating two superconductors. In 1962

  18. Neurotoxicology of Synthetic Cathinone Analogs.

    PubMed

    Angoa-Pérez, Mariana; Anneken, John H; Kuhn, Donald M

    The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties. Most of the literature on synthetic cathinones has focused on describing their properties as psychostimulants, their behavioral effects on locomotion, memory, and potential for abuse, whereas descriptions of their neurotoxic properties are not abundant. The biochemical gauges of neurotoxicity induced by non-keto analogs are well studied in humans and experimental animals and include their ability to induce neuroinflammation, oxidative stress, excitotoxicity, temperature alterations as well as dysregulation of neurotransmitter systems and induce changes in monoamine transporters and receptors. These neurotoxicity gauges will serve as parameters to discuss the effects of the four previously mentioned synthetic cathinones alone or in combination with either another cathinone or with some of their non-keto analogs. Bath salts are not a defined combination of drugs and may consist of one synthetic cathinone compound or combinations of more cathinones. Furthermore, this review also presents some of the mechanisms that are thought to underlie this toxicity. A better understanding of the cellular and molecular mechanisms involved in the synthetic cathinones-induced neurotoxicity should contribute to generate modern therapeutic approaches to prevent or attenuate the adverse consequences of use of these

  19. Simple Electronic Analog of a Josephson Junction.

    ERIC Educational Resources Information Center

    Henry, R. W.; And Others

    1981-01-01

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

  20. Thermal analog device reduces machining errors

    NASA Technical Reports Server (NTRS)

    Mcclure, E. R.

    1972-01-01

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

  1. Basic Electricity--a Novel Analogy.

    ERIC Educational Resources Information Center

    Grant, Richard

    1996-01-01

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

  2. Simple Electronic Analog of a Josephson Junction.

    ERIC Educational Resources Information Center

    Henry, R. W.; And Others

    1981-01-01

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

  3. Program Documentation for the Analog Digitization Program,

    DTIC Science & Technology

    COMPUTER PROGRAM DOCUMENTATION, *ANALOG TO DIGITAL CONVERTERS, REAL TIME, COMPUTER LOGIC, INPUT OUTPUT PROCESSING, SAMPLING, INPUT OUTPUT DEVICES...FLOW CHARTING, ANALOG SIGNALS, DISK RECORDING SYSTEMS, DIGITAL RECORDING SYSTEMS, ASSEMBLY LANGUAGES.

  4. Third order digital-to-analog converter

    NASA Technical Reports Server (NTRS)

    Dotson, W. P.

    1972-01-01

    System, consisting of sample and hold digital-to-analog converter, clock circuit, sample delay circuit, initial condition circuit and interpolator circuit, improves accuracy of reconstructed analog signal without increasing sample rates.

  5. Abstract analogical reasoning in high-functioning children with autism spectrum disorders.

    PubMed

    Green, Adam E; Kenworthy, Lauren; Mosner, Maya G; Gallagher, Natalie M; Fearon, Edward W; Balhana, Carlos D; Yerys, Benjamin E

    2014-12-01

    Children with autism spectrum disorders (ASD) exhibit a deficit in spontaneously recognizing abstract similarities that are crucial for generalizing learning to new situations. This may contribute to deficits in the development of appropriate schemas for navigating novel situations, including social interactions. Analogical reasoning is the central cognitive mechanism that enables typically developing children to understand abstract similarities between different situations. Intriguingly, studies of high-functioning children with ASD point to a relative cognitive strength in basic, nonabstract forms of analogical reasoning. If this analogical reasoning ability extends to abstract analogical reasoning (i.e., between superficially dissimilar situations), it may provide a bridge between a cognitive capability and core ASD deficits in areas such as generalization and categorization. This study tested whether preserved analogical reasoning abilities in ASD can be extended to abstract analogical reasoning, using photographs of real-world items and situations. Abstractness of the analogies was determined via a quantitative measure of semantic distance derived from latent semantic analysis. Children with ASD performed as well as typically developing children at identifying abstract analogical similarities when explicitly instructed to apply analogical reasoning. Individual differences in abstract analogical reasoning ability predicted individual differences in a measure of social function in the ASD group. Preliminary analyses indicated that children with ASD, but not typically developing children, showed an effect of age on abstract analogical reasoning. These results provide new evidence that children with ASD are capable of identifying abstract similarities through analogical reasoning, pointing to abstract analogical reasoning as a potential lever for improving generalization skills and social function in ASD. © 2014 International Society for Autism Research, Wiley

  6. Hegel, Analogy, and Extraterrestrial Life

    NASA Astrophysics Data System (ADS)

    Ross, Joseph T.

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

  7. The Micro-Category Account of Analogy

    ERIC Educational Resources Information Center

    Green, Adam E.; Fugelsang, Jonathan A.; Kraemer, David J. M.; Dunbar, Kevin N.

    2008-01-01

    Here, we investigate how activation of mental representations of categories during analogical reasoning influences subsequent cognitive processing. Specifically, we present and test the central predictions of the "Micro-Category" account of analogy. This account emphasizes the role of categories in aligning terms for analogical mapping. In a…

  8. Analogical Reasoning: A Review of the Literature.

    ERIC Educational Resources Information Center

    Dawis, Rene V.; Siojo, Luis T.

    The mathematical and philosophical origins of "analogy" are described and their influence on the thinking of intelligence theorists is traced. Theories of intelligence and cognition bearing on analogical reasoning are examined, specifically those of Spearman, Thorndike, Guilford and Piaget. The analogy test item is shown to be a paradigm…

  9. Reasoning by Analogy in Constructing Mathematical Ideas.

    ERIC Educational Resources Information Center

    English, Lyn D.

    A powerful way of understanding something new is by analogy with something already known. An analogy is defined as a mapping from one structure, which is already known (the base or source), to another structure that is to be inferred or discovered (the target). The research community has given considerable attention to analogical reasoning in the…

  10. Stimulation of chemiluminescence by synthetic muramyl dipeptide and analogs.

    PubMed

    Masihi, K N; Azuma, I; Brehmer, W; Lange, W

    1983-04-01

    The effect on respiratory burst of murine splenic cells after in vitro exposure to synthetic muramyl dipeptide (MDP) and 6-O-acyl and quinonyl derivatives was studied at an early phase of interaction by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. The MDP molecule enhanced CL, but the degree of CL response varied with the kinds of fatty acids introduced in the chemical structure of synthetic glycopeptide analogs. A 6-O-acyl derivative possessing an alpha-branched fatty acid chain, B30-MDP, stimulated maximum levels of CL activity. High CL responses were obtained with L8-MDP having a short chain of linear fatty acids and with QS-10-MDP-66 containing a ubiquinone compound. CL was also stimulated by MDP and its analogs in the spleen cells of nude mice lacking mature T lymphocytes, but the extent of stimulation was decreased compared with that of normal spleen cells.

  11. Relativistic Velocity Addition Law from Machine Gun Analogy

    NASA Astrophysics Data System (ADS)

    Rothenstein, Bernhard; Popescu, Stefan

    2009-01-01

    Many derivations of the relativistic addition law of parallel velocities without use of the Lorentz transformations (LT) are known.1-5 Some of them are based on thought experiments that require knowledge of the time dilation and the length contraction effects.1,4,5 Other derivations involve the Doppler effect in the optic domain considered from three inertial reference frames in relative motion.6 A few derivations simply involve only the principle of constancy of the light velocity.2 Such derivations are interesting for the teaching of special relativity theory since the relativistic addition of velocities leads directly to the LT.7 The derivation we propose is based on a machine gun-target analogy8 of the acoustic Doppler effect, considered from the rest frame of the machine gun and from the rest frame of the target.

  12. Are all analogies created equal? Prefrontal cortical functioning may predict types of analogical reasoning.

    PubMed

    Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-06-01

    Abstract The proposed theory can account for analogies based on learned relationships between elements in the source and target domains. However, its explanatory power regarding the discovery of new relationships during analogical reasoning is limited. We offer an alternative perspective for the role of PFC in analogical thought that may better address different types of analogical mappings.

  13. Nanaomycin H: A new nanaomycin analog.

    PubMed

    Nakashima, Takuji; Kimura, Toru; Miyano, Rei; Matsuo, Hirotaka; Hirose, Tomoyasu; Kimishima, Aoi; Nonaka, Kenichi; Iwatsuki, Masato; Nakanishi, Jun; Takahashi, Yōko; Ōmura, Satoshi

    2017-06-01

    Physicochemical screening identified a new nanaomycin analog, nanaomycin H, which was isolated from a culture broth of Streptomyces rosa subsp. notoensis OS-3966. This microorganism is already known to produce seven nanaomycin compounds, (nanaomycin A to G). Structural elucidation of nanaomycin H showed it to be a pyranonaphthoquinone with a mycothiol moiety. A N-acetylcysteine S-conjugate of nanaomycin H, without α-glucosamine linked to myo-inositol moiety, mercapturic acid derivative, was also detected in the same culture broth. Mercapturic acid derivatives of secondary metabolites are known to be produced for xenobiotic metabolism outside microbial cells. Mycothiol acts as a detoxifier to help prevent cell damage from factors such as oxidative stress. The production of O2(-) generated by reduction of nanaomycin A is correlated with antibacterial activity. Mycothiol-containing nanaomycin H proved to be markedly decreased in O2(-) and did not express any notable antimicrobial activity. It is suggested that nanaomycin H is produced in the detoxification process. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Analog analysis of a tracked air-cushion vehicle.

    NASA Technical Reports Server (NTRS)

    Leatherwood, J. D.

    1972-01-01

    The dynamics of tracked air-cushion vehicles considered for high-speed ground transportation systems are examined using a vehicle model represented by a one-degree-of-freedom system. The respective equations of motion are derived, and the control system is discussed. The equations obtained for the cushion are solved using an analog computer. The computer showed the effect of the control technique on the relative motion between vehicle and guideway.

  15. Molecular mechanics models for tetracycline analogs.

    PubMed

    Aleksandrov, Alexey; Simonson, Thomas

    2009-01-30

    Tetracyclines (Tcs) are an important family of antibiotics that bind to the ribosome and several proteins. To model Tc interactions with protein and RNA, we have developed a molecular mechanics force field for 12 tetracyclines, consistent with the CHARMM force field. We considered each Tc variant in its zwitterionic tautomer, with and without a bound Mg(2+). We used structures from the Cambridge Crystallographic Data Base to identify the conformations likely to be present in solution and in biomolecular complexes. A conformational search by simulated annealing was undertaken, using the MM3 force field, for tetracycline, anhydrotetracycline, doxycycline, and tigecycline. Resulting, low-energy structures were optimized with an ab initio method. We found that Tc and its analogs all adopt an extended conformation in the zwitterionic tautomer and a twisted one in the neutral tautomer, and the zwitterionic-extended state is the most stable in solution. Intermolecular force field parameters were derived from a standard supermolecule approach: we considered the ab initio energies and geometries of a water molecule interacting with each Tc analog at several different positions. The final, rms deviation between the ab initio and force field energies, averaged over all forms, was 0.35 kcal/mol. Intramolecular parameters were adopted from either the standard CHARMM force field, the ab initio structure, or the earlier, plain Tc force field. The model reproduces the ab initio geometry and flexibility of each Tc. As tests, we describe MD and free energy simulations of a solvated complex between three Tcs and the Tet repressor protein. (c) 2008 Wiley Periodicals, Inc.

  16. [Analogies between the thymus and epidermis].

    PubMed

    De Panfilis, G

    1990-11-01

    In this paper, similarities between epidermis and thymus are reviewed. Both epidermis and thymus deal with an epithelial stroma harbouring dendritic cells, which are bone-marrow derived. Both epithelia are keratinized, and a map can be constructed illustrating histo-topographic and antigenic similarities between thymic epithelial cells distributed in various thymic zones (i.e. subcapsular cortex, outer cortex, inner cortex, medulla, outer layers of Hassall's bodies, inner layers of Hassall's bodies) and keratinocytes of different epidermal layers. By contrast, a possible similarity between thymocytes and Langerhans cells is not so easy to demonstrate, although both cell types are CD1 positive. Rather, in our opinion a comparison is preferable of thymocytes to Thy-1 positive dendritic epidermal cells, due to morphological, antigenic, functional and especially lineage similarities. Similarities between thymus and epidermis are clearly important dealing with analogous molecular interactions, namely, thymic epithelial cells/thymocytes versus keratinocytes/T-lymphocytes. Indeed, our recent investigations demonstrated that a subset of keratinocytes is ICAM-1 positive, and the whole keratinocyte population is LFA-3 positive. Since the interaction thymic epithelial cells (ICAM-1 and LFA-3 positive)/thymocytes (LFA-1 and CD2 positive) has been shown to be necessary for promotion of activation and maturation of thymocytes, the interaction keratinocytes (ICAM-1 and LFA-3 positive, as we demonstrated)/T-lymphocytes (LFA-1 and CD2 positive as well) might be, by analogy, important not only for the "homing" of T-lymphocytes within the epidermis, but also for the epidermis being considered a peripheral inductive site for T-cell activation and maturation.

  17. Reliability of analog quantum simulation

    DOE PAGES

    Sarovar, Mohan; Zhang, Jun; Zeng, Lishan

    2017-01-03

    Analog quantum simulators (AQS) will likely be the first nontrivial application of quantum technology for predictive simulation. However, there remain questions regarding the degree of confidence that can be placed in the results of AQS since they do not naturally incorporate error correction. Specifically, how do we know whether an analog simulation of a quantum model will produce predictions that agree with the ideal model in the presence of inevitable imperfections? At the same time there is a widely held expectation that certain quantum simulation questions will be robust to errors and perturbations in the underlying hardware. Resolving these twomore » points of view is a critical step in making the most of this promising technology. In this paper we formalize the notion of AQS reliability by determining sensitivity of AQS outputs to underlying parameters, and formulate conditions for robust simulation. Our approach naturally reveals the importance of model symmetries in dictating the robust properties. Finally, to demonstrate the approach, we characterize the robust features of a variety of quantum many-body models.« less

  18. Noscapine and its Analogs as Chemotherapeutic Agent: Current updates.

    PubMed

    Tomar, Vartika; Kukreti, Shrikant; Prakash, Satya; Madan, Jitender; Chandra, Ramesh

    2017-01-01

    Recently, noscapine was reported as anticancer drug. Unlike, colchicine and podophyllotoxin, noscapine did not depolymerize microtubules even at stoichiometric concentrations but rather only mitigated their dynamics. Other microtubule-interacting chemotherapeutics, although quite effective, have therapy-limiting toxicities including immunosuppression and peripheral neuropathies. Recurrent cancers often become resistant. Noscapine however remains effective in some such instances, e.g., taxane-resistant ovarian cancer. Noscapine and analogs also do not show signs of neurotoxicity or immunosuppression. In addition, 9-bromo noscapine, Red-9-Br-Nos and other analogs were characterized for their structure and further studied in detail. On the other hand, noscapine was shown to be neuroprotective in mouse model of neurodegenerative disease and in stroke patients. Like low doses of colchicine, noscapine and its analog 9-Br-Noscapine also show anti-inflammatory activities. There are indications of a preventive use of noscapine in ischemiareperfusion injury and fibrosis. The entire biosynthetic pathway of noscapine is encoded as gene cluster within 401 kilo bases of genomic DNA, opening up opportunities for the large-scale biotechnological production of noscapine for medicinal needs. Thus, noscapine and its derivatives (noscapinoids) might be cost-effective and safe components for cancer chemotherapy. Owing to its low toxicity, it also might be useful for preventive use in high-risk situations. This brief review is an update of current research activity and patents on noscapine and its analogs.

  19. Fault diagnosis of analog circuits

    NASA Astrophysics Data System (ADS)

    Bandler, J. W.; Salama, A. E.

    1985-08-01

    Theory and algorithms associated with four main categories of modern techniques used to locate faults in analog circuits are presented. These four general approaches are: the fault dictionary (FDA), the parameter identification (PIA), the fault verification (FVA), and the approximation (AA) approaches. The preliminaries and problems associated with the FDA, such as fault dictionary construction, the methods of optimum measurement selection, fault isolation criteria, and efficient methods of fault simulation, are discussed. The PIA techniques that utilize either linear or nonlinear systems of equations for identification of network elements are examined. Description of the FVA includes node-fault diagnosis, branch-fault diagnosis, subnetwork testability conditions, as well as combinatorial techniques, the failure-bound technique, and the network decomposition technique. In the AA, probabilistic methods and optimization-based methods are considered. In addition, the artificial intelligence technique and the different measures of testability are presented. A series of block diagrams is included.

  20. The Young Solar Analogs Project

    NASA Astrophysics Data System (ADS)

    Gray, Richard O.; Saken, J. M.; Corbally, C. J.; Fuller, V.; Kahvaz, Y.; Lambert, R.; Newsome, I.; Seeds, M.

    2013-01-01

    We are carrying out a long-term project of measuring chromospheric activity and brightness variations in 31 young solar analogs (YSAs) using facilities at the Dark Sky Observatory (DSO - Appalachian State University) and the Vatican Advanced Technology Telescope (VATT). These YSAs are solar-type (spectral types F8 - K2) stars with ages ranging from 0.3 - 1.5 Gyr. The goal of this project is to gain better understanding of the magnetic activity of the early Sun, and especially how that activity may have impacted the development of life on the Earth. This project will also yield insights into the space environments experienced by young Earth analogs. We are currently in the 6th year of spectroscopic measurements of these stars: these data include Ca II H & K chromospheric flux measurements, and narrow-band measurements in the photospheric G-band, both obtained with the G/M spectrograph on the DSO 32-inch telescope. We will present evidence of activity cycles in a number of our stars, as well as periods determined from rotational modulation of the spectroscopic indices. The relationship between the Ca II activity index and the G-band index will be explored. NSF support for our project has provided funds for the construction of a robotic photometric telescope to monitor the program stars in a 5-passband system (Strömgren-v, Johnson-Cousins B, V, and R, and a 3-nm wide Hα filter). The robotic telescope has been functional since April 2012 and observes the program stars on every clear night; combined with the Piggy-back telescope attached to the DSO 32-inch, we now have photometric observations on over 130 nights stretching over nearly 2 years. We will examine the relationships between variations in the Ca II H & K index, the G-band index and the photometric bands. This project is supported by the National Science Foundation, grant AST-1109158.

  1. The Young Solar Analogs Project

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

  2. Priming analogical reasoning with false memories.

    PubMed

    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.

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

    PubMed

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

    2012-01-01

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

  4. Phytotoxicity of brominated diphenyl ether-47 (BDE-47) and its hydroxylated and methoxylated analogues (6-OH-BDE-47 and 6-MeO-BDE-47) to maize (Zea mays L.).

    PubMed

    Xu, Xuehui; Huang, Honglin; Wen, Bei; Wang, Sen; Zhang, Shuzhen

    2015-03-16

    Polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), and hydroxylated PBDEs (OH-PBDEs) are widely found in various environmental media, which is of concern given their biological toxicity. In this study, the phytotoxicities of BDE-47, 6-MeO-BDE-47, and 6-OH-BDE-47 to maize (Zea mays L.) were investigated by an in vivo exposure experiment. Results showed that BDE-47, 6-MeO-BDE-47, and 6-OH-BDE-47 inhibited seed germination and seedling development, and elevated malondialdehyde (MDA), carbonyl groups, and phosphorylated histone H2AX levels in maize roots, suggesting the inducement of lipid peroxidation, protein carbonylation, and DNA damage to maize. Exposure to BDE-47, 6-MeO-BDE-47, and 6-OH-BDE-47 caused the overproduction of H2O2, O2(•-), and •OH, and elevated the activities of antioxidant enzymes in the roots. In addition, 6-OH-BDE-47 caused more severe damage and reactive oxygen species (ROS) generation in maize than did BDE-47 and 6-MeO-BDE-47. These results demonstrated the phytotoxicities of BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 to maize, and clarified that overproduction of ROS was the key mechanism leading to toxicity. This study offers useful information for a more comprehensive understanding of the environmental behaviors and toxicities of PBDEs, MeO-PBDEs, and OH-PBDEs.

  5. The biomolecule, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile: FT-IR, Laser-Raman spectra and DFT.

    PubMed

    Sert, Yusuf; El-Emam, Ali A; Al-Deeb, Omar A; Al-Turkistani, Abdulghafoor A; Ucun, Fatih; Cırak, Cağrı

    2014-05-21

    In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400cm(-1)) and Laser-Raman spectra (4000-100cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated using the same theoretical calculations.

  6. The biomolecule, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile: FT-IR, Laser-Raman spectra and DFT

    NASA Astrophysics Data System (ADS)

    Sert, Yusuf; El-Emam, Ali A.; Al-Deeb, Omar A.; Al-Turkistani, Abdulghafoor A.; Ucun, Fatih; Çırak, Çağrı

    In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 2-[(2-methoxyl)sulfanyl]-4-(2-methylpropyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400 cm-1) and Laser-Raman spectra (4000-100 cm-1) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the other related molecular energy values of the compound have been investigated using the same theoretical calculations.

  7. AnalogExplorer2 – Stereochemistry sensitive graphical analysis of large analog series

    PubMed Central

    Hu, Ye; Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2015-01-01

    AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use. PMID:26913194

  8. AnalogExplorer2 - Stereochemistry sensitive graphical analysis of large analog series.

    PubMed

    Hu, Ye; Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2015-01-01

    AnalogExplorer is a computational methodology for the extraction and organization of series of structural analogs from compound data sets and their graphical analysis. The method is suitable for the analysis of large analog series originating from lead optimization programs. Herein we report AnalogExplorer2 designed to explicitly take stereochemical information during graphical analysis into account and describe a freely available deposition of the original AnalogExplorer program, AnalogExplorer2, and exemplary compound sets to illustrate their use.

  9. Resveratrol analogs: promising chemopreventive agents.

    PubMed

    Ogas, Talysa; Kondratyuk, Tamara P; Pezzuto, John M

    2013-07-01

    Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target specificity in the nanomolar range. Aromatase inhibition was enhanced over 6000-fold by using 1,3-thiazole as the central ring of resveratrol. Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to selective QR1 induction with a CD value of 87 nM. Several derivatives have been selected for evaluation of synergistic effects. Preliminary results with pairs of compounds are promising and further experiments, in a constant multidrug manner, will allow us to create polygonograms for larger combinations of derivatives. The objective is to develop a highly efficacious cocktail of derivatives based on the structure of resveratrol.

  10. Design and Analysis of Reconfigurable Analog System

    DTIC Science & Technology

    2011-02-01

    34010010" �" �" �" �" �" �" �±" N3 N2 N± P1 P2 P3 * Current sources $RR = 1; *Ramp Rate (slope of the...2008/12/12/31e83bac-500f-4182- acca -4d360295fd9c.pdf, Analog Devices, Analog Dialogue 39-06, June 2005. [15] D. A. Johns, K. Martin "Analog Integrated

  11. Classical Analogs of a Diatomic Chain

    SciTech Connect

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

    2010-12-21

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

  12. Comprehending Speaker Intent in Rebuttal Analogy Use: The Role of Irony Mapping, Absurdity Comparison and Argumentative Convention.

    ERIC Educational Resources Information Center

    Colston, Herbert L.

    2000-01-01

    Investigated the role that irony mapping, absurdity comparison, and argumentative convention play in interpreters' derivations of speaker's intentions in using rebuttal analogies. Three rebuttal types were rated on argumentativeness and social attack in verbal conflict and nonverbal conflict scenarios. Results found that analogies with ironic…

  13. Fermilab accelerator control system: Analog monitoring facilities

    SciTech Connect

    Seino, K.; Anderson, L.; Smedinghoff, J.

    1987-10-01

    Thousands of analog signals are monitored in different areas of the Fermilab accelerator complex. For general purposes, analog signals are sent over coaxial or twinaxial cables with varying lengths, collected at fan-in boxes and digitized with 12 bit multiplexed ADCs. For higher resolution requirements, analog signals are digitized at sources and are serially sent to the control system. This paper surveys ADC subsystems that are used with the accelerator control systems and discusses practical problems and solutions, and it describes how analog data are presented on the console system.

  14. Robust hyperchaotic synchronization via analog transmission line

    NASA Astrophysics Data System (ADS)

    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.

  15. Real World: Analog Testing in Extreme Environments

    NASA Image and Video Library

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

  16. Novel catecholate-type siderophore analogs based on a myo-inositol scaffold.

    PubMed

    Schnabelrauch, M; Egbe, D A; Heinisch, L; Reissbrodt, R; Möllmann, U

    1998-09-01

    A novel 1,3,5-triamino-myo-inositol derivative is presented as a readily available scaffold for the design of tripodal siderophore mimetics. Based on this scaffold, various hexadentate catecholate-type siderophore analogs were synthesized by attaching the catechols to the inositol scaffold via spacer units of different structure and length. The potential to tune the polarity of the inositol containing siderophore analogs has also been demonstrated by varying the protection group strategy. The siderophore activity of the prepared siderophore analogs was examined by cross-feeding tests with various Gram-negative bacteria and mycobacteria.

  17. Synthesis and antiproliferative activity of novel sugiol beta-amino alcohol analogs.

    PubMed

    Córdova, I; León, L G; León, F; San Andrés, L; Luis, J G; Padrón, J M

    2006-11-01

    A series of beta-amino alcohol analogs of sugiol were synthesized in a straightforward manner. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, SW1573 and WiDr. The most potent analogs induced considerably growth inhibition in the range 1.5-6.7 microM. The results showed that beta-amino alcohol analogs are more potent than the parent compound. In addition, the derivatives with secondary amine fragments showed more active than those bearing tertiary amines.

  18. Phaeofurans and Sorbicillin Analogs from a Fungicolous Phaeoacremonium Species (NRRL 32148)

    PubMed Central

    Reátegui, Ricardo F.; Wicklow, Donald T.; Gloer, James B.

    2008-01-01

    Two new benzofuran-derived metabolites of polyketide origin called phaeofurans A and B (1–2), along with three sorbicillin analogs (3–5) have been obtained from a fungicolous isolate of the genus Phaeoacremonium (NRRL 32148). The structures were determined by analysis of MS and 2D NMR data. The antifungal effects of the extract were ascribed to the sorbicillin analogs. PMID:16441079

  19. The facilitatory effect of negative feedback on the emergence of analogical reasoning abilities.

    PubMed

    Ball, Linden J; Hoyle, Alison M; Towse, Andrea S

    2010-09-01

    This paper focuses on the development of analogical reasoning abilities in 5- and 6-year-old children. Our particular interest relates to the way in which analogizing is influenced by the provision of task-based feedback coupled with a self-explanation requirement. Both feedback and self-explanation provide children with opportunities to engage in self-reflective thinking about the process of analogical reasoning. To examine the role of such metacognitive factors in analogical strategy development the reported study combined a proportional analogy paradigm with a small-scale microgenetic approach involving multiple testing sessions over a restricted time period. The key manipulation involved exposing participants either to the correct or incorrect analogy completions of another reasoner that they were then asked to explain. The data revealed that the development of an effective analogizing strategy embodying a 'relational shift' from superficial to relational responding was modulated by the feedback condition that the child was placed in, with a negative feedback intervention providing the greatest developmental benefit. We suggest that the value of negative feedback for the acquisition of analogical reasoning abilities derives from the way in which a self-reflective analysis of the reasons for erroneous responses sensitizes the child to a deeper understanding of how to make effective relational mappings.

  20. Theoretical ingredients of a Casimir analog computer.

    PubMed

    Rodriguez, Alejandro W; McCauley, Alexander P; Joannopoulos, John D; Johnson, Steven G

    2010-05-25

    We derive a correspondence between the contour integration of the Casimir stress tensor in the complex-frequency plane and the electromagnetic response of a physical dissipative medium in a finite real-frequency bandwidth. The consequences of this correspondence are at least threefold: First, the correspondence makes it easier to understand Casimir systems from the perspective of conventional classical electromagnetism, based on real-frequency responses, in contrast to the standard imaginary-frequency point of view based on Wick rotations. Second, it forms the starting point of finite-difference time-domain numerical techniques for calculation of Casimir forces in arbitrary geometries. Finally, this correspondence is also key to a technique for computing quantum Casimir forces at micrometer scales using antenna measurements at tabletop (e.g., centimeter) scales, forming a type of analog computer for the Casimir force. Superficially, relationships between the Casimir force and the classical electromagnetic Green's function are well known, so one might expect that any experimental measurement of the Green's function would suffice to calculate the Casimir force. However, we show that the standard forms of this relationship lead to infeasible experiments involving infinite bandwidth or exponentially growing fields, and a fundamentally different formulation is therefore required.

  1. Theoretical ingredients of a Casimir analog computer

    PubMed Central

    Rodriguez, Alejandro W.; McCauley, Alexander P.; Joannopoulos, John D.; Johnson, Steven G.

    2010-01-01

    We derive a correspondence between the contour integration of the Casimir stress tensor in the complex-frequency plane and the electromagnetic response of a physical dissipative medium in a finite real-frequency bandwidth. The consequences of this correspondence are at least threefold: First, the correspondence makes it easier to understand Casimir systems from the perspective of conventional classical electromagnetism, based on real-frequency responses, in contrast to the standard imaginary-frequency point of view based on Wick rotations. Second, it forms the starting point of finite-difference time-domain numerical techniques for calculation of Casimir forces in arbitrary geometries. Finally, this correspondence is also key to a technique for computing quantum Casimir forces at micrometer scales using antenna measurements at tabletop (e.g., centimeter) scales, forming a type of analog computer for the Casimir force. Superficially, relationships between the Casimir force and the classical electromagnetic Green’s function are well known, so one might expect that any experimental measurement of the Green’s function would suffice to calculate the Casimir force. However, we show that the standard forms of this relationship lead to infeasible experiments involving infinite bandwidth or exponentially growing fields, and a fundamentally different formulation is therefore required. PMID:20460309

  2. More shock recovery experiments on mesosiderite analogs

    NASA Technical Reports Server (NTRS)

    Rowan, L. R.; Mittlefehldt, D. W.

    1994-01-01

    Mesosiderites, a small but unique group of stony-iron meteorites with affinities to howardites, eucrites, and pallasites, remain enigmatic in terms of their petrogenesis. They are composed of approximately equal weight proportions of Fe-Ni metal plus troilite and gabbroic, basaltic, and orthopyroxenitic materials. The metal and silicates, which display variable grain sizes and shapes, are delicately intermingled, forming irregular grain boundaries that have been attributed to a wide range of origins from subsolidus metamorphism to supersolidus igneous processes. Perhaps the most relevant question regarding the petrogenesis of mesosiderites is: what is the source and duration of heating that could produce the unequilibrated textures and chemistry of these meteorites? A leading candidate appears to be impacts of metallic core fragments with a differentiated asteroidal surface. This provides not only a suitable source of heat, but also the metal component uniquely required by mesosiderites. A series of shock recovery experiments on mesosiderite analogs has been continued. Textural and chemical similarities have been found that support an impact-derived origin for these unusual meteorites.

  3. Intracranial Fluid Redistribution During a Spaceflight Analog

    NASA Technical Reports Server (NTRS)

    Koppelmans, Vincent; Pasternak, Ofer; Bloomberg, Jacob J.; De Dios, Yiri E.; Wood, Scott J.; Riascos, Roy; Reuter-Lorenz, Patrica A.; Kofman, Igor S.; Mulavara, Ajitkumar P.; Seidler, Rachael D.

    2017-01-01

    The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

  4. Resveratrol and its methoxy-derivatives as modulators of DNA damage induced by ionising radiation.

    PubMed

    Traversi, Gianandrea; Fiore, Mario; Leone, Stefano; Basso, Emiliano; Di Muzio, Elena; Polticelli, Fabio; Degrassi, Francesca; Cozzi, Renata

    2016-07-01

    Various naturally occurring stilbene-like compounds that are related to resveratrol (RSV) possess some of the beneficial effects of the parent molecule and provide even further benefits. Therefore, a series of methoxylated analogues of RSV were prepared with the aim of increasing antitumour and proapoptotic activity. In a previous article, we studied two methoxy-derivatives, pterostilbene (PTERO) and trimethoxystilbene (TRIMETHOXY), in which the first was formed by the substitution of two hydroxyl groups with two methoxy groups (trans-3,5-dimethoxy-4'-hydroxystilbene) and the second was formed by the replacement of all three OH groups with methoxy groups (trans-3,5,4'-trimethoxystilbene). Both methoxy-derivatives showed stronger antioxidant activity when compared with RSV. In the present article, we focused on the analysis of the ability of RSV and its two methoxylated derivatives to protect proliferating non-tumoural cells from the damage induced by ionising radiation (IR). First we showed that the methoxy derivatives, contrary to their parental compound, are unable to affect topoisomerase enzyme and consequently are not clastogenic per se Second we showed that both PTERO and TRIMETHOXY more efficiently reduce the chromosome damage induced by IR. Furthermore, TRIMETHOXY, but not PTERO, causes a delay in cell proliferation, particularly in mitosis progression increasing the number of cells in metaphase at the expense of prophases and ana/telophases. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. The Aplidin analogs PM01215 and PM02781 inhibit angiogenesis in vitro and in vivo.

    PubMed

    Borjan, Bojana; Steiner, Normann; Karbon, Silvia; Kern, Johann; Francesch, Andrés; Hermann, Martin; Willenbacher, Wolfgang; Gunsilius, Eberhard; Untergasser, Gerold

    2015-10-19

    Novel synthesized analogs of Aplidin, PM01215 and PM02781, were tested for antiangiogenic effects on primary human endothelial cells in vitro and for inhibition of angiogenesis and tumor growth in vivo. Antiangiogenic activity of both derivatives was evaluated by real-time cell proliferation, capillary tube formation and vascular endothelial growth factor (VEGF)-induced spheroid sprouting assays. Distribution of endothelial cells in the different phases of the cell cycle was analyzed by flow cytometry. Aplidin analogs were tested in vivo in chicken chorioallantoic membrane (CAM) assays. Both derivatives inhibited angiogenic capacities of human endothelial cells (HUVECs) in vitro at low nanomolar concentrations. Antiangiogenic effects of both analogs were observed in the CAM. In addition, growth of human multiple myeloma xenografts in vivo in CAM was significantly reduced after application of both analogs. On the molecular level, both derivatives induced cell cycle arrest in G1 phase. This growth arrest of endothelial cells correlated with induction of the cell cycle inhibitor p16(INK4A) and increased senescence-associated beta galactosidase activity. In addition, Aplidin analogs induced oxidative stress and decreased production of the vascular maturation factors Vasohibin-1 and Dickkopf-3. From these findings we conclude that both analogs are promising agents for the development of antiangiogenic drugs acting independent on classical inhibition of VEGF signaling.

  6. Expert analogy use in a naturalistic setting

    PubMed Central

    Kretz, Donald R.; Krawczyk, Daniel C.

    2014-01-01

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

  7. Children's Use of Analogy during Collaborative Reasoning

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  8. The Pennies-as-Electrons Analogy

    ERIC Educational Resources Information Center

    Ashmann, Scott

    2009-01-01

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

  9. Piperazine-based nucleic acid analogs

    DOEpatents

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

    2005-01-11

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

  10. Analogical Processes and College Developmental Reading

    ERIC Educational Resources Information Center

    Paulson, Eric J.

    2014-01-01

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

  11. Mathematical Analogs and the Teaching of Fractions.

    ERIC Educational Resources Information Center

    Charles, Kathy; Nason, Rod; Cooper, Tom

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

  12. Understanding the Development of Analogical Reasoning Ability.

    ERIC Educational Resources Information Center

    Goldman, Susan R.; Bisanz, Jeffrey

    This paper takes the position that theories about individual differences in childhood and theories about cognitive development both would be enhanced if the two lines of research were integrated. The heuristic value of this position is illustrated in the context of analogical reasoning tasks. A general model of analogy solution and potential…

  13. Rotanone analogs: method of preparation and use

    DOEpatents

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

    2013-10-08

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

  14. A Mechanical Analogy for the Photoelectric Effect

    ERIC Educational Resources Information Center

    Kovacevic, Milan S.; Djordjevich, Alexandar

    2006-01-01

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

  15. 38 CFR 4.20 - Analogous ratings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  16. A Mechanical Analogy for the Photoelectric Effect

    ERIC Educational Resources Information Center

    Kovacevic, Milan S.; Djordjevich, Alexandar

    2006-01-01

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

  17. Analogical Reasoning in Restructuring Scientific Knowledge.

    ERIC Educational Resources Information Center

    Mason, Lucia; Sorzio, Paolo

    1996-01-01

    Presents the results of an experiment that evaluated the efficiency of analogy in the conceptual restructuring of a science topic. The experiment involved a fifth-grade class studying water and heat flow. Discovered that analogy can act as an effective trigger for restructuring knowledge. (MJP)

  18. Structure Mapping in Analogy and Similarity.

    ERIC Educational Resources Information Center

    Gentner, Dedre; Markman, Arthur B.

    1997-01-01

    It is suggested that both similarity and analogy involve a process of structural alignment and mapping. The structure mapping process is described as it has been worked out for analogy, and this view is then extended to similarity and used to generate new predictions. (SLD)

  19. The Multidimensionality of Verbal Analogy Items

    ERIC Educational Resources Information Center

    Ullstadius, Eva; Carlstedt, Berit; Gustafsson, Jan-Eric

    2008-01-01

    The influence of general and verbal ability on each of 72 verbal analogy test items were investigated with new factor analytical techniques. The analogy items together with the Computerized Swedish Enlistment Battery (CAT-SEB) were given randomly to two samples of 18-year-old male conscripts (n = 8566 and n = 5289). Thirty-two of the 72 items had…

  20. The Pennies-as-Electrons Analogy

    ERIC Educational Resources Information Center

    Ashmann, Scott

    2009-01-01

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

  1. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

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

    2014-01-01

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

  2. Use of Analogy in Computer Language Acquisition.

    ERIC Educational Resources Information Center

    Pohl, Heidi L.; Nutter, Jane Terry

    1985-01-01

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

  3. The Multidimensionality of Verbal Analogy Items

    ERIC Educational Resources Information Center

    Ullstadius, Eva; Carlstedt, Berit; Gustafsson, Jan-Eric

    2008-01-01

    The influence of general and verbal ability on each of 72 verbal analogy test items were investigated with new factor analytical techniques. The analogy items together with the Computerized Swedish Enlistment Battery (CAT-SEB) were given randomly to two samples of 18-year-old male conscripts (n = 8566 and n = 5289). Thirty-two of the 72 items had…

  4. Verbal Analogical Reasoning in Children and Adolescents.

    ERIC Educational Resources Information Center

    Nippold, Marilyn A.

    1986-01-01

    Verbal analogical reasoning tasks are described as potentially valuable in the assessment and management of subtle linguistic defects less easily detected by standardized language tests. Semantic and structural factors that should be considered in the development of verbal analogies as test items are cited, as well as adaptations for nonreaders.…

  5. Understanding the Development of Analogical Reasoning Ability.

    ERIC Educational Resources Information Center

    Goldman, Susan R.; Bisanz, Jeffrey

    This paper takes the position that theories about individual differences in childhood and theories about cognitive development both would be enhanced if the two lines of research were integrated. The heuristic value of this position is illustrated in the context of analogical reasoning tasks. A general model of analogy solution and potential…

  6. Response Generation Norms for Verbal Analogies.

    ERIC Educational Resources Information Center

    Ingram, Albert; Pellegrino, James W.

    Normative data were collected for the generation of responses to 150 incomplete verbal analogies. Two types of normative data are provided: (a) the probabilities associated with each response produced for each analogy base and (b) the probabilities that initial responses represented the appropriate semantic relationship, with a division of…

  7. Student-Generated Analogies in Biology.

    ERIC Educational Resources Information Center

    Middleton, James L.

    1991-01-01

    Discusses the advantages of and strategies in having students create analogies to facilitate learning biology. Presents a vocabulary worksheet to facilitate analogy creation and describes its use. The author discusses the use of instructional strategies including forced associations, metaphorical sketches, mnemonics, and association memorization.…

  8. Young Children's Analogical Reasoning in Science Domains

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

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

  9. An Analog Computer for Electronic Engineering Education

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  10. Young Children's Analogical Reasoning in Science Domains

    ERIC Educational Resources Information Center

    Haglund, Jesper; Jeppsson, Fredrik; Andersson, Johanna

    2012-01-01

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

  11. An Analog Computer for Electronic Engineering Education

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  12. Novel Analog For Muscle Deconditioning

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  13. Novel Analog For Muscle Deconditioning

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  14. Solar System Analog; WMO Statement

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

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

  15. Novel epigallocatechin gallate analogs as potential anticancer agents: a patent review (2009 – present)

    PubMed Central

    Landis-Piwowar, Kristin; Chen, Di; Foldes, Robert; Chan, Tak-Hang; Dou, Qing Ping

    2013-01-01

    Introduction Over the past three years numerous patents and patent applications have been published relating to scientific advances in the use of the green tea polyphenol epigallocatechin gallate (EGCG) (the most abundant, and bioactive compound in green tea) and its analogs as anticancer agents. EGCG affects multiple molecular targets involved in cancer cell proliferation and survival; however, polyphenolic catechins, such as EGCG, generally exhibit poor oral bioavailability. Since the anticancer activity of polyphenols largely depends on their susceptibility to biotransformation reactions, numerous EGCG derivatives, analogs and prodrugs have been designed to improve the stability, bioavailability and anticancer potency of the native compound. Areas covered This review focuses on the applications of EGCG and its analogs, derivatives and prodrugs in the prevention and treatment of human cancers. A comprehensive description of patents related to EGCG and its derivatives, analogs and prodrugs and their uses as anticancer agents is included. Expert opinion EGCG targets multiple essential survival proteins and pathways in human cancer cells. Because it is unstable physiologically, numerous alterations to the EGCG molecule have been patented, either to improve the integrity of the native compound or to generate a more stable yet similarly efficacious molecule. EGCG and its derivatives, analogs and prodrugs could be developed into future drugs for chemoprevention, chemosensitization, radiosensitization and/or cancer interception. PMID:23230990

  16. Structure-activity relationship studies on natural and synthetic bile acid analogs.

    PubMed

    Roda, A; Grigolo, B; Pellicciari, R; Natalini, B

    1989-12-01

    The objective of our research was to develop ursodiol analogs that are structurally modified to modulate hepatic side-chain amidation and prevent 7-dehydroxylation by intestinal bacteria while at the same time maintaining the critical micellar concentration (CMC) and hydrophilicity of ursodiol. More than 20 naturally occurring bile acids were screened for physicochemical properties. Then, two generations of analogs were studied, and those with physicochemical properties similar to ursodiol's were analyzed for physiologic properties. The first generation of analogs included molecules with steric and/or electronic hindrance on the side chain; the second group consisted of the same molecules conjugated with glycine or taurine and also "pseudoconjugated" analogs (23-hydroxylated, esterified, and amidated with other amino acids). Of the first-generation analogs, only cyclopropane D derivative and trans-olefin were useful to our purposes, being conjugated by the liver and almost completely recovered in bile. These two analogs were deconjugated and 7-dehydroxylated but with slower kinetics. The hydrophilicity of the molecules could be augmented by increasing the polarity of the steroid ring. Among the pseudoconjugated analogs, the CMC values were similar to those of the natural analogs, although hydrophobicity differed among the group. The analogs that were not deconjugated were not 7-dehydroxylated either. All of the pseudoconjugated bile acids were efficiently taken up by the liver, and their recovery in bile was similar to that of glycine and taurine ursodiol. From these studies we now know that side chain configuration and conformation are important in the conjugation and deconjugation processes. Mild modification of the side chain can prevent 7-dehydroxylation and thus yield a bile acid more resistant to intestinal bacteria and more bioavailable. Prevention of hepatic conjugation improves biliary secretion and recovery of many analogs.

  17. An Analog Earth Climate Model

    NASA Astrophysics Data System (ADS)

    Varekamp, J. C.

    2010-12-01

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

  18. Investigation of Celestial Solid Analogs

    NASA Technical Reports Server (NTRS)

    Sievers, A. J.

    2003-01-01

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

  19. Analog regulation of metabolic demand

    PubMed Central

    2011-01-01

    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 results show that DNA

  20. Namibian Analogs To Titan Dunes

    NASA Astrophysics Data System (ADS)

    Wall, Stephen D.; Lopes, R.; Kirk, R.; Stofan, E.; Farr, T.; Van der Ploeg, P.; Lorenz, R.; Radebaugh, J.

    2009-09-01

    Titan's equatorial dunes, observed in Cassini SAR, have been described as longitudinal, similar to longitudinal dunes in the Namib sand sea in southern Africa. Their "Y” junctions and the way they divert around topography are used as evidence of equatorial wind flow direction. In two instances of such diversion they exhibit overlying or crosshatched patterns in two distinct directions that have been interpreted as a transition to transverse dunes. Here we describe field observations of the Namibian dunes and these comparisons, we present images of the dunes from terrestrial SAR missions, and we discuss implications to both the Titan dunes and the wind regime that created them. Selected portions of the Namibian dunes resemble Titan's dunes in peak-to-peak distance and length. They are morphologically similar to Titan, and specific superficial analogs are common, but they also differ. For example, when Titan dunes encounter topography they either terminate abruptly, "climb” the upslope, or divert around; only the latter behavior is seen in remote sensing images of Namibia. Namib linear dunes do transition to transverse as they divert, but at considerably smaller wavelength, while at Titan the wavelengths are of the same scale. Crosshatching of similar-wavelength dunes does occur in Namibia, but not near obstacles. Many additional aeolian features that are seen at Namibia such as star dunes, serpentine ridges and scours have not been detected on Titan, although they might be below the Cassini SAR's 300-m resolution. These similarities and differences allow us to explore mechanisms of Titan dune formation, in some cases giving us clues as to what larger scale evidence to look for in SAR images. Viewed at similar resolution, they provide interesting comparisons with the Titan dunes, both in likeness and differences. A part of this work was carried out at JPL under contract with NASA.

  1. Rhenium(I) Carbonyl Complexes of 2,4,6-Tris(2-pyridyl)-1,3,5-triazine (TPT). Rhenium(I)-Promoted Methoxylation of the Triazine Ring Carbon Atom in Dinuclear Rhenium Complexes

    PubMed Central

    Chen, Xiaoyuan; Femia, Frank J.; Babich, John W.; Zubieta, Jon A.

    2010-01-01

    2,4,6-Tris(2-pyridyl)-1,3,5-triazine (TPT) bridged dinuclear rhenium(I) tricarbonyl halide complexes with the composition (μ-TPT)[ReX(CO)3]2 (3, X = Cl; 4, X = Br) can be made either by one-pot reaction of TPT with 2 equiv of [ReX(CO)5] (X = Cl and Br) in chloroform or by reacting mononuclear [ReX(CO)3(TPT)] 2 (1, X = Cl; 2, X = Br) with an excess amount of [ReX(CO)5]. Crystal data are as follows. 1: monoclinic, P21/c, a = 11.751(1) Å, b = 11.376(1) Å, c = 15.562(2) Å, β = 103.584(2)°, V = 2022.0(4) Å3, Z = 4. 2: monoclinic, P21/c, a = 11.896(1) Å, b = 11.396(1) Å, c = 15.655(1) Å, β = 104.474(2)°, V = 2054.9(3) Å3, Z = 4. 3: triclinic, P1‒, a = 11.541(2) Å, b = 12.119(2) Å, c = 13.199(2) Å, α = 80.377(2)°, β = 76.204(3)°, γ = 66.826-(2)°, V = 1642.5(4) Å3, Z ) 2. Crystals of 4 crystallized from acetone: triclinic, P1‒, a = 11.586(5) Å, b = 12.144(5) Å, c = 13.364(6) Å, α = 80.599(7)°, β = 76.271(8)°, γ = 67.158(8)°, V = 1678.0(12) Å3, Z = 2. Crystals of 4′ are obtained from CH2Cl2–pentane solution: monoclinic, C2/c, a = 17.555(4) Å, b = 15.277(3) Å, c = 13.093(3) Å, β = 111.179(3)°, V = 3274.0(12) Å3, Z = 4. By contrast, similar reactions in the presence of methanol yielded complexes with the composition [μ-C3N3(OMe)(py)2(pyH)][ReX(CO)3]2 (5, X = Cl; 6, X = Br). Crystal data for 5: monoclinic, C2/c, a = 26.952(2) Å, b = 16.602(1) Å, c = 14.641(1) Å, β = 116.147(1)°, V = 5880.5(8) Å3, Z = 8. 6: monoclinic, C2/c, a = 27.513(3) Å, b = 16.740(2) Å, c = 14.837(2) Å, β = 116.925(2)°, V = 6092.8(10) Å3, Z = 8. An unusual metal-induced methoxylation at the carbon atom of the triazine ring of the bridging TPT ligand was observed. The nucleophilic attack of MeO− on C(3) results in a tetrahedral geometry around the carbon atom. Concomitantly, the uncoordinated pyridyl ring is protonated and rotated into a perpendicular orientation relative to the central C3N3 ring. Reaction of TPT with [NEt4]2[ReBr3-(CO)3] in

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

    SciTech Connect

    McConnell, D.S.

    1991-01-01

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

  3. 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells.

    PubMed

    Ai, Hui-Han; Zhou, Zi-Long; Sun, Lu-Guo; Yang, Mei-Ting; Li, Wei; Yu, Chun-Lei; Song, Zhen-Bo; Huang, Yan-Xin; Wu, Yin; Liu, Lei; Yang, Xiao-Guang; Zhao, Yu-Qing; Bao, Yong-Li; Li, Yu-Xin

    2017-09-01

    The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.

  4. Fostering Multilateral Involvement in Analog Research

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2015-01-01

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

  5. Observed Methods for Generating Analogies in Scientific Problem Solving. Revised.

    ERIC Educational Resources Information Center

    Clement, John

    Evidence from video tapes of experts thinking aloud and using analogies in scientific problem solving is presented. Four processes appear to be important in using an analogy: (1) generating the analogy; (2) establishing confidence in the validity of the analogy relation; (3) understanding the analogous case; and (4) applying findings to the…

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  8. Preparation of 2-hydroxy-5-oxoproline and analogs thereof

    DOEpatents

    Martinez, Rodolfo A.; Unkefer, Pat J.

    2001-01-01

    The compound 2-hydroxy-5-oxoproline and analogs thereof may be used to produce an increase in carbon dioxide fixation, growth, dry weight, nutritional value (proteins and amino acids), nodulation and nitrogen fixation and photosynthetically derived chemical energy when applied to plants through their roots and/or through their foliar portions. The present invention includes an essentially quantitative chemical synthesis for this compound which is performed in a single step reaction of Fremy's Salt (potassium nitrosodisulphonate) with either glutamine or 2-pyrrolidone-5-carboxylic acid. Fremy's salt (potassium nitrosodisulphonate) is available commercially, or can be readily synthesized.

  9. Structure-activity relationships of strychnine analogs at glycine receptors.

    PubMed

    Mohsen, Amal M Y; Heller, Eberhard; Holzgrabe, Ulrike; Jensen, Anders A; Zlotos, Darius P

    2014-08-01

    Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC50 value of 1.6 μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21) = C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  10. Simultaneous separation of chlorinated/brominated dioxins, polychlorinated biphenyls, polybrominated diphenyl ethers and their methoxylated derivatives from hydroxylated analogues on molecularly imprinted polymers prior to gas/liquid chromatography and mass spectrometry.

    PubMed

    Roszko, Marek; Szymczyk, Krystyna; Jędrzejczak, Renata

    2015-11-01

    Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are important contaminants in the environment. In recent years also polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) have been reported as emerging environmental stressors. It has been suggested that hydroxylated polybrominated biphenyl ethers (OH-BDEs) are important - may be even the most important - precursors of brominated dioxins/furans. The aim of this study was to develop a robust, time-saving analytical procedure to collectively separate in animal tissues such compounds prior to determination of individual substances with a gas/liquid chromatograph coupled to an ion trap/time-of-flight mass spectrometer (GC/IT-MS or UPLC/TOF-MS). Two OH-CB/BDE separation methods including alkaline extraction and molecularly imprinted polymers (MIP) were compared. Performance of both methods was validated: absolute recovery values were in the 47-90% range depending on the compound, while recovery relative standard deviation was below 20% in most cases. Levels of the studied compounds have been assessed in some real life samples.

  11. Biotransformation of furanocoumarins by fungi: preparation of imperation analogs.

    PubMed

    Xin, Xiu-Lan; Wang, Yan; Wang, Ge; Wang, Chao; Huang, Shan-Shan; Huo, Xiao-Kui; Su, Dong-Hai; Tian, Xiang-Ge

    2017-01-31

    Imperation analogs have the furanocoumarin skeleton, with the isopentenyl group, which displayed significant bioactivities. The biotransformation of furanocoumarins imperation, isoimperation and phellopterin (1-3) by fungi has been proved to be an efficient method for the structural modification. Ten transformed furanocoumarin analogs were obtained by fungal biotransformation, including one new highly oxygenated furanocoumarin (4c). Aspergillus niger AS 3.739 displayed selectively transformed capability toward furanocouamrins (1-3) with one or two major products. So, seven hydroxylation and hydrolysis derivatives have been prepared efficiently. Additionally, the biotransformation of phellopterin gave multiple products (4a, 4b, 4c) by Cunninghamella blakesleana AS 3.970. The biotransformation time-courses of furanocoumarins have been established, which suggested the preferred incubation time. The bioactivities of furanocoumarin analogs have been investigated in an in vitro bioassay. And, furanocoumarins 1-3, 2a, and 2c displayed moderate anti-osteoporosis activities using MCET3-E1 cell line at the concentrations of 1, 10, and 100 μM.

  12. Deficits in Analogical Reasoning in Adolescents with Traumatic Brain Injury

    PubMed Central

    Krawczyk, Daniel C.; Hanten, Gerri; Wilde, Elisabeth A.; Li, Xiaoqi; Schnelle, Kathleen P.; Merkley, Tricia L.; Vasquez, Ana C.; Cook, Lori G.; McClelland, Michelle; Chapman, Sandra B.; Levin, Harvey S.

    2010-01-01

    Individuals with traumatic brain injury (TBI) exhibit deficits in executive control, which may impact their reasoning abilities. Analogical reasoning requires working memory and inhibitory abilities. In this study, we tested adolescents with moderate to severe TBI and typically developing (TD) controls on a set of picture analogy problems. Three factors were varied: complexity (number of relations in the problems), distraction (distractor item present or absent), and animacy (living or non-living items in the problems). We found that TD adolescents performed significantly better overall than TBI adolescents. There was also an age effect present in the TBI group where older participants performed better than younger ones. This age effect was not observed in the TD group. Performance was affected by complexity and distraction. Further, TBI participants exhibited lower performance with distractors present than TD participants. The reasoning deficits exhibited by the TBI participants were correlated with measures of executive function that required working memory updating, attention, and attentional screening. Using MRI-derived measures of cortical thickness, correlations were carried out between task accuracy and cortical thickness. The TD adolescents showed negative correlations between thickness and task accuracy in frontal and temporal regions consistent with cortical maturation in these regions. This study demonstrates that adolescent TBI results in impairments in analogical reasoning ability. Further, TBI youth have difficulty effectively screening out distraction, which may lead to failures in comprehension of the relations among items in visual scenes. Lastly, TBI youth fail to show robust cortical–behavior correlations as observed in TD individuals. PMID:20844604

  13. A new sensitive HPLC assay for methoxyamine and its analogs.

    PubMed

    Wang, E; Struble, E; Liu, P; Cheung, A P

    2002-10-15

    Methoxyamine (MOA) and its analogs are polymerization regulators, building blocks and intermediates for agrichemicals and pharmaceuticals. MOA induces mutagenesis of nucleic acids and has been considered for anti-cancer and anti-virus therapy. It has been studied as a DNA repair modifier in anti-cancer therapy. HPLC procedures available in the literature for MOA are all based on electrochemical detection, which is not commonly available. This paper describes the development and validation of a HPLC assay with UV detection for MOA and its analogs. The analytes are first reacted with o-phthalaldehyde to form an oxime derivative before chromatography with an ODS column. Detection is achieved by UV at 254 nm. The chromatography resolves MOA from its decomposition products and analogs. The assay is reproducible (R.S.D. < 0.8%), linear (r(2) = 0.9997), and accurate (error < 1%). The method is sensitive and has a lower detection limit of 5 pmol (0.4 ng of MOA.HCl), which is comparable to that of electrochemical detection. Copyright 2002 Elsevier Science B.V.

  14. 'Quality of life' and the analogy with the Nazis.

    PubMed

    Cohen, C B

    1983-05-01

    The introduction of 'quality of life' judgments into treatment decisions is viewed as pernicious by some who claim that these presuppose the Nazi position that those who are 'devoid of value' must be exterminated. 'Quality of life' judgments are said to deny the equal value of human beings and to assume that some lives are not 'worthy to be lived'. It is argued that the analogy misconstrues the senses of 'value' and 'quality' employed by Naziism and a 'quality of life' position. This leads the analogizers incorrectly to claim that both views assimilate the value of human beings to the value of their condition. A 'quality of life' position is grounded in recognition of the logical priority of the value of human beings as self-reflective evaluators and agents, which is a matter of kind, not degree. The 'quality of life' is explicated in terms of the standards of well-being of individuals, which are derived from their basic human needs and their individual priorities and goals. The use of 'quality of life' judgments is morally required to ensure that considerations of justice and individual autonomy govern treatment decisions. The purported analogy misconstrues the views of both the Nazi position and a 'quality of life' position and so is seriously misdirected.

  15. Modulation of Alpha-Synuclein Aggregation by Dopamine Analogs

    PubMed Central

    Latawiec, Diane; Herrera, Fernando; Bek, Alpan; Losasso, Valeria; Candotti, Michela; Benetti, Federico; Carlino, Elvio; Kranjc, Agata; Lazzarino, Marco; Gustincich, Stefano; Carloni, Paolo; Legname, Giuseppe

    2010-01-01

    The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit α-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of α-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to α-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein. PMID:20169066

  16. Analog detection for cavity lifetime spectroscopy

    DOEpatents

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

    2001-05-15

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

  17. Analog detection for cavity lifetime spectroscopy

    DOEpatents

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

    2003-01-01

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

  18. Programmable Analog-To-Digital Converter

    NASA Technical Reports Server (NTRS)

    Kist, Edward H., Jr.

    1993-01-01

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

  19. Hybrid benzothiazole analogs as antiurease agent: Synthesis and molecular docking studies.

    PubMed

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Khan, Khalid Muhammad; Riaz, Muhammad

    2016-06-01

    Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and (1)H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4±0.10 to 34.43±2.10μM when compared with standard thiourea (IC50 19.46±1.20μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1-18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking.

  20. Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.

    PubMed

    Zughaier, Susu; Karna, Prasanthi; Stephens, David; Aneja, Ritu

    2010-02-11

    Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.

  1. Pyridine analogs inhibit the glucosyltransferase of Streptococcus mutans.

    PubMed Central

    Thaniyavarn, S; Taylor, K G; Singh, S; Doyle, R J

    1982-01-01

    Soluble glucan synthesis catalyzed by dextransucrase preparations from Streptococcus mutans 6715 were inhibited by pyridoxal-5-phosphate and several other pyridine analogs, including pyridoxine, pyridoxamine, pyridoxamine-5-phosphate, pyridoxal, and 4-pyridoxic acid. Pyridine and pyridine-4-carboxaldehyde were not effective inhibitors of the enzyme. Kinetic analyses suggested that pyridoxal-5-phosphate is a noncompetitive inhibitor of dextransucrase. The inactivation was dependent on time, pyridoxal-5-phosphate concentration, and hydrogen ion concentration. Apparent Ki values were 4.9 mM at pH 7.0 and 4.2 mM at pH 5.5. Dextransucrase activity could be restored by dialysis to remove the inhibitors. Maximum inhibition was observed after a 120-min incubation of the enzyme with pyridoxal-5-phosphate. The pH optima for inhibition by pyridoxal-5-phosphate were 4 and 7. The sucrose-dependent adherence of S. mutans cells to saliva-coated hydroxylapatite beads was also inhibited by pyridoxal-5-phosphate but only marginally by the other pyridine anatogs. In addition, pyridoxal-5-phosphate markedly reduced the rate of acid production by intact S. mutans cells from sucrose or glucose substrates. Another pyridoxal-5-phosphate analog, 2-methyl-5-hydroxypyridine, was also effective in preventing the production of acid by S. mutans from sucrose or glucose. When S. mutans cells were preincubated with pyridoxal-5-phosphate or pyridine analogs, significant reductions in the rate of D-glucose uptake were observed. It is suggested that the inhibition of dextransucrase occurs because of a change iun enzyme conformation which results from the binding of the pyridine derivatives. The results suggest that pyridoxal-5-phosphate or structural analogs may ultimately be useful in reducing the incidence of dental caries. PMID:6215355

  2. Computer Analogies: Teaching Molecular Biology and Ecology.

    ERIC Educational Resources Information Center

    Rice, Stanley; McArthur, John

    2002-01-01

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

  3. Analog Computer Laboratory with Biological Examples.

    ERIC Educational Resources Information Center

    Strebel, Donald E.

    1979-01-01

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

  4. Review of field-programmable analog arrays

    NASA Astrophysics Data System (ADS)

    Gulak, Glen; D'Mello, Dean R.

    1996-10-01

    The drive towards shorter design cycles for analog integrated circuits has given impetus to several developments in the area of field-programmable analog arrays (FPAAs). Various approaches have been taken in implementing topological and parametric programmability of analog circuits. Recent extensions of this work have married FPAAs to their digital counterparts (FPGAs) along with data conversion interfaces, to form field-programmable mixed signal arrays (FPMAs). This survey paper reviews work to data in the area of programmable analog and mixed signal circuits. The body of work reviewed includes university and industrial research, commercial products and patents. A time-line of important achievements in the area is drawn and the status of various activities is summarized.

  5. An Earth Analog to Mars Yellowknife Bay

    NASA Image and Video Library

    2013-03-12

    A sampling pit exposing clay-bearing lake sediments, deposited in a basaltic basin in southern Australia -- a modern terrestrial analog to the Yellowknife Bay area that NASA Curiosity rover is exploring.

  6. Analog Computer Laboratory with Biological Examples.

    ERIC Educational Resources Information Center

    Strebel, Donald E.

    1979-01-01

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

  7. CMOS analog switches for adaptive filters

    NASA Technical Reports Server (NTRS)

    Dixon, C. E.

    1980-01-01

    Adaptive active low-pass filters incorporate CMOS (Complimentary Metal-Oxide Semiconductor) analog switches (such as 4066 switch) that reduce variation in switch resistance when filter is switched to any selected transfer function.

  8. An Electrical Analog Computer for Poets

    ERIC Educational Resources Information Center

    Bruels, Mark C.

    1972-01-01

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

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

    ERIC Educational Resources Information Center

    Stewart, Peter A.

    1979-01-01

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

  10. Computer Analogies: Teaching Molecular Biology and Ecology.

    ERIC Educational Resources Information Center

    Rice, Stanley; McArthur, John

    2002-01-01

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

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

    ERIC Educational Resources Information Center

    Stewart, Peter A.

    1979-01-01

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

  12. NASA Now: Exploring Asteroids: An Analog Mission

    NASA Image and Video Library

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

  13. An Electronic Analog of the Diffraction Grating.

    ERIC Educational Resources Information Center

    MacLeod, A. M.

    1978-01-01

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

  14. An Analog Computer for Educational Laboratories

    ERIC Educational Resources Information Center

    Hamilton, J. A.

    1975-01-01

    Provides instructions for constructing a desk analog computer which is particularly convenient to the user and has a number of advantages over commercially available models, including lower cost for given computing power. (Author/MLH)

  15. Optical analog-to-digital converter

    DOEpatents

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

    2009-07-21

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

  16. Use of analogy in learning scientific concepts.

    PubMed

    Donnelly, C M; McDaniel, M A

    1993-07-01

    Four experiments compared learning of scientific concepts as expressed in either traditional literal form or through an analogy. Comprehension of basic-level details and inferential implications was measured through multiple-choice testing. In Experiment 1, literal or analogical renditions were presented in textual form only. In Experiment 2, text was accompanied by a dynamic video. In Experiment 3, the video and text literal rendition was compared with a text-only analogical rendition. In Experiment 4, subjects read only about a familiar domain. Subjects consistently answered basic-level questions most accurately when concepts were expressed literally, but answered inferential questions most accurately when concepts were expressed analogically. Analysis of individual differences (Experiment 2) indicated that this interaction strongly characterized the conceptual learning of science novices. The results are discussed within the framework of schema induction.

  17. An Electronic Analog of the Diffraction Grating.

    ERIC Educational Resources Information Center

    MacLeod, A. M.

    1978-01-01

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

  18. An Electrical Analog Computer for Poets

    ERIC Educational Resources Information Center

    Bruels, Mark C.

    1972-01-01

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

  19. Analog hardware for learning neural networks

    NASA Technical Reports Server (NTRS)

    Eberhardt, Silvio P. (Inventor)

    1991-01-01

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

  20. Synthetic heparin-binding growth factor analogs

    DOEpatents

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

    2007-01-23

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

  1. The Structure of Analogical Models in Science.

    DTIC Science & Technology

    1980-07-01

    analogies cannot. 8. A Freudian defense might claim that the theory merely reflects the illogic of the unconscious. But a theory about an unclarified...an initial comparison. To illustrate the points, analogies of historical importance are analyzed. Although the focus is on theory , some empirical...feature-list theory , the structure-mapping approach makes a strong distinction between objects and their attributes, on the one hand, and relationships, on

  2. ANALOG-TO-DIGITAL DATA CONVERTER

    DOEpatents

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

    1960-09-01

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

  3. Protein Structure Prediction with Visuospatial Analogy

    NASA Astrophysics Data System (ADS)

    Davies, Jim; Glasgow, Janice; Kuo, Tony

    We show that visuospatial representations and reasoning techniques can be used as a similarity metric for analogical protein structure prediction. Our system retrieves pairs of α-helices based on contact map similarity, then transfers and adapts the structure information to an unknown helix pair, showing that similar protein contact maps predict similar 3D protein structure. The success of this method provides support for the notion that changing representations can enable similarity metrics in analogy.

  4. Analog modelling of obduction processes

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

  5. Working memory predicts children's analogical reasoning.

    PubMed

    Simms, Nina K; Frausel, Rebecca R; Richland, Lindsey E

    2017-09-15

    Analogical reasoning is the cognitive skill of drawing relationships between representations, often between prior knowledge and new representations, that allows for bootstrapping cognitive and language development. Analogical reasoning proficiency develops substantially during childhood, although the mechanisms underlying this development have been debated, with developing cognitive resources as one proposed mechanism. We explored the role of executive function (EF) in supporting children's analogical reasoning development, with the goal of determining whether predicted aspects of EF were related to analogical development at the level of individual differences. We assessed 5- to 11-year-old children's working memory, inhibitory control, and cognitive flexibility using measures from the National Institutes of Health Toolbox Cognition battery. Individual differences in children's working memory best predicted performance on an analogical mapping task, even when controlling for age, suggesting a fundamental interrelationship between analogical reasoning and working memory development. These findings underscore the need to consider cognitive capacities in comprehensive theories of children's reasoning development. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. NASA Cribs: Human Exploration Research Analog

    NASA Image and Video Library

    2017-07-20

    Follow along as interns at NASA’s Johnson Space Center show you around the Human Exploration Research Analog (HERA), a mission simulation environment located onsite at the Johnson Space Center in Houston. HERA is a unique three-story habitat designed to serve as an analog for isolation, confinement, and remote conditions in exploration scenarios. This video gives a tour of where crew members live, work, sleep, and eat during the analog missions. Find out more about HERA mission activities: https://www.nasa.gov/analogs/hera Find out how to be a HERA crew member: https://www.nasa.gov/analogs/hera/want-to-participate For more on NASA internships: https://intern.nasa.gov/ For Johnson Space Center specific internships: https://pathways.jsc.nasa.gov/ https://www.nasa.gov/centers/johnson/education/interns/index.html HD download link: https://archive.org/details/jsc2017m000730_NASA-Cribs-Human-Exploration-Research-Analog --------------------------------- FOLLOW JOHNSON SPACE CENTER INTERNS! Facebook: @NASA.JSC.Students https://www.facebook.com/NASA.JSC.Students/ Instagram: @nasajscstudents https://www.instagram.com/nasajscstudents/ Twitter: @NASAJSCStudents https://twitter.com/nasajscstudents

  7. Phonological priming and orthographic analogies in reading.

    PubMed

    Goswami, U

    1990-04-01

    Recent work has demonstrated that children can use orthographic analogies between the spelling patterns in words to help in decoding new words (e.g., using beak to read peak; Goswami, 1986, 1988). However, one objection has been that these analogy effects may be due to phonological priming. Two experiments examined the phonological priming alternative. In Experiment 1, a single word reading task compared the use of analogies to read words that shared both orthography and phonology (e.g., most-post), that shared orthography only (e.g., most-cost), or that shared phonology only (e.g. most-toast--the phonological priming condition). Limited effects of phonological priming were found. Experiment 2 then presented the same words embedded in prose passages--"real reading." While the orthographic analogy effect remained robust, the small phonological priming effect disappeared. It is argued that phonological priming is an insufficient explanation of the analogy effect at the single word level, and plays no role in the use of analogies in story reading.

  8. Students' Pre- and Post-Teaching Analogical Reasoning When They Draw their Analogies

    NASA Astrophysics Data System (ADS)

    Braga Mozzer, Nilmara; Justi, Rosária

    2012-02-01

    Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in cognitive science literature about this issue. In this study, we investigated students' analogical reasoning as a creative process where an environment was set up to foster the students' generating and explaining their own analogies. Data were gathered from pre- and post-teaching interviews, in which the 13-14-year-old students were asked to make comparisons that could explain how atoms are bound. Such data supported the discussion about how students reasoned analogically. Our results made it evident that the task aims and the students' salient knowledge exerted a great influence on the drawing of analogies.

  9. Optical domain analog to digital conversion methods and apparatus

    SciTech Connect

    Vawter, Gregory A

    2014-05-13

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

  10. Analog Signal Correlating Using an Analog-Based Signal Conditioning Front End

    NASA Technical Reports Server (NTRS)

    Prokop, Norman; Krasowski, Michael

    2013-01-01

    This innovation is capable of correlating two analog signals by using an analog-based signal conditioning front end to hard-limit the analog signals through adaptive thresholding into a binary bit stream, then performing the correlation using a Hamming "similarity" calculator function embedded in a one-bit digital correlator (OBDC). By converting the analog signal into a bit stream, the calculation of the correlation function is simplified, and less hardware resources are needed. This binary representation allows the hardware to move from a DSP where instructions are performed serially, into digital logic where calculations can be performed in parallel, greatly speeding up calculations.

  11. Influences of Stocking Salmon Carcass Analogs on Salmonids in Yakima River Tributaries, 2001-2002 Technical Report.

    SciTech Connect

    Pearsons, Todd N.; Johnson, Christopher L.

    2003-04-01

    The benefits that marine derived nutrients from adult salmon carcasses provide to juvenile salmonids are increasingly being recognized. Current estimates suggest that only 6-7% of marine-derived nitrogen and phosphorus that were historically available to salmonids in the Pacific Northwest are currently available. Food limitation may be a major constraint limiting the restoration of salmonids. A variety of methods have been proposed to offset this nutrient deficit including: allowing greater salmon spawning escapement, stocking hatchery salmon carcasses, and stocking inorganic nutrients. Unfortunately, each of these methods has some ecological or socio-economic shortcoming. We intend to overcome many of these shortcomings by making and evaluating a pathogen free product that simulates a salmon carcass (analog). Abundant sources of marine derived nutrients are available such as fish offal from commercial fishing and salmon carcasses from hatcheries. However, a method for recycling these nutrients into a pathogen free analog that degrades at a similar rate as a natural salmon carcass has never been developed. We endeavored to (1) develop a salmon carcass analog that will increase the food available to salmonids, (2) determine the pathways that salmonids use to acquire food from analogs, and (3) determine the benefits to salmonids and the potential for application to salmonid restoration. We used a before-after-control-impact-paired design in six tributaries of the upper Yakima basin to determine the utility of stocking carcass analogs. Our preliminary results suggest that the introduction of carcass analogs into food-limited streams can be used to restore food pathways previously provided by anadromous salmon. The analogs probably reproduced both of the major food pathways that salmon carcasses produce: direct consumption and food chain enhancement. Trout and salmon fed directly on the carcass analogs during the late summer and presumably benefited from the increased

  12. Phencyclidine analog use in Sweden--intoxication cases involving 3-MeO-PCP and 4-MeO-PCP from the STRIDA project.

    PubMed

    Bäckberg, Matilda; Beck, Olof; Helander, Anders

    2015-11-01

    3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC-high-resolution MS (LC-HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure ≥ 140 mmHg; 7 cases), tachycardia (≥ 100/min; 5 cases), and altered mental

  13. Exploring the Use of Multiple Analogical Models when Teaching and Learning Chemical Equilibrium

    ERIC Educational Resources Information Center

    Harrison, Allan G.; De Jong, Onno

    2005-01-01

    This study describes the multiple analogical models used to introduce and teach Grade 12 chemical equilibrium. We examine the teacher's reasons for using models, explain each model's development during the lessons, and analyze the understandings students derived from the models. A case study approach was used and the data were drawn from the…

  14. Educational Implications of Analogy: A View from Case-Based Reasoning.

    ERIC Educational Resources Information Center

    Kolodner, Janet L.

    1997-01-01

    Case-based reasoning (CBR) focuses on analogy in the context of solving real-world problems. Its research methodology of computational modeling is aimed at deriving hypotheses about cognition. As a plausible educational model, CBR can help refine education philosophy and practice and contribute to the design of educational software. (SLD)

  15. In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

    USDA-ARS?s Scientific Manuscript database

    Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

  16. Educational Implications of Analogy: A View from Case-Based Reasoning.

    ERIC Educational Resources Information Center

    Kolodner, Janet L.

    1997-01-01

    Case-based reasoning (CBR) focuses on analogy in the context of solving real-world problems. Its research methodology of computational modeling is aimed at deriving hypotheses about cognition. As a plausible educational model, CBR can help refine education philosophy and practice and contribute to the design of educational software. (SLD)

  17. Exploring the Use of Multiple Analogical Models when Teaching and Learning Chemical Equilibrium

    ERIC Educational Resources Information Center

    Harrison, Allan G.; De Jong, Onno

    2005-01-01

    This study describes the multiple analogical models used to introduce and teach Grade 12 chemical equilibrium. We examine the teacher's reasons for using models, explain each model's development during the lessons, and analyze the understandings students derived from the models. A case study approach was used and the data were drawn from the…

  18. Synthesis, biological evaluation, and live cell imaging of novel fluorescent duocarmycin analogs.

    PubMed

    Tietze, Lutz F; Behrendt, Frank; Pestel, Galina F; Schuberth, Ingrid; Mitkovski, Mišo

    2012-11-01

    For a better understanding of the mode of action of duocarmycin and its analogs, the novel fluorescent duocarmycin derivatives 13-15 and 17b-19b were synthesized, and their bioactivity as well as their cellular uptake investigated using confocal laser scanning microscopy (CLSM) in live-cell imaging experiments. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  19. Synthesis of cardiac glycoside analogs by catalyst-controlled, regioselective glycosylation of digitoxin.

    PubMed

    Beale, Thomas M; Taylor, Mark S

    2013-03-15

    The cardiac glycoside natural product digitoxin was selectively glycosylated at one of its five hydroxyl groups using a borinic acid derived catalyst. This method provided access to the glycosylation pattern characteristic of a subclass of natural products from Digitalis purpurea. Variation of the glycosyl donor was tolerated, enabling the synthesis of novel cardiac glycoside analogs from readily available materials.

  20. An Effective Model to Increase Student Attitude and Achievement: Narrative Including Analogies

    ERIC Educational Resources Information Center

    Akkuzu, Nalan; Akcay, Husamettin

    2011-01-01

    This study describes the analogical models and narratives used to introduce and teach Grade 9 chemical covalent compounds which are relatively abstract and difficult for students. We explained each model's development during the lessons and analyzed understanding students derived from these learning materials. In this context, achievement,…

  1. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    DTIC Science & Technology

    2014-09-01

    Scheinberg DA. Vaccination with Synthetic Analog Peptides Derived from WT1 Oncoprotein Induces T Cell Responses in Patients with Complete Remission ...TITLE:Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of...TITLE:Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality

  2. Spectroscopy of jet-cooled tyrosine derivatives

    NASA Astrophysics Data System (ADS)

    Teh, Chin Khuan; Sulkes, Mark

    1991-05-01

    Using fluorescence-based techniques (excitation and emission spectra lifetimes), we have studied the jet-cooled tyrosine derivatives tyramine and 3-(4-hydroxyphenyl) propionic acid (HPA). For solvent addition resulting in small, mainly one adduct complexes, there is a high degree of analogy with the results for the corresponding analogs of the amino acid tryptophan. In particular, for tyramine, as had been the case with its tryptophan analog tryptamine, addition of one -OH bearing solvent molecule at the α-amine apparently results in a complex in a single conformation.

  3. A Low-Cost BIST Based on Histogram Testing for Analog to Digital Converters

    NASA Astrophysics Data System (ADS)

    Kim, Kicheol; Kim, Youbean; Kim, Incheol; Son, Hyeonuk; Kang, Sungho

    In this letter a histogram-based BIST (Built-In Self-Test) approach for deriving the main characteristic parameters of an ADC (Analog to Digital Converter) such as offset, gain and non-linearities is proposed. The BIST uses a ramp signal as an input signal and two counters as a response analyzer to calculate the derived static parameters. Experimental results show that the proposed method reduces the hardware overhead and testing time while detecting any static faults in an ADC.

  4. NaturAnalogs for the Unsaturated Zone

    SciTech Connect

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  5. Analog forecasting with dynamics-adapted kernels

    NASA Astrophysics Data System (ADS)

    Zhao, Zhizhen; Giannakis, Dimitrios

    2016-09-01

    Analog forecasting is a nonparametric technique introduced by Lorenz in 1969 which predicts the evolution of states of a dynamical system (or observables defined on the states) by following the evolution of the sample in a historical record of observations which most closely resembles the current initial data. Here, we introduce a suite of forecasting methods which improve traditional analog forecasting by combining ideas from kernel methods developed in harmonic analysis and machine learning and state-space reconstruction for dynamical systems. A key ingredient of our approach is to replace single-analog forecasting with weighted ensembles of analogs constructed using local similarity kernels. The kernels used here employ a number of dynamics-dependent features designed to improve forecast skill, including Takens’ delay-coordinate maps (to recover information in the initial data lost through partial observations) and a directional dependence on the dynamical vector field generating the data. Mathematically, our approach is closely related to kernel methods for out-of-sample extension of functions, and we discuss alternative strategies based on the Nyström method and the multiscale Laplacian pyramids technique. We illustrate these techniques in applications to forecasting in a low-order deterministic model for atmospheric dynamics with chaotic metastability, and interannual-scale forecasting in the North Pacific sector of a comprehensive climate model. We find that forecasts based on kernel-weighted ensembles have significantly higher skill than the conventional approach following a single analog.

  6. Neurotoxic Alkaloids: Saxitoxin and Its Analogs

    PubMed Central

    Wiese, Maria; D’Agostino, Paul M.; Mihali, Troco K.; Moffitt, Michelle C.; Neilan, Brett A.

    2010-01-01

    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. PMID:20714432

  7. Analogy, higher order thinking, and education.

    PubMed

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  8. Airframe Noise Prediction by Acoustic Analogy: Revisited

    NASA Technical Reports Server (NTRS)

    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

  9. Rules vs. analogy in English past tenses: a computational/experimental study.

    PubMed

    Albright, Adam; Hayes, Bruce

    2003-12-01

    Are morphological patterns learned in the form of rules? Some models deny this, attributing all morphology to analogical mechanisms. The dual mechanism model (Pinker, S., & Prince, A. (1998). On language and connectionism: analysis of a parallel distributed processing model of language acquisition. Cognition, 28, 73-193) posits that speakers do internalize rules, but that these rules are few and cover only regular processes; the remaining patterns are attributed to analogy. This article advocates a third approach, which uses multiple stochastic rules and no analogy. We propose a model that employs inductive learning to discover multiple rules, and assigns them confidence scores based on their performance in the lexicon. Our model is supported over the two alternatives by new "wug test" data on English past tenses, which show that participant ratings of novel pasts depend on the phonological shape of the stem, both for irregulars and, surprisingly, also for regulars. The latter observation cannot be explained under the dual mechanism approach, which derives all regulars with a single rule. To evaluate the alternative hypothesis that all morphology is analogical, we implemented a purely analogical model, which evaluates novel pasts based solely on their similarity to existing verbs. Tested against experimental data, this analogical model also failed in key respects: it could not locate patterns that require abstract structural characterizations, and it favored implausible responses based on single, highly similar exemplars. We conclude that speakers extend morphological patterns based on abstract structural properties, of a kind appropriately described with rules.

  10. Glycopeptide antibiotic analogs efficient against vancomycin-resistant bacteria: a patent evaluation (WO2013022763).

    PubMed

    Olsufyeva, Eugenia N; Preobrazhenskaya, Maria N

    2013-12-01

    The patent claims the preparation of vancomycin analogs equally active against bacterial strains that are primarily sensitive or resistant to this antibiotic. The pseudopeptide core of new compounds carries the amidine group that replaces the carboxamide linking group in the D ring-bearing amino acid residue of the glycopeptide. An elegant method of synthesis of amidine containing glycopeptides via thioamides was developed. The key glycopeptide thioamide analogs were prepared by total multistep synthesis. These analogs can be readily converted to the antibiotic's amidine as well as to alkylamidines, amidrazones, hydroxyamidines and similar analogs. The new analogs are capable of circumventing bacterial resistance derived from the D-Ala-D-Ala to D-Ala-D-Lac alteration - the mechanism operational in the resistant strains VanA and VanB. The interaction of the carboxamide, thioamide and amidine fragments of vancomycin analogs with the targets in resistant and sensitive bacteria was investigated. The novel compounds demonstrated potent activity against VanA-resistant bacteria Enterococcus faecalis (minimal inhibitory concentration = 0.3 - 0.6 μg/ml). However data on susceptible strains and resistant clinical isolates are lacking to further document the interest of the compounds. The results provide evidence for structural modifications that can improve the therapeutic efficacy of vancomycin, in particular, for treatment of vancomycin-resistant infections.

  11. Structural characterization of native high-methoxylated pectin using nuclear magnetic resonance spectroscopy and ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Comparative use of 2,5-dihydroxybenzoic acid and nor-harmane as UV-MALDI matrices.

    PubMed

    Monge, María Eugenia; Negri, R Martín; Kolender, Adriana A; Erra-Balsells, Rosa

    2007-01-01

    The successful analysis by ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (UV-MALDI-TOF MS) of native and hydrolyzed high-methoxylated pectin samples is described. In order to find the optimal conditions for UV-MALDI-TOF MS analysis several experimental variables were studied such as: different UV-MALDI matrices (nor-harmane, 2,5-dihydroxybenzoic acid), sample preparation methods (mixture, sandwich), inorganic salt addition (doping salts, NaCl, KCl, NH(4)Cl), ion mode (positive, negative), linear and reflectron mode, etc. nor-Harmane has never been used as a UV-MALDI matrix for the analysis of pectins but its use avoids pre-treatment of the sample, such as an enzymatic digestion or an acid hydrolysis, and there is no need to add salts, making the analysis easier and faster. This study suggested an alternative way of analyzing native high-methoxylated pectins, with UV-MALDI-TOF MS, by using nor-harmane as the matrix in negative ion mode. The analysis by (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy of the native and hydrolyzed pectin is also briefly described.

  12. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

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

    ERIC Educational Resources Information Center

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

  14. The Effect of Analogy-Based Teaching on Students' Achievement and Students' Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students' achievement and students' views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The achievement…

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

    ERIC Educational Resources Information Center

    Schmidt, Gwenda L.; Cardillo, Eileen R.; Kranjec, Alexander; Lehet, Matthew; Widick, Page; Chatterjee, Anjan

    2012-01-01

    Current research on analogy processing assumes that different conceptual relations are treated similarly. However, just as words and concepts are related in distinct ways, different kinds of analogies may employ distinct types of relationships. An important distinction in how words are related is the difference between associative (dog-bone) and…

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

    ERIC Educational Resources Information Center

    Remigio, Krisette B.; Yangco, Rosanelia T.; Espinosa, Allen A.

    2014-01-01

    The study examined the reasoning skills of first year high school students after learning general science concepts through analogies. Two intact heterogeneous sections were randomly assigned to Analogy-Enhanced Instruction (AEI) group and Non Analogy-Enhanced (NAEI) group. Various analogies were incorporated in the lessons of the AEI group for…

  17. The Importance of Explicitly Mapping Instructional Analogies in Science Education

    ERIC Educational Resources Information Center

    Asay, Loretta Johnson

    2013-01-01

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With…

  18. Value and Limitations of Analogs in Teaching Mathematics.

    ERIC Educational Resources Information Center

    Halford, Graeme S.; Boulton-Lewis, Gillian M.

    Analogical reasoning is frequently used in acquisition of mathematical concepts. Concrete representations used to teach mathematics are essentially analogs of mathematical concepts, and it is argued that analogies enter into mathematical concept acquisition in numerous other ways as well. According to Gentner's theory, analogies entail a…

  19. The Importance of Explicitly Mapping Instructional Analogies in Science Education

    ERIC Educational Resources Information Center

    Asay, Loretta Johnson

    2013-01-01

    Analogies are ubiquitous during instruction in science classrooms, yet research about the effectiveness of using analogies has produced mixed results. An aspect seldom studied is a model of instruction when using analogies. The few existing models for instruction with analogies have not often been examined quantitatively. The Teaching With…

  20. Changes in analogical reasoning in adulthood.

    PubMed

    Clark, E; Gardner, M K; Brown, G; Howell, R J

    1990-01-01

    This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).