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Sample records for cyclic-imide peptidomimetics derivative

  1. Distinct molecular structures and hydrogen bond patterns of α,α-diethyl-substituted cyclic imide, lactam, and acetamide derivatives in the crystalline phase

    Science.gov (United States)

    Krivoshein, Arcadius V.; Ordonez, Carlos; Khrustalev, Victor N.; Timofeeva, Tatiana V.

    2016-10-01

    α,α-Dialkyl- and α-alkyl-α-aryl-substituted cyclic imides, lactams, and acetamides show promising anticonvulsant, anxiolytic, and anesthetic activities. While a number of crystal structures of various α-substituted cyclic imides, lactams, and acetamides were reported, no in-depth comparison of crystal structures and solid-state properties of structurally matched compounds have been carried out so far. In this paper, we report molecular structure and intermolecular interactions of three α,α-diethyl-substituted compounds - 3,3-diethylpyrrolidine-2,5-dione, 3,3-diethylpyrrolidin-2-one, and 2,2-diethylacetamide - in the crystalline phase, as studied using single-crystal X-ray diffraction and IR spectroscopy. We found considerable differences in the patterns of H-bonding and packing of the molecules in crystals. These differences correlate with the compounds' melting points and are of significance to physical pharmacy and formulation development of neuroactive drugs.

  2. Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: antinociceptive activity, molecular modeling and in silico ADMET screening.

    Science.gov (United States)

    de Oliveira, Kely N; Souza, Márcia M; Sathler, Plínio Cunha; Magalhães, Uiaran O; Rodrigues, Carlos R; Castro, Helena C; Palm, Patrícia R; Sarda, Maicon; Perotto, Pablo E; Cezar, Sabrina; de Brito, Monique A; Ferreira, Ariane S S R; Cabral, Lúcio Mendes; Machado, Clodoaldo; Nunes, Ricardo J

    2012-10-01

    In this paper, we describe the antinociceptive activity, molecular modeling and in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and 11 showed the most potent analgesic activity (ID(50) = 5.1 and 6.8 μmol/kg, respectively). Interestingly, all derivatives evaluated in this study have a better analgesic profile than the control drugs, acetyl salicylic acid and acetaminophen. Derivative 9 was the most promising compound; with a level of activity that was 24 times higher than the control drugs. Our SAR study showed a relationship among the distribution of the frontier orbital HOMO coefficients, HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski "rule-of-five", which is theoretically important for good drug absorption and permeation.

  3. Hydrogen bonding in cyclic imides and amide carboxylic acid derivatives from the facile reaction of cis-cyclohexane-1,2-carboxylic anhydride with o- and p-anisidine and m- and p-aminobenzoic acids.

    Science.gov (United States)

    Smith, Graham; Wermuth, Urs D

    2012-09-01

    The structures of the open-chain amide carboxylic acid rac-cis-2-[(2-methoxyphenyl)carbamoyl]cyclohexane-1-carboxylic acid, C(15)H(19)NO(4), (I), and the cyclic imides rac-cis-2-(4-methoxyphenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione, C(15)H(17)NO(3), (II), chiral cis-3-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)benzoic acid, C(15)H(15)NO(4), (III), and rac-cis-4-(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)benzoic acid monohydrate, C(15)H(15)NO(4)·H(2)O, (IV), are reported. In the amide acid (I), the phenylcarbamoyl group is essentially planar [maximum deviation from the least-squares plane = 0.060 (1) Å for the amide O atom] and the molecules form discrete centrosymmetric dimers through intermolecular cyclic carboxy-carboxy O-H···O hydrogen-bonding interactions [graph-set notation R(2)(2)(8)]. The cyclic imides (II)-(IV) are conformationally similar, with comparable benzene ring rotations about the imide N-C(ar) bond [dihedral angles between the benzene and isoindole rings = 51.55 (7)° in (II), 59.22 (12)° in (III) and 51.99 (14)° in (IV)]. Unlike (II), in which only weak intermolecular C-H···O(imide) hydrogen bonding is present, the crystal packing of imides (III) and (IV) shows strong intermolecular carboxylic acid O-H···O hydrogen-bonding associations. With (III), these involve imide O-atom acceptors, giving one-dimensional zigzag chains [graph-set C(9)], while with the monohydrate (IV), the hydrogen bond involves the partially disordered water molecule which also bridges molecules through both imide and carboxy O-atom acceptors in a cyclic R(4)(4)(12) association, giving a two-dimensional sheet structure. The structures reported here expand the structural database for compounds of this series formed from the facile reaction of cis-cyclohexane-1,2-dicarboxylic anhydride with substituted anilines, in which there is a much larger incidence of cyclic imides compared to amide carboxylic acids.

  4. Synthesis of new N-substituted cyclic imides with an expected anxiolytic activity. XVII. Derivatives of 1-ethoxybicyclo[2.2.2]-oct-5-one-2,3-dicarboximide.

    Science.gov (United States)

    Kossakowski, J; Jarocka, M

    2001-10-01

    The preparation of a number of derivatives of 1-ethoxybicyclo[2.2.2]-oct-5-one-2,3-dicarboximide with potential anxiolytic activity has been described. The aim of our study was to obtain new analogs of tandospirone.

  5. Synthesis of new N-substituted cyclic imides with an expected anxiolytic activity. XXII. Derivatives of 1-methoxy-5-bicyclo[2.2.2]-oct-5-one-2,3-dicarboximide.

    Science.gov (United States)

    Kossakowski, Jerzy; Jarocka-Wierzba, Monika

    2003-01-01

    Continuing our studies with the design of new anxiolytics we have now synthesized a series of new compounds, derivatives of 1-methoxybicyclo[2.2.2]-oct-5-one-2,3-dicarboximide bearing a 4-aryl-1-piperazinylbutyl group attached to the imide nitrogen.

  6. Synthesis of cyclic imides from nitriles and diols using hydrogen transfer as a substrate-activating strategy.

    Science.gov (United States)

    Kim, Jaewoon; Hong, Soon Hyeok

    2014-09-05

    An atom-economical and versatile method for the synthesis of cyclic imides from nitriles and diols was developed. The method utilizes a Ru-catalyzed transfer-hydrogenation reaction in which the substrates, diols, and nitriles are simultaneously activated into lactones and amines in a redox-neutral manner to afford the corresponding cyclic imides with evolution of H2 gas as the sole byproduct. This operationally simple and catalytic synthetic method provides a sustainable and easily accessible route to cyclic imides.

  7. Rodent repellents: Preparation and properties of thiouronium compounds and cyclic imides

    Science.gov (United States)

    Bellack, E.; DeWitt, J.B.

    1954-01-01

    Syntheses and bioassays of cyclic imides and thiouronium compounds were carried out as part of a search for materials capable of preventing rodent damage to packaged commodities. Previous studies had shown that repellent activity was associated with functional groups containing nitrogen and sulfur, and was enhanced by the presence of ionic linkages. Twenty-seven thiouronium compounds and 40 imides, including 1 0 compounds not described previously, were prepared for these tests. Ten imides and 26 thiouronium compounds were repellent under the conditions of test. Information obtained in these studies will be utilized in the development and selection of more effective materials for prevention of rodent damage to foods and other commodities.

  8. Versatile and sustainable synthesis of cyclic imides from dicarboxylic acids and amines by Nb2O5 as a base-tolerant heterogeneous Lewis acid catalyst.

    Science.gov (United States)

    Ali, Md Ayub; Siddiki, S M A Hakim; Kon, Kenichi; Hasegawa, Junya; Shimizu, Ken-Ichi

    2014-10-27

    Catalytic condensation of dicarboxylics acid and amines without excess amount of activating reagents is the most atom-efficient but unprecedented synthetic method of cyclic imides. Here we present the first general catalytic method, proceeding selectively and efficiently in the presence of a commercial Nb2 O5 as a reusable and base-tolerant heterogeneous Lewis acid catalyst. The method is effective for the direct synthesis of pharmaceutically or industrially important cyclic imides, such as phensuximide, N-hydroxyphthalimide (NHPI), and unsubstituted cyclic imides from dicarboxylic acid or anhydrides with amines, hydroxylamine, or ammonia. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Spectroscopic Identification of Cyclic Imide b2-Ions from Peptides Containing Gln and Asn Residues

    Science.gov (United States)

    Grzetic, Josipa; Oomens, Jos

    2013-08-01

    In mass-spectrometry based peptide sequencing, formation of b- and y-type fragments by cleavage of the amide C-N bond constitutes the main dissociation pathway of protonated peptides under low-energy collision induced dissociation (CID). The structure of the b 2 fragment ion from peptides containing glutamine (Gln) and asparagine (Asn) residues is investigated here by infrared ion spectroscopy using the free electron laser FELIX. The spectra are compared with theoretical spectra calculated using density functional theory for different possible isomeric structures as well as to experimental spectra of synthesized model systems. The spectra unambiguously show that the b2-ions do not possess the common oxazolone structure, nor do they possess the alternative diketopiperazine structure. Instead, cyclic imide structures are formed through nucleophilic attack by the amide nitrogen atom of the Gln and Asn side chains. The alternative pathway involving nucleophilic attack from the side-chain amide oxygen atom leading to cyclic isoimide structures, which had been suggested by several authors, can clearly be excluded based on the present IR spectra. This mechanism is perhaps surprising as the amide oxygen atom is considered to be the better nucleophile; however, computations show that the products formed via attack by the amide nitrogen are considerably lower in energy. Hence, b2-ions with Asn or Gln in the second position form structures with a five-membered succinimide or a six-membered glutarimide ring, respectively. b2-Ions formed from peptides with Asn in the first position are spectroscopically shown to possess the classical oxazolone structure.

  10. A combinatorial approach for the design of complementarity-determining region-derived peptidomimetics with in vitro anti-tumoral activity.

    Science.gov (United States)

    Timmerman, Peter; Barderas, Rodrigo; Desmet, Johan; Altschuh, Danièle; Shochat, Susana; Hollestelle, Martine J; Höppener, Jo W M; Monasterio, Alberto; Casal, J Ignacio; Meloen, Rob H

    2009-12-04

    The great success of therapeutic monoclonal antibodies has fueled research toward mimicry of their binding sites and the development of new strategies for peptide-based mimetics production. Here, we describe a new combinatorial approach for the production of peptidomimetics using the complementarity-determining regions (CDRs) from gastrin17 (pyroEGPWLEEEEEAYGWMDF-NH(2)) antibodies as starting material for cyclic peptide synthesis in a microarray format. Gastrin17 is a trophic factor in gastrointestinal tumors, including pancreatic cancer, which makes it an interesting target for development of therapeutic antibodies. Screening of microarrays containing bicyclic peptidomimetics identified a high number of gastrin binders. A strong correlation was observed between gastrin binding and overall charge of the peptidomimetic. Most of the best gastrin binders proceeded from CDRs containing charged residues. In contrast, CDRs from high affinity antibodies containing mostly neutral residues failed to yield good binders. Our experiments revealed essential differences in the mode of antigen binding between CDR-derived peptidomimetics (K(d) values in micromolar range) and the parental monoclonal antibodies (K(d) values in nanomolar range). However, chemically derived peptidomimetics from gastrin binders were very effective in gastrin neutralization studies using cell-based assays, yielding a neutralizing activity in pancreatic tumoral cell lines comparable with that of gastrin-specific monoclonal antibodies. These data support the use of combinatorial CDR-peptide microarrays as a tool for the development of a new generation of chemically synthesized cyclic peptidomimetics with functional activity.

  11. Pyrazole derived ultra-short antimicrobial peptidomimetics with potent anti-biofilm activity.

    Science.gov (United States)

    Ahn, Mija; Gunasekaran, Pethaiah; Rajasekaran, Ganesan; Kim, Eun Young; Lee, Soo-Jae; Bang, Geul; Cho, Kun; Hyun, Jae-Kyung; Lee, Hyun-Ju; Jeon, Young Ho; Kim, Nam-Hyung; Ryu, Eun Kyoung; Shin, Song Yub; Bang, Jeong Kyu

    2017-01-05

    In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin. Besides its higher selectivity (therapeutic index) toward bacterial cells than LL-37, Py11 showed highly increased proteolytic stability against trypsin digestion and maintained its antimicrobial activity in the presence of physiological salts. Interestingly, Py11 exhibited higher anti-biofilm activity against MDRPA compared to LL-37. The results from fluorescence spectroscopy and transmission electron microscopy (TEM) suggested that Py11 kills bacterial cells possibly by integrity disruption damaging the cell membrane, leading to the cytosol leakage and eventual cell lysis. Furthermore, Py11 displayed significant anti-inflammatory (endotoxin-neutralizing) activity by inhibiting LPS-induced production of nitric oxide (NO) and TNF-α. Collectively, our results suggest that Py11 may serve as a model compound for the design of antimicrobial and antisepsis agents.

  12. New glyme-cyclic imide lithium salt complexes as thermally stable electrolytes for lithium batteries

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Takashi; Hachida, Takeshi; Yoshida, Kazuki; Tachikawa, Naoki; Dokko, Kaoru; Watanabe, Masayoshi [Department of Chemistry and Biotechnology, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501 (Japan)

    2010-09-15

    New glyme-Li salt complexes were prepared by mixing equimolar amounts of a novel cyclic imide lithium salt LiN(C{sub 2}F{sub 4}S{sub 2}O{sub 4}) (LiCTFSI) and a glyme (triglyme (G3) or tetraglyme (G4)). The glyme-Li salt complexes, [Li(G3)][CTFSI] and [Li(G4)][CTFSI], are solid and liquid, respectively, at room temperature. The thermal stability of [Li(G4)][CTFSI] is much higher than that of pure G4, and the vapor pressure of [Li(G4)][CTFSI] is negligible at temperatures lower than 100 C. Although the viscosity of [Li(G4)][CTFSI] is high (132.0 mPa s at 30 C), because of its high molar concentration (ca. 3 mol dm{sup -3}), its ionic conductivity at 30 C is relatively high, i.e., 0.8 mS cm{sup -1}, which is slightly lower than that of a conventional organic electrolyte solution (1 mol dm{sup -3} LiTFSI dissolved in propylene carbonate). The self-diffusion coefficients of a Li{sup +} cation, a CTFSI{sup -} anion, and a glyme molecule were measured by the pulsed gradient spin-echo NMR method (PGSE-NMR). The ionicity (dissociativity) of [Li(G4)][CTFSI] at 30 C is ca. 0.5, as estimated from the PGSE-NMR diffusivity measurements and the ionic conductivity measurements. Results of linear sweep voltammetry revealed that [Li(G4)][CTFSI] is electrochemically stable in an electrode potential range of 0-4.5 V vs. Li/Li{sup +}. The reversible deposition-stripping behavior of lithium was observed by cyclic voltammetry. The [LiCoO{sub 2} vertical stroke [Li(G4)][CTFSI] vertical stroke Li metal] cell showed a stable charge-discharge cycling behavior during 50 cycles, indicating that the [Li(G4)][CTFSI] complex is applicable to a 4 V class lithium secondary battery. (author)

  13. Avaliação da sensibilidade de cepas de Malassezia furfur a imidas cíclicas Sensibility of evaluations of Malassezia furfur strains at cyclic imides

    Directory of Open Access Journals (Sweden)

    Edeltrudes de Oliveira Lima

    2002-12-01

    Full Text Available Malassezia furfur (Pityrosporum orbiculare é um fungo lipofílico, que está associado a pitiríase versicolor, foliculite, dermatite seborréica e atópica, fungemia e infecções sistêmicas. O tratamento é feito com soluções antimicóticas ou derivados imidazólicos, particularmente, o cetoconazol. Dentro das perspectivas de avaliação de novas alternativas para a terapêutica das infecções micóticas, determinou-se, nesse estudo, a atividade antifúngica de compostos imídicos. As imidas 3,4-dicloro-N-fenil-maleimida (6,3 µg/ml, 3,4-dicloro-N-benzil-maleimida (25 µg/ml e 3,4dicloro-N-fenil-propil-maleimida (20 µg/ml foram os compostos que apresentaram melhor atividade inibitória contra as cepas de M. furfur.Malassezia furfur (Pityrosporum orbiculare is a lipophilic microrganism and it has also been associated with pityriasis versicolor, folliculitis, seborrheic and atopic dermatitis, fungemia and systemic infections. The treatment comprehends antimicotics or imidazol derivatives solutions, specially cetoconazol. With purpose of evaluating new alternatives to the therapeutics of mycosis infections, the antifungical activity of cyclic imides was determinated in the present study. The imides 3,4-cichloro-N-phenylmaleimide (6,3 µg/ml, 3,4dichloro-N-benzyl-maleimide (25 µg/mL and 3,4dichloro-N-phenyl-propyl-maleimide (25 µg/mL were the compounds which produced the best activities of inhibition against strains of M. furfur.

  14. Synthesis and anxiolytic activity of N-substituted cyclic imides N-[4-[(4-aryl)-1-piperazinyl]alkyl]-5,7-dioxabicyclo[2.2.2]octane-2, 3-dicarboximide.

    Science.gov (United States)

    Zawadowski, T; Kossakowski, J; Rump, S; Jakowicz, I; Płaźnik, A

    1995-01-01

    The preparation of N-substituted cyclic imides N-[4-[(4-aryl)-1-piperazinyl]alkyl]-5,7-dioxabicyclo[2.2.2]octane- 2, 3-dicarboximides by condensation of N-(3-chloropropyl)- or N-(4-chlorobutyl)imides with appropriate amine has been described. One of compounds was tested in the Vogel's test and displayed an expected activity on CNS.

  15. Cyclopropane-derived peptidomimetics. Design, synthesis, and evaluation of novel enkephalin analogues.

    Science.gov (United States)

    Martin, S F; Dwyer, M P; Hartmann, B; Knight, K S

    2000-03-10

    It is known that peptide mimics containing trans-substituted cyclopropanes stabilize extended conformations of oligopeptides, and molecular modeling studies now suggest that the corresponding cis-cyclopropane dipeptide isosteres could stabilize a reverse turn. To begin to assess this possibility, a series of cis-substituted cyclopropanes were incorporated as replacements of the Gly(2)-Gly(3) and Phe(4)-Leu(5) dipeptide subunits in Leu-enkephalin (H(2)N-Tyr-Gly-Gly-Phe-Leu-OH), which is believed to bind to opiod receptors in a conformation containing a beta-turn. General methods for the synthesis of the cyclopropane-containing dipeptide isosteres -XaaPsi[COcpCO]Yaa- and -XaaPsi[NHcpNH]Yaa-were developed by a sequence that featured the enantioselective cyclization of allylic diazoacetates catalyzed by the chiral rhodium complexes Rh(2)[(5S)-MEPY](4) and Rh(2)[(5R)-MEPY](4). A useful modification of the Weinreb amidation procedure was applied to the opening of the intermediate lactones with dipeptides, and a novel method for the synthesis of substituted diaminocyclopropanes was also developed. The Leu-enkephalin analogues were tested in a panel of binding and functional assays, and although those derivatives containing cyclopropane replacements of the Gly(2)-Gly(3) exhibited low micromolar affinity for the mu-receptor, analogues containing such replacements for the Phe(4)-Leu(5) subunit did not bind with significant affinity to any of the opioid receptors. These results are discussed.

  16. A combinatorial approach for the design of complementarity-determining region-derived peptidomimetics with in vitro anti-tumoral activity

    NARCIS (Netherlands)

    Timmerman, P.; Barderas, R.; Desmet, J.; Altschuh, D.; Shochat, S.; Hollestelle, M.J.; Höppener, J.W.M.; Monasterio, A.; Casal, J.I.; Meloen, R.H.

    2009-01-01

    The great success of therapeutic monoclonal antibodies has fueled research toward mimicry of their binding sites and the development of new strategies for peptide-based mimetics production. Here, we describe a new combinatorial approach for the production of peptidomimetics using the

  17. Discovery of novel histidine-derived lipo-amino acids: applied in the synthesis of ultra-short antimicrobial peptidomimetics having potent antimicrobial activity, salt resistance and protease stability.

    Science.gov (United States)

    Ahn, Mija; Murugan, Ravichandran N; Jacob, Binu; Hyun, Jae-Kyung; Cheong, Chaejoon; Hwang, Eunha; Park, Hyo-Nam; Seo, Ji-Hyung; Srinivasrao, G; Lee, Kyung S; Shin, Song Yub; Bang, Jeong Kyu

    2013-10-01

    Here we report for the first time the synthesis of Histidine (His) derived lipo-amino acids having pendant lipid tails at N(τ)- and N(π)-positions on imidazole group of His and applied it into synthesis of lipo-peptides. The attachment of His-derived lipo-amino acid into the very short inactive cationic peptides endows potent antimicrobial activity against Gram-positive and Gram-negative bacteria without hemolytic activity. Furthermore, our designed His-derived lipo-peptidomimetics (HDLPs) consisting of two or three residues displayed strong anti-MRSA activity and protease stability as well as retained potent antimicrobial activity under high salt concentration. Our results demonstrate that the novel lipo-amino acid is highly flexible to synthesize and carry out the extensive structure-activity relationship (SAR) on lipo-antimicrobial peptidomimetics and represents a unique amenable platform for modifying parameters important for antimicrobial activity. Through this study, we proved that the discovery of His-derived lipo-amino acid and the corresponding HDLPs are an excellent candidate as a lead compound for the development of novel antimicrobial agents. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. A Combinatorial Approach for the Design of Complementarity-determining Region-derived Peptidomimetics with in Vitro Anti-tumoral Activity*

    OpenAIRE

    Timmerman, Peter; Barderas, Rodrigo; Desmet, Johan; Altschuh, Danièle; Shochat, Susana; Hollestelle, Martine J.; Höppener, Jo W. M.; Monasterio, Alberto; Casal, J. Ignacio; Meloen, Rob H.

    2009-01-01

    The great success of therapeutic monoclonal antibodies has fueled research toward mimicry of their binding sites and the development of new strategies for peptide-based mimetics production. Here, we describe a new combinatorial approach for the production of peptidomimetics using the complementarity-determining regions (CDRs) from gastrin17 (pyroEGPWLEEEEEAYGWMDF-NH2) antibodies as starting material for cyclic peptide synthesis in a microarray format. Gastrin17 is a trophic factor in gastroin...

  19. Synthesis of new derivatives of 1,2,3,4,7-pentamethylbicyclo[2.2.1]hept-2-ene-5,6-dicarboximide with an expected anxiolytic activity.

    Science.gov (United States)

    Kossakowski, J; Kuśmierczyk, J

    2000-01-01

    The preparation of a number of derivatives of 1,2,3,4,7-pentamethylbicyclo[2.2.1]hept-2-ene-5,6-dicarboximide with potential anxiolytic activity has been described. The aim of our study was to obtain new analogues of tandospirone, that is derivatives of cyclic imides [1].

  20. Synthesis of conformationally constrained aryl- or heteroarylpiperazinyl derivatives of selected imides as 5-HT1A receptor ligands.

    Science.gov (United States)

    Kossakowski, Jerzy; Krawiecka, Mariola; Kuran, Bozena

    2006-08-23

    The preparation of a number of cyclic imide 5-HT(1A) receptor ligand derivatives has been described. Their structures were conformationally constrained by introducing rigid linkers containing unsaturated bonds or aromatic benzene rings. These compounds are expected to possess anxiolytic and antidepressant activity.

  1. A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds.

    Science.gov (United States)

    Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R

    2015-04-21

    Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

  2. Structure Based Antibody-Like Peptidomimetics

    Directory of Open Access Journals (Sweden)

    Mark I. Greene

    2012-02-01

    Full Text Available Biologics such as monoclonal antibodies (mAb and soluble receptors represent new classes of therapeutic agents for treatment of several diseases. High affinity and high specificity biologics can be utilized for variety of clinical purposes. Monoclonal antibodies have been used as diagnostic agents when coupled with radionuclide, immune modulatory agents or in the treatment of cancers. Among other limitations of using large molecules for therapy the actual cost of biologics has become an issue. There is an effort among chemists and biologists to reduce the size of biologics which includes monoclonal antibodies and receptors without a reduction of biological efficacy. Single chain antibody, camel antibodies, Fv fragments are examples of this type of deconstructive process. Small high-affinity peptides have been identified using phage screening. Our laboratory used a structure-based approach to develop small-size peptidomimetics from the three-dimensional structure of proteins with immunoglobulin folds as exemplified by CD4 and antibodies. Peptides derived either from the receptor or their cognate ligand mimics the functions of the parental macromolecule. These constrained peptides not only provide a platform for developing small molecule drugs, but also provide insight into the atomic features of protein-protein interactions. A general overview of the reduction of monoclonal antibodies to small exocyclic peptide and its prospects as a useful diagnostic and as a drug in the treatment of cancer are discussed.

  3. Peptidomimetics as protein arginine deiminase 4 (PAD4) inhibitors.

    Science.gov (United States)

    Trabocchi, Andrea; Pala, Nicolino; Krimmelbein, Ilga; Menchi, Gloria; Guarna, Antonio; Sechi, Mario; Dreker, Tobias; Scozzafava, Andrea; Supuran, Claudiu T; Carta, Fabrizio

    2015-06-01

    The protein arginine deiminase 4 (PAD4) is a calcium-dependent enzyme, which catalyses the irreversible conversion of peptidyl-arginines into peptidyl-citrullines and plays an important role in several diseases such as in the rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Creutzfeldt-Jacob's disease and cancer. In this study, we report the inhibition profiles and computational docking toward the PAD4 enzyme of a series of 1,2,3-triazole peptidomimetic-based derivatives incorporating the β-phenylalanine and guanidine scaffolds. Several effective, low micromolar PAD4 inhibitors are reported in this study.

  4. Design, synthesis, and biological evaluation of (S)-valine thiazole-derived cyclic and noncyclic peptidomimetic oligomers as modulators of human P-glycoprotein (ABCB1).

    Science.gov (United States)

    Singh, Satyakam; Prasad, Nagarajan Rajendra; Kapoor, Khyati; Chufan, Eduardo E; Patel, Bhargav A; Ambudkar, Suresh V; Talele, Tanaji T

    2014-01-01

    Multidrug resistance caused by ATP binding cassette transporter P-glycoprotein (P-gp) through extrusion of anticancer drugs from the cells is a major cause of failure in cancer chemotherapy. Previously, selenazole-containing cyclic peptides were reported as P-gp inhibitors and were also used for co-crystallization with mouse P-gp, which has 87 % homology to human P-gp. It has been reported that human P-gp can simultaneously accommodate two to three moderately sized molecules at the drug binding pocket. Our in silico analysis, based on the homology model of human P-gp, spurred our efforts to investigate the optimal size of (S)-valine-derived thiazole units that can be accommodated at the drug binding pocket. Towards this goal, we synthesized varying lengths of linear and cyclic derivatives of (S)-valine-derived thiazole units to investigate the optimal size, lipophilicity, and structural form (linear or cyclic) of valine-derived thiazole peptides that can be accommodated in the P-gp binding pocket and affects its activity, previously an unexplored concept. Among these oligomers, lipophilic linear (13) and cyclic trimer (17) derivatives of QZ59S-SSS were found to be the most and equally potent inhibitors of human P-gp (IC50 =1.5 μM). As the cyclic trimer and linear trimer compounds are equipotent, future studies should focus on noncyclic counterparts of cyclic peptides maintaining linear trimer length. A binding model of the linear trimer 13 within the drug binding site on the homology model of human P-gp represents an opportunity for future optimization, specifically replacing valine and thiazole groups in the noncyclic form.

  5. Peptidomimetics and metalloprotease inhibitors as anticancer drugs

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the de-velopment of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeu-tic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.

  6. Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA.

    Directory of Open Access Journals (Sweden)

    Wilko Duprez

    Full Text Available Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB--or peptides--complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a Proteus mirabilis DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an in silico template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.

  7. Boron-containing peptidomimetics--a novel class of selective anti-tubercular drugs.

    Science.gov (United States)

    Gorovoy, Alexey S; Gozhina, Olga V; Svendsen, John S; Domorad, Anna A; Tetz, George V; Tetz, Victor V; Lejon, Tore

    2013-03-01

    Medical treatment for tuberculosis is complicated nowadays by the appearance of new multiresistant strains, and therefore, new antibiotics are in great need. Here, we report the synthesis and in vitro testing of a new class of highly selective antimicrobial boron-containing peptidomimetics with compounds exhibiting activity against Mycobacterium tuberculosis at ≤5 μg/mL. The new approach developed makes it possible to synthesize variously substituted β-aminoboronic acids and their derivatives with a high level of diastereoselectivity.

  8. Antimicrobial activity of peptidomimetics against multidrug-resistant Escherichia coli

    DEFF Research Database (Denmark)

    Jahnsen, Rasmus D; Frimodt-Møller, Niels; Franzyk, Henrik

    2012-01-01

    -lactamase-producing Escherichia coli was assessed by testing an array comprising different types of cationic peptidomimetics obtained by a general monomer-based solid-phase synthesis protocol. Most of the peptidomimetics possessed high to moderate activity toward multidrug-resistant E. coli as opposed to the corresponding...

  9. A Potent Peptidomimetic Inhibitor of Botulinum Neurotoxin Serotype A has a Very Different Conformation than SNAP-25 Substrate

    Science.gov (United States)

    2008-10-07

    paradigm for peptidomimetic in- hibitor binding in the BoNT/A LC substrate cleft and rationalizes the SAR of related derivatives. This can serve as the...moiety such as a morpholino group would be expected to reduce the entropic penalty associated with this hydrophobic residue so close to the solvent

  10. Synthesis of new N-substituted cyclic imides with an expected anxiolytic activity. XVI. Derivatives of 1-acetoxy-7,7-dimethylbicyclo[2.2.2]octan-5-one-2,3-dicarboximide.

    Science.gov (United States)

    Kossakowski, Jerzy; Hejchman, Elzbieta

    2003-01-01

    The preparation of a potential anxiety-relieving compounds N-[4-(4-aryl)-1-piperazinyl)butyl]-1-acetoxy-7,7-dimethyl-bicyclo[2.2.2]octan-5-one-2,3-dicarboximides has been described. N-[4-(4-2-methoxyphenyl)-1-piperazinyl)butyl]-1-acetoxy-7,7-dimethyl-bicyclo[2.2.2]octan-5-one-2,3-dicarboximide III showed a strong sedative effect in Writh's test.

  11. Self-assembly of small peptidomimetic cyclophanes.

    Science.gov (United States)

    Becerril, Jorge; Burguete, M Isabel; Escuder, Beatriu; Galindo, Francisco; Gavara, Raquel; Miravet, Juan F; Luis, Santiago V; Peris, Gabriel

    2004-08-20

    The self-assembly of a series of small peptidomimetic cyclophanes in organic solvents was studied. X-ray diffraction, NMR spectroscopy, and molecular modelling were used to understand the structural features of these self-assembling compounds both at the molecular and supramolecular level. The factors that could influence the formation of gels rather than crystals were studied and a model for the arrangement of molecules in the gel was proposed. Furthermore, scanning electron microscopy revealed that in some cases these compounds undergo a transcription of chirality when going from organogelator to helicoidal gel fibres.

  12. Bioinformatic Identification of Peptidomimetic-Based Inhibitors against Plasmodium falciparum Antigen AMA1

    Science.gov (United States)

    2014-01-01

    Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a valuable vaccine candidate and exported on the merozoite surface at the time of erythrocyte invasion. PfAMA1 interacts with rhoptry neck protein PfRON2, a component of the rhoptry protein complex, which forms the tight junction at the time of invasion. Phage display studies have identified a 15-residue (F1) and a 20-residue (R1) peptide that bind to PfAMA1 and block the invasion of erythrocytes. Cocrystal structures of central region of PfAMA1 containing disulfide-linked clusters (domains I and II) with R1 peptide and a peptide derived from PfRON2 showed strong structural similarity in binding. The peptides bound to a hydrophobic groove surrounded by domain I and II loops. In this study, peptidomimetics based on the crucial PfAMA1-binding residues of PfRON2 peptide have been identified. Top 5 peptidomimetics when checked for their docking on the region of PfAMA1 encompassing the hydrophobic groove were found to dock on the groove. Drug-like molecules having structural similarity to the top 5 peptidomimetics were identified based on their binding ability to PfAMA1 hydrophobic groove in blind docking. These inhibitors provide potential lead compounds, which could be used in the development of antimalarials targeting PfAMA1. PMID:25580351

  13. Spectrum and activity of novel antimicrobial peptidomimetics

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line

    Antibiotics have been an effective weapon against bacterial infections for over 50 years. However, bacterial resistance towards conventional antibiotics has increased considerably within the last decades and the number of antibacterial agents available for treating complicated bacterial infection...... design, with a 1:1 ratio between cationic a-amino acids and hydrophobic ß-peptoids, amino acid composition and chirality in the ß-peptoid unit only had a minor influence on antibacterial activity. By using an ATP leakage assay we determined that the mechanism of action of the chimeras...... Concentration (MIC). The findings show that all of the chimeras included in the study have a similar mechanism of action that was independent on bacterial species. However, the study showed that the detailed interaction with the cell membrane may be different, since there were large variations in the amount...... protocol encompassing 500 generations, 10 out of 10 lineages of Escherichia coli developed resistance towards the chimera they had been exposed to. This was the first time resistance was successfully developed towards peptidomimetics, though several studies have reported resistance towards AMPs. Resistance...

  14. Characterization of a proteolytically stable multifunctional host defense peptidomimetic

    DEFF Research Database (Denmark)

    Jahnsen, Rasmus D; Haney, Evan F; Franzyk, Henrik

    2013-01-01

    The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentra......The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory...

  15. Peptoids and peptide-peptoid hybrid biopolymers as peptidomimetics.

    Science.gov (United States)

    Stawikowski, Maciej J

    2013-01-01

    Peptoids (oligomers of N-substituted glycine residues) and peptide-peptoid hybrid polymers (peptomers) are interesting classes of compounds mimicking structure and function of biologically active peptides. The oligomeric peptidomimetics such as peptoids are particularly important compounds since they provide access to an enormous molecular diversity, by variation of the building blocks. The modular structure of peptoids, ease of synthesis, and high compatibility with existing peptide chemistry synthetic protocols, make peptoids and peptoid-containing peptidomimetics ideal tools for structure-activity and drug discovery related studies.

  16. Expedient Synthesis of N1-Substituted Triazole Peptidomimetics.

    Science.gov (United States)

    Coffey, Steven B; Aspnes, Gary; Londregan, Allyn T

    2015-12-14

    A general procedure for the rapid diversification of peptide scaffolds is described. A one-pot click reaction between a peptide-alkyne and a series of in situ generated aryl/alkyl azides affords novel N1-substituted triazole peptidomimetics. This transformation is of broad scope, operates under mild conditions, and is parallel chemical synthesis compatible.

  17. Synthesis of conformationally constrained peptidomimetics using multicomponent reactions

    NARCIS (Netherlands)

    Scheffelaar, R.; Klein Nijenhuis, R.A.; Paravidino, M.; Lutz, M.; Spek, A.L.; Ehlers, A.W.; de Kanter, F.J.J.; Groen, M.B.; Orru, R.V.A.; Ruijter, E.

    2009-01-01

    A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-in

  18. High-Affinity, Small-Molecule Peptidomimetic Inhibitors of MLL1/WDR5 Protein-Protein Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Karatas, Hacer; Townsend, Elizabeth C; Cao, Fang; Chen, Yong; Bernard, Denzil; Liu, Liu; Lei, Ming; Dou, Yali; Wang, Shaomeng [Michigan; (HHMI)

    2013-02-12

    Mixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase, and targeting the MLL1 enzymatic activity has been proposed as a novel therapeutic strategy for the treatment of acute leukemia harboring MLL1 fusion proteins. The MLL1/WDR5 protein–protein interaction is essential for MLL1 enzymatic activity. In the present study, we designed a large number of peptidomimetics to target the MLL1/WDR5 interaction based upon -CO-ARA-NH–, the minimum binding motif derived from MLL1. Our study led to the design of high-affinity peptidomimetics, which bind to WDR5 with Ki < 1 nM and function as potent antagonists of MLL1 activity in a fully reconstituted in vitro H3K4 methyltransferase assay. Determination of co-crystal structures of two potent peptidomimetics in complex with WDR5 establishes their structural basis for high-affinity binding to WDR5. Evaluation of one such peptidomimetic, MM-102, in bone marrow cells transduced with MLL1-AF9 fusion construct shows that the compound effectively decreases the expression of HoxA9 and Meis-1, two critical MLL1 target genes in MLL1 fusion protein mediated leukemogenesis. MM-102 also specifically inhibits cell growth and induces apoptosis in leukemia cells harboring MLL1 fusion proteins. Our study provides the first proof-of-concept for the design of small-molecule inhibitors of the WDR5/MLL1 protein–protein interaction as a novel therapeutic approach for acute leukemia harboring MLL1 fusion proteins.

  19. Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design.

    Directory of Open Access Journals (Sweden)

    Kevin Drew

    Full Text Available Peptidomimetics are classes of molecules that mimic structural and functional attributes of polypeptides. Peptidomimetic oligomers can frequently be synthesized using efficient solid phase synthesis procedures similar to peptide synthesis. Conformationally ordered peptidomimetic oligomers are finding broad applications for molecular recognition and for inhibiting protein-protein interactions. One critical limitation is the limited set of design tools for identifying oligomer sequences that can adopt desired conformations. Here, we present expansions to the ROSETTA platform that enable structure prediction and design of five non-peptidic oligomer scaffolds (noncanonical backbones, oligooxopiperazines, oligo-peptoids, [Formula: see text]-peptides, hydrogen bond surrogate helices and oligosaccharides. This work is complementary to prior additions to model noncanonical protein side chains in ROSETTA. The main purpose of our manuscript is to give a detailed description to current and future developers of how each of these noncanonical backbones was implemented. Furthermore, we provide a general outline for implementation of new backbone types not discussed here. To illustrate the utility of this approach, we describe the first tests of the ROSETTA molecular mechanics energy function in the context of oligooxopiperazines, using quantum mechanical calculations as comparison points, scanning through backbone and side chain torsion angles for a model peptidomimetic. Finally, as an example of a novel design application, we describe the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein-protein interaction. For the general biological and bioengineering community, several noncanonical backbones have been incorporated into web applications that allow users to freely and rapidly test the presented protocols (http://rosie.rosettacommons.org. This work helps address the peptidomimetic community's need for an automated and expandable

  20. Development of a peptidomimetic antagonist of neuropeptide FF receptors for the prevention of opioid-induced hyperalgesia.

    Science.gov (United States)

    Bihel, Frédéric; Humbert, Jean-Paul; Schneider, Séverine; Bertin, Isabelle; Wagner, Patrick; Schmitt, Martine; Laboureyras, Emilie; Petit-Demoulière, Benoît; Schneider, Elodie; Mollereau, Catherine; Simonnet, Guy; Simonin, Frédéric; Bourguignon, Jean-Jacques

    2015-03-18

    Through the development of a new class of unnatural ornithine derivatives as bioisosteres of arginine, we have designed an orally active peptidomimetic antagonist of neuropeptide FF receptors (NPFFR). Systemic low-dose administration of this compound to rats blocked opioid-induced hyperalgesia, without any apparent side-effects. Interestingly, we also observed that this compound potentiated opioid-induced analgesia. This unnatural ornithine derivative provides a novel therapeutic approach for both improving analgesia and reducing hyperalgesia induced by opioids in patients being treated for chronic pain.

  1. Rational Design of Calpain Inhibitors Based on Calpastatin Peptidomimetics.

    Science.gov (United States)

    Low, Kristin E; Ler, Spencer; Chen, Kevin J; Campbell, Robert L; Hickey, Jennifer L; Tan, Joanne; Scully, Conor C G; Davies, Peter L; Yudin, Andrei K; Zaretsky, Serge

    2016-06-01

    Our previously reported structures of calpain bound to its endogenous inhibitor calpastatin have motivated the use of aziridine aldehyde-mediated peptide macrocyclization toward the design of cyclic peptides and peptidomimetics as calpain inhibitors. Inspired by nature's hint that a β-turn loop within calpastatin forms a broad interaction around calpain's active site cysteine, we have constructed and tested a library of 45 peptidic compounds based on this loop sequence. Four molecules have shown reproducibly low micromolar inhibition of calpain-2. Further systematic sequence changes led to the development of probes that displayed increased potency and specificity of inhibition against calpain over other cysteine proteases. Calculated Ki values were in the low micromolar range, rivaling other peptidomimetic calpain inhibitors and presenting an improved selectivity profile against other therapeutically relevant proteases. Competitive and mixed inhibition against calpain-2 was observed, and an allosteric inhibition site on the enzyme was identified for a noncompetitive inhibitor.

  2. Synthesis and evaluation of RGD peptidomimetics aimed at surface bioderivatization of polymer substrates.

    Science.gov (United States)

    Boxus, T; Touillaux, R; Dive, G; Marchand-Brynaert, J

    1998-09-01

    Several RGD peptidomimetics have been prepared, in a convergent way, from the common ortho-aminotyrosine template (O-substituted with an anchorage-arm or a methyl group, and alpha N-substituted with a fluorine tag for XPS analysis), and various omega-aminoacid derivatives. The most flexible compounds have shown a biological activity similar to that of the peptide reference (RGDS) in the platelet aggregation test. The compound 16a could be fitted (by modelisation) with DMP 728 and c(RGDfV), two cyclic peptides that are good ligands of integrins. The compound 16b has been covalently fixed on the surface of a poly(ethylene terephthalate) membrane used as support for mammalian cell cultivation.

  3. Combining Elements from Two Antagonists of Formyl Peptide Receptor 2 Generates More Potent Peptidomimetic Antagonists.

    Science.gov (United States)

    Skovbakke, Sarah Line; Holdfeldt, André; Nielsen, Christina; Hansen, Anna Mette; Perez-Gassol, Iris; Dahlgren, Claes; Forsman, Huamei; Franzyk, Henrik

    2017-08-24

    Structural optimization of a peptidomimetic antagonist of formyl peptide receptor 2 (FPR2) was explored by an approach involving combination of elements from the two most potent FPR2 antagonists described: a Rhodamine B-conjugated 10-residue gelsonin-derived peptide (i.e., PBP10, RhB-QRLFQVKGRR-OH) and the palmitoylated α-peptide/β-peptoid hybrid Pam-(Lys-βNspe)6-NH2. This generated an array of hybrid compounds from which a new subclass of receptor-selective antagonists was identified. The most potent representatives displayed activity in the low nanomolar range. The resulting stable and potent FPR2-selective antagonists (i.e., RhB-(Lys-βNphe)n-NH2; n = 4-6) are expected to become valuable tools in further elucidation of the physiological role of FPR2 in health and disease.

  4. Efficient macrocyclization of U-turn preorganized peptidomimetics: the role of intramolecular H-bond and solvophobic effects.

    Science.gov (United States)

    Becerril, Jorge; Bolte, Michael; Burguete, M Isabel; Galindo, Francisco; García-España, Enrique; Luis, Santiago V; Miravet, Juan F

    2003-06-04

    Simple peptidomimetic molecules derived from amino acids were reacted with meta- and para-bis(bromomethyl)benzene in acetonitrile to very efficiently yield macrocyclic structures. The cyclization reaction does not require high dilution techniques and seems to be insensitive to the size of the formed macrocycle. The analysis of data obtained by (1)H NMR, single-crystal X-ray diffraction, fluorescence measurements, and molecular mechanics indicate that folded conformations can preorganize the system for an efficient cyclization. The role played by intramolecular hydrogen-bonding and solvophobic effects in the presence of folded conformations is analyzed.

  5. Selectivity in the potentiation of antibacterial activity of α-peptide/β-peptoid peptidomimetics and antimicrobial peptides by human blood plasma

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line; Knapp, Kolja M.; Franzyk, Henrik;

    2013-01-01

    Antimicrobial peptides (AMPs) are promising leads for novel antibiotics; however, their activity is often compromised under physiological conditions. The purpose of this study was to determine the activity of alpha-peptide/beta-peptoid peptidomimetics and AMPs against Escherichia coli...... and Staphylococcus aureus in the presence of human blood-derived matrices and immune effectors. The minimum inhibitory concentration (MIC) of two peptidomimetics against E. coli decreased by up to one order of magnitude when determined in 50% blood plasma as compared to MHB media. The MIC of a membrane-active AMP......, LL-I/3, also decreased, whereas two intracellularly acting AMPs were not potentiated by plasma. Blood serum had no effect on activity against E. coli and neither matrix had an effect on activity against S. aureus. Unexpectedly, physiological concentrations of human serum albumin did not influence...

  6. An in silico insight into novel therapeutic interaction of LTNF peptide-LT10 and design of structure based peptidomimetics for putative anti-diabetic activity.

    Directory of Open Access Journals (Sweden)

    Sonali Gopichand Chavan

    Full Text Available Lethal Toxin Neutralizing Factor (LTNF obtained from Opossum serum (Didephis virginiana is known to exhibit toxin-neutralizing activity for envenomation caused by animals, plants and bacteria. Small synthetic peptide- LT10 (10mer derived from N-terminal fraction of LTNF exhibit similar anti-lethal and anti-allergic property. In our in silico study, we identified Insulin Degrading Enzyme (IDE as a potential target of LT10 peptide followed by molecular docking and molecular dynamic (MD simulation studies which revealed relatively stable interaction of LT10 peptide with IDE. Moreover, their detailed interaction analyses dictate IDE-inhibitory interactions of LT10 peptide. This prediction of LT10 peptide as a novel putative IDE-inhibitor suggests its possible role in anti-diabetic treatment since IDE- inhibitors are known to assist treatment of Diabetes mellitus by enhancing insulin signalling. Furthermore, series of structure based peptidomimetics were designed from LT10 peptide and screened for their inhibitory interactions which ultimately led to a small set of peptidomimetic inhibitors of IDE. These peptidomimetic thus might provide a new class of IDE-inhibitors, those derived from LT10 peptide.

  7. Anti-inflammatory Properties of Antimicrobial Peptides and Peptidomimetics

    DEFF Research Database (Denmark)

    Skovbakke, Sarah Line; Franzyk, Henrik

    2017-01-01

    and peptidomimetics appear to display promising activity. However, in this ongoing search for potential antisepsis drug leads, it will be preferable that the assays used by different research groups lead to readily comparable data for the most efficient compounds. Here, we propose and describe standardized methods...... to be used for testing of novel compounds for their LPS- and LTA-neutralizing capacity with a focus on functional suppression of pro-inflammatory responses in cell-based systems. To best mimic the human in vivo conditions, we suggest the use of freshly isolated human leukocytes combined with an appropriate...

  8. Transport of peptidomimetic drugs by the intestinal Di/tri-peptide transporter, PepT1

    DEFF Research Database (Denmark)

    Brodin, Birger; Nielsen, Carsten Uhd; Steffansen, Bente;

    2002-01-01

    peptide transport mechanism and enter the systemic circulation. As the number of new peptide and peptidomimetic drugs are rapidly increasing, the peptide transport system has gained increasing attention as a possible drug delivery system for small peptides and peptide-like compounds. In this paper we give...... capable of transporting a number of orally administered peptidomimetic drugs. Absorbed peptides may be hydrolysed in the cells due to the high peptidase activity present in the cytosol. Peptidomimetic drugs may, if resistant to the cellular enzyme activity, pass the basolateral membrane via a basolateral...

  9. Adaptive Evolution of Escherichia coli to an α-Peptide/β-Peptoid Peptidomimetic Induces Stable Resistance

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line; Franzyk, Henrik; Holch, Anne

    2013-01-01

    Antimicrobial peptides (AMPs) and synthetic analogues thereof target conserved structures of bacterial cell envelopes and hence, development of resistance has been considered an unlikely event. However, recently bacterial resistance to AMPs has been observed, and the aim of the present study...... was to determine whether bacterial resistance may also evolve against synthetic AMP analogues, e.g. α-peptide/β-peptoid peptidomimetics. E. coli ATCC 25922 was exposed to increasing concentrations of a peptidomimetic (10 lineages), polymyxin B (10 lineages), or MilliQ water (4 lineages) in a re......-32×) to the selection agent. Five transfers (∼35 generations) in unsupplemented media did not abolish resistance indicating that resistance was heritable. Single isolates from peptidomimetic-exposed lineage populations displayed MICs against the peptidomimetic from wild-type MIC to 32×MIC revealing heterogeneous...

  10. New opioid peptides, peptidomimetics, and heterocyclic compounds from combinatorial libraries.

    Science.gov (United States)

    Dooley, C T; Houghten, R A

    1999-01-01

    Here we review the use of combinatorial libraries in opioid receptor assays. Following a brief description of the history of the combinatorial field, methods for the generation of synthetic libraries and the deconvolution of mixture-based libraries are presented. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides from combinatorial libraries is reviewed. The peptides found are composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids, and range from tetrapeptides to decapeptides. Likewise, new opioid compounds identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (e.g., polyamine, urea) and heterocyclic (e.g., bicyclic guanidine) libraries, are reviewed.

  11. Conformationally Constrained Histidines in the Design of Peptidomimetics: Strategies for the χ-Space Control

    Directory of Open Access Journals (Sweden)

    Adriano Mollica

    2011-05-01

    Full Text Available A successful design of peptidomimetics must come to terms with χ-space control. The incorporation of χ-space constrained amino acids into bioactive peptides renders the χ1 and χ2 torsional angles of pharmacophore amino acids critical for activity and selectivity as with other relevant structural features of the template. This review describes histidine analogues characterized by replacement of native α and/or β-hydrogen atoms with alkyl substituents as well as analogues with α, β-didehydro unsaturation or Cα-Cβ cyclopropane insertion (ACC derivatives. Attention is also dedicated to the relevant field of β-aminoacid chemistry by describing the synthesis of β2- and β3-models (β-hHis. Structural modifications leading to cyclic imino derivatives such as spinacine, aza-histidine and analogues with shortening or elongation of the native side chain (nor-histidine and homo-histidine, respectively are also described. Examples of the use of the described analogues to replace native histidine in bioactive peptides are also given.

  12. Peptidomimetics with beta-peptoid resudies as carriers for intracellular delivery of small interfering RNA (siRNA)

    DEFF Research Database (Denmark)

    Foged, Camilla

    complexes with and transport small interfering RNA (siRNA) into the cell cytoplasm. These new compounds are peptidomimetic dodecamers based on alternating repeats of chiral N-alkylated ß-alanine residues (ß-peptoids) and a-amino acids with a net charge of +6. Complexes of siRNA and peptidomimetics were...

  13. Synthesis of Peptidomimetic Conjugates of Acyclic Nucleoside Phosphonates

    Science.gov (United States)

    Serpi, Michaela; Zakharova, Valeria M.; Krylov, Ivan S.; McKenna, Charles E.

    2010-01-01

    Cyclic nucleoside phosphonates connected through a P-O-C linkage to a promoiety represent a class of prodrugs designed to overcome the low oral bioavailability of parent antiviral acyclic nucleoside phosphonates. In our prodrug approach, a non-toxic promoiety such as an amino acid or dipeptide is conjugated to the cyclic form of the parent drug by esterification of the phosphonic acid moiety by an alcoholic amino acid side chain (Ser, Tyr, and analogues) or through a glycol linker. For the biological evaluation and investigation of the pharmacokinetic profiles of these modified nucleoside phosphonates, a reliable synthetic procedure that allows preparation of sufficient amount of potential prodrugs is needed. This unit describes a method for generating peptidomimetic conjugates of two potent antiviral acyclic nucleoside phosphonates: 1-[(2S)-3-hydroxy-2-phosphonomethoxypropyl]cytosine ((S)-HPMPC, and 9-[(2S)-3-hydroxy-2-phosphonomethoxypropyl]adenine ((S)-HPMPA). Two alternate strategies allowing synthesizing selected amino acid, dipeptide, or ethylene glycol-linked amino acid prodrugs of (S)-HPMPC and (S)-HPMPA in solution and using a solid-phase approach are presented. PMID:21154529

  14. Synthesis and evaluation of diverse analogs of amygdalin as potential peptidomimetics of peptide T.

    Science.gov (United States)

    Araya, Eyleen; Rodriguez, Alex; Rubio, Jaime; Spada, Alessandro; Joglar, Jesus; Llebaria, Amadeu; Lagunas, Carmen; Fernandez, Andres G; Spisani, Susanna; Perez, Juan J

    2005-03-01

    Peptide T (ASTTTNYT) is a promising molecule to prevent the neuropsychometric symptoms of patients suffering AIDS and for the treatment of psoriasis. In order to fully prove its therapeutic benefits, efforts were put forward to design peptidomimetics of the peptide. In this direction, in a recent computational study the natural product amygdalin was identified as a prospective peptidomimetic of the peptide and later proved to exhibit a similar chemotactic profile to the peptide. However, the cyanide moiety of amygdalin provides to the molecule a toxic profile. The present study reports the synthesis of a set of amygdalin analogs lacking the cyanide group with improved chemotactic profiles.

  15. The Potential Therapeutic Application of Peptides and Peptidomimetics in Cardiovascular Disease.

    Science.gov (United States)

    Recio, Carlota; Maione, Francesco; Iqbal, Asif J; Mascolo, Nicola; De Feo, Vincenzo

    2016-01-01

    Cardiovascular disease (CVD) remains a leading cause of mortality and morbidity worldwide. Numerous therapies are currently under investigation to improve pathological cardiovascular complications, but yet, there have been very few new medications approved for intervention/treatment. Therefore, new approaches to treat CVD are urgently required. Attempts to prevent vascular complications usually involve amelioration of contributing risk factors and underlying processes such as inflammation, obesity, hyperglycaemia, or hypercholesterolemia. Historically, the development of peptides as therapeutic agents has been avoided by the Pharmaceutical industry due to their low stability, size, rate of degradation, and poor delivery. However, more recently, resurgence has taken place in developing peptides and their mimetics for therapeutic intervention. As a result, increased attention has been placed upon using peptides that mimic the function of mediators involved in pathologic processes during vascular damage. This review will provide an overview on novel targets and experimental therapeutic approaches based on peptidomimetics for modulation in CVD. We aim to specifically examine apolipoprotein A-I (apoA-I) and apoE mimetic peptides and their role in cholesterol transport during atherosclerosis, suppressors of cytokine signaling (SOCS)1-derived peptides and annexin-A1 as potent inhibitors of inflammation, incretin mimetics and their function in glucose-insulin tolerance, among others. With improvements in technology and synthesis platforms the future looks promising for the development of novel peptides and mimetics for therapeutic use. However, within the area of CVD much more work is required to identify and improve our understanding of peptide structure, interaction, and function in order to select the best targets to take forward for treatment.

  16. Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice

    NARCIS (Netherlands)

    Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Beljaars, Leonie; van den Born, Jacob; de Borst, Martin H.; van Goor, Harry; Hillebrands, Jan-Luuk; Poelstra, Klaas

    2016-01-01

    Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-γ is a pro-inflammatory cytokine with anti-fibrotic properties. Clinical use of interferon-γ is hampered due to inflammation-mediated systemic side effects. We used an interferon-γ peptidomimetic (mimγ)

  17. Design and synthesis of triazole-based peptidomimetics of a PSD-95 PDZ domain inhibitor

    DEFF Research Database (Denmark)

    Bach, Anders; Pedersen, Thomas B.; Strømgaard, Kristian

    2016-01-01

    PSD-95 PDZ domains are biologically important and promising drug targets. Here, we discover a triazole-based peptidomimetic, 10, by ‘click chemistry’. Compound 10 inhibits the PDZ2/GluN2B interaction with affinity similar to tripeptide SAV and better than current small-molecules. Thus, 10...... represents a new class of PSD-95 PDZ inhibitors....

  18. Rapid Multistep Synthesis of a Bioactive Peptidomimetic Oligomer for the Undergraduate Laboratory

    Science.gov (United States)

    Utku, Yeliz; Rohatgi, Abhinav; Yoo, Barney; Kirshenbaum, Kent; Zuckermann, Ronald N.; Pohl, Nicola L.

    2010-01-01

    Peptidomimetic compounds are increasingly important in drug-discovery applications. We introduce the synthesis of an N-substituted glycine oligomer, a bioactive "peptoid" trimer. The six-step protocol is conducted on solid-phase resin, enabling the synthesis to be performed by undergraduate organic chemistry students. This synthesis lab was…

  19. Cyclic dipeptide based cell-penetrating peptidomimetics for effective DNA delivery.

    Science.gov (United States)

    Madhu, Chilakapati; Voshavar, Chandrashekhar; Rajasekhar, K; Govindaraju, Thimmaiah

    2017-04-11

    An unnatural CDP-amino acid (kd) is used in the design and synthesis of novel cell penetrating peptidomimetic (Kkd-5). The balanced cationic nature and structural rigidity of Kkd-5 resulted in serum stability, non-toxicity to cells, and interaction with membrane and DNA, all of which facilitated efficient cellular uptake and DNA delivery.

  20. Tricks with clicks: modification of peptidomimetic oligomers via copper-catalyzed azide-alkyne [3 + 2] cycloaddition.

    Science.gov (United States)

    Holub, Justin M; Kirshenbaum, Kent

    2010-04-01

    This tutorial review examines recent developments involving use of Copper-catalyzed Azide-Alkyne [3 + 2] Cycloaddition (CuAAC) reactions in the synthesis, modification, and conformational control of peptidomimetic oligomers. CuAAC reactions have been used to address a variety of objectives including: (i) ligation of peptidomimetic oligomers; (ii) synthesis of ordered "foldamer" architectures; (iii) conjugation of ligands to peptidomimetic scaffolds; and (iv) macrocyclization of peptidomimetics using triazole linkages as conformational constraints. Variations in synthesis protocols, such as the use of different solvent systems, temperatures and copper species are evaluated herein to present a range of variables for the optimization of CuAAC reactions. The overall objectives of these studies are assessed to highlight the widespread applications of the products, which range from bioactive ligands to new materials.

  1. Radiolabeled divalent peptidomimetic vitronectin receptor antagonists as potential tumor radiotherapeutic and imaging agents.

    Science.gov (United States)

    Harris, Thomas D; Cheesman, Edward; Harris, Anthony R; Sachleben, Richard; Edwards, D Scott; Liu, Shuang; Bartis, Judit; Ellars, Charles; Onthank, Dave; Yalamanchili, Padmaja; Heminway, Stuart; Silva, Paula; Robinson, Simon; Lazewatsky, Joel; Rajopadhye, Milind; Barrett, John

    2007-01-01

    The integrin receptor alphavbeta3 is overexpressed on the endothelial cells of growing tumors and on some tumor cells themselves. A radiolabeled alphavbeta3 antagonists belonging to the quinolin-4-one class of peptidomimetics (TA138) was previously shown to exhibit high affinity for integrin alphavbeta3 and high selectivity versus other integrin receptors. 111In-TA138 exhibited high tumor uptake in the c-neu Oncomouse mammary adenocarcinoma model and produced excellent scintigraphic images. This study describes the synthesis of eight divalent versions of TA138 and their evaluation as potential tumor radiotherapeutic agents. The two main variables in this study were the length of the spacer bridging the biotargeting moieties and the total negative charge of the molecules imparted by the cysteic acid pharmacokinetic modifiers. Receptor affinity was evaluated in a panel of integrin receptor affinity assays, and biodistribution studies using the 111In-labeled derivatives were carried out in the c-neu Oncomouse model. All divalent agents maintained the high receptor affinity and selectivity of TA138, and six of the eight 111In derivatives exhibited blood clearance that was faster than 111In-TA138 at 24 h postinjection (PI). All divalent agents exhibited tumor uptake and retention at 24 h PI that was higher than 111In-TA138. Tumor/organ ratios were improved for most of the divalent agents at 24 h PI in critical nontarget organs marrow, kidney, and liver, with the agents having intermediate-length spacers (29-43 A) showing the largest improvement. As an example, 111In-15 showed tumor uptake of 14.3% ID/g at 24 h PI and tumor/organ ratios as follows: marrow, 3.24; kidney, 7.29; liver, 8.51. A comparison of therapeutic indices for 90Y-TA138 and 177Lu-15 indicate an improved therapeutic index for the divalent agent. The implications for radiotherapeutic applications and the mechanism of this multivalent effect are discussed.

  2. A conformationally constrained peptidomimetic binds to the extracellular region of HER2 protein.

    Science.gov (United States)

    Banappagari, Sashikanth; Ronald, Sharon; Satyanarayanajois, Seetharama D

    2010-12-01

    Human epidermal growth factor receptor 2 (HER2) is a member of the human epidermal growth factor receptor kinases (other members include EGFR or HER1, HER3, and HER4) that are involved in signaling cascades for cell growth and differentiation. It is well established that HER2-mediated heterodimerization has important implications in cancer. Deregulation of signaling pathways and overexpression of HER2 is known to occur in cancer cells, indicating a role of HER2 in tumorigenesis. Therefore, blocking HER2-mediated signaling has potential therapeutic value. We have designed several peptidomimetics to inhibit HER2-mediated signaling for cell growth. One of the compounds (HERP5, Arg-beta Naph-Phe) exhibited antiproliferative activity with IC(50) values in the micromolar-to-nanomolar range in breast cancer cell lines. Binding of fluorescently labeled HERP5 to HER2 protein was evaluated by fluorescence assay, microscopy, and circular dichroism spectroscopy. Results indicated that HERP5 binds to the extracellular region of the HER2 protein. Structure of the peptidomimetic HERP5 was studied by NMR and molecular dynamics simulations. Based on these results a model was proposed for HER2-EGFR dimerization and possible blocking by HERP5 peptidomimetic using a protein-protein docking method.

  3. Eco-Friendly Insecticide Discovery via Peptidomimetics: Design, Synthesis, and Aphicidal Activity of Novel Insect Kinin Analogues.

    Science.gov (United States)

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

    2015-05-13

    Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides.

  4. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 3. Structure-activity studies of ketomethylene-containing peptidomimetics.

    Science.gov (United States)

    Dragovich, P S; Prins, T J; Zhou, R; Fuhrman, S A; Patick, A K; Matthews, D A; Ford, C E; Meador, J W; Ferre, R A; Worland, S T

    1999-04-08

    The structure-based design, chemical synthesis, and biological evaluation of various ketomethylene-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of a peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The ketomethylene-containing inhibitors typically display slightly reduced 3CP inhibition activity relative to the corresponding peptide-derived molecules, but they also exhibit significantly improved antiviral properties. Optimization of the ketomethylene-containing compounds is shown to provide several highly active 3C protease inhibitors which function as potent antirhinoviral agents (EC90 = <1 microM) against multiple virus serotypes in cell culture.

  5. Spectroscopic Identification of Cyclic Imide b2-Ions from Peptides Containing Gln and Asn Residues

    NARCIS (Netherlands)

    J. Grzetic; J. Oomens

    2013-01-01

    In mass-spectrometry based peptide sequencing, formation of b- and y-type fragments by cleavage of the amide C-N bond constitutes the main dissociation pathway of protonated peptides under low-energy collision induced dissociation (CID). The structure of the b (2) fragment ion from peptides containi

  6. Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone

    DEFF Research Database (Denmark)

    Jing, Xiaona; Yang, Mingjun; Kasimova, Marina Robertovna

    2012-01-01

    . The presence of guanidinium groups and α-chiral β-peptoid residues was also found to have a significant positive effect on uptake in living cells. Together, the findings provide an improved understanding on the behavior of cell-penetrating peptidomimetics in the presence of lipid bilayers and live cells....... to evaluate the effect of α-chirality in the β-peptoid residues and the presence of guanidinium groups in the α-amino acid residues on membrane interaction. The molecular properties of the peptidomimetics in solution (surface and intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were...

  7. Polyethylene terephthalate membrane grafted with peptidomimetics: endothelial cell compatibility and retention under shear stress.

    Science.gov (United States)

    Rémy, Murielle; Bareille, Reine; Rerat, Vincent; Bourget, Chantal; Marchand-Brynaert, Jacqueline; Bordenave, Laurence

    2013-01-01

    The present work aimed to treat a polyethylene terephthalate (PET) surface to make the biomaterial more 'attractive' in terms of attachment and shear stress response to endothelial cells with a view to possible applications in vascular grafting. A surface wet-chemistry protocol was applied to graft track-etched PET membranes with RGD peptidomimetics based on the tyrosine template and active at the nano-level vs. isolated human αvβ3 receptor, which was monitored by X-ray photoelectron spectroscopy, contact angle measurement and atomic force microscopy for characterization. A primary culture of human saphenous vein endothelial cells was used before and after sterilization of the membranes (heat treatment or γ-ray irradiation) to test the benefit of grafting. The optimal surface concentrations of grafted molecules were around 50 pmol/cm². Compared to GRGDS, the peptidomimetics promoted cell attachment with similar or slightly better performances. Endothelialized grafted supports were further exposed to 2 h of shear stress mimicking arterial conditions. Cells were lost on non-grafted PET whereas cells on grafted polymers sterilized by γ-ray irradiation withstood forces with no significant difference in focal contacts. At the mRNA level, cells on functionalized PET were able to respond to shear stress with NFkB upregulation. Thus, grafting of peptidomimetics as ligands of the αvβ3 integrin could be a relevant strategy to improve the adhesion of human endothelial cells and to obtain an efficient endothelialized PET for the surgery of small-diameter vascular prostheses.

  8. Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes

    DEFF Research Database (Denmark)

    Andreev, Konstantin; Bianchi, Christopher; Laursen, Jonas Striegler

    2014-01-01

    Antimicrobial peptides or their synthetic mimics are a promising class of potential new antibiotics. Herein we assess the effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial α-peptide-β-peptoid chimeras. Langmuir...... of the measurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecular mechanisms of peptidomimetic interaction with bacterial membranes. We found guanidino group-containing chimeras...

  9. A graftable LDV peptidomimetic: design, synthesis and application to a blood filtration membrane.

    Science.gov (United States)

    Momtaz, Maryam; Rerat, Vincent; Gharbi, Sonia; Gérard, Estelle; Pourcelle, Vincent; Marchand-Brynaert, Jacqueline

    2008-02-01

    A graftable LDV (Leu-Asp-Val) peptidomimetic molecule (B-c) has been prepared from 3-(5-amino-2-hydroxy)phenyl-propionic acid, as alpha(4)beta(1) (VLA-4) integrin ligand. For that purpose, the mechanism of 3-(4-azidophenyl)propionic acid rearrangement has been revisited. Activation of Durapore DVPP-hydrophilic membrane, by surface wet chemistry using triazine trifluoride, followed by covalent coupling of B-c produced a modified filter (0.8% of derivatisation from XPS analysis) with improved capacity of leukocyte retention.

  10. Discovery of Novel Peptidomimetics as Irreversible CHIKV NsP2 Protease Inhibitors Using Quantum Mechanical-Based Ligand Descriptors.

    Science.gov (United States)

    El-labbad, Eman M; Ismail, Mohammed A H; Abou Ei Ella, Dalal A; Ahmed, Marawan; Wang, Feng; Barakat, Khaled H; Abouzid, Khaled A M

    2015-12-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Recent outbreaks of CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs against this important emerging virus have been reported. In this study, the design, synthesis, and antiviral activity screening of new topographical peptidomimetics revealed three potential prototype agents 3a, 4b, and 5d showing 93-100% maximum inhibition of CHIKV replication in cell-based assay having EC90 of 8.76-9.57 μg/mL. Intensive molecular modeling studies including covalent docking, lowest unoccupied molecular orbital energies, and the atomic condensed Fukui functions calculations strongly suggested the covalent binding of peptidomimetics 3a, 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme inactivation via Michael adduct formation between α/β-unsaturated ketone functionality in our designed peptidomimetics and active site catalytic cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b satisfied the Lipinski rule of five for drug-likeness and showed promising intestinal absorption and aqueous solubility via computational admet studies making them promising hits for further optimization.

  11. An index for characterization of natural and non-natural amino acids for peptidomimetics.

    Directory of Open Access Journals (Sweden)

    Guizhao Liang

    Full Text Available Bioactive peptides and peptidomimetics play a pivotal role in the regulation of many biological processes such as cellular apoptosis, host defense, and biomineralization. In this work, we develop a novel structural matrix, Index of Natural and Non-natural Amino Acids (NNAAIndex, to systematically characterize a total of 155 physiochemical properties of 22 natural and 593 non-natural amino acids, followed by clustering the structural matrix into 6 representative property patterns including geometric characteristics, H-bond, connectivity, accessible surface area, integy moments index, and volume and shape. As a proof-of-principle, the NNAAIndex, combined with partial least squares regression or linear discriminant analysis, is used to develop different QSAR models for the design of new peptidomimetics using three different peptide datasets, i.e., 48 bitter-tasting dipeptides, 58 angiotensin-converting enzyme inhibitors, and 20 inorganic-binding peptides. A comparative analysis with other QSAR techniques demonstrates that the NNAAIndex method offers a stable and predictive modeling technique for in silico large-scale design of natural and non-natural peptides with desirable bioactivities for a wide range of applications.

  12. Phosphoramidate-based peptidomimetic inhibitors of membrane type-1 matrix metalloproteinase.

    Science.gov (United States)

    Mendes, Desiree E; Wong-On-Wing, Annie; Berkman, Clifford E

    2016-01-01

    Membrane-type I matrix metalloproteinases (MT1-MMP) is an enzyme critical to the remodeling and homeostasis of extracellular matrix, and when over expressed it contributes to metastasis and cancer cell progression. Because of its role and implication as a biomarker that is upregulated in various cancers, MT1-MMP has become an attractive target for drug discovery. A small pilot library of peptidomimetics containing a phosphoramidate core as a zinc-binding group was synthesized and tested for inhibitory potency against MT1-MMP. From this library, a novel two residue peptidomimetic scaffold was identified that confers potency against MT1-MMP at submicromolar concentrations. The results of this study confirm that for this scaffold, valine is favored as a P1 residue and leucine in the P1' position. Furthermore, steric tolerance was observed for the N-terminus, thus implicating that a second-generation library could be constructed to extend the scaffold to P2 without concomitant loss of affinity within the MT1-MMP catalytic domain.

  13. Peptidomimetic Star Polymers for Targeting Biological Ion Channels

    Science.gov (United States)

    Chen, Rong; Lu, Derong; Xie, Zili; Feng, Jing; Jia, Zhongfan; Ho, Junming; Coote, Michelle L.; Wu, Yingliang; Monteiro, Michael J.; Chung, Shin-Ho

    2016-01-01

    Four end-functionalized star polymers that could attenuate the flow of ionic currents across biological ion channels were first de novo designed computationally, then synthesized and tested experimentally on mammalian K+ channels. The 4-arm ethylene glycol conjugate star polymers with lysine or a tripeptide attached to the end of each arm were specifically designed to mimic the action of scorpion toxins on K+ channels. Molecular dynamics simulations showed that the lysine side chain of the polymers physically occludes the pore of Kv1.3, a target for immuno-suppression therapy. Two of the compounds tested were potent inhibitors of Kv1.3. The dissociation constants of these two compounds were computed to be 0.1 μM and 0.7 μM, respectively, within 3-fold to the values derived from subsequent experiments. These results demonstrate the power of computational methods in molecular design and the potential of star polymers as a new infinitely modifiable platform for ion channel drug discovery. PMID:27007701

  14. Peptidomimetic Star Polymers for Targeting Biological Ion Channels.

    Directory of Open Access Journals (Sweden)

    Rong Chen

    Full Text Available Four end-functionalized star polymers that could attenuate the flow of ionic currents across biological ion channels were first de novo designed computationally, then synthesized and tested experimentally on mammalian K+ channels. The 4-arm ethylene glycol conjugate star polymers with lysine or a tripeptide attached to the end of each arm were specifically designed to mimic the action of scorpion toxins on K+ channels. Molecular dynamics simulations showed that the lysine side chain of the polymers physically occludes the pore of Kv1.3, a target for immuno-suppression therapy. Two of the compounds tested were potent inhibitors of Kv1.3. The dissociation constants of these two compounds were computed to be 0.1 μM and 0.7 μM, respectively, within 3-fold to the values derived from subsequent experiments. These results demonstrate the power of computational methods in molecular design and the potential of star polymers as a new infinitely modifiable platform for ion channel drug discovery.

  15. Design and Synthesis of a Novel Peptidomimetic Inhibitor of Caspase-3

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Caspases, a family of cysteine proteases, comprise of highly homologous enzymes that play an important role in apoptotic cell death. Caspase-3 shows key functions in apoptosis, mediating apoptotic cascade from the intrinsic and extrinsic activation pathways. Therefore, caspase-3 is an attractive target for therapeutic intervention. For instance,inhibitors of caspase-3 have been described as promising cardioprotectants, neuroprotectants and antiarthritic agents.A novel peptidomimetic inhibitor of caspase-3, has been designed, which still has the properties of a reversible inhibitor, while the P1 site at the C-terminal remains, and only L-amino acid has been replaced by D-amino acid. Also presented here is the synthesis of the inhibitor and its inhibitory activity against caspase-3, which was tested by the fluorescent activity assay.

  16. Development of a peptidomimetic ligand for efficient isolation and purification of factor VIII via affinity chromatography.

    Science.gov (United States)

    Knör, Sebastian; Khrenov, Alexey V; Laufer, Burkhardt; Saenko, Evgueni L; Hauser, Charlotte A E; Kessler, Horst

    2007-09-06

    Hemophilia A, one of the most severe bleeding disorders, results from an inherited deficiency of factor VIII (FVIII) function. Treatment by injection of FVIII has been a common procedure for decades. Nevertheless, the production and purification of FVIII remains a challenging task. Current procedures using immunoaffinity chromatography are expensive and suffer from the instability of the applied antibody ligands, which elute along with the product and contaminate it. Recently, FVIII was purified by use of octapeptide ligands, but their low protease-resistance limits their application. We here report the systematic rational and combinatorial optimization procedure that allowed us to transfer the octapeptide ligands into a small peptidomimetic. This compound is the smallest ligand known for separation of such a large protein (330 kDa). It not only binds and purifies FVIII with high efficiency but also is stable, protease-resistant, and cheap to produce in preparative scale. Hence it offers a valuable alternative to antibody-based purification procedures.

  17. Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms

    Science.gov (United States)

    Wang, Xiaohui; Su, Haihuan; Wang, Wenda; Chen, Changshui; Cao, Xiufang

    2016-09-01

    A series of novel peptidomimetics bearing dehydroepiandrosterone moiety were designed, synthesized, and evaluated for their inhibition activities against cell proliferation. According to the preliminary studies on inhibitory activities, some of the newly prepared compounds indicated significantly inhibition activities against human hepatoma cancer (HepG2), human lung cancer (A549), human melanoma (A875) cell lines compared with the control 5-fluorouracil. Especially, compounds Ii (IC50 IC50 < 13 μM) exhibited obvious inhibition activities against all tested cell lines. The highly potential compound Ik induced apoptosis in HepG2 cells were analyzed by flow cytometry, and the apoptotic effects of compound Ik were further evaluated using Annexin V-FITC/propidium iodide dual staining assay, which revealed these highly potential compounds induced cell death in HepG2 cells at least partly by apoptosis.

  18. Anti-virulence approaches and novel peptidomimetics for combating resistant and biofilm associated bacteria

    DEFF Research Database (Denmark)

    Liu, Yang

    Anti-virulence approaches and novel peptidomimetics for combating resistant and biofilm associated bacteria The misuse and overuse of antibiotics has a broad impact on the environment. Antibiotic resistance has become a major threat for modern medical treatment of infectious diseases....... There are multiple mechanisms leading to antibiotic resistance such as expression of cell membrane efflux pumps and antibiotic-degrading enzymes. Moreover, bacterial biofilm communities are widely accepted as a major resistance mechanism in infection sites. Biofilms are surface-associated microbial communities...... consisting of microcolonies embedded in self-produced extracellular polymer substances (EPS). EPS can contribute to cell-cell adhesion and restrict antibiotic penetration. Biofilm cells show much greater resistance to stressful conditions than their free-living counterparts. Conventional treatment strategies...

  19. αvβ3- or α5β1-Integrin-Selective Peptidomimetics for Surface Coating.

    Science.gov (United States)

    Mas-Moruno, Carlos; Fraioli, Roberta; Rechenmacher, Florian; Neubauer, Stefanie; Kapp, Tobias G; Kessler, Horst

    2016-06-13

    Engineering biomaterials with integrin-binding activity is a very powerful approach to promote cell adhesion, modulate cell behavior, and induce specific biological responses at the surface level. The aim of this Review is to illustrate the evolution of surface-coating molecules in this field: from peptides and proteins with relatively low integrin-binding activity and receptor selectivity to highly active and selective peptidomimetic ligands. In particular, we will bring into focus the difficult challenge of achieving selectivity between the two closely related integrin subtypes αvβ3 and α5β1. The functionalization of surfaces with such peptidomimetics opens the way for a new generation of highly specific cell-instructive surfaces to dissect the biological role of integrin subtypes and for application in tissue engineering and regenerative medicine.

  20. Surface modification of polypropylene nonwovens with LDV peptidomimetics and their application in the leukodepletion of blood products.

    Science.gov (United States)

    Gérard, Estelle; Bessy, Emilie; Hénard, Grégory; Verpoort, Thierry; Marchand-Brynaert, Jacqueline

    2012-08-01

    For clinical indications and according to European standards, a depletion of the leukocytes from whole blood has to be realized before transfusion to a patient. In this study, the surface of a layer of meltblown oxygen-plasma treated polypropylene nonwoven (O(2)-PP), making part of the composition of leukodepletion filters, was modified with bioactive molecules to enhance the adhesion of leukocytes. These synthetic small molecules (called peptidomimetics) mimic the "Leu-Asp-Val" (LDV) tripeptide sequence recognized by the α(4)β(1) integrin, a receptor expressed on leukocytes. Their activity, as ligands of the α(4)β(1) integrin, was confirmed through cell adhesion assays. The peptidomimetics were covalently immobilized on O(2)-PP nonwoven via activation of the hydroxyl- and carboxyl-functions displayed on the polymer surface with trifluoro-triazine reagent, or were simply deposited on the O(2)-PP surface. The treated materials were characterized by X-ray photoelectron spectroscopy, wettability, and morphological analyses, before and after steam sterilization. Experimental filters composed of 10 layers of O(2)-PP nonwovens and a last layer modified with the peptidomimetics were evaluated, using whole blood filtration assays, for their leukodepletion efficiency, the recovery of red cells and platelets and the waste of blood, with an objective to design new filters fulfilling practical and medical criteria. Copyright © 2012 Wiley Periodicals, Inc.

  1. Water-structuring technology with the molecular chaperone proteins: indicated application of the α-crystallin domains and imidazole-containing peptidomimetics in cosmetic skin care systems or dermatological therapeutic drug carrier formulations.

    Science.gov (United States)

    Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

    2011-01-01

    Changes in structural proteins and hydration during aging are responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, and apparent dryness. Impairment in protein hydration may add to the ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin. At Innovative Vision Products, Inc., we have pioneered a molecular chaperone protein-activated therapeutic or cosmetic platform to enable simultaneous analysis of water-binding and structuring characteristics for biology-related or skin aging and skin disease-related pathways. This cutting-edge technology has changed the hydration of proteins in photoaged skin which so that they are more compact and interact with water to limited degree. The mechanisms of skin diseases, aging, and cellular and signaling pathways mediated by targeting with molecular chaperone protein(s) are considered. Skin lesions that are growing, spreading, or pigmented, and those that occur on exposed areas of skin are likely to be treated by these emerging pharmacological chaperones that could have cosmetic or dermatological benefits. Examples of such chaperones are anti-/trans-glycation-imidazole-containing peptidomimetic(s) (natural L-carnosine derivatives and mimetics) combined with the molecular chaperone protein α-crystallin derived from a natural source, brine shrimp (Artemia franciscana) cysts, or with recombinant human αA-crystallin. This patented biotechnology represents an efficient tool with which to mitigate the consequences of free radical-induced skin damage. The article is organized to provide in one place all of the relevant technical information, such as high-performance nuclear magnetic resonance and electron spin resonance application tools, and to describe the entire process from sample preparation to data analysis, which is moving from biological studies to biotechnology batches of the product. The proposed biotechnology results in

  2. Delivery of siRNA Complexed with Palmitoylated α-Peptide/β-Peptoid Cell-Penetrating Peptidomimetics: Membrane Interaction and Structural Characterization of a Lipid-Based Nanocarrier System

    DEFF Research Database (Denmark)

    Jing, Xiaona; Foged, Camilla; Martin-Bertelsen, Birte;

    2016-01-01

    on the interaction with model membranes and the cellular uptake. Palmitoylation enhanced the peptidomimetic adsorption to supported lipid bilayers as studied by ellipsometry. However, both palmitoylation and increased peptidomimetic chain length were found to be beneficial in the cellular uptake studies using...

  3. A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics

    Directory of Open Access Journals (Sweden)

    Porcu Giampiero

    2010-07-01

    Full Text Available Abstract Background Farnesyltransferase inhibitors (FTIs are anticancer agents developed to inhibit Ras oncoprotein activities. FTIs of different chemical structure act via a conserved mechanism in eukaryotic cells. They have low toxicity and are active on a wide range of tumors in cellular and animal models, independently of the Ras activation state. Their ultimate mechanism of action, however, remains undetermined. FTase has hundred of substrates in human cells, many of which play a pivotal role in either tumorigenesis or in pro-survival pathways. This lack of knowledge probably accounts for the failure of FTIs at clinical stage III for most of the malignancies treated, with the notable exception of haematological malignancies. Understanding which cellular pathways are the ultimate targets of FTIs in different tumor types and the basis of FTI resistance is required to improve the efficacy of FTIs in cancer treatment. Results Here we used a yeast-based cellular assay to define the transcriptional changes consequent to FTI peptidomimetic administration in conditions that do not substantially change Ras membrane/cytosol distribution. Yeast and cancer cell lines were used to validate the results of the network analysis. The transcriptome of yeast cells treated with FTase inhibitor I was compared with that of untreated cells and with an isogenic strain genetically inhibited for FTase activity (Δram1. Cells treated with GGTI-298 were analyzed in a parallel study to validate the specificity of the FTI response. Network analysis, based on gene ontology criteria, identified a cell cycle gene cluster up-regulated by FTI treatment that has the Aurora A kinase IPL1 and the checkpoint protein MAD2 as hubs. Moreover, TORC1-S6K-downstream effectors were found to be down-regulated in yeast and mammalian FTI-treated cells. Notably only FTIs, but not genetic inhibition of FTase, elicited up-regulation of ABC/transporters. Conclusions This work provides a view

  4. Conformer and pharmacophore based identification of peptidomimetic inhibitors of chikungunya virus nsP2 protease.

    Science.gov (United States)

    Dhindwal, Sonali; Kesari, Pooja; Singh, Harvijay; Kumar, Pravindra; Tomar, Shailly

    2016-12-02

    Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery. In this study, the crystal structure of the C-terminal domain of ChikV nsP2 protease (PDB ID: 4ZTB) was used for structure based identification and rational designing of peptidomimetic inhibitors against nsP2 protease. The interactions of the junction residues of nsP3/4 polyprotein in the active site of nsP2 protease have been mimicked to identify and design potential inhibitory molecules. Molecular docking of the nsP3/4 junction peptide in the active site of ChikV nsP2 protease provided the structural insight of the probable binding mode of nsP3/4 peptide and pigeonholed the molecular interactions critical for the substrate binding. Further, the shape and pharmacophoric properties of the viral nsP3/4 substrate peptide were taken into consideration and the mimetic molecules were identified and designed. The designed mimetic compounds were then analyzed by docking and their binding affinity was assessed by molecular dynamics simulations.

  5. Cyclic isoDGR and RGD peptidomimetics containing bifunctional diketopiperazine scaffolds are integrin antagonists.

    Science.gov (United States)

    Panzeri, Silvia; Zanella, Simone; Arosio, Daniela; Vahdati, Leila; Dal Corso, Alberto; Pignataro, Luca; Paolillo, Mayra; Schinelli, Sergio; Belvisi, Laura; Gennari, Cesare; Piarulli, Umberto

    2015-04-13

    The cyclo[DKP-isoDGR] peptidomimetics 2-5, containing bifunctional diketopiperazine (DKP) scaffolds that differ in the configuration of the two DKP stereocenters and in the substitution at the DKP nitrogen atoms, were prepared and examined in vitro in competitive binding assays with purified αv β3 and αv β5 integrin receptors. IC50 values ranged from low nanomolar (ligand 3) to submicromolar with αv β3 integrin. The biological activities of ligands cyclo[DKP3-RGD] 1 and cyclo[DKP3-isoDGR] 3, bearing the same bifunctional DKP scaffold and showing similar αV β3 integrin binding values, were compared in terms of their cellular effects in human U373 glioblastoma cells. Compounds 1 and 3 displayed overlapping inhibitory effects on the FAK/Akt integrin activated transduction pathway and on integrin-mediated cell infiltration processes, and qualify therefore, despite the different RGD and isoDGR sequences, as integrin antagonists. Both compounds induced apoptosis in glioma cells after 72 hour treatment.

  6. Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum.

    Science.gov (United States)

    Weldon, David J; Shah, Falgun; Chittiboyina, Amar G; Sheri, Anjaneyulu; Chada, Raji Reddy; Gut, Jiri; Rosenthal, Philip J; Shivakumar, Develeena; Sherman, Woody; Desai, Prashant; Jung, Jae-Chul; Avery, Mitchell A

    2014-03-01

    A new series of peptidomimetic pseudo-prolyl-homophenylalanylketones were designed, synthesized and evaluated for inhibition of the Plasmodium falciparum cysteine proteases falcipain-2 (FP-2) and falcipain-3 (FP-3). In addition, the parasite killing activity of these compounds in human blood-cultured P. falciparum was examined. Of twenty-two (22) compounds synthesized, one peptidomimetic comprising a homophenylalanine-based α-hydroxyketone linked Cbz-protected hydroxyproline (39) showed the most potency (IC50 80 nM against FP-2 and 60 nM against FP-3). In silico analysis of these peptidomimetic analogs offered important protein-ligand structural insights including the role, by WaterMap, of water molecules in the active sites of these protease isoforms. The pseudo-dipeptide 39 and related compounds may serve as a promising direction forward in the design of competitive inhibitors of falcipains for the effective treatment of malaria. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Surface coating of siRNA-peptidomimetic nano-self-assemblies with anionic lipid bilayers: Enhanced gene silencing and reduced adversed effects in vitro

    DEFF Research Database (Denmark)

    Zeng, Xianghui; de Groot, A. M.; Sijts, Alice

    2015-01-01

    not display any noticeable cytotoxicity and immunogenicity in vitro. In contrast, the corresponding nanocomplexes mediated a reduced silencing effect with a more narrow safety window. The surface coating with anionic lipid bilayers led to partial decomplexation of the siRNA–peptidomimetic nanocomplex core...... of the liposomes, which facilitated siRNA release. Additionally, the optimal anionic liposomes showed efficient intracellular uptake and endosomal escape. Therefore, these findings suggest that a more efficacious and safe formulation can be achieved by surface coating of the siRNA–peptidomimetic nano...... a series of proteolytically stable palmitoylated α-peptide/β-peptoid peptidomimetics with a systematically varied number of repeating lysine and homoarginine residues was shown to self-assemble with small interfering RNA (siRNA). The resulting well-defined nanocomplexes were coated with anionic lipids...

  8. Advances in peptidic and peptidomimetic-based approaches to inhibit STAT signaling in human diseases.

    Science.gov (United States)

    Szelag, Malgorzata; Wesoly, Joanna; Bluyssen, Hans A R

    2016-01-01

    STATs promote fundamental cellular processes, marking them as convergence points of many oncogenic and inflammatory pathways. Therefore, aberrant activation of STAT signaling is implicated in a plethora of human diseases, like cancer, inflammation and auto-immunity. Identification of STAT-specific inhibitors is the topic of great practical importance, and various inhibitory strategies are being pursued. An interesting approach includes peptides and peptide-like biopolymers, because they allow the manipulation of STAT signaling without the transfer of genetic material. Phosphopeptides and peptidomimetics directly target STATs by inhibiting dimerization. Despite that a large number of efficient peptide- based STAT3-specific inhibitors have been reported to date, none of them was able to meet the pharmacological requirements to serve as a potent anti-cancer drug. The existing limitations, like metabolic instability and poor cell permeability during in vivo tests, excluded these macromolecules from further clinical development. To overcome these liabilities, in the last five years many advances have been made to develop next generation STAT-specific inhibitors. Here we discuss the pitfalls of current STAT inhibitory strategies and review the progress on the development of peptide-like prodrugs directly targeting STATs. Novel strategies involve screening of high-complexity libraries of random peptides, as specific STAT3 or STAT5 DNA-binding inhibitors, to construct cell permeable peptide aptamers and aptides for cancer therapy. Another new direction is synthesis of negative dominant α-helical mimetics of the STAT3 N-domain, preventing oligomerization on DNA. Moreover, construction of phosphopeptide conjugates with molecules mediating cellular uptake offers new therapeutic possibilities in treatment of cancer, asthma and allergy.

  9. Structure-activity relationships of 111In- and 99mTc-labeled quinolin-4-one peptidomimetics as ligands for the vitronectin receptor: potential tumor imaging agents.

    Science.gov (United States)

    Harris, Thomas D; Kalogeropoulos, Shirley; Nguyen, Tiffany; Dwyer, Gregory; Edwards, D Scott; Liu, Shuang; Bartis, Judit; Ellars, Charles; Onthank, Dave; Yalamanchili, Padmaja; Heminway, Stuart; Robinson, Simon; Lazewatsky, Joel; Barrett, John

    2006-01-01

    The integrin receptor alpha(v)beta(3) is overexpressed on the endothelial cells of growing tumors and on some tumor cells themselves. Radiolabeled alpha(v)beta(3) antagonists have demonstrated potential application as tumor imaging agents and as radiotherapeutic agents. This report describes the total synthesis of eight new HYNIC and DOTA conjugates of receptor alpha(v)beta(3) antagonists belonging to the quinolin-4-one class of peptidomimetics, and their radiolabeling with (99m)Tc (for HYNIC) and (111)In (for DOTA). Tethering of the radionuclide-chelator complexes was achieved at two different sites on the quinolin-4-one molecule. All such derivatives maintained high affinity for receptor alpha(v)beta(3) and high selectivity versus receptors alpha(IIb)beta(3), alpha(v)beta(5), alpha(5)beta(1). Biodistribution of the radiolabeled compounds was evaluated in the c-neu Oncomouse mammary adenocarcinoma model. DOTA conjugate (111)In-TA138 presented the best biodistribution profile. Tumor uptake at 2 h postinjection was 9.39% of injected dose/g of tissue (%ID/g). Activity levels in selected organs was as follows: blood, 0.54% ID/g; liver, 1.94% ID/g; kidney, 2.33% ID/g; lung, 2.74% ID/g; bone, 1.56% ID/g. A complete biodistribution analysis of (111)In-TA138 and the other radiolabeled compounds of this study are presented and discussed. A scintigraphic imaging study with (111)In-TA138 showed a clear delineation of the tumors and rapid clearance of activity from nontarget tissues.

  10. Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identificaiton of agonists and antagonists

    Science.gov (United States)

    The neuropeptidergic system in insects is considered to be an excellent target for pest control strategies. One promising biorational approach is the use of peptidomimetics modified from endogenous ligands to enhance biostability and bioavailability. In this study, we functionally characterized fiv...

  11. Desirability-based multi-criteria virtual screening of selective antimicrobial cyclic β-hairpin cationic peptidomimetics.

    Science.gov (United States)

    Cruz-Monteagudo, Maykel; Romero, Yansy; Cordeiro, M Natália D S; Borges, Fernanda

    2013-01-01

    Today, emerging and increasing resistance to antibiotics has become a threat to public health worldwide. Antimicrobial peptides own unique action mechanisms making peptide antibiotics an attractive therapeutic option against resistant bacteria. However, their high haemolytic activity lacks the selectivity required for a human antibiotic. Therefore, additional efforts are needed to develop new antimicrobial peptides that possess greater selectivity for bacterial cells over erythrocytes. In this article, we introduce a chemoinformatics approach to simultaneously deal with these two conflicting properties consisting on a multi-criteria virtual screening strategy based on the use of a desirability-based multi-criteria classifier combined with similarity and chemometrics concepts. Here we propose a new quantitative feature encoding information related to the desirability, the degree of credibility ascribed to this desirability and the similarity of a candidate to a highly desirable query, which can be used as ranking criterion in a virtual screening campaign, the Desirability-Credibility- Similarity (DCS) Score. The enrichment ability of a multi-criteria virtual screening strategy based on the use of the DCS Score it is also assessed and compared to other virtual screening options. The results obtained evidenced that the use of the DCS score seems to be an efficient virtual screening strategy rendering promising overall and initial enrichment performance. Specifically, by using the DCS score it was possible to rank a selective antibacterial peptidomimetic earlier than a biologically inactive or non selective antibacterial peptidomimetic with a probability of ca. 0.9.

  12. NMR-assisted computational studies of peptidomimetic inhibitors bound in the hydrophobic pocket of HIV-1 glycoprotein 41

    Science.gov (United States)

    Gochin, Miriam; Whitby, Landon R.; Phillips, Aaron H.; Boger, Dale L.

    2013-07-01

    Due to the inherently flexible nature of a protein-protein interaction surface, it is difficult both to inhibit the association with a small molecule, and to predict how it might bind to the surface. In this study, we have examined small molecules that mediate the interaction between a WWI motif on the C-helix of HIV-1 glycoprotein-41 (gp41) and a deep hydrophobic pocket contained in the interior N-helical trimer. Association between these two components of gp41 leads to virus-cell and cell-cell fusion, which could be abrogated in the presence of an inhibitor that binds tightly in the pocket. We have studied a comprehensive combinatorial library of α-helical peptidomimetics, and found that compounds with strongly hydrophobic side chains had the highest affinity. Computational docking studies produced multiple possible binding modes due to the flexibility of both the binding site and the peptidomimetic compounds. We applied a transferred paramagnetic relaxation enhancement experiment to two selected members of the library, and showed that addition of a few experimental constraints enabled definitive identification of unique binding poses. Computational docking results were extremely sensitive to side chain conformations, and slight variations could preclude observation of the experimentally validated poses. Different receptor structures were required for docking simulations to sample the correct pose for the two compounds. The study demonstrated the sensitivity of predicted poses to receptor structure and indicated the importance of experimental verification when docking to a malleable protein-protein interaction surface.

  13. The Synthetic Amphipathic Peptidomimetic LTX109 Is a Potent Fungicide That Disturbs Plasma Membrane Integrity in a Sphingolipid Dependent Manner

    DEFF Research Database (Denmark)

    Bojsen, Rasmus; Torbensen, Rasmus; Larsen, Camilla Eggert;

    2013-01-01

    The peptidomimetic LTX109 (arginine-tertbutyl tryptophan-arginine-phenylethan) was previously shown to have antibacterial properties. Here, we investigated the activity of this novel antimicrobial peptidomimetic on the yeast Saccharomyces cerevisiae. We found that LTX109 was an efficient fungicid...... observations are consistent with a model in which LTX109 kills S. cerevisiae by nonspecific destabilization of the plasma membrane through direct or indirect interaction with the sphingolipids....... that killed all viable cells in an exponentially growing population as well as a large proportion of cells in biofilm formed on an abiotic surface. LTX109 had similar killing kinetics to the membrane-permeabilizing fungicide amphotericin B, which led us to investigate the ability of LTX109 to disrupt plasma...... membrane integrity. S. cerevisiae cells exposed to a high concentration of LTX109 showed rapid release of potassium and amino acids, suggesting that LTX109 acted by destabilizing the plasma membrane. This was supported by the finding that cells were permeable to the fluorescent nucleic acid stain SYTOX...

  14. Disaggregation of Amylin Aggregate by Novel Conformationally Restricted Aminobenzoic Acid containing α/β and α/γ Hybrid Peptidomimetics

    Science.gov (United States)

    Paul, Ashim; Kalita, Sourav; Kalita, Sujan; Sukumar, Piruthivi; Mandal, Bhubaneswar

    2017-01-01

    Diabetes has emerged as a threat to the current world. More than ninety five per cent of all the diabetic population has type 2 diabetes mellitus (T2DM). Aggregates of Amylin hormone, which is co-secreted with insulin from the pancreatic β-cells, inhibit the activities of insulin and glucagon and cause T2DM. Importance of the conformationally restricted peptides for drug design against T2DM has been invigorated by recent FDA approval of Symlin, which is a large conformationally restricted peptide. However, Symlin still has some issues including solubility, oral bioavailability and cost of preparation. Herein, we introduced a novel strategy for conformationally restricted peptide design adopting a minimalistic approach for cost reduction. We have demonstrated efficient inhibition of amyloid formation of Amylin and its disruption by a novel class of conformationally restricted β-sheet breaker hybrid peptidomimetics (BSBHps). We have inserted β, γ and δ -aminobenzoic acid separately into an amyloidogenic peptide sequence, synthesized α/β, α/γ and α/δ hybrid peptidomimetics, respectively. Interestingly, we observed the aggregation inhibitory efficacy of α/β and α/γ BSBHps, but not of α/δ analogues. They also disrupt existing amyloids into non-toxic forms. Results may be useful for newer drug design against T2DM as well as other amyloidoses and understanding amyloidogenesis.

  15. Synthesis of Conformationally Constrained Aryl- or Heteroarylpiperazinyl Derivatives of Selected Imides as 5-HT1A Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Bożena Kuran

    2006-08-01

    Full Text Available The preparation of a number of cyclic imide 5-HT1A receptor ligandderivatives has been described. Their structures were conformationally constrained byintroducing rigid linkers containing unsaturated bonds or aromatic benzene rings. Thesecompounds are expected to possess anxiolytic and antidepressant activity.

  16. Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model

    DEFF Research Database (Denmark)

    Cavanagh, Jorunn Pauline; Granslo, Hildegunn Norbakken; Fredheim, Elizabeth Aarag

    2013-01-01

    Objectives Biofilm-forming Staphylococcus epidermidis is a prevalent cause of peritonitis during peritoneal dialysis. We compared the efficacy of a synthetic antimicrobial peptidomimetic (Ltx21) versus vancomycin in a murine model mimicking a device-related peritonitis. Methods Silicone implants......, pre-colonized with an S. epidermidis biofilm, were inserted into the peritoneal cavity of BALB/c mice. Three groups (36 mice in each) with pre-colonized implants received intraperitoneal treatment with Ltx21, vancomycin or placebo. Mice were euthanized on day 3 (n = 12), day 6 (n = 12) or day 8 (n...... = 12) post-implantation. Controls were mice with sterile implants (n = 18) and mice without surgery (n = 6). Bacterial reductions in cfu were analysed from implants and peritoneal fluid (PF). Inflammatory responses in serum and PF were measured. Results Vancomycin resulted in a stronger reduction...

  17. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 6. Structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics.

    Science.gov (United States)

    Dragovich, Peter S; Prins, Thomas J; Zhou, Ru; Brown, Edward L; Maldonado, Fausto C; Fuhrman, Shella A; Zalman, Leora S; Tuntland, Tove; Lee, Caroline A; Patick, Amy K; Matthews, David A; Hendrickson, Thomas F; Kosa, Maha B; Liu, Bo; Batugo, Minerva R; Gleeson, Jean-Paul R; Sakata, Sylvie K; Chen, Lijian; Guzman, Mark C; Meador, James W; Ferre, Rose Ann; Worland, Stephen T

    2002-04-11

    The structure-based design, chemical synthesis, and biological evaluation of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of a peptidomimetic binding determinant and a Michael acceptor moiety, which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The 2-pyridone-containing inhibitors typically display improved 3CP inhibition properties relative to related peptide-derived molecules along with more favorable antiviral properties. The cocrystal structure of one pyridone-derived 3CP inhibitor complexed with HRV-2 3CP is also described along with certain ab initio conformation analyses. Optimization of the 2-pyridone-containing compounds is shown to provide several highly active 3CP inhibitors (k(obs)/[I] > 500,00 M(-1) s(-1)) that function as potent antirhinoviral agents (EC(50) = <0.05 microM) against multiple virus serotypes in cell culture. One 2-pyridone-containing 3CP inhibitor is shown to be bioavailable in the dog after oral dosing (F = 48%).

  18. The synthetic amphipathic peptidomimetic LTX109 is a potent fungicide that disturbs plasma membrane integrity in a sphingolipid dependent manner.

    Science.gov (United States)

    Bojsen, Rasmus; Torbensen, Rasmus; Larsen, Camilla Eggert; Folkesson, Anders; Regenberg, Birgitte

    2013-01-01

    The peptidomimetic LTX109 (arginine-tertbutyl tryptophan-arginine-phenylethan) was previously shown to have antibacterial properties. Here, we investigated the activity of this novel antimicrobial peptidomimetic on the yeast Saccharomyces cerevisiae. We found that LTX109 was an efficient fungicide that killed all viable cells in an exponentially growing population as well as a large proportion of cells in biofilm formed on an abiotic surface. LTX109 had similar killing kinetics to the membrane-permeabilizing fungicide amphotericin B, which led us to investigate the ability of LTX109 to disrupt plasma membrane integrity. S. cerevisiae cells exposed to a high concentration of LTX109 showed rapid release of potassium and amino acids, suggesting that LTX109 acted by destabilizing the plasma membrane. This was supported by the finding that cells were permeable to the fluorescent nucleic acid stain SYTOX Green after a few minutes of LTX109 treatment. We screened a haploid S. cerevisiae gene deletion library for mutants resistant to LTX109 to uncover potential molecular targets. Eight genes conferred LTX109 resistance when deleted and six were involved in the sphingolipid biosynthetic pathway (SUR1, SUR2, SKN1, IPT1, FEN1 and ORM2). The involvement of all of these genes in the biosynthetic pathway for the fungal-specific lipids mannosylinositol phosphorylceramide (MIPC) and mannosyl di-(inositol phosphoryl) ceramide (M(IP)2C) suggested that these lipids were essential for LTX109 sensitivity. Our observations are consistent with a model in which LTX109 kills S. cerevisiae by nonspecific destabilization of the plasma membrane through direct or indirect interaction with the sphingolipids.

  19. The synthetic amphipathic peptidomimetic LTX109 is a potent fungicide that disturbs plasma membrane integrity in a sphingolipid dependent manner.

    Directory of Open Access Journals (Sweden)

    Rasmus Bojsen

    Full Text Available The peptidomimetic LTX109 (arginine-tertbutyl tryptophan-arginine-phenylethan was previously shown to have antibacterial properties. Here, we investigated the activity of this novel antimicrobial peptidomimetic on the yeast Saccharomyces cerevisiae. We found that LTX109 was an efficient fungicide that killed all viable cells in an exponentially growing population as well as a large proportion of cells in biofilm formed on an abiotic surface. LTX109 had similar killing kinetics to the membrane-permeabilizing fungicide amphotericin B, which led us to investigate the ability of LTX109 to disrupt plasma membrane integrity. S. cerevisiae cells exposed to a high concentration of LTX109 showed rapid release of potassium and amino acids, suggesting that LTX109 acted by destabilizing the plasma membrane. This was supported by the finding that cells were permeable to the fluorescent nucleic acid stain SYTOX Green after a few minutes of LTX109 treatment. We screened a haploid S. cerevisiae gene deletion library for mutants resistant to LTX109 to uncover potential molecular targets. Eight genes conferred LTX109 resistance when deleted and six were involved in the sphingolipid biosynthetic pathway (SUR1, SUR2, SKN1, IPT1, FEN1 and ORM2. The involvement of all of these genes in the biosynthetic pathway for the fungal-specific lipids mannosylinositol phosphorylceramide (MIPC and mannosyl di-(inositol phosphoryl ceramide (M(IP2C suggested that these lipids were essential for LTX109 sensitivity. Our observations are consistent with a model in which LTX109 kills S. cerevisiae by nonspecific destabilization of the plasma membrane through direct or indirect interaction with the sphingolipids.

  20. Improved in vitro evaluation of novel antimicrobials: potential synergy between human plasma and antibacterial peptidomimetics, AMPs and antibiotics against human pathogenic bacteria

    DEFF Research Database (Denmark)

    Citterio, Linda; Franzyk, Henrik; Palarasah, Yaseelan;

    2016-01-01

    Stable peptidomimetics mimicking natural antimicrobial peptides (AMPs) have emerged as a promising class of potential novel antibiotics. In the present study, we aimed at determining whether the antibacterial activity of two α-peptide/β-peptoid peptidomimetics against a range of bacterial pathogens...... was affected by conditions mimicking in vivo settings. Their activity was enhanced to an unexpected degree in the presence of human blood plasma for thirteen pathogenic Gram-positive and Gram-negative bacteria. MIC values typically decreased 2- to 16-fold in the presence of a human plasma concentration...... treatments might be lower than traditionally deduced from MICs determined in laboratory media. Thus, antibiotics previously considered too toxic could be developed into usable last-resort drugs, due to ensuing lowered risk of side effects. In contrast, the activity of the compounds was significantly...

  1. Improved in vitro evaluation of novel antimicrobials: potential synergy between human plasma and antibacterial peptidomimetics, AMPs and antibiotics against human pathogenic bacteria.

    Science.gov (United States)

    Citterio, Linda; Franzyk, Henrik; Palarasah, Yaseelan; Andersen, Thomas Emil; Mateiu, Ramona Valentina; Gram, Lone

    2016-01-01

    Stable peptidomimetics mimicking natural antimicrobial peptides (AMPs) have emerged as a promising class of potential novel antibiotics. In the present study, we aimed at determining whether the antibacterial activity of two α-peptide/β-peptoid peptidomimetics against a range of bacterial pathogens was affected by conditions mimicking in vivo settings. Their activity was enhanced to an unexpected degree in the presence of human blood plasma for thirteen pathogenic Gram-positive and Gram-negative bacteria. MIC values typically decreased 2- to 16-fold in the presence of a human plasma concentration that alone did not damage the cell membrane. Hence, MIC and MBC data collected in these settings appear to represent a more appropriate basis for in vivo experiments preceding clinical trials. In fact, concentrations of peptidomimetics and peptide antibiotics (e.g. polymyxin B) required for in vivo treatments might be lower than traditionally deduced from MICs determined in laboratory media. Thus, antibiotics previously considered too toxic could be developed into usable last-resort drugs, due to ensuing lowered risk of side effects. In contrast, the activity of the compounds was significantly decreased in heat-inactivated plasma. We hypothesize that synergistic interactions with complement proteins and/or clotting factors most likely are involved.

  2. RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

    Science.gov (United States)

    Russo, P; Ottoboni, C; Crippa, A; Riou, J F; O'Connor, P M

    2001-04-01

    A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.

  3. Light Activation of a Cysteine Protease Inhibitor: Caging of a Peptidomimetic Nitrile with RuII(bpy)2

    Science.gov (United States)

    Respondek, Tomasz; Garner, Robert N.; Herroon, Mackenzie K.; Podgorski, Izabela; Turro, Claudia; Kodanko, Jeremy J.

    2013-01-01

    A novel method for caging protease inhibitors is described. The complex [RuII(bpy)2(1)2](PF6)2 (2) was prepared from the nitrile-based peptidomimetic inhibitor Ac-Phe-NHCH2CN (1). 1H NMR, UV-vis and IR spectroscopic and mass spectrometric data confirm that two equiv of inhibitor 1 bind to RuII through the nitrile functional group. Complex 2 shows excellent stability in aqueous solution in the dark and fast release of 1 upon irradiation with visible light. Due to binding to the RuII center, the nitriles of complex 2 are caged, and 2 does not act as a potent enzyme inhibitor. However, when 2 is irradiated, it releases 1 that inhibits the cysteine proteases papain and cathepsins B, K and L, up to two times more potently than 1 alone. Ratios for IC50 values for 2 range from 6:1 to 33:1 under dark vs. light conditions, against isolated enzymes and in human cell lysates, confirming a high level of photoinduced enzyme inhibition is obtained with this method. PMID:21973207

  4. The peptidomimetic Lau-(Lys-βNSpe)6-NH2 antagonizes formyl peptide receptor 2 expressed in mouse neutrophils.

    Science.gov (United States)

    Skovbakke, Sarah Line; Winther, Malene; Gabl, Michael; Holdfeldt, André; Linden, Sara; Wang, Ji Ming; Dahlgren, Claes; Franzyk, Henrik; Forsman, Huamei

    2016-11-01

    The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the human and murine FPR family members is required. Compared to FPR1 and FPR2 expressed by human neutrophils, very little is known about agonist/antagonist recognition patterns for their murine orthologues, but now we have identified two potent and selective formylated peptide agonists (fMIFL and PSMα2) for Fpr1 and Fpr2, respectively. These peptides were used to determine the inhibition profile of a set of antagonists with known specificities for the two FPRs in relation to the corresponding murine receptors. Some of the most potent and selective antagonists for the human receptors proved to be devoid of effect on their murine orthologues as determined by their inability to inhibit superoxide release from murine neutrophils upon stimulation with receptor-specific agonists. The Boc-FLFLF peptide was found to be a selective antagonist for Fpr1, whereas the lipidated peptidomimetic Lau-(Lys-βNSpe)6-NH2 and the hexapeptide WRW4 were identified as Fpr2-selective antagonists. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

    Directory of Open Access Journals (Sweden)

    Giordano Lesma

    2014-06-01

    Full Text Available An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid components has been developed. The reactions proceeded smoothly and in a stereocontrolled manner with regard to the new center of the Ugi products due to the stereoinduction of the amine chiral residue. A wide variety of novel chiral 3,3-disubstituted 3-aminooxindoles were obtained, a selection of which were subjected to post-Ugi transformations, paving the way to application as peptidomimetics.

  6. Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and L-carnosine in ophthalmic and skin care products.

    Science.gov (United States)

    Babizhayev, Mark A

    2006-04-11

    Apart from genetically programmed cell aging, different external aggressors related to oxidative stress and lipid peroxidation (LPO) can accelerate the skin aging phenomenon. Oxidative stress associated with the formation of lipid peroxides is suggested to contribute to pathological processes in aging and systemic diseases known as the risk factors for cataract. Despite the fact that L-carnosine-related peptidomimetics N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) (NAC) and carcinine (beta-alanylhistamine) are metabolically related to L-carnosine and have been demonstrated to occur in tissues of many vertebrates, including humans, these compounds were shown resistant toward enzymatic hydrolysis. A series of related biocompatible imidazole-containing peptidomimetics were synthesized in order to confer resistance to enzymatic hydrolysis and ex vivo improvement of protective antioxidative properties related to L-carnosine. The included findings revealed a greater role of N-acetylcarnosine (NAC) and carcinine ex vivo in the prolongation and potentiation of physiological responses to the therapeutical and cosmetics treatments with L-carnosine as antioxidant. 3-D molecular conformation studies proposed the antioxidant activity of peptidomimetics (carcinine, L-prolylhistamine, N-acetylcarnosine, L-carnosine) for metal ion binding, quenching of a number free radicals, and binding of hydroperoxide or aldehyde (including dialdehyde LPO products) in an imidazole-peroxide adducts. NAC can act as a time release (carrier) stable version of L-carnosine during application in ophthalmic pharmaceutical and cosmetics formulations which include lubricants. Carcinine, L-prolylhistamine show efficient deactivation of lipid hydroperoxides monitored by HPLC and protection of membrane phospholipids and water soluble proteins from the lipid peroxides-induced damages. This activity is superior over the lipophilic antioxidant vitamin E. The biologically significant applications of

  7. Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases.

    Science.gov (United States)

    Chuck, Chi-Pang; Chen, Chao; Ke, Zhihai; Wan, David Chi-Cheong; Chow, Hak-Fun; Wong, Kam-Bo

    2013-01-01

    Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6-49 μM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ~10x more potent than the other inhibitors tested. Crystal structures of the enzyme-inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1-S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 μM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin I metabolism in aorta of apoE-knockout mice.

    Science.gov (United States)

    Olszanecki, R; Suski, M; Gebska, A; Toton-Zuranska, J; Kus, K; Madej, J; Bujak-Gizycka, B; Jawien, J; Korbut, R

    2013-06-01

    The detrimental role of over activation of renin-angiotensin system (RAS) in atherogenesis is widely recognized. Recently, we have demonstrated that Ang-(1-7) peptidomimetic - AVE0991, as well as known beta-adrenolytic agent nebivolol, exert anti-atherogenic actions in mouse model of atherosclerosis - apoE-knockout mice. Here, using LC-ESI-MS ex vivo system, we tested whether prolonged treatment of apoE-knockout mice by these drugs can influence RAS in aorta of apoE-knockout mice in regard to generation of most active metabolites of Ang I-Ang II and Ang-(1-7). As compared to wild type animals there was increased generation of Ang II in aorta of apoE-knockout mice, while the formation of Ang-(1-7) did not differ between both groups. Either treatment with AVE0991 or nebivolol resulted in significant attenuation of Ang II production in aorta of apoE-knockout mice. In conclusion, for the first time we directly demonstrated that there is increase in ability of aortic tissue to generate Ang II in mouse model of atherosclerosis of apoE knockout mice, and that such effect could be efficiently attenuated either by treatment of nebivolol or Ang-(1-7) peptidomimetic - AVE0991. The exact mechanism(s) responsible for interference of both drugs with RAS require further investigation.

  9. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 8. Pharmacological optimization of orally bioavailable 2-pyridone-containing peptidomimetics.

    Science.gov (United States)

    Dragovich, Peter S; Prins, Thomas J; Zhou, Ru; Johnson, Theodore O; Hua, Ye; Luu, Hiep T; Sakata, Sylvie K; Brown, Edward L; Maldonado, Fausto C; Tuntland, Tove; Lee, Caroline A; Fuhrman, Shella A; Zalman, Leora S; Patick, Amy K; Matthews, David A; Wu, Ellen Y; Guo, Ming; Borer, Bennett C; Nayyar, Naresh K; Moran, Terence; Chen, Lijian; Rejto, Paul A; Rose, Peter W; Guzman, Mark C; Dovalsantos, Elena Z; Lee, Steven; McGee, Kevin; Mohajeri, Michael; Liese, Andreas; Tao, Junhua; Kosa, Maha B; Liu, Bo; Batugo, Minerva R; Gleeson, Jean-Paul R; Wu, Zhen Ping; Liu, Jia; Meador, James W; Ferre, Rose Ann

    2003-10-09

    The optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors following oral administration to either beagle dogs or CM-monkeys is described. The molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an alpha,beta-unsaturated ester Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. Modification of the ester contained within these compounds is detailed along with alteration of the P(2) substituent present in the peptidomimetic portion of the inhibitors. The pharmacokinetics of several inhibitors in both dogs and monkeys are described (7 h plasma concentrations after oral administration) along with their human plasma stabilities, stabilities in incubations with human, dog, and monkey microsomes and hepatocytes, Caco-2 permeabilities, and aqueous solubilities. Compounds containing an alpha,beta-unsaturated ethyl ester fragment and either an ethyl or propargyl P(2) moiety displayed the most promising combination of 3C enzyme inhibition (k(obs)/[I] 170 000-223 000 M(-1) s(-1)), antiviral activity (EC(50) = 0.047-0.058 microM, mean vs seven HRV serotypes), and pharmacokinetics following oral administration (7 h dog plasma levels = 0.248-0.682 microM; 7 h CM-monkey plasma levels = 0.057-0.896 microM).

  10. Thiazole-valine peptidomimetic (TTT-28) antagonizes multidrug resistance in vitro and in vivo by selectively inhibiting the efflux activity of ABCB1

    Science.gov (United States)

    Wang, Yi-Jun; Patel, Bhargav A.; Anreddy, Nagaraju; Zhang, Yun-Kai; Zhang, Guan-Nan; Alqahtani, Saeed; Singh, Satyakam; Shukla, Suneet; Kaddoumi, Amal; Ambudkar, Suresh V.; Talele, Tanaji T.; Chen, Zhe-Sheng

    2017-01-01

    Multidrug resistance (MDR) attenuates the chemotherapy efficacy and increases the probability of cancer recurrence. The accelerated drug efflux mediated by ATP-binding cassette (ABC) transporters is one of the major MDR mechanisms. This study investigated if TTT-28, a newly synthesized thiazole-valine peptidomimetic, could reverse ABCB1-mediated MDR in vitro and in vivo. TTT-28 reversed the ABCB1-mediated MDR and increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells by selectively blocking the efflux function of ABCB1, but not interfering with the expression level and localization of ABCB1. Animal study revealed that TTT-28 enhanced the intratumoral concentration of paclitaxel and promoted apoptosis, thereby potently inhibiting the growth of ABCB1 overexpressing tumors. But TTT-28 did not induce the toxicity (cardiotoxicity/myelosuppression) of paclitaxel in mice. In this study, we synthesized and evaluated a novel selective inhibitor of ABCB1 (TTT-28) with high efficacy and low toxicity. The identification and characterization of this new thiazole-valine peptidomimetic will facilitate design and synthesis of a new generation of ABCB1 inhibitors, leading to further research on multidrug resistance and combination chemotherapy. Furthermore, the strategy that co-administer MDR-ABCB1 inhibitor to overcome the resistance of one FDA approved, widely used chemotherapeutic paclitaxel, may be promising direction for the field of adjuvant chemotherapy. PMID:28181548

  11. Benzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy.

    Science.gov (United States)

    Premnath, Padmavathy Nandha; Craig, Sandra N; Liu, Shu; McInnes, Campbell

    2016-08-01

    Inhibition of cyclin dependent kinase 2 (CDK2) in complex with cyclin A in G1/S phase of the cell cycle has been shown to promote selective apoptosis of cancer cells through the E2F1 pathway. An alternative approach to catalytic inhibition is to target the substrate recruitment site also known as the cyclin binding groove (CBG) to generate selective non-ATP competitive inhibitors. The REPLACE strategy has been applied to identify fragment alternatives and substituted benzoic acid derivatives were evaluated as a promising scaffold to present appropriate functionality to mimic key peptide determinants. Fragment Ligated Inhibitory Peptides (FLIPs) are described which potently inhibit both CDK2/cyclin A and CDK4/cyclin D1 and have preliminary anti-tumor activity. A structural rationale for binding was obtained through molecular modeling further demonstrating their potential for further development as next generation non ATP competitive CDK inhibitors.

  12. The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

    Directory of Open Access Journals (Sweden)

    Francesco Airaghi

    2013-01-01

    Full Text Available Aiming at restricting the conformational freedom of tryptophan-containing peptide ligands, we designed a THBC (tetrahydro-β-carboline-DKP (diketopiperazine-based peptidomimetic scaffold capable of arranging in an unusual α-turn conformation. The synthesis is based on a diastereoselective Pictet–Spengler condensation to give the THBC core, followed by an intramolecular lactamization to complete the tetracyclic THBC-DKP fused ring system. The presence of conformers bearing the intramolecular thirteen-membered hydrogen bond that characterizes the α-turn structure is confirmed by 1H NMR conformational studies. To the best of our knowledge, this scaffold represents one of the rare examples of a designed constrained α-turn mimic.

  13. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease

    Science.gov (United States)

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P1 and P2 positions of the inhibitor, and an aldehyde warhead is attached to the P1. We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg- H (Bz—benzoyl) that are composed mainly of unusual amino acid residues in all positions P1-P4. The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  14. MicroPET/CT imaging of {alpha}{sub v}{beta}{sub 3} integrin via a novel {sup 68}Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Menichetti, Luca; Kusmic, Claudia; Panetta, Daniele; Petroni, Debora; Salvadori, Piero A. [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Arosio, Daniela; Manzoni, Leonardo [CNR-Institute of Molecular Science and Technologies (ISTM), Milan (Italy); Matteucci, Marco [Scuola Superiore Sant' Anna, Pisa (Italy); Casagrande, Cesare [University of Milan, Department of Chemistry, Milan (Italy); L' Abbate, Antonio [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Scuola Superiore Sant' Anna, Pisa (Italy)

    2013-08-15

    The {alpha}{sub v}{beta}{sub 3} integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel {sup 68}Ga-2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI. A straightforward labelling chemistry to attach the radionuclide {sup 68}Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for {alpha}{sub v}{beta}{sub 3} integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the {sup 68}Ga-NOTA-RGD with the flow tracer {sup 13}N-NH{sub 3} imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin {beta}{sub 3}. NOTA-RGD conjugate displayed a binding affinity for {alpha}{sub v}{beta}{sub 3} integrin of 27.9 {+-} 6.8 nM. {sup 68}Ga-NOTA-RGD showed stability without detectable degradation or formation of by-products in urine up to 2 h following injection in the rat. MI hearts exhibited {sup 68}Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry. As compared to similar imaging approaches using the {sup 18}F-galacto-derivative, we documented for the first time with microPET/CT imaging the {sup 68}Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to

  15. Effect of SI-591, a new class of cathepsin K inhibitor with peptidomimetic structure, on bone metabolism in vitro and in vivo.

    Science.gov (United States)

    Fujii, Toshiaki; Ishikawa, Mizuho; Kubo, Akiko; Tanaka, Yoshitaka

    2015-12-01

    SI-591[N-[1-[[[(1S)-3-[[(3S)-hexahydro-2-oxo-1H-azepin-3-yl]amino]-1-(1-methylethyl)-2,3-dioxopropyl]amino]carbonyl]cyclohexyl]-2-furancarboxamide] is an orally bioavailable compound that was synthesized as one of several unique peptidomimetic compounds without a basic group. This compound was found to have the ability to inhibit cathepsin K, a lysosomal cysteine protease. Cathepsin K is known to be expressed in osteoclasts and involved in bone loss processes. In this study, SI-591 was shown to inhibit the activity of various purified cathepsin molecules at nanomolar concentrations but had high selectivity for cathepsin K over other subtypes including B and L. SI-591 also decreased the level of CTX-I, a bone resorption marker, which was released from osteoclasts in vitro in a dose-dependent manner. The mobilization of calcium from the bones to the blood stream is known to increase in rats fed with a low calcium diet; SI-591 inhibited this increase in serum calcium level at an oral dose of 3mg/kg. Furthermore, SI-591 significantly decreased the level of CTX-I and DPD, bone resorption markers, at oral doses of 10mg/kg or less in ovariectomized rats, while it did not affect the level of BGP, a bone formation marker. In addition, SI-591 prevented bone mineral density loss in the lumber vertebrae and femurs in ovariectomized rats. These results suggest that SI-591 inhibits bone resorption without affecting osteoblast maturation. Therefore, SI-591, a novel cathepsin K inhibitor, could be a promising agent for the treatment of postmenopausal osteoporosis.

  16. The proteolytically stable peptidomimetic Pam-(Lys-βNSpe)6-NH2 selectively inhibits human neutrophil activation via formyl peptide receptor 2.

    Science.gov (United States)

    Skovbakke, Sarah Line; Heegaard, Peter M H; Larsen, Camilla J; Franzyk, Henrik; Forsman, Huamei; Dahlgren, Claes

    2015-01-15

    Immunomodulatory host defense peptides (HDPs) are considered to be lead compounds for novel anti-sepsis and anti-inflammatory agents. However, development of drugs based on HDPs has been hampered by problems with toxicity and low bioavailability due to in vivo proteolysis. Here, a subclass of proteolytically stable HDP mimics consisting of lipidated α-peptide/β-peptoid oligomers was investigated for their effect on neutrophil function. The most promising compound, Pam-(Lys-βNSpe)6-NH2, was shown to inhibit formyl peptide receptor 2 (FPR2) agonist-induced neutrophil granule mobilization and release of reactive oxygen species. The potency of Pam-(Lys-βNSpe)6-NH2 was comparable to that of PBP10, the most potent FPR2-selective inhibitor known. The immunomodulatory effects of structural analogs of Pam-(Lys-βNSpe)6-NH2 emphasized the importance of both the lipid and peptidomimetic parts. By using imaging flow cytometry in primary neutrophils and FPR-transfected cell lines, we found that a fluorescently labeled analog of Pam-(Lys-βNSpe)6-NH2 interacted selectively with FPR2. Furthermore, the interaction between Pam-(Lys-βNSpe)6-NH2 and FPR2 was found to prevent binding of the FPR2-specific activating peptide agonist Cy5-WKYMWM, while the binding of an FPR1-selective agonist was not inhibited. To our knowledge, Pam-(Lys-βNSpe)6-NH2 is the first HDP mimic found to inhibit activation of human neutrophils via direct interaction with FPR2. Hence, we consider Pam-(Lys-βNSpe)6-NH2 to be a convenient tool in the further dissection of the role of FPR2 in inflammation and homeostasis as well as for investigation of the importance of neutrophil stimulation in anti-infective therapy involving HDPs. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. De novo design and synthesis of ultra-short peptidomimetic antibiotics having dual antimicrobial and anti-inflammatory activities.

    Directory of Open Access Journals (Sweden)

    Ravichandran N Murugan

    Full Text Available BACKGROUND: Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length and poor protease stability. METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π- and N(τ-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti-methicillin-resistant Staphylococcus aureus (MRSA activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. CONCLUSION/SIGNIFICANCE: The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.

  18. Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes.

    Science.gov (United States)

    Lerner, E C; Qian, Y; Blaskovich, M A; Fossum, R D; Vogt, A; Sun, J; Cox, A D; Der, C J; Hamilton, A D; Sebti, S M

    1995-11-10

    Ras-induced malignant transformation requires Ras farnesylation, a lipid posttranslational modification catalyzed by farnesyltransferase (FTase). Inhibitors of this enzyme have been shown to block Ras-dependent transformation, but the mechanism by which this occurs remains largely unknown. We have designed FTI-276, a peptide mimetic of the COOH-terminal Cys-Val-Ile-Met of K-Ras4B that inhibited potently FTase in vitro (IC50 = 500 pM) and was highly selective for FTase over geranylgeranyltransferase I (GGTase I) (IC50 = 50 nM). FTI-277, the methyl ester derivative of FTI-276, was extremely potent (IC50 = 100 nM) at inhibiting H-Ras, but not the geranylgeranylated Rap1A processing in whole cells. Treatment of H-Ras oncogene-transformed NIH 3T3 cells with FTI-277 blocked recruitment to the plasma membrane and subsequent activation of the serine/threonine kinase c-Raf-1 in cells transformed by farnesylated Ras (H-RasF), but not geranylgeranylated, Ras (H-RasGG). FTI-277 induced accumulation of cytoplasmic non-farnesylated H-Ras that was able to bind Raf and form cytoplasmic Ras/Raf complexes in which Raf kinase was not activated. Furthermore, FTI-277 blocked constitutive activation of mitogen-activated protein kinase (MAPK) in H-RasF, but not H-RasGG, or Raf-transformed cells. FTI-277 also inhibited oncogenic K-Ras4B processing and constitutive activation of MAPK, but the concentrations required were 100-fold higher than those needed for H-Ras inhibition. The results demonstrate that FTI-277 blocks Ras oncogenic signaling by accumulating inactive Ras/Raf complexes in the cytoplasm, hence preventing constitutive activation of the MAPK cascade.

  19. Sulphonamide 1,4-dithia-7-azaspiro[4,4]nonane derivatives as gelatinase A inhibitors.

    Science.gov (United States)

    Shi, Leilei; Wang, Qiang; Wang, Haina; Zhou, Hua; Li, Yonggang; Li, Xun

    2013-12-15

    Gelatinase A, a zinc-containing endopeptidase, has been shown to be an essential therapeutic target for tumor intervention owing to its participation in almost all types of solid tumors. Based on our previous work with respect to quinoxalinone peptidomimetics, a novel series of sulphonamide-containing 1,4-dithia-7-azaspiro[4,4]nonane (DAN) derivatives have been synthesized and evaluated as potential gelatinase A inhibitors hereby. The results revealed that the majority of tested compounds displayed satisfactory inhibition activity against gelatinase A. Among the tested compounds, 2b, 3a, 4a-d, 6a, 6d, 7a-d exhibited more potent gelatinase A inhibition than the positive control LY52. Furthermore, two test compounds 2b and 6a demonstrated moderate anti-proliferative in vitro and anti-metastatic activities in vivo, which might be utilized as potential leads in future chemical optimization.

  20. Data on human neutrophil activation induced by pepducins with amino acid sequences derived from β2AR and CXCR4

    Directory of Open Access Journals (Sweden)

    André Holdfeldt

    2016-09-01

    Full Text Available The data described here is related to the research article titled (Gabl et al., 2016 [1]. Pepducins with peptide sequence derived from one of the intracellular domains of a given G-protein coupled receptor (GPCR can either activate or inhibit cell functions. Here we include data on human neutrophil function induced by pepducins derived from β2AR (ICL3-8 and CXCR4 (ATI-2341, respectively. ICL3-8 exerts neither direct activating effect on the NADPH-oxidase as measured by superoxide release nor inhibitory effect on FPR signaling. ATI-2341 dose-dependently triggers neutrophil activation and these cells were subsequently desensitized in their response to FPR2 specific agonists F2Pal10 and WKYMVM. Moreover, the ATI-2341 response is inhibited by PBP10 and the peptidomimetic Pam-(Lys-betaNSpe6-NH2 (both are FPR2 specific inhibitors, but not to the FPR1 specific inhibitor cyclosporine H.

  1. Synthesis of two D-glucosamine derived 3,4-epoxides as potential scaffolds for combinatorial chemistry

    DEFF Research Database (Denmark)

    Svejgaard, L.; Fuglsang, H.; Jensen, P.B.

    2003-01-01

    Combinatorial chemistry allows the synthesis of libraries of compounds by combination of building blocks or by combinatorial elaboration of a central scaffold.([1,2]) Carbohydrates hold great promise as scaffolds due to their high degree of functionalization, relative conformational rigidity......, commercial availability of many stereoisomeric forms, and their well-described chemistry. Hirschmann, Nicolaou, Smith, and their coworkers pioneered the use of carbohydrates as scaffolds in their design and synthesis Of beta-D-glucose derived non-peptide peptidomimetics of the peptide hormone somatostatin...... (SRIF).([3,4]) However, only relatively few examples on the application of carbohydrates as scaffolds in combinatorial chemistry have been described.([5-11]) For example, Brill et al. anchored a 1,6-anhydro-beta-D-glucopyranoside (levoglucosan) derived epoxide to a solid support and introduced diversity...

  2. In vivo biokinetic and metabolic characterization of the {sup 68}Ga-labelled α5β1-selective peptidomimetic FR366

    Energy Technology Data Exchange (ETDEWEB)

    D' Alessandria, Calogero; Pohle, Karolin; Schwaiger, Markus [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Muenchen (Germany); Rechenmacher, Florian; Neubauer, Stefanie; Kessler, Horst [Technische Universitaet Muenchen, Institute for Advanced Study (IAS) and Center of Integrated Protein Science (CIPSM), Department Chemie, Garching (Germany); Notni, Johannes; Wester, Hans-Juergen [Technische Universitaet Muenchen, Lehrstuhl fuer Pharmazeutische Radiochemie, Garching (Germany); Beer, Ambros J. [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Muenchen (Germany); Ulm University, Department of Nuclear Medicine, Ulm (Germany)

    2016-05-15

    Integrins are transmembrane receptors responsible for cell-cell adhesion and cell-extracellular matrix binding and play an important role in angiogenesis and tumour metastasis. For this reason, integrins are increasingly used as targets for molecular imaging. Up to now interest has mostly been focused on the integrin subtype αvβ3. However, targeting of other subtypes such as the integrin α5β1 is also of high interest due to its central role in colonization of metastatic cells, resistance of tumour cells to chemotherapy and ionizing radiation, and tumour aggressiveness. Recently, a highly active antagonist ligand (2,2'-(7-(1-carboxy-4-((6-((3-(4-(((S)-1-carboxy-2-(2- (3-guanidinobenzamido)acet amido)ethyl)carbamoyl)-3,5-dimethylphenoxy) propyl)amino)-6-oxohexyl)amino)-4-oxo butyl)-1,4,7-triazonane-1,4-diyl)diacetic acid, FR366) for the integrin subtype α5β1 with high selectivity versus αvβ3, has been developed and tested successfully in preliminary in vitro and in vivo experiments. Here, we present our results of an investigation of the use of {sup 68}Ga-labelled α5β1 ligand in PET imaging. The free α5β1 peptidomimetic ligand was functionalized with a spacer (6-aminohexanoic acid) and the bifunctional chelator 1-((1,3-dicarboxy)propyl) -4,7-(carboxymethyl)-1,4,7-triazacyclononane (NODAGA) to yield FR366 and labelled with {sup 68}Ga. To confirm selective in vivo targeting of α5β1, female BALB/c nude mice xenografted with α5β1-expressing RKO cells in the right shoulder and α5β1/αvβ3-expressing M21 cells in the left shoulder were subjected to PET/CT scans and biodistribution experiments. Specificity of tracer uptake was proven by blocking studies. Metabolic stability of the injected tracer was measured in urine and in plasma. MicroPET/CT scans with radiolabelled FR366 showed a good tumour-to-normal tissue ratio with low uptake in the liver (0.32 ± 0.14 %ID/g) and good retention of {sup 68}Ga-NODAGA-FR366 in the tumour (0.71 ± 0.20 %ID/g and 0

  3. Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Karatas, Hacer; Li, Yangbing; Liu, Liu; Ji, Jiao; Lee, Shirley; Chen, Yong; Yang, Jiuling; Huang, Liyue; Bernard, Denzil; Xu, Jing; Townsend, Elizabeth C.; Cao, Fang; Ran, Xu; Li, Xiaoqin; Wen, Bo; Sun, Duxin; Stuckey, Jeanne A; Lei, Ming; Dou, Yali; Wang, Shaomeng (Michigan)

    2017-06-06

    We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis for their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.

  4. Synthesis, structure, and biological applications of α-fluorinated β-amino acids and derivatives.

    Science.gov (United States)

    March, Taryn L; Johnston, Martin R; Duggan, Peter J; Gardiner, James

    2012-11-01

    This review gives a broad overview of the state of play with respect to the synthesis, conformational properties, and biological activity of α-fluorinated β-amino acids and derivatives. General methods are described for the preparation of monosubstituted α-fluoro-β-amino acids (Scheme 1). Nucleophilic methods for the introduction of fluorine predominantly involve the reaction of DAST with alcohols derived from α-amino acids, whereas electrophilic sources of fluorine such as NFSI have been used in conjunction with Arndt-Eistert homologation, conjugate addition or organocatalyzed Mannich reactions. α,α-Difluoro-β-amino acids have also been prepared using DAST; however, this area of synthesis is largely dominated by the use of difluorinated Reformatsky reagents to introduce the difluoro ester functionality (Scheme 9). α-Fluoro-β-amino acids and derivatives analyzed by X-ray crystal and NMR solution techniques are found to adopt preferred conformations which are thought to result from stereoelectronic effects associated with F located close to amines, amides, and esters (Figs. 2-6). α-Fluoro amide and β-fluoro ethylamide/amine effects can influence the secondary structure of α-fluoro-β-amino acid-containing derivatives including peptides and peptidomimetics (Figs. 7-9). α-Fluoro-β-amino acids are also components of a diverse range of bioactive anticancer (e.g., 5-fluorouracil), antifungal, and antiinsomnia agents as well as protease inhibitors where such fluorinated analogs have shown increased potency and spectrum of activity.

  5. Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.02,6]decane skeleton

    Directory of Open Access Journals (Sweden)

    Matthias Breuning

    2009-12-01

    Full Text Available An enantioselective route to four tricyclic amino acids and N-tosylamides, composed of a central norbornane framework with a 2-endo,3-endo-annelated pyrrolidine ring and a 5-endo-C1 or -C2 side chain, has been developed. A key intermediate was the chiral, N-Boc-protected ketone (1R,2S,6S,7R-4-azatricyclo[5.2.1.02,6]decan-8-one, available from inexpensive endo-carbic anhydride in five steps and 47% yield. The rigid scaffold makes these amino acid derivatives promising candidates for β-turn-inducing building blocks in peptidomimetics and for chiral auxiliaries in asymmetric organocatalysis.

  6. Structure-based design and synthesis of N(omega)-nitro-L-arginine-containing peptidomimetics as selective inhibitors of neuronal nitric oxide synthase. Displacement of the heme structural water.

    Science.gov (United States)

    Seo, Jiwon; Igarashi, Jotato; Li, Huiying; Martasek, Pavel; Roman, Linda J; Poulos, Thomas L; Silverman, Richard B

    2007-05-03

    The neuronal isoform of nitric oxide synthase (nNOS), the enzyme responsible for the production of nitric oxide in the central nervous system, represents an attractive target for the treatment of various neurodegenerative disorders. X-ray crystal structures of complexes of nNOS with two nNOS-selective inhibitors, (4S)-N-{4-amino-5-[(2-aminoethylamino]pentyl}-N'-nitroguanidine (1) and 4-N-(Nomega-nitro-l-argininyl)-trans-4-amino-l-proline amide (2), led to the discovery of a conserved structural water molecule that was hydrogen bonded between the two heme propionates and the inhibitors (Figure 2). On the basis of this observation, we hypothesized that by attaching a hydrogen bond donor group to the amide nitrogen of 2 or to the secondary amine nitrogen of 1, the inhibitor molecules could displace the structural water molecule and obtain a direct interaction with the heme cofactor. To test this hypothesis, peptidomimetic analogues 3-5, which have either an N-hydroxyl (3 and 5) or N-amino (4) donor group, were designed and synthesized. X-ray crystal structures of nNOS with inhibitors 3 and 5 bound verified that the N-hydroxyl group had, indeed, displaced the structural water molecule and provided a direct interaction with the heme propionate moiety (Figures 5 and 6). Surprisingly, in vitro activity assay results indicated that the addition of a hydroxyl group (3) only increased the potency slightly against the neuronal isoform over the parent compound (1). Rationalizations for the small increase in potency are consistent with other changes in the crystal structures.

  7. The Lipidated Peptidomimetic Lau-((S)-Aoc)-(Lys-βNphe)6-NH2 Is a Novel Formyl Peptide Receptor 2 Agonist That Activates Both Human and Mouse Neutrophil NADPH Oxidase.

    Science.gov (United States)

    Holdfeldt, André; Skovbakke, Sarah Line; Winther, Malene; Gabl, Michael; Nielsen, Christina; Perez-Gassol, Iris; Larsen, Camilla Josephine; Wang, Ji Ming; Karlsson, Anna; Dahlgren, Claes; Forsman, Huamei; Franzyk, Henrik

    2016-09-16

    Neutrophils expressing formyl peptide receptor 2 (FPR2) play key roles in host defense, immune regulation, and resolution of inflammation. Consequently, the search for FPR2-specific modulators has attracted much attention due to its therapeutic potential. Earlier described agonists for this receptor display potent activity for the human receptor (FPR2) but low activity for the mouse receptor orthologue (Fpr2), rendering them inapplicable in murine models of human disease. Here we describe a novel FPR2 agonist, the proteolytically stable α-peptide/β-peptoid hybrid Lau-((S)-Aoc)-(Lys-βNphe)6-NH2 (F2M2), showing comparable potency in activating human and mouse neutrophils by inducing a rise in intracellular Ca(2+) concentration and assembly of the superoxide-generating NADPH oxidase. This FPR2/Fpr2 agonist contains a headgroup consisting of a 2-aminooctanoic acid (Aoc) residue acylated with lauric acid (C12 fatty acid), which is linked to a peptide/peptoid repeat ((Lys-βNphe)6-NH2). Both the fatty acid moiety and the (S)-Aoc residue were required for FPR2/Fpr2 activation. This type of proteolytically stable FPR2-specific peptidomimetics may serve as valuable tools for future analysis of FPR2 signaling as well as for development of prophylactic immunomodulatory therapy. This novel class of cross-species FPR2/Fpr2 agonists should enable translation of results obtained with mouse neutrophils (and disease models) into enhanced understanding of human inflammatory and immune diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Specific binding of photoaffinity-labeling peptidomimetics of Pro-Leu-Gly-NH2 to the dopamine D2L receptor: evidence for the allosteric modulation of the dopamine receptor.

    Science.gov (United States)

    Mann, Amandeep; Verma, Vaneeta; Basu, Dipannita; Skoblenick, Kevin J; Beyaert, Michael G R; Fisher, Abigail; Thomas, Nancy; Johnson, Rodney L; Mishra, Ram K

    2010-09-01

    The present study was undertaken to investigate the mechanistic role of l-prolyl-l-leucyl-glycinamide (PLG) in modulating agonist binding to the dopamine D(2L) receptor. Competition and displacement assays indicate that the photoaffinity-labeling peptidomimetics of PLG, 3(R)-[(4(S)-(4-azido-2-hydroxy-benzoyl) amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride (1a) and 3(R)-[(4(S)-(4-azido-2-hydroxy-5-iodo-benzoyl)amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride (1b) bind at the same site as PLG. Autoradiography was used to establish the covalent binding of [(125)I]-1b to an approximately 51kDa protein in bovine striatal membranes. Western blot analysis with a dopamine D(2L)-specific antibody, in combination with autoradiography, following a two-dimensional gel separation, suggested this approximately 51kDa protein to be the dopamine D(2L) receptor. Further evidence for binding of 1b to dopamine D(2L) was provided by samples immunoprecipitated with the D(2L) antibody. These samples were analyzed by western blotting in parallel with autoradiography of [(125)I]-1b labeled protein. Both methods revealed bands at approximately 51kDa. Furthermore, PLG is shown to compete with 1b for binding to the dopamine D(2L) receptor as determined by autoradiography, as well as competition experiments with PLG and 1a. Collectively, these findings suggest the successful development of a photoaffinity-labeling agent, compound 1b, that has been used to elucidate the interaction of PLG specifically with the dopamine D(2L) receptor.

  9. Hemoglobin derivatives

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003371.htm Hemoglobin derivatives To use the sharing features on this page, please enable JavaScript. Hemoglobin derivatives are altered forms of hemoglobin . Hemoglobin is ...

  10. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded and inheren...... and inherently static, capital itself is unprecedentedly mobile, fluid and fungible. As such derivatives raise the specter of ‘financial weapons of mass destruction’....

  11. Integrin αvβ3 Targeting RGD-Peptidomimetic Agents%以整合素αvβ3为靶点的肿瘤靶向制剂

    Institute of Scientific and Technical Information of China (English)

    杨旺桂; 刘芳; 边疆

    2014-01-01

    As RGD can specifically bind to integrin αvβ3, which is up-regulated in both tumor and tumor-en-dothelial cells, this enables the targeting of diagnostics and therapeutics of tumor using the affinity between RGD and its receptor. Previous studies and data from clinical trials demonstrated RGD imaging agents can target tumor tissues. RGD-nano antitumor agents(RGD-liposome, RGD-micelle, RGD-nanoparticle) have greater cellular uptake and higher cytotoxic in vitro, make more effective in tumor growth inhibition and prolong survival times in xeno-graft models. Tumor incidence increases year by year, but therapeutics and efficacy are still very limited. The ad-vantage of RGD-peptidomimetic agents in targeting of diagnostics and therapeutics deserve special attention.%整合素αvβ3在肿瘤细胞及肿瘤血管内皮细胞中高表达,RGD序列作为其配体,可与其进行特异性结合,为肿瘤的诊断和靶向治疗提供了理论基础。RGD诊断试剂的前期研究和临床试验数据表明其具有良好的肿瘤组织靶向性。RGD-纳米抗肿瘤制剂(RGD-脂质体、RGD-胶束和RGD-纳米粒)在体外可提高细胞对药物的吸收率,增强细胞毒性;在动物移植瘤模型中,能更好地抑制肿瘤的生长,延长了动物的生存时间。在肿瘤发病率居高不下,治疗手段和疗效都较为有限的今天,RGD靶向制剂在肿瘤诊断和治疗中所具有的优势值得特别关注。

  12. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded...

  13. Derivative Chameleons

    CERN Document Server

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field \\phi, but also of its derivatives via higher order co-ordinate invariants. Specifically we consider the first such non-trivial conformal factor A(\\phi,X), where X is the canonical kinetic term for \\phi. The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for \\phi. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning...

  14. Derivative chameleons

    Science.gov (United States)

    Noller, Johannes

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field phi, but also of its derivatives via higher order co-ordinate invariants (such as ∂μphi∂μphi,squphi,...). Specifically we consider the first such non-trivial conformal factor A(phi,∂μphi∂μphi). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for phi → phi+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  15. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    ." - Steen Parsholt, Chairman and CEO, Aon Nordic Region. "Andersen has done a wonderful job of developing a comprehensive text that deals with risk management in global markets. I would recommend this book to any student or businessman who has a need to better understand the risks and risk management...... management practice. Of particular note is the global and integrated approach chosen in this book which should be of special interest to aspiring managers active in global and international markets." - Dr Jean-Pierre Zigrand, Lecturer in Finance, London School of Economics, UK. More than 90 per cent...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  16. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  17. On $n$-derivations

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Sattari

    2016-06-01

    Full Text Available In this article, the notion of $n-$derivation is introduced for all integers $ngeq 2$. Although all derivations are $n-$derivations,  in general these notions are not equivalent. Some properties of ordinary derivations are  investigated for $n-$derivations. Also, we show that under certain mild condition  $n-$derivations are derivations.

  18. δ-Peptides from RuAAC-Derived 1,5-Disubstituted Triazole Units

    KAUST Repository

    Johansson, Johan R.

    2014-02-14

    Non-natural peptides with structures and functions similar to natural peptides have emerged lately in biomedical as well as nanotechnological contexts. They are interesting for pharmaceutical applications since they can adopt structures with new targeting potentials and because they are generally not prone to degradation by proteases. We report here a new set of peptidomimetics derived from δ-peptides, consisting of n units of a 1,5-disubstituted 1,2,3-triazole amino acid (5Tzl). The monomer was prepared using ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) chemistry using [RuCl2Cp]x as the catalyst, allowing for simpler purification and resulting in excellent yields. This achiral monomer was used to prepare peptide oligomers that are water soluble independent of peptide chain length. Conformational analysis and structural investigations of the oligomers were performed by 2D NOESY NMR experiments, and by quantum chemical calculations using the ωB97X-D functional. These data indicate that several conformations may co-exist with slight energetic differences. Together with their increased hydrophilicity, this feature of homo-5Tzl may prove essential for mimicking natural peptides composed of α-amino acids, where the various secondary structures are achieved by side chain effects and not by the rigidity of the peptide backbone. The improved synthetic method allows for facile variation of the 5Tzl amino acid side chains, further increasing the versatility of these compounds. A new set of non-natural peptides composed of 1,5-disubstituted 1,2,3-triazole amino acids is presented. These peptides benefit from: a) modular synthesis of the monomers, allowing variation of the side chains; b) increased solubility of the oligomers in water, irrespective of peptide length; c) flexibility of the backbone allowing these foldamers to adopt several conformations. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

    Directory of Open Access Journals (Sweden)

    Samantha Caputo

    2016-01-01

    Full Text Available Enantiomerically pure β-aminoalcohols, produced through an organocatalytic Mannich reaction, were subjected to an Ugi multicomponent reaction under classical or Lewis acid-promoted conditions with diastereoselectivities ranging from moderate to good. This approach represents a step-economical path to enantiomerically pure, polyfunctionalized peptidomimetics endowed with three stereogenic centers, allowing the introduction of five diversity inputs.

  20. Derived logarithmic geometry I

    OpenAIRE

    Steffen, Sagave; Timo, Schurg; Gabriele, Vezzosi

    2016-01-01

    In order to develop the foundations of logarithmic derived geometry, we introduce a model category of logarithmic simplicial rings and a notion of derived log \\'etale maps and use this to define derived log stacks.

  1. Preparation and study of dialkyl nitroxide radicals; Preparation et etude de radicaux nitroxydes diacyles

    Energy Technology Data Exchange (ETDEWEB)

    Chenavas, P. [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1969-07-01

    These radicals are obtained by oxidation of N-hydroxy-imides with lead tetracetate or p-nitro-perbenzoic acid. These imides are prepared by heating dicarboxylic acids anhydrides with benzyloxy-amine followed by catalytic hydrogenation of N-benzyloxy-imides so obtained. Two series of radicals have mainly been studied, the first concerning five-membered cyclic imides, the second six-membered cyclic imides, these molecules having methyls substituents or no on the carbon ring. N. M. R. spectra of some O-benzyl-imides have been analysed. These different results have made it possible to study the conformation and stereochemistry of these imides. (author) [French] Ces radicaux sont obtenus par oxydation d'imides N-hydroxyles par le tetracetate de plomb ou l'acide p-nitroperbenzoique; ces imides sont prepares par chauffage d'anhydrides de diacides en presence de benzyloxyamine suivie d'une hydrogenation catalytique des N-benzyloxyimides ainsi obtenus. Deux series de radicaux ont principalement ete etudies: la premiere relative a des imides cycliques a cinq chainons, la seconde a des imides cycliques a six chainons, ces molecules ayant des substituants methyles ou non sur la chaine carbonee. Les derives O-benzyles de quelques-uns de ces imides ont ete analyses en R. M. N. Ces differents resultats ont permis une etude de la conformation et de la stereochimie de ces imides. (auteur)

  2. Interest rate derivatives

    DEFF Research Database (Denmark)

    Svenstrup, Mikkel

    This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered.......This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered....

  3. A NEW FRACTAL DERIVATION

    OpenAIRE

    Ji-Huan He

    2011-01-01

    A new fractal derive is defined, which is very easy for engineering applications to discontinuous problems, two simple examples are given to elucidate to establish governing equations with fractal derive and how to solve such equations, respectively.

  4. Derived equivalence of algebras

    Institute of Scientific and Technical Information of China (English)

    杜先能

    1997-01-01

    The derived equivalence and stable equivalence of algebras RmA and RmB are studied It is proved, using the tilting complex, that RmA and RmB are derived-equivalent whenever algebras A and B are derived-equivalent

  5. Perfect Derived Propagators

    CERN Document Server

    Schulte, Christian

    2008-01-01

    When implementing a propagator for a constraint, one must decide about variants: When implementing min, should one also implement max? Should one implement linear equations both with and without coefficients? Constraint variants are ubiquitous: implementing them requires considerable (if not prohibitive) effort and decreases maintainability, but will deliver better performance. This paper shows how to use variable views, previously introduced for an implementation architecture, to derive perfect propagator variants. A model for views and derived propagators is introduced. Derived propagators are proved to be indeed perfect in that they inherit essential properties such as correctness and domain and bounds consistency. Techniques for systematically deriving propagators such as transformation, generalization, specialization, and channeling are developed for several variable domains. We evaluate the massive impact of derived propagators. Without derived propagators, Gecode would require 140000 rather than 40000 ...

  6. LR-PARSING DERIVED

    NARCIS (Netherlands)

    Hesselink, Wim H.

    1992-01-01

    The LR(k)-parsing algorithm is derived, i.e., presented and proved as an interplay between program development and parsing theory. The program development uses invariants and the new concept of weakest angelic precondition. The parsing theory involved relates rightmost derivability to three other tr

  7. 4-Aminoquinoline derivatives

    DEFF Research Database (Denmark)

    Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum;

    2016-01-01

    Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives...

  8. Financial Derivatives in China

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Francis Repka sees bright prospects for the future development of the financial derivatives market in China. Repka,Vice President of the Asian Bond Finance Department of Societe Generale, says the situation in France just after the birth of derivatives was very similar to the situation in China today.

  9. Numerical Integration with Derivatives

    Institute of Scientific and Technical Information of China (English)

    Hu Cheng

    2006-01-01

    A new formula with derivatives for numerical integration was presented. Based on this formula and the Richardson extrapolation process, a numerical integration method was established. It can converge faster than the Romberg's. With the same accuracy, the computation of the new numerical integration with derivatives is only half of that of Romberg's numerical integration.

  10. Taxation of Derivatives

    DEFF Research Database (Denmark)

    Dyppel, Katja Joo

    2013-01-01

    The main objective for this thesis is to analyse and systematise the Danish legislation on taxation of derivatives. According to financial terminology, a derivative is a financial instrument. Its value is derived from changes in the value of one or more underlying assets.The most common derivatives...... in the Danish tax legislation. However, contracts known as forwards (terminskontrakter) and options (aftaler om køberetter og salgsretter) are generally included in the term financials contracts covered by the Danish Act on Taxation of Gains and Losses on Claims and Debt. The main part of the analysis deals...... with the scope of sections 29-33 of the Danish Act on Taxation of Gains and Losses on Claims and Debt and the tax consequences for the covered financial contracts. In the analysis of taxation of derivatives, the fundamental issues of qualification and tax treatment of the instruments are dealt with....

  11. Discovery of 5-substituted tetrahydronaphthalen-2yl-methyl with N-phenyl-N-(piperidin-4-yl)propionamide derivatives as potent opioid receptor ligands.

    Science.gov (United States)

    Deekonda, Srinivas; Wugalter, Lauren; Kulkarni, Vinod; Rankin, David; Largent-Milnes, Tally M; Davis, Peg; Bassirirad, Neemah M; Lai, Josephine; Vanderah, Todd W; Porreca, Frank; Hruby, Victor J

    2015-09-15

    A new series of novel opioid ligands have been designed and synthesized based on the 4-anilidopiperidine scaffold containing a 5-substituted tetrahydronaphthalen-2yl)methyl group with different N-phenyl-N-(piperidin-4-yl)propionamide derivatives to study the biological effects of these substituents on μ and δ opioid receptor interactions. Recently our group reported novel 4-anilidopiperidine analogues, in which several aromatic ring-contained amino acids were conjugated with N-phenyl-N-(piperidin-4-yl)propionamide and examined their biological activities at the μ and δ opioid receptors. In continuation of our efforts in these novel 4-anilidopiperidine analogues, we took a peptidomimetic approach in the present design, in which we substituted aromatic amino acids with tetrahydronaphthalen-2yl methyl moiety with amino, amide and hydroxyl substitutions at the 5th position. In in vitro assays these ligands, showed very good binding affinity and highly selective toward the μ opioid receptor. Among these, the lead ligand 20 showed excellent binding affinity (2 nM) and 5000 fold selectivity toward the μ opioid receptor, as well as functional selectivity in GPI assays (55.20 ± 4.30 nM) and weak or no agonist activities in MVD assays. Based on the in vitro bioassay results the lead compound 20 was chosen for in vivo assessment for efficacy in naïve rats after intrathecal administration. Compound 20 was not significantly effective in alleviating acute pain. This discrepancy between high in vitro binding affinity, moderate in vitro activity, and low in vivo activity may reflect differences in pharmacodynamics (i.e., engaging signaling pathways) or pharmacokinetics (i.e., metabolic stability). In sum, our data suggest that further optimization of this compound 20 is required to enhance in vivo activity.

  12. Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children.

    Directory of Open Access Journals (Sweden)

    Patrick Georges Cech

    Full Text Available BACKGROUND: This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children. METHODS: The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90. RESULTS: No serious or severe adverse events (AEs related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014. In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02. CONCLUSION: These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines. TRIAL REGISTRATION: ClinicalTrials.gov NCT00513669.

  13. Superstability of Generalized Derivations

    Directory of Open Access Journals (Sweden)

    Ansari-Piri Esmaeil

    2010-01-01

    Full Text Available We investigate the superstability of the functional equation , where and are the mappings on Banach algebra . We have also proved the superstability of generalized derivations associated to the linear functional equation , where .

  14. Amphetamine derivative related deaths.

    Science.gov (United States)

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  15. Derivations in a tetrahedron

    Science.gov (United States)

    Vladeva, Dimitrinka I.; Trendafilov, Ivan D.

    2015-11-01

    One of the natural questions which often appeared in algebra and analysis whether a map can be defined by its "local" properties. In this paper we consider maps which acts like a derivation on semirings of a special type.

  16. Gorenstein derived functions

    DEFF Research Database (Denmark)

    Holm, Henrik Granau

    2004-01-01

    Over any associative ring R it is standard to derive HomR(􀀀;􀀀) using projective resolutions in the rst variable, or injective resolutions in the second variable, and doing this, one obtains Extn R(􀀀;􀀀) in both cases. We examine the situation where projective...... and injective modules are replaced by Gorenstein projective and Gorenstein injective ones, respectively. Furthermore, we derive the tensor product 􀀀 R 􀀀 using Gorenstein at modules....

  17. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  18. Comprehensive Peptidomimetic Libraries Targeting Protein–Protein Interactions

    Science.gov (United States)

    Whitby, Landon R.

    2012-01-01

    Conspectus Transient protein–protein interactions (PPIs) are essential components in cellular signaling pathways as well as important processes such as viral infection, replication, and immune suppression. The unknown or uncharacterized PPIs involved in such interaction networks often represent compelling therapeutic targets for drug discovery. To date, however, the main strategies for discovery of small molecule modulators of PPIs are typically limited to structurally characterized targets. Recent developments in molecular scaffolds that mimic the side chain display of peptide secondary structures have yielded effective designs, however, few screening libraries of such mimetics currently exist that can be used to interrogate PPI targets. We initiated a program to prepare a comprehensive small molecule library designed to mimic the three major recognition motifs that mediate PPIs (α-helix, β-turn, and β-strand). Three libraries built around templates designed to mimic each such secondary structure and substituted with all triplet combinations of groups representing the 20 natural amino acid side chains would contain a member capable of mimicking the key interaction residues of most targetable PPIs. We summarize herein the results of the design, synthesis, and validation of an 8,000 member α-helix mimetic library and a 4,200 member β-turn mimetic library. The screening of these libraries is expected not only to provide lead structures against α-helix or β-turn mediated protein–protein or peptide–receptor interactions even if the nature of the interaction is unknown, but also yield key insights into the recognition motif (α-helix or β-turn), and identify the key residues mediating the interaction. Consistent with this expectation, the screening of the libraries against p53/MDM2 and HIV-1 gp41 (α-helix mimetic library) or the opioid receptors (β-turn mimetic library) led to the discovery of library members expected to mimic the known endogenous ligands. These efforts led to the discovery of high affinity α-helix mimetics (Ki = 0.7 µM) against HIV-1 gp41 as well as high affinity and selective β-turn mimetics (Ki = 80 nM) against the κ-opioid receptor. The results suggest that the use of such comprehensive libraries of peptide secondary structure mimetics, built around effective molecular scaffolds, constitutes a powerful method of interrogating PPIs, providing small molecule modulators of PPI networks for therapeutic target validation, lead compound discovery, and identification of modulators of biological processes for study. PMID:22799570

  19. Comprehensive peptidomimetic libraries targeting protein-protein interactions.

    Science.gov (United States)

    Whitby, Landon R; Boger, Dale L

    2012-10-16

    Transient protein-protein interactions (PPIs) are essential components in cellular signaling pathways as well as in important processes such as viral infection, replication, and immune suppression. The unknown or uncharacterized PPIs involved in such interaction networks often represent compelling therapeutic targets for drug discovery. To date, however, the main strategies for discovery of small molecule modulators of PPIs are typically limited to structurally characterized targets. Recent developments in molecular scaffolds that mimic the side chain display of peptide secondary structures have yielded effective designs, but few screening libraries of such mimetics are available to interrogate PPI targets. We initiated a program to prepare a comprehensive small molecule library designed to mimic the three major recognition motifs that mediate PPIs (α-helix, β-turn, and β-strand). Three libraries would be built around templates designed to mimic each such secondary structure and substituted with all triplet combinations of groups representing the 20 natural amino acid side chains. When combined, the three libraries would contain a member capable of mimicking the key interaction and recognition residues of most targetable PPIs. In this Account, we summarize the results of the design, synthesis, and validation of an 8000 member α-helix mimetic library and a 4200 member β-turn mimetic library. We expect that the screening of these libraries will not only provide lead structures against α-helix- or β-turn-mediated protein-protein or peptide-receptor interactions, even if the nature of the interaction is unknown, but also yield key insights into the recognition motif (α-helix or β-turn) and identify the key residues mediating the interaction. Consistent with this expectation, the screening of the libraries against p53/MDM2 and HIV-1 gp41 (α-helix mimetic library) or the opioid receptors (β-turn mimetic library) led to the discovery of library members expected to mimic the known endogenous ligands. These efforts led to the discovery of high-affinity α-helix mimetics (K(i) = 0.7 μM) against HIV-1 gp41 as well as high-affinity and selective β-turn mimetics (K(i) = 80 nM) against the κ-opioid receptor. The results suggest that the use of such comprehensive libraries of peptide secondary structure mimetics, built around effective molecular scaffolds, constitutes a powerful method of interrogating PPIs. These structures provide small molecule modulators of PPI networks for therapeutic target validation, lead compound discovery, and the identification of modulators of biological processes for further study.

  20. Superstability of Generalized Derivations

    Directory of Open Access Journals (Sweden)

    Esmaeil Ansari-Piri

    2010-01-01

    Full Text Available We investigate the superstability of the functional equation f(xy=xf(y+g(xy, where f and g are the mappings on Banach algebra A. We have also proved the superstability of generalized derivations associated to the linear functional equation f(γx+βy=γf(x+βf(y, where γ,β∈ℂ.

  1. Quinazolin-4-one derivatives

    DEFF Research Database (Denmark)

    Mosley, Cara A; Acker, Timothy M; Hansen, Kasper Bø;

    2010-01-01

    We describe a new class of subunit-selective antagonists of N-methyl D-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives ...

  2. Oxygenated Derivatives of Hydrocarbons

    Science.gov (United States)

    For the book entitled “Insect Hydrocarbons: Biology, Biochemistry and Chemical Ecology”, this chapter presents a comprehensive review of the occurrence, structure and function of oxygenated derivatives of hydrocarbons. The book chapter focuses on the occurrence, structural identification and functi...

  3. Deriving diffeomorphism symmetry

    CERN Document Server

    Kleppe, Astri

    2014-01-01

    In an earlier article, we have "derived" space, as a part of the Random Dynamics project. In order to get locality we need to obtain reparametrization symmetry, or equivalently, diffeomorphism symmetry. There we sketched a procedure for how to get locality by first obtaining reparametrization symmetry, or equivalently, diffeomorphism symmetry. This is the object of the present article.

  4. Approximate *-derivations and approximate quadratic *-derivations on C*-algebras

    Directory of Open Access Journals (Sweden)

    Park Choonkil

    2011-01-01

    Full Text Available Abstract In this paper, we prove the stability of *-derivations and of quadratic *-derivations on Banach *-algebras. We moreover prove the superstability of *-derivations and of quadratic *-derivations on C*-algebras. 2000 Mathematics Subject Classification: 39B52; 47B47; 46L05; 39B72.

  5. Fractional Derivative Cosmology

    CERN Document Server

    Roberts, Mark D

    2009-01-01

    The degree by which a function can be differentiated need not be restricted to integer values. Usually most of the field equations of physics are taken to be second order, curiosity asks what happens if this is only approximately the case and the field equations are nearly second order. For Robertson-Walker cosmology there is a simple fractional modification of the Friedman and conservation equations. In general fractional gravitational equations similar to Einstein's are hard to define as this requires fractional derivative geometry. What fractional derivative geometry might entail is briefly looked at and it turns out that even asking very simple questions in two dimensions leads to ambiguous or intractable results. A two dimensional line element which depends on the Gamma-function is looked at.

  6. Systems of integrable derivations

    Directory of Open Access Journals (Sweden)

    Vittoria Bonanzinga

    1994-05-01

    Full Text Available Let A be a commutative k-algebra, with k a subring of A. We give the definition of n-dimensional differentiation of A over k which formally extends the known one of unidimensional differentiation and we study the group of all n-dimensional differentiation of A over k. In the second part of the work we give some theorems of strong integrability for systems of derivations in terms of n-dimensional differentiation.

  7. Dynamic Stability Derivatives

    Science.gov (United States)

    2015-06-01

    time; i.e., is evaluated at the steady-state reference flight condition. However, this derivation provides no definitive information about limits of...dimensional straight- tapered wing in unsteady flow. Assume that the lift is defined by a function that depends on properties of the fluid (density...kinematic viscocity, and speed-of-sound; wing geometric characteristics (area, mean aerodynamic chord and taper ratio); and its motion (free-stream

  8. Multifunctional Cinnamic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  9. Endostatin derivative angiogenesis inhibitors

    Institute of Scientific and Technical Information of China (English)

    ZHENG Meng-jie

    2009-01-01

    Objective To throw light on the superiority of the anti-angiogenesis activity of endostatin (ES) derivatives by reviewing the recent progress in the field of ES molecular structure modification.Data sources The data used in this article were mainly from PubMed with relevant English articles published from 1971 to May 2008.The search terms were "endostatin" and "angiothesis".Study selection Articles involved in the ES molecular structure modification and the original milestone articles were selected.Results A number of ES derivatives were designed and studied to improve its clinical relevance.The modified ES with polyethylene glycol (PEG),low molecular weight heparin (LMWH) and IgG Fc domain extended the circulation half-life.Meanwhile the recombinant ESs showed more potent anti-tumor activity than native ES in mouse xenografts.Mutated ES also changed its anti-angiogenesis activity.Conclusions The anti-angiogenesis treatment remains a promising tumor therapeutic strategy.New ES derivatives would be a good choice to meet the future challenge on clinical application of ES.

  10. The peptide derived from the Ig-like domain of human herpesvirus 8 K1 protein induces death in hematological cancer cells

    Directory of Open Access Journals (Sweden)

    Daniluk Urszula

    2012-08-01

    -3 peptide can selectively induce the death of malignant hematological cell lines by Fas- and/or TNFRI-dependent mechanisms, suggesting the K1-derived peptide or peptidomimetic may have promising therapeutic potential for the treatment of hematological cancers.

  11. Credit derivatives and risk management

    OpenAIRE

    Michael S. Gibson

    2007-01-01

    The striking growth of credit derivatives suggests that market participants find them to be useful tools for risk management. I illustrate the value of credit derivatives with three examples. A commercial bank can use credit derivatives to manage the risk of its loan portfolio. An investment bank can use credit derivatives to manage the risks it incurs when underwriting securities. An investor, such as an insurance company, asset manager, or hedge fund, can use credit derivatives to align its...

  12. Essays on Derivatives Pricing

    DEFF Research Database (Denmark)

    Kokholm, Thomas

    The field of quantitative finance has been criticized in the mainstream media lately and been accused of being one of the causes of the financial crisis. Convenient as this explanation may be, my belief is that a part of the solution to the crisis is to use more (and not less) sophisticated....... With the existence of a liquid market for derivatives with variance as underlying, such as VIX options, VIX futures and a well-developed over-the-counter market for options on variance swaps, it is important to consider models that are able to fit these markets while consistently pricing vanilla options...

  13. In defense of derivations

    Science.gov (United States)

    Mungan, Carl E.

    2016-05-01

    At the 2015 AAPT Summer Meeting, I presented four derivations of the formula for motional emf. Such physics derivations involve the construction of explanatory frameworks involving diagrams and mathematical models. Although textbooks devote considerable space to such explanations, many teachers and students spend their time on worksheets, end-of-chapter problems, and the like. The book is reduced to a bank of solved (i.e., example) and unsolved (i.e., homework) questions, along with equations in colored boxes that presumably are to be used to answer those questions. Such an approach encourages fragmentation of knowledge, the view that there is only one right answer to a problem with the goal of physics being to find that answer (neatly boxed of course), and the inability to reason about even a slightly different (much less a novel) situation. If we are to develop scientific literacy, significant course time must be devoted to explaining the structure of and support for the models and equations we use.

  14. Generalized Derivations and Bilocal Jordan Derivations of Nest Algebras

    Directory of Open Access Journals (Sweden)

    Dangui Yan

    2011-01-01

    Full Text Available Let H be a complex Hilbert space and B(H the collection of all linear bounded operators, A is the closed subspace lattice including 0 an H, then A is a nest, accordingly alg A={T∈B(H:TN⊆N,  ∀N∈A} is a nest algebra. It will be shown that of nest algebra, generalized derivations are generalized inner derivations, and bilocal Jordan derivations are inner derivations.

  15. Acquiring Knowledge of Derived Nominals and Derived Adjectives in Context

    Science.gov (United States)

    Marinellie, Sally A.; Kneile, Lynn A.

    2012-01-01

    Purpose: This research investigated children's ability to acquire semantic and syntactic knowledge of derived nominals and derived adjectives in the context of short passages. The study also investigated the relation of morphological awareness and the ability to acquire knowledge of derived words in context. Method: A total of 106 children in…

  16. Experts' Understanding of Partial Derivatives Using the Partial Derivative Machine

    Science.gov (United States)

    Roundy, David; Weber, Eric; Dray, Tevian; Bajracharya, Rabindra R.; Dorko, Allison; Smith, Emily M.; Manogue, Corinne A.

    2015-01-01

    Partial derivatives are used in a variety of different ways within physics. Thermodynamics, in particular, uses partial derivatives in ways that students often find especially confusing. We are at the beginning of a study of the teaching of partial derivatives, with a goal of better aligning the teaching of multivariable calculus with the needs of…

  17. Elevation Derivatives for National Applications

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Elevation Derivatives for National Applications (EDNA) is a seamless, nationwide, multi-layered three-dimensional (3D) hydrologic database derived from a version of...

  18. Elevation Derivatives for National Applications

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Elevation Derivatives for National Applications (EDNA) is a seamless, nationwide, multi-layered three-dimensional (3D) hydrologic database derived from a version of...

  19. Algae Derived Biofuel

    Energy Technology Data Exchange (ETDEWEB)

    Jahan, Kauser [Rowan Univ., Glassboro, NJ (United States)

    2015-03-31

    One of the most promising fuel alternatives is algae biodiesel. Algae reproduce quickly, produce oils more efficiently than crop plants, and require relatively few nutrients for growth. These nutrients can potentially be derived from inexpensive waste sources such as flue gas and wastewater, providing a mutual benefit of helping to mitigate carbon dioxide waste. Algae can also be grown on land unsuitable for agricultural purposes, eliminating competition with food sources. This project focused on cultivating select algae species under various environmental conditions to optimize oil yield. Membrane studies were also conducted to transfer carbon di-oxide more efficiently. An LCA study was also conducted to investigate the energy intensive steps in algae cultivation.

  20. Original and Derived Judgment

    DEFF Research Database (Denmark)

    Foss, Kirsten; Foss, Nicolai Juul; Klein, Peter G.

    Recent work links entrepreneurship to the economic theory of firm using the Knightian concept of entrepreneurship as judgment. When judgment is complementary to other as-sets, and these assets or their services are traded in well-functioning markets, it makes sense for entrepreneurs to hire labor...... and own assets. The entrepreneur's role, then, is to arrange or organize the human and capital assets under his control. We extend this Knightian concept of the firm by developing a theory of delegation under Knightian uncertainty. What we call original judgment belongs exclusively to owners, but owners...... may delegate a wide range of decision rights to subordinates, who exercise derived judgment. We call these employees "proxy-entrepreneurs," and ask how the firm's or-ganizational structure — its formal and informal systems of rewards and punishments, rules for settling disputes and renegotiating...

  1. On Q-derived polynomials

    NARCIS (Netherlands)

    R.J. Stroeker (Roel)

    2002-01-01

    textabstractA Q-derived polynomial is a univariate polynomial, defined over the rationals, with the property that its zeros, and those of all its derivatives are rational numbers. There is a conjecture that says that Q-derived polynomials of degree 4 with distinct roots for themselves and all their

  2. On Q-derived polynomials

    NARCIS (Netherlands)

    R.J. Stroeker (Roel)

    2006-01-01

    textabstractA Q-derived polynomial is a univariate polynomial, defined over the rationals, with the property that its zeros, and those of all its derivatives are rational numbers. There is a conjecture that says that Q-derived polynomials of degree 4 with distinct roots for themselves and all their

  3. Local derivations on Jordan triples

    OpenAIRE

    Mackey, Michael

    2013-01-01

    R. V. Kadison (J. Algebra 130 (1990) 494–509) defined the notion of local derivation on an algebra and proved that every continuous local derivation on a von Neumann algebra is a derivation. We provide the analogous result in the setting of Jordan triples.

  4. Bicyclic glutamic acid derivatives.

    Science.gov (United States)

    Meyer, Udo; Bisel, Philippe; Weckert, Edgar; Frahm, August Wilhelm

    2006-05-15

    For the second-generation asymmetric synthesis of the trans-tris(homoglutamic) acids via Strecker reaction of chiral ketimines, the cyanide addition as the key stereodifferentiating step produces mixtures of diastereomeric alpha-amino nitrile esters the composition of which is independent of the reaction temperature and the type of the solvent, respectively. The subsequent hydrolysis is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic glutamic acid derivatives, gained from in situ stereomer differentiating cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters. Separation was achieved by CC. The pure secondary trans-alpha-amino alpha-carbamoyl-gamma-esters cyclise on heating and treatment with concentrated H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha-amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular primary alpha-amino imides. The configuration of all compounds was completely established by NMR methods, CD-spectra, and by X-ray analyses of the (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1-phenylethylamino)cyclopentanecarboxamide.

  5. Data Derivation Investigation

    Directory of Open Access Journals (Sweden)

    S. S. Kadam

    2014-06-01

    Full Text Available Malicious software is a major issue in today’s computer world. Such software can silently reside in user’s computer and can easily interact with computing resources. It is necessary to improve the honesty of host and its system data. For improvement in security and honesty of host, this work is introduced. This mechanism ensures the correct origin or provenance of critical system information and prevents utilization of host resources by malware. Using this mechanism the source where a piece of data is generated can be identified. A cryptographic origin approach ensures system properties and system- data integrity at kernel level. A frame work is used for restricting outbound malware traffic. This frame work identifies network activities of malware. This frame work can be used as powerful personal firewall for investigating outgoing traffic of a host. Specifically, our derivation verification scheme requires outgoing network packets to flow through a checkpoint on a host, to obtain proper origin proofs for later verification.

  6. Data Derivation Investigation

    Directory of Open Access Journals (Sweden)

    S. S. Kadam

    2015-11-01

    Full Text Available Malicious software is a major issue in today’s computer world. Such software can silently reside in user’s computer and can easily interact with computing resources. It is necessary to improve the honesty of host and its system data. For improvement in security and honesty of host, this work is introduced. This mechanism ensures the correct origin or provenance of critical system information and prevents utilization of host resources by malware. Using this mechanism the source where a piece of data is generated can be identified. A cryptographic origin approach ensures system  properties and system- data integrity at kernel level. A frame work is used for restricting outbound malware traffic. This frame work identifies network activities of malware. This frame work can be used as powerful personal firewall for investigating outgoing traffic of a host. Specifically, our derivation verification scheme requires outgoing network packets to flow through a checkpoint on a host, to obtain proper origin proofs for later verification.

  7. Piroxicam derivatives THz classification

    Science.gov (United States)

    Sterczewski, Lukasz A.; Grzelczak, Michal P.; Nowak, Kacper; Szlachetko, Bogusław; Plinska, Stanislawa; Szczesniak-Siega, Berenika; Malinka, Wieslaw; Plinski, Edward F.

    2016-02-01

    In this paper we report a new approach to linking the terahertz spectral shapes of drug candidates having a similar molecular structure to their chemical and physical parameters. We examined 27 newly-synthesized derivatives of a well-known nonsteroidal anti-inflammatory drug Piroxicam used for treatment of inflammatory arthritis and chemoprevention of colon cancer. The testing was carried out by means of terahertz pulsed spectroscopy (TPS). Using chemometric techniques we evaluated their spectral similarity in the terahertz range and attempted to link the position on the principal component analysis (PCA) score map to the similarity of molecular descriptors. A simplified spectral model preserved 75% and 85.1% of the variance in 2 and 3 dimensions respectively, compared to the input 1137. We have found that in 85% of the investigated samples a similarity of the physical and chemical parameters corresponds to a similarity in the terahertz spectra. The effects of data preprocessing on the generated maps are also discussed. The technique presented can support the choice of the most promising drug candidates for clinical trials in pharmacological research.

  8. Experts' understanding of partial derivatives using the Partial Derivative Machine

    CERN Document Server

    Roundy, David; Dray, Tevian; Manogue, Corinne A; Weber, Eric

    2014-01-01

    Partial derivatives are used in a variety of different ways within physics. Most notably, thermodynamics uses partial derivatives in ways that students often find confusing. As part of a collaboration with mathematics faculty, we are at the beginning of a study of the teaching of partial derivatives, a goal of better aligning the teaching of multivariable calculus with the needs of students in STEM disciplines. As a part of this project, we have performed a pilot study of expert understanding of partial derivatives across three disciplines: physics, engineering and mathematics. Our interviews made use of the Partial Derivative Machine (PDM), which is a mechanical system featuring four observable and controllable properties, of which any two are independent. Using the PDM, we probed expert understanding of partial derivatives in an experimental context in which there is not a known functional form. Through these three interviews, we found that the mathematicians exhibited a striking difference in their underst...

  9. Derivations, Products of Derivations, and Commutativity in Near-rings

    Institute of Scientific and Technical Information of China (English)

    Howard E. Bell; Nurcan Argac

    2001-01-01

    For a zero-symmetric 3-prime near-ring N, we study three kinds of conditions: (a) conditions involving two derivations d1, d2 which imply that d1 = 0 or d2 = 0; (b) conditions involving derivations which force (N, +) to be abelian or N to be a commutative ring; (c) the condition that dn (S) is multiplicatively central for some derivation d and subset S of N.

  10. Design and pre-clinical profiling of a Plasmodium falciparum MSP-3 derived component for a multi-valent virosomal malaria vaccine

    Directory of Open Access Journals (Sweden)

    Boato Francesca

    2009-12-01

    Full Text Available Abstract Background Clinical profiling of two components for a synthetic peptide-based virosomal malaria vaccine has yielded promising results, encouraging the search for additional components for inclusion in a final multi-valent vaccine formulation. This report describes the immunological characterization of linear and cyclized synthetic peptides comprising amino acids 211-237 of Plasmodium falciparum merozoite surface protein (MSP-3. Methods These peptides were coupled to phosphatidylethanolamine (PE; the conjugates were intercalated into immunopotentiating reconstituted influenza virosomes (IRIVs and then used for immunizations in mice to evaluate their capacity to elicit P. falciparum cross-reactive antibodies. Results While all MSP-3-derived peptides were able to elicit parasite-binding antibodies, stabilization of turn structures by cyclization had no immune-enhancing effect. Therefore, further pre-clinical profiling was focused on FB-12, a PE conjugate of the linear peptide. Consistent with the immunological results obtained in mice, all FB-12 immunized rabbits tested seroconverted and consistently elicited antibodies that interacted with blood stage parasites. It was observed that a dose of 50 μg was superior to a dose of 10 μg and that influenza pre-existing immunity improved the immunogenicity of FB-12 in rabbits. FB-12 production was successfully up-scaled and the immunogenicity of a vaccine formulation, produced according to the rules of Good Manufacturing Practice (GMP, was tested in mice and rabbits. All animals tested developed parasite-binding antibodies. Comparison of ELISA and IFA titers as well as the characterization of a panel of anti-FB-12 monoclonal antibodies indicated that at least the majority of antibodies specific for the virosomally formulated synthetic peptide were parasite cross-reactive. Conclusion These results reconfirm the suitability of IRIVs as a carrier/adjuvant system for the induction of strong humoral

  11. Nonholonomic constraints with fractional derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Tarasov, Vasily E [Skobeltsyn Institute of Nuclear Physics, Moscow State University, Moscow 119992 (Russian Federation); Zaslavsky, George M [Courant Institute of Mathematical Sciences, New York University, 251 Mercer St, New York, NY 10012 (United States)

    2006-08-04

    We consider the fractional generalization of nonholonomic constraints defined by equations with fractional derivatives and provide some examples. The corresponding equations of motion are derived using variational principle. We prove that fractional constraints can be used to describe the evolution of dynamical systems in which some coordinates and velocities are related to velocities through a power-law memory function.

  12. Thiamine phosphorylated derivatives and bioelectrogenesis.

    Science.gov (United States)

    Schoffeniels, E

    1983-09-01

    Kinetic as well as thermodynamic considerations favour the idea that the change in sodium conductance explaining the action potential, must result from a bimolecular reaction system. The fact that thiamine phosphorylated derivatives are associated with the specific protein forming the sodium channel could well mean that these thiamine derivatives and more specifically thiamine triphosphate are directly involved in the conductance change.

  13. Phosphorus derivatives of salicylic acid

    Science.gov (United States)

    Chvertkina, L. V.; Khoklov, P. S.; Mironov, Vladimir F.

    1992-10-01

    The present state of work on the methods of synthesis, chemical properties, and practical applications of phosphorus-containing derivatives of salicylic acid has been reviewed. The characteristics of the chemical transformations of cyclic and acyclic phosphorus derivatives of salicylic acid related to the coordination state of the phosphorus atom have been examined. The bibliography includes 158 references.

  14. Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations.

    Science.gov (United States)

    Zhou, Ziniu; Scott, William L; O'Donnell, Martin J

    2016-03-15

    A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an α-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six- and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields.

  15. Tame-wild dichotomy for derived categories

    OpenAIRE

    Bekkert, Viktor I.; Drozd, Yuriy A.

    2003-01-01

    We prove that every finite dimensional algebra over an algebraically closed field is either derived tame or derived wild. The proof is based on the technique of matrix problems (boxes and reduction algorithm). It implies, in particular, that any degeneration of a derived wild algebra is derived wild; respectively, any deformation of a derived tame algebra is derived tame.

  16. Derivatives of Frobenius and Derivatives of Hodge weights

    OpenAIRE

    2016-01-01

    In this paper we study the derivatives of Frobenius and the derivatives of Hodge weights for families of Galois representations with triangulations. We generalize the Fontaine-Mazur $\\CL$-invariant and use it to build a formula which is a generalization of the Greenberg-Stevens-Colmez formula. For the purpose of proving this formula we show two auxiliary results called projection vanishing property and "projection vanishing implying $\\CL$-invariants" property.

  17. Cytochalasin derivatives from a jellyfish-derived fungus Phoma sp.

    Science.gov (United States)

    Kim, Eun La; Wang, Haibo; Park, Ju Hee; Hong, Jongki; Choi, Jae Sue; Im, Dong Soon; Chung, Hae Young; Jung, Jee H

    2015-01-01

    Four new cytochalasin derivatives (1-4), together with proxiphomin (5), were isolated from a jellyfish-derived fungus Phoma sp. The planar structures and relative stereochemistry were established by analysis of 1D and 2D NMR data. The absolute configuration was defined by the modified Mosher's method. The compounds showed moderate cytotoxicity against a small panel of human solid tumor cell lines (A549, KB, and HCT116).

  18. Twisted derivations of Hopf algebras

    CERN Document Server

    Davydov, Alexei

    2012-01-01

    In the paper we introduce the notion of twisted derivation of a bialgebra. Twisted derivations appear as infinitesimal symmetries of the category of representations. More precisely they are infinitesimal versions of twisted automorphisms of bialgebras. Twisted derivations naturally form a Lie algebra (the tangent algebra of the group of twisted automorphisms). Moreover this Lie algebra fits into a crossed module (tangent to the crossed module of twisted automorphisms). Here we calculate this crossed module for universal enveloping algebras and for the Sweedler's Hopf algebra.

  19. Jordan-H\\"older theorems for derived categories of derived discrete algebras

    OpenAIRE

    Qin, Yongyun

    2015-01-01

    For any positive integer $n$, $n$-derived-simple derived discrete algebras are classified up to derived equivalence. Furthermore, the Jordan-H\\"older theorems for all kinds of derived categories of derived discrete algebras are obtained.

  20. View-based Propagator Derivation

    CERN Document Server

    Schulte, Christian

    2009-01-01

    When implementing a propagator for a constraint, one must decide about variants: When implementing min, should one also implement max? Should one implement linear constraints both with unit and non-unit coefficients? Constraint variants are ubiquitous: implementing them requires considerable (if not prohibitive) effort and decreases maintainability, but will deliver better performance than resorting to constraint decomposition. This paper shows how to use views to derive perfect propagator variants. A model for views and derived propagators is introduced. Derived propagators are proved to be indeed perfect in that they inherit essential properties such as correctness and domain and bounds consistency. Techniques for systematically deriving propagators such as transformation, generalization, specialization, and type conversion are developed. The paper introduces an implementation architecture for views that is independent of the underlying constraint programming system. A detailed evaluation of views implement...

  1. Higher Derivatives and Canonical Formalism

    OpenAIRE

    HAMAMOTO, Shinji

    1995-01-01

    A canonical formalism for higher-derivative theories is presented on the basis of Dirac's method for constrained systems. It is shown that this formalism shares a path integral expression with Ostrogradski's canonical formalism.

  2. Derivations of generalized Weyl algebras

    Institute of Scientific and Technical Information of China (English)

    SU; Yucai(苏育才)

    2003-01-01

    A class of the associative and Lie algebras A[D] = A × F[D] of Weyl type are studied, where Ais a commutative associative algebra with an identity element over a field F of characteristic zero, and F[D] isthe polynomial algebra of a finite dimensional commutative subalgebra of locally finite derivations of A suchthat A is D-simple. The derivations of these associative and Lie algebras are precisely determined.

  3. Sol-gel derived sorbents

    Science.gov (United States)

    Sigman, Michael E.; Dindal, Amy B.

    2003-11-11

    Described is a method for producing copolymerized sol-gel derived sorbent particles for the production of copolymerized sol-gel derived sorbent material. The method for producing copolymerized sol-gel derived sorbent particles comprises adding a basic solution to an aqueous metal alkoxide mixture for a pH.ltoreq.8 to hydrolyze the metal alkoxides. Then, allowing the mixture to react at room temperature for a precalculated period of time for the mixture to undergo an increased in viscosity to obtain a desired pore size and surface area. The copolymerized mixture is then added to an immiscible, nonpolar solvent that has been heated to a sufficient temperature wherein the copolymerized mixture forms a solid upon the addition. The solid is recovered from the mixture, and is ready for use in an active sampling trap or activated for use in a passive sampling trap.

  4. Variational approach and deformed derivatives

    Science.gov (United States)

    Weberszpil, J.; Helayël-Neto, J. A.

    2016-05-01

    Recently, we have demonstrated that there exists a possible relationship between q-deformed algebras in two different contexts of Statistical Mechanics, namely, the Tsallis' framework and the Kaniadakis' scenario, with a local form of fractional-derivative operators for fractal media, the so-called Hausdorff derivatives, mapped into a continuous medium with a fractal measure. Here, in this paper, we present an extension of the traditional calculus of variations for systems containing deformed-derivatives embedded into the Lagrangian and the Lagrangian densities for classical and field systems. The results extend the classical Euler-Lagrange equations and the Hamiltonian formalism. The resulting dynamical equations seem to be compatible with those found in the literature, specially with mass-dependent and with nonlinear equations for systems in classical and quantum mechanics. Examples are presented to illustrate applications of the formulation. Also, the conserved ​Noether current is worked out.

  5. Variational Approach and Deformed Derivatives

    CERN Document Server

    Weberszpil, José

    2015-01-01

    Recently, we have demonstrated that there exists a possible relationship between q-deformed algebras in two different contexts of Statistical Mechanics, namely, the Tsallis' framework and the Kaniadakis' scenario, with a local form of fractional-derivative operators for fractal media, the so-called Hausdorff derivatives, mapped into a continuous medium with a fractal measure. Here, in this paper, we present an extension of the traditional calculus of variations for systems containing deformed-derivatives embedded into the Lagrangian and the Lagrangian densities for classical and field systems. The results extend the classical Euler-Lagrange equations and the Hamiltonian formalism. The resulting dynamical equations seem to be compatible with those found in the literature, specially with mass-dependent and with nonlinear equations for systems in classical and quantum mechanics. Examples are presented to illustrate applications of the formulation. Also, the conserved Nether current, are worked out.

  6. Fractional Derivatives in Dengue Epidemics

    Science.gov (United States)

    Pooseh, Shakoor; Rodrigues, Helena Sofia; Torres, Delfim F. M.

    2011-09-01

    We introduce the use of fractional calculus, i.e., the use of integrals and derivatives of non-integer (arbitrary) order, in epidemiology. The proposed approach is illustrated with an outbreak of dengue disease, which is motivated by the first dengue epidemic ever recorded in the Cape Verde islands off the coast of west Africa, in 2009. Numerical simulations show that in some cases the fractional models fit better the reality when compared with the standard differential models. The classical results are obtained as particular cases by considering the order of the derivatives to take an integer value.

  7. Risk Factors in Derivatives Markets

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2015-02-01

    Full Text Available The objective of the article is to analyse and present the classification of risks actual to derivative securities. The analysis is based on classical and modern literature findings and analysis of newest statistical data. The analysis led to the conclusion, that the main risks typical for derivatives contracts and their traders are market risk, liquidity risk, credit and counterparty risk, legal risk and transactions risk. Pricing risk and systemic risk is also quite important. The analysis showed that market risk is the most important kind of risk that in many situations influences the level of remaining risks.

  8. Fractional derivatives in Dengue epidemics

    CERN Document Server

    Pooseh, Shakoor; Torres, Delfim F M

    2011-01-01

    We introduce the use of fractional calculus, i.e., the use of integrals and derivatives of non-integer (arbitrary) order, in epidemiology. The proposed approach is illustrated with an outbreak of dengue disease, which is motivated by the first dengue epidemic ever recorded in the Cape Verde islands off the coast of west Africa, in 2009. Numerical simulations show that in some cases the fractional models fit better the reality when compared with the standard differential models. The classical results are obtained as particular cases by considering the order of the derivatives to take an integer value.

  9. Synthesis of Novel 3-Aryl Isoindolinone Derivatives

    Institute of Scientific and Technical Information of China (English)

    HU Chen-ming; ZHENG Lian-you; PEI Ya-zhong; BAI Xu

    2013-01-01

    A library of novel 3-aryl isoindolinone derivatives with aromatic amino acid derivative fragments was designed and synthesized.Two synthetic routes were employed to construct 3-aryl isoindolinone ring system for different amino acid derivatives.

  10. Asymptotic aspect of derivations in Banach algebras.

    Science.gov (United States)

    Roh, Jaiok; Chang, Ick-Soon

    2017-01-01

    We prove that every approximate linear left derivation on a semisimple Banach algebra is continuous. Also, we consider linear derivations on Banach algebras and we first study the conditions for a linear derivation on a Banach algebra. Then we examine the functional inequalities related to a linear derivation and their stability. We finally take central linear derivations with radical ranges on semiprime Banach algebras and a continuous linear generalized left derivation on a semisimple Banach algebra.

  11. On Generalized Derivations in Nearrings

    Directory of Open Access Journals (Sweden)

    Mohd Rais Khan

    2013-01-01

    Full Text Available The aim of this paper is to investigate some results of nearrings satisfying certain identities involving generalized derivations. Furthermore, we give some examples to demonstrate the restrictions imposed on the hypothesis of various results which are not superfluous.

  12. Bounded Densities and Their Derivatives

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, V.

    2009-01-01

    This paper describes how one can compute interval-valued statistical measures given limited information about the underlying distribution. The particular focus is on a bounded derivative of a probability density function and its combination with other available statistical evidence for computing ...

  13. Derived Categories of BHK Mirrors

    CERN Document Server

    Favero, David

    2016-01-01

    We prove a derived analogue to the results of Borisov, Clarke, Kelly, and Shoemaker on the birationality of Berglund-Hubsch-Krawitz mirrors. Heavily bootstrapping off work of Seidel and Sheridan, we obtain Homological Mirror Symmetry for Berglund-Hubsch-Krawitz mirror pencils to hypersurfaces in projective space.

  14. Push-outs of derivations

    DEFF Research Database (Denmark)

    Grønbæk, Niels

    2008-01-01

    Let A be a Banach algebra and let X be a Banach A-bimodule. In studying H¹(A,X) it is often useful to extend a given derivation D: A->X to a Banach algebra B containing A as an ideal, thereby exploiting (or establishing) hereditary properties. This is usually done using (bounded/unbounded) approx......Let A be a Banach algebra and let X be a Banach A-bimodule. In studying H¹(A,X) it is often useful to extend a given derivation D: A->X to a Banach algebra B containing A as an ideal, thereby exploiting (or establishing) hereditary properties. This is usually done using (bounded....../unbounded) approximate identities to obtain the extension as a limit of operators b->D(ba)-b.D(a), a in A, in an appropriate operator topology, the main point in the proof being to show that the limit map is in fact a derivation. In this paper we make clear which part of this approach is analytic and which algebraic...... by presenting an algebraic scheme that gives derivations in all situations at the cost of enlarging the module. We use our construction to give improvements and shorter proofs of some results from the literature and to give a necessary and sufficient condition that biprojectivity and biflatness are inherited...

  15. Starches and their sugar derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Leroy, P. (Societe Roquette Freres, 62 - Lestrem (France))

    1982-12-01

    After reviewing the composition of natural starches and their uses, the author deals with starch transformation processes, either by physical processing or chemical treatment. He describes particularly the various starch hydrolysis products together with their derivatives, amongst which are sought products which could replace sugar.

  16. Derivations of certain operator algebras

    Directory of Open Access Journals (Sweden)

    Jiankui Li

    2000-01-01

    conditions under which any derivation δ from into L(H must be inner. The conditions include (1 H−≠H, (2 0+≠0, (3 there is a nontrivial projection in which is in , and (4 δ is norm continuous. We also give some pplications.

  17. MCR Synthesis of Praziquantel Derivatives

    NARCIS (Netherlands)

    Liu, Haixia; William, Samia; Herdtweck, Eberhardt; Botros, Sanaa; Domling, Alexander

    2012-01-01

    Schistosomiasis, a high volume neglected tropical disease affecting more than 200 million people worldwide, can only be effectively treated by the tetrahydroisoquinoline drug praziquantel (PZQ). Herein, we describe an efficient approach to access PZQ derivatives by the Ugi 4-component reaction follo

  18. Antileishmanial activity of polycyclic derivatives

    Directory of Open Access Journals (Sweden)

    Sarciron M.E.

    2005-09-01

    Full Text Available 33 polycyclic derivatives have been studied and tested on Leishmania donovani and L. major promastigotes. Their antileishmanial activity was assessed in vitro and an assay of their cytotoxicity was realized on human myelomonocytic cell line. The reference molecules used in the assays were amphotericin B and pentamidine. Among the compounds tested, 29 possess an antileishmanial activity; 25 of those were more active against L. donovani than amphotericin B, and nine were as effective as amphotericin B against L. major. Many synthesized derivatives were more active against L.donovani than against L. major. The cytotoxicity studies have shown that among the thirty-three derivatives tested, 12 molecules have an IC50 towards THP-1 cells about equal than that reference drugs, the 21 other derivatives are much less toxic. A 3D QSAR study was undertaken and has permitted to predict activity against L. donovani and L. major and to highlight critical area to optimize activity against the two species.

  19. Type-2 fuzzy fractional derivatives

    Science.gov (United States)

    Mazandarani, Mehran; Najariyan, Marzieh

    2014-07-01

    In this paper, we introduce two definitions of the differentiability of type-2 fuzzy number-valued functions of fractional order. The definitions are in the sense of Riemann-Liouville and Caputo derivative of order β ɛ (0, 1), and based on type-2 Hukuhara difference and H2-differentiability. The existence and uniqueness of the solutions of type-2 fuzzy fractional differential equations (T2FFDEs) under Caputo type-2 fuzzy fractional derivative and the definition of Laplace transform of type-2 fuzzy number-valued functions are also given. Moreover, the approximate solution to T2FFDE by a Predictor-Evaluate-Corrector-Evaluate (PECE) method is presented. Finally, the approximate solutions of two examples of linear and nonlinear T2FFDEs are obtained using the PECE method, and some cases of T2FFDEs applications in some sciences are presented.

  20. Derivative couplings in massive bigravity

    CERN Document Server

    Gao, Xian

    2016-01-01

    In this work we study the cosmological perturbations in massive bigravity in the presence of non-minimal derivative couplings. For this purpose we consider a specific subclass of Horndeski scalar-tensor interactions that live on the unique composite effective metric. For the viability of the model both metrics have to be dynamical. Nevertheless, the number of allowed kinetic terms is crucial. We adapt to the restriction of having one single kinetic term. After deriving the full set of equations of motion for flat Friedmann-Lemaitre-Robertson-Walker background, we study linear perturbations on top of it. We show explicitly that only four tensor, two vector and two scalar degrees of freedom propagate, one of which being the Horndeski scalar, while the Boulware-Deser ghost can be integrated out.

  1. Derivative couplings in massive bigravity

    Science.gov (United States)

    Gao, Xian; Heisenberg, Lavinia

    2016-03-01

    In this work we study the cosmological perturbations in massive bigravity in the presence of non-minimal derivative couplings. For this purpose we consider a specific subclass of Horndeski scalar-tensor interactions that live on the unique composite effective metric. For the viability of the model both metrics have to be dynamical. Nevertheless, the number of allowed kinetic terms is crucial. We adapt to the restriction of having one single kinetic term. After deriving the full set of equations of motion for flat Friedmann-Lemaitre-Robertson-Walker background, we study linear perturbations on top of it. We show explicitly that only four tensor, two vector and two scalar degrees of freedom propagate, one of which being the Horndeski scalar, while the Boulware-Deser ghost can be integrated out.

  2. Central Clearing of OTC Derivatives

    DEFF Research Database (Denmark)

    Cont, Rama; Kokholm, Thomas

    2014-01-01

    is determined by the tradeoff between multilateral netting across dealers on one hand and bilateral netting across asset classes on the other hand. We find this tradeoff to be sensitive to assumptions on heterogeneity of asset classes in terms of `riskyness' of the asset class as well as correlation...... classes are realistically taken into account. We argue that empirically plausible specifications of model parameters lead to the conclusion that central clearing does reduce interdealer exposures: the gain from multilateral netting in a CCP overweighs the loss of netting across asset classes in bilateral...... netting agreements. When a CCP exists for interest rate derivatives, adding a CCP for credit derivatives is shown to decrease overall exposures. These findings are shown to be robust to the statistical assumptions of the model as well as the choice of risk measure used to quantify exposures....

  3. Synthese asymetrique glycidol et derives

    OpenAIRE

    2014-01-01

    La steereochilie (derive du grec ,singnifiant solide ) se refere a la chimie en trois dimensions(1) puisque la plupart des molecules sont tridimensionnelles, la stereochimie s'insere de fait dans pratiquement toute la chimie dans l'evaluation de la pensée chimique ,le concept de la sereochimie est venu relativement tard , une grande paati de la chimie ,souvent excellente de 19éme siecle, l'ingnore .

  4. Phonological Derivation in Optimality Theory

    CERN Document Server

    Ellison, T M

    1994-01-01

    Optimality Theory is a constraint-based theory of phonology which allows constraints to be violated. Consequently, implementing the theory presents problems for declarative constraint-based processing frameworks. On the basis of two regularity assumptions, that candidate sets are regular and that constraints can be modelled by transducers, this paper presents and proves correct algorithms for computing the action of constraints, and hence deriving surface forms.

  5. On Derivations Of Genetic Algebras

    Science.gov (United States)

    Mukhamedov, Farrukh; Qaralleh, Izzat

    2014-11-01

    A genetic algebra is a (possibly non-associative) algebra used to model inheritance in genetics. In application of genetics this algebra often has a basis corresponding to genetically different gametes, and the structure constant of the algebra encode the probabilities of producing offspring of various types. In this paper, we find the connection between the genetic algebras and evolution algebras. Moreover, we prove the existence of nontrivial derivations of genetic algebras in dimension two.

  6. Clearing and settlement of exchange traded derivatives

    OpenAIRE

    John McPartland

    2009-01-01

    Derivatives are a class of financial instruments that derive their value from some underlying commodity, security, index, or other asset. Futures and options are common forms of derivatives. This article explains how clearing and settlement systems for exchange traded derivatives work.

  7. Derivation of Hamiltonians for accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Symon, K.R.

    1997-09-12

    In this report various forms of the Hamiltonian for particle motion in an accelerator will be derived. Except where noted, the treatment will apply generally to linear and circular accelerators, storage rings, and beamlines. The generic term accelerator will be used to refer to any of these devices. The author will use the usual accelerator coordinate system, which will be introduced first, along with a list of handy formulas. He then starts from the general Hamiltonian for a particle in an electromagnetic field, using the accelerator coordinate system, with time t as independent variable. He switches to a form more convenient for most purposes using the distance s along the reference orbit as independent variable. In section 2, formulas will be derived for the vector potentials that describe the various lattice components. In sections 3, 4, and 5, special forms of the Hamiltonian will be derived for transverse horizontal and vertical motion, for longitudinal motion, and for synchrobetatron coupling of horizontal and longitudinal motions. Hamiltonians will be expanded to fourth order in the variables.

  8. Generalized derivations and general relativity

    CERN Document Server

    Heller, M; Pysiak, L; Sasin, W

    2013-01-01

    We construct differential geometry (connection, curvature, etc.) based on generalized derivations of an algebra A. Such a derivation, introduced by Bresar in 1991, is given by a linear mapping u: A -> A such that there exists a usual derivation d of A satisfying the generalized Leibniz rule u(a b) = u(a) b + a d(b) for all a,b in A. The generalized geometry "is tested" in the case of the algebra of smooth functions on a manifold. We then apply this machinery to study the generalized general relativity. We define the Einstein-Hilbert action and deduce from it Einstein's field equations. We show that for a special class of metrics containing, besides the usual metric components, only one non-zero term, the action reduces to O'Hanlon action that is a Brans-Dicke action with potential and with the parameter \\omega equal to zero. We also show that the generalized Einstein equations (with zero energy-stress tensor) are equivalent to those of the Kaluza-Klein theory satisfying a "modified cylinder condition" and hav...

  9. Push-Outs of Derivations

    Indian Academy of Sciences (India)

    Niels Grønbæk

    2008-05-01

    Let $\\mathfrak{A}$ be a Banach algebra and let be a Banach $\\mathfrak{A}$-bimodule. In studying $\\mathcal{H}^1(\\mathfrak{A},X)$ it is often useful to extend a given derivation $D:\\mathfrak{A}→ X$ to a Banach algebra $\\mathfrak{B}$ containing $\\mathfrak{A}$ as an ideal, thereby exploiting (or establishing) hereditary properties. This is usually done using (bounded/unbounded) approximate identities to obtain the extension as a limit of operators $b\\mapsto D(ba)-b.D(a), a\\in\\mathfrak{A}$ in an appropriate operator topology, the main point in the proof being to show that the limit map is in fact a derivation. In this paper we make clear which part of this approach is analytic and which algebraic by presenting an algebraic scheme that gives derivations in all situations at the cost of enlarging the module. We use our construction to give improvements and shorter proofs of some results from the literature and to give a necessary and sufficient condition that biprojectivity and biflatness is inherited to ideals.

  10. Whither the common law derivative action

    OpenAIRE

    Yap, JL

    2009-01-01

    The common law derivative action was developed as a result of decades of case law in common law jurisdictions. Hong Kong and Singapore continue to retain the common law derivative action within their respective legal frameworks, despite both having enacted statutory derivative actions. This paper considers the situations in which the common law derivative action continues to have practical application in each of these jurisdictions. It then considers whether the common law derivative acti...

  11. Hypoxic radiosensitizers: substituted styryl derivatives.

    Science.gov (United States)

    Nudelman, A; Falb, E; Odesa, Y; Shmueli-Broide, N

    1994-10-01

    A number of novel styryl epoxides, N-substituted-styryl-ethanolamines, N-mono and N,N'-bis-(2-hydroxyethyl)-cinnamamides--analogues to the known radiosensitizers RSU-1069, pimonidazole and etanidazole--display selective hypoxic radiosensitizing activity. The styryl group, especially when substituted by electron withdrawing groups, was found to be bioisosteric to the nitroimidazolyl functionality. The most active derivative 2-(2'-nitrophenyl)ethen-1-yl-oxirane 8a displayed a sensitizer enhancement ratio (SER) of 5 relative to misonidazole.

  12. Asymptotic vacua with higher derivatives

    Directory of Open Access Journals (Sweden)

    Spiros Cotsakis

    2016-04-01

    Full Text Available We study limits of vacuum, isotropic universes in the full, effective, four-dimensional theory with higher derivatives. We show that all flat vacua as well as general curved ones are globally attracted by the standard, square root scaling solution at early times. Open vacua asymptote to horizon-free, Milne states in both directions while closed universes exhibit more complex logarithmic singularities, starting from initial data sets of a possibly smaller dimension. We also discuss the relation of our results to the asymptotic stability of the passage through the singularity in ekpyrotic and cyclic cosmologies.

  13. Asymptotic vacua with higher derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Cotsakis, Spiros, E-mail: skot@aegean.gr [Department of Mathematics, American University of the Middle East, P.O. Box 220 Dasman, 15453 (Kuwait); Kadry, Seifedine, E-mail: Seifedine.Kadry@aum.edu.kw [Department of Mathematics, American University of the Middle East, P.O. Box 220 Dasman, 15453 (Kuwait); Kolionis, Georgios, E-mail: gkolionis@aegean.gr [Research group of Geometry, Dynamical Systems and Cosmology, University of the Aegean, Karlovassi 83200, Samos (Greece); Tsokaros, Antonios, E-mail: atsok@aegean.gr [Research group of Geometry, Dynamical Systems and Cosmology, University of the Aegean, Karlovassi 83200, Samos (Greece)

    2016-04-10

    We study limits of vacuum, isotropic universes in the full, effective, four-dimensional theory with higher derivatives. We show that all flat vacua as well as general curved ones are globally attracted by the standard, square root scaling solution at early times. Open vacua asymptote to horizon-free, Milne states in both directions while closed universes exhibit more complex logarithmic singularities, starting from initial data sets of a possibly smaller dimension. We also discuss the relation of our results to the asymptotic stability of the passage through the singularity in ekpyrotic and cyclic cosmologies.

  14. Cosmology with Nonminimal Derivative Couplings

    CERN Document Server

    Amendola, L

    1993-01-01

    We study a theory which generalizes the nonminimal coupling of matter to gravity by including derivative couplings. This leads to several interesting new dynamical phenomena in cosmology. In particular, the range of parameters in which inflationary attractors exist is greatly expanded. We also numerically integrate the field equations and draw the phase space of the model in second order approximation. The model introduced here may display different inflationary epochs, generating a non-scale-invariant fluctuation spectrum without the need of two or more fields. Finally, we comment on the bubble spectrum arising during a first-order phase transition occurring in our model.

  15. Mechanized derivation of linear invariants.

    Science.gov (United States)

    Cavender, J A

    1989-05-01

    Linear invariants, discovered by Lake, promise to provide a versatile way of inferring phylogenies on the basis of nucleic acid sequences (the method that he called "evolutionary parsimony"). A semigroup of Markov transition matrices embodies the assumptions underlying the method, and alternative semigroups exist. The set of all linear invariants may be derived from the semigroup by using an algorithm described here. Under assumptions no stronger than Lake's, there are greater than 50 independent linear invariants for each of the 15 rooted trees linking four species.

  16. Noether theorems and higher derivatives

    CERN Document Server

    Townsend, Paul K

    2016-01-01

    A simple proof of Noether's first theorem involves the promotion of a constant symmetry parameter $\\epsilon$ to an arbitrary function of time; the Noether charge $Q$ is then the coefficient of $\\dot\\epsilon$ in the variation of the action. Here we examine the validity of this proof for Lagrangian mechanics with arbitrarily-high time derivatives, in which context "higher-level" analogs of Noether's theorem can be similarly proved, and "Noetherian charges" read off from, e.g. the coefficient of $\\ddot \\epsilon$ in the variation of the action. While $Q=0$ implies a restricted gauge invariance, an unrestricted gauge invariance requires zero Noetherian charges too. Some illustrative examples are considered.

  17. Synthesis of oleanolic disaccharide derivatives

    Institute of Scientific and Technical Information of China (English)

    Shu Chen Pei; Jian Bo Wu; Fan Lei; Shan Qian; Li Hai; Yong Wu

    2012-01-01

    Oleanolic acid 1 exists widely in food,medicinal herbs and other plants and possesses many attractive biological activities.Recently,some oleanolic derivatives were reported to have interesting anti-tumor activities.Herein,using association principle of drug design,OA disaccharide 17 was designed and synthesized by coupling α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl disaccharide moiety,which has proved to be a unique sugar sequence with strongly antitumor activity,and modified OA with a nitrile at C-17.

  18. Stable Hemiaminals: 2-Aminopyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Anna Kwiecień

    2015-08-01

    Full Text Available Stable hemiaminals can be obtained in the one-pot reaction between 2-aminopyrimidine and nitrobenzaldehyde derivatives. Ten new hemiaminals have been obtained, six of them in crystal state. The molecular stability of these intermediates results from the presence of both electron-withdrawing nitro groups as substituents on the phenyl ring and pyrimidine ring, so no further stabilisation by intramolecular interaction is required. Hemiaminal molecules possess a tetrahedral carbon atom constituting a stereogenic centre. As the result of crystallisation in centrosymmetric space groups both enantiomers are present in the crystal structure.

  19. Data derived NARMAX Dst model

    OpenAIRE

    Boynton, R J; M. A. Balikhin; S. A. Billings; Sharma, A.S.; Amariutei, O.A

    2011-01-01

    The NARMAX OLS-ERR methodology is applied to identify a mathematical model for the dynamics of the Dst index. The NARMAX OLS-ERR algorithm, which is widely used in the field of system identification, is able to identify a mathematical model for a wide class of nonlinear systems using input and output data. Solar wind-magnetosphere coupling functions, derived from analytical or data based methods, are employed as the inputs to such models and the outputs are geomagnetic indices. The newly dedu...

  20. A new procedure for N1-alkylation of imidazolidin-4-ones and its NMR characterization

    Science.gov (United States)

    Vale, Nuno; Figueiredo, Patrícia

    2016-12-01

    N1-unsubstituted imidazolidin-4-ones of primaquine (PQ) can be stabilized by N1-alkylation under basic conditions. Here we report the development, with our conditions, of peptidomimetic derivatives of PQ with L-amino acid and alkyl derivatives. The new derivatives represent potential new therapeutics for use against protozoan parasites, through enzymatic protection of aminopeptidases.

  1. Deriving Laws from Ordering Relations

    Science.gov (United States)

    Knuth, Kevin H.

    2004-01-01

    The effect of Richard T. Cox's contribution to probability theory was to generalize Boolean implication among logical statements to degrees of implication, which are manipulated using rules derived from consistency with Boolean algebra. These rules are known as the sum rule, the product rule and Bayes Theorem, and the measure resulting from this generalization is probability. In this paper, I will describe how Cox s technique can be further generalized to include other algebras and hence other problems in science and mathematics. The result is a methodology that can be used to generalize an algebra to a calculus by relying on consistency with order theory to derive the laws of the calculus. My goals are to clear up the mysteries as to why the same basic structure found in probability theory appears in other contexts, to better understand the foundations of probability theory, and to extend these ideas to other areas by developing new mathematics and new physics. The relevance of this methodology will be demonstrated using examples from probability theory, number theory, geometry, information theory, and quantum mechanics.

  2. Relative Derived Equivalences and Relative Homological Dimensions

    Institute of Scientific and Technical Information of China (English)

    Sheng Yong PAN

    2016-01-01

    Let A be a small abelian category. For a closed subbifunctor F of Ext1A (−,−), Buan has generalized the construction of Verdier’s quotient category to get a relative derived category, where he localized with respect to F-acyclic complexes. In this paper, the homological properties of relative derived categories are discussed, and the relation with derived categories is given. For Artin algebras, using relative derived categories, we give a relative version on derived equivalences induced by F-tilting complexes. We discuss the relationships between relative homological dimensions and relative derived equivalences.

  3. Penetratin and derivatives acting as antifungal agents

    NARCIS (Netherlands)

    Masman, Marcelo F.; Rodriguez, Ana M.; Raimondi, Marcela; Zacchino, Susana A.; Luiten, Paul G. M.; Somlai, Csaba; Kortvelyesi, Tamas; Penke, Botond; Enriz, Ricardo D.

    2009-01-01

    The synthesis, in vitro evaluation, and conformational study of RQIKTWFQNRRMKWKK-NH(2) (penetratin) and related derivatives acting as antifungal agents are reported. Penetratin and some of its derivatives displayed antifungal activity against the human opportunistic pathogenic standardized ATCC stra

  4. Derived bracket construction up to homotopy

    CERN Document Server

    Uchino, K

    2012-01-01

    We will introduce the notion of higher derived bracket construction in the category of operads and prove that the higher derived bracket construction of Lie operad is equivalent with the cobar construction of Leibniz operad.

  5. Derived limits for surface contamination

    CERN Document Server

    Wrixon, A D; Linsley, G S; White, D F

    1979-01-01

    Derived limits (DLs) for surface contamination were first established for use in the nuclear energy industry where a wide variety of radionuclides is encountered. They were later used in factories, hospitals, and universities, where the radionuclides used are normally fewer in number, either known or readily identifiable, and often of low toxicity. In these situations the current limits are frequently over-restrictive. This report describes a reassessment of the values in the light of more recent information on the possible pathways of exposure and the dose equivalent limits given in ICRP Publication 26. The reassessment is prompted also by the introduction of SI units. The results of the reassessment are used to produce a classification of DLs for all radionuclides for active and inactive area surfaces and for skin.

  6. Topological Derivatives in Shape Optimization

    CERN Document Server

    Novotny, Antonio André

    2013-01-01

    The topological derivative is defined as the first term (correction) of the asymptotic expansion of a given shape functional with respect to a small parameter that measures the size of singular domain perturbations, such as holes, inclusions, defects, source-terms and cracks. Over the last decade, topological asymptotic analysis has become a broad, rich and fascinating research area from both theoretical and numerical standpoints. It has applications in many different fields such as shape and topology optimization, inverse problems, imaging processing and mechanical modeling including synthesis and/or optimal design of microstructures, sensitivity analysis in fracture mechanics and damage evolution modeling. Since there is no monograph on the subject at present, the authors provide here the first account of the theory which combines classical sensitivity analysis in shape optimization with asymptotic analysis by means of compound asymptotic expansions for elliptic boundary value problems. This book is intende...

  7. Higgs Potential from Derivative Interactions

    CERN Document Server

    Quadri, A

    2016-01-01

    A formulation of the linear $\\sigma$ model with derivative interactions is studied. The theory is on-shell equivalent to the model with a quartic Higgs potential. The mass of the scalar mode only appears in the quadratic part and not in the interaction vertices, unlike in the ordinary formulation of the theory. Renormalization of the model is discussed. A natural non power-counting renormalizable extension of the theory is presented. The model is physically equivalent to the inclusion of a dimension six effective operator $\\partial_\\mu (\\Phi^\\dagger \\Phi) \\partial^\\mu (\\Phi^\\dagger \\Phi)$. The resulting UV divergences are arranged in a perturbation series around the power-counting renormalizable theory. UV completion of the non-power-counting renormalizable model through a symmetric deformation of the propagator of the massive physical scalar is addressed.

  8. Adipose-Derived Stem Cells

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Quaade, Marlene Louise; Sheikh, Søren Paludan

    2015-01-01

    Emerging evidence has shown that adipose tissue is the richest and most accessible source of mesenchymal stem cells. Many different therapies for chronic wounds exist with varying success rates. The capacity of adipose-derived stem cells (ASCs) to promote angiogenesis, secrete growth factors......, regulate the inflammatory process, and differentiate into multiple cell types makes them a potential ideal therapy for chronic wounds. The aim of this article was to review all preclinical trials using ASCs in problem wound models. A systematic search was performed and 12 studies were found where different...... chronic wound models across different animals were treated with ASCs. Different ASC sources and delivery methods were used in the described studies. Studies demonstrated improved wound healing with utilization of ASC, and this treatment modality has so far shown great potential. However, more preclinical...

  9. Iron and iron derived radicals

    Energy Technology Data Exchange (ETDEWEB)

    Borg, D.C.; Schaich, K.M.

    1987-04-01

    We have discussed some reactions of iron and iron-derived oxygen radicals that may be important in the production or treatment of tissue injury. Our conclusions challenge, to some extent, the usual lines of thought in this field of research. Insofar as they are born out by subsequent developments, the lessons they teach are two: Think fastexclamation Think smallexclamation In other words, think of the many fast reactions that can rapidly alter the production and fate of highly reactive intermediates, and when considering the impact of competitive reactions on such species, think how they affect the microenvironment (on the molecular scale) ''seen'' by each reactive molecule. 21 refs., 3 figs., 1 tab.

  10. Towards a Derivation of Space

    CERN Document Server

    Nielsen, H B

    2014-01-01

    This attempt to "derive" space is part of the Random Dynamics project. The Random Dynamics philosophy is that what we observe at our low energy level can be interpreted as some Taylor tail of the physics taking place at a higher energy level, and all the concepts like numbers, space, symmetry, as well as the known physical laws, emerge from a "fundamental world machinery" being a most general, random mathematical structure. Here we concentrate on obtaining spacetime in such a Random Dynamics way. Because of quantum mechanics, we get space identified with about half the dimension of the phase space of a very extended wave packet, which we call "the Snake". In the last section we also explain locality from diffeomorphism symmetry.

  11. Silsesquioxane-derived ceramic fibres

    Science.gov (United States)

    Hurwitz, F. I.; Farmer, S. C.; Terepka, F. M.; Leonhardt, T. A.

    1991-01-01

    Fibers formed from blends of silsesquioxane polymers were characterized to study the pyrolytic conversion of these precursors to ceramics. The morphology of fibers pyrolyzed to 1400 C revealed primarily amorphous glasses whose conversion to beta-SiC is a function of both blend composition and pyrolysis conditions. Formation of beta-SiC crystallites within the glassy phase is favored by higher than stoichiometric C/Si ratios, while carbothermal reduction of Si-O bonds to form SiC with loss of SiO and CO occurs at higher methyl/phenylpropyl silsesquioxane (lower C/Si) ratios. As the carbothermal reduction is assumed to be diffusion controlled, the fibers can serve as model systems to gain understanding of the silsesquioxane pyrolysis behavior, and therefore are useful in the development of polysilsesquioxane-derived ceramic matrices and coatings as well.

  12. Financial Derivatives (Based on Two Supports Evaluation

    Directory of Open Access Journals (Sweden)

    Tiberiu Socaciu

    2011-10-01

    Full Text Available In this paper we build a PDE like Black-Scholes equation in hypothesis of a financial derivative that is dependent on two supports (usual is dependent only on one support, like am
    option based on gold, when national currency has a great float.
    Keywords: Financial derivatives, derivatives evaluation, derivatives based on two supports, extended Itō like lemma.

  13. Polymer-Derived Ceramic Fibers

    Science.gov (United States)

    Ichikawa, Hiroshi

    2016-07-01

    SiC-based ceramic fibers are derived from polycarbosilane or polymetallocarbosilane precursors and are classified into three groups according to their chemical composition, oxygen content, and C/Si atomic ratio. The first-generation fibers are Si-C-O (Nicalon) fibers and Si-Ti-C-O (Tyranno Lox M) fibers. Both fibers contain more than 10-wt% oxygen owing to oxidation during curing and lead to degradation in strength at temperatures exceeding 1,300°C. The maximum use temperature is 1,100°C. The second-generation fibers are SiC (Hi-Nicalon) fibers and Si-Zr-C-O (Tyranno ZMI) fibers. The oxygen content of these fibers is reduced to less than 1 wt% by electron beam irradiation curing in He. The thermal stability of these fibers is improved (they are stable up to 1,500°C), but their creep resistance is limited to a maximum of 1,150°C because their C/Si atomic ratio results in excess carbon. The third-generation fibers are stoichiometric SiC fibers, i.e., Hi-Nicalon Type S (hereafter Type S), Tyranno SA, and Sylramic™ fibers. They exhibit improved thermal stability and creep resistance up to 1,400°C. Stoichiometric SiC fibers meet many of the requirements for the use of ceramic matrix composites for high-temperature structural application. SiBN3C fibers derived from polyborosilazane also show promise for structural applications, remain in the amorphous state up to 1,800°C, and have good high-temperature creep resistance.

  14. 6 CFR 7.26 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... amended, 32 CFR 2001.22, and internal DHS guidance provided by the Chief Security Officer. ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Derivative classification. 7.26 Section 7.26... INFORMATION Classified Information § 7.26 Derivative classification. (a) Derivative classification is...

  15. 32 CFR 2001.22 - Derivative classification.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Derivative classification. 2001.22 Section 2001... Identification and Markings § 2001.22 Derivative classification. (a) General. Information classified derivatively on the basis of source documents or classification guides shall bear all markings prescribed...

  16. Derivations and identities for Kravchuk polynomials

    OpenAIRE

    Bedratyuk, Leonid

    2012-01-01

    We introduce the notion of Kravchuk derivations of the polynomial algebra. We prove that any element of the kernel of the derivation gives a polynomial identity satisfied by the Kravchuk polynomials. Also, we prove that any kernel element of the basic Weitzenb\\"ok derivations yields a polynomial identity satisfied by the Kravchuk polynomials. We describe the corresponding intertwining maps.

  17. 12 CFR 563.172 - Financial derivatives.

    Science.gov (United States)

    2010-01-01

    ... underlying assets, indices, or reference rates. The most common types of financial derivatives are futures, forward commitments, options, and swaps. A mortgage derivative security, such as a collateralized mortgage... Interest Rate Risk, Investment Securities, and Derivatives Activities,” and other applicable...

  18. On the objectivity of time derivatives

    Directory of Open Access Journals (Sweden)

    Matolcsi, Tamas

    2008-02-01

    Full Text Available A four-dimensional treatment of nonrelativistic space-time gives a natural frame to deal with objective time derivatives. In this framework some well known objective time derivatives of continuum mechanics appear as Lie-derivatives. Their coordinatized forms depends on the tensorial properties of the relevant physical quantities.

  19. CPHD filter derivation for extended targets

    CERN Document Server

    Orguner, Umut

    2010-01-01

    This document derives the CPHD filter for extended targets. Only the update step is derived here. Target generated measurements, false alarms and prior are all assumed to be independent identically distributed cluster processes. We also prove here that the derived CPHD filter for extended targets reduce to PHD filter for extended targets and CPHD filter for standard targets under suitable assumptions.

  20. Covariant derivative of fermions and all that

    CERN Document Server

    Shapiro, Ilya L

    2016-01-01

    We present detailed pedagogical derivation of covariant derivative of fermions and some related expressions, including commutator of covariant derivatives and energy-momentum tensor of a free Dirac field. The text represents a part of the initial chapter of a one-semester course on semiclassical gravity.

  1. Bioactive Terpenes from Marine-Derived Fungi

    Directory of Open Access Journals (Sweden)

    Ahmed M. Elissawy

    2015-04-01

    Full Text Available Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  2. Bioactive terpenes from marine-derived fungi.

    Science.gov (United States)

    Elissawy, Ahmed M; El-Shazly, Mohamed; Ebada, Sherif S; Singab, AbdelNasser B; Proksch, Peter

    2015-04-03

    Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years' reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  3. Shock wave dynamics derivatives and related topics

    CERN Document Server

    Emanuel, George

    2012-01-01

    Working knowledge of the relations of various quantities and their derivatives across a shock wave is useful for any advanced research involving shock waves. Although these relations can be derived in principle by any diligent student of the subject, the derivations are often not trivial, and once derived, neither the approach nor the result can be confidently verified. Comprehensive and analytical, Shock Wave Dynamics: Derivatives and Related Topics includes not only the final results but also the methods, which are of great practical value as examples of mathematical procedure in this field.

  4. Jordan Higher Derivable Mappings on Rings

    Directory of Open Access Journals (Sweden)

    Mohammad Ashraf

    2014-01-01

    Full Text Available Let R be a ring. We say that a family of maps D={dn}n∈N is a Jordan higher derivable map (without assumption of additivity on R if d0=IR (the identity map on R and dn(ab+ba=∑p+q=n‍dp(adq(b+∑p+q=n‍dp(bdq(a hold for all a,b∈R and for each n∈N. In this paper, we show that every Jordan higher derivable map on a ring under certain assumptions becomes a higher derivation. As its application, we get that every Jordan higher derivable map on Banach algebra is an additive higher derivation.

  5. Representations of partial derivatives in thermodynamics

    Science.gov (United States)

    Thompson, John R.; Manogue, Corinne A.; Roundy, David J.; Mountcastle, Donald B.

    2012-02-01

    One of the mathematical objects that students become familiar with in thermodynamics, often for the first time, is the partial derivative of a multivariable function. The symbolic representation of a partial derivative and related quantities present difficulties for students in both mathematical and physical contexts, most notably what it means to keep one or more variables fixed while taking the derivative with respect to a different variable. Material properties are themselves written as partial derivatives of various state functions (e.g., compressibility is a partial derivative of volume with respect to pressure). Research in courses at the University of Maine and Oregon State University yields findings related to the many ways that partial derivatives can be represented and interpreted in thermodynamics. Research has informed curricular development that elicits many of the difficulties using different representations (e.g., geometric) and different contexts (e.g., connecting partial derivatives to specific experiments).

  6. Option Derivatives in Electricity Hedging

    Directory of Open Access Journals (Sweden)

    P. Pavlátka

    2010-01-01

    Full Text Available Despite the high volatility of electricity prices, there is still little demand for electricity power options, and the liquidity on the power exchanges of these power derivatives is quite low. One of the reasons is the uncertainty about how to evaluate these electricity options and about finding the right fair value of this product. Hedging of electricity is associated mainly with products such as futures and forwards. However, due to new trends in electricity trading and hedging, it is also useful to think more about options and the principles for working with them in hedging various portfolio positions and counterparties. We can quite often encounter a situation when we need to have a perfect hedge for our customer’s (end user consuming electricity portfolio, or we have to evaluate the volumetric risk (inability of a customer to predict consumption, which is very similar to selling options. Now comes the moment to compare the effects of using options or futures to hedge these open positions. From a practical viewpoint, the Black-Scholes prices appear to be the best available and the simplest method for evaluating option premiums, but there are some limitations that we have to consider.

  7. Animal-derived pharmaceutical proteins.

    Science.gov (United States)

    Redwan, el-Rashdy M

    2009-01-01

    Livestock animals have made a significant contribution to human health and well-being throughout humankind's history. A significant contribution of farm animals to human health are the longstanding use of bovine and porcine for production of insulin (for treatment of diabetes), gelatin (for pharmaceutical and other purposes), as well as horse and sheep antibody against natural venoms, toxins, drugs and microbial peptides. Gelatin being the biggest animal protein consumed in human health, follows with antibodies fragments. The chronic problem of animal-derived therapeutics, especially those of high molecular weight, is the immunogenicity induction in addition to their biosafety. However, the invertebrates and lower vertebrates donate the human being a several crucial emergency saving life small-peptides or their analogs such as Refludan, Prialt, Exendin. Not only, but the farm animals are enormously using as models for novel surgical strategies, testing of biodegradable implants and sources of tissue replacements, such as skin and heart valves. Recently, they are being harnessing as bioreactor for production of biopharmaceutical related products through gene farming with efficiency far greater than any conventional microbial or cell-culture production systems. Only 16 transgenic cows would be covering the worldwide needs from human growth hormone. The transgenic, especially animal, technology would be solving a several biopharmaceutical products disadvantages, such as cost, biosafety, immunogenicity and the availability dimensions.

  8. 21 CFR 184.1685 - Rennet (animal-derived) and chymosin preparation (fermentation-derived).

    Science.gov (United States)

    2010-04-01

    ... (fermentation-derived). 184.1685 Section 184.1685 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... (animal-derived) and chymosin preparation (fermentation-derived). (a)(1) Rennet and bovine rennet are... clear solution containing the active enzyme chymosin (E.C. 3.4.23.4). It is derived, via fermentation...

  9. Die derivation der slowenischen substantive

    Directory of Open Access Journals (Sweden)

    ]ože Toporišič

    1975-11-01

    Full Text Available Von der traditionellen slowenischen Wortbildungslehre von Substantiven mit den Suffixen (s. g. Derivation wird die betreffende Problematik so dargestellt, dass man - nach Miklošič's Vorbild - von Suffixen mit einem charakteristischen Konsonanten (oder mit eine charakteristischen Konsonantengruppe aus gehend bei verschiedenen Wortartbasen (Zeitwort, Adjektiv, Substantiv die semantischen kategorien von Wortbildungen mit »demselben« Suffix aufzählt. Aber schon bei A. Bajec (Besedotvorje slovenskega jezika, 1950 findet man auch das Kapitel »Die Suffixe nach ihren Bedeutungen, worin Suffixe für 24 Bedeutungsgruppen festgehalten sind. In der Slovenska slovnica (1956 gibt es 16, im Slovenski knjižni jezik 2 (1966 aber 13 solcher Gruppen von Suffixen. Der vorliegende Ausatz geht ebenfalls von den semantischen Kategorien aus, versucht aber die Zahl der Bedeutungskategorien, die aus verhalen, adjekvsehen oder substantiviseher Basen mit Hilfe von Suffixen gebildet werden, auf 6 grosse Gruppen zu reduzieren. Diese 6 Gruppen sind: 1. die Namen der Agenten, des Eigenschaftstragers und der Verbundenheit; 2. die Namen der Werkzeuge, 3. die Namen der Handlung, der Eigenschaft und des Zustandes, 4. die Namen der vergegenständlichten Tat oder Eigenschaft, 5. die Namen der Lokalisierung und 6. Verschiedene. Nur bei den Wortbildungen aus einer substantivischen Basis gibt es noch eine besondere, die s. g. Modifikationsbedeutungsgruppe (Feminativa und Maskulinativa, Kollektiva, Gradativa, Iuvenalia, Diminutiva, Diminutivhipokoristika, Diminutivpeirotiva und Peiorativa. - Dabei wird keine Riick­ sicht darauf genommen, ob diese Suffixe genain slowenisch oder aus anderen Sprachen übernommen sind. Die Berechtigung dafiir gibt uns nicht nur die produktive Wortbildung mit den entlehnten (nichtautochtonen Suffixen im gegenwärtigen Slowenisch, sondern (was noch wichtiger ist auch das richtige Verständnisvermögen der Sprecher für solche Wortbildungen im

  10. A derivational rephrasing experiment for question answering

    CERN Document Server

    Jacquemin, Bernard

    2010-01-01

    In Knowledge Management, variations in information expressions have proven a real challenge. In particular, classical semantic relations (e.g. synonymy) do not connect words with different parts-of-speech. The method proposed tries to address this issue. It consists in building a derivational resource from a morphological derivation tool together with derivational guidelines from a dictionary in order to store only correct derivatives. This resource, combined with a syntactic parser, a semantic disambiguator and some derivational patterns, helps to reformulate an original sentence while keeping the initial meaning in a convincing manner This approach has been evaluated in three different ways: the precision of the derivatives produced from a lemma; its ability to provide well-formed reformulations from an original sentence, preserving the initial meaning; its impact on the results coping with a real issue, ie a question answering task . The evaluation of this approach through a question answering system shows...

  11. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Kunikazu Moribe

    2011-01-01

    Full Text Available Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.

  12. Speeding up Derivative Configuration from Product Platforms

    Directory of Open Access Journals (Sweden)

    Ruben Heradio

    2014-06-01

    Full Text Available To compete in the global marketplace, manufacturers try to differentiate their products by focusing on individual customer needs. Fulfilling this goal requires that companies shift from mass production to mass customization. Under this approach, a generic architecture, named product platform, is designed to support the derivation of customized products through a configuration process that determines which components the product comprises. When a customer configures a derivative, typically not every combination of available components is valid. To guarantee that all dependencies and incompatibilities among the derivative constituent components are satisfied, automated configurators are used. Flexible product platforms provide a big number of interrelated components, and so, the configuration of all, but trivial, derivatives involves considerable effort to select which components the derivative should include. Our approach alleviates that effort by speeding up the derivative configuration using a heuristic based on the information theory concept of entropy.

  13. Weather Derivatives – Origin, Types and Application

    Directory of Open Access Journals (Sweden)

    Piotr Binkowski

    2008-03-01

    Full Text Available The number of companies that are exposed to the revenues loss risk caused by weather variability is still increasing. The businesses that are mostly exposed to weather risk are following: energy, agriculture, constructions and transport. That situation has initiated dynamic growth of weather derivatives markets as well as the awareness of the weather risk among the market participants. Presently, the weather derivatives markets evaluate rapidly in all the mature economies: USA, Asia and Europe. Constructing weather derivatives relies on qu- antifying climate factors in the form of indexes, what is quite simple task, more difficultly can be gathering precise historical data of required climate factors. Taking into consideration so far development of derivatives ñ especially the financial derivatives based on different types of indexes ñ financial market has at disposal wide range of different types of proved derivatives (futures, forward, options, swaps, which can be successfully utilised on the weather-driven markets both for hedging weather risk and speculating.

  14. Generalized derivations of Lie triple systems

    Directory of Open Access Journals (Sweden)

    Zhou Jia

    2016-01-01

    Full Text Available In this paper, we present some basic properties concerning the derivation algebra Der (T, the quasiderivation algebra QDer (T and the generalized derivation algebra GDer (T of a Lie triple system T, with the relationship Der (T ⊆ QDer (T ⊆ GDer (T ⊆ End (T. Furthermore, we completely determine those Lie triple systems T with condition QDer (T = End (T. We also show that the quasiderivations of T can be embedded as derivations in a larger Lie triple system.

  15. Biological activities of substituted trichostatic acid derivatives

    Indian Academy of Sciences (India)

    Cédric Charrier; Joëlle Roche; Jean-Pierre Gesson; Philippe Bertrand

    2009-07-01

    New substituted trichostatic acid derivatives have been synthesized and evaluated for their biological activities towards the H661 non-small lung cancer cell line. These syntheses were achieved by alkylation of propiophenones to introduce the side chain with a terminal precursor of hydroxamic acid and aminobenzamide derivatives. The first fluorinated derivatives of trichostatic acid are described, such as 6-fluoro trichostatin A, with antiproliferative activities in the micromolar range and with histone deacetylase inhibitory activity.

  16. Ophthalmic use of blood-derived products.

    Science.gov (United States)

    Nugent, Ryan B; Lee, Graham A

    2015-01-01

    There is a wide spectrum of blood-derived products that have been used in many different medical and surgical specialties with success. Blood-derived products for clinical use can be extracted from autologous or allogeneic specimens of blood, but recombinant products are also commonly used. A number of blood derivatives have been used for a wide range of ocular conditions, from the ocular surface to the retina. With stringent preparation guidelines, the potential risk of transmission of blood-borne diseases is minimized. We review blood-derived products and how they are improving the management of ocular disease.

  17. Anisotropic higher derivative gravity and inflationary universe

    CERN Document Server

    Kao, W F

    2006-01-01

    Stability analysis of the Kantowski-Sachs type universe in pure higher derivative gravity theory is studied in details. The non-redundant generalized Friedmann equation of the system is derived by introducing a reduced one dimensional generalized KS type action. This method greatly reduces the labor in deriving field equations of any complicate models. Existence and stability of inflationary solution in the presence of higher derivative terms are also studied in details. Implications to the choice of physical theories are discussed in details in this paper.

  18. Early alternative derivations of Fechner's law.

    Science.gov (United States)

    Masin, Sergio Cesare; Zudini, Verena; Antonelli, Mauro

    2009-01-01

    Historians of psychology, notably Boring, fostered Fechner's idea that Weber's law is the indispensable basis for the derivation of the logarithmic psychophysical law. However, it is shown here that Bernoulli in 1738 and Thurstone in 1931 derived the logarithmic law using principles other than Weber's law and that Fechner and Thurstone based their derivations on the principles originally employed by Bernoulli. It is concluded that awareness of researchers about Bernoulli's and Thurstone's derivations could expand the directions of research on the form of the psychophysical law. (c) 2009 Wiley Periodicals, Inc.

  19. Higher derivations on rings and modules

    Directory of Open Access Journals (Sweden)

    Paul E. Bland

    2005-01-01

    Full Text Available Let τ be a hereditary torsion theory on ModR and suppose that Qτ:ModR→ModR is the localization functor. It is shown that for all R-modules M, every higher derivation defined on M can be extended uniquely to a higher derivation defined on Qτ(M if and only if τ is a higher differential torsion theory. It is also shown that if τ is a TTF theory and Cτ:M→M is the colocalization functor, then a higher derivation defined on M can be lifted uniquely to a higher derivation defined on Cτ(M.

  20. Generalized gravitational entropy from total derivative action

    Science.gov (United States)

    Dong, Xi; Miao, Rong-Xin

    2015-12-01

    We investigate the generalized gravitational entropy from total derivative terms in the gravitational action. Following the method of Lewkowycz and Maldacena, we find that the generalized gravitational entropy from total derivatives vanishes. We compare our results with the work of Astaneh, Patrushev, and Solodukhin. We find that if total derivatives produced nonzero entropy, the holographic and the field-theoretic universal terms of entanglement entropy would not match. Furthermore, the second law of thermodynamics could be violated if the entropy of total derivatives did not vanish.

  1. Generalized Gravitational Entropy from Total Derivative Action

    CERN Document Server

    Dong, Xi

    2015-01-01

    We investigate the generalized gravitational entropy from total derivative terms in the gravitational action. Following the method of Lewkowycz and Maldacena, we find that the generalized gravitational entropy from total derivatives vanishes. We compare our results with the work of Astaneh, Patrushev, and Solodukhin. We find that if total derivatives produced nonzero entropy, the holographic and the field-theoretic universal terms of entanglement entropy would not match. Furthermore, the second law of thermodynamics could be violated if the entropy of total derivatives did not vanish.

  2. Synthesis of Polynuclear Heterocyclic Compounds Derived from Thieno[2,3-d]pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    N. A. Hassan

    2000-06-01

    Full Text Available Reaction of 2-hydrazino-3-methyl-3,4-dihydrothieno[2,3-d]pyrimidin-4-one derivatives 2a,b with aliphatic acids afforded the thienotriazolopyrimidinone derivatives 3a-d, with nitrous acid yielded tetrazolothienopyrimidinone derivatives 4a,b and with carbon disulphide furnished 3-mercaptothienotriazolopyrimidinone derivatives 5a,b. Also, 2a,b reacted with aldehydes to afford the arylhydrazones 6a-f which cyclized into thienotriazolopyrimidinone derivatives 7a-f. Furthermore, 2a,b condensed with ethyl acetoacetate and ethyl cyanoacetate to afford 2-(1-pyrazolyl derivatives 9a,b and 10a,b, respectively. On the other hand, 2-hydrazino derivatives 2a,b condensed with a-halo-ketones to yield thienpyrimidotriazinone derivatives 11a,b and with β-diketones, to form 2-(1-pyrazolyl derivatives 12a-f.

  3. Combinatorial assembly of small molecules into bivalent antagonists of TrkC or TrkA receptors.

    Directory of Open Access Journals (Sweden)

    Fouad Brahimi

    Full Text Available A library of peptidomimetics was assembled combinatorially into dimers on a triazine-based core. The pharmacophore corresponds to β-turns of the neurotrophin polypeptides neurotrophin-3 (NT-3, nerve growth factor (NGF, or brain-derived neurotrophic factor (BDNF. These are the natural ligands for TrkC, TrkA, and TrkB receptors, respectively. The linker length and the side-chain orientation of each monomer within the bivalent mimics were systematically altered, and the impact of these changes on the function of each ligand was evaluated. While the monovalent peptidomimetics had no detectable binding or bioactivity, four bivalent peptidomimetics (2c, 2d, 2e, 3f are selective TrkC ligands with antagonistic activity, and two bivalent peptidomimetics (1a, 1b are TrkC and TrkA ligands with antagonistic activity. All these bivalent compounds block ligand-dependent receptor activation and cell survival, without affecting neuritogenic differentiation. This work adds to our understanding of how the neurotrophins function through Trk receptors, and demonstrates that peptidomimetics can be designed to selectively disturb specific biological signals, and may be used as pharmacological probes or as therapeutic leads. The concept of altering side-chain, linker length, and sequence orientation of a subunit within a pharmacophore provides an easy modular approach to generate larger libraries with diversified bioactivity.

  4. Superstability for Generalized Module Left Derivations and Generalized Module Derivations on a Banach Module (I

    Directory of Open Access Journals (Sweden)

    Rassias JM

    2009-01-01

    Full Text Available We discuss the superstability of generalized module left derivations and generalized module derivations on a Banach module. Let be a Banach algebra and a Banach -module, and . The mappings , and are defined and it is proved that if (resp., is dominated by then is a generalized (resp., linear module- left derivation and is a (resp., linear module- left derivation. It is also shown that if (resp., is dominated by then is a generalized (resp., linear module- derivation and is a (resp., linear module- derivation.

  5. 17 CFR 200.506 - Derivative classification.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Derivative classification. 200...; CONDUCT AND ETHICS; AND INFORMATION AND REQUESTS Classification and Declassification of National Security Information and Material § 200.506 Derivative classification. Any document that includes...

  6. 5 CFR 2500.5 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Derivative classification. 2500.5 Section 2500.5 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF THE PRESIDENT INFORMATION SECURITY REGULATION § 2500.5 Derivative classification. The Office of Administration serves only as...

  7. 45 CFR 601.5 - Derivative classification.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Derivative classification. 601.5 Section 601.5... CLASSIFICATION AND DECLASSIFICATION OF NATIONAL SECURITY INFORMATION § 601.5 Derivative classification. Distinct from “original” classification is the determination that information is in substance the same...

  8. 12 CFR 403.4 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Derivative classification. 403.4 Section 403.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CLASSIFICATION, DECLASSIFICATION, AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of...

  9. 28 CFR 17.26 - Derivative classification.

    Science.gov (United States)

    2010-07-01

    ..., the ISOO implementing directives in 32 CFR 2001.22, and internal Department directions provided by the... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Derivative classification. 17.26 Section... ACCESS TO CLASSIFIED INFORMATION Classified Information § 17.26 Derivative classification. (a)...

  10. 22 CFR 9.6 - Derivative classification.

    Science.gov (United States)

    2010-04-01

    ... CFR 2001.22. (c) Department of State Classification Guide. The Department of State Classification... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Derivative classification. 9.6 Section 9.6... classification. (a) Definition. Derivative classification is the incorporating, paraphrasing, restating...

  11. Biology-Derived Algorithms in Engineering Optimization

    CERN Document Server

    Yang, Xin-She

    2010-01-01

    Biology-derived algorithms are an important part of computational sciences, which are essential to many scientific disciplines and engineering applications. Many computational methods are derived from or based on the analogy to natural evolution and biological activities, and these biologically inspired computations include genetic algorithms, neural networks, cellular automata, and other algorithms.

  12. Understanding the Derivative through the Calculus Triangle

    Science.gov (United States)

    Weber, Eric; Tallman, Michael; Byerley, Cameron; Thompson, Patrick W.

    2012-01-01

    Typical treatments of the derivative do not clearly convey the idea that the derivative function represents the original function's rate of change. Revealing the relationship between a function and its rate-of-change function for static values of "x" does not facilitate productive ways of thinking about generating the rate-of-change function or…

  13. Generalized Derivative Based Kernelized Learning Vector Quantization

    NARCIS (Netherlands)

    Schleif, Frank-Michael; Villmann, Thomas; Hammer, Barbara; Schneider, Petra; Biehl, Michael; Fyfe, Colin; Tino, Peter; Charles, Darryl; Garcia-Osoro, Cesar; Yin, Hujun

    2010-01-01

    We derive a novel derivative based version of kernelized Generalized Learning Vector Quantization (KGLVQ) as an effective, easy to interpret, prototype based and kernelized classifier. It is called D-KGLVQ and we provide generalization error bounds, experimental results on real world data, showing t

  14. Structure-activity relationships of bumetanide derivatives

    DEFF Research Database (Denmark)

    Pedersen, Kasper Lykke; Töllner, Kathrin; Römermann, Kerstin;

    2015-01-01

    of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. EXPERIMENTAL APPROACH: In this study...

  15. An All-Orders Derivative Expansion

    OpenAIRE

    Dunne, Gerald(Department of Physics, University of Connecticut, Storrs, CT, 06269, U.S.A.)

    1996-01-01

    We evaluate the exact $QED_{2+1}$ effective action for fermions in the presence of a family of static but spatially inhomogeneous magnetic field profiles. This exact result yields an all-orders derivative expansion of the effective action, and indicates that the derivative expansion is an asymptotic, rather than a convergent, expansion.

  16. Stabilization of biomass-derived pyrolysis oils

    NARCIS (Netherlands)

    Venderbosch, R. H.; Ardiyanti, A. R.; Wildschut, J.; Oasmaa, A.; Heeres, H. J.

    2010-01-01

    BACKGROUND: Biomass is the only renewable feedstock containing carbon, and therefore the only alternative to fossil-derived crude oil derivatives. However, the main problems concerning the application of biomass for biofuels and bio-based chemicals are related to transport and handling, the limited

  17. The Option Value in Timing Derivative Trades

    NARCIS (Netherlands)

    Drost, Feico; van der Heijden, T.G.E.; Werker, Bas

    2015-01-01

    Risk-neutral traders executing derivative trades on behalf of portfolio managers maximize their expected profit compared to trading at pre-determined times by timing trades, using the quickly changing risk exposures of derivative baskets. The optimal order submission strategy is a sequence of stop o

  18. Properties of derivations on some convolution algebras

    DEFF Research Database (Denmark)

    Pedersen, Thomas Vils

    2014-01-01

    For all convolution algebras L1[0; 1); L1 loc and A(!) = T n L1(!n), the derivations are of the form Dμf = Xf μ for suitable measures μ, where (Xf)(t) = tf(t). We describe the (weakly) compact as well as the (weakly) Montel derivations on these algebras in terms of properties of the measure μ...

  19. Microbial Degradation of Indole and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar Arora

    2015-01-01

    Full Text Available Indole and its derivatives, including 3-methylindole and 4-chloroindole, are environmental pollutants that are present worldwide. Microbial degradation of indole and its derivatives can occur in several aerobic and anaerobic pathways; these pathways involve different known and characterized genes. In this minireview, we summarize and explain the microbial degradation of indole, indole-3-acetic acid, 4-chloroindole, and methylindole.

  20. Green's Theorem for Generalized Fractional Derivatives

    CERN Document Server

    Odzijewicz, Tatiana; Torres, Delfim F M

    2012-01-01

    We study three types of generalized partial fractional operators. An extension of Green's theorem, by considering partial fractional derivatives with more general kernels, is proved. New results are obtained, even in the particular case when the generalized operators are reduced to the standard partial fractional derivatives and fractional integrals in the sense of Riemann-Liouville or Caputo.

  1. Adsorption and desorption of cellulose derivatives

    NARCIS (Netherlands)

    Hoogendam, C.W.

    1998-01-01

    Cellulose derivatives, in particular carboxymethyl cellulose (CMC) are used in many (industrial) applications. The aim of this work is to obtain insight into the adsorption mechanism of cellulose derivatives on solid-liquid interfaces.

    In chapter 1

  2. Stereoselective synthesis of partially protected azasugar derivatives

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoliu; DUAN Kefang; TIAN Jun; XU Xiaoming

    2007-01-01

    Five-membered azasugar derivatives with partially protected hydroxyl groups,and their fluorinated derivatives were synthesized via the key intermediates of norbornyl-like bicyclic acetals using o-xylose and o-glucose as starting materials.The glycosylation of the azasugar intermediate and 1-methylenesugar was also explored.

  3. Heteropolyacids in synthesis of benzoyl hydrazone derivatives

    Directory of Open Access Journals (Sweden)

    Sodeh Sadjadi

    2009-12-01

    Full Text Available Keggin type of heteropolyacids as green reusable and efficient catalyst was used in the synthesis of benzoyl hydrazones from reaction of benzoic acid hydrazide and aldehyde and ketone derivatives. The synthesis of N-acetyl and N-benzoyl derivatives has also been performed by the reaction of obtained benzoyl hydrazones with acylcholorides in presence of this kind of heteropolyacids.

  4. Simplicial approach to derived differential manifolds

    CERN Document Server

    Borisov, Dennis

    2011-01-01

    Derived differential manifolds are constructed using the usual homotopy theory of simplicial rings of smooth functions. They are proved to be equivalent to derived differential manifolds of finite type, constructed using homotopy sheaves of homotopy rings (D.Spivak), thus preserving the classical cobordism ring. This reduction to the usual algebraic homotopy can potentially lead to virtual fundamental classes beyond obstruction theory.

  5. Covariant derivative expansion of the heat kernel

    Energy Technology Data Exchange (ETDEWEB)

    Salcedo, L.L. [Universidad de Granada, Departamento de Fisica Moderna, Granada (Spain)

    2004-11-01

    Using the technique of labeled operators, compact explicit expressions are given for all traced heat kernel coefficients containing zero, two, four and six covariant derivatives, and for diagonal coefficients with zero, two and four derivatives. The results apply to boundaryless flat space-times and arbitrary non-Abelian scalar and gauge background fields. (orig.)

  6. Adsorption and desorption of cellulose derivatives.

    NARCIS (Netherlands)

    Hoogendam, C.W.

    1998-01-01

    Cellulose derivatives, in particular carboxymethyl cellulose (CMC) are used in many (industrial) applications. The aim of this work is to obtain insight into the adsorption mechanism of cellulose derivatives on solid-liquid interfaces.In chapter 1 of this thesis we discuss some appl

  7. Generalized Fractional Derivative Anisotropic Viscoelastic Characterization

    Directory of Open Access Journals (Sweden)

    Harry H. Hilton

    2012-01-01

    Full Text Available Isotropic linear and nonlinear fractional derivative constitutive relations are formulated and examined in terms of many parameter generalized Kelvin models and are analytically extended to cover general anisotropic homogeneous or non-homogeneous as well as functionally graded viscoelastic material behavior. Equivalent integral constitutive relations, which are computationally more powerful, are derived from fractional differential ones and the associated anisotropic temperature-moisture-degree-of-cure shift functions and reduced times are established. Approximate Fourier transform inversions for fractional derivative relations are formulated and their accuracy is evaluated. The efficacy of integer and fractional derivative constitutive relations is compared and the preferential use of either characterization in analyzing isotropic and anisotropic real materials must be examined on a case-by-case basis. Approximate protocols for curve fitting analytical fractional derivative results to experimental data are formulated and evaluated.

  8. Additive Lie ($\\xi$-Lie) Derivations and Generalized Lie ($\\xi$-Lie) Derivations on Prime Algebras

    CERN Document Server

    Qi, Xiaofei

    2010-01-01

    The additive (generalized) $\\xi$-Lie derivations on prime algebras are characterized. It is shown, under some suitable assumption, that an additive map $L$ is an additive (generalized) Lie derivation if and only if it is the sum of an additive (generalized) derivation and an additive map from the algebra into its center vanishing all commutators; is an additive (generalized) $\\xi$-Lie derivation with $\\xi\

  9. Risk management, derivatives and shariah compliance

    Science.gov (United States)

    Bacha, Obiyathulla Ismath

    2013-04-01

    Despite the impressive growth of Islamic Banking and Finance (IBF), a number of weaknesses remain. The most important of this is perhaps the lack of shariah compliant risk management tools. While the risk sharing philosophy of Islamic Finance requires the acceptance of risk to justify returns, the shariah also requires adherents to avoid unnecessary risk-maysir. The requirement to avoid maysir is in essence a call for the prudent management of risk. Contemporary risk management revolves around financial engineering, the building blocks of which are financial derivatives. Despite the proven efficacy of derivatives in the management of risk in the conventional space, shariah scholars appear to be suspicious and uneasy with their use in IBF. Some have imposed outright prohibition of their use. This paper re-examines the issue of contemporary derivative instruments and shariah compliance. The shariah compatibility of derivatives is shown in a number of ways. First, by way of qualitative evaluation of whether derivatives can be made to comply with the key prohibitions of the sharia. Second, by way of comparing the payoff profiles of derivatives with risk sharing finance and Bai Salam contracts. Finally, the equivalence between shariah compliant derivatives like the IPRS and Islamic FX Currency Forwards with conventional ones is presented.

  10. Tailoring Cytotoxicity of Antimicrobial Peptidomimetics with High Activity against Multidrug-Resistant Escherichia coli

    DEFF Research Database (Denmark)

    Jahnsen, Rasmus D; Sandberg-Schaal, Anne; Vissing, Karina Juul

    2014-01-01

    Infections with multidrug-resistant pathogens are an increasing concern for public health. Recently, subtypes of peptide-peptoid hybrids were demonstrated to display potent activity against multidrug-resistant Gram-negative bacteria. Here, structural variation of these antibacterial peptidomimeti...

  11. Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    and in vitro biochemical studies on MPC6 on AR. He also helped write the paper on MPC6 function and activity in prostate cancer. Funding Support...analysis, biostatistics, com- putational analysis): Y. Wang, K. Imberg-Kazdan, S.K. Logan, K. Kirshenbaum, M.J. Garabedian Writing , review, and/or...Ribeiro-Viana R, Berzi A, Ramdasi R, Daghetti A, et al. A multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus . Biomaterials

  12. Multivalent Peptidomimetic Conjugates as Inhibitors of Androgen Receptor Function in Therapy-Resistant Prostate Cancer

    Science.gov (United States)

    2016-10-01

    biochemical studies on MPC6 on AR. He also helped write the paper on MPC6 function and activity in prostate cancer. Funding Support: CDMRP Name: Kendall...analysis): Y. Wang, K. Imberg-Kazdan, S.K. Logan, K. Kirshenbaum, M.J. Garabedian Writing , review, and/or revision of the manuscript: Y. Wang, D.C. Dehigas...al. A multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus . Biomaterials 2014;35:4175–84. 33. Liu LL, Xie N, Sun S

  13. Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – neurokinin-1 antagonist peptidomimetics

    Science.gov (United States)

    Guillemyn, Karel; Kleczkowska, Patrycia; Lesniak, Anna; Dyniewicz, Jolanta; Van der Poorten, Olivier; Van den Eynde, Isabelle; Keresztes, Attila; Varga, Eva; Lai, Josephine; Porreca, Frank; Chung, Nga N.; Lemieux, Carole; Mika, Joanna; Rojewska, Ewelina; Makuch, Wioletta; Van Duppen, Joost; Przewlocka, Barbara; Broeck, Jozef Vanden; Lipkowski, Andrzej W.; Schiller, Peter W.; Tourwé, Dirk; Ballet, Steven

    2014-01-01

    A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3’,5’-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-β-Ala-NMe-Bn) were selected for in vivo behavioral assays, which were conducted in acute (tail-flick) and neuropathic pain models (cold plate and von Frey) in rats. Compared to the parent opioid compound 33 (without NK1R pharmacophore), hybrid 22 was more active in the neuropathic pain models. Attenuation of neuropathic pain emerged from NK1R antagonism as demonstrated by the pure NK1R antagonist 6. Surprisingly, despite a lower in vitro activity at NK1R in comparison with 4, compound 22 was more active in the neuropathic pain models. Although potent analgesic effects were observed for 4 and 22, upon chronic administration, both manifested a tolerance profile similar to that of morphine and cross tolerance with morphine in a neuropathic pain model in rat. PMID:25544687

  14. Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.

    Science.gov (United States)

    Betti, Cecilia; Starnowska, Joanna; Mika, Joanna; Dyniewicz, Jolanta; Frankiewicz, Lukasz; Novoa, Alexandre; Bochynska, Marta; Keresztes, Attila; Kosson, Piotr; Makuch, Wioletta; Van Duppen, Joost; Chung, Nga N; Vanden Broeck, Jozef; Lipkowski, Andrzej W; Schiller, Peter W; Janssens, Frans; Ceusters, Marc; Sommen, François; Meert, Theo; Przewlocka, Barbara; Tourwé, Dirk; Ballet, Steven

    2015-12-10

    Herein, the synthesis and biological evaluation of dual opioid agonists-neurokinin 1 receptor (NK1R) antagonists is described. In these multitarget ligands, the two pharmacophores do not overlap, and this allowed maintaining high NK1R affinity and antagonist potency in compounds 12 and 13. Although the fusion of the two ligands resulted in slightly diminished opioid agonism at the μ- and δ-opioid receptors (MOR and DOR, respectively), as compared to the opioid parent peptide, balanced MOR/DOR activities were obtained. Compared to morphine, compounds 12 and 13 produced more potent antinociceptive effects in both acute (tail-flick) and neuropathic pain models (von Frey and cold plate). Similarly to morphine, analgesic tolerance developed after repetitive administration of these compounds. To our delight, compound 12 did not produce cross-tolerance with morphine and high antihyperalgesic and antiallodynic effects could be reinstated after chronic administration of each of the two compounds.

  15. Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - neurokinin-1 antagonist peptidomimetics.

    Science.gov (United States)

    Guillemyn, Karel; Kleczkowska, Patrycia; Lesniak, Anna; Dyniewicz, Jolanta; Van der Poorten, Olivier; Van den Eynde, Isabelle; Keresztes, Attila; Varga, Eva; Lai, Josephine; Porreca, Frank; Chung, Nga N; Lemieux, Carole; Mika, Joanna; Rojewska, Ewelina; Makuch, Wioletta; Van Duppen, Joost; Przewlocka, Barbara; Vanden Broeck, Jozef; Lipkowski, Andrzej W; Schiller, Peter W; Tourwé, Dirk; Ballet, Steven

    2015-03-06

    A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3',5'-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-β-Ala-NMe-Bn) were selected for in vivo behavioural assays, which were conducted in acute (tail-flick) and neuropathic pain models (cold plate and von Frey) in rats. Compared to the parent opioid compound 33 (without NK1R pharmacophore), hybrid 22 was more active in the neuropathic pain models. Attenuation of neuropathic pain emerged from NK1R antagonism as demonstrated by the pure NK1R antagonist 6. Surprisingly, despite a lower in vitro activity at NK1R in comparison with 4, compound 22 was more active in the neuropathic pain models. Although potent analgesic effects were observed for 4 and 22, upon chronic administration, both manifested a tolerance profile similar to that of morphine and cross tolerance with morphine in a neuropathic pain model in rat.

  16. Guanidino Groups Greatly Enhance the Action of Antimicrobial Peptidomimetics Against Bacterial Cytoplasmic Membranes

    Science.gov (United States)

    2014-05-28

    to mimic the approach of the compound from the extracellular fluid to the outer leaflet of the membrane. After injection both XR and GIXD measurements... milk powder, and 3% (w/v) tryptone soy powder. All experiments were carried out with bacteria incubated for one night (approximately 18 h) at 37 °C...condensed phase ~25–50 μm in diameter separated from each other by brightly colored “ fluid ” (disordered) areas. Fig. 2 shows the dynamics of surface

  17. A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli.

    Science.gov (United States)

    Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio; Moehle, Kerstin; Zerbe, Katja; Omasits, Ulrich; Ahrens, Christian H; Pessi, Gabriella; Eberl, Leo; Robinson, John A

    2016-01-22

    Increasing antibacterial resistance presents a major challenge in antibiotic discovery. One attractive target in Gram-negative bacteria is the unique asymmetric outer membrane (OM), which acts as a permeability barrier that protects the cell from external stresses, such as the presence of antibiotics. We describe a novel β-hairpin macrocyclic peptide JB-95 with potent antimicrobial activity against Escherichia coli. This peptide exhibits no cellular lytic activity, but electron microscopy and fluorescence studies reveal an ability to selectively disrupt the OM but not the inner membrane of E. coli. The selective targeting of the OM probably occurs through interactions of JB-95 with selected β-barrel OM proteins, including BamA and LptD as shown by photolabeling experiments. Membrane proteomic studies reveal rapid depletion of many β-barrel OM proteins from JB-95-treated E. coli, consistent with induction of a membrane stress response and/or direct inhibition of the Bam folding machine. The results suggest that lethal disruption of the OM by JB-95 occurs through a novel mechanism of action at key interaction sites within clusters of β-barrel proteins in the OM. These findings open new avenues for developing antibiotics that specifically target β-barrel proteins and the integrity of the Gram-negative OM.

  18. Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases

    DEFF Research Database (Denmark)

    Knuhtsen, Astrid; Legrand, Baptiste; Van der Poorten, Olivier

    2016-01-01

    Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non...... with the original hit using circular dichroism and NMR spectroscopy. Introducing two constrained tryptophan residue mimics (l-Aia) spaced by a single amino acid was found to induce a unique turn structure stabilized by a hydrogen bond and aromatic π-stacking interaction between the two l-Aia residues....

  19. Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice

    NARCIS (Netherlands)

    Poosti, Fariba; Bansal, Ruchi; Yazdani, Saleh; Prakash, Jai; Beljaars, Leonie; van den Born, Jacob; de Borst, Martin H.; Goor, van Harry; Hillebrands, Jan-Luuk; Poelstra, Klaas

    2016-01-01

    Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is lacking. Interferon-gamma is a pro-inflammatory cytokine with anti-fibrotic properties. Clinical use of interferon-gamma is hampered due to inflammation-mediated systemic side effects. We used an interferon-gamma

  20. Coevolutionary analysis of resistance-evading peptidomimetic inhibitors of HIV-1 protease.

    Science.gov (United States)

    Rosin, C D; Belew, R K; Morris, G M; Olson, A J; Goodsell, D S

    1999-02-16

    We have developed a coevolutionary method for the computational design of HIV-1 protease inhibitors selected for their ability to retain efficacy in the face of protease mutation. For HIV-1 protease, typical drug design techniques are shown to be ineffective for the design of resistance-evading inhibitors: An inhibitor that is a direct analogue of one of the natural substrates will be susceptible to resistance mutation, as will inhibitors designed to fill the active site of the wild-type or a mutant enzyme. Two design principles are demonstrated: (i) For enzymes with broad substrate specificity, such as HIV-1 protease, resistance-evading inhibitors are best designed against the immutable properties of the active site-the properties that must be conserved in any mutant protease to retain the ability to bind and cleave all of the native substrates. (ii) Robust resistance-evading inhibitors can be designed by optimizing activity simultaneously against a large set of mutant enzymes, incorporating as much of the mutational space as possible.

  1. Metal-Binding Ability of Leu-Enkephalin, Related Glycoconjugates and Peptidomimetics

    Directory of Open Access Journals (Sweden)

    Zsuzsa Majer

    2015-12-01

    Full Text Available Both the chemistry and consequences of the nonenzymatic reaction between reducing sugars and reactive amino groups of amino acids, peptides and proteins (known as the Maillard reaction, have received considerable attention in food and health science fields. This initial reaction results in Amadori and similar products formation, followed by degradation to advanced glycation end products (AGEs. It is well established that AGEs are associated with color and odor of thermally processed or stored food, as well as with pathogen products in a number of diseases. The model systems of early stage Maillard reaction products (MRP were prepared between endogenous opioid peptide leucine enkephalin (1 and D-glucose / D-glucuronic acid. The complexation ability of prepared MRP with metal ions (Ca2+, Zn2+, Al3+, Pb2+ and Cu2+ was investigated and compared to the complexation ability of parent peptide using ECD and FTIR spectroscopic measurements.

  2. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens

    Directory of Open Access Journals (Sweden)

    Carrie L. Shaffer

    2016-04-01

    Full Text Available Bacteria utilize complex type IV secretion systems (T4SSs to translocate diverse effector proteins or DNA into target cells. Despite the importance of T4SSs in bacterial pathogenesis, the mechanism by which these translocation machineries deliver cargo across the bacterial envelope remains poorly understood, and very few studies have investigated the use of synthetic molecules to disrupt T4SS-mediated transport. Here, we describe two synthetic small molecules (C10 and KSK85 that disrupt T4SS-dependent processes in multiple bacterial pathogens. Helicobacter pylori exploits a pilus appendage associated with the cag T4SS to inject an oncogenic effector protein (CagA and peptidoglycan into gastric epithelial cells. In H. pylori, KSK85 impedes biogenesis of the pilus appendage associated with the cag T4SS, while C10 disrupts cag T4SS activity without perturbing pilus assembly. In addition to the effects in H. pylori, we demonstrate that these compounds disrupt interbacterial DNA transfer by conjugative T4SSs in Escherichia coli and impede vir T4SS-mediated DNA delivery by Agrobacterium tumefaciens in a plant model of infection. Of note, C10 effectively disarmed dissemination of a derepressed IncF plasmid into a recipient bacterial population, thus demonstrating the potential of these compounds in mitigating the spread of antibiotic resistance determinants driven by conjugation. To our knowledge, this study is the first report of synthetic small molecules that impair delivery of both effector protein and DNA cargos by diverse T4SSs.

  3. Transport of peptidomimetic drugs by the intestinal Di/tri-peptide transporter, PepT1

    DEFF Research Database (Denmark)

    Brodin, Birger; Nielsen, Carsten Uhd; Steffansen, Bente

    2002-01-01

    The apical membrane of small intestinal enterocytes possess an uptake system for di- and tripeptides. The physiological function of the system is to transport small peptides resulting from digestion of dietary protein. Moreover, due to the broad substrate specificity of the system, it is also cap...... an updated introduction to the transport system and discuss the substrate characteristics of the di/tri-peptide transporter system with special emphasis on chemically modified substrates and prodrugs....

  4. Structural Optimization, Biological Evaluation and Application of Peptidomimetic Prostate Specific Antigen Inhibitors

    Science.gov (United States)

    Kostova, Maya B.; Rosen, D. Marc; Chen, Ying; Mease, Ronnie C.; Denmeade, Samuel R.

    2013-01-01

    Prostate-Specific Antigen (PSA) is a serine protease produced at high levels by normal and malignant prostate epithelial cells that is used extensively as a biomarker in the clinical management of prostate cancer. To better understand PSA’s role in prostate cancer progression we prepared a library of peptidyl boronic acid based inhibitors. To enhance selectivity for PSA vs. other serine proteases, we modified the P1 site of the inhibitors to incorporate a bromopropylglycine group. This allowed the inhibitors to participate in halogen bond formation with the serine found at the bottom of the specificity pocket. The best of these Ahx-FSQn(boro)Bpg had PSA Ki of 72 nM and chymotrypsin Ki of 580 nM. In vivo studies using PSA-producing xenografts demonstrated that candidate inhibitors had minimal effect on growth but significantly altered serum levels of PSA. Biodistribution of 125I labeled peptides showed low levels of uptake into tumors compared to other normal tissues. PMID:23692593

  5. Solid-Phase Synthesis of Smac Peptidomimetics Incorporating Triazoloprolines and Biarylalanines

    DEFF Research Database (Denmark)

    Le Quement, Sebastian T.; Ishoey, Mette; Petersen, Mette T.;

    2011-01-01

    -Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide–alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities...

  6. Fragment-based library generation for the discovery of a peptidomimetic p53-Mdm4 inhibitor

    NARCIS (Netherlands)

    Boltjes, André; Huang, Yijun; van de Velde, Rob; Rijkee, Laurie; Wolf, Siglinde; Gaugler, James; Lesniak, Katarzyna; Guzik, Katarzyna; Holak, Tad A.; Dömling, Alexander

    2014-01-01

    On the basis of our recently resolved first cocrystal structure of Mdm4 in complex with a small molecule inhibitor (PDB ID 3LBJ ), we devised an approach for the generation of potential Mdm4 selective ligands. We performed the Ugi four-component reaction (Ugi-4CR) in 96-well plates with an indole fr

  7. Monocyte-Derived Suppressor Cells in Transplantation.

    Science.gov (United States)

    Ochando, Jordi; Conde, Patricia; Bronte, Vincenzo

    Myeloid-derived suppressor cells (MDSC) are cells of myeloid origin with enhanced suppressive function. They are negative regulators of the immune responses and comprise a heterogeneous mixture of immunosuppressive cells of monocytic (M-MDSC) and granulocytic (G-MDSC) origin. A more recent nomenclature proposes the term "suppressive monocyte derived cells" (suppressive MCs) to define CSF1/CSF2-dependent mouse suppressor cells that develop from common monocyte progenitors (cMoPs) after birth. Here, we review the literature about monocytic-derived cells with demonstrated suppressor function in vitro and in vivo within the context of solid organ transplantation.

  8. Derived Categories and Zero-Brane Stability

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, Albion

    2001-07-25

    We define a particular class of topological field theories associated to open strings and prove the resulting D-branes and open strings form the bounded derived category of coherent sheaves. This derivation is a variant of some ideas proposed recently by Douglas. We then argue that any 0-brane on any Calabi-Yau threefold must become unstable along some path in the Kahler moduli space. As a byproduct of this analysis we see how the derived category can be invariant under a birational transformation.

  9. Catalytic Synthesis Methods for Triazolopyrimidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A new method for catalyzed synthesis of triazolopyrimidine derivatives is reported. Aikylamine reaction with dialkyl cyanodithioiminocarbonate was catalyzed by quaternary ammonium salts at room temperature to yield 3-alkylamine-5-amino-1,2,4-triazole in good quality and high yields. After imidization and reaction with an α,β-unsaturated acid derivative, the reaction intermediate was hydrolyzed in the presence of a Lewis acid to obtain the target product. This novel catalytic method for triazolopyrimidine derivatives can be carried out under inexpen-sive and mild conditions, and is safe and environmentally friendly. IH NMR results for all intermediates are re-ported.

  10. Mechanism of Platinum Derivatives Induced Kidney Injury

    Directory of Open Access Journals (Sweden)

    Feifei YAN

    2015-09-01

    Full Text Available Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung cancer, and colorectal cancer. Two major problems exist, however, in the clinic use of platinum derivatives. One is the development of tumor resistance to the drug during therapy, leading to treatment failure. The other is the drug’s toxicity such as the cisplatin’s nephrotoxicity, which limits the dose that can be administered. This paper describes the mechanism of platinum derivatives induced kidney injury.

  11. SYNTHESIS AND CHARACTERIZATION OF TITANOCENE POLYMER DERIVATIVES

    Institute of Scientific and Technical Information of China (English)

    WANG Zhuting; SUN Shumen

    1988-01-01

    Titanocene polymer derivatives with potential antitumor properties were synthesized by interfacial condensation. The preformed polymers used are PAA (polyacrylic acid), CPSMA (1:1 alternating copolymer of styrene and maleic anhydride) and DVEMA (1:2 copolymer of divinyl ether and maleic anhydride). The ratio of practical and theoretical titanium content is 73.6%, 92.2% and 86.2% for PAA, CPSMA and DVEMA polymer derivatives respectively. The IR spectra of the polymer derivatives possess the characteristic absorptions of titanocene. XPS (X-ray photoelectron spectroscopy) of O1s and Ti2p3/2 supports the existence of Ti-O bonding.

  12. Test Derivation Through Critical Path Transitions

    Institute of Scientific and Technical Information of China (English)

    李卫东; 魏道政

    1992-01-01

    In this paper, a new technique called test derivation is presented,aiming at the promotion of the random testing efficiency for combinational circuits,Combined with a fault simulator based on critical path tracing method,we introduce the concept of seed test derivation and attempt to generate a group of new tests from the seed test by means of critical path transition.The neccessary conditions and efficient algorithms are proposed to guarantee the usefulness of the newly derived tests and the correctness of the critical path transitions.Also,examples are given to demonstrate the effectiveness of the technique.

  13. Derivation of GFDM Based on OFDM Principles

    Energy Technology Data Exchange (ETDEWEB)

    Hussein Moradi; Behrouz Farhang-Boroujeny

    2015-06-01

    This paper starts with discussing the principle based on which the celebrated orthogonal frequency division multiplexing (OFDM) signals are constructed. It then extends the same principle to construct the newly introduced generalized frequency division multiplexing (GFDM) signals. This novel derivation sheds light on some interesting properties of GFDM. In particular, our derivation seamlessly leads to an implementation of GFDM transmitter which has significantly lower complexity than what has been reported so far. Our derivation also facilitates a trivial understanding of how GFDM (similar to OFDM) can be applied in MIMO channels.

  14. Higher Derivative Corrections To Extended Supersymmetric Theories

    CERN Document Server

    Braun, G A

    2004-01-01

    We investigate higher-derivative terms in N = 2 supersymmetric effective actions. We systematically construct such terms in harmonic superspace despite the infinite redundancy in their description due to the infinite number of auxiliary fields. We write all 3- and 4-derivative terms on Higgs, Coulomb, and mixed branches, modulo the existence of superspace Chern-Simons-like terms. Among these terms are several with only holomorphic dependence on fields, and at least one satisfies a non-renormalization theorem. We then search for superspace Chern-Simons-like terms, which are those gauge-invariant terms which cannot be written solely in terms of field strength superfields and covariant derivatives, but in which gauge potential superfield appears explicitly. We find a class of four- derivative terms with N = 2 supersymmetry which, though locally on the Coulomb branch can be written solely in terms of field strengths, globally on the Coulomb branch are superspace Chern- Simons-like.

  15. MANGROVE-DERIVED NUTRIENTS AND CORAL REEFS

    Science.gov (United States)

    Understanding the consequences of the declining global cover of mangroves due to anthropogenic disturbance necessitates consideration of how mangrove-derived nutrients contribute to threatened coral reef systems. We sampled potential sources of organic matter and a suite of sessi...

  16. A New Synthetic Approach to Coumestan Derivatives

    Institute of Scientific and Technical Information of China (English)

    GONG, Deng-Huang; LI, Chao-Zhong; YUAN, Cheng-Ye

    2001-01-01

    A new method for the preparation of coumestan derivatives was described involving an intramolecular palladium-catalyzed ring closure reaction of coumarins obtained from condensation of substituted o-hydroxyphenylacetic acid and o-hydroxybenzaldehyde.

  17. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  18. Plant-derived nanostructures: types and applications

    Science.gov (United States)

    Plant-derived nanostructures and nanoparticles (NPs) have functional applications in numerous disciplines such as health care, food and feed, cosmetics, biomedical science, energy science, drug-gene delivery, environmental health, and so on. Consequently, it is imperative for res...

  19. Two New Butenolide Derivatives from Erigeron acer

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Two new butenolide derivatives, named as erigeracerin A and erigeracerin B, which are a pair of epimers, were isolated from Erigeron acer. Their structures were elucidated by spectroscopic analysis including 2D NMR and HR-ESI-MS.

  20. Truncation Analysis for the Derivative Schrodinger Equation

    Institute of Scientific and Technical Information of China (English)

    XU Peng Cheng; CHANG Qian Shun; GUO Bo Ling

    2002-01-01

    The truncation equation for the derivative nonlinear Schrodinger equation has been dis-cussed in this paper. The existence of a special heteroclinic orbit has been found by using geometricalsingular perturbation theory together with Melnikov's technique.

  1. Prediction on amphiphilicity of hypocrellin derivatives

    Institute of Scientific and Technical Information of China (English)

    谢杰; 马江华; 赵井泉

    2002-01-01

    Hypocrellins are most suitable for photodynamic therapy (PDT) of the diseases occurring in the superficial layer, such as microvascular diseases, because of their special absorption spectral properties. However, hypocrellins and most of their derivatives are basically lipophilic, while the hydrophilic derivatives lose the PDT activity in vivo. Therefore, the key problem for practical application of PDT of microvascular diseases focuses on finding the derivatives which possess optimized amphiphilicity. Herein, we developed a theoretical method to estimate the amphiphilicity of a molecule by the calculated average polarity. Compared with the experimentally measured results, the method is proved to be applicable. Based on the computation and available experimental results, it can be concluded that the derivative must have the polarities around 0.22 for optimized amphiphilicity.

  2. Prediction on amphiphilicity of hypocrellin derivatives

    Institute of Scientific and Technical Information of China (English)

    谢杰; 马江华; 赵井泉

    2002-01-01

    Hypocrellins are most suitable for photodynamic therapy (PDT) of the diseases occurring in the superficial layer, such as microvascular diseases, because of their special absorption spectral properties. However, hypocrellins and most of their derivatives are basically lipophilic, while the hydrophilic derivatives lose the PDT activity in vivo. Therefore, the key problem for practical application of PDT of microvascular diseases focuses on finding the derivatives which possess optimized amphiphilicity. Herein, we developed a theoretical method to estimate the amphi-philicity of a molecule by the calculated average polarity. Compared with the experimentally measured results, the method is proved to be applicable. Based on the computation and available experimental results, it can be concluded that the derivative must have the polarities around C.22 for optimized amphiphilicity.

  3. Polyimides Derived from Novel Asymmetric Benzophenone Dianhydrides

    Science.gov (United States)

    Chuang, Chun-Hua (Inventor)

    2015-01-01

    This invention relates to the composition and processes for preparing thermoset polyimides derived from an asymmetric dianhydride, namely 2,3,3',4'-benzophenone dianhydride (a-BTDA) with at least one diamine, and a monofunctional terminal endcaps. The monofunctional terminating groups include 4-phenylethynylphthalic anhydride ester-acid derivatives, phenylethyl trimellitic anhydride (PETA) and its ester derivatives as well as 3-phenylethynylaniline. The process of polyimide composite comprises impregnating monomer reactants of dianhydride or its ester-acid derivatives, diamine and with monofunctional reactive endcaps into glass, carbon, quartz or synthetic fibers and fabrics, and then stack up into laminates and subsequently heated to between 150-375.degree. C. either at atmosphere or under pressure to promote the curing and crosslinking of the reactive endcaps to form a network of thermoset polyimides.

  4. SYNTHESES AND PROPERTIES OF POLYMERIZABLE METALLOPHTHALOCYANINE DERIVATIVES

    Institute of Scientific and Technical Information of China (English)

    LIU Yunqi; YAMADA Akira; SHIGEHARA Kiyotaka; HARA Masahiko

    1988-01-01

    Metallophthalocyanine derivatives with polymerizable vinyl groups were synthesized, characterized and polymerized. Preliminary results on their Langmuir-Blodgett (LB) film formation and the electronic properties of (Indium-Tin Oxide/LB-film/Al) Schottky devices were reported.

  5. Synthesis of Nucleoside Derivatives Containing Benzophenoxazinone Moiety

    Institute of Scientific and Technical Information of China (English)

    Yu GAO; Wu Xin ZOU; Ling WU; Jin Shui LI; Ji Tao WANG; Ji Ben MENG

    2004-01-01

    Two new nucleoside derivatives containing benzophenoxazinone moiety were synthesized. Their luminescence spectra show that they have strong near infrared fluorescence. Our study provides a new method for direct introduction of near infrared fluorescent probe to bioactive molecules.

  6. PHARMACOLOGICAL SCREENING OF SOME NEW AMINOPYRIDINIUM DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Subramaniyan Navaneethakrishnan

    2012-05-01

    Full Text Available Aminopyridinium derivative such as Ethyl-2-(4-chloroamino pyridinium acetate (compound A,Ethyl-2-(4-bromoamino pyridinium acetate (compound B, Ethyl-2-(3-chloroaminopyridinium acetate (compound C have been evaluated for analgesic, anti anxiety and locomotor activity. All the aminopyridinium derivative prepared by the dose (50&100mg/kg/i.p, which shown significant analgesic activity when compared to morphine (5mg/kg/i.p.In case of open field exploratory and elevated plus maze test, the aminopyridinium derivatives prepared by the dose( 50&100mg/Kg/oral reverse the anxiety behavior of the mice when compared to lorazepam (0.5mg/kg/oral. Among this, compound C (100/mg/kg produce better effect than others. Locomotor activity in the activity cage, the reaction time of Aminopyridinium derivative A, B&C produce more effective Central nerve depressant effect than Diazepam (2mg/kg/i.p drug.

  7. SYNTHESIS AND BIOLOGICAL SCREENING OF BENZIMIDAZOLE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Ankur Shukla

    2012-03-01

    Full Text Available The synthesis of benzimidazoles derivative involves subsequent synthesis of 4-(2-chloro-ethoxy-benzaldehyde, 4 methyl benzaldehyde followed by benzimidazoles derivative by reaction between amines derivatives and o-phenylenediamine in dimethyl farmamide (DMF as solvent in the presence of iodine as a catalyst. Iodine is a commercial and environmentally benign catalyst. The yield of all benzimidazole derivatives was found to be in the range of 75 – 94%. The purity of the compounds was ascertained by melting point and TLC. The synthesized compounds were characterized by using IR,1H NMR, and MASS spectral data together with elemental analysis. The synthesized benzimidazole compounds were screened for analgesic and anticonvulsant activity in albino rat (100-200gm by using Writhing test and maximal electroshock (MES. Out of all compound studied only PS-3, PS-4, PS-5 and PS-6 showed significant analgesic activities and response against MES test.

  8. Regional Ecological Corridors - MLCCS derived 2008

    Data.gov (United States)

    Minnesota Department of Natural Resources — Identification of potential ecological corridors between the MLCCS derived ecological patches (ear_eco08py3). This was generated using cost / distance analysis,...

  9. Photochemistry of hypocrellin derivatives under aerobic conditions

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Hypocrellins are a novel type of photosensitizers. A series of new hypocrellin B (HB) derivatives have been synthesized to overcome their limitations, I.e. To improve their red absorption and amphiphilicity. The generation of reactive oxygen species (including superoxide anion radical, hydroxyl radical and singlet oxygen) is investigated in the presence of oxygen. The chemical structures of HB derivatives affect not only the generation efficiencies of superoxide and hydroxyl radicals, but also quantum yields of singlet oxygen.

  10. Higher time derivatives, stability and Fermi Statistics

    CERN Document Server

    Lopez-Sarrion, Justo

    2011-01-01

    We show that statistics is crucial for the instability problem derived from higher time derivatives. In fact, and contrary to previous statements, we check that when dealing with Fermi systems, the Hamiltonian is well bounded and the quantum states are normalizable. Although, ghost states are still present, they do not affect unitarity under certain conditions. We first analyze a quantum oscillator involving Grassman variables and then we generalize it to a Dirac field. Finally, we discuss some physical implications

  11. Synthesis of Pharmacological Heterocyclic Derivatives Based Surfactants.

    Science.gov (United States)

    El-Sayed, Refat; Fadda, Ahmed A

    2016-01-01

    Synthesis of chromenopyrimidine derivatives and the related fused system carried out by the reaction of chromene derivative 1 with various reagents under suitable reaction conditions. Condensation of stearoyl chloride with these heterocycles, then, propoxylated the products using propylene oxide to produce surface active agents having a twofold capacity as surface and antimicrobial dynamic specialists which may be served in the production of medications, pesticides, beautifying agents or may be utilized as an antimicrobial. Some of the surface properties and antimicrobial activity were resolved.

  12. Three essays on credit derivatives and liquidity

    OpenAIRE

    Arakelyan, Armen

    2012-01-01

    This thesis consists of three empirical essays on pricing credit derivatives and the impact of liquidity on the prices of credit derivatives. In essay one, I investigate empirically the pricing of Collateralized Debt Obligations (CDO) within the framework of copula models. In essay two I analyze the impact of illiquidity on Credit Default Swap (CDS) spreads on an individual level. In essay three I analyze the effect of market wide illiquidity on portfolio CDS spreads on an aggrega...

  13. Synthesis of furan from allenic sulfide derivatives

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper, we report the synthesis of furan derivatives from allenic sulfides. By the reaction with NaH, β-Hydroxyl allenic sulfides were found to generate furan products in excellent yields with the removal of phenylthio group. β-Aldehyde allenic sulfides were found to give similar furan products with one more substituent when treated with additional nucleophilic reagents. β-ketone allenic sulfides can also cyclize to give furan derivatives with the promotion of P2O5.

  14. DERIVATIONS AND EXTENSIONS OF LIE COLOR ALGEBRA

    Institute of Scientific and Technical Information of China (English)

    Zhang Qingcheng; Zhang Yongzheng

    2008-01-01

    In this article, the authors obtain some results concerning derivations of fi-nitely generated Lie color algebras and discuss the relation between skew derivation space SkDer(L) and central extension H2(L, F) on some Lie color algebras. Meanwhile, they generalize the notion of double extension to quadratic Lie color algebras, a sufficient con-dition for a quadratic Lie color algebra to be a double extension and further properties are given.

  15. The period functions' higher order derivatives

    CERN Document Server

    Sabatini, Marco

    2012-01-01

    We prove a formula for the $n$-th derivative of the period function $T$ in a period annulus of a planar differential system. For $n = 1$, we obtain Freire, Gasull and Guillamon formula for the period's first derivative \\cite{FGG}. We apply such a result to hamiltonian systems with separable variables and other systems. We give some sufficient conditions for the period function of conservative second order O.D.E.'s to be convex.

  16. Synthesis of furan from allenic sulfide derivatives

    Institute of Scientific and Technical Information of China (English)

    PENG LingLing; ZHANG Xiu; MA Jie; ZHONG ZhenZhen; ZHANG Zhe; ZHANG Yan; WANG JianBo

    2009-01-01

    In this paper, we report the synthesis of furan derivatives from allenic sulfides. By the reaction with NaH.,β-Hydroxyl allenic sulfides were found to generate furan products in excellent yields with the removal of phenylthio group.β-Aldehyde allenic sulfides were found to give similar furan products with one more substituent when treated with additional nucleophilic reagents. β-ketone allenic sulfides can also cyclize to give furan derivatives with the promotion of P2O5.

  17. Terpenes from Marine-Derived Fungi

    OpenAIRE

    Rainer Ebel

    2010-01-01

    Terpenes from marine-derived fungi show a pronounced degree of structural diversity, and due to their interesting biological and pharmacological properties many of them have aroused interest from synthetic chemists and the pharmaceutical industry alike. The aim of this paper is to give an overview of the structural diversity of terpenes from marine-derived fungi, highlighting individual examples of chemical structures and placing them in a context of other terpenes of fungal origin. Wherever ...

  18. Fluorescence of fullerene derivatives at room temperature

    Energy Technology Data Exchange (ETDEWEB)

    Lin, S.K.; Shiu, L.L.; Chien, K.M.; Luh, T.Y.; Lin, T.I. (National Taiwan Univ., Taipei (Taiwan, Province of China))

    1995-01-05

    The absorption and fluorescence spectral properties of fullerene (C[sub 60]) and its derivatives C[sub 60]C[sub 4]H[sub 6], C[sub 60]C[sub 5]H[sub 6], C[sub 60]CHCO[sub 2]Et, and C[sub 60]NCO[sub 2]Et at room temperature were investigated. Breaking the structural symmetry of C[sub 60] results in enhancing the fluorescence quantum yield 2-3-fold in some derivatives. Thus, the room temperature fluorescence of fullerene compounds could be detected more rapidly. New absorption bands and altered fluorescence spectra were observed in the derivatives. The Stokes' shifts of the derivatives are small, about 4-5 nm, compared to 68 nm for the parent compound. The time-resolved fluorescence decay study indicates that all four fullerene derivatives have a single fluorescence lifetime of ca. 1.2-1.4 as, which is about the same as that for C[sub 60] (ca. 1.3 ns). Aliphatic solvents have little influence on the absorption or fluorescence spectral profile except on the extinction coefficient whereas aromatic and polar solvents strongly interact with the fullerene derivatives, causing a peak broadening effect. 31 refs., 7 figs., 3 tabs.

  19. Quadratic forms and Clifford algebras on derived stacks

    OpenAIRE

    Vezzosi, Gabriele

    2013-01-01

    In this paper we present an approach to quadratic structures in derived algebraic geometry. We define derived n-shifted quadratic complexes, over derived affine stacks and over general derived stacks, and give several examples of those. We define the associated notion of derived Clifford algebra, in all these contexts, and compare it with its classical version, when they both apply. Finally, we prove three main existence results for derived shifted quadratic forms over derived stacks, define ...

  20. Novel Poly(imide dioxime) Sorbents: Development and testing for enhanced extraction of uranium from natural seawater

    Energy Technology Data Exchange (ETDEWEB)

    Das, Sadananda; Brown, Suree S.; Mayes, Richard T.; Janke, Christopher J.; Tsouris, Costas; Kuo, Li-Jung; Gill, Gary A.; Dai, Sheng

    2016-04-09

    A new series of amidoxime-based polymer adsorbents were synthesized at the Oak Ridge National Laboratory (ORNL) by electron beam induced grafting of acrylonitrile and itaconic acid onto polyethylene fiber. Hydroxylamine derivatives of poly(acrylonitrile) (PAN) moiety are demonstrated to possess two kinds of functional groups: open-chain amidoxime and cyclic imide dioxime. The open-chain amidoxime is shown to convert to imide dioxime on heat treatment in the presence of an aprotic solvent, like dimethylsulfoxide (DMSO). The formation of amidoxime and imide dioxime was confirmed by 13-C CPMAS spectra. The adsorbents were evaluated for uranium adsorption efficiency at ORNL with simulated seawater spiked with 8 ppm uranium and 5 gallon seawater in a batch reactor, and in flow-through columns with natural seawater at the Marine Science Laboratory (MSL) of Pacific Northwest National Laboratory (PNNL) at Sequim Bay, WA. The DMSO-heat-treated sorbents adsorbed uranium as high as 4.48 g-U/kg-ads. from seawater. Experimental evidence is presented that the poly(imide dioxime) is primarily responsible for enhanced uranium adsorption capacity from natural seawater. The conjugated system in the imide dioxime ligand possesses increased electron donation ability, which is believed to significantly enhance the uranyl coordination in seawater

  1. Crystallisation and crystal forms of carbohydrate derivatives

    Science.gov (United States)

    Lennon, Lorna

    This thesis is focused on the synthesis and solid state analysis of carbohydrate derivatives, including many novel compounds. Although the synthetic chemistry surrounding carbohydrates is well established in the literature, the crystal chemistry of carbohydrates is less well studied. Therefore this research aims to improve understanding of the solid state properties of carbohydrate derivatives through gaining more information on their supramolecular bonding. Chapter One focuses on an introduction to the solid state of organic compounds, with a background to crystallisation, including issues that can arise during crystal growth. Chapter Two is based on glucopyranuronate derivatives which are understudied in terms of their solid state forms. This chapter reports on the formation of novel glucuronamides and utilising the functionality of the amide bond for crystallisation. TEMPO oxidation was completed to form glucopyranuronates by oxidation of the primary alcohol groups of glucosides to the carboxylic acid derivatives, to increase functionality for enhanced crystal growth. Chapter Three reports on the synthesis of glucopyranoside derivatives by O-glycosylation reactions and displays crystal structures, including a number of previously unsolved acetate protected and deprotected crystal structures. More complex glycoside derivatives were also researched in an aim to study the resultant supramolecular motifs. Chapter Four contains the synthesis of aryl cellobioside derivatives including the novel crystal structures that were solved for the acetate protected and deprotected compounds. Research was carried out to determine if 1-deoxycellodextrins could act as putative isostructures for cellulose. Our research displays the presence of isostructural references with 1-deoxycellotriose shown to be similar to cellulose III11, 1-deoxycellotetraose correlates with cellulose IV11 and 1-deoxycellopentose shows isostructurality similar to that of cellulose II. Chapter Five contains

  2. Synthesis of new triazole-based trifluoromethyl scaffolds

    Directory of Open Access Journals (Sweden)

    2008-05-01

    Full Text Available Trifluoromethyl propargylamines react with various azide derivatives to afford 1,4-disubstituted 1,2,3-triazoles through a Huisgen 1,3-dipolar cycloaddition. The reaction is catalyzed by a Cu(I species in acetonitrile, and the corresponding products are obtained in good yields. This process thus offers an entry to new trifluoromethyl peptidomimetics as interesting scaffolds.

  3. Additive Lie (ζ-Lie) Derivations and Generalized Lie (ζ-Lie)Derivations on Prime Algebras

    Institute of Scientific and Technical Information of China (English)

    Xiao Fei QI; Jin Chuan HOU

    2013-01-01

    The additive (generalized) ζ-Lie derivations on prime algebras are characterized.It is shown,under some suitable assumptions,that an additive map L is an additive generalized Lie derivation if and only if it is the sum of an additive generalized derivation and an additive map from the algebra into its center vanishing all commutators; is an additive (generalized) ζ-Lie derivation with ζ ≠ 1 if and only if it is an additive (generalized) derivation satisfying L(ζA) =ζL(A) for all A.These results are then used to characterize additive (generalized) ζ-Lie derivations on several operator algebras such as Banach space standard operator algebras and von Neumman algebras.

  4. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.

    OpenAIRE

    Nagy, A.; Rossant, J.; Nagy, R.; Abramow-Newerly, W; Roder, J C

    1993-01-01

    Several newly generated mouse embryonic stem (ES) cell lines were tested for their ability to produce completely ES cell-derived mice at early passage numbers by ES cell tetraploid embryo aggregation. One line, designated R1, produced live offspring which were completely ES cell-derived as judged by isoenzyme analysis and coat color. These cell culture-derived animals were normal, viable, and fertile. However, prolonged in vitro culture negatively affected this initial totipotency of R1, and...

  5. Machian derivation of the Friedmann equation

    Science.gov (United States)

    Telkamp, Herman

    2016-08-01

    Despite all fundamental objections against Newtonian concepts in cosmology, the Friedmann equation derives from these in an astoundingly simple way through application of the shell theorem and conservation of Newtonian energy in an infinite universe. However, Friedmann universes in general possess a finite gravitational horizon, as a result of which the application of the shell theorem fails and the Newtonian derivation collapses. Hence, unlike the general relativistic derivation, the Newtonian derivation does not prove the Friedmann equation in general, but exclusively in the Newtonian case of an infinite horizon. We show that in the presence of a gravitational horizon the Friedmann equation can be derived from conservation of Machian energy, without invoking the shell theorem. Whereas in the Newtonian case total energy translates to curvature energy density, in the Machian case total energy takes on different identities, depending on the evolution of the horizon; we show that in the de Sitter universe Machian total energy density is constant, i.e. appears as cosmological constant.

  6. Deriving Framework Usages Based on Behavioral Models

    Science.gov (United States)

    Zenmyo, Teruyoshi; Kobayashi, Takashi; Saeki, Motoshi

    One of the critical issue in framework-based software development is a huge introduction cost caused by technical gap between developers and users of frameworks. This paper proposes a technique for deriving framework usages to implement a given requirements specification. By using the derived usages, the users can use the frameworks without understanding the framework in detail. Requirements specifications which describe definite behavioral requirements cannot be related to frameworks in as-is since the frameworks do not have definite control structure so that the users can customize them to suit given requirements specifications. To cope with this issue, a new technique based on satisfiability problems (SAT) is employed to derive the control structures of the framework model. In the proposed technique, requirements specifications and frameworks are modeled based on Labeled Transition Systems (LTSs) with branch conditions represented by predicates. Truth assignments of the branch conditions in the framework models are not given initially for representing the customizable control structure. The derivation of truth assignments of the branch conditions is regarded as the SAT by assuming relations between termination states of the requirements specification model and ones of the framework model. This derivation technique is incorporated into a technique we have proposed previously for relating actions of requirements specifications to ones of frameworks. Furthermore, this paper discuss a case study of typical use cases in e-commerce systems.

  7. Structure Activity Relationship of Brevenal Hydrazide Derivatives

    Directory of Open Access Journals (Sweden)

    Allan Goodman

    2014-03-01

    Full Text Available Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia brevis. This organism is also responsible for the production of the neurotoxic compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads to adverse effects such as gastrointestinal maladies and bronchoconstriction. Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial attributes when administered alone. For example, in an asthmatic sheep model, brevenal has been shown to increase tracheal mucosal velocity, an attribute which has led to its development as a potential treatment for Cystic Fibrosis. The mechanism of action of brevenal is poorly understood and the exact binding site has not been elucidated. In an attempt to further understand the mechanism of action of brevenal and potentially develop a second generation drug candidate, a series of brevenal derivatives were prepared through modification of the aldehyde moiety. These derivatives include aliphatic, aromatic and heteroaromatic hydrazide derivatives. The brevenal derivatives were tested using in vitro synaptosome binding assays to determine the ability of the compounds to displace brevetoxin and brevenal from their native receptors. A sheep inhalation model was used to determine if instillation of the brevenal derivatives resulted in bronchoconstriction. Only small modifications were tolerated, with larger moieties leading to loss of affinity for the brevenal receptor and bronchoconstriction in the sheep model.

  8. Multiscale analysis of the CMB temperature derivatives

    Science.gov (United States)

    Marcos-Caballero, A.; Martínez-González, E.; Vielva, P.

    2017-02-01

    We study the Planck CMB temperature at different scales through its derivatives up to second order, which allows one to characterize the local shape and isotropy of the field. The problem of having an incomplete sky in the calculation and statistical characterization of the derivatives is addressed in the paper. The analysis confirms the existence of a low variance in the CMB at large scales, which is also noticeable in the derivatives. Moreover, deviations from the standard model in the gradient, curvature and the eccentricity tensor are studied in terms of extreme values on the data. As it is expected, the Cold Spot is detected as one of the most prominent peaks in terms of curvature, but additionally, when the information of the temperature and its Laplacian are combined, another feature with similar probability at the scale of 10o is also observed. However, the p-value of these two deviations increase above the 6% when they are referred to the variance calculated from the theoretical fiducial model, indicating that these deviations can be associated to the low variance anomaly. Finally, an estimator of the directional anisotropy for spinorial quantities is introduced, which is applied to the spinors derived from the field derivatives. An anisotropic direction whose probability is <1% is detected in the eccentricity tensor.

  9. Adaptive synchronization of the complex dynamical network with non-derivative and derivative coupling

    Science.gov (United States)

    Xu, Yuhua; Zhou, Wuneng; Fang, Jian'an; Sun, Wen

    2010-04-01

    This Letter investigates the synchronization of a general complex dynamical network with non-derivative and derivative coupling. Based on LaSalle's invariance principle, adaptive synchronization criteria are obtained. Analytical result shows that under the designed adaptive controllers, a general complex dynamical network with non-derivative and derivative coupling can asymptotically synchronize to a given trajectory, and several useful criteria for synchronization are given. What is more, the coupling matrix is not assumed to be symmetric or irreducible. Finally, simulations results show the method is effective.

  10. Adaptive synchronization of the complex dynamical network with non-derivative and derivative coupling

    Energy Technology Data Exchange (ETDEWEB)

    Xu Yuhua, E-mail: yuhuaxu2004@163.co [College of Information Science and Technology, Donghua University, Shanghai 201620 (China) and Department of Maths, Yunyang Teachers' College, Hubei 442000 (China); Zhou Wuneng, E-mail: wnzhou@163.co [College of Information Science and Technology, Donghua University, Shanghai 201620 (China); Fang Jian' an [College of Information Science and Technology, Donghua University, Shanghai 201620 (China); Sun Wen [School of Mathematics and Information, Yangtze University, Hubei Jingzhou 434023 (China)

    2010-04-05

    This Letter investigates the synchronization of a general complex dynamical network with non-derivative and derivative coupling. Based on LaSalle's invariance principle, adaptive synchronization criteria are obtained. Analytical result shows that under the designed adaptive controllers, a general complex dynamical network with non-derivative and derivative coupling can asymptotically synchronize to a given trajectory, and several useful criteria for synchronization are given. What is more, the coupling matrix is not assumed to be symmetric or irreducible. Finally, simulations results show the method is effective.

  11. Chromone derivatives from a sponge-derived strain of the fungus Corynespora cassiicola.

    Science.gov (United States)

    Zhao, Dong-Lin; Shao, Chang-Lun; Gan, Li-She; Wang, Mei; Wang, Chang-Yun

    2015-02-27

    Twelve new chromone derivatives, corynechromones A-L (1-12), were isolated from the sponge-derived fungus Corynespora cassiicola XS-200900I7. Among them, 1/2, 3/4, 5/6, and 7/8 were pairs of epimers. The planar structures were determined by extensive NMR spectroscopic data. The absolute configurations of 1-10 were assigned by the modified Mosher's method and TDDFT ECD calculations together with comparison of their CD spectra. These are the first chromone derivatives reported from the genus Corynespora. A possible rule to determine the absolute configurations at C-2 in chromone derivatives by CD was proposed.

  12. Conversion of 3-Carbethoxy-4-methyl Coumarin Derivatives into Several New Annelated Coumarin Derivatives

    Institute of Scientific and Technical Information of China (English)

    BAKEER; HadeerMohammed

    2003-01-01

    The reaction of ethyl esters of 4-methyl-2-oxo-2H-l-benzo(naphtho) pyran.3-carboxylic acids (1) with aromatic aldehy-des in the presence of piperidine yielded 4-styryl-3-carboxami-dopiperidyl connmrin derivatives 4. The reaction of hydrazlne hydrate with 1 gave acetophenone hydrozone derivatives 5 and acetophenone azine derivatives 6. The reaction of 1 with prima-ry amines afforded compomlds 7—9. And the treatment of la with Grignard reagents afforded 3-aroyl-4-methyl coumarin derivatives 10.

  13. Studies on Synthesis of Some Novel Heterocyclic Azlactone Derivatives and Imidazolinone Derivatives and their Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Rakesh N. Mistry

    2005-01-01

    Full Text Available p - Methyl benzoic acid on reaction with phosphorus pentachloride gives p - methyl benzoyl chloride derivative which on condensation with glycine gives p - methyl benzoyl glycine derivative. Now, this p - methyl benzoyl glycine derivative on condensation with various substituted aldehydes gives corresponding substituted 4 - [aryl methylidine] - 2 - [p - methyl phenyl] - oxazole - 5 - one derivatives [1(a-j]. Further, these derivatives [1(a-j] on condensation with 4 , 4’ - diamino diphenyl sulphone gives corresponding substituted imidazolinone - dibenzsulphone derivatives [2(a-j], on condensation with 4 , 4’ - diamino diphenyl methane gives corresponding substituted imidazolinone - dibenzmethane derivatives [3(a-j], on condensation with 4,4’- diamino benzanilide gives corresponding substituted imidazolinone - benzanilide derivatives [4(a-j] and on condensation with 2 - amino pyridine gives corresponding substituted imidazolinone - pyridine derivatives [5(a-j] respectively. Structure elucidation of synthesised compounds has been made on the basis of elemental analysis, I.R. spectral studies and 1H N.M.R. spectral studies. The antimicrobial activity of the synthesised compounds has been studied against the cultures “Staphylococcus aureus”, “Escherichia coli” and “Candela albicans”.

  14. Synthesis and antiproliferative activity of new tonantzitlolone-derived diterpene derivatives.

    Science.gov (United States)

    Busch, Torsten; Dräger, Gerald; Kunst, Eike; Benson, Hannah; Sasse, Florenz; Siems, Karsten; Kirschning, Andreas

    2016-10-14

    The synthesis of the diterpene (+)-tonantzitlolone A and a series of derivatives is reported. The study includes the determination of their antiproliferative activities against selected cancer cell lines.

  15. A REMARK ON THE DERIVATE OF SET-VALUED MAPPING

    Institute of Scientific and Technical Information of China (English)

    CheaBing

    1994-01-01

    The derivate of set-valued mappings was defined by Hakuhara M in [1] and is called H-derivate. This paper shows a necessary and sufficient condition for a set-valued mapping to be derivable in term of Hderivate and the conditions in which lirnit and derivate ,derivate and integyal are exchanged respectively.

  16. Symmetric Partial Derivatives%对称偏导数

    Institute of Scientific and Technical Information of China (English)

    徐永平

    2001-01-01

    In this paper, symmetric partial derivatives and symmetric total differential of a function of several variables are defined. The relationship between partial derivative and the symmetric partial derivative, the total differential and the symmetric total derivative are discussed. By means of the concept of symmetric partial derivatives, the existence theorem of the total differential of a function of several is obtained.

  17. INTERPOLATION INEQUALITIES AND DECAY ESTIMATES FOR DERIVATIVES

    Institute of Scientific and Technical Information of China (English)

    Lu Xuguang

    2000-01-01

    Under the only assumption of the cone property for a given domain Ω∈Rn, it is proved that interpolation inequalities for intermediate derivatives of functions in the Sobolev spaces Wm,p (Ω) or even in some weighted Sobolve spaces Wwm,p (Ω) still hold. That is, the usual additional restrictions that Ω is bounded or has the uni form cone property are both removed. The main tools used are polynomial inequalities, by which it is also ob tained pointwise version interpolation inequalities for smooth and analytic functions. Such pointwise version in equalities give explicit decay estimates for derivatives at infinity in unbounded domains which have the cone property. As an application of the decay estimates, a previous result on radial basis function approximation of smooth functions is extended to the derivative-simultaneous approximation.

  18. Another derivation of generalized Langevin equations

    CERN Document Server

    Dengler, R

    2015-01-01

    The formal derivation of Langevin equations (and, equivalently Fokker-Planck equations) with projection operator techniques of Mori, Zwanzig, Kawasaki and others can well be called a pearl of theoretical physics. The derivation relies on classical mechanics, and encompasses everything an omnipotent engineer can construct from point particles and potentials: solids, liquids, liquid crystals, conductors, polymers, systems with spin-like degrees of freedom ... Einstein relations and Onsager reciprocity theorem come for free. It apparently not has widely found its way into textbooks, but has been reproduced dozens of times on the fly with many references to the literature and without adding much substantially new. Here we follow the tradition, but strive to produce a self-contained text. Furthermore, we address questions that naturally arise in the derivation. Among other things the meaning of the divergence of the Poisson brackets is explained, and the role of nonlinear damping coefficients is clarified.

  19. Synthesis of Calix[4]resorcinarene Amide Derivatives

    Institute of Scientific and Technical Information of China (English)

    Chao Guo YAN; Yun GE

    2004-01-01

    Three different synthetic routes were developed to introduce carbamoyloxy functional groups at the upper periphery of two calix[4]resorcinarenes. By treating activated esters 2a-b with excess corresponding amine such as 3-(dimethylamino)propylamine 3, α-phenethylamine 4 and triethylenetetramine 5, six amide derivatives 6a~8b were obtained in high yield (Route 1). The pyridine-linked amide derivatives 9a-b were prepared by using acid chloride intermediate (Route 2). The amide derivatives 10a-b were obtained in moderate yields by direct alkylation of phenolic hydroxyl groups of 1a-b with N,N-dipropylchloroacetoamide in the presence of K2CO3/KI in acetone (Route 3).

  20. Analytics of Quinine and its Derivatives.

    Science.gov (United States)

    Kluska, Mariusz; Marciniuk-Kluska, Anna; Prukała, Dorota; Prukała, Wiesław

    2016-01-01

    The objective of this study was to perform a synthesis and analysis of the most important information on quinine and its derivatives, which are still very important in the treatment of malaria. The analysis of stereoisomers of quinine and its derivatives was conducted using two techniques, high-performance liquid chromatography and capillary electrophoresis. Particularly noteworthy is the technique used for the determination of isotachophoresis, referred to as one of the so-called green chemistry techniques. Particular attention was paid to properties and the use of quinine and its derivatives in the treatment of malaria. The analytical part will supplement knowledge about quinidine, quinine, and cinchonidine, and will contribute to the growth of research on the so-much-needed drugs against malaria.

  1. Funding climate adaptation strategies with climate derivatives

    Directory of Open Access Journals (Sweden)

    L. Richard Little

    2015-01-01

    Full Text Available Climate adaptation requires large capital investments that could be provided not only by traditional sources like governments and banks, but also by derivatives markets. Such markets would allow two parties with different tolerances and expectations about climate risks to transact for their mutual benefit and, in so doing, finance climate adaptation. Here we calculate the price of a derivative called a European put option, based on future sea surface temperature (SST in Tasmania, Australia, with an 18 °C strike threshold. This price represents a quantifiable indicator of climate risk, and forms the basis for aquaculture industries exposed to the risk of higher SST to finance adaptation strategies through the sale of derivative contracts. Such contracts provide a real incentive to parties with different climate outlooks, or risk exposure to take a market assessment of climate change.

  2. Photochemistry of hypocrellin derivatives under anaerobic conditions

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To improve the red absorption and solubility of hypocrellin, we have synthesized a series of hypocrellin B derivatives. The photochemistry of these new compounds in anaerobic media has been investigated by using electronic paramagnetic resonance (EPR) and spectrophotometric methods. The semiquinone anion radicals can be produced by self-electron transfer on irradiation, with the formation efficiency and EPR hyperfine structures of the semiquinone anion radicals dependent on the structures of the derivatives. When an electron donor is present, the electron transfer from electron donor to hypocrellin B derivatives enhanced the production of the corresponding semiquinone anion radical; in addition, the semiquinone anion radical and hydroquinone can be detected spectrophotometrically. Structural modifications exert little effect on the absorption position of semiquinone anion radical and hydroquinone, but influence their formation efficiency significantly.

  3. Optimal hedging of Derivatives with transaction costs

    CERN Document Server

    Aurell, E; Aurell, Erik; Muratore-Ginanneschi, Paolo

    2005-01-01

    We investigate the optimal strategy over a finite time horizon for a portfolio of stock and bond and a derivative in an multiplicative Markovian market model with transaction costs (friction). The optimization problem is solved by a Hamilton-Bellman-Jacobi equation, which by the verification theorem has well-behaved solutions if certain conditions on a potential are satisfied. In the case at hand, these conditions simply imply arbitrage-free ("Black-Scholes") pricing of the derivative. While pricing is hence not changed by friction allow a portfolio to fluctuate around a delta hedge. In the limit of weak friction, we determine the optimal control to essentially be of two parts: a strong control, which tries to bring the stock-and-derivative portfolio towards a Black-Scholes delta hedge; and a weak control, which moves the portfolio by adding or subtracting a Black-Scholes hedge. For simplicity we assume growth-optimal investment criteria and quadratic friction.

  4. Derivatives on the isotropic tensor functions

    Institute of Scientific and Technical Information of China (English)

    DUI; Guansuo; WANG; Zhengdao; JIN; Ming

    2006-01-01

    The derivative of the isotropic tensor function plays an important part in continuum mechanics and computational mechanics, and also it is still an opening problem. By means of a scalar response function and solving a tensor equation, this problem is well studied. A compact explicit expression for the derivative of the isotropic tensor function is presented, which is valid for both distinct and repeated eigenvalue cases. Throughout the analysis, the formulation holds for general isotropic tensor functions without need to solve eigenvector problems or determine coefficients. On the theoretical side, a very simple solution of a tensor equation is obtained. As an application to continuum mechanics, a base-free expression for the Hill's strain rate is given, which is more compact than the existent results. Finally, with an example we compute the derivative of an exponent tensor function. And the efficiency of the present formulations is demonstrated.

  5. Langmuir-Blodgett Films of Graphene Derivatives

    DEFF Research Database (Denmark)

    Petersen, Søren Vermehren

    The work presented in this PhD thesis can be divided into two main categories: 1) Syn-thesis and Langmuir-Blodgett assembly of graphene derivatives and 2) Application and characterization of graphene derivatives as an interface material in molecular electron-ics. While the first category could...... be divided further, the synthesis and Langmuir-Blodgett results are intertwined in such a way that it would be more confusing to pre-sent them separately. The Langmuir-Blodgett deposition also played a crucial, but more isolated, part in the investigation of graphene derivatives as interface material...... were investigated using the Langmuir-Blodgett technique. It was found that reduction of graphene oxide back into graphene did not seem possible in solution, while still maintaining its monolayer character. Instead, an alternative route for graphene synthesis was then designed. This involved...

  6. Deriving Trading Rules Using Gene Expression Programming

    Directory of Open Access Journals (Sweden)

    Adrian VISOIU

    2011-01-01

    Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

  7. Real-time cosmography with redshift derivatives

    Science.gov (United States)

    Martins, C. J. A. P.; Martinelli, M.; Calabrese, E.; Ramos, M. P. L. P.

    2016-08-01

    The drift in the redshift of objects passively following the cosmological expansion has long been recognized as a key model-independent probe of cosmology. Here, we study the cosmological relevance of measurements of time or redshift derivatives of this drift, arguing that the combination of first and second redshift derivatives is a powerful test of the Λ CDM cosmological model. In particular, the latter can be obtained numerically from a set of measurements of the drift at different redshifts. We show that, in the low-redshift limit, a measurement of the derivative of the drift can provide a constraint on the jerk parameter, which is j =1 for flat Λ CDM , while generically j ≠1 for other models. We emphasize that such a measurement is well within the reach of the ELT-HIRES and SKA Phase 2 array surveys.

  8. Horava gravity with mixed derivative terms

    CERN Document Server

    Colombo, Mattia; Sotiriou, Thomas P

    2014-01-01

    Horava gravity has been constructed so as to exhibit anisotropic scaling in the ultraviolet, as this renders the theory power-counting renormalizable. However, when coupled to matter, the theory has been shown to suffer from quadratic divergences. A way to cure these divergences is to add terms with both time and space derivatives. We consider this extended version of the theory in detail. We perform a perturbative analysis that includes all modes, determine the propagators and discuss how including mixed-derivative terms affects them. We also consider the Lifshitz scalar with mixed-derivative terms as a toy model for power counting arguments and discuss the influence of such terms on renormalizability.

  9. Electrical derivative measurement of quantum cascade lasers

    Science.gov (United States)

    Guo, Dingkai; Cheng, Liwei; Chen, Xing; Choa, Fow-Sen; Fan, Jenyu; Worchesky, Terry

    2011-02-01

    The electrical derivative characteristics of quantum cascade lasers (QCLs) are investigated to test the QCL threshold, leakage current, and possibly explore carrier transport. QCL thresholds can be identified by searching for the slope peak of the first derivative of the I-V curves and can be further confirmed with its alignment to the peak of the second derivative of the I-V curves. Leakage current in QCLs with oxide-blocked ridge waveguides and buried heterostructure (BH) waveguides are studied and compared. The oxide-blocking structures provide the lowest leakage current although the capped-mesa-BH (CMBH) QCLs provide the toughest durability under highly stressful operations. The leakage current of CMBH QCLs are also compared at different temperatures.

  10. On Semiprime Rings with Generalized Derivations

    Directory of Open Access Journals (Sweden)

    Shakir Ali

    2010-09-01

    Full Text Available Let R be a ring and F and G be generalized derivations of R with associated derivations d and g respectively. In the present paper,we shall investigate the commutativity of semiprime ring R admitting generalized derivations F and G satisfying any one of the properties: (iF(xx = xG(x, (ii [F(x, d(y] = [x,y], (iii F([x,y] = [d(x, F(y], (iv d(xF(y = xy, (v F(x^2 = x^2, (vi [F(x,y] = [x,G(y], (vii F([x, y] = [F(x, y] + [d(y, x] and (viii F(x ◦ y = F(x ◦ y −d(y ◦ x for all x, y in some appropriate subset of R.

  11. Real-time cosmography with redshift derivatives

    CERN Document Server

    Martins, C J A P; Calabrese, E; Ramos, M P L P

    2016-01-01

    The drift in the redshift of objects passively following the cosmological expansion has long been recognized as a key model-independent probe of cosmology. Here, we study the cosmological relevance of measurements of time or redshift derivatives of this drift, arguing that the combination of first and second redshift derivatives is a powerful test of the $\\Lambda$CDM cosmological model. In particular, the latter can be obtained numerically from a set of measurements of the drift at different redshifts. We show that, in the low-redshift limit, a measurement of the derivative of the drift can provide a constraint on the jerk parameter, which is $j=1$ for flat $\\Lambda$CDM, while generically $j\

  12. Vulnerable Derivatives and Good Deal Bounds

    DEFF Research Database (Denmark)

    Murgoci, Agatha

    2013-01-01

    can be obtained. We provide a link between the objective probability measure and the range of potential risk-neutral measures, which has an intuitive economic meaning. We also provide tight pricing bounds for European calls and show how to extend the call formula to pricing other financial products......We price vulnerable derivatives – i.e. derivatives where the counterparty may default. These are basically the derivatives traded on the over-the-counter (OTC) markets. Default is modelled in a structural framework. The technique employed for pricing is good deal bounds (GDBs). The method imposes...... a new restriction in the arbitrage free model by setting upper bounds on the Sharpe ratios (SRs) of the assets. The potential prices that are eliminated represent unreasonably good deals. The constraint on the SR translates into a constraint on the stochastic discount factor. Thus, tight pricing bounds...

  13. Second derivatives for approximate spin projection methods.

    Science.gov (United States)

    Thompson, Lee M; Hratchian, Hrant P

    2015-02-07

    The use of broken-symmetry electronic structure methods is required in order to obtain correct behavior of electronically strained open-shell systems, such as transition states, biradicals, and transition metals. This approach often has issues with spin contamination, which can lead to significant errors in predicted energies, geometries, and properties. Approximate projection schemes are able to correct for spin contamination and can often yield improved results. To fully make use of these methods and to carry out exploration of the potential energy surface, it is desirable to develop an efficient second energy derivative theory. In this paper, we formulate the analytical second derivatives for the Yamaguchi approximate projection scheme, building on recent work that has yielded an efficient implementation of the analytical first derivatives.

  14. Synthesis of azido derivatives of mucobromic acid

    Directory of Open Access Journals (Sweden)

    N. Mbebe

    2013-04-01

    Full Text Available Mucobromic acid is a highly reactive multicentered molecule. It was converted to its corresponding but unstable diazido derivative by reaction with two equivalents of sodium azide. The resultant 3,4-diazido-5-hydroxyfuran-2(5H-one was obtained in moderate yield (42% but decomposed readily even at low temperatures. Its more stable analogue 3,4-diazido-5-methoxyfuran-2(5H-one was obtained in excellent yield after reacting 5-methoxy-3,4-dibromofuranone with two equivalents of sodium azide. The 4,5-dibromopyridazinones which are in effect masked mucobromic acid derivatives, underwent nucleophilic substitution reactions with various nucleophiles, including azides and afforded corresponding azidopyridazinones in good yields. The synthesized azido-furanone and pyridazinone derivatives are earmarked for click reactions.DOI: http://dx.doi.org/10.4314/bcse.v27i1.17

  15. Hydrodynamic Nambu Brackets derived by Geometric Constraints

    CERN Document Server

    Blender, Richard

    2015-01-01

    A geometric approach to derive the Nambu brackets for ideal two-dimensional (2D) hydrodynamics is suggested. The derivation is based on two-forms with vanishing integrals in a periodic domain, and with resulting dynamics constrained by an orthogonality condition. As a result, 2D hydrodynamics with vorticity as dynamic variable emerges as a generic model, with conservation laws which can be interpreted as enstrophy and energy functionals. Generalized forms like surface quasi-geostrophy and fractional Poisson equations for the stream-function are also included as results from the derivation. The formalism is extended to a hydrodynamic system coupled to a second degree of freedom, with the Rayleigh-B\\'{e}nard convection as an example. This system is reformulated in terms of constitutive conservation laws with two additive brackets which represent individual processes: a first representing inviscid 2D hydrodynamics, and a second representing the coupling between hydrodynamics and thermodynamics. The results can b...

  16. Halogenated coumarin derivatives as novel seed protectants.

    Science.gov (United States)

    Brooker, N; Windorski, J; Bluml, E

    2008-01-01

    Development of new and improved antifungal compounds that are target-specific is backed by a strong Federal, public and commercial mandate. Many plant-derived chemicals have proven fungicidal properties, including the coumarins (1,2-Benzopyrone) found in a variety of plants such as clover, sweet woodruff and grasses. Preliminary research has shown the coumarins to be a highly active group of molecules with a wide range of antimicrobial activity against both fungi and bacteria. It is believed that these cyclic compounds behave as natural pesticidal defence molecules for plants and they represent a starting point for the exploration of new derivative compounds possessing a range of improved antifungal activity. Within this study, derivatives of coumarin that were modified with halogenated side groups were screened for their antifungal activity against a range of soil-borne plant pathogenic fungi. Fungi included in this in vitro screen included Macrophomina phaseolina (charcoal rot), Phytophthora spp. (damping off and seedling rot), Rhizoctonia spp. (damping off and root rot) and Pythium spp. (seedling blight), four phylogenetically diverse and economically important plant pathogens. Studies indicate that these halogenated coumarin derivatives work very effectively in vitro to inhibit fungal growth and some coumarin derivatives have higher antifungal activity and stability as compared to the original coumarin compound alone. The highly active coumarin derivatives are brominated, iodinated and chlorinated compounds and results suggest that besides being highly active, very small amounts can be used to achieve LD100 rates. In addition to the in vitro fungal inhibition assays, results of polymer seed coating compatibility and phytotoxicity testing using these compounds as seed treatments will also be reported. These results support additional research in this area of natural pesticide development.

  17. Preparation of 7-substituted ginkgolide derivatives

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Strømgaard, Kristian; Shindou, Hideo

    2003-01-01

    of these derivatives as assayed by cloned PAF receptors. In two cases nucleophilic attack on a 7beta-O-triflate ginkgolide B did not lead to the expected products, but gave rise to two unprecedented ginkgolide derivatives, one with a novel rearranged skeleton. Furthermore, standard reduction of 7alpha-azido ginkgolide...... B did not give the expected primary amine, but instead yielded alkylated amines depending on the solvent employed. Pharmacological testing with cloned PAF receptors showed that ginkgolides with 7alpha-substitutents had increased affinity compared to 7beta-substituents, in particular 7alpha...

  18. Method of thermal derivative gradient analysis (TDGA

    Directory of Open Access Journals (Sweden)

    M. Cholewa

    2009-07-01

    Full Text Available In this work a concept of thermal analysis was shown, using for crystallization kinetics description the temperature derivatives after time and direction. Method of thermal derivative gradient analysis (TDGA is assigned for alloys and metals investigation as well as cast composites in range of solidification. The construction and operation characteristics were presented for the test stand including processing modules and probes together with thermocouples location. Authors presented examples of results interpretation for AlSi11 alloy castings with diversified wall thickness and at different pouring temperature.

  19. Orchard navigation using derivative free Kalman filtering

    DEFF Research Database (Denmark)

    Hansen, Søren; Bayramoglu, Enis; Andersen, Jens Christian

    2011-01-01

    This paper describes the use of derivative free filters for mobile robot localization and navigation in an orchard. The localization algorithm fuses odometry and gyro measurements with line features representing the surrounding fruit trees of the orchard. The line features are created on basis of 2......D laser scanner data by a least square algorithm. The three derivative free filters are compared to an EKF based localization method on a typical run covering four rows in the orchard. The Matlab R toolbox Kalmtool is used for easy switching between different filter implementations without the need...

  20. Access to new antimicrobial 4-methylumbelliferone derivatives

    Indian Academy of Sciences (India)

    Marwa Zayane; Anis Romdhane; Mejda Daami-Remadi; Hichem Ben Jannet

    2015-09-01

    Synthesis of some novel coumarin esters has been accomplished through iodine-catalyzed method using 4-methylumbelliferone as the starting material. Condensation of hydrazide, which was obtained in two steps from 4-methylumbelliferone, with some arylaldhydes provided hydrazone derivatives, while the reaction with phenylthioisocyanate leads to the thiosemicarbazide that evolved into two new compounds. Finally, condensation reaction of hydrazide with three diketones afforded new pyrrole and pyrazole derivatives. Structures of all synthesized compounds were established on the basis of spectroscopic methods including 1H NMR, 13C NMR and ES-HRMS. They were finally tested for their antimicrobial activity and the structure-activity relationship was discussed.

  1. Derivation of the blackfold effective theory

    CERN Document Server

    Camps, Joan

    2012-01-01

    We study fluctuations and deformations of black branes over length scales larger than the horizon radius. We prove that the Einstein equations for the perturbed p-brane yield, as constraints, the equations of the effective blackfold theory. We solve the Einstein equations for the perturbed geometry and show that it remains regular on and outside the black brane horizon. This study provides an ab initio derivation of the blackfold effective theory and gives explicit expressions for the metrics near the new black holes and black branes that result from it, to leading order in a derivative expansion.

  2. High ethanol producing derivatives of Thermoanaerobacter ethanolicus

    Science.gov (United States)

    Ljungdahl, Lars G.; Carriera, Laura H.

    1983-01-01

    Derivatives of the newly discovered microorganism Thermoanaerobacter ethanolicus which under anaerobic and thermophilic conditions continuously ferment substrates such as starch, cellobiose, glucose, xylose and other sugars to produce recoverable amounts of ethanol solving the problem of fermentations yielding low concentrations of ethanol using the parent strain of the microorganism Thermoanaerobacter ethanolicus are disclosed. These new derivatives are ethanol tolerant up to 10% (v/v) ethanol during fermentation. The process includes the use of an aqueous fermentation medium, containing the substrate at a substrate concentration greater than 1% (w/v).

  3. Quantum mechanics of 4-derivative theories

    Energy Technology Data Exchange (ETDEWEB)

    Salvio, Alberto [Universidad Autonoma de Madrid and Instituto de Fisica Teorica IFT-UAM/CSIC, Departamento de Fisica Teorica, Madrid (Spain); Strumia, Alessandro [Dipartimento di Fisica, Universita di Pisa (Italy); CERN, Theory Division, Geneva (Switzerland); INFN, Pisa (Italy)

    2016-04-15

    A renormalizable theory of gravity is obtained if the dimension-less 4-derivative kinetic term of the graviton, which classically suffers from negative unbounded energy, admits a sensible quantization. We find that a 4-derivative degree of freedom involves a canonical coordinate with unusual time-inversion parity, and that a correspondingly unusual representation must be employed for the relative quantum operator. The resulting theory has positive energy eigenvalues, normalizable wavefunctions, unitary evolution in a negative-norm configuration space. We present a formalism for quantum mechanics with a generic norm. (orig.)

  4. Synthesis and Characterization of Two Danazol Derivatives

    Directory of Open Access Journals (Sweden)

    Lauro Figueroa-Valverde

    2010-01-01

    Full Text Available Two danazol derivatives were synthesized and characterized by spectral analyses. In order to characterize the structural and chemical requirements of danazol derivatives, several parameters such as logP, π, Rm and Vm were evaluated. The results showed an increase in the values of logP for the compound 6 in comparison with 3. The compound 3 showed an increase in the values of π, R Vm and V Vm with respect to 6. These data indicate a high degree of lipophilicity and a low steric impediment for compound 6 in comparison with 3.

  5. Special relativity derived from spacetime magma.

    Science.gov (United States)

    Greensite, Fred

    2014-01-01

    We present a derivation of relativistic spacetime largely untethered from specific physical considerations, in constrast to the many physically-based derivations that have appeared in the last few decades. The argument proceeds from the inherent magma (groupoid) existing on the union of spacetime frame components [Formula: see text] and Euclidean [Formula: see text] which is consistent with an "inversion symmetry" constraint from which the Minkowski norm results. In this context, the latter is also characterized as one member of a class of "inverse norms" which play major roles with respect to various unital [Formula: see text]-algebras more generally.

  6. Photoluminescence in anthracene and it's derivatives

    Science.gov (United States)

    Vyas, Arpita; Mirgane, Nitin A.; Moharil, S. V.; Muley, Aarti Iyer

    2016-05-01

    The anthracene and it's derivative 9-chloro acridine and Anthracene-9-ylmethylacetate have prepared in Poly vinyl alcohol(PVOH). Their photoluminescence properties have studied. The pure anthracene has an emission at 424 and 443nm. The intense peak is observed at 465nm and shoulder at 407nm. The derivatives of anthracene Anthracene-9-ylmethylacetate shows an emission around 440nm for the excitation at 393nm and 9-chloro acridine shows emission around 360nm for the excitation at 290nm. The major problem of this organic material is the stability. The composites prepared in the medium of PVOH are more stable.

  7. Scale up of proteoliposome derived Cochleate production.

    Science.gov (United States)

    Zayas, Caridad; Bracho, Gustavo; Lastre, Miriam; González, Domingo; Gil, Danay; Acevedo, Reinaldo; del Campo, Judith; Taboada, Carlos; Solís, Rosa L; Barberá, Ramón; Pérez, Oliver

    2006-04-12

    Cochleate are highly stable structures with promising immunological features. Cochleate structures are usually obtaining from commercial lipids. Proteoliposome derived Cochleate are derived from an outer membrane vesicles of Neisseria meningitidis B. Previously, we obtained Cochleates using dialysis procedures. In order to increase the production process, we used a crossflow system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The raw material and solutions used in the production process are already approved for human application. This work demonstrates that CFS is very efficient process to obtain Cochleate structures with a yield of more than 80% and the immunogenicity comparable to that obtained by dialysis membrane.

  8. Contact allergy to isoeugenol and its derivatives

    DEFF Research Database (Denmark)

    Tanaka, Susumu; Royds, C; Buckley, Christopher D

    2004-01-01

    A total of 2261 (808 male, 1453 female) consecutive patients attending contact dermatitis clinics were patch tested to isoeugenol and its derivatives listed in the EU Inventory of Fragrance Ingredients. Positive reactions were found to isoeugenol in 40, transisoeugenol in 40, isoeugenyl acetate...... and 15/16 of those to isoeugenyl phenylacetate but in none of those 6 positive to isoeugenyl methyl ether and in neither of those 2 positive to benzyl isoeugenyl ether. Concomitant contact allergy between isoeugenol and its derivatives may occur through chemical cross-reactivity or local skin metabolism...

  9. Mesogenic benzothiazole derivatives with methoxy substituents

    Indian Academy of Sciences (India)

    A K Prajapati; N L Bonde

    2006-03-01

    Two new mesogenic homologous series containing 6-methoxybenzothiazole ring at the terminus of the molecule, viz. 2-(4'--alkoxyphenylazo)-6-methoxybenzothiazoles and 2-[4'-(4"--alkoxybenzoyloxy) phenylazo]-6-methoxybenzothiazoles were synthesized. In series I, -butyloxy to -tetradecyloxy derivatives exhibit nematic mesophase. Smectic A mesophase commences from the -dodecyloxy derivative as a monotropic phase and is retained up to the last member synthesized. All the members of series II exhibit enantiotropic nematic mesophase. The mesomorphic properties of the present series are compared with other structurally related series to evaluate the effect of the benzothiazole ring and the methoxy substituent on mesomorphism.

  10. Derivation of Mayer Series from Canonical Ensemble

    Science.gov (United States)

    Wang, Xian-Zhi

    2016-02-01

    Mayer derived the Mayer series from both the canonical ensemble and the grand canonical ensemble by use of the cluster expansion method. In 2002, we conjectured a recursion formula of the canonical partition function of a fluid (X.Z. Wang, Phys. Rev. E 66 (2002) 056102). In this paper we give a proof for this formula by developing an appropriate expansion of the integrand of the canonical partition function. We further derive the Mayer series solely from the canonical ensemble by use of this recursion formula.

  11. Synthesis and Antidiabetic Evaluation of Benzothiazole Derivatives

    Energy Technology Data Exchange (ETDEWEB)

    G, Mariappan; P, Prabhat; L, Sutharson; J, Banerjee; U, Patangia; S, Nath [Himalayan Pharmacy Institute, Majhitar (India)

    2012-04-15

    A novel series of benzothiazole derivatives were synthesized and assayed in vivo to investigate their hypogly-cemic activity by streptozotocin-induced diebetic model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well known antidiabetic agent as a reference drug. All the compounds were effective, amongst them 3d showed more prominent activity at 100 mg/kg p.o. The experimental results are statistically significant at p<0.01 and p<0.05 level.

  12. Antiretroviral (HIV-1) activity of azulene derivatives.

    Science.gov (United States)

    Peet, Julia; Selyutina, Anastasia; Bredihhin, Aleksei

    2016-04-15

    The antiretroviral activity of azulene derivatives was detected for the first time. A series of eighteen diversely substituted azulenes was synthesized and tested in vitro using HIV-1 based virus-like particles (VLPs) and infectious HIV-1 virus in U2OS and TZM-bl cell lines. Among the compounds tested, the 2-hydroxyazulenes demonstrated the most significant activity by inhibiting HIV-1 replication with IC50 of 2-10 and 8-20 μM for the VLPs and the infectious virus, respectively. These results indicate that azulene derivatives may be potentially useful candidates for the development of antiretroviral agents.

  13. Special relativity derived from spacetime magma.

    Directory of Open Access Journals (Sweden)

    Fred Greensite

    Full Text Available We present a derivation of relativistic spacetime largely untethered from specific physical considerations, in constrast to the many physically-based derivations that have appeared in the last few decades. The argument proceeds from the inherent magma (groupoid existing on the union of spacetime frame components [Formula: see text] and Euclidean [Formula: see text] which is consistent with an "inversion symmetry" constraint from which the Minkowski norm results. In this context, the latter is also characterized as one member of a class of "inverse norms" which play major roles with respect to various unital [Formula: see text]-algebras more generally.

  14. On Dirichlet's Derivation of the Ellipsoid Potential

    CERN Document Server

    Dittrich, W

    2016-01-01

    Newton's potential of a massive homogeneous ellipsoid is derived via Dirichlet's discontinuous factor. At first we review part of Dirichlet's work in an English translation of the original German, and then continue with an extension of his method into the complex plane. With this trick it becomes possible to first calculate the potential and thereafter the force components exerted on a test mass by the ellipsoid. This is remarkable in so far as all other famous researchers prior to Dirichlet merely calculated the attraction components. Unfortunately, Dirichlet's derivation is to a large extent mathematically unacceptable which, however, can be corrected by treating the problem in the complex plane.

  15. Derivation of sink strengths in bounded media

    Energy Technology Data Exchange (ETDEWEB)

    Brailsford, A.D. (Ford Motor Co., Dearborn, MI (USA). Engineering and Research Staff)

    1981-11-01

    Several reasons for the need to extend the rate theory of point defect recovery processes to bounded media are cited. This paper is concerned with the essential first step, the derivation of the strength of sinks near a free surface. The Effective Medium method is used. Sink strengths so derived are shown to be formally the same as those found in an unbounded system. Image effects associated with the surface are proved to be small when the sink is located more than a few sink radii from the surface.

  16. Quantum mechanics of 4-derivative theories.

    Science.gov (United States)

    Salvio, Alberto; Strumia, Alessandro

    2016-01-01

    A renormalizable theory of gravity is obtained if the dimension-less 4-derivative kinetic term of the graviton, which classically suffers from negative unbounded energy, admits a sensible quantization. We find that a 4-derivative degree of freedom involves a canonical coordinate with unusual time-inversion parity, and that a correspondingly unusual representation must be employed for the relative quantum operator. The resulting theory has positive energy eigenvalues, normalizable wavefunctions, unitary evolution in a negative-norm configuration space. We present a formalism for quantum mechanics with a generic norm.

  17. Terpenes from marine-derived fungi.

    Science.gov (United States)

    Ebel, Rainer

    2010-08-13

    Terpenes from marine-derived fungi show a pronounced degree of structural diversity, and due to their interesting biological and pharmacological properties many of them have aroused interest from synthetic chemists and the pharmaceutical industry alike. The aim of this paper is to give an overview of the structural diversity of terpenes from marine-derived fungi, highlighting individual examples of chemical structures and placing them in a context of other terpenes of fungal origin. Wherever possible, information regarding the biological activity is presented.

  18. Derivation and characterization of a pig embryonic stem cell-derived exocrine pancreatic cell line

    Science.gov (United States)

    The establishment and initial characterization of a pig embryonic stem cell-derived pancreatic cell line, PICM-31, and a colony-cloned derivative cell line, PICM-31A, is described. The cell lines were propagated for several months at split ratios of 1:3 or 1:5 at each passage on STO feeder cells af...

  19. Optimal economic order quantity for buyer-distributor-vendor supply chain with backlogging derived without derivatives

    Science.gov (United States)

    Teng, Jinn-Tsair; Cárdenas-Barrón, Leopoldo Eduardo; Lou, Kuo-Ren; Wee, Hui Ming

    2013-05-01

    In this article, we first complement an inappropriate mathematical error on the total cost in the previously published paper by Chung and Wee [2007, 'Optimal the Economic Lot Size of a Three-stage Supply Chain With Backlogging Derived Without Derivatives', European Journal of Operational Research, 183, 933-943] related to buyer-distributor-vendor three-stage supply chain with backlogging derived without derivatives. Then, an arithmetic-geometric inequality method is proposed not only to simplify the algebraic method of completing prefect squares, but also to complement their shortcomings. In addition, we provide a closed-form solution to integral number of deliveries for the distributor and the vendor without using complex derivatives. Furthermore, our method can solve many cases in which their method cannot, because they did not consider that a squared root of a negative number does not exist. Finally, we use some numerical examples to show that our proposed optimal solution is cheaper to operate than theirs.

  20. 46 CFR 503.55 - Derivative classification.

    Science.gov (United States)

    2010-10-01

    ... markings prescribed by 32 CFR 2001.20 through 2001.23 and shall otherwise conform to the requirements of 32 CFR 2001.20 through 2001.23. ... 46 Shipping 9 2010-10-01 2010-10-01 false Derivative classification. 503.55 Section...

  1. 5 CFR 1312.7 - Derivative classification.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Derivative classification. 1312.7 Section 1312.7 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET OMB DIRECTIVES CLASSIFICATION, DOWNGRADING, DECLASSIFICATION AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION Classification...

  2. Synthesis of isothiocyanate-derived mercapturic acids

    NARCIS (Netherlands)

    Vermeulen, M.; Zwanenburg, B.; Chittenden, G.J.F.; Verhagen, H.

    2003-01-01

    Twelve mercapturic acids derived from saturated and unsaturated aliphatic and aromatic isothiocyanates were synthesised, by adding isothiocyanate to a solution of N-acetyl-L-cysteine and sodium bicarbonate, in a typical yield of 77%. Isothiocyanates were synthesised first by adding the corresponding

  3. Curcumin derivatives as HIV-1 protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Z.; Li, J.; Craik, C.S.; Ortiz de Montellano, P.R. [Univ. of California, San Francisco, CA (United States)

    1993-12-31

    Curcumin, a non-toxic natural compound from Curcuma longa, has been found to be an HIV-1 protease inhibitor. Some of its derivatives were synthesized and their inhibitory activity against the HIV-1 protease was tested. Curcumin analogues containing boron enhanced the inhibitory activity. At least of the the synthesized compounds irreversibly inhibits the HIV-1 protease.

  4. Intramolecular Cycloaddition of Imines of Cysteine Derivatives

    Directory of Open Access Journals (Sweden)

    Teresa M. V. D. Pinho e Melo

    1998-02-01

    Full Text Available Azomethine ylides were generated from Schiffs bases of S-allylcysteine methyl ester and their intramolecular 1,3-dipolar cycloadditions were studied. These reactions led to the synthesis of thieno[3,4-b]pyrrole derivatives in good yield.

  5. Derived Transformation of Children's Pregambling Game Playing

    Science.gov (United States)

    Dymond, Simon; Bateman, Helena; Dixon, Mark R.

    2010-01-01

    Contemporary behavior-analytic perspectives on gambling emphasize the impact of verbal relations, or derived relational responding and the transformation of stimulus functions, on the initiation and maintenance of gambling. Approached in this way, it is possible to undertake experimental analysis of the role of verbal/mediational variables in…

  6. Microscopic Derivation of Ginzburg-Landau Theory

    DEFF Research Database (Denmark)

    Frank, Rupert; Hainzl, Christian; Seiringer, Robert

    2012-01-01

    We give the first rigorous derivation of the celebrated Ginzburg-Landau (GL) theory, starting from the microscopic Bardeen-Cooper-Schrieffer (BCS) model. Close to the critical temperature, GL arises as an effective theory on the macroscopic scale. The relevant scaling limit is semiclassical...

  7. Derivation of the Ideal Gas Law

    Science.gov (United States)

    Laugier, Alexander; Garai, Jozsef

    2007-01-01

    Undergraduate and graduate physics and chemistry books usually state that combining the gas laws results in the ideal gas law. Leaving the derivation to the students implies that this should be a simple task, most likely a substitution. Boyle's law, Charles's law, and the Avogadro's principle are given under certain conditions; therefore, direct…

  8. Sol-Gel Derived Hafnia Coatings

    Science.gov (United States)

    Feldman, Jay D.; Stackpoole, Mairead; Blum, Yigal; Sacks, Michael; Ellerby, Don; Johnson, Sylvia M.; Venkatapathy, Ethiras (Technical Monitor)

    2002-01-01

    Sol-gel derived hafnia coatings are being developed to provide an oxidation protection layer on ultra-high temperature ceramics for potential use in turbine engines (ultra-efficient engine technology being developed by NASA). Coatings using hafnia sol hafnia filler particles will be discussed along with sol synthesis and characterization.

  9. Current-induced forces: a simple derivation

    DEFF Research Database (Denmark)

    Todorov, Tchavdar N.; Dundas, Daniel; Lü, Jing-Tao;

    2014-01-01

    We revisit the problem of forces on atoms under current in nanoscale conductors. We derive and discuss the five principal kinds of force under steady-state conditions from a simple standpoint that-with the help of background literature-should be accessible to physics undergraduates. The discussion...

  10. Simple Derivation of the Lindblad Equation

    Science.gov (United States)

    Pearle, Philip

    2012-01-01

    The Lindblad equation is an evolution equation for the density matrix in quantum theory. It is the general linear, Markovian, form which ensures that the density matrix is Hermitian, trace 1, positive and completely positive. Some elementary examples of the Lindblad equation are given. The derivation of the Lindblad equation presented here is…

  11. Formal Derivation of Concurrent Garbage Collectors

    NARCIS (Netherlands)

    Pavlovic, Dusko; Pepper, Peter; Smith, Douglas R.

    Concurrent garbage collectors are notoriously difficult to implement correctly. Previous approaches to the issue of producing correct collectors have mainly been based on posit-and-prove verification or on the application of domain-specific templates and transformations. We show how to derive the

  12. Enabling quaternion derivatives: the generalized HR calculus.

    Science.gov (United States)

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C; Mandic, Danilo P

    2015-08-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis.

  13. Approximate methods for derivation of covariance data

    Energy Technology Data Exchange (ETDEWEB)

    Tagesen, S. [Vienna Univ. (Austria). Inst. fuer Radiumforschung und Kernphysik; Larson, D.C. [Oak Ridge National Lab., TN (United States)

    1992-12-31

    Several approaches for the derivation of covariance information for evaluated nuclear data files (EFF2 and ENDF/B-VI) have been developed and used at IRK and ORNL respectively. Considerations, governing the choice of a distinct method depending on the quantity and quality of available data are presented, advantages/disadvantages are discussed and examples of results are given.

  14. Ethos Derived from Karaoke Performance in Taiwan.

    Science.gov (United States)

    Ma, Ringo

    Karaoke (singing along to music videos) has swept Taiwan with such force that many people go to singing schools to improve their singing. Three cases in this paper demonstrate how the ethos, or credibility, of the singer is a combination of initial and derived ethos. Who the singer is tends to determine how much attention he or she receives…

  15. Synthesis of novel 15-membered macrolide derivatives

    Institute of Scientific and Technical Information of China (English)

    Rui Qing Xian; Shu Tao Ma; Bo Jiao

    2008-01-01

    In order to develop new antibiotics effective against resistant bacteria,a series of novel 15-membered macrolide derivatives were designed and synthesized by the modification of hydroxyl groups at C-11,C-12 and C-4" positions.Their structures were confirmed by MS,IR,1H NMR or 13C NMR.

  16. Enabling quaternion derivatives: the generalized HR calculus

    Science.gov (United States)

    Xu, Dongpo; Jahanchahi, Cyrus; Took, Clive C.; Mandic, Danilo P.

    2015-01-01

    Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non-analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis. PMID:26361555

  17. Biotransformation of indole derivatives by mycelial cultures.

    Science.gov (United States)

    Alarcón, Julio; Cid, Eliseo; Lillo, Luis; Céspedesa, Carlos; Aguila, Sergio; Alderete, Joel B

    2008-01-01

    Biotransformation of tryptophan to tryptamine and 3-methyl-indole by Psilocybe coprophila was performed. On the other hand, Aspergillus niger was able to transform tryptophan to 5-hydroxy-tryptophan. P. coprophila biotransformed 5-hydroxy-tryptophan to 5-hydroxytryptamine. These results prove once more that fungi are good tools to establish hydroxyindole derivatives.

  18. INVESTIGATION OF ANTIFUNGAL ACTIVITY OF QUINOLINIUM DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. A. Alexandrova

    2013-01-01

    Full Text Available Abstract. Antifungal activity (Candida albicans, Candida krusei of some substituted quinolinium derivatives has been investigated. It was established that the most perspective compound for detail investigation of antifungal activity by labeled biomarkers method was N-phenylbenzoquinaldinium tetrafluoroborate.

  19. Synthesis and Characterization of Novel Sulfonylurea Derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guang-liang; LI Yao-xian; ZHANG Suo-qin; GAO Fei-fei

    2005-01-01

    On the basis of study on the mechanism of action of sulfonylurea herbicides, nine sulfonylurea derivatives of iso-xazolidinone were designed and synthesized. The structures of these compounds were confirmed by means of IR, MS, NMR and elemental analysis. The results of preliminary active tests indicate that the compounds have some herbicidal activity. The structure-activity relationship was also studied.

  20. Glycosylation of a Newly Functionalized Orthoester Derivative

    Directory of Open Access Journals (Sweden)

    Kohei Kawa

    2014-02-01

    Full Text Available Tandem glycosylation of the 6-O-Fmoc-substituted benzyl orthoester derivative 2a was carried out in moderate yields by electrogenerated acid (EGA. The Fmoc group was effectively removed under mild basic conditions, and the product was submitted to the subsequent glycosylation.

  1. Econometric Analysis of Financial Derivatives : An overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze. Th

  2. New lycosinine derivative from Hippeastrum breviflorum

    Directory of Open Access Journals (Sweden)

    Camila Sebben

    2015-08-01

    Full Text Available AbstractA new lycosinine derivative, 9-O-demethyllycosinine B, was isolated from the native Brazilian Hippeastrum breviflorumHerb., Amaryllidaceae, along with the well-known alkaloids lycosinine B and lycorine. The structure of the new compound was established by physical and spectroscopic methods. 9-O-demethyllycosinine B is the third lycosinine variant identified in the Amaryllidaceae family.

  3. Synthesis and application of epoxy starch derivatives

    NARCIS (Netherlands)

    Huijbrechts, A.M.L.; Haar, ter R.; Schols, H.A.; Franssen, M.C.R.; Boeriu, C.G.; Sudhölter, E.J.R.

    2010-01-01

    Epoxy starch derivatives were synthesized by epoxidation of allylated starch. The reaction was performed with low substituted 1-allyloxy-2-hydroxypropyl-waxy maize starch (AHP-WMS; degree of substitution (DS) of 0.23) using hydrogen peroxide and acetonitrile Via a two step spectrophotometric assay,

  4. Diclofenac derivatives with insulin-sensitizing activity

    Institute of Scientific and Technical Information of China (English)

    Jian Ta Wang; Ying Wang; Ji Quan Zhang; Xing Cui; Yi Zhang; Gao Feng Zhu; Lei Tang

    2011-01-01

    A series of diclofenac derivatives were synthesized. The insulin-sensitizing activity of 28 new compounds was evaluated in 3T3-L1 cells. The compounds 10a and 10f exhibited similar insulin-sensitizing activity with positive drag rosiglitazone.

  5. Synthesis of isothiocyanate-derived mercapturic acids

    NARCIS (Netherlands)

    Vermeulen, M.; Zwanenburg, B.; Chittenden, G.J.F.; Verhagen, H.

    2003-01-01

    Twelve mercapturic acids derived from saturated and unsaturated aliphatic and aromatic isothiocyanates were synthesised, by adding isothiocyanate to a solution of N-acetyl-L-cysteine and sodium bicarbonate, in a typical yield of 77%. Isothiocyanates were synthesised first by adding the corresponding

  6. Interest Rate Derivative Pricing with Stochastic Volatility

    NARCIS (Netherlands)

    Chen, B.

    2012-01-01

    One purpose of exotic derivative pricing models is to enable financial institutions to quantify and manage their financial risk, arising from large books of portfolios. These portfolios consist of many non-standard exotic financial products. Risk is managed by means of the evaluation of sensitivity

  7. Organogels Derived from Potassium 8-Nitroquinolinecarboxylate

    Institute of Scientific and Technical Information of China (English)

    HU,Hai-Yu; YANG,Yong; XIANG,Jun-Feng; CHEN,Chuan-Feng

    2007-01-01

    A new class of organogels derived from potassium 8-nitroquinoline-2-carboxylate was selectively formed in (V∶ V= 1∶ 1) THF/MeOH, and their superstructures were characterized by atomic force microscopy, scanning electron microscopy and transmission electron microscopy.

  8. Generalized Jackknife Estimators of Weighted Average Derivatives

    DEFF Research Database (Denmark)

    Cattaneo, Matias D.; Crump, Richard K.; Jansson, Michael

    With the aim of improving the quality of asymptotic distributional approximations for nonlinear functionals of nonparametric estimators, this paper revisits the large-sample properties of an important member of that class, namely a kernel-based weighted average derivative estimator. Asymptotic li...

  9. Bootstrapping Density-Weighted Average Derivatives

    DEFF Research Database (Denmark)

    Cattaneo, Matias D.; Crump, Richard K.; Jansson, Michael

    Employing the "small bandwidth" asymptotic framework of Cattaneo, Crump, and Jansson (2009), this paper studies the properties of a variety of bootstrap-based inference procedures associated with the kernel-based density-weighted averaged derivative estimator proposed by Powell, Stock, and Stoker...

  10. Higher-Derivative Supergravity and Moduli Stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Ciupke, David; Westphal, Alexander [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Louis, Jan [Hamburg Univ. (Germany). Fachberich Physik; Hamburg Univ. (Germany). Zentrum fuer Mathematische Physik

    2015-05-15

    We review the ghost-free four-derivative terms for chiral superfields in N=1 supersymmetry and supergravity. These terms induce cubic polynomial equations of motion for the chiral auxiliary fields and correct the scalar potential. We discuss the different solutions and argue that only one of them is consistent with the principles of effective field theory. Special attention is paid to the corrections along flat directions which can be stabilized or destabilized by the higher-derivative terms. We then compute these higher-derivative terms explicitly for the type IIB string compactified on a Calabi-Yau orientifold with fluxes via Kaluza-Klein reducing the (α'){sup 3}R{sup 4} corrections in ten dimensions for the respective N=1 Kaehler moduli sector. We prove that together with flux and the known (α'){sup 3}-corrections the higher-derivative term stabilizes all Calabi-Yau manifolds with positive Euler number, provided the sign of the new correction is negative.

  11. Derivation of the Ideal Gas Law

    Science.gov (United States)

    Laugier, Alexander; Garai, Jozsef

    2007-01-01

    Undergraduate and graduate physics and chemistry books usually state that combining the gas laws results in the ideal gas law. Leaving the derivation to the students implies that this should be a simple task, most likely a substitution. Boyle's law, Charles's law, and the Avogadro's principle are given under certain conditions; therefore, direct…

  12. Derived Transformation of Children's Pregambling Game Playing

    Science.gov (United States)

    Dymond, Simon; Bateman, Helena; Dixon, Mark R.

    2010-01-01

    Contemporary behavior-analytic perspectives on gambling emphasize the impact of verbal relations, or derived relational responding and the transformation of stimulus functions, on the initiation and maintenance of gambling. Approached in this way, it is possible to undertake experimental analysis of the role of verbal/mediational variables in…

  13. Endothelial derived hyperpolarization in renal interlobar arteries

    DEFF Research Database (Denmark)

    Brasen, Jens Christian; Sørensen, Charlotte M.

    2015-01-01

    In small arteries, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are connect by myoendothelial junctions (MEJ), usually extending from the EC. Ca2+ activated K+ channels (IKCa and SKCa) located in the MEJ are suggested to play a role in NO-independent endothelium derived...

  14. QSAR Study of Sucrose and Guanidine Derivatives

    African Journals Online (AJOL)

    NICO

    design, but there have been several applications of QSAR to the taste properties of ... by selection of relevant grid points by the genetic algorithm method to ... The geometry optimization of all the derivatives and evalu- ation of values of the ... form of the solution to the quantum mechanical equation as expressed in the ...

  15. Methodology for deriving optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2010-03-01

    Full Text Available This research describes a quantitive methodology for deriving optimal exploration target zones based on a probalistic mineral prospectivity map.The Rodalquilar mineral district is located in the Sierra del Cabo de Gata volcanic field, in the south...

  16. Actuarial risk measures for financial derivative pricing

    NARCIS (Netherlands)

    M.J. Goovaerts; R.J.A. Laeven

    2008-01-01

    We present an axiomatic characterization of price measures that are superadditive and comonotonic additive for normally distributed random variables. The price representation derived involves a probability measure transform that is closely related to the Esscher transform, and we call it the Esscher

  17. [Sulphonylurea derivatives or insulin with metformin?

    NARCIS (Netherlands)

    Tack, C.J.; Laar, F.A. van de

    2014-01-01

    If pharmacological treatment of glycaemia with metformin in patients with type 2 diabetes fails, a second agent is advised, however, the optimal choice is unclear. Most guidelines suggest the addition of sulphonylurea (SU) derivatives as the first option, but sometimes insulin is preferred as there

  18. Generalized Voigt functions and their derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Sampoorna, M. [Indian Institute of Astrophysics, Koramangala, Bangalore 560 034 (India) and Laboratoire Cassiopee (CNRS, UMR 6202), Observatoire de la Cote d' Azur, BP 4229, F-06304 Nice Cedex 4 (France)]. E-mail: sampoorna@iiap.res.in; Nagendra, K.N. [Indian Institute of Astrophysics, Koramangala, Bangalore 560 034 (India); Laboratoire Cassiopee (CNRS, UMR 6202), Observatoire de la Cote d' Azur, BP 4229, F-06304 Nice Cedex 4 (France); Frisch, H. [Laboratoire Cassiopee (CNRS, UMR 6202), Observatoire de la Cote d' Azur, BP 4229, F-06304 Nice Cedex 4 (France)

    2007-03-15

    This paper deals with a special class of functions called generalized Voigt functions H{sup (n)}(x,a) and G{sup (n)}(x,a) and their partial derivatives, which are useful in the theory of polarized spectral line formation in stochastic media. For n=0 they reduce to the usual Voigt and Faraday-Voigt functions H(x,a) and G(x,a). A detailed study is made of these new functions. Simple recurrence relations are established and employed for the calculation of the functions themselves and of their partial derivatives. Asymptotic expansions are given for large values of x and a. They are used to examine the range of applicability of the recurrence relations and to construct a numerical algorithm for the calculation of the generalized Voigt functions and of their derivatives valid in a large (x,a) domain. It is also shown that the partial derivatives of the usual H(x,a) and G(x,a) can be expressed in terms of H{sup (n)}(x,a) and G{sup (n)}(x,a)

  19. Risk Management and Financial Derivatives: An Overview

    NARCIS (Netherlands)

    S.M. Hammoudeh (Shawkat); M.J. McAleer (Michael)

    2012-01-01

    textabstractRisk management is crucial for optimal portfolio management. One of the fastest growing areas in empirical finance is the expansion of financial derivatives. The purpose of this special issue on “Risk Management and Financial Derivatives” is to highlight some areas in which novel econome

  20. Efficient pricing algorithms for exotic derivatives

    NARCIS (Netherlands)

    R. Lord (Roger)

    2008-01-01

    textabstractSince the Nobel-prize winning papers of Black and Scholes and Merton in 1973, the derivatives market has evolved into a multi-trillion dollar market. Structures which were once considered as exotic are now commonplace, appearing in retail products such as mortgages and investment notes.

  1. Theoretical derivation of heliostat tracking errors distribution

    Energy Technology Data Exchange (ETDEWEB)

    Badescu, Viorel [Candida Oancea Institute of Solar Energy, Faculty of Mechanical Engineering, Polytechnic University of Bucharest, Spl. Independentei 313, Bucharest 060042 (Romania)

    2008-12-15

    The tracking error probability distribution is derived on a pure theoretical basis. Methods of integral geometry and geometrical probabilities are used to this purpose. The distribution performs reasonably well when compared with measurements from a small database. The performance of the theoretical distribution is compared with that of other (empirical) probability distributions. The practical relevance of using the present approach is also explained. (author)

  2. New sulphide derivative from Ferula rutabensis.

    Science.gov (United States)

    Abdel-Sattar, Essam; El-Mekkawy, Sahar

    2009-01-01

    Reinvestigation of CH(2)Cl(2) extract of roots and rhizomes of Ferula rutabensis led to the isolation of a new trisulphide (1) and phthalic acid derivative (2). Their characterisation was based on their spectral data, including MS, 1D- and 2D-NMR.

  3. Deriving force field parameters for coordination complexes

    DEFF Research Database (Denmark)

    Norrby, Per-Ola; Brandt, Peter

    2001-01-01

    The process of deriving molecular mechanics force fields for coordination complexes is outlined. Force field basics are introduced with an emphasis on special requirements for metal complexes. The review is then focused on how to set up the initial model, define the target, refine the parameters,...

  4. Microscopic Derivation of Ginzburg-Landau Theory

    DEFF Research Database (Denmark)

    Frank, Rupert; Hainzl, Christian; Seiringer, Robert

    2012-01-01

    We give the first rigorous derivation of the celebrated Ginzburg-Landau (GL) theory, starting from the microscopic Bardeen-Cooper-Schrieffer (BCS) model. Close to the critical temperature, GL arises as an effective theory on the macroscopic scale. The relevant scaling limit is semiclassical...

  5. Corporate Governance Failures in Trading Financial Derivatives

    OpenAIRE

    Turegeldiyev, Anuar

    2013-01-01

    The ultimate goal of the following master thesis is to identify specific mistakes in corporate governance practices that have led to colossal losses in financial derivatives trading departments, to draw lessons from these cases, and to propose possible solutions to prevent such behavior and the consequences that follow.

  6. Synthesis and application of epoxy starch derivatives

    NARCIS (Netherlands)

    Huijbrechts, A.M.L.; Haar, ter R.; Schols, H.A.; Franssen, M.C.R.; Boeriu, C.G.; Sudhölter, E.J.R.

    2010-01-01

    Epoxy starch derivatives were synthesized by epoxidation of allylated starch. The reaction was performed with low substituted 1-allyloxy-2-hydroxypropyl-waxy maize starch (AHP-WMS; degree of substitution (DS) of 0.23) using hydrogen peroxide and acetonitrile Via a two step spectrophotometric assay,

  7. A novel chalcone derivative from Onychium japonicum

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A novel chalcone derivative was isolated from Onychium japonicum and its structure was elucidated by spectroscopic methods.The isolated compound showed cytotoxic activity against the human carcinoma cell lines Hela and BEL-7402 in vitro.(C) 2007 Hong Quan Duan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  8. ANTIMICROBIAL POTENT OXAZINE-2-AMINE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    GANESAMOORTHY THIRUNARAYANAN

    2016-07-01

    Full Text Available Objective: To synthesize thirteen effective microbial potent oxazine-2-amine derivatives and evaluate the antimicrobial activities of these compounds. Material and methods: The solvent-free solid fly-ash: H2SO4 catalyzed cyclization of 4-bromo-1-naphthyl chalcones and urea under microwave irradiation technique was utilized for the synthesis of oxazine derivatives. The synthesized oxazines were characterized by their physical constants and spectroscopic data. The Bauer-Kirby disc-diffusion method of measurement of zone of inhibition was used for evaluation antimicrobial activity of synthesized oxazines. Results: The cyclization was effective and this reaction gave more than 80% yield. The catalyst was reused up to five times consecutively without appreciable decreasing of yield. All compounds were active against their microbial strains. Conclusions: This solvent-free synthetic method was effective for the synthesis of oxazine derivatives. The amino, dimethylamino, halogens, methoxy and methyl substituted oxazines shows significant antibacterial activity. Chloro, hydroxy and nitro substituted oxazine derivative have shown significant antifungal activity.

  9. Orchard navigation using derivative free Kalman filtering

    DEFF Research Database (Denmark)

    Hansen, Søren; Bayramoglu, Enis; Andersen, Jens Christian

    2011-01-01

    This paper describes the use of derivative free filters for mobile robot localization and navigation in an orchard. The localization algorithm fuses odometry and gyro measurements with line features representing the surrounding fruit trees of the orchard. The line features are created on basis of 2...

  10. Potentials of Arbitrary Forces with Fractional Derivatives

    Science.gov (United States)

    Rabei, Eqab M.; Alhalholy, Tareq S.; Rousan, Akram

    The Laplace transform of fractional integrals and fractional derivatives is used to develop a general formula for determining the potentials of arbitrary forces: conservative and nonconservative in order to introduce dissipative effects (such as friction) into Lagrangian and Hamiltonian mechanics. The results are found to be in exact agreement with Riewe's results of special cases. Illustrative examples are given.

  11. Chemistry of Phosphorylated Formaldehyde Derivatives. Part I

    Directory of Open Access Journals (Sweden)

    Vasily P. Morgalyuk

    2014-08-01

    Full Text Available The underinvestigated derivatives of unstable phosphorylated formaldehyde acetals and some of the structurally related compounds, such as thioacetals, aminonitriles, aminomethylphosphinoyl compounds, are considered. Separately considered are halogen aminals of phosphorylated formaldehyde, acetals of phosphorylated formaldehyde of H-phosphinate-type and a phosphorylated gem-diol of formaldehyde. Synthetic methods, chemical properties and examples of practical applications are given.

  12. Reheating in nonminimal derivative coupling model

    CERN Document Server

    Sadjadi, H Mohseni

    2012-01-01

    We consider a model with nonminimal derivative coupling of inflaton to gravity. The reheating process during rapid oscillation of the inflaton is studied and the reheating temperature is obtained. Behaviors of the inflaton and produced radiation in this era are discussed.

  13. $\\Phi$-derivable approximations in gauge theories

    CERN Document Server

    Arrizabalaga, A

    2003-01-01

    We discuss the method of $\\Phi$-derivable approximations in gauge theories. There, two complications arise, namely the violation of Bose symmetry in correlation functions and the gauge dependence. For the latter we argue that the error introduced by the gauge dependent terms is controlled, therefore not invalidating the method.

  14. Deriving Process Congruences from Reaction Rules

    DEFF Research Database (Denmark)

    Sobocinski, Pawel

    This thesis is concerned with the development of a theory which, given a formalism with a reduction semantics, allows the derivation of a canonical labelled transition system on which bisimilarity as well as other other equiv� alences are congruences; provided that the contexts of the formalism f...

  15. Synthesis of [60]Fullerene-Podophyllotoxin Derivative

    Institute of Scientific and Technical Information of China (English)

    GUO,Li-Wei(郭礼伟); GAO,Xiang(高翔); ZHANG,Dan-Wei(张丹维); WU,Shi-Hui(吴世晖); WU,Hou-Ming(吴厚铭)

    2002-01-01

    The [60]fullerene-podophyllotoxin derivative (3) was obtained by the phosphine promeoted[2 + 3]cycloaddition reaction ofpodophyllotoxin buta-2,3-dienoate (2) and [60]fullerene. The structures of starting mateerial (2) and product (3) were confirmed by UV-vis, IR, NMR and MS spectroscopies.

  16. Synthesis of 8-Heteroaryl-2'-deoxyguanosine Derivatives.

    Science.gov (United States)

    Hobley, Gerard; Gubala, Vladimir; Rivera-Sánchez, María Del C; Rivera, José M

    2008-06-01

    We describe the synthesis of 8-heteroaromatic-2'-deoxyguanosine analogues using Suzuki-Miyaura or Stille conditions. Unprotected and protected 8-bromo-2'-deoxyguanosine was coupled with commercially available heteroarylboronic acids or the trialkyltin derivatives of 2-pyridylbromides either with or without microwave irradiation in good yields.

  17. Derivation of a poroelastic flexural shell model

    CERN Document Server

    Mikelic, Andro

    2015-01-01

    In this paper we investigate the limit behavior of the solution to quasi-static Biot's equations in thin poroelastic flexural shells as the thickness of the shell tends to zero and extend the results obtained for the poroelastic plate by Marciniak-Czochra and Mikeli\\'c. We choose Terzaghi's time corresponding to the shell thickness and obtain the strong convergence of the three-dimensional solid displacement, fluid pressure and total poroelastic stress to the solution of the new class of shell equations. The derived bending equation is coupled with the pressure equation and it contains the bending moment due to the variation in pore pressure across the shell thickness. The effective pressure equation is parabolic only in the normal direction. As additional terms it contains the time derivative of the middle-surface flexural strain. Derivation of the model presents an extension of the results on the derivation of classical linear elastic shells by Ciarlet and collaborators to the poroelastic shells case. The n...

  18. Econometric Analysis of Financial Derivatives : An overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  19. Econometric Analysis of Financial Derivatives: An Overview

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael)

    2014-01-01

    markdownabstract__Abstract__ One of the fastest growing areas in empirical finance, and also one of the least rigorously analyzed, especially from a financial econometrics perspective, is the econometric analysis of financial derivatives, which are typically complicated and difficult to analyze.

  20. Supersymmetric higher derivative couplings and their applications

    NARCIS (Netherlands)

    Lodato, I.

    2014-01-01

    After an elementary introduction on black hole physics, supersymmetry and effective theories, which motivates the importance of higher derivative couplings in supergravity, we give an exhaustive treatment of the covariant phase space formalism with many examples explicitly worked out. This sets the

  1. Platelet derivatives in regenerative medicine: an update.

    Science.gov (United States)

    De Pascale, Maria Rosaria; Sommese, Linda; Casamassimi, Amelia; Napoli, Claudio

    2015-01-01

    Prior preclinical and clinical studies support the use of platelet-derived products for the treatment of soft and hard tissue lesions. These regenerative effects are controlled by autocrine and paracrine biomolecules including growth factors and cytokines contained in platelet alpha granules. Each growth factor is involved in a phase of the healing process, such as inflammation, collagen synthesis, tissue granulation, and angiogenesis collectively promoting tissue restitution. Platelet derivatives have been prepared as platelet-rich plasma, platelet gel, platelet-rich fibrin, and platelet eye drops. These products vary in their structure, growth factors, composition, and cytokine concentrations. Here, we review the current use of platelet-derived biological products focusing on the rationale for their use and the main requirements for their preparation. Variation in the apparent therapeutic efficacy may have resulted from a lack of reproducible, standardized protocols for preparation. Despite several individual studies showing favorable treatment effects, some randomized controlled trials as well as meta-analyses have found no constant clinical benefit from the application of platelet-derived products for prevention of tissue lesions. Recently, 3 published studies in dentistry showed an improvement in bone density. Seven published studies showed positive results in joint regeneration. Five published studies demonstrated an improvement in the wound healing, and an improvement of eye epithelial healing was observed in 2 reports. Currently, at least 14 ongoing clinical trials in phase 3 or 4 have been designed with large groups of treated patients (n > 100). Because the rationale of the therapy with platelet-derived compounds is still debated, a definitive insight can be acquired only when these large randomized trials will be completed.

  2. Synthesis of F-18 labeled raloxifene derivative

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K. C.; Moon, B. S.; Jun, K. S. [KIRAMS, Seoul (Korea, Republic of); Lee, J. H.; Ji, D. Y. [Inha University, Incheon (Korea, Republic of)

    2005-07-01

    Raloxifene, [6-hydroxy-2-(4-hydroxy-phenyl) benzo [b] thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)phenyl] methanone, a tissue-selective estrogen mixed agonist/antagonist, classified as a selective estrogen receptor modulator (SERM), is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis, breast cancer, uterine dysfunction, and other disorders of the female reproductive system. Based on SAR studies of substituted raloxifenes, we synthesized 3 kinds of fluoroalkylated raloxifene derivatives. These compounds show high relative binding affinities (RBA) to the estrogen receptor in vitro (RBA of estradiol = 100%). The RBA values for compounds 1, 2 and 3 are 89, 60, and 45%, respectively, which are all higher than that of raloxifene itself (34%). Among these compounds, we selected to take the best RBA value one and F-18 labeled. Using 2 kinds of labeling method ; 1) Radiolabeling using [{sup 18}F]KF was carried out in anhydrous acetonitrile for 10 min at 120 .deg. C. 2) Radiolabeling using [{sup 18}F]KF was carried out in anhydrous acetonitrile for 15 min at 120 .deg. C in ionic liquid, [bmim][OTf]. Deprotection step added 1N HCl and reacted for 3 min at 120 .deg. C. [{sup 18}F]Fluoroethyl raloxifene derivative obtained 5-23% decay corrected labeling yield by HPLC system (C18 xterra, 10 i, 34% Acetonitrile/0.1 M formate buffer, flow rate: 4 mL/1 min, collection time : 28-29 min) and total time was around 70 min. Fluoroethyl raloxifene derivative has the best RBA value among the other synthesized derivatives and chose it for radiolabeling. [{sup 18}F]Fluoroethyl raloxifene derivative prepared 5-23% decay corrected labeling yield. This preparation is on going for labeling optimizing and preparing of in vitro and in vivo test.

  3. Familial Follicular-Cell Derived Carcinoma

    Directory of Open Access Journals (Sweden)

    Eun Ju eSon

    2012-05-01

    Full Text Available Follicular cell-derived well-differentiated thyroid cancer, papillary (PTC and follicular thyroid carcinomas (FTC compose 95% of all thyroid malignancies. Familial follicular cell-derived well-differentiated thyroid cancers contribute to 5% of those cases. These familial follicular cell derived carcinomas or non-medullary thyroid carcinomas (NMTC divide into two clinical-pathological groups. One group, syndromic-associated, composed by predominately non-thyroidal tumors, is comprised of Pendred syndrome, Warner syndrome, Carney complex type 1, PTEN-hamartoma tumor syndrome (Cowden disease; PHTS, familial adenomatous polyposis (FAP/Gardner syndrome. Additionally other less established links correlated to the development of follicular cell-derived tumors have also included Ataxia-teleangiectasia syndrome, McCune Albright syndrome, and Peutz-Jeghers syndrome. The subsequent group encompasses syndromes typified by non-medullary thyroid carcinomas or NMTC, as well as, pure familial (f PTC with or without oxyphilia, fPTC with multinodular goiter and fPTC with papillary renal cell carcinoma. This heterogeneous group of diseases has not a established genotype-phenotype correlation as the well-known genetic events identified in the familial C-cell-derived tumors or medullary thyroid carcinomas (MTC. Clinicians should be have the knowledge to identify the likelihood of a patient presenting with thyroid cancer having an additional underlying familial syndrome stemming from characteristics through morphological findings that would alert the pathologist to have the patient undergo subsequent molecular genetics evaluations. This review will discuss the clinical and pathological findings of the patients with familial papillary thyroid carcinoma, such as familial adenomatous polyposis, Carney complex, Werner syndrome, and Pendred syndrome and the heterogeneous group of familial papillary thyroid carcinoma.

  4. A New Grünwald-Letnikov Derivative Derived from a Second-Order Scheme

    Directory of Open Access Journals (Sweden)

    B. A. Jacobs

    2015-01-01

    Full Text Available A novel derivation of a second-order accurate Grünwald-Letnikov-type approximation to the fractional derivative of a function is presented. This scheme is shown to be second-order accurate under certain modifications to account for poor accuracy in approximating the asymptotic behavior near the lower limit of differentiation. Some example functions are chosen and numerical results are presented to illustrate the efficacy of this new method over some other popular choices for discretizing fractional derivatives.

  5. Inconsistency of Minkowski higher-derivative theories

    Science.gov (United States)

    Aglietti, Ugo G.; Anselmi, Damiano

    2017-02-01

    We show that Minkowski higher-derivative quantum field theories are generically inconsistent, because they generate nonlocal, non-hermitian ultraviolet divergences, which cannot be removed by means of standard renormalization procedures. By "Minkowski theories" we mean theories that are defined directly in Minkowski spacetime. The problems occur when the propagators have complex poles, so that the correlation functions cannot be obtained as the analytic continuations of their Euclidean versions. The usual power counting rules fail and are replaced by much weaker ones. Self-energies generate complex divergences proportional to inverse powers of D'Alembertians. Three-point functions give more involved nonlocal divergences, which couple to infrared effects. We illustrate the violations of the locality and hermiticity of counterterms in scalar models and higher-derivative gravity.

  6. Fundamentals and advanced techniques in derivatives hedging

    CERN Document Server

    Bouchard, Bruno

    2016-01-01

    This book covers the theory of derivatives pricing and hedging as well as techniques used in mathematical finance. The authors use a top-down approach, starting with fundamentals before moving to applications, and present theoretical developments alongside various exercises, providing many examples of practical interest. A large spectrum of concepts and mathematical tools that are usually found in separate monographs are presented here. In addition to the no-arbitrage theory in full generality, this book also explores models and practical hedging and pricing issues. Fundamentals and Advanced Techniques in Derivatives Hedging further introduces advanced methods in probability and analysis, including Malliavin calculus and the theory of viscosity solutions, as well as the recent theory of stochastic targets and its use in risk management, making it the first textbook covering this topic. Graduate students in applied mathematics with an understanding of probability theory and stochastic calculus will find this b...

  7. Bone Marrow-Derived Macrophages (BMM)

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Porse, Bo

    2008-01-01

    INTRODUCTIONBone marrow-derived macrophages (BMM) are primary macrophage cells, derived from bone marrow cells in vitro in the presence of growth factors. Macrophage colony-stimulating factor (M-CSF) is a lineage-specific growth factor that is responsible for the proliferation and differentiation...... of committed myeloid progenitors into cells of the macrophage/monocyte lineage. Mice lacking functional M-CSF are deficient in macrophages and osteoclasts and suffer from osteopetrosis. In this protocol, bone marrow cells are grown in culture dishes in the presence of M-CSF, which is secreted by L929 cells...... and is used in the form of L929-conditioned medium. Under these conditions, the bone marrow monocyte/macrophage progenitors will proliferate and differentiate into a homogenous population of mature BMMs. The efficiency of the differentiation is assessed using fluorescence-activated cell sorting (FACS...

  8. Electrochemical Behavior of Biologically Important Indole Derivatives

    Directory of Open Access Journals (Sweden)

    Cigdem Karaaslan

    2011-01-01

    Full Text Available Voltammetric techniques are most suitable to investigate the redox properties of a new drug. Use of electrochemistry is an important approach in drug discovery and research as well as quality control, drug stability, and determination of physiological activity. The indole nucleus is an essential element of a number of natural and synthetic products with significant biological activity. Indole derivatives are the well-known electroactive compounds that are readily oxidized at carbon-based electrodes, and thus analytical procedures, such as electrochemical detection and voltammetry, have been developed for the determination of biologically important indoles. This paper explains some of the relevant and recent achievements in the electrochemistry processes and parameters mainly related to biologically important indole derivatives in view of drug discovery and analysis.

  9. Cosmology with higher-derivative matter fields

    CERN Document Server

    Harko, Tiberiu; Saridakis, Emmanuel N

    2014-01-01

    We investigate the cosmological implications of a new class of modified gravity, where the field equations generically include higher-order derivatives of the matter fields, arising from the introduction of non-dynamical auxiliary fields in the action. Imposing a flat, homogeneous and isotropic geometry we extract the Friedmann equations, obtaining an effective dark-energy sector containing higher derivatives of the matter energy density and pressure. For the cases of dust, radiation, and stiff matter we analyze the cosmological behavior, finding accelerating, de Sitter, and non-accelerating phases, dominated by matter or dark energy. Additionally, the effective dark-energy equation-of-state parameter can be quintessence-like, cosmological-constant-like, or even phantom-like. The detailed study of these scenarios may provide signatures that could distinguish them from other candidates of modified gravity.

  10. The cytotoxic activity of ursolic acid derivatives.

    Science.gov (United States)

    Ma, Chao-Mei; Cai, Shao-Qing; Cui, Jing-Rong; Wang, Rui-Qing; Tu, Peng-Fei; Hattori, Masao; Daneshtalab, Mohsen

    2005-06-01

    Ursolic acid and 2alpha-hydroxyursolic acid isolated from apple peels were found to show growth inhibitory activity against four tumor cell lines, HL-60, BGC, Bel-7402 and Hela. Structural modifications were performed on the C-3, C-28 and C-11 positions of ursolic acid and the cytotoxicity of the derivatives was evaluated. The SAR revealed that the triterpenes possessing two hydrogen-bond forming groups (an H-donor and a carbonyl group) at positions 3 and 28 exhibit cytotoxic activity. The configuration at C-3 was found to be important for the activity. Introduction of an amino group increased the cytotoxicity greatly. A 3beta-amino derivative was 20 times more potent than the parent ursolic acid. The 28-aminoalkyl dimer compounds showed selective cytotoxicity.

  11. Synthesis of metronidazole derivatives as antigiardiasis agents

    Directory of Open Access Journals (Sweden)

    Khabnadideh S.

    2007-04-01

    Full Text Available Metronidazole (MTZ and its derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. In this investigation several novel imidazole and nitroimidazol derivatives namely: 2-(1H-1-imidazolyl-1-phenyl-1-ethanol 1a, 2-(2-methyl-1H-1-imidazolyl-1-phenyl-1-ethanol 1b, 2-(2-methyl-4-nitro-1H-1-imidazolyl-1-phenyl-1-ethanol 1c, 2-(1H-1-imidazolyl-1-cyclohexanol 2d and 2-(2-methyl-4-nitro-1H-1-imidazolyl-1-cyclohexanol 2e were prepared by the reaction of the corresponding imidazoles with styrene oxide or cyclohexene oxide respectively and their biological activity against Giardia lamblia cyst in compareison with MTZ were determined by flotation technique based on Bingham method. These compounds were less active than metronidazole but showed significant antigiardiasis activity.

  12. Carbon gels derived from natural resources

    Directory of Open Access Journals (Sweden)

    A. Celzard

    2012-12-01

    Full Text Available Most carbon gels investigated so far and reportedin the literature were prepared from resorcinolcrosslinked with formaldehyde in water, and weregenerally dried with supercritical CO2 before beingpyrolysed. In the present paper, through someselected examples, we show how valuable carbongels can be derived from other phenolic resourceshaving a natural origin. Special emphasis is givento tannin and lignin, both derived from wood, aspotential precursors of carbon aero- and cryogels.However, natural compounds not obeying the usualconcepts of sol-gel chemistry may also be used forpreparing carbon gels, such as cellulose, and evenglucose. In the latter case, hydrothermal treatmentforces the phase separation to occur, and leads tomonoliths which can be advantageously convertedinto carbon aerogels by supercritical drying andsubsequent pyrolysis.

  13. Synthesis and Antidiabetic Evaluation of Benzenesulfonamide Derivatives

    Science.gov (United States)

    Hosseinzadeh, Nouraddin; Seraj, Soodeh; Bakhshi-Dezffoli, Mohamad Ebrahim; Hasani, Mohammad; Khoshneviszadeh, Mehdi; Fallah-Bonekohal, Saeed; Abdollahi, Mohammad; Foroumadi, Alireza; Shafiee, Abbas

    2013-01-01

    The complex metabolic syndrome, diabetes mellitus, is a major human health concern in the world and is estimated to affect 300 million people by the year 2025. Several drugs such as sulfonylureas and biguanides are presently available to reduce hyperglycemia in diabetes mellitus. These drugs have side effects and thus searching for a new class of compounds is essential to overcome this problems. A series of seven novel N-(4-phenylthiazol-2-yl)benzenesulfonamides derivatives were synthesized and assayed in-vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well-known antidiabetic agent, as a reference drug. Four of the compounds were effective, amongst which 13 show more prominent activity at 100 mg/Kg p.o. The experimental results are statistically significant at p < 0.05 level. PMID:24250607

  14. A new chromone derivative from Berchemia lineata.

    Science.gov (United States)

    Shen, Yu-xia; Teng, Hong-li; Yang, Guang-zhong; Mei, Zhi-nan; Chen, Xiao-long

    2010-09-01

    To study the chemical constituents from the root of Berchemia lineata (L.) DC., nine compounds were isolated from the EtOAc extract by using silica gel, RP-C18 silica gel column chromatography and preparative HPLC. Based on the spectroscopic analysis, their structures were identified as 5-hydroxy-7-(2'-hydroxypropyl)-2-methyl-chromone (1), (-)-(1'R, 2'S)-erythro-5-hydroxy-7-(1', 2'-dihydroxypropyl)-2-methyl-chromone (2), naringenin (3), eriodictyol (4), (+)-aromadendrin (5), (+)-taxifolin (6), (+)-catechin (7), (+)-epigallocatechin (8) and quercetin (9). Among them, compound 2 is a new chromone derivative. Compound 1 is a known chromone derivative and isolated from this genus for the first time. Compounds 3-9 are known flavonoids and isolated from this plant for the first time.

  15. Investigations In Higher Derivative Field Theories

    CERN Document Server

    Paul, Biswajit

    2015-01-01

    Canonical analysis leading to formal quantisation of the higher derivative theories are considered. The first order formalism is adopted where all the configuration space variables along with their higher time derivatives are considered to be independent fields. A systematic algorithm of abstracting the independent gauge symmetries is developed which is an extension of the method developed by Banerjee et al. for the usual first order theories. For the massive relativistic particle model with curvature, we solve the mismatch in the no of independent gauge parameters and no of independent primary fist class constarints. In addition, we show a direct connection between the gauge symmetry and the $W_3$-algebra for the rigid relativistic particle. Also, BRST symmetries for both the massive and massless particle models have been considered and its connection to $W_3$-algebras is demonstrated. The exact mapping of this gauge symmetry is shown with the reparametrisation invariance. Different models from field theory,...

  16. Renewable polyethylene mimics derived from castor oil.

    Science.gov (United States)

    Türünç, Oĝuz; Montero de Espinosa, Lucas; Meier, Michael A R

    2011-09-01

    An increasing number of reports on the syntheses of carbohydrate- and plant oil-based polymers has been published in ongoing efforts to produce plastic materials from renewable resources. Although many of these polymers are biodegradable and this is a desirable property for certain applications, in some cases non-degradable polymers are needed for long-term use purposes. Polyolefins are one of the most important classes of materials that have already taken their places in our daily life. On the other hand, their production relies on fossil resources. Therefore, within this contribution, we discuss synthetic routes toward a number of polyethylene mimics derived from fatty acids via thiol-ene and ADMET polymerization reactions in order to establish more sustainable routes toward this important class of polymers. Two different diene monomers were thus prepared from castor oil derived platform chemicals, their polymerization via the two mentioned routes was optimized and compared to each other, and their thermal properties were investigated.

  17. Inconsistency of Minkowski higher-derivative theories

    Energy Technology Data Exchange (ETDEWEB)

    Aglietti, Ugo G. [Universita di Roma ' ' La Sapienza' ' , Dipartimento di Fisica, Rome (Italy); Anselmi, Damiano [Universita di Pisa, Dipartimento di Fisica ' ' Enrico Fermi' ' , Pisa (Italy); INFN, Sezione di Pisa, Pisa (Italy)

    2017-02-15

    We show that Minkowski higher-derivative quantum field theories are generically inconsistent, because they generate nonlocal, non-hermitian ultraviolet divergences, which cannot be removed by means of standard renormalization procedures. By ''Minkowski theories'' we mean theories that are defined directly in Minkowski spacetime. The problems occur when the propagators have complex poles, so that the correlation functions cannot be obtained as the analytic continuations of their Euclidean versions. The usual power counting rules fail and are replaced by much weaker ones. Self-energies generate complex divergences proportional to inverse powers of D'Alembertians. Three-point functions give more involved nonlocal divergences, which couple to infrared effects. We illustrate the violations of the locality and hermiticity of counterterms in scalar models and higher-derivative gravity. (orig.)

  18. Benzodicarbomethoxytetrathiafulvalene derivatives as soluble organic semiconductors.

    Science.gov (United States)

    Otón, Francisco; Pfattner, Raphael; Oxtoby, Neil S; Mas-Torrent, Marta; Wurst, Klaus; Fontrodona, Xavier; Olivier, Yoann; Cornil, Jérôme; Veciana, Jaume; Rovira, Concepció

    2011-01-07

    A series of new tetrathiafulvalene (TTF) derivatives bearing dimethoxycarbonyl and phenyl or phthalimidyl groups fused to the TTF core (6 and 15-18) has been synthesized as potential soluble semiconductor materials for organic field-effect transistors (OFETs). The electron-withdrawing substituents lower the energy of the HOMO and LUMO levels and increase the solubility and stability of the semiconducting material. Crystal structures of all new TTF derivatives are also described, and theoretical DFT calculations were carried out to study the potential of the crystals to be used in OFET. In the experimental study, the best performing device exhibited a hole mobility up to 7.5 × 10(-3) cm(2) V(-1) s(-1)).

  19. Synthesis and electroluminescence properties of benzothiazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Fu Huiying [Department of Materials Science, Fudan University, Shanghai 200433 (China); Gao Xindong [State Key Laboratory of Applied Surface Physics, Fudan University, Shanghai 200433 (China); Zhong Gaoyu; Zhong Zhiyang [Department of Materials Science, Fudan University, Shanghai 200433 (China); Xiao Fei, E-mail: feixiao@fudan.edu.c [Department of Materials Science, Fudan University, Shanghai 200433 (China); Shao Bingxian [Department of Materials Science, Fudan University, Shanghai 200433 (China)

    2009-10-15

    Benzothiazole-based blue fluorescent materials N-(4-(benzo[d]thiazol-2-yl)phenyl)-N-phenylbenzenamine (BPPA) and N-(4-(benzo[d]thiazol-2-yl)phenyl)-N-phenylnaphthalen-1-amine (BPNA) were synthesized for use in organic light-emitting diodes (OLEDs). Electroluminescent device with a configuration of ITO/NPB/BPPA/BCP/Alq{sub 3}/LiF/Al showed a maximum brightness of 3760 cd/m{sup 2} at 14.4 V with the CIE coordinates of (0.16, 0.16). A current efficiency of 3.01 cd/A and an external quantum efficiency of 2.37% at 20 mA/cm{sup 2} were obtained from this device. Molecules derived from BPPA and BPNA with incorporated dicyanomethylidene, which is a functional group for most red fluorescent molecules, were designed, synthesized and characterized to study the red fluorescence properties of the benzothiazole derivatives.

  20. Symbolic derivation of potential based constitutive equations

    Science.gov (United States)

    Arnold, S. M.; Tan, H. Q.

    1990-05-01

    Structural alloys used in high temperature applications exhibit complex thermomechanical behavior that is inherently time dependent and hereditary, as the current behavior depends not only on current conditions but on the thermomechanical history. Derivation of mathematical expressions (constitutive equations) which describe this high temperature material behavior can be quite time consuming, involved, and error-prone, thus intelligent application of symbolic systems to facilitate this tedious processes can be of significant benefit. Here a computerized package, running under MACSYMA, capable of efficiently deriving potential based constitutive models, in analytical form (involving tensors, partial differentiation, invariants, and the like) is presented. Special purpose utility algorithms are designed and implemented to perform partial differentiation (chain rule), tensor manipulation, case distinction and simplification. Four constitutive theories reported in the literature are utilized to verify implementation accuracy. It is expected that this symbolic package can and will provide a significant incentive to the development of new constitutive theories.