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Sample records for bisbenzamidine derivative pentamidine

  1. Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation

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    Ohba Reiko

    2010-02-01

    Full Text Available Abstract Background MRE11 is an important nuclease which functions in the end-resection step of homologous recombination (HR repair of DNA double-strand breaks (DSBs. As MRE11-deficient ATLD cells exhibit hyper radio-sensitivity and impaired DSB repair, MRE11 inhibitors could possibly function as potent radio-sensitizers. Therefore, we investigated whether a bisbenzamidine derivative, pentamidine, which can inhibit endoexonuclease activity, might influence DSB-induced damage responses via inhibition of MRE11. Results We first clarified that pentamidine inhibited MRE11 nuclease activity and also reduced ATM kinase activity in vitro. Pentamidine increased the radio-sensitivity of HeLa cells, suggesting that this compound could possibly influence DNA damage response factors in vivo. Indeed, we found that pentamidine reduced the accumulation of γ-H2AX, NBS1 and phospho-ATM at the sites of DSBs. Furthermore, pentamidine decreased HR activity in vivo. Pentamidine was found to inhibit the acetylation of histone H2A which could contribute both to inhibition of IR-induced focus formation and HR repair. These results suggest that pentamidine might exert its effects by inhibiting histone acetyltransferases. We found that pentamidine repressed the activity of Tip60 acetyltransferase which is known to acetylate histone H2A and that knockdown of Tip60 by siRNA reduced HR activity. Conclusion These results indicate that inhibition of Tip60 as well as hMRE11 nuclease by pentamidine underlies the radiosensitizing effects of this compound making it an excellent sensitizer for radiotherapy or chemotherapy.

  2. Synthesis of bisbenzamidine derivatives in benzo[c]thiophene series

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    Kožul, Mirjana; Stolić, Ivana; Žinić, Biserka; Bajić, Miroslav

    2005-01-01

    The synthesis of three new bisbenzamidine derivatives in benzo[c]thiophene series is reported. In multistep synthesis from substituted 1,4-diketone first the benzo[c]thiophene unit was built up and than the terminal bromine atoms were transformed to corresponding amidines.

  3. Evaluation of bisbenzamidines as inhibitors for matriptase-2.

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    Beckmann, Anna-Madeleine; Gilberg, Erik; Gattner, Susanne; Huang, Tien L; Vanden Eynde, Jean Jacques; Mayence, Annie; Bajorath, Jürgen; Stirnberg, Marit; Gütschow, Michael

    2016-08-01

    The serine protease matriptase-2 has attracted much attention as a potential target for the treatment of iron overload diseases. In this study, a series of 27 symmetric, achiral bisbenzamidines was evaluated for inhibitory activity against human matriptase-2, against the closely related enzyme human matriptase, as well as against human thrombin, bovine factor Xa and human trypsin. The conformationally restricted piperazine derivative 19 and the oxamide-derived bisbenzamidine 1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively.

  4. Analogs of pentamidine as potential anti-Pneumocystis chemotherapeutics.

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    Maciejewska, Dorota; Zabinski, Jerzy; Kaźmierczak, Pawel; Rezler, Mateusz; Krassowska-Świebocka, Barbara; Collins, Margaret S; Cushion, Melanie T

    2012-02-01

    A series of 20 pentamidine analogs were prepared using 2 general Schemes that evaluated heteroatoms, sulfobenzene and alkanediamide groups in the aliphatic linker and methoxy substituents attached to the benzene rings for efficacy against the fungal pathogen, Pneumocystis carinii in an ATP bioassay. All but one of the 20 bisamidines reduced the ATP content of the P. carinii over the 72 h of the assay period. The highest activities were associated with the lack of methoxy groups and the presence of the O, N and S heteroatoms. Activity (IC(50)) for compounds 1, 5, 6, 10 ranged from 1.1 to 2.13 μM. The compound 11 with similar activity (1.33 μM), bears a sulfobenzene group at a nitrogen in the aliphatic linker. The alkanediamide-linked bisbenzamidines showed a moderate inhibition of ATP. Generally, the inclusion of a heteroatom in the aliphatic linker and absence of methoxy groups at the benzene rings were associated with higher activities in this assay. Of note, most of the compounds had little to no cytotoxicity in mammalian cell cultures. Although not quite as potent as other pentamidine derivatives, these compounds hold promise for decreased side effects within the mammalian host.

  5. Pentamidine Injection

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    Pentamidine injection is used to treat pneumonia caused by a fungus called Pneumocystis carinii. It is in ... Pentamidine injection comes as powder to be mixed with liquid to be injected intramuscularly (into a muscle) ...

  6. Novel pentamidine derivatives: synthesis, anti-tumor properties and polynucleotide-binding activities.

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    Jarak, Ivana; Marjanović, Marko; Piantanida, Ivo; Kralj, Marijeta; Karminski-Zamola, Grace

    2011-07-01

    Novel amidino-substituted conformationally restricted derivatives of pentamidine were synthesized and their antiproliferative activity against several human cancer cell lines determined. It was found that introduction of furandicarboxamide core moiety (9, 10) increases antiproliferative activity as well as selectivity against certain tumor cell lines in comparison with amidino-substituted furan-mono-carboxamide (5, 6). Unlike the furan series where iso-propyl substituted amidine (10) exhibits more potent overall antiproliferative activity and selectivity toward certain cell lines, the same was found for unsubstituted amidines in pyridine series. Amongst all tested compounds the compound 10 is the only one that possesses antiproliferative activity against SW 620 cell line (4 μM). Spectroscopic studies of the interactions of prepared diamidines with double-stranded DNA and RNA polynucleotides show that all compounds preferentially bind into the minor groove of DNA, while most of them intercalate into RNA. The structure-dependant biological activity and the lack of DNA/RNA selective binding suggest that the mechanism of action of the here-presented compounds is controlled not only by the interactions with cellular nucleic acids, but also with other more specific protein targets.

  7. Pentamidine Oral Inhalation

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    Pentamidine is an anti-infective agent that helps to treat or prevent pneumonia caused by the organism ... Pentamidine comes as a solution to be inhaled using a nebulizer. It usually is used once every ...

  8. Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents

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    Vanden Eynde, Jean J.; Mayence, Annie; Mottamal, Madhusoodanan; Bacchi, Cyrus J.; Yarlett, Nigel; Kaiser, Marcel; Brun, Reto; Huang, Tien L.

    2016-01-01

    A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b.) subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54) and a chloroquine-resistant strain (K1). The in vitro cytotoxicity was determined against rat myoblast cells (L6). Seven compounds (5, 6, 10, 11, 12, 14, 15) showed high potency against both strains of T. brucei and P. falciparum with the inhibitory concentrations for 50% (IC50) in the nanomolar range (IC50 = 1–96 nM). None of the tested derivatives was significantly active against T. cruzi or L. donovani. Three of the more potent compounds (5, 6, 11) were evaluated in vivo in mice infected with the drug-sensitive (Lab 110 EATRO and KETRI 2002) or drug-resistant (KETRI 2538 and KETRI 1992) clinical isolates of T. brucei. Compounds 5 and 6 were highly effective in curing mice infected with the drug-sensitive strains, including a drug-resistant strain KETRI 2538, but were ineffective against KETRI 1992. Thermal melting of DNA and molecular modeling studies indicate AT-rich DNA sequences as possible binding sites for these compounds. Several of the tested compounds are suitable leads for the development of improved antiparasitic agents. PMID:27104545

  9. Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents

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    Jean J. Vanden Eynde

    2016-04-01

    Full Text Available A series of 15 alkanediamide-linked bisbenzamidines and related analogs was synthesized and tested in vitro against two Trypanosoma brucei (T.b. subspecies: T.b. brucei and T.b. rhodesiense, Trypanosoma cruzi, Leishmania donovani and two Plasmodium falciparum subspecies: a chloroquine-sensitive strain (NF54 and a chloroquine-resistant strain (K1. The in vitro cytotoxicity was determined against rat myoblast cells (L6. Seven compounds (5, 6, 10, 11, 12, 14, 15 showed high potency against both strains of T. brucei and P. falciparum with the inhibitory concentrations for 50% (IC50 in the nanomolar range (IC50 = 1–96 nM. None of the tested derivatives was significantly active against T. cruzi or L. donovani. Three of the more potent compounds (5, 6, 11 were evaluated in vivo in mice infected with the drug-sensitive (Lab 110 EATRO and KETRI 2002 or drug-resistant (KETRI 2538 and KETRI 1992 clinical isolates of T. brucei. Compounds 5 and 6 were highly effective in curing mice infected with the drug-sensitive strains, including a drug-resistant strain KETRI 2538, but were ineffective against KETRI 1992. Thermal melting of DNA and molecular modeling studies indicate AT-rich DNA sequences as possible binding sites for these compounds. Several of the tested compounds are suitable leads for the development of improved antiparasitic agents.

  10. Anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congeners.

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    Huang, Tien L; Vanden Eynde, Jean Jacques; Mayence, Annie; Donkor, Isaac O; Khan, Shabana I; Tekwani, Babu L

    2006-08-01

    A library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two Plasmodium falciparum strains and Leishmania donovani. The tested compounds were generally more effective against P. falciparum than L. donovani. The most active compounds against the chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indochina) strains of P. falciparum were bisbenzamidines linked with a 1,4-piperazinediyl or 1, 4-homopiperazinediyl moiety, with IC50 values (50% inhibitory concentration, inhibiting parasite growth by 50% in relation to drug-free control) as low as 7 nM based on the parasite lactate dehydrogenase assay. Seven piperazine-linked bisbenzamidines substituted at the amidinium nitrogens with a linear alkyl group of 3-6 carbons (22, 25, 27, 31) or cycloalkyl group of 4, 6 or 7 carbons (26, 32, 34) were more potent (IC50pentamidine as anti-plasmodial agents. The most active anti-leishmanial agents were 4,4'-[1,4-phenylenebis(methyleneoxy)]bisbenzenecarboximidamide (2, IC50 approximately 0.290 microM) and 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl] piperazine (44, IC50 approximately 0.410 microM), which were 10- and 7-fold more potent than pentamidine (IC50 approximately 2.90 microM). Several of the more active anti-plasmodial agents (e.g. 2, 31, 33, 36-38) were also potent anti-leishmanial agents, indicating broad antiprotozoal properties. However, a number of analogues that showed potent anti-plasmodial activity (1, 18, 21, 22, 25-28, 32, 43, 45) were not significantly active against the Leishmania parasite. This indicates differential modes of anti-plasmodial and anti-leishmanial actions for this class of compounds. These compounds provide important structure-activity relationship data for the design of improved chemotherapeutic agents against parasitic infections.

  11. Sequence-selective DNA recognition with peptide-bisbenzamidine conjugates.

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    Sánchez, Mateo I; Vázquez, Olalla; Vázquez, M Eugenio; Mascareñas, José L

    2013-07-22

    Transcription factors (TFs) are specialized proteins that play a key role in the regulation of genetic expression. Their mechanism of action involves the interaction with specific DNA sequences, which usually takes place through specialized domains of the protein. However, achieving an efficient binding usually requires the presence of the full protein. This is the case for bZIP and zinc finger TF families, which cannot interact with their target sites when the DNA binding fragments are presented as isolated monomers. Herein it is demonstrated that the DNA binding of these monomeric peptides can be restored when conjugated to aza-bisbenzamidines, which are readily accessible molecules that interact with A/T-rich sites by insertion into their minor groove. Importantly, the fluorogenic properties of the aza-benzamidine unit provide details of the DNA interaction that are eluded in electrophoresis mobility shift assays (EMSA). The hybrids based on the GCN4 bZIP protein preferentially bind to composite sequences containing tandem bisbenzamidine-GCN4 binding sites (TCAT⋅AAATT). Fluorescence reverse titrations show an interesting multiphasic profile consistent with the formation of competitive nonspecific complexes at low DNA/peptide ratios. On the other hand, the conjugate with the DNA binding domain of the zinc finger protein GAGA binds with high affinity (KD≈12 nM) and specificity to a composite AATTT⋅GAGA sequence containing both the bisbenzamidine and the TF consensus binding sites.

  12. Activity of pentamidine and pentamidine analogs against Toxoplasma gondii in cell cultures.

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    Lindsay, D S; Blagburn, B L; Hall, J. E.; Tidwell, R R

    1991-01-01

    The capabilities of pentamidine and nine pentamidine analogs to inhibit the development of Toxoplasma gondii were examined in vitro. Treatment of infected cultures with pentamidine and five of its analogs caused a significant (P less than 0.05) reduction in the numbers of tachyzoites produced. Analogs of pentamidine may be useful agents in the treatment of toxoplasmosis.

  13. Effects of pentamidine isethionate on Saccharomyces cerevisiae.

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    Ludewig, G.; Williams, J M; Li, Y.; Staben, C

    1994-01-01

    We used Saccharomyces cerevisiae as a model system in which to examine the mechanism of action of the anti-Pneumocystis drug pentamidine. Pentamidine at low concentrations inhibited S. cerevisiae growth on nonfermentable carbon sources (50% inhibitory concentration [IC50] of 1.25 micrograms/ml in glycerol). Pentamidine inhibited growth on fermentable energy sources only at much higher concentrations (IC50 of 250 micrograms/ml in glucose). Inhibition at low pentamidine concentrations in glycer...

  14. The antiprotozoal drug pentamidine ameliorates experimentally induced acute colitis in mice

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    Esposito Giuseppe

    2012-12-01

    Full Text Available Abstract Background Intestinal inflammation is partly driven by enteroglial-derived S100B protein. The antiprotozoal drug pentamidine directly blocks S100B activity. We aimed to investigate the effect of pentamidine on intestinal inflammation using an animal model of dextran sodium sulphate (DSS-induced acute colitis. Methods Mice were divided into: control group, colitis group (4% DSS for four days and two pentamidine-treated colitis groups (0.8 mg/kg and 4 mg/kg. Anti-inflammatory effect of pentamidine was assessed in colonic tissue by evaluating the disease activity index and the severity of histological changes. Colonic tissue were also used to evaluate cyclooxigenase-2, inducible nitric oxide synthase, S100B, glial fibrillary acidic protein, phosphorylated-p38 MAPkinase, p50, p65 protein expression, malondyaldheyde production, mieloperoxidase activity, and macrophage infiltration. Nitric oxide, prostaglandin E2, interleukin-1 beta, tumor necrosis factor alpha, and S100B levels were detected in plasma samples. Parallel measurements were performed in vitro on dissected mucosa and longitudinal muscle myenteric plexus (LMMP preparations after challenge with LPS + DSS or exogenous S100B protein in the presence or absence of pentamidine. Results Pentamidine treatment significantly ameliorated the severity of acute colitis in mice, as showed by macroscopic evaluation and histological/biochemical assays in colonic tissues and in plasma. Pentamidine effect on inflammatory mediators was almost completely abrogated in dissected mucosa but not in LMMP. Conclusions Pentamidine exerts a marked anti-inflammatory effect in a mice model of acute colitis, likely targeting S100B activity. Pentamidine might be an innovative molecule to broaden pharmacological tools against colitis.

  15. Pentamidine Dosage: A Base/Salt Confusion

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    Dorlo, Thomas P. C.; Kager, Piet A.

    2008-01-01

    Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past d...

  16. Pentamidine Is Not a Permeant but a Nanomolar Inhibitor of the Trypanosoma brucei Aquaglyceroporin-2.

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    Song, Jie; Baker, Nicola; Rothert, Monja; Henke, Björn; Jeacock, Laura; Horn, David; Beitz, Eric

    2016-02-01

    The chemotherapeutic arsenal against human African trypanosomiasis, sleeping sickness, is limited and can cause severe, often fatal, side effects. One of the classic and most widely used drugs is pentamidine, an aromatic diamidine compound introduced in the 1940s. Recently, a genome-wide loss-of-function screen and a subsequently generated trypanosome knockout strain revealed a specific aquaglyceroporin, TbAQP2, to be required for high-affinity uptake of pentamidine. Yet, the underlying mechanism remained unclear. Here, we show that TbAQP2 is not a direct transporter for the di-basic, positively charged pentamidine. Even though one of the two common cation filters of aquaglyceroporins, i.e. the aromatic/arginine selectivity filter, is unconventional in TbAQP2, positively charged compounds are still excluded from passing the channel. We found, instead, that the unique selectivity filter layout renders pentamidine a nanomolar inhibitor of TbAQP2 glycerol permeability. Full, non-covalent inhibition of an aqua(glycero)porin in the nanomolar range has not been achieved before. The remarkable affinity derives from an electrostatic interaction with Asp265 and shielding from water as shown by structure-function evaluation and point mutation of Asp265. Exchange of the preceding Leu264 to arginine abolished pentamidine-binding and parasites expressing this mutant were pentamidine-resistant. Our results indicate that TbAQP2 is a high-affinity receptor for pentamidine. Taken together with localization of TbAQP2 in the flagellar pocket of bloodstream trypanosomes, we propose that pentamidine uptake is by endocytosis.

  17. Pentamidine Is Not a Permeant but a Nanomolar Inhibitor of the Trypanosoma brucei Aquaglyceroporin-2.

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    Jie Song

    2016-02-01

    Full Text Available The chemotherapeutic arsenal against human African trypanosomiasis, sleeping sickness, is limited and can cause severe, often fatal, side effects. One of the classic and most widely used drugs is pentamidine, an aromatic diamidine compound introduced in the 1940s. Recently, a genome-wide loss-of-function screen and a subsequently generated trypanosome knockout strain revealed a specific aquaglyceroporin, TbAQP2, to be required for high-affinity uptake of pentamidine. Yet, the underlying mechanism remained unclear. Here, we show that TbAQP2 is not a direct transporter for the di-basic, positively charged pentamidine. Even though one of the two common cation filters of aquaglyceroporins, i.e. the aromatic/arginine selectivity filter, is unconventional in TbAQP2, positively charged compounds are still excluded from passing the channel. We found, instead, that the unique selectivity filter layout renders pentamidine a nanomolar inhibitor of TbAQP2 glycerol permeability. Full, non-covalent inhibition of an aqua(glyceroporin in the nanomolar range has not been achieved before. The remarkable affinity derives from an electrostatic interaction with Asp265 and shielding from water as shown by structure-function evaluation and point mutation of Asp265. Exchange of the preceding Leu264 to arginine abolished pentamidine-binding and parasites expressing this mutant were pentamidine-resistant. Our results indicate that TbAQP2 is a high-affinity receptor for pentamidine. Taken together with localization of TbAQP2 in the flagellar pocket of bloodstream trypanosomes, we propose that pentamidine uptake is by endocytosis.

  18. Effect of cimetidine on pentamidine induced hyperglycemia in rats.

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    Arino, Toru; Karakawa, Seiji; Ishiwata, Yasuyoshi; Nagata, Masashi; Yasuhara, Masato

    2012-10-15

    The antiprotozoal agent pentamidine, used for the treatment of Pneumocystis jirovecii pneumonia (PCP), is known to cause abnormalities in blood glucose homeostasis, such as hypoglycemia and hyperglycemia. Pentamidine has been reported to be a substrate of organic cation transporter 1 (OCT1). We investigated the combination effects of cimetidine, an OCT1 inhibitor, on the pharmacokinetics of pentamidine and on pentamidine-induced hyperglycemia. Pentamidine was infused intravenously to rats for 20 min at a dose of 7.5 or 15 mg/kg and serum samples were obtained periodically. The serum concentration of glucose did not change significantly after pentamidine infusion at 7.5mg/kg, while it increased with pentamidine at 15 mg/kg, and the maximal concentration of glucose was 167 ± 36 mg/dl, 30 min after the start of pentamidine infusion. Cimetidine (50mg/kg) enhanced the pentamidine-induced elevation of glucose concentration and the maximal concentration of glucose was 208 ± 33 mg/dl in the pentamidine 15 mg/kg treated group. Cimetidine combination significantly reduced total body clearance of pentamidine and increased pentamidine concentrations in the liver, kidneys, and lungs. A significant correlation was found between changes in serum glucose concentrations and serum concentrations of pentamidine 30 min after the start of pentamidine infusion. These results suggest that the hyperglycemic effect of pentamidine is dependent on the concentration of pentamidine and can be enhanced by cimetidine combination.

  19. Pentamidine analogs as inhibitors of [(3)H]MK-801 and [(3)H]ifenprodil binding to rat brain NMDA receptors.

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    Berger, Michael L; Maciejewska, Dorota; Vanden Eynde, Jean Jacques; Mottamal, Madhusoodanan; Żabiński, Jerzy; Kaźmierczak, Paweł; Rezler, Mateusz; Jarak, Ivana; Piantanida, Ivo; Karminski-Zamola, Grace; Mayence, Annie; Rebernik, Patrick; Kumar, Arvind; Ismail, Mohamed A; Boykin, David W; Huang, Tien L

    2015-08-01

    The anti-protozoal drug pentamidine is active against opportunistic Pneumocystis pneumonia, but in addition has several other biological targets, including the NMDA receptor (NR). Here we describe the inhibitory potencies of 76 pentamidine analogs at 2 binding sites of the NR, the channel binding site labeled with [(3)H]MK-801 and the [(3)H]ifenprodil binding site. Most analogs acted weaker at the ifenprodil than at the channel site. The spermine-sensitivity of NR inhibition by the majority of the compounds was reminiscent of other long-chain dicationic NR blockers. The potency of the parent compound as NR blocker was increased by modifying the heteroatoms in the bridge connecting the 2 benzamidine moieties and also by integrating the bridge into a seven-membered ring. Docking of the 45 most spermine-sensitive bisbenzamidines to a recently described acidic interface between the N-terminal domains of GluN1 and GluN2B mediating polyamine stimulation of the NR revealed the domain contributed by GluN1 as the most relevant target.

  20. Pentamidine dosage: a base/salt confusion.

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    Dorlo, Thomas P C; Kager, Piet A

    2008-05-28

    Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past decades and show the confusion in the calculation of the dosage of pentamidine in these guidelines and the subsequent published reports on clinical trials and reviews. At present, only pentamidine isethionate is available, but the advised dosage for HAT and leishmaniasis is (historically) based on the amount of pentamidine base. In the treatment of leishmaniasis this is probably resulting in a subtherapeutic treatment. There is thus a need for a new, more transparent and concise guideline concerning the dosage of pentamidine, at least in the treatment of HAT and leishmaniasis.

  1. Pentamidine dosage: a base/salt confusion.

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    Thomas P C Dorlo

    Full Text Available Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past decades and show the confusion in the calculation of the dosage of pentamidine in these guidelines and the subsequent published reports on clinical trials and reviews. At present, only pentamidine isethionate is available, but the advised dosage for HAT and leishmaniasis is (historically based on the amount of pentamidine base. In the treatment of leishmaniasis this is probably resulting in a subtherapeutic treatment. There is thus a need for a new, more transparent and concise guideline concerning the dosage of pentamidine, at least in the treatment of HAT and leishmaniasis.

  2. The effect of pentamidine on melanoma ex vivo.

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    Smith, Jason; Stewart, Benjamin J; Glaysher, Sharon; Peregrin, Katharine; Knight, Louise A; Weber, David J; Cree, Ian A

    2010-02-01

    Pentamidine is a small molecule inhibitor of the Ca(+)-binding protein S100B and disrupts the S100B-p53 protein-protein interaction; this is thought to restore wild-type p53 tumour suppressor function in melanoma. Additional anticancer effects may be the result of inhibition of regenerating liver family phosphatases. In this study, we have used a standardized ATP-tumour chemosensitivity assay to investigate the effect of pentamidine on cells derived from 18 skin melanoma samples and one uveal melanoma sample. The cells were tested at six concentrations from which the IC(50) and IC(90) were calculated. To allow comparison between samples, an index(sum) was calculated based on the percentage of tumour growth inhibition at each concentration. Of the skin melanoma samples tested, 78% exhibited an index(sum) less than 300 indicating strong inhibition. The median index(sum) of 237 also indicates considerable activity against these samples. The median IC(90) (30.2 micromol/l) may be clinically achievable in a proportion of patients. The uveal melanoma sample exhibited an index(sum) of 333 indicating moderate inhibition, and 86% inhibition at test drug concentration (37.96 micromol/l). These results show that pentamidine has activity against melanoma, and support the prospect of its development for therapeutic use.

  3. New prodrugs of the antiprotozoal drug pentamidine.

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    Kotthaus, Joscha; Kotthaus, Jürke; Schade, Dennis; Schwering, Ulrike; Hungeling, Helen; Müller-Fielitz, Helge; Raasch, Walter; Clement, Bernd

    2011-12-09

    Pentamidine is an effective antimicrobial agent that is approved for the treatment of African trypanosomiasis but suffers from poor oral bioavailability and central nervous system (CNS) penetration. This work deals with the development and systematic characterisation of new prodrugs of pentamidine. For this reason, numerous prodrugs that use different prodrug principles were synthesised and examined in vitro and in vivo. Another objective of the study was the determination of permeability of the different pentamidine prodrugs. While some of the prodrug principles applied in this study are known, such as the conversion of the amidine functions into amidoximes or the O-alkylation of amidoximes with a carboxymethyl residue, others were developed more recently and are described here for the first time. These newly developed methods aim to increase the affinity of the prodrug for the transporters and mediate an active uptake via carrier systems by conjugation of amidoximes with compounds that improve the overall solubility of the prodrug. The different principles chosen resulted in several pentamidine prodrugs with various advantages. The objective of this investigation was the systematic characterisation and evaluation of eight pentamidine prodrugs in order to identify the most appropriate strategy to improve the properties of the parent drug. For this reason, all prodrugs were examined with respect to their solubility, stability, enzymatic activation, distribution, CNS delivery, and oral bioavailability. The results of this work have allowed reliable conclusions to be drawn regarding the best prodrug principle for the antiprotozoal drug pentamidine.

  4. S100B Inhibitor Pentamidine Attenuates Reactive Gliosis and Reduces Neuronal Loss in a Mouse Model of Alzheimer's Disease.

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    Cirillo, Carla; Capoccia, Elena; Iuvone, Teresa; Cuomo, Rosario; Sarnelli, Giovanni; Steardo, Luca; Esposito, Giuseppe

    2015-01-01

    Among the different signaling molecules released during reactive gliosis occurring in Alzheimer's disease (AD), the astrocyte-derived S100B protein plays a key role in neuroinflammation, one of the hallmarks of the disease. The use of pharmacological tools targeting S100B may be crucial to embank its effects and some of the pathological features of AD. The antiprotozoal drug pentamidine is a good candidate since it directly blocks S100B activity by inhibiting its interaction with the tumor suppressor p53. We used a mouse model of amyloid beta- (Aβ-) induced AD, which is characterized by reactive gliosis and neuroinflammation in the brain, and we evaluated the effect of pentamidine on the main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary acidic protein, S100B, and RAGE protein expression, which are signs of reactive gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the expression of proinflammatory mediators and markers, thus reducing neuroinflammation in AD brain. In parallel, we observed a significant neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated that pentamidine inhibits Aβ-induced gliosis and neuroinflammation in an animal model of AD, thus playing a role in slowing down the course of the disease.

  5. Hydroxylation of pentamidine by rat liver microsomes.

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    Berger, B J; Reddy, V V; Le, S T; Lombardy, R J; Hall, J E; Tidwell, R R

    1991-03-01

    The antiprotozoal/antifungal drug pentamidine [1,5-bis(4-amidinophenoxy)pentane] has been recently shown to be metabolized by rat liver fractions to at least six putative metabolites as detected by high-performance liquid chromatography. Two minor metabolites have been previously identified as N-hydroxypentamidine and N,N'-dihydroxypentamidine. In this study, the two major microsomal metabolites have been identified as the 2-pentanol and 3-pentanol analogs of pentamidine [1,5-di(4-amidinophenoxy)-2-pentanol; and 1,5-bis(4-amidinophenoxy)-3-pentanol]. As well, a seventh putative metabolite has been discovered and identified as para-hydroxybenzamidine, a fragment of the original drug. Whereas the cytochromes P-450 have been demonstrated as the enzyme system responsible for pentamidine metabolism, hydroxylation of the drug was not inducible by phenobarbital, beta-naphthoflavone, clofibrate, isosafrole, pregnenolone-16 alpha-carbonitrile, ethanol or pentamidine pretreatment of rats. The kinetics of the production of the two major microsomal metabolites has been determined as Km = 56 +/- 19 microM and Vmax = 126 +/- 21 pmol/min/mg microsomal protein for the 2-pentanol analog, and Km = 28 +/- 0.28 microM and Vmax = 195 +/- 2.4 pmol/min/mg microsomal protein for the 3-pentanol analog. Therefore, the mixed-function oxidases readily convert pentamidine to hydroxylated metabolites, but exactly which isozyme(s) of cytochrome P-450 is responsible is not clear.

  6. Characterization of Leishmania (Leishmania) amazonensis promastigotes resistant to pentamidine.

    Science.gov (United States)

    Coelho, Adriano C; Gentil, Luciana G; da Silveira, José Franco; Cotrim, Paulo C

    2008-09-01

    Pentamidine is a second-line agent used in the treatment of leishmaniasis and its mode of action and mechanism of resistance is not well understood. It was previously demonstrated that transfection of promastigotes and amastigotes with the ABC transporter PRP1 gene confers resistance to pentamidine. To further clarify this point, we generated Leishmania amazonensis mutants resistant to pentamidine. Our results indicated that this ABC transporter is not associated with pentamidine resistance in lines generated by drug pressure through amplification or overexpression mechanisms of PRP1 gene.

  7. New pentamidine analogues in medicinal chemistry.

    Science.gov (United States)

    Porcheddu, A; Giacomelli, G; De Luca, L

    2012-01-01

    Sixty years after its introduction, 1,5-bis(4-amidinophenoxy)pentane (Pentamidine) is still one of the most used drugs for the treatment of the first stage of Human African trypanosomiasis and other neglected diseases such as malaria and leishmaniasis. These protozoan infections are prevalent in the poorest world areas such as sub-saharian and developing countries, however the increasing immigration from these countries to the richest part of the world and the overlap of HIV with parasitic infections result in a growing number of cases in developed nations. A great effort has been made to develop new generations of diamidines for the treatment of these infections transmitted by insects. This review summarises the synthesis and evaluation of pentamidine analogues reported in the last years in the effort to find new drugs with better pharmaceutical activity, higher lipophilicity and lower citotoxycicty.

  8. S100B Inhibitor Pentamidine Attenuates Reactive Gliosis and Reduces Neuronal Loss in a Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Carla Cirillo

    2015-01-01

    Full Text Available Among the different signaling molecules released during reactive gliosis occurring in Alzheimer’s disease (AD, the astrocyte-derived S100B protein plays a key role in neuroinflammation, one of the hallmarks of the disease. The use of pharmacological tools targeting S100B may be crucial to embank its effects and some of the pathological features of AD. The antiprotozoal drug pentamidine is a good candidate since it directly blocks S100B activity by inhibiting its interaction with the tumor suppressor p53. We used a mouse model of amyloid beta- (Aβ- induced AD, which is characterized by reactive gliosis and neuroinflammation in the brain, and we evaluated the effect of pentamidine on the main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary acidic protein, S100B, and RAGE protein expression, which are signs of reactive gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the expression of proinflammatory mediators and markers, thus reducing neuroinflammation in AD brain. In parallel, we observed a significant neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated that pentamidine inhibits Aβ-induced gliosis and neuroinflammation in an animal model of AD, thus playing a role in slowing down the course of the disease.

  9. Amino and chlorambucil analogues of pentamidine--synthesis and biological examinations.

    Science.gov (United States)

    Pućkowska, Anna; Drozdowska, Danuta; Rusak, Małgorzata; Bielawski, Tomasz; Bruzgo, Irena; Midura-Nowaczek, Krystyna

    2012-01-01

    The amino analogues of pentamidine with a polymethylene (n = 3 - 6) chain and their chlorambucil derivatives were synthesized. The obtained compounds revealed cytotoxic effect on MCF-7 human breast cancer cell line (IC50 = 22 - 95 +/- 2 pM), mainly by the induction of apoptosis. The topoisomerase I/II inhibition assay and the ethidium displacement assay with the use of pBR322 plasmid DNA were used to the study of mechanism by which the obtained compounds could act. All the compounds are able to bind with DNA and interfere in vitro with the activity of topoisomerase (I and II). The determination of association constants with the use of calf thymus DNA, T4 coliphage DNA, poly(dA-dT)2 and poly(dG-dC)2 showed that the tested compounds bind within minor groove of B-DNA, but not selectively. The alkylating activity of chlorambucil derivatives determined in vitro using a Preussmann test was similar to the activity of chlorambucil. The influence of all the compounds on the amidolytic activity of plasmin and trypsin was also examined. The plasmin activity was inhibited by pentamidine, chlorambucil and aromatic bis-amines (IC50 = 0.1 - 8 mM), whereas the trypsin activity was influenced only by pentamidine.

  10. In vitro activity of pentamidine against Tropheryma whipplei.

    Science.gov (United States)

    Rolain, Jean-Marc; Fenollar, Florence; Raoult, Didier

    2011-12-01

    Pentamidine is a group I intron splice inhibitor used as a chemotherapeutic agent to treat parasitic infections. It was recently found to be efficient intracellularly against Coxiella burnetii, the bacterial agent of Q fever. This in vitro activity was linked to the presence of self-splicing group I introns that disrupt the 23S rRNA of C. burnetii. However, there are several indications that pentamidine may have a wider range of antibacterial activity. The aim of this study was to determine the in vitro activity of pentamidine against Tropheryma whipplei, the agent of Whipple's disease, a chronic disease for which antibiotic treatment remains challenging. In vitro susceptibility testing of pentamidine and doxycycline was assessed both in axenic medium and in cell culture against three clinical isolates of T. whipplei using a quantitative real-time polymerase chain reaction (PCR) assay as previously described. Both doxycycline and pentamidine were found to be active against T. whipplei strains both in axenic medium and in cell culture, with minimum inhibitory concentration ranges of 0.5-1mg/L and 0.125-0.25mg/L for doxycycline and pentamidine, respectively. Pentamidine was effective in vitro against T. whipplei both intracellularly and in axenic medium. This is the first evidence of the direct efficacy of pentamidine against T. whipplei grown in axenic medium and in cells. Since pentamidine has been widely used in humans, we believe that it could be an alternative drug for the treatment of this chronic disease that should be further studied in clinical trials.

  11. Synthesis of pentamidine labelled with tritium and carbon-14

    Energy Technology Data Exchange (ETDEWEB)

    Hesk, D.; Jones, J.R. (Surrey Univ., Guildford (UK). Dept. of Chemistry); Lockley, W.J.S.; Wilkinson, D.J. (Fisons plc, Loughborough (UK). Pharmaceutical Div.)

    1990-11-01

    Tritium labelled pentamidine has been prepared with a specific activity of 90 mCi mmol{sup -1} using a one-step exchange reaction between the unlabelled drug and tritiated water. The labelling utilised a homogeneous rhodium trichloride catalyst and yielded pentamidine regiospecifically labelled in the positions ortho to the amidine groups. Carbon-14 labelled pentamidine was prepared via a seven-step procedure in which the isotope was introduced via a nucleophilic substitution of 4-bromo-phenol with copper(I) ({sup 14}C)cyanide. (author).

  12. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Directory of Open Access Journals (Sweden)

    Siddhesh Prabhavalkar

    2013-01-01

    Full Text Available Acute kidney injury (AKI is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pentamidine was used monthly as prophylaxis for Pneumocystis jirovecii pneumonia, and administration preceded the creatinine rise on each occasion. Graft function stabilised following discontinuation of the drug. This is the first report of nebulized pentamidine-induced reversible nephrotoxicity in a kidney allograft. This diagnosis should be considered in a case of unexplained acute renal allograft dysfunction.

  13. Pentamidine reverses the splicing defects associated with myotonic dystrophy.

    Science.gov (United States)

    Warf, M Bryan; Nakamori, Masayuki; Matthys, Catherine M; Thornton, Charles A; Berglund, J Andrew

    2009-11-03

    Myotonic dystrophy (DM) is a genetic disorder caused by the expression (as RNA) of expanded CTG or CCTG repeats. The alternative splicing factor MBNL1 is sequestered to the expanded RNA repeats, resulting in missplicing of a subset of pre-mRNAs linked to symptoms found in DM patients. Current data suggest that if MBNL1 is released from sequestration, disease symptoms may be alleviated. We identified the small molecules pentamidine and neomycin B as compounds that disrupt MBNL1 binding to CUG repeats in vitro. We show in cell culture that pentamidine was able to reverse the missplicing of 2 pre-mRNAs affected in DM, whereas neomycin B had no effect. Pentamidine also significantly reduced the formation of ribonuclear foci in tissue culture cells, releasing MBNL1 from the foci in the treated cells. Furthermore, pentamidine partially rescued splicing defects of 2 pre-mRNAs in mice expressing expanded CUG repeats.

  14. High-performance liquid chromatographic assay detects pentamidine metabolism by Fisher rat liver microsomes.

    Science.gov (United States)

    Tuttle, R H; Hall, J E; Tidwell, R R

    1997-01-24

    Fisher rat liver microsomes metabolized the antimicrobial drug pentamidine to four new compounds detected by gradient elution reversed-phase high-performance liquid chromatography with variable wavelength detection. Coelution experiments with pentamidine metabolite standards determined the new peaks to be previously identified hydroxylated metabolites of pentamidine, with 1,5-bis(4'-amidinophenoxy)-3-pentanol and 1,5-di-(4'-amidinophenoxy)-2-pentanol formed in the greatest amount. The data contradict a previous report that Fisher rat liver homogenates do not metabolize pentamidine. Pentamidine and its known primary metabolites have almost identical absorption spectra; thus, pentamidine metabolism must be evaluated using gradient elution HPLC to resolve pentamidine from its metabolites. The current assay has now been used to demonstrate that Fisher and Sprague-Dawley rat, mouse, rabbit and human liver microsomes all metabolize pentamidine in vitro.

  15. Role of the ABC transporter PRP1 (ABCC7) in pentamidine resistance in Leishmania amastigotes.

    Science.gov (United States)

    Coelho, Adriano C; Messier, Nadine; Ouellette, Marc; Cotrim, Paulo C

    2007-08-01

    Pentamidine is a second-line agent in the treatment of leishmaniasis whose mode of action and resistance mechanism are not well understood. In this work, we show that the intracellular ABC protein PRP1 (pentamidine resistance protein 1) (ABCC7) can confer resistance to pentamidine in Leishmania sp. parasites in the intracellular stage.

  16. Efficacy and tolerability of intravenous pentamidine isethionate for Pneumocystis jiroveci prophylaxis in a pediatric oncology population.

    Science.gov (United States)

    Orgel, Etan; Rushing, Teresa

    2014-03-01

    Cancer therapy routinely requires Pneumocystis jiroveci prophylaxis. In those intolerant of trimethoprim/sulfamethoxazole, aerosolized pentamidine is convenient and effective. Intravenous pentamidine is often substituted in young children but its efficacy remains controversial. In this retrospective study of a large pediatric oncology cohort, we confirm intravenous pentamidine to be effective and well-tolerated as second-line prophylaxis across all ages.

  17. Enzymatic response of the eucalypt defoliator Thyrinteina arnobia (Stoll) (Lepidoptera: Geometridae) to a bis-benzamidine proteinase Inhibitor. i.

    Science.gov (United States)

    Marinho-Prado, Jeanne Scardini; Lourenção, A L; Guedes, R N C; Pallini, A; Oliveira, J A; Oliveira, M G A

    2012-10-01

    Ingestion of proteinase inhibitors leads to hyperproduction of digestive proteinases, limiting the bioavailability of essential amino acids for protein synthesis, which affects insect growth and development. However, the effects of proteinase inhibitors on digestive enzymes can lead to an adaptive response by the insect. In here, we assessed the biochemical response of midgut proteinases from the eucalypt defoliator Thyrinteina arnobia (Stoll) to different concentrations of berenil, a bis-benzamidine proteinase inhibitor, on eucalyptus. Eucalyptus leaves were immersed in berenil solutions at different concentrations and fed to larvae of T. arnobia. Mortality was assessed daily. The proteolytic activity in the midgut of T. arnobia was assessed after feeding on plants sprayed with aqueous solutions of berenil, fed to fifth instars of T. arnobia for 48 h before midgut removal for enzymatic assays. Larvae of T. arnobia were able to overcome the effects of the lowest berenil concentrations by increasing their trypsin-like activity, but not as berenil concentration increased, despite the fact that the highest berenil concentration resulted in overproduction of trypsin-like proteinases. Berenil also prevented the increase of the cysteine proteinases activity in response to trypsin inhibition.

  18. Enucleation following treatment with intravenous pentamidine for Acanthamoeba sclerokeratitis

    Directory of Open Access Journals (Sweden)

    Rebecca A Kuennen

    2010-09-01

    Full Text Available Rebecca A Kuennen, Reynell Harder Smith, Thomas F Mauger, Elson CraigDepartment of Ophthalmology, The Ohio State University, Columbus, Ohio, USAPurpose: To describe the course and outcome of treatment of advanced Acanthamoeba sclerokeratitis with intravenous pentamidine.Methods: A case of advanced Acanthamoeba sclerokeratitis was resistant to conventional therapy and was treated with intravenous pentamidine. The eye was later removed due to incapacitating pain.Results: The eye showed Acanthamoeba organisms within the cornea and evidence of acute and chronic inflammation throughout the remainder of the eye. The patient has survived without orbital recurrence for 2 years.Conclusions: This case demonstrates late inflammation with active Acanthameoba keratitis following systemic pentamidine therapy.Keywords: keratitis, scleritis

  19. Cutaneous ulceration: an unusual complication of intravenous pentamidine therapy.

    Science.gov (United States)

    Bolognia, J L

    1991-01-01

    Pentamidine is one of two agents currently used to treat infections with Pneumocystis carinii. The intramuscular route of administration is associated with cutaneous side effects such as dermal necrosis, sterile abscesses and ulcer formation at the injection site, while urticaria may develop near the site of intravenous drug infusion. This is a report of a renal transplant patient with Pneumocystis pneumonia who developed chemical cellulitis and ulceration following the extravasation of intravenous pentamidine into the soft tissues of the left hand and forearm. The area healed slowly over 7 weeks, but there was a residual loss of cutaneous sensation. In a review of the literature no report of a similar case was found.

  20. Intravenous pentamidine for Pneumocystis carinii/jiroveci pneumonia prophylaxis in pediatric transplant patients.

    Science.gov (United States)

    Clark, Abigail; Hemmelgarn, Trina; Danziger-Isakov, Lara; Teusink, Ashley

    2015-05-01

    SMX/TMP is the current gold standard for prophylaxis against PCP in immunocompromised pediatric patients. Currently, there are several second-line options for prophylaxis but many, including intravenous (IV) pentamidine, have not been reported to be as effective or as safe as SMX/TMP in the pediatric transplant population. This study is to determine the efficacy and safety of IV pentamidine in preventing PCP in pediatric transplant patients. A retrospective chart review was conducted to evaluate all transplant patients that received at least one dose of IV pentamidine from January 2010 to July 2013. The primary outcome, IV pentamidine efficacy, was evaluated by the incidence of PCP diagnosis for 28 days after the last dose of IV pentamidine if patient was transitioned to another agent for PCP prophylaxis. Patients on IV pentamidine for entire course of PCP prophylaxis were followed at least six months after discontinuation of IV pentamidine. The safety of IV pentamidine was assessed by the incidence of adverse events leading to pentamidine discontinuation. All data were analyzed using descriptive statistics. All transplant patients at CCHMC who had received IV pentamidine were reviewed, and 333 patients met inclusion criteria. The overall incidence of PCP was found to be 0.3% for pediatric transplant patients on pentamidine. Pentamidine was found to be safe, and the incidence of adverse events leading to discontinuation was 6% with the most common reason being tachycardia 2.1%. IV pentamidine is safe and effective as PCP prophylaxis in pediatric transplant patients with a PCP breakthrough rate of 0.3% (1 of 333 patients), and only 20 adverse events led to discontinuation. We recommend that IV pentamidine be considered as a second-line option in pediatric transplant patients who cannot tolerate SMX/TMP.

  1. Cardiac arrest during treatment of Pneumocystis carinii pneumonia with intravenous pentamidine isethionate

    DEFF Research Database (Denmark)

    Balslev, U; Berild, D; Nielsen, T L

    1992-01-01

    A 27-year-old man, HIV-positive for 4 years, developed ventricular fibrillation and cardiac arrest during treatment of Pneumocystis carinii pneumonia with intravenous pentamidine isethionate. The dosage was 4 mg/kg/day for 18 days. Nephrotoxicity occurred and raised serum potassium. The plasma...... concentration of pentamidine was 580 nmol/l. Careful monitoring of renal and cardiac functions is recommended during intravenous therapy with pentamidine isethionate....

  2. Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids.

    Science.gov (United States)

    Torres-Gómez, Héctor; Hernández-Núñez, Emanuel; León-Rivera, Ismael; Guerrero-Alvarez, Jorge; Cedillo-Rivera, Roberto; Moo-Puc, Rosa; Argotte-Ramos, Rocío; Rodríguez-Gutiérrez, María Del Carmen; Chan-Bacab, Manuel Jesús; Navarrete-Vázquez, Gabriel

    2008-06-01

    A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)pentamidine, respectively. This compound was 23-, 108-, and 13-fold more active than pentamidine against T. vaginalis, E. histolytica and L. mexicana, respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these hybrids should provide new leads against protozoal diseases.

  3. Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story.

    Science.gov (United States)

    Baker, Nicola; de Koning, Harry P; Mäser, Pascal; Horn, David

    2013-03-01

    Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosoma brucei adenosine transporter is well known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss of function was linked to melarsoprol-pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites.

  4. Diabetes melutus associated with pentamidine isethionate in diffuse cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Jackson Mauricio Lopes Costa

    1995-12-01

    Full Text Available The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL, for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceratmi. He usedpentavalent antimonial (glucantime® and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat® was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeyng rigorous laboratory controls including a glucose tolerance test.

  5. Synthesis and antiprotozoal activity of pyridyl analogues of pentamidine.

    Science.gov (United States)

    Bakunova, Svetlana M; Bakunov, Stanislav A; Wenzler, Tanja; Barszcz, Todd; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-08-13

    A series of novel pyridyl analogues 1-18 of antiprotozoal drug 1,5-bis(4-amidinophenoxy)pentane (pentamidine) has been synthesized and tested for in vitro activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Antiprotozoal properties of compounds 1-18 depended on the placement of cationic moieties on the pyridine rings as well as the nature of substituents on the amidine groups. Diamidine 6 with cationic moieties adjacent to pyridine nitrogen atoms was the most promising compound in the series showing superior in vitro activities against T. brucei rhodesiense, P. falciparum, and L. donovani compared to pentamidine. An oral prodrug of diamidine 6, diamidoxime 9, administered at 25 mg/kg daily for 4 days, exhibited excellent antitrypanosomal efficacy in vivo curing all infected animals in the STIB900 acute mouse model of trypanosomiasis.

  6. Pharmacophore model for pentamidine analogs active against Plasmodium falciparum.

    Science.gov (United States)

    Athri, Prashanth; Wenzler, Tanja; Tidwell, Richard; Bakunova, Svetlana M; Wilson, W David

    2010-12-01

    Pentamidine and its analogs constitute a class of compounds that are known to be active against Plasmodium falciparum, which causes the most dangerous malarial infection. Malaria is a widespread disease known to affect hundreds of millions of people and presents a perceivable threat of spreading. Hence, there is a need for well-defined scaffolds that lead to new, effective treatment. Here we present a pentamidine-based pharmacophore constructed using GALAHAD that would aid targeted synthesis of leads with enhanced properties, as well as the development of lead scaffolds. The study was supported by high-quality biological in vitro data of 22 compounds against the P. falciparum strains NF54 and K1. The model established reveals the importance of hydrophobic phenyl rings with polar oxygen and amidine substituents and the hydrophobic linking chain for the activity against malaria.

  7. Coiled-coil conformation of a pentamidine-DNA complex.

    Science.gov (United States)

    Moreno, Tadeo; Pous, Joan; Subirana, Juan A; Campos, J Lourdes

    2010-03-01

    The coiled-coil structure formed by the complex of the DNA duplex d(ATATATATAT)(2) with pentamidine is presented. The duplex was found to have a mixed structure containing Watson-Crick and Hoogsteen base pairs. The drug stabilizes the coiled coil through the formation of cross-links between neighbouring duplexes. The central part of the drug is found in the minor groove as expected, whereas the charged terminal amidine groups protrude and interact with phosphates from neighbouring molecules. The formation of cross-links may be related to the biological effects of pentamidine, which is used as an antiprotozoal agent in trypanosomiasis, leishmaniasis and pneumonias associated with AIDS. The DNA sequence that was used is highly abundant in most eukaryotic genomes. However, very few data are available on DNA sequences which only contain A.T base pairs.

  8. The inhibition of monoamine oxidase by phenformin and pentamidine.

    Science.gov (United States)

    Barkhuizen, M; Petzer, A; Petzer, J P

    2014-09-01

    A computational study has suggested that phenformin, an oral hypoglycaemic drug, may bind to the active sites of the monoamine oxidase (MAO) A and B enzymes. The present study therefore investigates the MAO inhibitory properties of phenformin. Pentamidine, a structurally related diamidine compound, has previously been reported to be a MAO inhibitor and was included in this study as a reference compound. Using recombinant human MAO-A and MAO-B, this study finds that phenformin acts as a moderately potent MAO-A selective inhibitor with an IC50 value of 41 µM. Pentamidine, on the other hand, potently inhibits both MAO-A and MAO-B with IC50 values of 0.61 μM and 0.22 μM, respectively. An examination of the recoveries of the enzymatic activities after dilution and dialysis of the enzyme-inhibitor complexes shows that both compounds interact reversibly with the MAO enzymes. A kinetic analysis suggests that pentamidine acts as a competitive inhibitor with estimated Ki values of 0.41 μM and 0.22 μM for the inhibition of MAO-A and MAO-B, respectively. Phenformin also exhibited a competitive mode of MAO-A inhibition with an estimated Ki value of 65 µM. This study concludes that biguanide and amidine functional groups are most likely important structural features for the inhibition of the MAOs by phenformin and pentamidine, and compounds containing these and closely related functional groups should be considered as potential MAO inhibitors. Furthermore, the biguanide and amidine functional groups may act as useful moieties in the future design of MAO inhibitors.

  9. Alveolar targeting of aerosol pentamidine. Toward a rational delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Simonds, A.K.; Newman, S.P.; Johnson, M.A.; Talaee, N.; Lee, C.A.; Clarke, S.W. (Royal Free Hospital, London (England))

    1990-04-01

    Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with {sup 99m}Tc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects.

  10. Acute, rapidly progressive renal failure with simultaneous use of amphotericin B and pentamidine.

    OpenAIRE

    Antoniskis, D; Larsen, R.A.

    1990-01-01

    We report four cases of acute reversible renal failure in patients with acquired immune deficiency syndrome who received both amphotericin B (for systemic mycoses) and pentamidine isethionate (for Pneumocystis carinii pneumonia). The concurrent use of amphotericin B with either inhaled pentamidine or trimethoprim-sulfamethoxazole did not cause significant renal impairment.

  11. In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.

    NARCIS (Netherlands)

    Afeltra, J.; Meis, J.F.G.M.; Vitale, R.G.; Mouton, J.W.; Verweij, P.E.

    2002-01-01

    The susceptibilities of 70 strains of Aspergillus species were tested against seven different sulfa drugs and pentamidine by a microdilution method with RPMI 1640 and yeast nitrogen base media. Sulfamethoxazole, sulfadiazine, and pentamidine were active in vitro. The MICs obtained with RPMI 1640 wer

  12. Fatal bilateral pneumothoraces following administration of aerosolised pentamidine.

    Science.gov (United States)

    Green, Alison; Milne, Nathan; Ong, Beng Beng

    2011-10-01

    Aerosolised pentamidine (AP) is used for prophylaxis against infection with Pneumocystis jiroveci (carinii), a significant cause of morbidity and mortality for people with human immunodeficiency virus (HIV). In this article we report a 55 year old man with HIV and a background history of asthma since childhood, who suffered respiratory arrest and died within an hour of commencing AP prophylaxis. Autopsy revealed bilateral pneumothoraces. Common side effects of AP therapy include bronchospasm and coughing. Pneumothorax has been reported in several cases. To our knowledge, this is the first reported fatality from bilateral pneumothoraces.

  13. Mutation of the mitochondrial large ribosomal RNA can provide pentamidine resistance to Saccharomyces cerevisiae.

    Science.gov (United States)

    Örs, Ş Tomris; Akdoğan, Emel; Dunn, Cory D

    2014-09-01

    Pentamidine is used to treat several trypanosomal diseases, as well as opportunistic infection by pathogenic fungi. However, the relevant targets of this drug are unknown. We isolated dominant mutations providing pentamidine resistance to Saccharomyces cerevisiae, one of which was localized to mitochondrial DNA. Next-generation sequencing revealed alteration of a widely conserved base at the peptidyl transferase center of the mitochondrial 21S ribosomal RNA. Our results provide a potential rationale for the toxicity of this drug to patients, and we discuss whether blockade of mitochondrial translation is the mechanism by which pathogenic fungi or protists are killed by pentamidine.

  14. In vitro screening of pentamidine analogs against bacterial and fungal strains.

    Science.gov (United States)

    Maciejewska, Dorota; Żabiński, Jerzy; Kaźmierczak, Paweł; Wójciuk, Karolina; Kruszewski, Marcin; Kruszewska, Hanna

    2014-07-01

    A series of linear pentamidine analogs exhibiting low cytotoxicity, active against Pneumocystis carinii, were evaluated for in vitro activities against bacterial and fungal strains. The majority of the tested bis-amidines exhibited marked activities against Gram-positive strains. In view of the fact that the highest potency was found for 1,5-bis(4-amidinophenoxy)-3-thiapentane dihydrochloride 1j with the S atom in the middle of the aliphatic linker, four new pentamidines bearing S atoms were synthesized and also evaluated against MRSA strains. N,N'-Dialkylated pentamidines with S atoms in the linker are the promising lead structures for antimicrobials development.

  15. Risk Factors for Breakthrough Pneumocystis carinii Pneumonia on Aerosol Pentamidine Prophylaxis

    Directory of Open Access Journals (Sweden)

    RA McIvor

    1995-01-01

    Full Text Available OBJECTIVE: To identify baseline characteristics of human immunodeficiency virus (HIV-infected individuals on aerosol pentamidine for Pneumocystis carinii prophylaxis that are predictive of subsequent breakthrough Pneumocystis carinii pneumonia (PCP.

  16. A prospective Comparison of Porta-Sonic and Fisoneb Ultrasonic Nebulizers for Administering Aerosol Pentamidine

    Directory of Open Access Journals (Sweden)

    Andrew McIvor

    1994-01-01

    Full Text Available Objective: To report patient acceptability and overall therapeutic effectiveness of two different ultrasonic nebulizers, Fisoneb and Porta-sonic, for the administration of aerosol pentamidine for Pneumocysitis carinii prophylaxis in human immunodeficiency virus (hiv-infected individuals.

  17. Disposition of nebulized pentamidine measured using the direct radiolabel [sup 123]I-iodopentamidine

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Nunan, T.O.; Bateman, N.T. (Saint Thomas' Hospital, London (United Kingdom)); Thomas, S.H.L.; Page, C.J. (Newcastle upon Tyne Univ. (United Kingdom)); Blower, P.J. (Kent and Canterbury Hospital (United Kingdom) Kent Univ., Canterbury (United Kingdom))

    1993-01-01

    The pulmonary deposition of nebulized pentamidine (300 mg, Respirgard II nebulizer) was measured in seven human immunodeficiency virus (HIV)-positive men using a new radiopharmaceutical, [sup 123]I-iodopentamidine. Mean total pulmonary deposition was 15.3 mg or 5.1% of the initial nebulizer dose. Further studies in two of the patients showed that at 24h, 87% of deposited [sup 123]I was retained in the lungs. Small amounts of activity (expressed as a percentage of the initial nebulizer activity) were also detected over the thyroid (0.4%), bladder (1%) and gut (0.7%). The ratio of [sup 123]I activity to pentamidine concentration was similar in the nebulizer solution and urine. These results suggest that [sup 123]I-pentamidine may be sufficiently stable in vivo to be used to study the biodistribution of inhaled and parenteral pentamidine in humans. (author).

  18. Pentamidine reduces expression of hypoxia-inducible factor-1α in DU145 and MDA-MB-231 cancer cells.

    Science.gov (United States)

    Jung, Hui-Jung; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki; Park, Jong-Wook

    2011-04-01

    Pentamidine is an aromatic diamine used for the treatment of human protozoa infections. Recently, pentamidine has been reported to exhibit anticancer properties. In this study, we report that pentamidine inhibits expression of hypoxia-inducible factor (HIF)-1α in cancer cells. Pentamidine decreased HIF-1α protein translation and enhanced its protein degradation in DU145 prostate cancer and MDA-MB-231 breast cancer cells. In parallel with reduction of de novo synthesis of HIF-1α, pentamidine was able to suppress global protein translation, an effect accompanied by the reduction of eIF4F complex formation and also the induction of eIF2α phosphorylation. These results show that pentamidine is a potential inhibitor of HIF-1α and its potential as a cancer therapeutic reagent warrants further study.

  19. Flavonoid dimers as bivalent modulators for pentamidine and sodium stiboglucanate resistance in leishmania.

    Science.gov (United States)

    Wong, Iris L K; Chan, Kin-Fai; Burkett, Brendan A; Zhao, Yunzhe; Chai, Yi; Sun, Hongzhe; Chan, Tak Hang; Chow, Larry M C

    2007-03-01

    Drug resistance by overexpression of ATP-binding cassette (ABC) transporters is an impediment in the treatment of leishmaniasis. Flavonoids are known to reverse multidrug resistance (MDR) in Leishmania and mammalian cancers by inhibiting ABC transporters. Here, we found that synthetic flavonoid dimers with three (compound 9c) or four (compound 9d) ethylene glycol units exhibited a significantly higher reversing activity than other shorter or longer ethylene glycol-ligated dimers, with approximately 3-fold sensitization of pentamidine and sodium stibogluconate (SSG) resistance in Leishmania, respectively. This modulatory effect was dosage dependent and not observed in apigenin monomers with the linker, suggesting that the modulatory effect is due to its bivalent nature. The mechanism of reversal activity was due to increased intracellular accumulation of pentamidine and total antimony in Leishmania. Compared to other MDR modulators such as verapamil, reserpine, quinine, quinacrine, and quinidine, compounds 9c and 9d were the only agents that can reverse SSG resistance. In terms of reversing pentamidine resistance, 9c and 9d have activities comparable to those of reserpine and quinacrine. Modulators 9c and 9d exhibited reversal activity on pentamidine resistance among LeMDR1(-/-), LeMDR1(+/+), and LeMDR1-overexpressed mutants, suggesting that these modulators are specific to a non-LeMDR1 pentamidine transporter. The LeMDR1 copy number is inversely related to pentamidine resistance, suggesting that it might be involved in importing pentamidine into the mitochondria. In summary, bivalency could be a useful strategy for the development of more potent ABC transporter modulators and flavonoid dimers represent a promising reversal agent for overcoming pentamidine and SSG resistance in parasite Leishmania.

  20. Synthesis and antiprotozoal properties of pentamidine congeners bearing the benzofuran motif.

    Science.gov (United States)

    Bakunov, Stanislav A; Bakunova, Svetlana M; Bridges, Arlene S; Wenzler, Tanja; Barszcz, Todd; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-09-24

    Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicities for mammalian cells were influenced by the nature of cationic substituents, placement of the benzofuran fragment, and the length of the carbon linker between aromatic moieties. Several dications exhibited superior antiplasmodial and antileishmanial potencies compared to pentamidine.

  1. Evaluation of (131)I-pentamidine for scintigraphy of experimentally Leishmania tropica-infected hamsters.

    Science.gov (United States)

    Inceboz, Tonay; Lambrecht, Fatma Yurt; Eren, Mine Şencan; Girginkardeşler, Nogay; Bekiş, Recep; Yilmaz, Osman; Er, Özge; Özbilgin, Ahmet

    2014-06-01

    We aimed to assess the ability of (131)I-Pentamidine scintigraphy to detect the lesions of Leishmania tropica infection. An experimental model of cutaneous leishmaniasis was developed. The presence of cutaneous leishmaniasis was confirmed. Pentamidine was radioiodinated with (131)I. The radiolabeled pentamidine was validated by the requisite quality control tests to check its radiolabeling efficiency, in vitro stability. (131)I-Pentamidine (activity: 18.5 MBq/100 µl) was injected intracardiacally into infected hamsters. Static whole body images of the hamsters were acquired under the gamma camera at 5 and 30 min, 2, 6 and 24 h following the administration. On the scintigrams, anatomically adjusted regions of interest (ROIs) were drawn over the right feet (target) and left feet (not-target) and various organs. Accumulation of (131)I-Pentamidine at sites of infection is expressed as the target to non-target (T/NT) ratio. The results T/NT ratio decreased with time. In concluding the (131)I-Pentamidine has poor sensitivity in detection of L. tropica infection.

  2. Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis.

    Science.gov (United States)

    Soto, Jaime; Paz, David; Rivero, Daniela; Soto, Paula; Quispe, Jorge; Toledo, Julia; Berman, Jonathan

    2016-04-01

    A novel therapy, intralesional (IL) pentamidine, was compared to intralesional therapy with antimony (ILSb), a World Health Organization-recommended therapy, for single Bolivian Leishmania braziliensis lesions. In Study 1, 90 patients were randomized equally between three injections of ILSb over 5 days, five injections of ILSb over 11 days, and three injections of IL pentamidine (120 μg/mm(2)lesion area [ILPenta-120-3]) over 5 days. Cure rates at 6 months were 57% for ILSb-3 injections, 73% for ILSb-5 injections, and 72% for ILPenta-120-3 injections. Adverse effects were local irritation and injection-site pain-ILSb (60 patients): mild (25), moderate (4); IL pentamidine (30 patients): mild (4), moderate (3). In Study 2, 60 patients were randomized equally between five injections of ILSb and three injections of a double dose of IL pentamidine (240 μg/mm(2)[ILPenta-240-3]). In Study 2, cure rates were 67% for ILSb-5 injections and 73% for ILPenta-240-3. For three IL injections of pentamidine, efficacy was optimized at a dose of 120 μg/mm(2)lesion area. The cure rate of that regimen was similar to that for ILSb-5 injections and nonstatistically larger than that of ILSb-3 injections. IL pentamidine is an attractive alternative to ILSb on the basis of efficacy for Bolivian L. braziliensis, the threat of Sb-resistant parasites, tolerance, and patient convenience of three visits over 5 days.

  3. Melarsoprol- and pentamidine-resistant Trypanosoma brucei rhodesiense populations and their cross-resistance.

    Science.gov (United States)

    Bernhard, Sonja C; Nerima, Barbara; Mäser, Pascal; Brun, Reto

    2007-11-01

    Resistance to melarsoprol and pentamidine was induced in bloodstream-form Trypanosoma brucei rhodesiense STIB 900 in vitro, and drug sensitivity was determined for melarsoprol, pentamidine and furamidine. The resistant populations were also inoculated into immunosuppressed mice to verify infectivity and to monitor whether rodent passage selects for clones with altered drug sensitivity. After proliferation in the mouse, trypanosomes were isolated and their IC(50) values to the three drugs were determined. To assess the stability of drug-induced resistance, drug pressure was ceased for 2 months and the drug sensitivity was determined again. Resistance was stable, with a few exceptions that are discussed. Drug IC(50)s indicated cross-resistance among all drugs, but to varying extents: resistance of the melarsoprol-selected and pentamidine-selected trypanosomes to pentamidine was the same, but the pentamidine-selected trypanosome population showed lower resistance to melarsoprol than the melarsoprol-selected trypanosomes. Interestingly, both resistant populations revealed the same intermediate cross-resistance to furamidine. Resistant trypanosome populations were characterised by molecular means, referring to the status of the TbAT1 gene. The melarsoprol-selected population apparently had lost TbAT1, whereas in the pentamidine-selected trypanosome population it was still present.

  4. Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration.

    Science.gov (United States)

    Afrin, Lawrence B; Afrin, Jessica B

    2011-01-01

    Pneumocystis jirovecii prophylaxis is standard in allogeneic stem cell transplantation (alloSCT), sometimes with pentamidine at a low dose inhaled monthly. Human metabolism of pentamidine depends on cytochrome P450 2C19 (CYP2C19). The frequency of mutant CYP2C19 forms with decreased function (from 2% of Caucasians to 30% of Asians and 79% of certain Polynesians), together with common use of CYP2C19 inhibitors in the alloSCT process, creates risk for impaired pentamidine clearance resulting in toxicity ordinarily expected only with high doses given for active infection. We examined the charts of 32 consecutive pentamidine-prophylaxed alloSCT patients at our center. We assessed hospital charges for the management of toxicities unexplained at the time but likely attributable, in retrospect, to pentamidine. Twenty-eight percent experienced significant toxicities (incurring added charges of at least US$5000). Thirteen percent suffered major toxicity (incurring added charges of at least US$25, 000; median added charge $351, 701) and shorter survival (326 vs. 622 d for all pentamidine recipients), including 6% who died of pentamidine toxicities [one proven postmortem to have a (non-functional) homozygous CYP2C19*2 mutation]. Charges for care attributable to pentamidine toxicity exceeded what preemptive genotyping would have cost by 73-fold. These findings encourage routine use of preemptive CYP2C19 genotyping in alloSCT patients considered for pentamidine.

  5. Structure-activity study of pentamidine analogues as antiprotozoal agents.

    Science.gov (United States)

    Bakunova, Svetlana M; Bakunov, Stanislav A; Patrick, Donald A; Kumar, E V K Suresh; Ohemeng, Kwasi A; Bridges, Arlene S; Wenzler, Tanja; Barszcz, Todd; Jones, Susan Kilgore; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-04-09

    Diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC(50) = 4 nM). Nine congeners (2-4, 12, 27, 30, and 64-66) were more active against P. falciparum than artemisinin (IC(50) = 6 nM). Eight compounds (12, 32, 33, 44, 59, 62, 64, and 66) exhibited equal or better antileishmanial activities than 1 (IC(50) = 1.8 microM). Several congeners were more active than 1 in vivo, curing at least 2/4 infected animals in the acute mouse model of trypanosomiasis. The diimidazoline 66 was the most promising compound in the series, showing excellent in vitro activities and high selectivities against T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy in vivo.

  6. Pentamidine exerts in vitro and in vivo anti Trypanosoma cruzi activity and inhibits the polyamine transport in Trypanosoma cruzi.

    Science.gov (United States)

    Díaz, María V; Miranda, Mariana R; Campos-Estrada, Carolina; Reigada, Chantal; Maya, Juan D; Pereira, Claudio A; López-Muñoz, Rodrigo

    2014-06-01

    Pentamidine is an antiprotozoal and fungicide drug used in the treatment of leishmaniasis and African trypanosomiasis. Despite its extensive use as antiparasitic drug, little evidence exists about the effect of pentamidine in Trypanosoma cruzi, the etiological agent of Chagas' disease. Recent studies have shown that pentamidine blocks a polyamine transporter present in Leishmania major; consequently, its might also block these transporters in T. cruzi. Considering that T. cruzi lacks the ability to synthesize putrescine de novo, the inhibition of polyamine transport can bring a new therapeutic target against the parasite. In this work, we show that pentamidine decreases, not only the viability of T. cruzi trypomastigotes, but also the parasite burden of infected cells. In T. cruzi-infected mice pentamidine decreases the inflammation and parasite burden in hearts from infected mice. The treatment also decreases parasitemia, resulting in an increased survival rate. In addition, pentamidine strongly inhibits the putrescine and spermidine transport in T. cruzi epimastigotes and amastigotes. Thus, this study points to reevaluate the utility of pentamidine and introduce evidence of a potential new action mechanism. In the quest of new therapeutic strategies against Chagas disease, the extensive use of pentamidine in human has led to a well-known clinical profile, which could be an advantage over newly synthesized molecules that require more comprehensive trials prior to their clinical use.

  7. Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation.

    Science.gov (United States)

    Sun, Tao; Zhang, Yi

    2008-03-01

    The selective and potent inhibition of mitochondrial translation in Saccharomyces cerevisiae by pentamidine suggests a novel antimicrobial action for this drug. Electrophoresis mobility shift assay, T1 ribonuclease footprinting, hydroxyl radical footprinting and isothermal titration calorimetry collectively demonstrated that pentamidine non-specifically binds to two distinct classes of sites on tRNA. The binding was driven by favorable entropy changes indicative of a large hydrophobic interaction, suggesting that the aromatic rings of pentamidine are inserted into the stacked base pairs of tRNA helices. Pentamidine binding disrupts the tRNA secondary structure and masks the anticodon loop in the tertiary structure. Consistently, we showed that pentamidine specifically inhibits tRNA aminoacylation but not the cognate amino acid adenylation. Pentamidine inhibited protein translation in vitro with an EC(50) equivalent to that binds to tRNA and inhibits tRNA aminoacylation in vitro, but drastically higher than that inhibits translation in vivo, supporting the established notion that the antimicrobial activity of pentamidine is largely due to its selective accumulation by the pathogen rather than by the host cell. Therefore, interrupting tRNA aminoacylation by the entropy-driven non-specific binding is an important mechanism of pentamidine in inhibiting protein translation, providing new insights into the development of antimicrobial drugs.

  8. Is Aerosolized Pentamidine for Pneumocystis Pneumonia Prophylaxis in Renal Transplant Recipients Not as Safe as We Might Think?

    Science.gov (United States)

    Macesic, N; Urbancic, K; Ierino, F; Grayson, M L

    2016-04-01

    Outbreaks ofPneumocystispneumonia have been described in renal transplant recipients. Aerosolized pentamidine is frequently used for prophylaxis in this setting. We report our experience with aerosolized pentamidine use in 56 renal transplant recipients. We found high rates of adverse reactions in patients with chronic respiratory disease.

  9. Attenuation of Porphyromonas gingivalis oral infection by α-amylase and pentamidine.

    Science.gov (United States)

    Li, Ying; Miao, Yu-Song; Fu, Yun; Li, Xi-Ting; Yu, Shao-Jie

    2015-08-01

    The Porphyromonas gingivalis bacterium is one of the most influential pathogens in oral infections. In the current study, the antimicrobial activity of α-amylase and pentamidine against Porphyromonas gingivalis was evaluated. Their in vitro inhibitory activity was investigated with the agar overlay technique, and the minimal inhibitory and bactericidal concentrations were determined. Using the bactericidal concentration, the antimicrobial actions of the inhibitors were investigated. In the present study, multiple techniques were utilized, including scanning electron microscopy (SEM), general structural analysis and differential gene expression analysis. The results obtained from SEM and bactericidal analysis indicated a notable observation; the pentamidine and α-amylase treatment destroyed the structure of the bacterial cell membranes, which led to cell death. These results were used to further explore these inhibitors and the mechanisms by which they act. Downregulated expression levels were observed for a number of genes coding for hemagglutinins and gingipains, and various genes involved in hemin uptake, chromosome replication and energy production. However, the expression levels of genes associated with iron storage and oxidative stress were upregulated by α-amylase and pentamidine. A greater effect was noted in response to pentamidine treatment. The results of the present study demonstrate promising therapeutic potential for α-amylases and pentamidine. These molecules have the potential to be used to develop novel drugs and broaden the availability of pharmacological tools for the attenuation of oral infections caused by Porphyromonas gingivalis.

  10. Transport of dicationic drugs pentamidine and furamidine by human organic cation transporters.

    Science.gov (United States)

    Ming, Xin; Ju, Wujian; Wu, Huali; Tidwell, Richard R; Hall, James E; Thakker, Dhiren R

    2009-02-01

    The antiparasitic activity of aromatic diamidine drugs, pentamidine and furamidine, depends on their entry into the pathogenic protozoa via membrane transporters. However, no such diamidine transporter has been identified in mammalian cells. The goal of this study is to investigate whether these dicationic drugs are substrates for human organic cation transporters (hOCTs, solute carrier family 22A1-3) and whether hOCTs play a role in their tissue distribution, elimination, and toxicity. Inhibitory and substrate activities of pentamidine and furamidine were studied in stably transfected Chinese hamster ovary (CHO) cells. The results of [(3)H]1-methyl-4-phenylpyridinium uptake study showed that pentamidine is a potent inhibitor for all three OCT isoforms (IC50 pentamidine and furamidine was 4.4- and 9.3-fold greater, respectively, in CHO-hOCT1 cells compared with the mock cells. Ranitidine, an hOCT1 inhibitor, reversed this hOCT1-mediated potentiation of cytotoxicity. This is the first finding that dicationic drugs, such as pentamidine and furamidine, are substrates for hOCT1. In humans, aromatic diamidines are primarily eliminated in the bile but are distributed and cause toxicity in both liver and kidney. These transporters may play important roles in the disposition of aromatic diamidines in humans, as well as resultant drug-drug interactions and toxicity involving diamidine drugs.

  11. Diabetes melutus associated with pentamidine isethionate in diffuse cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Jackson Mauricio Lopes Costa

    1995-12-01

    Full Text Available The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL, for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceratmi. He usedpentavalent antimonial (glucantime® and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat® was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeyng rigorous laboratory controls including a glucose tolerance test.Os autores relatam o caso de um paciente procedente de Bacabal, MA, portador de leishmaniose cutânea difusa (LCD há 9 anos, apresentando um total de 168 lesões distribuídas pelo corpo, de caráter nódulo tumoral e algumas ulceradas, tendo sido submetido a tratamentos anteriores á base de antimonial pentavalente (gluc antime® e associação interferom gamma+glucantime® com melhora e posterior recidiva das lesões. Recentemente quando da utilização do medicamento isotianato de pentamidina (pentacarinat® na dose de 4mg/kg/peso/dia, aplicados 1M em dias alternados em 3 séries de 20, 10, 10 aplicações com intervalos entre as séries de 3 meses. Na evolução do tratamento desenvolveu um quadro de perda de peso 10kg, polidpsia, poliúria, xerostomia, lesões de membros inferiores com sinais de atividade. Glicemia em jejum 420mg/dl, presença de glicose e corpos cetônicos na urina. Instituída insulinoterapia houve melhora do quadro e retorno dos níveis glicêmicos permanecendo estãvel até o presente

  12. Diacetyldiamidoximeester of pentamidine, a prodrug for treatment of protozoal diseases: synthesis, in vitro and in vivo biotransformation.

    Science.gov (United States)

    Clement, Bernd; Bürenheide, Anja; Rieckert, Wolfgang; Schwarz, Jörg

    2006-11-01

    Pentamidine is an effective antimicrobial agent. To increase its poor oral bioavailability due to the strong basic amidine functionality, the less basic O-acetylamidoxime prodrug, the diacetyldiamidoximeester, was used, which has greatly improved lipophilicity. The objectives of this investigation were the synthesis of all potential metabolites of the double prodrug, the conformational analysis of its structure, and to study the in vitro and in vivo biotransformation by ester cleavage and N-reduction to pentamidine via four intermediate metabolites. The biotransformation of diacetyldiamidoximeester to pentamidine involving the reduction of the amidoxime function and the ester cleavage could be demonstrated. The kinetic parameters were determined. Amidoximes were efficiently metabolized by several enzyme systems located in microsomes and mitochondria of different organs including the final formation of the active metabolite pentamidine. The formation of pentamidine after oral administration of the diacetyldiamidoximeester to rats could be demonstrated as well.

  13. Pentamidine for the treatment of Pneumocystis carinii pneumonia and other protozoal diseases.

    Science.gov (United States)

    Pearson, R D; Hewlett, E L

    1985-11-01

    Pentamidine isethionate, discovered to have antiprotozoal activity in 1938, has recently been approved in the United States for the treatment of Pneumocystis carinii pneumonia. Despite frequent adverse reactions, which are at times life-threatening, pentamidine remains an important alternative to trimethoprim-sulfamethoxazole for the treatment of P. carinii pneumonia in patients with a history of allergy to sulfonamides or who have severe reactions or a lack of response to treatment with trimethoprim-sulfamethoxazole. Although not approved for other indications, pentamidine has been shown to be effective when used prophylactically against Trypanosoma brucei gambiense, the cause of West African sleeping sickness, as well as for treatment of the early hemolymphatic stage of that disease, and for treatment of some forms of leishmaniasis.

  14. Clindamycin-primaquine versus pentamidine for the second-line treatment of pneumocystis pneumonia.

    Science.gov (United States)

    Kim, Tark; Kim, Sung-Han; Park, Ki-Ho; Cho, Oh Hyun; Sung, Heungsup; Kim, Mi-Na; Choi, Sang-Ho; Jeong, Jin-Yong; Woo, Jun Hee; Kim, Yang Soo; Lee, Sang-Oh

    2009-10-01

    There are limited data on the efficacy of alternative regimens for treating patients with pneumocystis pneumonia (PCP). We compared the efficacy of clindamycin-primaquine (C-P) with that of pentamidine as a second line treatment for PCP. Among 91 patients receiving trimethoprim-sulfamethoxazole (TMP-SMX) as a first-line treatment for PCP, 31 (34%) did not respond and 7 (8%) had adverse reactions. Fourteen patients received C-P and 9 received pentamidine as a second-line regimen because of treatment failure or an adverse reaction to TMP-SMX. The response rate of patients to C-P was higher than the response rate to pentamidine (9/14; 64% vs 1/9; 11%; P = 0.03).

  15. Inhibitory effects on cytochrome p450 enzymes of pentamidine and its amidoxime pro-drug.

    Science.gov (United States)

    Bürenheide, Anja; Kunze, Thomas; Clement, Bernd

    2008-07-01

    Pentamidine is an antimicrobial drug, intravenously used in the treatment of trypanosomiasis, leishmaniasis or pneumocystis pneumonia. To elucidate potential drug interactions with pentamidine and N,N'-dihydroxypentamidine, respectively, the cytochrome P450 (CYP450) inhibitory properties of these compounds were determined. The study was performed in vitro by using human liver microsomes and marker substrates of several CYP450 isoenzymes. Marker activities were investigated by high-performance liquid chromatography in presence of known selective inhibitors or at different concentrations of pentamidine and N,N'-dihydroxypentamidine, respectively. No or only minor influence on CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1 and 3A4 marker activities could be observed, suggesting that neither of the tested substances would exert a significant effect on hepatic CYP450 isoenzymes responsible for the metabolism of co-administrated drugs in vivo. However, in vivo studies are needed before final conclusions can be drawn.

  16. Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Smaldone, G.C.; Fuhrer, J.; Steigbigel, R.T.; McPeck, M. (State Univ. of New York, Stony Brook (USA))

    1991-04-01

    Although aerosolized pentamidine (AP) has recently been approved for prophylaxis and is undergoing clinical trials for treatment of pneumocystis, pneumonia (PCP), factors important in the deposition of AP have not been described. Using radioaerosol techniques, deposition was measured in 22 patients receiving AP for prophylaxis or treatment of PCP. In all patients total and regional deposition of pentamidine, breathing pattern, pulmonary function (PFT), regional ventilation, and type of nebulizer were analyzed. Bronchoalveolar lavage (BAL) was performed 24 h after inhalation to assess the relationship between pentamidine levels in BAL fluid and measured aerosol deposition. The nebulizers tested were the Marquest Respirgard II and the Cadema AeroTech II, both previously characterized in our laboratory. The aerosol particles consist of water droplets containing dissolved pentamidine and technetium 99m bound to albumin. Analysis of particles sampled during inhalation via cascade impaction confirmed a close relationship between radioactivity in the droplets and the concentration of pentamidine as measured by HPLC (r = 0.971, p less than 0.0001; n = 18). Deposition was measured by capturing inhaled and exhaled particles on absolute filters and measuring radioactivity. This technique allows the determination of the deposition fraction (DF, the fraction of the amount inhaled that is deposited), which provides information on factors strictly related to the patient. To confirm the filter measurements, pentamidine deposition was also measured by gamma camera. The camera measurement was possible because each patient's thoracic attenuation of radioactivity was determined by a quantitative perfusion scan. Regional lung volume and ventilation were determined by xenon 133 equilibrium scan and washout.

  17. Pentamidine as secondary prophylaxis for visceral leishmaniasis in the immunocompromised host: report of four cases.

    Science.gov (United States)

    Patel, T A; Lockwood, D N

    2009-09-01

    We report a retrospective and descriptive study of four immunocompromised patients (three with HIV-1 and one with idiopathic CD4+-lymphopenia) with relapsing visceral leishmaniasis seen at the Hospital for Tropical Diseases, London, in whom pentamidine was used as secondary prophylaxis to prevent relapse. Patients experienced between one and four relapses before commencing prophylaxis with subsequent relapse-free periods ranging from 5 to 98 months. Based on these observational data, we recommend large trials to investigate the efficacy of pentamidine over other agents in preventing relapse of VL in the immunocompromised patient.

  18. Discovery of novel antileishmanial agents in an attempt to synthesize pentamidine-aplysinopsin hybrid molecule.

    Science.gov (United States)

    Porwal, Sharad; Chauhan, Shikha S; Chauhan, Prem M S; Shakya, Nishi; Verma, Aditya; Gupta, Suman

    2009-10-08

    In an attempt to synthesize pentamidine-aplysinopsin hybrid molecule 25, a lead molecule 8 (containing Z-configured aplysinopsin moiety) was identified for antileishmanial activity. Optimization of lead 8 provided 24 (containing E-configured aplysinopsin) possessing 10 times more activity and 401-fold less toxicity than the drug pentamidine in cell based assays. Synthesis of 24 was possible, surprisingly, because of two innate reactivities of indole-3-carbaldehyde which provided it in diastereo- and regio-selectively pure form without recourse to the long reaction pathway.

  19. The novel combination of chlorpromazine and pentamidine exerts synergistic antiproliferative effects through dual mitotic action.

    Science.gov (United States)

    Lee, Margaret S; Johansen, Lisa; Zhang, Yanzhen; Wilson, Amy; Keegan, Mitchell; Avery, William; Elliott, Peter; Borisy, Alexis A; Keith, Curtis T

    2007-12-01

    Combination therapy has proven successful in treating a wide variety of aggressive human cancers. Historically, combination treatments have been discovered through serendipity or lengthy trials using known anticancer agents with similar indications. We have used combination high-throughput screening to discover the unexpected synergistic combination of an antiparasitic agent, pentamidine, and a phenothiazine antipsychotic, chlorpromazine. This combination, CRx-026, inhibits the growth of tumor cell lines in vivo more effectively than either pentamidine or chlorpromazine alone. Here, we report that CRx-026 exerts its antiproliferative effect through synergistic dual mitotic action. Chlorpromazine is a potent and specific inhibitor of the mitotic kinesin KSP/Eg5 and inhibits tumor cell proliferation through mitotic arrest and accumulation of monopolar spindles. Pentamidine treatment results in chromosomal segregation defects and delayed progression through mitosis, consistent with inhibition of the phosphatase of regenerating liver family of phosphatases. We also show that CRx-026 synergizes in vitro and in vivo with the microtubule-binding agents paclitaxel and vinorelbine. These data support a model where dual action of pentamidine and chlorpromazine in mitosis results in synergistic antitumor effects and show the importance of systematic screening for combinations of targeted agents.

  20. Inhaled pentamidine for Pneumocystis jiroveci prophylaxis in a heart transplant recipient with allergy for trimethoprim sulfamethoxazole.

    Science.gov (United States)

    Altintas, Garip; Diken, Adem Ilkay; Diken, Ozlem Ercen; Hanedan, Onur; Kucuker, Seref Alp

    2011-02-01

    Pneumocystis jiroveci is an important cause of mortality and morbidity among heart transplant recipients. This raises the question of prophylactic treatment for this infection. Trimethoprimsulfamethoxazole is commonly used in P. jiroveci pneumonia prophylaxis with mild to severe adverse effects. We present the use of inhaled pentamidine as P. jiroveci prophylaxis in a patient with an allergy to trimethoprim sulfamethoxazole.

  1. Pulmonary deposition of aerosolised pentamidine using a new nebuliser: efficiency measurements in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, P.P. (Servizio di Fisica Sanitaria, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Versari, A. (Servizio di Radiologia e Medicina Nucleare, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Gafa, S.I. (Div. di Malattie Infettive, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Becquemin, M.H. (Service Central d' Explorations Functionnelles Respiratoires, Groupe Hospitalier Pitie-Salpetriere, Paris (France)); Barchi, E. (Div. di Malattie Infettive, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Serafini, D. (Servizio di Radiologia e Medicina Nucleare, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Roy, M. (Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France)); Salvo, D. (Servizio di Radiologia e Medicina Nucleare, Arcispedale S. Maria Nuova, Reggio Emilia (Italy)); Bouchikhi, A. (Service Central d' Explorations Functionnelles Respiratoires, Groupe Hospitalier Pitie-Salpetriere, Paris (France))

    1994-05-01

    We studied the performance of a new nebuliser (Pentasave) by comparison both in vitro and in vivo with a standard nebuliser (Respirgard II). In vitro, deposition of pentamidine labelled with technetium-99m human serum albumin was measured indirectly by capturing inhaled particles on an absolute filter and measuring radioactivity with a gamma camera. The nebulisers were initially assessed with a pentamidine dose of 100 mg in 5 ml al 44 psi and an air flow of 10 l/min for Respirgard II and 16 l/min for Pentasave. Nebuliser output, expressed as the percentage of the initial nebuliser radioactivity captured by the inhalation filter, was 15%[+-]2% (mean[+-]SD) for Respirgard II, and significantly increased to 23%[+-]3% for an initial version and to 33%[+-]2% for the final version of Pentasave. Measurements with a gamma camera in a group of ten patients with human immuno-deficiency virus infection were made in vivo. The results revealed that pulmonary drug distributions are good using both Respirgard II and Pentasave. We measured pulmonary pentamidine deposition of 20.22[+-]4.31 mg using Respirgard II (with 300 mg in 5 ml) and of 16.00[+-]7.18 mg using Pentasave (with 150 mg in 6 ml). These findings show that the therepeutic dose of pentamidine (9 mg) was widely exceeded with both nebulisers. (orig./MG)

  2. Development of a liposome formulation for improved biodistribution and tumor accumulation of pentamidine for oncology applications.

    Science.gov (United States)

    Mérian, Juliette; De Souza, Raquel; Dou, Yannan; Ekdawi, Sandra N; Ravenelle, François; Allen, Christine

    2015-07-05

    Pentamidine isethionate, widely used for the treatment of parasitic infections, has shown strong anticancer activity in cancer cells and models of melanoma and lung cancer. Systemic administration of pentamidine is associated with serious toxicities, particularly renal, affecting as many as 95% of patients (O'Brien et al., 1997). This work presents the development of a liposome pentamidine formulation for greater tumor accumulation and lower drug exposure to vulnerable tissues. Liposomes formulated with saturated/unsaturated phospholipids of different chain lengths, varying cholesterol content, and surface PEG were explored to understand the effects of such variations on drug release, encapsulation efficiency, stability and in vivo performance. Saturated phospholipids with longer chain lengths, higher cholesterol content and PEG resulted in greater stability. The optimal formulation obtained showed significantly lower clearance rate (3.6 ± 1.2 mL/h/Kg) and higher AUC0-inf (348 ± 31 μmol/L × h) in vivo when compared to free drug (414 ± 138 mL/h/Kg and 2.58 ± 0.74 μmol/L × h, respectively). In tumor-bearing mice, liposomal delivery decreased kidney drug levels by up to 5-fold at 6 and 24h post-administration. Tumor drug exposure was up to 12.7-fold greater with liposomal administration compared to free drug. Overall, the liposomal pentamidine formulation developed has significant potential for the treatment of solid tumors.

  3. In vitro synergistic interaction between amphotericin B and pentamidine against Scedosporium prolificans.

    NARCIS (Netherlands)

    Afeltra, J.; Danaoui, E.; Meis, J.F.G.M.; Rodriguez-Tudela, J.L.; Verweij, P.E.

    2002-01-01

    To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical Lab

  4. Pulmonary deposition of nebulised pentamidine isethionate: effect of nebuliser type, dose, and volume of fill.

    Science.gov (United States)

    O'Doherty, M; Thomas, S; Page, C; Bradbeer, C; Nunan, T; Bateman, N

    1990-01-01

    An estimate of the absolute pulmonary deposition of nebulised pentamidine isethionate was obtained in nine patients with AIDS. Two nebuliser systems were compared, System 22 Mizer (Medic-Aid) and Respirgard II (Marquest), with 50 and 150 mg doses of pentamidine in a 3 ml solution driven by an air flow of 6 l/min with the patient in the sitting position. The 50 mg pentamidine dose was repeated with a 6 ml fill with both devices. The nebuliser cloud was labelled with technetium-99m human serum albumin (Ventocol) and lung deposition was measured with a gamma camera. Of the two nebulisers studied, System 22 Mizer delivered more drug to the lungs as a whole and to each individual lung region, including the peripheral and upper zones. For the 50 mg dose the mean (SEM) total pulmonary deposition with the 3 and the 6 ml fill respectively was 2.63 (0.34) and 3.71 (0.41) mg for the System 22 Mizer and 1.37 (0.26) and 1.45 (0.18) mg for the Respirgard II. For the 150 mg dose the System 22 Mizer delivered 7.16 (1.02) mg and the Respirgard II 4.34 (0.57) mg. Increasing the volume of fill from 3 to 6 ml increased pulmonary deposition with System 22 Mizer, and this was related to an increase in nebuliser output. Neither pulmonary deposition nor nebuliser output was increased by using a 6 ml solution in the Respirgard II. Increasing the volume of fill prolonged the time required for nebulisation with both nebulisers. The System 22 Mizer produced more nonpulmonary (gastric and oropharyngeal) deposition of drug, more frequent local adverse effects (cough, burning in the throat, and a metallic taste), and small reductions in lung function, particularly with the 150 mg pentamidine dose. Thus nebuliser type, volume of fill, and nebuliser dose affect the pulmonary deposition of pentamidine. A 300 mg dose of pentamidine via a Respirgard II is generally recommended as providing effective prophylaxis; our results suggest that similar pulmonary deposition can be produced with System 22

  5. Adverse effects associated with intravenous pentamidine isethionate as treatment of Pneumocystis carinii pneumonia in AIDS patients

    DEFF Research Database (Denmark)

    Balslev, U; Nielsen, T L

    1992-01-01

    To evaluate the adverse effects of intravenous pentamidine isethionate, a retrospective study was carried out over a four-year period. Twenty-one acquired immunodeficiency syndrome (AIDS) patients received intravenous pentamidine as treatment of Pneumocystis carinii pneumonia (PCP). This was 13......% of the total number of patients with PCP in the department during that period. Four patients died during treatment and were not evaluated for side effects. Thirteen patients (13/17 = 76%) suffered from one or more minor side effects. The most common of these were gastrointestinal discomfort, pancreatitis......, nephro- and hepatotoxicity. Five patients (5/17 = 29%) experienced a major adverse effect. These were cardiac arrest (one patient), severe hypoglycaemia (one patient) and severe pancreatitis (three patients). In two patients, discontinuation of treatment was necessary due to adverse reactions. As long...

  6. [Trypanocidal activity and plasma kinetics of cis-Pt(II) pentamidine in the parasitized sheep].

    Science.gov (United States)

    Dreyfuss, G; Penicaut, B; Parrondo-Iglesias, E; Craciunescu, D; Dubost, G; Nicolas, J A

    1990-01-01

    The trypanocidal activity of cis-Pt(II) pentamidine had been demonstrated during the first phase of Trypanosoma brucei brucei sheep experimental trypanosomiasis. But a subcutaneous treatment with 5 mg.kg-1 (+2 x 12 mg.kg-1) was not effective during the brain phase of trypanosomiasis. The blood pharmacokinetics of this compound had a plasmatic peak between 45 and 60 min, followed by a low decreasing phase along several days. The curve shape allowed an important interval before the following injection, and showed a compound storage in internal organs and extravascular sites. A model of cis-Pt(II) pentamidine metabolism had been studied: this product could be used as a chemoprophylactic medicine against African trypanosomiasis and American leishmaniasis.

  7. [Diabetes mellitus induced by pentamidine, without previous episodes of hypoglycemia, in patients with AIDS].

    Science.gov (United States)

    Santos, I; del Arco, C; García-Polo, I; Noguerado, A; Caso, E; Gómez-Pan, A

    1990-12-01

    The onset of a pneumonia by P. carinii in AIDS patients have force scientist to look for others therapies against this parasite. It is more necessary when the first line treatment which is cotrimoxazol produced secondary effects or not therapeutic effects. Pentamidine which is an agent usually used to treat leishmaniasis and trypanosomiasis, but it is an alternative for P. carinii infection. The problems are the frequent and severe secondary effects when administered by continuous infusions and less when it is inhaled. Between those effects are the changes in carbohydrate metabolism which are 9% of them. It is frequent observe hypoglycemia during infusion following by hyperglycemia in 5% of the cases which convert the patients in diabetic insulinodependent. A case of a patient who developed diabetes mellitus insulinodependent, 10 days after the end of pentamidine treatment, without previous episodes of hypoglycemia, is presented. The medical literature is reviewed.

  8. Aerosolized pentamidine: Effect on diagnosis and presentation of Pneumocystis carinii pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Jules-Elysee, K.M.; Stover, D.E.; Zaman, M.B.; Bernard, E.M.; White, D.A. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

    1990-05-15

    The objective of this study was to determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. This was a retrospective study of fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.

  9. Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes.

    Science.gov (United States)

    Baker, Nicola; Glover, Lucy; Munday, Jane C; Aguinaga Andrés, David; Barrett, Michael P; de Koning, Harry P; Horn, David

    2012-07-03

    African trypanosomes cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy. Unfortunately, drug resistance is common and melarsoprol-resistant trypanosomes often display cross-resistance to pentamidine. Although melarsoprol/pentamidine cross-resistance (MPXR) has been an area of intense interest for several decades, our understanding of the underlying mechanisms remains incomplete. Recently, a locus encoding two closely related aquaglyceroporins, AQP2 and AQP3, was linked to MPXR in a high-throughput loss-of-function screen. Here, we show that AQP2 has an unconventional "selectivity filter." AQP2-specific gene knockout generated MPXR trypanosomes but did not affect resistance to a lipophilic arsenical, whereas recombinant AQP2 reversed MPXR in cells lacking native AQP2 and AQP3. AQP2 was also shown to be disrupted in a laboratory-selected MPXR strain. Both AQP2 and AQP3 gained access to the surface plasma membrane in insect life-cycle-stage trypanosomes but, remarkably, AQP2 was specifically restricted to the flagellar pocket in the bloodstream stage. We conclude that the unconventional aquaglyceroporin, AQP2, renders cells sensitive to both melarsoprol and pentamidine and that loss of AQP2 function could explain cases of innate and acquired MPXR.

  10. Computational repositioning and preclinical validation of pentamidine for renal cell cancer.

    Science.gov (United States)

    Zerbini, Luiz Fernando; Bhasin, Manoj K; de Vasconcellos, Jaira F; Paccez, Juliano D; Gu, Xuesong; Kung, Andrew L; Libermann, Towia A

    2014-07-01

    Although early stages of clear cell renal cell carcinoma (ccRCC) are curable, survival outcome for metastatic ccRCC remains poor. We previously established a highly accurate signature of differentially expressed genes that distinguish ccRCC from normal kidney. The purpose of this study was to apply a new individualized bioinformatics analysis (IBA) strategy to these transcriptome data in conjunction with Gene Set Enrichment Analysis of the Connectivity Map (C-MAP) database to identify and reposition FDA-approved drugs for anticancer therapy. Here, we demonstrate that one of the drugs predicted to revert the RCC gene signature toward normal kidney, pentamidine, is effective against RCC cells in culture and in a RCC xenograft model. ccRCC-specific gene expression signatures of individual patients were used to query the C-MAP software. Eight drugs with negative correlation and P-value pentamidine, slows tumor growth in the 786-O human ccRCC xenograft mouse model. Our findings suggest that pentamidine might be a new therapeutic agent to be combined with current standard-of-care regimens for patients with metastatic ccRCC and support our notion that IBA combined with C-MAP analysis enables repurposing of FDA-approved drugs for potential anti-RCC therapy.

  11. Pentamidine inhibits Coxiella burnetii growth and 23S rRNA intron splicing in vitro.

    Science.gov (United States)

    Minnick, Michael F; Hicks, Linda D; Battisti, James M; Raghavan, Rahul

    2010-10-01

    Coxiella burnetii is the bacterial agent of Q fever in humans. Acute Q fever generally manifests as a flu-like illness and is typically self-resolving. In contrast, chronic Q fever usually presents with endocarditis and is often life-threatening without appropriate antimicrobial therapy. Unfortunately, available options for the successful treatment of chronic Q fever are both limited and protracted (>18 months). Pentamidine, an RNA splice inhibitor used to treat fungal and protozoal infections, was shown to reduce intracellular growth of Coxiella by ca. 73% at a concentration of 1 microM (ca. 0.6 microg/mL) compared with untreated controls, with no detectable toxic effects on host cells. Bacterial targets of pentamidine include Cbu.L1917 and Cbu.L1951, two group I introns that disrupt the 23S rRNA gene of Coxiella, as demonstrated by the drug's ability to inhibit intron RNA splicing in vitro. Since both introns are highly conserved amongst all eight genotypes of the pathogen, pentamidine is predicted to be efficacious against numerous strains of C. burnetii. To our knowledge, this is the first report describing antibacterial activity for this antifungal/antiprotozoal agent.

  12. Metabolism is an important route of pentamidine elimination in the rat. Disposition of {sup 14}C-pentamidine and identification of metabolites in urine us liquid chromatography-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Bronner, U.; Nordin, J.; Abdi, Y.A.; Gustafsson, L.L. [Huddinge Univ. Hospital, Karolinska Inst., Unit of Tropical Pharmacology, Div. of Clinical Pharmacology and Div. of Infectious Diseases, huddinge (Sweden); Ericsson, Oe.; Wikstroem, I. [Huddinge Univ. Hospital, Hospital Pharmacy, Huddinge (Sweden); Hall, J.E. [Univ. of North Carolina at Chapel Hill, Dept. of Epidemiology, North Carolina (United States); Tidwell, R.R. [Univ. of North Carolina at Chapel Hill, Dept. of Pathology, North Carolina (United States)

    1995-08-01

    This study assesses the contribution of metabolism for the disposition of pentamidine in the rat. With the use of {sup 14}C-labelled compound, the excretion of radioactivity in urine and faeces has been studied in four rats during 44 days after a single intravenous injection of the drug. The urinary and faecal excretion of the radioactivity were of equal importance; 22{+-}2% (mean{+-}S.D.) and 25{+-}4% being detected in urine and faeces, respectively. The activity organs and tissues at 44 days after drug administration was also measured and amounted to 21{+-}5% of the administered dose. Using HPLC the proportion of metabolites in urine in relation to unchanged pentamidine increased with time after dose, being 76{+-}15% (mean{+-}S.D.) of the total excreted radioactivity on day 1 and 97{+-}1% on day 6. HPLC - tandem mass spectrometry was used for identification of metabolites in urine obtained from four rats given unlabelled pentamidine. Using synthetic reference compounds and the selective MS/MS mode four oxidized metabolites of pentamidine were identified either by direct injection into the system or by analyses of extracted urine. Thus, a substantial part of pentamidine is excreted as metabolites in urine. (au) 14 refs.

  13. In vitro synergistic combinations of pentamidine, polymyxin B, tigecycline and tobramycin with antifungal agents against Fusarium spp.

    Science.gov (United States)

    Pozzebon Venturini, Tarcieli; Rossato, Luana; Chassot, Francieli; Tairine Keller, Jéssica; Baldissera Piasentin, Fernanda; Morais Santurio, Janio; Hartz Alves, Sydney

    2016-08-01

    The genus Fusarium is characterized by hyaline filamentous fungi that cause infections predominantly in immunocompromised patients. The remarkable primary resistance to antifungal agents of this genus requires a search for new therapeutic possibilities. This study assessed the in vitro susceptibility of 25 clinical isolates of Fusarium against antifungal agents (amphotericin B, caspofungin, itraconazole and voriconazole) and antimicrobials (pentamidine, polymyxin B, tigecycline and tobramycin) according to the broth microdilution method (M38-A2). The interactions between antifungal and antimicrobial agents were evaluated by the microdilution checkerboard method. Pentamidine and polymyxin B showed MIC values ≥4 µg ml-1 against Fusarium spp. The highest rates of synergism were observed when amphotericin B or voriconazole was combined with tobramycin (80 % and 76 %, respectively), polymyxin B (76 % and 64 %) and pentamidine (72 % and 68 %). The most significant combinations deserve in vivo evaluations in order to verify their potential in the treatment of fusariosis.

  14. In vivo antileishmanial action of Ir-(COD-pentamidine tetraphenylborate on Leishmania donovani and Leishmania major mouse models

    Directory of Open Access Journals (Sweden)

    Loiseau P.M.

    2000-06-01

    Full Text Available lr-(COD-pentamidine tetraphenylborate which has previously been studied on promastigote forms of Leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. In vitro, the iridium complex had the same IC50 value on intracellular forms of Leishmania as pentamidine (15 μM. In vivo, the compound could not be injected intravenously due to the DMSO excipient so that the treatments were performed intraperitoneally or subcutaneously. On the L. donovani LV9 /Balb/C mouse model, the iridium complex was not toxic after intraperitoneal treatment at 232 mg/kg/day x 5 or 147 μmoles/ kg/day x 5, whereas all the mice died within five days when treated at the same dose with pentamidine isethionate. However, only 23 % of parasite suppression was observed with the iridium complex. On a L. major MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine at 6.7 μmoles/ kg/day x 5 (54 % of parasite suppression, the iridium complex exhibited 32 % of parasite suppression after a treatment at 76 μmoles/ kg/day x 5 administered subcutaneously. This slight activity is of interest since pentamidine isethionate is not active under these conditions. Transmission electron microscopy of amastigotes from infected and treated mice show aggregation of ribosomal material, distension of the nuclear membrane and kDNA depolymerization. The mechanism of action therefore involves several targets: membranes, ribosomes and kDNA. According to our results, the Iridium complex is a suitable candidate to be encapsulated in drug carriers such as liposomes or nanoparticles.

  15. A natural product inspired hybrid approach towards the synthesis of novel pentamidine based scaffolds as potential anti-parasitic agents.

    Science.gov (United States)

    Tyagi, Vikas; Khan, Shahnawaz; Shivahare, Rahul; Srivastava, Khushboo; Gupta, Suman; Kidwai, Saqib; Srivastava, Kumkum; Puri, S K; Chauhan, Prem M S

    2013-01-01

    A natural product inspired molecular hybridization approach led us to a series of novel pentamidine based pyrimidine and chalcone scaffolds. All the hybrids were evaluated for their anti-leishmanial potential. Most of the screened compounds have showed significant in vitro anti-leishmanial activity with less cytotoxicity in comparison to the standard drugs (pentamidine, sodium stibogluconate, and miltefosine). Additionally, anti-malarial screening of these compounds was also done and four compounds have shown superior activity against chloroquine resistance strain (K1) of Plasmodium falciparum.

  16. Theoretical models of pentamidine analogs activity based on their DNA minor groove complexes.

    Science.gov (United States)

    Zołek, Teresa; Maciejewska, Dorota

    2010-05-01

    The B-DNA binding property of pentamidine analogs was analyzed employing molecular dynamic simulations and UV-vis absorption spectroscopy. Their AATT and ATAT sequence preferences were also examined. In theoretical energy computations, we considered two solvation models: the implicit model I, where the solvent is characterized by a dielectric constant and the explicit model E, where water molecules are treated as discrete entities. The binding energy correlates well with the increase of melting temperature of the 5'-d(CGCGAATTCGCG)(2)-3' and 5'-d(CGCGATATCGCG)(2)-3' dodecamers after complexation with ligands (DeltaTm), and deduced models predicted adequately the DNA affinities of the studied diamidines.

  17. Repositioning antimicrobial agent pentamidine as a disruptor of the lateral interactions of transmembrane domain 5 of EBV latent membrane protein 1.

    Science.gov (United States)

    Wang, Xiaohui; Fiorini, Zeno; Smith, Christina; Zhang, Yingning; Li, Jing; Watkins, Linda R; Yin, Hang

    2012-01-01

    The lateral transmembrane protein-protein interactions (PPI) have been regarded as "undruggable" despite their importance in many essential biological processes. The homo-trimerization of transmembrane domain 5 (TMD-5) of latent membrane protein 1 (LMP-1) is critical for the constitutive oncogenic activation of the Epstein-Barr virus (EBV). Herein we repurpose the antimicrobial agent pentamidine as a regulator of LMP-1 TMD-5 lateral interactions. The results of ToxR assay, tryptophan fluorescence assay, courmarin fluorescence dequenching assay, and Bis-Tris sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) consistently show pentamidine disrupts LMP-1 TMD-5 lateral interactions. Furthermore, pentamidine inhibits LMP-1 signaling, inducing cellular apoptosis and suppressing cell proliferation in the EBV infected B cells. In contrast, EBV negative cells are less susceptible to pentamidine. This study provides a novel non-peptide small molecule agent for regulating LMP-1 TMD-5 lateral interactions.

  18. Repositioning antimicrobial agent pentamidine as a disruptor of the lateral interactions of transmembrane domain 5 of EBV latent membrane protein 1.

    Directory of Open Access Journals (Sweden)

    Xiaohui Wang

    Full Text Available The lateral transmembrane protein-protein interactions (PPI have been regarded as "undruggable" despite their importance in many essential biological processes. The homo-trimerization of transmembrane domain 5 (TMD-5 of latent membrane protein 1 (LMP-1 is critical for the constitutive oncogenic activation of the Epstein-Barr virus (EBV. Herein we repurpose the antimicrobial agent pentamidine as a regulator of LMP-1 TMD-5 lateral interactions. The results of ToxR assay, tryptophan fluorescence assay, courmarin fluorescence dequenching assay, and Bis-Tris sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE consistently show pentamidine disrupts LMP-1 TMD-5 lateral interactions. Furthermore, pentamidine inhibits LMP-1 signaling, inducing cellular apoptosis and suppressing cell proliferation in the EBV infected B cells. In contrast, EBV negative cells are less susceptible to pentamidine. This study provides a novel non-peptide small molecule agent for regulating LMP-1 TMD-5 lateral interactions.

  19. Pentamidine antagonizes the benznidazole's effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target.

    Science.gov (United States)

    Seguel, Verónica; Castro, Lorena; Reigada, Chantal; Cortes, Leonel; Díaz, María V; Miranda, Mariana R; Pereira, Claudio A; Lapier, Michel; Campos-Estrada, Carolina; Morello, Antonio; Kemmerling, Ulrike; Maya, Juan D; López-Muñoz, Rodrigo

    2016-12-01

    Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T. cruzi. In isolated trypomastigotes, we performed a dose-matrix scheme of combinations, where pentamidine antagonized the effect of benznidazole, mainly at concentrations below the EC50 of pentamidine. In T. cruzi-infected mammalian cells, pentamidine reversed the effect of benznidazole (measured by qPCR). In comparison, in infected BALB/c mice, pentamidine failed to get synergy with benznidazole, measured on mice survival, parasitemia and amastigote nest quantification. To further explain the in vitro antagonism, we explored whether pentamidine affects intracellular trypanothione levels, however, pentamidine produced no change in trypanothione concentrations. Finally, the T. cruzi polyamine permease (TcPAT12) was overexpressed in epimastigotes, showing that pentamidine has the same trypanocidal effect, independently of transporter expression levels. These results suggest that, in spite of the high potency in the putrescine transport blockade, TcPAT12 permease is not the main target of pentamidine, and could explain the lack of synergism between pentamidine and benznidazole.

  20. Effects of acute intravenous administration of pentamidine, a typical hERG-trafficking inhibitor, on the cardiac repolarization process of halothane-anesthetized dogs.

    Science.gov (United States)

    Yokoyama, Hirofumi; Nakamura, Yuji; Iwasaki, Hiroshi; Nagayama, Yukitoshi; Hoshiai, Kiyotaka; Mitsumori, Yoshitaka; Sugiyama, Atsushi

    2009-08-01

    Although acute treatment of pentamidine does not directly modify any ionic channel function in the heart at clinically relevant concentrations, its continuous exposure can prolong QT interval. Recent in vitro studies have indicated that hERG trafficking inhibition may play an important role in the onset of pentamidine-induced long QT syndrome. In this study, we examined acute in vivo electropharmacological effects of pentamidine using the halothane-anesthetized canine model (n = 5). The clinically relevant total dose of 4 mg/kg of pentamidine (namely, 1 mg/kg, i.v. over 10 min followed by 3 mg/kg, i.v. over 10 min with a pause of 20 min) decreased the mean blood pressure, ventricular contraction, preload to the left ventricle, and peripheral vascular resistance. Pentamidine also enhanced the atrioventricular conduction in parallel with its cardiohemodynamic actions, but it gradually prolonged both the ventricular repolarization period and effective refractory period, whereas no significant change was detected in the intraventricular conduction. Thus, acute administration of a clinically relevant dose of pentamidine can suppress cardiac function and vascular tone with reflex-mediated increase of sympathetic activity, whereas it may delay the repolarization process, suggesting that inhibition of potassium-channel trafficking might be induced more acutely in vivo than those previously expected in vitro.

  1. Pentamidine sensitizes chronic myelogenous leukemia K562 cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Qiu, Geng; Jiang, Jikai; Liu, Xiao-shan

    2012-11-01

    Pentamidine (PMD) is an anti-protozoa drug with potential anticancer activity. Here we show that PMD at clinically achievable plasma drug concentrations slightly inhibited the growth of human leukemia cell lines. PMD close to its therapeutic doses sensitized TRAIL-resistant K562 cells to the cytokine and potentiated TRAIL-induced apoptosis through activation of caspase-8 and -3. When we investigated the underlying mechanism, we observed that treatment with PMD increased DR5 expression at both mRNA and protein levels and down-regulated anti-apoptotic XIAP and Mcl-1 protein levels. This study provides a rationale for a more in-depth exploration into the combined treatment with PMD and TRAIL as a valuable strategy for leukemia therapy.

  2. Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

    Science.gov (United States)

    Chakraborty, Mouli; Selma-Soriano, Estela; Magny, Emile; Couso, Juan Pablo; Pérez-Alonso, Manuel; Charlet-Berguerand, Nicolas; Artero, Ruben; Llamusi, Beatriz

    2015-01-01

    ABSTRACT Up to 80% of individuals with myotonic dystrophy type 1 (DM1) will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats. PMID:26515653

  3. Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

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    Mouli Chakraborty

    2015-12-01

    Full Text Available Up to 80% of individuals with myotonic dystrophy type 1 (DM1 will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats.

  4. Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction.

    Science.gov (United States)

    Chakraborty, Mouli; Selma-Soriano, Estela; Magny, Emile; Couso, Juan Pablo; Pérez-Alonso, Manuel; Charlet-Berguerand, Nicolas; Artero, Ruben; Llamusi, Beatriz

    2015-12-01

    Up to 80% of individuals with myotonic dystrophy type 1 (DM1) will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats.

  5. Effect of free versus liposomal-complexed pentamidine isethionate on biological characteristics of Acanthamoeba castellanii in vitro.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Syed, Abdul; Tomas, Salvador; Prieto-Garcia, Jose; Khan, Naveed Ahmed

    2009-03-01

    Acanthamoeba is an opportunistic protozoan pathogen that can cause blinding keratitis and a rare but fatal encephalitis involving the central nervous system with a very poor prognosis. This is due to limited availability of effective anti-acanthamoebic drugs. Here, we tested whether the use of liposomes can improve the potency of pentamidine isethionate, an anti-amoebic compound. The liposomes consisted of l-alpha-phosphatidylcholine and cholesterol or ergosterol in a molar ratio of 1 : 5. Pentamidine isethionate was incorporated to achieve a final drug to lipid ratio of 1 : 5. At a drug concentration of 10 microg ml(-1), the liposomal drug was >12 times more effective than the free drug at preventing Acanthamoeba binding to human cells and significantly more effective in reducing parasite-mediated human cell cytopathogenicity, compared with the drug alone. Both the free and liposomal drug blocked Acanthamoeba encystation.

  6. Randomized single-blinded non-inferiority trial of 7 mg/kg pentamidine isethionate versus 4 mg/kg pentamidine isethionate for cutaneous leishmaniaisis in Suriname.

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    Ricardo V P F Hu

    2015-03-01

    Full Text Available Standard treatment of cutaneous leishmaniasis (CL in Suriname entails three injections of pentamidine isethionate (PI 4 mg/kg per injection in 7 days (7 day regimen. Compliance to treatment is low and may contribute to increasing therapy failure. A 3 day regimen, including 2 injections of 7 mg/kg in 3 days may increase compliance.In a randomized, single-blinded non-inferiority trial conducted in Suriname, 84 CL patients received the 7 day regimen and 79 CL patients received the 3 day regimen. Primary objective was the proportion of patients clinically cured at 6 weeks follow-up. Secondary objectives were clinical cure at 12 weeks follow-up; parasitological cure at 6 and 12 weeks; adverse and drug related toxicity events recorded one week after the end of treatment and health related quality of life. The non-inferiority margin was set at 15%, 1 sided test, α = 0.1.At 6 weeks follow-up 31 (39% patients in the 3 day regimen and 41 (49% patients in the 7 day regimen were clinically cured. Intention to treat (ITT analyses showed that the difference in proportion clinically cured was -9.6% (90% Confidence Interval (CI: -22.3% to 3.2%. Per protocol (PP analysis showed that the difference in proportion clinically cured was 0.2% (90% CI: -14.6% to 15.2%. ITT analysis showed that the difference in proportion parasitological cured at 6 weeks was -15.2% (90% CI:-28.0% to -2.5%. PP analyses showed similar results. Non-inferiority could not be concluded for all adverse and toxicological events.We cannot conclude that the 3 day regimen is non-inferior to the 7 day regimen regarding proportion clinically and parasitological cured. Therefore there is no evidence to change the current standard practice of the 7 day regimen for the treatment of CL in Suriname.

  7. Sirolimus-induced pneumonitis complicated by pentamidine-induced phospholipidosis in a renal transplant recipient: a case report.

    Science.gov (United States)

    Filippone, E J; Carson, J M; Beckford, R A; Jaffe, B C; Newman, E; Awsare, B K; Doria, C; Farber, J L

    2011-09-01

    The proliferation signal inhibitors (PSIs)-sirolimus, everolimus, and temsirolimus-have been associated with a noninfectious pneumonitis characterized by lymphocytic alveolitis and bronciolitis obliterans with organizing pneumonia (BOOP). This condition usually occurs within the first year. Herein we presented a case of a deceased donor renal transplant with interstitial pneumonitis developing 6 years after a switch from tacrolimus to sirolimus due to chronic graft dysfunction. After the addition of intravenous pentamidine due to the suspicion of Pneumocystis pneumonia, there was marked clinical deterioration requiring intubation. Open lung biopsy revealed sirolimus-induced pulmonary toxicity (BOOP) with the additional finding of a drug-induced phospholipidosis (DIPL) that we ascribe to pentamidine treatment. After cessation of both drugs and application of corticosteroid therapy, there was only partial improvement. Eight months later the residual interstitial fibrosis demands supplemental home oxygen. We review the literature on PSI-induced pneumonitis and discuss the pathophysiology of a potential interaction with pentamidine. We caution against its use in the setting of PSI-induced pneumonitis. It is currently unknown whether these concerns also apply to prescription of other more commonly used medications associated with DIPL, eg, amiodarone and aminoglycosides.

  8. Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol.

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    Fabrice E Graf

    Full Text Available The predominant mechanism of drug resistance in African trypanosomes is decreased drug uptake due to loss-of-function mutations in the genes for the transporters that mediate drug import. The role of transporters as determinants of drug susceptibility is well documented from laboratory-selected Trypanosoma brucei mutants. But clinical isolates, especially of T. b. gambiense, are less amenable to experimental investigation since they do not readily grow in culture without prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field isolates that (i have been adapted to axenic in vitro cultivation and (ii mostly stem from treatment-refractory cases. For each isolate, we quantify the sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well-characterized aminopurine permease P2 which transports several trypanocides including melarsoprol, pentamidine, and diminazene. We find that diminazene-resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set of point mutations in TbAT1 that was previously described from lab mutants. Aquaglyceroporin 2 has only recently been identified as a second transporter involved in melarsoprol/pentamidine cross-resistance. Here we describe two different kinds of TbAQP2 mutations found in T. b. gambiense field isolates: simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b. gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less sensitive to melarsoprol than the reference isolates. We thus demonstrate for the first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2 gene loss also occur in the field, and that the T. b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol.

  9. Aquaporin 2 mutations in Trypanosoma brucei gambiense field isolates correlate with decreased susceptibility to pentamidine and melarsoprol.

    Science.gov (United States)

    Graf, Fabrice E; Ludin, Philipp; Wenzler, Tanja; Kaiser, Marcel; Brun, Reto; Pyana, Patient Pati; Büscher, Philippe; de Koning, Harry P; Horn, David; Mäser, Pascal

    2013-01-01

    The predominant mechanism of drug resistance in African trypanosomes is decreased drug uptake due to loss-of-function mutations in the genes for the transporters that mediate drug import. The role of transporters as determinants of drug susceptibility is well documented from laboratory-selected Trypanosoma brucei mutants. But clinical isolates, especially of T. b. gambiense, are less amenable to experimental investigation since they do not readily grow in culture without prior adaptation. Here we analyze a selected panel of 16 T. brucei ssp. field isolates that (i) have been adapted to axenic in vitro cultivation and (ii) mostly stem from treatment-refractory cases. For each isolate, we quantify the sensitivity to melarsoprol, pentamidine, and diminazene, and sequence the genomic loci of the transporter genes TbAT1 and TbAQP2. The former encodes the well-characterized aminopurine permease P2 which transports several trypanocides including melarsoprol, pentamidine, and diminazene. We find that diminazene-resistant field isolates of T. b. brucei and T. b. rhodesiense carry the same set of point mutations in TbAT1 that was previously described from lab mutants. Aquaglyceroporin 2 has only recently been identified as a second transporter involved in melarsoprol/pentamidine cross-resistance. Here we describe two different kinds of TbAQP2 mutations found in T. b. gambiense field isolates: simple loss of TbAQP2, or loss of wild-type TbAQP2 allele combined with the formation of a novel type of TbAQP2/3 chimera. The identified mutant T. b. gambiense are 40- to 50-fold less sensitive to pentamidine and 3- to 5-times less sensitive to melarsoprol than the reference isolates. We thus demonstrate for the first time that rearrangements of the TbAQP2/TbAQP3 locus accompanied by TbAQP2 gene loss also occur in the field, and that the T. b. gambiense carrying such mutations correlate with a significantly reduced susceptibility to pentamidine and melarsoprol.

  10. Chimerization at the AQP2–AQP3 locus is the genetic basis of melarsoprol–pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates

    Directory of Open Access Journals (Sweden)

    Fabrice E. Graf

    2015-08-01

    Full Text Available Aquaglyceroporin-2 is a known determinant of melarsoprol–pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2–AQP3 tandem locus was described from melarsoprol–pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2–aqp3 null T. b. brucei does not. This proves that AQP2–AQP3 chimerization is the cause of melarsoprol–pentamidine cross-resistance in the T. b. gambiense isolates.

  11. Chimerization at the AQP2-AQP3 locus is the genetic basis of melarsoprol-pentamidine cross-resistance in clinical Trypanosoma brucei gambiense isolates.

    Science.gov (United States)

    Graf, Fabrice E; Baker, Nicola; Munday, Jane C; de Koning, Harry P; Horn, David; Mäser, Pascal

    2015-08-01

    Aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2-AQP3 tandem locus was described from melarsoprol-pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2-aqp3 null T. b. brucei does not. This proves that AQP2-AQP3 chimerization is the cause of melarsoprol-pentamidine cross-resistance in the T. b. gambiense isolates.

  12. Physical characterization of pentamidine isethionate during freeze-drying-relevance to development of stable lyophilized product.

    Science.gov (United States)

    Sundaramurthi, Prakash; Burcusa, Michael R; Suryanarayanan, Raj

    2012-05-01

    The purpose of this study was to perform physical characterization of pentamidine isethionate (PI) in frozen and freeze-dried systems and to monitor the phase behavior during all the stages of freeze-drying. Frozen aqueous PI solutions as well as the final lyophiles were characterized by differential scanning calorimetry and X-ray diffractometry. The effect of cosolutes, cosolvents, and processing conditions on the PI crystallization behavior during freeze-drying was evaluated. In frozen aqueous solutions, irrespective of the cooling rate and the initial solute concentration, PI readily crystallized as a trihydrate (C(19) H(24) N(4) O(2) ·3H(2) O). It dehydrated to a poorly crystalline anhydrate upon drying at 100 mTorr. The presence of a readily crystallizing cosolute or an organic cosolvent did not influence the physical form of PI in the final lyophile. On the contrary, even in the absence of cosolutes and cosolvents, the crystalline trihydrate was retained when the chamber pressure was increased to 500 mTorr. By altering the drying conditions, it was possible to obtain either a crystalline trihydrate or a poorly crystalline anhydrate. The stability of PI is dependent on its physical form and only the amorphous PI undergoes discoloration. The PI stability can be enhanced by retaining it in a crystalline state in the lyophile.

  13. Pentamidine movement across the murine blood-brain and blood-cerebrospinal fluid barriers: effect of trypanosome infection, combination therapy, P-glycoprotein, and multidrug resistance-associated protein.

    Science.gov (United States)

    Sanderson, Lisa; Dogruel, Murat; Rodgers, Jean; De Koning, Harry Pieter; Thomas, Sarah Ann

    2009-06-01

    During the first stage of human African trypanosomiasis (HAT), Trypanosoma brucei gambiense is found mainly in the blood, and pentamidine treatment is used. Pentamidine is predominantly ineffective once the parasites have invaded the central nervous system (CNS). This lack of efficacy is thought to be due to the inability of pentamidine to cross the blood-brain barrier, although this has never been explored directly. This study addresses this using brain perfusion in healthy mice, P-glycoprotein-deficient mice, and in a murine model of HAT (T. brucei brucei). The influence of additional antitrypanosomal drugs on pentamidine delivery to the CNS also was investigated. Results revealed that [(3)H]pentamidine can cross the blood-brain barrier, although a proportion was retained by the capillary endothelium and failed to reach the healthy or trypanosome-infected brain (up to day 21 p.i.). The CNS distribution of pentamidine was increased in the final (possibly terminal) stage of trypanosome infection, partly because of loss of barrier integrity (days 28-35 p.i.) as measured by [(14)C]sucrose and [(3)H]suramin. Furthermore, pentamidine distribution to the CNS involved influx and efflux [via P-glycoprotein and multidrug resistance-associated protein (MRP)] transporters and was affected by the other antitrypanosomal agents, suramin, melarsoprol, and nifurtimox, but not eflornithine. These interactions could contribute to side effects or lead to the development of parasite resistance to the drugs. Thus, great care must be taken when designing drug combinations containing pentamidine or other diamidine analogs. However, coadministration of P-glycoprotein and/or MRP inhibitors with pentamidine or other diamidines might provide a means of improving efficacy against CNS stage HAT.

  14. Divalent Metal Ion Complexes of S100B in the Absence And Presence 5 of Pentamidine

    Energy Technology Data Exchange (ETDEWEB)

    Charpentier, T.H.; Wilder, P.T.; Liriano, M.A.; Varney, K.M.; Pozharski, E.; MacKerell, A.D.; Jr.; Coop, A.; Toth, E.A.; Weber, D.J.

    2009-05-12

    As part of an effort to inhibit S100B, structures of pentamidine (Pnt) bound to Ca{sup 2+}-loaded and Zn{sup 2+},Ca{sup 2+}-loaded S100B were determined by X-ray crystallography at 2.15 {angstrom} (R{sub free} = 0.266) and 1.85 {angstrom} (R{sub free} = 0.243) resolution, respectively. These data were compared to X-ray structures solved in the absence of Pnt, including Ca{sup 2+}-loaded S100B and Zn{sup 2+},Ca{sup 2+}-loaded S100B determined here (1.88 {angstrom}; R{sub free} = 0.267). In the presence and absence of Zn{sup 2+}, electron density corresponding to two Pnt molecules per S100B subunit was mapped for both drug-bound structures. One Pnt binding site (site 1) was adjacent to a p53 peptide binding site on S100B ({+-} Zn{sup 2+}), and the second Pnt molecule was mapped to the dimer interface (site 2; {+-} Zn{sup 2+}) and in a pocket near residues that define the Zn{sup 2+} binding site on S100B. In addition, a conformational change in S100B was observed upon the addition of Zn{sup 2+} to Ca{sup 2+}-S100B, which changed the conformation and orientation of Pnt bound to sites 1 and 2 of Pnt-Zn{sup 2+},Ca{sup 2+}-S100B when compared to Pnt-Ca{sup 2+}-S100B. That Pnt can adapt to this Zn{sup 2+}-dependent conformational change was unexpected and provides a new mode for S100B inhibition by this drug. These data will be useful for developing novel inhibitors of both Ca{sup 2+}- and Ca{sup 2+},Zn{sup 2+}-bound S100B.

  15. S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells.

    Science.gov (United States)

    Capoccia, Elena; Cirillo, Carla; Marchetto, Annalisa; Tiberi, Samanta; Sawikr, Youssef; Pesce, Marcella; D'Alessandro, Alessandra; Scuderi, Caterina; Sarnelli, Giovanni; Cuomo, Rosario; Steardo, Luca; Esposito, Giuseppe

    2015-06-01

    S100 calcium-binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B-p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro. The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide-formazan assay. Significant dose-dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 µM (58.5±5%; Ppentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B-cell lymphoma-2 (Bcl-2)-associated X protein (100%, Ppentamidine significantly upregulated the protein expression levels of p53 (681±87.5%, Ppentamidine compared with untreated cells (88±4.2%, Ppentamidine and S100B-p53 inhibitors may represent a novel approach for the treatment of glioma.

  16. A CONTROLLED TRIAL OF AEROSOLIZED PENTAMIDINE OR TRIMETHOPRIM SULFAMETHOXAZOLE AS PRIMARY PROPHYLAXIS AGAINST PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

    NARCIS (Netherlands)

    SCHNEIDER, MME; HOEPELMAN, AIM; SCHATTENKERK, JKME; NIELSEN, TL; VANDERGRAAF, Y; FRISSEN, JPHJ; VANDERENDE, IME; KOLSTERS, AFP; BORLEFFS, JCC

    1992-01-01

    Background. Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is recommended for patients with human immunodeficiency virus (HIV) infection if their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter). Either aerosolized pentamidine or trimethoprim-sulfamethoxaz

  17. Functional genetic identification of PRP1, an ABC transporter superfamily member conferring pentamidine resistance in Leishmania major.

    Science.gov (United States)

    Coelho, Adriano C; Beverley, Stephen M; Cotrim, Paulo C

    2003-08-31

    Pentamidine (PEN) is a second-line agent in the treatment of leishmaniasis whose mode of action and resistance is not well understood. Here, we used a genetic strategy to search for loci able to mediate PEN resistance (PENr) when overexpressed in Leishmania major. A shuttle cosmid library containing genomic DNA inserts was transfected into wild-type promastigotes and screened for PEN-resistant transfectants. Two different cosmids identifying the same locus were found, which differed from other known Leishmania drug resistance genes. The PENr gene was mapped by deletion and transposon mutagenesis to an open reading frame (ORF) belonging to the P-glycoprotein (PGP)/MRP ATP-binding cassette (ABC) transporter superfamily that we named pentamidine resistance protein 1 (PRP1). The predicted PRP1 protein encodes 1,807 amino acids with the typical dimeric structure involving 10 transmembrane domains and two nucleotide-binding domains (NBDs). PRP1-mediated PENr could be reversed by verapamil and PRP1 overexpressors showed cross-resistance to trivalent antimony but not to pentavalent antimony (glucantime). Although the degree of PENr was modest (1.7- to 3.7-fold), this may be significant in clinical drug resistance given the marginal efficacy of PEN against Leishmania.

  18. Inhibiting the clathrin-mediated endocytosis pathway rescues K(IR)2.1 downregulation by pentamidine.

    Science.gov (United States)

    Varkevisser, Rosanne; Houtman, Marien J C; Waasdorp, Maaike; Man, Joyce C K; Heukers, Raimond; Takanari, Hiroki; Tieland, Ralph G; van Bergen En Henegouwen, Paul M P; Vos, Marc A; van der Heyden, Marcel A G

    2013-02-01

    Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. We showed that the antiprotozoic pentamidine decreased K(IR)2.x carried I(K1) current and that inhibiting protein degradation in the lysosome increased intracellular K(IR)2.1 levels. In this study, we aim to identify and then inhibit preceding steps in clathrin-mediated endocytosis of K(IR)2.1 to further restore normal levels of functional K(IR)2.1 channels. K(IR)2.1 trafficking in HEK293 cells was studied by live cell imaging, immunofluorescence microscopy, and Western blot following pharmacological intervention with dynasore (Dyn), chlorpromazine (CPZ), bafilomycin A1 (Baf), or chloroquine (CQ). K(IR)2.1 function was determined by patch-clamp electrophysiology. CQ induced lysosomal build-up of full length (3.8 ± 0.8-fold) and N-terminal cleaved K(IR)2.1 protein. Baf induced late endosomal build-up of full length protein only (6.1 ± 1.6-fold). CPZ and Dyn increased plasma membrane-localized channel and protein levels (2.6 ± 0.4- and 4.2 ± 1.1-fold, respectively). Dyn increased I(K1) (at -60 mV) from 31 ± 6 to 55 ± 7 pA/pF (N = 9 and 13 respectively, p Pentamidine (10 μM, 48 h) reduced K(IR)2.1 levels to 0.6 ± 0.1-fold, which could be rescued by Baf (3.2 ± 0.9), CPZ (1.2 ± 0.3), or Dyn (1.2 ± 0.3). Taken together, the clathrin-mediated endocytosis pathway functions in K(IR)2.1 degradation. Pentamidine-induced downregulation of K(IR)2.1 can be rescued at the level of the plasma membrane, implying that acquired trafficking defects can be rescued.

  19. Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Gabriele Pohlig

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days and stage 1 HAT patients (for up to 10 days, and demonstrated efficacy comparable to pentamidine.This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to

  20. Comparative Analysis of the Omics Technologies Used to Study Antimonial, Amphotericin B, and Pentamidine Resistance in Leishmania

    Directory of Open Access Journals (Sweden)

    Gagandeep Kaur

    2014-01-01

    Full Text Available Leishmaniasis is a serious threat in developing countries due to its endemic nature and debilitating symptoms. Extensive research and investigations have been carried out to learn about the mechanism of drug resistance in Leishmania but results obtained in the laboratory are not in agreement with those obtained from the field. Also the lack of knowledge about the mode of action for a number of drugs makes the study of drug resistance more complex. A major concern in recent times has been regarding the role of parasitic virulence in drug resistance for Leishmania. Researchers have employed various techniques to unravel the facts about resistance and virulence in Leishmania. With advent of advanced and more specific means of detection, further hints about probable mechanisms of conferring resistance are expected. This review aims to provide a consolidated picture along with a comparative account of the work done so far to study the mechanism of antimony, amphotericin B, and pentamidine resistance using various techniques.

  1. Effect of terfenadine and pentamidine on the HERG channel and its intracellular trafficking: combined analysis with automated voltage clamp and confocal microscopy.

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    Tanaka, Hikaru; Takahashi, Yukiko; Hamaguchi, Shogo; Iida-Tanaka, Naoko; Oka, Takayuki; Nishio, Masato; Ohtsuki, Atsushi; Namekata, Iyuki

    2014-01-01

    The effects of terfenadine and pentamidine on the human ether-a-go-go related gene (hERG) channel current and its intracellular trafficking were evaluated. Green fluorescent protein (GFP)-linked hERG channels were expressed in HEK293 cells, and the membrane current was measured by an automated whole cell voltage clamp system. To evaluate drug effects on channel trafficking to the cell membrane, the fraction of channel present on the cell membrane was quantified by current measurement after drug washout and confocal microscopy. Terfenadine directly blocked the hERG channel current but had no effect on trafficking of hERG channels to the cell membrane after application in culture medium for 2 d. In contrast, pentamidine had no direct effect on the hERG channel current but reduced trafficking of hERG channels. The two drugs inhibited hERG channel function through different mechanisms: terfenadine through direct channel blockade and pentamidine through inhibition of channel trafficking to the cell membrane. Combined use of automated voltage clamp and confocal microscopic analyses would provide insights into the mechanisms of drug-induced QT-prolongation and arrhythmogenesis.

  2. Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

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    Coelho Adriano C.

    2004-01-01

    Full Text Available Pentamidine (PEN is an alternative compound to treat antimony-resistant leishmaniasis patients, which cellular target remains unclear. One approach to the identification of prospective targets is to identify genes able to mediate PEN resistance following overexpression. Starting from a genomic library of transfected parasites bearing a multicopy episomal cosmid vector containing wild-type Leishmania major DNA, we isolated one locus capable to render PEN resistance to wild type cells after DNA transfection. In order to map this Leishmania locus, cosmid insert was deleted by two successive sets of partial digestion with restriction enzymes, followed by transfection into wild type cells, overexpression, induction and functional tests in the presence of PEN. To determine the Leishmania gene related to PEN resistance, nucleotide sequencing experiments were done through insertion of the transposon Mariner element of Drosophila melanogaster (mosK into the deleted insert to work as primer island. Using general molecular techniques, we described here this method that permits a quickly identification of a functional gene facilitating nucleotide sequence experiments from large DNA fragments. Followed experiments revealed the presence of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has now been analyzed.

  3. Three optimized and validated (using accuracy profiles) LC methods for the determination of pentamidine and new analogs in rat plasma.

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    Hambÿe, S; Stanicki, D; Colet, J-M; Aliouat, E M; Vanden Eynde, J J; Blankert, B

    2011-01-15

    Three novel LC-UV methods for the determination of pentamidine (PTMD) and two of its new analogs in rat plasma are described. The chromatographic conditions (wavelength, acetonitrile percentage in the mobile phase, internal standard) were optimized to have an efficient selectivity. A pre-step of extraction was simultaneously developed for each compound. For PTMD, a solid phase extraction (SPE) with Oasis(®) HLB cartridges was selected, while for the analogs we used protein precipitation with acetonitrile. SPE for PTMD gave excellent results in terms of extraction yield (99.7 ± 2.8) whereas the recoveries for the analogs were not so high but were reproducible as well (64.6 ± 2.6 and 36.8 ± 1.6 for analog 1 and 2, respectively). By means of a recent strategy based on accuracy profiles (β-expectation tolerance interval), the methods were successfully validated. β was fixed at 95% and the acceptability limits at ± 15% as recommended by the FDA. The method was successfully validated for PTMD (29.6-586.54 ng/mL), analog 1 (74.23-742.3 ng/mL) and analog 2 (178.12-890.6 ng/mL). The first concentration level tested was considered as the LLOQ (lower limit of quantification) for PTMD and analog 1 whereas for analog 2, the LLOQ was not the first level tested and was raised to 178.12 ng/mL.

  4. The diamidine diminazene aceturate is a substrate for the high-affinity pentamidine transporter: implications for the development of high resistance levels in trypanosomes.

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    Teka, Ibrahim A; Kazibwe, Anne J N; El-Sabbagh, Nasser; Al-Salabi, Mohammed I; Ward, Christopher P; Eze, Anthonius A; Munday, Jane C; Mäser, Pascal; Matovu, Enock; Barrett, Michael P; de Koning, Harry P

    2011-07-01

    African trypanosomiasis is a disease of humans and livestock in many areas south of the Sahara. Resistance to the few existing drugs is a major impediment to the control of these diseases, and we investigated how resistance to the main veterinary drug diminazene aceturate correlates with changes in drug transport in resistant strains. The strain tbat1(-/-), lacking the TbAT1/P2 aminopurine transporter implicated previously in diminazene transport, was adapted to higher levels of diminazene resistance. The resulting cell line was designated ABR and was highly cross-resistant to other diamidines and moderately resistant to cymelarsan. Procyclic trypanosomes were shown to be a convenient model to study diamidine uptake in Trypanosoma brucei brucei given the lack of TbAT1/P2 and a 10-fold higher activity of the high-affinity pentamidine transporter (HAPT1). Diminazene could be transported by HAPT1 in procyclic trypanosomes. This drug transport activity was lacking in the ABR line, as reported previously for the pentamidine-adapted line B48. The K(m) for diminazene transport in bloodstream tbat1(-/-) trypanosomes was consistent with uptake by HAPT1. Diminazene transport in ABR and B48 cells was reduced compared with tbat1(-/-), but their resistance phenotype was different: B48 displayed higher levels of resistance to pentamidine and the melaminophenyl arsenicals, whereas ABR displayed higher resistance to diminazene. These results establish a loss of HAPT1 function as a contributing factor to diminazene resistance but equally demonstrate for the first time that adaptations other than those determining the initial rates of drug uptake contribute to diamidine and arsenical resistance in African trypanosomes.

  5. Use of Pentamidine As Secondary Prophylaxis to Prevent Visceral Leishmaniasis Relapse in HIV Infected Patients, the First Twelve Months of a Prospective Cohort Study.

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    Ermias Diro

    Full Text Available Visceral leishmaniasis (VL has become an important opportunistic infection in persons with HIV-infection in VL-endemic areas. The co-infection leads to profound immunosuppression and high rate of annual VL recurrence. This study assessed the effectiveness, safety and feasibility of monthly pentamidine infusions to prevent recurrence of VL in HIV co-infected patients.A single-arm, open-label trial was conducted at two leishmaniasis treatment centers in northwest Ethiopia. HIV-infected patients with a VL episode were included after parasitological cure. Monthly infusions of 4 mg/kg pentamidine-isethionate diluted in normal-saline were started for 12 months. All received antiretroviral therapy (ART. Time-to-relapse or death was the primary end point.Seventy-four patients were included. The probability of relapse-free survival at 6 months and at 12 months was 79% and 71% respectively. Renal failure, a possible drug-related serious adverse event, occurred in two patients with severe pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12 doses. Main reasons to discontinue were: 15 relapsed, five died and seven became lost to follow-up. More patients failed among those with a CD4+cell count ≤ 50 cells/μl, 5/7 (71.4% than those with counts above 200 cells/μl, 2/12 (16.7%, (p = 0.005.Pentamidine secondary prophylaxis led to a 29% failure rate within one year, much lower than reported in historical controls (50%-100%. Patients with low CD4+cell counts are at increased risk of relapse despite effective initial VL treatment, ART and secondary prophylaxis. VL should be detected and treated early enough in patients with HIV infection before profound immune deficiency installs.

  6. American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis resistant to meglumine antimoniate, but with good response to pentamidine: a case report.

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    Pimentel, Maria Inês Fernandes; Baptista, Cibele; Rubin, Evelyn Figueiredo; Vasconcellos, Erica de Camargo Ferreira e; Lyra, Marcelo Rosandiski; Salgueiro, Mariza de Matos; Saheki, Maurício Naoto; Rosalino, Cláudia Maria Valete; Madeira, Maria de Fátima; Silva, Aline Fagundes da; Confort, Eliame Mouta; Schubach, Armando de Oliveira

    2011-01-01

    This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed following two systemic treatments with meglumine antimoniate. The patient was treated with amphotericin B, which was interrupted due to poor tolerance. Following isolation of Leishmania sp., six intralesional infiltrations of meglumine antimoniate resulted in no response. Leishmania sp promastigotes were again isolated. The patient was submitted to intramuscular 4 mg/kg pentamidine. Parasites from the first and second biopsies were identified as Leishmania (Viannia) braziliensis; those isolated from the first biopsy were more sensitive to meglumine antimoniate in vitro than those isolated from the second biopsy. No relapse was observed.

  7. American cutaneous leishmaniasis caused by Leishmania (Viannia braziliensis resistant to meglumine antimoniate, but with good response to pentamidine: a case report

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    Maria Inês Fernandes Pimentel

    2011-04-01

    Full Text Available This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed following two systemic treatments with meglumine antimoniate. The patient was treated with amphotericin B, which was interrupted due to poor tolerance. Following isolation of Leishmania sp., six intralesional infiltrations of meglumine antimoniate resulted in no response. Leishmania sp promastigotes were again isolated. The patient was submitted to intramuscular 4mg/kg pentamidine. Parasites from the first and second biopsies were identified as Leishmania (Viannia braziliensis; those isolated from the first biopsy were more sensitive to meglumine antimoniate in vitro than those isolated from the second biopsy. No relapse was observed.

  8. Ultra high performance liquid chromatography method for the determination of pentamidine and analog in rat biological fluids.

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    Hambÿe, S; Helvenstein, M; Verdy, L; Kahvecioglu, Z; Conotte, R; Vanden Eynde, J-J; Colet, J-M; Blankert, B

    2014-07-01

    Pentamidine isethionate (PTMD) is an antiprotozoal agent used in different parasitic diseases as Human African Trypanosomiasis or Pneumocystis pneumonia. Given its side effects, numerous analogs are still under development worldwide. PTMD has been recently described having a potential activity in myotonic dystrophy (type 1). Here we present an UPLC method coupled to fluo or PDA detection for PTMD and one analog determination in rat plasma or urine. The chromatographic separation was achieved on a Acquity UPLC® HSS T3 analytical column using a mobile phase combining formic acid 0.1% (v/v) and acetonitrile (ACN) at a constant flow rate of 0.4 mL/min. Preliminary, an innovative μSPE (solid phase extraction) procedure using Oasis® WCX sorbent was processed and gave satisfying and reproducible results in terms of extraction yields. Additionally, the methods were successfully validated using the accuracy profiles approach (β=95% and acceptance limits=15%) over the ranges 2.88-287.52 ng/mL and from 143.76 ng/mL to 1.72 μg/mL in rat plasma and urine for PTMD and for EBAB, from 4.23 to 423.39 ng/mL and from 211.69 ng/mL to 2.54 μg/mL for plasma and urine, respectively. The validated protocols were applied to a pharmacokinetic (PK) study on rats and permitted to point out some relevant PK parameters on PTMD and its studied analog.

  9. The study of inhibition effect of Pentamidine on human ovarian cancer cell CAOV3%喷他脒对人卵巢癌CAOV3细胞的抑制作用研究

    Institute of Scientific and Technical Information of China (English)

    吴岩印; 张明月; 丁虹; 孙国栋; 唐艳超; 杨敏; 范茂丹

    2012-01-01

    Objective To study the inhibitive effect of pentamidine on human ovarian carcinoma CA-0V3 cell. Methods The inhibitive effect of pentamidine in different concentrations on human ovarian carcinoma CA0V3 cell was observed by using a MTT assay. Results The growth of human ovarian cancer cell CAOV3 was slightly inhibited with a low concentrations of pentamidine, and was obviously inhibited with a high concentration of pentamidine. The inhibitive effect was closely related to the time of treatment. Conclusion The growth of ovarian cancer CAOV3 cell was inhibited in different concentrations of pentamidine,and the inhibition was related with time of treatment.%目的 探讨喷他脒对人卵巢癌CAOV3细胞的抑制作用.方法 用比色实验法检测不同浓度喷他脒对人卵巢癌CAOV3细胞抑制作用.结果 低浓度喷他脒对人卵巢癌CAOV3细胞有轻微抑制作用;高浓度喷他脒对人卵巢癌CAOV3细胞抑制作用明显,且与作用时间密切相关.结论 经不同浓度的喷他脒处理后,卵巢癌CAOV3细胞生长明显受到抑制,且这种抑制作用呈时间及浓度依赖性.

  10. Efficacy of a diarylheptanoid derivative against Leishmania amazonensis

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    Alves Luciana Vignólio

    2003-01-01

    Full Text Available The activity of several diarylheptanoid derivatives (curcuminoids was previously evaluated against Leishmania amazonensis promastigotes and among them the most active compound was the [1-(4-methoxy-phenyl-7-(3,4-methoxy-4-hydroxy-phenyl-1,6-heptadien-3, 5-dione]. This derivative was chosen to be assayed in vivo in a treatment trial. For these experiments, the curcuminoid compound was used in a concentration equivalent to the IC50/24 h, obtained from the previous study. Balb/c mice were inoculated subcutaneously in the footpad with L. amazonensis infective promastigotes and 4 weeks after the inoculation, the animals were treated with different schemes, varying from 1 to 3 doses. In all the experiments, Pentamidine Isethionate was used as reference drug under the same experimental conditions. The results showed that one dose was not enough to heal the lesion, however, with 2 and 3 doses the efficiency of the assayed compound was clear. On the other hand, treatment with Pentamidine Isethionate using the three different schemes was not satisfactory when compared to the curcuminoid derivative.

  11. Synthesis of limonene β-amino alcohol derivatives in support of new antileishmanial therapies

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    Stela R Ferrarini

    2008-12-01

    Full Text Available A series of seven limonene β-amino alcohol derivatives has been regioselectively synthesised in moderate to good yields. Two of these compounds were found to be significantly effective against in vitro cultures of the Leishmania (Viannia braziliensis promastigote form in the micromolar range. The activities found for 3b and 3f were about 100-fold more potent than the standard drug, Pentamidine, in the same test, while limonene did not display any activity. This is the first report of antileishmanial activity by limonene β-amino alcohol derivatives.

  12. 喷他脒对卵巢癌SKOV3细胞抑制作用的体内体外研究%Inhibitory effect of pentamidine on ovarian cancer SKOV3 cell line in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    丁虹; 吴岩印; 张明月; 郑安桔; 吕雯

    2012-01-01

    目的 探讨喷他脒对人卵巢癌SKOV3细胞株及卵巢癌SKOV3细胞株裸鼠皮下移植瘤的抑制作用.方法 通过MTT法测定卵巢癌细胞生长抑制率,流式细胞仪检测细胞凋亡率;建立人卵巢癌SKOV3细胞裸鼠转移瘤模型,按不同剂量喷他脒给药,观察并记录各组裸鼠及其皮下移植瘤的生长情况,计算肿瘤体积和肿瘤生长抑制率.结果 经不同浓度的喷他脒处理后,卵巢癌SKOV3细胞生长明显受到抑制,且这种抑制作用呈时间及浓度依赖性,凋亡率增加.在卵巢癌裸鼠皮下移植瘤动物模型中,喷他脒能够明显抑制移植瘤的生长,且呈剂量依赖改变,高剂量的10 mg/kg组喷他脒对肿瘤抑制作用更明显.结论 (1)喷他脒可以抑制卵巢癌细胞的增殖及诱导凋亡.(2)高、中、低3种喷他脒给药剂量对荷瘤裸鼠无明显毒性作用.(3)喷他脒对荷瘤裸鼠皮下移植瘤的生长有抑制作用,并呈剂量依赖.%Objective To investigate the inhibitory effect of pentamidine on ovarian cancer SKOV3 cell line in vitro and in vivo. Methods The cultured human ovarian SKOV3 cells were treated with different concentrations of pentamidine (0. 1,1. 0,10. 0 and 100.0 μmol/L)and the cell proliferation was evaluated by MTT assay. Flow cytometry was applied to measure the apoptosis rate of cells. Thirty-two nude mice were subcutaneously inoculated with human ovarian cancer SKOV3 cells,and randomly divided into 4 groups with 8 animals in each group:high-dose group (10 mg/kg pentamidine) ,moderate-dose group (5 mg/kg pentamidine) ,low-dose group (2.5 mg/kg pentamidine) and control group (same volume of PBS). Tumor size was measured and the growth inhibition rate was calculated. Results The growth of SKOV3 cells was inhibited and apoptosis was induced by different concentrations of pentamidine in vitro. Pentamidine significantly inhibited tumor formation and growth in nude mice in a dose-dependent manner. No marked toxic effects were

  13. [Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti-infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris 2012].

    Science.gov (United States)

    Peron, N; Le Guen, P; Andrieu, V; Bardot, S; Ravilly, S; Oudyi, M; Dubus, J-C

    2013-12-01

    The working group on aerosol therapy (GAT) of the Société de pneumologie de langue française (SPLF) organized its third "Aerosolstorming" in 2012. During the course of one day, different aspects of inhaled therapy were discussed, and these will be treated separately in two articles, this one being the first. Inhaled products represent a large volume of prescriptions both in the community and in hospital settings and they involve various specialties particularly ENT and respiratory care. Technical aspects of the development of these products, their mode of administration and compliance with their indications are key elements for the effective therapeutic use of inhaled treatments. In this first article, we will review issues concerning generic inhaled products, the existence of inhaled antidotes, new anti-infective agents and indications for inhaled pentamidine.

  14. Antileishmanial activity of polycyclic derivatives

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    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.

  15. Inhibition of lysosomal degradation rescues pentamidine-mediated decreases of K(IR)2.1 ion channel expression but not that of K(v)11.1.

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    Nalos, Lukas; de Boer, Teun P; Houtman, Marien J C; Rook, Martin B; Vos, Marc A; van der Heyden, Marcel A G

    2011-02-10

    The antiprotozoal drug pentamidine inhibits two types of cardiac rectifier potassium currents, which can precipitate life-threatening arrhythmias. Here, we use pentamidine as a tool to investigate whether a single drug affects trafficking of two structurally different potassium channels by identical or different mechanisms, and whether the adverse drug effect can be suppressed in a channel specific fashion. Whole cell patch clamp, Western blot, real time PCR, and confocal laser scanning microscopy were used to determine potassium current density, ion channel protein levels, mRNA expression levels, and subcellular localization, respectively. We demonstrate that pentamidine inhibits delayed (I(Kr)) and inward (I(K1)) rectifier currents in cultured adult canine cardiomyocytes. In HEK293 cells, pentamidine inhibits functional K(v)11.1 channels, responsible for I(Kr), by interfering at the level of full glycosylation, yielding less mature form of K(v)11.1 at the plasma membrane. In contrast, total K(IR)2.1 expression levels, underlying I(K1), are strongly decreased, which cannot be explained from mRNA expression levels. No changes in molecular size of K(IR)2.1 protein were observed, excluding interference in overt glycosylation. Remaining K(IR)2.1 protein is mainly expressed at the plasma membrane. Inhibition of lysosomal protein degradation is able to partially rescue K(IR)2.1 levels, but not those of K(v)11.1. We conclude that 1) a single drug can interfere in cardiac potassium channel trafficking in a subtype specific mode and 2) adverse drug effects can be corrected in a channel specific manner.

  16. Aerosolised pentamidine for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome Aerosol de pentamidina no tratamento da pneumonia por Pneumocystis carinii em pacientes com a síndrome da imunodeficiência adquirida

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    Adriana Weinberg

    1990-08-01

    Full Text Available The goal of this study was to evaluate inhaled pentamidine for the treatment of patients with mild and moderate Pneumocystis carinii pneumonitis. Eight adults with AIDS and pneumocystis pneumonia (4 with a first episode and 4 with a repeat pneumocystosis received daily inhalations of aerosol pentamidine isethionate for 21 days. Six patients were treated with doses of 300 mg of pentamidine and the remaining 2 received 600 mg every day. In the 300 mg treatment group, 2 individuals showed discrete and transient neutropenia. However, both subjects that received 600 mg of aerosol pentamidine daily developed leukopenia. One of them had major toxicity (overall severe intolerance of 12.5% that required drug discontinuation and did not allow any analysis of the treatment efficacy. Of the 7 evaluable patients, 6 (88% completed the treatment successfuly. One subject of the 300 mg regimen experienced an early recurrence. In conclusion, inhaled pentamidine is an effective treatment for mild and moderate cases of P. carinii pneumonia. It is less toxic than standard anti-pneumocystis therapy and is suitable for outpatient use.O objetivo deste estudo consistiu em avaliar pentamidina inalatória para o tratamento de pneumonia leve a moderada, causada por Pneumocystis carinii. Oito adultos com a síndrome da imunodeficiência humana e pneumocistose (4 apresentando o primeiro episódio e 4 na vigência de pneumocistose de repetição receberam inalações diárias de isetionato de pentamidina por 21 dias. Seis pacientes foram tratados com doses de 300 mg de pentamidina e os 2 restantes receberam 600 mg diariamente. No grupo de 300 mg, 2 indivíduos desenvolveram neutropenia leve e transitória. Porém, ambos os pacientes recebendo 600 mg de pentamidina aerosol apresentaram leucopenia. Um deles teve toxicidade importante (intolerância global de 12,5%, que levou a suspensão da droga e impediu a avaliação da sua eficácia. Entre os 7 pacientes que puderam ser

  17. A controlled, randomized nonblinded clinical trial to assess the efficacy of amphotericin B deoxycholate as compared to pentamidine for the treatment of antimony unresponsive visceral leishmaniasis cases in Bihar, India

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    Vidya N

    2008-12-01

    Full Text Available Vidya Nand Rabi Das1, Niyamat Ali Siddiqui2, Krishna Pandey3, Vijay Pratap Singh2, Roshan K Topno4, Dharmendra Singh5, Rakesh Bihari Verma2, Alok Ranjan2, Prabhat Kumar Sinha1, Pradeep Das61Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research, Patna, Bihar, India; 2Department of Biostatistics; 3Department of Clinical Medicine; 4Department of Epidemiology; 5Department of Molecular Biology; 6Director and Institutional Head, Rajendra Memorial Research Institute of Medical Sciences, Indian Council of Medical Research, Patna, Bihar, IndiaBackground: There is significant variation in Amphotericin B (AMB efficacy and relapses in antimony unresponsive visceral leishmaniasis (VL cases over a period of time (10–15 years. Keeping in mind the above mentioned view this study was undertaken with an objective to assess the magnitude of cure and relapse rates of AMB in the treatment of antimony unresponsive VL cases.Methods: In a controlled, randomized nonblinded clinical trial, we evaluated the cure and relapse rate of Amphotericin B deoxycholate as compared to pentamidine. A total of 82 sodium stibogluconate (SSG unresponsive and parasitologically confirmed VL cases were included in this study and randomized into two groups, test (Amphotericin B and control (Pentamidine. Both the groups were treated with recommended dosages (as per World Health Organization guidelines of respective medicines. All the patients were followed up on 1st, 2nd, and 6th month after end of treatment.Results: Apparent cure rate in the Amphotericin B group was found to be 95% (39/41 compared with 83% (34/41 in the Pentamidine group, which shows significant statistical difference (p = 0.05. The ultimate cure rate was found 92% (38/41 in the Amphotericin B group compared to 73% (30/41 in the Pentamidine group, which shows a significant statistical difference (Yates corrected chi-square = 4.42, p = 0.04. Similarly

  18. Treatment of visceral leishmaniasis with intravenous pentamidine and oral fluconazole in an HIV-positive patient with chronic renal failure--a case report and brief review of the literature.

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    Rybniker, Jan; Goede, Valentin; Mertens, Jessica; Ortmann, Monika; Kulas, Wolfgang; Kochanek, Matthias; Benzing, Thomas; Arribas, José R; Fätkenheuer, Gerd

    2010-06-01

    We report the case of an HIV-positive patient with visceral leishmaniasis and several relapses after treatment with the two first-line anti-leishmanial drugs, liposomal amphotericin B and miltefosine. End-stage renal failure occurred in 2007 when the patient was on long-term treatment with miltefosine. A relapse of leishmaniasis in 2008 was successfully treated with a novel combination regimen of intravenous pentamidine and oral fluconazole. Secondary prophylaxis with fluconazole monotherapy did not prevent parasitological relapse of leishmaniasis.

  19. Leishmanicidal activities of novel synthetic furoxan and benzofuroxan derivatives.

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    Dutra, Luiz Antônio; de Almeida, Letícia; Passalacqua, Thais G; Reis, Juliana Santana; Torres, Fabio A E; Martinez, Isabel; Peccinini, Rosangela Gonçalves; Chin, Chung Man; Chegaev, Konstantin; Guglielmo, Stefano; Fruttero, Roberta; Graminha, Marcia A S; dos Santos, Jean Leandro

    2014-08-01

    A novel series of furoxan (1,2,5-oxadiazole 2-oxide) (compounds 3, 4a and -b, 13a and -b, and 14a to -f) and benzofuroxan (benzo[c][1,2,5]oxadiazole 1-oxide) (compounds 7 and 8a to -c) derivatives were synthesized, characterized, and evaluated for in vitro activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. The furoxan derivatives exhibited the ability to generate nitric oxide at different levels (7.8% to 27.4%). The benzofuroxan derivative 8a was able to increase nitrite production in medium supernatant from murine macrophages infected with L. amazonensis at 0.75 mM after 48 h. Furoxan and benzofuroxan derivatives showed remarkable leishmanicidal activity against both promastigote and intracellular amastigote forms. Compounds 8a, 14a and -b, and 14d exerted selective leishmanicidal activities superior to those of amphotericin B and pentamidine. In vitro studies at pH 5.4 reveal that compound 8a is stable until 8 h and that compound 14a behaves as a prodrug, releasing the active aldehyde 13a. These compounds have emerged as promising novel drug candidates for the treatment of leishmaniasis.

  20. 喷他脒对卵巢癌Skov-3细胞及其裸鼠移植瘤PRL-3的抑制作用%Inhibitory effects of pentamidine on cell growth and PRL-3 expression in human epithelial ovarian cancer Skov-3 cell line

    Institute of Scientific and Technical Information of China (English)

    吕雯; 丁虹; 吴岩印; 张明月

    2012-01-01

    目的 探讨喷他脒对卵巢癌Skov-3细胞及其裸鼠移植瘤PRL-3的抑制作用.方法 (1)M TT法检测不同浓度喷他脒对Skov-3细胞的生长抑制作用;(2)RT-PCR法检测不同浓度喷他脒处理后的Skov-3细胞PRL-3的表达;(3)建立人卵巢癌Skov-3 细胞裸鼠转移瘤模型,按喷他脒给药剂量分4组,记录裸鼠皮下移植瘤的生长情况,绘制肿瘤生长曲线.采用RT-PCR方法检测裸鼠移植肿瘤的PRL-3表达情况.结果 喷他脒对卵巢癌Skov-3细胞体外生长有抑制作用,呈浓度依赖性(P<0.05);喷他脒中高剂量组予5次给药后裸鼠移植瘤生长速度均与对照组有差异(P<0.05);中、高剂量喷他脒抑制人Skov-3卵巢癌细胞裸鼠皮下移植瘤的PRL-3表达,且随剂量增加而抑制作用更明显(P<0.05).结论 喷他脒对卵巢癌Skov-3细胞体外生长及裸鼠Skov-3皮下移植瘤均有有抑制作用;喷他脒可抑制Skov-3卵巢癌细胞及裸鼠Skov-3皮下移植瘤PRL-3的表达.%Objective To investigate the inhibitory effect of pentamidine on cell growth and PRL-3 expression of ovarian cancer Skov-3 cell line in vitro and in vivo. Methods Human epithelial ovarian cancer Skov-3 cells were treated with different concentrations pentamidine in vitro; the cell growth was evaluated by MTT assay, the expression of PRL-3 was detected by RT-PCR. The Skov-3 cells were subcutaneously inoculated into nude mice to establish the animal ovarian cancer model. Thirty two tumor-bearing nude mice were randomly divided into 4 groups, and each group received different dose of pentamidine. Tumor growth was observed and tumor volume was continuously measured, then the growth inhibition rate was calculated. The PRL-3 expression in excised tumor was detected by RT-PCR. Results Pentamidine inhibited cell proliferation in vitro in a dose-dependent manner (P<0.05). The growth of xenograft tumor in nude mice treated with medium-and large-dosage of pentamidine was significantly slower than

  1. Synthesis, biological evaluation and SAR of sulfonamide 4-methoxychalcone derivatives with potential antileishmanial activity.

    Science.gov (United States)

    Andrighetti-Fröhner, Carla R; de Oliveira, Kely N; Gaspar-Silva, Daniela; Pacheco, Letícia K; Joussef, Antônio C; Steindel, Mário; Simões, Cláudia M O; de Souza, Alessandra M T; Magalhaes, Uiaran O; Afonso, Ilídio F; Rodrigues, Carlos R; Nunes, Ricardo J; Castro, Helena C

    2009-02-01

    Despite clinical importance of leishmaniasis, an infectious disease that affects 12 thousand million people in 88 countries, the treatment is still unsatisfactory due to its limited efficacy, cost expensive and undesirable side effects. Aiming to develop new antileishmanial lead compounds, we used a rational approach to synthesize a new set of sulfonamide 4-methoxychalcone derivatives (3a-3i) and evaluate the sulfonamide and methoxy moieties as promising adding-groups to chalcones. For that purpose we tested this new set against Leishmania braziliensis promastigotes and intracellular amastigotes and determined its cell toxicity profile. Interestingly all compounds presented a concentration-dependent antileishmanial profile and the benzylamino derivative (3i) showed a biological activity better than pentamidine. None of these compounds affected Trypanosoma cruzi epimastigotes, which suggests a specific antileishmanial profile. The structure-activity analysis of these sulfonamide 4-methoxychalcone derivatives pointed the molecular volume, the HOMO density concentrated in the chalcone moiety and the conformational structure of the compounds as important structural and stereoelectronic features for the antileishmanial activity. In addition, these compounds also fulfilled Lipinski rule of 5 and presented druglikeness similar to antileishmanial drugs. Altogether these results point the sulfonamide 4-methoxychalcone derivatives as potential lead compounds for designing new candidates for leishmaniasis treatment.

  2. 4-(1H-Pyrazol-1-yl Benzenesulfonamide Derivatives: Identifying New Active Antileishmanial Structures for Use against a Neglected Disease

    Directory of Open Access Journals (Sweden)

    Leonor L. Leon

    2012-11-01

    Full Text Available Leishmaniasis is a neglected disease responsible for about 56,000 deaths every year. Despite its importance, there are no effective, safe and proper treatments for leishmaniasis due to strain resistance and/or drug side-effects. In this work we report the synthesis, molecular modeling, cytotoxicity and the antileishmanial profile of a series of 4-(1H-pyrazol-1-ylbenzenesulfonamides. Our experimental data showed an active profile for some compounds against Leishmania infantum and Leishmania amazonensis. The profile of two compounds against L. infantum was similar to that of pentamidine, but with lower cytotoxicity. Molecular modeling evaluation indicated that changes in electronic regions, orientation as well as lipophilicity of the derivatives were areas to improve the interaction with the parasitic target. Overall the compounds represent feasible prototypes for designing new molecules against L. infantum and L. amazonensis.

  3. Estudo clínico randomizado comparando antimoniato de meglumina, pentamidina e anfotericina B para o tratamento da leishmaniose cutânea ocasionada por Leishmania guyanensis A randomized clinical trial comparing meglumine antimoniate, pentamidine and amphotericin B for the treatment of cutaneous leishmaniasis by Leishmania guyanensis

    Directory of Open Access Journals (Sweden)

    Leandro Ourives Neves

    2011-12-01

    performed to support their use. Moreover, treatment outcome may depend on the causative species of Leishmania. OBJECTIVES: To evaluate and compare the efficacy and tolerability of meglumine antimoniate, pentamidine isethionate, and amphotericin B in the treatment of ATL caused by Leishmania (Viannia guyanensis. METHODS: 185 patients were selected according to the eligibility criteria and randomly allocated into three groups - two groups with 74 patients each, and one group with 37 patients, which underwent meglumine, pentamidine and amphotericin B treatment, respectively. Doses, mode of administration and time periods of treatment followed the current recommendations for each drug. Patients were re-examined one, two and six months after completion of treatment. RESULTS: No differences were observed among the therapeutic groups in relation to gender, age, number or site of lesions. Intention-to-treat (ITT analysis showed efficacy of 58.1% for pentamidine and 55.5% for meglumine (p=0.857. The amphotericin B group was analyzed separately, since 28 patients (75.7% in this group refused to continue participating in the study. Mild or moderate adverse effects were reported by 74 (40% patients, especially arthralgia (20.3% in the meglumine group, and pain (35.1% or induration (10.8% at the site of injection in the pentamidine group. CONCLUSION: Pentamidine and meglumine show similar efficacy in the treatment of ATL caused by L. guyanensis. Given the low efficacy of both drugs, there is an urgent need for new therapeutical approaches.

  4. 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 ...

  5. 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’....

  6. 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...

  7. 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.

  8. 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...

  9. 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.

  10. Antileishmanial activity of semisynthetic lupane triterpenoids betulin and betulinic acid derivatives: synergistic effects with miltefosine.

    Directory of Open Access Journals (Sweden)

    Maria C Sousa

    Full Text Available Leishmaniasis is a neglected tropical disease (NTDs, endemic in 88 countries, affecting more than 12 million people. The treatment consists in pentavalent antimony compounds, amphotericin B, pentamidine and miltefosine, among others. However, these current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, it is important to continue the search for new effective and less toxic treatments. The anti-Leishmania activity of sixteen semisynthetic lupane triterpenoids derivatives of betulin (BT01 to BT09 and betulinic acid (AB10 to AB16 were evaluated. Drug interactions between the active compounds and one current antileishmanial drug, miltefosine, were assessed using the fixed ratio isobologram method. In addition, effects on the cell cycle, apoptosis/necrosis events, morphology and DNA integrity were studied. The derivatives BT06 (3β-Hydroxy-(20R-lupan-29-oxo-28-yl-1H-imidazole-1-carboxylate and AB13 (28-(1H-imidazole-1-yl-3,28-dioxo-lup-1,20(29-dien-2-yl-1H-imidazole-1-carboxylate were found to be the most active, with IC50 values of 50.8 µM and 25.8 µM, respectively. Interactions between these two compounds and miltefosine were classified as synergistic, with the most effective association being between AB13 and miltefosine, where decreases of IC50 values to 6 µM were observed, similar to the miltefosine activity alone. AB13 induced significant morphological changes, while both derivatives produced anti-proliferative activity through cell cycle arrest at the G0/G1 phase. Neither of these derivatives induced significant apoptosis/necrosis, as indicated by phosphatidylserine externalization and DNA fragmentation assays. In addition, neither of the derivatives induced death in macrophage cell lines. Thus, they do not present any potential risk of toxicity for the host cells. This study has identified the betulin derivative BT06 and the betulinic acid derivative AB13 as promising

  11. 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.

  12. Reversible supramolecular assembly at specific DNA sites: nickel-promoted bivalent DNA binding with designed peptide and bipyridyl-bis(benzamidine) components.

    Science.gov (United States)

    Sánchez, Mateo I; Mosquera, Jesús; Vázquez, M Eugenio; Mascareñas, José L

    2014-09-01

    At specific DNA sites, nickel(II) salts promote the assembly of designed components, namely a bis(histidine)-modified peptide that is derived from a bZIP transcription factor and a bis(benzamidine) unit that is equipped with a bipyridine. This programmed supramolecular system with emergent properties reproduces some key characteristics of naturally occurring DNA-binding proteins, such as bivalence, selectivity, responsiveness to external agents, and reversibility.

  13. Bisbenzamidines as Antifungal Agents. Are Both Amidine Functions Required to Observe an Anti-Pneumocystis carinii Activity?

    Directory of Open Access Journals (Sweden)

    Julien Laurent

    2010-06-01

    Full Text Available A library of 19 novel 4-(4-phenylpiperazine-1-ylbenzamidines has been synthesized and evaluated in vitro against Pneumocystis carinii. Among these compounds, N-ethyl- and N-hexyl-4-(4-phenylpiperazine-1-ylbenzamidines emerged as the most promising compounds, with inhibition percentages at 10.0 µg/mL of 87% and 96%, respectively. Those compounds remained active at 0.1 µg/mL.

  14. 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.

  15. Estudo comparativo da eficácia de isotionato de pentamidina administrada em três doses durante uma semana e de N-metil-glucamina 20mgSbV/kg/dia durante 20 dias para o tratamento da forma cutânea da leishmaniose tegumentar americana A comparative study between the efficacy of pentamidine isothionate given in three doses for one week and N-methil-glucamine in a dose of 20mgSbV/day for 20 days to treat cutaneous leishmaniasis

    Directory of Open Access Journals (Sweden)

    Carmen Déa Ribeiro de Paula

    2003-06-01

    Full Text Available Setenta e nove pacientes com leishmaniose tegumentar americana, forma cutânea, foram divididos em dois grupos: o grupo experimental (I, formado por 38 pessoas que receberam isotionato de pentamidina, 4mg/kg/dia, três aplicações, IM, durante uma semana, e o grupo controle (II, formado por 41 doentes tratados com N-metilglucamina, 20mgSbV/kg/dia por 20 dias, EV. Foram identificados, por técnica de anticorpos monoclonais, 21 isolados com predominância de Leishmania (Viannia braziliensis. Encontrou-se cura clínica em 71,05% do grupo experimental e 73,17% do grupo controle (p=0,47. Alterações de ECG foram mais freqüentes utilizando antimonial pentavalente, com significância (pSeventy-nine patients with cutaneous leishmaniasis were included in this study. The experimental group (n = 38 was treated with pentamidine isothionate in a dose of 4mg/kg/day on alternate days, for one week. The control group (n = 41 was treated with N-methylglucamine in a dose of 20mgSbV/kg/day for 20 days. Twenty-one isolates were identified using monoclonal antibody technique. We characterized Leishmania (Viannia braziliensis, most frequently. There was a cure rate of 71.05% of the patients in the experimental group and 73.17% in the control group (p = 0.47.We found a statistical significance regarding frequency of ECG alterations between the experimental and control group (p<0.05. In our study pentamidine was as effective as antimonial for the treatment of american cutaneous leishmaniasis. It proved to be a safer drug considering heart toxicity. Moreover, it requires less time to complete the treatment.

  16. 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.

  17. 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

  18. Comparison of Meglumine Antimoniate and Pentamidine for Peruvian Cutaneous Leishmaniasis

    Science.gov (United States)

    2005-01-01

    Unit No. 5, San Diego, California; Hospital Instituto Peruano Seguro Social , Cusco, Peru; Universidad Peruana Cayetano Heredia; Lima, Peru; National...Preventive Medicine Unit No. 5, Naval Station, 3235 Albacore Alley, San Diego, CA 92136, Maria Cruz-Saldarriaga, Hospital Instituto Peruano Seguro ... Social , Cusco, Peru. Alejandro Llanos Cuentas, Juan Echevarria, and Cesar Miranda-Verastegui, Universidad Peruana Cayetano Heredia, Casilla Postal 4314

  19. Preparation and stability of a radioiodinated pentamidine isethionate analog

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J. (Kent and Canterbury Hospital (United Kingdom) Kent Univ., Canterbury (United Kingdom)); Smith, C.M.; Smith, R.J.; Moores, G.E. (Kent Univ., Canterbury (United Kingdom)); O' Doherty, M.J. (Kent and Canterbury Hospital (United Kingdom))

    1992-10-01

    Iodopentamidine isethionate was heated for 70 min with [I-123]- or [I-125]-sodium iodide and ammonium sulphate in the absence of solvent at 140[sup o]C. The product, [I-123]- or [I-125]-iodopentamidine isethionate, was purified by ion exchange chromatography. It was stable at room temperature in aqueous solution over several days, in human blood in vitro for at least 24 h (showing no binding to either cells or proteins), in urine over at least 15 h, and during nebulization in both ultrasonic and jet nebulizers. (Author).

  20. 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 ...

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. Taxation of Derivatives

    DEFF Research Database (Denmark)

    Dyppel, Katja Joo

    2013-01-01

    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.......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...

  6. 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.

  7. 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....

  8. 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...

  9. Essays on Derivatives Pricing

    DEFF Research Database (Denmark)

    Kokholm, Thomas

    financial models, and most importantly, to be aware of their limitations. Following that belief, this thesis consists of three independent and self-contained papers, all dealing with topics in derivatives pricing. The first paper considers the pricing of traffic light options, which are appropriate....... 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...

  10. 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.

  11. 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...

  12. 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 ...

  13. 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.

  14. NMR of amino-guanidine and derivates; RMN de aminoguanidina e derivados

    Energy Technology Data Exchange (ETDEWEB)

    Tinoco, L.W.; Figueroa Villar, Jose Daniel; Borges, M.N.; Messeder, J.C. [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Secao de Quimica

    1993-12-31

    The parasitic disease known in Brazil as `Doenca de Chagas` affects millions of Brazilians and its cure is not known yet. In the search for new drugs it was discovered that bi-cationic compounds such as pentamidine compounds are active against similar diseases, however, preliminary tests for Trypanosoma cruzi (the causing agent of Doenca de Chagas) were negative. However, our preliminary studies indicate that such compounds do have active role against Trypanosoma cruzi. This work presents the preliminary NMR spectra of these compounds in order to contribute to the above mentioned issue 1 refs., figs., 5 tabs.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. 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…

  3. 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...

  4. 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.

  5. Original and Derived Judgment

    DEFF Research Database (Denmark)

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

    2007-01-01

    Recent work links entrepreneurship to the economic theory of the firm, using the concept of entrepreneurship as judgment introduced by Frank Knight. When judgment is complementary to other assets, it makes sense for entrepreneurs to hire labour and to own assets. The entrepreneur's role, then......, is to arrange or organize the human and capital assets under his or her control. We extend this Knightian concept of the firm by developing a theory of delegation under Knightian uncetainty. 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 organizational structure - its formal and informal systems of rewards and punishments, rules for settling disputes and renegotiating agreements, means of evaluating performance and so on - can...

  6. 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...

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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.

  14. Central Clearing of OTC Derivatives

    DEFF Research Database (Denmark)

    Cont, Rama; Kokholm, Thomas

    2014-01-01

    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....

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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).

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...... quantities of interest. To be able to utilise the evidence about the derivative it is suggested to adapt the ‘conventional’ problem statement to variational calculus and the way to do so is demonstrated. A number of examples are given throughout the paper....

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  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. 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 .

  3. 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.

  4. 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.

  5. 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...

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. 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.

  8. 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.

  9. 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.

  10. 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...

  11. 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...

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Time derivative of earthquake acceleration

    Institute of Scientific and Technical Information of China (English)

    Mai Tong; Guo-Quan Wang; George C.Lee

    2005-01-01

    Unlike acceleration, velocity, and displacement, the time derivative of acceleration (TDoA) of ground motion has not been extensively studied. In this paper, the basic characteristics of TDoA are evaluated based on records from the 1999Chi-Chi, earthquake (Mw 7.6) and one of its aftershocks (Mw 6.2). It is found that the maximum TDoA at a free-field station was over 31,200 crm/s3 (31.8 g/s); and the duration of "strong" TDoA, between the first and the last time points exceeding 2,000 cm/s3 (2 g/s), was almost one minute near the epicenter area. Since ground TDoA sensors are not commonly available,the time series are calculated by direct numerical differentiation of acceleration time series. Relative error analysis shows that the error is non-transitive and total error is within 4%. The density function of TDoA amplitude, frequency content and spatial distribution of peak ground jerk (PGJ) are evaluated. The study also includes examination of some TDoA responses from a seven-story building and comparison of ground TDoA with the limit TDoA used in the transportation industry for ride comfort. Some potential impacts of TDoA on humans have also been reviewed.

  1. 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.

  2. 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.

  3. 21 CFR 184.1685 - Rennet (animal-derived) and chymosin preparation (fermentation-derived).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Rennet (animal-derived) and chymosin preparation (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...

  4. 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

  5. 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  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. 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.

  18. 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...

  19. 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.)

  20. 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.

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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)...

  7. 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...

  8. 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

  9. 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.

  10. 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

  11. 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…

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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\

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  9. 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.

  10. 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,...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. 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.

  5. 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 ...

  6. 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.

  7. 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 ...

  8. 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

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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).

  10. 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.

  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. 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.

  13. 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.

  14. 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......" variance estimator derived from the "small bandwidth" asymptotic framework. The results of a small-scale Monte Carlo experiment are found to be consistent with the theory and indicate in particular that sensitivity with respect to the bandwidth choice can be ameliorated by using the "robust...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.)

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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…

  17. 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...

  18. 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.

  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. 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,...

  1. 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

  2. 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…

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. [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

  8. 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)

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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...

  18. 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...

  19. 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.

  20. 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...

  1. 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…

  2. 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.

  3. 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)

  4. 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

  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. 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.

  7. 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…

  8. 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.

  9. 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,

  10. 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.

  11. 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.

  12. 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.

  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. 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

  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. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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)).

  4. 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.

  5. 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.

  6. Synthesis and biological evaluation of formazan derivatives.

    Science.gov (United States)

    Mariappan, Gurusamy; Korim, Rejaul; Joshi, Nand Madhwa; Alam, Faruk; Hazarika, Rajib; Kumar, Deepak; Uriah, Tiewlasubon

    2010-10-01

    The formazan derivatives (FM1-FM5) were synthesized by the reaction of benzaldehyde phenylhydrazone with substituted aromatic and hetero aromatic amines. The structures of the synthesized compounds were then elucidated using UV, IR, (1)H NMR and mass spectral data. The synthesized derivatives were screened for anticonvulsant, antibacterial and antiviral activities. All the compounds showed remarkable antibacterial activity at 250 μg/ml, but FM4 and FM3 did not show any inhibition on Staphylococcus aureus and Vibriocholera, respectively. All the compounds showed significant anticonvulsant effect at 100 mg/kg p.o. and the experimental data were statistically significant at P<0.001 level. But none of the compounds was effective against Japanese encephalitis virus.

  7. Synthesis and biological evaluation of formazan derivatives

    Directory of Open Access Journals (Sweden)

    Gurusamy Mariappan

    2010-01-01

    Full Text Available The formazan derivatives (FM1-FM5 were synthesized by the reaction of benzaldehyde phenylhydrazone with substituted aromatic and hetero aromatic amines. The structures of the synthesized compounds were then elucidated using UV, IR, 1 H NMR and mass spectral data. The synthesized derivatives were screened for anticonvulsant, antibacterial and antiviral activities. All the compounds showed remarkable antibacterial activity at 250 μg/ml, but FM4 and FM3 did not show any inhibition on Staphylococcus aureus and Vibriocholera, respectively. All the compounds showed significant anticonvulsant effect at 100 mg/kg p.o. and the experimental data were statistically significant at P<0.001 level. But none of the compounds was effective against Japanese encephalitis virus.

  8. Derivation of evolutionary payoffs from observable behavior

    CERN Document Server

    Feigel, Alexander; Engel, Assaf

    2008-01-01

    Interpretation of animal behavior, especially as cooperative or selfish, is a challenge for evolutionary theory. Strategy of a competition should follow from corresponding Darwinian payoffs for the available behavioral options. The payoffs and decision making processes, however, are difficult to observe and quantify. Here we present a general method for the derivation of evolutionary payoffs from observable statistics of interactions. The method is applied to combat of male bowl and doily spiders, to predator inspection by sticklebacks and to territorial defense by lions, demonstrating animal behavior as a new type of game theoretical equilibrium. Games animals play may be derived unequivocally from their observable behavior, the reconstruction, however, can be subjected to fundamental limitations due to our inability to observe all information exchange mechanisms (communication).

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Renminbi Derivatives: Recent Development and Issues

    Institute of Scientific and Technical Information of China (English)

    Wensheng Peng; Chang Shu; Raymond Yip

    2007-01-01

    This study reviews the developments in the onshore and offshore renminbi derivatives markets. The onshore market has seen a rapid build-up in the market infrastructure and price discovery mechanism in the past year, with empirical evidence suggesting that its pricing is increasingly determined by financial fundamentals, such as the covered interest rate parity. However, the growth of the market has been restrained by restrictions on the participant base, limited variations in the RMB/US$ exchange rate, market participants'lack of technical capacity and experience, and inadequate supporting financial market infrastructure. The non-deliverable forward (NDF) market, concentrated in Hong Kong and Singapore, is more developed, but has the drawback that its pricing is not tied to financial fundamentals. The comparison between onshore and offshore markets suggests that two issues are of particular importance for future derivatives market development in China: the balance between regulation and development, and the relationship between onshore and offshore markets.

  16. Synthesis of β-Amino Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    Zhao Yonghua; Ma Zhihua; Jiang Nan; Wang Jianbo

    2004-01-01

    In recent years, β-amino acids and their derivatives have attracted considerable attention due to their occurrence in biologically active natural products, such as dolastatins,cyclohexylnorstatine and Taxol. β-Amino acids also find application in the synthesis of β-lactams,piperidines, indolizidines. Moreover, the peptides consisting of β-amino acids, the so-called β-peptides, have been extensively studied recently. Consequently, considerable efforts have been directed to the synthesis of β-amino acids and their derivatives1. In particular, stereoselective synthesis of β-amino acids has been a challenging project, and there are only limited methods available. In this presentation, we report our efforts in this area.

  17. Perturbative unitarity of Higgs derivative interactions

    CERN Document Server

    Kikuta, Yohei

    2012-01-01

    We study the perturbative unitarity bound given by dimension six derivative interactions consisting of Higgs doublets. These operators emerge from kinetic terms of composite Higgs models or integrating out heavy particles that interact with Higgs doublets. They lead to new phenomena beyond the Standard Model. One of characteristic contributions by derivative interactions appear in vector boson scattering processes. Longitudinal modes of massive vector bosons can be regarded as Nambu Goldstone bosons eaten by each vector field with the equivalence theorem. Since their effects become larger and larger as the collision energy of vector bosons increases, vector boson scattering processes become important in a high energy region around the TeV scale. On the other hand, in such a high energy region, we have to take the unitarity of amplitudes into account. We have obtained the unitarity condition in terms of the parameter included in the effective Lagrangian for one Higgs doublet models. Applying it to some of mode...

  18. Synthesis and bioactivity of novel phthalimide derivatives

    Institute of Scientific and Technical Information of China (English)

    Tao Wang; Yi Hua Zhang; Hui Ji; Yan Ping Chen; Si Xun Peng

    2008-01-01

    Novel phthalimide derivatives (4a, 4b and 6a-6e) were designed as hybrids of thalidomide and NO-ASA, and their chemicalsynthesis and in vitro biological activities were presented. The preliminary results showed that compared to thalidomide 4a and 4bexhibited enhanced activities against ECV304 and HepG2 cells, whereas 6c was more potent against HepG2 cells.

  19. Oxidative rearrangements of tricyclic vinylcyclobutane derivatives

    OpenAIRE

    Grota, Juliane; Mattay, Jochen; Piech, Krzysztof; Bally, Thomas

    2006-01-01

    Three tricyclic vinylcyclobutanes (3-methylenetricyclo[5.3.0.02,6]decanes 1-3) have been subjected to ionization by photoinduced electron transfer in solution and by X-irradiation in Ar matrices. All three compounds undergo oxidative cycloreversion; the cleavage of the four-membered ring, however, occurs in a different direction depending on the presence of a methyl group in position 6 of the tricyclic framework. In those derivatives, cycloreversion is found to lead to 1-methyl-8-methylene-1,...

  20. Aging and Rejuvenation with Fractional Derivatives

    Science.gov (United States)

    2007-11-02

    Science, University of North Texas, P. O. Box 311427, Denton, Texas 76203-1427, USA 2Dipartimento di Fisica dell’Università di Pisa and INFM, via...interval 2,m,3, yield a generalized master equation equivalent to the sum of an ordinary Markov contribution and a fractional derivative term. We show...though these processes are associated with quite different physical phenomena [14]. His general argu- ments rested on three assumptions: (1) microscopic

  1. Anthranilic acid derivatives from Inula japonica

    Institute of Scientific and Technical Information of China (English)

    Jiang Jiang Qin; Hui Zi Jin; Jian Jun Fu; Xiao Jia Hu; Yan Zhu; Yun Heng Shen; Shi Kai Yan; Wei Dong Zhang

    2008-01-01

    Three new anthranilic acid derivatives, N-heneicosanoylanthranilic acid (1b), N-tricosanoylanthranilic acid (1d), N-tetra-cosanoylanthranilic acid (1e), and two known N-arachidylanthranilic acid (1a) and N-docosanoylanthranilic acid (1c) were isolatedfrom the aerial parts of Inula japonica Thunb. Their structures were established by spectroscopic and chemical methods.2008 Hui Zi Jin. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  2. Synthesis and biological evaluation of indazole derivatives.

    Science.gov (United States)

    Claramunt, Rosa M; López, Concepción; López, Ana; Pérez-Medina, Carlos; Pérez-Torralba, Marta; Alkorta, Ibon; Elguero, José; Escames, Germaine; Acuña-Castroviejo, Darío

    2011-04-01

    The inhibition of neuronal and inducible nitric oxide synthases (nNOS and iNOS) by a series of 36 indazoles has been evaluated, showing that most of the assayed derivatives are better iNOS than nNOS inhibitors. A parabolic model relating the iNOS inhibition percentage with the difference, E(rel), between stacking and apical interaction energies of indazoles with the active site of the NOS enzyme has been established.

  3. Derived length for arbitrary topological spaces

    Directory of Open Access Journals (Sweden)

    A. J. Jayanthan

    1992-01-01

    Full Text Available The notion of derived length is as old as that of ordinal numbers itself. It is also known as the Cantor-Bendixon length. It is defined only for dispersed (that is scattered spaces. In this paper this notion has been extended in a natural way for all topological spaces such that all its pleasing properties are retained. In this process we solve a problem posed by V. Kannan. ([1] Page 158.

  4. Eisenhart lift for higher derivative systems

    CERN Document Server

    Galajinsky, Anton

    2016-01-01

    The Eisenhart lift provides an elegant geometric description of a dynamical system of second order in terms of null geodesics of the Brinkmann-type metric. In this work, we attempt to generalize the Eisenhart method so as to encompass higher derivative models. The analysis relies upon Ostrogradsky's Hamiltonian. A consistent geometric description seems feasible only for a particular class of potentials. The scheme is exemplified by the Pais-Uhlenbeck oscillator.

  5. On Butterfly effect in Higher Derivative Gravities

    CERN Document Server

    Alishahiha, Mohsen; Naseh, Ali; Taghavi, Seyed Farid

    2016-01-01

    We study butterfly effect in $D$-dimensional gravitational theories containing terms quadratic in Ricci scalar and Ricci tensor. One observes that due to higher order derivatives in the corresponding equations of motion there are two butterfly velocities. The velocities are determined by the dimension of operators whose sources are provided by the metric. The three dimensional TMG model is also studied where we get two butterfly velocities at generic point of the moduli space of parameters. At critical point two velocities coincide.

  6. A Facile Synthesis of Pyrrolidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    SHAO Zhi-Hui; CHEN Jing-Bo; WANG Cheng-Ying; LIU Xiao-Long; REN Zhou-Yang; TU Yong-Qiang; ZHANG Hong-Bin

    2003-01-01

    @@ The Amaryllidaceae alkaloids have attracted considerable attention for their interesting biological activities. [1] Many of these tyrosine derived alkaloids[2] incorporate a hexahydroindole moiety in the structural skeletons. New approaches towards the synthesis of hexahydroindole core have been a topical interest for the synthetic community.Herein we report an experimentally very simple method for the synthesis of hexahydroindole by aminocylization. Four kinds of N-substituted have been demonstrate to be effective to this cyclization. The results were summarized in Figure 1.

  7. Eosinophil secretion of granule-derived cytokines

    Directory of Open Access Journals (Sweden)

    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  8. Higher derivative super Yang-Mills theories

    NARCIS (Netherlands)

    Bergshoeff, E.; Rakowski, M.; Sezgin, E.

    1987-01-01

    The most general higher derivative Yang-Mills actions of the type (F^2 + α^2F^4) which are globally supersymmetric up to order α^2 in six- and ten-dimensional spacetimes are given. The F^4-terms turn out to occur in the combination α^2[tr F^4 - ¼(tr F^2)^2], where the trace is over the Lorentz i

  9. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  10. Einstein solvmanifolds with a simple Einstein derivation

    OpenAIRE

    Nikolayevsky, Y.

    2007-01-01

    The structure of a solvable Lie groups admitting an Einstein left-invariant metric is, in a sense, completely determined by the nilradical of its Lie algebra. We give an easy-to-check necessary and sufficient condition for a nilpotent algebra to be an Einstein nilradical whose Einstein derivation has simple eigenvalues. As an application, we classify filiform Einstein nilradicals (modulo known classification results on filiform graded Lie algebras).

  11. Nile Blue derivatives as lysosomotropic photosensitizers

    Science.gov (United States)

    Lin, Chi-Wei; Shulok, Janine R.; Kirley, S. D.; Cincotta, Louis; Foley, James W.

    1991-06-01

    The benzophenoxazines, including several Nile blue analogues, are a unique group of dyes that localize selectively in animal tumors. Chemical modifications of Nile blue A can yield derivatives with high 1O2 quantum yields. These derivatives represent a group of potentially effective photosensitizers for selective phototherapy of malignant tumors. In vitro evaluation of these derivatives has indicated that those with high 1O2 yields are very effective in mediating the photocytotoxicity of tumor cells. This photodynamic effect is most likely mediated through the action of 1O2, since photoirradiation under D2O enhanced and under hypoxic conditions diminished the photocytotoxic action. The subcellular localization of these photosensitizers in bladder tumor cells in culture was examined by light and fluorescence microscopies as well as by histochemical and biochemical studies. The results indicate that these dyes are localized primarily in the lysosome. The cellular uptake and retention of these dyes is energy- and pH-dependent. Agents such as nigericin, which alter the transmembrane pH gradient, reduced uptake and enhanced efflux of the dyes, while agents such as valinomycin, which reduce cellular membrane potential, had no effect on the uptake. These findings are consistent with having ion-trapping as the mechanism for the uptake of these dyes. Photoirradiation of sensitizer-treated cells obliterated lysosomes in a light-dose and drug-dose dependent fashion. Release of the hydrolytic enzymes may be the main cause for subsequent cell death since the cytolytic effect was reduced by a specific inhibitor of lysosomal proteolytic enzyme. A lysosomotropic photosensitization mechanism is therefore proposed for the photocytotoxic action of the Nile blue derivatives. This mechanism may provide an approach to the development of new photosensitizers for the effective and selective destruction of malignant tumors.

  12. Particle production in higher derivative theory

    Indian Academy of Sciences (India)

    G P Singh; A Beesham; R V Deshpande

    2000-05-01

    The effect of particle production on the evolution of the spatially flat Friedmann–Lemaitre–Robertson–Walker cosmological model during the early stages of the universe is analysed in the framework of higher derivative theory. The universe has been considered as an open thermodynamic system where particle production gives rise to a supplementary negative creation pressure in addition to the thermodynamic pressure. The dynamical behaviour of both exponential as well as power law solutions have been discussed.

  13. TD-DFT Study on Pyrazoline Derivatives

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The molecular structures of ground state and first single excited state for pyrazoline derivatives are optimized with DFT B3LYP method and ab initio "configuration interaction with single excitations"(CIS) method, respectively. The frontier molecular orbital characteristics have been analyzed systematically, and the electronic transition mechanism has been discussed. Electronic spectra are calculated by using TD-DFT method. These results are consistent with those from the experiment.

  14. Time-delay and fractional derivatives

    OpenAIRE

    Tenreiro Machado JA

    2011-01-01

    This paper proposes the calculation of fractional algorithms based on time-delay systems. The study starts by analyzing the memory properties of fractional operators and their relation with time delay. Based on the Fourier analysis an approximation of fractional derivatives through time-delayed samples is developed. Furthermore, the parameters of the proposed approximation are estimated by means of genetic algorithms. The results demonstrate the feasibility of the new perspective.

  15. Two Unusual Flavanol Derivatives from Brainea insignis

    Institute of Scientific and Technical Information of China (English)

    杨明惠; 蔡乐; 沈晓静; 赵冕; 尹田鹏; 丁中涛

    2012-01-01

    Two new flavanol derivatives, bearing phenylpropionic acid moiety at C-4 through a C--C bonding, named brainin B (1) and brainin C (2), were isolated from Brainea insignis. Their structures were elucidated by NMR and MS spectrometry, Brainins B and C were tested for their antioxidant properties in DPPH (2,2-diphenyl-l-picryl- hydrazyl) radical scavenging, and both compounds displayed potent antioxidant activities.

  16. Literature Review of Polymer Derived Ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Reuben James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-25

    Polymer Derived Ceramics (PDCs), also known as preceramic polymers, are valuable coating agents that are used to produce surface barriers on substrates such as stainless steel. These barriers protect against a multitude of environmental threats, and have been used since their research and development in 19772. This paper seeks to review and demonstrate the remarkable properties and versatility that PDCs have to offer, while also giving a brief overview of the processing techniques used today.

  17. Measurements of brain-derived neurotrophic factor

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Klein, Anders Bue; Vinberg, Maj;

    2007-01-01

    Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing...... reproducibility. Female gender is associated with higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF Val66Met polymorphism were un-associated....

  18. Photopolymerization induced by a benzophenone derivative photoinitiator

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A benzophenone derivative photoinitiator, HBP-TDI-HQ-TDI-HBP (HTCTH), was synthesized based on 4-hydroxy benzophenone (HBP), toluene-2,4-diisocyanate (TDI) and hydroquinone (HQ). HTCTH was a more effective photoinitiator which had longer wavelength absorption in the UV-vis absorption spectra than the low molecular counterpart benzophenone (BP). It showed that both rate of polymerization (Rp) and final conversion (P) increased with increase of amine and HTCTH concentration in photopolymerization.

  19. Synthesis of new 2-quinazolylacetonitrile derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hwan; Min, Kyung Su [Yeungnam Univ., Gyongsan (Korea, Republic of)

    2001-12-01

    2-Quinazolylacetonitrile derivatives containing H-chelate have been synthesized from 2-cyanomethylquinazoline using electrophiles such as 4-chloroquinazoline, 4-chloro-2-phenylquinazoline, 4,6-dichloropyrimidine, 4,6-dichloro-2-phenylpyrimidine, 4,6-dichloro-5-phenylpyrimidine, 2-chloroquinoxaline, 1,3-dichloroisoquinoline, 2,6-dichloropyrazine and 4,6-dichloro-2,5-diphenylpyrimidine. These H-chelates may serve as a polymethine chromophore system. Structures of the target molecules were identified by spectral methods.

  20. A new bibenzyl derivative from Pleione bulbocodioides

    Institute of Scientific and Technical Information of China (English)

    Xin Qiao Liu; Qiao Yu Yuan; Yuan Qiang Guo

    2008-01-01

    A new bibenzyl derivative 1, named 2-(4"-hydrixybenzyl)-3-(3'-hydroxyphenethyl)-5-methoxy-cyclohexa-2,5-diene-1,4-dione, and two known stilbenoids (2, 3) were isolated from the tubers of Pleione bulbocodioides (Franch.) Rolfe. Their structureswere elucidated by spectroscopic methods.2008 Xin Qiao Liu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  1. The Synthesis of 6-Alkyl-5-Fluorouracil Derivatives

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    6-alkyl-5-fluorouracil derivatives (5a~5f) were synthesized by facile alkylation of lithiation of 5-fluorouracil derivatives with mthyl iodide (MeI) or alkyl trifluoromethanesulfonate (ROTf) in yield of 42~58%. We found that the methylated product was ethyl-substituted derivatives, not methyl-substituted derivatives.

  2. On Functional Inequalities Originating from Module Jordan Left Derivations

    Directory of Open Access Journals (Sweden)

    Ick-Soon Chang

    2008-06-01

    Full Text Available We first examine the generalized Hyers-Ulam stability of functional inequality associated with module Jordan left derivation (resp., module Jordan derivation. Secondly, we study the functional inequality with linear Jordan left derivation (resp., linear Jordan derivation mapping into the Jacobson radical.

  3. 14 CFR 1203.500 - Use of derivative classification.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Use of derivative classification. 1203.500... PROGRAM Derivative Classification § 1203.500 Use of derivative classification. The application of derivative classification markings is a responsibility of those who incorporate, paraphrase, restate,...

  4. On Functional Inequalities Originating from Module Jordan Left Derivations

    Directory of Open Access Journals (Sweden)

    Kang Sheon-Young

    2008-01-01

    Full Text Available Abstract We first examine the generalized Hyers-Ulam stability of functional inequality associated with module Jordan left derivation (resp., module Jordan derivation. Secondly, we study the functional inequality with linear Jordan left derivation (resp., linear Jordan derivation mapping into the Jacobson radical.

  5. On Functional Inequalities Originating from Module Jordan Left Derivations

    OpenAIRE

    Kang Sheon-Young; Chang Ick-Soon; Kim Hark-Mahn

    2008-01-01

    Abstract We first examine the generalized Hyers-Ulam stability of functional inequality associated with module Jordan left derivation (resp., module Jordan derivation). Secondly, we study the functional inequality with linear Jordan left derivation (resp., linear Jordan derivation) mapping into the Jacobson radical.

  6. 77 FR 7028 - Changes To Implement Derivation Proceedings

    Science.gov (United States)

    2012-02-10

    ... Patent and Trademark Office 37 CFR Part 42 RIN 0651-AC74 Changes To Implement Derivation Proceedings... the provisions of the Leahy- Smith America Invents Act that create a new derivation proceeding to be... administrative proceeding called a derivation proceeding. Derivation proceedings were created to ensure that...

  7. EVALUATION OF ANTIOXIDANT POTENTIAL OF PYRAZOLONE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. Mariappan

    2010-06-01

    Full Text Available In this article the antioxidant property of pyrazolones derivatives (PYZ1 to PYZ10 are reported. It was assessed by estimation of Malonaldehyde (MDA and 4-Hydroxyl-2-noneal (4-HNE as lipid peroxidation markers in myocardial ischemic reperfusion injury. The inhibition of lipid peroxidation was compared with the standard ascorbic acid. Among synthesized derivatives PYZ2, PYZ3, PYZ7, PYZ8, PYZ9, and PYZ10 were found to have potent antioxidant effect against MDA marker. In case of 4-HNE, PYZ4, PYZ5, PYZ6, PYZ7, PYZ8, PYZ9 and PYZ10 were found to have effective antioxidant activity and the rest of the compounds are moderately active. Comparatively PYZ7, PYZ8, PYZ9 and PYZ10 are having effective role to control both MDA and 4-HNE generation. All the experimental data were statistically significant at p<0.05 level. Interestingly, beyond its NSAID property, this study explores the protective role of pyrazolone derivatives in ischemic heart injury.

  8. Healthy degenerate theories with higher derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Motohashi, Hayato [Kavli Institute for Cosmological Physics, The University of Chicago,Chicago, Illinois 60637 (United States); Noui, Karim [Laboratoire de Mathématiques et Physique Théorique,Université François Rabelais,Parc de Grandmont, 37200 Tours (France); Laboratoire APC - Astroparticule et Cosmologie,Université Paris Diderot Paris 7,75013 Paris (France); Suyama, Teruaki [Research Center for the Early Universe (RESCEU), Graduate School of Science,The University of Tokyo, Tokyo 113-0033 (Japan); Yamaguchi, Masahide [Department of Physics, Tokyo Institute of Technology,2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551 (Japan); Langlois, David [Laboratoire APC - Astroparticule et Cosmologie,Université Paris Diderot Paris 7,75013 Paris (France)

    2016-07-20

    In the context of classical mechanics, we study the conditions under which higher-order derivative theories can evade the so-called Ostrogradsky instability. More precisely, we consider general Lagrangians with second order time derivatives, of the form L(ϕ{sup ¨a}, ϕ-dot {sup a},ϕ{sup a}; q-dot {sup i},q{sup i}) with a=1,⋯,n and i=1,⋯,m. For n=1, assuming that the q{sup i}’s form a nondegenerate subsystem, we confirm that the degeneracy of the kinetic matrix eliminates the Ostrogradsky instability. The degeneracy implies, in the Hamiltonian formulation of the theory, the existence of a primary constraint, which generates a secondary constraint, thus eliminating the Ostrogradsky ghost. For n>1, we show that, in addition to the degeneracy of the kinetic matrix, one needs to impose extra conditions to ensure the presence of a sufficient number of secondary constraints that can eliminate all the Ostrogradsky ghosts. When these conditions that ensure the disappearance of the Ostrogradsky instability are satisfied, we show that the Euler-Lagrange equations, which involve a priori higher order derivatives, can be reduced to a second order system.

  9. Forest Area Derivation from SENTINEL-1 Data

    Science.gov (United States)

    Dostálová, Alena; Hollaus, Markus; Milenković, Milutin; Wagner, Wolfgang

    2016-06-01

    The recently launched Sentinel-1A provides the high resolution Synthetic Aperture Radar (SAR) data with very high temporal coverage over large parts of European continent. Short revisit time and dual polarization availability supports its usability for forestry applications. The following study presents an analysis of the potential of the multi-temporal dual-polarization Sentinel-1A data for the forest area derivation using the standard methods based on Otsu thresholding and K-means clustering. Sentinel-1 data collected in winter season 2014-2015 over a test area in eastern Austria were used to derive forest area mask with spatial resolution of 10m and minimum mapping unit of 500 m2. The validation with reference forest mask derived from airborne full-waveform laser scanning data revealed overall accuracy of 92 % and kappa statistics of 0.81. Even better results can be achieved when using external mask for urban areas, which might be misclassified as forests when using the introduced approach based on SAR data only. The Sentinel-1 data and the described methods are well suited for forest change detection between consecutive years.

  10. Exosomes Derived from Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Bo Yu

    2014-03-01

    Full Text Available The functional mechanisms of mesenchymal stem cells (MSCs have become a research focus in recent years. Accumulating evidence supports the notion that MSCs act in a paracrine manner. Therefore, the biological factors in conditioned medium, including exosomes and soluble factors, derived from MSC cultures are being explored extensively. The results from most investigations show that MSC-conditioned medium or its components mediate some biological functions of MSCs. Several studies have reported that MSC-derived exosomes have functions similar to those of MSCs, such as repairing tissue damage, suppressing inflammatory responses, and modulating the immune system. However, the mechanisms are still not fully understood and the results remain controversial. Compared with cells, exosomes are more stable and reservable, have no risk of aneuploidy, a lower possibility of immune rejection following in vivo allogeneic administration, and may provide an alternative therapy for various diseases. In this review, we summarize the properties and biological functions of MSC-derived exosomes and discuss the related mechanisms.

  11. FOREST AREA DERIVATION FROM SENTINEL-1 DATA

    Directory of Open Access Journals (Sweden)

    A. Dostálová

    2016-06-01

    Full Text Available The recently launched Sentinel-1A provides the high resolution Synthetic Aperture Radar (SAR data with very high temporal coverage over large parts of European continent. Short revisit time and dual polarization availability supports its usability for forestry applications. The following study presents an analysis of the potential of the multi-temporal dual-polarization Sentinel-1A data for the forest area derivation using the standard methods based on Otsu thresholding and K-means clustering. Sentinel-1 data collected in winter season 2014-2015 over a test area in eastern Austria were used to derive forest area mask with spatial resolution of 10m and minimum mapping unit of 500 m2. The validation with reference forest mask derived from airborne full-waveform laser scanning data revealed overall accuracy of 92 % and kappa statistics of 0.81. Even better results can be achieved when using external mask for urban areas, which might be misclassified as forests when using the introduced approach based on SAR data only. The Sentinel-1 data and the described methods are well suited for forest change detection between consecutive years.

  12. Derivation of naive human embryonic stem cells.

    Science.gov (United States)

    Ware, Carol B; Nelson, Angelique M; Mecham, Brigham; Hesson, Jennifer; Zhou, Wenyu; Jonlin, Erica C; Jimenez-Caliani, Antonio J; Deng, Xinxian; Cavanaugh, Christopher; Cook, Savannah; Tesar, Paul J; Okada, Jeffrey; Margaretha, Lilyana; Sperber, Henrik; Choi, Michael; Blau, C Anthony; Treuting, Piper M; Hawkins, R David; Cirulli, Vincenzo; Ruohola-Baker, Hannele

    2014-03-25

    The naïve pluripotent state has been shown in mice to lead to broad and more robust developmental potential relative to primed mouse epiblast cells. The human naïve ES cell state has eluded derivation without the use of transgenes, and forced expression of OCT4, KLF4, and KLF2 allows maintenance of human cells in a naïve state [Hanna J, et al. (2010) Proc Natl Acad Sci USA 107(20):9222-9227]. We describe two routes to generate nontransgenic naïve human ES cells (hESCs). The first is by reverse toggling of preexisting primed hESC lines by preculture in the histone deacetylase inhibitors butyrate and suberoylanilide hydroxamic acid, followed by culture in MEK/ERK and GSK3 inhibitors (2i) with FGF2. The second route is by direct derivation from a human embryo in 2i with FGF2. We show that human naïve cells meet mouse criteria for the naïve state by growth characteristics, antibody labeling profile, gene expression, X-inactivation profile, mitochondrial morphology, microRNA profile and development in the context of teratomas. hESCs can exist in a naïve state without the need for transgenes. Direct derivation is an elusive, but attainable, process, leading to cells at the earliest stage of in vitro pluripotency described for humans. Reverse toggling of primed cells to naïve is efficient and reproducible.

  13. Naturally Occurring Cinnamic Acid Sugar Ester Derivatives

    Directory of Open Access Journals (Sweden)

    Yuxin Tian

    2016-10-01

    Full Text Available Cinnamic acid sugar ester derivatives (CASEDs are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3′,6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM, presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae. This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

  14. Healthy degenerate theories with higher derivatives

    Science.gov (United States)

    Motohashi, Hayato; Noui, Karim; Suyama, Teruaki; Yamaguchi, Masahide; Langlois, David

    2016-07-01

    In the context of classical mechanics, we study the conditions under which higher-order derivative theories can evade the so-called Ostrogradsky instability. More precisely, we consider general Lagrangians with second order time derivatives, of the form L(̈phia, dot phia, phia; qi, qi) with a = 1,⋯,n and i = 1,⋯,m. For n = 1, assuming that the qi's form a nondegenerate subsystem, we confirm that the degeneracy of the kinetic matrix eliminates the Ostrogradsky instability. The degeneracy implies, in the Hamiltonian formulation of the theory, the existence of a primary constraint, which generates a secondary constraint, thus eliminating the Ostrogradsky ghost. For n > 1, we show that, in addition to the degeneracy of the kinetic matrix, one needs to impose extra conditions to ensure the presence of a sufficient number of secondary constraints that can eliminate all the Ostrogradsky ghosts. When these conditions that ensure the disappearance of the Ostrogradsky instability are satisfied, we show that the Euler-Lagrange equations, which involve a priori higher order derivatives, can be reduced to a second order system.

  15. P-Splines Using Derivative Information

    KAUST Repository

    Calderon, Christopher P.

    2010-01-01

    Time series associated with single-molecule experiments and/or simulations contain a wealth of multiscale information about complex biomolecular systems. We demonstrate how a collection of Penalized-splines (P-splines) can be useful in quantitatively summarizing such data. In this work, functions estimated using P-splines are associated with stochastic differential equations (SDEs). It is shown how quantities estimated in a single SDE summarize fast-scale phenomena, whereas variation between curves associated with different SDEs partially reflects noise induced by motion evolving on a slower time scale. P-splines assist in "semiparametrically" estimating nonlinear SDEs in situations where a time-dependent external force is applied to a single-molecule system. The P-splines introduced simultaneously use function and derivative scatterplot information to refine curve estimates. We refer to the approach as the PuDI (P-splines using Derivative Information) method. It is shown how generalized least squares ideas fit seamlessly into the PuDI method. Applications demonstrating how utilizing uncertainty information/approximations along with generalized least squares techniques improve PuDI fits are presented. Although the primary application here is in estimating nonlinear SDEs, the PuDI method is applicable to situations where both unbiased function and derivative estimates are available.

  16. Affinity of guanosine derivatives for polycytidylate revisited

    Science.gov (United States)

    Kanavarioti, A.; Hurley, T. B.; Baird, E. E.

    1995-01-01

    Evidence is presented for complexation of guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) with polycytidylate (poly(C)) at pH 8.0 and 23 degrees C in the presence of 1.0 M NaCl2 and 0.2 M MgCl2 in water. The association of 2-MeImpG with poly(C) was investigated using UV-vis spectroscopy as well as by monitoring the kinetics of the nucleophilic substitution reaction of the imidazole moiety by amines. The results of both methods are consistent with moderately strong poly(C) 2-MeImpG complexation and the spectrophotometric measurements allowed the construction of a binding isotherm with a concentration of 2-MeImpG equal to 5.55 +/- 0.15 mM at half occupancy. UV spectroscopy was employed to establish the binding of other guanosine derivatives on poly(C). These derivatives are guanosine 5'-monophosphate (5'GMP), guanosine 5'-monophosphate imidazolide (ImpG), and guanosine 5'-monophosphate morpholidate (morpG). Within experimental error these guanosine derivatives exhibit the same affinity for poly(C) as 2-MeImpG.

  17. Peano on derivative of measures, strict derivative of distributive set functions

    CERN Document Server

    Greco, Gabriele H; Pagani, Enrico M

    2010-01-01

    By retracing research on coexistent magnitudes (grandeurs coexistantes) by Cauchy (1841), Peano in "Applicazioni geometriche del calcolo infinitesimale" (1887) defines the "density" (strict derivative) of a "mass" (a distributive set function) with respect to a "volume" (a positive distributive set function), proves its continuity (whenever the strict derivative exists) and shows the validity of the mass-density paradigm: "mass" is recovered from "density" by integration with respect to "volume". It is remarkable that Peano's strict derivative provides a consistent mathematical ground to the concept of "infinitesimal ratio" between two magnitudes, successfully used since Kepler. In this way the classical (i.e., pre-Lebesgue) measure theory reaches a complete and definitive form in Peano's Applicazioni geometriche. A primary aim of the present paper is a detailed exposition of Peano's work of 1887 leading to the concept of strict derivative of distributive set functions and their use. Moreover, we compare Pean...

  18. Local and 2-Local derivations on noncommutative Arens algebras

    CERN Document Server

    Ayupov, Sh A; Nurjanov, B O; Alauatdinov, A K

    2011-01-01

    The paper is devoted to so-called local and 2-local derivations on the noncommutative Arens algebra $L^\\omega(M, \\tau)$ associated with a von Neumann algebra $M$ and a faithful normal semi-finite trace $\\tau.$ We prove that every 2-local derivation on $L^\\omega(M, \\tau)$ is a spatial derivation, and if $M$ is a finite von Neumann algebra, then each local derivation on $L^\\omega(M, \\tau)$ is also a spatial derivation and every 2-local derivation on $M$ is in fact an inner derivation.

  19. Biologic rhythms derived from Siberian mammoths' hairs.

    Directory of Open Access Journals (Sweden)

    Mike Spilde

    Full Text Available Hair is preserved for millennia in permafrost; it enshrines a record of biologic rhythms and offers a glimpse at chronobiology as it was in extinct animals. Here we compare biologic rhythms gleaned from mammoth's hairs with those of modern human hair. Four mammoths' hairs came from varying locations in Siberia 4600 km, four time zones, apart ranging in age between 18,000 and 20,000 years before present. We used two contemporaneous human hairs for comparison. Power spectra derived from hydrogen isotope ratios along the length of the hairs gave insight into biologic rhythms, which were different in the mammoths depending on location and differed from humans. Hair growth for mammoths was ∼31 cms/year and ∼16 cms/year for humans. Recurrent annual rhythms of slow and fast growth varying from 3.4 weeks/cycles to 8.7 weeks/cycles for slow periods and 1.2 weeks/cycles to 2.2 weeks/cycles for fast periods were identified in mammoth's hairs. The mineral content of mammoth's hairs was measured by electron microprobe analysis (k-ratios, which showed no differences in sulfur amongst the mammoth hairs but significantly more iron then in human hair. The fractal nature of the data derived from the hairs became evident in Mandelbrot sets derived from hydrogen isotope ratios, mineral content and geographic location. Confocal microscopy and scanning electron microscopy showed varied degrees of preservation of the cuticle largely independent of age but not location of the specimens. X-ray fluorescence microprobe and fluorescence computed micro-tomography analyses allowed evaluation of metal distribution and visualization of hollow tubes in the mammoth's hairs. Seasonal variations in iron and copper content combined with spectral analyses gave insights into variation in food intake of the animals. Biologic rhythms gleaned from power spectral plots obtained by modern methods revealed life style and behavior of extinct mega-fauna.

  20. Stemness is derived from thyroid cancer cells

    Directory of Open Access Journals (Sweden)

    Risheng eMa

    2014-07-01

    Full Text Available Background: One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs. Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT from malignant cells since EMT is known to confer stem-like characteristics. Methods: To examine the status of stemness in thyroid papillary cancer we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E/TPO-Cre. This construct is only activated at the time of thyroid peroxidase (TPO expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells which do not express TPO.Results: There was decreased expression of thyroid specific genes such as Tg and NIS and increased expression of stemness markers such as Oct4, Rex1, CD15 and Sox2 in the thyroid carcinoma tissue from 6 week old BRAFV600E mice. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a derived cancer thyroid cell line in which overexpression of Snail caused up-regulation of vimentin expression and up regulation of stemness markers Oct4, Rex1, CD15 with enhanced migration ability of the cells. Conclusions: Our findings support our earlier hypothesis that stemness in thyroid cancer is derived via EMT rather than from resident thyroid stem cells. In mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E/TPO-Cre the neoplastic changes were dependent on thyroid cell differentiation and the onset of stemness must have been derived from differentiated thyroid epithelial cells.

  1. Properties of frequentist confidence levels derivatives

    CERN Document Server

    Martínez, Miriam Lucio; Dettori, Francesco

    2016-01-01

    In high energy physics, results from searches for new particles or rare processes are often reported using a modified frequentist approach, known as $\\rm{CL_s}$ method. In this paper, we study the properties of the derivatives of $\\rm{CL_s}$ and $\\rm{CL_{s+b}}$ as signal strength estimators if the confidence levels are interpreted as credible intervals. Our approach allows obtaining best fit points and $\\chi^2$ functions which can be used for phenomenology studies. In addition, this approach can be used to incorporate $\\rm{CL_s}$ results into Bayesian combinations.

  2. N-Salicylideneamine Derivatives with TEMPO Substituents

    Directory of Open Access Journals (Sweden)

    Shin’ichi Nakatsuji

    2004-08-01

    Full Text Available Three N-salicylideneamine derivatives bearing TEMPO (2,2,6,6-tetra- methyl-1-piperidinyloxy substituents were prepared in order to study their structure and property relationships and to investigate the possibilities of the existence of heat and/or light responsive magnetic properties. Curie-Weiss behavior with weak ferromagnetic intermolecular spin-spin interactions was observed in one of the radicals, while antiferromagnetic interactions were predominant for the other radicals and the structure-property relationships were investigated for the radical compounds from their crystal structures obtained by X-ray analyses. Preliminary results of the examination of their responses towards light and heat are also described.

  3. Cationically polymerizable monomers derived from renewable sources

    Energy Technology Data Exchange (ETDEWEB)

    Crivello, J.V.

    1992-10-01

    The objectives of this project are to design and synthesize novel monomers which orginate from renewable biological sources and to carry out their rapid, efficient, pollution-free and energy efficient cationic polymerization to useful products under the influence of ultraviolet light or heat. A summary of the results of the past year's research on cationically polymerizable monomers derived from renewable sources is presented. Three major areas of investigation corresponding to the different classes of naturally occurring starting materials were investigated; epoxidized terpenes and natural rubber and vinyl ethers from alcohols and carbohydrates.

  4. [A new eremophilane derivative from Senecio dianthus].

    Science.gov (United States)

    Han, He-Dong; Hu, Hai-Qing; Li, Yan; Wang, Xiao-Ling

    2013-10-01

    A new eremophilane derivative, 4,5,11-trimethyl-9( 10), 7 ( 11) -eremophiladien-8-keto-12-carboxylic acid-beta-D-glucopyranoside( which named dianthuside A) 1 and four known compounds, 5,7,4'-trihydroxy-flavonone-3-0-beta-D-glucoside (2), quercetin-3-0-beta-D-glucoside(3) ,hyperin(4) and rutin(5) have been isolated from the aerial part of Senecio dianthus. Their structures were elucidated by physicochemical properties and spectroscopic data analysis. Compounds 2, 4 and 5 were isolated from this plant for the first time.

  5. Sesquiterpenoid derivatives from Ferula ferulaeoides (Steud.) Korov.

    Science.gov (United States)

    Meng, He; Li, Guoyu; Huang, Jian; Zhang, Ke; Wei, Xiuyan; Ma, Yueping; Zhang, Cui; Wang, Jinhui

    2013-02-01

    Eight sesquiterpenoids, named Ferulaeone A-H (1-8), and seven known sesquiterpenoid derivatives were isolated from the roots of Ferula ferulaeoides (Steud.) Korov. Their structures were established by comprehensive spectroscopic analysis, and biosynthetic pathways leading to these compounds were proposed. The cytotoxicity of all these isolates against HepG2, MCF-7, and C6 cancer cell lines was evaluated and compounds 6-11, 13 exihibited various degrees of cytotoxic effect. Among them, compounds 9-11 displayed the highest potency against C6 with IC(50) values 34, 36, and 31 μM, respectively.

  6. Synthesis and Pharmacological Activity of Diterpenylnaphthoquinone Derivatives

    Directory of Open Access Journals (Sweden)

    Guillermo Schmeda-Hirschmann

    2011-10-01

    Full Text Available New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5, gastric epithelial adenocarcinoma (AGS, and hepatocellular carcinoma (Hep G2. Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells.

  7. Nanocomposites Derived from Polymers and Inorganic Nanoparticles

    Directory of Open Access Journals (Sweden)

    In-Yup Jeon

    2010-06-01

    Full Text Available Polymers are considered to be good hosting matrices for composite materials because they can easily be tailored to yield a variety of bulk physical properties. Moreover, organic polymers generally have long-term stability and good processability. Inorganic nanoparticles possess outstanding optical, catalytic, electronic and magnetic properties, which are significantly different their bulk states. By combining the attractive functionalities of both components, nanocomposites derived from organic polymers and inorganic nanoparticles are expected to display synergistically improved properties. The potential applications of the resultant nanocomposites are various, e.g. automotive, aerospace, opto-electronics, etc. Here, we review recent progress in polymer-based inorganic nanoparticle composites.

  8. Analytically Derived Wind Wave Growth Relations

    Institute of Scientific and Technical Information of China (English)

    管长龙; 孙群

    2002-01-01

    By the use of the 3/2 power law presented by Toba combined with the significant wave energy balance equation forwind wave, wind wave growth at a limited fetch is analytically investigated. The new wind wave growth relations(WWGRs) are analytically derived with sheltering coefficient and wind drag coefficient as parameters. The geometricalaverage of observational values of sheltering coefficient and the arithmetic average of observational values of wind drag co-efficient are applied to determine the new WWGRs. Comparisons with existing empirical WWGRs are made.

  9. Photoelectrochemical Properties of Graphene and Its Derivatives

    Directory of Open Access Journals (Sweden)

    Alberto Adán-Más

    2013-07-01

    Full Text Available Graphene and its derivatives combine a numerous range of supreme properties that can be useful in many applications. The purpose of this review is to analyse the photoelectrochemical properties of pristine graphene, graphene oxide (GO and reduced graphene oxide (rGO and their impact on semiconductor catalysts/quantum dots. The mechanism that this group of materials follows to improve their performance will be cleared by explaining how those properties can be exploited in several applications such as photo-catalysts (degradation of pollutants and photovoltaics (solar cells.

  10. Catalysts derived from waste slag for transesterification

    Institute of Scientific and Technical Information of China (English)

    Xiaowei Zhang; Wei Huang

    2011-01-01

    MgO-CaO/SiO2 solid catalysts derived from waste slag (WS) of metal magnesium plant were prepared.The catalytic performances were evaluated in the transesterification of rapeseed oil with methanol to biodiesel in a 500 mL three-necked reactor under atmospheric pressure.The basic strengh of the catalyst reached 22.0 measured by indicators accroding to Hammett scale.The results show that the MgO-CaO/SiO2 is an excellent catalyst for transesterification, and the conversion of rapeseed oil reach 98% under the optimum condition.

  11. Black holes in higher derivative gravity.

    Science.gov (United States)

    Lü, H; Perkins, A; Pope, C N; Stelle, K S

    2015-05-01

    Extensions of Einstein gravity with higher-order derivative terms arise in string theory and other effective theories, as well as being of interest in their own right. In this Letter we study static black-hole solutions in the example of Einstein gravity with additional quadratic curvature terms. A Lichnerowicz-type theorem simplifies the analysis by establishing that they must have vanishing Ricci scalar curvature. By numerical methods we then demonstrate the existence of further black-hole solutions over and above the Schwarzschild solution. We discuss some of their thermodynamic properties, and show that they obey the first law of thermodynamics.

  12. VARIOUS APPROACHES FOR SYNTHESIS OF IMIDAZOLE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    Bharti Ashish

    2011-04-01

    Full Text Available Imidazole, a five-membered heterocycle having three carbon atoms, two nitrogen atoms, and two double bonds, having efficient antimalarial, anti-inflammatory, antibacterial activity against Escherichia coil, Staphylococcus aureus and Pseudomonas aeruginosa, anti-cancer, mutagenic activity against Salmonella typhimurium, antifungal, antimicrobial, insecticidal, anti-allergic activity etc. The presence of heterocyclic structures exerts various physiologic effects on the body. In the present study we have reviewed several newer approches of synthesizing the substituted imidazole derivatives via catalytic reaction & by the application of various suitable reagents.

  13. Adipose derived stem cells and nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Alessandro Faroni; Richard JP Smith; Adam J Reid

    2014-01-01

    Injuries to peripheral nerves are common and cause life-changing problems for patients along-side high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacriifcing a section of nerve from elsewhere in the body to pro-vide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacriifce of a functional nerve. Stem cells are prime candidates as accelerators of re-generation in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.

  14. Derivation of an applied nonlinear Schroedinger equation

    Energy Technology Data Exchange (ETDEWEB)

    Pitts, Todd Alan [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Laine, Mark Richard [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Schwarz, Jens [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Rambo, Patrick K. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Karelitz, David B. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    We derive from first principles a mathematical physics model useful for understanding nonlinear optical propagation (including filamentation). All assumptions necessary for the development are clearly explained. We include the Kerr effect, Raman scattering, and ionization (as well as linear and nonlinear shock, diffraction and dispersion). We explain the phenomenological sub-models and each assumption required to arrive at a complete and consistent theoretical description. The development includes the relationship between shock and ionization and demonstrates why inclusion of Drude model impedance effects alters the nature of the shock operator. Unclassified Unlimited Release

  15. A Simplified Procedure for Safety Requirements Derivation

    Directory of Open Access Journals (Sweden)

    Eugen Ioan Gergely

    2008-05-01

    Full Text Available The paper develops a procedure for analysis of PLC-controlled system risk due to component failure and for derivation of safety integrity requirements for components, focusing on software requirements. The approach allows fully integrated treatment of random and systematic failure. It can be applied at different levels of design detail and at different stages of the system development lifecycle. The procedure does not address how to assess failure rates, but provides a foundation for integrating PLC software assessment into system riskassessment and for making trade-offs in design.

  16. Boundary layer heights derived from velocity spectra

    Energy Technology Data Exchange (ETDEWEB)

    Hoejstrup, J.; Barthelmie, R.J. [Risoe National Lab., Roskilde (Denmark); Kaellstrand, B. [Univ. of Uppsala, Uppsala (Sweden)

    1997-10-01

    It is a well-known fact that the height of the mixed layer determines the size of the largest and most energetic eddies that can be observed in the unstable boundary layer, and consequently a peak can be observed in the power spectra of the along-wind velocity component at scales comparable to the mixed layer depth. We will now show how the mixed layer depth can be derived from the u-specta and the results will be compared with direct measurements using pibal and tethersonde measurements. (au)

  17. A new selaginellin derivative from Selaginella pulvinata.

    Science.gov (United States)

    Cao, Yuan; Wu, Yong-Ping; Duan, Jin-Ao

    2015-02-01

    Abstract: A new selaginellin derivative named as selaginellin S (1) was isolated from the whole plants of Selaginella pulvinata (Hook. et Grev.) Maxim. (Selaginellaceae), together with a known one (selaginellin M, 2). Compounds 1 and 2 were separated and purified by silica gel and Sephadex LH-20 column chromatography. Their structures were determined on the basis of extensive spectroscopic analysis including IR, MS, 1D and 2D NMR experiments, as well as ECD calculations. Compound 1 is a key intermidiant in the biosynthesis pathway of selaginellins. Compound 2 is first reported in this plant.

  18. Derivation of an Applied Nonlinear Schroedinger Equation.

    Energy Technology Data Exchange (ETDEWEB)

    Pitts, Todd Alan; Laine, Mark Richard; Schwarz, Jens; Rambo, Patrick K.; Karelitz, David B.

    2015-01-01

    We derive from first principles a mathematical physics model useful for understanding nonlinear optical propagation (including filamentation). All assumptions necessary for the development are clearly explained. We include the Kerr effect, Raman scattering, and ionization (as well as linear and nonlinear shock, diffraction and dispersion). We explain the phenomenological sub-models and each assumption required to arrive at a complete and consistent theoretical description. The development includes the relationship between shock and ionization and demonstrates why inclusion of Drude model impedance effects alters the nature of the shock operator. Unclassified Unlimited Release

  19. Derivational and Semantic Relations of Croatian Verbs

    Directory of Open Access Journals (Sweden)

    Krešimir Šojat

    2012-12-01

    Full Text Available This paper deals with certain morphosemantic relations between Croatian verbs and discusses their inclusion in Croatian WordNet. The morphosemantic relations in question are the semantic relations between unprefixed infinitives and their prefixed derivatives. We introduce the criteria for the division of aspectual pairs and further discuss verb prefixation which results in combinations of prefixes and base forms that can vary in terms of meaning from compositional to completely idiosyncratic. The focus is on the regularities in semantic modifications of base forms modified by one prefix. The aim of this procedure is to establish a set of morphosemantic relations based on regular or reoccuring meaning alternations.

  20. Medicinal Chemistry Perspective of Fused Isoxazole Derivatives.

    Science.gov (United States)

    Barmade, Mahesh A; Murumkar, Prashant R; Sharma, Mayank Kumar; Yadav, Mange Ram

    2016-01-01

    Nitrogen containing heterocyclic rings with an oxygen atom is considered as one of the best combination in medicinal chemistry due to their diversified biological activities. Isoxazole, a five membered heterocyclic azole ring is found in naturally occuring ibetonic acid along with some of the marketed drugs such as valdecoxib, flucloxacillin, cloxacillin, dicloxacillin, and danazol. It is also significant for showing antipsychotic activity in risperidone and anticonvulsant activity in zonisamide, the marketed drugs. This review article covers research articles reported till date covering biological activity along with SAR of fused isoxazole derivatives.