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Sample records for analogue induces apoptosis-like

  1. Leishmania donovani: intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells.

    Science.gov (United States)

    Sen, Nilkantha; Das, Benu Brata; Ganguly, Agneyo; Banerjee, Bijoylaxhmi; Sen, Tanusree; Majumder, Hemanta K

    2006-11-01

    Leishmaniasis presents a spectrum of diseases ranging from benign cutaneous lesions to the often-fatal visceralizing form. Luteolin, a dietary flavone induces apoptosis-like death in both promastigote and amastigote forms of Leishmania, the causative agent of the diseases. Here, we have elucidated the mechanism of action of luteolin by analyzing the mitochondrial and cytosolic changes associated with apoptosis-like death of leishmanial cells. In Leishmania donovani, treatment with luteolin induces the loss of both maxicircles and minicircles which resulted in the formation of dyskinetoplastid cells. The loss of mitochondrial DNA causes reduction in the activities of complex I, II, III, and IV of electron transport chain. However, the mitochondrial ATPase activity of complex V remains almost unaltered during treatment with luteolin but the sensitivity to oligomycin is lost. The inactivation of ETC complex is associated with decrease in mitochondrial as well as glycolytic ATP production, which is responsible for depolarization of Deltapsi(m) and alteration in mitochondrial structure. This event is followed by the release of cytochrome c from mitochondria in mt-DNA depleted leishmanial cells and causes an activation of caspase like proteases. Collectively our results provide the first insight into the mechanistic pathway of apoptosis-like death where inhibition of glycolytic ATP production is an essential event responsible for depolarization of Deltapsi(m) in mt-DNA depleted cells to propagate apoptosis-like death in leishmanial cells. PMID:16707127

  2. Praziquantel induced oxidative stress and apoptosis-like cell death in Raillietina echinobothrida.

    Science.gov (United States)

    Giri, Bikash Ranjan; Roy, Bishnupada

    2016-07-01

    Praziquantel (PZQ) is an anthelmintic drug used against trematode and cestode parasites of humans and veterinary animals. Since praziquantel was introduced as a broadspectrum anthelmintic, numerous studies described its successful use against helminth parasites, but its exact mechanism of action is feebly understood. Therefore, the present study was carried out to evaluate the possible role of PZQ induced oxidative stress in apoptosis-like cell death in the poultry tapeworm Raillietina echinobothrida. Parasite viability assay revealed a time-dependent reduction in the worm viability compared to the control. Transmission electron microscopy showed typical apoptotic features like condensed nucleus, damaged nuclear envelope and altered mitochondrial membrane in PZQ exposed parasites. Results revealed chromatin condensation and DNA fragmentation in PZQ exposed parasites. There was a notable decline in the level of glutathione and glutathione-s-transferase activity leading to the augmented generation of reactive oxygen species. This led to the alterations in the mitochondrial membrane potential with increased active caspase-3/7, confirms the involvement of mitochondria in the event. The present study suggests that PZQ exerts oxidative stress leading to apoptosis-like events in the parasites resulting their death. PMID:27005397

  3. Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae.

    Science.gov (United States)

    Muzaffar, Suhail; Bose, Chinchu; Banerji, Ashok; Nair, Bipin G; Chattoo, Bharat B

    2016-01-01

    Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. PMID:26381667

  4. Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

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    Anders P Hakansson

    Full Text Available BACKGROUND: Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. METHODOLOGY/PRINCIPAL FINDINGS: We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity to execute cell death. CONCLUSIONS/SIGNIFICANCE: Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.

  5. A Nanodot Array Modulates Cell Adhesion and Induces an Apoptosis-Like Abnormality in NIH-3T3 Cells

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    Hung Yao-Ching

    2009-01-01

    Full Text Available Abstract Micro-structures that mimic the extracellular substratum promote cell growth and differentiation, while the cellular reaction to a nanostructure is poorly defined. To evaluate the cellular response to a nanoscaled surface, NIH 3T3 cells were grown on nanodot arrays with dot diameters ranging from 10 to 200 nm. The nanodot arrays were fabricated by AAO processing on TaN-coated wafers. A thin layer of platinum, 5 nm in thickness, was sputtered onto the structure to improve biocompatibility. The cells grew normally on the 10-nm array and on flat surfaces. However, 50-nm, 100-nm, and 200-nm nanodot arrays induced apoptosis-like events. Abnormality was triggered after as few as 24 h of incubation on a 200-nm dot array. For cells grown on the 50-nm array, the abnormality started after 72 h of incubation. The number of filopodia extended from the cell bodies was lower for the abnormal cells. Immunostaining using antibodies against vinculin and actin filament was performed. Both the number of focal adhesions and the amount of cytoskeleton were decreased in cells grown on the 100-nm and 200-nm arrays. Pre-coatings of fibronectin (FN or type I collagen promoted cellular anchorage and prevented the nanotopography-induced programed cell death. In summary, nanotopography, in the form of nanodot arrays, induced an apoptosis-like abnormality for cultured NIH 3T3 cells. The occurrence of the abnormality was mediated by the formation of focal adhesions.

  6. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica

    Science.gov (United States)

    Pais-Morales, Jonnatan; Betanzos, Abigail; García-Rivera, Guillermina; Chávez-Munguía, Bibiana; Shibayama, Mineko; Orozco, Esther

    2016-01-01

    Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis. PMID:26731663

  7. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica.

    Science.gov (United States)

    Pais-Morales, Jonnatan; Betanzos, Abigail; García-Rivera, Guillermina; Chávez-Munguía, Bibiana; Shibayama, Mineko; Orozco, Esther

    2016-01-01

    Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound) on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis. PMID:26731663

  8. Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans

    Science.gov (United States)

    Movahed, Elaheh; Tan, Grace Min Yi; Munusamy, Komathy; Yeow, Tee Cian; Tay, Sun Tee; Wong, Won Fen; Looi, Chung Yeng

    2016-01-01

    Objectives: Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans. Methods: Minimal inhibitory concentration (MIC) of triclosan in different C. neoformans strains was first examined. The in vitro interactions between triclosan and two standard anti-fungal drugs (amphotericin B and fluconazole) were further evaluated by microdilution checkerboard assay. Mechanism of triclosan fungicidal activity was then investigated by viewing the cell morphology under transmission electron microscope. Results: We reported that triclosan potently inhibited the growth of C. neoformans. A combination of triclosan with amphotericin B or with fluconazole enhanced their fungicidal effects. Triclosan-treated C. neoformans displayed characteristics such as nuclear chromatin condensation, extensive intracellular vacuolation and mitochondrial swelling, indicating that triclosan triggered apoptosis-like cell death. Conclusion: In summary, our report suggests triclosan as an independent drug or synergent for C. neoformans treatment. PMID:27047474

  9. Resveratrol Induces Apoptosis-Like Death and Prevents In Vitro and In Vivo Virulence of Entamoeba histolytica.

    Directory of Open Access Journals (Sweden)

    Jonnatan Pais-Morales

    Full Text Available Entamoeba histolytica causes amoebiasis, an infection that kills 100,000 individuals each year. Metronidazole and its derivatives are currently used against this protozoan, but these drugs present adverse effects on human health. Here, we investigated the effect of resveratrol (a natural compound on E. histolytica trophozoites viability, as well as its influence on the parasite virulence. Trophozoites growth was arrested by 72 μM resveratrol and the IC50 was determined as 220 μM at 48 h. Cells appeared smaller, rounded and in clusters, with debris-containing vacuoles and with abnormally condensed chromatin. Resveratrol triggered reactive oxygen species production. It caused lipid peroxidation and produced phosphatidylserine externalization and DNA fragmentation this latter evidenced by TUNEL assays. It also provoked an increase of intracellular Ca2+ concentration, activated calpain and decreased superoxide dismutase activity, indicating that an apoptosis-like event occurred; however, autophagy was not detected. Cytopathic activity, phagocytosis, encystment and in vivo virulence were diminished dramatically by pre-incubation of trophozoites with resveratrol, evidencing that resveratrol attenuated the trophozoite virulence in vitro. Interestingly, after the inoculation of virulent trophozoites, animals treated with the drug did not develop or developed very small abscesses. Our findings propose that resveratrol could be an alternative to contend amoebiasis.

  10. Plumbagin, a plant-derived naphthoquinone metabolite induces mitochondria mediated apoptosis-like cell death in Leishmania donovani: an ultrastructural and physiological study.

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    Awasthi, Bhanu Priya; Kathuria, Manoj; Pant, Garima; Kumari, Neema; Mitra, Kalyan

    2016-08-01

    Naphthoquinones are known to exhibit a broad range of biological activities against microbes, cancer and parasitic diseases and have been widely used in Indian traditional medicine. Plumbagin is a plant-derived naphthoquinone metabolite (5-hydroxy-2-methyl-1,4-naphthoquinone) reported to inhibit trypanothione reductase, the principal enzyme and a validated drug target involved in detoxification of oxidative stress in Leishmania. Here, we report the mechanistic aspects of cell death induced by plumbagin including physiological effects in the promastigote form and ultrastructural alterations in both promastigote and amastigote forms of Leishmania donovani which till now remained largely unknown. Our observations show that oxidative stress induced by plumbagin resulted in depolarization of the mitochondrial membrane, depletion in ATP levels, elevation of cytosolic calcium, increase in caspase 3/7-like protease activity and lipid peroxidation in promastigotes. Apoptosis-like cell death induction post plumbagin treatment was confirmed by biochemical assays like Annexin V/FITC staining, TUNEL as well as morphological and ultrastructural studies. These findings collectively highlight the mode of action and importance of oxidative stress inducing agents in effectively killing both forms of the Leishmania parasite and opens up the possibility of exploring plumbagin and its derivatives as promising candidates in the chemotherapy of Leishmaniasis. PMID:27315817

  11. Caffeine-Induced Premature Chromosome Condensation Results in the Apoptosis-Like Programmed Cell Death in Root Meristems of Vicia faba.

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    Dorota Rybaczek

    Full Text Available We have demonstrated that the activation of apoptosis-like programmed cell death (AL-PCD was a secondary result of caffeine (CF induced premature chromosome condensation (PCC in hydroxyurea-synchronized Vicia faba root meristem cells. Initiation of the apoptotic-like cell degradation pathway seemed to be the result of DNA damage generated by treatment with hydroxyurea (HU [double-stranded breaks (DSBs mostly] and co-treatment with HU/CF [single-stranded breaks (SSBs mainly]. A single chromosome comet assay was successfully used to study different types of DNA damage (neutral variant-DSBs versus alkaline-DSBs or SSBs. The immunocytochemical detection of H2AXS139Ph and PARP-2 were used as markers for DSBs and SSBs, respectively. Acridine orange and ethidium bromide (AO/EB were applied for quantitative immunofluorescence measurements of dead, dying and living cells. Apoptotic-type DNA fragmentation and positive TUNEL reaction finally proved that CF triggers AL-PCD in stressed V. faba root meristem cells. In addition, the results obtained under transmission electron microscopy (TEM further revealed apoptotic-like features at the ultrastructural level of PCC-type cells: (i extensive vacuolization; (ii abnormal chromatin condensation, its marginalization and concomitant degradation; (iii formation of autophagy-like vesicles (iv protoplast shrinkage (v fragmentation of cell nuclei and (vi extensive degeneration of the cells. The results obtained have been discussed with respect to the vacuolar/autolytic type of plant-specific AL-PCD.

  12. Heat-Modified Citrus Pectin Induces Apoptosis-Like Cell Death and Autophagy in HepG2 and A549 Cancer Cells

    OpenAIRE

    Leclere, Lionel; Fransolet, Maude; Cote, Francois; Cambier, Pierre; Arnould, Thierry; Van Cutsem, Pierre; Michiels, Carine

    2015-01-01

    Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs...

  13. Rubrene analogues with the aggregation-induced emission enhancement behaviour

    DEFF Research Database (Denmark)

    Zhang, Xiaoxu; Sørensen, Jakob Kryger; Fu, Xiaowei;

    2014-01-01

    In the light of the principle of aggregation-induced emission enhancement (AIEE), the rubrene analogue with orange light-emitting properties is designed and synthesized by substituting the phenyl side groups of rubrene with thienyl groups. To the best of our knowledge, this is the first report on...

  14. An Electric Analogue to Gravity Induced Vacuum Dominance

    CERN Document Server

    Oikonomou, V K

    2013-01-01

    It is shown that when a strong electric field is turned on as a background in a charged scalar field, the vacuum state of the scalar field becomes exponentially amplified. This is an analogue to gravity induced vacuum amplification, where the vacuum state becomes exponentially amplified for some geometries.

  15. Antibacterial activity of curcumin via apoptosis-like response in Escherichia coli.

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    Yun, Dae Gyu; Lee, Dong Gun

    2016-06-01

    Curcumin, a naturally occurring phenolic compound, has been shown to exhibit antimicrobial activity against Candida albicans, Escherichia coli, Pseudomonas aeruginosa, etc., but the mechanism remains unclear. The present study was designed to investigate the novel antibacterial mechanism of curcumin that shows an apoptosis-like response in E. coli. We found that curcumin induces membrane damage at relatively high concentrations, but there was no effect at the minimum inhibitory concentration (MIC). At the MIC, curcumin-treated cells displayed various apoptotic markers such as reactive oxygen species (ROS) accumulation, membrane depolarization, and Ca(2+) influx. Expression of RecA protein, which mediates a bacterial apoptosis-like response, was also increased by curcumin. In order to evaluate the influence of RecA on the appearance of other apoptotic markers, phosphatidylserine (PS) exposure and DNA fragmentation were examined and compared with a RecA deletion strain (ΔRecA). These markers were detected in E. coli wild-type cells, but not in ΔRecA cells. In conclusion, our data demonstrate that curcumin induces an apoptosis-like response in E. coli that involves RecA. PMID:26960318

  16. The fusarium mycotoxin deoxynivalenol can inhibit plant apoptosis-like programmed cell death.

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    Mark Diamond

    Full Text Available The Fusarium genus of fungi is responsible for commercially devastating crop diseases and the contamination of cereals with harmful mycotoxins. Fusarium mycotoxins aid infection, establishment, and spread of the fungus within the host plant. We investigated the effects of the Fusarium mycotoxin deoxynivalenol (DON on the viability of Arabidopsis cells. Although it is known to trigger apoptosis in animal cells, DON treatment at low concentrations surprisingly did not kill these cells. On the contrary, we found that DON inhibited apoptosis-like programmed cell death (PCD in Arabidopsis cells subjected to abiotic stress treatment in a manner independent of mitochondrial cytochrome c release. This suggested that Fusarium may utilise mycotoxins to suppress plant apoptosis-like PCD. To test this, we infected Arabidopsis cells with a wild type and a DON-minus mutant strain of F. graminearum and found that only the DON producing strain could inhibit death induced by heat treatment. These results indicate that mycotoxins may be capable of disarming plant apoptosis-like PCD and thereby suggest a novel way that some fungi can influence plant cell fate.

  17. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina;

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...

  18. All-dielectric metasurface analogue of electromagnetically induced transparency.

    Science.gov (United States)

    Yang, Yuanmu; Kravchenko, Ivan I; Briggs, Dayrl P; Valentine, Jason

    2014-01-01

    Metasurface analogues of electromagnetically induced transparency (EIT) have been a focus of the nanophotonics field in recent years, due to their ability to produce high-quality factor (Q-factor) resonances. Such resonances are expected to be useful for applications such as low-loss slow-light devices and highly sensitive optical sensors. However, ohmic losses limit the achievable Q-factors in conventional plasmonic EIT metasurfaces to values <~10, significantly hampering device performance. Here we experimentally demonstrate a classical analogue of EIT using all-dielectric silicon-based metasurfaces. Due to extremely low absorption loss and coherent interaction of neighbouring meta-atoms, a Q-factor of 483 is observed, leading to a refractive index sensor with a figure-of-merit of 103. Furthermore, we show that the dielectric metasurfaces can be engineered to confine the optical field in either the silicon resonator or the environment, allowing one to tailor light-matter interaction at the nanoscale. PMID:25511508

  19. Nucleic Acid Analogue Induced Transcription of Double Stranded DNA

    DEFF Research Database (Denmark)

    1998-01-01

    RNA is transcribed from a double stranded DNA template by forming a complex by hybridizing to the template at a desired transcription initiation site one or more oligonucleic acid analogues of the PNA type capable of forming a transcription initiation site with the DNA and exposing the complex to...... displacement of one strand of the DNA locally by the PNA hybridization....

  20. Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

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    Michelle Visagie

    Full Text Available 2-Methoxyestradiol (2ME2 is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.

  1. Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro

    Science.gov (United States)

    Dechristopher, Brian A.; Loy, Brian A.; Marsden, Matthew D.; Schrier, Adam J.; Zack, Jerome A.; Wender, Paul A.

    2012-09-01

    Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the step-economical syntheses of seven members of a new family of designed bryostatin analogues using a highly convergent Prins-macrocyclization strategy. We also demonstrate for the first time that such analogues effectively induce latent HIV activation in vitro with potencies similar to or better than bryostatin. Significantly, these analogues are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current clinical candidate for latent virus induction. This study provides the first demonstration that designed, synthetically accessible bryostatin analogues could serve as superior candidates for the eradication of HIV/AIDS through induction of latent viral reservoirs in conjunction with current antiretroviral therapy.

  2. The effects of ACTH- and vasopressin-analogues on CO2-induced retrograde amnesia in rats

    NARCIS (Netherlands)

    Rigter, H.; Riezen, H. van; Wied, D. de

    1974-01-01

    Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO2 until respiratory arrest occurred. The ACTH-analogue ACTH4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. Th

  3. Analogue of Electromagnetically Induced Transparency in a Terahertz Metamaterial

    OpenAIRE

    Chiam, Sher-Yi; Bettiol, Andrew A; Singh, Ranjan; Zhang, Weili; Rockstuhl, Carsten; Lederer, Falk

    2009-01-01

    We experimentally demonstrate at terahertz frequencies that a planar metamaterial exhibits a spectral response resembling electromagnetically induced transparency. The metamaterial unit cell consists of a split ring surrounded by another closed ring where their dimensions are such that their excitable lowest order modes have identical resonance frequencies but very different life times. Terahertz time-domain spectroscopy verifies that the interference of these two resonances results in a narr...

  4. Experimental evidence of optical analogue of electromagnetically induced transparency in graphene

    CERN Document Server

    Gao, Lei; Liu, Min; Huang, Wei; Li, Yu Jia; Gao, Cong

    2016-01-01

    We demonstrate the first experimental observation of coherent population oscillation, an optical analogue of electromagnetically induced transparency, in graphene based on phase sensitive pump-probe system. Degenerate four-wave-mixing between pump and probe modifies the dispersion and absorption of the population oscillation process in graphene, and leads to enhance and depression of modulation instability with asymmetry in frequency. The analytically predicted asymmetrical burning hole fully consists with the experiments.

  5. Reflection-type electromagnetically induced transparency analogue in terahertz metamaterials

    International Nuclear Information System (INIS)

    A reflection-type electromagnetically induced transparency (EIT) metamaterial is proposed, which is composed of a dielectric spacer sandwiched with metallic patterns and metallic plane. Experimental results of THz time domain spectrum (THz-TDS) exhibit a typical reflection of EIT at 0.865 THz, which are in excellent agreement with the full-wave simulations. A multi-reflection theory is adopted to analyze the physical mechanism of the reflection-type EIT, showing that the reflection-type EIT is a superposition of multiple reflection of the transmission EIT. Such a reflection-type EIT provides many applications based on the EIT effect, such as slow light devices and nonlinear elements. (electromagnetism, optics, acoustics, heat transfer, classical mechanics, and fluid dynamics)

  6. Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1-naphthylalanine or 2-naphthylalanine.

    Science.gov (United States)

    Asano, Akiko; Minoura, Katsuhiko; Yamada, Takeshi; Doi, Mitsunobu

    2016-03-01

    We designed five ascidiacyclamide analogues [cyclo(-Xxx(1) -oxazoline(2) -d-Val(3) -thiazole(4) -l-Ile(5) -oxazoline(6) -d-Val(7) -thiazole(8) -)] incorporating l-1-naphthylalanine (l-1Nal), l-2-naphthylalanine (l-2Nal), d-phenylalanine (d-Phe), d-1-naphthylalanine (d-1Nal) or d-2-naphthylalanine (d-2Nal) into the Xxx(1) position of the peptide. The conformations of these analogues were then examined using (1) H NMR, CD spectroscopy, and X-ray diffraction. These analyses suggested that d-enantiomer-incorporated ASCs [(d-Phe), (d-1Nal), and (d-2Nal)ASC] transformed from the folded to the open structure in solution more easily than l-enantiomer-incorporated ASCs [(l-Phe), (l-1Nal), and (l-2Nal)ASC]. Structural comparison of the two analogues containing isomeric naphthyl groups showed that the 1-naphthyl isomer induced a more stable open structure than the 2-naphthyl isomer. In particular, [d-1Nal]ASC showed the most significant transformation from the folded to the open structure in solution, and exhibited the strongest cytotoxicity toward HL-60 cells. PMID:26856689

  7. Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

    OpenAIRE

    Yogendra Nayak; Venkatachalam Hillemane; Vijay Kumar Daroji; Jayashree, B. S.; Unnikrishnan, M. K.

    2014-01-01

    Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG) >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glu...

  8. Antidiabetic Activity of Benzopyrone Analogues in Nicotinamide-Streptozotocin Induced Type 2 Diabetes in Rats

    Directory of Open Access Journals (Sweden)

    Yogendra Nayak

    2014-01-01

    Full Text Available Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D was induced in Wistar rats by streptozotocin (60 mg/kg, i.p. followed by nicotinamide (120 mg/kg i.p.. Rats having fasting blood glucose (FBG >200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT, and insulin tolerance test (ITT were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

  9. Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP

    International Nuclear Information System (INIS)

    The mitotic selection procedure for cell cycle analysis was utilized to investigate the concentration-dependent modification of x-radiation-induced division delay in Chinese hamster ovary (CHO) cells by methyl xanthines (caffeine, theophylline, and theobromine) and by dibutyryl cyclic AMP. The methyl xanthines (concentrations from 0.5 to 1000 μg/ml) all reduced radiation-induced division delay with the effect being linear between approximately 100 and 1000 μg/ml. After doses of 100-300 rad, delay was reduced by 75, 94 or 83 per cent at 1000 μg/ml for each drug, respectively. However, the addition of dibutyryl cyclic AMP had an opposite effect: radiation-induced delay was increased by the concentration range of 0.3 to 300 μg/ml. These results indicate that in mammalian cells the control of cell cycle progression and the modification of radiation-induced division delay are not simply related to intracellular levels of cyclic AMP. Rather, there appear to be at least two competing mechanisms which are differentially affected by caffeine analogues or by direct addition of dibutyryl cyclic AMP. The direct effect of caffeine and the methyl xanthines on membrane calcium permeability is considered. (author)

  10. YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death

    Directory of Open Access Journals (Sweden)

    Ji Cao

    2009-01-01

    Full Text Available Overexpression of multidrug resistance proteins P-glycoprotein (P-gp, MDR1 causes resistance of the tumor cells against a variety of chemotherapeutic agents. 3-(1-methyl-1H-indol-3-yl-1-phenyl-4-(1-(3-(piperidin-1-ylpropyl-1H-pyrazolo[3,4-b]pyridine-3-yl-1H-pyrrole-2,5-dione (YQ36 is a novel analogue of bisindolylmaleimide, which has been reported to overcome multidrug resistance. Here, we dedicated to investigate the anticancer activity of YQ36 on KB/VCR cells. The results revealed that YQ36 exhibited great antiproliferative activity on three parental cell lines and MDR1 overexpressed cell lines. Moreover, the hypersensitivity of YQ36 was confirmed on the base of great apoptosis induction and unaltered intracellular drug accumulation in KB/VCR cells. Further results suggested that YQ36 could not be considered as a substrate of P-gp, which contributed to its successfully escaping from the efflux mediated by P-gp. Interestingly, we observed that YQ36 could accumulate in nucleus and induce DNA damage. YQ36 could also induce the activation of caspase-3, imposing effects on the mitochondrial function. Collectively, our data demonstrated that YQ36 exhibited potent activities against MDR cells, inducing DNA damage and triggering subsequent apoptosis via mitochondrial pathway.

  11. Reaction analogues in the radiation-induced deamination and dephosphorylation of bio-organic molecules 2: Oxygenated solutions

    International Nuclear Information System (INIS)

    The OH-induced deamination and dephosphorylation of simple peptides and phosphate esters in oxygenated solutions involve the fomation and subsequent degradation of the perodyl radicals RCONHC(/dot O/)R2 and /bigcirc P/ OC(/dot O/2)R2 respectively. Reaction analogues in the degradation of peroxyl and alkoxyl radicals in these two systems are evaluated with reference to the OH-induced main-chain cleavage of protein and DNA. 25 refs

  12. Behavioral and electroencephalographic effects of delta sleep inducing peptide and its analogue on metaphit-induced audiogenic seizures in rats

    Directory of Open Access Journals (Sweden)

    Stanojlović Olivera P.

    2004-01-01

    Full Text Available INTRODUCTION Delta sleep inducing peptide (DSIP is well known natural somnogenic peptide that has many other physiological functions. DSIP analogues representing hepta-and octapeptides (also known as long as well as tetrapeptide (termed short, used in our experiments were synthesized with a view to evaluate the peptide specificity in sleep. The effects of DSIP and its analogue DSIP1-4 on metaphit 1-[1(3-isothiocyanatophenyl-ciclohexyl-piperidine] induced audiogenic seizures were evaluated in rats. METHODS Male Wistar albino rats were divided into 4 groups: 1. Saline; 2. Metaphit; 3. Metaphit + DSIP, and 4. Metaphit + DSIP1-4. To examine the blocking effects of DSIP and its analogue on fully developed metaphit seizures, the last two groups were injected after the 8th audiogenic testing. Animals were injected with metaphit (10 mg/kg intraperitoneally (i.p. and exposed to sound stimulation (100±3 dB, 60 s at hourly intervals. The incidence and severity (running, clonus and tonus of seizures were analyzed. For electroencephalographic (EEG recordings, three gold-plated electrodes were used. Convulsive behavior was assessed by incidence of motor seizure and by seizure severity grade, determined by descriptive rating scale ranging from 0 to 3:0- no response, 1 -wild running only; 2-wild running followed by clonic seizures of all four limbs with body rollover; 3 - wild running progressing to generalized clonic convulsions followed by tonic extension of fore-and hind legs and tail. Sound onset, seizure events, and sound offset, along with the animal's behavior (convulsive or other were characterized with EEG changes. RESULTS In most animals, the administration of metaphit resulted in electroencephalographic abnormalities, elicited epileptic-form activity in the form of spikes, polyspikes and spike-wave complexes. Maximum incidence and severity of metaphit convulsions occurred 8 h after the injection (9/12, 75%, then abated gradually and disappeared 30 h

  13. Pyrazine analogues are active components of wolf urine that induce avoidance and freezing behaviours in mice.

    Directory of Open Access Journals (Sweden)

    Kazumi Osada

    Full Text Available BACKGROUND: The common grey wolf (Canis lupus is found throughout the entire Northern hemisphere and preys on many kinds of mammals. The urine of the wolf contains a number of volatile constituents that can potentially be used for predator-prey chemosignalling. Although wolf urine is put to practical use to keep rabbits, rodents, deer and so on at bay, we are unaware of any prior behavioural studies or chemical analyses regarding the fear-inducing impact of wolf urine on laboratory mice. METHODOLOGY/PRINCIPAL FINDINGS: Three wolf urine samples harvested at different times were used in this study. All of them induced stereotypical fear-associated behaviors (i.e., avoidance and freezing in female mice. The levels of certain urinary volatiles varied widely among the samples. To identify the volatiles that provoked avoidance and freezing, behavioural, chemical, and immunohistochemical analyses were performed. One of the urine samples (sample C had higher levels of 2,6-dimethylpyrazine (DMP, trimethylpyrazine (TMP, and 3-ethyl-2,5-dimethyl pyrazine (EDMP compared with the other two urine samples (samples A and B. In addition, sample C induced avoidance and freezing behaviours more effectively than samples A and B. Moreover, only sample C led to pronounced expression of Fos-immunoreactive cells in the accessory olfactory bulb (AOB of female mice. Freezing behaviour and Fos immunoreactivity were markedly enhanced when the mice were confronted with a mixture of purified DMP, TMP, and EDMP vs. any one pyrazine alone. CONCLUSIONS/SIGNIFICANCE: The current results suggest that wolf urinary volatiles can engender aversive and fear-related responses in mice. Pyrazine analogues were identified as the predominant active components among these volatiles to induce avoidance and freezing behaviours via stimulation of the murine AOB.

  14. Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

    Science.gov (United States)

    Prasad, Karothu Durga; Trinath, Jamma; Biswas, Ansuman; Sekar, Kanagaraj; Balaji, Kithiganahalli N.; Guru Row, Tayur N.

    2014-11-01

    Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis.

  15. Hypoglycemic activity of curcumin synthetic analogues in alloxan-induced diabetic rats.

    Science.gov (United States)

    Das, Kusal K; Razzaghi-Asl, Nima; Tikare, Swati N; Di Santo, Roberto; Costi, Roberta; Messore, Antonella; Pescatori, Luca; Crucitti, Giuliana Cuzzucoli; Jargar, Jameel G; Dhundasi, Salim A; Saso, Luciano

    2016-01-01

    The currently available therapies for type 2 diabetes have been unable to achieve normoglycemic status in the majority of patients. The reason may be attributed to the limitations of the drug itself or its side effects. In an effort to develop potent and safe oral antidiabetic agents, we evaluated the in vitro and in vivo hypoglycemic effects of 10 synthetic polyphenolic curcumin analogues on alloxan-induced male diabetic albino rats. In vitro studies showed 7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione (4) to be the most potential hypoglycemic agent followed by 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one (10). Structure activity relationship (SAR) of the tested compounds was elucidated and the results were interpreted in terms of in vitro hypoglycemic activities. Furthermore, oral glucose tolerance test (OGTT) with compounds 4, 10 and reference hypoglycemic drug glipizide showed that compound 4 and glipizide had relatively similar effects on the reduction of blood glucose levels within 2 h. Thus, compound 4 might be regarded as a potential hypoglycemic agent being able to reduce glucose concentration both in vitro and in vivo. PMID:25683079

  16. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway.

    Science.gov (United States)

    He, Qin; Sha, Sha; Sun, Lei; Zhang, Jing; Dong, Ming

    2016-08-01

    The incidence of nonalcoholic fatty liver disease (NAFLD) keeps rising year by year, and NAFLD is rapidly becoming the most common liver disease worldwide. Clinical studies have found that glucagon-like peptide-1 (GLP-1) analogue, liraglutide (LRG), cannot only reduce glucose levels, but also improve hepatic lipase, especially in patients also with type 2 diabetes mellitus (T2DM). In addition, enhancing autophagy decreases lipid accumulation in hepatocytes. The aim of the present study is to explore the effect of LRG on hepatocyte steatosis and the possible role of autophagy. We set up an obesity mouse model with a high-fat diet (HFD) and induced hepatocyte steatosis with free fatty acids (FFA) in human L-O2 cells. LRG and two inhibitors of autophagy, Chloroquine (CQ) and bafilomycin A1 (Baf), were added into each group, respectively. The lipid profiles and morphological modifications of each group were tested. Immunohistochemistry, immunofluorescence staining and transmission electron microscopy (TEM) were used to measure autophagy in this study. The autophagy protein expression of SQSTM1 (P62), and LC3B, along with the signaling pathway proteins of mTOR, phosphorylated mTOR (p-mTOR), AMPK, phosphorylated AMPK (p-AMPK) and Beclin1, were evaluated by western blot. Our results showed that LRG improved hepatocyte steatosis by inducing autophagy, and the AMPK/mTOR pathway is involved. These findings suggest an important mechanism for the positive effects of LRG on hepatic steatosis, and provide new evidence for clinical use of LRG in NAFLD. PMID:27208776

  17. Strong electron donation induced differential nonradiative decay pathways for para and meta GFP chromophore analogues.

    Science.gov (United States)

    Chatterjee, Tanmay; Mandal, Mrinal; Gude, Venkatesh; Bag, Partha Pratim; Mandal, Prasun K

    2015-08-28

    Z-E Isomerisation because of rotation around the exocyclic double bond (known as the τ-twist) and not any other internal conversion has been reported to be the major nonradiative decay channel for non-hydroxylic unconstrained para and meta GFP chromophore analogues. The equation Φf + 2ΦZE = 1 has been shown to hold well for both para and meta GFP chromophore analogues. If the above equation holds true, then upon reducing the extent of Z-E isomerisation (ΦZE), the fluorescence quantum yield (Φf) should increase. To probe the above proposition two sets of non-hydroxylic unconstrained para and meta GFP chromophore analogues were synthesized. Quite interestingly by introducing the strongly electron donating -NEt2 group to the benzenic moiety these para and meta GFP chromophore analogues were shown to exhibit differential optical behaviour w.r.t. the extent of the solvatochromic shift, Φf, ΦZE, and τf. For the first time it has been shown that the well accepted equation Φf + 2ΦZE = 1 does not hold at all for these non-hydroxylic unconstrained meta analogues. Although ΦZE has been shown to be value for these meta analogues. After detailed investigation into the nonradiative excited state decay channel, contrary to literature reports, energy gap law governed internal conversion and not Z-E isomerisation was shown to be the major nonradiative decay channel for these meta analogues. Two models are put forward to understand the differential optical behaviour of these para and meta GFP chromophore analogues. Support from X-ray crystal structures, NMR experiments, and computational calculations has also been provided. PMID:26176350

  18. Tyrosol and Its Analogues Inhibit Alpha-Melanocyte-Stimulating Hormone Induced Melanogenesis

    Directory of Open Access Journals (Sweden)

    Kuo-Ching Wen

    2013-11-01

    Full Text Available Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, 2-hydroxyphenylacetic acid (7, or salidroside (11 resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1, 4-hydroxyphenylacetic acid (5 and 2-hydroxyphenylacetic acid (7 suppressed MC1R expression. Tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, and 2-hydroxyphenylacetic acid (7 inhibited α-MSH induced TRP-1 expression, but salidroside (11 did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1, 4-hydroxyphenylacetic acid (5, 3-hydroxyphenylacetic acid (6, and 2-hydroxyphenylacetic acid (7 at concentrations below 4 mM and salidroside (11 at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.

  19. Curcumin and Its Analogue Induce Apoptosis in Leukemia Cells and Have Additive Effects with Bortezomib in Cellular and Xenograft Models

    Directory of Open Access Journals (Sweden)

    L. I. Nagy

    2015-01-01

    Full Text Available Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.

  20. The effects of experimentally induced rumination versus distraction on analogue posttraumatic stress symptoms

    NARCIS (Netherlands)

    T. Ehring; N. Fuchs; I. Kläsener

    2009-01-01

    Rumination has been suggested to be an important factor maintaining posttraumatic stress disorder (PTSD). Using an analogue design, this study aimed to experimentally test the hypothesis that trauma-related rumination maintains PTSD symptoms. Fifty-one participants were first asked to give a detaile

  1. Effect of humanin analogues on experimentally induced impairment of spatial memory in rats

    Czech Academy of Sciences Publication Activity Database

    Krejčová, G.; Patočka, J.; Slaninová, Jiřina

    2004-01-01

    Roč. 10, - (2004), s. 636-639. ISSN 1075-2617 R&D Projects: GA ČR GA305/03/1100 Institutional research plan: CEZ:AV0Z4055905 Keywords : humanin analogue * Alzheimer's disease * 3-quinuclidinyl benzilate Subject RIV: CE - Biochemistry Impact factor: 1.652, year: 2004

  2. Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid β-induced damage.

    Science.gov (United States)

    Gurer-Orhan, Hande; Karaaslan, Cigdem; Ozcan, Senem; Firuzi, Omidreza; Tavakkoli, Marjan; Saso, Luciano; Suzen, Sibel

    2016-04-15

    Oxidative stress has been recognized as a contributing factor in ageing and various diseases including cancer and neuropathological disorders. Indole derivatives such as the neurohormone melatonin (MLT) constitute an important class of therapeutic agent in medicinal chemistry. MLT can scavenge different reactive oxygen species and can also stimulate the synthesis of antioxidant enzymes. As a part of our ongoing studies, a series of new indole-based hydrazide/hydrazone derivatives were synthesized as MLT analogues. Their antioxidant activity was investigated in human erythrocytes by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Possible inherent cytotoxicity of the compounds was investigated in CHO-K1 cells by lactate dehydrogenase leakage test. Protection of neuronal PC12 cells against amyloid β-induced damage was examined by MTT assay and their ability in reduction of ROS generation induced by amyloid β was tested. MLT analogues having an o-halogenated aromatic moiety exhibited effective antioxidant properties without having any membrane-damaging effect. Moreover, derivatives having o-halogenated and dihalogenated aromatic side chain significantly protected neuronal cells at concentrations of 10 and 100μM. In conclusion, MLT derivatives represent promising scaffolds for discovery of effective antioxidant and neuroprotective agents. PMID:26970662

  3. Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue.

    OpenAIRE

    DeGrado, W F; Musso, G F; Lieber, M; Kaiser, E T; Kézdy, F J

    1982-01-01

    The cytotoxic peptide from honeybee venom, melittin, and a synthetic peptide analogue of it lyse human erythrocytes in a biphasic process. The kinetics of the lysis in 0.30 M sucrose, 0.01 M sodium phosphate, pH 7.30 at 4 degrees C were investigated. Our results show that melittin rapidly binds to the outer surface of the erythrocyte membrane, and the surface-bound monomers produce transient openings through which approximately 40 hemoglobin molecules can escape. Concomitantly, the melittin l...

  4. Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death.

    Science.gov (United States)

    Staveness, Daryl; Abdelnabi, Rana; Schrier, Adam J; Loy, Brian A; Verma, Vishal A; DeChristopher, Brian A; Near, Katherine E; Neyts, Johan; Delang, Leen; Leyssen, Pieter; Wender, Paul A

    2016-04-22

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer's disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PKC modulator, is inactive in these assays. These new findings indicate that the observed anti-CHIKV activity is not solely mediated by PKC modulation, suggesting possible as yet unidentified targets for CHIKV therapeutic intervention. The high potency and low toxicity of these bryologs make them promising new leads for the development of a CHIKV treatment. PMID:26900625

  5. Deterministic control of all-optical analogue to electromagnetically induced transparency in coherently-coupled silicon photonic crystal cavities

    CERN Document Server

    Yang, Xiaodong; Kwong, Dim-Lee; Wong, Chee Wei

    2008-01-01

    Quantum coherence in atomic systems has led to fascinating outcomes, such as laser cooling and trapping, Bose-Einstein condensates, and electromagnetically-induced-transparency (EIT). In EIT, the sharp cancellation of medium absorption has led to phenomena such as lasing without inversion, freezing light, and dynamic storage of light in a solid-state system. Similar to atomic systems, EIT-like effects can be observed through classical and optical means. Here we report the first experimental deterministic tuning of all-optical analogue to EIT in coherently-coupled standing-wave photonic crystal cavities. Our observations include transparency-resonance lifetimes more than three times the single loaded cavity, Fano-type lineshapes, and stepwise control of the coherent cavity-cavity interference. Our system, with wavelength-scale localization and coupled to a single waveguide, is analyzed well through the coupled-mode formalism which examines the delay in both transparency- and Fano-like lineshapes. Our observati...

  6. The Vitamine D3 Analogue (1α Hydroxyvitamin D3) Aggravates Carbon Tetrachloride-Induced Hepatotoxicity In Albino Rats

    International Nuclear Information System (INIS)

    Provitamin D, cholecalciferol, undergoes hydroxylation at the 25 and the 1α position in the liver and the kidney, respectively, before it turns into a hormonally active form regulating calcium homeostasis. The main purpose of the present study is to assess the potential of the 1α hydroxyvitamin D3 analogue to aggravate the ability of carbon tetrachloride (CCl4) to cause hepatotoxicity in albino rats. For this purpose, four groups of male albino rats, each of five, were used as follow: control group (G 1) received no treatment, CCl4 treated group (G 2) received CCl4 at a dose of 0.2 ml/100 g body weight in sunflower oil (1/1) v/v ratio two times per week for three weeks subcutaneously, 1α hydroxyvitamin D3 treated group (G 3) received a total dose of 5 ng/g body weight of 1α hydroxyvitamin D3 dissolved in propyl alcohol divided into six doses each given twice weekly for three weeks via the subcutaneous route, and CCl4 + 1α hydroxyvitamin D3 treated group (G 4) received the same dose of CCl4 and 1α hydroxyvitamin D3 concomitantly as previously described. Liver tissues from sacrificed animals were fixed in 10% formalin before sectioning and stained with eosin and hematoxyline then were examined histopathologically. Sera from control and treated animals were separated from blood and examined for ALT, AST, alkaline phosphatase and LDH levels. Serum total protein, albumin, globulin, A/G, bilirubin, creatinine, phosphorous and Ca levels were also monitored. Data from the present study showed that administration of 1α hydroxyvitamin D3 aggravated CCl4-induced hepatotoxicity as evidenced by the exacerbation of the rise in serum ALT, AST, alkaline phosphatase levels. The analogue, however, had no effect on serum liver enzymes in CCl4 untreated rats. Though, CCl4 caused significant impairment of kidney function as shown by the rise in serum creatinine and urea levels which were differentially affected by the analogue. In conclusion, the 1α hydroxyvitamin D3 compound

  7. Analogues of methotrexate in rheumatoid arthritis. 1. Effects of 10-deazaaminopterin analogues on type II collagen-induced arthritis in mice.

    Science.gov (United States)

    DeGraw, J I; Colwell, W T; Crase, J; Smith, R L; Piper, J R; Waud, W R; Sirotnak, F M

    1997-01-31

    Carbonation of the dianions (LDA) of 5-methylthiophene-2-carboxylic, 2-methylpyridine-5-carboxylic, and 3-methylpyridine-6-carboxylic acids provided the respective carboxy heteroarylacetic acids. The crude diacids were directly esterified in MeOH-HCl to afford the diesters. Alkylation of the sodio anions with ethyl iodide yielded the appropriate alpha-ethyl diesters. The anions of the various diester substrates were then alkylated by 2,4-diamino-6-(bromomethyl)-pteridine followed by ester saponification at room temperature to afford the respective 2,4-diamino-4-deoxy-10-carboxy-10-deazapteroic acids. The 10-carboxyl group was readily decarboxylated by heating in DMSO at temperatures of 110-135 degrees C to give the diamino 10-deaza heteropteroic acid intermediates. Coupling with diethyl L-glutamate followed by ester hydrolysis afforded the target aminopterins. The analogues were evaluated for antiinflammatory effect in the mouse type II collagen model. The thiophene analogue of 10-ethyl-10-deazaaminopterin was found to be an effective inhibitor in terms of reduced visual evidence of inflammation and swelling as determined by caliper measurement. PMID:9022804

  8. The effects of the phyllolitorin analogue [desTrp3,Leu8]phyllolitorin on scratching induced by bombesin and related peptides in rats

    OpenAIRE

    Johnson, Mark D; Ko, Mei-Chuan; Choo, Kevin S.; Traynor, John R.; Mosberg, Henry I.; Naughton, Norah N.; Woods, James H

    1999-01-01

    Bombesin along with several closely related neuropeptides elicit scratching behavior when administered centrally. The first part of the study was designed to determine the antagonistic effects of a novel phyllolitorin analogue wdesTrp3,Leu8]phyllolitorin (DTP) on scratching induced by three peptides (bombesin, neuromedin-C, and [Leu8]phyllolitorin). In addition, the binding affinity of each peptide for the bombesin receptor site was determined. DTP (30 μg) inhibited scratching induced by thes...

  9. Induction of apoptosis-like cell death by coelomocyte extracts from Eisenia andrei earthworms.

    Science.gov (United States)

    Mácsik, Levente László; Somogyi, Ildikó; Opper, Balázs; Bovári-Biri, Judit; Pollák, Edit; Molnár, László; Németh, Péter; Engelmann, Péter

    2015-10-01

    Earthworm's innate immunity is maintained by cellular and humoral components. Our objective was to characterize the cytotoxicity leading to target cell death caused by earthworm coelomocytes. Coelomocyte lysates induced strong cytotoxicity in tumor cell lines. Transmission electron microscopy revealed cell membrane and intracellular damage in cells treated with coelomocyte lysates. Using TUNEL-assay, within 5 min of incubation we detected DNA fragmentation. Moreover, we found phosphatidylserine translocation in target cell-membranes. Furthermore, we detected dose-dependent Ca(2+) influx and decrease of mitochondrial membrane potential in coelomocyte lysate-treated cells. Interestingly, caspase 3/8 activation was undetectable in exposed tumor cells. One such cytotoxic molecule, lysenin identified in earthworms binds to sphingomyelin and causes target cell lysis in vertebrates. Pretreatment with our anti-lysenin monoclonal antibody rescued the majority but not all target cells from coelomocyte induced death. These data suggest that, not only lysenin but also other factors participate in the caspase-independent apoptosis induced by coelomocytes. PMID:26049811

  10. Curcumin analogue T83 exhibits potent antitumor activity and induces radiosensitivity through inactivation of Jab1 in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus–associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC. NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting. A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy. Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC

  11. Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition

    OpenAIRE

    Kwon, Do-Yeon; Lee, Hye Eun; Weitzel, Douglas H.; PARK, KYUNGHYE; Lee, Sun Hee; Lee, Chen-Ting; Stephenson, Tesia N.; Park, Hyeri; Fitzgerald, Michael C.; Chi, Jen-Tsan; Mook, Robert A.; Dewhirst, Mark W.; Lee, You Mie; Hong, Jiyong

    2015-01-01

    To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from Saururus cernuus, manassantins A (1) and B (2) are potent inhibitors of HIF-1 activi...

  12. Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Yong Son

    2013-01-01

    Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

  13. Corosolic acid analogue, a natural triterpenoid saponin, induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro.

    Science.gov (United States)

    Qu, Liping; Zhang, Huiqing; Yang, Yanlong; Yang, Geliang; Xin, Hailiang; Ling, Changquan

    2016-08-01

    Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine. Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines. Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40 μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4'-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays. Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24 h, the IC50 values were 34.6, 30.8 and 30.5 μg/mL, respectively. TEO (40 μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio. Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway. PMID:26810384

  14. Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Jun Lu

    Full Text Available Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa, a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs.The rapid delayed rectifier potassium current (IKr, L-type Ca2+ current (ICa,L and action potential duration (APD were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90 (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.

  15. Microbial community induces a plant defense system under growing on the lunar regolith analogue

    Science.gov (United States)

    Zaetz, Irina; Mytrokhyn, Olexander; Lukashov, Dmitry; Mashkovska, Svitlana; Kozyrovska, Natalia; Foing, Bernard H.

    The lunar rock considered as a potential source of chemical elements essential for plant nutrition, however, this substrate is of a low bioavailability. The use of microorganisms for decomposition of silicate rocks and stimulation of plant growth is a key idea in precursory scenario of growing pioneer plants for a lunar base (Kozyrovska et al., 2004; 2006; Zaetz et al., 2006). In model experiments a consortium of well-defined plant-associated bacteria were used for growing of French marigold (Tagetes patula L.) in anorthosite, analogous to a lunar rock. Inoculated plants appeared better seed germination, more fast development and also increased accumulation of K, Mg, Mn, Co, Cu and lowered level of the toxic Zn, Ni, Cr, comparing to control tagetes'. Bacteria regulate metal homeostasis in plants by changing their bioavailability and by stimulating of plant defense mechanisms. Inoculated plants were being accommodated to growth under stress conditions on anorthosite used as a substrate. In contrast, control plants manifested a heavy metal-induced oxidative stress, as quantified by protein carbonyl accumulation. Depending on the plant organ sampled and developmental stage there were increases or loses in the antioxidant enzyme activities (guaiacol peroxidase and glutathione-S-transferase). These changes were most evident in inoculated plants. Production of phenolic compounds, known as antioxidants and heavy metal chelators, is rised in variants of inoculated marigolds. Guaiacol peroxidase plays the main role, finally, in a reducing toxicity of heavy metals in plant leaves, while glutathione-S-transferase and phenolics overcome stress in roots.

  16. Stability of Continental Lithosphere based on Analogue Experiments with Microwave Induced Internal Heating

    Science.gov (United States)

    Fourel, Loic; Limare, Angela; Surducan, Emanoil; Surducan, Vasile; Neamtu, Camelia; Vilella, Kenny; Farnetani, Cinzia; Kaminski, Edouard; Jaupart, Claude

    2015-04-01

    the base. Experimental fluids are mixtures of hydroxyethylcellulose, water and isopropanol or silicon oils. Viscosities are varied within a wide range depending on concentration. The temperature field is visualised via laser induced fluorescence and the velocity field is determined using Particle Image Velocimetry (PIV). An intrinsic density contrast ensures the initial stability of the two layers of fluid and a higher heating rate is applied to the top layer. We characterise the stability of the upper layer depending on the parameters in the system and confront our results to marginal stability analysis.

  17. Apoptosis-like death in Leishmania donovani promastigotes induced by eugenol-rich oil of Syzygium aromaticum.

    Science.gov (United States)

    Islamuddin, Mohammad; Sahal, Dinkar; Afrin, Farhat

    2014-01-01

    Leishmaniasis consists of a complex spectrum of infectious diseases with worldwide distribution of which visceral leishmaniasis or kala-azar caused by Leishmania donovani is the most devastating. In the absence of vaccines, chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice are expensive and associated with multiple adverse side effects. Because of these limitations, the development of new antileishmanial compounds is imperative and plants offer prospects in this regard. The present work was conducted to study the antileishmanial potential of oil from Syzygium aromaticum flower buds (clove). The S. aromaticum oil was characterized by gas chromatography and GC-MS and eugenol as well as eugenyl acetate were found to be the most abundant compounds, composing 59.75 % and 29.24 %, respectively of the oil. Our findings have shown that eugenol-rich essential oil from S. aromaticum (EROSA) possesses significant activity against L. donovani, with 50 % inhibitory concentration of 21 ± 0.16 µg ml(-1) and 15.24 ± 0.14 µg ml(-1), respectively, against promastigotes and intracellular amastigotes. Alterations in cellular morphology and growth reversibility assay substantiated the leishmanicidal activity of EROSA. The leishmanicidal effect was mediated via apoptosis as confirmed by externalization of phosphatidylserine, DNA nicking by TdT-mediated dUTP nick-end labelling (TUNEL) assay, dyskinetoplastidy, cell cycle arrest at sub-G0-G1 phase, loss of mitochondrial membrane potential and reactive oxygen species generation. EROSA presented no adverse cytotoxic effects against murine macrophages even at 200 µg ml(-1). Our studies authenticate the promising antileishmanial activity of EROSA, which is mediated by programmed cell death, and, accordingly, EROSA may be a source of novel agents for the treatment of leishmaniasis. PMID:24161990

  18. Inhibition of Chikungunya Virus-Induced Cell Death by Salicylate-Derived Bryostatin Analogues Provides Additional Evidence for a PKC-Independent Pathway.

    Science.gov (United States)

    Staveness, Daryl; Abdelnabi, Rana; Near, Katherine E; Nakagawa, Yu; Neyts, Johan; Delang, Leen; Leyssen, Pieter; Wender, Paul A

    2016-04-22

    Chikungunya virus (CHIKV) has been spreading rapidly, with over one million confirmed or suspected cases in the Americas since late 2013. Infection with CHIKV causes devastating arthritic and arthralgic symptoms. Currently, there is no therapy to treat this disease, and the only medications focus on relief of symptoms. Recently, protein kinase C (PKC) modulators have been reported to inhibit CHIKV-induced cell death in cell assays. The salicylate-derived bryostatin analogues described here are structurally simplified PKC modulators that are more synthetically accessible than the natural product bryostatin 1, a PKC modulator and clinical lead for the treatment of cancer, Alzheimer's disease, and HIV eradication. Evaluation of the anti-CHIKV activity of these salicylate-derived bryostatin analogues in cell culture indicates that they are among the most potent cell-protective agents reported to date. Given that they are more accessible and significantly more active than the parent natural product, they represent new therapeutic leads for controlling CHIKV infection. Significantly, these analogues also provide evidence for the involvement of a PKC-independent pathway. This adds a fundamentally distinct aspect to the importance or involvement of PKC modulation in inhibition of chikungunya virus replication, a topic of recent and growing interest. PMID:26900711

  19. Synthesis, Characterization and In Vitro Anticancer Activity of C-5 Curcumin Analogues with Potential to Inhibit TNF-α-Induced NF-κB Activation

    Directory of Open Access Journals (Sweden)

    Amit Anthwal

    2014-01-01

    Full Text Available In a search of new compounds active against cancer, synthesis of a series of C-5 curcumin analogues was carried out. The new compounds demonstrated good cytotoxicity against chronic myeloid leukemia (KBM5 and colon cancer (HCT116 cell lines. Further, these compounds were found to have better potential to inhibit TNF-α-induced NF-κB activation in comparison to curcumin, which show their potential to act as anti-inflammatory agents. Some compounds were found to show higher cytotoxicity against cancer cell lines in comparison to curcumin used as standard.

  20. The use of a-methyl-D-glucoside, a synthetic analogue of maltose, as inducer of amylase by Aspergillus sp in solid-state and submerged fermentations

    OpenAIRE

    Moreira Fabiana G.; Lenartovicz Veridiana; Souza Cristina G. M.; Ramos Edivan P.; Peralta Rosane M.

    2001-01-01

    The use of a methyl-D-glucoside (alphaMG), a synthetic analogue of maltose, as carbon source and inducer of amylase synthesis to several species of Aspergillus was studied in submerged and solid-state fermentations. Among a group of ten species, A. tamarii, A. fumigatus and A. flavus were able to produce biomass and high specific amylolytic activity in submerged cultures containing alphaMG as the only carbon source. In solid state fermentation, the enrichment of basal wheat bran or corn cob m...

  1. NATURAL ANALOGUE SYNTHESIS REPORT

    International Nuclear Information System (INIS)

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature along with results of quantitative studies conducted specifically for the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement-drift degradation, waste-form degradation, waste-package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated-zone (SZ) transport, impact of radionuclide release on the biosphere

  2. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

    Energy Technology Data Exchange (ETDEWEB)

    Nygaard, Gyrid [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway); Herfindal, Lars; Kopperud, Reidun [Department of Biomedicine, University of Bergen, Bergen (Norway); Aragay, Anna M. [Department of Biomedicine, University of Bergen, Bergen (Norway); Molecular Biology Institute of Barcelona (IBMB, CSIC), Barcelona (Spain); Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune [Department of Biomedicine, University of Bergen, Bergen (Norway); Selheim, Frode, E-mail: Frode.Selheim@biomed.uib.no [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway)

    2014-07-04

    Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation.

  3. The use of a-methyl-D-glucoside, a synthetic analogue of maltose, as inducer of amylase by Aspergillus sp in solid-state and submerged fermentations

    Directory of Open Access Journals (Sweden)

    Moreira Fabiana G.

    2001-01-01

    Full Text Available The use of a methyl-D-glucoside (alphaMG, a synthetic analogue of maltose, as carbon source and inducer of amylase synthesis to several species of Aspergillus was studied in submerged and solid-state fermentations. Among a group of ten species, A. tamarii, A. fumigatus and A. flavus were able to produce biomass and high specific amylolytic activity in submerged cultures containing alphaMG as the only carbon source. In solid state fermentation, the enrichment of basal wheat bran or corn cob medium with alphaMG increased up to 3 times the production of amylases. In both submerged and solid state fermentations, alphaMG was more effective inducer of amylases than maltose and starch.

  4. The polyamine analogue N1,N11-diethylnorspermine can induce chondrocyte apoptosis independently of its ability to alter metabolism and levels of natural polyamines.

    Science.gov (United States)

    Stanic', Ivana; Facchini, Annalisa; Borzì, Rosa Maria; Stefanelli, Claudio; Flamigni, Flavio

    2009-04-01

    We have been investigating the effects of natural polyamines and polyamine analogues on the survival and apoptosis of chondrocytes, which are cells critical for cartilage integrity. Treatment of human C-28/I2 chondrocytes with N(1),N(11)-diethylnorspermine (DENSPM), a polyamine analogue with clinical relevance as an experimental anticancer agent, rapidly induced spermidine/spermine N(1)-acetyltransferase (SSAT) and spermine oxidase (SMO), key enzymes of polyamine catabolism and down-regulated ornithine decarboxylase, the first enzyme of polyamine biosynthesis, thus depleting all main polyamines within 24 h. The treatment with DENSPM did not provoke cell death and caspase activation when given alone for 24 h, but caused a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide (CHX). In other cellular models, enhanced polyamine catabolism or polyamine depletion has been implicated as mechanisms involved in DENSPM-related apoptosis. However, the simultaneous addition of DENSPM and CHX rapidly increased caspase activity in C-28/I2 cells in the absence of SSAT and SMO induction or significant reduction of polyamine levels. Moreover, caspase activation induced by DENSPM plus CHX was not prevented by a N(1)-acetylpolyamine oxidase (PAO)/SMO inhibitor, and depletion of all polyamines obtained by specific inhibitors of polyamine biosynthesis did not reproduce DENSPM effects in the presence of CHX. DENSPM/CHX-induced apoptosis was associated with changes in the amount or activation of signalling kinases, Akt and MAPKs, and increased uptake of DENSPM. In conclusion, the results suggest that DENSPM can favour apoptosis in chondrocytes independently of its effects on polyamine metabolism and levels. PMID:19097065

  5. Effect of a somatostatin analogue (SMS 201-995) on antral gastrin cell hyperplasia and hypergastrinemia induced by a histamine H2-receptor antagonist.

    Science.gov (United States)

    Kimura, K

    1993-05-01

    The effect of a somatostatin analogue, SMS 201-995 (SMS), on antral gastrin cell hyperplasia (AGH) and hypergastrinemia associated with 14-day administration of the histamine H2-receptor antagonist (H2-RA) famotidine was studied in rats. When the famotidine group was compared with the control group, the antral gastrin cell (G-cell) number was significantly increased (P SMS group was compared with the famotidine group, the G-cell number was significantly decreased (P < 0.01) by approximately 30%, and the serum gastrin level was significantly decreased (P < 0.01) by approximately 40%. These findings suggest that SMS may be useful for inhibiting AGH and hypergastrinemia induced by long-term H2-RA administration. PMID:8511502

  6. Andrographolide Analogue Induces Apoptosis and Autophagy Mediated Cell Death in U937 Cells by Inhibition of PI3K/Akt/mTOR Pathway.

    Directory of Open Access Journals (Sweden)

    Deepak Kumar

    Full Text Available Current chemotherapeutic agents based on apoptosis induction are lacking in desired efficacy. Therefore, there is continuous effort to bring about new dimension in control and gradual eradication of cancer by means of ever evolving therapeutic strategies. Various forms of PCD are being increasingly implicated in anti-cancer therapy and the complex interplay among them is vital for the ultimate fate of proliferating cells. We elaborated and illustrated the underlying mechanism of the most potent Andrographolide analogue (AG-4 mediated action that involved the induction of dual modes of cell death-apoptosis and autophagy in human leukemic U937 cells.AG-4 induced cytotoxicity was associated with redox imbalance and apoptosis which involved mitochondrial depolarisation, altered apoptotic protein expressions, activation of the caspase cascade leading to cell cycle arrest. Incubation with caspase inhibitor Z-VAD-fmk or Bax siRNA decreased cytotoxic efficacy of AG-4 emphasising critical roles of caspase and Bax. In addition, AG-4 induced autophagy as evident from LC3-II accumulation, increased Atg protein expressions and autophagosome formation. Pre-treatment with 3-MA or Atg 5 siRNA suppressed the cytotoxic effect of AG-4 implying the pro-death role of autophagy. Furthermore, incubation with Z-VAD-fmk or Bax siRNA subdued AG-4 induced autophagy and pre-treatment with 3-MA or Atg 5 siRNA curbed AG-4 induced apoptosis-implying that apoptosis and autophagy acted as partners in the context of AG-4 mediated action. AG-4 also inhibited PI3K/Akt/mTOR pathway. Inhibition of mTOR or Akt augmented AG-4 induced apoptosis and autophagy signifying its crucial role in its mechanism of action.Thus, these findings prove the dual ability of AG-4 to induce apoptosis and autophagy which provide a new perspective to it as a potential molecule targeting PCD for future cancer therapeutics.

  7. Protective effects of compound FLZ, a novel synthetic analogue of squamosamide, on β-amyloid-induced rat brain mitochondrial dysfunction in vitro

    Institute of Scientific and Technical Information of China (English)

    Fang FANG; Geng-tao LIU

    2009-01-01

    Aim: The aim of the present study was to assess the effects of N-[2-(4-hydroxyphenyl)ethyl]-2-(2,5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl) acrylamide (compound FLZ), a novel synthetic analogue of squamosamide, on the dysfunction of rat brain mitochondria induced by Aβ25-35 in vitro.Methods: Isolated rat brain mitochondria were incubated with aged Aβ25-35 for 30 min in the presence and absence of FLZ (1-100 μmol/L). The activities of key mitochondrial enzymes, the production of hydrogen peroxide (H2O2) and superoxide anion (O.-2), and the levels of glutathione (GSH) in mitochondria were examined. Mitochondrial swelling and the release of cytochrome c from mitochondria were assessed by biochemical and Western blot methods, respectively.Results: Incubation of mitochondria with aged Aβ25-35 inhibited the activities of α-ketoglutarate dehydrogenase (α-KGDH),pyruvate dehydrogenase (PDH) and respiratory chain complex IV. It also resulted in increased H2O2 and O.-2 production,and decreased the GSH level in mitochondria. Furthermore, it induced mitochondrial swelling and cytochrome c release from the mitochondria. The addition of FLZ (100 μmol/L) prior to treatment with Aβ25-35 significantly prevented these toxic effects of Aβ25-35 on the mitochondria.Conclusion: FLZ has a protective effect against Aβ25-35-induced mitochondrial dysfunction in vitro.

  8. Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells.

    Science.gov (United States)

    Dong, Yinhui; Yin, Shutao; Song, Xinhua; Huo, Yazhen; Fan, Lihong; Ye, Min; Hu, Hongbo

    2016-04-01

    Curcumin-based structural modification for developing more effective curcumin analogues has been drawning increasing attention. As alternative approach, using LC/MS guided purification, we previously obtained a series of novel natural terpene-conjugated curcuminoids from turmeric, and some of them exhibited even more potent anti-cancer activity against multiple types of cancer cells than curcumin. The purpose of this follow-up study was designed to decipher the mechanisms involved in anti-cancer activity of these novel curcumin analogues. Apoptosis was evaluated using sub-G1 analysis by flow cytometry and Cell Death ELISA Kit. Changes of protein expression were analyzed by western blotting. RNA interference was employed to inhibit expression of specific protein. We found that bisabolocurcumin ether (T1) and demethoxybisabolocurcumin ether (T2) were able to trigger much stronger apoptosis induction in multiple types of cancer cells than curcumin, which was attributed to persistent and stronger ROS generation. ROS induction by T1 resulted in activation of p38/H2AX axis and p53. Inhibition of p38/H2AX led to a significant reduction of apoptosis, whereas inactivation of p53 caused a dramatically enhanced H2AX phosphorylation and apoptosis induction, suggesting activation of p38/H2AX contributed to apoptosis induction by T1, whereas p53 activation protected novel curcumins-induced apoptosis via suppression of H2AX activation. Our findings provide mechanistic support for the potential use of terpene-conjugated curcuminoids as a novel class of cancer chemopreventive agents. © 2015 Wiley Periodicals, Inc. PMID:25647442

  9. Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines.

    Science.gov (United States)

    Mohd Aluwi, Mohd Fadhlizil Fasihi; Rullah, Kamal; Yamin, Bohari M; Leong, Sze Wei; Abdul Bahari, Mohd Nazri; Lim, Sock Jin; Mohd Faudzi, Siti Munirah; Jalil, Juriyati; Abas, Faridah; Mohd Fauzi, Norsyahida; Ismail, Nor Hadiani; Jantan, Ibrahim; Lam, Kok Wai

    2016-05-15

    The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD. PMID:27040659

  10. Topical application of a vitamin D analogue exacerbates atopic dermatitis and induces the atopic dermatitis-like phenotype in Stat6VT mice.

    Science.gov (United States)

    Turner, Matthew J; Dasilva-Arnold, Sonia C; Yi, Qiaofang; Mehrotra, Purvi; Kaplan, Mark H; Travers, Jeffrey B

    2013-01-01

    Calcipotriene is a topical vitamin D3 analogue approved for the treatment of plaque and scalp psoriasis. We report the case of a 2-year-old boy whose atopic dermatitis (AD) flared in response to application of calcipotriene 0.005% cream and solution for a mistaken diagnosis of plaque and scalp psoriasis. We investigated whether the patient's eruption was secondary to an allergic contact dermatitis. In the Stat6VT mouse model of AD we tested whether calcipotriene could induce the otherwise-spontaneous AD-like phenotype. Closed patch testing was done on the patient with calcipotriene solution and cream, moisturizing cream, and 51% isopropanol. Stat6VT and wild-type (WT) mice were treated for 7 days with calcipotriene solution or vehicle (isopropanol) applied to the right and left upper back skin, respectively, after which mice were followed longitudinally for 10 weeks. Biopsy specimens from prior treatment sites were then collected for histology and RNA isolation. RNA was analyzed for interleukin (IL-4) expression using quantitative polymerase chain reaction. Patch testing was negative. Stat6VT mice, in contrast to WT mice, developed a persistent eczematous dermatitis at sites of calcipotriene application. Clinical and histologic features and high IL-4 transcript levels were consistent with the spontaneous AD-like phenotype seen in Stat6VT mice. At sites of active disease, calcipotriene can worsen a flare of AD. In Stat6VT mice, calcipotriene can induce the AD-like phenotype. PMID:23889122

  11. Analogue MIMO Detection

    Directory of Open Access Journals (Sweden)

    McNamara Darren

    2006-01-01

    Full Text Available In this contribution we propose an analogue receiver that can perform turbo detection in MIMO systems. We present the case for a receiver that is built from nonlinear analogue devices, which perform detection in a "free-flow" network (no notion of iterations. This contribution can be viewed as an extension of analogue turbo decoder concepts to include MIMO detection. These first analogue implementations report reductions of few orders of magnitude in the number of required transistors and in consumed energy, and the same order of improvement in processing speed. It is anticipated that such analogue MIMO decoder could bring about the same advantages, when compared to traditional digital implementations.

  12. Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV‐3 and A-2780 cancer cells

    International Nuclear Information System (INIS)

    In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC50 = 0.71 μM) and SKOV-3 (IC50 = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.

  13. Resveratrol analogue 3,4,4′,5-tetramethoxystilbene inhibits growth, arrests cell cycle and induces apoptosis in ovarian SKOV‐3 and A-2780 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Piotrowska, Hanna; Myszkowski, Krzysztof; Ziółkowska, Alicja [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kulcenty, Katarzyna [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Wierzchowski, Marcin [Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Poznan (Poland); Kaczmarek, Mariusz [Department of Clinical Immunology, Poznan University of Medical Sciences, Poznan (Poland); Murias, Marek [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland); Kwiatkowska-Borowczyk, Eliza [Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan (Poland); Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Poznan (Poland); Jodynis-Liebert, Jadwiga, E-mail: liebert@ump.edu.pl [Department of Toxicology, Poznan University of Medical Sciences, Poznan (Poland)

    2012-08-15

    In the screening studies, cytotoxicity of 12 methylated resveratrol analogues on 11 human cancer cell lines was examined. The most active compound 3,4,4′5-tetramethoxystilbene (DMU-212) and two ovarian cancer cell lines A-2780 (IC{sub 50} = 0.71 μM) and SKOV-3 (IC{sub 50} = 11.51 μM) were selected for further investigation. To determine the mechanism of DMU-212 cytotoxicity, its ability to induce apoptosis was examined. DMU-212 arrested cell cycle in the G2/M or G0/G1 phase which resulted in apoptosis of both cell lines. The expression level of 84 apoptosis-related genes was investigated. In SKOV-3 cells DMU-212 caused up-regulation of pro-apoptotic Bax, Apaf-1 and p53 genes, specific to intrinsic pathway of apoptosis, and a decrease in Bcl-2 and Bcl 2110 mRNA expressions. Conversely, in A-2780 cells an increased expression of pro-apoptotic genes Fas, FasL, TNF, TNFRSF10A, TNFRSF21, TNFRSF16 specific to extracellular mechanism of apoptosis was observed. There are no data published so far regarding the receptor mediated apoptosis induced by DMU-212. The activation of caspase-3/7 was correlated with decreased TRAF-1 and BIRC-2 expression level in A-2780 cells exposed to DMU-212. DMU-212 caused a decrease in CYP1A1 and CYP1B1 mRNA levels in A-2780 by 50% and 75%, and in SKOV-3 cells by 15% and 45%, respectively. The protein expression was also reduced in both cell lines. It is noteworthy that the expression of CYP1B1 protein was entirely inhibited in A-2780 cells treated with DMU-212. It can be suggested that different CYP1B1 expression patterns in either ovarian cell line may affect their sensitivity to cytotoxic activity of DMU-212. -- Highlights: ► DMU-212 was the most cytotoxic among 12 O-methylated resveratrol analogues. ► DMU-212 arrested cell cycle at G2/M and G0/G1phase ► DMU-212 triggered mitochondria- and receptor‐mediated apoptosis. ► DMU-212 entirely inhibited CYP1B1 protein expression in A-2780 cells.

  14. Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664 or nitroglycerin

    Directory of Open Access Journals (Sweden)

    Sidi Avner

    2008-01-01

    Full Text Available In patients at risk for sudden ethanol (ETOH intravascular absorption, prompt treatment of pulmonary hypertension (PHTN will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664 and nitroglycerin (NTG during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT, as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP, and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg ( n = 7 normal saline, a 500-μg/kg bolus of UK343-664 ( n = 8, or NTG 1 μg/kg ( n = 8; each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP, and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR. Within 2 minutes after treatment with either drug, CVP, heart rate (HR, and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241±579 and 1224±494 dyne · cm/sec 5 , which were threefold-to-fourfold increased baseline values, to 672±308 and 538±203 dyne · cm/sec 5 respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from

  15. The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64.

    Science.gov (United States)

    McCarthy, Desmond A; Macey, Marion G; Streetly, Matthew; Schey, Stephen A; Brown, K Alun

    2006-07-01

    A major limitation to the treatment of multiple myeloma by the thalidomide analogue CC-4047 (Actimid) is the development of a severe neutropenia. We investigated the hypothesis that this effect may have been due to CC-4047 enhancing the removal of neutrophils from the circulation by altering the expression of surface adhesion molecules required for endothelial binding, by binding to platelets, or by enhancing apoptosis. Flow cytometric analysis was used to examine the expression of neutrophil surface molecules, platelet binding and apoptosis in whole blood samples from 19 patients with multiple myeloma who were assigned to receive either 1, 2, 5 or 10 mg of CC-4047 every other day (e.o.d.) for 28 days. CC-4047 induced dose-related decreases in neutrophil numbers and increases in the percentage of CD64-positive neutrophils, but had little, or no effect on the expression of CD11b, CD62L or CD162, neutrophil-platelet binding, or apoptosis. Relative decreases in the neutrophil count were inversely associated with relative increases in the intensity of CD64 expression on neutrophils (r=- 0.307; p=0.028). Although seven patients developed severe neutropenia, none suffered severe or recurrent bacterial infections. The percentage of CD64-positive neutrophils was still increased in eight patients who continued receiving 1-5 mg CC-4047 e.o.d. for several months afterwards, but neutrophil counts were similar to pre-treatment values. PMID:16714224

  16. Intratracheal Administration of Prostacyclin Analogue-incorporated Nanoparticles Ameliorates the Development of Monocrotaline and Sugen-Hypoxia-induced Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Kondo, Megumi; Miura, Daiji; Matoba, Tetsuya; Egashira, Kensuke; Ito, Hiroshi

    2016-04-01

    Nanoparticles (NPs) have been used as novel drug delivery systems. Drug-incorporated NPs for local delivery might optimize the efficacy and minimize the side effects of drugs. Intravenous prostacyclin improves long-term survival in patients with pulmonary arterial hypertension (PAH), but it causes serious side effects such as catheter-related infections. We investigated the efficacy and safety of intratracheal administration of a prostacyclin analogue, beraprost (BPS), incorporated NPs in Sugen-hypoxia-normoxia and monocrotaline rat models of PAH and in human PAH pulmonary arterial smooth muscle cells (PASMCs). After a single administration, BPS NPs significantly decreased right ventricular pressure, right ventricular hypertrophy, and pulmonary artery muscularization in the 2 rat models. BPS NPs significantly improved the survival rate in the monocrotaline rat model. No infiltration of inflammatory cells, hemorrhage, or fibrosis was found in the liver, kidney, spleen, and heart after the administration of BPS NPs. No liver or kidney dysfunction was found in the blood examinations. BPS and BPS NPs significantly inhibited the proliferation of human PAH PASMCs after 24 hours of treatment. BPS NPs significantly continued to inhibit the proliferation of human PAH PASMCs at 24 hours after the removal of BPS NPs. BPS NPs significantly induced apoptosis in PAH PASMCs compared to that in non-PAH PASMCs. Intratracheal administration of BPS NPs ameliorates pulmonary hypertension in PAH rat models by a sustained antiproliferative effect and a proapoptotic effect on PAH PASMCs. PMID:26745002

  17. Radiation-Induced Defects in Kaolinite as Tracers of Past Occurrence of Radionuclides in a Natural Analogue of High Level Nuclear Waste Repository

    Science.gov (United States)

    Allard, T.; Fourdrin, C.; Calas, G.

    2007-05-01

    Understanding the processes controlling migrations of radioelements at the Earth's surface is an important issue for the long-term safety assessment of high level nuclear waste repositories (HLNWR). Evidence of past occurrence and transfer of radionuclides can be found using radiation-induced defects in minerals. Clay minerals are particularly relevant because of their widespread occurrence at the Earth's surface and their finely divided nature which provides high contact area with radioactive fluids. Owing to its sensitivity to radiations, kaolinite can be used as natural, in situ dosimeter. Kaolinite is known to contain radiation-induced defects which are detected by Electron Paramagnetic Resonance. They are differentiated by their nature, their production kinetics and their thermal stability. One of these defects is stable at the scale of geological periods and provides a record of past radionuclide occurrence. Based on artificial irradiations, a methodology has been subsequently proposed to determine paleodose cumulated by kaolinite since its formation. The paleodose can be used to derive equivalent radioelement concentrations, provided that the age of kaolinite formation can be constrained. This allows quantitative reconstruction of past transfers of radioelements in natural systems. An example is given for the Nopal I U-deposit (Chihuahua, Mexico), hosted in hydrothermally altered volcanic tufs and considered as analogue of the Yucca Mountain site. The paleodoses experienced by kaolinites were determined from the concentration of defects and dosimetry parameters of experimental irradiations. Using few geochemical assumption, a equivalent U-content responsible for defects in kaolinite was calculated from the paleodose, a dose rate balance and model ages of kaolinites constrained by tectonic phases. In a former study, the ages were assumptions derived from regional tectonic events. In thepresent study, ages of mineralization events are measured from U

  18. Synthesis of caged Garcinia xanthone analogues

    OpenAIRE

    Cho, Woo Cheal

    2009-01-01

    A new synthetic strategy is developed toward the synthesis of the caged Garcinia xanthone analogues. The key to the strategy is a Pd-catalyzed reverse prenylation reaction. This new synthetic approach provides a rapid and efficient access to various caged analogues, including cluvenone which is known to induce apoptosis and exhibit significant cytotoxicity in various cancer cell lines. Evaluation of their growth inhibitory activities also leads to identification of the pharmacophoric motif of...

  19. Heterometallic trinuclear {CoLn(III)} (Ln = Gd, Tb, Ho and Er) complexes in a bent geometry. Field-induced single-ion magnetic behavior of the Er(III) and Tb(III) analogues.

    Science.gov (United States)

    Goura, Joydeb; Brambleby, Jamie; Topping, Craig V; Goddard, Paul A; Suriya Narayanan, Ramakirushnan; Bar, Arun Kumar; Chandrasekhar, Vadapalli

    2016-05-31

    Through the use of a multi-site compartmental ligand, 2-methoxy-6-[{2-(2-hydroxyethylamino)ethylimino}methyl]phenol (LH3), the family of heterometallic, trinuclear complexes of the formula [CoLn(L)2(μ-O2CCH3)2(H2O)3]·NO3·xMeOH·yH2O has been expanded beyond Ln = Dy(III) to include Gd(III) (), Tb(III) (), Ho(III) () and Er(III) () for , and (x = 1; y = 1) and for (x = 0; y = 2). The metallic core of these complexes consists of a (Co(III)-Ln(III)-Co(III)) motif bridged in a bent geometry resulting in six-coordinated distorted Co(III) octahedra and nine-coordinated Ln(III) monocapped square-antiprisms. The magnetic characterization of these compounds reveals the erbium and terbium analogues to display a field induced single-ion magnetic behavior similar to the dysprosium analogue but at lower temperatures. The energy barrier for the reversal of the magnetization of the CoTb(III) analogue is Ueff ≥ 15.6(4) K, while for the CoEr(III) analogue Ueff ≥ 9.9(8) K. The magnetic properties are discussed in terms of distortions of the 4f electron cloud. PMID:27180723

  20. Chiral mononuclear lanthanide complexes and the field-induced single-ion magnet behaviour of a Dy analogue.

    Science.gov (United States)

    Lin, Shuang-Yan; Wang, Chao; Zhao, Lang; Wu, Jianfeng; Tang, Jinkui

    2015-01-01

    Three pairs of homochiral mononuclear lanthanide complexes, with the general formula [LnH4LRRRRRR/SSSSSS(SCN)2](SCN)2·xCH3OH·yH2O(Ln = Dy (R/S-Dy1), Ho (R/S-Ho1) and Er (R/S-Er1)), have been obtained via self-assembly between chiral macrocyclic ligands and the respective thiocyanates, all of which show a saddle-type conformation with seven-coordinated metal ions. Magnetic measurements revealed that the Dy complex shows field-induced single-ion magnet behaviour, which is rarely reported in a seven-coordinated lanthanide-based SIM encapsulated in a macrocyclic ligand. The absolute configuration of all enantiomers was determined by single crystal X-ray crystallography and confirmed by electronic CD and VCD spectra. PMID:25369972

  1. Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats.

    Science.gov (United States)

    Abbas, Amr M

    2016-09-01

    Myocardial infarction (MI) is a common cause of mortality worldwide. Isorhapontigenin is a derivative of stilbene with chemical structure similar to resveratrol. The omega-3 fatty acids (FA) have beneficial effects on neurodegenerative, inflammatory, and cardiovascular diseases. The aim of this study was to investigate the effects of pretreatment with isorhapontigenin and omega-3 FA on rat model of isoproterenol-induced MI. Fifty-six rats were divided into seven groups: normal, normal + isorhapontigenin, normal + omega-3 FA, MI, MI + isorhapontigenin, MI + omega-3 FA, and MI + isorhapontigenin + omega-3 FA. Serum levels of cardiac marker enzymes [lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB)], cardiac troponin I (cTnI), inflammatory markers [tumor necrosis factor-alpha (TNF-α) and interleukin-6], and lipid profile [triglycerides, total cholesterol (T.Ch), high and low density lipoproteins (HDL, LDL), and phospholipids] as well as cardiac levels of malondialdehyde and anti-oxidants [reduced glutathione (GSH), superoxide dismutase (SOD), and catalase)] were measured in all rats. ECG and histopathological examination were performed. Isoproterenol caused a significant elevation of ST segment, decreased R wave amplitude, HDL, and anti-oxidants, and increased LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, triglycerides, T.Ch, LDL, and phospholipids. Omega-3 FA or isorhapontigenin significantly decreased the ST segment elevation, LDH, CK-MB, cTnI, TNF-α, interleukin-6, malondialdehyde, and phospholipids and increased R wave amplitude and anti-oxidants. The effects of combined omega-3 FA and isorhapontigenin were more significant than either of them alone. Therefore, we conclude that omega-3 FA and isorhapontigenin have a cardioprotective effect on rats with isoproterenol-induced MI through their anti-oxidant and anti-inflammatory actions. PMID:27193109

  2. Raloxifene analogue LY117018 suppresses oxidative stress-induced endothelial cell apoptosis through activation of ERK1/2 signaling pathway.

    Science.gov (United States)

    Yu, Jing; Eto, Masato; Kozaki, Koichi; Akishita, Masahiro; Okabe, Tetsuro; Ouchi, Yasuyoshi

    2008-07-28

    A selective estrogen receptor modulator, raloxifene, has been shown to reduce cardiovascular events in relatively high-risk postmenopausal women with osteoporosis. However, the mechanisms by which raloxifene exerts a pharmacological effect on cardiovascular organs have not been fully elucidated. The present study was designed to examine whether the raloxifene analogue, 6-hydroxy-2-(p-hydroxyphenyl)-benzo(b) thien-3-yl-p-(2-(pyrrolidinyl)ethoxy phenyl ketone (LY117018), could inhibit apoptosis and to clarify the signaling pathway in vascular endothelial cells. LY117018 significantly inhibited hydrogen peroxide-induced apoptosis in bovine carotid artery endothelial cells. The anti-apoptotic effect of LY117018 was abolished by an estrogen receptor antagonist, 7alpha,7beta-(9[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl) estra-1,3,5(10)-triene-3,17-diol (ICI 182,780). Mitogen-activated protein kinases (MAPK), including p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase1/2 (ERK1/2), and Akt, have been shown to act as apoptotic or anti-apoptotic signals. Phosphorylation of p38, JNK, ERK1/2 and Akt was examined. LY117018 increased ERK1/2 phosphorylation but did not enhance the phosphorylation of p38, JNK, or Akt. The anti-apoptotic effect of LY117018 was prevented by treatment with 2-[2'-amino-3'-methoxyphenyl]-oxanaphthalen-4-one (PD98059), an upstream inhibitor of ERK1/2. LY117018 stimulated an increase in ERK1/2 phosphorylation, which was diminished by ICI 182,780. The activation of ERK/1/2 by LY117018 was not inhibited by the transcription inhibitor, actinomycin D. These results suggest that estrogen receptors and the ERK1/2 signaling pathway are involved in the anti-apoptotic action of LY117018 in vascular endothelial cells. PMID:18541231

  3. Chemical and isotopic characterization of water-rock interactions in shales induced by the intrusion of a basaltic dike: A natural analogue for radioactive waste disposal

    International Nuclear Information System (INIS)

    Disposal of nuclear waste in deep geological formations is expected to induce thermal fluxes for hundreds of years with maximum temperature reaching about 100-150 deg. C in the nearfield argillaceous environment. The long-term behavior of clays subjected to such thermal gradients needs to be perfectly understood in safety assessment considerations. In this respect, a Toarcian argillaceous unit thermally disturbed by the intrusion of a 1.1-m wide basaltic dike at the Perthus pass (Herault, France), was studied in detail as a natural analogue. The thermal imprint induced by the dike was evaluated by a mineralogical, chemical and K-Ar study of the <2 μm clay fraction of shale samples collected at increasing distance from the basalt. The data suggest that the mineral composition of the shales was not significantly disturbed when the temperature was below 100-150 deg. C. Closer to the dike at 150-300 deg. C, changes such as progressive dissolution of chlorite and kaolinite, increased content of the mixed layers illite-smectite with more illite layers, complete decalcification and subsequent increased content of quartz, were found. At the eastern contact with the dike, the mineral and chemical compositions of both the shales and the basalt suggest water-rock interactions subsequent to the intrusion with precipitation of palagonite and renewed but discrete deposition of carbonate. A pencil cleavage developed in the shales during the dike emplacement probably favored water circulation along the contact. Strontium isotopic data suggest that the fluids of probable meteoric origin, reacted with Bathonian and Bajocian limestones before entering the underlying Toarcian shales. By analogy with deep geological radioactive waste repositories, the results report discrete mineralogical variations of the clays when subjected to temperatures of 100-150 deg. C that are expected in deep storage conditions. Beyond 150 deg. C, significant mineralogical changes may alter the physical and

  4. Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.

    Directory of Open Access Journals (Sweden)

    Guang-Rong Yan

    Full Text Available Oxidative stress is considered to be a major factor contributing to pathogenesis and progression of many diseases. A novel andrographolide-lipoic acid conjugate (AL-1 could protect pancreatic β-cells from reactive oxygen species (ROS-induced oxidative injury. However, its protective mechanism is still unclear. In this work, we used proteomics to identify AL-1-regulated proteins in β-cells and found that 13 of the 71 proteins regulated by AL-1 were closely associated with antioxidation. These differential proteins were mainly involved in the ERK1/2 and AKT1 signaling pathways. Functional investigation demonstrated that AL-1 exerted its protective effects on H2O2-induced cell death of β-cells by generating NADPH oxidase-dependent ROS to activate ERK1/2 and AKT1 signaling pathways. As a consequence, the expressions of antioxidant proteins including Trx1, Prx1 and Prx5, and anti-apoptotic proteins including PDCD6IP, prohibitin, galectin-1 and HSP were upregulated. AL-1 probably worked as a "vaccinum" to activate the cellular antioxidant system by inducing the generation of low concentration ROS which then reciprocally protected β-cells from oxidative damage caused by high-level ROS from H2O2. To the best of our knowledge, this is the first comprehensive proteomic analysis illustrating a novel molecular mechanism for the protective effects of antioxidants on β-cells from H2O2-induced cell death.

  5. Nonstationary analogue black holes

    International Nuclear Information System (INIS)

    We study the existence of analogue nonstationary spherically symmetric black holes. The prime example is the acoustic model see Unruh (1981 Phys. Rev. Lett. 46 1351). We consider also a more general class of metrics that could be useful in other physical models of analogue black and white holes. We give examples of the appearance of black holes and of disappearance of white holes. We also discuss the relation between the apparent and the event horizons for the case of analogue black holes. In the end we study the inverse problem of determination of black or white holes by boundary measurements for the spherically symmetric nonstationary metrics. (paper)

  6. Synthesis of Tonghaosu Analogues

    Institute of Scientific and Technical Information of China (English)

    SUN Hai; LIN Yingjie; WU Yulin; WU Yikang

    2009-01-01

    Several new analogues of natural antifeedant tonghaosu were synthesized via m-CPBA (m-chloroperoxybenzoic acid) oxidation of corresponding 3-(a-furyl)propanols, Luche reduction of the resulting enone, epoxidation, acid-mediated spiroketalization, and radical mediated dehydration.

  7. Cobalamin analogues in humans

    DEFF Research Database (Denmark)

    Hardlei, Tore Forsingdal; Obeid, Rima; Herrmann, Wolfgang;

    2013-01-01

    BACKGROUND: Haptocorrin (HC) carries cobalamin analogues (CorA), but whether CorA are produced in the body is unknown. All cobalamins (Cbl) to the foetus are delivered by the Cbl-specific protein transcobalamin (TC), and therefore analysis of cord serum for CorA may help to clarify the origin of ......A in the human body are derived from Cbl....

  8. ACTINOMYCIN D ANALOGUES

    DEFF Research Database (Denmark)

    1997-01-01

    The present invention relates to new compounds being structurally and functionally similar to Actinomycin D and to combinatorial libraries of such compounds. The Actinomycin D analogues according to the present invention comprise two linear or cyclic peptide moieties constituted by $g...

  9. CEC natural analogue working group

    International Nuclear Information System (INIS)

    The second meeting of the CEC Natural Analogue Working Group took place on June 17-19, 1986, hosted by the Swiss NAGRA in Interlaken (CH). A review of recent progress in natural analogue programmes was carried out, and complemented by detailed discussions about geomicrobiology, archaeological analogues, natural colloids, and use of analogues to increase confidence in safety assessments for radioactive waste disposal. A statement drafted by the Group, and the presentations made, are put together in this report

  10. CEC Natural Analogue Working Group

    International Nuclear Information System (INIS)

    The central theme for the third meeting of the CEC analogue working group was ''How can analogue data be used for performance assessments, both in support of the results and for presentation to the public''. This report puts together the most recent achievements in this field, together with a review of on-going natural analogue programmes

  11. Natural analogue working group

    International Nuclear Information System (INIS)

    A Natural Analogue Working Group was established by the Commission of the European Communities in 1985. The purpose of this group is to bring together modellers with earth scientists and others, so that maximum benefit can be obtained from natural analogue studies with a view to safe geological disposal of radioactive waste. The first meeting of this group was held in Brussels from November 5 to 7, 1985. The discussions mainly concerned the identification of the modellers' needs and of the earth scientists' capacity to provide for them. Following the debates, a written statement was produced by the Group; this document forms the core of the present Report. Notes and outlines of many of the presentations made are grouped in four appendixes. The valuable contribution of all those involved in the meeting is gratefully acknowledged

  12. Gastric inhibitory polypeptide analogues

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2002-01-01

    and its analogues are attractive as therapeutic agents for type 2 diabetes mellitus, analogues of GIP are unlikely to be effective. On the other hand, GIP seems to play an important role in lipid metabolism, promoting the disposal of ingested lipids, and mice with a targeted deletion of the GIP...... of GIP and GLP-1 receptors, the incretin effect is essential for normal glucose tolerance. In patients with type 2 diabetes mellitus it turns out that the incretin effect is severely impaired or abolished. The explanation seems to be that both the secretion of GLP-1 and the effect of GIP are impaired...... (whereas both the secretion of GIP and the effect of GLP-1 are near normal). The impaired GLP-1 secretion is probably a consequence of diabetic metabolic disturbances. The known genetic variations in the GIP receptor sequence are not associated with type 2 diabetes mellitus, but a defective insulinotropic...

  13. Aspartame and Its Analogues

    Science.gov (United States)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  14. Solvent H-bond accepting ability induced conformational change and its influence towards fluorescence enhancement and dual fluorescence of hydroxy meta-GFP chromophore analogue.

    Science.gov (United States)

    Chatterjee, Tanmay; Mandal, Mrinal; Mandal, Prasun K

    2016-09-21

    The effect of structural rigidity towards enhancement of fluorescence quantum yield of GFP chromophore analogues has been documented. In the present study, a new way of enhancing the fluorescence quantum yield of two ortho-meta GFP chromophore analogues meta-methoxy-ortho-hydroxy-benzylimidazolidinone (abbreviated as mOMe-HBDI) and meta-diethylamino-ortho-hydroxyl imidazolidinone (abbreviated as MOHIM) has been reported. This enhancement is controlled by the H-bond accepting ability (denoted as β value) of the solvent and happens only in the case of GFP chromophore analogues having ortho (hydroxyl)-meta (electron donating group) and not in the case of analogues having a para electron donating group. The ground state (solid) conformation of mOMe-HBDI has been obtained from single crystal X-ray analysis, exhibiting the existence of strong intramolecular H-bonding. However, in solution phase, as the solvent β value increases, the strength of intramolecular H-bonding decreases. This process has strong influence on the relative conformational orientation of phenyl and imidazolidinone rings. For mOMe-HBDI, fluorescence quantum yield increases with increase in β value of the solvents. However, the effect of solvent polarity cannot be completely ruled out. The lower wavelength emission band (∼480 nm) has been assigned to the normal charge-transferred (CT) species, whereas the highly Stokes shifted emission band (∼660 nm) has been assigned to the proton-transferred (PT) tautomer species for mOMe-HBDI. In solvents of low β value (say hexane) only the PT band and in solvents of high β value (say DMSO) only the CT band is observed. Quite interestingly, in solvents of intermediate β value both CT and PT bands, thus dual emission, are observed. For mOMe-HBDI when fluorescence decay is monitored at the normal CT emission band, it is observed to be biexponential in nature. The short component increases from ∼0.2 ns to 0.6 ns and the long component increases from 1 to 3

  15. The Palmottu analogue project

    International Nuclear Information System (INIS)

    The report gives a summary of the results of investigations carried out in 1992 at the Palmottu natural analogue study site, which is a small U-Th mineralization in Nummi-Pusula, southwestern Finland. Additionally, the report includes several separate articles dealing with various aspects of the Palmottu Analogue Project: (1) deep groundwater flow, (2) interpretation of hydraulic connections, (3) characterization of groundwater colloids, (4) uranium mineral-groundwater equilibrium, (5) water-rock interaction and (6) modelling of in situ matrix diffusion. The Palmottu Analogue Project aims at a more profound understanding of radionuclide transport processes in fractured crystalline bedrock. The essential factors controlling transport are groundwater flow and interaction between water and rock. Accordingly, the study includes (1) structural interpretations partly based on geophysical measurements, (2) hydrological studies including hydraulic drill-hole measurements, (3) flow modelling, (4) hydrogeochemical characterization of groundwater, uranium chemistry and colloid chemistry, (5) mineralogical studies, (6) geochemical interpretation and modelling, (7) studies of radionuclide mobilization and retardation including matrix diffusion, and (8) modelling of uranium series data. Palaeohydrogeological aspects, due to the anticipated future glaciation of the Fennoscandian Shield, are of special interest. Quaternary sediments are studied to gain information on post-glacial migration in the overburden. (orig.)

  16. RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sá-Júnior, Paulo Luiz de [Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Pasqualoto, Kerly Fernanda Mesquita [Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Ferreira, Adilson Kleber [Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Tavares, Maurício Temotheo; Damião, Mariana Celestina Frojuello Costa Bernstorff [Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, Postal Code: 05508-000, Sao Paulo (Brazil); Azevedo, Ricardo Alexandre de [Biochemistry and Biophysical Laboratory, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Câmara, Diana Aparecida Dias; Pereira, Alexandre; Madeiro de Souza, Dener [Laboratory of Genetics, Butantan Institute, Vital Brasil Avenue 1500, Postal Code: 05503-900, Sao Paulo (Brazil); Parise Filho, Roberto, E-mail: roberto.parise@usp.br [Department of Pharmacy, School of Pharmaceutical Sciences, University of Sao Paulo, Prof. Lineu Prestes Avenue, 580, Postal Code: 05508-000, Sao Paulo (Brazil)

    2013-02-01

    Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is the primary pungent compound in red peppers, was reported to selectively inhibit the growth of a variety tumor cell lines. Here, we report for the first time a novel synthetic capsaicin-like analogue, RPF101, which presents a high antitumor activity on MCF-7 cell line, inducing arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. Furthermore, it causes cellular morphologic changes characteristic of apoptosis and a decrease of Δψm. Molecular modeling studies corroborated the biological findings and suggested that RPF101, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. All these findings support the fact that RPF101 is a promising anticancer agent. -- Highlights: ► We report for the first time that RPF101 possesses anticancer properties. ► RPF101 induces apoptosis of human breast cancer cells. ► RPF 101 decreases mitochondrial potential and induces DNA fragmentation.

  17. RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Capsaicin, which is the primary pungent compound in red peppers, was reported to selectively inhibit the growth of a variety tumor cell lines. Here, we report for the first time a novel synthetic capsaicin-like analogue, RPF101, which presents a high antitumor activity on MCF-7 cell line, inducing arrest of the cell cycle at the G2/M phase through a disruption of the microtubule network. Furthermore, it causes cellular morphologic changes characteristic of apoptosis and a decrease of Δψm. Molecular modeling studies corroborated the biological findings and suggested that RPF101, besides being a more reactive molecule towards its target, may also present a better pharmacokinetic profile than capsaicin. All these findings support the fact that RPF101 is a promising anticancer agent. -- Highlights: ► We report for the first time that RPF101 possesses anticancer properties. ► RPF101 induces apoptosis of human breast cancer cells. ► RPF 101 decreases mitochondrial potential and induces DNA fragmentation.

  18. The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice.

    Directory of Open Access Journals (Sweden)

    Emil Egecioglu

    Full Text Available The gastrointestinal peptide glucagon-like peptide 1 (GLP-1 is known to regulate consummatory behavior and is released in response to nutrient ingestion. Analogues of this peptide recently emerged as novel pharmacotherapies for treatment of type II diabetes since they reduce gastric emptying, glucagon secretion as well as enhance glucose-dependent insulin secretion. The findings that GLP-1 targets reward related areas including mesolimbic dopamine areas indicate that the physiological role of GLP-1 extends beyond food intake and glucose homeostasis control to include reward regulation. The present series of experiments was therefore designed to investigate the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4, on established nicotine-induced effects on the mesolimbic dopamine system in mice. Specifically, we show that treatment with Ex4, at a dose with no effect per se, attenuate nicotine-induced locomotor stimulation, accumbal dopamine release as well as the expression of conditioned place preference in mice. In accordance, Ex4 also blocks nicotine-induced expression of locomotor sensitization in mice. Given that development of nicotine addiction largely depends on the effects of nicotine on the mesolimbic dopamine system these findings indicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for nicotine cessations in humans.

  19. Archaeological analogues and corrosion

    International Nuclear Information System (INIS)

    One solution retained for the management of high-level and long living radioactive wastes is the disposal in deep underground. Among the studies carried out by the Andra for the evaluation this solution, one concerns the research on metals corrosion for the development of reliable containers. Laboratory corrosion tests are in progress and are compared to the corrosion state of archaeological metal specimens of several hundred years old. Gallic or Mesopotamian remnants are some of these archaeological analogues which are analyzed using the most advanced techniques of materials science. (J.S.)

  20. A novel synthetic C-1 analogue of 7-deoxypancratistatin induces apoptosis in p53 positive and negative human colorectal cancer cells by targeting the mitochondria: enhancement of activity by tamoxifen.

    Science.gov (United States)

    Ma, Dennis; Tremblay, Phillip; Mahngar, Kevinjeet; Akbari-Asl, Pardis; Collins, Jonathan; Hudlicky, Tomas; McNulty, James; Pandey, Siyaram

    2012-06-01

    The natural compound pancratistatin (PST), isolated from the Hymenocallis littoralis plant, specifically induces apoptosis in many cancer cell lines. Unlike many other chemotherapeutics, PST is not genotoxic and has minimal adverse effects on non-cancerous cells. However, its availability for preclinical and clinical work is limited due to its low availability in its natural source and difficulties in its chemical synthesis. Several synthetic analogues of 7-deoxypancratistatin with different modifications at C-1 were synthesized and screened for apoptosis inducing activity in human colorectal cancer (CRC) cells. We found that a C-1 acetoxymethyl derivative of 7-deoxypancratistatin, JC-TH-acetate-4 (JCTH-4), was effective in inducing apoptosis in both p53 positive (HCT 116) and p53 negative (HT-29) human CRC cell lines, demonstrating similar efficacy to that of natural PST. JCTH-4 was able to decrease mitochondrial membrane potential (MMP), increase levels of reactive oxygen species in isolated mitochondria, cause release of the apoptogenic factor cytochrome c (Cyto c) from isolated mitochondria, and induce autophagy in HCT 116 and HT-29 cells. Interestingly, when JCTH-4 was administered with tamoxifen (TAM), there was an enhanced effect in apoptosis induction, reactive oxygen species (ROS) production and Cyto c release by isolated mitochondria, and autophagic induction by CRC cells. Minimal toxicity was exhibited by a normal human fetal fibroblast (NFF) and a normal colon fibroblast (CCD-18Co) cell line. Hence, JCTH-4 is a novel compound capable of selectively inducing apoptosis and autophagy in CRC cells alone and in combination with TAM and may serve as a safer and more effective alternative to current cancer therapies. PMID:21494837

  1. Radiolabeled somatostatin analogues

    International Nuclear Information System (INIS)

    Somatostatin is a naturally occurring tetradecapeptide that inhibits the secretion of many hormones. Large numbers of binding sites with high affinity for somatostatin have been reported in a variety of tumors. An octapeptide analogue of somatostatin, octreotide (Sandostatin), is currently used in the treatment of patients with somatostatin receptor-positive tumors to limit hormonal hyper secretion. In an effort to utilize the high specificity of octreotide for scintigraphic imaging of somatostatin receptor-positive tumors, a tyrosine derivative of octreotide was prepared and labeled with the radioactive isotope, I-123. While the early clinical results obtained with this radiopharmaceutical were encouraging, the I-123 labeling procedure proved cumbersome and variable. To circumvent these difficulties, researchers at University Hospital Rotterdam (Holland) and Sandoz Research Institute (Switzerland) developed an In-111 labeled analogue of octreotide. This radiopharmaceutical is easy to prepare and has proven to be even more effective than the I-123 derivative in the scintigraphic imaging of tumors. These radiopharmaceutical developments and clinical observations are discussed in light of their relevance to the generation of new radiolabeled peptides for the diagnosis and potential radiotherapy of cancer. (authors). 30 refs., 5 figs

  2. Vorticity in analogue gravity

    CERN Document Server

    Cropp, Bethan; Turcati, Rodrigo

    2015-01-01

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

  3. Alligator Rivers analogue project

    International Nuclear Information System (INIS)

    Australian Nuclear Science and Technology Organization has extensively evaluated uranium ore bodies in the Alligator Rivers Uranium Province in Australia as analogues of radioactive waste repositories. The work was extended for a three-year program as an international project based on the Koongarra uranium deposit and sponsored by the OECD Nuclear Energy Agency. The technical program comprises six major sub-projects involving modelling and experimental work: modelling of radionuclide migration; hydrogeology of the Koongarra uranium deposit; uranium/thorium series disequilibria studies; groundwater and colloid studies; fission product studies; transuranic nuclide studies; an outline of the technical programs and a summary of progress in the technical sub-projects is given. This is followed by a series of technical reports which briefly describe current research tasks, and which have been separately indexed

  4. Structural analogues of diosgenyl saponins: synthesis and anticancer activity.

    Science.gov (United States)

    Kaskiw, Matthew J; Tassotto, Mary Lynn; Mok, Mac; Tokar, Stacey L; Pycko, Roxanne; Th'ng, John; Jiang, Zi-Hua

    2009-11-15

    Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroidal saponins and exhibits potent anticancer activity in several human cancer cells through apoptosis-inducing pathways. In this paper, we describe the synthesis of several diosgenyl saponin analogues containing either a 2-amino-2-deoxy-beta-d-glucopyranosyl residue or an alpha-l-rhamnopyranosyl-(1-->4)-2-amino-2-deoxy-beta-d-glucopyranosyl residue with different acyl substituents on the amino group. The cytotoxic activity of these compounds was evaluated in MCF-7 breast cancer cells and HeLa cervical cancer cells. Structure-activity relationship studies show that the disaccharide saponin analogues are in general less active than their corresponding monosaccharide analogues. The incorporation of an aromatic nitro functionality into these saponin analogues does not exhibit significant effect on their cytotoxic activity. PMID:19819703

  5. The effects of substance P analogues on the scratching, biting and licking response induced by intrathecal injection of N-methyl-D-aspartate in mice.

    OpenAIRE

    Sakurada, T.; Manome, Y.; Tan-No, K.; Sakurada, S.; Kisara, K.

    1990-01-01

    1. Intrathecal (i.t.) administration of N-methyl-D-aspartate (NMDA) elicited a dose-dependent behavioural response consisting of licking, biting and scratching in mice. 2. Repeated i.t. injections of 0.4 nmol NMDA, at 5 min intervals, resulted in the rapid development of desensitization to this NMDA-induced behavioural phenomenon. 3. The NMDA-induced response was dose-dependently inhibited by the simultaneous injection of a selective NMDA-receptor antagonist, D-2-amino-5-phosphonovaleric acid...

  6. NASA/ESMD Analogue Mission Plans

    Science.gov (United States)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  7. Protein kinase C activity is not involved in N-formylmethionyl-leucyl-phenylalanine-induced phospholipase D activation in human neutrophils, but is essential for concomitant NADPH oxidase activation: studies with a staurosporine analogue with improved selectivity for protein kinase C.

    Science.gov (United States)

    Kessels, G C; Krause, K H; Verhoeven, A J

    1993-06-15

    Stimulation of human neutrophils by the receptor agonist N-formylmethionyl-leucyl-phenylalanine (fMLP) results in a respiratory burst, catalysed by an NADPH oxidase. Concomitantly, phospholipase D (PLD) is activated. To investigate the role of protein kinase C (PKC) in these neutrophil responses, we have compared the effects of staurosporine and a structural analogue of staurosporine (cgp41251), that reflects a higher selectivity towards PKC [Meyer, Regenass, Fabbro, Alteri, Rösel, Müller, Caravatti and Matter (1989) Int. J. Cancer 43, 851-856]. Both staurosporine and cgp41251 dose-dependently inhibited the production of superoxide induced by phorbol 12-myristate 13-acetate (PMA). Both compounds also caused inhibition of the fMLP-induced respiratory burst, but with a lower efficacy during the initiation phase of this response. This latter observation cannot be taken as evidence against PKC involvement in the activation of the respiratory burst, because pretreatment of neutrophils with ionomycin before PMA stimulation also results in a lower efficacy of inhibition. Activation of PLD by fMLP was enhanced in the presence of staurosporine, but not in the presence of cgp41251. Enhancement of PLD activation was also observed in the presence of H-89, an inhibitor of cyclic-AMP-dependent protein kinase (PKA). Both staurosporine and H-89 reversed the dibutyryl-cyclic-AMP-induced inhibition of PLD activation, whereas cgp41251 was without effect. These results indicate that the potentiating effect of staurosporine on PLD activation induced by fMLP does not reflect a feedback inhibition by PKC activation, but instead a feedback inhibition by PKC activation. Taken together, our results indicate that in human neutrophils: (i) PKC activity is not essential for fMLP-induced activation of PLD; (ii) PKC activity does play an essential role in the activation of the respiratory burst by fMLP, other than mediating or modulating PLD activation; (iii) there exists a negative

  8. Biological and molecular mechanisms of sulfur mustard analogue-induced toxicity in JB6 and HaCaT cells: possible role of ataxia telangiectasia-mutated/ataxia telangiectasia-Rad3-related cell cycle checkpoint pathway.

    Science.gov (United States)

    Tewari-Singh, Neera; Gu, Mallikarjuna; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2010-06-21

    Effective medical treatment and preventive measures for chemical warfare agent sulfur mustard (HD)-caused incapacitating skin toxicity are lacking, because of limited knowledge of its mechanism of action. The proliferating basal epidermal cells are primary major sites of attack during HD-caused skin injury. Therefore, employing mouse JB6 and human HaCaT epidermal cells, here, we investigated the molecular mechanism of HD analogue 2-chloroethyl ethyl sulfide (CEES)-induced skin cytotoxicity. As compared to the control, up to 1 mM CEES treatment of these cells for 2, 4, and 24 h caused dose-dependent decreases in cell viability and proliferation as measured by DNA synthesis, together with S and G2-M phase arrest in cell cycle progression. Mechanistic studies showed phosphorylation of DNA damage sensors and checkpoint kinases, ataxia telangiectasia-mutated (ATM) at ser1981 and ataxia telangiectasia-Rad3-related (ATR) at ser428 within 30 min of CEES exposure, and modulation of S and G2-M phase-associated cell cycle regulatory proteins, which are downstream targets of ATM and ATR kinases. Hoechst-propidium iodide staining demonstrated that CEES-induced cell death was both necrotic and apoptotic in nature, and the latter was induced at 4 and 24 h of CEES treatment in HaCaT and JB6 cells, respectively. An increase in caspase-3 activity and both caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage coinciding with CEES-caused apoptosis in both cell lines suggested the involvement of the caspase pathway. Together, our findings suggest a DNA-damaging effect of CEES that activates ATM/ATR cell cycle checkpoint signaling as well as caspase-PARP pathways, leading to cell cycle arrest and apoptosis/necrosis in both JB6 and HaCaT cells. The identified molecular targets, quantitative biomarkers, and epidermal cell models in this study have the potential and usefulness in rapid development of effective prophylactic and therapeutic interventions against HD-induced skin toxicity

  9. Insulin analogues and cancer: a note of caution

    Directory of Open Access Journals (Sweden)

    Joseph A.M.J.L. eJanssen

    2014-05-01

    Full Text Available Abstract In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. At present, the available data suggest that insulin analogues are safe. In line with these findings, we observed that serum of diabetic patients treated with insulin analogues, compared to that of diabetic patients treated with human insulin, did not induce an increased phosphorylation of tyrosine residues of the insulin-like growth factor-I receptor (IGF-IR. However, the classical model of the IGF-IR signaling may be insufficient to explain (all mitogenic effects of insulin analogues since also non-canonical signaling pathways of the IGF-IR may play a major role in this respect. Although phosphorylation of tyrosine residues of the IGF-IR is generally considered to be the initial activation step within the intracellular IGF-IR signaling pathway, it has been found that cells undergo a signaling switch under hyperglycemic conditions. After this switch, a completely different mechanism is utilized to activate the mitogenic (mitogen-activated protein kinase (MAPK pathways of the IGF-IR that is independent from tyrosine phosphorylation of the IGF-IR. At present it is unknown whether activation of this alternative intracellular pathway of the IGF-IR occurs during hyperglycemia in vivo and whether it is stronger in patients treated with (some insulin analogues than in patients treated with human insulin. In addition, it is unknown whether the insulin receptors (IRs also undergo a signaling switch during hyperglycemia. This should be investigated in future studies. Finally, relative overexpression of IR isoform A (IR-A in (pre cancer tissues may play a key role in the development and progression of human cancers during treatment with insulin (analogues. Further

  10. Direct Observation of Short-Range Structural Coherence During a Charge Transfer Induced Spin Transition in a CoFe Prussian Blue Analogue by Transmission Electron Microscopy.

    Science.gov (United States)

    Itoi, Miho; Jike, Toyoharu; Nishio-Hamane, Daisuke; Udagawa, Seiichi; Tsuda, Tetsuya; Kuwabata, Susumu; Boukheddaden, Kamel; Andrus, Matthew J; Talham, Daniel R

    2015-11-25

    The local structure within the Co-Fe atomic array of the photoswitchable coordination polymer magnet, K0.3Co[Fe(CN)6]0.77·nH2O, is directly observed during charge transfer induced spin transition (CTIST), a solid-solid phase change, using high-resolution transmission electron microscopy (HRTEM). Along with the low-spin (LS) or thermally quenched high-spin (HS) states normally observed in CTIST solids at low temperature, slow cooling of K0.3Co[Fe(CN)6]0.77·nH2O results in an intermediate phase containing both HS and LS domains with short coherence length. By mapping individual metal-metal distances, the nanometer-scale HS domains are directly visualized within the LS array. Temperature-dependent analyses allow monitoring of HS domain coarsening along the warming branch of the CTIST, providing direct visualization of the elastic process and insight into the mechanism of phase propagation. Normally sensitive to electron beam damage, the low-temperature TEM measurements of the porous coordination polymer are enabled by using appropriate ionic liquids instead of usual conductive thin-film coatings, an approach that should find general utility in related classes of materials. PMID:26510096

  11. Condensed matter analogues of cosmology

    Science.gov (United States)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  12. Vitamin E analogues and immune response in cancer treatment

    Czech Academy of Sciences Publication Activity Database

    Tomasetti, M.; Neužil, Jiří

    2007-01-01

    Roč. 76, - (2007), s. 463-491. ISSN 0083-6729 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : vitamin E analogues * inducers of apoptosis * immune surveillance Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.889, year: 2007

  13. Vitamin E analogue, D-alpha tocopherol succinate, enhances x-ray induced growth delay of human adenocarcinoma cancer cell line

    International Nuclear Information System (INIS)

    The purpose of this study was to assess the effects of d-alpha Tocopherol succinate (alpha-TS) in modifying radiation-induced viability reduction and apoptosis occurrence in the model for normal and cancer cells. Our hypothesis was that alpha-TS enhances the growth-inhibitory effect of x-irradiation in cancer cells and that the effect is more pronounced in these cells than in normal cells. Murine NIH 3T3 Swiss albino embryonic cells and HT29 human Caucasian colon adenocarcinoma cells were used in the experiments. Alpha-TS was added to the cultures 1 h prior to irradiation with doses of 2 or 5Gy of x-ray. After irradiation cells were incubated for 73 h. Trypan blue exclusion viability test and estimation of apoptosis and necrosis were made. Apoptotic and necrotic cells were counted in fluorescence microscope using fluorescence dyes: propidium iodide and Hoechst 33342. For experiments with the dose of 5 Gy at least five series of experiments were performed. At lower doses (up to approximately 25μM/ml) treatment with alpha-TS alone enhanced growth of both cell lines. At higher doses treatment with alpha-TS alone delayed the growth of the cell cultures, accompanied by 20-25% necrosis. At the concentrations higher than 25μM/mL alpha-TS alone caused growth delay of both cell cultures, being much more pronounced for the cancer cell line HT29. At the concentrations of 50 μM/mL, responsible for about 30-60% of growth delay, there was observed a synergy effect for x-rays and alpha-TS for both cell lines. The effect was more pronounced for HT29 cells (DMF=0.48 for HT29 versus DMF=0.73 for NIH 3T3). These results may confirm the views of the literature reports suggesting that use of vitamin E together with radiation could be favorable for colon cancer treatment; however, more experiments using more advanced techniques are needed

  14. Introduction to electronic analogue computers

    CERN Document Server

    Wass, C A A

    1965-01-01

    Introduction to Electronic Analogue Computers, Second Revised Edition is based on the ideas and experience of a group of workers at the Royal Aircraft Establishment, Farnborough, Hants. This edition is almost entirely the work of Mr. K. C. Garner, of the College of Aeronautics, Cranfield. As various advances have been made in the technology involving electronic analogue computers, this book presents discussions on the said progress, including some acquaintance with the capabilities of electronic circuits and equipment. This text also provides a mathematical background including simple differen

  15. q-Analogue of Wright Function

    Directory of Open Access Journals (Sweden)

    Moustafa El-Shahed

    2008-05-01

    Full Text Available We introduce a q-analogues of Wright function and its auxiliary functions as Barnes integral representations and series expansion. The relations between q-analogues of Wright function and some other functions are investigated.

  16. Superconductive analogue of spin glasses

    International Nuclear Information System (INIS)

    The properties of granular superconductors in magnetic fields, namely the existence of a new superconductive state analogue of the low-temperature superconductive state in spin glasses are discussed in the frame of the infinite-range model and the finite-range models. Experiments for elucidation of spin-glass superconductive state in real systems are suggested. 30 refs

  17. Novel acetylcholine and carbamoylcholine analogues

    DEFF Research Database (Denmark)

    Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Christensen, Jeppe K.;

    2008-01-01

    A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity for this ...

  18. Status of natural analogue studies

    International Nuclear Information System (INIS)

    This report is based on the materials for the meeting at the Nuclear Safety Commission of Japan held on September 1993. Details are as follows: Alteration of glass as the study of alteration of natural minerals; alteration of uranium minerals, migration of uranium and thorium series radionuclides, alteration of chlorite, fixation of uranium alteration of minerals and migration of uranium as the study of alligator rivers analogue project held at Koongarra uranium deposit, Australia. (author)

  19. Visual analogue measurement of pain.

    OpenAIRE

    Campbell, W. I.; Lewis, S.

    1990-01-01

    Two separate studies were carried out to determine if three visual analogue scales for various feelings including pain could be marked consistently by patients, without reference to previously completed scales. Sixty patients undergoing extraction of their lower third molars had measurements of acute preoperative anxiety, expected postoperative pain and postoperative perceived pain three times in quick succession. There was no significant difference between the three measurements for any of t...

  20. Policy issues in space analogues

    Science.gov (United States)

    Auger, Robin N.; Facktor, Debra D.

    Space mission planning is increasingly focusing on destinations beyond Earth orbit. Advancements in technology will inevitably be required to enable long-duration human spaceflight missions, and breakthroughs in the policy arena will also be needed to achieve success in such missions. By exploring how policy issues have been addressed in analogous extreme environments, policymakers can develop a framework for addressing these issues as they apply to long-term human spaceflight. Policy issues that need to be addressed include: crew selection, training, organization, and activities, medical testing, illness, injury, and death; communication; legal accountability and liability; mission safety and risk management; and environmental contamination. This paper outlines the approach of a study underway by The George Washington University and ANSER to examine how these policy issues have been addressed in several analogues and how the experiences of these analogues can help formulate policies for long-duration human spaceflight missions. Analogues being studied include Antarctic bases, submarine voyages, undersea stations, Biosphere 2, and the U.S. Skylab and Russian Mir space stations.

  1. Template polymerization of nucleotide analogues

    Science.gov (United States)

    Orgel, L. E.

    1991-01-01

    Recent work on the template-directed reactions of the natural D-nucleotides has made it clear that l-nucleotides and nucleotide-like derivatives of other sugars would strongly inhibit the formation of long oligonucleotides. Consequently, attention is focusing on molecules simpler than nucleotides that might have acted as monomers of an information transfer system. We have begun a general exploration of the template directed reactions of diverse peptide analogues. I will present work by Dr. Taifeng Wu on oxidative oligomerization of phosphorothioates and of Dr. Mary Tohidi on the cyclic polymerization of nucleoside and related cyclic pyrophosphates.

  2. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    Science.gov (United States)

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  3. Analogue imprecision in MLP training

    CERN Document Server

    Edwards, PJ

    1996-01-01

    Hardware inaccuracy and imprecision are important considerations when implementing neural algorithms. This book presents a study of synaptic weight noise as a typical fault model for analogue VLSI realisations of MLP neural networks and examines the implications for learning and network performance. The aim of the book is to present a study of how including an imprecision model into a learning scheme as a"fault tolerance hint" can aid understanding of accuracy and precision requirements for a particular implementation. In addition the study shows how such a scheme can give rise to significant

  4. A novel peptide sansalvamide analogue inhibits pancreatic cancer cell growth through G0/G1 cell-cycle arrest

    International Nuclear Information System (INIS)

    Patients with pancreatic cancer have little hope for cure because no effective therapies are available. Sansalvamide A is a cyclic depsipeptide produced by a marine fungus. We investigated the effect of a novel sansalvamide A analogue on growth, cell-cycle phases, and induction of apoptosis in human pancreatic cancer cells in vitro. The sansalvamide analogue caused marked time- and concentration-dependent inhibition of DNA synthesis and cell proliferation of two human pancreatic cancer cell lines (AsPC-1 and S2-013). The analogue induced G0/G1 phase cell-cycle arrest and morphological changes suggesting induction of apoptosis. Apoptosis was confirmed by annexin V binding. This novel sansalvamide analogue inhibits growth of pancreatic cancer cells through G0/G1 arrest and induces apoptosis. Sansalvamide analogues may be valuable for the treatment of pancreatic cancer

  5. The Valles natural analogue project

    Energy Technology Data Exchange (ETDEWEB)

    Stockman, H.; Krumhansl, J.; Ho, C. [Sandia National Labs., Albuquerque, NM (United States); McConnell, V. [Alaska Univ., Fairbanks, AK (United States). Geophysical Inst.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  6. The Valles natural analogue project

    International Nuclear Information System (INIS)

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and 39Ar/4O isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks

  7. Conjunctival changes induced by prostaglandin analogues and timolol maleate: a histomorphometric study Alterações conjuntivais induzidas por análogos de prostaglandinas e maleato de timolol: estudo histomorfométrico

    Directory of Open Access Journals (Sweden)

    Heloisa Helena Abil Russ

    2007-12-01

    Full Text Available PURPOSE: To compare histological changes induced by antiglaucoma medications in the rabbit conjunctiva. METHODS: Fifty New Zealand rabbits were divided in 5 groups of 10 animals. The left eyes were treated daily with one drop of bimatoprost 0.03%, travoprost 0.004%, latanoprost 0.005%, timolol maleate 0.5% or artificial tears containing benzalkonium chloride (BAK for 30 days. The right eyes served as controls. Superior limbic conjunctival biopsies were performed at the 8th and 30th day in 5 rabbits of each group. The conjunctiva was fixed with 10% formaldehyde, followed by HE and PAS staining. Morphohistometric quantitative analyses were performed to evaluate the following parameters: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels. RESULTS: At the 8th and 30th posttreatment days, all groups, except one that received artificial tears, exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin (PG analogues groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (p=0.0035. The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (p=0.0006, and at the 30th day in those treated with bimatoprost (p=0.0021 and latanoprost (p=0.009. CONCLUSIONS: Although a moderate, diffuse inflammatory infiltrate was observed in PG-treated eyes, no changes in conjunctival epithelial thickness or subconjunctival collagen density were observed with these medications, suggesting that these drugs induce fewer changes than timolol maleate in the rabbit conjunctiva.OBJETIVOS: Comparar alterações histológicas induzidas por medicação anti-glaucomatosa na conjuntiva de coelhos. MÉTODOS: Cinqüenta coelhos da raça Nova Zelândia foram divididos em 5 grupos de 10 animais. Os olhos

  8. Stereochemical Assignment of Strigolactone Analogues Confirms Their Selective Biological Activity.

    Science.gov (United States)

    Artuso, Emma; Ghibaudi, Elena; Lace, Beatrice; Marabello, Domenica; Vinciguerra, Daniele; Lombardi, Chiara; Koltai, Hinanit; Kapulnik, Yoram; Novero, Mara; Occhiato, Ernesto G; Scarpi, Dina; Parisotto, Stefano; Deagostino, Annamaria; Venturello, Paolo; Mayzlish-Gati, Einav; Bier, Ariel; Prandi, Cristina

    2015-11-25

    Strigolactones (SLs) are new plant hormones with various developmental functions. They are also soil signaling chemicals that are required for establishing beneficial mycorrhizal plant/fungus symbiosis. In addition, SLs play an essential role in inducing seed germination in root-parasitic weeds, which are one of the seven most serious biological threats to food security. There are around 20 natural SLs that are produced by plants in very low quantities. Therefore, most of the knowledge on SL signal transduction and associated molecular events is based on the application of synthetic analogues. Stereochemistry plays a crucial role in the structure-activity relationship of SLs, as compounds with an unnatural D-ring configuration may induce biological effects that are unrelated to SLs. We have synthesized a series of strigolactone analogues, whose absolute configuration has been elucidated and related with their biological activity, thus confirming the high specificity of the response. Analogues bearing the R-configured butenolide moiety showed enhanced biological activity, which highlights the importance of this stereochemical motif. PMID:26502774

  9. Analogues of neuroactive polyamine wasp toxins that lack inner basic sites exhibit enhanced antagonism toward a muscle-type mammalian nicotinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Stromgaard, K; Brierley, M J; Andersen, K; Sløk, F A; Mellor, I R; Usherwood, P N; Krogsgaard-Larsen, P; Jaroszewski, J W

    1999-01-01

    noncompetitively antagonized the nicotinic acetylcholine receptor (nAChR) in a concentration-, time-, and voltage-dependent manner. The amplitudes of acetylcholine-induced currents were compared at their peaks and at the end of a 1 s application in the presence or absence of the analogues. Most of the analogues...... properties (stepwise macroscopic pK(a) values) were determined by (13)C NMR titrations. All analogues are fully protonated at physiological pH. The effects of these compounds on acetylcholine-induced currents in TE671 cells clamped at various holding potentials were determined. All of the analogues...

  10. The chaos machine: analogue computing rediscovered (1)

    OpenAIRE

    Ambaum, Maarten H. P.; Harrison, R. Giles

    2011-01-01

    Analogue computers provide actual rather than virtual representations of model systems. They are powerful and engaging computing machines that are cheap and simple to build. This two-part Retronics article helps you build (and understand!) your own analogue computer to simulate the Lorenz butterfly that's become iconic for Chaos theory.

  11. Strategy and methodology of dynamical analogue prediction

    Institute of Scientific and Technical Information of China (English)

    REN; HongLi; CHOU; JiFan

    2007-01-01

    In order to effectively improve numerical prediction level by using current models and data, the strategy and methodology of dynamical analogue prediction (DAP) is deeply studied in the present paper. A new idea to predict the prediction errors of dynamical model on the basis of historical analogue information is put forward so as to transform the dynamical prediction problem into the estimation problem of prediction errors. In terms of such an idea, a new prediction method of final analogue correction of errors (FACE) is developed. Furthermore, the FACE is applied to extra-seasonal prediction experiments on an operational atmosphere-ocean coupled general circulation model. Prediction results of summer mean circulation and total precipitation show that the FACE can to some extent reduce prediction errors, recover prediction variances, and improve prediction skills. Besides, sensitive experiments also show that predictions based on the FACE are evidently influenced by the number of analogues, analogue-selected variables and analogy metric.

  12. Fully analogue photonic reservoir computer

    Science.gov (United States)

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-03-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers.

  13. The Greenland Analogue Project. Yearly Report 2009

    International Nuclear Information System (INIS)

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  14. The Greenland Analogue Project. Yearly Report 2009

    Energy Technology Data Exchange (ETDEWEB)

    2010-12-15

    A deep geological repository for spent nuclear fuel needs to be designed to keep used nuclear fuel isolated from mankind and the environment for a million years. Within this time frame glacial conditions are expected in regions that have been glaciated in the past two to ten million years. Climate induced changes such as the growth of ice sheets and permafrost will influence and alter the ground surface and subsurface environment, including its hydrology, which may impact repository safety. Glaciation impact assessments have to-date used over-simplified models and conservative assumptions, for example in the representation of ice sheet hydrology, that do not reflect the complexity of natural systems and processes. This is largely due to lack of direct observations of such processes from existing ice sheets, which if more readily available could help reduce uncertainties and provide a strong scientific basis for the treatment of glacial impacts in safety assessments. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with glacial cycles and their impact on the long-term performance of deep geological repositories for spent nuclear fuel will be significantly improved by studying a modern analogue. To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of

  15. Antimicrobial Activity of Resveratrol Analogues

    Directory of Open Access Journals (Sweden)

    Malik Chalal

    2014-06-01

    Full Text Available Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew. Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold. The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups and antimicrobial activity.

  16. Antimicrobial activity of resveratrol analogues.

    Science.gov (United States)

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity. PMID:24918540

  17. Computer-aided rational design of novel EBF analogues with an aromatic ring.

    Science.gov (United States)

    Wang, Shanshan; Sun, Yufeng; Du, Shaoqing; Qin, Yaoguo; Duan, Hongxia; Yang, Xinling

    2016-06-01

    Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π-π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1-D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. Graphical abstract The design strategy of new EBF analogues based on the OBP7 structure. PMID:27251400

  18. Heterocyclic chalcone analogues as potential anticancer agents.

    Science.gov (United States)

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep

    2013-03-01

    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties. PMID:22721390

  19. Acoustojet: acoustic analogue of photonic jet phenomenon

    CERN Document Server

    Minin, Igor V

    2016-01-01

    It has been demonstrated for the first time that an existence of acoustic analogue of photonic jet phenomenon, called acoustojet, providing for subwavelength localization of acoustic field in the shadow area of arbitrary 3D penetrable mesoscale particle, is possible.

  20. International video project on natural analogues

    International Nuclear Information System (INIS)

    A natural analogue can be defined as a natural process which has occurred in the past and is studied in order to test predictions about the future evolution of similar processes. In recent years, natural analogues have been used increasingly to test the mathematical models required for repository performance assessment. Analogues are, however, also of considerable use in public relations as they allow many of the principles involved in demonstrating repository safety to be illustrated in a clear manner using natural systems with which man is familiar. The international Natural Analogue Working Group (NAWG), organised under the auspices of the CEC, has recognised that such PR applications are of considerable importance and should be supported from a technical level. At the NAWG meeting in Pitlochry, Scotland (June 1990), it was recommended that the possibilities for making a video film on this topic be investigated and Nagra was requested to take the lead role in setting up such a project

  1. Total Synthesis of the Analogue of Icogenin

    Institute of Scientific and Technical Information of China (English)

    Shu Jie HOU; Peng XU; Liang ZHOU; De Quan YU; Ping Sheng LEI; Chuan Chun ZOU

    2006-01-01

    One of the analogues of icogenin, a natural furostanol saponin showing strong cytotoxic effect on cancer cell, was first synthesized via convergent strategy by using diosgenin and available monosaccharides as starting materials,

  2. Natural analogues and radionuclide transport model validation

    International Nuclear Information System (INIS)

    In this paper, some possible roles for natural analogues are discussed from the point of view of those involved with the development of mathematical models for radionuclide transport and with the use of these models in repository safety assessments. The characteristic features of a safety assessment are outlined in order to address the questions of where natural analogues can be used to improve our understanding of the processes involved and where they can assist in validating the models that are used. Natural analogues have the potential to provide useful information about some critical processes, especially long-term chemical processes and migration rates. There is likely to be considerable uncertainty and ambiguity associated with the interpretation of natural analogues, and thus it is their general features which should be emphasized, and models with appropriate levels of sophistication should be used. Experience gained in modelling the Koongarra uranium deposit in northern Australia is drawn upon. (author)

  3. Current european regulatory perspectives on insulin analogues

    OpenAIRE

    Enzmann Harald G; Weise Martina

    2011-01-01

    Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing aut...

  4. Analogue of the Event Horizon in Fibers

    OpenAIRE

    Konig, Friedrich; Philbin, Thomas G.; Kuklewicz, Chris; Robertson, Scott; Hill, Stephen; Leonhardt, Ulf

    2010-01-01

    In conclusion, we have developed a theory for artificial event horizons in fibers. Experimentally, light was blue-shifted by a near group velocity-matched pulse. The measured data was explained by the presence of an optical group velocity horizon inside the fiber. A very good agreement between theory and experiment was observed. The blue shifting corresponds to the optical analogue of trans-Planckian frequency shifts in astrophysics (t'Hooft, 1985; Jacobson, 1991). The temperature of analogue...

  5. Newer insulin analogues and inhaled insulin

    OpenAIRE

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  6. Somatostatin analogue treatment of neuroendocrine tumours.

    OpenAIRE

    de Herder, W. W.; van der Lely, A.J.; Lamberts, S. W.

    1996-01-01

    The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. So...

  7. Synthesis and study of new paramagnetic resveratrol analogues.

    Science.gov (United States)

    Kálai, Tamás; Borza, Erzsébet; Antus, Csenge; Radnai, Balázs; Gulyás-Fekete, Gergely; Fehér, Andrea; Sümegi, Balázs; Hideg, Kálmán

    2011-12-15

    New resveratrol analogues containing five- and six-membered nitroxides and isoindoline nitroxides were synthesized. These new compounds were compared to resveratrol based on their ABTS radical scavenging ability as well on their capacity to suppress inflammatory process in macrophages induced by lipopolysaccharides. The ABTS and ROS scavenging activities of new molecules were the same or weaker than that of resveratrol, but some of paramagnetic resveratrol derivatives suppressed nitrite and TNFα production more efficiently than resveratrol. Based on these results the new nitroxide and phenol containing hybrid molecules can be considered as new antioxidant and anti-inflammatory agents. PMID:22088309

  8. The antiviral activity of tetrazole phosphonic acids and their analogues.

    OpenAIRE

    Hutchinson, D W; Naylor, M.

    1985-01-01

    5-(Phosphonomethyl)-1H-tetrazole and a number of related tetrazoles have been prepared and their effects on the replication of Herpes Simplex Viruses-1 and -2 have been investigated as well as their abilities to inhibit the DNA polymerases induced by these viruses and the RNA transcriptase activity of influenza virus A. Contrary to an earlier report, 5-(phosphonomethyl)-1H-tetrazole was not an efficient inhibitor of the replication of HSV-1 and HSV-2 in tissue culture. Analogues of 5-(phospho...

  9. An Analogue of the Antibiotic Teicoplanin Prevents Flavivirus Entry In Vitro

    NARCIS (Netherlands)

    De Burghgraeve, Tine; Kaptein, Suzanne J. F.; Ayala Nunez, Vanesa; Mondotte, Juan A.; Pastorino, Boris; Printsevskaya, Svetlana S.; de Lamballerie, Xavier; Jacobs, Michael; Preobrazhenskaya, Maria; Gamarnik, Andrea V.; Smit, Jolanda M.; Neyts, Johan

    2012-01-01

    There is an urgent need for potent inhibitors of dengue virus (DENV) replication for the treatment and/or prophylaxis of infections with this virus. We here report on an aglycon analogue of the antibiotic teicoplanin (code name LCTA-949) that inhibits DENV-induced cytopathic effect (CPE) in a dose-d

  10. Glucagonlike Peptide 2 Analogue Teduglutide

    Science.gov (United States)

    Chaturvedi, Lakshmi S.; Basson, Marc D.

    2015-01-01

    IMPORTANCE Short bowel syndrome occurs when a shortened intestine cannot absorb sufficient nutrients or fluids. Teduglutide is a recombinant analogue of human glucagonlike peptide 2 that reduces dependence on parenteral nutrition in patients with short bowel syndrome by promoting enterocytic proliferation, increasing the absorptive surface area. However, enterocyte function depends not only on the number of cells that are present but also on differentiated features that facilitate nutrient absorption and digestion. OBJECTIVE To test the hypothesis that teduglutide impairs human intestinal epithelial differentiation. DESIGN AND SETTING We investigated the effects of teduglutide in the modulation of proliferation and differentiation in human Caco-2 intestinal epithelial cells at a basic science laboratory. This was an in vitro study using Caco-2 cells, a human-derived intestinal epithelial cell line commonly used to model enterocytic biology. EXPOSURE Cells were exposed to teduglutide or vehicle control. MAINOUTCOMESAND MEASURES We analyzed the cell cycle by bromodeoxyuridine incorporation or propidium iodide staining and flow cytometry and measured cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We used quantitative reverse transcription–polymerase chain reaction to assay the expression of the enterocytic differentiation markers villin, sucrase-isomaltase, glucose transporter 2 (GLUT2), and dipeptidyl peptidase 4 (DPP-4), as well as that of the putative differentiation signals schlafen 12 (SLFN12) and caudal-related homeobox intestine-specific transcription factor (Cdx2). Villin promoter activity was measured by a luciferase-based assay. RESULTS The MTS assay demonstrated that teduglutide increased cell numbers by a mean (SD) of 10% (2%) over untreated controls at a maximal 500nM (n = 6, P < .05). Teduglutide increased bromodeoxyuridine-positive cells vs untreated controls by a mean (SD

  11. Convergent syntheses of LeX analogues

    Directory of Open Access Journals (Sweden)

    An Wang

    2010-02-01

    Full Text Available The synthesis of three Lex derivatives from one common protected trisaccharide is reported. These analogues will be used respectively for competitive binding experiments, conjugation to carrier proteins and immobilization on gold. An N-acetylglucosamine monosaccharide acceptor was first glycosylated at O-4 with a galactosyl imidate. This coupling was performed at 40 °C under excess of BF3·OEt2 activation and proceeded best if the acceptor carried a 6-chlorohexyl rather than a 6-azidohexyl aglycon. The 6-chlorohexyl disaccharide was then converted to an acceptor and submitted to fucosylation yielding the corresponding protected 6-chlorohexyl Lex trisaccharide. This protected trisaccharide was used as a precursor to the 6-azidohexyl, 6-acetylthiohexyl and 6-benzylthiohexyl trisaccharide analogues which were obtained in excellent yields (70–95%. In turn, we describe the deprotection of these intermediates in one single step using dissolving metal conditions. Under these conditions, the 6-chlorohexyl and 6-azidohexyl intermediates led respectively to the n-hexyl and 6-aminohexyl trisaccharide targets. Unexpectedly, the 6-acetylthiohexyl analogue underwent desulfurization and gave the n-hexyl glycoside product, whereas the 6-benzylthiohexyl analogue gave the desired disulfide trisaccharide dimer. This study constitutes a particularly efficient and convergent preparation of these three Lex analogues.

  12. Newer insulin analogues and inhaled insulin

    Directory of Open Access Journals (Sweden)

    Girish C

    2006-03-01

    Full Text Available Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera is recently approved by FDA and appears promising.

  13. Synthesis of apoptotic chalcone analogues in HepG2 human hepatocellular carcinoma cells.

    Science.gov (United States)

    Park, Cheon-Soo; Ahn, Yongchel; Lee, Dahae; Moon, Sung Won; Kim, Ki Hyun; Yamabe, Noriko; Hwang, Gwi Seo; Jang, Hyuk Jai; Lee, Heesu; Kang, Ki Sung; Lee, Jae Wook

    2015-12-15

    Eight chalcone analogues were prepared and evaluated for their cytotoxic effects in human hepatoma HepG2 cells. Compound 5 had a potent cytotoxic effect. The percentage of apoptotic cells was significantly higher in compound 5-treated cells than in control cells. Exposure to compound 5 for 24h induced cleavage of caspase-8 and -3, and poly (ADP-ribose) polymerase (PARP). Our findings suggest that compound 5 is the active chalcone analogue that contributes to cell death in HepG2 cells via the extrinsic apoptotic pathway. PMID:26564263

  14. The Canadian space agency planetary analogue materials suite

    Science.gov (United States)

    Cloutis, Edward A.; Mann, Paul; Izawa, Matthew R. M.; Applin, Daniel M.; Samson, Claire; Kruzelecky, Roman; Glotch, Timothy D.; Mertzman, Stanley A.; Mertzman, Karen R.; Haltigin, Timothy W.; Fry, Christopher

    2015-12-01

    The Canadian Space Agency (CSA) recently commissioned the development of a suite of over fifty well-characterized planetary analogue materials. These materials are terrestrial rocks and minerals that are similar to those known or suspected to occur on the lunar or martian surfaces. These include: Mars analogue sedimentary, hydrothermal, igneous and low-temperature alteration rock suites; lunar analogue basaltic and anorthositic rock suites; and a generic impactite rock suite from a variety of terrestrial impact structures. Representative thin sections of the materials have been characterized by optical microscopy and electron probe microanalysis (EPMA). Reflectance spectra have been collected in the ultraviolet, visible, near-infrared and mid-infrared, covering 0.2-25 μm. Thermal infrared emission spectra were collected from 5 to 50 μm. Raman spectra with 532 nm excitation, and laser-induced fluorescence spectra with 405 nm excitation were also measured. Bulk chemical analysis was carried out using X-ray fluorescence, with Fe valence determined by wet chemistry. Chemical and mineralogical data were collected using a field-portable Terra XRD-XRF instrument similar to CheMin on the MSL Curiosity rover. Laser-induced breakdown spectroscopy (LIBS) data similar to those measured by ChemCam on MSL were collected for powdered samples, cut slab surfaces, and as depth profiles into weathered surfaces where present. Three-dimensional laser camera images of rock textures were collected for selected samples. The CSA intends to make available sample powders (science community. Aiming to complement existing planetary analogue rock and mineral libraries, the CSA suite represents a new resource for planetary scientists and engineers. We envision many potential applications for these materials in the definition, development and testing of new analytical instruments for use in planetary missions, as well as possible calibration and ground-truthing of remote sensing data sets

  15. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem A.

    2016-02-04

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  16. Geomagnetic properties of Proxima Centauri b analogues

    CERN Document Server

    Zuluaga, Jorge I

    2016-01-01

    The recent discovery of a planet around the closest star, Proxima Centauri, could represent a quantum leap on the testability of models in exoplanet sciences. Unlike any other discovered exoplanet, models of planetary processes in Proxima b could be contrasted against near future telescopic observations and far future in-situ measurements. In this paper we study the geomagnetic properties of Proxima b analogues, namely, solid planets with masses close but larger than Earth's mass, periods of rotation of several days and habitable surface conditions. Assuming different planetary masses, bulk compositions and periods of rotations, we calculate for each planetary analogue its radius, heat flux, time of inner core formation, dynamo lifetime and minimum dipole magnetic moment. We find that most ($\\gtrsim$70\\%) Proxima b analogues develop intrinsic dynamos that last at least 3 Gyr, although only half of them are older than the present age of the host star ($4-6$ Gyr). Relying in our planetary evolution models, we p...

  17. Classical Simulated Annealing Using Quantum Analogues

    Science.gov (United States)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-06-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  18. Classical Simulated Annealing Using Quantum Analogues

    Science.gov (United States)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-08-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  19. Somatostatin analogues for acute bleeding oesophageal varices

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C.; Hrobjartsson, A.

    2008-01-01

    BACKGROUND: Somatostatin and its derivatives are sometimes used for emergency treatment of bleeding oesophageal varices in patients with cirrhosis of the liver. OBJECTIVES: To study whether somatostatin or its analogues improve survival or reduce the need for blood transfusions in patients with...... bleeding oesophageal varices. SEARCH STRATEGY: PubMed and The Cochrane Library were searched (November 2007). Reference lists of publications, contacts with authors. SELECTION CRITERIA: All randomised trials comparing somatostatin or analogues with placebo or no treatment in patients suspected of acute or...

  20. Natural analogues in radioactive waste disposal

    International Nuclear Information System (INIS)

    In order to validate predictive models of the very long-term processes which effect the performance of radioactive waste repositories, there has been increasing interest in the information which can be obtained from studying similar mechanisms in natural systems. Although such analogues have been studied for many years, performance assessment methodology has now matured to the point where it can enlist the support which analogues can offer. Consequently this book assesses the safety levels attributable to underground depositories for radioactive waste be examining natural depositories to radioactive material and their degree of migration

  1. Slow Sound in a duct, effective transonic flows and analogue black holes

    CERN Document Server

    Aurégan, Yves; Michel, Florent; Pagneux, Vincent; Parentani, Renaud

    2015-01-01

    We propose a new system suitable for studying analogue gravity effects, consisting of a gas flowing in a duct with a compliant wall. Effective transonic flows are obtained from uniform, low Mach number flows through the reduction of the one-dimensional speed of sound induced by the wall compliance. We show that the modified equation for linear perturbations can be written in a Hamiltonian form. We perform a one-dimensional reduction consistent with the canonical formulation, and deduce the analogue metric along with the first dispersive term. In a weak dispersive regime, the spectrum emitted from a sonic horizon is numerically shown to be Planckian, and with a temperature fixed by the analogue surface gravity.

  2. Laser flash synthesis of graphene and its inorganic analogues: An innovative breakthrough with immense promise

    OpenAIRE

    Kumar, Prashant

    2013-01-01

    Laser-based green synthetic approaches for 2D atomic sheets of graphene, graphene nanoribbons and inorganic analogues of graphene are relatively new techniques. There are several significant laser-based approaches for graphene synthesis such as (a) laser exfoliation, (b) intercalation and exfoliation in liquid nitrogen, (c) pulsed laser deposition, (d) laser induced ultrafast chemical vapour deposition, (e) laser induced catalyst-free growth of graphene from solid carbon sources, (f) epitaxia...

  3. Neuroprotective actions of a histidine analogue in models of ischemic stroke.

    Science.gov (United States)

    Tang, Sung-Chun; Arumugam, Thiruma V; Cutler, Roy G; Jo, Dong-Gyu; Magnus, Tim; Chan, Sic L; Mughal, Mohamed R; Telljohann, Richard S; Nassar, Matthew; Ouyang, Xin; Calderan, Andrea; Ruzza, Paolo; Guiotto, Andrea; Mattson, Mark P

    2007-05-01

    Histidine is a naturally occurring amino acid with antioxidant properties, which is present in low amounts in tissues throughout the body. We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE). We now report that the histidine analogue histidyl hydrazide is effective in reducing brain damage and improving functional outcome in a mouse model of focal ischemic stroke when administered intravenously at a dose of 20 mg/kg, either 30 min before or 60 min and 3 h after the onset of middle cerebral artery occlusion. The histidine analogue also protected cultured rat primary neurons against death induced by HNE, chemical hypoxia, glucose deprivation, and combined oxygen and glucose deprivation. The histidine analogue prevented neuronal apoptosis as indicated by decreased production of cleaved caspase-3 protein. These findings suggest a therapeutic potential for HNE-scavenging histidine analogues in the treatment of stroke and related neurodegenerative conditions. PMID:17254011

  4. Analogue alternative the electronic analogue computer in Britain and the USA, 1930-1975

    CERN Document Server

    Small, James S

    2013-01-01

    We are in the midst of a digital revolution - until recently, the majority of appliances used in everyday life have been developed with analogue technology. Now, either at home or out and about, we are surrounded by digital technology such as digital 'film', audio systems, computers and telephones. From the late 1940s until the 1970s, analogue technology was a genuine alternative to digital, and the two competing technologies ran parallel with each other. During this period, a community of engineers, scientists, academics and businessmen continued to develop and promote the analogue computer.

  5. The PAAG group and natural analogues

    International Nuclear Information System (INIS)

    An overview is given of how OECD/NEA is organized with regard to questions dealing with management of radioactive wastes. The role of the two advisory groups, PAAG and ISAG, to the Radioactive waste management Committee is discussed with specific regard to the use of natural analogues in safety assessments

  6. Second-Generation Fluorescent Quadracyclic Adenine Analogues

    DEFF Research Database (Denmark)

    Dumat, Blaise; Bood, Mattias; Wranne, Moa S.;

    2015-01-01

    quadracyclic adenine analogues. The compounds were efficiently synthesized from a common intermediate through a two-step pathway with the Suzuki-Miyaura coupling as the key step. Two of the compounds, qAN1 and qAN4, display brightnesses (epsilon Phi(F)) of 1700 and 2300, respectively, in water and behave as...

  7. Synthesis of C-Arylnucleoside Analogues

    Directory of Open Access Journals (Sweden)

    Christophe Len

    2015-03-01

    Full Text Available Modified nucleoside analogues are of great biological importance as antiviral and antitumoral agents. There is special interest in the preparation of C-aryl nucleosides with an aromatic ring in different positions of the glycone for their biological activity. Different chemical synthesis strategies for these targets are described in this review.

  8. Synthesis and antimicrobial activity of squalamine analogue.

    Science.gov (United States)

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  9. Somatostatin analogue scintigraphy and tuberculosis: case report

    International Nuclear Information System (INIS)

    Scintigraphy using a radiolabelled somatostatin analogue (111 In-pentetreotide) is useful in the detection of neuroendocrine tumors. But this radiopharmaceutical accumulates also in solid tumours or in inflammatory diseases such as granulomatosis. We present a case of 111 In-pentetreotide uptake in a tuberculous adenopathy. (author)

  10. Ultrasound exfoliation of inorganic analogues of graphene

    Czech Academy of Sciences Publication Activity Database

    Štengl, Václav; Henych, Jiří; Slušná, Michaela; Ecorchard, Petra

    2014-01-01

    Roč. 9, APR (2014), s. 1-14. ISSN 1556-276X R&D Projects: GA ČR(CZ) GA14-05146S Institutional support: RVO:61388980 Keywords : Ultrasound * Exfoliation * Graphene inorganic analogues Subject RIV: CA - Inorganic Chemistry Impact factor: 2.779, year: 2014

  11. Phosphate analogues in the dissection of mechanism.

    OpenAIRE

    Heidi J. Korhonen; Conway, Louis P.; Hodgson, David R. W.

    2014-01-01

    Phosphoryl group transfer is central to genetic replication, cellular signalling and many metabolic processes. Understanding the mechanisms of phosphorylation and phosphate ester and anhydride cleavage is key to efforts towards biotechnological and biomedical exploitation of phosphate-handling enzymes. Analogues of phosphate esters and anhydrides are indispensable tools, alongside protein mutagenesis and computational methods, for the dissection of phosphoryl transfer mechanisms. Hydrolysable...

  12. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    Science.gov (United States)

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. PMID:27301366

  13. Synthesis of a simplified triazole analogue of pateamine A.

    Science.gov (United States)

    Hemi Cumming, A; Brown, Sarah L; Tao, Xu; Cuyamendous, Claire; Field, Jessica J; Miller, John H; Harvey, Joanne E; Teesdale-Spittle, Paul H

    2016-06-14

    Pateamine A is a naturally occurring metabolite extracted from the marine sponge Mycale hentscheli. It exhibits potent cytotoxicity towards cancer cell lines and has been shown to target protein translation initiation via inhibition of the function of eukaryotic initiation factor 4A proteins. We have synthesised a simplified analogue of pateamine A, consisting of the skeletal core of the natural product but with the thiazole heterocycle replaced by a triazole. The convergent design of the synthesis features a base-induced opening of a δ-valerolactone to access the Z,E-dienoate moiety, Julia-Kocienski olefination and copper-catalysed azide-alkyne cycloaddition. Bioactivity testing of the simplified pateamine A analogue (3) indicated a significant reduction in cytotoxicity, compared to natural pateamine A. We propose that this reduced activity is due mainly to the substitution of the thiazole for the triazole heterocycle. This supports the hypothesis that the thiazole of pateamine A is important for binding to its biological target. PMID:27180995

  14. Functional and structural characteristics of anticancer peptide Pep27 analogues

    Directory of Open Access Journals (Sweden)

    Seo Youn-Kyung

    2005-07-01

    Full Text Available Abstract Background A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. Results Pep27anal2 characterized substituting (2R→W, (4E→W, (11S→W and (13Q→W in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC50 values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601. Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. Conclusion The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents.

  15. Recent advances in topoisomerase I-targeting agents, camptothecin analogues.

    Science.gov (United States)

    Kim, Dae-Kee; Lee, Namkyu

    2002-12-01

    The present review concentrates on camptothecin (CPT) analogues, the most extensively studied topoisomerase I (topo I) inhibitors, and provides concise information on the structural features of human topo I enzyme, mechanisms of interaction of CPT with topo I, structure-activity relationship study of CPT analogues including the influence of lactone stability on antitumor activity, and recent updates of valuable CPT analogues. PMID:12370044

  16. Mitochondrial DNA D-loop AG/TC transition mutation in cortical neurons of mice after long-term exposure to nucleoside analogues.

    Science.gov (United States)

    Zhang, Yulin; Wang, Bishi; Liang, Qi; Qiao, Luxin; Xu, Bin; Zhang, Hongwei; Yang, Sufang; Chen, Jun; Guo, Hongliang; Wu, Jian; Chen, Dexi

    2015-10-01

    With the wide application of combined antiretroviral therapy, the prognosis of human immunodeficiency virus (HIV)-1 infected patient has been significantly improved. However, long-term administration of antiretroviral drugs can result in various drug-associated toxicities. Among them, nucleoside analogues were confirmed to inhibit DNA polymerase gamma, resulting in mitochondrial toxicity. Our previous study indicated that long-term exposure of mice to nucleoside analogue could induce mitochondria DNA (mtDNA) loss in cortical neurons. Herein, we further identify mitochondrial toxicity of four nucleoside analogues (zidovudine (AZT), stavudine (D4T), lamivudine (3TC), and didanosine (DDI)) by cloning and sequencing mtDNA D-loop region in mice neurons captured with laser capture microdissection. The results showed that mutation of neuronal mtDNA D-loop sequences increased in mice treated with each of the four nucleoside analogues for 4 months and D4T and DDI induced more severe D-loop lesion than the other two nucleoside analogues. The major type of D-loop point mutations induced by four nucleoside analogues was transition, in particular of "A→G" and "T→C" transition, but the point transition sites were variable. Our findings suggest that long-term exposure to nucleoside analogue can result in mtDNA D-loop region lesion in mouse cortical neurons. PMID:26015313

  17. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    Science.gov (United States)

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  18. Neurotoxicity Caused by the Treatment with Platinum Analogues

    Directory of Open Access Journals (Sweden)

    Sousana Amptoulach

    2011-01-01

    Full Text Available Platinum agents (cisplatin, carboplatin, and oxaliplatin are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

  19. Confirmation via Analogue Simulation: A Bayesian Analysis

    CERN Document Server

    Dardashti, Radin; Thebault, Karim P Y; Winsberg, Eric

    2016-01-01

    Analogue simulation is a novel mode of scientific inference found increasingly within modern physics, and yet all but neglected in the philosophical literature. Experiments conducted upon a table-top 'source system' are taken to provide insight into features of an inaccessible 'target system', based upon a syntactic isomorphism between the relevant modelling frameworks. An important example is the use of acoustic 'dumb hole' systems to simulate gravitational black holes. In a recent paper it was argued that there exists circumstances in which confirmation via analogue simulation can obtain; in particular when the robustness of the isomorphism is established via universality arguments. The current paper supports these claims via an analysis in terms of Bayesian confirmation theory.

  20. Holographic Fluids with Vorticity and Analogue Gravity

    CERN Document Server

    Leigh, Robert G; Petropoulos, P Marios

    2012-01-01

    We study holographic three-dimensional fluids with vorticity in local equilibrium and discuss their relevance to analogue gravity systems. The Fefferman-Graham expansion leads to the fluid's description in terms of a comoving and rotating Papapetrou-Randers frame. A suitable Lorentz transformation brings the fluid to the non-inertial Zermelo frame, which clarifies its interpretation as moving media for light/sound propagation. We apply our general results to the Lorentzian Kerr-AdS_4 and Taub-NUT-AdS_4 geometries that describe fluids in cyclonic and vortex flows respectively. In the latter case we associate the appearance of closed timelike curves to analogue optical horizons. In addition, we derive the classical rotational Hall viscosity of three-dimensional fluids with vorticity. Our formula remarkably resembles the corresponding result in magnetized plasmas.

  1. Design and synthesis of new fluconazole analogues.

    Science.gov (United States)

    Pore, Vandana S; Agalave, Sandip G; Singh, Pratiksha; Shukla, Praveen K; Kumar, Vikash; Siddiqi, Mohammad I

    2015-06-21

    We have synthesized new fluconazole analogues containing two different 1,2,3-triazole units in the side chain. The synthesis of new amide analogues using a variety of acids is also described. All the compounds showed very good antifungal activity. A hemolysis study of the most active compounds 6e and 13j showed that both compounds did not cause any hemolysis at the dilutions tested. These compounds did not exhibit any toxicity to L929 cells at MIC and lower concentrations. In the docking study, the overall binding mode of 6e and 13j appeared to be reasonable and provided a good insight into the structural basis of inhibition of Candida albicans Cyp51 by these compounds. PMID:25975803

  2. Studies of natural analogues and geological systems

    International Nuclear Information System (INIS)

    This review has involved studies of natural analogues and natural geological systems leading to the identification and quantification of processes and features of importance to the performance and safety of repositories for radioactive waste. The features and processes selected for the study comprise general geochemical issues related to the performance of the near- and far-field, the performance and durability of construction materials and the effects of glaciation. For each of these areas a number of potentially important processes for repository performance have been described, and evidence for their existence, as well as quantification of parameters of models describing the processes have been sought from major natural analogue studies and site investigations. The review has aimed at covering a relatively broad range of issues at the expense of in-depth analysis. The quantitative data presented are in most cases compilations of data from the literature; in a few cases results of evaluations made within the current project are included

  3. Relational Quadrilateralland. Analogues of Isospin and Hypercharge

    OpenAIRE

    Anderson, Edward

    2012-01-01

    I consider the momenta and conserved quantities for CP^2 interpreted as the space of quadrilaterals. This builds on seminar I and II's kinematics via making use of MacFarlane's work considering the SU(3)-like (and thus particle physics-like) conserved quantities that occur for CP^2. I perform the additional step of further interpreting that as the configuration space of all relational quadrilaterals and thus an interesting toy model for whole-universe, relational and geometrodynamical-analogu...

  4. Electromagnetic wave analogue of electronic diode

    OpenAIRE

    Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.; Fedotov, Vassili A.; Zheludev, Nikolay I.

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by ...

  5. Acremolin : : Synthesis, Structural Revision and Analogues

    OpenAIRE

    Januar, Lawrence Alexander

    2014-01-01

    This thesis presents the total synthesis of the natural product acremolin and its structural reassignment along with attempts towards synthesizing analogues of natural product. Acremolin is a natural product reported as a 1H- azirine-containing guanine derivative isolated from Acremonium strictum. Due to the known structural instability of 1H-azirines systems, the original assignment is highly improbable. Two alternative structures were proposed based on the evaluation of spectroscopic data r...

  6. Analogue memories for high speed detectors signals

    CERN Document Server

    Caponetto, L H

    2000-01-01

    An analogue memory chip family has been developed as a switched capacitor cell array. The family is an ongoing prototyping project within the readout system of the silicon drift detectors for the Inner Tracker System of the ALICE experiment. All chips consist of several capturing channels whose cells number is varying within the family. Chips design choices and performances are briefly discussed here. (5 refs).

  7. SYNTHESIS AND BIOEVALUATION OF KETOCONAZOLE THIOSEMICARBAZONE ANALOGUES

    OpenAIRE

    Y. Murti

    2011-01-01

    Ketoconazole (KTZ) is a synthetic antifungal drug used to prevent and treat fungal infections, especially in immunocompromised patients such as those with AIDS. Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including C. albicans. Thus new effective agents with less toxicity against fungal infection are urgently required. With this view, ketoconazole thiosemicarbazone analogues (Compounds 1-10) were synthesized wherein condensation of different thiosemic...

  8. Analogues of a transformation formula of Ramanujan

    OpenAIRE

    Dixit, Atul

    2009-01-01

    We derive two new analogues of a transformation formula of Ramanujan involving the Gamma and Riemann zeta functions present in the Lost Notebook. Both involve infinite series consisting of Hurwitz zeta functions and yield modular relations. As a special case of the first formula, we obtain an identity involving polygamma functions given by Andrew P. Guinand and as a limiting case of the second formula, we derive the transformation formula of Ramanujan.

  9. The Brookhaven electron analogue, 1953--1957

    International Nuclear Information System (INIS)

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary

  10. Analogue cosmology in a hadronic fluid

    CERN Document Server

    Bilic, N

    2013-01-01

    The expansion of hadronic matter that takes place immediately after a heavy ion collision has certain similarity with the cosmological expansion. We study the analogue geometry of the expanding hadronic fluid, using the the formalism of relativistic acoustic geometry. We show that the propagation of massless pions provides a geometric analog of expanding spacetime equivalent to an open (k=-1)FRW cosmology. Here, we study general conditions for the formation of a trapped region with the inner boundary as a marginally trapped surface.

  11. Applying Acylated Fucose Analogues to Metabolic Glycoengineering

    OpenAIRE

    Julia Rosenlöcher; Verena Böhrsch; Michael Sacharjat; Véronique Blanchard; Christoph Giese; Volker Sandig; Christian P R Hackenberger; Stephan Hinderlich

    2015-01-01

    Manipulations of cell surface glycosylation or glycan decoration of selected proteins hold immense potential for exploring structure-activity relations or increasing glycoprotein quality. Metabolic glycoengineering describes the strategy where exogenously supplied sugar analogues intercept biosynthetic pathways and are incorporated into glycoconjugates. Low membrane permeability, which so far limited the large-scale adaption of this technology, can be addressed by the introduction of acylated...

  12. The Brookhaven electron analogue, 1953--1957

    Energy Technology Data Exchange (ETDEWEB)

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  13. Instructional influences on analogue functional analysis outcomes.

    OpenAIRE

    Northup, John; Kodak, Tiffany; Grow, Laura; Lee, Jennifer; Coyne, Amanda

    2004-01-01

    Analogue assessments were conducted with a common contingency (escape from tasks) that varied only by three different instructions describing the contingency. In one condition, the contingency was described as "taking a break," in another condition it was described as "time-out," and no description of the contingency was provided in a third condition. The participant was a typically developing 5-year-old child with a diagnosis of attention deficit hyperactivity disorder. Rates of inappropriat...

  14. Analogue to Digital and Digital to Analogue Converters (ADCs and DACs): A Review Update

    CERN Document Server

    Pickering, J

    2015-01-01

    This is a review paper updated from that presented for CAS 2004. Essentially, since then, commercial components have continued to extend their performance boundaries but the basic building blocks and the techniques for choosing the best device and implementing it in a design have not changed. Analogue to digital and digital to analogue converters are crucial components in the continued drive to replace analogue circuitry with more controllable and less costly digital processing. This paper discusses the technologies available to perform in the likely measurement and control applications that arise within accelerators. It covers much of the terminology and 'specmanship' together with an application-oriented analysis of the realisable performance of the various types. Finally, some hints and warnings on system integration problems are given.

  15. Receptor-isoform-selective insulin analogues give tissue-preferential effects

    DEFF Research Database (Denmark)

    Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi;

    2011-01-01

    inducing glycogen accumulation (75%) and lipogenesis (130%) than for affecting muscle (45%). For the same blood-glucose-lowering effect upon acute intravenous dosing of mice, INS-B gave a significantly higher degree of IR phosphorylation in liver than HI. These in vitro and in vivo results indicate that...... insulin analogues with IR-isoform-preferential binding affinity are able to elicit tissue-selective biological responses, depending on IR-A/IR-B expression....

  16. Clinical and Luteolytic Effects of Fenprostalene (A Prostaglandin F2α Analogue) in Mares

    OpenAIRE

    Bosu, W.T.K.; McKinnon, A. O.; Lissemore, K; Kelton, D.

    1983-01-01

    A study was carried out to determine the luteolytic effect of fenprostalene, a prostaglandin F2α analogue, in mares Ten mares, that included seven cyclic mares, lactating mares and a pregnant mare were used in two experiments. In the first experiment, seven mares were treated subcutaneously with 250 μg fenprostalene and in the second experiment ten mares, including the seven mares used in the first experiment, were treated with fenprostalene and artificially inseminated during the induced est...

  17. Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

    CERN Document Server

    Bilki, B; Xia, L.; Eigen, G.; Thomson, M.A.; Ward, D.R.; Benchekroun, D.; Hoummada, A.; Khoulaki, Y.; Chang, S.; Khan, A.; Kim, D.H.; Kong, D.J.; Oh, Y.D.; Blazey, G.C.; Dyshkant, A.; Francis, K.; Lima, J.G.R.; Salcido, R.; Zutshi, V.; Salvatore, F.; Kawagoe, K.; Miyazaki, Y.; Sudo, Y.; Suehara, T.; Tomita, T.; Ueno, H.; Yoshioka, T.; Apostolakis, J.; Dannheim, D.; Folger, G.; Ivantchenko, V.; Klempt, W.; Lucaci-Timoce, A. -I.; Ribon, A.; Schlatter, D.; Sicking, E.; Uzhinskiy, V.; Giraud, J.; Grondin, D.; Hostachy, J. -Y.; Morin, L.; Brianne, E.; Cornett, U.; David, D.; Ebrahimi, A.; Falley, G.; Gadow, K.; Göttlicher, P.; Günter, C.; Hartbrich, O.; Hermberg, B.; Karstensen, S.; Krivan, F.; Krüger, K.; Lu, S.; Lutz, B.; Morozov, S.; Morgunov, V.; Neubüser, C.; Reinecke, M.; Sefkow, F.; Smirnov, P.; Tran, H.L.; Buhmann, P.; Garutti, E.; Laurien, S.; Matysek, M.; Ramilli, M.; Briggl, K.; Eckert, P.; Harion, T.; Munwes, Y.; Schultz-Coulon, H. -Ch.; Shen, W.; Stamen, R.; van Doren, B.; Wilson, G.W.; Wing, M.; Combaret, C.; Caponetto, L.; Eté, R.; Grenier, G.; Han, R.; Ianigro, J.C.; Kieffer, R.; Laktineh, I.; Lumb, N.; Mathez, H.; Mirabito, L.; Petrukhin, A.; Steen, A.; Antequera, J. Berenguer; Alamillo, E. Calvo; Fouz, M. -C.; Marin, J.; Puerta-Pelayo, J.; Verdugo, A.; Corriveau, F.; Bobchenko, B.; Chistov, R.; Chadeeva, M.; Danilov, M.; Drutskoy, A.; Epifantsev, A.; Markin, O.; Mironov, D.; Mizuk, R.; Novikov, E.; Rusinov, V.; Tarkovsky, E.; Besson, D.; Buzhan, P.; Ilyin, A.; Popova, E.; Gabriel, M.; Kiesling, C.; van der Kolk, N.; Simon, F.; Soldner, C.; Szalay, M.; Tesar, M.; Weuste, L.; Amjad, M.S.; Bonis, J.; di Lorenzo, S. Conforti; Cornebise, P.; Dulucq, F.; Fleury, J.; Frisson, T.; Martin-Chassard, G.; Poschl, R.; Raux, L.; Richard, F.; Pöschl, R.; Rouëné, J.; Seguin-Moreau, N.; de la Taille, Ch.; Anduze, M.; Boudry, V.; Brient, J-C.; Clerc, C.; Cornat, R.; Frotin, M.; Gastaldi, F.; Matthieu, A.; de Freitas, P. Mora; Musat, G.; Ruan, M.; Videau, H.; Zacek, J.; Cvach, J.; Gallus, P.; Havranek, M.; Janata, M.; Kvasnicka, J.; Lednicky, D.; Marcisovsky, M.; Polak, I.; Popule, J.; Tomasek, L.; Tomasek, M.; Sicho, P.; Smolik, J.; Vrba, V.; Zalesak, J.; Jeans, D.; Weber, S.

    2015-01-01

    Showers produced by positive hadrons in the highly granular CALICE scintillatorsteel analogue hadronic calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using GEANT4 version 9.6 are compared.

  18. Uncovering Mass Segregation with Galaxy Analogues in Dark Matter Simulations

    CERN Document Server

    Joshi, Gandhali D; Wadsley, James

    2016-01-01

    We investigate mass segregation in group and cluster environments by identifying galaxy analogues in high-resolution dark matter simulations. Subhalos identified by the AHF and ROCKSTAR halo finders have similar mass functions, independent of resolution, but different radial distributions due to significantly different subhalo hierarchies. We propose a simple way to classify subhalos as galaxy analogues. The radial distributions of galaxy analogues agree well at large halo-centric radii for both AHF and ROCKSTAR but disagree near parent halo centres where the phase-space information used by ROCKSTAR is essential. We see clear mass segregation at small radii (within $0.5\\,r_{vir}$) with average galaxy analogue mass decreasing with radius. Beyond the virial radius, we find a mild trend where the average galaxy analogue mass increases with radius. These mass segregation trends are strongest in small groups and dominated by the segregation of low mass analogues. The lack of mass segregation in massive galaxy anal...

  19. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa;

    2016-01-01

    Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant...... women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...

  20. Anomalous isobaric analogue resonance in 71As

    International Nuclear Information System (INIS)

    In 1971 G. M. Temmer et al., reported observing five anomalous substructures in a spin 1/2+ isobaric analogue resonance in 71As at E/sub p/ = 5.05 MeV. They suggested that these substructures could be interpreted as ''hallway states'' coupling a ''doorway state'' to compound nuclear states. Although doorway states are well established interpretations of isobaric analogue resonances, hallway states have no such acreditation. The case investigated in this paper was the first reported evidence suggesting the existence of hallway states in an isobaric analogue resonance. In this work the validity of the hallway state interpretation was ascertained for two of the five substructures. The spin and parity of these two substructures were determined to be 5/2+; therefore, their interpretation as hallway states is incorrect since it would not conserve angular momentum. The spins and parities of all the substructures were determined by measuring the analyzing power of the elastic reaction 70Ge(p(pol),p0) from an energy E/sub p/ = 4.92 MeV to an energy E/sub p/ = 5.23 MeV in 10 keV steps. The analyzing power was then remeasured over the last two substructures at E = 5.05 MeV and E = 5.14 MeV in 5 keV steps. These last two substructures also decayed strongly to the 2+ first excited state in 70Ge. The angular correlation between the first inelastic proton and the subsequently emitted gamma ray was measured in the Goldfarb--Seyler geometry and was then expanded in terms of cosine functions. The expansion coefficients implied that the spins of these two resonances were greater than or equal to 5/2, in agreement with the analyzing power measurements

  1. The Greenland analogue project. Yearly report 2010

    International Nuclear Information System (INIS)

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  2. The Greenland analogue project. Yearly report 2010

    Energy Technology Data Exchange (ETDEWEB)

    Harper, J.; Brinkerhoff, D.; Johnson, J. [University of Montana, Missoula (United States); Ruskeeniemi, T.; Engstroem, J.; Kukkonen, I. [Geological Survey of Finland (Finland)] [and others

    2012-04-15

    A four-year field and modelling study of the Greenland ice sheet and subsurface conditions, Greenland Analogue Project (GAP), has been initiated collaboratively by SKB, Posiva and NWMO to advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository. The study site encompasses a land terminus portion of the Greenland ice sheet, east of Kangerlussuaq, and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project begins in 2009 and is scheduled for completion in 2012. Our current understanding of the hydrological, hydrogeological and hydrogeochemical processes associated with cold climate conditions and glacial cycles, and their impact on the long-term performance of deep geological repositories for spent nuclear fuel, will be significantly improved by studying a modern analogue. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a better understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. This report was produced by the GAP team members and presents an overview of the activities within the GAP during the interval January 1 to December 31, 2010, as well as research results obtained during this time frame. Research for the GAP is ongoing, and additional results related to the data presented here may become available in the future and will be presented in subsequent annual reports. (orig.)

  3. Relativistic analogues of nonrelativistic integrals in R-matrix calculations

    International Nuclear Information System (INIS)

    Relativistic analogues of integrals are applied to the nonrelativistic R-matrix code to demonstrate the possibilities of the method. An expression for the relativistic analogue of the multipole integral is obtained. Energy levels and electron impact excitation cross sections for transitions in C2+, Fe22+ and W70+, calculated with different codes, are compared. It is found that the relativistic analogues of integrals method shows good agreement with results calculated using a relativistic code. (letter to the editor)

  4. U.S. Nuclear Regulatory Commission natural analogue research program

    Energy Technology Data Exchange (ETDEWEB)

    Kovach, L.A.; Ott, W.R. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process.

  5. Digital and analogue industrial radiography, application fields

    International Nuclear Information System (INIS)

    Full text: Reusable phosphor screens for computer radiography (CR), amorphous selenium screens for direct radiography (DR), film digitalisation (FD) constitute imaging methods accepted by industry and are used for non-destructive radiographic testing (RT). Economic pressures are involving and affecting digital RT technology. Standards and codes for film radiography and radioscopy qualification do no longer cover the wide range of digital RT applications. It will be our task to optimise the performance of digital RT characterisation and to create appropriate examination methods to use all these new and existent technologies. In the meantime, an increasing automation and control of manual methods of analogue radiography can as well be expected. (author)

  6. Technical Considerations in Magnetic Analogue Models

    CERN Document Server

    Adams, Patrick W M

    2016-01-01

    The analogy between vorticity and magnetic fields has been a subject of interest to researchers for a considerable period of time, mainly because of the structural similarities between the systems of equations that govern the evolution of the two fields. We recently presented the analysis of magnetic fields and hydrodynamics vorticity fields and argued for a formal theory of analogue magnetism. This article provides in depth technical details of the relevant considerations for the simulation procedures and extends the analyses to a range of fluids.

  7. Natural Analogues of CO2 Geological Storage

    International Nuclear Information System (INIS)

    Geological storage of carbon dioxide is nowadays, internationally considered as the most effective method for greenhouse gas emission mitigation, in order to minimize the global climate change universally accepted. Nevertheless, the possible risks derived of this long-term storage have a direct influence on its public acceptance. Among the favourable geological formations to store CO2, depleted oil and gas fields, deep saline reservoirs, and unamiable coal seams are highlighted. One of the most important objectives of the R and D projects related to the CO2 geological storage is the evaluation of the CO2 leakage rate through the above mentioned geological formations. Therefore, it is absolutely necessary to increase our knowledge on the interaction among CO2, storage and sealing formations, as well as on the flow paths and the physical resistance of the sealing formation. The quantification of the CO2 leakage rate is essential to evaluate the effects on the human and animal health, as well as for the ecosystem and water quality. To achieve these objectives, the study of the natural analogues is very useful in order to know the natural leakage rate to the atmosphere, its flow paths, the physical, chemical and mineralogical modifications due to the long term interaction processes among the CO2 and the storage and sealing formations, as well as the effects on the groundwaters and ecosystems. In this report, we have tried to summarise the main characteristics of the natural reservoirs and surficial sources of CO2, which are both natural analogues of the geological storage and CO2 leakage, studied in EEUU, Europe and Australia. The main objective of this summary is to find the possible applications for long-term risk prediction and for the performance assessment by means of conceptual and numerical modelling, which will allow to validate the predictive models of the CO2 storage behaviour, to design and develop suitable monitoring techniques to control the CO2 behaviour

  8. Materials analogue of zero-stiffness structures

    Science.gov (United States)

    Kumar, Arun; Subramaniam, Anandh

    2011-04-01

    Anglepoise lamps and certain tensegrities are examples of zero-stiffness structures. These structures are in a state of neutral equilibrium with respect to changes in configuration of the system. Using Eshelby's example of an edge dislocation in a thin plate that can bend, we report the discovery of a non-trivial new class of material structures as an analogue to zero-stiffness structures. For extended positions of the edge dislocation in these structures, the dislocation experiences a zero image force. Salient features of these material structures along with the key differences from conventional zero-stiffness structures are pointed out.

  9. Analogues of Euler and Poisson Summation Formulae

    Indian Academy of Sciences (India)

    Vivek V Rane

    2003-08-01

    Euler–Maclaurin and Poisson analogues of the summations $\\sum_{a < n ≤ b}(n)f(n), \\sum_{a < n ≤ b}d(n) f(n), \\sum_{a < n ≤ b}d(n)(n) f(n)$ have been obtained in a unified manner, where (()) is a periodic complex sequence; () is the divisor function and () is a sufficiently smooth function on [, ]. We also state a generalised Abel's summation formula, generalised Euler's summation formula and Euler's summation formula in several variables.

  10. Analogue cosmology in a hadronic fluid

    Directory of Open Access Journals (Sweden)

    Bilić Neven

    2014-01-01

    Full Text Available Analog gravity models of general relativity seem promising routes to providing laboratory tests of the foundation of quantum field theory in curved space-time. In contrast to general relativity, where geometry of a spacetime is determined by the Einstein equations, in analog models geometry and evolution of analog spacetime are determined by the equations of fluid mechanics. In this paper we study the analogue gravity model based on massless pions propagating in a expanding hadronic fluid. The analog expanding spacetime takes the form of an FRW universe, with the apparent and trapping horizons defined in the standard way.

  11. Phonon analogue of topological nodal semimetals

    Science.gov (United States)

    Po, Hoi Chun; Bahri, Yasaman; Vishwanath, Ashvin

    2015-03-01

    Recently, Kane and Lubensky proposed a mapping between bosonic phonon problems on isostatic lattices to chiral fermion systems based on factorization of the dynamical matrix [Nat. Phys. 10, 39 (2014)]. The existence of topologically protected zero modes in such mechanical problems is related to their presence in the fermionic system and is dictated by a local index theorem. Here we adopt the proposed mapping to construct a two-dimensional mechanical analogue of a fermionic topological nodal semimetal that hosts a robust bulk node in its linearized phonon spectrum. Such topologically protected soft modes with tunable wavevector may be useful in designing mechanical structures with fault-tolerant properties.

  12. Electronic analogue simulator of radio cardiograms

    International Nuclear Information System (INIS)

    The various parameters of the heart pump and of the blood circulation can be determined by radio-cardio-graphical techniques. The curves thus obtained can be more easily used in radiocardiography if the electronic analogue simulator described here is employed. The experimental and simulated radio-cardiograms are made to coincide by varying the electrical parameters of the simulator. Using simple charts it is possible to obtain directly the actual original physiological parameters from these electrical parameters. Some examples are given showing the excellent accuracy obtained in the determination of ejection indices by the simulator. (authors)

  13. Satellite television analogue and digital reception techniques

    CERN Document Server

    Benoit, Herve

    1999-01-01

    Satellite television is part of the lives of millions of television viewers worldwide and its influence is set to increase significantly with the launch of digital satellite television services.This comprehensive reference book, written by the author of the highly successful 'Digital Television', provides a technical overview of both analogue and digital satellite TV. Written concisely and thoroughly, it covers all aspects of satellite TV necessary to understand its operation and installation. It also covers the evolution of satellite television, and contains a detailed glossary of tec

  14. Scintigraphy with labelled analogues of the somatostatin; Scintigraphie aux analogues marques de la somatostatine (octreoscan)

    Energy Technology Data Exchange (ETDEWEB)

    Duet, M.; Ajzenberg, C.; Warnet, A.; Mundler, O. [Hopital Lariboisiere, 75 - Paris (France)

    1998-02-01

    The receptors of the somatostatin have been localized in a big number of tumors, whom a great number are neuro-endocrine tumors. However, some tumors that have not this differentiation (breast cancer, lymphomas, cerebral tumors) possess them as well. Analogues of somatostatin, labelled with isotopes having a gamma emission, allow from now their detection in vivo. (N.C.)

  15. Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.

    Science.gov (United States)

    Rana, Sandeep; Blowers, Elizabeth C; Tebbe, Calvin; Contreras, Jacob I; Radhakrishnan, Prakash; Kizhake, Smitha; Zhou, Tian; Rajule, Rajkumar N; Arnst, Jamie L; Munkarah, Adnan R; Rattan, Ramandeep; Natarajan, Amarnath

    2016-05-26

    Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents. PMID:27077228

  16. Self-Powered Analogue Smart Skin.

    Science.gov (United States)

    Shi, Mayue; Zhang, Jinxin; Chen, Haotian; Han, Mengdi; Shankaregowda, Smitha A; Su, Zongming; Meng, Bo; Cheng, Xiaoliang; Zhang, Haixia

    2016-04-26

    The progress of smart skin technology presents unprecedented opportunities for artificial intelligence. Resolution enhancement and energy conservation are critical to improve the perception and standby time of robots. Here, we present a self-powered analogue smart skin for detecting contact location and velocity of the object, based on a single-electrode contact electrification effect and planar electrostatic induction. Using an analogue localizing method, the resolution of this two-dimensional smart skin can be achieved at 1.9 mm with only four terminals, which notably decreases the terminal number of smart skins. The sensitivity of this smart skin is remarkable, which can even perceive the perturbation of a honey bee. Meanwhile, benefiting from the triboelectric mechanism, extra power supply is unnecessary for this smart skin. Therefore, it solves the problems of batteries and connecting wires for smart skins. With microstructured poly(dimethylsiloxane) films and silver nanowire electrodes, it can be covered on the skin with transparency, flexibility, and high sensitivity. PMID:27010713

  17. Alligator Rivers Analogue project - Geologic Setting

    International Nuclear Information System (INIS)

    In this volume the author synthesizes the results of the investigations carried over more than 20 years in the Koongarra area. It describes its regional geologic setting, geological evolution and the exploration activities carried out to date. The secondary ore of the Koongarra No. 1 uranium orebody provides a natural analogue suitable for validation of models for radionuclide transport. Although the primary uranium mineralisation occurs as uraninite veins and veinlets in fractures and brecciated zones that cross cut the steeply dipping (55 deg.C) host schists, weathering and dispersion of uranium within the zone of weathered schists has formed this secondary ore. The interaction of the weathering processes with the mineralogy and geochemistry of the unweathered host schists, and the primary hydrothermal alteration halo with and around the primary uranium mineralisation, has also been critical in the development of the secondary ore. This secondary ore natural analogue being at a shallow depth, plus the availability of open boreholes and drill core/borehole samples, has facilitated groundwater and rock investigations. 49 refs., 4 tabs., 42 figs

  18. Long-term predictions using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Ewing, R.C. [Univ. of New Mexico, Albuquerque, NM (United States)

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  19. Natural analogue synthesis report, TDR-NBS-GS-000027 rev00 icn02

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, A.; Nieder-Westermann, G.; Stuckless, J.; Dobson, P.; Unger, A.J.A.; Kwicklis, E.; Lichtner, P.; Carey, B.; Wolde, G.; Murrel,M.; Kneafsey, T.J.; Meijer, A.; Faybishenko, B.

    2002-04-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M&O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide release

  20. Natural analogue synthesis report, TDR-NBS-GS-000027 REV00 ICN02

    International Nuclear Information System (INIS)

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the Yucca Mountain Site Description (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide

  1. Topical vitamin D analogue calcipotriol reduces skin fibrosis in experimental scleroderma.

    Science.gov (United States)

    Usategui, Alicia; Criado, Gabriel; Del Rey, Manuel J; Faré, Regina; Pablos, José L

    2014-10-01

    Vitamin D analogues can reduce TGF-β pro-fibrotic signaling in dermal fibroblasts, but they may also induce a potentially pro-fibrotic thymic stromal lymphopoietin (TSLP)-dependent Th2 cytokine local response. We have analyzed the net effect of topical vitamin D analogue calcipotriol (CPT) on the cytokine profile and the development of fibrosis in experimental model of bleomycin-induced fibrosis. Mice were simultaneously treated with topical CPT or vehicle cream and skin fibrosis was measured by collagen deposition, Masson's trichrome staining and hydroxyproline content. Cytokine and TSLP gene expression was evaluated by quantitative RT-PCR. We showed that in bleomycin injected skin, CPT administration significantly enhanced TSLP and IL-13 gene expression, but did not modify the expression of other cytokines. Skin fibrosis and hydroxyproline content were significantly reduced in CPT compared to vehicle-treated mice. In normal skin, topical administration of CPT lacked a direct pro-fibrotic effect. Our results demonstrate that topical CPT superinduces the expression of the TSLP/IL-13 Th2 axis in fibrotic skin, but it has a net anti-fibrotic effect. These data support the therapeutic use of topical vitamin D analogues for skin fibrosis. PMID:24788893

  2. Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

    Directory of Open Access Journals (Sweden)

    Xu-Wen Li

    2013-07-01

    Full Text Available Aurachins are myxobacterial 3-farnesyl-4(1H-quinolone derived compounds initially described as respiratory chain inhibitors, more specifically as inhibitors of various cytochrome complexes. They are also known as potent antibiotic compounds. We describe herein the first synthesis of aurachin D through a key Conrad–Limpach reaction. The same strategy was used to reach some ring as opposed to chain analogues, allowing for the description of structure–activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was found on Plasmodium falciparum with a selectivity index of 345, compared to Vero cells, for the natural product and its geranyl analogue. The loss of mitochondrial membrane potential induced by aurachins in human U-2 OS osteosarcoma cells was studied, showing the best activity for aurachin D and a naphthalene analogue, yet without totally explaining the observed cytotoxic activity of the compounds. Finally, a synthetic entry is given to the complete carboheterocyclic core of aurachin H through the N-oxidation/epoxidation of aurachin D and a shorter chain analogue, followed by subsequent biomimetic cyclization.

  3. Insulin analogues and severe hypoglycaemia in type 1 diabetes

    DEFF Research Database (Denmark)

    Kristensen, P L; Hansen, L S; Jespersen, M J;

    2012-01-01

    The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed...

  4. Black Hole Analogue in Bose–Einstein Condensation

    Indian Academy of Sciences (India)

    Tangmei He

    2014-09-01

    We have proposed a black hole analogue in a Bose–Einstein condensation. By introducing the Painlevé co-ordinates and using K–G equations, we have obtained the critical temperature of the black hole analogue in a Bose–Einstein condensation.

  5. A q-Analogue of Rucinski-Voigt Numbers

    OpenAIRE

    Roberto B. Corcino; Charles B. Montero

    2012-01-01

    A q-analogue of Rucinski-Voigt numbers is defined by means of a recurrence relation, and some properties including the orthogonality and inverse relations with the q-analogue of the limit of the differences of the generalized factorial are obtained.

  6. Somatostatin analogue in short term management of hyperinsulinism.

    OpenAIRE

    Kirk, J M; Di Silvio, L; Hindmarsh, P. C.; Brook, C G

    1988-01-01

    Five infants with hypoglycaemia due to hyperinsulinism were treated for between three and 11 days with a somatostatin analogue, which raised the mean blood glucose concentration and lowered the glucose requirements in all. Somatostatin analogue appears to be useful in the short term management of these patients.

  7. Space Analogue Environments: Are the Populations Comparable?

    Science.gov (United States)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that

  8. Automated Layout Generation of Analogue and Mixed-Signal ASIC's

    DEFF Research Database (Denmark)

    Bloch, Rene

    The research and development carried out in this Ph.D. study focusses on two key areas of the design flow for analogue and mixed-signal integrated circuit design, the mixed-signal floorplanning and the analogue layout generation.A novel approach to floorplanning is presented which provides true...... flow.A new design flow for automated layout generation of general analogue integrated circuits is presented. The design flow provides an automated design path from a sized circuit schematic to the final layout containing the placed, but unrouted, devices of the circuit. The analogue circuit layout is...... generated using a full-custom layout style and is based on a library of CMOS process independent device generators. The placement for the analogue circuit is derived using the interactive floorplan optimization algorithm described above. This ensures that a high degree of user control is implemented in the...

  9. Development of new mitomycin C and porfiromycin analogues.

    Science.gov (United States)

    Iyengar, B S; Lin, H J; Cheng, L; Remers, W A; Bradner, W T

    1981-08-01

    New mitomycin C and porfiromycin analogues were prepared by treating mitomycin A and N-methylmitomycin A with a variety of amines, including aziridines, allylamines, propargylamines, chloroalkylamines, hydroxyalkylamines, glycine derivatives, aralkylamines, and heterocyclic amines. All analogues were evaluated against P-388 murine leukemia and selected ones were examined for their leukopenic properties. Certain analogues were found to be superior to mitomycin C in potency, efficacy, and therapeutic ratio in the P-388 assay. The most active substituents at the mitosane 7 position included aziridine, 2-methylaziridine, propargylamine, furfurylamine, methyl glycinate, and 3-aminopyridine. Mitomycin A and the 7-aziridino, 7-(2-methylaziridino), and 3-aminopyridine analogues were less leukopenic than mitomycin C. Certain other analogues, including propargylamino and methyl glycinate, were highly leukopenic. The three compounds tested against B-16 melanoma in mice were significantly more effective than mitomycin C in this assay. Previously established structure--activity relationships were found inadequate to account for all of the new data. PMID:7328599

  10. The development of somatostatin analogues mediated tumor targeting and therapy

    International Nuclear Information System (INIS)

    Radionuclide labelled somatostatin analogues have been widely used in the detection of neuro-endocrine tumors. Till now, most of somatostatin analogues only have high affinity to somatostatin receptor 2 (SSTR2), further clinical applications was limitted. A new generation of somatostatin analogues such as 1, 4, 7, 10-tetraazacyclodocecane-N, N', N'', N''' -tetaraacetic acid-Na 13- octertide (DOTA-NOC) etc, binding to somatostatin receptors not only SSTR2 but other subtypes has been used mainly in preclinical study. In this review, we discussed these new somatostatin analogues, chelating agent, and their new labelled compounds, these new radionuclide labelled somatostatin analogues may hold great promise for the receptor-mediated tumor imaging and treatments. (authors)

  11. Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation

    Science.gov (United States)

    ZHOU, DAI-YING; ZHAO, SU-QING; DU, ZHI-YUN; ZHENG, XI; ZHANG, KUN

    2016-01-01

    The concentrations required for curcumin to exert its anticancer activity (IC50, 20 µM) are difficult to achieve in the blood plasma of patients, due to the low bioavailability of the compound. Therefore, much effort has been devoted to the development of curcumin analogues that exhibit stronger anticancer activity and a lower IC50 than curcumin. The present study investigated twelve pyridine analogues of curcumin, labeled as groups AN, BN, EN and FN, to determine their effects in CWR-22Rv1 human prostate cancer cells. The inhibitory effects of these compounds on testosterone (TT)-induced androgen receptor (AR) activity was determined by performing an AR-linked luciferase assay and by TT-induced expression of prostate-specific antigen. The results of the current study suggested that the FN group of analogues had the strongest inhibitory effect of growth on CWR-22Rv1 cultured cells, and were the most potent inhibitor of AR activity compared with curcumin, and the AN, BN and EN analogues. Thus, the results of the present study indicate the inhibition of the AR pathways as a potential mechanism for the anticancer effect of curcumin analogues in human prostate cancer cells. Furthermore, curcumin analogues with pyridine as a distal ring and tetrahydrothiopyran-4-one as a linker may be good candidates for the development of novel drugs for the treatment of prostate cancer, by targeting the AR signaling pathway. PMID:27313760

  12. Electromagnetic wave analogue of electronic diode

    CERN Document Server

    Shadrivov, Ilya V; Kivshar, Yuri S; Fedotov, Vassili A; Zheludev, Nikolay I

    2010-01-01

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of the polarization state rotation and is also a key component of optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by an extraordinary strong nonlinear wave propagation effect in the same way as electronic diode function is provided by a nonlinear current characteristic of a semiconductor junction. The effect exploited in this new electromagnetic diode is an intensity-dependent polarization change in an artificial chiral metamolecule. This microwave effect exceeds a similar optical effect previously observed in natural crystals by more than 12 orders of magnitude and a direction-dependent transmission that differing by a factor of 65.

  13. Gravitational analogue of the Witten effect

    Energy Technology Data Exchange (ETDEWEB)

    Foda, O. (International Centre for Theoretical Physics, Trieste (Italy))

    1985-07-22

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP violation, the Witten effect (a shift in the electric charge of a magnetic monopole due to CP non-conservation) is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a thetaR tildeR term in the lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed.

  14. Helical chirality induction of expanded porphyrin analogues

    Indian Academy of Sciences (India)

    Jun-Ichiro Setsune

    2012-11-01

    Expanded porphyrin analogues with unique figure-eight conformation were prepared by way of useful pyrrole intermediates such as bis(azafulvene)s and 2-borylpyrrole. Supramolecular chirogenesis of cyclooctapyrrole O1 with 32-cycloconjugation was successfully applied to determine absolute configuration of chiral carboxylic acids. Dinuclear CuII complex of cyclooctapyrrole O2 with interrupted -conjugation was resolved by HPLC into enantiomers and their helical handedness was determined by theoretical simulation of their CD spectral pattern. Enantioselective induction of helicity in the metal helicate formation in the presence of a chiral promoter was demonstrated by using ()-(+)-1-(1-phenyl)ethylamine that favoured , helicity. Dinuclear CoII complexes of cyclotetrapyrroletetrapyridine O3 were found to be substitution labile and pick up amino acid anions in water. Those amino acid complexes of O3Co2 were rendered to adopt a particular unidirectional helical conformation preferentially depending on the ligated amino acid anion.

  15. Electromagnetic wave analogue of an electronic diode

    International Nuclear Information System (INIS)

    An electronic diode is a nonlinear semiconductor circuit component that allows conduction of electrical current in one direction only. A component with similar functionality for electromagnetic waves, an electromagnetic isolator, is based on the Faraday effect of rotation of the polarization state and is also a key component in optical and microwave systems. Here we demonstrate a chiral electromagnetic diode, which is a direct analogue of an electronic diode: its functionality is underpinned by an extraordinarily strong nonlinear wave propagation effect in the same way as the electronic diode function is provided by the nonlinear current characteristic of a semiconductor junction. The effect exploited in this new electromagnetic diode is an intensity-dependent polarization change in an artificial chiral metamolecule. This microwave effect exceeds a similar optical effect previously observed in natural crystals by more than 12 orders of magnitude and a direction-dependent transmission that differs by a factor of 65.

  16. SYNTHESIS AND BIOEVALUATION OF KETOCONAZOLE THIOSEMICARBAZONE ANALOGUES

    Directory of Open Access Journals (Sweden)

    Y. Murti

    2011-12-01

    Full Text Available Ketoconazole (KTZ is a synthetic antifungal drug used to prevent and treat fungal infections, especially in immunocompromised patients such as those with AIDS. Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including C. albicans. Thus new effective agents with less toxicity against fungal infection are urgently required. With this view, ketoconazole thiosemicarbazone analogues (Compounds 1-10 were synthesized wherein condensation of different thiosemicarbazides substituted by different cyclic and aromatic amines with the KTZ was done. Investigation of in-vitro antifungal activity of compounds was done by broth microdilution assay method against five pathogenic fungi Aspergillus niger, Candida albicans, Candida krusei, Candida glabrata and Candida tropicalis. Ketoconazole was used as reference for inhibitory activity against fungi. All the compounds were found potent antifungal agents, while compounds 8, 9 and 10 exhibited excellent in-vitro antifungal activity showing importance of halogenated compounds.

  17. The gravitational analogue of the Witten effect

    International Nuclear Information System (INIS)

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP violation, the Witten effect (a shift in the electric charge of a magnetic monopole due to CP non-conservation) is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a thetaR tildeR term in the lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed. (orig.)

  18. The gravitational analogue of the Witten effect

    International Nuclear Information System (INIS)

    In the presence of massive fermions, and assuming a non-vanishing theta-parameter as the only source of CP-violation, the Witten effect [a shift in the electric charge of a magnetic monopole due to CP-non-conservation] is shown to follow from an anomalous chiral commutator. Next, given the gravitational contribution to the chiral anomaly, the corresponding anomalous commutator for Dirac fermion currents in a gravitational background is derived. From that, we infer the equivalence of a theta R-tilde R term in the Lagrangian to a shift in the mass parameter of the NUT metric, in proportion to theta. This is interpreted as the gravitational analogue of the Witten effect. Its relevance to certain Kaluza-Klein monopoles is briefly discussed. (author)

  19. Jupiter analogues and planets of active stars

    Directory of Open Access Journals (Sweden)

    Henning T.

    2013-04-01

    Full Text Available Combined results are now available from a 15 year long search for Jupiter analogues around solar-type stars using the ESO CAT + CES, ESO 3.6 m + CES, and ESO 3.6 m + HARPS instruments. They comprise planet (co-discoveries (ι Hor and HR 506 and confirmations (three planets in HR 3259 as well as non-confirmations of planets (HR 4523 and ɛ Eri announced elsewhere. A long-term trend in ɛ Ind found by our survey is probably attributable to a Jovian planet with a period >30 yr, but we cannot fully exclude stellar activity effects as the cause. A 3.8 year periodic variation in HR 8323 can be attributed to stellar activity.

  20. Solution Processed PEDOT Analogues in Electrochemical Supercapacitors.

    Science.gov (United States)

    Österholm, Anna M; Ponder, James F; Kerszulis, Justin A; Reynolds, John R

    2016-06-01

    We have designed fully soluble ProDOTx-EDOTy copolymers that are electrochemically equivalent to electropolymerized PEDOT without using any surfactants or dispersants. We show that these copolymers can be incorporated as active layers in solution processed thin film supercapacitors to demonstrate capacitance, stability, and voltage similar to the values of those that use electrodeposited PEDOT as the active material with the added advantage of the possibility for large scale, high-throughput processing. These Type I supercapacitors provide exceptional cell voltages (up to 1.6 V), highly symmetrical charge/discharge behavior, promising long-term stability exceeding 50 000 charge/discharge cycles, as well as energy (4-18 Wh/kg) and power densities (0.8-3.3 kW/kg) that are comparable to those of electrochemically synthesized analogues. PMID:27195798

  1. MAQARIN natural analogue study: phase III

    International Nuclear Information System (INIS)

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH)2 type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the 'alkali disturbed zone' of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  2. Current european regulatory perspectives on insulin analogues.

    Science.gov (United States)

    Enzmann, Harald G; Weise, Martina

    2011-01-01

    Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions. PMID:21736748

  3. Evolving a polymerase for hydrophobic base analogues.

    Science.gov (United States)

    Loakes, David; Gallego, José; Pinheiro, Vitor B; Kool, Eric T; Holliger, Philipp

    2009-10-21

    Hydrophobic base analogues (HBAs) have shown great promise for the expansion of the chemical and coding potential of nucleic acids but are generally poor polymerase substrates. While extensive synthetic efforts have yielded examples of HBAs with favorable substrate properties, their discovery has remained challenging. Here we describe a complementary strategy for improving HBA substrate properties by directed evolution of a dedicated polymerase using compartmentalized self-replication (CSR) with the archetypal HBA 5-nitroindole (d5NI) and its derivative 5-nitroindole-3-carboxamide (d5NIC) as selection substrates. Starting from a repertoire of chimeric polymerases generated by molecular breeding of DNA polymerase genes from the genus Thermus, we isolated a polymerase (5D4) with a generically enhanced ability to utilize HBAs. The selected polymerase. 5D4 was able to form and extend d5NI and d5NIC (d5NI(C)) self-pairs as well as d5NI(C) heteropairs with all four bases with efficiencies approaching, or exceeding, those of the cognate Watson-Crick pairs, despite significant distortions caused by the intercalation of the d5NI(C) heterocycles into the opposing strand base stack, as shown by nuclear magnetic resonance spectroscopy (NMR). Unlike Taq polymerase, 5D4 was also able to extend HBA pairs such as Pyrene: varphi (abasic site), d5NI: varphi, and isocarbostyril (ICS): 7-azaindole (7AI), allowed bypass of a chemically diverse spectrum of HBAs, and enabled PCR amplification with primers comprising multiple d5NI(C)-substitutions, while maintaining high levels of catalytic activity and fidelity. The selected polymerase 5D4 promises to expand the range of nucleobase analogues amenable to replication and should find numerous applications, including the synthesis and replication of nucleic acid polymers with expanded chemical and functional diversity. PMID:19778048

  4. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg Univ. (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Inst., Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  5. Natural analogues of nuclear waste glass corrosion

    International Nuclear Information System (INIS)

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses

  6. Natural analogues of nuclear waste glass corrosion.

    Energy Technology Data Exchange (ETDEWEB)

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  7. MAQARIN natural analogue study: phase III

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, W.R.; Mazurek, M.; Waber, H.N. [Univ. of Berne (Switzerland). Institutes of Geology, Mineralogy and Petrology, Rock-Water Interaction Group (GGWW); Arlinger, J.; Erlandson, A.C.; Hallbeck, L.; Pedersen, K. [Goeteborg University (Sweden). Dept. of General and Marine Microbiology; Boehlmann, W.; Fritz, P.; Geyer, S.; Geyer, W.; Hanschman, G.; Kopinke, F.D.; Poerschmann, J. [Umweltforschungszentrum Leipzig-Halle (Germany); Chambers, A.V.; Haworth, A.; Ilett, D.; Linklater, C.M.; Tweed, C.J. [AEA Technology plc, Harwell (United Kingdom); Chenery, S.R.N.; Kemp, S.J.; Milodowski, A.E.; Pearce, J.M.; Reeder, S.; Rochelle, C.A.; Smith, B.; Wetton, P.D.; Wragg, J. [British Geological Survey, Keyworth (United Kingdom); Clark, I.D. [Univ. of Ottawa (Canada). Dept. of Geology; Hodginson, E.; Hughes, C.R. [Univ. of Manchester (United Kingdom). Dept. of Earth Sciences; Hyslop, E.K. [British Geological Survey, Edinburgh (United Kingdom); Karlsson, F. [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Khoury, H.N.; Salameh, E. [Univ. of Jordan, Amman (Jordan); Lagerblad, B. [Cement Institute, Stockholm (Sweden); Longworth, G. [Univ. of Manchester (United Kingdom). Dept. of Geology; Pitty, A.F. [Private consultant, Norwich (United Kingdom); Savage, D. [QuantiSci Ltd, Melton Mowbray (United Kingdom); Smellie, J.A.T. [ed.] [Conterra AB, Uppsala (Sweden)

    1998-12-01

    This report represents the conclusion to Phase III of the Maqarin Natural Analogue Study. The main thrust was to establish the origin and chemistry of the Western Springs hyper alkaline groundwaters (Na/K enriched Ca(OH){sub 2} type) and to study their interaction with rocks of different compositions, as natural analogues to key processes that might occur at an early stage within the `alkali disturbed zone` of cementitious repositories in different host rocks. Whilst earlier studies at Maqarin were very much site-specific and process-oriented, Phase III provided a regional perspective to the geological evolution of the Maqarin region. This was made possible by greater field access which allowed a more systematic structural and geomorphological study of the area. This has resulted in a greater understanding of the age and spatial relationships concerning formation of the cement zones through spontaneous combustion of the Bituminous Marls, and the subsequent formation of high pH groundwaters at the Eastern and Western Springs locations. At the Western Springs locality, hydrochemical and hydrogeological evaluation of new and published data (plus access to unpublished data), together with detailed mineralogical and geochemical studies, helped to clarify the very earliest stage of cement leachate/host rock interaction. The data were used also to test coupled flow/transport codes developed to assess the long-term evolution of a cementitious repository. Additional objectives addressed include: a) rock matrix diffusion, b) the occurrence and chemical controls on zeolite composition, e) the occurrence and chemical controls on clay stability, and d) the role of microbes, organics and colloids in trace element transport. The Maqarin site now provides a consistent picture explaining the origin of the hyperalkaline groundwaters, and is therefore a unique location for the examination of the mechanisms and processes associated with cementitious repositories. Application of these

  8. Current european regulatory perspectives on insulin analogues

    Directory of Open Access Journals (Sweden)

    Enzmann Harald G

    2011-07-01

    Full Text Available Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions.

  9. Platonic solids generate their four-dimensional analogues

    CERN Document Server

    Dechant, Pierre-Philippe

    2013-01-01

    In this paper, we show how regular convex 4-polytopes - the analogues of the Platonic solids in four dimensions - can be constructed from three-dimensional considerations concerning the Platonic solids alone. Via the Cartan-Dieudonne theorem, the reflective symmetries of the Platonic solids generate rotations. In a Clifford algebra framework, the space of spinors generating such three-dimensional rotations has a natural four-dimensional Euclidean structure. The spinors arising from the Platonic Solids can thus in turn be interpreted as vertices in four-dimensional space, giving a simple construction of the 4D polytopes 16-cell, 24-cell, the F_4 root system and the 600-cell. In particular, these polytopes have `mysterious' symmetries, that are almost trivial when seen from the three-dimensional spinorial point of view. In fact, all these induced polytopes are also known to be root systems and thus generate rank-4 Coxeter groups, which can be shown to be a general property of the spinor construction. These cons...

  10. Solid-phase synthesis of polyamine toxin analogues

    DEFF Research Database (Denmark)

    Kromann, Hasse; Krikstolaityte, Sonata; Andersen, Anne J; Andersen, Kim; Krogsgaard-Larsen, Povl; Jaroszewski, Jerzy W; Egebjerg, Jan; Strømgaard, Kristian

    2002-01-01

    receptors, in particular Ca(2+)-permeable AMPA and kainate receptors. We have previously shown that an analogue of PhTX-433 with one of the amino groups replaced by a methylene group, philanthotoxin-83 (PhTX-83) is a selective and potent antagonist of AMPA receptors. We now describe the solid-phase...... synthesis of analogues of PhTX-83 and the electrophysiological characterization of these analogues on cloned AMPA and kainate receptors. The polyamine portion of PhTX-83 was modified systematically by changing the position of the secondary amino group along the polyamine chain. In another series of...

  11. Recent developments in naturally derived antimalarials: cryptolepine analogues.

    Science.gov (United States)

    Wright, Colin W

    2007-06-01

    Increasing resistance of Plasmodium falciparum to commonly used antimalarial drugs has made the need for new agents increasingly urgent. In this paper, the potential of cryptolepine, an alkaloid from the West African shrub Cryptolepis sanguinolenta, as a lead towards new antimalarial agents is discussed. Several cryptolepine analogues have been synthesized that have promising in-vitro and in-vivo antimalarial activity. Studies on the antimalarial modes of action of these analogues indicate that they may have different or additional modes of action to the parent compound. Elucidation of the mode of action may facilitate the development of more potent antimalarial cryptolepine analogues. PMID:17637183

  12. Platonic solids generate their four-dimensional analogues.

    Science.gov (United States)

    Dechant, Pierre Philippe

    2013-11-01

    This paper shows how regular convex 4-polytopes - the analogues of the Platonic solids in four dimensions - can be constructed from three-dimensional considerations concerning the Platonic solids alone. Via the Cartan-Dieudonné theorem, the reflective symmetries of the Platonic solids generate rotations. In a Clifford algebra framework, the space of spinors generating such three-dimensional rotations has a natural four-dimensional Euclidean structure. The spinors arising from the Platonic solids can thus in turn be interpreted as vertices in four-dimensional space, giving a simple construction of the four-dimensional polytopes 16-cell, 24-cell, the F4 root system and the 600-cell. In particular, these polytopes have `mysterious' symmetries, that are almost trivial when seen from the three-dimensional spinorial point of view. In fact, all these induced polytopes are also known to be root systems and thus generate rank-4 Coxeter groups, which can be shown to be a general property of the spinor construction. These considerations thus also apply to other root systems such as A(1)\\oplus I(2)(n) which induces I(2)(n)\\oplus I(2)(n), explaining the existence of the grand antiprism and the snub 24-cell, as well as their symmetries. These results are discussed in the wider mathematical context of Arnold's trinities and the McKay correspondence. These results are thus a novel link between the geometries of three and four dimensions, with interesting potential applications on both sides of the correspondence, to real three-dimensional systems with polyhedral symmetries such as (quasi)crystals and viruses, as well as four-dimensional geometries arising for instance in Grand Unified Theories and string and M-theory. PMID:24132220

  13. Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug.

    Science.gov (United States)

    Cameron, Amy R; Logie, Lisa; Patel, Kashyap; Bacon, Sandra; Forteath, Calum; Harthill, Jean; Roberts, Adam; Sutherland, Calum; Stewart, Derek; Viollet, Benoit; Sakamoto, Kei; McDougall, Gordon; Foretz, Marc; Rena, Graham

    2016-08-01

    Anti-hyperglycaemic effects of the hydroxybenzoic acid salicylate might stem from effects of the drug on mitochondrial uncoupling, activation of AMP-activated protein kinase, and inhibition of NF-κB signalling. Here, we have gauged the contribution of these effects to control of hepatocyte glucose production, comparing salicylate with inactive hydroxybenzoic acid analogues of the drug. In rat H4IIE hepatoma cells, salicylate was the only drug tested that activated AMPK. Salicylate also reduced mTOR signalling, but this property was observed widely among the analogues. In a sub-panel of analogues, salicylate alone reduced promoter activity of the key gluconeogenic enzyme glucose 6-phosphatase and suppressed basal glucose production in mouse primary hepatocytes. Both salicylate and 2,6 dihydroxybenzoic acid suppressed TNFα-induced IκB degradation, and in genetic knockout experiments, we found that the effect of salicylate on IκB degradation was AMPK-independent. Previous data also identified AMPK-independent regulation of glucose but we found that direct inhibition of neither NF-κB nor mTOR signalling suppressed glucose production, suggesting that other factors besides these cell signalling pathways may need to be considered to account for this response to salicylate. We found, for example, that H4IIE cells were exquisitely sensitive to uncoupling with modest doses of salicylate, which occurred on a similar time course to another anti-hyperglycaemic uncoupling agent 2,4-dinitrophenol, while there was no discernible effect at all of two salicylate analogues which are not anti-hyperglycaemic. This finding supports much earlier literature suggesting that salicylates exert anti-hyperglycaemic effects at least in part through uncoupling. PMID:27130437

  14. Developing Skin Analogues for a Robotic Octopus

    Institute of Scientific and Technical Information of China (English)

    Jinping Hou; Richard H.C.Bonser; George Jeronimidis

    2012-01-01

    In order to fabricate a biomimetic skin for an octopus inspired robot,a new process was developed based on mechanical properties measured from real octopus skin.Various knitted nylon textiles were tested and the one of 10-denier nylon was chosen as reinforcement.A combination of Ecoflex 0030 and 0010 silicone rubbers was used as matrix of the composite to obtain the right stiffness for the skin-analogue system.The open mould fabrication process developed allows air bubble to escape easily and the artificial skin produced was thin and waterproof.Material properties of the biomimetic skin were characterised using static tensile and instrumented scissors cutting tests.The Young's moduli of the artificial skin are 0.08 MPa and 0.13 MPa in the longitudinal and transverse directions,which are much lower than those of the octopus skin.The strength and fracture toughness of the artificial skin,on the other hand are higher than those of real octopus skins.Conically-shaped skin prototypes to be used to cover the robotic arm unit were manufactured and tested.The biomimetic skin prototype was stiff enough to maintain it conical shape when filled with water.The driving force for elongation was reduced significantly compared with previous prototypes.

  15. Progress in the Alligator Rivers analogue project

    International Nuclear Information System (INIS)

    The OECD Nuclear Energy Agency (NEA) Steering Committee agreed on 1 October 1987 to sponsor the International Alligator Rivers Analogue Project (ARAP) for a three year program with a formal starting date of 1 September 1987. The participants are six organisations from five NEA Member States with ANSTO as the managing participant. A detailed tehnical program was agreed by a Joint Technical Committee and this comprises six main technical sub-projects: modelling of radionuclide migration, hydrogeology at Koongarra, uranium/thorium series disequilibria studies, colloid and groundwater studies, fission product studies and transuranic nuclide studies. A modelling workshop for participants and contractors was held in Sydney in February 1988 and a field visit was undertaken in May 1988. Laboratory studies on samples obtained in previous field visits were carried out from September 1987. Data from the project are being provided for participants as case 8 in the INTRAVAL model validation project coordinated by the Swedish Nuclear Power Inspectorate. A Joint Technical Committee meeting to approve the technical program and budjet for the second year will be held in Sydney in July 1988

  16. A positive Grassmannian analogue of the permutohedron

    CERN Document Server

    Williams, Lauren K

    2015-01-01

    The classical permutohedron Perm is the convex hull of the points (w(1),...,w(n)) in R^n where w ranges over all permutations in the symmetric group. This polytope has many beautiful properties -- for example it provides a way to visualize the weak Bruhat order: if we orient the permutohedron so that the longest permutation w_0 is at the "top" and the identity e is at the "bottom," then the one-skeleton of Perm is the Hasse diagram of the weak Bruhat order. Equivalently, the paths from e to w_0 along the edges of Perm are in bijection with the reduced decompositions of w_0. Moreover, the two-dimensional faces of the permutohedron correspond to braid and commuting moves, which by the Tits Lemma, connect any two reduced expressions of w_0. In this note we introduce some polytopes Br(k,n) (which we call bridge polytopes) which provide a positive Grassmannian analogue of the permutohedron. In this setting, BCFW bridge decompositions of reduced plabic graphs play the role of reduced decompositions. We define Br(k,...

  17. Alligator Rivers Analogue project. Groundwater Chemistry

    International Nuclear Information System (INIS)

    The objective of this volume is to provide an account of the groundwater sampling and analysis program undertaken at Koongarra, as part of the Alligator Rivers Analogue Project. Chemical parameters were investigated in groundwaters at various locations and depths in the vicinity of the Koongarra orebody. Measurements of the pH, redox state, conductivity, and bicarbonate alkalinity provided a starting point for interpreting water chemistry. Groundwater samples were obtained using submersible pumps, or, in a few cases, bailers. The concentrations of major cations and anions, such as magnesium and phosphate, were determined using a variety of standard techniques. Numerous elements were routinely analysed using quantitative or semi-quantitative ICPMS. Uranium series radionuclides and environmental isotopes were measured using radiochemical techniques and mass spectrometry. The distributions of isotopes such as deuterium, tritium, 210Pb, 13C and 14C enabled groundwater mixing and flow-paths to be studied. The occurrence and distributions of major species at Koongarra are presented in this volume, using both cross-sections and contour plans. Chemical and isotopic data for groundwater analyses carried out during the project are included in the Appendices. 47 refs., 16 tabs., 58 figs

  18. Spectroscopy analogue-to-digital converters

    International Nuclear Information System (INIS)

    A review of world trends in the branch of electronic constructions for spectroscopy analogue-to-digital converters (ADC) applied in different fields of nuclear physics and techniques has been done. Data sheets and graphical comparison of main parameters for ADC that have appeared in world literature are also added. Recent methods applied for conversion of voltage pulse amplitude with linear coding scale have been described. Future trends up to year 1990 anticipating the increase of spectroscopy ADC resolution up to 15 bits and the shortening of ADC conversion time down to 1 μs have been presented. The dynamic development of very fast converters with low accuracy has been predicted. Present ADC are capable of sampling pulses from nuclear detectors with repetition rate up to 100 MHz. Examples of different correction methods for deleting ADC measurement errors show that both hardware and software tools may be used. On the ground of these methods one can use for spectroscopy ADC design commercially available integrated circuits with large scale integration. Then good metrology parameters, simplicity of realization and small overall dimensions may be obtained. These correction methods make a compromise between speed and precision of ADC operation possible. 81 refs., 22 figs., 3 tabs. (author)

  19. Glucagon-like peptide-1 analogues: An overview

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2013-01-01

    Full Text Available Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia and suppression of glucagon (fasting hyperglycemia, amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly, DPP-4-resistant analogues (lixisenatide, albiglutide, and analogues of human GLP-1 (liraglutide, taspoglutide. Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.

  20. Analogue gravitational phenomena in Bose-Einstein condensates

    CERN Document Server

    Finazzi, Stefano

    2012-01-01

    Analogue gravity is based on the simple observation that perturbations propagating in several physical systems can be described by a quantum field theory in a curved spacetime. While phenomena like Hawking radiation are hardly detectable in astrophysical black holes, these effects may be experimentally tested in analogue systems. In this Thesis, focusing on Bose-Einstein condensates, we present our recent results about analogue models of gravity from three main perspectives: as laboratory tests of quantum field theory in curved spacetime, for the techniques that they provide to address various issues in general relativity, and as toy models of quantum gravity. The robustness of Hawking-like particle creation is investigated in flows with a single black hole horizon. Furthermore, we find that condensates with two (white and black) horizons develop a dynamical instability known in general relativity as black hole laser effect. Using techniques borrowed from analogue gravity, we also show that warp drives, which...

  1. Generalised insulin oedema after intensification of treatment with insulin analogues

    OpenAIRE

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  2. Analogue and Mixed-Signal Integrated Circuits for Space Applications

    CERN Document Server

    2014-01-01

    The purpose of AMICSA 2014 (organised in collaboration of ESA and CERN) is to provide an international forum for the presentation and discussion of recent advances in analogue and mixed-signal VLSI design techniques and technologies for space applications.

  3. Defining Analytical Strategies for Mars Sample Return with Analogue Missions

    Science.gov (United States)

    Osinski, G. R.; Sapers, H. M.; Francis, R.; Pontefract, A.; Tornabene, L. L.; Haltigin, T.

    2016-05-01

    The characterization of biosignatures in MSR samples will require integrated, cross-platform laboratory analyses carefully correlated and calibrated with Rover-based technologies. Analogue missions provide context for implementation and assessment.

  4. A q-Analogue of the Dirichlet L-Function

    Institute of Scientific and Technical Information of China (English)

    Min-Soo Kim; Jin-Woo Son

    2002-01-01

    In this paper, we will treat some interesting formulae which are slightly different from Kim's results by more or less the same method in [4-9]. At first, we consider a new definition of a q-analogue of Bernoulli numbers and polynomials.We construct a q-analogue of the Riemann ζ-function, Hurwitz ζ-function, and Dirichlet L-series. Also, we investigate the relation between the q-analogue of generalized Bernoulli numbers and the generalized Euler numbers. As an application, we prove that the q-analogue of Bernoulli numbers occurs in the coefficients of some Stirling type series for the p-adic analytic q-log-gamma function.

  5. Practical enantiospecific syntheses of lysobisphosphatidic acid and its analogues.

    Science.gov (United States)

    Jiang, Guowei; Xu, Yong; Prestwich, Glenn D

    2006-02-01

    We describe a versatile, efficient, and practical method for the preparation of enantiomerically pure lysobisphosphatidic acid (LBPA), bisether analogues, and phosphorothioate analogues of LBPA from solketal. Phosphorylation of a protected sn-2-O-oleoyl glycerol with 2-cyanoethyl bis(N,N-diisopropylamino)phosphite, followed by oxidation and deprotection, generated the enantiomers of 2,2'-LBPA. The corresponding phosphorothioate analogues were obtained by oxidation with sulfur. The (R,R) and (S,S) enantiomers of both LBPA and phosphorothioate LBPA were synthesized from (S)- and (R)-solketal, respectively. The ether analogue of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer were synthesized from the same enantiomer (S)-solketal by simply changing the sequence of deprotection steps. PMID:16438504

  6. Trustworthiness and Influence: A Reexamination in an Extended Counseling Analogue.

    Science.gov (United States)

    Rothmeier, Rosemarie C.; Dixon, David N.

    1980-01-01

    The study demonstrated that: (1) interviewer trustworthiness can be manipulated in an analogue interview setting; and (2) interviewer trustworthiness is related to interpersonal influence in the interview setting. Findings follow a pattern of outcomes predicted by cognitive dissonance theory. (Author)

  7. Synthesis and evaluation of novel carbocyclic carbohydrate analogues

    OpenAIRE

    Adamson, Christopher William

    2016-01-01

    Carbohydrate analogues play an indispensible role in the study of glycan processing enzymes. These compounds have attracted attention as probes of enzyme mechanisms, as chemical tools for the elucidation of enzyme function and as potential pharmaceuticals. The development of organocatalytic aldol chemistry has fundamentally altered the way chemists approach the synthesis of carbohydrate analogues. In this thesis I highlight a novel strategy toward the synthesis of carbocyclic carbohydrate ana...

  8. Biological evaluation of a novel sorafenib analogue, t-CUPM

    OpenAIRE

    Wecksler, Aaron T.; Hwang, Sung Hee; Liu, Jun-Yan; Wettersten, Hiromi I.; Morisseau, Christophe; Wu, Jian; Robert H. Weiss; Hammock, Bruce D.

    2014-01-01

    Sorafenib (Nexavar®) is currently the only FDA-approved small molecule targeted therapy for advanced hepatocellular carcinoma. The use of structural analogues and derivatives of sorafenib has enabled the elucidation of critical targets and mechanism(s) of cell death for human cancer lines. We previously performed a structure-activity relationship study on a series of sorafenib analogues designed to investigate the inhibition overlap between the major targets of sorafenib Raf-1 kinase and VEGF...

  9. Analogue Signal Processing: Collected Papers 1994-95

    DEFF Research Database (Denmark)

    1996-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of Electronics Institute, Technical University of Denmark, in 1994 and 1995....

  10. Analogue Signal Processing: Collected Papers 1996-97

    DEFF Research Database (Denmark)

    1997-01-01

    This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997.......This document is a collection of the papers presented at international conferences and in international journals by the analogue signal processing group of the Department of Information Technology, Technical University of Denmark, in 1996 and 1997....

  11. Analogue symmetry breaking in superallowed Fermi β-decay

    International Nuclear Information System (INIS)

    The change in the Fermi matrix element due to deviations from perfect analogue symmetry has been estimated in a single-particle model with both harmonic oscillator and Saxon-Woods radial wave functions. A limitation of earlier calculations, in which the ground state of the A-1 nucleus was taken as the unique parent, is removed to allow the whole spectrum of parent states to be operative. This improvement leads to slightly larger analogue symmetry breaking effects. (Auth.)

  12. Long Acting Somatostatin Analogue: Clinical Potential for Gastrointestinal Disease

    OpenAIRE

    Richard N Fedorak

    1989-01-01

    Name somatostatin is found throughout the gastrointestinal tract and has a wide variety of biological actions. Nevertheless, its short biological half-life and limited stability necessitate its use via continuous parenteral infusion and, thus, limits its therapeutic usefulness The development of long acting somatostatin analogues have lead to a re-examination of the therapeutic usefulness of somatostatin in gastrointestinal disease. Somatostatin analogues appear most beneficial tn preventing ...

  13. Co–Fe Prussian Blue Analogue Intercalated into Diamagnetic Mg–Al Layered Double Hydroxides

    OpenAIRE

    Cuijuan Zhang; Takashi Yamamoto; Yasuaki Einaga

    2016-01-01

    A heterostructure of diamagnetic magnesium‒aluminium layered double hydroxides (Mg‒Al LDHs) and photomag‐ netic cobalt‒iron Prussian Blue analogue (Co‒Fe PBA) was designed, synthesized and then designated as LDH‒PB. The cyanide-bridged Co‒Fe PBA was two-dimensionally intercalated into the Mg‒Al LDH template by the stepwise anion exchange method. LDH‒PB showed ferrimagnetic properties with in-plane antiferromagnetic exchange interactions, as well as small photo-induced magnetization by visible...

  14. $Z_3$-graded analogues of Clifford algebras and generalization of supersymmetry

    OpenAIRE

    Abramov, V.

    1996-01-01

    We define and study the ternary analogues of Clifford algebras. It is proved that the ternary Clifford algebra with $N$ generators is isomorphic to the subalgebra of the elements of grade zero of the ternary Clifford algebra with $N+1$ generators. In the case $N=3$ the ternary commutator of cubic matrices induced by the ternary commutator of the elements of grade zero is derived. We apply the ternary Clifford algebra with one generator to construct the $Z_3$-graded generalization of the simpl...

  15. Cladribine Analogues via O6-(Benzotriazolyl Derivatives of Guanine Nucleosides

    Directory of Open Access Journals (Sweden)

    Sakilam Satishkumar

    2015-10-01

    Full Text Available Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxytris(dimethylaminophosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL, T-cell lymphoma (TCL and chronic lymphocytic leukemia (CLL, cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active.

  16. Application of natural analogues in the Yucca Mountain project - overview

    International Nuclear Information System (INIS)

    The Natural Analogue Synthesis Report (NASR) [1] provides a compilation of information from analogues that test, corroborate, and add confidence to process models and model predictions pertinent to total system performance assessment (TSPA). The report updated previous work [2] with new literature examples and results of quantitative studies conducted by the Yucca Mountain Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate greater understanding of processes expected to occur during postclosure of a proposed Yucca Mountain repository. Natural analogues, as used here, refer to either natural or anthropogenic systems in which processes similar to those expected to occur in a nuclear waste repository are thought to have occurred over long time periods (decades to millenia) and large spatial scales (up to tens of kilometers). In the past, the YMP has used analogues for testing and building confidence in conceptual and numerical process models in a number of ways. Yucca Mountain mineral alteration phases provided a self-analogue for postclosure alteration [3]. Thermodynamic parameters for silica minerals of the Wairakai, New Zealand geothermal field were added to databases used in geochemical modeling [4]. Scoping calculations of radionuclide transport using the Yucca Mountain TSPA numerical model were conducted for the Peqa Blanca site [5]. Eruption parameters from the Cerro Negro volcano, Nicaragua, were used to verify codes that model ash plume dispersion [6]. Analogues have also been used in supplemental science and performance analyses to provide multiple lines of evidence in support of both analyses and model reports (AMRs) [7]; in screening arguments for inclusion or exclusion of features, events, and processes (FEP)s in TSPAs; in the quantification of uncertainties [7]; in expert elicitations of volcanic and seismic hazards [8, 9] and in peer reviews [10]. Natural analogues may be applied

  17. Analogue gravitational phenomena in Bose-Einstein condensates

    Science.gov (United States)

    Finazzi, Stefano

    2012-08-01

    Analogue gravity is based on the simple observation that perturbations propagating in several physical systems can be described by a quantum field theory in a curved spacetime. While phenomena like Hawking radiation are hardly detectable in astrophysical black holes, these effects may be experimentally tested in analogue systems. In this Thesis, focusing on Bose-Einstein condensates, we present our recent results about analogue models of gravity from three main perspectives: as laboratory tests of quantum field theory in curved spacetime, for the techniques that they provide to address various issues in general relativity, and as toy models of quantum gravity. The robustness of Hawking-like particle creation is investigated in flows with a single black hole horizon. Furthermore, we find that condensates with two (white and black) horizons develop a dynamical instability known in general relativity as black hole laser effect. Using techniques borrowed from analogue gravity, we also show that warp drives, which are general relativistic spacetimes allowing faster-than-light travel, are unstable. Finally, the cosmological constant issue is investigated from an analogue gravity perspective and relativistic Bose-Einstein condensates are proposed as new analogue systems with novel interesting properties.

  18. Isolation and characterization of propoxyphenyl linked sildenafil and thiosildenafil analogues in health supplements.

    Science.gov (United States)

    Kee, Chee-Leong; Ge, Xiaowei; Koh, Hwee-Ling; Low, Min-Yong

    2012-11-01

    Two new phosphodiesterase-5 inhibitors (PDE-5) which consist of one sildenafil analogue and one thiosildenafil analogue have been found in heath supplements. The structural properties of these analogues have been elucidated by NMR, high resolution MS, MS(2), UV and IR spectroscopy. The sildenafil analogue is very similar to aildenafil and the thiosildenafil analogue is similar to thioaildenafil, except the ethoxy group bonded to phenyl ring is replaced by a propoxy group. Hence, the sildenafil analogue is named as propoxyphenyl aildenafil or propoxyphenyl methisosildenafil and the thiosildenafil analogue as propoxyphenyl thioaildenafil or propoxyphenyl thiomethisosildenafil. PMID:22840979

  19. Noise-induced linearisation

    OpenAIRE

    Dykman, Mark; Luchinsky, D. G.; Mannella, R.; McClintock, Peter V. E.; Short, H. E.; Stein, N. D.; Stocks, N. G.

    1994-01-01

    It is found that the response of a nonlinear dynamical system can be linearised, and its frequency dispersion diminished, by the addition of external noise of sufficient intensity. Taking as an example an overdamped bistable system driven by a low-frequency periodic field, this noise-induced linearisation is investigated through analogue electronic experiments. The wider implications are considered.

  20. The Greenland Analogue Project, Yearly Report 2009

    International Nuclear Information System (INIS)

    To advance the understanding of processes associated with glaciation and their impact on the long-term performance of a deep geological repository, the Greenland Analogue Project (GAP), a four-year field and modelling study of the Greenland ice sheet and sub-surface conditions, has been initiated collaboratively by SKB, Posiva and NWMO. The study site encompasses a land terminus portion of the Greenland ice sheet east of Kangerlussuaq and is in many ways considered to be an appropriate analogue of the conditions that are expected to prevail in much of Canada and Fennoscandia during future glacial cycles. The project is planned to run from 2009 until 2012. The GAP will conduct the first in situ investigations of some of the parameters and processes needed to achieve a realistic understanding of how an ice sheet may impact a deep repository, and will provide measurements, observations and data that may significantly improve our safety assessments and risk analyses of glaciation scenarios. The project includes three sub-projects (A-C) with specific individual objectives, which collectively aim at contributing knowledge and input to the overall project aim. Three field campaigns were carried out in SPA during 2009. These campaigns focused on: (1) deployment and maintenance of AWS and GPS stations and to test the deep-look radar equipment; (2) investigating the hydrological processes and feedbacks and testing of passive seismic equipment; (3) downloading of weather station data and GPS data and winterizing the equipment. An extensive archive of real-time satellite remote sensing datasets has been obtained to be able to better constraint the surface elevation and dynamics of basal hydrological mechanisms. From this archive it has been possible to obtain Russell Glacier Cachment (RGC)-wide constraints on annual, seasonal and specific temporal snapshots of surface speed, initial lake and moulin distribution, drainage and network connections along with the temporal

  1. Hydrophobic surfactant proteins and their analogues.

    Science.gov (United States)

    Walther, Frans J; Waring, Alan J; Sherman, Mark A; Zasadzinski, Joseph A; Gordon, Larry M

    2007-01-01

    Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments. PMID:17575474

  2. Habitability & Astrobiology Research in Mars Terrestrial Analogues

    Science.gov (United States)

    Foing, Bernard

    2014-05-01

    We performed a series of field research campaigns (ILEWG EuroMoonMars) in the extreme Utah desert relevant to Mars environments, and in order to help in the interpretation of Mars missions measurements from orbit (MEX, MRO) or from the surface (MER, MSL), or Moon geochemistry (SMART-1, LRO). We shall give an update on the sample analysis in the context of habitability and astrobiology. Methods & Results: In the frame of ILEWG EuroMoonMars campaigns (2009 to 2013) we deployed at Mars Desert Research station, near Hanksville Utah, a suite of instruments and techniques [A, 1, 2, 9-11] including sample collection, context imaging from remote to local and microscale, drilling, spectrometers and life sensors. We analyzed how geological and geochemical evolution affected local parameters (mineralogy, organics content, environment variations) and the habitability and signature of organics and biota. Among the important findings are the diversity in the composition of soil samples even when collected in close proximity, the low abundances of detectable PAHs and amino acids and the presence of biota of all three domains of life with significant heterogeneity. An extraordinary variety of putative extremophiles was observed [3,4,9]. A dominant factor seems to be soil porosity and lower clay-sized particle content [6-8]. A protocol was developed for sterile sampling, contamination issues, and the diagnostics of biodiversity via PCR and DGGE analysis in soils and rocks samples [10, 11]. We compare the 2009 campaign results [1-9] to new measurements from 2010-2013 campaigns [10-12] relevant to: comparison between remote sensing and in-situ measurements; the study of minerals; the detection of organics and signs of life. Keywords: field analogue research, astrobiology, habitability, life detection, Earth-Moon-Mars, organics References [A] Foing, Stoker & Ehrenfreund (Editors, 2011) "Astrobiology field Research in Moon/Mars Analogue Environments", Special Issue of International

  3. Prophylactic Efficacy of Amifostine, DRDE-07, and their Analogues against Percutaneously Administered Nitrogen Mustards and Sulphur Mustard

    OpenAIRE

    Manoj Sharma; Vijayaraghavan, R.; Uma Pathak; K. Ganesan

    2009-01-01

    Nitrogen mustards (HN-1, HN-2 and HN-3) and sulphur mustard are alkylating and blister-inducing chemical warfare agents. This study was aimed at investigating the prophylactic efficacy of amifostine, DRDE-07, and their analogues and some recommended antidotes against dermally-applied nitrogen mustards and sulphur mustard in preventing their systemic toxicity in mice. The antidotes were administered as single oral dose, 30 min prior to the mustard agent application. For DRDE-07, 0.2 LD50 (249 ...

  4. Nonspecific blockade of vascular free radical signals by methylated arginine analogues

    Directory of Open Access Journals (Sweden)

    Pedro M.A.

    1998-01-01

    Full Text Available Methylated arginine analogues are often used as probes of the effect of nitric oxide; however, their specificity is unclear and seems to be frequently overestimated. This study analyzed the effects of NG-methyl-L-arginine (L-NMMA on the endothelium-dependent release of vascular superoxide radicals triggered by increased flow. Plasma ascorbyl radical signals measured by direct electron paramagnetic resonance spectroscopy in 25 rabbits increased by 3.8 ± 0.7 nmol/l vs baseline (28.7 ± 1.4 nmol/l, P<0.001 in response to papaverine-induced flow increases of 121 ± 12%. In contrast, after similar papaverine-induced flow increases simultaneously with L-NMMA infusions, ascorbyl levels were not significantly changed compared to baseline. Similar results were obtained in isolated rabbit aortas perfused ex vivo with the spin trap a-phenyl-N-tert-butylnitrone (N = 22. However, in both preparations, this complete blockade was not reversed by co-infusion of excess L-arginine and was also obtained by N-methyl-D-arginine, thus indicating that it is not related to nitric oxide synthase. L-arginine alone was ineffective, as previously demonstrated for NG-methyl-L-arginine ester (L-NAME. In vitro, neither L-arginine nor its analogues scavenged superoxide radicals. This nonspecific activity of methylated arginine analogues underscores the need for careful controls in order to assess nitric oxide effects, particularly those related to interactions with active oxygen species.

  5. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin. PMID:26872656

  6. Phosphonate analogues of carboxypeptidase A substrates are potent transition-state analogue inhibitors.

    Science.gov (United States)

    Hanson, J E; Kaplan, A P; Bartlett, P A

    1989-07-25

    Analogues of tri- and tetrapeptide substrates of carboxypeptidase A in which the scissile peptide linkage is replaced with a phosphonate moiety (-PO2--O-) were synthesized and evaluated as inhibitors of the enzyme. The inhibitors terminated with either L-lactate or L-phenyllactate [designated (O) Ala and (O) Phe, respectively] in the P1' position. Transition-state analogy was shown for a series of 14 tri- and tetrapeptide derivatives containing the structure RCO-AlaP-(O)Ala [RCO-AP(O)A, AP indicates the phosphonic acid analogue of alanine] by the correlation of the Ki values for the inhibitors and the Km/kcat values for the corresponding amide substrates. This correlation supports a transition state for the enzymatic reaction that resembles the tetrahedral intermediate formed upon addition of water to the scissile carbonyl group. The inhibitors containing (O) Phe at the P1' position proved to be the most potent reversible inhibitors of carboxypeptidase A reported to date: the dissociation constants of ZAFP(O)F, ZAAP(O)F, and ZFAP(O)F are 4, 3, and 1 pM, respectively. Because of the high affinity of these inhibitors, their dissociation constants could not be determined by steady-state methods. Instead, the course of the association and dissociation processes was monitored for each inhibitor as its equilibrium with the enzyme was established in both the forward and reverse directions. A phosphonamidate analogue, ZAAPF, in which the peptide linkage is replaced with a -PO2-NH- moiety, was prepared and shown to hydrolyze rapidly at neutral pH (t1/2 = 20 min at pH 7.5). This inhibitor is bound an order of magnitude less tightly than the corresponding phosphonate, ZAAP(O)F, a result that contrasts with the 840-fold higher affinity of phosphonamidates for thermolysin [Bartlett, P. A., & Marlowe, C. K. (1987) Science 235, 569-571], a zinc peptidase with a similar arrangement of active-site catalytic residues. PMID:2790000

  7. Synthesis of hyaluronic-acid-related oligosaccharides and analogues, as their 4-methoxyphenyl glycosides, having N-acetyl-β-D-glucosamine at the reducing end

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Halkes, K.M.; Slaghek, T.M.; Hyppönen, T.K.; Kruiskamp, P.H.; Ogawa, T.; Kamerling, J.P.

    1998-01-01

    To contribute to the possibilities to study the ability of oligosaccharide fragments of hyaluronic acid to induce angiogenesis, several hyaluronic-acid-related oligosaccharides and their 6-O-sulfated analogues were synthesised as their 4-methoxyphenyl glycosides having 2-acetamido-2-deoxy-D-glucopyr

  8. Terrestrial research in Mars analogue environments

    Science.gov (United States)

    Osipov, G.

    Fatty acids (FA) content was measured by GC-MS SIM technique in Sulfide ores of present day (Mid-Atlantic Ridge and others) and ancient (Ural Paleocene, Russia) black smokers; Early Proterozoic kerites of Volyn; Siberian, Canadian and Antarctic permafrosts and also in rocks of East-European platform Achaean crystalline basement. Analysis was shown presence those and only those fatty acids which are specific to microorganisms. FA with 12 up 19 of carbon atoms are thought to be a bacterial biomass sign. 3-Hydroxy fatty acids also found in samples and are strong specific markers of gram-negative bacteria. Cultivation yield living bacteria in some cases. The East-European platform Achaean crystalline basement rocks opened by Vorotilov Deep Well (VDW) drilled through Puchezh-Katunski impact structure were studied within depths 2575 - 2805 m. 34 microbial lipid markers were detected by GC-MS and 22 species were identified. Bacteria of g. Bacillus reached 6,8 % in subsurface communities. However, members of gg. Clostridium (37,1 - 33,2 %) and Rhodococcus (27,6 - 33,7 %) were absolute dominants within studied depth interval. Some lipid patterns of kerite samples could be assessed to definite genera or, in special cases, to species of contemporary microorganisms. For instance, 2-hydroxylauric acid is specific to Pseudomonas putida group or Acinetobacter spp., and hydroxymyristic together with hydroxypalmitic are specific to P.cepacea and cyanobacteria. 3-hydroxystearic acid was known as component of Acetobacter diazothrophycus and Gloebacter violaceous cyanobacterium. 10-hydroxystearic acid associated with Nocardia spp., which oxidizes oleic acid in organic substrates. 10-methylhexadecanoic (10Me16) acid together with 10Me14, 10Me15 and 10Me17 analogues are markers of actinomycetes. Significant part of Black Smokers organic matter is probably biogenic. Fatty acid features strongly assigns it to bacterial, microeucariotic and planta cells. Par example 3-hydroxy acids are

  9. Alligator Rivers Analogue project. Geochemistry of 239Pu, 129I, 99Tc and 36Cl

    International Nuclear Information System (INIS)

    One objective of this research programme has been to evaluate the applicability of uranium orebodies as natural analogues for testing radionuclide release-rate models used in performance assessment activities. The investigated nuclides included three of the most persistent radioactive constituents of high-level wastes from nuclear fission power reactors: plutonium-239, iodine-129, and technetium-99. The feasibility of uranium minerals as analogues for the behavior of these nuclear reaction products (NRP) in spent fuel relies upon a capability to characterise NRP concentrations in the source minerals. Measured abundances of natural 239Pu, 99Tc and 129I in uranium ores are compared to calculated abundances in order to evaluate the degree to retention of these radionuclides by the ore. This modelling study also shows the extent to which various NRP are correlated, such that one provides a constraint on the production rates of others. Under most conditions, 36Cl, another long-lived neutron-capture product found in uranium ores, is shown to be an ideal in-situ monitor of the 235U fission rate, which is the dominant source term for 129I and possibly a significant one for 99Tc. Similarly, 239Pu/U ratios can be used to establish limits on the 238U neutron-induced fission rate; the ratios measured in this study suggest that 238U induced fission comprises 129I and 99Tc. 79 refs., 21 tabs., 18 figs

  10. (+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only.

    Science.gov (United States)

    Fride, Ester; Feigin, Cfir; Ponde, Datta E; Breuer, Aviva; Hanus, Lumír; Arshavsky, Nina; Mechoulam, Raphael

    2004-12-15

    Delta9-Tetrahydrocannabinol (Delta9-THC) and (-)-cannabidiol are major constituents of the Cannabis sativa plant with different pharmacological profiles: (-)-Delta9-tetrahydrocannabinol, but not (-)-cannabidiol, activates cannabinoid CB1 and CB2 receptors and induces psychoactive and peripheral effects. We have tested a series of (+)-cannabidiol derivatives, namely, (+)-cannabidiol-DMH (DMH-1,1-dimethylheptyl-), (+)-7-OH-cannabidiol-DMH, (+)-7-OH- cannabidiol, (+)-7-COOH- cannabidiol and (+)-7-COOH-cannabidiol-DMH, for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice. Although all (+)-cannabidiols bind to cannabinoid CB1 and CB2 receptors, only (+)-7-OH-cannabidiol-DMH was centrally active, while all (+)-cannabidiol analogues completely arrested defecation. The effects of (+)-cannabidiol-DMH and (+)-7-OH-cannabidiol-DMH were partially antagonized by the cannabinoid CB1 receptor antagonist N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716), but not by the cannabinoid CB2 receptor antagonist N-[-(1S)-endo-1,3,3-trimethil bicyclo [2.2.1] heptan-2-yl-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), and had no effect on CB1(-/-) receptor knockout mice. (+)-Cannabidiol-DMH inhibited the peripheral pain response and arachidonic-acid-induced inflammation of the ear. We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions. PMID:15588739

  11. Review of insulin and its analogues in diabetes mellitus.

    Science.gov (United States)

    Mane, Krishnappa; Chaluvaraju, Kc; Niranjan, Ms; Zaranappa, Tr; Manjuthej, Tr

    2012-03-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin's, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  12. On the robustness of entanglement in analogue gravity systems

    International Nuclear Information System (INIS)

    We investigate the possibility of generating quantum-correlated quasi-particles utilizing analogue gravity systems. The quantumness of these correlations is a key aspect of analogue gravity effects and their presence allows for a clear separation between classical and quantum analogue gravity effects. However, experiments in analogue systems, such as Bose–Einstein condensates (BECs) and shallow water waves, are always conducted at non-ideal conditions, in particular, one is dealing with dispersive media at non-zero temperatures. We analyse the influence of the initial temperature on the entanglement generation in analogue gravity phenomena. We lay out all the necessary steps to calculate the entanglement generated between quasi-particle modes and we analytically derive an upper bound on the maximal temperature at which given modes can still be entangled. We further investigate a mechanism to enhance the quantum correlations. As a particular example, we analyse the robustness of the entanglement creation against thermal noise in a sudden quench of an ideally homogeneous BEC, taking into account the super-sonic dispersion relations. (paper)

  13. Introduction of an electron push-pull system yields a planar Red Kaede fluorescence protein chromophore analogue stabilized by a C = O… interaction

    Indian Academy of Sciences (India)

    Ashish Singh; Basanta Kumar Rajbongshi; Gurunath Ramanathan

    2015-05-01

    Crystal structures of four red kaede fluorescence protein chromophore analogues are reported here. Molecules I-III adopt a non-planar geometry stabilized by … stacking and hydrogen bonding. Introduction of an electron push-pull system induces molecule IV to be planar and a C = O… supramolecular interaction is observed as well. Strong electron withdrawing and donating groups also ensure formation of a higher order two and three dimensional supramolecular architecture through hydrogen bonds in molecules I and IV. All the analogues exhibit good photoluminescence properties and emit in the red region with excellent quantum yields.

  14. Selective cytotoxicity against human osteosarcoma cells by a novel synthetic C-1 analogue of 7-deoxypancratistatin is potentiated by curcumin.

    Directory of Open Access Journals (Sweden)

    Dennis Ma

    Full Text Available The natural compound pancratistatin (PST is a non-genotoxic inducer of apoptosis in a variety of cancers. It exhibits cancer selectivity as non-cancerous cells are markedly less sensitive to PST. Nonetheless, PST is not readily synthesized and is present in very low quantities in its natural source to be applied clinically. We have previously synthesized and evaluated several synthetic analogues of 7-deoxypancratistatin, and found that JC-TH-acetate-4 (JCTH-4, a C-1 acetoxymethyl analogue, possessed similar apoptosis inducing activity compared to PST. In this study, notoriously chemoresistant osteosarcoma (OS cells (Saos-2, U-2 OS were substantially susceptible to JCTH-4-induced apoptosis through mitochondrial targeting; JCTH-4 induced collapse of mitochondrial membrane potential (MMP, increased reactive oxygen species (ROS production in isolated mitochondria, and caused release of apoptosis inducing factor (AIF and endonuclease G (EndoG from isolated mitochondria. Furthermore, JCTH-4 selectively induced autophagy in OS cells. Additionally, we investigated the combinatory effect of JCTH-4 with the natural compound curcumin (CC, a compound found in turmeric spice, previously shown to possess antiproliferative properties. CC alone had no observable effect on Saos-2 and U-2 OS cells. However, when present with JCTH-4, CC was able to enhance the cytotoxicity of JCTH-4 selectively in OS cells. Such cytotoxicity by JCTH-4 alone and in combination with CC was not observed in normal human osteoblasts (HOb and normal human fetal fibroblasts (NFF. Therefore, this report illustrates a new window in combination therapy, utilizing a novel synthetic analogue of PST with the natural compound CC, for the treatment of OS.

  15. Gold Nanoparticles Decorated with Mannose-6-phosphate Analogues

    Directory of Open Access Journals (Sweden)

    Stéphanie Combemale

    2014-01-01

    Full Text Available Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b introduction of spacers on the mannose-6-phosphate analogues via Huisgen’s cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity.

  16. Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

    Science.gov (United States)

    López-Suárez, Laura; Riesgo, Lorena; Bravo, Fernando; Ransom, Tanya T; Beutler, John A; Echavarren, Antonio M

    2016-05-01

    We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC). PMID:27005578

  17. Controlled analogue experiments on propagation of seismic electromagnetic signals

    Institute of Scientific and Technical Information of China (English)

    HUANG Qinghua

    2005-01-01

    This study presented a method of laboratory analogue experiments based on a geographical scaling model and a waveguide model to investigate the characteristics of the propagation of seismic electromagnetic signals in the crust and the atmosphere. Some controlled experiments were done to evaluate the possible influence on the experimental results from the background electromagnetic field, geographical conditions, boundary effects, the source of electromagnetic signals (position, magnitude, and frequency), and media conductivity. The reliability and the extensibility of the above analogue experimental method were also investigated. This study indicated that such kind of analogue experimental method provided an intuitionistic way of studying the propagation of seismic electromagnetic signals, which is one of the most difficult research topics in seismo-electro- magnetism.

  18. Synthesis and cytotoxic activity of novel curcumin analogues

    Institute of Scientific and Technical Information of China (English)

    Qin Zhang; Yao Fu; Hao Wei Wang; Tao Gong; Yong Qin; Zhi Rong Zhang

    2008-01-01

    Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues (1A-1C, 1E) with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.

  19. Radiation Tests of the VELO ECS and Analogue Repeater Mezzanines

    CERN Document Server

    Eklund, L; Van der Gracht, A; Vollhardt, A

    2006-01-01

    The VELO front-end control system and analogue link is based on commercial components where the radiation tolerance is assured by a radiation qualification procedure. This note reports on the radiation qualification of the components required for the VELO ECS mezzanine and analogue repeater mezzanines. They are located at the VELO vacuum vessel where the expected maximal dose is 73 kRad during 10 years of operation. The qualification was done by irradiating prototype circuits at the Paul Scherrer Institut in Villigen, Switzerland. The ECS mezzanine prototypes were irradiated to a dose of 780 kRad and the analogue driver test channels were irradiated to a dose of 600 kRad. All devices were fully functional after the irradiation and only a small increase in current consumption was observed.

  20. Ensemble meteorological reconstruction using circulation analogues of 1781–1785

    Directory of Open Access Journals (Sweden)

    P. Yiou

    2013-09-01

    Full Text Available This paper uses a method of atmospheric flow analogues to reconstruct an ensemble of atmospheric variables (namely sea-level pressure, surface temperature and wind speed between 1781 and 1785. The properties of this ensemble are investigated and tested against observations of temperature. The goal of the paper is to assess whether the atmospheric circulation during the Laki volcanic eruption (in 1783 and the subsequent winter were similar to the conditions that prevailed in the winter 2009/2010 and during spring 2010. We find that the three months following the Laki eruption in June 1783 barely have analogues in 2010. The cold winter of 1783/1784 yields circulation analogues in 2009/2010. Our analysis suggests that it is unlikely that the Laki eruption was responsible for the cold winter of 1783/1784, of the relatively short memory of the atmospheric circulation.

  1. Gas Chromatographic Retention Indices of 2-chlorobenzylidenemalononitrile and its Analogues

    Directory of Open Access Journals (Sweden)

    P. K. Gutch

    2012-09-01

    Full Text Available Normal 0 false false false EN-GB X-NONE X-NONE Riot control agent, 2-chlorobenzylidenemalononitrile (CS and its analogues have both skin irritating and lacrymating properties. Herein, we report retention indices (RI of CS and its thirteen analogues relative to the homologues n-alkanes series. These values are determined on nonpolar BP-1 and polar BP-10 capillary column under programmed temperature and isothermal chromatographic condition. The analogues differ in substitution at ortho or para position of phenyl ring and retention indices are found to vary according to the nature of the substituent.Defence Science Journal, 2012, 62(5, pp.319-323, DOI:http://dx.doi.org/10.14429/dsj.62.1167

  2. Co–Fe Prussian Blue Analogue Intercalated into Diamagnetic Mg–Al Layered Double Hydroxides

    Directory of Open Access Journals (Sweden)

    Cuijuan Zhang

    2016-04-01

    Full Text Available A heterostructure of diamagnetic magnesium‒aluminium layered double hydroxides (Mg‒Al LDHs and photomag‐ netic cobalt‒iron Prussian Blue analogue (Co‒Fe PBA was designed, synthesized and then designated as LDH‒PB. The cyanide-bridged Co‒Fe PBA was two-dimensionally intercalated into the Mg‒Al LDH template by the stepwise anion exchange method. LDH‒PB showed ferrimagnetic properties with in-plane antiferromagnetic exchange interactions, as well as small photo-induced magnetization by visible light illumination due to the low dimensional structures and the characteristic photo-induced electronic states of the mixed valence of FeIII(low spin, S = 1/2‒CN‒ CoII(high spin, S = 3/2‒NC‒FeII (low spin, S = 0.

  3. A synthetic analogue of melittin aggregates in large oligomers.

    OpenAIRE

    John, E.; Jähnig, F

    1992-01-01

    An analogue of melittin synthesized in the group of E. T. Kaiser (DeGrado, W. F., F. J. Keźdy, and E. T. Kaiser. 1981. J. Am. Chem. Soc. 103:679-681) was investigated by Raman spectroscopy and fluorescence anisotropy decay. In water, the analogue is completely alpha-helical and aggregates in large oligomers of about 50 monomers. In vesicle membranes, it undergoes orientational fluctuations similar to melittin. The most significant difference from melittin, therefore, is the formation of strai...

  4. Concise synthesis of new bridged-nicotine analogues

    DEFF Research Database (Denmark)

    Crestey, François; Hooyberghs, Geert; Kristensen, Jesper Langgaard

    2012-01-01

    This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively.......This study describes a very efficient strategy for the synthesis of two new bridged-nicotine analogues. Starting from either 4- or 3-chloropyridine the desired tricyclic ring systems are accessed in just three steps in 23% and 40% overall yield, respectively....

  5. Natural analogues, paradigm for manmade repositories for radioactive wastes

    International Nuclear Information System (INIS)

    Natural analogues are given by nature. They show the results of natural processes which have lasted thousands or millions of years. They provide an excellent example of what could happen in an underground site, offering in the same time the opportunity to test by observation and measurement, many of the geochemical processes that are expected to influence in a realistic and appropriate way, the predicted reliability of the radioactive waste repository over long periods of geological time. The natural analogue studies attempt to understand the multiprocessing complexity of the natural system, which contrasts with the limitations of the laboratory experiments and bring arguments to overcome the difficult time scale issue. By this the natural analogues are a useful paradigm for manmade repository for radioactive wastes. The paper discusses the implicit link in the public mind between natural analogues and manmade waste repository with an accent of the positive impact on public acceptance. It is also discussed the decisive qualities of the natural analogues concerning providing valid long term data and increasing the confidence of the public for manmade repositories. The debate is conducting in terms of sustainable development, having at base high-level principles in order to protect humans and their environment, both now and in the future, from potential hazards arising from such wastes. Safe radwaste management involves the application of technology and resources in a regulated manner so that the public, workers and the environment are protected in accordance with the accepted national and international standards. There are at least seven high-level principles which are mentioned in the paper. It is presented the general concept of the deep geological repository, very important for an acceptable solution for the management of nuclear waste, what is a prerequisite for a renewal of nuclear power. Further are introduced natural and archaeological (manufactured) analogue

  6. Synthesis of Conformationally Locked Versions of Puromycin Analogues

    Science.gov (United States)

    Saneyoshi, Hisao; Michel, Benoît Y.; Choi, Yongseok; Strazewski, Peter; Marquez, Victor E.

    2009-01-01

    Conformationally locked North and South versions of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the Staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3′-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3′-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time. PMID:18991379

  7. Naturally occurring crystalline phases: analogues for radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Haaker, R.F.; Ewing, R.C.

    1981-01-01

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included.

  8. Naturally occurring crystalline phases: analogues for radioactive waste forms

    International Nuclear Information System (INIS)

    Naturally occurring mineral analogues to crystalline phases that are constituents of crystalline radioactive waste forms provide a basis for comparison by which the long-term stability of these phases may be estimated. The crystal structures and the crystal chemistry of the following natural analogues are presented: baddeleyite, hematite, nepheline; pollucite, scheelite;sodalite, spinel, apatite, monazite, uraninite, hollandite-priderite, perovskite, and zirconolite. For each phase in geochemistry, occurrence, alteration and radiation effects are described. A selected bibliography for each phase is included

  9. Concise synthesis of ether analogues of lysobisphosphatidic acid.

    Science.gov (United States)

    Jiang, Guowei; Xu, Yong; Falguières, Thomas; Gruenberg, Jean; Prestwich, Glenn D

    2005-09-01

    We describe a versatile, efficient method for the preparation of ether analogues of (S,S)-lysobisphosphatidic acid (LBPA) and its enantiomer from (S)-solketal. Phosphorylation of a protected sn-2-O-octadecenyl glyceryl ether with 2-cyanoethyl bis-N,N-diisopropylamino phosphine and subsequent deprotection generated the bisether LBPA analogues. By simply changing the sequence of deprotection steps, we obtained the (R,R)- and (S,S)-enantiomers of 2,2'-bisether LBPA. An ELISA assay with anti-LBPA monoclonal antibodies showed that the bisether LBPAs were recognized with the same affinity as the natural 2,2'-bisoleolyl LBPA. [reaction: see text] PMID:16119911

  10. Design of a saturated analogue and digital current transducer

    International Nuclear Information System (INIS)

    This project describes the development of a new analogue and digital current transducer, providing a range of new theoretical design methods for these novel devices. The main control feature is the limit cycling operation, and the novel use of the embedded sigma-delta modulator sensor structure to derive a low component count digital sensor. The research programme was initiated into the design, development and evaluation of a novel non-Hall sensing analogue and digital current transducer. These transducers are used for measurement of high currents in power systems applications. The investigation is concerned with a new design which uses a magnetic ferrite core without an air gap for current measurement. The motivation for this work was to design a new control circuit which provides a low component count, and utilises the non-linear properties of the magnetic ferrite core to transmit direct current. The use of a limit cycle control circuit was believed to be particularly suitable for the analogue and digital transducers, for two main reasons: the low component count, and the output signal is directly digital. In line with the motivations outlined above, the outcome of the research has witnessed the design, development and evaluation of a practically realisable analogue and digital current transducer. The design procedure, which is documented in this thesis, is considered to be a major contribution to the field of transducers design and development using a control systems approach. Mathematical models for both analogue and digital transducers were developed and the resulting model based predictions were found to be in good agreement with measured results. Simplification of the new model sensing device was achieved by approximating the non-linear ferrite core using FFT analysis. This is also considered to be a significant contribution. The development analogue and digital current censors employed a sampled data control systems design and utilised limit cycling

  11. effect of luteinizing hormone-releasing hormone analogue on the sexual behavior of sacalia quadriocellata

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    luteinizing hormone-releasing hormone (lhrh) is known to influence sexual behavior in many vertebrate taxa,but there have been no systematic studies on the role of lhrh in sexual behavior of turtles.we tested the hypotheses that exogenous lhrh analogues would induce sexual behavior of male four-eyed turtle,sacalia quadriocellata.we examined this by challenging males with intramuscular injections of mammalian luteinizing hormone-releasing hormone analogue (lhrh-a),human chorionic gonadotropin (hcg),or a combination of the two,and subsequently exposing them to sexually receptive females for behavioral observation.our data show that the injection of only hcg could not,while that of only lhrh-a could,facilitate sexual behavior along with testicular recrudescence and spermatogenesis in s.quadriocellata.the injection of both lhrh-a and hcg would induce more drastic sexual behavior of the animals than that of lhrh-a alone,indicating hcg enhances the effects of lhrh-a induced sexual behavior.however,different pharmacological dosages of lhrh-a (0.5 μg,1 μg,2 μg per 100 g bodyweight) did not correspond to different activity levels.though the mechanism of lhrh effect was not determined,this study may support that the sexual behavior ofs.quadriocellata which occurs at the beginning of the injection despite regression of the gonads.this is the first report on the exogenous lhrh-a induced sexual behavior for this species.

  12. Ovarian ablation in the adjuvant treatment of breast cancer: GnRH-analogues, ovarectomy or radiocastration - 'The philosopher's stone' instead of 'Chamber of secrets'?

    International Nuclear Information System (INIS)

    Background: Ovarian suppression in the adjuvant treatment of perimenopausal women with breast cancer is an important option. The therapeutic goal can be accomplished by administration of GnRH-analogues, ovarectomy or radiocastration. Patients and methods: We describe the advantages and the therapy related side effects and compare the different treatment modalities with each other. Results: Because of its reversibility and patients' compliance GnRH-analogues seem to be advantageous especially in younger premenopausal women. When longer term side effects of artificially induced menopause are less important, therapeutic alternatives such as radiocastration or ovarectomy are effective without obvious superiority between these options. Conclusion: Even in the background of the increasing use of GnRH-analogues radiocastration remains still a therapeutic alternative because of its cost-effectiveness and feasibility. This accounts especially for peri- or premenopausal women above the age of 45. (orig.)

  13. Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco A, H.; Cardona, W. [Universidad Andres Bello, Vina del Mar (Chile). Dept. de Ciencias Quimicas]. E-mail: hcarrasco@unab.cl; Espinoza C, L.; Gallardo, C.; Catalan M, K. [Universidad Tecnica Federico Santa Maria, Valparaiso (Chile). Dept. de Quimica; Cardile, V.; Lombardo, L. [University of Catania (Italy). Dept. of Physiological Sciences; Cuellar F, M. [Universidad de Valparaiso (Chile). Facultad de Farmacia; Russo, A. [University of Catania (Italy). Dept. of Biological Chemistry, Medical Chemistry and Molecular Biology

    2008-07-01

    Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl- 2-methoxy-5-nitrophenyl acetate (5) were significantly (p < 0,001) more active than eugenol, with IC{sub 50} values in DU-145 cells of 19.02 x 10{sup -6} and 21.5 x 10{sup -6} mol L{sup -1}, respectively, and in KB cells of 18.11 x 10{sup -6} and 21.26 x 10{sup -6} mol L{sup -1}, respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues. (author)

  14. Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

    International Nuclear Information System (INIS)

    Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl- 2-methoxy-5-nitrophenyl acetate (5) were significantly (p 50 values in DU-145 cells of 19.02 x 10-6 and 21.5 x 10-6 mol L-1, respectively, and in KB cells of 18.11 x 10-6 and 21.26 x 10-6 mol L-1, respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues. (author)

  15. Proteome analysis demonstrates profound alterations in human dendritic cell nature by TX527, an analogue of vitamin D

    DEFF Research Database (Denmark)

    Ferreira, G. B.; van Etten, E.; Lage, K.; Hansen, Daniel Aaen; Moreau, Yves; Workman, Christopher; Waer, M.; Verstuyf, A.; Waelkens, E.; Overbergh, L.; Mathieu, C.

    2009-01-01

    Structural analogues of vitamin D have been put forward as therapeutic agents able to exploit the immunomodulatory effects of vitamin D, without its undesired calcemic side effects. We have demonstrated that TX527 affects dendritic cell (DC) maturation in vitro, resulting in the generation of a...... tolerogenic cell. In the present study, we aimed to explore the global protein changes induced by the analogue in immature DC (iDC) and mature human DC and to correlate them with alterations in DC morphology and function. Human CD14(+) monocytes were differentiated toward iDC or mature DCs, in the presence or...... absence of TX527 (10(-8) M) (n = 4). Protein samples were separated into two different pH ranges (pH4-7 and 6-9), analyzed by 2-D DIGE and differentially expressed spots (p...

  16. Analogue fuel manipulator crane and intellectual controller for low temperature nuclear heating reactor

    International Nuclear Information System (INIS)

    The prime structure of analogue fuel manipulator crane is described. It mainly discusses the structure of intellectual controller, operating principle, driving circuits of executive parts and control process of the analogue fuel manipulator crane

  17. Analogue Electrical Circuit for Simulation of the Duffing-Holmes Equation

    DEFF Research Database (Denmark)

    Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.; Bumeliene, S.; Lindberg, Erik

    2008-01-01

    An extremely simple second order analogue electrical circuit for simulating the two-well Duffing-Holmes mathematical oscillator is described. Numerical results and analogue electrical simulations are illustrated with the snapshots of chaotic waveforms, phase portraits (Lissajous figures) and...

  18. Relative thermal diffusivities of perovskite and post-perovskite analogues

    Science.gov (United States)

    Hunt, S. A.; McCormack, R.; Walker, A.; Dobson, D. P.; Li, L.

    2010-12-01

    Using our new X-radiography based variation of the Ångstrom method we have measured the thermal diffusivity of both the perovskite and post-perovskite structure of CaIrO3 at high pressure. The Ångstrom method for measuring thermal diffusivity at high pressure uses a stationary thermal wave which is induced into the sample by sinusoidally varying the power applied to the cylindrical furnace, surrounding the sample. The thermal diffusivity (κ ) is determined from the phase lag, Φ 0 - Φ R, and amplitude difference, θ 0 / θ R, of the thermal wave between points at the axis of the sample and radius, R (e.g. Khedari et al., 1995). Our method differs from previous multi-anvil implementations of the Ångstrom method in that instead of using thermocouples to monitor the temperature variation we use thin strips of metal foil, which are placed at discrete intervals along the sample length and imaged X-radiographically. The metal strips monitor the thermal expansion of a slice across the sample in response to the sinusoidal temperature profile. This represents an improvement over previous methods since (i) the change in temperature is averaged along the sample length, (ii) we measure the phase of the thermal wave at all radii and (iii) since the expansion of the sample is observed as a proxy for the change in temperature there are no problems associated with contact thermal resistance at the thermocouples. Furthermore, this development does away with the need to prepare long cylinders of weakly metastable phases with a thermocouple inserted precisely down the middle; a process which is technically extremely difficult. Using this method we have measured the thermal diffusivity of NaCl, olivine, majorite and a number of other upper-mantle and transition-zone phases and found that our measurements are in agreement with previously published data. In this present study on the CaIrO3 analogue of perovskite and post-perovskite, we find that the thermal diffusivity of the post

  19. An Analysis of an Autoclitic Analogue in Pigeons

    Science.gov (United States)

    Kuroda, Toshikazu; Lattal, Kennon A.; García-Penagos, Andrés

    2014-01-01

    Using a conditional discrimination procedure, pigeons were exposed to a nonverbal analogue of qualifying autoclitics such as "definitely" and "maybe." It has been suggested that these autoclitics are similar to tacts except that they are under the control of private discriminative stimuli. Instead of the conventional assumption…

  20. Brassinosteroids: Synthesis and activity of some fluoro analogues

    Czech Academy of Sciences Publication Activity Database

    Slavíková, Barbora; Kohout, Ladislav; Buděšínský, Miloš; Swaczynová, Jana; Kasal, Alexander

    2008-01-01

    Roč. 51, č. 13 (2008), s. 3979-3984. ISSN 0022-2623 R&D Projects: GA AV ČR IAA400550609 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50380511 Keywords : brassinosteroids * fluoro analogues Subject RIV: CC - Organic Chemistry Impact factor: 4.898, year: 2008

  1. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    Science.gov (United States)

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

  2. Design and Synthesis of Muramyl Dipeptide Cyclic Analogue

    Institute of Scientific and Technical Information of China (English)

    SuoDeZHANG; GangLIU; 等

    2002-01-01

    A new conformationalloy restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our “Meshed-Bag Gathered-Bunch” method with a combination of Fmoc,ally and N-1-(4,4-dimethyl-2,6-dioxocyclo-hexylidene) ethyl chemical protection strategy.

  3. Treatment with insulin (analogues) and breast cancer risk in diabetics

    DEFF Research Database (Denmark)

    Bronsveld, Heleen K; Ter Braak, Bas; Karlstad, Øystein;

    2015-01-01

    animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However, the...

  4. Synthesis, DNA interaction and antimicrobial activities of three rimantadine analogues

    International Nuclear Information System (INIS)

    The interactions of three rimantadine analogues (RAs) with calf thymus deoxyribonucleic acid (ct-DNA) in buffer solution (pH 7.4) were investigated using berberine (BR) as a probe by various methods. Fluorescence studies revealed that the RAs interacted with DNA in vitro and the quenchings were all static. Furthermore, the binding modes of these compounds to DNA were disclosed as groove binding supported by absorption spectroscopy, viscosity measurement and denatured DNA experiment. The antimicrobial activities of the RAs were also evaluated in Staphylococcus aureus and Escherichia coli, and they all exhibited good bacteriostasic effects. The results might provide an important reference for investigation of the molecular mechanism associated with the DNA binding of the RAs. - Highlights: • Three rimantadine analogues were synthesized. • The RAs effectively quenched the intrinsic fluorescence of DNA via a static combination. • These analogues can bind to DNA via groove binding mode. • The antimicrobial activities of three analogues were also evaluated by the disk diffusion method

  5. Photonic analogue of Zitterbewegung in binary waveguide arrays

    OpenAIRE

    Longhi, S.

    2009-01-01

    An optical analogue of Zitterbewegung (ZB), i.e. of the trembling motion of Dirac electrons caused by the interference between positive and negative energy states, is proposed for spatial beam propagation in binary waveguide arrays. In this optical system ZB is simply observable as a quiver spatial oscillatory motion of the beam center of mass around its mean trajectory.

  6. New phosphorus analogues of nitrogen classics--no carbon copies.

    Science.gov (United States)

    Gudat, Dietrich

    2014-05-01

    Getting heavy: The recently prepared phosphorus analogues of two old acquaintances, urea and dinitrogen tetroxide, bear some structural resemblance to their archetypes but are no carbon copies. Their syntheses and chemical properties reveal rather certain peculiarities, which back the doctrine that the electronic properties of the heavier elements in a group differ from those of the lightest congener. PMID:24718995

  7. Conformation analysis of Se and Te containing nucleoside analogues

    Czech Academy of Sciences Publication Activity Database

    Poštová Slavětínská, Lenka; Rejman, Dominik; Kleinpeter, E.; Pohl, Radek

    Santiago de Compostela : -, 2013. s. 221-221. [SMASH 2013. 22.9.2013-25.9.2013, Santiago de Compostela] R&D Projects: GA ČR GA13-24880S Institutional support: RVO:61388963 Keywords : low-temperature NMR * DFT * nucleoside analogues Subject RIV: CC - Organic Chemistry

  8. Synthesis, DNA interaction and antimicrobial activities of three rimantadine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bing-Mi; Zhang, Jun [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Wang, Xin, E-mail: wangxinlnu@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Zhang, Li-Ping; Liu, Yang [Department of Pharmacy, Liaoning University, Shenyang 110036 (China); Niu, Hua-Ying [Jinan Dachpharm Development Co., Ltd., Jinan 250100 (China); Liu, Bin, E-mail: liubinzehao@163.com [Department of Pharmacy, Liaoning University, Shenyang 110036 (China)

    2015-03-15

    The interactions of three rimantadine analogues (RAs) with calf thymus deoxyribonucleic acid (ct-DNA) in buffer solution (pH 7.4) were investigated using berberine (BR) as a probe by various methods. Fluorescence studies revealed that the RAs interacted with DNA in vitro and the quenchings were all static. Furthermore, the binding modes of these compounds to DNA were disclosed as groove binding supported by absorption spectroscopy, viscosity measurement and denatured DNA experiment. The antimicrobial activities of the RAs were also evaluated in Staphylococcus aureus and Escherichia coli, and they all exhibited good bacteriostasic effects. The results might provide an important reference for investigation of the molecular mechanism associated with the DNA binding of the RAs. - Highlights: • Three rimantadine analogues were synthesized. • The RAs effectively quenched the intrinsic fluorescence of DNA via a static combination. • These analogues can bind to DNA via groove binding mode. • The antimicrobial activities of three analogues were also evaluated by the disk diffusion method.

  9. Cyclization of nucleotide analogues as an obstacle to polymerization

    Science.gov (United States)

    Hill, A. R. Jr; Nord, L. D.; Orgel, L. E.; Robins, R. K.

    1988-01-01

    Cyclization of activated nucleotide analogues by intramolecular phosphodiester-bond formation is likely to compete very effectively with template-directed condensation except in the cases of ribo- and arabinonucleotides. This could have excluded derivatives of most sugars from growing polyribonucleotide chains and thus reduced chain-termination in prebiotic polynucleotide synthesis.

  10. Geochemical modelling of the Broubster natural analogue site Caithness, Scotland

    International Nuclear Information System (INIS)

    The results of a modelling study carried out to improve understanding of speciation and actinide migration mechanisms operating at Broubster (UK) are described. This work is part of the CEC coordinated project Mirage - Second phase (Migration of radionuclides in the geosphere), research area Natural analogues

  11. Cognitive mechanisms and posttraumatic stress disorder: Clinical and analogue research.

    NARCIS (Netherlands)

    I.M. Engelhard; M. Kindt

    2005-01-01

    The contributions to this special issue "Journal of Behavior Therapy & Experimental Psychiatry," are driven by influential cognitive theories of Posttraumatic stress disorder (PTSD). They include clinical and analogue research and address different aspects of PTSD. Two papers focus on the clarificat

  12. Synthesis and biological evaluation of novel gramicidin s analogues

    NARCIS (Netherlands)

    Tuin, A.W.; Palachanis, D.K.; Buizert, A.; Grotenbreg, G.M.; Spalburg, E.; Neeling, A.J. de; Mars-Groenendijk, R.H.; Noort, D.; Marel, G.A. van der; Overkleeft, H.S.; Overhand, M.

    2009-01-01

    The synthesis of three new analogues of the cyclic cationic antimicrobial peptide Gramicidin S is described. These derivatives contain a modified turn region in which the DPhe-Pro motif has been replaced by a constrained furanoid sugar amino acid or a flexible linear aminoethoxy acetic acid moiety.

  13. Using natural analogue studies in the secondary science curriculum

    International Nuclear Information System (INIS)

    This paper discusses an atomic theory unit of a high school chemistry course taught in Nevada. The unit is based on the application of natural analogues to nuclear waste issues. The paper focuses on the students' reactions to the subject material

  14. Analogue Building Blocks Based on Digital CMOS Gates

    DEFF Research Database (Denmark)

    Mucha, Igor

    1996-01-01

    Low-performance analogue circuits built of digital MOS gates are presented. Depending on the threshold voltages of the technology used the final circuits can be operated using low supply voltages. The main advantage using the proposed circuits is the simplicity and ultimate compatibility with the...

  15. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    Directory of Open Access Journals (Sweden)

    Maarten Walmagh

    2015-06-01

    Full Text Available Trehalose (α-d-glucopyranosyl α-d-glucopyranoside is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals, medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (α-d-glucopyranosyl α-d-galactopyranoside or galactotrehalose (α-d-galactopyranosyl α-d-galactopyranoside, offer similar benefits as trehalose, but show additional features such as prebiotic or low-calorie sweetener due to their resistance against hydrolysis during digestion. Unfortunately, large-scale chemical production processes for trehalose analogues are not readily available at the moment due to the lack of efficient synthesis methods. Most of the procedures reported in literature suffer from low yields, elevated costs and are far from environmentally friendly. “Greener” alternatives found in the biocatalysis field, including galactosidases, trehalose phosphorylases and TreT-type trehalose synthases are suggested as primary candidates for trehalose analogue production instead. Significant progress has been made in the last decade to turn these into highly efficient biocatalysts and to broaden the variety of useful donor and acceptor sugars. In this review, we aim to provide an overview of the latest insights and future perspectives in trehalose analogue chemistry, applications and production pathways with emphasis on biocatalysis.

  16. Watson's basic analogue of Ramanujan's entry 40 and its generalization

    OpenAIRE

    Gupta, Dharma P.; David R. Masson

    1993-01-01

    We generalize Watson's $ q $-analogue of Ramanujan's Entry 40 continued fraction by deriving solutions to a $ {}_{10} \\phi_9 $ series contiguous relation and applying Pincherle's theorem. Watson's result is recovered as a special terminating case, while a limit case yields a new continued fraction associated with an $ \\ephis $ series contiguous relation.

  17. Solistatinol, a novel phenolic compactin analogue from Penicillium solitum

    DEFF Research Database (Denmark)

    Larsen, Thomas Ostenfeld; Lange, Lene; Schnorr, Kirk;

    2007-01-01

    Solistatinol, a novel phenolic compactin analogue, has been isolated from Penicillium solitum using a UV-guided strategy. The structure and relative stereochemistry were determined by NMR spectroscopy and mass spectrometry. The absolute stereochemistry was determined by chemical degradation and c...

  18. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...

  19. Lysine-vasopressin analogues with glycoconjugates in position 8

    Czech Academy of Sciences Publication Activity Database

    Marcinkowska, A.; Borovičková, Lenka; Slaninová, Jiřina; Grzonka, Z.

    2006-01-01

    Roč. 80, č. 5 (2006), s. 759-766. ISSN 0137-5083 Institutional research plan: CEZ:AV0Z40550506 Keywords : glycoconjugates * glycopeptides * lysine -vasopressin analogues Subject RIV: CC - Organic Chemistry Impact factor: 0.491, year: 2006

  20. Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin

    OpenAIRE

    Sarah E Holden; Poole, Chris D; Morgan, Christopher Ll.; Currie, Craig J

    2011-01-01

    Article summary Article focus Insulin analogues have become increasingly popular in recent years. Insulin analogues are more costly than their human insulin alternatives. The aim of this cross-sectional study is to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Key messages If all dispensations for analogue insulin between 2000 and 2009 had used a human insulin alternative, the NHS w...

  1. Cholecystokinin receptors: disparity between phosphoinositide breakdown and amylase releasing activity of CCK analogues in pancreas

    International Nuclear Information System (INIS)

    Cholecystokinin (CCK) peptides are a family of hormones which also occur in brain. In pancreas CCK stimulates the release of amylase, a process that is dependent on the mobilization of intracellular Ca2+. Recent evidence suggests that inositol 1,4,5-trisphosphate, the breakdown product of phosphatidylinositol 4,5-bisphosphate, is responsible for the rise in intracellular Ca2+. Their laboratory has developed assays to study synthetic CCK analogues using radioligand binding, PI breakdown and amylase release. They have shown that there are good correlations among these three assay systems for the carboxy terminal fragments of CCK8. Recently, they have discovered synthetic analogues of CCK4 that are full agonists in amylase release but are ineffective in causing PI breakdown. In particular, A-61576, Boc-5-amino-2-indolemethylene-pent-2-ene-1-oyl-Leu-Asp-Phe-NH2, is a full agonist in the amylase releasing assay, but is devoid of PI stimulating activity. A-61576 completely reverses the stimulation of PI response induced by CCK8, indicative of an antagonist. Since a mechanism other than the PI breakdown is responsible for amylase release by A-61576, they suggest that separate receptors are responsible for PI breakdown and amylase release

  2. Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ye-Hui Shi

    2016-04-01

    Full Text Available Recent studies have shown that sulforaphane (SFN selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH+ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX increased the ALDH+ subpopulation.

  3. Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines.

    Science.gov (United States)

    Shi, Ye-Hui; Dai, Dong-Fang; Li, Jing; Dong, Yan-Wei; Jiang, Yin; Li, Huan-Gong; Gao, Yuan; Chong, Chuan-Ke; Li, Hui-Ying; Chu, Xiao-Qian; Yang, Cheng; Zhang, Quan; Tong, Zhong-Sheng; Bai, Cui-Gai; Chen, Yue

    2016-01-01

    Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation. PMID:27110751

  4. Mitochondria-Targeted Analogues of Metformin Exhibit Enhanced Antiproliferative and Radiosensitizing Effects in Pancreatic Cancer Cells.

    Science.gov (United States)

    Cheng, Gang; Zielonka, Jacek; Ouari, Olivier; Lopez, Marcos; McAllister, Donna; Boyle, Kathleen; Barrios, Christy S; Weber, James J; Johnson, Bryon D; Hardy, Micael; Dwinell, Michael B; Kalyanaraman, Balaraman

    2016-07-01

    Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+)). In particular, the analogue Mito-Met10, synthesized by attaching TPP(+) to Met via a 10-carbon aliphatic side chain, was nearly 1,000 times more efficacious than Met at inhibiting cell proliferation in pancreatic ductal adenocarcinoma (PDAC). Notably, in PDAC cells, Mito-Met10 potently inhibited mitochondrial complex I, stimulating superoxide and AMPK activation, but had no effect in nontransformed control cells. Moreover, Mito-Met10 potently triggered G1 cell-cycle phase arrest in PDAC cells, enhanced their radiosensitivity, and more potently abrogated PDAC growth in preclinical mouse models, compared with Met. Collectively, our findings show how improving the mitochondrial targeting of Met enhances its anticancer activities, including aggressive cancers like PDAC in great need of more effective therapeutic options. Cancer Res; 76(13); 3904-15. ©2016 AACR. PMID:27216187

  5. Synthesis and Antiproliferative Activities of 5-Azacytidine Analogues in Human Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Lin-Xiang Zhao

    2008-07-01

    Full Text Available Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl Snucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.

  6. Collective properties of quantum matter: from Hawking radiation analogues to quantum Hall effect in graphene

    CERN Document Server

    de Nova, J R M

    2015-01-01

    The work is divided in three parts. We devote the first part to the study of analog Hawking radiation in Bose-Einstein condensates. We study numerically the birth of a sonic black hole in an outcoupled Bose-Einstein condensate after relaxing the confinement provided by an optical lattice. We also study possible signatures of spontaneous Hawking radiation. We propose that the violation of CS inequalities is a smoking gun of the presence of the Hawking effect. We compare this criterion with the presence of entaglement, finding that both are equivalent under usual assumptions. Finally, we study a different gravitational analogue: the so-called black-hole laser. The most interesting result is the appearance of a regime of continuous and periodic emission of solitons, providing the most strong analogue with optical lasers. In the second part, we analyze the effect of the introduction of a short Bragg pulse in a thermal cloud. We show that the induced periodic density pattern decays to the equilibrium profile. Howe...

  7. Charge deficient analogues of the natural polyamines.

    Science.gov (United States)

    Weisell, Janne; Hyvönen, Mervi T; Alhonen, Leena; Vepsäläinen, Jouko; Keinänen, Tuomo A; Khomutov, Alex R

    2014-01-01

    Mitochondrial dysfunction, either inherited or acquired, is associated with several diseases in humans. Depending on the cell type and location, cells are prone to multiple types of insults that may compromise their proper function. Generally, these insults are overcome by defensive mechanisms but sometimes they lead to sustained damage, requiring the action of scavenging and repair machineries to retain the viability of the cells. As a final measure, severely damaged cells are targeted to a controlled cell death pathway in order to not to compromise the well-being of the whole tissue. The polyamines, spermine and spermidine are essential cellular constituents, participating in many vital functions such as proliferation and differentiation, immune response and scavenging of reactive oxygen species. Therefore, dysregulation of polyamine metabolism is often associated with different pathological states. Polyamine acetylating enzyme spermidine/spermine-N(1)-acetyltransferase is induced by inflammation, drugs and by several other environmental insults. Resulting accelerated polyamine acetylation with accompanying polyamine biosynthesis induction i.e. activation of polyamine futile cycle generates excessive amount of hydrogen peroxide, hampers cell energy metabolism and induces mitochondrial dysfunction and biogenesis. Therefore, the drugs inhibiting polyamine metabolism are valuable in protecting mitochondria and cell energy metabolism. Here we review the current literature focusing on the applicability of chargedeficient polyamine analogs as drugs to modulate polyamine metabolism. Alteration of pK(a) of amino group(s) in a respective analog is achieved by fluorine substitution of hydrogen atom, hydroxylamine substitution of methylamine or by reducing the numbers of carbon atoms between amine groups to two instead of three or four. PMID:23701551

  8. Deficiencies in fat-soluble vitamins in long-term users of somatostatin analogue

    NARCIS (Netherlands)

    Fiebrich, H. -B.; van den Berg, G.; Kema, I. P.; Links, T. P.; Kleibeuker, J. H.; van Beek, A. P.; Walenkamp, A. M. E.; Sluiter, W. J.; de Vries, E. G. E.

    2010-01-01

    P>Background Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels rema

  9. On Using Current Steering Logic in Mixed Analogue-digital Circuits

    DEFF Research Database (Denmark)

    Lehmann, Torsten

    1998-01-01

    The authors investigate power supply noise in mixed analogue-digital circuits, arising from communication between the analogue and digital parts of the circuit. Current steering techniques and proper buffering are used to show which noise currents can be reduced and which cannot. In addition, a...... high-swing current steering buffer for driving analogue switches or external digital signals is proposed....

  10. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    Energy Technology Data Exchange (ETDEWEB)

    Skagius, K. [Kemakta Consultants co., Stockholm (Sweden); Wingefors, S. [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    1992-12-31

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  11. Alligator Rivers Analogue project. Application of scenario development method in evaluation of the Koongarra Analogue. Final Report - Volume 16

    International Nuclear Information System (INIS)

    The study of natural analogues has been established as one of the most important methods for validation of concepts and models applied for the assessment of long-term performance of repositories for nuclear waste. The objectives of such studies range from detailed investigations of processes and features on a small scale to attempts of explaining the evolution of whole sites. For studies of specific processes it may well be as important to consider the larger scale settings as boundary conditions. This appreciation of context and an integrated view may be as important for evaluation of most natural analogues as for performance assessments. This is more evident the more the evaluation depends on a knowledge about the evolution of the natural analogue. The attempted formulation of scenarios of the Koongarra Analogue has been based on the external conditions and external features. A rapid weathering of the host rock, i.e. the chlorite schist, is assumed to have started around the onset of the Pleistocene Ice Age (ca 1.6 Ma BP). The eventual oxidation and mobilization of the uranium ore could then have occurred under unsaturated or saturated conditions. This leads to the following major scenarios: (1) Uranyl Phosphates formed under unsaturated conditions, with a periodical evolution of the dispersion fan in conjunction with alternating dry (glacial) and wet (interglacial) periods during the Pleistocene Ice Age; (2) Uranyl Phosphates formed under unsaturated conditions as a single event, taking place either early or late during the Pleistocene Ice Age; (3)Uranyl Phosphates formed under saturated conditions, in conjunction with periods of higher and lower flow due to the climatic cycling. Although the original objectives may not have been fully achieved, this work is believed to contribute to a better understanding of the Koongarra Analogue as well as to give a basis for further scenario work

  12. Electron Irradiation of Interstellar Ice Analogues

    Science.gov (United States)

    Nair, B. G.; Mason, N. J.

    2011-05-01

    Molecular synthesis in the Universe primarily occurs in the icy mantles on dust grains in dense interstellar dust clouds. The interaction of photons, electrons and cosmic rays with these ice mantles triggers complex chemical synthesis leading to the formation of complex molecules. Such molecular reactions can only be understood by systematic laboratory studies. In our experiments astrophysical environments are recreated in the laboratory using an ultra high vacuum chamber (UHV) capable of reaching pressures of the order of 10 -10 mBar containing a liquid helium cryostat capable of attaining a temperature of 20 K. Ice films are deposited on a ZnSe substrate (cooled by cryostat) by background deposition and irradiated with electrons of 1KeV energy. Chemical changes induced by electron irradiation were monitored by an infrared spectrometer. By varying the temperature, we also investigate the temperature dependence on the kinetics of the reactions. In this poster we will present the first results of electron irradiation of simple organic molecules like formamide (HCONH2) and allyl alcohol (CH2CHCH2OH).

  13. Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues.

    Science.gov (United States)

    Ziegler, Hanne L; Franzyk, Henrik; Sairafianpour, Majid; Tabatabai, Mehrnoush; Tehrani, Mahboubeh D; Bagherzadeh, Karim; Hägerstrand, Henry; Staerk, Dan; Jaroszewski, Jerzy W

    2004-01-01

    The natural triterpene betulinic acid and its analogues (betulinic aldehyde, lupeol, betulin, methyl betulinate and betulinic acid amide) caused concentration-dependent alterations of erythrocyte membrane shape towards stomatocytes or echinocytes according to their hydrogen bonding properties. Thus, the analogues with a functional group having a capacity of donating a hydrogen bond (COOH, CH(2)OH, CONH(2)) caused formation of echinocytes, whereas those lacking this ability (CH(3), CHO, COOCH(3)) induced formation of stomatocytes. Both kinds of erythrocyte alterations were prohibitive with respect to Plasmodium falciparum invasion and growth; all compounds were inhibitory with IC(50) values in the range 7-28 microM, and the growth inhibition correlated well with the extent of membrane curvature changes assessed by transmission electron microscopy. Erythrocytes pre-loaded with betulinic acid or its analogues and extensively washed in order to remove excess of the chemicals could not serve as hosts for P. falciparum parasites. Betulinic acid and congeners can be responsible for in vitro antiplasmodial activity of plant extracts, as shown for Zataria multiflora Boiss. (Labiatae) and Zizyphus vulgaris Lam. (Rhamnaceae). The activity is evidently due to the incorporation of the compounds into the lipid bilayer of erythrocytes, and may be caused by modifications of cholesterol-rich membrane rafts, recently shown to play an important role in parasite vacuolization. The established link between erythrocyte membrane modifications and antiplasmodial activity may provide a novel target for potential antimalarial drugs. PMID:14697777

  14. The development of amine substituted analogues of MPTP as unique tools for the study of MPTP toxicity and Parkinson's disease.

    Science.gov (United States)

    Johannessen, J N; Savitt, J M; Markey, C J; Bacon, J P; Weisz, A; Hanselman, D S; Markey, S P

    1987-02-23

    We are currently developing amino-substituted MPTP analogues as useful probes for understanding the mechanism of MPTP toxicity and Parkinson's disease. One analogue, 4'-amino MPTP, induces a loss of striatal dopamine and is thus a suitable substitute for MPTP. This probe will be used as a histologically fixable MPTP which can be used to answer detailed anatomical questions concerning the sites of MPTP, MPP+ uptake and storage. In addition, antibodies have been raised against MPTP and MPP+ in rabbits using diazo-linked bovine serum albumin conjugates. The antibodies have been characterized with regard to their recognition of relevant structural analogues using an enzymelinked immunoassay (ELISA) procedure. Antibodies to MPTP detected MPTP in mouse brain extracts derived from as little as 5 micrograms of tissue. The antibodies will be used for immunohistochemical localization of 4'-NH2-MPTP and 4'-NH2-MPP+ in brain, as well as probes for the screening of parkinsonian brain tissue for any MPTP- or MPP+-like materials which might exist. PMID:2433563

  15. An analogue conceptual rainfall-runoff model for educational purposes

    Science.gov (United States)

    Herrnegger, Mathew; Riedl, Michael; Schulz, Karsten

    2016-04-01

    Conceptual rainfall-runoff models, in which runoff processes are modelled with a series of connected linear and non-linear reservoirs, remain widely applied tools in science and practice. Additionally, the concept is appreciated in teaching due to its somewhat simplicity in explaining and exploring hydrological processes of catchments. However, when a series of reservoirs are used, the model system becomes highly parametrized and complex and the traceability of the model results becomes more difficult to explain to an audience not accustomed to numerical modelling. Since normally the simulations are performed with a not visible digital code, the results are also not easily comprehensible. This contribution therefore presents a liquid analogue model, in which a conceptual rainfall-runoff model is reproduced by a physical model. This consists of different acrylic glass containers representing different storage components within a catchment, e.g. soil water or groundwater storage. The containers are equipped and connected with pipes, in which water movement represents different flow processes, e.g. surface runoff, percolation or base flow. Water from a storage container is pumped to the upper part of the model and represents effective rainfall input. The water then flows by gravity through the different pipes and storages. Valves are used for controlling the flows within the analogue model, comparable to the parameterization procedure in numerical models. Additionally, an inexpensive microcontroller-based board and sensors are used to measure storage water levels, with online visualization of the states as time series data, building a bridge between the analogue and digital world. The ability to physically witness the different flows and water levels in the storages makes the analogue model attractive to the audience. Hands-on experiments can be performed with students, in which different scenarios or catchment types can be simulated, not only with the analogue but

  16. Glucagon-like peptide-1 analogue, liraglutide, in experimental cerebral malaria

    DEFF Research Database (Denmark)

    DellaValle, Brian; Hempel, Casper; Staalsoe, Trine;

    2016-01-01

    BACKGROUND: Cerebral malaria from Plasmodium falciparum infection is major cause of death in the tropics. The pathogenesis of the disease is complex and the contribution of reactive oxygen and nitrogen species (ROS/RNS) in the brain is incompletely understood. Insulinotropic glucagon-like peptide-1...... (GLP-1) mimetics have potent neuroprotective effects in animal models of neuropathology associated with ROS/RNS dysfunction. This study investigates the effect of the GLP-1 analogue, liraglutide against the clinical outcome of experimental cerebral malaria (ECM) and Plasmodium falciparum growth....... Furthermore the role of oxidative stress on ECM pathogenesis is evaluated. METHODS: ECM was induced in Plasmodium berghei ANKA-infected C57Bl/6j mice. Infected Balb/c (non-cerebral malaria) and uninfected C57Bl/6j mice were included as controls. Mice were treated twice-daily with vehicle or liraglutide (200...

  17. Graft Copolymers of Maleic Anhydride and Its Isostructural Analogues: High Performance Engineering Materials

    CERN Document Server

    Rzayev, Zakir M O

    2011-01-01

    This review summarizes the main advances published over the last 15 years outlining the different methods of grafting, including reactive extruder systems, surface modification, grafting and graft copolymerization of synthetic and natural polymers with maleic anhydride and its isostructural analogues such as maleimides and maleates, and anhydrides, esters and imides of citraconic and itaconic acids, derivatives of fumaric acid, etc. Special attention is spared to the grafting of conventional and non-conventional synthetic and natural polymers, including biodegradable polymers, mechanism of grafting and graft copolymerization, in situ grafting reactions in melt by reactive extrusion systems, in solutions and solid state (photo- and plasma-induced graftings), and H-bonding effect in the reactive blend processing. The structural phenomena, unique properties and application areas of these copolymers and their various modifications and composites as high performance engineering materials have been also described.

  18. Induced corepresentations of locally compact quantum groups

    OpenAIRE

    Kustermans, Johan

    2000-01-01

    We introduce the construction of induced corepresentations in the setting of locally compact quantum groups and prove that the resulting induced corepresentations are unitary under some mild integrability condition. We also establish a quantum analogue of the classical bijective correspondence between quasi-invariant measures and certain measures on the larger locally compact group.

  19. Comparison of misoprostol (pge1) analogue with dinoprostone (pge2) for induction of labour

    International Nuclear Information System (INIS)

    Objective: To compare the results of induction of labour with misoprostol (PGE1 analogue) with dinoprostone (PGE2 analogue) in terms of induction delivery interval, mode of delivery, and the need for oxytocin augmentation. Setting: Department of Obstetrics and Gynaecology, Combined Military Hospital, Rawalpindi. Duration of Study: Six months Study Design: Randomized controlled trial. Subject and Method: Total 100 subjects were included in this study. These patients were divided in groups-A and B. Group-A was induced with prostin tablet i.e. dinoprostone PGE2 3 mg tablets maximum of 2 doses, 6 hours apart. Group-B induced with prosotec 50 mu gm 4 hourly, 4 doses. The subjects were full term pregnant women who were either primigravida, 2nd or 3rd gravid and had bishop score less than 5. Results: The patients included in the study were between the ages of 19 to 37 years. The mean age of group-A was 26.72 +- 4.62 years and of group-B was 28.4 +- 4.94 years (p value > 0.05). All the patients in both groups were between 37 to 42 weeks of gestation. The mean gestational age of group-A was 39.74 +- 2.09 weeks and in group-B it was 39.62 +- 1.55 weeks (p > 0.05). Oxytocin augmentation was required in late 1st stage and 2nd stage in group-A in 68% cases but it was required in only 30% cases in group-B cases. The maximum duration of labour was more than 11 hours in 24% cases in group-A but only 6% in group-B. Conclusion: Misoprostol (PGE1 analogue) is a useful drug for labour induction. There is short induction delivery interval and reduced need for the use of oxytocin augmentation. There are also less failure rates of induction with misoprostol. Rate of instrumental delivery and caesarean section is also less. (author)

  20. α-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive mice.

    Directory of Open Access Journals (Sweden)

    Petteri Rinne

    Full Text Available Melanocyte-stimulating hormones, α-, β- and γ-MSH, regulate important physiological functions including energy homeostasis, inflammation and sodium metabolism. Previous studies have shown that α-MSH increases sodium excretion and promotes vascular function in rodents, but it is unexplored whether these characteristics of α-MSH could translate into therapeutic benefits in the treatment of hypertension. Therefore, we first assessed the diuretic and natriuretic properties of the stable α-MSH analogue [Nle(4, D-Phe(7]-α-MSH (NDP-α-MSH and investigated whether it has protective effects in deoxycorticosterone acetate (DOCA-salt hypertensive mice. Adult male C57Bl/6N mice were subjected to DOCA-salt treatment and randomized to receive intraperitoneal injections of either saline as vehicle or NDP-α-MSH (0.3 mg/kg/day for 14 days starting 7 days after the DOCA-salt treatment. Systemic hemodynamics, serum and urine electrolytes, and oxidative stress markers were assessed in control sham-operated and DOCA-salt mice. NDP-α-MSH elicited marked diuretic and natriuretic responses that were reversible with the MC3/4 receptor antagonist SHU9119. Chronic NDP-α-MSH treatment attenuated blood pressure elevation in DOCA-salt mice without affecting the blood pressure of normotensive control animals. Owing to the enhanced sodium excretion, NDP-α-MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt treatment mildly increased oxidative stress at the tissue level, but NDP-α-MSH had no significant effects on the oxidative stress markers. In conclusion, treatment with NDP-α-MSH increases urinary sodium excretion and protects against DOCA-salt-induced hypertension. These findings point to the potential future use of α-MSH analogues in the treatment of hypertension.

  1. Noncommutative analogue Aharonov-Bohm effect and superresonance

    CERN Document Server

    Anacleto, M A; Passos, E

    2012-01-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  2. Noncommutative analogue Aharonov-Bohm effect and superresonance

    Science.gov (United States)

    Anacleto, M. A.; Brito, F. A.; Passos, E.

    2013-06-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in this background. We mainly show that the scattering of planar waves by a draining bathtub vortex leads to a modified AB effect and due to spacetime noncommutativity, the phase shift persists even in the limit where the parameters associated with the circulation and draining vanish. Finally, we also find that the analogue AB effect and superresonance are competing phenomena at a noncommutative spacetime.

  3. Alligator Rivers Analogue Project an OECD/NEA international project

    International Nuclear Information System (INIS)

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as natural analogue of the far field behaviour of high level waste repository following groundwater ingress. A number of mathematical modelling approaches were developed for processes as divers as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained. 6 refs., 1 tab., 1 fig

  4. Alligator rivers analogue project an OECD/NEA international project

    International Nuclear Information System (INIS)

    The Koongarra uranium deposit in the Alligator Rivers Region of the Northern Territory of Australia was studied as a natural analogue of the far field behaviour of high level waste repositories following groundwater ingress. A number of mathematical modelling approaches were developed for processes as diverse as groundwater transport, host rock weathering, radionuclide sorption, evolution of the uranium dispersion fan and the distribution of uranium series nuclides between mineral assemblages in weathered host rock. Some of these models are relevant to performance assessment at the level of individual processes and subsystem performance. Through the project, new insights into the application of the natural analogue approach to the assessment of potential waste repository sites were obtained

  5. Analogue Wormholes and Black Hole LASER Effect in Hydrodynamics

    CERN Document Server

    Peloquin, Cédric; Philbin, Thomas; Rousseaux, Germain

    2015-01-01

    We numerically study water wave packets on a spatially varying counter-current in the presence of surface tension. Depending on the details of the velocity profile, we show that traversable and bi-directional analogue wormholes exist in fluid mechanics. The limitations on traversability of wormholes in general relativity are absent here because of the dispersion of water waves and the ability to form flow profiles that are not solutions of Einstein's equations. We observe that negative energy can be trapped between analogue horizons forming a LASER-like cavity. Six horizons are involved in the trapping cavity because of the existence of two dispersive scales, in contrast to previous treatments which considered two horizons and one dispersive scale.

  6. Matrices with restricted entries and q-analogues of permutations

    CERN Document Server

    Lewis, Joel Brewster; Morales, Alejandro H; Panova, Greta; Sam, Steven V; Zhang, Yan

    2010-01-01

    We study the functions that count matrices of given rank over a finite field with specified positions equal to zero. We show that these matrices are $q$-analogues of permutations with certain restricted values. We obtain a simple closed formula for the number of invertible matrices with zero diagonal, a $q$-analogue of derangements, and a curious relationship between invertible skew-symmetric matrices and invertible symmetric matrices with zero diagonal. In addition, we provide recursions to enumerate matrices and symmetric matrices with zero diagonal by rank, and we frame some of our results in the context of Lie theory. Finally, we provide a brief exposition of polynomiality results for enumeration questions related to those mentioned, and give several open questions.

  7. Somatostatin analogues labelled with 99mTc

    International Nuclear Information System (INIS)

    Biological and radiochemical studies have been carried out on two labelled somatostatin analogues, the peptide RC-150 and the Tyr3-Octreotide. Both analogues have been labelled with 99mTc using the direct and the indirect method and MAG-3 and HYNIC as chelating agents. By the direct method RC-150 was labelled using sodium ascorbate and dithionite as reducing agents. The radiochemical purity was 70%. By the indirect method, in the case of RC-160 with MAG-3 a radiochemical purity higher than 70% was attained while a purity of 100% was reached in the case of Tyr3-Octreotide with HYNIC. The biological distribution of HYNIC-Tyr3-Octreotide has been studied in rats. (author)

  8. QSAR Studies on Influenza Neuraminidase Inhibitors——Acylthiourea Analogue

    Institute of Scientific and Technical Information of China (English)

    JING Ju-Hua; LIANG Gui-Zhao; MEI Hu; ZHANG Qiao-Xia; LI Zhi-Liang; LV Feng-Lin

    2009-01-01

    The quantitative structure-activity relationship (QSAR) of 30 acylthiourea analogues was studied by using a three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) to describe their chemical structures. The descriptors obtained were screened by stepwise multiple regression (SMR) and a partial least-squares (PLS) regression model was built. The correlation coefficient r2 of the established model and Leave-One-Out (LOP) Cross-Validation (CV) correlation coefficient q2 are 0.624 and 0.409, respectively. The model has favorable stability and good prediction capability, and further QSAR analysis showed that hydrophobic interaction has the most important effect on the activity of acylthiourea analogue and 3D-HoVAIF was applicable to the molecular structural characterization and biologicalactivity prediction.

  9. Acoustic clouds: standing sound waves around a black hole analogue

    CERN Document Server

    Benone, Carolina L; Herdeiro, Carlos; Radu, Eugen

    2014-01-01

    Under certain conditions sound waves in fluids experience an acoustic horizon with analogue properties to those of a black hole event horizon. In particular, a draining bathtub-like model can give rise to a rotating acoustic horizon and hence a rotating black hole (acoustic) analogue. We show that sound waves, when enclosed in a cylindrical cavity, can form stationary waves around such rotating acoustic black holes. These acoustic perturbations display similar properties to the scalar clouds that have been studied around Kerr and Kerr-Newman black holes; thus they are dubbed acoustic clouds. We make the comparison between scalar clouds around Kerr black holes and acoustic clouds around the draining bathtub explicit by studying also the properties of scalar clouds around Kerr black holes enclosed in a cavity. Acoustic clouds suggest the possibility of testing, experimentally, the existence and properties of black hole clouds, using analog models.

  10. Optical analogue of relativistic Dirac solitons in binary waveguide arrays

    International Nuclear Information System (INIS)

    We study analytically and numerically an optical analogue of Dirac solitons in binary waveguide arrays in the presence of Kerr nonlinearity. Pseudo-relativistic soliton solutions of the coupled-mode equations describing dynamics in the array are analytically derived. We demonstrate that with the found soliton solutions, the coupled mode equations can be converted into the nonlinear relativistic 1D Dirac equation. This paves the way for using binary waveguide arrays as a classical simulator of quantum nonlinear effects arising from the Dirac equation, something that is thought to be impossible to achieve in conventional (i.e. linear) quantum field theory. -- Highlights: •An optical analogue of Dirac solitons in nonlinear binary waveguide arrays is suggested. •Analytical solutions to pseudo-relativistic solitons are presented. •A correspondence of optical coupled-mode equations with the nonlinear relativistic Dirac equation is established

  11. Higher dimensional analogues of Donaldson-Witten theory

    International Nuclear Information System (INIS)

    We present a Donaldson-Witten type field theory in eight dimension on manifolds with Spin(7) holonomy. We prove that the stress tensor is BRST exact for metric variations preserving the holonomy and we give the invariants for this class of variations. In six and seven dimensions we propose similar theories on Calabi-Yau threefolds and manifolds of G2 holonomy respectively. We point out that these theories arise by considering supersymmetric Yang-Mills theory defined on such manifolds. The theories are invariant under metric variations preserving the holonomy structure without the need for twisting. This statement is a higher dimensional analogue of the fact that Donaldson-Witten field theory on hyper-Kaehler 4-manifolds is topological without twisting. Higher dimensional analogues of Floer cohomology are briefly outlined. All of these theories arise naturally within the context of string theory. (author). 24 refs

  12. The theory of Hawking radiation in laboratory analogues

    CERN Document Server

    Robertson, Scott

    2015-01-01

    Hawking radiation, despite being known to theoretical physics for nearly forty years, remains elusive and undetected. It also suffers, in its original context of gravitational black holes, from practical and conceptual difficulties. Of particular note is the trans-Planckian problem, which is concerned with the apparent origin of the radiation in absurdly high frequencies. In order to gain better theoretical understanding and, it is hoped, experimental verification of Hawking radiation, much study is being devoted to laboratory systems which use moving media to model the spacetime geometry of black holes, and which, by analogy, are also thought to emit Hawking radiation. These analogue systems typically exhibit dispersion, which regularizes the wave behaviour at the horizon at the cost of a more complicated theoretical framework. This tutorial serves as an introduction to Hawking radiation and its analogues, developing the moving medium analogy for black holes and demonstrating how dispersion can be incorporat...

  13. Modelling a river catchment using an electrical circuit analogue

    Directory of Open Access Journals (Sweden)

    C. G. Collier

    1998-01-01

    Full Text Available An electrical circuit analogue of a river catchment is described from which is derived an hydrological model of river flow called the River Electrical Water Analogue Research and Development (REWARD model. The model is based upon an analytic solution to the equation governing the flow of electricity in an inductance-capacitance-resistance (LCR circuit. An interpretation of L, C and R in terms of catchment parameters and physical processes is proposed, and tested for the River Irwell catchment in northwest England. Hydrograph characteristics evaluated using the model are compared with observed hydrographs, confirming that the modelling approach does provide a reliable framework within which to investigate the impact of variations in model input data.

  14. Are structural analogues to bisphenol A a safe alternative?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Gitte Alsing;

    2013-01-01

    weight, behavioral changes in children, cardiovascular disease, and diabetes. Regulatory initiatives and increased public awareness, related to the potential adverse effects of BPA, has led to an incitement to find alternative compounds. Structural analogues of BPA are available on the market, some......Bisphenol A (BPA) is often used in polycarbonate plastics, coatings of food and drink cans, and in thermal papers. Foods are thought to be a major human exposure route and human biomonitoring data suggest widespread exposure. BPA is suspected of contributing to effects such as increased birth...... of which are found in foods and have been measured in humans. Due to the structural analogy there is an inherent risk that these compounds may lead to similar effects as BPA. The aim of this study was to characterize the toxicological profile of BPA and the five analogues using in vitro assays assessing...

  15. Establishment of antenna membrane states FEM on analogue method

    Institute of Scientific and Technical Information of China (English)

    JIANG Wen-hui; CAO Xi-bin; ZHAO Yang

    2008-01-01

    On the basis of choosing the basic element as the bar and choosing the basic mesh as the triangle as well as supposing the conditions of the element,the membrane states of an antenna reflector were researched by the analogue method,because the membrane effect Was not omitted during the ending deployment process of the radial rib antenna.The expressions of the bar element's section area and density were obtained.while the expression of the stress state during the ending deployment process of antenna was attained.During the establishment process of the analogue method,the analysis method of the net shell structure was employed.Moreover,during the backward deduction of membrane stress,the continuation method Was adopted.Because the expression of the membrane stress state can realize the analysis on the antenna membrane state.this research has great significance of theoretical direction to the normal operation of the space deployable antenna.

  16. Effect of sulfur analogue of lysine on bacterial protein biosynthesis

    International Nuclear Information System (INIS)

    S-(beta-Aminoethyl)-L-cysteine, a sulfur analogue of lysine inhibited strongly growth of Escherichia coli A-19, and weakly that of Corynebacterium sp. isolated from soil, but did not inhibit growth of Aerobacter aerogenes. In Corynebacterium sp. the inhibitory effect was markedly enhanced in the presence of L-threonine. The inhibition of growth by S-(beta-aminoethyl)-L-cysteine was rapidly reversed by the addition of L-lysine. S-(beta-Aminoethyl)-L-cysteine inhibited protein synthesis and the activity of lysyl-tRNA synthetase from E. coli and A. aerogenes. All the other lysine analogues tested inhibited the activity of enzyme, but S-(beta-aminoethyl)-L-cysteine derivatives, S-(beta-N-acetyl-aminoethyl)-L-cysteine and S-(beta-aminoethyl)-alpha-N-acetyl-L-cysteine were not effective. (auth.)

  17. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil

    2010-09-01

    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  18. Novel Azetidine-Containing TZT-1027 Analogues as Antitumor Agents

    Science.gov (United States)

    Yan, Qi; Wang, Yujie; Zhang, Wei; Li, Yingxia

    2016-01-01

    A conformational restriction strategy was used to design and synthesize nine TZT-1027 analogues. 3-Aryl-azetidine moiety was used to replace phenylethyl group of TZT-1027 at the C-terminus. These analogues exhibited moderate to excellent antiproliferative activities, and the most potent compound 1a showed IC50 values of 2.2 nM against A549 and 2.1 nM against HCT116 cell lines, respectively. However, 1a could not achieve effective inhibition at all the dose levels in the A549 xenograft model (up to 5 mg/kg, injection, once a day), which is only 16%–35% inhibition at the end of the experiment. PMID:27136567

  19. Using fuzzy sets for data interpretation in natural analogue studies

    International Nuclear Information System (INIS)

    Natural analogue studies can play a key role in deep geological radioactive disposal systems safety assessment. These studies can help develop a better understanding of complex natural processes and, therefore, provide valuable means of confidence building in the safety assessment. In evaluation of natural analogues, there are, however, several sources of uncertainties that stem from factors such as complexity; lack of data; and ignorance. Often, analysts have to simplify the mathematical models in order to cope with the various sources of complexity and this ads uncertainty to the model results. The uncertainties reflected in model predictions must be addressed to understand their impact on safety assessment and therefore, the utility of natural analogues. Fuzzy sets can be used to represent the information regarding the natural processes and their mutual connections. With this methodology we are able to quantify and propagate the epistemic uncertainties in both processes and, thereby, assign degrees of truth to the similarities between them. An example calculation with literature data is provided. In conclusion: Fuzzy sets are an effective way of quantifying semi-quantitative information such as natural analogues data. Epistemic uncertainty that stems from complexity and lack of knowledge regarding natural processes are represented by the degrees of membership. It also facilitates the propagation of this uncertainty throughout the performance assessment by the extension principle. This principle allows calculation with fuzzy numbers, where fuzzy input results in fuzzy output. This may be one of the main applications of fuzzy sets theory to radioactive waste disposal facility performance assessment. Through the translation of natural data into fuzzy numbers, the effect of parameters in important processes in one site can be quantified and compared to processes in other sites with different conditions. The approach presented in this paper can be extended to

  20. Fluorescent synthetic analogues of salmon GnRH

    Czech Academy of Sciences Publication Activity Database

    Barth, Tomislav; Barthová, J.; Kronovetr, J.; Hamáčková, J.; Kozák, P.; Hauzerová, Linda; Kouřil, J.

    Barcelona : European Aquaculture Society, 2004, s. 144-145. ISBN 90-71625-18-4. [ Aquaculture Europe 2004. International Conference Biotechnologies for Quality. Barcelona (ES), 20.10.2004-23.10.2004] R&D Projects: GA AV ČR IBS4055006; GA MZe QF3028 Institutional research plan: CEZ:AV0Z4055905 Keywords : GnRH * fluorescent * analogues Subject RIV: CE - Biochemistry

  1. Noncommutative analogue Aharonov-Bohm effect and superresonance

    OpenAIRE

    M.A. Anacleto; Brito, F. A.; E. Passos

    2012-01-01

    We consider the idea of modeling a rotating acoustic black hole by an idealized draining bathtub vortex which is a planar circulating flow phenomenon with a sink at the origin. We find the acoustic metric for this phenomenon from a noncommutative Abelian Higgs model. As such the acoustic metric not only describes a rotating acoustic black hole but also inherits the noncommutative characteristic of the spacetime. We address the issues of superresonance and analogue Aharonov-Bohm (AB) effect in...

  2. Challenges for digitisation – learning from analogue mission planning teams

    OpenAIRE

    Stanton, Neville A.; Walker, Guy H.; Salmon, Paul M.; Jenkins, Daniel P.; Rafferty, Laura A.

    2009-01-01

    This paper aims to consider the conventional, analogue, mission planning process with the objective of identifying the decision making constraints and challenges for digitisation. Prototypes of digital mission planning systems are beginning to be devised and demonstrated, but there has been concern expressed over the design of such systems which fail to understand and incorporate the human aspects of socio-technical systems design. Previous research has identified many of the potential pitfal...

  3. Trehalose Analogues: Latest Insights in Properties and Biocatalytic Production

    OpenAIRE

    Maarten Walmagh; Renfei Zhao; Tom Desmet

    2015-01-01

    Trehalose (alpha-d-glucopyranosyl alpha-d-glucopyranoside) is a non-reducing sugar with unique stabilizing properties due to its symmetrical, low energy structure consisting of two 1,1-anomerically bound glucose moieties. Many applications of this beneficial sugar have been reported in the novel food (nutricals), medical, pharmaceutical and cosmetic industries. Trehalose analogues, like lactotrehalose (alpha-d-glucopyranosyl alpha-d-galactopyranoside) or galactotrehalose (alpha-d-galactopyran...

  4. Application of FPGA's in Flexible Analogue Electronic Image Generator Design

    OpenAIRE

    Peter Kulla; Stefan Slavik; Josef Huska

    2006-01-01

    This paper focuses on usage of the FPGAs (Field Programmable Gate Arrays) Xilinx as a part of our more complex work dedicated to design of flexible analogue electronic images generator for application in TV measurement technique or/and TV service technique or/and education process. The FPGAs performs here the role of component colour R, G, B, synchronization and blanking signals source. These signals are next processed and amplified in other parts of the generator as NTSC/PAL source ...

  5. A Multidimensional Analogue of the Simpson's Formula of Integral

    CERN Document Server

    Fujii, Kazuyuki

    2009-01-01

    The Simpson's formula is obtained by approximating the integral of a function on some interval by the integral of the quadratic polynomial determined by the function. However, a multidimensional analogue of the formula has not been given as far as we know. In this paper such a formula is given. Our formula is simple and beautiful, so it may be convenient in Mathematics or Mathematical Physics.

  6. Challenging the evolutionary strategy for synthesis of analogue computational circuits

    OpenAIRE

    Sapargaliyev, YA; Kalganova, TG

    2010-01-01

    There are very few reports in the past on applications of Evolutionary Strategy (ES) towards the synthesis of analogue circuits. Moreover, even fewer reports are on the synthesis of computational circuits. Last fact is mainly due to the dif-ficulty in designing of the complex nonlinear functions that these circuits perform. In this paper, the evolving power of the ES is challenged to design four computational circuits: cube root, cubing, square root and squaring functions. The synthesis succe...

  7. Synthetic analogues of natural semiochemicals as promising insect control agents

    International Nuclear Information System (INIS)

    After decades of research and development, insect pheromones and other semiochemicals became indispensable tools of ecologically based agricultural pest and disease vector management programmes with main uses as: 1) detection and population monitoring of emerging and migrating insects, 2) mass trapping of insects, 3) combined formulation of semiochemicals and insecticides ('lure-and-kill'), and 4) mating disruption with specially formulated pheromone components. In spite of their demonstrated safety and biodegradability, the direct application of these semiochemicals for pest control has not fulfilled initial expectations. Nonetheless considerable field experience has been accumulated (Carde and Minks 1995). Evidently, two important factors limit the practical potential of these substances: 1) inherent in their particular mode of action, semiochemicals, especially pheromones, are effectively cleared by specific enzymes in the insect antennae, and 2) some of these compounds contain labile functional moieties that are prone to degradation (oxidation, isomerisation and polymerisation) under field conditions. Appropriate chemical modifications of these natural compounds, however, can circumvent these problems by providing synthetic analogues (sometimes also called parapheromones or antipheromones; for early studies, see Roelofs and Comeau 1971, Payne et al. 1973) which in ideal cases are not only more potent and environmentally acceptable but more economical as well. It should also be mentioned that many effective attractants have been discovered through the empirical screening of synthetic chemicals, some of which have actually turned out to be structural relatives of natural semiochemicals of the particular insect. In this paper, selected case studies of analogues of sex pheromones and kairomones will be presented. The examples from our work include nitrile bioisosteres of labile aldehyde pheromone components of the cranberry girdler moth, Chrysoteuchia topiaria

  8. Documenting the Analogue Past in Marijke van Warmerdam's Film Installations

    OpenAIRE

    Noordegraaf, J.

    2013-01-01

    Dutch visual artist Marijke van Warmerdam is best known for her film-based installations, which present simple settings or actions, such as a girl performing a handstand, in short, 16mm film loops that are projected in the gallery space. In 2011 van Warmerdam took the decision to digitize most of her film installations. From a conservation perspective this is remarkable, since the disappearance of the analogue 16mm projectors from the gallery space significantly alters the experience of van W...

  9. The Two-Dimensional Analogue of General Relativity

    OpenAIRE

    Lemos, José P. S.; Sá, Paulo M.

    1993-01-01

    General Relativity in three or more dimensions can be obtained by taking the limit $\\omega\\rightarrow\\infty$ in the Brans-Dicke theory. In two dimensions General Relativity is an unacceptable theory. We show that the two-dimensional closest analogue of General Relativity is a theory that also arises in the limit $\\omega\\rightarrow\\infty$ of the two-dimensional Brans-Dicke theory.

  10. Developing hypnotic analogues of clinical delusions : Mirrored-self misidentification

    OpenAIRE

    Barnier, Amanda; Cox, Rochelle; O'Connor, Akira Robert; Coltheart, Max; Langdon, Robyn; Breen, Nora; Turner, Martha

    2008-01-01

    Introduction. Despite current research interest in delusional beliefs, there are no viable models for studying delusions in the laboratory. However, hypnosis offers a technique for creating transient delusions that are resistant to challenge. The aim of this study was to develop an hypnotic analogue of one important delusion, mirrored-self misidentification. Methods. Twelve high hypnotisable participants received an hypnotic suggestion to see either a stranger in the mirror, a mirror as a win...

  11. Dimerization and DNA recognition rules of mithramycin and its analogues.

    Science.gov (United States)

    Weidenbach, Stevi; Hou, Caixia; Chen, Jhong-Min; Tsodikov, Oleg V; Rohr, Jürgen

    2016-03-01

    The antineoplastic and antibiotic natural product mithramycin (MTM) is used against cancer-related hypercalcemia and, experimentally, against Ewing sarcoma and lung cancers. MTM exerts its cytotoxic effect by binding DNA as a divalent metal ion (Me(2+))-coordinated dimer and disrupting the function of transcription factors. A precise molecular mechanism of action of MTM, needed to develop MTM analogues selective against desired transcription factors, is lacking. Although it is known that MTM binds G/C-rich DNA, the exact DNA recognition rules that would allow one to map MTM binding sites remain incompletely understood. Towards this goal, we quantitatively investigated dimerization of MTM and several of its analogues, MTM SDK (for Short side chain, DiKeto), MTM SA-Trp (for Short side chain and Acid), MTM SA-Ala, and a biosynthetic precursor premithramycin B (PreMTM B), and measured the binding affinities of these molecules to DNA oligomers of different sequences and structural forms at physiological salt concentrations. We show that MTM and its analogues form stable dimers even in the absence of DNA. All molecules, except for PreMTM B, can bind DNA with the following rank order of affinities (strong to weak): MTM=MTM SDK>MTM SA-Trp>MTM SA-Ala. An X(G/C)(G/C)X motif, where X is any base, is necessary and sufficient for MTM binding to DNA, without a strong dependence on DNA conformation. These recognition rules will aid in mapping MTM sites across different promoters towards development of MTM analogues as useful anticancer agents. PMID:26760230

  12. Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF.

    Science.gov (United States)

    Ertas, Erdal; Demirtas, İlknur; Ozturk, Turan

    2015-01-01

    This review aims to give an overview of the current status of our research on the synthesis of π-electron donor bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF, ET) analogues prepared from 1,8-diketones via a ring forming reaction. The new synthesized π-electron donors have vinyl moieties producing extended π-electron delocalization over the substituent phenyl rings at the peripheries. PMID:25977714

  13. Matrix diffusion model. In situ tests using natural analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rasilainen, K. [VTT Energy, Espoo (Finland)

    1997-11-01

    Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories. 98 refs. The thesis includes also eight previous publications by author.

  14. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Melis, Marleen; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, V 220, Rotterdam (Netherlands); Boerman, Otto C. [Radboud University Hospital, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-05-15

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  15. On Quantum Analogue of The Caldero-Chapoton Formula

    OpenAIRE

    Rupel, Dylan

    2010-01-01

    Let $Q$ be any invertible valued quiver without oriented cycles. We study connections between the category of valued representations of $Q$ and expansions of cluster variables in terms of the initial cluster in quantum cluster algebras. We show that an analogue of the Caldero-Chapoton formula holds for all quantum cluster algebras of finite type and for any cluster variable in an almost acyclic cluster.

  16. Matrix diffusion model. In situ tests using natural analogues

    International Nuclear Information System (INIS)

    Matrix diffusion is an important retarding and dispersing mechanism for substances carried by groundwater in fractured bedrock. Natural analogues provide, unlike laboratory or field experiments, a possibility to test the model of matrix diffusion in situ over long periods of time. This thesis documents quantitative model tests against in situ observations, done to support modelling of matrix diffusion in performance assessments of nuclear waste repositories

  17. Ruling out stray thermal radiation in analogue black holes

    OpenAIRE

    Doukas, Jason; Adesso, Gerardo; Fuentes, Ivette

    2014-01-01

    Experimental searches for the thermal radiation from analogue black holes require the measurement of very low temperatures in regimes where other thermal noises may interfere or even mimic the sought-after effect. In this letter, we parameterize the family of bosonic thermal channels which give rise to such thermal effects and show that by use of coherent states and homodyne detection one can rule out the non-Hawking contributions and identify those candidate sources which arise from Hawking-...

  18. Drug-likeness of Phytic Acid and Its Analogues

    OpenAIRE

    Joy, Amitha; Balaji, S.

    2015-01-01

    Inositol hexakisphosphate is known to be the phosphorous reserve in plants particularly in the seeds. Though it has been known for its antinutrient properties for many years, recent research shed light to reveal it as a novel anticancer agent. Hence the present study investigates the drug-likeness of phytic acid and its analogues through bioinformatics methods. Two potential cancer drug targets such as mitogen activated kinase and inositol 1,4,5-triphosphate receptor are included in the study...

  19. Unstable analogues of the Lichtenbaum-Quillen conjecture

    OpenAIRE

    Anton, Marian; Roberts, Joshua

    2012-01-01

    This survey is mostly concerned with unstable analogues of the Lichtenbaum-Quillen Conjecture. The Lichtenbaum-Quillen Conjecture (now implied by the Voevodsky-Rost Theorem) attempts to describe the algebraic K-theory of rings of integers in number fields in terms of much more accessible "etale models". Suitable versions of the conjecture predict the cohomology of infinite general linear groups of rings of S-integers over suitable number fields; our survey focuses on an unstable version of th...

  20. Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

    International Nuclear Information System (INIS)

    This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower

  1. Simulated Milky Way analogues: implications for dark matter direct searches

    CERN Document Server

    Bozorgnia, Nassim; Schaller, Matthieu; Lovell, Mark; Bertone, Gianfranco; Frenk, Carlos S; Crain, Robert A; Navarro, Julio F; Schaye, Joop; Theuns, Tom

    2016-01-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best fit Maxwellian distribution (with peak speed of 223 - 289 km/s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter...

  2. q-bosons and the q-analogue quantized field

    International Nuclear Information System (INIS)

    The q-analogue coherent states |z >q are used to identify physical signatures for the presence of a q-analogue quantized radiation field in the | >q classical limit where |z| is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/|z|) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, HN = ℎω(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (ΔN)2/ → 0 as |z| → ∞. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, φq, still exhibits normal classical behavior. The standard number-phase uncertainty-relation, ΔN Δφq = 1/2, and the approximate commutation relation, [N,φq] = i, still hold for the single-mode q-analogue quantized field. So, N and φq are almost canonically conjugate operators in the |z >q classical limit. The |z >q CS's minimize this uncertainty relation for moderate |z|2

  3. Upgrading of analogue cameras using modern PC based computer

    International Nuclear Information System (INIS)

    Aim: The use of computers along with analogue cameras enables them to perform tasks involving time-activity parameters. The INFORMENU system converts a modern PC computer into a dedicated nuclear medicine computer system with a total cost affordable to emerging economic countries, and easily adaptable to all existing cameras. Materials and Methods: In collaboration with nuclear medicine physicians, an application including hardware and software was developed by a private firm. The system runs smoothly on Windows 98 and its operation is very easy. The main features are comparable to the brand commercial computer systems; such as image resolution until 1024 x 1024, low count loss at high count rate, uniformity correction, integrated graphical and text reporting, and user defined clinical protocols. Results: The system is used in more than 20 private and public institutions. The count loss is less than 1% in all the routine work, improvement of uniformity correction of 3-5 times, improved utility of the analogue cameras. Conclusion: The INFORMENU system improves the utility of analogue cameras permitting the inclusion of dynamic clinical protocols and quantifications, helping the development of the nuclear medicine practice. The operation and maintenance costs were lowered. The end users improve their knowledge of modern nuclear medicine

  4. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G. Saulnier and W. Statham

    2006-04-16

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table.

  5. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    International Nuclear Information System (INIS)

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. The Pena Blanca Natural Analogue Performance Assessment Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash-flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following analogous characteristics as compared to the Yucca Mountain repository site: (1) Analogous source--UO2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geology--(i.e. fractured, welded, and altered rhyolitic ash-flow tuffs); (3) Analogous climate--Semiarid to arid; (4) Analogous setting--Volcanic tuffs overlie carbonate rocks; and (5) Analogous geochemistry--Oxidizing conditions Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table

  6. Natural analogue studies as supplements to biomineralization research

    Energy Technology Data Exchange (ETDEWEB)

    McNeil, M.B. [Nuclear Regulatory Commission, Washington, DC (United States)

    1995-09-01

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu{sub 4}SO{sub 4}(OH){sub 6{center_dot}}H{sub 2}O] and mineral morphologies unusual in corrosion [malachite, Cu{sub 2}CO{sub 3}(OH){sub 2}, rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena].

  7. Simulated Milky Way analogues: implications for dark matter direct searches

    Science.gov (United States)

    Bozorgnia, Nassim; Calore, Francesca; Schaller, Matthieu; Lovell, Mark; Bertone, Gianfranco; Frenk, Carlos S.; Crain, Robert A.; Navarro, Julio F.; Schaye, Joop; Theuns, Tom

    2016-05-01

    We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the EAGLE and APOSTLE projects. We identify Milky Way analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best fit Maxwellian distribution (with peak speed of 223–289 km/s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter mass, the halo-to-halo variation of the local dark matter density results in an overall shift of the allowed regions and exclusion limits for the cross section. However, the compatibility of the possible hints for a dark matter signal from DAMA and CDMS-Si and null results from LUX and SuperCDMS is not improved.

  8. Natural analogue studies as supplements to biomineralization research

    International Nuclear Information System (INIS)

    Chemical reactions can alter the chemistry and crystal structure of solid objects over archeological or geological times, while preserving external physical shapes. The reactions resulting in these structures offer natural analogues to laboratory experiments in biomineralization and to biologically influenced alteration of nuclear waste packages, and thus, they offer the only available way of validating models that purport waste package behavior over archaeological or geological times. Potential uses of such analogues in the construction and validation of hypothetical mechanisms of microbiological corrosion and biomineralization are reviewed. Evidence from such analogues suggests that biofilms can control materials alteration in ways usually overlooked. The newly hypothesized mechanisms involve control by biofilms of the cation flow near the solid surface and offer plausible mechanisms for the formation of mixed-cation minerals under conditions that would lead to dealloying in abiotic experiments; they also account for the formation of unusual minerals [such as posnjakite, Cu4SO4(OH)6·H2O] and mineral morphologies unusual in corrosion [malachite, Cu2CO3(OH)2, rarely forms botryoidally under corrosion conditions and its occasional presence on archaeological objects that appear to have undergone microbiological corrosion may be related to biofilm phenomena

  9. Contact zones and hydrothermal systems as analogues to repository conditions

    International Nuclear Information System (INIS)

    Radioactive waste isolation efforts in the US are currently focused on examining basalt, tuff, salt, and crystalline rock as candidate rock types to encompass waste repositories. As analogues to near-field conditions, the distributions of radio- and trace-elements have been examined across contacts between these rocks and dikes and stocks that have intruded them. The intensive study of the Stripa quartz monzonite has also offered the opportunity to observe the distribution of uranium and its daughters in groundwater and its relationship to U associated with fracture-filling and alteration minerals. Investigations of intrusive contact zones to date have included (1) a tertiary stock into Precambrian gneiss, (2) a stock into ash flow tuff, (3) a rhyodacite dike into Columbia River basalt, and (4) a kimberlite dike into salt. With respect to temperature and pressure, these contact zones may be considered ''worst-case scenario'' analogues. Results indicate that there has been no appreciable migration of radioelements from the more radioactive intrusives into the less radioactive country rocks, either in response to the intrusions or in the fracture-controlled hydrological systems that developed following emplacement. In many cases, the radioelements are locked up in accessory minerals, suggesting that artificial analogues to these would make ideal waste forms. Emphasis should now shift to examination of active hydrothermal systems, studying the distribution of key elements in water, fractures, and alteration minerals under pressure and temperature conditions most similar to those expected in the near-field environment of a repository. 14 refs

  10. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  11. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia

  12. Post-exercise abdominal, subcutaneous adipose tissue lipolysis in fasting subjects is inhibited by infusion of the somatostatin analogue octreotide

    DEFF Research Database (Denmark)

    Enevoldsen, Lotte H; Polak, Jan; Simonsen, Lene;

    2007-01-01

    To determine whether blockade of the exercise-induced increase in growth hormone (GH) secretion may affect the regional lipolytic rate in the post-exercise recovery period, the aim of the present experiments was to study the effect of infusion of the somatostatin analogue octreotide on the s.......c., abdominal adipose tissue metabolism, before, during and after exercise in healthy, fasting, young male subjects. The adipose tissue net releases of fatty acids and glycerol were measured by arterio-venous catheterizations and simultaneous measurements of adipose tissue blood flow with the local Xe...

  13. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    International Nuclear Information System (INIS)

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H2O2 or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H2O2 and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H2O2-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia/reperfusion (I/R) injury in vivo. • Compound 14

  14. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    International Nuclear Information System (INIS)

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO2 uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 ± 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory analysis

  15. THE PENA BLANCA NATURAL ANALOGUE PERFORMANCE ASSESSMENT MODEL

    Energy Technology Data Exchange (ETDEWEB)

    G.J. Saulnier Jr; W. Statham

    2006-03-10

    The Nopal I uranium mine in the Sierra Pena Blanca, Chihuahua, Mexico serves as a natural analogue to the Yucca Mountain repository. The Pena Blanca Natural Analogue Performance Assessment Model simulates the mobilization and transport of radionuclides that are released from the mine and transported to the saturated zone. the Pena Blanca Natural Analogue Model uses probabilistic simulations of hydrogeologic processes that are analogous to the processes that occur at the Yucca Mountain site. The Nopal I uranium deposit lies in fractured, welded, and altered rhyolitic ash flow tuffs that overlie carbonate rocks, a setting analogous to the geologic formations at the Yucca Mountain site. The Nopal I mine site has the following characteristics as compared to the Yucca Mountain repository site. (1) Analogous source: UO{sub 2} uranium ore deposit = spent nuclear fuel in the repository; (2) Analogous geologic setting: fractured, welded, and altered rhyolitic ash flow tuffs overlying carbonate rocks; (3) Analogous climate: Semiarid to arid; (4) Analogous geochemistry: Oxidizing conditions; and (5) Analogous hydrogeology: The ore deposit lies in the unsaturated zone above the water table. The Nopal I deposit is approximately 8 {+-} 0.5 million years old and has been exposed to oxidizing conditions during the last 3.2 to 3.4 million years. The Pena Blanca Natural Analogue Model considers that the uranium oxide and uranium silicates in the ore deposit were originally analogous to uranium-oxide spent nuclear fuel. The Pena Blanca site has been characterized using field and laboratory investigations of its fault and fracture distribution, mineralogy, fracture fillings, seepage into the mine adits, regional hydrology, and mineralization that shows the extent of radionuclide migration. Three boreholes were drilled at the Nopal I mine site in 2003 and these boreholes have provided samples for lithologic characterization, water-level measurements, and water samples for laboratory

  16. Opioid profiles of Cys2-containing enkephalin analogues.

    Science.gov (United States)

    Pencheva, Nevena; Milanov, Peter; Vezenkov, Lubomir; Pajpanova, Tamara; Naydenova, Emilia

    2004-09-13

    To elucidate the structural features determining delta-opioid receptor properties of enkephalin analogues containing Cys(O2NH2) in position 2, a series of Cys2-containing derivatives were synthesized and tested for their effectiveness in depressing electrically evoked contractions of the mouse vas deferens (predominantly enkephalin-selective delta-opioid receptors) and the guinea-pig ileum (mu- and kappa-opioid receptors). The peptidase resistance of the compounds was also tested. The ratio IC50 in the guinea-pig ileum/IC50 in the mouse vas deferens, indicating selectivity for delta-opioid receptors, was high for Cys(O2NH2)2-containing analogues and especially for [Cys(O2NH2)2, Leu5]enkephalin, which was about seven times more selective than delta-opioid receptor selective ligand cyclic [D-Pen2, D-Pen5]enkephalin (DPDPE). The dissociation constant (KA) and relative efficacy (e(rel)) of the compounds in the mouse-isolated vas deferens were determined using explicit formulae derived by fitting of the data points with two-parametric hyperbolic function. The obtained values for KA and e(rel) suggest that: (i) incorporation of Cys(O2NH2)2 in the molecule of [Leu5]enkephalin highly increases the efficacy and does not change significantly the affinity of the respective analogues to delta-opioid receptors; [Cys(O2NH2)2, Leu5]enkephalin has higher affinity than DPDPE, but is less resistant to enzyme degradation; the effect of this modification on the efficacy is decreased when methionine is in position 5; (ii) D-configuration of Cys(O2NH2)2-containing analogues increases their peptidase resistance, but reduces efficacy and affinity of the peptides towards delta-opioid receptors; (iii) the substitution of Cys(O2NH2) with Hcy(O2NH2) reduces the efficacy, affinity and potency of the respective analogues and maintains their sensitivity to endogenous peptidases; (iv) the substitution of the sulfonamide group with benzyl group in the molecule of Cys in position 2 decreases their

  17. Compound A398, a novel podophyllotoxin analogue: cytotoxicity and induction of apoptosis in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Alethéia L Silveira

    Full Text Available Despite advances in oncology research, cancer is one of the leading causes of death worldwide. Thus, there is a demand for the development of more selective and effective antitumor agents. This study showed that A398, a novel podophyllotoxin analogue, was cytotoxic to the HT-29, MCF-7, MOLT-4 and HL-60 tumor cell lines, being less active in human peripheral blood mononuclear cells and normal cell lines FGH and IEC-6. Tests using the HepG2 lineage indicated that its metabolites do not contribute to its cytotoxicity. In the HL-60 cells, A398 induced apoptosis in a time and concentration-dependent manner, promoting mitochondrial depolarization, inhibition of Bcl-2, phosphatidylserine exposure, activation of caspases -8, -9 and -3, and DNA fragmentation. The production of reactive oxygen species does not seem to be a crucial event for the apoptotic process. Pretreatment with specific inhibitors of kinases ERK1/2, JNK and p38 resulted in an increased percentage of death induced by A398. These results indicate that the compound induced apoptosis through activation of intrinsic and extrinsic death pathways with the mechanism involving the inhibition of the MAPKs and Bcl-2. Taken together, our findings suggest that A398 has an anticancer potential, proving itself to be a candidate for preclinical studies.

  18. Analogue modelling of the influence of ice shelf collapse on the flow of ice sheets grounded below sea-level

    Science.gov (United States)

    Corti, Giacomo; Zeoli, Antonio

    2016-04-01

    The sudden breakup of ice shelves is expected to result in significant acceleration of inland glaciers, a process related to the removal of the buttressing effect exerted by the ice shelf on the tributary glaciers. This effect has been tested in previous analogue models, which however applied to ice sheets grounded above sea level (e.g., East Antarctic Ice Sheet; Antarctic Peninsula and the Larsen Ice Shelf). In this work we expand these previous results by performing small-scale laboratory models that analyse the influence of ice shelf collapse on the flow of ice streams draining an ice sheet grounded below sea level (e.g., the West Antarctic Ice Sheet). The analogue models, with dimensions (width, length, thickness) of 120x70x1.5cm were performed at the Tectonic Modelling Laboratory of CNR-IGG of Florence, Italy, by using Polydimethilsyloxane (PDMS) as analogue for the flowing ice. This transparent, Newtonian silicone has been shown to well approximate the rheology of natural ice. The silicone was allowed to flow into a water reservoir simulating natural conditions in which ice streams flow into the sea, terminating in extensive ice shelves which act as a buttress for their glaciers and slow their flow. The geometric scaling ratio was 10(-5), such that 1cm in the models simulated 1km in nature; velocity of PDMS (a few mm per hour) simulated natural velocities of 100-1000 m/year. Instability of glacier flow was induced by manually removing a basal silicone platform (floating on water) exerting backstresses to the flowing analogue glacier: the simple set-up adopted in the experiments isolates the effect of the removal of the buttressing effect that the floating platform exerts on the flowing glaciers, thus offering insights into the influence of this parameter on the flow perturbations resulting from a collapse event. The experimental results showed a significant increase in glacier velocity close to its outlet following ice shelf breakup, a process similar to what

  19. The risk factors and mutation patterns of HBV gene mutation induced by nucleos(t)ide analogue therapy%核苷(酸)类药物引起HBV基因突变的危险因素与模式分析

    Institute of Scientific and Technical Information of China (English)

    张小曼; 肖子鸿; 张纯瑜; 魏开鹏; 潘兴南

    2015-01-01

    目的 分析应用核苷(酸)类药物(NA)治疗慢性乙型肝炎(CHB)患者耐药基因突变发生的危险因素和突变模式.方法 选取本院经NA治疗的209例CHB患者,采用直接测序法检测患者血清标本中的HBV基因分型及耐药位点,并对结果进行分析,对可能影响HBV逆转录酶(RT)区耐药基因突变的危险因素,包括年龄、性别、基因型、HBeAg状态、HBV DNA水平、HBsAg阳性时间、家族史、病期、核苷(酸)类药物选择以及用药时间等进行统计分析,筛选出独立危险因素.结果 年龄、基因型、NA药物选择及用药时间与HBV RT区耐药基因突变发生相关.209例患者测序结果中86例发现有耐药基因突变,突变率为41.15%,B型和C型基因患者耐药突变率分别33.67%和47.75%,差异具有统计学意义(χ2= 4.25,P< 0.05),但Logistic回归分析表明基因型不是HBV耐药基因突变发生的独立危险因素.HBV RT区突变以rtM204V/I(79.1%)、rtA181V/T/A/S(19.8%)和rtN236T(11.6%)突变株为主,rtM204V位点变异大多伴随了rtL180M突变.结论 年龄大于45岁、曾使用LAM或LDT进行长时间治疗的CHB人群更容易导致HBV突变的发生,在使用NA治疗慢性乙型肝炎患者过程中,出现的变异模式复杂多样,应及时监测患者耐药基因以指导临床用药.%Objective To analyze the risk factors that affect gene mutations in HBV reverse transcriptase gene and the mutation patterns in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogue therapy.Methods Among the 209 patients with CHB treated with nucleos(t)ide analogue therapy, HBV reverse transcriptase gene was analyzed by a direct PCR sequencing assay. The factors including age, sex, genotype, HBeAg status, level of serum HBV DNA, course of diseases, HBsAg positive time, family history of CHB, drug of choice and therapeutic time were analyzed, respectively. Independent risk factors related to HBV gene mutation were screened by statistical

  20. How many collisions for a neutron in a Tripoli non analogue simulation?

    International Nuclear Information System (INIS)

    In an analogue simulation, flux, current, etc. are estimated, and for each particle, the number of shocks is counted and the distance covered is calculated. When the attenuation is significant the natural simulation remains inefficient: it becomes necessary to use variance reduction methods in which the solution of the adjoint transport equation is essential; this is the non analogue simulation. This study analyzes the average behaviour during analogue and non analogue simulations for one-energy group, one dimension transport problem with isotropic shocks. Comparisons between these simulations give hints about why an optimal simulation exists. The penetration problem and the results of the analogue simulation are first presented; then the non analogue simulations are run with path stretching and angular biasing of the scattering kernel, the most important biasing techniques of the Monte Carlo transport TRIPOLI code. (from authors) 11 figs., 3 tabs., 3 refs

  1. Combretastatin A-4 analogues with benzoxazolone scaffold: Synthesis, structure and biological activity.

    Science.gov (United States)

    Gerova, Mariana S; Stateva, Silviya R; Radonova, Elena M; Kalenderska, Rositsa B; Rusew, Rusi I; Nikolova, Rositsa P; Chanev, Christo D; Shivachev, Boris L; Apostolova, Margarita D; Petrov, Ognyan I

    2016-09-14

    In order to design and synthesize a new class of heterocyclic analogues of natural combretastatin A-4 and its synthetic derivative AVE8062, the benzoxazolone ring was selected as a scaffold for a bioisosteric replacement of the ring B of both molecules. A library of 28 cis- and trans-styrylbenzoxazolones was obtained by a modified Wittig reaction under Boden's conditions. Structures of the newly synthesized compounds bearing the 3,4,5-trimethoxy-, 3,4-dimethoxy-, 3,5-dimethoxy-, and 4-methoxystyryl fragment at position 4, 5, 6 or 7 of benzoxazolone core were determined on the basis of spectral and X ray data. The in vitro cytotoxicity of styrylbenzoxazolones against different cell lines was examined. Stilbene derivative 16Z, (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzoxazolone, showed highest antiproliferative potential of the series, with IC50 of 0.25 μM against combretastatin resistant cell line HT-29, 0.19 μM against HepG2, 0.28 μM against EA.hy926 and 0.73 μM against K562 cells. Furthermore, the results of flow cytometric analysis confirmed that 16Z induced cell cycle arrest in G2/M phase in the cell lines like combretastatin A-4. This arrest is followed by an abnormal exit of cells from mitosis without cytokinesis into a pseudo G1-like multinucleate state leading to late apoptosis and cell death. Accordingly, synthetic analogue 16Z was identified as the most promising potential anticancer agent in present study, and was selected as lead compound for further detailed investigations. PMID:27187864

  2. Quantum Analogues: From Phase Transitions to Black Holes and Cosmology

    International Nuclear Information System (INIS)

    'And I cherish more than anything else the analogies, my most trustworthy masters. They know all the secrets of nature, and they ought to be least neglected in geometry.' These words of the great astronomer Johannes Kepler embody the philosophy behind the research recounted in this interesting book-a book composed of nine selected lectures (and a nice introduction by Bill Unruh) from the international workshop on 'Quantum Simulations via Analogues', which was held in the Max Planck Institute for the Physics of Complex Systems in Dresden during the summer of 2005. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. However the last decade has seen a remarkable and steady development of analogue gravity models based on condensed matter systems, leading to some hundreds of published articles, numerous workshops, and several books. While the main driver for this booming field has definitely been the puzzling physics associated with quantum effects in black holes, more recently much attention has also been devoted to other interesting issues-such as cosmological particle production or the cosmological constant problem. Moreover, together with these new themes there has been a persistent interest in the possibility of simulating cosmic topological defects in the laboratory (although it should be said that momentum for this line of research has been somewhat weakened by the progressive decrease of interest in cosmological topological defects as an alternative to inflationary scenarios). All these aspects are faithfully accounted for in this book, which does a good job at presenting a vivid snapshot of many (if not quite all) of the most interesting lines of research in the field. All the articles have a self-consistent structure-which allows one to read them in arbitrary order and appreciate the full richness of each topic. However, when considered together I would say that they also provide a

  3. Quantitative comparisons of analogue models of brittle wedge dynamics

    Science.gov (United States)

    Schreurs, Guido

    2010-05-01

    Analogue model experiments are widely used to gain insights into the evolution of geological structures. In this study, we present a direct comparison of experimental results of 14 analogue modelling laboratories using prescribed set-ups. A quantitative analysis of the results will document the variability among models and will allow an appraisal of reproducibility and limits of interpretation. This has direct implications for comparisons between structures in analogue models and natural field examples. All laboratories used the same frictional analogue materials (quartz and corundum sand) and prescribed model-building techniques (sieving and levelling). Although each laboratory used its own experimental apparatus, the same type of self-adhesive foil was used to cover the base and all the walls of the experimental apparatus in order to guarantee identical boundary conditions (i.e. identical shear stresses at the base and walls). Three experimental set-ups using only brittle frictional materials were examined. In each of the three set-ups the model was shortened by a vertical wall, which moved with respect to the fixed base and the three remaining sidewalls. The minimum width of the model (dimension parallel to mobile wall) was also prescribed. In the first experimental set-up, a quartz sand wedge with a surface slope of ˜20° was pushed by a mobile wall. All models conformed to the critical taper theory, maintained a stable surface slope and did not show internal deformation. In the next two experimental set-ups, a horizontal sand pack consisting of alternating quartz sand and corundum sand layers was shortened from one side by the mobile wall. In one of the set-ups a thin rigid sheet covered part of the model base and was attached to the mobile wall (i.e. a basal velocity discontinuity distant from the mobile wall). In the other set-up a basal rigid sheet was absent and the basal velocity discontinuity was located at the mobile wall. In both types of experiments

  4. Alligator Rivers Analogue Project. Final Report - Volume 1

    International Nuclear Information System (INIS)

    This summary report, which highlights the work and findings of the Alligator Rivers Analogue Project (ARAP) is one of a series of 16 volumes, listed below. Detailed descriptions and results are provided in Volumes 2 to 16. Full acknowledgment to individual contributions is provided in the individual reports, and in Appendix I of this report. The findings from the technical studies are discussed in the context of assessments of the long-term performance of geological repositories for radioactive wastes, which are being undertaken in many countries. They are also considered in an integrated 'Scenario Development' approach, aimed to understand the formation of the ore deposit. Despite their inherent uncertainties, the findings provide a basis for assessing the way in which radionuclides will migrate in environments with a variety of geologic settings and over a range of different geologic timescales. Thus, section 2 of this report discusses the concept of using uranium deposits as natural analogues and refers to a number of such studies, including those at the Koongarra deposit in the Alligator Rivers Region of the Northern Territory of Australia. Section 3 reviews early scientific work in the Alligator Rivers Region and summarises the results of the analogue studies undertaken between 1981 and 1987 that were funded by the US Nuclear Regulatory Commission (USNRC) and the UK Department of the Environment (UKDoE). Section 4 describes the objectives of ARAP and the manner in which the study was conducted and provides a general outline of the project and a summary of the findings. A general description of the Koongarra ore deposit, the focus of ARAP, is provided in Section 5, with Sections 6-13 providing summaries of the work carried out to characterise the site in detail and provide data for modelling. Sections 14-18 discuss how this data was used in modelling and how the results may be applied for performance assessment studies. Finally, Section 19 considers the

  5. Dynamics of water in prussian blue analogues: Neutron scattering study

    Science.gov (United States)

    Sharma, V. K.; Mitra, S.; Thakur, N.; Yusuf, S. M.; Juranyi, Fanni; Mukhopadhyay, R.

    2014-07-01

    Dynamics of crystal water in Prussian blue (PB), Fe(III)4[Fe(II)(CN)6]3.14H2O and its analogue Prussian green (PG), ferriferricynaide, Fe(III)4[Fe(III)(CN)6]4.16H2O have been investigated using Quasielastic Neutron Scattering (QENS) technique. PB and its analogue compounds are important materials for their various interesting multifunctional properties. It is known that crystal water plays a crucial role towards the multifunctional properties of Prussian blue analogue compounds. Three structurally distinguishable water molecules: (i) coordinated water molecules at empty nitrogen sites, (ii) non-coordinated water molecules in the spherical cavities, and (iii) at interstitial sites exist in PB. Here spherical cavities are created due to the vacant sites of Fe(CN)6 units. However, PG does not have any such vacant N or Fe(CN)6 units, and only one kind of water molecules, exists only at interstitial sites. QENS experiments have been carried out on both the compounds in the temperature range of 260-360 K to elucidate the dynamical behavior of different kinds of water molecules. Dynamics is found to be much more pronounced in case of PB, compared to PG. A detailed data analysis showed that localized translational diffusion model could describe the observed data for both PB and PG systems. The average diffusion coefficient is found to be much larger in the PB than PG. The obtained domain of dynamics is found to be consistent with the geometry of the structure of the two systems. Combining the data of the two systems, a quantitative estimate of the dynamics, corresponding to the water molecules at different locations is made.

  6. Properties of granular analogue model materials: A community wide survey

    Science.gov (United States)

    Klinkmüller, Matthias; Schreurs, Guido; Rosenau, Matthias; Kemnitz, Helga

    2016-04-01

    We report the material properties of 26 granular analogue materials used in 14 analogue modelling laboratories. We determined physical characteristics such as bulk density, grain size distribution, and grain shape, and performed ring shear tests to determine friction angles and cohesion, and uniaxial compression tests to evaluate the compaction behaviour. Mean grain size of the materials varied between (c. 100 and 400 micrometer). Analysis of grain shape factors show that the four different classes of granular materials (14 quartz sands, 5 dyed quartz sands, 4 heavy mineral sands and 3 size fractions of glass beads) can be broadly divided into two groups consisting of 12 angular and 14 rounded materials. Grain shape has an influence on friction angles, with most angular materials having higher internal friction angles (between c. 35° and 40°) than rounded materials, whereas well-rounded glass beads have the lowest internal friction angles (between c. 25° and 30°). We interpret this as an effect of intergranular sliding versus rolling . Most angular materials have also higher basal friction angles (tested for a specific foil) than more rounded materials, suggesting that angular grains scratch and wear the foil., Most materials have a cohesion in the order of 10-100 Pa except for well-rounded glass beads, which show a trend towards a quasi-cohesionless (C tests reveal that rounded grains generally show less compaction than angular grains. We interpret this to be related to the initial packing density reached during sieving which is higher for rounded grains than for angular grains. Ring-shear test data show that angular grains undergo a longer strain-hardening phase than more rounded materials. This might explain why analogue models consisting of angular grains accommodate deformation in a more distributed manner prior to strain localisation than models consisting of rounded grains. Also, models build with angular grains will tend to show more dilatancy during

  7. Palmottu natural analogue: A summary of the studies

    Energy Technology Data Exchange (ETDEWEB)

    Ahonen, L.; Kaija, J.; Paananen, M.; Ruskeeniemi, T.; Hakkarainen, V.

    2004-07-01

    This report is a review of research activities performed in the framework of Palmottu natural analogue studies. This uranium occurrence at Nummi-Pusula, Southern Finland has been a target of extensive studies since 1987, initially as a national analogue study 1996 - 2000, later on as an EU-financed international study 1996 - 2000. After that, up to 2003, Palmottu data has been used in an IAEA coordinated research project 'The use of selected safety indicators in the assessment of radioactive waste disposal'. The report gives an extensive summary of the hydrogeological research conducted, with a special emphasis on the methodology used. A wide variety of borehole geophysical and hydrogeological methods was used during the study, and are described in the report. An areal geohydrological model, based mainly on map- and airborne survey data, is presented, as well as a three-dimensional structural model of the site. Bedrock groundwater studies at Palmottu included development and use of new sampling methods. Swedish SKB sampling equipment was also used in the redoxpotential measurements and groundwater sampling. A summary of the representative groundwater Eh-values is presented in the report. For uranium, distribution in different geological units were estimated. Isotope values of some samples indicate a potential contribution of glacial melt water. Different modelling tasks were included in the Palmottu analogue study: modelling of speciation and solubility of dissolved elements, blind predictive modelling (BPM) with an intercomparison of results between different groups, and comparative transport modelling using different conceptual approaches. A updated list of Palmottu-related publications and reports is included in the report. (orig.)

  8. Palmottu natural analogue: A summary of the studies

    International Nuclear Information System (INIS)

    This report is a review of research activities performed in the framework of Palmottu natural analogue studies. This uranium occurrence at Nummi-Pusula, Southern Finland has been a target of extensive studies since 1987, initially as a national analogue study 1996 - 2000, later on as an EU-financed international study 1996 - 2000. After that, up to 2003, Palmottu data has been used in an IAEA coordinated research project 'The use of selected safety indicators in the assessment of radioactive waste disposal'. The report gives an extensive summary of the hydrogeological research conducted, with a special emphasis on the methodology used. A wide variety of borehole geophysical and hydrogeological methods was used during the study, and are described in the report. An areal geohydrological model, based mainly on map- and airborne survey data, is presented, as well as a three-dimensional structural model of the site. Bedrock groundwater studies at Palmottu included development and use of new sampling methods. Swedish SKB sampling equipment was also used in the redoxpotential measurements and groundwater sampling. A summary of the representative groundwater Eh-values is presented in the report. For uranium, distribution in different geological units were estimated. Isotope values of some samples indicate a potential contribution of glacial melt water. Different modelling tasks were included in the Palmottu analogue study: modelling of speciation and solubility of dissolved elements, blind predictive modelling (BPM) with an intercomparison of results between different groups, and comparative transport modelling using different conceptual approaches. A updated list of Palmottu-related publications and reports is included in the report. (orig.)

  9. Critical behaviour of dynamic analogues of equilibrium lattice models

    International Nuclear Information System (INIS)

    It is not difficult to construct chaotic Coupled Map Lattices (CMLs) that display the type of synchronization usually associated to Phase Transitions (PTs) in equilibrium statistical models. These CMLs show the emergence of an order parameter that signals longrange order in the lattice, without losing its chaotic character (the existence of a positive sector in the Lyapunov spectrum). This order parameter remains null for small couplings, and changes to non-zero values for couplings above some critical value. Around this critical coupling one also has strong fluctuations in both long- and short-range correlations. In this work two examples are reviewed, the Miller-Huse CML, which is a dynamical analogue to the Ising model, and a recently constructed dynamical analogue to the q = 3 Potts Model. Both models are constructed using fully hyperbolic continuous piece-wise linear mappings, and a diffusive coupling. It is shown for both examples how the symmetries of the models allows one to connect to the corresponding equilibrium classes. The critical behaviour of Miller-Huse in two dimensions (2D) under simultaneous updating is revisited, and new results for this model in a triangular lattice are shown, including a careful evaluation of the effects of the leading correction to scaling. It is concluded that this model does belong to the 2D Ising Universality Class. For the dynamical analogue to the q = 3 Potts Model a well defined order-disorder PT is also found. The phase diagrams for both simultaneous and sequential updating of the model are obtained. For simultaneous updating a line of continuous PTs is found. The corresponding critical exponents-again, including a leading correction to scaling- are consistent with those of the equilibrium Potts Model

  10. Anti-inflammatory and Immune Regulatory Properties of 5-Androsten-3{beta}, 17{beta}-Diol (HE2100), and Synthetic Analogue HE3204: Implications for Treatment of Autoimmune Diseases.

    NARCIS (Netherlands)

    Auci, D.; Nicoletti, F.; Mangano, K.; Pieters, R.; Nierkens, S.; Morgan, L.; Offner, H.; Frincke, J.; Reading, C.

    2005-01-01

    5-Androsten-3beta, 17beta-diol (HE2100), and a synthetic analogue HE3204 are regarded as immune-regulating hormones, because both induce changes in the reporter antigen-popliteal lymph node assay (RA-PLNA). Mice were injected in the footpad with either HE2100 or HE3204 (0.01-3 mg), and a nonsensitiz

  11. Enantioselective reduction of acetophenone analogues using carrot and celeriac enzymes system

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The enantioselective reduction of acetophenone analogues catalyzed by carrot and celeriac was performed in moderate conversions and excellent enantiomeric excesses.The steric factors and electronic effects of the substituents at the aromatic ring were found to significantly affect the efficiency of the enantioselective reduction of acetophenone analogues,while they had a little effect on the enantioselectivity of acetophenone analogues reduction.It was also found that the conversions of acetophenone anal...

  12. Cytotoxic purine nucleoside analogues bind to A1, A2A and A3 adenosine receptors

    OpenAIRE

    Jensen, Kyle; Johnson, L’Aurelle A.; Jacobson, Pamala A.; Kachler, Sonja; Kirstein, Mark N.; Lamba, Jatinder; Klotz, Karl-Norbert

    2012-01-01

    Fludarabine, clofarabine and cladribine are anti-cancer agents which are analogues of the purine nucleoside adenosine. These agents have been associated with cardiac and neurological toxicities. Because these agents are analogues of adenosine, they may act through adenosine receptors to elicit their toxic effects. The objective of this study was to evaluate the ability of cytotoxic nucleoside analogues to bind and activate adenosine receptor subtypes (A1, A2A, A2B, and A3). Radioligand bindin...

  13. Quality of casein based Mozzarella cheese analogue as affected by stabilizer blends

    OpenAIRE

    Jana, A. H.; Patel, H. G.; Suneeta, Pinto; Prajapati, J. P.

    2010-01-01

    Suitability of xanthan gum (XG)-locust bean gum (LBG), carrageenan (CAR)-LBG, and XG-CAR in 1:1 proportion at 0.42% in the formulation was assessed in the manufacture of Mozzarella cheese analogue. The stabilizer blends did not significantly influence the composition, texture profile, organoleptic, baking qualities and pizza-related characteristics of cheese analogues. Considering the influence of stabilizer blend on the sensory quality of analogue and sensory rating of pizza pie, XG-LBG blen...

  14. Presence and formation of cobalamin analogues in multivitamin-mineral pills.

    OpenAIRE

    Kondo, H.; Binder, M J; Kolhouse, J F; Smythe, W. R.; Podell, E R; Allen, R. H.

    1982-01-01

    Because the origin of cobalamin (vitamin B12) analogues in animal chows and animal and human blood and tissues is unknown, we investigated the possibility that multivitamin interactions might convert cobalamin to cobalamin analogues. We homogenized three popular multivitamin-mineral pills in water, incubated them at 37 degrees C for 2 h, and isolated the cobalamin. Using paper chromatography we observed that 20-90% of the cobalamin was present as cobalamin analogues. Studies using CN-[57Co]co...

  15. Development of labelled somatostatin and its analogues for the diagnosis and treatment of tumors

    International Nuclear Information System (INIS)

    For recent years, the labelling and application of Somatostatin and Its Analogues have been becoming more and more important in the both diagnosis and treatment of a variety of tumors, especially the neuroendocrine tumors. This paper's goals are to deal with the chemical aspects of the radiolabelling of somatostatin and its analogues. It reviews the selected radionuclide and bifunctional chelating agents may be used in the labeling of Somatostatin and its analogues are comparatively assessed. (author). 30 refs., 3 tabs

  16. The thermoelastic properties of post-perovskite analogue phases

    OpenAIRE

    Lindsay-Scott, A.

    2011-01-01

    Post-perovskite MgSiO3 is a major component of the D'' zone at the base of the lower mantle, so knowledge of its physical properties is essential to understanding mantle dynamics. Unfortunately, MgSiO3 post-perovskite is stable only at Mbar pressures. This difficulty can be addressed by combining computer simulations with experiments on analogue post-perovskite ABX3 phases, stable at ambient pressure and temperature. In this project, the properties of MgSiO3 and other oxide and...

  17. Analogue Aharonov-Bohm effect in neo-Newtonian theory

    CERN Document Server

    Anacleto, M A; Brito, F A; Passos, E

    2015-01-01

    We address the issues of the scattering of massless planar scalar waves by an acoustic black hole in neo-Newtonian hydrodynamics. We then compute the differential cross section through the use of the partial wave approach in the neo-Newtonian theory which is a modification of the usual Newtonian theory that correctly incorporates the effects of pressure. We mainly show that the scattering of planar waves leads to a modified analogue Aharonov-Bohm effect due to a nontrivial response of the parameters defining the equation of state.

  18. Analogue Aharonov-Bohm effect in neo-Newtonian theory

    Science.gov (United States)

    Anacleto, M. A.; Salako, I. G.; Brito, F. A.; Passos, E.

    2015-12-01

    We address the issues of the scattering of massless planar scalar waves by an acoustic black hole in neo-Newtonian hydrodynamics. We then compute the differential cross section through the use of the partial wave approach in the neo-Newtonian theory which is a modification of the usual Newtonian theory that correctly incorporates the effects of pressure. We mainly show that the scattering of planar waves leads to a modified analogue Aharonov-Bohm effect due to a nontrivial response of the parameters defining the equation of state.

  19. Are Structural Analogues to Bisphenol A Safe Alternatives?

    DEFF Research Database (Denmark)

    Rosenmai, Anna Kjerstine; Dybdahl, Marianne; Pedersen, Mikael;

    2014-01-01

    Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus, a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives......, there is a risk of effects similar to BPA.Objectives: The aim was to elucidate and compare the hazards of bisphenol B (BPB), bisphenol E (BPE), bisphenol F (BPF), bisphenol S (BPS) and 4-cumylphenol (HPP) to BPA.Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect...

  20. Characterizing the magnetic fields of the first tau Sco analogues

    OpenAIRE

    Petit, V.; Kochukhov, O.; Massa, D. L.; Marcolino, W. L. F.; Wade, G. A.; Ignace, R.

    2011-01-01

    The B0.2 V magnetic star tau Sco stands out from the larger population of massive OB stars due to its high X-ray activity, peculiar wind diagnostics and complex magnetic field. Recently, Petit et al. 2011 presented the discovery of the first two tau Sco analogues -- HD 66665 and HD 63425, identified by the striking similarity of their UV spectra to that of tau Sco. ESPaDOnS and Narval spectropolarimetric observations were obtained by the Magnetism in Massive Stars CFHT and TBL Large Programs,...

  1. Efficient algorithm for a quantum analogue of 2-SAT

    CERN Document Server

    Bravyi, S B

    2006-01-01

    Complexity of a quantum analogue of the satisfiability problem is studied. Quantum k-SAT is a problem of verifying whether there exists n-qubit pure state such that its k-qubit reduced density matrices have support on prescribed subspaces. We present a classical algorithm solving quantum 2-SAT in a polynomial time. It generalizes the well-known algorithm for the classical 2-SAT. Besides, we show that for any k>=4 quantum k-SAT is complete in the complexity class QMA with one-sided error.

  2. Astrobiology Field Research in Moon/Mars Analogue Environments: Preface

    Science.gov (United States)

    Foing, B. H.; Stoker, C.; Ehrenfreund, P.

    2011-01-01

    Extreme environments on Earth often provide similar terrain conditions to landing/operation sites on Moon and Mars. Several field campaigns (EuroGeoMars2009 and DOMMEX/ILEWG EuroMoonMars from November 2009 to March 2010) were conducted at the Mars Desert Research Station (MDRS) in Utah. Some of the key astrobiology results are presented in this special issue on Astrobiology field research in Moon/Mars analogue environments relevant to investigate the link between geology, minerals, organics and biota. Preliminary results from a multidisciplinary field campaign at Rio Tinto in Spain are presented.

  3. Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues

    OpenAIRE

    Chen, Lisa S.; Plunkett, William; Gandhi, Varsha

    2008-01-01

    The nucleotide substrate specificity of yeast poly(A) polymerase (yPAP) was examined with various ATP analogues of clinical relevance. The triphosphate derivatives of cladribine (2-Cl-dATP), clofarabine (Cl-F-ara-ATP), fludarabine (F-ara-ATP), and related derivatives were incubated with yPAP and 32P-radiolabeled RNA oligonucleotide primers in the absence of ATP to assay polyadenylation. While 2-Cl-ATP resulted in primer elongation, ara-ATP and F-ara-ATP were poor substrates for yPAP. In contr...

  4. Process standardization for rennet casein based Mozzarella cheese analogue

    OpenAIRE

    Shah, Rahul; Jana, Atanu H.; Aparnathi, K. D.; Prajapati, P. S.

    2010-01-01

    A process for manufacture of Mozzarella cheese analogue (MCA) using rennet casein and plastic cream as protein and fat sources respectively was standardized. The formulation comprised of 25% plastic cream (72% fat), 27% rennet casein along with 3% tri-sodium citrate as emulsifying salt, 2% maltodextrin as binder, 0.55% lactic acid as pH regulator, 1% common salt for seasoning, 1% Mozzarella cheese bud as flavouring and 40.4% water. The process involved (a) dissolving the dry mixture of casein...

  5. Analogue Aharonov-Bohm effect in neo-Newtonian theory

    OpenAIRE

    Anacleto, M.A.(Departamento de Física, Universidade Federal de Campina Grande, Caixa Postal 10071, 58109-970 Campina Grande, Paraíba, Brazil); Salako, I. G.; Brito, F. A.; Passos, E.

    2015-01-01

    We address the issues of the scattering of massless planar scalar waves by an acoustic black hole in neo-Newtonian hydrodynamics. We then compute the differential cross section through the use of the partial wave approach in the neo-Newtonian theory which is a modification of the usual Newtonian theory that correctly incorporates the effects of pressure. We mainly show that the scattering of planar waves leads to a modified analogue Aharonov-Bohm effect due to a nontrivial response of the par...

  6. Computer integrated analogue electronics laboratory for undergraduate teaching

    Directory of Open Access Journals (Sweden)

    Marko A. Dimitrijević

    2005-11-01

    Full Text Available Computer system for laboratory exercises in basic analogue electronics was developed. It is aimed to emphasize the learning of electronic component and circuit behavior and to develop other praxis to teaching measurement skills. Hardware part of the system is based on PC computers with acquisition cards and circuits whose parameters are measured. The software part is realized using LabVIEW programming tool. The main goal of this system is to simplify manipulation of instruments, faster measurement and acquisition of the results, providing students to concentrate on measurement essence.

  7. Pena Blanca Natural Analogue Project: Summary of activities

    International Nuclear Information System (INIS)

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  8. Design and synthesis of harzialactone analogues: promising anticancer agents.

    Science.gov (United States)

    Pawar, Vishwas U; Ghosh, Sougata; Chopade, Balu A; Shinde, Vaishali S

    2010-12-15

    New homologues of harzialactone were synthesized using D-glucose as chiral template. Wittig reaction to introduce aromatic moiety in 10 and chemoselective anomeric oxidation of 13 were used as key reactions in our synthesis. Anticancer activity of these target molecules was assessed against five cancer cell lines, P388D1, HL60, COLO-205, Zr-75-1 and HeLa. Both compound 5 and 6, showed significant activity against colon cancer (COLO-205) and cervical cancer (HeLa) and moderate with others. To the best of our knowledge, this is the first report of harzialactone analogues as potent inhibitors of human colon and cervical cancer. PMID:21074431

  9. Pena Blanca Natural Analogue Project: Summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.; Goldstein, S.; Dobson, P.F.; Goodell, P.; Ku, T.-L.; Abdel-Fattah, A.; Saulnier, G.; Fayek, M.; de la Garza, R.

    2011-02-01

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill cores. Data from site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  10. Tidal regimes and salt marshes - the River Hamble analogue

    International Nuclear Information System (INIS)

    Construction of estuarine tidal-energy barrages has a potentially major effect on the tidal regime of the estuary, particularly upstream of a barrage. Because tidal regime largely controls the distribution and species composition of intertidal plant and animal communities, it is important to understand how barrages may affect such communities. The main objectives of the research described in this report were to relate recent changes in tidal regime within an embanked area of salt marsh and mudflat to changes in the distribution of plant species. This was to test predictions about tidal control of species' range and to assess the site's suitability as an analogue of post-barrage conditions. (author)

  11. Uranium in groundwater in Palmottu analogue study site in Finland

    International Nuclear Information System (INIS)

    The small Precambrian U-Th deposit of Palmottu, Finland, has been studied as a natural geological analogue for a high-level radioactive waste repository. The chemical composition and physico-chemical characteristics of groundwater with tritium values in drill holes intersecting the deposit are given. Uranium concentrations and 234U/238U radioactivity ratios in groundwater, based on various sampling methods, are presented as depth profiles (from surface to 250 m). Factors affecting the distribution of uranium and the observed activity ratios in groundwater and particulate matter are discussed. (orig.)

  12. Stimulated emission and Hawking radiation in black hole analogues

    CERN Document Server

    Belgiorno, F

    2016-01-01

    Stimulated emission by black holes is discussed in light of the analogue gravity program. We first consider initial quantum states containing a definite number of particles, and then we take into account the case where the initial state is a coherent state. The latter case is particularly significant in the case where Hawking radiation is studied in dielectric black holes, and the emission is stimulated by a laser probe. We are particularly interested in the case of the electromagnetic field, for which stimulated radiation is calculated too.

  13. Pena blanca natural analogue project: summary of activities

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Schon S [Los Alamos National Laboratory; Goldstein, Steven J [Los Alamos National Laboratory; Abdel - Fattah, Amr I [Los Alamos National Laboratory

    2010-12-08

    The inactive Nopal I uranium mine in silicic tuff north of Chihuahua City, Chihuahua, Mexico, was studied as a natural analogue for an underground nuclear-waste repository in the unsaturated zone. Site stratigraphy was confirmed from new drill core. Datafrom site studies include chemical and isotopic compositions of saturated- and unsaturated-zone waters. A partial geochronology of uranium enrichment and mineralization was established. Evidence pertinent to uranium-series transport in the soil zone and changing redox conditions was collected. The investigations contributed to preliminary, scoping-level performance assessment modeling.

  14. Toward the Validation of Visual Analogue Scale for Anxiety

    OpenAIRE

    Facco, E; ZANETTE, G.; Favero, L; C. Bacci; Sivolella, S.; Cavallin, F.; Manani, G.

    2011-01-01

    Anxiety is a relevant problem in dental practice. The Visual Analogue Scale for Anxiety (VAS‐A), introduced in dentistry in 1988, has not yet been validated in large series. The aim of this study is to check VAS‐A effectiveness in more than 1000 patients submitted to implantology. The VAS‐A and the Dental Anxiety Scale (DAS) were administered preoperatively to 1114 patients (459 males and 655 females, age 54.7 ± 13.1 years). Statistical analysis was conducted with Pearson correlation coeffici...

  15. Synthetic studies towards d-modified paclitaxel analogues

    OpenAIRE

    Matović Radomir; Saičić Radomir N.; Ferjančić Zorana

    2012-01-01

    A synthetic sequence has been developed for the preparation of 9,10-O-diacetyl-4-desmethylene-4β-(3-butenyl)-4α-hydroxy-5-O-mesyltaxicin I-1,2-carbonate 3, an intermediate in the attempted synthesis of cyclobutane paclitaxel analogue. A series of reactions of 3 has been investigated, including the protection of sterically hindered C-4α hydroxy group and oxidative cleavage of the terminal double bond. Cyclization of 13 to the cyclobutane-containing intermediate failed due to unexpected i...

  16. Synthesis of Analogues of Thyroid Hormones: Nuclear Receptor Modulators

    Directory of Open Access Journals (Sweden)

    Guilherme Vieira de Castro

    2015-09-01

    Full Text Available Thyroid hormones are essential for the development and differentiation of all cells of the human body. This work reports the synthesis of some synthetic structural analogues of thyroid hormones, which may be modulators of the thyroid hormone receptor. The known compounds GC-1 (Sobetirome and CG-24 were successfully prepared and two novel analogous molecules were also synthesized by a new and efficient synthetic methodology. DOI: http://dx.doi.org/10.17807/orbital.v7i3.739  

  17. Hydrogeochemical modelling of the Needle's Eye natural analogue (Scotland)

    International Nuclear Information System (INIS)

    First a hydrodynamic model of the natural analogue site of Needle's Eye is built with the help of the METIS code. Then the transport of the uranium is simulated from its natural deposits through sediments rich in humic facies. The use of a distribution coefficient (Kd) in the treatment of the behaviour of the solute does not make it possible to reproduce the observed concentrations. With the coupled model STELE the precipitation of UO2 in the reducing environment of the sediments can be simulated. The results agree with observations in the aqueous and the solid phase. (author)

  18. Analysis of Vitamins D, Their Metabolites and Analogues

    Science.gov (United States)

    Makin, Hugh L. J.; Jones, Glenville; Kaufmann, Martin; Calverley, Martin J.

    The analysis of vitamins D and their metabolites and analogues has been reviewed by us on two occasions (Makin et al., 1995; Jones and Makin, 2000) over the last 10-15 years. In this chapter, we have drawn heavily on the 2000 review, up-dating it to take account of the developments in methodology that have occurred in the intervening years, but including elements of our 1995 review so that the reader can get a picture of the historical context as well as the modern developments.

  19. Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

    OpenAIRE

    Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

    2009-01-01

    8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the sub...

  20. Application of FPGA's in Flexible Analogue Electronic Image Generator Design

    Directory of Open Access Journals (Sweden)

    Peter Kulla

    2006-01-01

    Full Text Available This paper focuses on usage of the FPGAs (Field Programmable Gate Arrays Xilinx as a part of our more complex workdedicated to design of flexible analogue electronic images generator for application in TV measurement technique or/and TV servicetechnique or/and education process. The FPGAs performs here the role of component colour R, G, B, synchronization and blanking signals source. These signals are next processed and amplified in other parts of the generator as NTSC/PAL source encoder and RF modulator. The main aim of this paper is to show the possibilities how with suitable development software use a FPGAs in analog TV technology.

  1. Optical analogues of spherically symmetric black hole spacetimes

    International Nuclear Information System (INIS)

    We have given an analytical formalism for developing optical analogues of spherically symmetric black hole spacetimes, and demonstrated the exact similarity between the electromagnetic wave equations in an inhomogeneous medium in flat spacetime and in a general relativistic curved spacetime. The permittivity and permeability of the inhomogeneous optical medium act as the metric components of an effective optical spacetime. Manifest properties of black holes, like curved trajectories of light rays and quasi-normal modes follow directly from our formalism. It is also applied to the specific case of Schwarzschild spacetime. The formalism would facilitate table-top experiments to investigate black hole phenomena

  2. Synthesis of a Nitro Analogue of Plakoric Acid

    Institute of Scientific and Technical Information of China (English)

    ZHANG,Qi; JIN,Hong-Xia; LIU,He-Hua; WU,Yi-Kang

    2006-01-01

    Synthesis of a nitro analogue of plakoric acid is presented. The peroxy bond was incorporated into the substrate structure through a boron trifluoride etherate catalyzed methoxy-hydroperoxy group partial exchange reaction in djethyl ether with urea-hydrogen peroxide complex (UHP, a commercially available solid reagent) as the source of the hydrogen peroxide. Under the given conditions, only one of the two methoxyl groups underwent the MeO-OOH exchange and the resulting hydroperoxy hemiketal proceeded directly to the end product through an intramolecular Michael addition of the hydroperoxyl group to the nitro group activated carbon-carbon double bond.

  3. THE OBJECTIVE ANALOGUE PREDICTION MODEL FOR TROPICAL CYCLONE TRACK WITH COMPREHENSIVE ASSESSMENT OF THE ENVIRONMENT

    Institute of Scientific and Technical Information of China (English)

    钟元

    2002-01-01

    An objective analogue prediction model for tropical cyclone (TC) track is put forward that comprehensively assesses the environmental field. With the parameters of the tropical cyclone and environmental field at initial and future time, objective analogue criteria are set up in the model. Analogous samples are recognized by comprehensive assessment of historical TC cases for similarity with multivariate criteria, using non-linear analogue indexes especially defined for the purpose. When the historical tracks are coordinateconverted and weighted with reference to analogue indexes, forecast tracks are determined. As shown in model verification and forecast experiments, the model has forecasting skill.

  4. The Relationship Between Water Structure and Blood Compatibility in Poly(2-methoxyethyl Acrylate) (PMEA) Analogues.

    Science.gov (United States)

    Sato, Kazuhiro; Kobayashi, Shingo; Kusakari, Miho; Watahiki, Shogo; Oikawa, Masahiko; Hoshiba, Takashi; Tanaka, Masaru

    2015-09-01

    Six types of poly(2-methoxyethyl acrylate) (PMEA) analogues were synthesized and the water structure in the hydrated polymers was characterized using differential scanning calorimetry (DSC). The hydrated PMEA analogues exhibited the different amounts of intermediate water. Non-thrombogenicity evaluation was performed on PMEA analogues for platelet adhesion and protein adsorption. Platelet adhesion was suppressed on PMEA analogues. In addition, the protein adsorption and deformation were suppressed by increasing the amount of intermediate water. This study demonstrates that the amount of intermediate water might play a key role in expressing the blood compatibility of polymeric materials. PMID:26017931

  5. New metabolically stabilized analogues of lysophosphatidic acid: agonists, antagonists and enzyme inhibitors.

    Science.gov (United States)

    Prestwich, G D; Xu, Y; Qian, L; Gajewiak, J; Jiang, G

    2005-12-01

    Lysophosphatidic acid (LPA) is a metabolically labile natural phospholipid with a bewildering array of physiological effects. We describe herein a variety of long-lived receptor-specific agonists and antagonists for LPA receptors. Several LPA and PA (phosphatidic acid) analogues also inhibit LPP (lipid phosphate phosphatase). The sn-1 or sn-2 hydroxy groups have been replaced by fluorine, difluoromethyl, difluoroethyl, O-methyl or O-hydroxyethoxy groups to give non-migrating LPA analogues that resist acyltransferases. Alkyl ether replacement of acyl esters produced lipase and acyltransferase-resistant analogues. Replacement of the bridging oxygen in the monophosphate by an alpha-monofluoromethylene-, alpha-bromomethylene- or alpha,alpha-difluoromethylenephosphonate gave phosphatase-resistant analogues. Phosphorothioate analogues with O-acyl and O-alkyl chains are potent, long-lived agonists for LPA1 and LPA3 receptors. Most recently, we have (i) prepared stabilized O-alkyl analogues of lysobisphosphatidic acid, (ii) explored the structure-activity relationship of stabilized cyclic LPA analogues and (iii) synthesized neutral head group trifluoromethylsulphonamide analogues of LPA. Through collaborative studies, we have collected data for these stabilized analogues as selective LPA receptor (ant)agonists, LPP inhibitors, TREK (transmembrane calcium channel) K+ channel agonists, activators of the nuclear transcription factor PPAR-gamma (peroxisome-proliferator-activated receptor-gamma), promoters of cell motility and survival, and radioprotectants for human B-cells. PMID:16246118

  6. Cosmic dynamo analogue and decay of magnetic fields in 3D Ricci flows

    CERN Document Server

    de Andrade, Garcia

    2009-01-01

    Magnetic curvature effects, investigated by Barrow and Tsagas (BT) [Phys Rev D \\textbf{77},(2008)],as a mechanism for magnetic field decay in open Friedmann universes (${\\Lambda}<0$), are applied to dynamo geometric Ricci flows in 3D curved substrate in laboratory. By simple derivation, a covariant three-dimensional magnetic self-induced equation, presence of these curvature effects, indicates that de Sitter cosmological constant (${\\Lambda}\\ge{0}$), leads to enhancement in the fast kinematic dynamo action which adds to stretching of plasma flows. From the magnetic growth rate, the strong shear case, anti-de Sitter case (${\\Lambda}<0$) BT magnetic decaying fields are possible while for weak shear, fast dynamos are possible. The self-induced equation in Ricci flows is similar to the equation derived by BT in $(3+1)$-spacetime continuum. Lyapunov-de Sitter metric is obtained from Ricci flow eigenvalue problem. In de Sitter analogue there is a decay rate of ${\\gamma}\\approx{-{\\Lambda}}\\approx{-10^{-35}s^{-...

  7. Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell Lymphoid Malignancies.

    Science.gov (United States)

    Mędra, Aleksandra; Witkowska, Magdalena; Majchrzak, Agata; Cebula-Obrzut, Barbara; Bonner, Michael Y; Robak, Tadeusz; Arbiser, Jack L; Smolewski, Piotr

    2016-01-01

    Honokiol and triphenylmethanes are small molecules with anti-tumor properties. Recently, we synthesized new honokiol analogues (HAs) that possess common features of both groups. We assessed the anti-tumor effectiveness of HAs in B-cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma (BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma (MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly active against the majority of cells examined, with no significant impact on healthy lymphocytes. These active HAs induced caspase-dependent apoptosis, causing significant deregulation of several apoptosis-regulating proteins. Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak and survivin proteins. In conclusion, some of the HAs are potent tumor-selective inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro. Further preclinical studies of these agents are recommended. PMID:27483232

  8. Transdermal iontophoresis of gonadotropin releasing hormone (LHRH) and two analogues.

    Science.gov (United States)

    Miller, L L; Kolaskie, C J; Smith, G A; Rivier, J

    1990-06-01

    Gonadotropin releasing hormone (GnRH), as well as an antagonist [Ac-D2Nal,1 D4ClPhe,2 D3Pal,3 NicLys,5 DNicLys,6 ILys,8 DAla10] GnRH.HOAc (1) and a superagonist [DTrp6, Pro9-NHEt]GnRH (2), have been electrochemically driven across excised hairless mouse skin. Determined by HPLC analysis, the delivery rate from aqueous solution into isotonic saline at 0.5 mA cm-2 was as high as 19 nM cm-2 h-1 for 2. Because of its insolubility in water, analogue 1 could only be delivered from an acidic donor solution. Analogue 2 was also delivered in pulsatile fashion using current on/off cycles. For all three peptides, passive transport was negligible and stability is evident when in contact with the stratum corneum. Slow metabolism occurs when GnRH contacts the dermal side of hairless mouse skin. PMID:2203894

  9. A low-dimensional analogue of holographic baryons

    International Nuclear Information System (INIS)

    Baryons in holographic QCD correspond to topological solitons in the bulk. The most prominent example is the Sakai–Sugimoto model, where the bulk soliton in the five-dimensional spacetime of AdS-type can be approximated by the flat space self-dual Yang–Mills instanton with a small size. Recently, the validity of this approximation has been verified by comparison with the numerical field theory solution. However, multi-solitons and solitons with finite density are currently beyond numerical field theory computations. Various approximations have been applied to investigate these important issues and have led to proposals for finite density configurations that include dyonic salt and baryonic popcorn. Here we introduce and investigate a low-dimensional analogue of the Sakai–Sugimoto model, in which the bulk soliton can be approximated by a flat space sigma model instanton. The bulk theory is a baby Skyrme model in a three-dimensional spacetime with negative curvature. The advantage of the lower-dimensional theory is that numerical simulations of multi-solitons and finite density solutions can be performed and compared with flat space instanton approximations. In particular, analogues of dyonic salt and baryonic popcorn configurations are found and analysed. (paper)

  10. Quantum cosmological perfect fluid model and its classical analogue

    CERN Document Server

    Batista, A B; Gonçalves, S V B; Tossa, J; Tossa, Joel

    2002-01-01

    The quantization of gravity coupled to a perfect fluid model leads to a Schr\\"odinger-like equation, where the matter variable plays the role of time. The wave function can be determined, in the flat case, for an arbitrary barotropic equation of state $p = \\alpha\\rho$; solutions can also be found for the radiative non-flat case. The wave packets are constructed, from which the expectation value for the scale factor is determined. The quantum scenarios reveal a bouncing Universe, free from singularity. We show that such quantum cosmological perfect fluid models admit a universal classical analogue, represented by the addition, to the ordinary classical model, of a repulsive stiff matter fluid. The meaning of the existence of this universal classical analogue is discussed. The quantum cosmological perfect fluid model is, for a flat spatial section, formally equivalent to a free particle in ordinary quantum mechanics, for any value of $\\alpha$, while the radiative non-flat case is equivalent to the harmonic osci...

  11. A nonsingular Brans wormhole: an analogue to naked black holes

    International Nuclear Information System (INIS)

    In a recent paper, we showed that the Jordan frame vacuum Brans class I solution provided a wormhole analogue to a Horowitz-Ross naked black hole in the wormhole range -3/2 < ω < -4/3. Thereafter, the solution has been criticized by some authors that, because of the presence of singularity in that solution within this range, a wormhole interpretation of it is untenable. While the criticism is correct, we show here that (i) a singularity-free wormhole can actually be obtained from the class I solution by performing a kind of Wick rotation on it, resulting into what Brans listed as his independent class II solution, (ii) the class II solution has all the necessary properties of a regular wormhole in a revised range -2 < ω < -3/2 and finally, (iii) naked black holes, as described by Horowitz and Ross, are spacetimes where the tidal forces attain their maxima above the black hole horizon. We show that in the non-singular class II spacetime, this maxima is attained above the throat and thus can be treated as a wormhole analogue. Some related issues are also addressed.

  12. A nonsingular Brans wormhole: an analogue to naked black holes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Amrita; Nandi, Kamal K [Department of Mathematics, University of North Bengal, Raja Rammohunpur, Siliguri 734 013 (India); Izmailov, Ramil [Department of Theoretical Physics, Sterlitamak State Pedagogical Academy, 50, Lenin Prospect, Sterlitamak 453103 (Russian Federation); Laserra, Ettore, E-mail: amrita_852003@yahoo.co.in, E-mail: izmailov.ramil@gmail.com, E-mail: elaserra@unisa.it, E-mail: kamalnandi1952@yahoo.co.in [DMI, Universita di Salerno, Via Ponte Don Melillo, Fisciano 84084, Salerno (Italy)

    2011-08-07

    In a recent paper, we showed that the Jordan frame vacuum Brans class I solution provided a wormhole analogue to a Horowitz-Ross naked black hole in the wormhole range -3/2 < {omega} < -4/3. Thereafter, the solution has been criticized by some authors that, because of the presence of singularity in that solution within this range, a wormhole interpretation of it is untenable. While the criticism is correct, we show here that (i) a singularity-free wormhole can actually be obtained from the class I solution by performing a kind of Wick rotation on it, resulting into what Brans listed as his independent class II solution, (ii) the class II solution has all the necessary properties of a regular wormhole in a revised range -2 < {omega} < -3/2 and finally, (iii) naked black holes, as described by Horowitz and Ross, are spacetimes where the tidal forces attain their maxima above the black hole horizon. We show that in the non-singular class II spacetime, this maxima is attained above the throat and thus can be treated as a wormhole analogue. Some related issues are also addressed.

  13. Analogue White Hole Horizon and its Impact on Sediment Transport

    CERN Document Server

    Chatterjee, Debasmita; Ghosh, Subir; Mazumder, B S

    2015-01-01

    Motivated by the ideas of analogue gravity, we have performed experiments in a flume where an analogue White Hole horizon is generated, in the form of a wave blocking region, by suitably tuned uniform fluid (water) flow and counter-propagating shallow water waves. We corroborate earlier experimental observations by finding a critical wave frequency for a particular discharge above which the waves are effectively blocked beyond the horizon. An obstacle, in the form of a bottom wave, is introduced to generate a sharp blocking zone. All previous researchers used this obstacle. A novel part of our experiment is where we do not introduce the obstacle and find that wave blocking still takes place, albeit in a more diffused zone. Lastly we replace the fixed bottom wave obstacle by a movable sand bed to study the sediment transport and the impact of the horizon or wave blocking phenomenon on the sediment profile. We find signatures of the wave blocking zone in the ripple pattern.

  14. Process standardization for rennet casein based Mozzarella cheese analogue.

    Science.gov (United States)

    Shah, Rahul; Jana, Atanu H; Aparnathi, K D; Prajapati, P S

    2010-10-01

    A process for manufacture of Mozzarella cheese analogue (MCA) using rennet casein and plastic cream as protein and fat sources respectively was standardized. The formulation comprised of 25% plastic cream (72% fat), 27% rennet casein along with 3% tri-sodium citrate as emulsifying salt, 2% maltodextrin as binder, 0.55% lactic acid as pH regulator, 1% common salt for seasoning, 1% Mozzarella cheese bud as flavouring and 40.4% water. The process involved (a) dissolving the dry mixture of casein, maltodextrin, flavouring and common salt in hot emulsifying salt solution, (b) incorporation of half the quantity of acid solution in casein-maltodextrin dough, followed by addition and emulsification of plastic cream, and (c) addition of remaining half of the acid solution and heating the mass to 80 °C until a plastic cheese mass was obtained. The analogue was shaped in ball form, cooled and packaged in polyethylene bag. The MCA conformed to the PFA requirements for pizza cheese and had all the requisite baking characteristics expected of pizza cheese topping. PMID:23572688

  15. Capillary electrokinetic chromatography of insulin and related synthetic analogues.

    Science.gov (United States)

    Ortner, K; Buchberger, W; Himmelsbach, M

    2009-04-01

    With the implementation of recombinant DNA technology in the pharmaceutical industry, some synthetic insulins have been developed in order to improve the therapy of diabetes. These analogues differ only slightly in the amino acid sequence, therefore displaying a great challenge for analytical chemistry. Within the work presented in this paper, capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC) with sodium dodecylsulphate (SDS) as micelle-forming agent, and microemulsion electrokinetic chromatography (MEEKC) with microemulsions consisting of SDS, n-octane and 1-butanol were investigated for the separation of human insulin and five synthetic analogues. Best results were achieved with a solvent-modified MEKC system consisting of 100mM sodium dodecyl sulphate and 15% acetonitrile in 10mM borate buffer (pH 9.2). A similar system based on perfluorooctanoic acid as micelle-forming agent in ammonium acetate (pH 9.2) was successfully employed for the hyphenation with a quadrupole/time-of-flight mass spectrometer via a sheath-flow interface. In this case, detection limits at 10mg/L could be achieved. PMID:19027906

  16. Historical space psychology: Early terrestrial explorations as Mars analogues

    Science.gov (United States)

    Suedfeld, Peter

    2010-03-01

    The simulation and analogue environments used by psychologists to circumvent the difficulties of conducting research in space lack many of the unique characteristics of future explorations, especially the mission to Mars. This paper suggests that appropriate additional analogues would be the multi-year maritime and terrestrial explorations that mapped the surface of the Earth in previous centuries. These, like Mars, often involved a hazardous trek through unknown territory, flanked by extended, dangerous voyages to and from the exploration sites. Characteristic issues included interpersonal relationships under prolonged stress, stretches of boredom interspersed with intense work demands, the impossibility of rescue, resupply, or other help from home, chronic danger, physical discomfort and lack of privacy, and the crucial role of the leader. Illustrative examples of one important factor, leadership style, are discussed. The examination of such expeditions can help to identify the psychological stressors that are likely to be experienced by Mars explorers, and can also indicate countermeasures to reduce the damaging impact of those stressors.

  17. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    Science.gov (United States)

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  18. Mitochondria Superoxide Anion Production Contributes to Geranylgeraniol-Induced Death in Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    Milene Valéria Lopes

    2012-01-01

    Full Text Available Here we demonstrate the activity of geranylgeraniol, the major bioactive constituent from seeds of Bixa orellana, against Leishmania amazonensis. Geranylgeraniol was identified through 1H and 13C nuclear magnetic resonance imaging and DEPT. The compound inhibited the promastigote and intracellular amastigote forms, with IC50 of 11±1.0 and 17.5±0.7 μg/mL, respectively. This compound was also more toxic to parasites than to macrophages and did not cause lysis in human blood cells. Morphological and ultrastructural changes induced by geranylgeraniol were observed in the protozoan by electronic microscopy and included mainly mitochondria alterations and an abnormal chromatin condensation in the nucleus. These alterations were confirmed by Rh 123 and TUNEL assays. Additionally, geranylgeraniol induces an increase in superoxide anion production. Collectively, our in vitro studies indicate geranylgeraniol as a selective antileishmanial that appears to be mediated by apoptosis-like cell death.

  19. Climate Analogues for agricultural impact projection and adaptation – a reliability test

    Directory of Open Access Journals (Sweden)

    Swen P.M. Bos

    2015-10-01

    Full Text Available The climate analogue approach is often considered a valuable tool for climate change impact projection and adaptation planning, especially for complex systems that cannot be modelled reliably. Important examples are smallholder farming systems using agroforestry or other mixed-cropping approaches. For the projected climate at a particular site of interest, the analogue approach identifies locations where the current climate is similar to these projected conditions. By comparing baseline-analogue site pairs, information on climate impacts and opportunities for adaptation can be obtained. However, the climate analogue approach is only meaningful, if climate is a dominant driver of differences between baseline and analogue site pairs. For a smallholder farming setting on Mt. Elgon in Kenya, we tested this requirement by comparing yield potentials of maize and coffee (obtained from the IIASA Global Agro-ecological Zones dataset among 50 close analogue sites for different future climate scenarios and models, and by comparing local ecological knowledge and farm characteristics for one baseline-analogue pair.Yield potentials among the 50 closest analogue locations varied strongly within all climate scenarios, hinting at factors other than climate as major drivers of what the analogue approach might interpret as climate effects. However, on average future climatic conditions seemed more favourable to maize and coffee cultivation than current conditions. The detailed site comparison revealed substantial differences between farms in important characteristics, such as farm size and presence of cash crops, casting doubt on the usefulness of the comparison for climate change analysis. Climatic constraints were similar between sites, so that no apparent lessons for adaptation could be derived. Pests and diseases were also similar, indicating that climate change may not lead to strong changes in biotic constraints at the baseline site in the near future. From

  20. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    International Nuclear Information System (INIS)

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S2N2 and S3N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with 111In-DOTA-Tyr3-octreotide in AR42J rat pancreatic tumor cells yielded IC50 values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr3-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr3-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS3 and N2S2 coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of 99mTc-cyclized analogue 4.

  1. In vitro structure-activity relationship of Re-cyclized octreotide analogues

    Energy Technology Data Exchange (ETDEWEB)

    Dannoon, Shorouk F. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Ma Lixin [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Gallazzi, Fabio [Structural Biology Core, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: lewismic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: jurissons@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Nuclear Science and Engineering Institute, University of Missouri, Columbia, MO 65211 (United States)

    2010-07-15

    Introduction: Development of radiolabeled octreotide analogues is of interest for targeting somatostatin receptor (SSTR)-positive tumors for diagnostic and therapeutic purposes. We are investigating a direct labeling approach for incorporation of a Re ion into octreotide analogues, where the peptide sequences are cyclized via coordination to Re rather than through a disulfide bridge. Methods: Various octreotide analogue sequences and coordination systems (e.g., S{sub 2}N{sub 2} and S{sub 3}N) were synthesized and cyclized with nonradioactive Re. In vitro competitive binding assays with {sup 111}In-DOTA-Tyr{sup 3}-octreotide in AR42J rat pancreatic tumor cells yielded IC{sub 50} values as a measure of SSTR affinity of the Re-cyclized analogues. Three-dimensional structures of Re-cyclized Tyr{sup 3}-octreotate and its disulfide-bridged analogue were calculated from two-dimensional NMR experiments to visualize the effect of metal cyclization on the analogue's pharmacophore. Results: Only two of the 11 Re-cyclized analogues investigated showed moderate in vitro binding affinity toward somatostatin subtype 2 receptors. Three-dimensional molecular structures of Re- and disulfide-cyclized Tyr{sup 3}-octreotate were calculated, and both of their pharmacophore turns appear to be very similar with minor differences due to metal coordination to the amide nitrogen of one of the pharmacophore amino acids. Conclusions: Various Re-cyclized analogues were developed and analogue 4 had moderate affinity toward somatostatin subtype 2 receptors. In vitro stable studies that are in progress showed stable radiometal cyclization of octreotide analogues via NS{sub 3} and N{sub 2}S{sub 2} coordination forming five- and six-membered chelate rings. In vivo biodistribution studies are underway of {sup 99m}Tc-cyclized analogue 4.

  2. In vitro and in vivo activity of analogues of the kinin B2 receptor antagonist MEN1 1270.

    Science.gov (United States)

    Meini, S; Lecci, A; Carini, F; Tramontana, M; Giuliani, S; Maggi, C A; Ricci, R; Fabbri, G; Anichini, B; Harmat, N; Rizzi, A; Camarda, V; Regoli, D; Quartara, L

    2002-04-01

    In this study, we describe the in vitro and in vivo activities of a series of cyclic peptide analogues of the selective kinin B2 receptor antagonist MEN11270 on Chinese hamster ovary cells expressing the human B2 receptor (hB2R), the human isolated umbilical vein (hUV), the isolated guinea pig ileum (gpI), and bradykinin (BK) induced bronchoconstriction (BC) and hypotension in anaesthetized guinea pigs. Substitutions in the backbone of MEN1 1270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic-Arg)c(7gamma-10alpha)) aimed to increase the potency in inhibiting bronchospasm versus hypotension following the topical (intratracheal (i.t.)) or systemic (intravenous (i.v.)) application of these antagonists. A series of analogues were left unprotected from N-terminal cleavage by aminopeptidases (MEN12739, MEN13052, MEN13346, and MEN13371): these compounds maintained sizeable affinities for the hB2R (pKi = 9.4, 9.6, 9.7, and 8.6, respectively) and antagonist activities toward BK in the hUV (pA2 = 7.9, 8.3, 8.2, and 7.5) and gpI assays (pK(B) = 7.4, 7.8, 7.9, and 7.9), but the inhibition of BK-induced BC and hypotension in vivo was negligible following either i.v. or i.t. administration. Two analogues (MEN12388 and MEN13405) could be potential substrates of angiotensin-converting enzyme: these have good activity in the hB2R (pKi = 9.5 and 8.9, respectively), hUV (pA2 = 8.2 for MEN12388), and gpI assays (pK(B) = 8.4 and 8.0) but an in vivo activity 10- to 30-fold lower than the parent compound MEN1 1270 (pKi = 9.4, pA2 = 8.1, pKB = 8.3) when given by either the i.v. or the i.t. route. Other analogues were functionalized with a quaternary ammonium Lys derivative (MEN13031, MEN12374, and the previously mentioned MEN13052) or with an ethyl group on Arg (MEN13655 and the previously mentioned MEN13346 and MEN13405) in order to hinder or facilitate local absorption. MEN13346 and MEN13031 (pKi = 9.7and 9.5, pA2 = 8.2 and 7.9, pKB = 7.9 and 8.5, respectively) were 10- to 30-fold less

  3. Self-restoration effect and action mechanism of tribopairs consisting of analogue shaft-bushing induced by serpentine powders%蛇纹石微粉对类轴-轴瓦摩擦副的自修复效应及作用机理

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

      采用尺寸为0.5~4µm 的层片状蛇纹石粉末,通过高能球磨对其进行油基细化、改性和分散,然后添加到基础油(CD 15W/40柴油机润滑油)中制成含油溶性蛇纹石微粉的润滑剂。借助环–块摩擦磨损试验机研究蛇纹石颗粒作为润滑油添加剂对类轴–轴瓦摩擦副表面的自修复效应,并探讨其作用机理。结果表明:在载荷为600 N、蛇纹石颗粒含量(质量分数)为0.5%时,润滑油具有最佳的摩擦学性能及自修复性能,摩擦因数和磨痕宽度分别较基础油润滑时降低约9.7%和40.7%;磨损表面较平整光滑,其上形成厚约0.68µm 的自修复层。修复层主要由铁的多种氧化物、石墨、有机残留物及少量 FeS 组成,具有较高的力学性能;蛇纹石颗粒对摩擦副表面具有精细研磨作用,不仅能降低表面的粗糙度,而且在高压闪温条件下释放更多的活性氧参与摩擦界面的氧化反应,促进保护膜的形成并与石墨及有机残留物产生协同作用,实现摩擦表面的润滑与原位自修复。%The oil-soluble serpentine powders were prepared out of the flaky serpentine powders with particle size of 0.5~4 µm using the integral process of oil-based refinement, modification and dispersion with high-energy ball-milling method. The as-prepared additive was added to the Great Wall CD 15W/40 diesel oil to form various lubricants and their self-restoration effects on the tribosurfaces analogue of shaft-bushing contact were investigated using the ring-on-block friction and wear tester. In addition, the corresponding mechanism was discussed. Results indicate that the oil with 0.5%content of serpentine particles shows most excellent tribological properties and self-restoration performance at 600N. The friction coefficient and width of wear trace decrease by 9.7% and 40.7% relative to those of the base oil, respectively. The worn surface is smooth with a restoration film

  4. Sensitivity of an actinic reticuloid cell strain to near-ultraviolet radiation and its modification by Trolox-C, a vitamin E analogue

    Energy Technology Data Exchange (ETDEWEB)

    Kralli, A.; Moss, S.H.

    1987-06-01

    Near-UV radiation (365 nm)-induced lethality, as measured by colony-forming ability, showed an actinic reticuloid cell strain to be sensitive relative to normal human fibroblasts, when irradiated at 25/sup 0/C. This effect was not seen after far-UV (254 nm) irradiation. Trolox-C, a water-soluble analogue of vitamin E, incorporated in the pre-irradiation growth medium or in the post-irradiation plating medium, protected the actinic reticuloid cells to the extent that they were as resistant as normal cells. Plating medium containing Trolox-C did not provide differential protection against inactivation of the two cell strains by wavelengths in the far-UV region. The protection provided by Trolox-C, an analogue of the natural antioxidant vitamin E, suggests some free radical involvement in the aetiology of the disease.

  5. Characterization of Nucleobase Analogue FRET Acceptor tCnitro

    DEFF Research Database (Denmark)

    Preus, Søren; Börjesson, Karl; Kilså, Kristine; Albinsson, Bo; Wilhelmsson, L. Marcus

    2010-01-01

    The fluorescent nucleobase analogues of the tricyclic cytosine (tC) family, tC and tCO, possess high fluorescence quantum yields and single fluorescence lifetimes, even after incorporation into double-stranded DNA, which make these base analogues particularly useful as fluorescence resonance ener...

  6. Synthesis of Benzofuran Analogue of Go6976, an Isoform Selective Protein Kinase C Inhibitor

    Institute of Scientific and Technical Information of China (English)

    MA, Da-Wei; ZHANG, Xin-Rong; WU, Shi-Hui; TAO, Feng-Gang

    2001-01-01

    Based on the structure of Go6976, a known isoform-selective protein kinase C inhibitor, a benzofuran analogue (1) was designed. This analogue was synthesized by coupling of benzofuran 3-acetic acid and 8-oxo-tryptamine and subsequent intramolecular Dieckmann condensation, alkylation, oxidative photocyclization and cyanation reaction of mesylate.

  7. Biological evaluation of Tyr6 and Ser7 modified drosocin analogues

    NARCIS (Netherlands)

    Visser, P.C. de; Hooft, P.A.V. van; Vries, A.-M. de; Jong, A. de; Marel, G.A. van der; Overkleeft, H.S.; Noort, D.

    2005-01-01

    An array of analogues of the cationic antimicrobial peptide drosocin was synthesized containing substitutions of Tyr6 and Ser7 in order to increase the proteolytic stability. Stabilizing the N-terminus with unnatural amino acids increased the serum stability of analogues by almost a factor 30 over a

  8. New analogues of ACPD with selective activity for group II metabotropic glutamate receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Madsen, U; Mikiciuk-Olasik, E; Curry, K

    1997-01-01

    In this study we have determined the pharmacology of a series of 1-aminocyclopentane-1,3-dicarboxylic acid (1,3-ACPD) analogues at cloned metabotropic glutamic acid (mGlu) receptors. The new analogues comprise the four possible stereoisomers of 1-amino-1-carboxycyclopentane-3-acetic acid (1,3-hom...

  9. Unusual tubulin-clustering ability of specifically c7-modified colchicine analogues.

    Science.gov (United States)

    Zefirova, Olga N; Lemcke, Heiko; Lantow, Margareta; Nurieva, Evgeniya V; Wobith, Birgit; Onishchenko, Galina E; Hoenen, Antje; Griffiths, Gareth; Zefirov, Nikolay S; Kuznetsov, Sergei A

    2013-08-19

    Highly cytotoxic C7-modified colchicine analogues, exemplified by tubuloclustin, promote microtubule disassembly followed by the formation of very stable tubulin clusters, both in vitro and in cells. The proposed mechanism of action of tubuloclustin and its analogues, beyond that of colchicine, includes additional specific interactions with the α-tubulin subunit. PMID:23843347

  10. Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity

    DEFF Research Database (Denmark)

    Laursen, Jane B.; de Visser, P.C.; Nielsen, H.K.;

    2002-01-01

    in parallel with a series of differently substituted benzoic acid derivatives. Treatment with TFA-CH2Cl2 (5:995) released the expected saphenamycin analogues into solution. These new analogues were purified, characterized and screened for antimicrobial activity against Bacillus subtilis and Proteus mirabilis...

  11. Tetrodotoxin and its analogues in extracts from the toad Atelopus oxyrhynchus (family: Bufonidae).

    Science.gov (United States)

    Yotsu-Yamashita, M; Mebs, D; Yasumoto, T

    1992-11-01

    Tetrodotoxin and its analogues, 4-epitetrodotoxin and 4,9-anhydrotetrodotoxin, were detected in the toad Atelopus oxyrhynchus by HPLC analysis. The toxin and its analogues were still present in a specimen which lived 3.5 years in captivity. PMID:1336632

  12. Synthesis and biochemical evaluation of benzoylbenzophenone thiosemicarbazone analogues as potent and selective inhibitors of cathepsin L

    DEFF Research Database (Denmark)

    Parker, Erica N; Song, Jiangli; Kishore Kumar, G D;

    2015-01-01

    selective in their inhibition of cathepsin L compared to cathepsin B. Thiosemicarbazone analogue 32 inhibited invasion through Matrigel of MDA-MB-231 breast cancer cells by 70% at 10μM. Thiosemicarbazone analogue 8 significantly inhibited the invasive potential of PC-3ML prostate cancer cells by 92% at 5μ...

  13. How Analogue Research Can Advance Descriptive Evaluation Theory: Understanding (and Improving) Stakeholder Dialogue

    Science.gov (United States)

    Campbell, Bernadette; Mark, Melvin M.

    2015-01-01

    Evaluation theories can be tested in various ways. One approach, the experimental analogue study, is described and illustrated in this article. The approach is presented as a method worthy to use in the pursuit of what Alkin and others have called descriptive evaluation theory. Drawing on analogue studies conducted by the first author, we…

  14. Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12

    DEFF Research Database (Denmark)

    Nielsen, S F; Thastrup, Ole; Pedersen, R; Olsen, C E; Christensen, S B

    1995-01-01

    A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant ...

  15. Radiolabelled somatostatin analogues for radionuclide therapy of tumours

    International Nuclear Information System (INIS)

    Molecular imaging and therapy are rapidly developing and will become important topics in medicine in the 21st century. Radiolabelled peptides that bind to receptors form an important class of radiopharmaceuticals for tumour diagnosis and therapy. The specific receptor binding property of the peptide can be exploited by labelling with radionuclide and using the radiolabelled peptide as a vehicle to guide the radioactivity to tumours expressing a particular receptor. The high affinity of the peptide for the peptide-receptor complex facilitates high uptake of the radiolabel in receptor expressing tumours, while its relatively small size facilitates rapid clearance from blood, resulting in low background radioactivity. The use of radiolabelled peptides is growing rapidly due to these favourable characteristics, their low antigenicity and ease of production. Receptor binding peptides labelled with gamma radiation emitters or positron emitters enable non-evasive, whole body visualization. This process is referred to as peptide receptor scintigraphy and is being used to detect, stage and plan the therapy of receptor expressing tumours and also to follow tumours after therapy. In addition, labelled with a therapeutic beta emitter these peptide molecules have the potential to destroy receptor expressing tumours, an approach referred to as peptide receptor radionuclide therapy (PRRT). To date, five somatostatin receptor subtypes (sst1-sst5) have been identified and cloned. The diagnostic accuracy of 111In labelled octreotide to visualize tumour lesions after intravenous injection has been determined in a large series of patients with sst2 positive, mostly neuroendocrine tumours. Most interesting is the successful application of somatostatin analogues in PET, after labelling with positron emitters. The next logical step was to try to label these with therapeutic radionuclides and to treat receptor positive tumors with peptide receptor radionuclides. So far, 90Y and 177Lu are

  16. Cyprus natural analogue project (CNAP). Phase II Final Report

    International Nuclear Information System (INIS)

    Due to the extremely slow kinetics of bentonite reaction in low alkali cement leachates, natural analogues would appear to be the only viable method of studying bentonite reaction. As a result of a review of the available literature, several sites in Cyprus were selected as particularly promising for this purpose. This report presents the results of two short field campaigns in Cyprus in November/December, 2008 and February, 2009. The main aim of these campaigns was to establish if appropriate sites existed for a natural analogue study of bentonite-low alkali cement leachate reaction. Focus is on mineralogical changes and not changes in physical properties (such as porosity and permeability) of bentonite as the industrially-processed bentonite used in a repository will be completely different in terms of its engineering and hydrogeological properties to the unprocessed natural bentonite or analogue smectite-rich materials. The first campaign was in the form of a reconnaissance study to identify sites of likely interest and the second, follow-up, campaign focussed on obtaining preliminary groundwater and solid phase (bentonites/clay-rich sediments/altered igneous rocks/soils) samples which would allow a more detailed assessment of several of the potential sites. A large amount of information was collected during these short field campaigns and subsequent laboratory analysis of the collected samples so, to keep the main report down to a digestible size, much of the supporting information has been collated in seven appendices. These include full details of all 30 sites visited during both campaigns along with sample details, information on the analytical techniques, the analytical raw data and numerous photographs of the sites. The intention is that this report will provide full supporting information for a potential Phase III and a detailed database for our colleagues at the Geological Survey Department (GSD) in Cyprus. Consequently, all the information acquired

  17. Spectral Characterization of Phobos Analogues Under Simulated Environmental Conditions

    Science.gov (United States)

    Donaldson Hanna, K. L.; Bowles, N. E.; Edwards, C. S.; Glotch, T. D.; Greenhagen, B. T.; Pieters, C. M.; Thomas, I.

    2014-12-01

    The surface of Phobos holds many keys for understanding its formation and evolution as well as the history and dynamics of the Mars-Phobos system. Visible to near infrared (VNIR) observations suggests that Phobos' surface is compositionally heterogeneous with 'redder' and 'bluer' units that both appear to be anhydrous in nature. Lunar highland spectra have been identified as spectral analogues for the 'redder' and 'bluer' units while thermally metamorphosed CI/CM chondrites, lab-heated carbonaceous chondrites and highly space weathered mafic mineral assemblages have been identified as the best analogues for the 'bluer' surface units. Additionally, thermal infrared emissivity spectra indicate that if Phobos' surface is optically mature it may be rich in feldspar, which is consistent with VNIR observations of Phobos' surface being spectrally similar to lunar highland spectra. While remote observations provide key insights into the composition and evolution of planetary surfaces, a fundamentally important component to any remote compositional analysis of planetary surfaces is laboratory measurements of well-characterized samples measured under the appropriate environmental conditions. The vacuum environment of airless bodies creates a steep thermal gradient in the upper hundreds of microns of regolith. Lab studies of particulate rocks and minerals as well as selected lunar soils under vacuum and lunar-like conditions have identified significant effects of this thermal gradient on thermal infrared (TIR) spectral measurements. However recent lab measurements of carbonaceous chondrites demonstrated that simulated asteroid conditions do not affect the resulting emissivity spectra to the degree observed in lunar soils and is highly dependent on composition. Such lab studies demonstrate the high sensitivity of TIR emissivity spectra to environmental conditions under which they are measured and indicate that the near surface environment of all airless bodies do not

  18. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor.

    Directory of Open Access Journals (Sweden)

    Bryan L Roth

    Full Text Available In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as 'designer drugs' and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS-2-(ethylamino-2-(3-methoxyphenylcyclohexanone and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenylcyclohexanamine and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenylcyclohexyl]piperidine and 1-[1-(4-methoxyphenylcyclohexyl]piperidine, were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

  19. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  20. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine.

    Science.gov (United States)

    McKenna, D J; Guan, X M; Shulgin, A T

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives (+/-)fenfluramine, (+/-)norfenfluramine, (+/-)MDE, (+/-)PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners. PMID:1829838