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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. 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.

  3. 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.

  4. Hepatitis C virus induced a novel apoptosis-like death of pancreatic beta cells through a caspase 3-dependent pathway.

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    Qian Wang

    Full Text Available Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV infection is associated with the development of type 2 diabetes. Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV infection on the fate of the insulinoma cell line, MIN6. Our experiments demonstrate that the HCV virion itself is indispensable and has a dose- and time-dependent cytopathic effect on the cells. HCV infection inhibits cell proliferation and induces death of MIN6 cells with apoptotic characteristics, including cell surface exposure of phosphatidylserine, decreased mitochondrial membrane potential, activation of caspase 3 and poly (ADP-ribose polymerase, and DNA fragmentation in the nucleus. However, the fact that HCV-infected cells exhibit a dilated, low-density nucleus with intact plasma and nuclear membrane indicates that a novel apoptosis-like death occurs. HCV infection also causes endoplasmic reticulum (ER stress. Further, HCV RNA replication was detected in MIN6 cells, although the infection efficiency is very low and no progeny virus particle generates. Taken together, our data suggest that HCV infection induces death of pancreatic beta cells through an ER stress-involved, caspase 3-dependent, special pathway.

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

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    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

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

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    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.

  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.

  8. 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

  9. 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.

  10. 6-Br-5methylindirubin-3'oxime (5-Me-6-BIO) targeting the leishmanial glycogen synthase kinase-3 (GSK-3) short form affects cell-cycle progression and induces apoptosis-like death: exploitation of GSK-3 for treating leishmaniasis.

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    Xingi, Evangelia; Smirlis, Despina; Myrianthopoulos, Vassilios; Magiatis, Prokopios; Grant, Karen M; Meijer, Laurent; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Soteriadou, Ketty

    2009-10-01

    Indirubins known to target mammalian cyclin-dependent kinases (CDKs) and glycogen synthase kinase (GSK-3) were tested for their antileishmanial activity. 6-Br-indirubin-3'-oxime (6-BIO), 6-Br-indirubin-3'acetoxime and 6-Br-5methylindirubin-3'oxime (5-Me-6-BIO) were the most potent inhibitors of Leishmania donovani promastigote and amastigote growth (half maximal inhibitory concentration (IC(50)) values human GSK-3beta, for further studies. Kinase assays showed that 5-Me-6-BIO inhibited LdGSK-3s more potently than CRK3 (the CDK1 homologue in Leishmania), whilst 6-BIO was more selective for CRK3. Promastigotes treated with 5-Me-6-BIO accumulated in the S and G2/M cell-cycle phases and underwent apoptosis-like death. Interestingly, these phenotypes were completely reversed in parasites over-expressing LdGSK-3s. This finding strongly supports that LdGSK-3s is: (i) the intracellular target of 5-Me-6-BIO, and (ii) involved in cell-cycle control and in pathways leading to apoptosis-like death. 6-BIO treatment induced a G2/M arrest, consistent with inhibition of CRK3 and apoptosis-like death. These effects were partially reversed in parasites over-expressing LdGSK-3s suggesting that in vivo 6-BIO may also target LdGSK-3s. Molecular docking of 5-Me-6-BIO in CRK3 and 6-BIO in human GSK-3beta and LdGSK-3s active sites predict the existence of functional/structural differences that are sufficient to explain the observed difference in their affinity. In conclusion, LdGSK-3s is validated as a potential drug target in Leishmania and could be exploited for the development of selective indirubin-based leishmanicidals. PMID:19445946

  11. Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.

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    Lionel Leclere

    Full Text Available 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 from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3 protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments.

  12. 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.

  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 the synthesis of rubrene with AIEE behaviour, thus paving the way for the development of light-emitting rubrene derivatives. This journal is © 2014 The Royal Society of Chemistry....

  14. 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.

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

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    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...

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

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    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

  17. 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....

  18. 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.

  19. Electron Impact Induced Reactions of Ethyl Acetate and Its Sulphur Analogues

    DEFF Research Database (Denmark)

    Egsgaard, Helge; Larsen, Elfinn; Carlsen, Lars

    1983-01-01

    The electron impact induced reactions of ethyl acetate and its sulphur analogues have been studied by application of collision activation mass spectrometry and isotopic labelling with H-2 and O-18. The [M-C2H4]+·, [M-CH3]+ and [M-H2O]+· were selected for detailed investigations.......The electron impact induced reactions of ethyl acetate and its sulphur analogues have been studied by application of collision activation mass spectrometry and isotopic labelling with H-2 and O-18. The [M-C2H4]+·, [M-CH3]+ and [M-H2O]+· were selected for detailed investigations....

  20. 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

  1. Apoptosis-like death, an extreme SOS response in Escherichia coli.

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    Erental, Ariel; Kalderon, Ziva; Saada, Ann; Smith, Yoav; Engelberg-Kulka, Hanna

    2014-07-15

    In bacteria, SOS is a global response to DNA damage, mediated by the recA-lexA genes, resulting in cell cycle arrest, DNA repair, and mutagenesis. Previously, we reported that Escherichia coli responds to DNA damage via another recA-lexA-mediated pathway resulting in programmed cell death (PCD). We called it apoptosis-like death (ALD) because it is characterized by membrane depolarization and DNA fragmentation, which are hallmarks of eukaryotic mitochondrial apoptosis. Here, we show that ALD is an extreme SOS response that occurs only under conditions of severe DNA damage. Furthermore, we found that ALD is characterized by additional hallmarks of eukaryotic mitochondrial apoptosis, including (i) rRNA degradation by the endoribonuclease YbeY, (ii) upregulation of a unique set of genes that we called extensive-damage-induced (Edin) genes, (iii) a decrease in the activities of complexes I and II of the electron transport chain, and (iv) the formation of high levels of OH˙ through the Fenton reaction, eventually resulting in cell death. Our genetic and molecular studies on ALD provide additional insight for the evolution of mitochondria and the apoptotic pathway in eukaryotes. Importance: The SOS response is the first described and the most studied bacterial response to DNA damage. It is mediated by a set of two genes, recA-lexA, and it results in DNA repair and thereby in the survival of the bacterial culture. We have shown that Escherichia coli responds to DNA damage by an additional recA-lexA-mediated pathway resulting in an apoptosis-like death (ALD). Apoptosis is a mode of cell death that has previously been reported only in eukaryotes. We found that E. coli ALD is characterized by several hallmarks of eukaryotic mitochondrial apoptosis. Altogether, our results revealed that recA-lexA is a DNA damage response coordinator that permits two opposite responses: life, mediated by the SOS, and death, mediated by the ALD. The choice seems to be a function of the degree

  2. 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.

  3. Delta sleep-inducing peptide and its analogues alleviate the severity of metaphit-induced audiogenic seizures in rats

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    Stanojlović Olivera

    2007-01-01

    Full Text Available Introduction. We investigated the potential of delta sleep-inducing peptide (DSIP and its analogue DSIP-12 (a nonapeptide with alanine in position 2 of DISP molecule substituted by beta-alanine and tetrapeptide analogue DSIP1-4, to antagonize metaphit- (1-1(3-isothiocyanatophenyl-cyclohexyl piperidine induced generalized reflex audiogenic seizures in adult male Wistar albino rats. Material and Methods. Five groups of adult male Wistar rats were intraperitoneally treated with: 1. saline; 2. metaphit; 3. metaphit + DSIP; 4. metaphit + DSIP1-4 and 5. metaphit + DSIP-12. To examine the blocking effects of DSIP and its analogues on fully developed metaphit seizures, in the last three groups they were administered 8h after metaphit injection. The rats were stimulated using an electric bell (1003 dB, 5-8 kHz, 60 s one hour after metaphit injection and afterwards at hourly intervals during the experiment. For EEG recordings and power spectra three gold-plated screws were implanted into the skull. Results. In metaphit-treated animals EEGs appeared as polyspikes and spike-wave complexes, while power spectra were increasing. The incidence and severity of metaphit-induced audiogenic seizures reached a peak value at 7-12 h after injection. Both DSIP and DSIP analogues significantly increased power spectra of delta waves and decreased the incidence of seizures, as well as mean seizure grade and tonic component of metaphit-induced convulsions. Conclusion. Taken together, these results suggest that DSIP and its analogues should be considered as potential antiepileptic agents. .

  4. HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

    Science.gov (United States)

    Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

    2003-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

  5. 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

  6. 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...

  7. Novel analogue of colchicine induces selective pro-death autophagy and necrosis in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Kristen Larocque

    Full Text Available Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME, which is structurally similar to ZD 6126, and (S-3,8,9,10-tetramethoxyallocolchicine (Green 1, which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy.

  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. Attempts to induce mutations in Haemophilus influenzae with the base analogues 5-bromodeoxyuridine and 2-aminopurine

    Energy Technology Data Exchange (ETDEWEB)

    Kimball, R.F.; Perdue, S.W.

    1977-01-01

    Attempts were made to induce mutations in Haemophilus influenzae with the base analogues 5-bromodeoxyuridine and 2-aminopurine. These attempts were unsuccessful. Incorporation studies with BrdUrd showed, in agreement with earlier studies on Escherichia coli, that BrdUrd was discriminated against when dThd was also present but was incorporated to essentially the same extent as dThd when only BrdUrd was present. In this latter case, strands fully substituted with BrdUrd were produced, but survival data suggest that bacteria deriving their DNA by replication on such fully substituted templates were inviable. However, bacteria with about 20% of the thymine substituted with bromouracil were usually viable. No mutations could be detected in the descendants of such bacteria. The reasons for this are discussed and it is concluded that in all probability the replication system in species rarely if ever treats incorporated bromouracil as anything except a thymine analogue. The alternative possibility, that the negative results are a consequence of the absence of the reclex (SOS) error-prone repair system in this species, is considered much less likely.

  10. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

    Directory of Open Access Journals (Sweden)

    Ghada Allan

    Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

  11. 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.

  12. Indenes and tetralenes analogues attenuates lipopolysaccharide-induced inflammation: An in-vitro and in-vivo study.

    Science.gov (United States)

    Mohanty, Shilpa; Gautam, Yashveer; Maurya, Anil Kumar; Negi, Arvind S; Prakash, Om; Khan, Feroz; Bawankule, Dnyaneshwar Umrao

    2016-02-01

    In an effort to evaluate novel pharmacological activity of 1-chloro-2-formyl indene and tetralene analogues possessing potential antitubercular and antistaphylococcal agents, we explored its anti-inflammatory potential against lipopolysaccharide(LPS)-induced inflammation using in-vitro and in-vivo bioassay. Synthesized analogues significantly inhibited the production and expression of pro-inflammatory cytokines against LPS-induced inflammation in macrophages isolated from mice. Among all the analogues, TAF-5 (1-Chloro-2-formyl-1-tetralene) exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the therapeutic efficacy and safety of TAF-5 in in-vivo system using LPS-induced sepsis, a systemic inflammation model and acute oral toxicity respectively in mice. Oral administration of TAF-5 inhibited the pro-inflammatory cytokines in serum, attenuated the organs injuries and improved host survival in dose dependent manner. Acute oral toxicity study showed TAF-5 is non-toxic at higher dose in mice. These results suggest the suitability of indene and tetralene analogues as new chemical entities for further investigation towards the management of inflammation related diseases.

  13. The nematocysts venom of Chrysaora helvola Brandt leads to apoptosis-like cell death accompanied by uncoupling of oxidative phosphorylation.

    Science.gov (United States)

    Qu, Xiaosheng; Fan, LanLan; Zhong, Taozheng; Li, Gang; Xia, Xianghua; Long, Hairong; Huang, Danna; Shu, Wei

    2016-02-01

    The present work investigated the effects of the nematocysts venom (NV) from the Chrysaora helvola Brandt (C. helvola) jellyfish on the human nasopharyngeal carcinoma cell line, CNE-2. The medium lethal concentration (LC50), quantified by MTT assays, was 1.7 ± 0.53 μg/mL (n = 5). An atypical apoptosis-like cell death was confirmed by LDH release assay and Annexin V-FITC/PI staining-based flow cytometry. Interestingly, activation of caspase-4 other than caspase-3, -8, -9 and -1 was observed. Moreover, the NV stimuli caused a time-dependent loss of mitochondrial membrane potential (ΔΨm) as was an intracellular ROS burst. These results indicated that there was uncoupling of oxidative phosphorylation (UOP). An examination of the intracellular pH value by a pH-sensitive fluorescent probe, BCECF, suggested that the UOP was due to the time-dependent increase in the intracellular pH. This is the first report that jellyfish venom can induce UOP.

  14. 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.

  15. Novel incretin analogues improve autophagy and protect from mitochondrial stress induced by rotenone in SH-SY5Y cells.

    Science.gov (United States)

    Jalewa, Jaishree; Sharma, Mohit Kumar; Hölscher, Christian

    2016-10-01

    treated with the stressor Rotenone. The novel GLP-1/GIP dual receptor agonist was superior and effective at a tenfold lower concentration compared to the other analogues. The drugs protected the cells from rotenone-induced impairment in cell growth and Akt activation, mitochondrial damage, impairments of autophagy and apoptotic cell signalling. See paper for details.

  16. 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.

  17. 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

  18. Effects of juvenile hormone analogue on ecdysis prevention induced by precocene in Rhodnius prolixus (Hemiptera: Reduviidae

    Directory of Open Access Journals (Sweden)

    Patricia de Azambuja

    1984-12-01

    Full Text Available Precocene II, added to the meal of fourth-instar larvae of Rhodnius prolixus (25 mug/ml of blood, induced an in crease in the duration of the molting cycle. This effect was related to the decrease of both the nuclear area of the prothoracic gland cells and the mitotic activity in epidermal cellS. juvenile hormone analogue applied topically (60 mug/insect together with Precocene II treatment avoided atrophy of the prothoracic glands and induced a higher number of epidermal mitosis accelerating the time of subsequent ecdysis. A possible relationship between juvenile hormone and production of ecdysone is discussed.Adicionado ao sangue alimentar na dose de 25 mug/ml o precoceno II causou um aumento no período de intermuda em ninfas de 4o. estadio de Rhodnius prolixus. Este atraso da muda foi relacionado com a diminuição da área dos núcleos das celulas das glandulas protoracicas e com a queda da atividade mitotica das células da epiderme do inseto. Um análogo de hormônio juvenil aplicado topicamente (60 mug/inseto junto com o tratamento oral com precoceno II preveniu a atrofia das glândulas protorácicas e induziu um aumento no número de mitoses nas células da epiderme, diminuindo o período de intermuda nestes insetos.A possivel relação entre a ação do hormônio juvenil e a producao de ecdisona pelas glândulas protorácicas e discutida.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Optical analogue of spontaneous symmetry breaking induced by tachyon condensation in amplifying plasmonic arrays

    CERN Document Server

    Marini, A; Roy, S; Longhi, S; Biancalana, F

    2013-01-01

    We study analytically and numerically an optical analogue of tachyon condensation in amplifying plasmonic arrays. Optical propagation is modeled through coupled-mode equations, which in the continuous limit can be converted into a nonlinear one-dimensional Dirac-like equation for fermionic particles with imaginary mass, i.e. fermionic tachyons. We demonstrate that the vacuum state is unstable and acquires an expectation value with broken chiral symmetry, corresponding to the homogeneous nonlinear stationary solution of the system. The quantum field theory analogue of this process is the condensation of unstable fermionic tachyons into massive particles. This paves the way for using amplifying plasmonic arrays as a classical laboratory for spontaneous symmetry breaking effects in quantum field theory.

  4. 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...

  5. Analysis of Cancer-Targeting Alkylphosphocholine Analogue Permeability Characteristics Using a Human Induced Pluripotent Stem Cell Blood-Brain Barrier Model.

    Science.gov (United States)

    Clark, Paul A; Al-Ahmad, Abraham J; Qian, Tongcheng; Zhang, Ray R; Wilson, Hannah K; Weichert, Jamey P; Palecek, Sean P; Kuo, John S; Shusta, Eric V

    2016-09-01

    Cancer-targeting alkylphosphocholine (APC) analogues are being clinically developed for diagnostic imaging, intraoperative visualization, and therapeutic applications. These APC analogues derived from chemically synthesized phospholipid ethers were identified and optimized for cancer-targeting specificity using extensive structure-activity studies. While they strongly label human brain cancers associated with disrupted blood-brain barriers (BBB), APC permeability across intact BBB remains unknown. Three of our APC analogues, CLR1404 (PET radiotracer), CLR1501 (green fluorescence), and CLR1502 (near-infrared fluorescence), were tested for permeability across a BBB model composed of human induced pluripotent stem cell-derived brain microvascular endothelial cells (iPSC-derived BMECs). This in vitro BBB system has reproducibly consistent high barrier integrity marked by high transendothelial electrical resistance (TEER > 1500 Ω-cm(2)) and functional expression of drug efflux transporters. The radioiodinated and fluorescent APC analogues demonstrated fairly low permeability across the iPSC-BMEC (35 ± 5.7 (CLR1404), 54 ± 3.2 (CLR1501), and 26 ± 4.9 (CLR1502) × 10(-5) cm/min) compared with BBB-impermeable sucrose (13 ± 2.5) and BBB-permeable diazepam (170 ± 29). Only the fluorescent APC analogues (CLR1501, CLR1502) underwent BCRP and MRP polarized drug efflux transport in the brain-to-blood direction of the BBB model, and this efflux can be specifically blocked with pharmacological inhibition. None of the tested APC analogues appeared to undergo substantial P-gp transport. Limited permeability of the APC analogues across an intact BBB into normal brain likely contributes to the high tumor to background ratios observed in initial human trials. Moreover, addition of fluorescent moieties to APCs resulted in greater BMEC efflux via MRP and BCRP, and may affect fluorescence-guided applications. Overall, the characterization of APC analogue permeability across human BBB

  6. 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...

  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 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

  9. 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...

  10. Evaluation of copper-dependent proteasome-inhibitory and apoptosis-inducing activities of novel pyrrolidine dithiocarbamate analogues.

    Science.gov (United States)

    Yu, Zhiyong; Wang, Fei; Milacic, Vesna; Li, Xiaofeng; Cui, Qiuzhi Cindy; Zhang, Bin; Yan, Bing; Dou, Q Ping

    2007-12-01

    Apoptosis has a central role in the pathogenesis of many human diseases, one of which is cancer. One of the most important strategies to regulate apoptosis is via the ubiquitin-proteasome pathway. It has been shown that inhibition of proteasomal chymotrypsin-like activity is a strong apoptosis-inducing stimulus and that actively proliferating cancer cells are more sensitive to proteasome inhibitors than normal or untransformed cells. Dithioscarbamates are a class of metal-chelating compounds with various applications in medicine. We reported previously that certain members of dithiocarbamates, such as pyrrolidine dithiocarbamate (PDTC), diethyldithiocarbamate and disulfiram, are able to bind with tumor cellular copper, forming an active complex with proteasome-inhibitory, apoptosis-inducing and anti-cancer activities. In the current study, we synthesized eight PDTC analogues with substitutions made to the pyrrolidine ring and studied their structure-activity relationships. We found that substitution of the pyrrolidine ring with piperidine had almost no effect on their proteasome-inhibitory and anti-proliferative potencies in human breast cancer cells. However, after the pyrrolidine ring was substituted with morpholine, the activity of the mixtures slightly decreased but was completely lost when piperazine with the attached ethyl group was used for the substitution. This structure-activity relationship was confirmed by the results generated with the corresponding copper complexes. Our data further support the novel concept of using accumulated copper in human cancer cells as a selective approach for chemotherapy. PMID:17982703

  11. 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

  12. 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

  13. 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...

  14. 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.

  15. Radical-induced chemistry from VUV photolysis of interstellar ice analogues containing formaldehyde

    Science.gov (United States)

    Butscher, Teddy; Duvernay, Fabrice; Danger, Grégoire; Chiavassa, Thierry

    2016-09-01

    Surface processes and radical chemistry within interstellar ices are increasingly suspected to play an important role in the formation of complex organic molecules (COMs) observed in several astrophysical regions and cometary environments. We present new laboratory experiments on the low-temperature solid state formation of complex organic molecules - glycolaldehyde, ethylene glycol, and polyoxymethylene - through radical-induced reactivity from VUV photolysis of formaldehyde in water-free and water-dominated ices. Radical reactivity and endogenous formation of COMs were monitored in situ via infrared spectroscopy in the solid state and post photolysis with temperature programmed desorption (TPD) using a quadripole mass spectrometer. We show the ability of free radicals to be stored when formed at low temperature in water-dominated ices, and to react with other radicals or on double bonds of unsaturated molecules when the temperature increases. It experimentally confirms the role of thermal diffusion in radical reactivity. We propose a new pathway for formaldehyde polymerisation induced by HCO radicals that might explain some observations made by the Ptolemy instrument on board the Rosetta lander Philae. In addition, our results seem to indicate that H-atom additions on H2CO proceed preferentially through CH2OH intermediate radicals rather than the CH3O radical.

  16. 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

  17. Classical analogue of electromagnetically induced transparency with a metal-superconductor hybrid metamaterial.

    Science.gov (United States)

    Kurter, Cihan; Tassin, Philippe; Zhang, Lei; Koschny, Thomas; Zhuravel, Alexander P; Ustinov, Alexey V; Anlage, Steven M; Soukoulis, Costas M

    2011-07-22

    Metamaterials are engineered materials composed of small electrical circuits producing novel interactions with electromagnetic waves. Recently, a new class of metamaterials has been created to mimic the behavior of media displaying electromagnetically induced transparency (EIT). Here we introduce a planar EIT metamaterial that creates a very large loss contrast between the dark and radiative resonators by employing a superconducting Nb film in the dark element and a normal-metal Au film in the radiative element. Below the critical temperature of Nb, the resistance contrast opens up a transparency window along with a large enhancement in group delay, enabling a significant slowdown of waves. We further demonstrate precise control of the EIT response through changes in the superfluid density. Such tunable metamaterials may be useful for telecommunication because of their large delay-bandwidth products.

  18. 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.

  19. Photon-induced electro-chemical processes in airless icy bodies analogues

    Science.gov (United States)

    Marchione, Demian; Gudipati, Murthy

    2016-10-01

    Previous laboratory studies have shown that radiation-induced ionization of impurities in water-rich ices drives the formation of ionized species resulting in charge generation and accumulation in ices [1-3]. It is expected that some of these impurity ions are decomposed into smaller volatile species and ejected into the vacuum. These processes are relevant to the chemical composition of the near-surface tenuous (thin) atmosphere of icy bodies such as the Jovian satellites like Europa.Our work aims at investigating photocurrents from organic impurity embedded water ices of several microns thick and understanding how these measurements correlate with the desorption of volatiles during UV and electron irradiation. These experiments are performed in an ultrahigh vacuum chamber around Europa's surface temperature (100 – 150 K) conditions using a low-pressure hydrogen flow-discharge lamp emitting primarily at Lyα (121.6 nm), a 2 keV electron source, and a substrate-less electrode. Photoionization of organic impurities in the water matrix results in charge pair (electron and ion) separation within the ice, and hence in detectable currents that are measured as a function of the applied bias and the temperature (5 K – 200 K). Photodesorption products are also identified by a quadrupole mass spectrometer (QMS) and correlated with conductivity measurements. We will discuss these results in the context of expected Europa's surface photoconductivity and near-surface volatile production.References:[1] M. S. Gudipati, and L. J. Allamandola, Astrophysical Journal Letters, 2003, 596(2), L195-L198.[2] M. S. Gudipati, Journal of Physical Chemistry A, 2004, 108(20), 4412-4419.[3] S. H. Cuylle, L. J. Allamandola, and H. Linnartz, Astronomy and Astrophysics, 2014, 562, A22.This work has been carried out at Jet Propulsion Laboratory, California Institute of Technology under a contract with the National Aeronautics and Space Administration, and funded by NASA under Planetary

  20. Effect of somatostatin analogue octreotide injected into the third cerebral ventricle on pentagastrin-induced gastric acid secretion in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Gao; Xiu-Fen Hu

    2006-01-01

    AIM: To investigate the effect of long-lasting somatostatin analogue octreotide (Oct) injected into the third cerebral ventricle (TCV) on gastric acid secretion in rats.METHODS: TCVs were cannulated in male Wistar rats anesthetized with sodium pentobarbital. One week later acute gastric lumen perfusion was carried out and gastric acid was continuously washed with 37℃ saline by a perfusion pump. Gastric perfusion samples were collected every 10 min and titrated by 0.01 moL/L NaOH to neutral. On the basis of subcutaneous (sc) injection of pentagastrin (G-5, 160 μg/kg), Oct (0.025 μg, 0.05 μg,0.1 μg, n= 12 in each group) or vehicle (pyrogen-free physiological saline, n = 10) was injected into the TCV.Before and after the TCV injection, 1 h total acid output (TAO) was determined and experimental data were expressed in change rate (%) of TAO.RESULTS: Oct (0.025, 0.05 and 0.1 μg) injected into the TCV resulted in change rate of 1.56% (P>0.05),20.21% (P< 0.01) and 37.82% of TAO (P< 0.001),respectively. Moreover, comparison in change rate of TAO among these 3 doses showed P< 0.05 between 0.025μg and 0.05 μg, P< 0.01 between 0.025 μg and 0.1μg,and P< 0.05 between 0.05μg and 0.1 μg. However, sc injection of 0.05 μg Oct had no effect on G-5 stimulated gastric acid secretion.CONCLUSION: Octreotide injected into the third cerebral ventricle inhibits gastrin-induced gastric acid secretion in a dose-dependent manner.

  1. 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

  2. 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.

  3. 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

  4. Pesticide- and sex steroid analogue-induced endocrine disruption differentially targets hypothalamo-hypophyseal-gonadal system during gametogenesis in teleosts - A review.

    Science.gov (United States)

    Senthilkumaran, Balasubramanian

    2015-08-01

    Pesticide-induced endocrine disruption often mimics sex steroidal action resulting in physiological functional disarray of hypothalamo-hypophyseal-gonadal (HHG) system at multiple levels. Among various group of pesticides, organochlorine and organophosphate family of pesticides are known to impart sex steroidal mimicking activity with slightly higher resemblance to estrogens when compared to androgenic action. This review will highlight the effects of organochlorine (for e.g. endosulfan) and organophosphate (for e.g. malathion) pesticides in comparison with sex-steroid analogue-induced changes on HHG axis during gametogenesis in few teleost fish models. Interestingly, the effects of these compounds have produced differential effects in juveniles and adults which also vary based on exposure dosage and duration. Further, the treatments had caused at times sexually dimorphic effects indicating that the action of these compounds bring out serious implications in sexual development. A comprehensive overview has been provided by considering all these aspects to recognize the adverse impacts of pesticide-induced endocrine disruption with special reference to endosulfan and malathion as those had been applied even today or used before for controlling agricultural pests in several Asian countries including India. This review also compares the effects of sex-steroid analogues where in sex reversal to reproductive dysfunction is evident, which may imply the extent of sexual plasticity in teleosts compared to other vertebrates.

  5. 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.

  6. 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.

  7. 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

  8. Analogue computing methods

    CERN Document Server

    Welbourne, D

    1965-01-01

    Analogue Computing Methods presents the field of analogue computation and simulation in a compact and convenient form, providing an outline of models and analogues that have been produced to solve physical problems for the engineer and how to use and program the electronic analogue computer. This book consists of six chapters. The first chapter provides an introduction to analogue computation and discusses certain mathematical techniques. The electronic equipment of an analogue computer is covered in Chapter 2, while its use to solve simple problems, including the method of scaling is elaborat

  9. 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.

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

    Science.gov (United States)

    Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

    2014-07-01

    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.

  11. Depletion of the SR-Related Protein TbRRM1 Leads to Cell Cycle Arrest and Apoptosis-Like Death in Trypanosoma brucei

    Science.gov (United States)

    Levy, Gabriela V.; Moretti, Georgina; Tekiel, Valeria S.; Sánchez, Daniel O.

    2015-01-01

    Arginine-Serine (RS) domain-containing proteins are RNA binding proteins with multiple functions in RNA metabolism. In mammalian cells this group of proteins is also implicated in regulation and coordination of cell cycle and apoptosis. In trypanosomes, an early branching group within the eukaryotic lineage, this group of proteins is represented by 3 members, two of them are SR proteins and have been recently shown to be involved in rRNA processing as well as in pre-mRNA splicing and stability. Here we report our findings on the 3rd member, the SR-related protein TbRRM1. In the present study, we showed that TbRRM1 ablation by RNA-interference in T. brucei procyclic cells leads to cell-cycle block, abnormal cell elongation compatible with the nozzle phenotype and cell death by an apoptosis-like mechanism. Our results expand the role of the trypanosomal RS-domain containing proteins in key cellular processes such as cell cycle and apoptosis-like death, roles also carried out by the mammalian SR proteins, and thus suggesting a conserved function in this phylogenetically conserved protein family. PMID:26284933

  12. 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.

  13. 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

  14. 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.

  15. Hepatic gene mutations induced in Big Blue rats by both the potent rat liver azo-carcinogen 6BT and its reported noncarcinogenic analogue 5BT.

    Science.gov (United States)

    Fletcher, K; Soames, A R; Tinwell, H; Lefevre, P A; Ashby, J

    1999-01-01

    The potent rat liver carcinogen 6-p-dimethylaminophenylazobenzthiazole (6BT) and its reported noncarcinogenic analogue 5-p-dimethylaminophenylazobenzthiazole (5BT; evaluated for carcinogenicity under the similar limited bioassay conditions used for 6BT) have been studied in order to seek an explanation for their different carcinogenic activities. Both compounds act as DNA-damaging agents to the rat liver, and both have now been shown to induce lacI (-) gene mutations in the liver of Big Blue(trade mark) transgenic rats. Both compounds were mutagenic following ten daily gavage doses or following administration in diet for 10 days. Neither chemical induced cell proliferation in the liver following repeat gavage administrations. In contrast, dietary administration of 6BT, and to a lesser extent of 5BT, induced hepatic cell proliferation. The carcinogen 6BT, but not the noncarcinogen 5BT, caused proliferation of oval stem cells in the livers by both routes of administration. It is possible that mutations induced in oval cells by 6BT are responsible for its potent carcinogenicity, and that the comparative absence of these cells in 5BT-treated livers may account for the carcinogenic inactivity of 5BT. Equally, the proliferation of the oval cells may reflect changes in liver homeostasis associated with the liver toxicity observed at the dose level of 6BT used (which was, nonetheless, the dose level used in the positive cancer bioassays). It is concluded that the new data presented cannot explain the differing carcinogenic activities of 5BT and 6BT, and that the reported noncarcinogen 5BT may also be carcinogenic when adequately assessed for this activity.

  16. 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.

  17. 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.

  18. Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice.

    Science.gov (United States)

    Ming-Tatt, Lee; Khalivulla, Shaik Ibrahim; Akhtar, Muhammad Nadeem; Mohamad, Azam Shah; Perimal, Enoch Kumar; Khalid, Mohamed Hanief; Akira, Ahmad; Lajis, Nordin; Israf, Daud Ahmad; Sulaiman, Mohd Roslan

    2012-03-01

    This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of

  19. 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

  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. 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.

  3. 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...

  4. 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

  5. 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

  6. Survey of analogue spacetimes

    CERN Document Server

    Visser, Matt

    2013-01-01

    Analogue spacetimes, (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole, (mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid --- and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: Analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this introductory chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  7. 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.

  8. 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.

  9. 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...

  10. 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 ...

  11. 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

  12. 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

  13. Gastric inhibitory polypeptide analogues

    DEFF Research Database (Denmark)

    Holst, Jens Juul

    2002-01-01

    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...... 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 receptor...

  14. 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

  15. 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

  16. 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.)

  17. Quantum analogue computing.

    Science.gov (United States)

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  18. 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.

  19. 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.

  20. Double differential cross sections for proton induced electron emission from molecular analogues of DNA constituents for energies in the Bragg peak region

    Science.gov (United States)

    Rudek, Benedikt; Bennett, Daniel; Bug, Marion U.; Wang, Mingjie; Baek, Woon Yong; Buhr, Ticia; Hilgers, Gerhard; Champion, Christophe; Rabus, Hans

    2016-09-01

    For track structure simulations in the Bragg peak region, measured electron emission cross sections of DNA constituents are required as input for developing parameterized model functions representing the scattering probabilities. In the present work, double differential cross sections were measured for the electron emission from vapor-phase pyrimidine, tetrahydrofuran, and trimethyl phosphate that are structural analogues to the base, the sugar, and the phosphate residue of the DNA, respectively. The range of proton energies was from 75 keV to 135 keV, the angles ranged from 15° to 135°, and the electron energies were measured from 10 eV to 200 eV. Single differential and total electron emission cross sections are derived by integration over angle and electron energy and compared to the semi-empirical Hansen-Kocbach-Stolterfoht (HKS) model and a quantum mechanical calculation employing the first Born approximation with corrected boundary conditions (CB1). The CB1 provides the best prediction of double and single differential cross section, while total cross sections can be fitted with semi-empirical models. The cross sections of the three samples are proportional to their total number of valence electrons.

  1. 薄荷油诱导大鼠类阳虚状态的实验研究%Experimental study on the rat's analogue yang deficiency situation induced by spearmint oil

    Institute of Scientific and Technical Information of China (English)

    崔一然; 刘小青; 刘欣; 张冰

    2011-01-01

    Objective: To investigate the cold and chilly drug property of BOHE and judge possibility of the rat's analogue yang deficiency situation, according to observe to normal rat's index change induced by spearmint oil which is main component in Herba Menthae (BOHE). Methods: SD male rats were randomly divided into control and spearmint oil large, small dose group, which control group was administrated distilled water and spearmint oil group was administrated spearmint oil. The intragastric administration were continued to 14 days and were taken bloody each week and were detected on these correlated index of endocrine system, immune system, substance metabolism and so on. Results: Compared with the control group, the spearmint oil group appearance analogue yang deficiency situation in entirety symptom and behaviors, hypothalamus-hypophysistarget gland function disturbance, substance metabolism loss and immunologic function disorder. Conclusion: The current study indicated that spearmint oil can to some extent leaded to analogue yang deficiency situation, which is the cold and chilly drug property of BOHE expression.%目的:观察薄荷主要成分薄荷油对正常大鼠的影响,判断其诱导正常大鼠类阳虚状态的可能性,继而探讨薄倚寒凉药性表达.方法:将大鼠随机分为正常组、薄荷油大、小剂量组,持续灌胃14d;每周取血1次,检测内分泌系统、免疫系统、物质代谢等相关指标.结果:薄荷油组在整体症状、行为上表现出类阳虚证的特征,下丘脑-垂体-靶腺轴功能发生障碍、物质代谢低下、免疫功能紊乱.结论:提示薄荷的主要成分薄荷油能够在一定程度上诱导大鼠出现类阳虚状态,大鼠所出现的类阳虚状态表达了薄荷寒凉药性.

  2. 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

  3. 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

  4. A Short Term Analogue Memory

    DEFF Research Database (Denmark)

    Shah, Peter Jivan

    1992-01-01

    A short term analogue memory is described. It is based on a well-known sample-hold topology in which leakage currents have been minimized partly by circuit design and partly by layout techniques. Measurements on a test chip implemented in a standard 2.4 micron analogue CMOS process show a droop...

  5. 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.

  6. 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

  7. 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

  8. 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

  9. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival.

    Science.gov (United States)

    Fischer, Walter; Gustafsson, Lotta; Mossberg, Ann-Kristin; Gronli, Janne; Mork, Sverre; Bjerkvig, Rolf; Svanborg, Catharina

    2004-03-15

    Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from alpha-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and alpha-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all alpha-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm(3)). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.

  10. 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

  11. 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

  12. 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

  13. Orthotopic transplantation of cryopreserved mouse ovaries and gonadotrophin releasing hormone analogues in the restoration of function following chemotherapy-induced ovarian damage.

    Directory of Open Access Journals (Sweden)

    Qing Li

    Full Text Available Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I; cyclophosphamide only (group II; cyclophosphamide plus GnRHa (group III; cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV. Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide.

  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. Central effects of angiotensin II, its fragment and analogues.

    Science.gov (United States)

    Georgiev, V P; Klousha, V E; Petkov, V D; Markovska, V L; Svirskis, S V; Mountsinietse, R K; Anouans, Z E

    1984-01-01

    The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

  16. 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...

  17. 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.

  18. 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)

  19. What Can We Learn From Analogue Experiments?

    CERN Document Server

    Thebault, Karim P Y

    2016-01-01

    In 1981 Unruh proposed that fluid mechanical experiments could be used to probe key aspects of the quantum phenomenology of black holes. In particular, he claimed that an analogue to Hawking radiation could be created within a fluid mechanical `dumb hole', with the event horizon replaced by a sonic horizon. Since then an entire sub-field of `analogue gravity' has been created. In 2016 Steinhauer reported the experimental observation of quantum Hawking radiation and its entanglement in a Bose-Einstein condensate analogue black hole. What can we learn from such analogue experiments? In particular, in what sense can they provide evidence of novel phenomena such as black hole Hawking radiation?

  20. 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.

  1. 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

  2. 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

  3. 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

  4. CO2 Capture with Enzyme Synthetic Analogue

    Energy Technology Data Exchange (ETDEWEB)

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  5. Liquid Crystal Analogue of Abrikosov Vortex Flow in Superconductors

    CERN Document Server

    Tanaka, A; Hayakawa, R

    1996-01-01

    We extend the correspondence between the Renn-Lubensky Twist-Grain-Boundary-A phase in chiral liquid crystals and the Abrikosov mixed state in superconductors to dynamical aspects. We find that for a TGB sample with free boundaries, an external electric field applied along the helical axis induces a uniform translational motion of the grain boundary system - an analogue of the well-known mixed state flux flow. Likewise, an analogue of the mixed state Nernst effect is found. In much the same way in which the flux flow carries intercore electric fields generating Joule heat in an otherwise dissipation-free system, the grain boundary flow carries along polarized charges, resulting in a finite electric conductivity in a ferroelectric.

  6. 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.

  7. Fully analogue photonic reservoir computer.

    Science.gov (United States)

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

    2016-01-01

    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.

  8. 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;

    1999-01-01

    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...... 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...

  9. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  10. Synthesis and biological evaluation of febrifugine analogues.

    Science.gov (United States)

    Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

    2014-12-01

    A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity. PMID:25632466

  11. 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

  12. 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

  13. Space analogue studies in Antarctica

    Science.gov (United States)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  14. 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.

  15. Analogue model studies of induction effects at auroral latitudes

    Directory of Open Access Journals (Sweden)

    A. Viljanen

    Full Text Available In addition to field observations and numerical models, geomagnetic induction effects can be studied by scaled analogue model experiments. We present here results of analogue model studies of the auroral electrojet with an Earth model simulating the Arctic Ocean and inland conductivity structures in northern Fennoscandia. The main elements of the analogue model used were salt water simulating the host rock, an aluminium plate corresponding to the ocean and graphite pieces producing the inland highly conducting anomalies. The electrojet was a time-harmonic line current flowing at a (simulated height of 100 km above northern Fennoscandia. The period simulated was 9 min.

    The analogue model results confirmed the well-known rapid increase of the vertical field when the coast is approached from the continent. The increase of the horizontal field due to induced ocean currents was demonstrated above the ocean, as well as the essentially negligible effect of these currents on the horizontal field on the continent.

    The behaviour of the magnetic field is explained with a simple two-dimensional thin-sheet model. The range, or the adjustment distance, of the ocean effect inland was found to be some hundreds of kilometers, which also agrees with earlier results of the Siebert-Kertz separation of IMAGE magnetometer data. The modelled inland anomalies evidently had too large conductivities, but on the other hand, their influence decayed on scales of only some tens of kilometers.

    Analogue model results, thin-sheet calculations, and field observations show that the induction effect on the horizontal magnetic field Bx near the electrojet is negligible. On the other hand, the vertical component Bz is clearly affected by induced currents in the ocean. Evidence of this is the shift of the zero point of Bz 0-1° southwards

  16. Sulfur analogues of psychotomimetic agents. Monothio analogues of mescaline and isomescaline.

    Science.gov (United States)

    Jacob, P; Shulgin, A T

    1981-11-01

    Two monothio analogues of mescaline and three monothio analogues of 2,3,4-trimethoxyphenethylamine (isomescaline) have been synthesized and characterized. Only the two mescaline analogues (3-and 4-thiomescaline) were found to be psychotomimetics in man, being 6 and 12 times more potent than mescaline, respectively. All five compounds can serve as substrates for bovine plasma monoamine oxidase in vitro, but no positive correlation is apparent between the extent of enzymatic degradation and human psychotomimetic potency.

  17. 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.

  18. 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)

  19. 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,

  20. Second-Generation Fluorescent Quadracyclic Adenine Analogues

    DEFF Research Database (Denmark)

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

    2015-01-01

    Fluorescent base analogues comprise a group of increasingly important molecules for the investigation of nucleic acid structure, dynamics, and interactions with other molecules. Herein, we report on the quantum chemical calculation aided design, synthesis, and characterization of four new putativ...

  1. 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.

  2. 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

  3. The structure activity relationship of discodermolide analogues.

    Science.gov (United States)

    Shaw, Simon J

    2008-03-01

    The marine polyketide discodermolide is a member of a class of natural products that stabilize microtubules. Many analogues have been synthesized suggesting that few changes can be made to the internal carbon backbone. Both ends of the molecule, however, can be modified. The majority of analogues have been generated via modification of the lactone region. This suggests that significant simplifications can be made in this region provided that the lactone moiety is maintained.

  4. 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...

  5. 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...

  6. Proliferative and signaling activities of insulin analogues in endometrial cancer cells.

    Science.gov (United States)

    Aizen, Daniel; Sarfstein, Rive; Bruchim, Ilan; Weinstein, Doron; Laron, Zvi; Werner, Haim

    2015-05-01

    Insulin analogues have been developed to achieve further improvement in the therapy of diabetes. However, modifications introduced into the insulin molecule may enhance their affinity for the insulin-like growth factor-1 receptor (IGF1R). Hyperinsulinemia has been identified as a risk factor for endometrial cancer. We hypothesized that insulin analogues may elicit atypical proliferative and signaling activities in endometrial cancer cells. Our results demonstrate that glargine, but not detemir, stimulated cell proliferation, displayed an anti-apoptotic effect, and had a positive effect on cell cycle progression in endometrial cancer cell lines ECC-1 and USPC-1. In addition, we showed that glargine and detemir induced dual activation of the insulin receptor (INSR) and IGF1R in both cell types. Furthermore, we showed that glargine elicited signaling events that are markedly different from those induced by insulin. In conclusion, our data support the concept that, although insulin analogues were designed to display insulin-like metabolic effects, glargine and, possibly, additional analogues exhibit IGF1-like activities and, accordingly, may function as IGF1 analogues. PMID:25697343

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Control of proliferating potential of myeloid leukemia cells during long-term treatment with vitamin D3 analogues and other differentiation inducers in combination with antileukemic drugs: in vitro and in vivo studies.

    Science.gov (United States)

    Kasukabe, T; Honma, Y; Hozumi, M; Suda, T; Nishii, Y

    1987-01-15

    Growth inhibition of murine and human myeloid leukemia cells by differentiation inducers during long-term culture was examined to improve the strategy for therapy of myeloid leukemia by differentiation inducers. When the effect of 1 alpha,25-dihydroxyvitamin D3, a typical differentiation inducer, on proliferation of mouse myeloid leukemia M1 cells was examined at a constant product of time and concentration (480 nM in 20 days), the continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3 was the most effective for inhibition of cell proliferation. After 20 days, the cumulative cell number was reduced about 3 X 10(5) times by continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. Similar results were obtained when M1 cells were treated continuously with dexamethasone. M1 cells resistant to 1 alpha,25-dihydroxyvitamin D3 appeared about 25 days after the start of continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. On the other hand, when M1 cells were treated continuously with 1 alpha,25-dihydroxyvitamin D3 and noncytotoxic doses of antileukemic drugs such as 1-beta-D-arabinofuranosylcytosine and daunomycin, resistant cells did not appear for at least 35 days. A similar effect of 1 alpha,25-dihydroxyvitamin D3 and antileukemic drugs on cell proliferation was observed with the human monoblast-like cell line U937. The survival of syngeneic SL mice inoculated with M1 cells was prolonged more by treatment with both 1 alpha-hydroxyvitamin D3 and daunomycin than by treatment with either drug alone. These results suggest that continuous treatment with both differentiation inducers and certain antileukemic drugs may be more effective therapeutically than treatment with a differentiation inducer alone.

  15. Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts

    DEFF Research Database (Denmark)

    Kupisiewicz, Katarzyna; Boissy, Patrice; Abdallah, Basem M;

    2010-01-01

    The plant phytoalexin resveratrol was previously demonstrated to inhibit the differentiation and bone resorbing activity of osteoclasts, to promote the formation of osteoblasts from mesenchymal precursors in cultures, and inhibit myeloma cell proliferation, when used at high concentrations....... In the current study, we screened five structurally modified resveratrol analogues for their ability to modify the differentiation of osteoclasts and osteoblasts and proliferation of myeloma cells. Compared to resveratrol, analogues showed an up to 5,000-fold increased potency to inhibit osteoclast...... differentiation. To a lesser extent, resveratrol analogues also promoted osteoblast maturation. However, they did not antagonize the proliferation of myeloma cells. The potency of the best-performing candidate in vitro was tested in vivo in an ovariectomy-induced model of osteoporosis, but an effect on bone loss...

  16. 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.

  17. 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.

  18. 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...

  19. 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

  20. Anti-hyperalgesic effect of a benzilidine-cyclohexanone analogue on a mouse model of chronic constriction injury-induced neuropathic pain: Participation of the κ-opioid receptor and KATP.

    Science.gov (United States)

    Ming-Tatt, Lee; Khalivulla, Shaik Ibrahim; Akhtar, Muhammad Nadeem; Lajis, Nordin; Perimal, Enoch Kumar; Akira, Ahmad; Ali, Daud Israf; Sulaiman, Mohd Roslan

    2013-12-01

    The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.

  1. 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

  2. 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)

  3. Prussian Blue Analogues of Reduced Dimensionality

    NARCIS (Netherlands)

    Gengler, Regis Y. N.; Toma, Luminita M.; Pardo, Emilio; Lloret, Francesc; Ke, Xiaoxing; Van Tendeloo, Gustaaf; Gournis, Dimitrios; Rudolf, Petra

    2012-01-01

    Mixed-valence polycyanides (Prussian Blue analogues) possess a rich palette of properties spanning from room-temperature ferromagnetism to zero thermal expansion, which can be tuned by chemical modifications or the application of external stimuli (temperature, pressure, light irradiation). While mol

  4. The glaciogenic reservoir analogue studies project (GRASP)

    DEFF Research Database (Denmark)

    Moscariello, A.; Moreau, Julien; Vegt, P. van der;

    increasing the risk associated with developing effectively these reservoirs. Therefore a analogue-based predictive stratigraphical and sedimentological model can help to steer drilling strategy and reduce uncertainties and associated risks. For this purpose the GRASP joint industry programme was established...

  5. 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...

  6. [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.

  7. [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

  8. 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

  9. The effects of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatory signaling pathways and CLP-induced lethal sepsis in mice.

    Science.gov (United States)

    Tham, Chau Ling; Lam, Kok Wai; Rajajendram, Revathee; Cheah, Yoke Kqueen; Sulaiman, Mohd Roslan; Lajis, Nordin H; Kim, Min Kyu; Israf, Daud A

    2011-02-10

    We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.

  10. [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

  11. 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.

  12. 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.

  13. 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

  14. 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 recent bleeding from oesophageal varices. DATA COLLECTION AND ANALYSIS: The outcome measures extracted were: mortality, blood transfusions, use of balloon tamponade, initial haemostasis and rebleeding. Intention-to-treat analyses including all randomised patients were conducted if possible; a random...

  15. 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

  16. 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...

  17. 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 ...

  18. 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...

  19. 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.

  20. 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...

  1. 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).

  2. Synthesis of a Cyclic Analogue of Galardin

    Institute of Scientific and Technical Information of China (English)

    马大为; 吴问根; 钱静; 郎深慧; 叶其壮

    2001-01-01

    A cyclic analogue 4 of galardin,a known MMP inhibitor,is designed to improve its selectivity.The synthesis of 4starts from dimethyl(S)-malate using diaselective alkylation and subsequent cyclization and amide formation as key steps.The compound 4 showed MMP inhibitory activity on all MMPs tested with IC50 ranging from 20.1 μM to 104 μM.

  3. 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

  4. Platinum analogues in preclinical and clinical development.

    Science.gov (United States)

    Hamilton, T C; O'Dwyer, P J; Ozols, R F

    1993-11-01

    The impact of cisplatin on chemotherapy for solid tumors has led to the synthesis of many molecules with platinum as their central building block. These so-called platinum analogues have been developed with the obvious goals of improving the antitumor activity of cisplatin and hopefully, at the same time, altering the dose-limiting side effects of the prototype drug. At least 10 such molecules are in clinical development, whereas several others are at various stages of preclinical testing. PMID:8305533

  5. h-analogue of Fibonacci Numbers

    OpenAIRE

    Benaoum, H. B.

    2009-01-01

    In this paper, we introduce the h-analogue of Fibonacci numbers for non-commutative h-plane. For h h'= 1 and h = 0, these are just the usual Fibonacci numbers as it should be. We also derive a collection of identities for these numbers. Furthermore, h-Binet's formula for the h-Fibonacci numbers is found and the generating function that generates these numbers is obtained.

  6. Evaluation of bone targeting salmon calcitonin analogues in rats developing osteoporosis and adjuvant arthritis.

    Science.gov (United States)

    Bhandari, Krishna H; Asghar, Waheed; Newa, Madhuri; Jamali, Fakhreddin; Doschak, Michael R

    2015-01-01

    Synthetic analogues of the peptide hormone calcitonin have been used in medicine as biologic drug therapies for decades, to treat pathological conditions of excessive bone turnover, such as osteoporosis, where more bones are removed than replaced during bone remodeling. Osteoporosis and other chronic skeletal diseases, including inflammatory arthritis, exact a substantial and growing toll on aging populations worldwide however they respond poor to synthetic biologic drug therapy, due in part to the rapid half-life of elimination, which for calcitonin is 43 minutes. To address those shortcomings, we have developed and synthesized bone-targeting variants of calcitonin as a targeted drug delivery strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in highly specific reaction conditions. To evaluate their in vivo efficacy, bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and dose escalation was performed in female rats developing Osteoporosis. The bone-targeting calcitonin analogues were also tested in a separate cohort of male rats developing adjuvant-induced arthritis. Ovariectomized female rats developing Osteoporosis were administered daily sub-cutaneous injection of analogues equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis was developed in male rats by administering Mycobacterium butyricum through tail base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg of calcitonin was administered and the rats were measured for visible signs of inflammation to a 21 day endpoint. In both studies, the effect of drug intervention upon bone volume and bone mineral density (BMD) was assessed by measuring the trabecular bone volume percentage and BMD at the proximal tibial metaphysis using in vivo micro-computed tomography. With dose escalation studies, only bone targeting analogue dosed groups

  7. Thymidine Analogues for Tracking DNA Synthesis

    Directory of Open Access Journals (Sweden)

    Brenton L. Cavanagh

    2011-09-01

    Full Text Available Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in “tagging DNA synthesis” is the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU. The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using ‘Huisgen’s reaction’ (1,3-dipolar cycloaddition or ‘click chemistry’. This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other “unnatural bases”. These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.

  8. 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.

  9. 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.

  10. Synthesis of analogues of Eunicea gamma-cembranolides containing cyclic ethers via saponification.

    Science.gov (United States)

    Rodríguez, A D; Piña, I C; Acosta, A L; Ramírez, C; Soto, J J

    2001-02-01

    A method for the synthesis of derivatives of the lead structures euniolide (1), 12,13-bisepieupalmerin (2), and eupalmerin acetate (3) containing tetrahydrofuran and tetrahydropyran ring systems was developed on the basis of alkali-induced intramolecular oxacyclizations. Representatives of the new analogues were submitted to the in vitro antitumor cell-line-screening program of the National Cancer Institute (NCI). While it was shown that a variety of structural modifications are possible, these transformations led typically to nontoxic synthetic cembranoids.

  11. 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...

  12. 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...

  13. 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.)

  14. 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.)

  15. 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)

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 侧脑室注射Conantokin-G类似物拮抗吗啡诱导小鼠奖赏效应的研究%EFFECTS OF CONANTOKIN-G ANALOGUE INJECTION INTO LATERAL VENTRICLE ON MORPHINE-INDUCED REWARDING IN MICE

    Institute of Scientific and Technical Information of China (English)

    李江敏; 李鹏飞; 朱永平

    2013-01-01

    Objective:To analyze the effects of Glu-Con-G、Glu-Con-G[1-11] and Glu-Con-G[S16Y] on morphine dependence,providing a direction to design the structure of Conantokin-G analogues.Methods:Male Kunming mice (18-20 g) were used in this experiment.Conditioned place preference model was used for assessing the effects of Glu-Con-G、Glu-Con-G[1-11] and Glu-Con-G[S16Y] on morphine dependence.Results:Glu-Con-G (120,240,480,960 pmol),Glu-Con-G[1-11] (120,240,480 pmol) and Glu-Con-G[S16Y] (480,960 pmol) inhibited the expression and reinstatement of morphine-induced CPP by single intracerebroventricular administration,with no significant behavioral disorders under the experimental conditions.Conclusion:These results indicate that three Conantokin-G analogues can inhibit morphine dependence.They are expected to become potential anti-addictive drugs.%目的:探究Glu-Con-G、Glu-Con-G[1-11]和Glu-Con-G[S16Y]抗吗啡精神依赖的药效,为进一步设计、筛选抗吗啡依赖的芋螺毒素类似物提供理论和实验依据.方法:采用清洁级♂昆明种小鼠,用条件性位置偏爱(conditioned place preference,CPP)模型检测侧脑室给予3种芋螺毒素类似物对小鼠吗啡精神依赖效应及行为学的影响.结果:120、240、480、960 pmol Glu-Con-G,120、240、480 pmol Glu-Con-G[1-11]和480、960 pmol Glu-Con-G[S16Y]对吗啡诱导小鼠CPP的表达和复燃有抑制作用,且在最高受试剂量时均不影响小鼠的运动活性及探索行为.结论:Glu-Con-G、Glu-Con-G[1-11]、Glu-Con-G[S16Y]可拮抗吗啡诱导小鼠CPP的表达和复燃,具有抗吗啡依赖作用,且不影响其运动活性和探索行为,有望成为抗吗啡依赖的潜在药物.

  4. 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.;

    2009-01-01

    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...

  5. 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...

  6. 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.)

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Alpha-melanocyte stimulating hormone analogues and their inducers for the treatment of vitiligo%α黑素细胞刺激素类似物及其诱导剂治疗白癜风的研究进展

    Institute of Scientific and Technical Information of China (English)

    王晨; 张海萍

    2015-01-01

    Alpha-melanocyte stimulating hormone (α-MSH),the strongest endogenous immunomodulatory small-molecule neuroendocrine peptide among melanocyte stimulating hormones,is mainly produced in the pituitary gland.α-MSH can promote melanocytes to proliferate and produce melanosomes,regulate the differentiation of melanocytes through the microphthalmia-associated transcription factor,and finally cause skin pigmentation.Many studies have shown that α-MSH levels are decreased in the epidermis and sera in patients with vitiligo.The α-MSH analogue afamelanotide,which can induce the expression of α-MSH by melanocytes,and the sex steroid thyroid hormone metharmon-F,both can be used to treat vitiligo through action on melanocytes,and have been lately recommended for the treatment of vitiligo at clinics.%α黑素细胞刺激素作为黑素细胞刺激素中作用最强的一种内源性小分子神经内分泌免疫调节肽,主要在脑垂体中产生.α黑素细胞刺激素可以促进黑素细胞增殖、产生黑素小体以及通过小眼畸形相关转录因子调节黑素细胞分化,引起皮肤色素沉着.研究发现,白癜风患者表皮及血浆中的α黑素细胞刺激素浓度降低.临床推荐α黑素细胞刺激素的类似物afamelanotide和性类固醇甲状腺激素治疗白癜风,性类固醇甲状腺激素可诱导黑素细胞α黑素细胞刺激素的表达,两者均可利用α黑素细胞刺激素作用于黑素细胞的原理而治疗白癜风.

  13. Asymmetric gravitational spreading - Analogue experiments on the Svecofennian orogen

    Science.gov (United States)

    Nikkilä, Kaisa; Korja, Annakaisa; Koyi, Hemin; Eklund, Olav

    2015-04-01

    Over-thickened orogenic crust may suffer from rheological, gravitational and topographical unbalancing resulting in discharging via gravitational spreading. If the thickened orogen is also hot, then increased temperature may reduce the viscosity of the crust that may induce large-scale horizontal flow. The effect of flow on the crustal architecture has previously been modeled with symmetric two-way spreading or asymmetric one- or two-way spreading (like channel flow) experiments. Most models do not take into account of the contrasting mechanical properties of the juxtaposed terranes. We have made analogue experiments to study gravitational one-way spreading and the interplay between two crustal blocks with contrasting rheological properties. The models are 3 cm thick replicas of 60 km thick crust. They have three horizontal layers representing strong lower, weak middle and brittle upper crust. The models have cuts to study the effect of inherited crustal-scale weakness zones. The experiments have been conducted within a large centrifuge in the Hans Ramberg Tectonic Laboratory at Uppsala University. The analogue models propose that asymmetric, unilateral flow has different effect on the contrasting crustal units, in both horizontal and vertical directions. The laterally heterogeneous crust flows towards the direction of extension, and it rotates and extends the pre-existing weakness zones. The weakness zones facilitate exhumation and they increase strain rate. The weakness zones split the crust into subblocks, which stretch individually and which may show signatures of compression or rotation. The changes in thickness of the model reflect changes in the layers, which may thin or thicken depending on the mechanical properties of crustal layers. A consequence of this the total amount of flattening is less than the model extension. The results are compared to geophysical and geological data from Precambrian Svecofennian orogen in Fennoscandia. The comparison suggest

  14. 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.

  15. 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.

  16. 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...

  17. Basic entwinements: unassuming analogue inserts in basic digital modeling (courses)

    DEFF Research Database (Denmark)

    Wiesner, Thomas

    2012-01-01

    morphologies in a seemingly scaleless manipulative universe, simple, rapid-paced analogue sketching tool can be introduced to supplement a purely digital approach. Inserted casually, yet with almost acupunctural precision during digital coursework, the simple analogue sketching tools present a wide variety...

  18. 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.

  19. A novel root analogue dental implant using CT scan and CAD/CAM: selective laser melting technology.

    Science.gov (United States)

    Figliuzzi, M; Mangano, F; Mangano, C

    2012-07-01

    Direct laser metal forming (DLMF) is a new technique which allows solids with complex geometry to be produced by annealing metal powder microparticles in a focused laser beam, according to a computer-generated three-dimensional (3D) model. For dental implants, the fabrication process involves the laser-induced fusion of titanium microparticles, in order to build, layer by layer, the desired object. Modern computed tomography (CT) acquisition and 3D image conversion, combined with the DLMF process, allows the fabrication of custom-made, root-analogue implants (RAI), perfect copies of the radicular units that need replacing. This report demonstrates the successful clinical use of a custom-made, root-analogue DLMF implant. CT images of the residual non-restorable root of a right maxillary premolar were acquired and modified with specific software into a 3D model. From this model, a custom-made, root-analogue, DLMF implant was fabricated. Immediately after tooth extraction, the root-analogue implant was placed in the extraction socket and restored with a single crown. At the 1-year follow-up examination, the custom-made implant showed almost perfect functional and aesthetic integration. The possibility of fabricating custom-made, root-analogue DLMF implants opens new interesting perspectives for immediate placement of dental implants.

  20. 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.

  1. 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

  2. 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...

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.)

  12. 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)

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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

  20. Highly expressed N1-acetylpolyamine oxidase detoxifies polyamine analogue N1-cyclopropylmethyl-N11-ethylnorspermine in human lung cancer cell line A549

    Institute of Scientific and Technical Information of China (English)

    HAN Yu; REN Yu-san; CAO Chun-yu; REN Dong-ming; ZHOU Yong-qin; WANG Yan-lin

    2009-01-01

    Background The critical roles of polyamines in cell growth and differentiation have made polyamine metabolic pathway a promising target for antitumor therapy. Recent studies have demonstrated in vitro that some antitumor polyamine analogues could be used as substrates and oxidized by purified recombinant human N1-acetylpolyamine oxidase (APAO, an enzyme that catabolizes natural polyamines), indicating a potential role of APAO in determining the sensitivity of cancer cells to specific antitumor analogues. This study evaluated, in vivo, the effect of APAO on cytotoxicity of antitumor polyamine analogue, N1-cyclopropylmethyI-N11-ethylnorspermine (CPENS) and its mechanism when highly expressed in human lung cancer line A549.Methods A clone with high expression of APAO was obtained by transfecting A549 lung cancer cell line with pcDNA3.1/APAO plasmid and selecting with quantitative realtime PCR and APAO activity assay. Cell proliferation was determined by MTT method and apoptosis related events were evaluated by DNA fragmentation, sub-G1/flow cytometric assay, western blotting (for cytochrome C and Bax) and colorimetric assay (for casapse-3 activity). Results A clone highly expressing APAO was obtained. High expression of APAO in A549 cells inhibited accumulation of CPENS, decreased their sensitivity to the toxicity of CPENS and prevented CPENS induced apoptosis. Conclusion These results indicate a new drug resisting, mechanism in the tumor cells. High expression of APAO can greatly decrease the sensitivity of tumor cells to the specific polyamine analogues by detoxitying those analogues and prevent analogue induced apoptosis.

  1. 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

  2. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    Science.gov (United States)

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  3. Analogue to Digital and Digital to Analogue (AD/DA) Conversion Techniques: An Overview

    CERN Document Server

    CERN. Geneva

    2002-01-01

    The basic ideas behind modern Analogue to Digital and Digital to Analogue (AD/DA) conversion methods will be introduced: a general view of the importance of these devices will be given, along with the digital representation of time-varying, real-world analogue signals. Some CERN applications will be outlined. The variety of conversion methods, their limitations, error sources and measurement methods will form the major part of this presentation. A review of the technological progress in this field over the last 30 years will be presented, concluding with the present 'state of the art' and a quick look at what is just around the corner. This Technical Training Seminar is in the framework of the FEED-2002 Lecture Series, and it is a prerequisite to attending to any of the FEED-2002 Terms. FEED-2002 is a two-term course that will review the techniques dealing with closed loop systems, focussing on time-invariant linear systems. (free attendance, no registration required) More information on the FEED-2002 ...

  4. Structure, Stability and Interaction Studies on Nucleotide Analogue Systems

    Directory of Open Access Journals (Sweden)

    R. Kanakaraju

    2003-08-01

    Full Text Available Abstract: Most of the biological molecules have a good interaction with water molecules. The hydrogen bonding interactions with the structural analogues of nucleic acid phosphate group namely dimethyl phosphate anion (DMP and diethyl phosphate anion (DEP are studied employing the ab initio and density functional theory methods. Inspections have been made to locate the reactive sites for the interactions of isomeric forms of mono, di and tri hydrates of alkyl phosphate anion using the above theories. It reveals, water molecules have a very strong interaction with the phosphate group in both the molecules and their interactions induce the changes in the structural parameters of the PO4 group for both the DMP and DEP anions. The optimized structural parameters, total energy, dipole moment and rotational constants are calculated and are compared with the available experimental values. The chemical hardness and chemical potential for these complexes have been calculated at HF/6-31G* level of theory and discussed the conformational stability of these complexes.

  5. 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...

  6. Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues.

    Science.gov (United States)

    Roselli, Mariagrazia; Carocci, Alessia; Budriesi, Roberta; Micucci, Matteo; Toma, Maddalena; Di Cesare Mannelli, Lorenzo; Lovece, Angelo; Catalano, Alessia; Cavalluzzi, Maria Maddalena; Bruno, Claudio; De Palma, Annalisa; Contino, Marialessandra; Perrone, Maria Grazia; Colabufo, Nicola Antonio; Chiarini, Alberto; Franchini, Carlo; Ghelardini, Carla; Habtemariam, Solomon; Lentini, Giovanni

    2016-10-01

    Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation. PMID:27267000

  7. Synthesis of new triazole arotinoids analogues via "Click Chemistry" with potential anticancer activity

    Directory of Open Access Journals (Sweden)

    Mariana A. A. Aleixo

    2012-06-01

    Full Text Available Retinoids are  a  class  of  natural  and  synthetic  vitamin A analogues structurally related to all-trans-retinoic acid (ATRA. This class of compounds can inhibit cell proliferation and induce differentiation and apoptosis of cells, and several are used in cancer therapy. Using the concept of bioisosterism, new triazole analogues were designed from the molecular modification of the potent derivative arotinoid AM580. This compound has an amide grouping which is a bioisostere of 1,2,3-triazole ring. Through "Click Chemistry” approach, triazole analogues were obtained by reaction of Huisgen 1,3-dipolar cycloaddition between aryl azides and terminal acetylene, previously synthesized. The reagents used were CuI, triethylamine and mixture of ethanol:water. The first compound synthesized showed anticancer activity, while the second proved to be inactive. The molecular docking results showed that both compounds have high affinity for the retinoid RARα receptor (related to anticancer activity, but probably the second compound has antagonist activity on this receptor.

  8. 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.

  9. 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

  10. 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

  11. Doing it with Mirrors Classical analogues for Black Hole radiation

    CERN Document Server

    Srinivasan, K

    1998-01-01

    We construct analogues for the quantum phenomena of black hole radiation in the context of {\\it classical field theory}. Hawking radiation from a (radially) collapsing star is mathematically equivalent to radiation from a mirror moving along a specific trajectory in Minkowski spacetime. We construct a classical analogue for this quantum phenomenon and use it to construct a classical analogue for black hole radiation. The radiation spectrum in quantum field theory has the power spectrum as its classical analogue. Monochromatic light is continually reflected off a moving mirror or the silvered surface of a collapsing star.The reflected light is fourier analysed by the observer and the power spectrum is constructed. For a mirror moving along the standard black hole trajectory,it is seen that the power spectrum has a ``thermal'' nature. Mirror-observer configurations like an inertial mirror observed in an accelerated observer's frame and an accelerated mirror observed in a Rindler frame are investigated and condi...

  12. From BPA to its analogues: Is it a safe journey?

    Science.gov (United States)

    Usman, Afia; Ahmad, Masood

    2016-09-01

    Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID:27262103

  13. 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.

  14. 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.

  15. Synthesis of Novel Isoxazole-contained Analogues of Losartan

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A series of novel isoxazole-contained analogues of Losartan were designed and synthesized with 1,3-DC reaction. The regioselectivity of the reaction was discussed and the compounds are potential antihypertensive.

  16. 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.

  17. 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.

  18. Current prodrug strategies for improving oral absorption of nucleoside analogues

    Directory of Open Access Journals (Sweden)

    Youxi Zhang

    2014-04-01

    Full Text Available Nucleoside analogues are first line chemotherapy in various severe diseases: AIDS (acquired immunodeficiency disease syndrome, cytomegalovirus infections, cancer, etc. However, many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability. In order to get around this drawback, prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug. Alternatively, prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues. Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1. The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport, but is readily degraded to the parent drug once at the target. This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.

  19. 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.

  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. 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...

  2. 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 ...

  3. 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...

  4. 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....

  5. 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....

  6. 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...

  7. 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.

  8. 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

  9. Photochemistry of free and bound Zn-chlorophyll analogues to synthetic peptides depend on the quinone and pH.

    Science.gov (United States)

    Razeghifard, Reza

    2015-11-01

    A synthetic peptide was used as a scaffold to bind Zn-Chlorophyll (ZnChl) analogues through histidine ligation to study their photochemistry in the presence of different type of quinones. The Chl analogues were chlorin e6 (Ce6), chlorin e6 trimethyl ester, pyropheophorbide a, and pheophorbide a while the quinones were PPBQ, DMBQ, NPHQ, DBTQ, DCBQ and PBQ. The binding of each ZnChl analogue to the peptide was verified by native gel electrophoresis. First the photo-stability of the ZnChl analogues were tested under continuous light. The ZnCe6 and ZnCe6TM analogues showed the least stability judged by the loss of optical signal intensity at their Qy band. The photoactivity of each ZnChl analogue was measured in the presence of each of the six quinones using time-resolved EPR spectroscopy. DMBQ was found to be the most efficient electron acceptor when all four ZnChl analogues were compared. The light-induced electron transfer between the ZnChl analogues complexed with the peptide and DMBQ were also measured using time-resolved EPR spectroscopy. The ZnCe6-peptide complex exhibited the highest photoactivity. The electron transfer in the complex was faster and the photoactivity yield was higher than those values obtained for free ZnCe6 and DMBQ. The fast phase of kinetics can be attributed to intra-protein electron transfer in the complex since it was not observed in the presence of DMBQ-glutathione adduct. Unlike free ZnCe6, the ZnCe6-peptide complex was robust and demonstrated very similar photoactivity efficiency in pH values 10, 8.0 and 5.0. The electron transfer kinetics were pH dependent and appeared to be modulated by the peptide charge and possibly fold. The charge recombination rate was slowed by an order of magnitude when the pH value was changed from 10.0 to 5.0. The implications of constructing the photoactive peptide complexes in terms of artificial photosynthesis are discussed.

  10. 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

  11. 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

  12. Chemotactic peptide analogues. Synthesis and chemotactic activity of N-formyl-Met-Leu-Phe analogues containing (S)-phenylalaninol derivatives.

    Science.gov (United States)

    Zecchini, G P; Paradisi, M P; Torrini, I; Spisani, S

    1995-09-01

    The synthesis and the biological activity towards human neutrophils of some N-formyl-Met-Leu-Phe-OMe analogues containing (S)-phenylalaninol (Pheol) or its derivatives in place of the native phenylalanine are reported. While the analogue containing Pheol (4) was found to be devoid of significant biological activity, its esters 3 and 5, although inactive as chemoattractants, are able to strongly stimulate superoxide production and are active with a lower efficacy in the lysozyme release. PMID:7487425

  13. 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.

  14. 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 ...

  15. An evaluation of indirubin analogues as phosphorylase kinase inhibitors.

    Science.gov (United States)

    Begum, Jaida; Skamnaki, Vassiliki T; Moffatt, Colin; Bischler, Nicolas; Sarrou, Josephine; Skaltsounis, Alexios-Leandros; Leonidas, Demetres D; Oikonomakos, Nikos G; Hayes, Joseph M

    2015-09-01

    Phosphorylase kinase (PhK) has been linked with a number of conditions such as glycogen storage diseases, psoriasis, type 2 diabetes and more recently, cancer (Camus et al., 2012 [6]). However, with few reported structural studies on PhK inhibitors, this hinders a structure based drug design approach. In this study, the inhibitory potential of 38 indirubin analogues have been investigated. 11 of these ligands had IC50 values in the range 0.170-0.360μM, with indirubin-3'-acetoxime (1c) the most potent. 7-Bromoindirubin-3'-oxime (13b), an antitumor compound which induces caspase-independent cell-death (Ribas et al., 2006 [20]) is revealed as a specific inhibitor of PhK (IC50=1.8μM). Binding assay experiments performed using both PhK-holo and PhK-γtrnc confirmed the inhibitory effects to arise from binding at the kinase domain (γ subunit). High level computations using QM/MM-PBSA binding free energy calculations were in good agreement with experimental binding data, as determined using statistical analysis, and support binding at the ATP-binding site. The value of a QM description for the binding of halogenated ligands exhibiting σ-hole effects is highlighted. A new statistical metric, the 'sum of the modified logarithm of ranks' (SMLR), has been defined which measures performance of a model for both the "early recognition" (ranking earlier/higher) of active compounds and their relative ordering by potency. Through a detailed structure activity relationship analysis considering other kinases (CDK2, CDK5 and GSK-3α/β), 6'(Z) and 7(L) indirubin substitutions have been identified to achieve selective PhK inhibition. The key PhK binding site residues involved can also be targeted using other ligand scaffolds in future work. PMID:26364215

  16. 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.

  17. 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.

  18. Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives.

    Science.gov (United States)

    Monte, A P; Waldman, S R; Marona-Lewicka, D; Wainscott, D B; Nelson, D L; Sanders-Bush, E; Nichols, D E

    1997-09-12

    hallucinogens, that such compounds must be full agonists at the 5-HT2A receptor subtype. In contrast to the 2,5-dimethoxy-substituted phenethylamines, where rigidification of the methoxy groups had no deleterious effect on activity, the loss of activity in the 3,4,5-trioxygenated mescaline analogues may suggest that the 3 and 5 methoxy groups must remain conformationally mobile to enable receptor activation.

  19. Iron isotopes in an Archean ocean analogue

    Science.gov (United States)

    Busigny, Vincent; Planavsky, Noah J.; Jézéquel, Didier; Crowe, Sean; Louvat, Pascale; Moureau, Julien; Viollier, Eric; Lyons, Timothy W.

    2014-05-01

    Iron isotopes have been extensively used to trace the history of microbial metabolisms and the redox evolution of the oceans. Archean sedimentary rocks display greater variability in iron isotope ratios and more markedly negative values than those deposited in the Proterozoic and Phanerozoic. This increased variability has been linked to changes in either water column iron cycling or the extent of benthic microbial iron reduction through time. We tested these contrasting scenarios through a detailed study of anoxic and ferruginous Lac Pavin (France), which can serve as a modern analogue of the Archean ocean. A depth-profile in the water column of Lac Pavin shows a remarkable increase in dissolved Fe concentration (0.1-1200 μM) and δ56Fe values (-2.14‰ to +0.31‰) across the oxic-anoxic boundary to the lake bottom. The largest Fe isotope variability is found at the redox boundary and is related to partial oxidation of dissolved ferrous iron, leaving the residual Fe enriched in light isotopes. The analysis of four sediment cores collected along a lateral profile (one in the oxic layer, one at the redox boundary, one in the anoxic zone, and one at the bottom of the lake) indicates that bulk sediments, porewaters, and reactive Fe mostly have δ56Fe values near 0.0 ± 0.2‰, similar to detrital iron. In contrast, pyrite δ56Fe values in sub-chemocline cores (60, 65, and 92 m) are highly variable and show significant deviations from the detrital iron isotope composition (δ56Fepyrite between -1.51‰ and +0.09‰; average -0.93‰). Importantly, the pyrite δ56Fe values mirror the δ56Fe of dissolved iron at the redox boundary—where near quantitative sulfate and sulfide drawdown occurs—suggesting limited iron isotope fractionation during iron sulfide formation. This finding has important implications for the Archean environment. Specifically, this work suggests that in a ferruginous system, most of the Fe isotope variability observed in sedimentary pyrites can

  20. MARKOV GRAPHS OF ONE–DIMENSIONAL DYNAMICAL SYSTEMS AND THEIR DISCRETE ANALOGUES AND THEIR DISCRETE ANALOGUES

    Directory of Open Access Journals (Sweden)

    SERGIY KOZERENKO

    2016-04-01

    Full Text Available One feature of the famous Sharkovsky’s theorem is that it can be proved using digraphs of a special type (the so–called Markov graphs. The most general definition assigns a Markov graph to every continuous map from the topological graph to itself. We show that this definition is too broad, i.e. every finite digraph can be viewed as a Markov graph of some one–dimensional dynamical system on a tree. We therefore consider discrete analogues of Markov graphs for vertex maps on combinatorial trees and characterize all maps on trees whose discrete Markov graphs are of the following types: complete, complete bipartite, the disjoint union of cycles, with every arc being a loop.

  1. 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

  2. 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

  3. Sodium Metasilicate Cemented Analogue Material and Its Mechanical Properties

    Directory of Open Access Journals (Sweden)

    Songlin Yue

    2016-01-01

    Full Text Available Analogue material with appropriate properties is of great importance to the reliability of geomechanical model test, which is one of the mostly used approaches in field of geotechnical research. In this paper, a new type of analogue material is developed, which is composed of coarse aggregate (quartz sand and/or barite sand, fine aggregate (barite powder, and cementitious material (anhydrous sodium silicate. The components of each raw material are the key influencing factors, which significantly affect the physical and mechanical parameters of analogue materials. In order to establish the relationship between parameters and factors, the material properties including density, Young’s modulus, uniaxial compressive strength, and tensile strength were investigated by a series of orthogonal experiments with hundreds of samples. By orthogonal regression analysis, the regression equations of each parameter were obtained based on experimental data, which can predict the properties of the developed analogue materials according to proportions. The experiments and applications indicate that sodium metasilicate cemented analogue material is a type of low-strength and low-modulus material with designable density, which is insensitive to humidity and temperature and satisfies mechanical scaling criteria for weak rock or soft geological materials. Moreover, the developed material can be easily cast into structures with complex geometry shapes and simulate the deformation and failure processes of prototype rocks.

  4. (+)-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

  5. 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).

  6. Conception, synthesis, and biological evaluation of original discodermolide analogues.

    Science.gov (United States)

    de Lemos, Elsa; Agouridas, Evangelos; Sorin, Geoffroy; Guerreiro, Antonio; Commerçon, Alain; Pancrazi, Ange; Betzer, Jean-François; Lannou, Marie-Isabelle; Ardisson, Janick

    2011-08-29

    Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.

  7. 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.

  8. Synthesis and cytotoxic activities of semisynthetic zearalenone analogues.

    Science.gov (United States)

    Tadpetch, Kwanruthai; Kaewmee, Benyapa; Chantakaew, Kittisak; Kantee, Kawalee; Rukachaisirikul, Vatcharin; Phongpaichit, Souwalak

    2016-08-01

    Zearalenone is a β-resorcylic acid macrolide with various biological activities. Herein we report the synthesis and cytotoxic activities of 34 zearalenone analogues against human oral epidermoid carcinoma (KB) and human breast adenocarcinoma (MCF-7) cells as well as noncancerous Vero cells. Some zearalenone analogues showed moderately enhanced cytotoxic activities against the two cancer cell lines. We have discovered the potential lead compounds with diminished or no cytotoxicity to Vero cells. Preliminary structure-activity relationship studies revealed that the double bond at the 1' and 2' positions of zearalenone core was crucial for cytotoxic activities on both cell lines. In addition, for zearalenol analogues, the unprotected hydroxyl group at C-2 and an alkoxy substituent at C-4 played key roles on cytotoxic effects of both cell lines.

  9. 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.

  10. 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.

  11. Analogue modelling of syntectonic leucosomes in migmatitic schists

    Science.gov (United States)

    Druguet, Elena; Carreras, Jordi

    2006-10-01

    Migmatites from the Cap de Creus tectonometamorphic belt display a wide variety of structures, from those formed when the leucosomes were melt-bearing, to those developed during solid-state deformation. The observed field structures have been modelled by means of analogue experiments. The materials used in the models are layered plasticine as a schist analogue, and chocolate as analogue of the crystallizing leucosome. A model for the development of syntectonic migmatites is proposed in which initial melt-bearing patches, preferentially formed within fertile pelitic layers, progressively evolve towards lens-shaped veins. Furthermore, heterogeneous deformation of anisotropic metasediments facilitates formation of extensional sites for further melt accumulation and transport. Melt crystallization implies a rapid increase in effective viscosity of leucosomes producing a reversal in competence contrast with respect to the enclosing schists. During the whole process, deformation localizes around crystallizing veins, giving rise to different and contrasting structures for melt-bearing and for solid-state stages.

  12. 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.

  13. Binding of a new bisphenol analogue, bisphenol S to bovine serum albumin and calf thymus DNA.

    Science.gov (United States)

    Wang, Yan-Qing; Zhang, Hong-Mei; Cao, Jian; Tang, Bo-Ping

    2014-09-01

    Interactions of bisphenol S, a new bisphenol analogue with bovine serum albumin and calf thymus DNA were investigated using different spectroscopic methods and molecular modeling calculation. According to the analysis of experimental and theoretical data, we concluded that hydrophobic interactions and hydrogen bonding primarily mediated the binding processes of bisphenol S with bovine serum albumin and DNA. In addition, the electrostatic force should not be excluded. Molecular modeling studies indicated that the binding site of bisphenol S to bovine serum albumin located in the subdomain IB, while bisphenol S was a groove binder of DNA. In addition, BPS did not obviously induce second structural changes of bovine serum albumin, but it induced a conformational change of calf thymus DNA.

  14. 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.

  15. 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...

  16. 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.

  17. 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

  18. 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

  19. Five new discodermolide analogues from the marine sponge Discodermia species.

    Science.gov (United States)

    Gunasekera, Sarath P; Paul, Gopal K; Longley, Ross E; Isbrucker, Richard A; Pomponi, Shirley A

    2002-11-01

    Discodermolide (1) and five new discodermolide analogues trivially named 2-epi-discodermolide (2), 2-des-methyldiscodermolide (3), 5-hydroxymethyldiscodermolate (4), 19-des-aminocarbonyldiscodermolide (5), and 9(13)-cyclodiscodermolide (6) have been isolated from marine sponges belonging to the genus Discodermia collected from the Caribbean Sea. The isolation, structure elucidation, and biological activities of 2-6 are described. The natural analogues, which were isolated in trace amounts, exhibited significant variation of cytotoxicity against the cultured murine P-388 leukemia and A-549 human adenocarcinoma cells and suggested the importance of the C(7) through C(17) moiety for potency against cultured tumor cell lines.

  20. 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

  1. Analogue Kerr-like geometries in a MHD inflow

    CERN Document Server

    Noda, Sousuke; Takahashi, Masaaki

    2016-01-01

    We present a model of the analogue black hole in magnetohydrodynamic (MHD) flow. For a two dimensional axisymmetric stationary trans-magnetosonic inflow with a sink, using the dispersion relation of the MHD waves, we introduce the effective geometries for magnetoacoustic waves propagating in the MHD flow. Investigating the properties of the effective potentials for magnetoacoustic rays, we find that the effective geometries can be classified into five types which include analogue spacetimes of the Kerr black hole, ultra spinning stars with ergoregions and spinning stars without ergoregions. We address the effects of the magnetic pressure and the magnetic tension on each magnetoacoustic geometries.

  2. 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.

  3. 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)

  4. Nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in olefin metathesis: a computational study.

    Science.gov (United States)

    Pazio, A; Woźniak, K; Grela, K; Trzaskowski, B

    2015-12-14

    We used the density functional theory to evaluate the suitability of nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in ruthenium-based metathesis catalysts. We demonstrate that these analogues induce only minor structural changes in Hoveyda-Grubbs-like precatalysts, but have major impact on precatalyst initiation. Nitrenium ion-modified precatalysts are characterized by a weak Ru-N bond resulting in a relatively strong Ru-O bond and large free energy barriers for initiation, making them good candidates for efficient latent Ru-based catalysts. On the other hand the trivalent boron ligand, bearing a formal -1 charge, binds strongly to the ruthenium ion, weakening the Ru-O bond and facilitating its dissociation, to promote fast reaction initiation. We show that the calculated bond dissociation energy of the Ru-C/N/B bond may serve as an accurate indicator of the Ru-O bond strength and the rate of metathesis initiation.

  5. 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

  6. Aromaticity in Polyacene Analogues of Inorganic Ring Compounds

    CERN Document Server

    Chattaraj, P K; Chattaraj, Pratim Kumar; Roy, Debesh Ranjan

    2006-01-01

    The aromaticity in the polyacene analogues of several inorganic ring compounds (BN-acenes, CN-acenes, BO-acenes and Na6-acenes) is reported here for the first time. Conceptual density functional theory based reactivity descriptors and the nucleus independent chemical shift (NICS) values are used in this analysis.

  7. 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

  8. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues

    NARCIS (Netherlands)

    Atopkina, LN; Malinovskaya, GV; Elyakov, GB; Uvarova, NI; Woerdenbag, HJ; Koulman, A; Potier, P

    1999-01-01

    The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were ac

  9. Evaluation of the antibacterial spectrum of drosocin analogues

    NARCIS (Netherlands)

    Bikker, F.J.; Kaman-van Zanten, W.E.; Vries-van de Ruit, A.M.B.C. de; Voskamp-Visser, I.; Hooft, P.A.V. van; Mars-Groenendijk, R.H.; Visser, P.C. de; Noort, D.

    2006-01-01

    Drosocin is a 19-mer, cationic antimicrobial peptide from Drosophila melanogaster. The aim of the study was to examine the antibacterial spectrum of unglycosylated drosocin analogues. Furthermore, the amino acid sequence of DnaK, drosocin's intracellular target, from susceptible species was aligned

  10. 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.

  11. 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.

  12. Block-level Bayesian diagnosis of analogue electronic circuits

    NARCIS (Netherlands)

    Krishnan, S.; Doornbos, K.D.; Brand, R.; Kerkhoff, H.G.

    2010-01-01

    Daily experience with product designers, test and diagnosis engineers it is realized that the depth of interaction among them, ought be high for sucessfull diagnosis of analogue circuits. With this knowledge in mind, a responsibility was undertaken to choose a popular diagnostic method and define a

  13. 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

  14. 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…

  15. 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

  16. 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...

  17. Combined treatment of somatostatin analogues with pegvisomant in acromegaly

    NARCIS (Netherlands)

    S.E. Franck; A. Muhammad; A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)

    2016-01-01

    textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups ha

  18. 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....

  19. 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.

  20. 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...

  1. Synthesis and Characterization of the Tetrazole Analogues of α-Amino Acids

    Institute of Scientific and Technical Information of China (English)

    Yan Min HUO; Gen Hu LEI; Yin Mao WEI; Xiao Hui ZHENG

    2006-01-01

    The tetrazole analogues have been synthesized from fluorenylmethoxycarbonyl (Fmoc)protected amino acids by three steps. The structures of the analogues were characterized by HPLC-MS, 1H NMR and 13C NMR.

  2. Non-robust numerical simulations of analogue extension experiments

    Science.gov (United States)

    Naliboff, John; Buiter, Susanne

    2016-04-01

    Numerical and analogue models of lithospheric deformation provide significant insight into the tectonic processes that lead to specific structural and geophysical observations. As these two types of models contain distinct assumptions and tradeoffs, investigations drawing conclusions from both can reveal robust links between first-order processes and observations. Recent studies have focused on detailed comparisons between numerical and analogue experiments in both compressional and extensional tectonics, sometimes involving multiple lithospheric deformation codes and analogue setups. While such comparisons often show good agreement on first-order deformation styles, results frequently diverge on second-order structures, such as shear zone dip angles or spacing, and in certain cases even on first-order structures. Here, we present finite-element experiments that are designed to directly reproduce analogue "sandbox" extension experiments at the cm-scale. We use material properties and boundary conditions that are directly taken from analogue experiments and use a Drucker-Prager failure model to simulate shear zone formation in sand. We find that our numerical experiments are highly sensitive to numerous numerical parameters. For example, changes to the numerical resolution, velocity convergence parameters and elemental viscosity averaging commonly produce significant changes in first- and second-order structures accommodating deformation. The sensitivity of the numerical simulations to small parameter changes likely reflects a number of factors, including, but not limited to, high angles of internal friction assigned to sand, complex, unknown interactions between the brittle sand (used as an upper crust equivalent) and viscous silicone (lower crust), highly non-linear strain weakening processes and poor constraints on the cohesion of sand. Our numerical-analogue comparison is hampered by (a) an incomplete knowledge of the fine details of sand failure and sand

  3. 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

  4. The Origin of Bond Selectivity and Excited-State Reactivity in Retinal Analogues.

    Science.gov (United States)

    Schapiro, Igor

    2016-05-19

    The effect of different conformations and substitutions on the photoisomerization of a retinal protonated Schiff base model is investigated by nonadiabatic molecular dynamics simulations. Three groups of retinal analogues are studied: (i) conformational isomers, (ii) methyl-substituted retinals, and (iii) C11-C12 bond locked retinals. In total 259 trajectories are calculated in the gas phase starting from different initial conditions. The effect on bond selectivity, the directionality of the isomerization, excited-state lifetime, and product distribution is derived from the ensemble of trajectories. Among the group of four isomers (9-, 11-, 13-cis, and all-trans) the 11-cis analogue is the most selective in terms of isomerizing double bond, while the other three produce a mixture of isomers. However, there is no preference for isomerization directionality and the product formation for the 11-cis isomer. In the group of analogues with different methylation patterns, it is found that a methyl group at position C10 can introduce unidirectionality. This methyl group also speeds the photoisomerization. In case of the analogue that is demethylated at the positions C10 and C13, all trajectories isomerize successfully from cis to trans conformation. The three C11-C12 bond locked retinals are found to have very different properties, which depend on the number of methylene units bridging this bond. The five-membered ring imposes a too-large restriction; hence, all trajectories remain on the excited state in the simulation time of 300 fs. The seven-membered ring is more flexible with preference for isomerization of the C9-C10 bond. Interestingly, the eight-membered ring leads to the fastest isomerization time and full directionality of C11-C12 bond isomerization. The trends observed in these simulations can help to understand whether the effects are intrinsic to the chromophore or are induced by the protein environment, by comparing to the trends from experiment. Furthermore

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

    DEFF Research Database (Denmark)

    Tamaseviciute, E.; Tamasevicius, A.; Mykolaitis, G.;

    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 stro......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...

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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...

  12. Effect of a prostacyclin analogue, iloprost, on urinary aquaporin-2 excretion in humans.

    Science.gov (United States)

    Buemi, Michele; Di Pasquale, Giuseppe; Ruello, Antonella; Floccari, Fulvio; Aloisi, Carmela; Latassa, Giuseppe; Corsonello, Andrea; Sturiale, Alessio; Corica, Francesco; Frisina, Nicola

    2002-06-01

    The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 +/- 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI(2)), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 +/- 0.15 to 1.8 +/- 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 +/- 0.2 to 1.8 +/- 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 +/- 0.12 vs. 3.15 +/- 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI(2) analogue, iloprost, can induce U-AQP2 excretion independent of AVP.

  13. 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

  14. 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....

  15. Lose-weight effect to high fat diet-induced obese mice of an analogue of rimonabant%利莫那班改构物对高脂饮食诱导肥胖小鼠的减肥效应及机制

    Institute of Scientific and Technical Information of China (English)

    杨海冬; 高静; 李静; 范如霖; 姚虎; 冯建科

    2012-01-01

    目的:从新合成的利莫那班改构物中筛选对饮食诱导的肥胖小鼠具有减肥作用的化合物,探讨其减肥效应及机制.方法:采用放射性受体配体结合试验测定利莫那班改构物对CB1受体的IC50,高脂饮食法诱导建立肥胖小鼠模型,给予改构物ZH 10 mg/kg和30 mg/k治疗4周,检测体质量变化以及生殖器周围脂肪含量、脂肪细胞形态和血清胆固醇、三酰甘油含量的变化.结果:改构物ZH对CB1受体具有抑制作用,可显著减少小鼠的食物摄入量和体质量,降低生殖器周围脂肪、血清胆固醇及三酰甘油的含量.结论:ZH可通过抑制CB1受体,降低食欲产生减肥作用,同时能降低血脂水平.%Objective: A series of analogues of rimonabant were synthesized to investigate their lose-weight effect and mechanisms. Methods: The IC50 of analogues on the CB1 were determined by Radioactive-ligand receptor binding assay, male ICR mice were fed with high fat diet to build the obese mice model and treated with 10 mg/kg or 30 mg/kg ZH per day for 4 weeks. Body weight and the content/morphology of genital peripheral adipose tissue were detected, the content of total cholesterol (TC) and triacylglycerol (TG) in serum were also estimated. Results; ZH had the inhibition on the CB1, it could significantly reduce the food intake and body weight, the content of genital peripheral adipose tissue, TC and TG in serum were reduced. Conclusion; ZH could suppress the CB1, ZH reduced the weight through inhibiting appetite and blood lip-id levels.

  16. 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

  17. 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

  18. 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).

  19. 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

  20. 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

  1. 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.

  2. Acute stress increases sex differences in risk seeking in the balloon analogue risk task.

    Directory of Open Access Journals (Sweden)

    Nichole R Lighthall

    Full Text Available BACKGROUND: Decisions involving risk often must be made under stressful circumstances. Research on behavioral and brain differences in stress responses suggest that stress might have different effects on risk taking in males and females. METHODOLOGY/PRINCIPAL FINDINGS: In this study, participants played a computer game designed to measure risk taking (the Balloon Analogue Risk Task fifteen minutes after completing a stress challenge or control task. Stress increased risk taking among men but decreased it among women. CONCLUSIONS/SIGNIFICANCE: Acute stress amplifies sex differences in risk seeking; making women more risk avoidant and men more risk seeking. Evolutionary principles may explain these stress-induced sex differences in risk taking behavior.

  3. Structural bisphenol analogues differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor.

    Science.gov (United States)

    Roelofs, Maarke J E; van den Berg, Martin; Bovee, Toine F H; Piersma, Aldert H; van Duursen, Majorie B M

    2015-03-01

    Although much information on the endocrine activity of bisphenol A (BPA) is available, a proper human hazard assessment of analogues that are believed to have a less harmful toxicity profile is lacking. Here the possible effects of BPA, bisphenol F (BPF), bisphenol S (BPS), as well as the brominated structural analogue and widely used flame retardant tetrabromobisphenol A (TBBPA) on human glucocorticoid and androgen receptor (GR and AR) activation were assessed. BPA, BPF, and TBBPA showed clear GR and AR antagonism with IC50 values of 67 μM, 60 μM, and 22 nM for GR, and 39 μM, 20 μM, and 982 nM for AR, respectively, whereas BPS did not affect receptor activity. In addition, murine MA-10 Leydig cells exposed to the bisphenol analogues were assessed for changes in secreted steroid hormone levels. Testicular steroidogenesis was altered by all bisphenol analogues tested. TBBPA effects were more directed towards the male end products and induced testosterone synthesis, while BPF and BPS predominantly increased the levels of progestagens that are formed in the beginning of the steroidogenic pathway. The MA-10 Leydig cell assay shows added value over the widely used H295R steroidogenesis assay because of its fetal-like characteristics and specificity for the physiologically more relevant testicular Δ4 steroidogenic pathway. Therefore, adding an in vitro assay covering fetal testicular steroidogenesis, such as the MA-10 cell line, to the panel of tests used to screen potential endocrine disruptors, is highly recommendable.

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Truong X., E-mail: truong.tran@mpl.mpg.de [Department of Physics, Le Quy Don University, 236 Hoang Quoc Viet str., 10000 Hanoi (Viet Nam); Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); Longhi, Stefano [Department of Physics, Politecnico di Milano and Istituto di Fotonica e Nanotecnologie del Consiglio Nazionale delle Ricerche, Piazza L. da Vinci 32, I-20133 Milano (Italy); Biancalana, Fabio [Max Planck Institute for the Science of Light, Günther-Scharowsky str. 1, 91058 Erlangen (Germany); School of Engineering and Physical Sciences, Heriot-Watt University, EH14 4AS Edinburgh (United Kingdom)

    2014-01-15

    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.

  6. 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.

  7. 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.

  8. Geoscience in Support of a Mars Methane Analogue Mission

    Science.gov (United States)

    Boivin, Alexandre

    The Mars Methane Analogue Mission, funded by the Canadian Space Agency through its Analogue Missions program, simulates a Mars rover mission whose purpose is to detect, analyse, and determine the source of methane emissions on the planet's surface. As part of this project, both an electromagnetic induction sounder (EMIS) and a high-resolution triangulation-based 3D laser scanner were tested in the field to demonstrate the benefit of including these instruments on future rover missions. EMIS data was inverted in order to derive information on the conductivity and magnetic susceptibility of the near subsurface. 3D laser scanner data was processed with fracture detection as a goal in order to simplify the search for areas of potential methane seepage. Both instruments were found to be very valuable for future rover missions of this type.

  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. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...... 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...... 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...

  12. Analogue Transformations in Physics and their Application to Acoustic

    CERN Document Server

    García-Meca, C; Barceló, C; Jannes, G; Sánchez-Dehesa, J; Martínez, A

    2013-01-01

    Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an "analogue transformation acoustics" formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give an explicit design of a spacetime compressor for acoustic waves and a carpet cloak for a moving aircraft.

  13. 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

  14. 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

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. Stark absorption spectroscopy of peridinin and allene-modified analogues

    Energy Technology Data Exchange (ETDEWEB)

    Kusumoto, Toshiyuki; Horibe, Tomoko [Department of Physics and CREST-JST, Graduated School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kajikawa, Takayuki; Hasegawa, Shinji [Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1, Sanda, Hyogo 669-1337 (Japan); Iwashita, Takashi [Suntory Institute for Bioorganic Research, Wakayamadai 1-1-1, Shimamoto, Mishimagunn, Osaka 618-8503 (Japan); Cogdell, Richard J. [Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8QQ, Scotland (United Kingdom); Birge, Robert R.; Frank, Harry A. [Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060 (United States); Katsumura, Shigeo [Department of Chemistry, School of Science and Technology, Kwansei Gakuin University, Gakuen 2-1, Sanda, Hyogo 669-1337 (Japan); Hashimoto, Hideki, E-mail: hassy@sci.osaka-cu.ac.jp [Department of Physics and CREST-JST, Graduated School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan)

    2010-07-19

    Stark absorption spectra of peridinin (Per) and five allene-modified analogues and their angular dependence as a function of an externally applied electric field were measured in methyl methacrylate polymer at 77 K. In all cases, the energetically lowest absorption band has a significant change of static dipole-moment upon photoexcitation ({Delta}{mu}). In particular, Per has the largest value of |{Delta}{mu}|. The angles between {Delta}{mu} and the transition dipole-moment of all the analogues were determined. It is suggested that the allene group in Per plays a key role as the electron donor in the charge transfer process following photoexcitation. The results of MNDO-PSDCI calculations support this idea.

  20. 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.

  1. 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.

  2. 3D-QSAR Studies of Dimethoxyphenoxyphenoxy pyrimidines and Analogues

    Institute of Scientific and Technical Information of China (English)

    李爱秀; 王瑾玲; 苏华庆; 缪方明

    2000-01-01

    Three-dimensional quantitative structure-activity relationships (3DQSAR) of a series of dimethoxyphenoxyphenoxypyrimidines and analogues which are known to be photosystem Ⅱ (PS Ⅱ )inhibitors have been studied using comparative molecular field analysis (CoMFA) method. The results suggest that the steric and electronic properties of substitutes at m-position on the end phenyl ring have important influence on the Hill reaction inhibition.

  3. Dust Plasma Analogue for Interstellar 217.5 nm Extinction

    Directory of Open Access Journals (Sweden)

    Stefanović, I.

    2008-12-01

    Full Text Available The new ultraviolet (UV extinction measurements of carbonaceous nanoparticles in the range from 140 nm to 260 nm are presented. The plasma polymerized hydrocarbon nanoparticles were already proposed as a new astro analogue, which describe the infrared (IR extinction spectra in an excellent way. We use the same particles to find the possible carrier of the "mysterious" UV 217.5 nm extinction "bump" of interstellar media (ISM.

  4. 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

  5. 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...

  6. 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.

  7. 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

  8. 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...

  9. 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-...

  10. 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...

  11. 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.

  12. Sums of multiplicative characters analogue of Kloosterman sums

    CERN Document Server

    Xi, Ping

    2010-01-01

    Let $q$ be a positive integer, $\\chi$ a nontrivial character mod $q$. In this paper the authors prove some estimates for the character sum which is analogue of incomplete Kloostermann sums\\[\\sum_{\\substack{a\\in\\mathcal{I}\\\\ \\gcd(a,q)=1}}\\chi(ma+n\\overline{a}),\\] where $\\overline{a}$ is the multiplicative inverse of $a\\bmod q$, and $\\mathcal{I}$ is a subinterval of $[x+1,x+q]$ for certain integer $x.$

  13. 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...

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. 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

  19. 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.

  20. 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].

  1. 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.

  2. 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

  3. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation.

    Science.gov (United States)

    Shang, Luqing; Wang, Yaxin; Qing, Jie; Shu, Bo; Cao, Lin; Lou, Zhiyong; Gong, Peng; Sun, Yuna; Yin, Zheng

    2014-12-01

    Enterovirus 71 (EV71), one of the major causative agents of Hand-Foot-Mouth Disease (HFMD), causes severe pandemics and hundreds of deaths in the Asia-Pacific region annually and is an enormous public health threat. However, effective therapeutic antiviral drugs against EV71 are rare. Nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. We evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue NITD008, which has been reported to be an antiviral reagent that specifically inhibits flaviviruses, effectively suppressed the propagation of different strains of EV71 in RD, 293T and Vero cells with a relatively high selectivity index. Triphosphorylated NITD008 (ppp-NITD008) functions as a chain terminator to directly inhibit the RNA-dependent RNA polymerase activity of EV71, and it does not affect the EV71 VPg uridylylation process. A significant synergistic anti-EV71 effect of NITD008 with rupintrivir (AG7088) (a protease inhibitor) was documented, supporting the potential combination therapy of NITD008 with other inhibitors for the treatment of EV71 infections.

  4. 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...

  5. 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

  6. 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.

  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. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. The modulation of tumour necrosis factor-alpha, interleukin-1 alpha and glucose levels with GMDP and other analogues of muramyl dipeptide.

    Science.gov (United States)

    Adeleye, T A; Moreno, C; Ivanyi, J; Aston, R

    1994-02-01

    Immunomodulatory agent muramyl dipeptide (MDP) and seven of its analogues were tested for ability to counteract the toxic actions of lipopolysaccharide (LPS) in experimental mouse models. Female BALB/c mice were presensitized with Corynebacterium parvum (P. acnes) and given MDP or equimolar doses of one of its analogues after 2 weeks, followed by intravenous challenge with LPS 18 h later. This treatment produced a sharp increase in blood cytokine (TNF-alpha, IL-1 alpha) levels 4 h after LPS administration followed by a decline to control values after 6 h. Four analogues, GMDP, threonylMDP, GMDPBenz and GMDPOBut, were able to reduce the level of cytokines induced with LPS. For most of the analogues, the higher doses reduced the levels of TNF-alpha but slightly increased the concomitant IL-1 alpha levels. GMDP was the most effective compound tested in terms of reduction of TNF-alpha and IL-1 alpha levels, as well as for reduction of the hypoglycaemia caused by the administration of LPS. PMID:8167010

  14. Asymmetric Synthesis and Binding Study of New Long-Chain HPA-12 Analogues as Potent Ligands of the Ceramide Transfer Protein CERT.

    Science.gov (United States)

    Ďuriš, Andrej; Daïch, Adam; Santos, Cécile; Fleury, Laurence; Ausseil, Frédéric; Rodriguez, Frédéric; Ballereau, Stéphanie; Génisson, Yves; Berkeš, Dušan

    2016-05-01

    A series of 12 analogues of the Cer transfer protein (CERT) antagonist HPA-12 with long aliphatic chains were prepared as their (1R,3S)-syn and (1R,3R)-anti stereoisomers from pivotal chiral oxoamino acids. The enantioselective access to these intermediates as well as their ensuing transformation relied on a practical crystallization-induced asymmetric transformation (CIAT) process. Sonogashira coupling followed by triple bond reduction and thiophene ring hydrodesulfurization (HDS) into the corresponding alkane moieties was then implemented to complete the synthetic routes delivering the targeted HPA-12 analogues in concise 4- to 6-step reaction sequences. Ten compounds were evaluated regarding their ability to bind to the CERT START domain by using the recently developed time-resolved FRET-based homogeneous (HTR-FRET) binding assay. The introduction of a lipophilic appendage on the phenyl moiety led to an overall 10- to 1000-fold enhancement of the protein binding, with the highest effect being observed for a n-hexyl residue in the meta position. The importance of the phenyl ring for the activity was indicated by the reduced potency of the 3-deoxyphytoceramide aliphatic analogues. The 1,3-syn stereoisomers were systematically more potent than their 1,3-anti analogues. In silico studies were used to rationalized these trends, leading to a model of protein recognition coherent with the stronger binding of (1R,3S)-syn HPAs.

  15. 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

  16. 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

  17. Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

    Science.gov (United States)

    Maćczak, Aneta; Bukowska, Bożena; Michałowicz, Jaromir

    2015-01-01

    Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed its significant hemolytic and oxidative potential. Moreover, no study has been conducted to evaluate the effect of BPA analogues on red blood cells. The purpose of the present study was to compare the impact of BPA and its selected analogues such as bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on hemolytic and morphological changes and hemoglobin oxidation (methemoglobin formation) of human erythrocytes. The erythrocytes were incubated with different bisphenols concentrations ranging from 0.5 to 500μg/ml for 1, 4 and 24h. The compounds examined caused hemolysis in human erythrocytes with BPAF exhibiting the strongest effect. All bisphenols examined caused methemoglobin formation with BPA inducing the strongest oxidative potential. Flow cytometry analysis showed that all bisphenols (excluding BPS) induced significant changes in erythrocytes size. Changes in red blood cells shape were conducted using phase contrast microscopy. It was noticed that BPA and BPAF induced echinocytosis, BPF caused stomatocytosis, while BPS did not provoke significant changes in shape of red blood cells. Generally, the results showed that BPS, which is the main substituent of bisphenol A in polymers and thermal paper production, exhibited significantly lower disturbance of erythrocyte functions than BPA.

  18. 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

  19. Properties of granular analogue model materials: A community wide survey

    Science.gov (United States)

    Klinkmüller, M.; Schreurs, G.; Rosenau, M.; Kemnitz, H.

    2016-08-01

    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 μm. Analysis of grain shape factors shows 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 an internal cohesion in the order of 20-100 Pa except for well-rounded glass beads, which show a trend towards a quasi-cohesionless (C < 20 Pa) Coulomb-type material. The uniaxial confined compression tests reveal that rounded grains generally show less compaction than angular grains. We interpret this to be related to the initial packing density after sifting, 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.

  20. 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

  1. 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

  2. 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

  3. Prototype Analogue Optical Links for the CMS Tracker Readout System

    CERN Document Server

    Arbet-Engels, Vincent; Gill, Karl; Grabit, Robert; Mommaert, Chantal; Stefanini, Giorgio; Vasey, François

    1997-01-01

    The optical fibre links for the analogue readout of the CMS tracker are based on the direct modulation of edge-emitting lasers located inside the detector volume. The front-end signals are transmitted by single-mode optical fibres and detected in the counting room using PIN photodiodes. One channel link demonstrators consisting of commercially available optoelectronic devices have been fully characterized. The lasers, fibres, and PIN diodes are representative of the devices intended to be used in the final system. The link overall performance is discussed in terms of its static and dynamic responses and is shown to meet the technical specifications of the full readout chain.

  4. 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.

  5. 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...

  6. 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,...

  7. A Mutasynthetic Library of Platensimycin and Platencin Analogues.

    Science.gov (United States)

    Dong, Liao-Bin; Rudolf, Jeffrey D; Shen, Ben

    2016-09-16

    Inactivation of ptmB1, ptmB2, ptmT2, or ptmC in Streptomyces platensis SB12029, a platensimycin (PTM) and platencin (PTN) overproducer, revealed that PTM and PTN biosynthesis features two distinct moieties that are individually constructed and convergently coupled to afford PTM and PTN. A focused library of PTM and PTN analogues was generated by mutasynthesis in the ΔptmB1 mutant S. platensis SB12032. Of the 34 aryl variants tested, 18 were incorporated with high titers. PMID:27599271

  8. Stimulated Raman adiabatic passage analogues in classical physics

    Energy Technology Data Exchange (ETDEWEB)

    Rangelov, A A [University of Kassel, Heinrich-Plett-Str. 40, D-34132 Kassel (Germany); Vitanov, N V [Department of Physics, Sofia University, James Bourchier 5 blvd., 1164 Sofia (Bulgaria); Shore, B W [618 Escondido Cir., Livermore, CA (United States)

    2009-03-14

    Stimulated Raman adiabatic passage (STIRAP) is a well-established technique for producing coherent population transfer in a three-state quantum system. We here exploit the resemblance between the Schroedinger equation for such a quantum system and the Newton equation of motion for a classical system undergoing torque to discuss several classical analogues of STIRAP, notably the motion of a moving charged particle subject to the Lorentz force of a quasistatic magnetic field, the orientation of a magnetic moment in a slowly varying magnetic field and the Coriolis effect. Like STIRAP, these phenomena occur for counterintuitive motion of the torque and are robustly insensitive to small changes in the interaction properties.

  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. Coupling between mantle and surface processes: Insights from analogue modelling

    Science.gov (United States)

    Király, Ágnes; Sembroni, Andrea; Faccenna, Claudio; Funiciello, Francesca

    2014-05-01

    Thermal or density anomalies located beneath the lithosphere are thought to generate dynamic topography. Such a topographic signal compensates the viscous stresses originating from the anomaly driven mantle flow. It has been demonstrated that the erosion modulates the dynamic signal of topography changing the uplift rate by unload. The characteristic time for adjustments of dynamic topography due to surface erosion is likely similar to post-glacial rebound time (10000 - 50000 years). Here we present preliminary results of a new set of analogue models realized to study and quantify the contribution given by erosion to dynamic topography, during a process specifically driven by a positively buoyant deep anomaly. The adopted set up consists of a Plexiglas box (40x40x50 cm3) filled with glucose syrup as analogue upper mantle. A silicon plate positioned on the top of the syrup simulates the lithosphere. On the silicone plate is placed a thin layer of a high viscous glucose syrup which reproduces the upper, erodible layer of the crust. To simulate the positively buoyant anomaly we used an elastic, undeformable silicon ball free to rise by buoyancy in the syrup until the floating silicone plate is hit. The changes in topography have been monitored by using a 3D laser scan, while a side-view camera recorded the position of the rising ball in time. Data have been post-processed with image analysis techniques (e.g., Particle Image Velocimetry) in order to obtain the evolution of topography, uplift rate, erosion patterns of the top layer, bulge width and mantle circulation during the experiment. We ran experiments with and without the shallow, erodible crustal layer in order to quantify the effect of erosion on dynamic topography. Preliminary results showed that both the maximum topography and uplift rate are inversely proportional to the lithospheric thickness. The maximum uplift rate and the deformation of the lithospheric plate occurred just before the arrival of the

  11. Discodermolide analogues as the chemical component of combination bacteriolytic therapy.

    Science.gov (United States)

    Smith, Amos B; Freeze, B Scott; LaMarche, Matthew J; Sager, Jason; Kinzler, Kenneth W; Vogelstein, Bert

    2005-08-01

    The marine natural product (+)-discodermolide (1) and several simplified analogues of this microtubule-stabilizing agent have proven to be potent in vitro cell growth inhibitory agents in several human cancer cell lines. Here, we demonstrate the in vivo efficacy of discodermolide and several simplified congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3-anhydrodiscodermolide (3), as a chemical component of the combination bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically modified Clostridium novyi-NT spores caused rapid and complete regressions of tumors in mice bearing HCT116 colorectal cancer xenografts.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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.

  18. 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.

  19. Enantioselctive Syntheses of Sulfur Analogues of Flavan-3-Ols

    Directory of Open Access Journals (Sweden)

    Richard Lombardy

    2010-08-01

    Full Text Available The first enantioselective syntheses of sulfur flavan-3-ol analogues 1–8 have been accomplished, whereby the oxygen atom of the pyran ring has been replaced by a sulfur atom. The key steps were: (a Pd(0 catalyzed introduction of –S t-butyl group, (b Sharpless enantioselective dihydroxylation of the alkene, (c acid catalyzed ring closure to produce the thiopyran ring, and (d removal of benzyl groups using N,N-dimethylaniline and AlCl3. The compounds were isolated in high chemical and optical purity.

  20. 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...

  1. 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...

  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. 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  

  4. 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)

  5. 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...

  6. 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...

  7. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....

  8. 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...

  9. Biological activity of modified and exchanged 2-amino-5-nitrothiazole amide analogues of nitazoxanide.

    Science.gov (United States)

    Ballard, T Eric; Wang, Xia; Olekhnovich, Igor; Koerner, Taylor; Seymour, Craig; Hoffman, Paul S; Macdonald, Timothy L

    2010-06-15

    Head group analogues of the antibacterial and antiparasitic drug nitazoxanide (NTZ) are presented. A library of 39 analogues was synthesized and assayed for their ability to suppress growth of Helicobacter pylori, Campylobacter jejuni, Clostridium difficile and inhibit NTZ target pyruvate:ferredoxin oxidoreductase (PFOR). Two head groups assayed recapitulated NTZ activity and possessed improved activity over their 2-amino-5-nitrothiazole counterparts, demonstrating that head group modification is a viable route for the synthesis of NTZ-related antibacterial analogues. PMID:20488706

  10. 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

  11. 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

  12. 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.

  13. Semisynthetic analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, Sarath P; Longley, Ross E; Isbrucker, Richard A

    2002-12-01

    A series of 12 semisynthetic discodermolide analogues, 2-13, have been prepared using natural (+)-discodermolide (1) and evaluated for in vitro cytotoxicity against cultured murine P-388 leukemia and A-549 human adenocarcinoma cells. These semisynthetic analogues showed a significant variation of cytotoxicity and confirmed the importance of the C-7 through C-19 molecular fragment for potency. Specifically, these analogues suggested the importance of the C-11 and C-17 hydroxyl groups and the C-13 double bond for the potency of discodermolide. The preparation, structure elucidation, and biological activity of these new analogues are described.

  14. Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro

    Directory of Open Access Journals (Sweden)

    Jignesh Lunagariya

    2016-09-01

    Full Text Available Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1–2 μg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin, respectively.

  15. Design and Synthesis of Analogues of Marine Natural Product Galaxamide, an N-methylated Cyclic Pentapeptide, as Potential Anti-Tumor Agent in Vitro

    Science.gov (United States)

    Lunagariya, Jignesh; Zhong, Shenghui; Chen, Jianwei; Bai, Defa; Bhadja, Poonam; Long, Weili; Liao, Xiaojian; Tang, Xiaoli; Xu, Shihai

    2016-01-01

    Herein, we report design and synthesis of novel 26 galaxamide analogues with N-methylated cyclo-pentapeptide, and their in vitro anti-tumor activity towards the panel of human tumor cell line, such as, A549, A549/DPP, HepG2 and SMMC-7721 using MTT assay. We have also investigated the effect of galaxamide and its representative analogues on growth, cell-cycle phases, and induction of apoptosis in SMMC-7721 cells in vitro. Reckon with the significance of conformational space and N-Me aminoacid (aa) comprising this compound template, we designed the analogues with modification in N-Me-aa position, change in aa configuration from l to d aa and substitute one Leu-aa to d/l Phe-aa residue with respective to the parent structure. The efficient solid phase parallel synthesis approach is employed for the linear pentapeptide residue containing N-Me aa, followed by solution phase macrocyclisation to afford target cyclo pentapeptide compounds. In the present study, all galaxamide analogues exhibited growth inhibition in A549, A549/DPP, SMMC-7721 and HepG2 cell lines. Compounds 6, 18, and 22 exhibited interesting activities towards all cell line tested, while Compounds 1, 4, 15, and 22 showed strong activity towards SMMC-7221 cell line in the range of 1–2 μg/mL IC50. Flow cytometry experiment revealed that galaxamide analogues namely Compounds 6, 18, and 22 induced concentration dependent SMMC-7721 cell apoptosis after 48 h. These compounds induced G0/G1 phase cell-cycle arrest and morphological changes indicating induction of apoptosis. Thus, findings of our study suggest that the galaxamide and its analogues 6, 18 and 22 exerted growth inhibitory effect on SMMC-7721 cells by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Compound 1 showed promising anti-tumor activity towards SMMC-7721 cancer cell line, which is 9 and 10 fold higher than galaxamide and reference DPP (cisplatin), respectively. PMID:27598177

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Martian Analogues Emissivity Spectra From the Berlin Emissivity Database (BED)

    Science.gov (United States)

    Maturilli, A.; Helbert, J.; Moroz, L.

    2006-12-01

    Remote sensing infrared spectroscopy is the principal field of investigation for planetary surfaces composition. Past, present and future missions to bodies in the solar system include in their payload instruments measuring the emerging radiation in the infrared range. For the interpretation of the measured data an emissivity spectral library of planetary analog materials is needed. The Berlin Emissivity Database (BED) currently contains emissivity spectra of plagioclase and potassium feldspars, low Ca and high Ca pyroxenes, olivine, elemental sulphur, and Martian analogue minerals, measured in the wavelength range from 7 to 22 microns as a function of particle size. For each sample we measured the spectra of four particle size separates ranging from 0 to 250 microns. The device we used is built at DLR (Berlin) and is coupled to a Fourier transform infrared spectrometer (Bruker IFS 88), purged with dry air and equipped with a cooled detector (MCT). All spectra were acquired with a spectral resolution of 4 cm-1. We present here the results of our analysis on well knew and characterized Martian analogue minerals: JSC Mars-1, Salten Skov, and Palagonite from Mauna Kea, Hawaii. We are currently working to upgrade our emissivity facility. A new spectrometer (Bruker VERTEX 80v) and new detectors will allow us to measure the emissivity of samples in the wavelength range from 1 to 50 microns, even in a vacuum environment.

  3. 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

  4. 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)

  5. Spin Alignment in Analogues of The Local Sheet

    CERN Document Server

    Conidis, George J

    2014-01-01

    Tidal torque theory and simulations of large scale structure predict spin vectors of massive galaxies should be coplanar with sheets in the cosmic web. Recently demonstrated, the giants (K$_{s}$ $\\leq$ -22.5 mag) in the Local Volume beyond the Local Sheet have spin vectors directed close to the plane of the Local Supercluster, supporting the predictions of Tidal Torque Theory. However, the giants in the Local Sheet encircling the Local Group display a distinctly different arrangement, suggesting that the mass asymmetry of the Local Group or its progenitor torqued them from their primordial spin directions. To investigate the origin of the spin alignment of giants locally, analogues of the Local Sheet were identified in the SDSS DR9. Similar to the Local Sheet, analogues have an interacting pair of disk galaxies isolated from the remaining sheet members. Modified sheets in which there is no interacting pair of disk galaxies were identified as a control sample. Galaxies in face-on control sheets do not display ...

  6. 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.

  7. Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin.

    Science.gov (United States)

    Yadav, Babasaheb; Taurin, Sebastien; Rosengren, Rhonda J; Schumacher, Marc; Diederich, Marc; Somers-Edgar, Tiffany J; Larsen, Lesley

    2010-09-15

    A series of 18 heterocyclic cyclohexanone analogues of curcumin have been synthesised and screened for their activity in both adherent and non-adherent cancer cell models. Cytotoxicity towards MBA-MB-231 breast cancer cells, as well as ability to inhibit NF-kappaB transactivation in non-adherent K562 leukemia cells were investigated. Three of these analogues 3,5-bis(pyridine-4-yl)-1-methylpiperidin-4-one B1, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one B10, and 8-methyl-2,4-bis((pyridine-4-yl)methylene)-8-aza-bicyclo[3.2.1]octan-3-one C1 showed potent cytotoxicity towards MBA-MB-231, MDA-MB-468, and SkBr3 cell lines with EC50 values below 1 microM and inhibition of NF-kappaB activation below 7.5 microM. The lead drug candidate, B10, was also able to cause 43% of MDA-MB-231 cells to undergo apoptosis after 18 h. This level of activity warrants further investigation for the treatment of ER-negative breast cancer and/or chronic myelogenous leukemia as prototypical cellular models for solid and liquid tumors.

  8. State selective reactions of cosmic dust analogues at cryogenic temperatures

    CERN Document Server

    Perry, J S A

    2001-01-01

    Molecular hydrogen (H sub 2) is the most abundant molecule in interstellar space. It is crucial for initiating all of the chemistry in the Interstellar Medium (ISM) and consequently plays an important role in star formation. However, the amount of H sub 2 believed to exist in the ISM cannot be accounted for by formation through gas-phase reactions alone. The current, widely accepted theory, is that H sub 2 forms on the surface of cosmic dust grains. These grains are thought to be composed of amorphous forms of carbon or silicates with temperatures of around 10 K. This thesis describes a new experiment that has been constructed to study H sub 2 formation on the surface of cosmic dust analogues and presents the initial experimental results. The experiment simulates, through ultra-high vacuum and the use of cryogenics, the conditions of the ISM where cosmic dust grains and H sub 2 molecules exist. During the experiment, a beam of atomic hydrogen is aimed at a cosmic dust analogue target. H sub 2 formed on the ta...

  9. 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^{-...

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Mitochondria Superoxide Anion Production Contributes to Geranylgeraniol-Induced Death in Leishmania amazonensis.

    Science.gov (United States)

    Lopes, Milene Valéria; Desoti, Vânia Cristina; Caleare, Angelo de Oliveira; Ueda-Nakamura, Tânia; Silva, Sueli Oliveira; Nakamura, Celso Vataru

    2012-01-01

    Here we demonstrate the activity of geranylgeraniol, the major bioactive constituent from seeds of Bixa orellana, against Leishmania amazonensis. Geranylgeraniol was identified through (1)H and (13)C nuclear magnetic resonance imaging and DEPT. The compound inhibited the promastigote and intracellular amastigote forms, with IC(50) 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. PMID:23304195

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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…

  1. 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;

    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...

  2. Solid-phase synthesis of new saphenamycin analogues with antimicrobial activity

    DEFF Research Database (Denmark)

    Laursen, Jane B.; De Visser, Peter C.; Nielsen, Henrik 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...

  3. Acetylated analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.

    Science.gov (United States)

    Gunasekera, S P; Longley, R E; Isbrucker, R A

    2001-02-01

    A series of eight discodermolide acetates have been prepared using natural (+)-discodermolide and evaluated for in vitro cytotoxicity against the cultured murine P-388 leukemia cells. The acetylated analogues showed a significant variation of cytotoxicity and suggested the importance of C-11 and C-17 hydroxyl groups for potency. The preparation and structure elucidation of the new analogues are described.

  4. Characterization of Nucleobase Analogue FRET Acceptor tCnitro

    DEFF Research Database (Denmark)

    Preus, Søren; Börjesson, Karl; Kilså, Kristine;

    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...

  5. 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.

  6. Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

    DEFF Research Database (Denmark)

    Crestey, François; Jensen, Anders A.; Borch, Morten;

    2013-01-01

    The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype...

  7. 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

  8. Synthesis of the 4’-desmethoxy analogue of RU79115

    Directory of Open Access Journals (Sweden)

    MICHEL KLICH

    2004-11-01

    Full Text Available The synthesis, and biological activity in vitro of the 4’-desmethoxy analogue (3 of RU 79115 (2 is described. Comparison of the biological activity of the two analogues clearly indicated the importance of the 4’-methoxy group in conferring good gyrase B inhibitory activity as well as antibacterial activity.

  9. Insulin analogues in pregnancy and specific congenital anomalies; a literature review

    NARCIS (Netherlands)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-01-01

    BACKGROUND: 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. METHODS: We performed a literature search for

  10. 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

  11. 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.

  12. The sensitivity of an actinic reticuloid cell strain to near-ultraviolet radiation and its modification by trolox-C, a vitamin E analogue.

    Science.gov (United States)

    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 degrees 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.

  13. 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.

  14. Ultraviolet variability of the solar analogue star Alpha Centauri A

    International Nuclear Information System (INIS)

    Fifty-seven observations of the solar analogue Alpha Centauri A made by the International Ultraviolet Explorer over a 3-year interval have been examined for variability. The authors find that the ultraviolet continuum flux of this star in the 1,715-1,915-angstrom range varies by as much as 19% (with a standard deviation of ± 1.3%). However, nearly all of this range in variability can occur within one stellar rotation period. Consequently, if Alpha Cen A undergoes a stellar activity cycle similar to that of the Sun, the results indicate that the amplitude of this modulation is small, contrary to recently proposed empirical (theoretical) models of solar activity

  15. Classical aspects of Hawking radiation verified in analogue gravity experiment

    CERN Document Server

    Weinfurtner, Silke; Penrice, Matthew C J; Unruh, William G; Lawrenc, Gregory A

    2013-01-01

    There is an analogy between the propagation of fields on a curved spacetime and shallow water waves in an open channel flow. By placing a streamlined obstacle into an open channel flow we create a region of high velocity over the obstacle that can include wave horizons. Long (shallow water) waves propagating upstream towards this region are blocked and converted into short (deep water) waves. This is the analogue of the stimulated Hawking emission by a white hole (the time inverse of a black hole). The measurements of amplitudes of the converted waves demonstrate that they appear in pairs and are classically correlated; the spectra of the conversion process is described by a Boltzmann-distribution; and the Boltzmann-distribution is determined by the determined by the change in flow across the white hole horizon.

  16. Measurement of stimulated Hawking emission in an analogue system

    CERN Document Server

    Weinfurtner, Silke; Penrice, Matthew C J; Unruh, William G; Lawrence, Gregory A

    2010-01-01

    There is a mathematical analogy between the propagation of fields in a general relativistic space-time and long (shallow water) surface waves on moving water. Hawking argued that black holes emit thermal radiation via a quantum spontaneous emission. Similar arguments predict the same effect near wave horizons in fluid flow. By placing a streamlined obstacle into an open channel flow we create a region of high velocity over the obstacle that can include wave horizons. Long waves propagating upstream towards this region are blocked and converted into short (deep water) waves. This is the analogue of the stimulated emission by a white hole (the time inverse of a black hole), and our measurements of the amplitudes of the converted waves demonstrate the thermal nature of the conversion process for this system. Given the close relationship between stimulated and spontaneous emission, our findings attest to the generality of the Hawking process.

  17. Measurement of stimulated Hawking emission in an analogue system.

    Science.gov (United States)

    Weinfurtner, Silke; Tedford, Edmund W; Penrice, Matthew C J; Unruh, William G; Lawrence, Gregory A

    2011-01-14

    Hawking argued that black holes emit thermal radiation via a quantum spontaneous emission. To address this issue experimentally, we utilize the analogy between the propagation of fields around black holes and surface waves on moving water. By placing a streamlined obstacle into an open channel flow we create a region of high velocity over the obstacle that can include surface wave horizons. Long waves propagating upstream towards this region are blocked and converted into short (deep-water) waves. This is the analogue of the stimulated emission by a white hole (the time inverse of a black hole), and our measurements of the amplitudes of the converted waves demonstrate the thermal nature of the conversion process for this system. Given the close relationship between stimulated and spontaneous emission, our findings attest to the generality of the Hawking process. PMID:21405217

  18. Glutathione analogue sorbents selectively bind glutathione S-transferase isoenzymes.

    Science.gov (United States)

    Castro, V M; Kelley, M K; Engqvist-Goldstein, A; Kauvar, L M

    1993-06-01

    Novel affinity sorbents for glutathione S-transferases (GSTs) were created by binding glutathione (GSH) analogues to Sepharose 6B. The GSH molecule was modified at the glycine moiety and at the group attached to the sulphur of cysteine. When tested by affinity chromatography in a flow-through microplate format, several of these sorbents selectively bound GST isoenzymes. gamma E-C(Hx)-phi G (glutathione with a hexyl moiety bound to cysteine and phenylglycine substituted for glycine) specifically bound rat GST 7-7, the Pi-class isoenzyme, from liver, kidney and small intestine. gamma E-C(Bz)-beta A (benzyl bound to cysteine and beta-alanine substituted for glycine) was highly selective for rat subunits 3 and 4, which are Mu-class isoenzymes. By allowing purification of the isoenzymes under mild conditions that preserve activity, the novel sorbents should be useful in characterizing the biological roles of GSTs in both normal animal and cancer tissues.

  19. Characterizing the magnetic fields of the first tau Sco analogues

    CERN Document Server

    Kochukhov, V Petit O; 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, in order to characterize the stellar and magnetic properties of these stars. A magnetic field of similar surface strength was found on both stars, reinforcing the connection between the presence of a magnetic field and wind peculiarities. We present additional phase-resolved observations secured by the MiMeS collaboration for HD 66665 in order to measure its magnetic geometry, and correlate that geometry with diagnostics of mass-loss.

  20. Characterizing the magnetic fields of the first τ Sco analogues

    Science.gov (United States)

    Petit, V.; Kochukhov, O.; Massa, D. L.; Marcolino, W. L. F.; Wade, G. A.; Ignace, R.

    2012-05-01

    The B0.2 V magnetic star τ 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. [1] presented the discovery of the first two τ Sco analogues - HD66665 and HD63425, identified by the striking similarity of their UV spectra to that of τ Sco. ESPaDOnS and Narval spectropolarimetric observations were obtained by the Magnetism in Massive Stars CFHT and TBL Large Programs, in order to characterize the stellar and magnetic properties of these stars. A magnetic field of similar surface strength was found on both stars, reinforcing the connection between the presence of a magnetic field and wind peculiarities. We present additional phaseresolved observations secured by the MiMeS collaboration for HD66665 in order to measure its magnetic geometry, and correlate that geometry with diagnostics of mass-loss.

  1. Low-cost SI-POF analogue TIA and equaliser

    Science.gov (United States)

    Lope, Ignacio; García del Pozo, Jose Maria; Mateo, Javier; Urdangarín, Julen; Celma, Santiago

    2012-11-01

    This article proposes the two first blocks of an analogue front-end suitable for plastic optical fibre systems suitable for the standard IEEE 1394. These blocks consist of a preamplifier followed by an equaliser which employs low-cost commercial components and are designed with two different bipolar technologies. With a supply voltage of 3.3 V, the front-end consumes 396 mW. The total gain is 70 dBΩ and it operates at up to 800 Mb/s. At this bit rate, with fibre lengths of up to 30 m, the circuit has a BER ≤ 10-12 and a maximum jitter of 170 psrms.

  2. Novel Conformationally Constrained Analogues of Agomelatine as New Melatoninergic Ligands

    Directory of Open Access Journals (Sweden)

    Marouan Rami

    2012-12-01

    Full Text Available Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT1 and MT2 melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3, oxadiazole-5(4H-one (compound 4, tetrazole (compound 5, oxazolidinone (compound 7a, pyrrolidinone (compound 7b, imidazolidinedione (compound 12, thiazole (compounds 13 and 14 and isoxazole moieties (compound 15 led to a decrease of the melatoninergic binding affinities, particularly at MT1. Compounds 7a and 7b exhibiting nanomolar affinity towards the MT2 receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT2-selectivity.

  3. Novel C-Ring-Hydroxy-Substituted Controlled Deactivation Cannabinergic Analogues.

    Science.gov (United States)

    Kulkarni, Shashank; Nikas, Spyros P; Sharma, Rishi; Jiang, Shan; Paronis, Carol A; Leonard, Michael Z; Zhang, Bin; Honrao, Chandrashekhar; Mallipeddi, Srikrishnan; Raghav, Jimit Girish; Benchama, Othman; Järbe, Torbjörn U C; Bergman, Jack; Makriyannis, Alexandros

    2016-07-28

    In pursuit of safer controlled-deactivation cannabinoids with high potency and short duration of action, we report the design, synthesis, and pharmacological evaluation of novel C9- and C11-hydroxy-substituted hexahydrocannabinol (HHC) and tetrahydrocannabinol (THC) analogues in which a seven atom long side chain, with or without 1'-substituents, carries a metabolically labile 2',3'-ester group. Importantly, in vivo studies validated our controlled deactivation approach in rodents and non-human primates. The lead molecule identified here, namely, butyl-2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-3-yl]-2-methylpropanoate (AM7499), was found to exhibit remarkably high in vitro and in vivo potency with shorter duration of action than the currently existing classical cannabinoid agonists. PMID:27367336

  4. Does an all-sulphur analogue of heptamolybdate exist?

    Indian Academy of Sciences (India)

    Bikshandarkoil R Srinivasan

    2004-08-01

    The complexes [MoX4]2- (M = Mo; X = O or S) exist as the monomeric tetrahedral species in aqueous alkaline solutions. Acidification of tetraoxomolybdate results in the condensation of the tetrahedral units via a series of polyoxomolybdates leading to the ultimate formation of the trioxide MoO3. Heptamolybdate [Mo7O24]6- is the first major polyanion of the acidification reaction. In contrast, acidification of tetrathiomolybdates leads to the formation of amorphous molybdenum trisulphide via a dinuclear Mo(V) complex. The formation of the dinuclear Mo(V) complex precludes the formation of any higher nuclearity Mo(VI)-S complexes in aqueous solution. Thus it is shown that the all-sulphur analogue of heptamolybdate [Mo7S2]6- does not exist in alkaline medium and also cannot be isolated from aqueous acidic medium.

  5. Newton's cradle analogue with Bose-Einstein condensates

    Science.gov (United States)

    Franzosi, Roberto; Vaia, Ruggero

    2014-05-01

    We propose a possible experimental realization of a quantum analogue of Newton's cradle using a configuration which starts from a Bose-Einstein condensate. The system consists of atoms with two internal states trapped in a one-dimensional tube with a longitudinal optical lattice and maintained in a strong Tonks-Girardeau regime at maximal filling. In each site the wave-function is a superposition of the two atomic states and a disturbance of the wave-function propagates along the chain in analogy with the propagation of momentum in the classical Newton cradle. The quantum travelling signal is generally deteriorated by dispersion, which is large for a uniform chain and is known to be zero for a suitably engineered chain, but the latter is hardly realizable in practice. Starting from these opposite situations we show how the coherent behaviour can be enhanced with minimal experimental effort.

  6. Status of the International Alligator Rivers Analogue Project

    International Nuclear Information System (INIS)

    The International Alligator Rivers Analogue Project (ARAP) commenced on September 1, 1987 under the sponsorship of the OECD Nuclear Energy Agency. Six organizations from five NEA Member countries are participating in a three-year program with a budget of A $2.6 million (US $2 million) in 1987 dollars. The main objective is to contribute to the production of reliable and realistic models of radionuclide migration within geological environments relevant to the assessment of the safety of radioactive waste repositories. A detailed technical program was approved by a Joint Technical Committee and this comprises six main sub-projects: modelling of radionuclide migration, hydrogeology at the Koongarra uranium deposit, uranium/thorium series disequilibria studies, colloid and groundwater studies, fission product studies and transuranic nuclide studies. This paper discusses how collaborative research, service work and consulting contracts are being carried out by organizations in Australia, Japan, the UK and the USA

  7. The Mojave vadose zone: a subsurface biosphere analogue for Mars.

    Science.gov (United States)

    Abbey, William; Salas, Everett; Bhartia, Rohit; Beegle, Luther W

    2013-07-01

    If life ever evolved on the surface of Mars, it is unlikely that it would still survive there today, but as Mars evolved from a wet planet to an arid one, the subsurface environment may have presented a refuge from increasingly hostile surface conditions. Since the last glacial maximum, the Mojave Desert has experienced a similar shift from a wet to a dry environment, giving us the opportunity to study here on Earth how subsurface ecosystems in an arid environment adapt to increasingly barren surface conditions. In this paper, we advocate studying the vadose zone ecosystem of the Mojave Desert as an analogue for possible subsurface biospheres on Mars. We also describe several examples of Mars-like terrain found in the Mojave region and discuss ecological insights that might be gained by a thorough examination of the vadose zone in these specific terrains. Examples described include distributary fans (deltas, alluvial fans, etc.), paleosols overlain by basaltic lava flows, and evaporite deposits.

  8. Intertial Frame Dragging in an Acoustic Analogue spacetime

    CERN Document Server

    Chakraborty, Chandrachur; Majumdar, Parthasarathi

    2015-01-01

    We report an incipient exploration of the Lense-Thirring precession effect in a rotating {\\it acoustic analogue black hole} spacetime. An exact formula is deduced for the precession frequency of a gyroscope due to inertial frame dragging, close to the ergosphere of a `Draining Bathtub' acoustic spacetime which has been studied extensively for acoustic Hawking radiation of phonons and also for `superresonance'. The formula is verified by embedding the two dimensional spatial (acoustic) geometry into a three dimensional one where the similarity with standard Lense-Thirring precession results within a strong gravity framework is well known. Prospects of experimental detection of this new `fixed-metric' effect in acoustic geometries, are briefly discussed.

  9. Synthesis of lapachol analogues with possible antitumoral activity

    International Nuclear Information System (INIS)

    The lapachol is presented as a hydroxynaphthoquinone and, like many naphthoquinones, has had diverse biological activity, such as antiparasitic, antimicrobial, antifungal and anticancer even. The lateral alkyl chain has been an important factor in the activity of the 2-hydroxy-l,4-naphthoquinone. The synthesis of analogous compounds to lapachol is presented, by alkylating C3 of 2-hydroxy-l,4-naphthoquinone (lawsone) by tertiary carbocations, secondary and benzilic. Several methodologies of synthesis were used to achieve products formed, the reactions have presented yields moderate to good. The derivatives were characterized by spectroscopic methods (UV, IR, 1H-NMR, 13C-NMR), mass spectrometry and high-resolution melting points. Antitumor activity tests were performed in three cell lines, the results obtained have showed that some of the synthesized compounds, can become seeded in future research for the evaluation of the antitumor activity of other analogues lapachol. (author)

  10. Newton's cradle analogue with Bose–Einstein condensates

    International Nuclear Information System (INIS)

    We propose a possible experimental realization of a quantum analogue of Newton's cradle using a configuration which starts from a Bose–Einstein condensate. The system consists of atoms with two internal states trapped in a one-dimensional tube with a longitudinal optical lattice and maintained in a strong Tonks–Girardeau regime at maximal filling. In each site the wave-function is a superposition of the two atomic states and a disturbance of the wave-function propagates along the chain in analogy with the propagation of momentum in the classical Newton cradle. The quantum travelling signal is generally deteriorated by dispersion, which is large for a uniform chain and is known to be zero for a suitably engineered chain, but the latter is hardly realizable in practice. Starting from these opposite situations we show how the coherent behaviour can be enhanced with minimal experimental effort. (paper)

  11. Synthetic studies towards d-modified paclitaxel analogues

    Directory of Open Access Journals (Sweden)

    Matović Radomir

    2012-01-01

    Full Text Available 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 instability of the DMS protecting group under basic conditions. [Acknowledgments. Financial support of the Ministry of Education and Science of the Republic of Serbia is acknowledged (Project No. 172027

  12. Dynamic Analysis of Yinggehai Basin through Analogue Modeling

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The Yinggehai basin lies in the northwestern shelf of the South China Sea. The maximum depth of the Cenozoic sediments is 17 km. Present gas exploration was mainly in the Neogene strata. But it is estimated that the Paleoceue sediments (~8 km in thickness) has productive potential.So research on the Paleogene rifting structure will greatly enlarge the exploration area. 3D scaled sandbox is the analogue model for the Yinggehai basin. Comparing modeling with the basin by the positions and movement of depocenters, the geometric similarity, we aim to summarize the dynamic situation of Yinggehai basin during the rifting stage and to cast an objective prediction on the structures in the areas without data.

  13. On the quantum analogue of Galileo's leaning tower experiment

    International Nuclear Information System (INIS)

    The quantum analogue of Galileo's leaning tower experiment is revisited using wave packets evolving under the gravitational potential. We first calculate the position detection probabilities for particles projected upwards against gravity around the classical turning point and also around the point of initial projection, which exhibit mass dependence at both these points. We then compute the mean arrival time of freely falling particles using the quantum probability current, which also turns out to be mass dependent. The mass dependence of both the position detection probabilities and the mean arrival time vanish in the limit of large mass. Thus, compatibility between the weak equivalence principle and quantum mechanics is recovered in the macroscopic limit of the latter

  14. Toward the analogue of thermally generated electromagnetic fields

    CERN Document Server

    Osano, Bob

    2016-01-01

    Magnetic and vorticity fields evolution equations are known to obey the same equation when effects of dissipation and sources terms are negligible. We investigate the analogy between the two fields for non-vanishing dissipation and sources. In addition to the Reynolds (Re)and Prandtl (Pr_M) numbers, we define a new number (S_M) that is given by the ratio of the diffusive term to the Biermann battery term and which allows for a different classification of magnetised fluid behaviour. Numerical simulations of the two fields are then carried out given a parameter space made of Reynolds, Prandtl and Source numbers. We find it appropriate to present and discuss the findings against Prandtl numbers given that these provide the link between viscous and magnetic diffusion. Our simulations indicate that there exists a range of Prandtl numbers for which the fields remain analogues which raises the important question of how far the analogy goes.

  15. Mapping Densities in Analogue Laboratory Turbulent Plumes Using Dye Concentration

    Science.gov (United States)

    Fisher, M. A.; Kobs-Nawotniak, S. E.

    2014-12-01

    Changing tephra concentration in volcanic eruption columns is difficult to measure in the field due to fluid opacity. The bulk fluid erupted may be higher density than the surrounding atmosphere at the vent and then transition to positive buoyancy through the ingestion and heating of ambient air; thus, the concentration of the plume fluid as it rises is critical to determining whether the material rises in a sustained plume or collapses into a pyroclastic density current. We evaluate the changing concentration of an analogue plume via tracer dye intensity and relate it to plume radius expansion and vent distance. To calibrate our concentration metric, we calculated the density and dye concentration of pre-determined tracer-water mixtures. The density of the solution was directly measured using a micropipette and high precision balance. The calculated density falls within the standard error of the measured density for each step. Five photographs were taken of each concentration using a mounted Ex-FH100 digital camera with identical lighting. Using a MATLAB script, the RGB (Red-Green-Blue) color value was extracted from five pixels located at the same coordinates in each image, confirming that there was no inherent error caused by the camera and that the RGB value was the same across an entire image. We created a color map to convert from the RGB color value of a pixel in an image to its corresponding concentration. This method algorithm can then be applied to an analogue volcanic tank model, using the color variations in the plume eddies to determine the tracer concentration, and thereby density distribution, in the plume.

  16. Comparison of Two Kinds of 64Cu Labelled Octreotide Analogues

    Directory of Open Access Journals (Sweden)

    HAN Zhen-yi1;LIANG Ji-xin1;HU Ji2;LUO Hong-yi1;QING Jing2;CHEN Yu-qing2;LI Guang2;LI Hong-yu1,2

    2016-10-01

    Full Text Available Octreotide analogues DOTA-TOC and DOTA-TATE were labeled with 64Cu. The influences of the ratio of peptide mass to 64Cu activity, pH value, temperature and reaction time on labeling yield were investigated. The optimum labeling was determined. In vitro stability tests in saline and 10% bovine serum had been carried out. Biodistribution of the two radiolabelled compounds in normal mice and Micro PET imaging in nude mice bearing U87MG tumor had been evaluated. The results showed that the labeling yields of 64Cu-DOTA-TOC and 64Cu-DOTA-TATE were higher than 95%. Two kinds of octreotide analogues labeled with 64Cu were quite stable in saline and decomposed slowly in 10% bovine serum at 37 ℃. Biodistribution results in normal mice showed that two 64Cu labelled tracers had similar profiles. Both of the compounds washed out from the blood quickly. High uptake of radioactivity in liver and kidneys indicated the tracers were excreted via both hepatobiliary system and renal system. At the same time, compared to 64Cu-DOTA-TOC, higher radioactivity accumulation of 64Cu-DOTA-TATE in liver and kidneys was observed. Micro PET images of U87MG tumor-bearing nude mice with 64Cu-DOTA-TOC and 64Cu-DOTA-TATE showed the tumors very clearly. The radioactivity uptake of 64Cu-DOTA-TATE in tumor was higher than that of 64Cu-DOTA-TOC. This work has paved the way for further preclinical and clinical application of 64Cu-DOTA-TOC and 64Cu-DOTA-TATE as PET tumor imaging agents.

  17. Natural analogues of bitumen and bituminized radioactive waste

    International Nuclear Information System (INIS)

    Occurrences of natural bitumen provide possibilities to identify and assess materials, processes, phenomena and conditions in nature which can serve as model cases valid also with respect to a final repository. Natural bitumens meet the basic requirements for use as natural analogues. In natural sites, processes of bitumen formation and degradation often work simultaneously. The major processes are thermal alteration, evaporation, reaction with water, biodegradation, oxidation, weathering and radiation degradation. Progress in analytical organic geochemistry made during recent years has enabled a deeper understanding of the structural and compositional effects of these processes on bitumen. This is necessary in natural analogue applications. The time scales involved in degradation processes, as observed in natural occurrences, exceed the time scales dictated by the half-lives of most important fission products in low and medium level waste by orders of magnitude. Only exposure to the weather at the surface leads to a more rapid destruction of bitumen. Trace metals in bitumen arenot released until the matrix is completely destroyed. Products of radiation degradation and weathering of bitumen are able, to a certain degree, to delay migration of the metal ions released. Impregnation with bitumen may effectively reduce the microbial decomposition of easily destructable organic waste components, as can be deduced on the basis of the excellent preservation of fossils observed in bitumen. The complexity of all the natural sites described requires extensive understanding of the origin and kind of organic material in bitumen, its maturation, migration, alteration and degradation and of the geological and tectonic evolution of the site. The latter is used for establishing the time scale

  18. Identification of pyridine analogues as new predator-derived kairomones

    Directory of Open Access Journals (Sweden)

    Julien eBrechbühl

    2015-07-01

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

  19. Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues.

    Science.gov (United States)

    Beedie, Shaunna L; Peer, Cody J; Pisle, Steven; Gardner, Erin R; Mahony, Chris; Barnett, Shelby; Ambrozak, Agnieszka; Gütschow, Michael; Chau, Cindy H; Vargesson, Neil; Figg, William D

    2015-10-01

    Thalidomide has demonstrated clinical activity in various malignancies affecting immunomodulatory and angiogenic pathways. The development of novel thalidomide analogs with improved efficacy and decreased toxicity is an ongoing research effort. We recently designed and synthesized a new class of compounds, consisting of both tetrafluorinated thalidomide analogues (Gu973 and Gu998) and tetrafluorobenzamides (Gu1029 and Gu992). In this study, we demonstrate the antiangiogenic properties of these newly synthesized compounds. We examined the specific antiangiogenic characteristics in vitro using rat aortic rings with carboxyamidotriazole as a positive control. In addition, further in vitro efficacy was evaluated using human umbilical vein endothelial cells (HUVEC) and PC3 cells treated with 5 and 10 μmol/L doses of each compound. All compounds were seen to reduce microvessel outgrowth in rat aortic rings as well as to inhibit HUVECs to a greater extent, at lower concentrations than previously tested thalidomide analogs. The antiangiogenic properties of the compounds were also examined in vivo in fli1:EGFP zebrafish embryos, where all compounds were seen to inhibit the extent of outgrowth of newly developing blood vessels. In addition, Gu1029 and Gu973 reduced the anti-inflammatory response in mpo:GFP zebrafish embryos, whereas Gu998 and Gu992 showed no difference. The compounds' antitumor effects were also explored in vivo using the human prostate cancer PC3 xenograft model. All four compounds were also screened in vivo in chicken embryos to investigate their teratogenic potential. This study establishes these novel thalidomide analogues as a promising immunomodulatory class with anticancer effects that warrant further development to characterize their mechanisms of action.

  20. Nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in olefin metathesis: a computational study.

    Science.gov (United States)

    Pazio, A; Woźniak, K; Grela, K; Trzaskowski, B

    2015-12-14

    We used the density functional theory to evaluate the suitability of nitrenium ions and trivalent boron ligands as analogues of N-heterocyclic carbenes in ruthenium-based metathesis catalysts. We demonstrate that these analogues induce only minor structural changes in Hoveyda-Grubbs-like precatalysts, but have major impact on precatalyst initiation. Nitrenium ion-modified precatalysts are characterized by a weak Ru-N bond resulting in a relatively strong Ru-O bond and large free energy barriers for initiation, making them good candidates for efficient latent Ru-based catalysts. On the other hand the trivalent boron ligand, bearing a formal -1 charge, binds strongly to the ruthenium ion, weakening the Ru-O bond and facilitating its dissociation, to promote fast reaction initiation. We show that the calculated bond dissociation energy of the Ru-C/N/B bond may serve as an accurate indicator of the Ru-O bond strength and the rate of metathesis initiation. PMID:26525899