Sample records for a-4 derivative xn0502

  1. 47 CFR 0.502 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Purpose. 0.502 Section 0.502 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Mandatory Declassification of National Security Information § 0.502 Purpose. This subpart prescribes the procedures to be followed in submitting...

  2. 47 CFR 0.502 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Purpose. 0.502 Section 0.502 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMISSION ORGANIZATION Mandatory Declassification of National Security Information § 0.502 Purpose. This subpart prescribes the procedures to be followed in submitting...

  3. Fermi LAT detection of a new gamma-ray flare from FSRQ PKS 0502+049

    NASA Astrophysics Data System (ADS)

    Ojha, Roopesh; Dutka, Michael

    2013-03-01

    The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed increasing gamma-ray flux from a source positionally consistent with the flat spectrum radio quasar PKS 0502+049 (also known as 2FGL J0505.5+0501, Nolan et al. 2012 ApJS, 199, 31). PKS 0502+049 has coordinates RA=05h05m23.1847s DEC=+04d59m42.725s, J2000, (Johnston et al. 1995, AJ, 110, 880) and redshift z=0.954 (Drinkwater et al.

  4. Knowing Our Neighbors: 2MASS 2306-0502 (TRAPPIST-1) Revisited

    NASA Astrophysics Data System (ADS)

    Bartlett, Jennifer Lynn; Lurie, John; Jao, W.-C.; Ianna, P. A.; Riedel, A.; Finch, C.; Winters, J.; Subasavage, J.; Henry, T.

    2018-01-01

    Obtaining a well-understood, volume-limited (and ultimately volume-complete) sample of stellar systems within 25 pc is essential for determining the stellar luminosity function, the mass-luminosity relationship, the stellar velocity distribution, and the stellar multiplicity fraction. Such a sample also provides insight into the local star formation history. Towards that end, Research Consortium On Nearby Stars (RECONS) measures trigonometric parallaxes to establish which systems truly lie within the 25-pc radius of the Solar Neighborhood. Recent observations with the CTIO/SMARTS 0.9-m telescope allow us to update the astrometry and VRI photometry for 2MASS J23062928-0502285 (TRAPPIST-1). Extrasolar planet searches by others detected 7 Earth-sized planets transiting this cool dwarf.Based on our 2004—2016 observations, we measure a parallax of 78.76 ± 1.04 mas with a proper motion of 1034.8 ± 0.3 mas/yr in 118.5○ ± 0.03○ for 2MASS 2306-0502. During this 12.2-year period, we did not detect any perturbations in the astrometric residuals. Because this parallax is independent of the earlier CTIOPI/SMARTS 1.5-m result, we calculate its weighted mean parallax to be 79.29 ± 0.96 mas (12.6 ± 0.2 pc), which is ~4% farther than the original distance. Our improved parallax implies its radii and that of its planets would be ~4% larger than previously reported.During our astrometric observations, 2MASS 2306-0502 demonstrated an overall photometric variability of 11.6 mmag in I-band, which is less than the 20-mmag limit for significant variability. Removing a July 2009 flaring event drops the mean variability to 8.2 mmag.Our VRI photometry indicates the brightness of 2MASS 2306-0502 is 18.75, 16.54, 14.10 mag, respectively, based on 3 nights.Even as we continue to look for new neighbors, we should also keep an eye on old friends.NSF grants AST 05-07711 and AST 09-08402, NASA-SIM, Georgia State University, the University of Virginia, Hampden-Sydney College, and the

  5. Performance evaluation of the automated nucleated red blood cell enumeration on Sysmex XN analyser.

    PubMed

    Tantanate, C; Klinbua, C

    2015-06-01

    Presence of peripheral blood nucleated red blood cell (NRBC) is associated with pathological conditions and leads to the overestimation of white blood cell count in automated haematology analysers (HA). The authors evaluated NRBC enumeration by a new HA Sysmex XN (XN) to demonstrate the precision and comparability to manual count (MC) at the various NRBC values. Specimens with initially NRBC positive were included. For precision assessment, 8 levels of NRBCs were repeatedly analysed. For comparison study, 234 specimens were analysed by both XN and MC. For precision study, the percentage of coefficient of variation ranged from 14% to 45.6% and 1.2% to 4.4% for MC and XN, respectively. For comparison study between XN and MC, NRBCs ranged from 0% to 612.5%. Regression analysis demonstrated an r(2) of 0.98. The mean bias of 14.1% with 95% limits of agreement between -48.76% and 76.95% was found. The NRBC counts from XN appeared to be more in accordance with MC when the NRBCs were lower than 200% with the concordance rate of 94.2%. The automated NRBC enumeration by XN was precise and could replace the traditional MC, especially for the specimens with NRBCs lower than 200%. © 2014 John Wiley & Sons Ltd.

  6. Low-temperature sequential pulsed chemical vapor deposition of ternary B{sub x}Ga{sub 1-x}N and B{sub x}In{sub 1-x}N thin film alloys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Haider, Ali, E-mail: ali.haider@bilkent.edu.tr, E-mail: biyikli@unam.bilkent.edu.tr; Kizir, Seda; Ozgit-Akgun, Cagla

    In this work, the authors have performed sequential pulsed chemical vapor deposition of ternary B{sub x}Ga{sub 1-x}N and B{sub x}In{sub 1-x}N alloys at a growth temperature of 450 °C. Triethylboron, triethylgallium, trimethylindium, and N{sub 2} or N{sub 2}/H{sub 2} plasma have been utilized as boron, gallium, indium, and nitrogen precursors, respectively. The authors have studied the compositional dependence of structural, optical, and morphological properties of B{sub x}Ga{sub 1-x}N and B{sub x}In{sub 1-x}N ternary thin film alloys. Grazing incidence X-ray diffraction measurements showed that boron incorporation in wurtzite lattice of GaN and InN diminishes the crystallinity of B{sub x}Ga{sub 1-x}N and B{submore » x}In{sub 1-x}N sample. Refractive index decreased from 2.24 to 1.65 as the B concentration of B{sub x}Ga{sub 1-x}N increased from 35% to 88%. Similarly, refractive index of B{sub x}In{sub 1-x}N changed from 1.98 to 1.74 for increase in B concentration value from 32% to 87%, respectively. Optical transmission band edge values of the B{sub x}Ga{sub 1-x}N and B{sub x}In{sub 1-x}N films shifted to lower wavelengths with increasing boron content, indicating the tunability of energy band gap with alloy composition. Atomic force microscopy measurements revealed an increase in surface roughness with boron concentration of B{sub x}Ga{sub 1-x}N, while an opposite trend was observed for B{sub x}In{sub 1-x}N thin films.« less

  7. Quantification of process variables for carbothermic synthesis of UC 1-xN x fuel microspheres

    DOE PAGES

    Lindemer, Terrance B.; Silva, Chinthaka M.; Henry, Jr, John James; ...

    2016-11-05

    This report details the continued investigation of process variables involved in converting sol-gel-derived, urania-carbon microspheres to ~820-μm-dia. UC 1-xN x fuel kernels in flow-through, vertical Mo and W crucibles at temperatures up to 2123 K. Experiments included calcining of air-dried UO 3-H 2O-C microspheres in Ar and H 2-containing gases, conversion of the resulting UO 2-C kernels to dense UO2:2UC in the same gases and vacuum, and its conversion in N 2 to UC 1-xN x (x = ~0.85). The thermodynamics of the relevant reactions were applied extensively to interpret and control the process variables. Producing the precursor UO 2:2UCmore » kernel of ~96% theoretical density was required, but its subsequent conversion to UC 1-xN x at 2123 K was not accompanied by sintering and resulted in ~83-86% of theoretical density. Increasing the UC 1-xN x kernel nitride component to ~0.98 in flowing N 2-H 2 mixtures to evolve HCN was shown to be quantitatively consistent with present and past experiments and the only useful application of H 2 in the entire process.« less

  8. Performance evaluation of the new hematology analyzer Sysmex XN-series.

    PubMed

    Seo, J Y; Lee, S-T; Kim, S-H

    2015-04-01

    The Sysmex XN-series is a new automated hematology analyzer designed to improve the accuracy of cell counts and the specificity of the flagging events. The basic characteristics and the performance of new measurement channels of the XN were evaluated and compared with the Sysmex XE-2100 and the manual method. Fluorescent platelet count (PLT-F) was compared with the flow cytometric method. The low WBC mode and body fluid mode were also evaluated. For workflow analysis, 1005 samples were analyzed on both the XN and the XE-2100, and manual review rates were compared. All parameters measured by the XN correlated well with the XE-2100. PLT-F showed better correlation with the flow cytometric method (r(2)  = 0.80) compared with optical platelet count (r(2)  = 0.73) for platelet counts <70 × 10(9) /L. The low WBC mode reported accurate leukocyte differentials for samples with a WBC count <0.5 × 10(9) /L. Relatively good correlation was found for WBC counts between the manual method and the body fluid mode (r = 0.88). The XN made less flags than the XE-2100, while the sensitivities of both instruments were comparable. The XN provided reliable results on low cell counts, as well as reduced manual blood film reviews, while maintaining a proper level of diagnostic sensitivity. © 2014 John Wiley & Sons Ltd.

  9. Nb(x)Ti(1-x)N Superconducting-Nanowire Single-Photon Detectors

    NASA Technical Reports Server (NTRS)

    Stern, Jeffrey A.; Farr, William H.; Leduc, Henry G.; Bumble, Bruce

    2008-01-01

    Superconducting-nanowire single-photon detectors (SNSPDs) in which Nb(x)Ti(1-x)N (where x<1) films serve as the superconducting materials have shown promise as superior alternatives to previously developed SNSPDs in which NbN films serve as the superconducting materials. SNSPDs have potential utility in optical communications and quantum cryptography. Nb(x)Ti(1-x)N is a solid solution of NbN and TiN, and has many properties similar to those of NbN. It has been found to be generally easier to stabilize Nb(x)Ti(1-x)N in the high-superconducting-transition temperature phase than it is to so stabilize NbN. In addition, the resistivity and penetration depth of polycrystalline films of Nb(x)Ti(1-x)N have been found to be much smaller than those of films of NbN. These differences have been hypothesized to be attributable to better coupling at grain boundaries within Nb(x)Ti(1-x)N films.

  10. Nb(x)Ti(1-x)N Superconducting-Nanowire Single-Photon Detectors

    NASA Technical Reports Server (NTRS)

    Stem, Jeffrey A.; Farr, William H.; Leduc, Henry G.; Bumble, Bruce

    2008-01-01

    Superconducting-nanowire singlephoton detectors (SNSPDs) in which Nb(x)Ti(1-x)N (where x<1) films serve as the superconducting materials have shown promise as superior alternatives to previously developed SNSPDs in which NbN films serve as the superconducting materials. SNSPDs have potential utility in optical communications and quantum cryptography. Nb(x)Ti(1-x)N is a solid solution of NbN and TiN, and has many properties similar to those of NbN. It has been found to be generally easier to stabilize NbxTi1 xN in the high-superconducting-transitiontemperature phase than it is to so stabilize NbN. In addition, the resistivity and penetration depth of polycrystalline films of Nb(x)Ti(1-x)N have been found to be much smaller than those of films of NbN. These differences have been hypothesized to be attributable to better coupling at grain boundaries within Nb(x)Ti(1-x)N films.

  11. WalK(S221P), a naturally occurring mutation, confers vancomycin resistance in VISA strain XN108.

    PubMed

    Peng, Huagang; Hu, Qiwen; Shang, Weilong; Yuan, Jizhen; Zhang, Xiaopeng; Liu, Hui; Zheng, Ying; Hu, Zhen; Yang, Yi; Tan, Li; Li, Shu; Hu, Xiaomei; Li, Ming; Rao, Xiancai

    2017-04-01

    Vancomycin-intermediate Staphylococcus aureus (VISA) strains have spread globally. We previously isolated an ST239 VISA (XN108) with a vancomycin MIC of 12 mg/L. The mechanism for XN108 resistance to vancomycin was investigated in this study. Genome comparison was performed to characterize mutations that might contribute to the XN108 resistance phenotype. The novel mutation WalK(S221P) was identified and investigated using allelic replacement experiments. Vancomycin susceptibilities, autolytic activities and morphologies of the strains were examined. Autophosphorylation activities of WalK and the WalK(S221P) mutant were determined in vitro with [λ- 32 P]ATP, and binding activity of WalK(S221P)-activated WalR to the promoter region of its target gene lytM was determined by electrophoretic mobility shift assay. Genome comparison revealed three mutations, GraS(T136I), RpoB(H481N) and WalK(S221P), which might be responsible for vancomycin resistance in XN108. The introduction of WalK(S221P) to the vancomycin-susceptible strain N315 increased its vancomycin MIC from 1.5 to 8 mg/L, whereas the allelic replacement of WalK(S221P) with the native N315 WalK allele in XN108 decreased its vancomycin MIC from 12 to 4 mg/L. The VISA strains have thickened cell walls and decreased autolysis, consistent with observed changes in the expression of genes involved in cell wall metabolism and virulence regulation. WalK(S221P) exhibited reduced autophosphorylation, which may lead to reduced phosphorylation of WalR. WalK(S221P)-phosphorylated WalR also exhibited a reduced capacity to bind to the lytM promoter. The naturally occurring WalK(S221P) mutation plays a key role in vancomycin resistance in XN108. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Swift detection of an X-ray flare from the flaring blazar PKS 0502+049

    NASA Astrophysics Data System (ADS)

    Ojha, Roopesh; Dutka, Michael

    2013-03-01

    Following the recent gamma-ray flaring activity of the flat spectrum radio quasar PKS 0502+049 (also known as 2FGL J0505.5+0501, Nolan et al. 2012, ApJS, 199, 31), detected by Fermi LAT on 2013 March 2 (ATel#4858), a Swift target of opportunity observation was performed on March 13.

  13. First-principles calculation of the structural and elastic properties of ternary metal nitrides TaxMo1-xN and TaxW1-xN

    NASA Astrophysics Data System (ADS)

    Bouamama, Kh.; Djemia, P.; Benhamida, M.

    2015-09-01

    First-principles pseudo-potentials calculations of the mixing enthalpy, of the lattice constants a0 and of the single-crystal elastic constants cij for ternary metal nitrides TaxMe1-xN (Me=Mo or W) alloys considering the cubic B1-rocksalt structure is carried out. For disordered ternary alloys, we employ the virtual crystal approximation VCA in which the alloy pseudopotentials are constructed within a first-principles VCA scheme. The supercell method SC is also used for ordered structures in order to evaluate clustering effects. We find that the mixing enthalpy still remains negative for TaxMe1-xN alloys in the whole composition range which implies these cubic TaxMo1-xN and TaxW1-xN ordered solid solutions are stable. We investigate the effect of Mo and W alloying on the trend of the mechanical properties of TaN. The effective shear elastic constant c44, the Cauchy pressure (c12-c44), and the shear to bulk modulus G/B ratio are used to discuss, respectively, the mechanical stability of the ternary structure and the brittle/ductile behavior in reference to TaN, MeN alloys. We determine the onset transition from the unstable structure to the stable one B1-rocksalt from the elastic stability criteria when alloying MeN with Ta. In a second stage, in the frame of anisotropic elasticity, we estimate by one homogenization method the averaged constants of the polycrystalline TaxMe1-xN alloys considering the special case of an isotropic medium with no crystallographic texture.

  14. Creep and precipitation behaviors of AL6XN austenitic steel at elevated temperatures

    NASA Astrophysics Data System (ADS)

    Meng, L. J.; Sun, J.; Xing, H.

    2012-08-01

    Creep behaviors of the solution-treated AL6XN austenitic stainless steel have been investigated at 873-1023 K and 120-260 MPa. The results showed that the creep stress exponent and activation energy of the AL6XN steel are 5 and 395.4 kJ/mol, respectively in the power-law breakdown regime. TEM observations revealed that dislocations distributed homogenously in grains. The creep deformation mechanism is mainly attributed to viscous dislocation glide. Precipitates in the steel after creep deformation were additionally analyzed by TEM, and the results showed that there are four different types of precipitates, such as M23C6, M6C, σ phase and Laves phase. The M23C6 carbides were observed at grain boundaries in the steel after creep at 873 K. The M6C, σ phase and Laves phase precipitates were found when the creep temperature increases to 923-1023 K. Although the AL6XN steel exhibited low steady state creep rates, a high volume fraction of brittle precipitates of σ and Laves phases reduced the creep lifetime of the steel at elevated temperatures.

  15. Electronic and atomic structures of Ti{sub 1-x}Al{sub x}N thin films related to their damage behavior

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tuilier, M.-H.; Pac, M.-J.; Girleanu, M.

    2008-04-15

    Ti and Al K-edge x-ray absorption spectroscopy is used to investigate the electronic structure of Ti{sub 1-x}Al{sub x}N thin films deposited by reactive magnetron sputtering. The experimental near edge spectra of TiN and AlN are interpreted in the light of unoccupied density of state band structure calculations. The comparison of the structural parameters derived from x-ray absorption fine structure and x-ray diffraction reveals segregation between Al-rich and Ti-rich domains within the Ti{sub 1-x}Al{sub x}N films. Whereas x-ray diffraction probes only the crystallized domains, the structural information derived from extended x-ray absorption fine structure analysis turns on both crystalline and grainmore » boundaries. The results are discussed by considering the damage behavior of the films depending on the composition.« less

  16. What is the valence of Mn in Ga 1-xMn xN?

    DOE PAGES

    Berlijn, Tom; Jarrell, Mark; Nelson, Ryky; ...

    2015-11-04

    Motivated by the potential high Curie temperature of Ga 1-xMn xN, we investigate the controversial Mn valence in this diluted magnetic semiconductor. From a first-principles Wannier-function analysis of the high energy Hilbert space, we find unambiguously the Mn valence to be close to 2+(d 5), but in a mixed spin configuration with average magnetic moments of 4µ B. By integrating out high-energy degrees of freedom differently, we further demonstrate the feasibility of both effective d 4 and d 5 descriptions. These two descriptions offer simple pictures for local and extended properties of the system, and highlight the dual nature ofmore » its doped hole. Specifically, in the effective d 5 description, we demonstrate novel physical effects absent in previous studies. Thus, our derivation highlights the richness of low-energy sectors in interacting many-body systems and the generic need for multiple effective descriptions.« less

  17. A review of the synthesis of reduced defect density InxGa1-xN for all indium compositions

    NASA Astrophysics Data System (ADS)

    Clinton, Evan A.; Vadiee, Ehsan; Fabien, Chloe A. M.; Moseley, Michael W.; Gunning, Brendan P.; Doolittle, W. Alan; Fischer, Alec M.; Wei, Yong O.; Xie, Hongen; Ponce, Fernando A.

    2017-10-01

    A review of metal rich and nitrogen rich (N-rich), low-temperature grown InxGa1-xN is provided, focusing on two low-temperature approaches that have resulted in non-phase separated InxGa1-xN. The metal modulated epitaxy (MME) and N-rich, low temperature approaches to the reduction of defects in InxGa1-xN are described and are capable of growing InxGa1-xN throughout the miscibility gap. MME films remain smooth at all thicknesses but show device quality material primarily for x < 0.2 and x > 0.6. Low temperature, N-rich grown films show a critical thickness extend well beyond the theoretical values and results in slower relaxation through the 0.2 < x < 0.6 range most interesting for light emitters and solar cells. This reduced defect density results in improved optical emission, but due to increased roughening with increased thickness, low temperature, N-rich films are limited to thin layers. Future thick InxGa1-xN substrates are necessary to increase design freedom, as well as improve optoelectronic device performance. Initial results with films up to 800 nm are shown to display evidence of defect annihilation which could be promising for future thick optoelectronic templates and thick devices.

  18. Development of epitaxial Al xSc 1-xN for artificially structured metal/semiconductor superlattice metamaterials

    DOE PAGES

    Sands, Timothy D.; Stach, Eric A.; Saha, Bivas; ...

    2015-02-01

    Epitaxial nitride rocksalt metal/semiconductor superlattices are emerging as a novel class of artificially structured materials that have generated significant interest in recent years for their potential application in plasmonic and thermoelectric devices. Though most nitride metals are rocksalt, nitride semiconductors in general have hexagonal crystal structure. We report rocksalt aluminum scandium nitride (Al,Sc)N alloys as the semiconducting component in epitaxial rocksalt metal/semiconductor superlattices. The Al xSc 1-xN alloys when deposited directly on MgO substrates are stabilized in a homogeneous rocksalt (single) phase when x < 0.51. Employing 20 nm TiN as a seed layer on MgO substrates, the homogeneity rangemore » for stabilizing the rocksalt phase has been extended to x < 0.82 for a 120 nm film. The rocksalt Al xSc 1-xN alloys show moderate direct bandgap bowing with a bowing parameter, B = 1.41 ± 0.19 eV. The direct bandgap of metastable rocksalt AlN is extrapolated to be 4.70 ± 0.20 eV. The tunable lattice parameter, bandgap, dielectric permittivity, and electronic properties of rocksalt Al xSc 1-xN alloys enable high quality epitaxial rocksalt metal/Al xSc 1-xN superlattices with a wide range of accessible metamaterials properties.« less

  19. Surface States in the AlxGa1-xN Barrier in AlxGa1-xN/GaN Heterostructures

    NASA Astrophysics Data System (ADS)

    Liu, Jie; Shen, Bo; Wang, Mao-Jun; Zhou, Yu-Gang; Chen, Dun-Jun; Zhang, Rong; Shi, Yi; Zheng, You-Dou

    2004-01-01

    Frequency-dependent capacitance-voltage (C-V) measurements have been performed on modulation-doped Al0.22 Ga0.78N/GaN heterostructures to investigate the characteristics of the surface states in the AlxGa1-xN barrier. Numerical fittings based on the experimental data indicate that there are surface states with high density locating on the AlxGa1-xN barrier. The density of the surface states is about 1012 cm-2eV-1, and the time constant is about 1 mus. It is found that an insulating layer (Si3N4) between the metal contact and the surface of AlxGa1-xN can passivate the surface states effectively.

  20. GRAPhEME: a setup to measure (n, xn γ) reaction cross sections

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Henning, Greg; Bacquias, A.; Capdevielle, O.

    2015-07-01

    Most of nuclear reactor developments are using evaluated data base for numerical simulations. However, the considered databases present still large uncertainties and disagreements. To improve their level of precision, new measurements are needed, in particular for (n, xn) reactions, which are of great importance as they modify the neutron spectrum, the neutron population, and produce radioactive species. The IPHC group started an experimental program to measure (n, xn gamma) reaction cross sections using prompt gamma spectroscopy and neutron energy determination by time of flight. Measurements of (n, xn gamma) cross section have been performed for {sup 235,238}U, {sup 232}Th, {supmore » nat,182,183,184,186}W, {sup nat}Zr. The experimental setup is installed at the neutron beam at GELINA (Geel, Belgium). The setup has recently been upgraded with the addition of a highly segmented 36 pixels planar HPGe detector. Significant efforts have been made to reduce radiation background and electromagnetic perturbations. The setup is equipped with a high rate digital acquisition system. The analysis of the segmented detector data requires a specific procedure to account for cross signals between pixels. An overall attention is paid to the precision of the measurement. The setup characteristic and the analysis procedure will be presented along with the acquisition and analysis challenges. Examples of results and their impact on models will be discussed. (authors)« less

  1. Assessment of errors and biases in retrievals of XCO4">2, XCH4">4, XCO, and XN4">2O from a 0.5 cm-1 resolution solar-viewing spectrometer

    NASA Astrophysics Data System (ADS)

    Hedelius, Jacob K.; Viatte, Camille; Wunch, Debra; Roehl, Coleen M.; Toon, Geoffrey C.; Chen, Jia; Jones, Taylor; Wofsy, Steven C.; Franklin, Jonathan E.; Parker, Harrison; Dubey, Manvendra K.; Wennberg, Paul O.

    2016-08-01

    Bruker™ EM27/SUN instruments are commercial mobile solar-viewing near-IR spectrometers. They show promise for expanding the global density of atmospheric column measurements of greenhouse gases and are being marketed for such applications. They have been shown to measure the same variations of atmospheric gases within a day as the high-resolution spectrometers of the Total Carbon Column Observing Network (TCCON). However, there is little known about the long-term precision and uncertainty budgets of EM27/SUN measurements. In this study, which includes a comparison of 186 measurement days spanning 11 months, we note that atmospheric variations of Xgas within a single day are well captured by these low-resolution instruments, but over several months, the measurements drift noticeably. We present comparisons between EM27/SUN instruments and the TCCON using GGG as the retrieval algorithm. In addition, we perform several tests to evaluate the robustness of the performance and determine the largest sources of errors from these spectrometers. We include comparisons of XCO4">2, XCH4">4, XCO, and XN4">2O. Specifically we note EM27/SUN biases for January 2015 of 0.03, 0.75, -0.12, and 2.43 % for XCO4">2, XCH4">4, XCO, and XN4">2O respectively, with 1σ running precisions of 0.08 and 0.06 % for XCO4">2 and XCH4">4 from measurements in Pasadena. We also identify significant error caused by nonlinear sensitivity when using an extended spectral range detector used to measure CO and N2O.

  2. S0502: A SWOG Phase III Randomized Study of Imatinib, With or Without Bevacizumab, in Patients With Untreated Metastatic or Unresectable Gastrointestinal Stromal Tumors.

    PubMed

    Blanke, Charles D; Rankin, Cathy; Corless, Christopher; Eary, Janet F; Mulder, Karen; Okuno, Scott H; George, Suzanne; Heinrich, Michael

    2015-12-01

    Despite having significant rationale, S0502 failed to accrue for a number of reasons.Vetting a trial first, with scientific experts and funding agencies, does not guarantee success, especially when dealing with a rare tumor and/or one with an existing highly effective therapy.In the present case, adding an intravenous drug to an oral medication as part of a regimen expected to be continued for many years likely decreased patient (and physician) convenience and, thus, interest in the study. Imatinib mesylate, a potent inhibitor of the KIT and PDGFR tyrosine kinases, is highly effective in the treatment of advanced gastrointestinal stromal tumors (GISTs). However, most imatinib-treated tumors eventually become resistant, accounting for a median progression-free survival of 19-23 months. Expression of vascular endothelial growth factor (VEGF) correlates with poor prognosis in GIST; bevacizumab, a monoclonal antibody against VEGF, is effective in a variety of solid tumors. We postulated combination therapy with imatinib plus bevacizumab would benefit patients with advanced GIST, particularly those reliant on VEGFA-dependent angiogenesis. Patients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial, S0502. At registration, patients were randomly assigned to either imatinib 400 mg (standard) or 800 mg (patients with exon 9 KIT mutations), or imatinib plus bevacizumab, 7.5 mg/kg i.v. every 3 weeks. Patients were treated to progression, symptomatic deterioration, unacceptable toxicity, treatment delay greater than 4 weeks, or patient choice to withdraw from the study. The primary objective was to determine whether the addition of bevacizumab to imatinib would improve progression-free survival (PFS) in first-line treatment of incurable GIST. S0502 opened on April 15, 2008. As of fall 2009, only 12 patients from at least 178 eligible SWOG centers plus those participating through Cancer Trials Support Unit had been

  3. Evaluation of cell count and classification capabilities in body fluids using a fully automated Sysmex XN equipped with high-sensitive Analysis (hsA) mode and DI-60 hematology analyzer system.

    PubMed

    Takemura, Hiroyuki; Ai, Tomohiko; Kimura, Konobu; Nagasaka, Kaori; Takahashi, Toshihiro; Tsuchiya, Koji; Yang, Haeun; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Tabe, Yoko; Ohsaka, Akimichi

    2018-01-01

    The XN series automated hematology analyzer has been equipped with a body fluid (BF) mode to count and differentiate leukocytes in BF samples including cerebrospinal fluid (CSF). However, its diagnostic accuracy is not reliable for CSF samples with low cell concentration at the border between normal and pathologic level. To overcome this limitation, a new flow cytometry-based technology, termed "high sensitive analysis (hsA) mode," has been developed. In addition, the XN series analyzer has been equipped with the automated digital cell imaging analyzer DI-60 to classify cell morphology including normal leukocytes differential and abnormal malignant cells detection. Using various BF samples, we evaluated the performance of the XN-hsA mode and DI-60 compared to manual microscopic examination. The reproducibility of the XN-hsA mode showed good results in samples with low cell densities (coefficient of variation; % CV: 7.8% for 6 cells/μL). The linearity of the XN-hsA mode was established up to 938 cells/μL. The cell number obtained using the XN-hsA mode correlated highly with the corresponding microscopic examination. Good correlation was also observed between the DI-60 analyses and manual microscopic classification for all leukocyte types, except monocytes. In conclusion, the combined use of cell counting with the XN-hsA mode and automated morphological analyses using the DI-60 mode is potentially useful for the automated analysis of BF cells.

  4. Bilinear, trilinear forms, and exact solution of certain fourth order integrable difference equations

    NASA Astrophysics Data System (ADS)

    Sahadevan, R.; Rajakumar, S.

    2008-03-01

    A systematic investigation of finding bilinear or trilinear representations of fourth order autonomous ordinary difference equation, x(n +4)=F(x(n),x(n+1),x(n+2),x(n+3)) or xn +4=F(xn,xn +1,xn +2,xn +3), is made. As an illustration, we consider fourth order symplectic integrable difference equations reported by [Capel and Sahadevan, Physica A 289, 86 (2001)] and derived their bilinear or trilinear forms. Also, it is shown that the obtained bilinear representations admit exact solution of rational form.

  5. Energy structure and radiative lifetimes of InxGa1-xN /AlN quantum dots

    NASA Astrophysics Data System (ADS)

    Aleksandrov, Ivan A.; Zhuravlev, Konstantin S.

    2018-01-01

    We report calculations of the ground state transition energies and the radiative lifetimes in InxGa1-xN /AlN quantum dots with different size and indium content. The ground state transition energy and the radiative lifetime of the InxGa1-xN /AlN quantum dots can be varied over a wide range by changing the height of the quantum dot and the indium content. The sizes and compositions for quantum dots emitting in the wavelength range for fiber-optic telecommunications have been found. The radiative lifetime of the InxGa1-xN /AlN quantum dots increases with increase in quantum dot height at a constant indium content, and increases with increase in indium content at constant quantum dot height. For quantum dots with constant ground state transition energy the radiative lifetime decreases with increase in indium content.

  6. Mechanical, Anisotropic, and Electronic Properties of XN (X = C, Si, Ge): Theoretical Investigations.

    PubMed

    Ma, Zhenyang; Liu, Xuhong; Yu, Xinhai; Shi, Chunlei; Wang, Dayun

    2017-08-08

    The structural, mechanical, elastic anisotropic, and electronic properties of Pbca -XN (X = C, Si, Ge) are investigated in this work using the Perdew-Burke-Ernzerhof (PBE) functional, Perdew-Burke-Ernzerhof for solids (PBEsol) functional, and Ceperly and Alder, parameterized by Perdew and Zunger (CA-PZ) functional in the framework of density functional theory. The achieved results for the lattice parameters and band gap of Pbca -CN with the PBE functional in this research are in good accordance with other theoretical results. The band structures of Pbca -XN (X = C, Si, Ge) show that Pbca -SiN and Pbca -GeN are both direct band gap semiconductor materials with a band gap of 3.39 eV and 2.22 eV, respectively. Pbca -XN (X = C, Si, Ge) exhibits varying degrees of mechanical anisotropic properties with respect to the Poisson's ratio, bulk modulus, shear modulus, Young's modulus, and universal anisotropic index. The (001) plane and (010) plane of Pbca -CN/SiN/GeN both exhibit greater elastic anisotropy in the bulk modulus and Young's modulus than the (100) plane.

  7. Mechanical, Anisotropic, and Electronic Properties of XN (X = C, Si, Ge): Theoretical Investigations

    PubMed Central

    Ma, Zhenyang; Liu, Xuhong; Yu, Xinhai; Shi, Chunlei; Wang, Dayun

    2017-01-01

    The structural, mechanical, elastic anisotropic, and electronic properties of Pbca-XN (X = C, Si, Ge) are investigated in this work using the Perdew–Burke–Ernzerhof (PBE) functional, Perdew–Burke–Ernzerhof for solids (PBEsol) functional, and Ceperly and Alder, parameterized by Perdew and Zunger (CA–PZ) functional in the framework of density functional theory. The achieved results for the lattice parameters and band gap of Pbca-CN with the PBE functional in this research are in good accordance with other theoretical results. The band structures of Pbca-XN (X = C, Si, Ge) show that Pbca-SiN and Pbca-GeN are both direct band gap semiconductor materials with a band gap of 3.39 eV and 2.22 eV, respectively. Pbca-XN (X = C, Si, Ge) exhibits varying degrees of mechanical anisotropic properties with respect to the Poisson’s ratio, bulk modulus, shear modulus, Young’s modulus, and universal anisotropic index. The (001) plane and (010) plane of Pbca-CN/SiN/GeN both exhibit greater elastic anisotropy in the bulk modulus and Young’s modulus than the (100) plane. PMID:28786960

  8. Extent of agreement between the body fluid model of Sysmex XN-20 and the manual microscopy method.

    PubMed

    Huang, Wei-Hua; Lu, Lin-Peng; Wu, Kang; Guo, Fang-Yu; Guo, Jie; Yu, Jing-Long; Zhou, Dao-Yin; Sun, Yi; Deng, An-Mei

    2017-09-01

    Although the correlations concerning cellular component analysis between the Sysmex XN-20 body fluid (BF) model and manual microscopy have been investigated by several studies, the extent of agreement between these two methods has not been investigated. A total of 90 BF samples were prospectively collected and analyzed using the Sysmex XN-20 BF model and microscopy. The extent of agreement between these two methods was evaluated using the Bland-Altman approach. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of high-fluorescence (HF) BF cells for malignant diseases. The agreements of white blood cell (WBC), red blood cell (RBC), and percentages of neutrophils, lymphocytes, and monocytes between the Sysmex XN-20 BF model and manual microscopy were imperfect. The areas under the ROC curves for absolute and relative HF cells were 0.67 (95% confidence interval [CI]: 0.56-0.78) and 0.60 (95% CI: 0.48-0.72), respectively. Due to the Sysmex XN-20 BF model's imperfect agreement with manual microscopy and its weak diagnostic accuracy for malignant diseases, the current evidence does not support replacing manual microscopy with this model in clinical practice. © 2016 Wiley Periodicals, Inc.

  9. Tunneling Spectroscopy of MoN and NbxTi1-xN Thin Films Grown by Atomic Layer Deposition

    NASA Astrophysics Data System (ADS)

    Cao, Chaoyue; Groll, Nickolas; Klug, Jeffrey; Becker, Nicholas; Altin, Serdar; Proslier, Thomas; Zasadzinski, John

    2014-03-01

    Tunneling I(V) and dI/dV vs. V are reported on superconducting thin films of MoN and NbxTi1-xN using a point contact method with a Au tip. The films are grown by the chemical process of atomic layer deposition (ALD) onto various substrates (Si, quartz, sapphire) held at 450 C. Resistively measured superconducting Tc values up to 12K and 13K are found for the MoN and NbxTi1-xN respectively. Artificial tunnel barriers (1-3 nm thick) of Al2O3, also grown by ALD, are shown to provide much improved tunneling characteristics compared to the native oxides. Relatively high quality gap features are observed with zero-bias conductance values as low as ~ 10% of the high bias values. Gap parameters Δ ~ 2.0meV are found for the MoN and Δ ~ 2.0-2.4 meV for the NbxTi1-xN which follow the BCS temperature dependence and close near the measured film Tc indicating bulk superconductivity at the surface. The suitability of such conformal ALD grown films for potential superconducting devices is discussed. This work was supported by the U.S. Department of Energy, Office of Science under contract No. DE-AC02-06CH11357.

  10. Lattice damage and compositional changes in Xe ion irradiated InxGa1-xN (x = 0.32-1.0) single crystals

    DOE PAGES

    Zhang, Limin; Jiang, Weilin; Dissanayake, Amila C.; ...

    2016-06-27

    Lattice disorder and compositional changes in InxGa1-xN (x=0.32, 0.47, 0.7, 0.8 and 1.0) films on GaN/Al2O3 substrates, induced by room-temperature irradiation of 5 MeV Xe ions, have been investigated using both Rutherford backscattering spectrometry under ion-channeling conditions and time-of-flight secondary ion mass spectrometry. The results show that for a fluence of 3E13 cm-2, the relative level of lattice disorder in InxGa1-xN increases monotonically from 59% to 90% with increasing indium concentration x from 0.32 to 0.7; a further increase in x up to 1.0 leads to little increase in the disorder level. In contrast to Ga-rich InxGa1-xN (x=0.32 and 0.47),more » significant volume swelling of up to ~25% accompanied with oxidation in In-rich InxGa1-xN (x=0.7, 0.8 and 1.0) is observed. In addition, irradiation-induced atomic mixing occurs at the interface of In-rich InxGa1-xN and GaN. The results from this study indicate an extreme susceptibility of the high In-content InxGa1-xN to heavy-ion irradiation, and suggest that cautions must be exercised in applying ion-implantation techniques to these materials at room temperature. Further studies of the irradiation behavior at elevated temperatures are warranted.« less

  11. P-n junction diodes with polarization induced p-type graded InxGa1-xN layer

    NASA Astrophysics Data System (ADS)

    Enatsu, Yuuki; Gupta, Chirag; Keller, Stacia; Nakamura, Shuji; Mishra, Umesh K.

    2017-10-01

    In this study, p-n junction diodes with polarization induced p-type layer are demonstrated on Ga polar (0001) bulk GaN substrates. A quasi-p-type region is obtained by linearly grading the indium composition in un-doped InxGa1-xN layers from 0% to 5%, taking advantage of the piezoelectric and spontaneous polarization fields which exist in group III-nitride heterostructures grown in the typical (0001) or c-direction. The un-doped graded InxGa1-xN layers needed to be capped with a thin Mg-doped InxGa1-xN layer to make good ohmic contacts and to reduce the on-resistance of the p-n diodes. The Pol-p-n junction diodes exhibited similar characteristics compared to reference samples with traditional p-GaN:Mg layers. A rise in breakdown voltage from 30 to 110 V was observed when the thickness of the graded InGaN layer was increased from 100 to 600 nm at the same grade composition.

  12. Measurement of high energy neutrons via Lu(n,xn) reactions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Henry, E.A.; Becker, J.A.; Archer, D.E.

    High energy neutrons can be assayed by the use of the nuclear diagnostic material lutetium. We are measuring the (n,xn) cross sections for natural lutetium in order to develop it as a detector material. We are applying lutetium to diagnose the high energy neutrons produced in test target/blanket systems appropriate for the Accelerator Production of Tritium Project. 3 refs., 5 figs., 1 tab.

  13. Role of biaxial strain and microscopic ordering for structural and electronic properties of InxGa1 -xN

    NASA Astrophysics Data System (ADS)

    Cui, Ying; Lee, Sangheon; Freysoldt, Christoph; Neugebauer, Jörg

    2015-08-01

    The structural and electronic properties of InxGa1 -xN alloys are studied as a function of c -plane biaxial strain and In ordering by density functional theory with the Heyd-Scuseria-Ernzerhof (HSE) hybrid functional. A nonlinear variation of the c lattice parameter with In content is observed in biaxial strain and should be taken into account when deducing In content from interplanar distances. From compressive to tensile strain, the character of the top valence-band state changes, leading to a nonlinear variation of the band gap in InxGa1 -xN . Interestingly, the well-known bowing of the InxGa1 -xN band gap is largely removed for alloys grown strictly coherently on GaN, while the actual values for band gaps at x <0.33 are hardly affected by strain. Ordering plays a minor role for lattice constants but may induce changes of the band gap up to 0.15 eV.

  14. Composition and temperature dependent optical properties of AlxGa1-xN alloy by spectroscopic ellipsometry

    NASA Astrophysics Data System (ADS)

    Liu, Yao; Li, Qing Xuan; Wan, Ling Yu; Kucukgok, Bahadir; Ghafari, Ehsan; Ferguson, Ian T.; Zhang, Xiong; Wang, Shuchang; Feng, Zhe Chuan; Lu, Na

    2017-11-01

    A series of AlxGa1-xN/AlN/Sapphire films with x = 0.35-0.75 and different thickness of epi-layer were prepared by metalorganic chemical vapor deposition (MOCVD). Spectroscopic ellipsometry (SE) was used to study the temperature-dependent refractive indices and optical bandgaps of the AlxGa1-xN films ranging from 300 to 823 K. Parametric semiconductor (PSEMI) models were used to describe the dielectric functions of AlGaN/AlN layers. The fitting results of refractive index, energy bandgap, thickness and surface roughness at 300 K are in good agreement with photoluminescence (PL), scanning electron microscopy (SEM) measurements and the existing literature. Our finding indicates that the crystal quality of the samples with x = 0.47 and 0.60 are better than those with x = 0.35 and 0.75. As the temperature rises, the increasing of refractive index for the low Al content AlxGa1-xN layers is stronger than that of high Al content in the transparent region, and the reduction of bandgap with high Al content is larger than that of low Al content. For all the samples (x = 0.35-0.75), an analytical expression for temperature-dependent refractive index in the wavelength range of 195-1650 nm was obtained using the Sellmeier law, and the quantitative analysis of the SE-derived temperature-dependent bandgap was conducted by using the Bose-Einstein equation.

  15. Doping of AlxGa1-xN

    NASA Astrophysics Data System (ADS)

    Stampfl, C.; Van de Walle, Chris G.

    1998-01-01

    N-type AlxGa1-xN exhibits a dramatic decrease in the free-carrier concentration for x⩾0.40. Based on first-principles calculations, we propose that two effects are responsible for this behavior: (i) in the case of doping with oxygen (the most common unintentional donor), a DX transition occurs, which converts the shallow donor into a deep level; and (ii) compensation by the cation vacancy (VGa or VAl), a triple acceptor, increases with alloy composition x. For p-type doping, the calculations indicate that the doping efficiency decreases due to compensation by the nitrogen vacancy. In addition, an increase in the acceptor ionization energy is found with increasing x.

  16. Polyoxometalates from heteropoly "brown" precursors. A new structural class of mixed valence heteropolytungstates, [(XO4)W3IVW17VIO 62Hx]n-

    USGS Publications Warehouse

    Dickman, M.H.; Ozeki, T.; Evans, H.T.; Rong, C.; Jameson, G.B.; Pope, M.T.

    2000-01-01

    Reduction of the ??-Keggin anion [Xn+O4W12O36][8-n]- (X = H22+, B3+, Si4+) by six electrons results in the known tungsten "brown" species [Xn+O4(H2O)3WIV3WVI9O33][8-n]- in which three W atoms have been reduced from WVI to WIV, forming a metal-metal bonded triad. The WIV atoms have terminal water coordinated in place of terminal oxo groups. Additional tungstate can condense onto these water molecules in aqueous solution between pH = 4 and 6.5 to form the species reported here, [(XO4)WIV3WVI17O 62Hx]y-. The boron derivative (X = B3+) is more stable than the metatungstate (X = H22+), both of which have been characterized by elemental analysis, 183W NMR and X-ray crystal structure analysis. Eight additional tungstate groups condense in the form of a partial Keggin structure containing two triads and one dyad which is rotated 60?? relative to a hypothetical ??-isomer. ?? The Royal Society of Chemistry 2000.

  17. MedXN: an open source medication extraction and normalization tool for clinical text

    PubMed Central

    Sohn, Sunghwan; Clark, Cheryl; Halgrim, Scott R; Murphy, Sean P; Chute, Christopher G; Liu, Hongfang

    2014-01-01

    Objective We developed the Medication Extraction and Normalization (MedXN) system to extract comprehensive medication information and normalize it to the most appropriate RxNorm concept unique identifier (RxCUI) as specifically as possible. Methods Medication descriptions in clinical notes were decomposed into medication name and attributes, which were separately extracted using RxNorm dictionary lookup and regular expression. Then, each medication name and its attributes were combined together according to RxNorm convention to find the most appropriate RxNorm representation. To do this, we employed serialized hierarchical steps implemented in Apache's Unstructured Information Management Architecture. We also performed synonym expansion, removed false medications, and employed inference rules to improve the medication extraction and normalization performance. Results An evaluation on test data of 397 medication mentions showed F-measures of 0.975 for medication name and over 0.90 for most attributes. The RxCUI assignment produced F-measures of 0.932 for medication name and 0.864 for full medication information. Most false negative RxCUI assignments in full medication information are due to human assumption of missing attributes and medication names in the gold standard. Conclusions The MedXN system (http://sourceforge.net/projects/ohnlp/files/MedXN/) was able to extract comprehensive medication information with high accuracy and demonstrated good normalization capability to RxCUI as long as explicit evidence existed. More sophisticated inference rules might result in further improvements to specific RxCUI assignments for incomplete medication descriptions. PMID:24637954

  18. The Measurement of the Evaporation Residues Excitation Functions in the Fusion Reactions 144Sm (40Ar,xn) and 166Er(40Ar,xn)

    NASA Astrophysics Data System (ADS)

    Chernysheva, E. V.; Rodin, A. M.; Belozerov, A. V.; Dmitriev, S. N.; Gulyaev, A. V.; Gulyaeva, A. V.; Itkis, M. G.; Novoselov, A. S.; Oganessian, Yu. Ts.; Salamatin, V. S.; Stepantsov, S. V.; Vedeneev, V. Yu.; Yukhimchuk, S. A.; Krupa, L.; Kliman, J.; Motycak, S.; Sivacek, I.

    2015-06-01

    The evaporation residues excitation functions for the reactions 40Ar+144Sm→184Hg and 40Ar+166Er→206Rn were measured at the energies below and above the Coulomb barrier (Elab=142-207 MeV) using a mass-separator MASHA. The experimental data were compared with theoretical calculations using a Channel Coupling Model. The influence of experimental beam energy spread on the excitation functions was taking into account. It was found that structure of xn-cross sections correlate strongly with the nuclear structure of colliding nuclei.

  19. Spin-Orbit Effect on the Molecular Properties of TeXn (X = F, Cl, Br, and I; n = 1, 2, and 4): A Density Functional Theory and Ab Initio Study.

    PubMed

    Moon, Jiwon; Kim, Joonghan

    2016-09-29

    Density functional theory (DFT) and ab initio calculations, including spin-orbit coupling (SOC), were performed to investigate the spin-orbit (SO) effect on the molecular properties of tellurium halides, TeXn (X = F, Cl, Br, and I; n = 1, 2, and 4). SOC elongates the Te-X bond and slightly reduces the vibrational frequencies. Consideration of SOC leads to better agreement with experimental values. Møller-Plesset second-order perturbation theory (MP2) seriously underestimates the Te-X bond lengths. In contrast, B3LYP significantly overestimates them. SO-PBE0 and multireference configuration interactions with the Davidson correction (MRCI+Q), which include SOC via a state-interaction approach, give the Te-I bond length of TeI2 that matches the experimental value. On the basis of the calculated thermochemical energy and optimized molecular structure, TeI4 is unlikely to be stable. The use of PBE0 including SOC is strongly recommended for predicting the molecular properties of Te-containing compounds.

  20. Nanoscale Electrostructural Characterization of Compositionally Graded Al(x)Ga(1-x)N Heterostructures on GaN/Sapphire (0001) Substrate.

    PubMed

    Kuchuk, Andrian V; Lytvyn, Petro M; Li, Chen; Stanchu, Hryhorii V; Mazur, Yuriy I; Ware, Morgan E; Benamara, Mourad; Ratajczak, Renata; Dorogan, Vitaliy; Kladko, Vasyl P; Belyaev, Alexander E; Salamo, Gregory G

    2015-10-21

    We report on AlxGa1-xN heterostructures resulting from the coherent growth of a positive then a negative gradient of the Al concentration on a [0001]-oriented GaN substrate. These polarization-doped p-n junction structures were characterized at the nanoscale by a combination of averaging as well as depth-resolved experimental techniques including: cross-sectional transmission electron microscopy, high-resolution X-ray diffraction, Rutherford backscattering spectrometry, and scanning probe microscopy. We observed that a small miscut in the substrate orientation along with the accumulated strain during growth led to a change in the mosaic structure of the AlxGa1-xN film, resulting in the formation of macrosteps on the surface. Moreover, we found a lateral modulation of charge carriers on the surface which were directly correlated with these steps. Finally, using nanoscale probes of the charge density in cross sections of the samples, we have directly measured, semiquantitatively, both n- and p-type polarization doping resulting from the gradient concentration of the AlxGa1-xN layers.

  1. Performance evaluation of the Sysmex XN-1000 hematology analyzer in assessment of the white blood cell count differential in pediatric specimens.

    PubMed

    Becker, P-H; Fenneteau, O; Da Costa, L

    2016-02-01

    The automated XN-1000 hematology analyzer enables to perform a blood cell count and a leukocyte differential. When abnormal cells were detected, a flag was generated by the analyzer and a manual microscopic examination of the corresponding blood film was performed. We compared the white blood cell differentials provided by the automated hematology analyzer XN-1000 in a pediatric population (n = 765) with those obtained through microscopic examination by cytologists and those obtained using a previous version of this analyzer, the XE-2100. Leukocytes count as well as flags sensitivity and specificity was analyzed. The leukocytes count provided by the analyzer is in good accordance with the differential obtained by manual count in children older than 3 months. The sensitivity for blast detection is 99% and the detection of reactive cells is 63%. The flag specificity remains low (<35%) for blood samples collected from infants between 8 days and 2 years of age, but increases up to 67% thereafter. The results obtained with the XN-1000 analyzer show an improvement in comparison with those obtained with the XE-2100 analyzer. The automated WBC differential provided by the XN-1000 analyzer in the pediatric setting is accurate, but a meticulous microscopic examination of blood smears remains necessary for infants up to 3 months of age to validate the analyzer flags. © 2015 John Wiley & Sons Ltd.

  2. Lattice damage and compositional changes in Xe ion irradiated In{sub x}Ga{sub 1-x}N (x = 0.32−1.0) single crystals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Limin, E-mail: zhanglm@lzu.edu.cn; Peng, Jinxin; Ai, Wensi

    2016-06-28

    Lattice disorder and compositional changes in In{sub x}Ga{sub 1-x}N (x = 0.32, 0.47, 0.7, 0.8, and 1.0) films on GaN/Al{sub 2}O{sub 3} substrates, induced by room-temperature irradiation of 5 MeV Xe ions, have been investigated using both Rutherford backscattering spectrometry under ion-channeling conditions and time-of-flight secondary ion mass spectrometry. The results show that for a fluence of 3 × 10{sup 13 }cm{sup −2}, the relative level of lattice disorder in In{sub x}Ga{sub 1-x}N increases monotonically from 59% to 90% with increasing indium concentration x from 0.32 to 0.7; a further increase in x up to 1.0 leads to little increase in the disorder level. In contrastmore » to Ga-rich In{sub x}Ga{sub 1-x}N (x = 0.32 and 0.47), significant volume swelling of up to ∼25% accompanied with oxidation in In-rich In{sub x}Ga{sub 1-x}N (x = 0.7, 0.8, and 1.0) is observed. In addition, irradiation-induced atomic mixing occurs at the interface of In-rich In{sub x}Ga{sub 1-x}N and GaN. The results from this study indicate an extreme susceptibility of the high In-content In{sub x}Ga{sub 1-x}N to heavy-ion irradiation, and suggest that cautions must be exercised in applying ion-implantation techniques to these materials at room temperature. Further studies of the irradiation behavior at elevated temperatures are warranted.« less

  3. ^235U(n,xnγ) Excitation Function Measurements Using Gamma-Ray Spectroscopy at GEANIE

    NASA Astrophysics Data System (ADS)

    Younes, W.; Becker, J. A.; Bernstein, L. A.; Archer, D. E.; Stoyer, M. A.; Hauschild, K.; Drake, D. M.; Johns, G. D.; Nelson, R. O.; Wilburn, S. W.

    1998-04-01

    The ^235U(n,xn) cross sections (where x<=2) have previously been measured at several incident neutron energies. In particular, the ^235U(n,2n) cross section has been measured(J. Frehaut et al.), Nucl. Sci. Eng. 74,29 (1980). reliably up to peak near E_n≈ 11 MeV, but not along the tail which is predicted by some(M.B. Chadwick, private communication.) codes to yield significant (e.g. >= 10% of peak) cross section out to E_n≈ 30 MeV. We have measured gamma-ray spectra resulting from ^235U(n,xn) as a function of neutron energy in the range 1 MeV <~ En <~ 200 MeV using the GEANIE spectrometer at the LANSCE/WNR ``white'' neutron source. We will present excitation functions for the de-excitation gamma rays in ^234,235U compared to predictions from the Hauser-Feshbach-preequilibrium code GNASH(M.B. Chadwick and P.G. Young, Los Alamos Report No. LA-UR-93-104, 1993.).

  4. Geometric structure of thin SiO xN y films on Si(100)

    NASA Astrophysics Data System (ADS)

    Behrens, K.-M.; Klinkenberg, E.-D.; Finster, J.; Meiwes-Broer, K.-H.

    1998-05-01

    Thin films of amorphous stoichometric SiO xN y are deposited on radiation-heated Si(100) by rapid thermal low-pressure chemical vapour deposition. We studied the whole range of possible compositions. In order to determine the geometric structure, we used EXAFS and photoelectron spectroscopy. Tetrahedrons constitute the short-range units with a central Si atom connected to N and O. The distribution of the possible tetrahedrons can be described by a mixture of the Random Bonding Model and the Random Mixture Model. For low oxygen contents x/( x+ y)≤0.3, the geometric structure of the film is almost the structure of a-Si 3N 4, with the oxygen preferably on top of Si-N 3 triangles. Higher oxygen contents induce changes in the bond lengths, bond angles and coordination numbers.

  5. Understanding band alignments in semiconductor heterostructures: Composition dependence and type-I-type-II transition of natural band offsets in nonpolar zinc-blende AlxGa1 -xN /AlyGa1 -yN composites

    NASA Astrophysics Data System (ADS)

    Landmann, M.; Rauls, E.; Schmidt, W. G.

    2017-04-01

    The composition dependence of the natural band alignment at nonpolar AlxGa1 -xN /AlyGa1 -yN heterojunctions is investigated via hybrid functional based density functional theory. Accurate band-gap data are provided using Heyd-Scuseria-Ernzerhof (HSE) type hybrid functionals with a composition dependent exact-exchange contribution. The unstrained band alignment between zincblende (zb) AlxGa1 -xN semiconductor alloys is studied within the entire ternary composition range utilizing the Branch-point technique to align the energy levels related to the bulklike direct Γv→Γc and indirect, pseudodirect, respectively, Γv→Xc type transitions in zb-AlxGa1 -xN . While the zb-GaN/AlxGa1 -xN band edges consistently show a type-I alignment, the relative position of fundamental band edges changes to a type-II alignment in the Al-rich composition ranges of zb-AlxGa1 -xN /AlN and zb-AlxGa1 -xN /AlyGa1 -yN systems. The presence of a direct-indirect band-gap transition at xc=0.63 in zb-AlxGa1 -xN semiconductor alloys gives rise to a notably different composition dependence of band discontinuities in the direct and indirect energy-gap ranges. Below the critical direct-indirect Al/Ga-crossover concentration, the band offsets show a close to linear dependence on the alloy composition. In contrast, notable bowing characteristics of all band discontinuities are observed above the critical crossover composition.

  6. Stress controlled pulsed direct current co-sputtered Al{sub 1−x}Sc{sub x}N as piezoelectric phase for micromechanical sensor applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fichtner, Simon, E-mail: sif@tf.uni-kiel.de; Reimer, Tim; Chemnitz, Steffen

    2015-11-01

    Scandium alloyed aluminum nitride (Al{sub 1−x}Sc{sub x}N) thin films were fabricated by reactive pulsed direct current co-sputtering of separate scandium and aluminum targets with x ≤ 0.37. A significant improvement of the clamped transversal piezoelectric response to strain e{sub 31,f} from −1.28 C/m{sup 2} to −3.01 C/m{sup 2} was recorded, while dielectric constant and loss angle remain low. Further, the built-in stress level of Al{sub 1−x}Sc{sub x}N was found to be tuneable by varying pressure, Ar/N{sub 2} ratio, and Sc content. The thus resulting enhancement of the expectable signal to noise ratio by a factor of 2.1 and the abilitymore » to control built-in stress make the integration of Al{sub 1−x}Sc{sub x}N as the piezoelectric phase of micro-electro-mechanical system sensor applications highly attractive.« less

  7. Tuning of superconductivity by Ni substitution into noncentrosymmetric ThC o1 -xN ixC2

    NASA Astrophysics Data System (ADS)

    Grant, T. W.; Cigarroa, O. V.; Rosa, P. F. S.; Machado, A. J. S.; Fisk, Z.

    2017-07-01

    The recently discovered noncentrosymmetric superconductor ThCoC2 was observed to show unusual superconducting behavior with a critical temperature of Tc=2.65 K . Here we investigate the effect of nickel substitution on the superconducting state in ThC o1 -xN ixC2 . Magnetization, resistivity, and heat capacity measurements demonstrate Ni substitution has a dramatic effect with critical temperature increased up to Tc=12.1 K for x =0.4 Ni concentration, which is a rather high transition temperature for a noncentrosymmetric superconductor. In addition, the unusual superconducting characteristics observed in pure ThCoC2 appear to be suppressed or tuned with Ni substitution towards a more conventional fully gapped superconductor.

  8. 17 CFR 240.16a-4 - Derivative securities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Derivative securities. 240.16a....16a-4 Derivative securities. (a) For purposes of section 16 of the Act, both derivative securities and... securities, except that the acquisition or disposition of any derivative security shall be separately...

  9. Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK activation.

    PubMed

    Gallo, Cristina; Dallaglio, Katiuscia; Bassani, Barbara; Rossi, Teresa; Rossello, Armando; Noonan, Douglas M; D'Uva, Gabriele; Bruno, Antonino; Albini, Adriana

    2016-09-13

    Angiogenesis, a process characterized by the formation of new blood vessels from pre-existing ones, is a crucial step in tumor growth and dissemination. Recently, increased attention has been addressed to the ability of flavonoids to prevent cancer by suppressing angiogenesis, strategy that we named "angioprevention". Several natural compounds exert their anti-tumor properties by activating 5' adenosine monophosphate-activated protein kinase (AMPK), a key regulator of metabolism in cancer cells. Drugs with angiopreventive activities, in particular metformin, regulate AMPK in endothelial cells. Here we investigated the involvement of AMPK in the anti-angiogenic effects of xanthohumol (XN), the major prenylated flavonoid of the hop plant, and mechanisms of action. The anti-angiogenic activity of XN was more potent than epigallocatechin-3-gallate (EGCG). Treatment of endothelial cells with XN led to increased AMPK phosphorylation and activity. Functional studies using biochemical approaches confirmed that AMPK mediates XN anti-angiogenic activity. AMPK activation by XN was mediated by CAMMKβ, but not LKB1. Analysis of the downstream mechanisms showed that XN-induced AMPK activation reduced nitric oxide (NO) levels in endothelial cells by decreasing eNOS phosphorylation. Finally, AKT pathway was inactivated by XN as part of its anti-angiogenic activity, but independently from AMPK, suggesting that these two signaling pathways proceed autonomously. Our study dissects the molecular mechanism by which XN exerts its potent anti-angiogenic activity, pointing out AMPK as a crucial signal transducer.

  10. Band gap bowing and crossing of BxGa1-xN alloy investigated by hybrid functional method

    NASA Astrophysics Data System (ADS)

    Jiaping, Jiang; Yanqin, Gai; Gang, Tang

    2016-02-01

    The electronic properties of zinc-blende BxGa1-xN alloys are comparatively investigated by employing both the Perdewe-Burkee-Ernzerhof generalized-gradient approximation (PBE-GGA) and the Heyd-Scuseria-Ernzerhof screened hybrid functional methods (HSE06). HSE06 reproduced much closer ground-state properties to experiments. Large and composition-dependent bowing parameters bγ for the direct band gaps were obtained from both PBE and HSE06. The crossover composition where alloy switches from direct to indirect was predicted to occur at very similar x from PBE and HSE06. We can obtain direct gap BxGa1-xN with a gap value much larger than that of GaN by alloying x < 0.557 boron into GaN. Project supported by the Fundamental Research Funds for the Central Universities (No. 2010LKWL03), the Special Fund for Theoretical Physics (No. 11047130), and the National Natural Science Foundation of China (No. 11104345).

  11. 12 CFR 403.4 - Derivative classification.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of derivative classification. (1) Unlike original classification which is an initial determination, derivative classification... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Derivative classification. 403.4 Section 403.4...

  12. Characterization of Phase-Slip Centers created in superconducting NbxTi1-xN thin films close to Tc

    NASA Astrophysics Data System (ADS)

    Harrabi, Khalil; Maneval, Jean Paul; Maneval Collaboration

    The dissipative states induced by an over-critical (pair-breaking) current in superconducting NbxTi1-xN strips were investigated and characterized in the vicinity of the critical temperature Tc ( 8.7 K). The suppression of superconductivity then occurs locally and leads to the creation of a phase-slip center (PSC). In the case where the over-critical current is applied as a step pulse, the PSC voltage rise is preceded by a nucleation time td which can be analyzed through a Time-Dependent Ginzburg-Landau theory due to Tinkham. In conformity with previous work, we interpret the effective gap relaxation time of the theory as the film cooling time. By consideration of the respective weights of the electron and phonon specific heats, the phonon escape time can be derived from experiments. It is here found to be 1.8 ns for a 20 nm NbTiN film sputtered on polished crystalline Al2O3\\ King Fahd University of Peroleum and Minerals Saudi Arabia.

  13. 12 CFR 403.4 - Derivative classification.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false Derivative classification. 403.4 Section 403.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CLASSIFICATION, DECLASSIFICATION, AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of derivative...

  14. (n,xn) cross section measurements for Y-89 foils used as detectors for high energy neutron measurements in the deeply subcritical assembly "QUINTA"

    NASA Astrophysics Data System (ADS)

    Bielewicz, Marcin; Kilim, Stanisław; Strugalska-Gola, Elżbieta; Szuta, Marcin; Wojciechowski, Andrzej; Tyutyunnikov, Sergey; Prokofiev, Alexander; Passoth, Elke

    2017-09-01

    Study of the deep subcritical systems (QUINTA) using relativistic beams is performed within the project "Energy and Transmutation of Radioactive Wastes" (E&T - RAW). The experiment assembly was irradiated by deuteron/proton beam (Dubna NUCLOTRON). We calculated the neutron energy spectrum inside the whole assembly by using threshold energy (n,xn) reactions in yttrium (Y-89) foils. There are almost no experimental cross section data for those reactions. New Y-89(n,xn) cross section measurements were carried out at The Svedberg laboratory (TSL) in Uppsala, Sweden in 2015. In this paper we present preliminary results of those experiments.

  15. 12 CFR 403.4 - Derivative classification.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false Derivative classification. 403.4 Section 403.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CLASSIFICATION, DECLASSIFICATION, AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of derivative...

  16. 12 CFR 403.4 - Derivative classification.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false Derivative classification. 403.4 Section 403.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CLASSIFICATION, DECLASSIFICATION, AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of derivative...

  17. 12 CFR 403.4 - Derivative classification.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false Derivative classification. 403.4 Section 403.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES CLASSIFICATION, DECLASSIFICATION, AND SAFEGUARDING OF NATIONAL SECURITY INFORMATION § 403.4 Derivative classification. (a) Use of derivative...

  18. Transverse spin correlation function of the one-dimensional spin- {1}/{2} XY model

    NASA Astrophysics Data System (ADS)

    Tonegawa, Takashi

    1981-12-01

    The transverse spin pair correlation function pxn=< SxmSxm+ n>=< SxmSxm+ n> is calculated exactly in the thermodynamic limit of the system described by the one-dimensional, isotropic, spin- {1}/{2}, XY Hamiltonian H=-2J limit∑l=1N(S xlS xl+1+S ylS yl+1) . It is found that at absolute zero temperature ( T = 0), the correlation function ρ xn for n ≥ 0 is given by ρ x2p= {1}/{4}{2}/{π}2plimitΠj=1p-1{4j 2}/{4j 2-1 }2p-2jif n=2p , ρ x2p+1=± {1}/{4}{2}/{π}2p+1limitΠj=1p{4j 2}/{4j 2-1 }2p+2jif n=2p+1 , where the plus sign applies when J is positive and the minus sign applies when J is negative. From these the asymptotic behavior as n → ∞ of |ϱ xn| at T = 0 is derived to be |ρ xn| ˜ {a}/{n} with a = 0.147088⋯. For finite temperatures, ρ xn is calculated numerically. By using the results for ϱ xn, the transverse inverse correlation length and the wavenumber dependent transverse spin pair correlation function are also calculated exactly.

  19. First principles calculations of electronic structure and magnetic properties of Cr-based magnetic semiconductors Al{sub 1-x}Cr{sub x}X (X=N, P, As, Sb)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saeed, Y., E-mail: yasir_saeed54321@yahoo.co; Shaukat, A., E-mail: schaukat@gmail.co; Nazir, S., E-mail: nazirsafdar@gmail.co

    2010-01-15

    First principles calculations based on the density functional theory (DFT) within the local spin density approximation are performed to investigate the electronic structure and magnetic properties of Cr-based zinc blende diluted magnetic semiconductors Al{sub 1-x}Cr{sub x}X (X=N, P, As, Sb) for 0<=x<=0.50.The behaviour of magnetic moment of Al{sub 1-x}Cr{sub x}X at each Cr site as well as the change in the band gap value due to spin down electrons has been studied by increasing the concentration of Cr atom and through changing X from N to Sb. Furthermore, the role of p-d hybridization is analyzed in the electronic band structuremore » and exchange splitting of d-dominated bands. The interaction strength is stronger in Al{sub 1-x}Cr{sub x}N and becomes weaker in Al{sub 1-x}Cr{sub x}Sb. The band gap due to the spin down electrons decreases with the increased concentration of Cr in Al{sub 1-x}Cr{sub x}X, and as one moves down along the isoelectronic series in the group V from N to Sb. Our calculations also verify the half-metallic ferromagnetic character in Cr doped AlX. - Graphical abstract: The prototype structures of Cr doped AlX (X=N, P, As, Sb) compounds: (A) zinc blende AlP for x=0, (B) Cr{sub 1}Al{sub 7}P{sub 8} for x=0.125, (C) Cr{sub 1}Al{sub 3}P{sub 4} for x=0.25, (D) Cr{sub 1}Al{sub 1}P{sub 2} for x=0.5.« less

  20. Microstructure and dielectric properties of piezoelectric magnetron sputtered w-ScxAl1-xN thin films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zukauskaite, Agne; Wingqvist, Gunilla; Palisaitis, Justinas

    2012-01-01

    Piezoelectric wurtzite ScxAl1 xN (x = 0, 0.1, 0.2, 0.3) thin films were epitaxially grown by reactive magnetron co-sputtering from elemental Sc and Al targets. Al2O3(0001) wafers with TiN(111) seed and electrode layers were used as substrates. X-ray diffraction shows that an increase in the Sc content results in the degradation of the crystalline quality. Samples grown at 400 C possess true dielectric behavior with quite low dielectric losses and the leakage current is negligible. For ScAlN samples grown at 800 C, the crystal structure is poor and leakage current is high. Transmission electron microscopy with energy dispersive x-ray spectroscopymore » mapping shows a mass separation into ScN-rich and AlN-rich domains for x 0.2 when substrate temperature is increased from 400 to 800 C. The piezoelectric response of epitaxial ScxAl1 xN films measured by piezoresponse force microscopy and double beam interferometry shows up to 180% increase by the addition of Sc up to x = 0.2 independent of substrate temperature, in good agreement with previous theoretical predictions based on density-functional theory.« less

  1. Diffusion of Mg dopant in metal-organic vapor-phase epitaxy grown GaN and AlxGa1-xN

    NASA Astrophysics Data System (ADS)

    Köhler, K.; Gutt, R.; Wiegert, J.; Kirste, L.

    2013-02-01

    Diffusion of the p-type dopant Mg in GaN and AlxGa1-xN which is accompanied by segregation and affected by transient effects in metal-organic vapor-phase epitaxy reactors is investigated. We have grown 110 nm thick Mg doped GaN and Al0.1Ga0.9N layers on top of undoped GaN and Al0.1Ga0.9N layers, respectively, in a temperature range between 925 °C and 1050 °C where we placed special emphasis on the lower temperature limit without diffusion to allow separation of Mg transients, diffusion, and segregation. Hereby, AlxGa1-xN layers enable monitoring of the resolution limit by secondary ion mass spectrometry analyses for the respective samples; therefore, thin AlxGa1-xN marker layers are incorporated in the thick GaN layers. We found an upper limit of 1.25 × 1019 cm-3 for diffusing Mg atoms in both sample types. Owing to the marked influence of Mg segregation in Al0.1Ga0.9N, diffusion is only seen by using a GaN cap on top of the Al0.1Ga0.9N layer sequence. Diffusion in Al0.1Ga0.9N is shown to be increased by about 25%-30% compared to GaN. Post growth annealing experiments under conditions equivalent to those used for growth of the Mg doped samples showed negligible diffusion. Comparing the results to well established findings on other doped III-V compounds, diffusion is explained by an interstitial-substitutional mechanism with a diffusion coefficient, which is concentration dependent. Analysis of the temperature dependent diffusivity revealed an activation energy of 5.0 eV for GaN:Mg and 5.2 eV for Al0.1Ga0.9N:Mg.

  2. 17 CFR 240.16a-4 - Derivative securities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Derivative securities. 240.16a-4 Section 240.16a-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  3. Conducting transition metal nitride thin films with tailored cell sizes: The case of {delta}-Ti{sub x}Ta{sub 1-x}N

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koutsokeras, L. E.; Laboratoire PHYMAT, Universite de Poitiers-CNRS, UMR 6630, SP2MI, Teleport 2, Bd Marie et Pierre Curie, 86962 Chasseneuil-Futuroscope; Abadias, G.

    2008-07-07

    We present results on the stability and tailoring of the cell size of conducting {delta}-Ti{sub x}Ta{sub 1-x}N obtained by film growth and ab initio calculations. Despite the limited solubility of Ta in Ti, we show that TiN and TaN are soluble due to the hybrization of the d and sp electrons of the metal and N, respectively, that stabilizes the ternary system to the rocksalt structure. The stress-free cell sizes follow the Vegard's rule; nevertheless, process-dependent stresses expand the cell size of the as-grown films. The electronic properties of {delta}-Ti{sub x}Ta{sub 1-x}N films ({rho}=180 {omega} cm) are similar to thosemore » of TiN and TaN.« less

  4. 17 CFR 240.16a-4 - Derivative securities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Derivative securities. 240.16a-4 Section 240.16a-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  5. 17 CFR 240.16a-4 - Derivative securities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Derivative securities. 240.16a-4 Section 240.16a-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  6. 17 CFR 240.16a-4 - Derivative securities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Derivative securities. 240.16a-4 Section 240.16a-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  7. An assessment of the evaporation and condensation phenomena of lithium during the operation of a Li(d,xn) fusion relevant neutron source.

    PubMed

    Knaster, J; Kanemura, T; Kondo, K

    2016-12-01

    The flowing lithium target of a Li(d,xn) fusion relevant neutron source must evacuate the deuteron beam power and generate in a stable manner a flux of neutrons with a broad peak at 14 MeV capable to cause similar phenomena as would undergo the structural materials of plasma facing components of a DEMO like reactors. Whereas the physics of the beam-target interaction are understood and the stability of the lithium screen flowing at the nominal conditions of IFMIF (25 mm thick screen with +/-1 mm surface amplitudes flowing at 15 m/s and 523 K) has been demonstrated, a conclusive assessment of the evaporation and condensation of lithium during operation was missing. First attempts to determine evaporation rates started by Hertz in 1882 and have since been subject of continuous efforts driven by its practical importance; however intense surface evaporation is essentially a non-equilibrium process with its inherent theoretical difficulties. Hertz-Knudsen-Langmuir (HKL) equation with Schrage's 'accommodation factor' η = 1.66 provide excellent agreement with experiments for weak evaporation under certain conditions, which are present during a Li(d,xn) facility operation. An assessment of the impact under the known operational conditions for IFMIF (574 K and 10 -3 Pa on the free surface), with the sticking probability of 1 inherent to a hot lithium gas contained in room temperature steel walls, is carried out. An explanation of the main physical concepts to adequately place needed assumptions is included.

  8. Performance evaluation of the Sysmex(®) XP-300 in an oncology setting: evaluation and comparison of hematological parameters with the Sysmex(®) XN-3000.

    PubMed

    van Dievoet, M A; Louagie, H; Ghys, T

    2016-10-01

    The Sysmex XP-300(®) (XP-300) is a new, fully automated hematology analyzer, designed to generate complete blood counts (CBC) with 3-part differential. In our study, the XP-300 was evaluated as a point-of-care (POC) analyzer in an oncology setting. In which blood samples from patients with different pathologies and treatments, affecting hematopoiesis, were analyzed. Performance was evaluated according to the International Council for Standardization in Haematology (ICSH) guidelines and CLSI protocol H20-A2 . Beside precision, linearity and carry-over, a comparison study with the Sysmex(®) XN-3000 (XN-3000) and a manual reference leukocyte differential was performed. Flagging performance was also evaluated. XP-300 showed excellent precision and linearity results. For within- and between-run precision, the criteria, according to Ricos et al. , were met for all parameters tested, except for platelets in the low level. Less than or equal to 0.5% carry-over was seen for all parameters tested. Comparison studies showed an acceptable correlation with both XN-3000 and the manual reference leukocyte count. A suboptimal flagging performance was demonstrated. In the context of diagnosing cytopenia due to myelosuppressing agents or leukocytosis due to infection, the XP-300 showed good analytical performance. However, in the thrombocytopenic range, precision was suboptimal. In follow-up of hematological malignancies with the occurrence of abnormal cells, we advise verification with a more advanced analyzer or with microscopic review, although further studies with a higher prevalence of abnormal cells are needed. © 2016 John Wiley & Sons Ltd.

  9. Average and local crystal structures of (Ga 1–xZn x)(N 1–xO x) solid solution nanoparticles

    DOE PAGES

    Feygenson, Mikhail; Neuefeind, Joerg C.; Tyson, Trevor A.; ...

    2015-11-06

    We report the comprehensive study of the crystal structure of (Ga 1–xZn x)(N 1–xO x) solid solution nanoparticles by means of neutron and synchrotron x-ray scattering. In our study we used four different types of (Ga 1–xZn x)(N 1–xO x) nanoparticles, with diameters of 10–27 nm and x = 0.075–0.51, which show the narrow energy-band gaps from 2.21 to 2.61 eV. The Rietveld analysis of the neutron diffraction data revealed that the average crystal structure is the hexagonal wurtzite (space group P6 3mc), in agreement with previous reports on similar bulk materials. The pair-distribution function (PDF) analysis of the samemore » data found that the local structure is more disordered than the average one. It is best described by the model with a lower symmetry space group P1, where atoms are quasirandomly distorted from their nominal positions in the hexagonal wurtzite lattice.« less

  10. Conciliatory Inductive Model Explaining the Origin of Changes in the η(2)-SiH Bond Length Caused by Presence of Strongly Electronegative Atoms X (X = F, Cl) in Cp(OC)2Mn[η(2)-H(SiH3-nXn)] (n = 0-3) Complexes.

    PubMed

    Jabłoński, Mirosław

    2016-06-23

    Using three theoretical methods, QTAIM, IQA, and NCI, we analyze an influence of halogen atoms X (X = F, Cl) substituted at various positions in the -SiH3-nXn group on the charge density distribution within the η(2)-SiH bond and on the SiH bond energies in Cp(OC)2Mn[η(2)-H(SiH3-nXn)] complexes and isolated HSiH3-nXn molecules. It is shown that shortening of the η(2)-SiH bond in Cp(OC)2Mn[η(2)-H(SiH3-nXn)] complexes should be considered as a normal inductive result of halogenation. This η(2)-SiH bond's compression may, however, be overcome by a predominant elongation resulting from a contingent presence of a halogen atom at position trans to the η(2)-SiH bond. This trans effect is particularly large for bulky and highly polarizable chlorine. Moreover, peculiar properties of the trans chlorine atom are manifested in several ways. To explain the origin of all the observed changes in both the length and the electron charge distribution of the η(2)-SiH bond in investigated Cp(OC)2Mn[η(2)-H(SiH3-nXn)] complexes a new model, called the Conciliatory Inductive Model, is being proposed.

  11. Microstructure and dielectric properties of piezoelectric magnetron sputtered w-Sc{sub x}Al{sub 1-x}N thin films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zukauskaite, Agne; Wingqvist, Gunilla; Palisaitis, Justinas

    2012-05-01

    Piezoelectric wurtzite Sc{sub x}Al{sub 1-x}N (x = 0, 0.1, 0.2, 0.3) thin films were epitaxially grown by reactive magnetron co-sputtering from elemental Sc and Al targets. Al{sub 2}O{sub 3}(0001) wafers with TiN(111) seed and electrode layers were used as substrates. X-ray diffraction shows that an increase in the Sc content results in the degradation of the crystalline quality. Samples grown at 400 deg. C possess true dielectric behavior with quite low dielectric losses and the leakage current is negligible. For ScAlN samples grown at 800 deg. C, the crystal structure is poor and leakage current is high. Transmission electron microscopymore » with energy dispersive x-ray spectroscopy mapping shows a mass separation into ScN-rich and AlN-rich domains for x {>=} 0.2 when substrate temperature is increased from 400 to 800 deg. C. The piezoelectric response of epitaxial Sc{sub x}Al{sub 1-x}N films measured by piezoresponse force microscopy and double beam interferometry shows up to 180% increase by the addition of Sc up to x = 0.2 independent of substrate temperature, in good agreement with previous theoretical predictions based on density-functional theory.« less

  12. Effects of S-containing ligands on the structure and electronic properties of CdnSen/CdnTen nanoparticles (n = 3, 4, 6, and 9)

    NASA Astrophysics Data System (ADS)

    Lim, Emmanuel; Kuznetsov, Aleksey E.; Beratan, David N.

    2012-10-01

    To understand ligand capping effects on the structure and electronic properties of CdnXn (X = Se, Te; n = 3, 4, 6, and 9) species, we performed density functional theory studies of SCH2COOH-, SCH2CH2CO2H-, and SCH2CH2NH2-capped nanoparticles. CdnXn capping with all three capping groups was found to produce significant NP distortions. All three ligands destabilize the NP HOMOs and either stabilize or destabilize their LUMOs, leading to closure of the HOMO/LUMO gaps for all of the capped species, because the HOMO destabilization effect is generally large than the LUMO destabilization effect. The calculated absorption spectra of bare and capped NPs, exemplified by CdnXn with n = 4 and 6, show that all capping groups cause noticeable red shifts for n = 4 and mostly blue shifts for n = 6.

  13. Spin reorientation and magnetoelastic properties of ferromagnetic T b1 -xN dxC o2 systems with a morphotropic phase boundary

    NASA Astrophysics Data System (ADS)

    Murtaza, Adil; Yang, Sen; Chang, Tieyan; Ghani, Awais; Khan, Muhammad Tahir; Zhang, Rui; Zhou, Chao; Song, Xiaoping; Suchomel, Matthew; Ren, Yang

    2018-03-01

    The spin reorientation (SR) and magnetoelastic properties of pseudobinary ferromagnetic T b1 -xN dxC o2 (0 ≤x ≤1.0 ) systems involving a morphotropic phase boundary (MPB) were studied by high-resolution synchrotron x-ray diffraction (XRD), magnetization, and magnetostriction measurements. The easy magnetization direction of the Laves phase lies along the 〈111 〉 axis with x <0.65 , whereas it lies along the 〈100 〉 axis for x >0.65 below Curie temperature (TC). The temperature-dependent magnetization curves showed SR; this can be explained by a two-sublattice model. Based on the synchrotron (XRD) and magnetization measurements, the SR phase diagram for a MPB composition of T b0.35N d0.65C o2 was obtained. Contrary to previously reported ferromagnetic systems involving MPB, the MPB composition of T b0.35N d0.65C o2 exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The anisotropic magnetostriction (λS) first decreased until x =0.8 and then continuously increased in the negative direction with further increase of Nd concentration. The decrease in magnetostriction can be attributed to the decrease of spontaneous magnetostriction λ111 and increase of λ100 with opposite sign to λ111. This paper indicates an anomalous type of MPB in the ferromagnetic T b1 -xN dxC o2 system and provides an active way to design novel functional materials with exotic properties.

  14. Ultrafast Carrier dynamics of InxGa1-xN nanostructures grown directly on Si(111)

    NASA Astrophysics Data System (ADS)

    Kumar, Praveen; Devi, Pooja; Rodriguez⁠, P. E. D. S.; Kumar, Manish; Shivling, V. D.; Noetzel, Richard; Sharma, Chhavi; Sinha, R. K.; Kumar, Mahesh

    2018-05-01

    We show a flux dependence changes in structural, optical and electronic properties of InxGa1-xN nanostructures (NSs) namely nanocolumns (NCs), nanoflakes (NFs) and nanowall network (NWN) grown directly on Si(111) surface. Field emission scanning electron microscopy (FESEM) images were recorded to see morphological changes from NFs to NCs and NWNc etc, while high-resolution X-ray diffraction (HRXRD) ω-2θ scans were used to determine In incorporation. The maximum In incorporation was observed to be 20, 33 and 38% for the sharp transition from NFs to NCs and NWNs, respectively. The charge carrier dynamics of these grown NSs were probed using Ultrafast Femtosecond Transient Absorption Spectroscopy (UFTAS) with excitation at 350 nm pump wavelength. The UFTAS studies show the comparative charge carriers dynamics of the NWS, NCs and NFs. The charge carrier studies show a higher lifetime in NWNs as compare to NCs and NFs. Further, to examine electronic structure and level of degeneracy of these NSs, core-level and valence band spectra were analyzed by X-ray photoelectron spectroscopy (XPS), which manifest the upward band bending ranging from 0.2 eV to 0.4 eV.

  15. Spectroscopic analysis of the NIR emission in Tm implanted Al{sub x}Ga{sub 1-x}N layers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rodrigues, J., E-mail: joana.catarina@ua.pt; Esteves, T. C.; Santos, N. F.

    2016-08-28

    Al{sub x}Ga{sub 1-x}N samples, with different AlN molar fractions, x = 0, 0.15, 0.77, and 1, grown by halide vapor phase epitaxy were implanted with Tm ions. Photoluminescence (PL) measurements revealed that after thermal annealing all the samples exhibit intraionic Tm{sup 3+} luminescence. In samples with x > 0, the low temperature emission is dominated by the lines that appear in the near infrared (NIR) spectral region, corresponding to the overlapped {sup 1}G{sub 4} → {sup 3}H{sub 5} and {sup 3}H{sub 4} → {sup 3}H{sub 6} multiplet transitions. A detailed spectroscopic analysis of NIR emission of the thulium implanted and annealed Al{sub x}Ga{sub 1-x}Nmore » layers is presented by using temperature dependent steady-state PL, room temperature PL excitation, and time resolved PL. The results indicate that the excitonic features sensitive to the alloy disorder are involved in the excitation population processes of the Tm{sup 3+} luminescence and the highest thermal stability for the NIR emission occurs for the AlN:Tm sample.« less

  16. Synthesis and biological evaluation of vinylogous combretastatin A-4 derivatives.

    PubMed

    Kaffy, Julia; Pontikis, Renée; Florent, Jean-Claude; Monneret, Claude

    2005-07-21

    Stereospecific syntheses of the Z-E and E-Z vinylogues of combretastatin A-4, and two B-ring related analogues, were achieved through a Suzuki-Miyaura coupling. As compared to CA4, the derivative with a phenyl moiety has shown increased potency in its ability to inhibit tubulin polymerisation.

  17. Preferred site occupation of 3 d atoms in NixF e4 -xN (x =1 and 3) films revealed by x-ray absorption spectroscopy and magnetic circular dichroism

    NASA Astrophysics Data System (ADS)

    Takata, Fumiya; Ito, Keita; Takeda, Yukiharu; Saitoh, Yuji; Takanashi, Koki; Kimura, Akio; Suemasu, Takashi

    2018-02-01

    X-ray absorption spectroscopy (XAS) and x-ray magnetic circular dichroism measurements were performed at the Ni and Fe L2 ,3 absorption edges for N ixF e4 -xN (x =1 and 3) epitaxial films. Spectral line-shape analysis and element-specific magnetic moment evaluations are presented. Shoulders at approximately 2 eV above the Ni L2 ,3 main peaks in the XAS spectrum of N i3FeN were interpreted to originate from hybridization of orbitals between Ni 3 d at face-centered (II) sites and N 2 p at body-centered sites, while such features were missing in NiF e3N film. Similar shoulders were observed at Fe L2 ,3 edges in both films. These results indicate that the orbitals of Ni atoms did not hybridize with those of N atoms in the NiF e3N film. Hence, Ni atoms preferentially occupied corner (I) sites, where the hybridization was weak because of the relatively long distance between Ni at I sites and N atoms. The relatively large magnetic moment deduced from sum-rule analysis of NiF e3N also showed a good agreement with the presence of Ni atoms at I sites.

  18. Application of the BINS superheated drop detector spectrometer to the 9Be(p,xn) neutron energy spectrum determination

    NASA Astrophysics Data System (ADS)

    Di Fulvio, A.; Ciolini, R.; Mirzajani, N.; Romei, C.; d'Errico, F.; Bedogni, R.; Esposito, J.; Zafiropoulos, D.; Colautti, P.

    2013-07-01

    In the framework of TRASCO-BNCT project, a Bubble Interactive Neutron Spectrometer (BINS) device was applied to the characterization of the angle-and energy-differential neutron spectra generated by the 9Be(p,xn)reaction. The BINS spectrometer uses two superheated emulsion detectors, sequentially operated at different temperatures and thus provides a series of six sharp threshold responses, covering the 0.1-10 MeV neutron energy range. Spectrum unfolding of the data was performed by means of MAXED code. The obtained angle, energy-differential spectra were compared with those measured with a Bonner sphere spectrometer, a silicon telescope spectrometer and literature data.

  19. Symmetry properties of the configuration interaction space in relation to one- and two-particle operators: The splitting theorem

    NASA Astrophysics Data System (ADS)

    Živković, Tomislav P.

    1984-09-01

    The configuration interaction (CI) space Xn built upon n electrons moving over 2n orthonormalized orbitals χi is considered. It is shown that the space Xn splits into two complementary subspaces X+n and X-n having special properties: each state Ψ+∈X+n and Ψ-∈X-n is ``alternantlike'' in the sense that it has a uniform charge density distribution over all orbitals χi and vanishing bond-orders between all orbitals of the same parity. In addition, matrix elements Γ(ij;kl) of a two-particle density matrix vanish whenever four distinct orbitals are involved and there is an odd number of orbitals of the same parity. Further, Γ(ij;lj)=γ(il)/4 ( j≠i,l), whenever (i) and (l) are of different parity. This last relation shows the connection between a two-particle (Γ) and a one-particle (γ) density matrix. ``Elementary'' alternant and antialternant operators are identified. These operators connect either only the states in the same subspace, or only the states in different subspaces, and each one- and two-particle symmetric operator can be represented by their linear combination. Alternant Hamiltonians, which can be represented as linear combinations of elementary alternant operators, have alternantlike eigenstates. It is also shown that each symmetric Hamiltonian possessing alternantlike eigenstates can be represented as such a linear combination. In particular, the PPP Hamiltonian describing an alternant hydrocarbon system is such a case. Complementary subspaces X+n and X-n can be explicitly constructed using the so-called regular resonance structures (RRS's) which are normalized determinants containing mutually disjunct bond orbitals. Expressions for the derivation of matrix elements of one- and two-particle operators between different RRS's are also derived.

  20. Complete Genome Sequence of Staphylococcus aureus XN108, an ST239-MRSA-SCCmec III Strain with Intermediate Vancomycin Resistance Isolated in Mainland China

    PubMed Central

    Zhang, Xia; Xu, Xiaomeng; Yuan, Wenchang; Hu, Qiwen; Shang, Weilong; Hu, Xiaomei

    2014-01-01

    ST239-MRSA-SCCmec III (ST239, sequence type 239; MRSA, methicillin-resistant Staphylococcus aureus; SCCmec III, staphylococcal cassette chromosome mec type III) is the most predominant clone of hospital-acquired methicillin-resistant S. aureus in mainland China. We report here the complete genome sequence of XN108, the first vancomycin-intermediate S. aureus strain isolated from a steam-burned patient with a wound infection. PMID:25059856

  1. Amplified luminescence of heavily doped AlxGa1-xN structures under optical pumping

    NASA Astrophysics Data System (ADS)

    Bokhan, P. A.; Zhuravlev, K. S.; Zakrevskii, D. E.; Malin, T. V.; Osinnykh, I. V.; Fateev, N. V.

    2018-03-01

    Spectral, temporal, and polarisation characteristics of luminescence of heavily doped AlxGa1-xN films on a sapphire substrate are studied under pulsed pumping at the wavelength λ = 266 m. Spectra of spontaneous emission related to donor – acceptor transitions are inhomogeneously broadened with the FWHM of above 0.5 eV and cover the entire visible range. Spectra of radiation emitted from an edge of investigated structure comprise several narrow-band equidistant components, each of them being split to TE and TM modes with mutually orthogonal polarisations. This is related to plane waves propagating inside a plane waveguide along a zigzag path in the conditions of total internal reflection from waveguide surfaces. The optical gains measured for Al0.5Ga0.5N/AlN at λ ≈ 510 nm, Al0.74Ga0.26N/AlN at λ ≈ 468 nm, and AlN/Al0.6Ga0.4N/AlN/Al2O3 at λ ≈ 480 nm were, respectively, ~70, 20, and 44 cm-1. The luminescence quantum efficiencies measured for Al0.74Ga0.26N, Al0.65Ga0.35N, and Al0.5Ga0.5N films are, respectively, 0.79, 0.49, and 0.14; the transition cross sections calculated at emission band centres are ~10-18 cm2.

  2. Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol analogues.

    PubMed

    Nuti, Elisa; Bassani, Barbara; Camodeca, Caterina; Rosalia, Lea; Cantelmo, AnnaRita; Gallo, Cristina; Baci, Denisa; Bruno, Antonino; Orlandini, Elisabetta; Nencetti, Susanna; Noonan, Douglas M; Albini, Adriana; Rossello, Armando

    2017-09-29

    Angiogenesis induction is a hallmark of cancer. Antiangiogenic properties of Xanthohumol (XN), a naturally occurring prenylated chalcone from hops, have been widely reported. Here we describe the synthesis and study the antiangiogenic activity in vitro of a series of XN derivatives, where different substituents on the B-ring of the chalcone scaffold were inserted. The new XN derivatives inhibited human umbilical-vein endothelial cell (HUVEC) proliferation, adhesion, migration, invasion and their ability to form capillary-like structures in vitro at 10 μM concentration. The preliminary results indicate that the phenolic OH group in R, present in natural XN, is not necessary for having antiangiogenic activity. In fact, the most effective compound from this series, 13, was characterized by a para-methoxy group in R and a fluorine atom in R 2 on B-ring. This study paves the way for future development of synthetic analogues of XN to be used as cancer angiopreventive and chemopreventive agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Origin of background electron concentration in In xGa 1-xN alloys

    DOE PAGES

    Pantha, B. N.; Wang, H.; Khan, N.; ...

    2011-08-15

    The origin of high background electron concentration (n) in In xGa 1-xN alloys has been investigated. A shallow donor was identified as having an energy level (E D1) that decreases with x (E D1 = 16 meV at x = 0 and E D1 = 0 eV at x ~ 0.5) and that crossover the conduction band at x ~ 0.5. This shallow donor is believed to be the most probable cause of high n in InGaN. This understanding is consistent with the fact that n increases sharply with an increase in x and becomes constant for x > 0.5.more » A continuous reduction in n was obtained by increasing the V/III ratio during the epilayer growth, suggesting that nitrogen vacancy-related impurities are a potential cause of the shallow donors and high background electron concentration in InGaN« less

  4. Structural studies of 4-aminoantipyrine derivatives

    NASA Astrophysics Data System (ADS)

    Cunha, Silvio; Oliveira, Shana M.; Rodrigues, Manoel T.; Bastos, Rodrigo M.; Ferrari, Jailton; de Oliveira, Cecília M. A.; Kato, Lucília; Napolitano, Hamilton B.; Vencato, Ivo; Lariucci, Carlito

    2005-10-01

    Reaction of 4-aminoantipyrine with acetylacetone, ethyl acetoacetate, benzoyl isothiocyanate, phenyl isothiocyanate, maleic anhydride and methoxymethylene Meldrum's acid afforded a series of new antipyrine derivatives. The antibacterial activity of the synthesized compounds against Micrococcus luteus ATCC 9341, Staphilococcus aureus ATCC 29737, and Escherichia coli ATCC 8739 was evaluated and the minimal inhibitory concentration determined. Modest activity was found only to the maleamic acid obtained from the reaction of 4-aminoantipyrine and maleic anhydride. 1H NMR investigation of this maleamic acid showed that it is slowly converted to the corresponding toxic maleimide. The structures of three derivatives were determined by X-ray diffraction analysis.

  5. KSC-05PD-0502B

    NASA Technical Reports Server (NTRS)

    2005-01-01

    KENNEDY SPACE CENTER, FLA. At Astrotech in Titusville, Fla., Boeing technicians hold guide wires attached to the crane lifting the GOES-N satellite. Since its arrival on March 11, the satellite has been undergoing final testing by Boeing Satellite Systems of the imaging system, instrumentation, communications and power systems. Geostationary Operational Environmental Satellites (GOES) are sponsored by NASAs Goddard Space Flight Center and the National Oceanic and Atmospheric Administration. GOES-N is targeted to launch May 4 onboard a Boeing expendable launch vehicle Delta IV (4,2) with a 3-burn second stage operation.

  6. New approach to description of (d,xn) spectra at energies below 50 MeV in Monte Carlo simulation by intra-nuclear cascade code with Distorted Wave Born Approximation

    NASA Astrophysics Data System (ADS)

    Hashimoto, S.; Iwamoto, Y.; Sato, T.; Niita, K.; Boudard, A.; Cugnon, J.; David, J.-C.; Leray, S.; Mancusi, D.

    2014-08-01

    A new approach to describing neutron spectra of deuteron-induced reactions in the Monte Carlo simulation for particle transport has been developed by combining the Intra-Nuclear Cascade of Liège (INCL) and the Distorted Wave Born Approximation (DWBA) calculation. We incorporated this combined method into the Particle and Heavy Ion Transport code System (PHITS) and applied it to estimate (d,xn) spectra on natLi, 9Be, and natC targets at incident energies ranging from 10 to 40 MeV. Double differential cross sections obtained by INCL and DWBA successfully reproduced broad peaks and discrete peaks, respectively, at the same energies as those observed in experimental data. Furthermore, an excellent agreement was observed between experimental data and PHITS-derived results using the combined method in thick target neutron yields over a wide range of neutron emission angles in the reactions. We also applied the new method to estimate (d,xp) spectra in the reactions, and discussed the validity for the proton emission spectra.

  7. Fragmented red cells reference range (Sysmex XN(®) automated blood cell counter).

    PubMed

    Lesesve, Jean-François; Daigney, Amandine; Henry, Sylvain; Speyer, Elodie

    2015-01-01

    Fragmented red cells (FRCs) is a new parameter automatedly determined by recent blood cell counters. Their count might be of interest because FRCs are supposed to reflect schistocytes counts measured on a stained peripheral blood smear observed under the microscope. But FRCs depend from the technical procedure used to detect them and thus reference ranges are device-dependent. The XN-9000(®) is one of the last model from Sysmex series. We aimed to establish reference range for FRCs, from 2389 controls. The mean ± SD was 0.32% ± 0.81, the median 0.02% (95% confidence interval ot the mean: 0.29-0.35%). We observed that the percentage of red blood cells with less than 17 pg of hemoglobin content (Hypo-He) was correlated to FRC increase, Hypo-He increase resulting in spurious FRCs majoration. FRCs reference range should be useful for: 1) laboratory staff in order to select which blood smears to check optically; 2) Sysmex company to set-up more optimal rules proposed with the counter (automated making of blood smear).

  8. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED... Exchange Act of 1934 Exemption of Certain Transactions from Section 16(c) § 240.16c-4 Derivative securities...

  9. KSC-00pp0502

    NASA Image and Video Library

    2000-04-13

    At Launch Pad 39A, Greg Lohning, who is with NASA, inspects the wiring on the newly installed Power Drive Unit (PDU) in Space Shuttle Atlantis. The PDU controls the rudder/speed brake on the orbiter. Atlantis is scheduled to lift off April 24 at 4:15 p.m. EDT on mission STS-101, the third flight to the International Space Station. The primary mission is to carry logistics and supplies to the Space Station, plus the crew will be preparing the Station for the arrival of the Zvezda Service Module, expected to be launched by Russia in July 2000

  10. A flight investigation of the effect of mass distribution and control setting on the spinning of the XN2Y-1 airplane

    NASA Technical Reports Server (NTRS)

    Scudder, N F

    1935-01-01

    The investigation of the effect of mass distribution on the spinning of airplanes initiated with tests on the NY-1 airplane has been continued by tests on another airplane in order to increase the scope of the information and to observe particularly the behavior of an airplane that shows considerable change in sideslip angle for its various conditions of spinning. The XN2Y-1 naval training biplane was used for the present tests in which changes of ballast along the longitudinal and lateral axes and changes of aileron, stabilizer, and elevator settings were made. The effects of these changes on the steady spin were measured in flight.

  11. Increased IL-2 production in T cells by xanthohumol through enhanced NF-AT and AP-1 activity.

    PubMed

    Choi, Jin Myung; Kim, Hyun Jung; Lee, Kwang Youl; Choi, Hyun Jin; Lee, Ik-Soo; Kang, Bok Yun

    2009-01-01

    Xanthohumol (XN) is a major chalcone found in hop, which is used to add bitterness and flavor to beer. In this study, we investigated the effects of XN on the production of interlukin-2 (IL-2), a potent T cell growth factor. Treatment with XN significantly increased IL-2 production in mouse EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io) in a dose-dependent manner. To further characterize its regulatory mechanism of XN on increased IL-2 production, the effects of XN on IL-2 promoter activity and the activity of several transcription factors modulating IL-2 expression were analyzed. XN enhanced activity of the IL-2 promoter, which contains distal and proximal regulatory elements in PMA/Io-activated EL-4 T cells. Furthermore, the activity of NF-AT and AP-1 was enhanced but NF-kappaB activity was not influenced by XN in PMA/Io-activated EL-4 T cells. These results suggest that XN increased IL-2 production at the transcriptional levels via the up-regulation of NF-AT and AP-1 in PMA/Io-activated EL-4 T cells.

  12. A Comparison of Mindray BC-6800, Sysmex XN-2000, and Beckman Coulter LH750 Automated Hematology Analyzers: A Pediatric Study.

    PubMed

    Ciepiela, Olga; Kotuła, Iwona; Kierat, Szymon; Sieczkowska, Sandra; Podsiadłowska, Anna; Jenczelewska, Anna; Księżarczyk, Karolina; Demkow, Urszula

    2016-11-01

    Modern automated laboratory hematology analyzers allow the measurement of over 30 different hematological parameters useful in the diagnostic and clinical interpretation of patient symptoms. They use different methods to measure the same parameters. Thus, a comparison of complete blood count made by Mindray BC-6800, Sysmex XN-2000 and Beckman Coulter LH750 was performed. A comparison of results obtained by automated analysis of 807 anticoagulated blood samples from children and 125 manual microscopic differentiations were performed. This comparative study included white blood cell count, red blood cell count, and erythrocyte indices, as well as platelet count. The present study showed a poor level of agreement between white blood cell enumeration and differentiation of the three automated hematology analyzers under comparison. A very good agreement was found when comparing manual blood smear and automated granulocytes, monocytes, and lymphocytes differentiation. Red blood cell evaluation showed better agreement than white blood cells between the studied analyzers. To conclude, studied instruments did not ensure satisfactory interchangeability and did not facilitate a substitution of one analyzer by another. © 2016 Wiley Periodicals, Inc.

  13. Al xGa 1-xN (0⩽ x⩽1) nanocrystalline powder by pyrolysis route

    NASA Astrophysics Data System (ADS)

    Garcia, R.; Srinivasan, S.; Contreras, O. E.; Thomas, A. C.; Ponce, F. A.

    2007-10-01

    A novel method to synthesize nanocrystalline Al xGa 1-xN (0⩽ x⩽1) powders is presented in this work. AlGaN nanocrystallites with the wurtzite structure were produced by thermal decomposition of a gallium-aluminum complex compound at 1000 °C in a three-zone horizontal quartz tube reactor under high-purity ammonia atmosphere. The crystallites showed a hexagonal structure, high homogeneity, and a narrow particle-size distribution at around 50 nm. A continuous composition range from 0 to 1 mol fraction can be reached by this method, allowing high control on the gallium and aluminum composition by monitoring the stoichiometry of the reaction between the metal nitrates and carbohydrazide. Low-temperature photoluminescence and cathodoluminescence studies showed that some impurities, such as carbon and oxygen, are unintentionally present in the final product and affect the optical properties. Subsequent thermal treatments between 900 and 1100 °C under an ammonia atmosphere significantly improved the quality of these materials.

  14. Attempt to Measure (n, xn) Double-Differential Cross Sections for Incident Neutron Energies above 100 MeV

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watanabe, T.; Kunieda, S.; Shigyo, N.

    The experimental technique for measurement of (n, xn) double differential cross sections for incident neutron energy above 100 MeV has been attempted to be developed with continuous-energy neutrons up to 400 MeV. Neutrons were produced in the spallation reaction by the 800 MeV proton beam, which was incident on a thick, heavily shielded tungsten target at the WNR facility at Los Alamos National Laboratory. The energies of incident neutrons were determined by the time-of-flight method. Emitted neutrons were detected by the recoil proton method. A phoswich detector consisting of NaI(Tl) and NE102A plastic scintillators was used for detecting recoil protons.more » We compared the preliminary experimental cross section data with the calculations by PHITS and QMD codes.« less

  15. Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety.

    PubMed

    Karrouchi, K; Chemlal, L; Taoufik, J; Cherrah, Y; Radi, S; El Abbes Faouzi, M; Ansar, M

    2016-11-01

    A series of Schiff bases of 4-amino-1,2,4-triazole derivatives containing pyrazole (5a-h) were synthesized from condensation of 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (3) derivative with various aromatic aldehydes (4a-h). The structures of the synthesized compounds were elucidated by IR, 1 H NMR, 13 C NMR, and mass spectrometry. All the synthesized compounds (5a-h) were screened for their in vivo analgesic and in vitro antioxidant activities revealing significant analgesic and antioxidant properties. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  16. Ternary mixed crystal effects on interface optical phonon and electron-phonon coupling in zinc-blende GaN/AlxGa1-xN spherical quantum dots

    NASA Astrophysics Data System (ADS)

    Huang, Wen Deng; Chen, Guang De; Yuan, Zhao Lin; Yang, Chuang Hua; Ye, Hong Gang; Wu, Ye Long

    2016-02-01

    The theoretical investigations of the interface optical phonons, electron-phonon couplings and its ternary mixed effects in zinc-blende spherical quantum dots are obtained by using the dielectric continuum model and modified random-element isodisplacement model. The features of dispersion curves, electron-phonon coupling strengths, and its ternary mixed effects for interface optical phonons in a single zinc-blende GaN/AlxGa1-xN spherical quantum dot are calculated and discussed in detail. The numerical results show that there are three branches of interface optical phonons. One branch exists in low frequency region; another two branches exist in high frequency region. The interface optical phonons with small quantum number l have more important contributions to the electron-phonon interactions. It is also found that ternary mixed effects have important influences on the interface optical phonon properties in a single zinc-blende GaN/AlxGa1-xN quantum dot. With the increase of Al component, the interface optical phonon frequencies appear linear changes, and the electron-phonon coupling strengths appear non-linear changes in high frequency region. But in low frequency region, the frequencies appear non-linear changes, and the electron-phonon coupling strengths appear linear changes.

  17. Pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazole derivatives as antifungal agents.

    PubMed

    Vicentini, Chiara Beatrice; Romagnoli, Carlo; Manfredini, Stefano; Rossi, Damiano; Mares, Donatella

    2011-05-01

    The diseases of plants and humans due to pathogenic fungi are increasing. Among the substances used to combat fungi, the azoles are of primary interest, both in agricultural field both in health. To avoid fungal resistance phenomena, the synthesis and tests of new derivatives are necessary. This article discusses the synthesis and the antifungal activity of pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazole derivatives against three fungi that are pathogenic only for plants and two fungi that are opportunistic in humans and plants. The compounds were prepared starting from 2-cyano-3-ethoxy-2-butenethioamide. The antifungal activity of the compounds was determined by measuring the inhibition of growth of the fungi tested at 20, 50, and 100 µg/mL in comparison with the controls. Results demonstrated that several compounds were able to control the mycelial growth of the tested fungi, even if they showed different sensitivity to the different azole-derivatives. In general Magnaporthe grisea (T.T. Hebert) Yaegashi & Udagawa was the most sensitive fungus, being blocked almost entirely by 4-chloro derivative even at 20 µg/mL, a concentration at which the reference commercial compound tricyclazole was nearly ineffective. These findings demonstrate that the pyrazolo[3,4-c]isothiazole derivatives have a wide spectrum of activity on phytopathogenic and opportunistic fungi. In particular the 4-chloro derivative seems to have a great potential as new product to combat M. grisea in the agricultural field.

  18. Phase degradation in BxGa1-xN films grown at low temperature by metalorganic vapor phase epitaxy

    NASA Astrophysics Data System (ADS)

    Gunning, Brendan P.; Moseley, Michael W.; Koleske, Daniel D.; Allerman, Andrew A.; Lee, Stephen R.

    2017-04-01

    Using metalorganic vapor phase epitaxy, a comprehensive study of BxGa1-xN growth on GaN and AlN templates is described. BGaN growth at high-temperature and high-pressure results in rough surfaces and poor boron incorporation efficiency, while growth at low-temperature and low-pressure (750-900 °C and 20 Torr) using nitrogen carrier gas results in improved surface morphology and boron incorporation up to 7.4% as determined by nuclear reaction analysis. However, further structural analysis by transmission electron microscopy and x-ray pole figures points to severe degradation of the high boron composition films, into a twinned cubic structure with a high density of stacking faults and little or no room temperature photoluminescence emission. Films with <1% triethylboron (TEB) flow show more intense, narrower x-ray diffraction peaks, near-band-edge photoluminescence emission at 362 nm, and primarily wurtzite-phase structure in the x-ray pole figures. For films with >1% TEB flow, the crystal structure becomes dominated by the cubic phase. Only when the TEB flow is zero (pure GaN), does the cubic phase entirely disappear from the x-ray pole figure, suggesting that under these growth conditions even very low boron compositions lead to mixed crystalline phases.

  19. Fabrication of Calix[4]arene Derivative Monolayers to Control Orientation of Antibody Immobilization

    PubMed Central

    Chen, Hongxia; Liu, Feng; Qi, Fangjie; Koh, Kwangnak; Wang, Keming

    2014-01-01

    Three calix[4]arene (Cal-4) derivatives which separately contain ethylester (1), carboxylic acid (2), and crownether (3) at the lower rim with a common reactive thiol at the upper rim were synthesized and constructed to self-assembled monolayers (SAMs) on Au films. After spectroscopic characterization of the monolayers, surface coverage and orientation of antibody immobilized on the Cal-4 derivative SAMs were studied by surface plasmon resonance (SPR) technique. Experimental results revealed that the antibody could be immobilized on the Cal-4 derivatives spontaneously. The orientation of absorbed antibody on the Cal-4 derivative SAMs is related to the SAM’s dipole moment. The possible orientations of the antibody immobilized on the Cal-4 derivative 1 SAM are lying-on or side-on, while on the Cal-4 derivative 2 and Cal-4 derivative 3 head-on and end-on respectively. These experimental results demonstrate the surface dipole moment of Cal-4 derivative appears to be an important factor to antibody orientation. Cal-4 derivatives are useful in developing site direct protein chips. PMID:24690993

  20. Isoxazole-type derivatives related to combretastatin A-4, synthesis and biological evaluation.

    PubMed

    Kaffy, Julia; Pontikis, Renée; Carrez, Danièle; Croisy, Alain; Monneret, Claude; Florent, Jean-Claude

    2006-06-15

    Novel combretastatin analogues bearing various five-membered heterocycles with consecutive oxygen and nitrogen atoms, in place of the olefinic bridge of CA4, have been synthesized (isoxazole, isoxazoline, oxadiazole, etc). These compounds have been evaluated for cytotoxicity and their ability to inhibit the tubulin assembly. On the basis of the relative position of the aromatic A- and B-rings on the heterocyclic moiety, they could be split in two classes, the alpha,gamma- or alpha,beta-diaryl heterocyclic derivatives. In the first series, the 3,5-diaryloxadiazole 9a displayed comparable antitubulin activity to that of CA4, but was devoid of cytotoxic effects. Among the alpha,beta-diaryl heterocyclic derivatives, the 4,5-diarylisoxazole 35 exhibited greater antitubulin activity than that of CA4 (0.75 vs 1.2 microM), but modest antiproliferative activity. These data showed that minor alteration in the chemical structure of the heterocyclic ring and its relative orientation with regard to the two phenyl rings of CA4 could dramatically influence the tubulin binding properties.

  1. Pharmacogenetics in American Indian populations: analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai Tribes.

    PubMed

    Fohner, Alison; Muzquiz, LeeAnna I; Austin, Melissa A; Gaedigk, Andrea; Gordon, Adam; Thornton, Timothy; Rieder, Mark J; Pershouse, Mark A; Putnam, Elizabeth A; Howlett, Kevin; Beatty, Patrick; Thummel, Kenneth E; Woodahl, Erica L

    2013-08-01

    Cytochrome P450 enzymes play a dominant role in drug elimination and variation in these genes is a major source of interindividual differences in drug response. Little is known, however, about pharmacogenetic variation in American Indian and Alaska Native (AI/AN) populations. We have developed a partnership with the Confederated Salish and Kootenai Tribes (CSKT) in northwestern Montana to address this knowledge gap. We resequenced CYP2D6 in 187 CSKT individuals and CYP3A4, CYP3A5, and CYP2C9 in 94 CSKT individuals. We identified 67 variants in CYP2D6, 15 in CYP3A4, 10 in CYP3A5, and 41 in CYP2C9. The most common CYP2D6 alleles were CYP2D6*4 and *41 (20.86 and 11.23%, respectively). CYP2D6*3, *5, *6, *9, *10, *17, *28, *33, *35, *49, *1xN, *2xN, and *4xN frequencies were less than 2%. CYP3A5*3, CYP3A4*1G, and *1B were detected with frequencies of 92.47, 26.81, and 2.20%, respectively. Allelic variation in CYP2C9 was low: CYP2C9*2 (5.17%) and *3 (2.69%). In general, allele frequencies in CYP2D6, CYP2C9, and CYP3A5 were similar to those observed in European Americans. There was, however, a marked divergence in CYP3A4 for the CYP3A4*1G allele. We also observed low levels of linkage between CYP3A4*1G and CYP3A5*1 in the CSKT. The combination of nonfunctional CYP3A5*3 and putative reduced function CYP3A4*1G alleles may predict diminished clearance of CYP3A substrates. These results highlight the importance of carrying out pharmacogenomic research in AI/AN populations and show that extrapolation from other populations is not appropriate. This information could help optimize drug therapy for the CSKT population.

  2. Pharmacogenetics in American Indian Populations: Analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai Tribes

    PubMed Central

    Fohner, Alison; Muzquiz, LeeAnna I.; Austin, Melissa A.; Gaedigk, Andrea; Gordon, Adam; Thornton, Timothy; Rieder, Mark J.; Pershouse, Mark A.; Putnam, Elizabeth A.; Howlett, Kevin; Beatty, Patrick; Thummel, Kenneth E.; Woodahl, Erica L.

    2014-01-01

    Objectives Cytochrome P450 enzymes play a dominant role in drug elimination and variation in these genes is a major source of interindividual differences in drug response. Little is known, however, about pharmacogenetic variation in American Indian and Alaska Native (AI/AN) populations. We have developed a partnership with the Confederated Salish and Kootenai Tribes (CSKT) in northwestern Montana to address this knowledge gap. Methods We resequenced CYP2D6 in 187 CSKT subjects and CYP3A4, CYP3A5, and CYP2C9 in 94 CSKT subjects. Results We identified 67 variants in CYP2D6, 15 in CYP3A4, 10 in CYP3A5, and 41 in CYP2C9. The most common CYP2D6 alleles were CYP2D6*4 and *41 (20.86 and 11.23%, respectively). CYP2D6*3, *5, *6, *9, *10, *17, *28, *33, *35, *49, *1xN, *2xN, and *4xN frequencies were less than 2%. CYP3A5*3, CYP3A4*1G, and *1B were detected with frequencies of 92.47, 26.81, and 2.20%, respectively. Allelic variation in CYP2C9 was low: CYP2C9*2 (5.17%) and *3 (2.69%). In general, allele frequencies in CYP2D6, CYP2C9 and CYP3A5 were similar to those observed in European Americans. There was, however, a marked divergence in CYP3A4 for the CYP3A4*1G allele. We also observed low levels of linkage between CYP3A4*1G and CYP3A5*1 in the CSKT. The combination of nonfunctional CYP3A5*3 and putative reduced function CYP3A4*1G alleles may predict diminished clearance of CYP3A substrates. Conclusions These results highlight the importance of conducting pharmacogenomic research in AI/AN populations and demonstrate that extrapolation from other populations is not appropriate. This information could help to optimize drug therapy for the CSKT population. PMID:23778323

  3. Valence, exchange interaction, and location of Mn ions in polycrystalline M nxG a1 -xN (x ≤0.04 )

    NASA Astrophysics Data System (ADS)

    Furrer, A.; Krämer, K. W.; Podlesnyak, A.; Pomjakushin, V.; Sheptyakov, D.; Safonova, O. V.

    2018-04-01

    We present an experimental study for polycrystalline samples of the diluted magnetic semiconductor M nxG a1 -xN (x ≤0.04 ) in order to address some of the existing controversial issues. X-ray and neutron diffraction, x-ray absorption near-edge structure, and electron paramagnetic resonance experiments were used to characterize the structural, electronic, and magnetic properties of the samples, and inelastic neutron scattering was employed to determine the magnetic excitations associated with Mn monomers and dimers. Our main conclusions are as follows: (i) The valence of the Mn ions is 2 + . (ii) The M n2 + ions experience a substantial single-ion axial anisotropy with parameter D =0.027 (3 )meV . (iii) Nearest-neighbor M n2 + ions are coupled antiferromagnetically. The exchange parameter J =-0.140 (7 )meV is independent of the Mn content x ; i.e., there is no evidence for hole-induced modifications of J towards a potentially high Curie temperature postulated in the literature.

  4. Synthesis of 4,19-disubstituted derivatives of DOC. Radioreceptor assay of some corticosteroid derivatives in human mononuclear leukocytes.

    PubMed

    Harnik, M; Kashman, Y; Cojocaru, M; Bauer, H; Laux, M; Lewicka, S; Vecsei, P

    1990-10-01

    Several new 4,19-substituted steroids and previously synthesized corticosteroids were assayed for affinity to type 1 receptors in human mononuclear leukocytes. 11 beta,19-epoxy-4,21-dihydroxypregn-4-ene-3,20-dione (2) was hydrogenated with Pd-C to yield a mixture of all four dihydro derivatives 5, accompanied by 4,21-diacetoxy-11 beta,19-epoxy-3-hydroxypregnan-20-one (6) and 21-acetoxy-11 beta,19-epoxy-4-hydroxypregnane-3,20-dione (7). With hot acetic + p-toluenesulfonic acid 5 underwent rearrangement to 21-acetoxy-11 beta,19-epoxypregn-5-ene-4,20-dione (8) Pd-C hydrogenation of 3,21-diacetoxy-5 beta,19-cyclopregna-2,9(11)-diene-4,20-dione (10) gave 3,21-diacetoxy-5 beta,19-cyclopregn-5-ene-4,20-dione (11) and the 9,11-dihydro derivative of the latter. Treatment of 10 with warm HCl furnished 19-chloro-4,21-dihydroxypregna-4,9(11)-diene-3,20-dione (13). Pd-C hydrogenation of its diacetate 14 afforded the 4,5-dihydro derivative 18, 19-chloro-21-acetoxypregn-9(11)-en-20-one (15), its 4-acetoxy derivative 16 and the 3,4-diacetoxy derivative 17. When tested in a radioreceptor assay in human mononuclear leukocytes the synthesized compounds showed only low relative binding affinities (RBA) to type 1 receptor, the highest being 0.72% for 13 (aldosterone = 100%). For comparison, other RBA in this system were: 19-noraldosterone, 20%; 18-deoxyaldosterone, 5.8%; 18-deoxy-19-noraldosterone, 4.7%; 18,21-anhydroaldosterone, 0.37%; 17-isoaldosterone, 7.6% and apoaldosterone, 4.3%

  5. Synthesis and in vitro cytotoxicity of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives.

    PubMed

    Chern, Jyh-Haur; Shia, Kak-Shan; Chang, Chung-Ming; Lee, Chung-Chi; Lee, Yen-Chun; Tai, Chia-Liang; Lin, Ying-Ting; Chang, Chih-Shiang; Tseng, Huan-Yi

    2004-03-08

    A series of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives were synthesized and their anticancer cytotoxicity were evaluated in in vitro assay. It was found that the bulky aryl functionality in the 5-position of the 2-cyanoimino-4-imidazolidinone compounds was essential for the cytotoxicity of these heterocyclic compounds. Some of the derivatives exhibited modest cytotoxicity against a variety of cancer cell lines. One of the derivatives, [1-[6-(4-chlorophenoxy)hexyl]-5-oxo-4-phenyl-3-(4-pyridyl)tetrahydro-1H-2-imidazolyliden]aminomethanenitrile (Compound 11), exhibited the most potent cytotoxic activity with IC(50) in the nanomolar range. The cytotoxicity of these derivatives was selection with no apparent toxic effect toward normal fibroblasts.

  6. Antitrypanosomal and antioxidant properties of 4-hydroxycoumarins derivatives.

    PubMed

    Pérez-Cruz, Fernanda; Serra, Silvia; Delogu, Giovanna; Lapier, Michel; Maya, Juan Diego; Olea-Azar, Claudio; Santana, Lourdes; Uriarte, Eugenio

    2012-09-01

    In the present communication we prepared a series of six 4-hydroxycoumarin derivatives, isosters of quercetin, recognized as an antioxidant natural compound, with the aim of evaluating the antitrypanosomal activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, and the antioxidant properties. We have used the 4-hydroxycoumarin moiety (compound 1) as the molecular template for the synthesis of compounds 2-7. These derivates have shown moderate trypanocidal activity. However they have been proved to be good antioxidants. In particular compound 7 is the most active antioxidant and it is, therefore, a potential candidate for a successful employment in conditions characterized by free radicals overproduction. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Full-scale characterization of UVLED Al(x)Ga(1-x)N nanowires via advanced electron microscopy.

    PubMed

    Phillips, Patrick J; Carnevale, Santino D; Kumar, Rajan; Myers, Roberto C; Klie, Robert F

    2013-06-25

    III-Nitride semiconductor heterostructures continue to attract a great deal of attention due to the wide range of wavelengths at which they can emit light, and the subsequent desire to employ them in optoelectronic applications. Recently, a new type of pn-junction which relies on polarization-induced doping has shown promise for use as an ultraviolet light emitting diode (UVLED); nanowire growth of this device has been successfully demonstrated. However, as these devices are still in their infancy, in order to more fully understand their physical and electronic properties, they require a multitude of characterization techniques. Specifically, the present contribution will discuss the application of advanced scanning transmission electron microscopy (STEM) to AlxGa1-xN UVLED nanowires. In addition to structural data, chemical and electronic properties will also be probed through various spectroscopy techniques, with the focus remaining on practically applying the knowledge gained via STEM to the growth procedures in order to optimize device peformance.

  8. A Thermodynamic Model to Estimate the Formation of Complex Nitrides of Al x Mg(1- x)N in Silicon Steel

    NASA Astrophysics Data System (ADS)

    Luo, Yan; Zhang, Lifeng; Li, Ming; Sridhar, Seetharaman

    2018-06-01

    A complex nitride of Al x Mg(1- x)N was observed in silicon steels. A thermodynamic model was developed to predict the ferrite/nitride equilibrium in the Fe-Al-Mg-N alloy system, using published binary solubility products for stoichiometric phases. The model was used to estimate the solubility product of nitride compound, equilibrium ferrite, and nitride compositions, and the amounts of each phase, as a function of steel composition and temperature. In the current model, the molar ratio Al/(Al + Mg) in the complex nitride was great due to the low dissolved magnesium in steel. For a steel containing 0.52 wt pct Als, 10 ppm T.Mg., and 20 ppm T.N. at 1100 K (827 °C), the complex nitride was expressed by Al0.99496Mg0.00504N and the solubility product of this complex nitride was 2.95 × 10-7. In addition, the solution temperature of the complex nitride increased with increasing the nitrogen and aluminum in steel. The good agreement between the prediction and the detected precipitate compositions validated the current model.

  9. Xerostomia: a day and night difference.

    PubMed

    Dijkema, Tim; Raaijmakers, Cornelis P J; Braam, Pètra M; Roesink, Judith M; Monninkhof, Evelyn M; Terhaard, Chris H J

    2012-08-01

    To compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT. A cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6 weeks, 6 months and 1 year after RT. No attempt was made to spare the submandibular gland(s). The XQ contained specific questions concerning the sensation of dry mouth during day- (XD) and nighttime (XN), scored on a 5-point Likert scale. Patients with no or mild (grade 1-3) xerostomia and patients with more severe (grade 4-5) complaints were grouped together. Before RT, no association existed between dry mouth complaints and PF or SMF. At 6 weeks, 6 months and 1 year after RT; 37%, 51% and 36% had grade 4-5 XD and 65%, 64% and 56% had grade 4-5 XN, respectively. Patients with grade 4-5 XD and XN had significantly worse SMF at all time points after RT compared to patients with grade 1-3 XD and XN, while PF was significantly worse only at 6 weeks after RT. In multivariate analyses, SMF was consistently the most important factor related to XN after treatment. PF significantly influenced XD at 6 weeks and 1 year after RT. Differentiating between complaints during day- and nighttime in xerostomia research is necessary. Dry mouth at night is a frequent problem after (parotid-sparing) RT for HNC and is explained by submandibular gland dysfunction. Sparing of the contralateral submandibular gland, in addition to parotid gland sparing, may result in improved patient-reported xerostomia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Photovoltaic conversion efficiency of InN/InxGa1-xN quantum dot intermediate band solar cells

    NASA Astrophysics Data System (ADS)

    Ben Afkir, N.; Feddi, E.; Dujardin, F.; Zazoui, M.; Meziane, J.

    2018-04-01

    The behavior of InN/InxGa1-xN spherical quantum dots solar cell is investigated, considering the internal electric field induced by the polarization of the junction. In order to determine the position of the intermediate band (IB), we present an efficient numerical technique based on difference finite method to solve the 3D time-independent Schrödinger's equation in spherical coordinates. The resultant n × n Hamiltonian matrix when considering n discrete points in spatial direction is diagonalized in order to calculate energy levels. Thus, the interband and intersubband transitions are determined, taking into consideration the effect of the internal electric field, size dots, interdot distances, and indium content on the energy levels, optical transition, photo-generated current density, open-circuit voltage and power conversion efficiency of the QD-IBSCs.

  11. Synthesis of ( 2S, 4S)-4-phenylamino-5-oxoproline derivatives.

    PubMed

    Nizova, I A; Krasnov, V P; Levit, G L; Kodess, M I

    2002-01-01

    The paper describes the synthesis of ( 2S, 4S)-4-(N-Ts)- and ( 2S, 4S)-4-(N-Boc)-phenylamino-5-oxoprolines (pyroglutamic acid). These derivatives have been shown to be useful for synthesis of their amides and peptides in spite of steric hindrances caused by bulky groups adjacent to the reaction centre. Under the conditions applied no lactam ring opening and no loss of stereochemical integrity of any of the chiral centres were observed, which has been confirmed by NMR techniques.

  12. Radiation-induced segregation at grain boundaries in AL-6XN stainless steels irradiated by hydrogen ions

    NASA Astrophysics Data System (ADS)

    Long, Yunxiang; Zheng, Zhongcheng; Guo, Liping; Zhang, Weiping; Shen, Zhenyu; Tang, Rui

    2018-04-01

    The effect of high concentration of hydrogen on the segregation of radiation-induced segregation (RIS) in AL-6XN stainless steels has been investigated by transmission electron microscopy (TEM) with energy-dispersive X-ray spectroscopy. Specimens were irradiated with 100 keV H2+ ions from 1 dpa to 5 dpa at 380 °C to investigated the dose dependence of grain boundary RIS. A specimen was irradiated to 5 dpa at 290 °C to study the effect of irradiation temperature. The trends of Cr depletion and Ni enrichment with irradiation dose is similar to that of other austenitic steels reported in the literatures, but the higher concentration of hydrogen made the RIS profile wider. An abnormal phenomenon that the degree of RIS increased with decreasing irradiation temperature was found, indicating that with the retention of hydrogen in the steels, temperature dependence of RIS is dominated by the quantity of retained hydrogen, rather than by thermal segregation processes.

  13. Insights into Interfacial Changes and Photoelectrochemical Stability of In(x)Ga(1-x)N (0001) Photoanode Surfaces in Liquid Environments.

    PubMed

    Caccamo, Lorenzo; Cocco, Giulio; Martín, Gemma; Zhou, Hao; Fundling, Sönke; Gad, Alaaeldin; Mohajerani, Matin Sadat; Abdelfatah, Mahmoud; Estradé, Sonia; Peiró, Francesca; Dziony, Wanja; Bremers, Heiko; Hangleiter, Andreas; Mayrhofer, Leonhard; Lilienkamp, Gerhard; Moseler, Michael; Daum, Winfried; Waag, Andreas

    2016-03-01

    The long-term stability of InGaN photoanodes in liquid environments is an essential requirement for their use in photoelectrochemistry. In this paper, we investigate the relationships between the compositional changes at the surface of n-type In(x)Ga(1-x)N (x ∼ 0.10) and its photoelectrochemical stability in phosphate buffer solutions with pH 7.4 and 11.3. Surface analyses reveal that InGaN undergoes oxidation under photoelectrochemical operation conditions (i.e., under solar light illumination and constant bias of 0.5 VRHE), forming a thin amorphous oxide layer having a pH-dependent chemical composition. We found that the formed oxide is mainly composed of Ga-O bonds at pH 7.4, whereas at pH 11.3 the In-O bonds are dominant. The photoelectrical properties of InGaN photoanodes are intimately related to the chemical composition of their surface oxides. For instance, after the formation of the oxide layer (mainly Ga-O bonds) at pH 7.4, no photocurrent flow was observed, whereas the oxide layer (mainly In-O bonds) at pH 11.3 contributes to enhance the photocurrent, possibly because of its reported high photocatalytic activity. Once a critical oxide thickness was reached, especially at pH 7.4, no significant changes in the photoelectrical properties were observed for the rest of the test duration. This study provides new insights into the oxidation processes occurring at the InGaN/liquid interface, which can be exploited to improve InGaN stability and enhance photoanode performance for biosensing and water-splitting applications.

  14. THE SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF SOME 4-HYDROXYCOUMARIN DERIVATIVES

    PubMed Central

    Završnik, Davorka; Muratović, Samija; Špirtović, Selma; Softić, Dženita; Medić-Šarić, Marica

    2008-01-01

    Due to exceptional reactivity of 4-hydroxycoumarin, the synthesis of new coumarin derivatives of dimer and tetramer type has been carried out. The synthesis was carried out from 4-hydroxycoumarin and various aromatic aldehydes. In this way, compounds of the dimer 3,3’-(benzilidene)bis (4-hydroxycoumarin) type, as well as of the tetramer 3,3,’3’,’3’’’-(1,4-dim- ethylenphenyl)tetra (4-hydroxycoumarin) type were prepared. The newly synthesized derivatives contain different functional groups, and as such they could exhibit microbiological activity. Therefore, we tested the microbiological activity of these derivatives on various species of bacteria and fungi. The tested compounds have shown different activity in terms of growth inhibition of microorganisms. Newly synthesized derivatives exhibit antibacterial activities, manifested as growth inhibition on Grampositive bacteria types (Bacillus, Staphylococcus), while the activity against Candida was much weaker. The same compound did not show any antimicrobial activity against two Gram-negative bacteria types (Escherichia coli, Pseudomonas aeruginosa). The compound 1 showed the best microbiological activity. The obtained results confirmed its good antibacterial and antimycotic activities against different microorganisms. PMID:18816263

  15. Synthesis and antitumour activity of 4-aminoquinazoline derivatives

    NASA Astrophysics Data System (ADS)

    Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

    2016-07-01

    Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

  16. Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest

    PubMed Central

    Tarade, Daniel; Ma, Dennis; Pignanelli, Christopher; Mansour, Fadi; Simard, Daniel; van den Berg, Sean; Gauld, James; McNulty, James; Pandey, Siyaram

    2017-01-01

    The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents. PMID:28253265

  17. Antileishmanial activity study and theoretical calculations for 4-amino-1,2,4-triazole derivatives

    NASA Astrophysics Data System (ADS)

    Süleymanoğlu, Nevin; Ünver, Yasemin; Ustabaş, Reşat; Direkel, Şahin; Alpaslan, Gökhan

    2017-09-01

    4-amino-1,2,4-triazole derivatives; 4-amino-1-((5-mercapto-1,3,4-oxadiazole-2-yl)methyl)-3-(thiophene-2-ylmethyl)-1H-1,2,4-triazole-5(4H)-one (1) and 4-amino-1-((4-amino-5 mercapto-4H-1,2,4-triazole-3-yl)methyl)-3-(thiophene-2-ylmethyl)-1H-1,2,4-triazole-5(4H)-one (2) were studied theoretically by Density Functional Theory (DFT) method with 6-311++G(d,p) basis set, structural and some spectroscopic parameters were determined. Significant differences between the experimental and calculated values of vibrational frequencies and chemical shifts were explained by the presence of intermolecular (Ssbnd H⋯O and Ssbnd H⋯N type) hydrogen bonds in structures. The Molecular Electrostatic Potential (MEP) maps obtained at B3LYP/6-311G++(d,p) support the existence of hydrogen bonds. Compounds were tested against to Leishmania infantum promastigots by microdilution broth assay with Alamar Blue Dye. Antileishmanial activity of 4-amino-1,2,4-triazole derivative (2) is remarkable.

  18. Facile synthesis, structural elucidation and spectral analysis of pyrrole 4-imidazole derivatives

    NASA Astrophysics Data System (ADS)

    Singh, R. N.; Rawat, Poonam; Baboo, Vikas

    2015-12-01

    In this work pyrrole 4-imidazole derivatives (3A-3D): benzimidazoles and pyrrole 4-imidazoline have been synthesized by condensation, cyclization and oxidation of ethyl 4-formyl-3,5-dimethyl-1H-pyrrole carboxylate and phenylene diamine derivatives/ethylene diamine. The structure of these biheterocyclic compounds have been derived by elemental and spectroscopic - IR, UV, MS, 1H and 13C NMR analysis as well as theoretical study. The static first hyperpolarizability, β0 values for pyrrole 4-imidazole derivatives, (3A-3D) have been calculated as 10.901 × 10-31, 19.607 × 10-31, 40.323 × 10-31, 5.686 × 10-31 esu, respectively. The gradual increase in β0 value of synthesized pyrrole-benzimidazole derivatives from 3A to 3C is due to addition of acceptors -Cl atom in 3B to -NO2 group in 3C on benzimidazole side. The experimental absorption spectra found to be in UV region and the high β0 values show that the synthesized pyrrole-imidazoles are suitable as non-linear optical (NLO) materials.

  19. Rice Protein Matrix Enhances Circulating Levels of Xanthohumol Following Acute Oral Intake of Spent Hops in Humans.

    PubMed

    O'Connor, Annalouise; Konda, Veera; Reed, Ralph L; Christensen, J Mark; Stevens, Jan F; Contractor, Nikhat

    2018-03-01

    Xanthohumol (XN), a prenylated flavonoid found in hops, exhibits anti-inflammatory and antioxidant properties. However, poor bioavailability may limit therapeutic applications. As food components are known to modulate polyphenol absorption, the objective is to determine whether a protein matrix could enhance the bioavailability of XN post oral consumption in humans. This is a randomized, double-blind, crossover study in healthy participants (n = 6) evaluating XN and its major metabolites (isoxanthohumol [IX], 6- and 8-prenylnaringenin [6-PN, 8-PN]) for 6 h following consumption of 12.4 mg of XN delivered via a spent hops-rice protein matrix preparation or a control spent hops preparation. Plasma XN and metabolites are measured by LC-MS/MS. C max , T max , and area-under-the-curve (AUC) values were determined. Circulating XN and metabolite response to each treatment was not bioequivalent. Plasma concentrations of XN and XN + metabolites (AUC) are greater with consumption of the spent hops-rice protein matrix preparation. Compared to a standard spent hops powder, a protein-rich spent hops matrix demonstrates enhanced plasma levels of XN and metabolites following acute oral intake. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Phase stability tuning in the NbxZr1-xN thin-film system for large stacking fault density and enhanced mechanical strength

    NASA Astrophysics Data System (ADS)

    Joelsson, T.; Hultman, L.; Hugosson, H. W.; Molina-Aldareguia, J. M.

    2005-03-01

    The phase stability of hexagonal WC-structure and cubic NaCl-structure 4d transition metal nitrides was calculated using first-principles density functional theory. It is predicted that there is a multiphase or polytypic region for the 4d transition metal nitrides with a valence electron concentration around 9.5 to 9.7 per formula unit. For verification, epitaxial NbxZr1-xN (0⩽x⩽1) was grown by reactive magnetron sputter deposition on MgO(001) substrates and analyzed with transmission electron microscopy (TEM) and x-ray diffraction. The defects observed in the films were threading dislocations due to nucleation and growth on the lattice-mismatched substrate and planar defects (stacking faults) parallel to the substrate surface. The highest defect density was found at the x =0.5 composition. The nanoindentation hardness of the films varied between 21GPa for the binary nitrides, and 26GPa for Nb0.5Zr0.5N. Unlike the cubic binary nitrides, no slip on the preferred ⟨11¯0⟩{110} slip system was observed. The increase in hardness is attributed to the increase in defect density at x =0.5, as the defects act as obstacles for dislocation glide during deformation. The findings present routes for the design of wear-resistant nitride coatings by phase stability tuning.

  1. Comparison of five automated hematology analyzers in a university hospital setting: Abbott Cell-Dyn Sapphire, Beckman Coulter DxH 800, Siemens Advia 2120i, Sysmex XE-5000, and Sysmex XN-2000.

    PubMed

    Bruegel, Mathias; Nagel, Dorothea; Funk, Manuela; Fuhrmann, Petra; Zander, Johannes; Teupser, Daniel

    2015-06-01

    Various types of automated hematology analyzers are used in clinical laboratories. Here, we performed a side-by-side comparison of five current top of the range routine hematology analyzers in the setting of a university hospital central laboratory. Complete blood counts (CBC), differentials, reticulocyte and nucleated red blood cell (NRBC) counts of 349 patient samples, randomly taken out of routine diagnostics, were analyzed with Cell-Dyn Sapphire (Abbott), DxH 800 (Beckman Coulter), Advia 2120i (Siemens), XE-5000 and XN-2000 (Sysmex). Inter-instrument comparison of CBCs including reticulocyte and NRBC counts and investigation of flagging quality in relation to microscopy were performed with the complete set of samples. Inter-instrument comparison of five-part differential was performed using samples without atypical cells in blood smear (n=292). Automated five-part differentials and NRBCs were additionally compared with microscopy. The five analyzers showed a good concordance for basic blood count parameters. Correlations between instruments were less well for reticulocyte counts, NRBCs, and differentials. The poorest concordance for NRBCs with microscopy was observed for Advia 2120i (Kendall's τb=0.37). The highest flagging sensitivity for blasts was observed for XN-2000 (97% compared to 65%-76% for other analyzers), whereas overall specificity was comparable between different instruments. To the best of our knowledge, this is the most comprehensive side-by-side comparison of five current top of the range routine hematology analyzers. Variable analyzer quality and parameter specific limitations must be considered in defining laboratory algorithms in clinical practice.

  2. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  3. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  4. 17 CFR 240.16c-4 - Derivative securities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Derivative securities. 240.16c-4 Section 240.16c-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  5. Formation of Ge nanoparticles in SiO xN y by ion implantation and thermal annealing

    DOE PAGES

    Mirzaei, Sahar; Kremer, F.; Sprouster, D. J.; ...

    2015-10-20

    Germanium nanoparticles embedded within dielectric matrices hold much promise for applications in optoelectronic and electronic devices. Here we investigate the formation of Ge nanoparticles in amorphous SiO 1.67N 0.14 as a function of implanted atom concentration and thermal annealing temperature. Using x-ray absorption spectroscopy and other complementary techniques, we show Ge nanoparticles exhibit significant finite-size effects such that the coordination number decreases and structural disorder increases as the nanoparticle size decreases. While the composition of SiO 1.67N 0.14 is close to that of SiO 2, we demonstrate that the addition of this small fraction of N yields a much reducedmore » nanoparticle size relative to those formed in SiO 2 under comparable implantation and annealing conditions. We attribute this difference to an increase in an atomic density and a much reduced diffusivity of Ge in the oxynitride matrix. Finally, these results demonstrate the potential for tailoring Ge nanoparticle sizes and structural properties in the SiO xN y matrices by controlling the oxynitride stoichiometry.« less

  6. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-methoxybenzene] derivatives. 721.1300 Section 721.1300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.1300 [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives... identified generically as [(dinitrophenyl)azo]-[2,4-di-a-mino-5-methoxybenzene] derivatives (P-83-817 and P...

  7. Birkhoffian symplectic algorithms derived from Hamiltonian symplectic algorithms

    NASA Astrophysics Data System (ADS)

    Xin-Lei, Kong; Hui-Bin, Wu; Feng-Xiang, Mei

    2016-01-01

    In this paper, we focus on the construction of structure preserving algorithms for Birkhoffian systems, based on existing symplectic schemes for the Hamiltonian equations. The key of the method is to seek an invertible transformation which drives the Birkhoffian equations reduce to the Hamiltonian equations. When there exists such a transformation, applying the corresponding inverse map to symplectic discretization of the Hamiltonian equations, then resulting difference schemes are verified to be Birkhoffian symplectic for the original Birkhoffian equations. To illustrate the operation process of the method, we construct several desirable algorithms for the linear damped oscillator and the single pendulum with linear dissipation respectively. All of them exhibit excellent numerical behavior, especially in preserving conserved quantities. Project supported by the National Natural Science Foundation of China (Grant No. 11272050), the Excellent Young Teachers Program of North China University of Technology (Grant No. XN132), and the Construction Plan for Innovative Research Team of North China University of Technology (Grant No. XN129).

  8. A semi-automatic microextraction in packed sorbent, using a digitally controlled syringe, combined with ultra-high pressure liquid chromatography as a new and ultra-fast approach for the determination of prenylflavonoids in beers.

    PubMed

    Gonçalves, João L; Alves, Vera L; Rodrigues, Fátima P; Figueira, José A; Câmara, José S

    2013-08-23

    In this work a highly selective and sensitive analytical procedure based on semi-automatic microextraction by packed sorbents (MEPS) technique, using a new digitally controlled syringe (eVol(®)) combined with ultra-high pressure liquid chromatography (UHPLC), is proposed to determine the prenylated chalcone derived from the hop (Humulus lupulus L.), xanthohumol (XN), and its isomeric flavonone isoxanthohumol (IXN) in beers. Extraction and UHPLC parameters were accurately optimized to achieve the highest recoveries and to enhance the analytical characteristics of the method. Important parameters affecting MEPS performance, namely the type of sorbent material (C2, C8, C18, SIL, and M1), elution solvent system, number of extraction cycles (extract-discard), sample volume, elution volume, and sample pH, were evaluated. The optimal experimental conditions involves the loading of 500μL of sample through a C18 sorbent in a MEPS syringe placed in the semi-automatic eVol(®) syringe followed by elution using 250μL of acetonitrile (ACN) in a 10 extractions cycle (about 5min for the entire sample preparation step). The obtained extract is directly analyzed in the UHPLC system using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and ACN (eluent B) in the gradient elution mode (10min total analysis). Under optimized conditions good results were obtained in terms of linearity within the established concentration range with correlation coefficients (R) values higher than 0.986, with a residual deviation for each calibration point below 12%. The limit of detection (LOD) and limit of quantification (LOQ) obtained were 0.4ngmL(-1) and 1.0ngmL(-1) for IXN, and 0.9ngmL(-1) and 3.0ngmL(-1) for XN, respectively. Precision was lower than 4.6% for IXN and 8.4% for XN. Typical recoveries ranged between 67.1% and 99.3% for IXN and between 74.2% and 99.9% for XN, with relative standard deviations %RSD no larger than 8%. The applicability of the proposed analytical

  9. High internal quantum efficiency ultraviolet to green luminescence peaks from pseudomorphic m-plane Al{sub 1−x}In{sub x}N epilayers grown on a low defect density m-plane freestanding GaN substrate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chichibu, S. F., E-mail: chichibulab@yahoo.co.jp; Hazu, K.; Furusawa, K.

    2014-12-07

    Structural and optical qualities of half-a-μm-thick m-plane Al{sub 1−x}In{sub x}N epilayers grown by metalorganic vapor phase epitaxy were remarkably improved via coherent growth on a low defect density m-plane freestanding GaN substrate prepared by hydride vapor phase epitaxy. All the epilayers unexceptionally suffer from uniaxial or biaxial anisotropic in-plane stress. However, full-width at half-maximum values of the x-ray ω-rocking curves were nearly unchanged as the underlayer values being 80 ∼ 150 arc sec for (101{sup ¯}0) and (101{sup ¯}2) diffractions with both 〈0001〉 and 〈112{sup ¯}0〉 azimuths, as long as pseudomorphic structure was maintained. Such Al{sub 1−x}In{sub x}N epilayers commonly exhibited a broadmore » but predominant luminescence peak in ultraviolet (x ≤ 0.14) to green (x = 0.30) wavelengths. Its equivalent value of the internal quantum efficiency at room temperature was as high as 67% for x = 0.14 and 44% for x = 0.30. Because its high-energy cutoff commonly converged with the bandgap energy, the emission peak is assigned to originate from the extended near-band-edge states with strong carrier localization.« less

  10. Structural & oxidation behavior of TiN & AlxTi1-xN coatings deposited by CA-PVD technique

    NASA Astrophysics Data System (ADS)

    Thorat, Nirmala; Mundotia, Rajesh; Varma, Ranjana; Kale, Ashwin; Mhatre, Umesh; Patel, Nainesh

    2018-04-01

    Coatings with thermal stability at elevated temperatures are prerequisite for various high speed machining and high temperature applications. The present work compares the oxidation behavior of the AlxTi1-xN coating prepared with different Al composition. Coated samples were tested at different temperatures in the range of 400 - 800 C to study their oxidation behavior. Percentage weight gain of all the samples were evaluated using high accuracy weighing balance. The depth of oxide layers were studied using Calo-test instrument. The XRD analysis was carried out to specify the phase structure. Higher oxidation rate was observed for TiN coating at all the oxidation temperatures. Oxidation rate was higher for Al13Ti87N and Al70Ti30N coatings compared to Al60Ti40N and Al50Ti50N coatings which exhibits better oxygen diffusion barrier at all the temperature.

  11. 14-Amino-4,5-Epoxymorphinan Derivatives and Their Pharmacological Actions

    NASA Astrophysics Data System (ADS)

    Lewis, John W.; Husbands, Stephen M.

    14-Hydroxy-7,8-dihydromorphinone (oxymorphone) and its derivatives (oxycodone, naloxone, naltrexone) have become among the most important clinical agents to have been produced from opium. 14-Aminocodeinone and its 7,8-dihydro and morphinone derivatives are of more recent origin thanks to the work of Professor Gordon Kirby and his collaborators. The 14-amino parent compounds have proved of limited interest but their 14-acylamino- and 14-alkylamino derivatives have been extensively studied. The 4'-substituted cinnamoylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones, C-CAM and M-CAM are the best available selective MOR irreversible antagonists and the related dihydrocodeinone MC-CAM, 4'-chlorocinnamoylamino-17-cyclopropylmethyl-7,8-dihydronorcodeinone, is a long-acting MOR partial agonist with extended MOR-pseudoirreversible antagonist activity that could be a candidate for pharmacotherapy of opiate abuse/dependence.

  12. 4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ku, Bo Mi; Ryu, Hyung Won; Lee, Yeon Kyung

    2010-11-19

    Research highlights: {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) has anti-cancer property for glioma. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) increased tropomyosin expreesion through activattion of PKA signaling. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) inhibits glioma cell migration and invasion. {yields} In vivo administration of 4'-acetoamido-4-hydroxychalcone (AHC) reduced tumor growth. -- Abstract: Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, andmore » tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.« less

  13. Biolabeling with 2,4-dichlorophenoxyacetic acid derivatives: the 2,4-D tag.

    PubMed

    Bade, Steffen; Röckendorf, Niels; Franek, Milan; Gorris, Hans H; Lindner, Buko; Olivier, Verena; Schaper, Klaus-Jürgen; Frey, Andreas

    2009-12-01

    Many bioanalytic and diagnostic procedures rely on labels with which the molecule of interest can be tracked in or discriminated from accompanying like substances. Herein, we describe a new labeling and detection system based on derivatives of 2,4-dichlorophenoxyacetic acid (2,4-D) and anti-2,4-D antibodies. The 2,4-D system is highly sensitive with a K(D) of 7 x 10(-11) M for the hapten-antibody pair, can be used on a large variety of biomolecules such as proteins, peptides, carbohydrates, and nucleic acids, is not hampered by endogenous backgrounds because 2,4-D is a xenobiotic, and is robust because 2,4-D is a very stable compound that withstands the conditions of most reactions usually performed on biomolecules. With this unique blend of properties, the 2,4-D system compares favorably with its rivals digoxigenin (DIG)/anti-DIG and biotin/(strept)avidin and provides an interesting and powerful tool in biomolecular labeling.

  14. 17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... derivatives clearing organization rules and clearing new products. 39.4 Section 39.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.4 Procedures for implementing derivatives clearing organization rules and clearing new products. (a) Request for approval of...

  15. Synthesis and Biological Evaluation of Some [1,2,4]Triazolo[4,3-a]quinoxaline Derivatives as Novel Anticonvulsant Agents

    PubMed Central

    Ghiaty, Adel; El-Morsy, Ahmed; El-Gamal, Kamal

    2013-01-01

    2-([1,2,4]Triazolo[4,3-a]quinoxalin-4-ylthio)acetic acid hydrazide (10) was used as a precursor for the syntheses of novel quinoxaline derivatives with potential anticonvulsant properties. The newly synthesized compounds have been characterized by IR, 1H NMR, and mass spectral data followed by elemental analysis. The anticonvulsant evaluation was carried out for eleven of the synthesized compounds using metrazol induced convulsions model and phenobarbitone sodium as a standard. Among this set of tested compounds, two of them (14, and 15b) showed the best anticonvulsant activities. PMID:24198971

  16. Ugi-Smiles couplings of 4-substituted pyridine derivatives: a fast access to chloroquine analogues.

    PubMed

    El Kaïm, Laurent; Grimaud, Laurence; Pravin, Patil

    2012-01-20

    4-Hydroxy and mercapto pyridines were successfully tested in Ugi-Smiles couplings. Such multicomponent reactions applied to quinoline derivatives afford a very convenient and short synthesis of antimalarial analogues. © 2011 American Chemical Society

  17. Reliability Modeling of Critical Electronic Devices.

    DTIC Science & Technology

    1983-05-01

    form are given below: 1) Xn = K 7E = AS + B 2) Xn = K TTE = A(S)B 3) Xn = K TE = A exp(BS) 24 A- where Xn = predicted normalized failure rate 0 0 K...naval, sheltered NS 5 7.3 a,. naval, unsheltered NU 10 16.8 naval, undersea , unsheltered NUU 14 20.6 naval, benign, submarine NSB 4 6.0 naval, hydrofoil... undersea , launch USL 18 37.1 3 S missile, free flight MFF 9 12.6 airbreathing missile, flight MFA 11 17.6 space, flight SF 2 2.1 Notes: (1) includes bomber

  18. CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis.

    PubMed

    Zaldivar, Mirko Moreno; Pauels, Katrin; von Hundelshausen, Philipp; Berres, Marie-Luise; Schmitz, Petra; Bornemann, Jörg; Kowalska, M Anna; Gassler, Nikolaus; Streetz, Konrad L; Weiskirchen, Ralf; Trautwein, Christian; Weber, Christian; Wasmuth, Hermann E

    2010-04-01

    Liver fibrosis is a major cause of morbidity and mortality worldwide. Platelets are involved in liver damage, but the underlying molecular mechanisms remain elusive. Here, we investigate the platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) as a molecular mediator of fibrotic liver damage. Serum concentrations and intrahepatic messenger RNA of CXCL4 were measured in patients with chronic liver diseases and mice after toxic liver injury. Platelet aggregation in early fibrosis was determined by electron microscopy in patients and by immunohistochemistry in mice. Cxcl4(-/-) and wild-type mice were subjected to two models of chronic liver injury (CCl(4) and thioacetamide). The fibrotic phenotype was analyzed by histological, biochemical, and molecular analyses. Intrahepatic infiltration of immune cells was investigated by fluorescence-activated cell sorting, and stellate cells were stimulated with recombinant Cxcl4 in vitro. The results showed that patients with advanced hepatitis C virus-induced fibrosis or nonalcoholic steatohepatitis had increased serum levels and intrahepatic CXCL4 messenger RNA concentrations. Platelets were found directly adjacent to collagen fibrils. The CCl(4) and thioacetamide treatment led to an increase of hepatic Cxcl4 levels, platelet activation, and aggregation in early fibrosis in mice. Accordingly, genetic deletion of Cxcl4 in mice significantly reduced histological and biochemical liver damage in vivo, which was accompanied by changes in the expression of fibrosis-related genes (Timp-1 [tissue inhibitor of matrix metalloproteinase 1], Mmp9 [matrix metalloproteinase 9], Tgf-beta [transforming growth factor beta], IL10 [interleukin 10]). Functionally, Cxcl4(-/-) mice showed a strongly decreased infiltration of neutrophils (Ly6G) and CD8(+) T cells into the liver. In vitro, recombinant murine Cxcl4 stimulated the proliferation, chemotaxis, and chemokine expression of hepatic stellate cells. The results underscore an important role

  19. Synthesis and decreasing Aβ content evaluation of arctigenin-4-yl carbamate derivatives.

    PubMed

    Xu, Xingyu; Li, Cong; Lei, Min; Zhu, Zhiyuan; Yan, Jianming; Shen, Xu; Hu, Lihong

    2016-07-01

    A series of arctigenin-4-yl carbamate derivatives were synthesized and evaluated for potency in reducing β-amyloid (Aβ) content in HEK293-APPswe cells. Most of the arctigenin-4-yl aralkyl or aryl carbamate derivatives showed improved potency in reducing Aβ content. Among the synthesized compounds, arctigenin-4-yl (3-chlorophenyl)carbamate (20) exhibited the strongest potency with 78.7% Aβ content reduction at 20μM. Furthermore, the effect of arctigenin-4-yl (4-chlorophenyl)carbamate (19) and arctigenin-4-yl (3-chlorophenyl)carbamate (20) on lowing Aβ content was better than arctigenin under the concentrations of 1, 10 and 20μM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Synthesis, molecular docking and biological evaluation of novel 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives

    NASA Astrophysics Data System (ADS)

    Ravichandiran, Palanisamy; Athinarayanan, Jegan; Premnath, Dhanaraj; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali A.; Vasanthkumar, Samuel

    2015-03-01

    A novel series of 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives have been synthesized and examined for their in vitro antibacterial activity against a panel of Gram-positive and Gram-negative bacteria. Among these, N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6-ylamino)phenylsulfonyl)phenyl)-3,5-bis(trifluoromethyl)benzamide (3n) (0.4 μg/mL) and 4-ethyl-N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6-ylamino)phenylsulfonyl)phenyl)benzamide (3l) (0.6 μg/mL) systems exhibited a potent inhibitory activity against Gram-positive organism Bacillus subtilis, when compare to the other synthesized compounds. Sparfloxacin (9.76 μg/mL), Norfloxacin (no activity) were employed as the standard drugs. An evaluation of the cytotoxicity of the title compounds (1, 2, 3a-n) revealed that they displayed low toxicity (26-115 mg/L) against cervical cancer cell line (SiHa). The results of these studies suggest that, phenothiazin-5-one derivatives are interesting binding agents for the development of new Gram-positive and Gram-negative antibacterial agents. To understand the interactions with protein receptors, docking simulation was done with crystal structures of B.subtilis (YmaH) and histone deacetylase (HDAC8) to determine the probable binding conformation.

  1. Synthesis and biological evaluation of 3-substituted-4-(4-methylthio phenyl)-1H-pyrrole derivatives as potential anticancer agents.

    PubMed

    Lan, Lan; Qin, Weixi; Zhan, Xiaoping; Liu, Zenglu; Mao, Zhenmin

    2014-01-01

    A novel series of 3-substituted-4-(4-methylthio phenyl)-1H-pyrrole derivatives were synthesized via Van Leusen pyrrole synthesis. The in vitro anticancer activity against a panel of 16 cancer cell lines and 2 normal cell lines was investigated by MTT assay. It was found that some of the pyrrole compounds showed similar antiproliferative activity against cancer cells compared with Paclitaxel, but little impact on normal cell lines, which indicated that the novel pyrrole derivatives could be used as potential anticancer candidates for possessing both selectivity and good therapeutic efficacy. Structure-activity relationship analysis found that 3-phenylacetyl-4- (4-methylthio phenyl)-1H-pyrrole derivatives displayed the most strong anticancer activity, among which [4-(4-methylthio phenyl)-1H-pyrrol- 3-yl] (4-methoxy phenyl) methanone (3j) was employed to investigate the effect of these pyrrole analogues on cell cycle by propidium iodide (PI) staining on cell flow cytometry. Cell necrotic effect of 10.0 µM 3j against MGC80-3 cells were also observed under fluorescence microscope and transmission electron microscope by ultrathin sections observation.

  2. Texture and microstructure evolution in single-phase Ti{sub x}Ta{sub 1-x}N alloys of rocksalt structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koutsokeras, L. E.; Department of Materials Science and Engineering, University of Ioannina, GR-45100 Ioannina; Abadias, G.

    2011-08-15

    The mechanisms controlling the structural and morphological features (texture and microstructure) of ternary transition metal nitride thin films of the Ti{sub x}Ta{sub 1-x}N system, grown by various physical vapor deposition techniques, are reported. Films deposited by pulsed laser deposition, dual cathode magnetron sputtering, and dual ion beam sputtering have been investigated by means of x-ray diffraction in various geometries and scanning electron microscopy. We studied the effects of composition, energetic, and kinetics in the evolution of the microstructure and texture of the films. We obtain films with single and mixed texture as well as films with columnar ''zone-T'' and globularmore » type morphology. The results have shown that the texture evolution of ternary transition metal nitrides as well as the microstructural features of such films can be well understood in the framework of the kinetic mechanisms proposed for their binary counterparts, thus giving these mechanisms a global application.« less

  3. Xanthohumol Prevents DNA Damage by Dietary Carcinogens: Results of a Human Intervention Trial.

    PubMed

    Pichler, Christoph; Ferk, Franziska; Al-Serori, Halh; Huber, Wolfgang; Jäger, Walter; Waldherr, Monika; Mišík, Miroslav; Kundi, Michael; Nersesyan, Armen; Herbacek, Irene; Knasmueller, Siegfried

    2017-02-01

    Xanthohumol (XN) is a hop flavonoid contained in beers and soft drinks. In vitro and animal studies indicated that XN has DNA and cancer protective properties. To find out if it causes DNA protective effects in humans, an intervention trial was conducted in which the participants (n = 22) consumed a XN containing drink (12 mg XN/P/d). We monitored prevention of DNA damage induced by representatives of major groups of dietary carcinogens [i.e., nitrosodimethylamine (NDMA) benzo(a)pyrene (B(a)P) and the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)]. Lymphocytes were collected before, during, and after the intervention and incubated with the carcinogens and with human liver homogenate (S9). We found substantial reduction of B(a)P and IQ (P < 0.001 for both substances) induced DNA damage after consumption of the beverage; also, with the nitrosamine a moderate, but significant protective effect was found. The results of a follow-up trial (n = 10) with XN pills showed that the effects are caused by the flavonoid and were confirmed in γH2AX experiments. To elucidate the underlying mechanisms we measured several parameters of glutathione related detoxification. We found clear induction of α-GST (by 42.8%, P < 0.05), but no alteration of π-GST. This observation provides a partial explanation for the DNA protective effects and indicates that the flavonoid also protects against other carcinogens that are detoxified by α-GST. Taken together, our findings support the assumption that XN has anticarcinogenic properties in humans. Cancer Prev Res; 10(2); 153-60. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Synthesis and Characterization of Mesoporous Silica Functionalized with Calix[4]arene Derivatives

    PubMed Central

    Alahmadi, Sana M.; Mohamad, Sharifah; Maah, Mohd Jamil

    2012-01-01

    This work reports a new method to covalently attach calix[4]arene derivatives onto MCM-41, using a diisocyanate as a linker. The modified mesoporous silicates were characterized by fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and elemental analysis. The FTIR spectra and TGA analysis verified that the calix[4]arene derivates are covalently attached to the mesoporous silica. The preservation of the MCM-41 channel system was checked by X-ray diffraction and nitrogen adsorption analysis. PMID:23202977

  5. Systemic fungicidal activity of 1,4-oxathiin derivatives.

    PubMed

    Schmeling, B V; Kulka, M

    1966-04-29

    Treatment of pinto bean and barley seed with 1,4-oxathiin derivatives gave disease control by systemic fungicidal action of such pathogenic fungi as Uromyces phaseoli and Ustilago nuda. The two chemicals, D735 and F461, were highly specific and selective against the pathogens without injury of the hosts.

  6. 17 CFR 4.32 - Trading on a Registered Derivatives Transaction Execution Facility for Non-Institutional Customers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Trading on a Registered Derivatives Transaction Execution Facility for Non-Institutional Customers. 4.32 Section 4.32 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION COMMODITY POOL OPERATORS AND COMMODITY TRADING...

  7. Novel series of 1,2,4-trioxane derivatives as antimalarial agents.

    PubMed

    Rudrapal, Mithun; Chetia, Dipak; Singh, Vineeta

    2017-12-01

    Among three series of 1,2,4-trioxane derivatives, five compounds showed good in vitro antimalarial activity, three compounds of which exhibited better activity against P. falciparum resistant (RKL9) strain than the sensitive (3D7) one. Two best compounds were one from aryl series and the other from heteroaryl series with IC 50 values of 1.24 µM and 1.24 µM and 1.06 µM and 1.17 µM, against sensitive and resistant strains, respectively. Further, trioxane derivatives exhibited good binding affinity for the P. falciparum cysteine protease falcipain 2 receptor (PDB id: 3BPF) with well defined drug-like and pharmacokinetic properties based on Lipinski's rule of five with additional physicochemical and ADMET parameters. In view of having antimalarial potential, 1,2,4-trioxane derivative(s) reported herein may be useful as novel antimalarial lead(s) in the discovery and development of future antimalarial drug candidates as P. falciparum falcipain 2 inhibitors against resistant malaria.

  8. Spectrofluorimetric and Potentiometric Determination of Acidity Constants of 4-(4'-Acetyloxy-3'-Methoxybenzylidene)-5-Oxazolone Derivatives.

    PubMed

    Taskiran, Derya Topkaya; Urut, Gulsiye Ozturk; Ayata, Sevda; Alp, Serap

    2017-03-01

    4-(4'-acetyloxy-3'-methoxybenzylidene)-5-oxazolone fluorescent molecules bearing four different aryl groups attached to the 2-position of 5-oxazolone ring have been investigated by spectrophotometric and potentiometric techniques in solution media. The acidity constants (pKa) of the fluorescent molecules were precisely determined in acetone, acetonitrile, dimethylformamide and in 1:1 mixture of toluene-isopropanol. The studied derivatives were titrated with tetrabutylammonium hydroxide and non-aqueous perchloric acid by scanning the basic and acidic region of the pH scale. A computerizable derivative method was used in order to descript precisely the end point and pKa values. The molecules investigated performed well-shaped and stoichiometric potentiometric titration curves.

  9. THz spectra of 1,4-naphthoquinones and its four derivatives

    NASA Astrophysics Data System (ADS)

    Wang, Weining; Li, Hongqi; Luo, Xiang; Zeng, Xiaoni

    2008-03-01

    Recently some naphthoquinone derivatives have been found with anticancer or other therapeutic properties, but also have some negative side effects. Numerous research projects have been conducted to investigate their properties and therapeutic mechanisms. With Terahertz Time-Domain Spectroscopy (THz-TDS), we have successfully obtained THz spectra of 1,4-naphthoquinone and its four derivatives in a series of naphthazarin - juglone - 1,4-naphthoquinone - menadione - plumbagin, in the range between 0.2 and 2.4~2.8 THz. Although these molecules are almost identical to each other, they have very distinctive THz spectra so that they can be identified much more easily than using conventional spectroscopy. We have comparatively analyzed their THz spectra, and found some possible correlations between THz spectra and molecular structures. These THz spectra cannot only be used as spectral fingerprint, but also provide us their conformational properties that can be used in study of their interaction with biomolecules to reveal their pharmaceutical mechanisms.

  10. Synthesis of 4-alkyl and 4-(beta-alkylvinyl) derivatives of primaquine as potential antimalarials.

    PubMed

    Carroll, F I; Berrang, B D; Linn, C P

    1979-11-01

    4(beta-Alkylvinyl)-6-methoxy-8-nitroquinolines (6) were prepared from 6-methoxy-8-nitroquinoline-4-carboxaldehyde (5) via a Wittig reaction. Stannous chloride reduction of 6 gave 4-(beta-alkylvinyl)-8-amino-6-methoxyquinolines (8), whereas catalytic reduction of 6 using Raney nickel catalyst gave 4-alkyl-8-amino-6-methoxyquinolines (7). Alkylation of 7 and 8 with 4-iodo-1-phthalimidopentane, followed by removal of the phthaloyl-protecting group with hydrazine, gave 4-alkyl and 4-(beta-alkylvinyl) derivatives of primiquine, respectively. These compounds were evaluated for antimalarial activity against P. berghei and P. berghei yoelii in mice and against P. cynomolgi in rhesus monkeys. Several of the compounds were active in the P. bergheii yoelii screen. None of the compounds showed significant activity in the other two screens.

  11. Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.

    PubMed

    Ouyang, Jingfeng; Huang, Wei; Yu, Wanwan; Xiong, Wei; Mula, Ramanjaneya V R; Zou, Hongbin; Yu, Yongping

    2014-02-05

    Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3β (HNF 3β) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Gut-derived lipopolysaccharide promotes T-cell-mediated hepatitis in mice through Toll-like receptor 4.

    PubMed

    Lin, Yan; Yu, Le-Xing; Yan, He-Xin; Yang, Wen; Tang, Liang; Zhang, Hui-Lu; Liu, Qiong; Zou, Shan-Shan; He, Ya-Qin; Wang, Chao; Wu, Meng-Chao; Wang, Hong-Yang

    2012-09-01

    Robust clinical and epidemiologic data support the role of inflammation as a key player in hepatocellular carcinoma (HCC) development. Our previous data showed that gut-derived lipopolysaccharide (LPS) promote HCC development by activating Toll-like receptor 4 (TLR4) expressed on myeloid-derived cells. However, the effects of gut-derived LPS on other types of liver injury models are yet to be studied. The purpose of this study was to determine the importance of gut-derived LPS and TLR4 signaling in a T-cell-mediated hepatitis-Con A-induced hepatitis model, which mimic the viral hepatitis. Reduction of endotoxin using antibiotics regimen or genetic ablation of TLR4 in mice significantly alleviate Con A-induced liver injury by inhibiting the infiltration of T lymphocytes into the liver and the activation of CD4(+) T lymphocytes as well as the production of T helper 1 cytokines; in contrast, exogenous LPS can promote Con A-induced hepatitis and CD4(+) T cells activation in vivo and in vitro. Reconstitution of TLR4-expressing myeloid cells in TLR4-deficient mice restored Con A-induced liver injury and inflammation, indicating the major cell target of LPS. In addition, TLR4 may positively regulate the target hepatocellular apoptosis via the perforin/granzyme B pathway. These data suggest that gut-derived LPS and TLR4 play important positive roles in Con A-induced hepatitis and modulation of the gut microbiotia may represent a new avenue for therapeutic intervention to treat acute hepatitis induced by hepatitis virus infection, thus to prevent hepatocellular carcinoma.

  13. Face-to-Face Packing of 2,3,9,10-Tetrasubstituted Pentacene Derivatives Revealed through a Solid State [4 + 4] Thermal Cycloaddition and Molecular Dynamic Simulation.

    PubMed

    Pal, Bikash; Lin, Bo-Chao; Dela Cerna, Mark Vincent Carreon; Hsu, Chao-Ping; Lin, Chih-Hsiu

    2016-08-05

    2,3,9,10-Substituted pentacene tetraesters and pentacene diester-dinitriles were synthesized. These pentacene derivatives underwent an unusual solid state [4 + 4] thermal dimerization with good efficiency and complete stereoselectivity. This observation indicates this series of pentacene derivatives adopt π-π stacking geometry with large mutual overlap in solid state. This notion was confirmed by molecualr dynamic simulation.

  14. Depth profile of production yields of natPb(p, xn) 206,205,204,203,202,201Bi nuclear reactions

    NASA Astrophysics Data System (ADS)

    Mokhtari Oranj, Leila; Jung, Nam-Suk; Kim, Dong-Hyun; Lee, Arim; Bae, Oryun; Lee, Hee-Seock

    2016-11-01

    Experimental and simulation studies on the depth profiles of production yields of natPb(p, xn) 206,205,204,203,202,201Bi nuclear reactions were carried out. Irradiation experiments were performed at the high-intensity proton linac facility (KOMAC) in Korea. The targets, irradiated by 100-MeV protons, were arranged in a stack consisting of natural Pb, Al, Au foils and Pb plates. The proton beam intensity was determined by activation analysis method using 27Al(p, 3p1n)24Na, 197Au(p, p1n)196Au, and 197Au(p, p3n)194Au monitor reactions and also by Gafchromic film dosimetry method. The yields of produced radio-nuclei in the natPb activation foils and monitor foils were measured by HPGe spectroscopy system. Monte Carlo simulations were performed by FLUKA, PHITS/DCHAIN-SP, and MCNPX/FISPACT codes and the calculated data were compared with the experimental results. A satisfactory agreement was observed between the present experimental data and the simulations.

  15. InxAl1-xN chiral nanorods mimicking the polarization features of scarab beetles

    NASA Astrophysics Data System (ADS)

    Magnusson, R.; Birch, J.; Hsiao, C.-L.; Sandström, P.; Arwin, H.; Järrendahl, K.

    2015-03-01

    The scarab beetle Cetonia aurata is known to reflect light with brilliant colors and a high degree of circular polarization. Both color and polarization effects originate from the beetles exoskeleton and have been attributed to a Bragg reflection of the incident light due to a twisted laminar structure. Our strategy for mimicking the optical properties of the Cetonia aurata was therefore to design and fabricate transparent, chiral films. A series of films with tailored transparent structures of helicoidal InxAl1-xN nanorods were grown on sapphire substrates using UHV magnetron sputtering. The value of x is tailored to gradually decrease from one side to the other in each nanorod normal to its growth direction. This introduces an in-plane anisotropy with different refractive indices in the direction of the gradient and perpendicular to it. By rotating the sample during film growth the in-plane optical axis will be rotated from bottom to top and thereby creating a chiral film. Based on Muellermatrix ellipsometry, optical modeling has been done suggesting that both the exoskeleton of Cetonia aurata and our artificial material can be modeled by an anisotropic film made up of a stack of thin layers, each one with its in-plane optical axis slightly rotated with respect to the previous layer. Simulations based on the optical modeling were used to investigate how pitch and thickness of the film together with the optical properties of the constitutive materials affects the width and spectral position of the Bragg reflection band.

  16. Human embryonic stem cell lines derived from single blastomeres of two 4-cell stage embryos

    PubMed Central

    Geens, Mieke; Mateizel, Ileana; Sermon, Karen; De Rycke, Martine; Spits, Claudia; Cauffman, Greet; Devroey, Paul; Tournaye, Herman; Liebaers, Inge; Van de Velde, Hilde

    2009-01-01

    BACKGROUND Recently, we demonstrated that single blastomeres of a 4-cell stage human embryo are able to develop into blastocysts with inner cell mass and trophectoderm. To further investigate potency at the 4-cell stage, we aimed to derive pluripotent human embryonic stem cells (hESC) from single blastomeres. METHODS Four 4-cell stage embryos were split on Day 2 of preimplantation development and the 16 blastomeres were individually cultured in sequential medium. On Day 3 or 4, the blastomere-derived embryos were plated on inactivated mouse embryonic fibroblasts (MEFs). RESULTS Ten out of sixteen blastomere-derived morulae attached to the MEFs, and two produced an outgrowth. They were mechanically passaged onto fresh MEFs as described for blastocyst ICM-derived hESC, and shown to express the typical stemness markers by immunocytochemistry and/or RT–PCR. In vivo pluripotency was confirmed by the presence of all three germ layers in the teratoma obtained after injection in immunodeficient mice. The first hESC line displays a mosaic normal/abnormal 46, XX, dup(7)(q33qter), del(18)(q23qter) karyotype. The second hESC line displays a normal 46, XY karyotype. CONCLUSION We report the successful derivation and characterization of two hESC lines from single blastomeres of four split 4-cell stage human embryos. These two hESC lines were derived from distinct embryos, proving that at least one of the 4-cell stage blastomeres is pluripotent. PMID:19633307

  17. Implementation of "Marginalism" in Day to Day Life.

    DTIC Science & Technology

    1998-06-01

    1985. 4. Golden, B.L., E.A Wasil and P.T. Harker, The Analytic Hierarchy Process, Spring-Verlag Berlin, Heidelberg, 1989. 5. Agor , Weston H , The...A. H . Maslow was a psychologist whose work on human motivation has been influential in fields such as organization development and industrial...benefit from Xi is the partial derivative of the objective function, 50/aXi. Consider a constraint function: < H >(X1,X2, ,Xn)=0 The marginal cost of

  18. Substituent effect on photophysical properties of bi-1,3,4-oxadiazole derivatives in solution

    NASA Astrophysics Data System (ADS)

    Chen, Fangyi; Tian, Taiji; Zhao, Chengxiao; Bai, Binglian; Li, Min; Wang, Haitao

    2016-04-01

    A series of phenyl substituted bi-1,3,4-oxadiazole derivatives were designed and synthesized; the effect of substituent on the photophysical properties and molecular electronic structures was fully studied by the combination of experimental techniques and theoretical calculations. Compared to parent compound without any substituent (BOXD), fluoro-substituent shows little effect on the absorption and emission spectra, whilst a little larger spectral red-shift could be observed for methoxy-, nitro-substituted derivatives and thienyl-substituted bi-1,3,4-oxadiazole (TBOXD). These spectral changes can be well explained by theoretically calculated HOMO and LUMO energy level changes. All these molecules show high fluorescence quantum yield except for nitro-substituted derivative in dilute solutions. The quantum yield of BOXD changes with the concentration and exhibits a high value at the concentrated solution. This work revealed the influence of substituent on the photophysical properties of bi-1,3,4-oxadizaole derivatives in dilute solutions and provided guidance for designing molecules with potential application.

  19. Synthesis and characterization of a series of Group 4 phenoxy-thiol derivatives

    DOE PAGES

    Boyle, Timothy J.; Neville, Michael L.; Parkes, Marie V.

    2016-02-11

    In this study, a series of Group 4 phenoxy-thiols were developed from the reaction products of a series of metal tert-butoxides ([M(OBu t) 4]) with four equivalents of 4-mercaptophenol (H-4MP). The products were found by single crystal X-ray diffraction to adopt the general structure [(HOBu t)(4MP) 3M(μ-4MP)] 2 [where M = Ti (1), Zr (2), Hf (3)] from toluene and [(py) 2M(4MP)] where M = Ti (4), Zr (5) and [(py)(4MP) 3Hf(μ-4MP)] 2 (6) from pyridine (py). Varying the [Ti(OR) 4] precursors (OR = iso-propoxide (OPr i) or neo-pentoxide (ONep)) in toluene led to [(HOR)(4MP) 3Ti(μ-4MP)] 2 (OR = OPrmore » i (7), ONep (8)), which were structurally similar to 1. Lower stoichiometric reactions in toluene led to partial substitution by the 4MP ligands yielding [H][Ti(μ-4MP)(4MP)(ONep) 3] 2 (9). Independent of the stoichiometry, all of the Ti derivatives were found to be red in color, whereas the heavier congeners were colorless. Attempts to understand this phenomenon led to investigation with a series of varied –SH substituted phenols. From the reaction of H-2MP and H-3MP (2-mercaptophenol and 3-mercaptophenol, respectively), the isolated products had identical arrangements: [(ONep) 2(2MP)Ti(μ,η2-2MP)] 2 (10) and [(HOR)(3MP)M(μ-3MP)] 2 (M/OR = Ti/ONep (11); Zr/OBu t (12)) with a similar red color. Based on the simulated and observed UV–Vis spectra, it was reasoned that the color was generated due to a ligand-to-metal charge transfer for Ti that was not available for the larger congeners.« less

  20. Stratospheric CH4 and CO2 profiles derived from SCIAMACHY solar occultation measurements

    NASA Astrophysics Data System (ADS)

    Noël, S.; Bramstedt, K.; Hilker, M.; Liebing, P.; Plieninger, J.; Reuter, M.; Rozanov, A.; Bovensmann, H.; Burrows, J. P.

    2015-11-01

    Stratospheric profiles of methane (CH4) and carbon dioxide (CO2) have been derived from solar occultation measurements of the SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY). The retrieval is performed using a method called "Onion Peeling DOAS" (ONPD) which combines an onion peeling approach with a weighting function DOAS (Differential Optical Absorption Spectroscopy) fit. By use of updated pointing information and optimisation of the data selection and of the retrieval approach the altitude range for reasonable CH4 could be extended to about 17 to 45 km. Furthermore, the quality of the derived CO2 has been assessed such that now the first stratospheric profiles of CO2 from SCIAMACHY are available. Comparisons with independent data sets yield an estimated accuracy of the new SCIAMACHY stratospheric profiles of about 5-10 % for CH4 and 2-3 % for CO2. The accuracy of the products is currently mainly restricted by the appearance of unexpected vertical oscillations in the derived profiles which need further investigation. Using the improved ONPD retrieval, CH4 and CO2 stratospheric data sets covering the whole SCIAMACHY time series (August 2002-April 2012) and the latitudinal range between about 50 and 70° N have been derived. Based on these time series, CH4 and CO2 trends have been estimated, which are in reasonable agreement with total column trends for these gases. This shows that the new SCIAMACHY data sets can provide valuable information about the stratosphere.

  1. Correlated high-resolution x-ray diffraction photoluminescence and atom probe tomography analysis of continuous and discontinuous In xGa 1-xN quantum wells

    DOE PAGES

    Ren, Xiaochen; Riley, James R.; Koleske, Daniel; ...

    2015-07-14

    In this study, atom probe tomography (APT) is used to characterize the influence of hydrogen dosing duringGaN barrier growth on the indium distribution of In xGa 1-xN quantum wells, and correlatedmicro-photoluminescence is used to measure changes in the emission spectrum and efficiency. We found that relative to the control growth, hydrogen dosing leads to a 50% increase in emission intensity arising from discontinuous quantum wells that are narrower, of lower indium content, and with more abrupt interfaces. Additionally, simulations of carrier distributions based on APT composition profiles indicate that the greater carrier confinement leads to an increased radiative recombination rate.more » Furthermore, APT analysis of quantum well profiles enables refinement of x-ray diffractionanalysis for more accurate nondestructive measurements of composition.« less

  2. Phase transition and ductile behavior of IrxOs1-xN alloys from theoretical point of view

    NASA Astrophysics Data System (ADS)

    Sarwan, Madhu; Singh, Sadhna

    2018-05-01

    Present paper reports theoretical investigation of less explored nitrides of Iridium and Osmium using semi-empirical model with charge transfer effect (CTE). This work indicates the presence of structural phase transition in these nitrides from zinc-blend (B3) to rock-salt (B1) structure on application of pressure on them. Transitions occurred at 71 GPa and 86 GPa, with sudden drops in volume of 9.54% and 8.35% in IrN and OsN. The effect of pressure on elastic properties for B3-IrN and B3-OsN is investigated for the first time. On the basis of mechanical properties, it is observed that both compounds are ductile in nature. The present study is extended to investigate transition metal alloy IrxOs1-xN via Vegard's law. To widen the applicability of our model and to explore this alloy we report structural, elastic, mechanical and thermophysical properties. The effect of pressure on Debye temperature with different concentration (x = 0, 0.25, 0.5, 0.75, 1) have also been analyzed. The results are in general in good agreement with available theoretical results.

  3. Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway

    PubMed Central

    ZHOU, HAO; YANG, JUNJIE; XIN, TING; ZHANG, TAO; HU, SHUNYIN; ZHOU, SHANSHAN; CHEN, GUANGHUI; CHEN, YUNDAI

    2015-01-01

    Adipose-derived stem cells (ADSCs) are considered a suitable source of cells for the repair of tissue following acute myocardial infarction (AMI); however, the transplantation efficiency of ADSCs remains low. Therefore, identification of an efficient method to enhance the migration of engrafted cells to the target site is required. The present study used exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, to optimize the migratory capacity of ADSCs. The aim was to determine the effect and mechanisms of Ex-4 on the migration of ADSCs to neonatal rat ventricular cardiomyocyte-derived conditioned medium (NRVC-CM). The ADSCs and cardiomyocytes were cultured in vitro. Following incubation of the ADSCs with Ex-4, cell proliferation was measured using an MTT assay and the expression levels of CXC chemokine receptor 4 (CXCR4) were investigated by reverse transctiption quantitative polymerase chain reaction (RT-qPCR), western blot analysis and flow cytometry. In addition, the expression levels of stromal cell-derived factor-1α (SDF-1α) were evaluated in the NRVC-CM treated with Ex-4 by ELISA, RT-qPCR and western blot analysis. The migration of the ADSCs to the NRVC-CM was examined using a Transwell assay. Changes in the protein expression levels of phosphorylated (p−)Akt were examined in the two types of cell by western blot analysis. The results suggested that Ex-4 promoted the proliferation and expression of CXCR4 in the ADSCs, increased the secretion of SDF-1α in the cardiomyocytes and increased the expression levels of p-Akt in both cells. However, the alterations to the SDF-1α/C XC R4 cascade in the cells were abrogated following pretreatment with LY-294002, a phosphoinositide 3-kinase(PI3K) inhibitor. Furthermore, a Transwell migration assay revealed marked translocation of the ADSCs through the membranes, towards the NRVC-CM, following treatment with Ex-4. However, these effects were reduced significantly by pretreatment of the cells with the SDF-1

  4. PDAC-derived exosomes enrich the microenvironment in MDSCs in a SMAD4-dependent manner through a new calcium related axis.

    PubMed

    Basso, Daniela; Gnatta, Elisa; Padoan, Andrea; Fogar, Paola; Furlanello, Sara; Aita, Ada; Bozzato, Dania; Zambon, Carlo-Federico; Arrigoni, Giorgio; Frasson, Chiara; Franchin, Cinzia; Moz, Stefania; Brefort, Thomas; Laufer, Thomas; Navaglia, Filippo; Pedrazzoli, Sergio; Basso, Giuseppe; Plebani, Mario

    2017-10-17

    Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4 , deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4 -dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3- SMAD4 +) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs. Exo expanded myeloid derived suppressor cells (gMDSC and mMDSC, flow cytometry) and altered intracellular calcium fluxes in an SMAD4 dependent manner. BxPC3- SMAD4 +, but mainly BxPC3 Exo, increased calcium fluxes of PBMCs ( p = 0.007) and this increased intracellular calcium trafficking characterized mMDSCs. The analysis of de-regulated Exo-miRNAs and transfection experiments revealed hsa-miR-494-3p and has-miR-1260a as potential mediators of SMAD4- associated de-regulated calcium fluxes. Eleven main biological processes were identified by the analysis of SMAD4 -associated de-regulated Exo-proteins, including translation, cell adhesion, cell signaling and glycolysis. A reverse Warburg effect was observed by treating PBMCs with PDAC-derived Exo: BxPC3 Exo induced a higher glucose consumption and lactate production than BxPC3- SMAD4 + Exo. PDAC-derived Exo from cells with , but mainly from those without SMAD4 expression, create an immunosuppressive myeloid cell background by increasing calcium fluxes and glycolysis through the transfer of SMAD4 -related differentially expressed miRNAs and proteins.

  5. PDAC-derived exosomes enrich the microenvironment in MDSCs in a SMAD4-dependent manner through a new calcium related axis

    PubMed Central

    Basso, Daniela; Gnatta, Elisa; Padoan, Andrea; Fogar, Paola; Furlanello, Sara; Aita, Ada; Bozzato, Dania; Zambon, Carlo-Federico; Arrigoni, Giorgio; Frasson, Chiara; Franchin, Cinzia; Moz, Stefania; Brefort, Thomas; Laufer, Thomas; Navaglia, Filippo; Pedrazzoli, Sergio; Basso, Giuseppe; Plebani, Mario

    2017-01-01

    Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs. Exo expanded myeloid derived suppressor cells (gMDSC and mMDSC, flow cytometry) and altered intracellular calcium fluxes in an SMAD4 dependent manner. BxPC3-SMAD4+, but mainly BxPC3 Exo, increased calcium fluxes of PBMCs (p = 0.007) and this increased intracellular calcium trafficking characterized mMDSCs. The analysis of de-regulated Exo-miRNAs and transfection experiments revealed hsa-miR-494-3p and has-miR-1260a as potential mediators of SMAD4-associated de-regulated calcium fluxes. Eleven main biological processes were identified by the analysis of SMAD4-associated de-regulated Exo-proteins, including translation, cell adhesion, cell signaling and glycolysis. A reverse Warburg effect was observed by treating PBMCs with PDAC-derived Exo: BxPC3 Exo induced a higher glucose consumption and lactate production than BxPC3-SMAD4+ Exo. Conclusion: PDAC-derived Exo from cells with, but mainly from those without SMAD4 expression, create an immunosuppressive myeloid cell background by increasing calcium fluxes and glycolysis through the transfer of SMAD4-related differentially expressed miRNAs and proteins. PMID:29156694

  6. Chemical and structural order in silicon oxynitrides by methods of surface physics

    NASA Astrophysics Data System (ADS)

    Finster, J.; Heeg, J.; Klinkenberg, E.-D.

    A large number of thin amorphous layers of SiO xN y and several (crystalline) reference compounds (SiO 2, Si 3N 4, Si 2N 2O) are studied. Although XANES and SEXAFS are well sulted to derive structural and chemical order, for these compounds many problems remain to be solved. We show how core level spectra (XPS, AES) can be used to gain such information (e.g. random bonding structure, N coordination, oxidation behaviour).

  7. Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor

    PubMed Central

    Auerbach, David J.; Lin, Yin; Miao, Huiyi; Cimbro, Raffaello; DiFiore, Michelle J.; Gianolini, Monica E.; Furci, Lucinda; Biswas, Priscilla; Fauci, Anthony S.; Lusso, Paolo

    2012-01-01

    The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection. PMID:22645343

  8. Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor.

    PubMed

    Auerbach, David J; Lin, Yin; Miao, Huiyi; Cimbro, Raffaello; Difiore, Michelle J; Gianolini, Monica E; Furci, Lucinda; Biswas, Priscilla; Fauci, Anthony S; Lusso, Paolo

    2012-06-12

    The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection.

  9. Stratospheric CH4 and CO2 profiles derived from SCIAMACHY solar occultation measurements

    NASA Astrophysics Data System (ADS)

    Noël, Stefan; Bramstedt, Klaus; Hilker, Michael; Liebing, Patricia; Plieninger, Johannes; Reuter, Max; Rozanov, Alexei; Sioris, Christopher E.; Bovensmann, Heinrich; Burrows, John P.

    2016-04-01

    Stratospheric profiles of methane (CH4) and carbon dioxide (CO2) have been derived from solar occultation measurements of the SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY). The retrieval is performed using a method called onion peeling DOAS (ONPD), which combines an onion peeling approach with a weighting function DOAS (differential optical absorption spectroscopy) fit in the spectral region between 1559 and 1671 nm. By use of updated pointing information and optimisation of the data selection as well as of the retrieval approach, the altitude range for reasonable CH4 could be broadened from 20 to 40 km to about 17 to 45 km. Furthermore, the quality of the derived CO2 has been assessed such that now the first stratospheric profiles (17-45 km) of CO2 from SCIAMACHY are available. Comparisons with independent data sets yield an estimated accuracy of the new SCIAMACHY stratospheric profiles of about 5-10 % for CH4 and 2-3 % for CO2. The accuracy of the products is currently mainly restricted by the appearance of unexpected vertical oscillations in the derived profiles which need further investigation. Using the improved ONPD retrieval, CH4 and CO2 stratospheric data sets covering the whole SCIAMACHY time series (August 2002-April 2012) and the latitudinal range between about 50 and 70° N have been derived. Based on these time series, CH4 and CO2 trends have been estimated. CH4 trends above about 20 km are not significantly different from zero and the trend at 17 km is about 3 ppbv year-1. The derived CO2 trends show a general decrease with altitude with values of about 1.9 ppmv year-1 at 21 km and about 1.3 ppmv year-1 at 39 km. These results are in reasonable agreement with total column trends for these gases. This shows that the new SCIAMACHY data sets can provide valuable information about the stratosphere.

  10. KSC-06pd0502

    NASA Image and Video Library

    2006-03-15

    KENNEDY SPACE CENTER, FLA. - During a simulated emergency landing of a shuttle crew at NASA Kennedy Space Center's Shuttle Landing Facility, medevac personnel tend to an "injured astronaut" in the helicopter. The astronaut will be taken to an area hospital participating in the simulation. Known as a Mode VI exercise, the operation uses volunteer workers from the Center to pose as astronauts. The purpose of the simulation is to exercise emergency preparedness personnel, equipment and facilities in rescuing astronauts from a downed orbiter and providing immediate medical attention. Photo credit: NASA/Kim Shiflett

  11. Cobalt Ion Promoted Redox Cascade: A Route to Spiro Oxazine-Oxazepine Derivatives and a Dinuclear Cobalt(III) Complex of an N-(1,4-Naphthoquinone)-o-aminophenol Derivative.

    PubMed

    Mondal, Sandip; Bera, Sachinath; Maity, Suvendu; Ghosh, Prasanta

    2017-11-06

    The study discloses that the redox activity of N-(1,4-naphthoquinone)-o-aminophenol derivatives (L R H 2 ) containing a (phenol)-NH-(1,4-naphthoquinone) fragment is notably different from that of a (phenol)-NH-(phenol) precursor. The former is a platform for a redox cascade. L R H 2 is redox noninnocent and exists in Cat-N-(1,4-naphthoquinone)(2-) (L R 2- ) and SQ-N-(1,4-naphthoquinone) (L R •- ) states in the complexes. Reactions of L R H 2 with cobalt(II) salts in MeOH in air promote a cascade affording spiro oxazine-oxazepine derivatives ( OX L R ) in good yields, when R = H, Me, t Bu. Spiro oxazine-oxazepine derivatives are bioactive, and such a molecule has so far not been isolated by a schematic route. In this context this cascade is significant. Dimerization of L R H 2 → OX L R in MeOH is a (6H + + 6e) oxidation reaction and is composed of formations of four covalent bonds and 6-exo-trig and 7-endo-trig cyclization based on C-O coupling reactions, where MeOH is the source of a proton and the ester function. It was established that the active cascade precursor is [(L Me •- )Co III Cl 2 ] (A). Notably, formation of a spiro derivative was not detected in CH 3 CN and the reaction ends up furnishing A. The route of the reaction is tunable by R, when R = NO 2 , it is a (2e + 4H + ) oxidation reaction affording a dinuclear L R 2- complex of cobalt(III) of the type [(L NO2 2- ) 2 Co III 2 (OMe) 2 (H 2 O) 2 ] (1) in good yields. No cascade occurs with zinc(II) ion even in MeOH and produces a L Me •- complex of type [(L Me •- )Zn II Cl 2 ] (2). The intermediate A and 2 exhibit strong EPR signals at g = 2.008 and 1.999, confrming the existence of L Me •- coordinated to low-spin cobalt(III) and zinc(II) ions. The intermediates of L R H 2 → OX L R conversion were analyzed by ESI mass spectrometry. The molecular geometries of OX L R and 1 were confirmed by X-ray crystallography, and the spectral features were elucidated by TD DFT calculations.

  12. Analytical characterization of three cathinone derivatives, 4-MPD, 4F-PHP and bk-EPDP, purchased as bulk powder from online vendors.

    PubMed

    Apirakkan, Orapan; Frinculescu, Anca; Shine, Trevor; Parkin, Mark C; Cilibrizzi, Agostino; Frascione, Nunzianda; Abbate, Vincenzo

    2018-02-01

    Novel emerging drugs of abuse, also referred as new psychoactive substances, constitute an ever-changing mixture of chemical compounds designed to circumvent legislative controls by means of chemical modifications of previously banned recreational drugs. One such class, synthetic cathinones, namely β-keto derivatives of amphetamines, has been largely abused over the past decade. A number of new synthetic cathinones are detected each year, either in bulk powders/crystals or in biological matrices. It is therefore important to continuously monitor the supply of new synthetic derivatives and promptly report them. By using complementary analytical techniques (i.e. one- and two-dimensional NMR, FT-IR, GC-MS, HRMS and HPLC-UV), this study investigates the detection, identification and full characterization of 1-(4-methylphenyl)-2-(methylamino)pentanone (4-methylpentedrone, 4-MPD), 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexanone (4F-PHP) and 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)-1-pentanone (bk-EPDP), three emerging cathinone derivatives. Copyright © 2017 John Wiley & Sons, Ltd.

  13. 17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Procedures for implementing derivatives clearing organization rules and clearing new products. 39.4 Section 39.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.4 Procedures for...

  14. KSC-08pd0502

    NASA Image and Video Library

    2008-02-23

    KENNEDY SPACE CENTER, FLA. -- In NASA Kennedy Space Center's News Room, STS-123 Mission Specialist Takao Doi, of the Japan Aerospace Exploration Agency, shows his enthusiasm for his upcoming flight during an interview. The crew for space shuttle Endeavour's STS-123 mission is at Kennedy for a full launch dress rehearsal, known as the terminal countdown demonstration test or TCDT. The terminal countdown demonstration test provides astronauts and ground crews with an opportunity to participate in various simulated countdown activities, including equipment familiarization and emergency training. Endeavour is targeted to launch March 11 at 2:28 a.m. EDT on a 16-day mission to the International Space Station. On the mission, Endeavour and its crew will deliver the first section of the Japan Aerospace Exploration Agency's Kibo laboratory and the Canadian Space Agency's two-armed robotic system, Dextre. Photo credit: NASA/Amanda Diller

  15. FABP4 plasma levels are increased in familial combined hyperlipidemia.

    PubMed

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L; Ascaso, Juan F; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-05-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) microg/l and 19.2 (9.2) microg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia.

  16. Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4.

    PubMed

    Nguyen, Thi Thanh Binh; Lomberget, Thierry; Tran, Ngoc Chau; Colomb, Evelyne; Nachtergaele, Lore; Thoret, Sylviane; Dubois, Joëlle; Guillaume, Joren; Abdayem, Rawad; Haftek, Marek; Barret, Roland

    2012-12-01

    A novel series of combretastatin A-4 heterocyclic analogues was prepared by replacement of the B ring with indole, benzofurane or benzothiophene, attached at the C2 position. These compounds were evaluated for their abilities to inhibit tubulin assembly: derivative cis3b, having a benzothiophene, showed an activity similar to those of colchicine or deoxypodophyllotoxine. The antiproliferative and antimitotic properties of cis3b against keratinocyte cancer cell lines were also evaluated and the intracellular organization of microtubules in the cells after treatment with both stereoisomers of 3b was also determined, using confocal microscopy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. a New Set-Up for Total Reaction Cross Section Measuring

    NASA Astrophysics Data System (ADS)

    Sobolev, Yu. G.; Ivanov, M. P.; Kugler, A.; Penionzhkevich, Yu. E.

    2013-06-01

    The experimental method and set-up based on 4 n-Υ-technique for direct and modelindependent measuring of the total reaction cross section σR have been presented. The excitation function σR(E) for 6He+197Au reaction at the Coulomb barrier energy region has been measured. The measured data are compared with the summarized cross section which has been prepared by summing of measured cross sections of main reaction channels: 1n-transfer and 197Au(6He, xn)203-xnT1 with x = 2÷7 evaporation reaction channels.

  18. 17 CFR 4.32 - Trading on a Registered Derivatives Transaction Execution Facility for Non-Institutional Customers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Trading on a Registered... Securities Exchanges COMMODITY FUTURES TRADING COMMISSION COMMODITY POOL OPERATORS AND COMMODITY TRADING ADVISORS Commodity Trading Advisors § 4.32 Trading on a Registered Derivatives Transaction Execution...

  19. 17 CFR 4.32 - Trading on a Registered Derivatives Transaction Execution Facility for Non-Institutional Customers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Trading on a Registered... Securities Exchanges COMMODITY FUTURES TRADING COMMISSION COMMODITY POOL OPERATORS AND COMMODITY TRADING ADVISORS Commodity Trading Advisors § 4.32 Trading on a Registered Derivatives Transaction Execution...

  20. KSC-99pp0502

    NASA Image and Video Library

    1999-05-07

    The Shuttle Radar Topography Mission (SRTM) is moved into the Space Station Processing Facility to prepare it for launch targeted for September 1999. The primary payload on mission STS-99, the SRTM consists of a specially modified radar system that will fly onboard the Space Shuttle during the 11-day mission. This radar system will gather data that will result in the most accurate and complete topographic map of the Earth's surface that has ever been assembled. SRTM is an international project spearheaded by the National Imagery and Mapping Agency and NASA, with participation of the German Aerospace Center DLR. Its objective is to obtain the most complete high-resolution digital topographic database of the Earth

  1. 17 CFR 240.15c3-4 - Internal risk management control systems for OTC derivatives dealers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... unenforceable; (6) Procedures are in place to identify and address any deficiencies in the operating systems and... control systems for OTC derivatives dealers. 240.15c3-4 Section 240.15c3-4 Commodity and Securities...-Counter Markets § 240.15c3-4 Internal risk management control systems for OTC derivatives dealers. (a) An...

  2. 17 CFR 240.15c3-4 - Internal risk management control systems for OTC derivatives dealers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... unenforceable; (6) Procedures are in place to identify and address any deficiencies in the operating systems and... control systems for OTC derivatives dealers. 240.15c3-4 Section 240.15c3-4 Commodity and Securities...-Counter Markets § 240.15c3-4 Internal risk management control systems for OTC derivatives dealers. (a) An...

  3. 17 CFR 240.15c3-4 - Internal risk management control systems for OTC derivatives dealers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... unenforceable; (6) Procedures are in place to identify and address any deficiencies in the operating systems and... control systems for OTC derivatives dealers. 240.15c3-4 Section 240.15c3-4 Commodity and Securities...-Counter Markets § 240.15c3-4 Internal risk management control systems for OTC derivatives dealers. (a) An...

  4. Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study

    PubMed Central

    Prachayasittikul, Veda; Pingaew, Ratchanok; Worachartcheewan, Apilak; Sitthimonchai, Somkid; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

    2017-01-01

    A series of 2-amino(chloro)-3-chloro-1,4-naphthoquinone derivatives (1-11) were investigated for their aromatase inhibitory activities. 1,4-Naphthoquinones 1 and 4 were found to be the most potent compounds affording IC50 values 5.2 times lower than the reference drug, ketoconazole. A quantitative structure-activity relationship (QSAR) model provided good predictive performance (R2CV = 0.9783 and RMSECV = 0.0748) and indicated mass (Mor04m and H8m), electronegativity (Mor08e), van der Waals volume (G1v) and structural information content index (SIC2) descriptors as key descriptors governing the activity. To investigate the effects of structural modifications on aromatase inhibitory activity, the model was employed to predict the activities of an additional set of 39 structurally modified compounds constructed in silico. The prediction suggested that the 2,3-disubstitution of 1,4-naphthoquinone ring with halogen atoms (i.e., Br, I and F) is the most effective modification for potent activity (1a, 1b and 1c). Importantly, compound 1b was predicted to be more potent than its parent compound 1 (11.90-fold) and the reference drug, letrozole (1.03-fold). The study suggests the 1,4-naphthoquinone derivatives as promising compounds to be further developed as a novel class of aromatase inhibitors. PMID:28827987

  5. Synthesis, Urease Inhibition, Antioxidant, Antibacterial, and Molecular Docking Studies of 1,3,4-Oxadiazole Derivatives

    PubMed Central

    Hanif, Muhammad; Shoaib, Khurram; Saleem, Muhammad; Hasan Rama, Nasim; Zaib, Sumera; Iqbal, Jamshed

    2012-01-01

    A series of eighteen 1,3,4-oxadiazole derivatives have been synthesized by treating aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide yielding potassium salts of 1,3,4-oxadiazoles. Upon neutralization with 1 N hydrochloric acid yielded crude crystals of 1,3,4-oxadiazoles, which were purified by recrystallization in boiling methanol. The synthesized 1,3,4-oxadiazoles derivatives were evaluated in vitro for their urease inhibitory activities, most of the investigated compounds were potent inhibitors of Jack bean urease. The molecular docking studies were performed by docking them into the crystal structure of Jack bean urease to observe the mode of interaction of synthesized compounds. The synthesized compounds were also tested for antibacterial and antioxidant activities and some derivatives exhibited very promising results. PMID:22934191

  6. Synthesis and activity of phenyl derivatives containing 5,6-dimethylthieno[2,3-d]pyrimidin-4(1H)-one or 4H-pyrimido[5,4-b]indol-4-one heterocyclic system as potential nonsteroidal anti-inflammatory drugs.

    PubMed

    Santagati, Andrea; Granata, Giuseppe; Santagati, Maria; Cutuli, Vincenza; Mangano, Nunzio Guido; Caruso, Antonina

    2002-01-01

    The synthesis, the analgesic and anti-inflammatory activities of two series of phenyl derivatives containing 5,6-dimethyl-thieno[2,3-d]pyrimidin-4(1H)-one and 4H-pyrimido[5,4-b]indol-4-one system, respectively, are reported. Two of these derivatives, 6A and 9B, showed interesting activities. The results of the pharmacological assays are discussed.

  7. A novel series of 1, 4-Dihydropyridine (DHP) derivatives bearing thiazolidin-4-one: From synthesis to structure

    NASA Astrophysics Data System (ADS)

    Bade, Tahseen S.; Ebrahimi, Hossein Pasha; Alsalim, Tahseen A.; Titinchi, Salam J. J.; Abbo, Hanna S.; Bolandnazar, Zeinab; Ebrahimi, Amirpasha

    2017-06-01

    A novel series of 1, 4-Dihydropyridine (DHP) thiazolidin-4-one compounds derived from dihydropyridine hydrazones Schiff bases with thioglycolic acid were synthesized through an efficient Hantzsch reaction and experimentally characterized by spectral methods using IR, 1H NMR, 13C NMR, and mass spectroscopic methods. Herein, DHPs were synthesized by an improved Hantzsch procedure in the excellent yields by three different conditions including reflux condensation, fusion, and the microwave irradiation. An additional comparison of applied methodology routes was used to confirm the advantages including short reaction time, good yields, and operational simplicity. Furthermore, the structural and electronic properties of the studied molecules were theoretically investigated by performing density functional theory (DFT) to access reliable results to the experimental values. The molecular geometry, HOMO, and LUMO of the studied compounds were calculated. The theoretical 13C chemical shift results were also calculated using the gauge independent atomic orbital (GIAO) approach and their respective linear correlations were obtained.

  8. Recruitment of bone marrow-derived cells to the periodontal ligament via the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 axis.

    PubMed

    Kaku, M; Kitami, M; Rosales Rocabado, J M; Ida, T; Akiba, Y; Uoshima, K

    2017-08-01

    The periodontal ligament (PDL) is a non-mineralized connective tissue that exists between the alveolar bone and root surface cementum and plays important roles in tooth function. The PDL harbors a remarkable reserve of multipotent stem cells, which maintain various types of cells. However, the sources of these stem cells, other than their developmental origin, are not well understood. To elucidate the recruitment of bone marrow (BM)-derived stem cells in the PDL, green fluorescent protein (GFP)-expressing BM-derived cells were transplanted into the femoral BM of immunodeficient rats, and the distribution and expression of stem cell markers in the PDL were analyzed in vivo. To evaluate the functional significance of BM-derived cells to the PDL, tooth replantation was performed and the expression of stromal cell-derived factor (SDF)-1, a critical chemotactic signal for mesenchymal stem cell recruitment, was analyzed. To confirm the SDF-1-dependency of BM-derived cell migration to the PDL, PDL-conditioned medium (CM) was prepared, and BM-derived cell migration was analyzed using a transwell culture system. Four weeks after cell transplantation, GFP-positive cells were detected in the PDL, and some of them were also positive for stem cell markers (i.e., CD29, SSEA4, and αSMA). Seven days after tooth replantation, the number of GFP- and SDF-1-positive cells significantly increased in PDL. Concurrently, the concentration of SDF-1 and the number of colony-forming units of fibroblasts in peripheral blood were increased. BM-derived cell migration increased in PDL-CM and was inhibited by an inhibitor of C-X-C chemokine receptor type 4 (CXCR4), an SDF-1 receptor. These results indicate that stem cells and their progeny in PDL are not only derived from their developmental origin but are also supplied from the BM via the blood as the need arises. Moreover, this BM-derived cell recruitment appears to be regulated, at least partially, by the SDF-1/CXCR4 axis. © 2017 John Wiley

  9. Identification of a novel HLA-A*02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene

    PubMed Central

    YOSHIMURA, MAYUKO; TADA, YOSHITAKA; OFUZI, KAZUYA; YAMAMOTO, MASAKAZU; NAKATSURA, TETSUYA

    2014-01-01

    Cancer immunotherapy is a promising new approach to cancer treatment. It has been demonstrated that a high number of tumor-specific cytotoxic T cells (CTLs) is associated with increased disease-specific survival in lung cancer patients. Identification of superior CTL epitopes from tumor antigens is essential for the development of immunotherapy for malignant tumors. The EML4-ALK fusion gene was recently identified in a subset of non-small cell lung cancers (NSCLCs). In this study we searched for HLA-A*02:01- and HLA-A*24:02-restricted epitopes derived from EML4-ALK by screening predicted EML4-ALK-derived candidate peptides for the induction of tumor-reactive CTLs. Nine EML4-ALK-derived peptides were selected by a computer algorithm based on a permissive HLA-A*02:01 or HLA-A*24:02 binding motif. One of the nine peptides induced peptide-specific CTLs from human peripheral blood mononuclear cells. We were able to generate a peptide-specific CTL clone. This CTL clone specifically recognized peptide-pulsed T2 cells and H2228 cells expressing HLA-A*02:01 and EML4-ALK that had been treated with IFN-γ 48 h prior to examination. CTL activity was inhibited by an anti-HLA-class I monoclonal antibody (W6/32), consistent with a class I-restricted mechanism of cytotoxicity. These results suggest that this peptide (RLSALESRV) is a novel HLA-A*02:01-restricted CTL epitope and that it may be a new target for antigen-specific immunotherapy against EML4-ALK-positive cancers. PMID:24842630

  10. Identification of a novel HLA-A 02:01-restricted cytotoxic T lymphocyte epitope derived from the EML4-ALK fusion gene.

    PubMed

    Yoshimura, Mayuko; Tada, Yoshitaka; Ofuzi, Kazuya; Yamamoto, Masakazu; Nakatsura, Tetsuya

    2014-07-01

    Cancer immunotherapy is a promising new approach to cancer treatment. It has been demonstrated that a high number of tumor-specific cytotoxic T cells (CTLs) is associated with increased disease-specific survival in lung cancer patients. Identification of superior CTL epitopes from tumor antigens is essential for the development of immunotherapy for malignant tumors. The EML4-ALK fusion gene was recently identified in a subset of non-small cell lung cancers (NSCLCs). In this study we searched for HLA-A 02:01- and HLA-A 24:02‑restricted epitopes derived from EML4-ALK by screening predicted EML4-ALK‑derived candidate peptides for the induction of tumor‑reactive CTLs. Nine EML4-ALK‑derived peptides were selected by a computer algorithm based on a permissive HLA-A 02:01 or HLA-A 24:02 binding motif. One of the nine peptides induced peptide-specific CTLs from human peripheral blood mononuclear cells. We were able to generate a peptide‑specific CTL clone. This CTL clone specifically recognized peptide‑pulsed T2 cells and H2228 cells expressing HLA-A 02:01 and EML4-ALK that had been treated with IFN-γ 48 h prior to examination. CTL activity was inhibited by an anti-HLA‑class I monoclonal antibody (W6/32), consistent with a class I-restricted mechanism of cytotoxicity. These results suggest that this peptide (RLSALESRV) is a novel HLA-A 02:01-restricted CTL epitope and that it may be a new target for antigen-specific immunotherapy against EML4‑ALK-positive cancers.

  11. CRM1 inhibitory and antiproliferative activities of novel 4'-alkyl substituted klavuzon derivatives.

    PubMed

    Kanbur, Tuğçe; Kara, Murat; Kutluer, Meltem; Şen, Ayhan; Delman, Murat; Alkan, Aylin; Otaş, Hasan Ozan; Akçok, İsmail; Çağır, Ali

    2017-08-15

    Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4'-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4'-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Formation of a 1,4-diamino-2,3-disila-1,3-butadiene derivative.

    PubMed

    Mondal, Kartik Chandra; Roesky, Herbert W; Dittrich, Birger; Holzmann, Nicole; Hermann, Markus; Frenking, Gernot; Meents, Alke

    2013-10-30

    A 1,4-diamino-2,3-disila-1,3-butadiene derivative of composition (Me2-cAAC)2(Si2Cl2) (Me2-cAAC = :C(CMe2)2(CH2)N-2,6-iPr2C6H3) was synthesized by reduction of the Me2-cAAC:SiCl4 adduct with KC8. This compound is stable at 0 °C for 3 months in an inert atmosphere. Theoretical studies reveal that the silicon atoms exhibit pyramidal coordination, where the Cl-Si-Si-Cl dihedral angle is twisted by 43.3° (calcd 45.9°). The two silicon-carbon bonds are intermediates between single and double Si-C bonds due to twisting of the C-Si-Si-C dihedral angle (163.6°).

  13. Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.

    PubMed

    Miki, Takashi; Kori, Masakuni; Mabuchi, Hiroshi; Tozawa, Ryu-ichi; Nishimoto, Tomoyuki; Sugiyama, Yasuo; Teshima, Koichiro; Yukimasa, Hidefumi

    2002-09-26

    Modification of the carboxyl group at the 3-position and introduction of protective groups to the hydroxy group of the 4,1-benzoxazepine derivative 2 (metabolite of 1) were carried out, and the inhibitory activity for squalene synthase and cholesterol synthesis in the liver was investigated. Among these compounds, the glycine derivative 3a and beta-alanine derivative 3f exhibited the most potent inhibition of squalene synthase prepared from HepG2 cells (IC(50) = 15 nM). On the other hand, the piperidine-4-acetic acid derivative 4a, which was prepared by acetylation of 3j, was the most effective inhibitor of cholesterol synthesis in rat liver (ED(50) = 2.9 mg/kg, po). After oral administration, 4a was absorbed and rapidly hydrolyzed to deacylated 3j. Compound 3j was detected mainly in the liver, but the plasma level of 3j was found to be low. Compounds 3j and 4a were found to be competitive inhibitors with respect to farnesyl pyrophosphate. Further evaluation of 4a as a cholesterol-lowering and antiatherosclerotic agent is underway.

  14. Occupation Time Laws for Birth and Death Processes

    DTIC Science & Technology

    1960-07-30

    given consists of the birth and death rates X,, ji,,. We present a theory in which the hypotheses (3), (4), and (6) are derived from knowledge of the...asymptotic behavior of the birth and death rates X.,A. as n -- oo. Both the methods and the results can be extended to general diffusion processes and...Linear growth. Let (110) Xn = it + a, n> 0, An = n+ b, nn> 1,jio=O. This describes a model of biological growth where the birth and death rates are

  15. A method for deriving a 4D-interpolated balanced planning target for mobile tumor radiotherapy.

    PubMed

    Roland, Teboh; Hales, Russell; McNutt, Todd; Wong, John; Simari, Patricio; Tryggestad, Erik

    2012-01-01

    Tumor control and normal tissue toxicity are strongly correlated to the tumor and normal tissue volumes receiving high prescribed dose levels in the course of radiotherapy. Planning target definition is, therefore, crucial to ensure favorable clinical outcomes. This is especially important for stereotactic body radiation therapy of lung cancers, characterized by high fractional doses and steep dose gradients. The shift in recent years from population-based to patient-specific treatment margins, as facilitated by the emergence of 4D medical imaging capabilities, is a major improvement. The commonly used motion-encompassing, or internal-target volume (ITV), target definition approach provides a high likelihood of coverage for the mobile tumor but inevitably exposes healthy tissue to high prescribed dose levels. The goal of this work was to generate an interpolated balanced planning target that takes into account both tumor coverage and normal tissue sparing from high prescribed dose levels, thereby improving on the ITV approach. For each 4DCT dataset, 4D deformable image registration was used to derive two bounding targets, namely, a 4D-intersection and a 4D-composite target which minimized normal tissue exposure to high prescribed dose levels and maximized tumor coverage, respectively. Through definition of an "effective overlap volume histogram" the authors derived an "interpolated balanced planning target" intended to balance normal tissue sparing from prescribed doses with tumor coverage. To demonstrate the dosimetric efficacy of the interpolated balanced planning target, the authors performed 4D treatment planning based on deformable image registration of 4D-CT data for five previously treated lung cancer patients. Two 4D plans were generated per patient, one based on the interpolated balanced planning target and the other based on the conventional ITV target. Plans were compared for tumor coverage and the degree of normal tissue sparing resulting from the new

  16. Design, synthesis, and structure-activity relationships of 3,4-dihydropyridopyrimidin-2(1H)-one derivatives as a novel class of sodium/calcium exchanger inhibitor.

    PubMed

    Hasegawa, Hirohiko; Muraoka, Masami; Ohmori, Mikiko; Matsui, Kazuki; Kojima, Atsuyuki

    2005-10-01

    Design, synthesis, and structure-activity relationships for 3,4-dihydropyridopyrimidin-2(1H)-one derivatives, which are aza-3,4-dihydro-2(1H)-quinazolinone derivatives, as the sodium/calcium (Na+/Ca2+) exchanger inhibitors are discussed. These studies based on 3,4-dihydro-2(1H)-quinazolinone derivatives led to the discovery of a structurally novel and potent Na+/Ca2+ exchanger inhibitor, 3,4-dihydropyridopyrimidin-2(1H)-one derivative (26), with an IC30 value of 0.02 microM. Compound 26 directly inhibited the Na+-dependent Ca2+ influx via the Na+/Ca2+ exchanger after Na+-free treatment in cardiomyocytes.

  17. Search for new potential anticonvulsants with anxiolytic and antidepressant properties among derivatives of 4,4-diphenylpyrrolidin-2-one.

    PubMed

    Malawska, Katarzyna; Rak, Aleksandra; Gryzło, Beata; Sałat, Kinga; Michałowska, Małgorzata; Żmudzka, Elżbieta; Lodarski, Krzysztof; Malawska, Barbara; Kulig, Katarzyna

    2017-02-01

    The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction. The obtained compounds were assessed and tested for their anticonvulsant activity in two screening mouse models of seizures, i.e., the maximal electroshock (MES) test and in the subcutaneous pentylenetetrazole (scPTZ) test. The effect of these compounds on animals' motor coordination was measured in the rotarod test. A selected 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) was evaluated in vivo for its anxiolytic- and antidepressant-like properties. Its impact on animals' locomotor activity was also evaluated. Compound 8 showed protection (25%) in the MES and in the scPTZ tests at the dose of 100mg/kg and was not neurotoxic. In the four-plate test, compound 8 at the dose of 30mg/kg showed a statistically significant (p<0.05) anxiolytic-like activity. In the forced swim test, it reduced the immobility time by 24.3% (significant at p<0.05), which indicates its potential antidepressant-like properties. In the locomotor activity test, compound 8 significantly reduced animals' locomotor activity by 79.9%. The results obtained make a new derivative of 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) a promising lead structure for further development. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  18. Development and optimization of the synthesis of new thiazolidin-4-one derivatives of ibuprofen.

    PubMed

    Vasincu, Ioana; Apotrosoaei, Maria; Panzariu, Andreea; Buron, F; Routier, S; Profire, Lenuta

    2014-01-01

    Ibuprofen, an important nonsteroidal anti-inflammatory agent, is one of the most prescribed drugs for the treatment of pain and inflammation from various rheumatic diseases, but some side effects can occur on long-term use. The method for synthesis optimization of new derivatives of Ibuprofen with thiazolidin-4-one moiety, with improved pharmacological and toxicological profile. To optimize the derivatization method of free carboxyl group of Ibuprofen (2-(4-isobutylphenyl)propionic acid) the reaction conditions were varied (reagent ratio, catalyst, reaction medium). The most favorable method was proved to be the reaction between ibuprofen hydrazone and mercaptoacetic acid, in excess, at 80-85 degrees C, for 6 h with 96% conversion rate. The synthesis of 2-phenyl-3-[2-(4-(isobutyl)phenyl)-2-methyl]acetamido-thiazolidin-4-one derivative was optimized in view of applying it as a general procedure for the synthesis of other derivatives with related structure. The chemical structure and molecular weight of the synthesized compound were confirmed by spectral methods (IR, 1H NMR, 13C NMR, HR-MS).

  19. Annulation of β-naphthols and 4-hydroxycoumarins with vinylsulfonium salts: synthesis of dihydrofuran derivatives.

    PubMed

    Chen, Zi-Cong; Tong, Lang; Du, Zhi-Bo; Mao, Zhi-Feng; Zhang, Xue-Jing; Zou, Yong; Yan, Ming

    2018-04-18

    A new synthetic approach to dihydrofuran derivatives via the annulation reaction of β-naphthols and 4-hydroxycoumarins with vinylsulfonium salts has been developed. A variety of dihydrofuran derivatives were prepared in moderate to good yields under mild conditions. The products could be readily transformed to the corresponding furans via the dehydrogenation with DDQ.

  20. Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity.

    PubMed

    Di Pisa, Flavio; Landi, Giacomo; Dello Iacono, Lucia; Pozzi, Cecilia; Borsari, Chiara; Ferrari, Stefania; Santucci, Matteo; Santarem, Nuno; Cordeiro-da-Silva, Anabela; Moraes, Carolina B; Alcantara, Laura M; Fontana, Vanessa; Freitas-Junior, Lucio H; Gul, Sheraz; Kuzikov, Maria; Behrens, Birte; Pöhner, Ina; Wade, Rebecca C; Costi, Maria Paola; Mangani, Stefano

    2017-03-08

    Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues ( 1 - 3 ) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes ( Trypanosoma brucei PTR1- Tb PTR1 and Leishmania major-Lm PTR1) and parasites ( Trypanosoma brucei and Leishmania infantum ). A crystal structure of Tb PTR1 in complex with compound 1 and the first crystal structures of Lm PTR1-flavanone complexes (compounds 1 and 3 ) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.

  1. Anion-π interaction in metal-organic networks formed by metal halides and tetracyanopyrazine

    NASA Astrophysics Data System (ADS)

    Rosokha, Sergiy V.; Kumar, Amar

    2017-06-01

    Co-crystallization of tetracyanopyrazine, TCP, with the tetraalkylammonium salts of linear [CuBr2]-, planar [PtCl4]2- or [Pt2Br6]2-, or octahedral [PtBr6]2- complexes resulted in formation of the alternating [MlXn]m-/TCP stacks separated by the Alk4N+ cations. These hybrid stacks showed multiple short contacts between halide ligands of the [MlXn]m- complexes and carbon atoms of the TCP acceptor indicating strong anion-π bonding between these species. It confirmed that the anion-π interaction is sufficiently strong to bring together such disparate components as ionic metal complexes and neutral aromatic molecules regardless of the geometry of the coordination compound. Structural features of the solid-state stacks and [MlXn]m-·TCP dyads resulted from the quantum-mechanical computations suggests that the molecular-orbital (weakly-covalent) component play an important role in association of the [MlXn]m- complexes with the TCP acceptor.

  2. Synthesis, crystal structure, and luminescence properties of a new nitride polymorph, β-Sr0.98Eu0.02AlSi4N7

    NASA Astrophysics Data System (ADS)

    Yoshimura, Fumitaka; Yamane, Hisanori; Nagasako, Makoto

    2018-02-01

    Prismatic vermilion single crystals 200 μm-2 mm in size, together with a white powder, were obtained by heating a mixture of binary nitrides containing Mg3N2 at 2030 °C under 0.85 MPa of N2. Yellow, thick-platelet single crystals with sizes of 150-500 μm were also found to grow at or near the surface of the product. Single crystal X-ray diffraction demonstrated that the vermilion crystals were orthorhombic Sr0.98Eu0.02AlSi4N7, which has been prepared in previous studies and is termed the α phase of this compound. The yellow crystals were revealed to be a new polymorph of Sr0.98Eu0.02AlSi4N7 (β phase) that crystalized in a monoclinic cell (a = 8.1062(1) Å, b = 9.0953(1) Å, c = 8.9802(2) Å, β = 111.6550(5)°, space group P21) with twins that could be examined by transmission and scanning transmission electron microscopy. β-Sr0.98Eu0.02AlSi4N7 was found to have a three-dimensional network structure formed by the stacking of two types of layers. One is a dreier layer of (Al/Si)N4 tetrahedra that consists of N vertex-sharing double chains of (Al/Si)N4 tetrahedra extending in the c-axis direction with Sr and Eu atoms aligned between the chains, while the other is a layer of (Al/Si)N4 tetrahedra connected by sharing N edges and vertexes. The crystal structure of β-Sr0.98Eu0.02AlSi4N7 is similar to those of certain oxynitrides, such as Sr3Al3+xSi13-xN21-xO2+x:Eu2+ (x ≈ 0) and Sr4.9Eu0.1Al5+xSi21-xN35-xO2+x (x ≈ 0). The peak wavelength and full width at half maximum in the emission spectrum obtained from single crystals of β-Sr0.98Eu0.02AlSi4N7 under excitation at 400 nm were 541 and 66 nm, respectively.

  3. Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.

    PubMed

    Kryza, Thomas; Silva, Lakmali M; Bock, Nathalie; Fuhrman-Luck, Ruth A; Stephens, Carson R; Gao, Jin; Samaratunga, Hema; Lawrence, Mitchell G; Hooper, John D; Dong, Ying; Risbridger, Gail P; Clements, Judith A

    2017-10-01

    The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  4. The first genetic characterization of a D4 measles virus strain derived from a patient with subacute sclerosing panencephalitis.

    PubMed

    Ivancic-Jelecki, Jelena; Baricevic, Marijana; Santak, Maja; Harcet, Matija; Tešović, Goran; Marusic Della Marina, Branka; Forcic, Dubravko

    2013-07-01

    Measles virus (MV) strains derived from patients with subacute sclerosing panencephalitis (SSPE), SSPE strains, possess numerous mutations when compared to viruses belonging to the same genotype and circulating in similar time period. Although many SSPE strains have been extensively characterized, none of them belongs to D4 genotype which currently predominates in Europe where it has caused a number of recent outbreaks/epidemics. We sequenced an MV derived from a patient with long-term SSPE; the virus was named MVs/Zagreb.CRO/30.06[D4] (SSPE). Initial genetic analysis showed that it belongs to D4 genotype. The sequences of genes encoding matrix and fusion proteins indicate premature protein terminations. Putative hemagglutin (H) protein is lengthened for 20 amino acids, which is the longest H protein elongation so far found in SSPE viruses. Nucleotides 1421 A, 1422 G, 1507 C and 1542 C in nucleoprotein gene open reading frame seem to be specific for this D4 strain, differentiating it from other D4 non-SSPE strains. Besides, a unique mutation at position 543 of H protein was found, histidine instead of tyrosine. As persistent MV infections are initially established by "normal" wild-type MV strains, the presented comparative analyses describe alterations that could be involved in the maintenance of persistent infection, disease development and progression. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. A novel biphenyl urea derivate inhibits the invasion of breast cancer through the modulation of CXCR4

    PubMed Central

    Zhan, Yingzhuan; Zhang, Han; Li, Jing; Zhang, Yanmin; Zhang, Jie; He, Langchong

    2015-01-01

    The increased migration and invasion of breast carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. CXCR4, the receptor for stromal-derived factor-1, is reportedly involved in breast carcinogenesis and invasion. In this study, we investigated a novel biphenyl urea derivate, TPD7 for its ability to affect CXCR4 expression as well as function in breast cancer cells. We demonstrated that TPD7 inhibited the breast cancer proliferation and down-regulated the CXCR4 expression on breast cancer cells both over-expressing and low-expressing HER2, an oncogene known to induce the chemokine receptor. Treatments with pharmacological proteasome inhibitors partial suppressed TPD7-induced decrease in CXCR4 expression. Real-time PCR analysis revealed that down-regulation of CXCR4 by TPD7 also occurred at the translational level. Inhibition of CXCR4 expression by TPD7 further correlated with the suppression of SDF-1α-induced migration and invasion in breast tumour cells, knockdown of CXCR4 attenuated TPD7-inhibitory effects. In addition, TPD7 treatment significantly suppressed matrix metalloproteinase (MMP)-2 and MMP-9 expression, the downstream targets of CXCR4, perhaps via inactivation of the ERK signaling pathway. Overall, our results showed that TPD7 exerted its anti-invasive effect through the down-regulation of CXCR4 expression and thus had the potential for the treatment of breast cancer. PMID:25753200

  6. Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary Aspergillosis.

    PubMed

    Caffrey-Carr, Alayna K; Hilmer, Kimberly M; Kowalski, Caitlin H; Shepardson, Kelly M; Temple, Rachel M; Cramer, Robert A; Obar, Joshua J

    2017-01-01

    Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how immune competent hosts maintain control of fungal infections while constantly being exposed to fungi is rapidly emerging. It is known that timely neutrophil recruitment to and activation in the lungs is critical to the host defense against development of invasive pulmonary aspergillosis, but the inflammatory sequelae necessary remains to be fully defined. Here, we show that 5-Lipoxygenase (5-LO) and Leukotriene B 4 (LTB 4 ) are critical for leukocyte recruitment and resistance to pulmonary A. fumigatus challenge in a fungal-strain-dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal anti-fungal response and in vivo LTB 4 production was at least partially dependent on myeloid-derived hypoxia inducible factor-1α. Overall, this study reveals a role for host-derived leukotriene synthesis in innate immunity to A. fumigatus .

  7. Synthesis of 2,4-dihydroxychalcone derivatives as potential antidepressant effect.

    PubMed

    Guan, L-P; Zhao, D-H; Chang, Y; Wen, Z-S; Tang, L-M; Huang, F-F

    2013-01-01

    In this study, twelve 2,4-dihydroxychalcone derivatives were synthesized and evaluated for antidepressant activities using the forced swimming test (FST). The pharmacological test showed that 6 compounds significantly reduced the immobility times in the FST at a dose of 10 mg/kg, indicative of antidepressant activity. Among the derivatives, compounds designated 3d and 3 h exhibited the best antidepressant activity, with reduced immobility time by 32.05% and 34.33%, respectively. In the 5-hydroxytryptophan-induced head-twitch test and yohimbine-induced mortality test, compounds 3d and 3 h increased head-twitch and increased the mortality rate. The mechanisms of the antidepressant effects of compounds 3d and 3 h may be related with the 5-HTP and NE nervous system. © Georg Thieme Verlag KG Stuttgart · New York.

  8. FABP4 plasma levels are increased in familial combined hyperlipidemia

    PubMed Central

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L.; Ascaso, Juan F.; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-01-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia. PMID:20388924

  9. 4-Mercaptophenylboronic acid SAMs on gold: comparison with SAMs derived from thiophenol, 4-mercaptophenol, and 4-mercaptobenzoic acid.

    PubMed

    Barriet, David; Yam, Chi Ming; Shmakova, Olga E; Jamison, Andrew C; Lee, T Randall

    2007-08-14

    We report the formation and characterization of self-assembled monolayers (SAMs) derived from the adsorption of 4-mercaptophenylboronic acid (MPBA) on gold. For comparison, SAMs derived from the adsorption of thiophenol (TP), 4-mercaptophenol (MP), and 4-mercaptobenzoic acid (MBA) were also examined. The structure and properties of the SAMs were evaluated by ellipsometry, contact-angle goniometry, polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). Specifically, ellipsometry was used to assess the formation of monolayer films, and contact angle measurements were used to determine the surface hydrophilicity and homogeneity. Separately, PM-IRRAS was used to evaluate the molecular composition and orientation as well as the intermolecular hydrogen bonding within the SAMs. Finally, XPS was used to evaluate the film composition and surface coverage (i.e., packing density), which was observed to increase in the following order: TP < MP < MPBA < MBA. A rationalization for the observed packing differences is presented. The XPS data indicate further that ultrahigh vacuum conditions induce the partial dehydration of MPBA SAMs with the concomitant formation of surface boronic anhydride species. Overall, the analytical data collectively show that the MPBA moieties in the SAMs exist in the acid form rather than the anhydride form under ambient laboratory conditions. Furthermore, stability studies find that MPBA SAMs are surprisingly labile in basic solution, where the terminal B-C bonds are cleaved by the attack of hydroxide ion and strongly basic amine nucleophiles. The unanticipated lability observed here should be considered by those wishing to use MPBA moieties in carbohydrate-sensing applications.

  10. Electrochemical, spectroscopic, and DFT study of C60(CF3)n frontier orbitals (n = 2-18): the link between double bonds in pentagons and reduction potentials.

    PubMed

    Popov, Alexey A; Kareev, Ivan E; Shustova, Natalia B; Stukalin, Evgeny B; Lebedkin, Sergey F; Seppelt, Konrad; Strauss, Steven H; Boltalina, Olga V; Dunsch, Lothar

    2007-09-19

    The frontier orbitals of 22 isolated and characterized C(60)(CF(3))(n) derivatives, including seven reported here for the first time, have been investigated by electronic spectroscopy (n = 2 [1], 4 [1], 6 [2], 8 [5], 10 [6], 12 [3]; the number of isomers for each composition is shown in square brackets) fluorescence spectroscopy (n = 10 [4]), cyclic voltammetry under air-free conditions (all compounds with n 4 [1] and 10 [1]), and quantum chemical calculations at the DFT level of theory (all compounds including n = 16 [3] and 18 [2]). DFT calculations are also reported for several hypothetical C(60)(CF(3))(n) derivatives. The X-ray structure of one of the compounds, 1,6,11,16,18,26,36,41,44,57-C(60)(CF(3))(10), is reported here for the first time. Most of the compounds with n a linear function of the DFT-predicted LUMO energies (average E1/2 deviation from the least-squares line is 0.02 V). This linear relationship was used to predict the 0/- E(1/2) values for the n = 16 and 18 derivatives, and none of the predicted values is more positive than the 0/- E(1/2) value for one of the isomers of C(60)(CF(3))(10). In general, reduction potentials for the 0/- couple are shifted anodically relative to the C(60)(0/-) couple. However, the 0/- E(1/2) values for a given composition are strongly dependent on the addition pattern of the CF3 groups. In addition, LUMO energies for isomers of C(60)(X)(n) (n = 2, 4, 6, 8, 10, and 12) that are structurally related to many of the CF(3) derivatives were calculated and compared for X = CH(3), H, Ph, NH(2), CH(2)F, CHF(2), F, NO(2), and CN. The experimental and computational results for the C(60)(CF(3))(n) compounds and the computational results for more than 50 additional C(60)(X)(n

  11. 4-hydroxyphenylacetic acid derivatives of inositol from dandelion (Taraxacum officinale) root characterised using LC-SPE-NMR and LC-MS techniques.

    PubMed

    Kenny, O; Smyth, T J; Hewage, C M; Brunton, N P; McLoughlin, P

    2014-02-01

    The combination of hyphenated techniques, LC-SPE-NMR and LC-MS, to isolate and identify minor isomeric compounds from an ethyl acetate fraction of Taraxacum officinale root was employed in this study. Two distinct fractions of 4-hydroxyphenylacetic acid derivatives of inositol were isolated and characterised by spectroscopic methods. The (1)H NMR spectra and MS data revealed two groups of compounds, one of which were derivatives of the di-4-hydroxyphenylacetic acid derivative of the inositol compound tetrahydroxy-5-[2-(4-hydroxyphenyl)acetyl] oxycyclohexyl-2-(4-hydroxyphenyl) acetate, while the other group consisted of similar tri-substituted inositol derivatives. For both fractions the derivatives of inositols vary in the number of 4-hydroxyphenylacetic acid groups present and their position and geometry on the inositol ring. In total, three di-substituted and three tri-substituted 4-hydroxyphenylacetic acid inositol derivates were identified for the first time along with a further two previously reported di-substituted inositol derivatives. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Synthesis and serotonergic activity of variously substituted (3-amido)phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT1B receptor.

    PubMed

    Moloney, Gerard P; Garavelas, Agatha; Martin, Graeme R; Maxwell, Miles; Glen, Robert C

    2004-04-01

    The synthesis and vascular 5-HT(1B) receptor activity of a novel series of substituted 3-amido phenylpiperazine and 4-(4-methyl-1-piperazinyl)-1-benzo[b]thiophene derivatives is described. Modifications to the amido linked sidechains of the 3-amidophenyl-piperazine derivatives and to the 2-sidechain of the 1-benzo[b]thiophene derivatives have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B) receptor of pK(B) > 7.0. From the 3-amidophenyl-piperazine series, N-(4-(4-chlorophenyl)thiazol-2-yl-3-(4-methyl-1-piperazinyl)benzamide (30) and from the benzo[b]thiophene-4-piperazine series N-(2-ethylphenyl)-4-(4-methyl-1- piperazinyl)-1-benzo[b]thiophene-2-carboxamide (38) were identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT(1B) receptor mediated agonist activity in the rabbit femoral artery) and competitive vascular 5-HT(1B) receptor antagonist. The affinity of compounds from these two series of compounds for the vascular 5-HT(1B) receptor is discussed as well as a proposed mode of binding to the receptor pharmacophore.

  13. Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells.

    PubMed

    Cheng, Jie; Li, Wenxin; Kang, Bo; Zhou, Yanwen; Song, Jiasheng; Dan, Songsong; Yang, Ying; Zhang, Xiaoqian; Li, Jingchao; Yin, Shengyong; Cao, Hongcui; Yao, Hangping; Zhu, Chenggang; Yi, Wen; Zhao, Qingwei; Xu, Xiaowei; Zheng, Min; Zheng, Shusen; Li, Lanjuan; Shen, Binghui; Wang, Ying-Jie

    2015-06-10

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that responds to environmental toxicants, is increasingly recognized as a key player in embryogenesis and tumorigenesis. Here we show that a variety of tryptophan derivatives that act as endogenous AhR ligands can affect the transcription level of the master pluripotency factor Oct4. Among them, ITE enhances the binding of the AhR to the promoter of Oct4 and suppresses its transcription. Reduction of endogenous ITE levels in cancer cells by tryptophan deprivation or hypoxia leads to Oct4 elevation, which can be reverted by administration with synthetic ITE. Consequently, synthetic ITE induces the differentiation of stem-like cancer cells and reduces their tumorigenic potential in both subcutaneous and orthotopic xenograft tumour models. Thus, our results reveal a role of tryptophan derivatives and the AhR signalling pathway in regulating cancer cell stemness and open a new therapeutic avenue to target stem-like cancer cells.

  14. Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells

    PubMed Central

    Cheng, Jie; Li, Wenxin; Kang, Bo; Zhou, Yanwen; Song, Jiasheng; Dan, Songsong; Yang, Ying; Zhang, Xiaoqian; Li, Jingchao; Yin, Shengyong; Cao, Hongcui; Yao, Hangping; Zhu, Chenggang; Yi, Wen; Zhao, Qingwei; Xu, Xiaowei; Zheng, Min; Zheng, Shusen; Li, Lanjuan; Shen, Binghui; Wang, Ying-Jie

    2015-01-01

    The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that responds to environmental toxicants, is increasingly recognized as a key player in embryogenesis and tumorigenesis. Here we show that a variety of tryptophan derivatives that act as endogenous AhR ligands can affect the transcription level of the master pluripotency factor Oct4. Among them, ITE enhances the binding of the AhR to the promoter of Oct4 and suppresses its transcription. Reduction of endogenous ITE levels in cancer cells by tryptophan deprivation or hypoxia leads to Oct4 elevation, which can be reverted by administration with synthetic ITE. Consequently, synthetic ITE induces the differentiation of stem-like cancer cells and reduces their tumorigenic potential in both subcutaneous and orthotopic xenograft tumour models. Thus, our results reveal a role of tryptophan derivatives and the AhR signalling pathway in regulating cancer cell stemness and open a new therapeutic avenue to target stem-like cancer cells. PMID:26059097

  15. Synthesis and characterization of a Eu-DTPA-PEGO-MSH(4) derivative for evaluation of binding of multivalent molecules to melanocortin receptors.

    PubMed

    Xu, Liping; Vagner, Josef; Alleti, Ramesh; Rao, Venkataramanarao; Jagadish, Bhumasamudram; Morse, David L; Hruby, Victor J; Gillies, Robert J; Mash, Eugene A

    2010-04-15

    A labeled variant of MSH(4), a tetrapeptide that binds to the human melanocortin 4 receptor (hMC4R) with low microM affinity, was prepared by solid-phase synthesis methods, purified, and characterized. The labeled ligand, Eu-DTPA-PEGO-His-dPhe-Arg-Trp-NH(2), exhibited a K(d) for hMC4R of 9.1+/-1.4 microM, approximately 10-fold lower affinity than the parental ligand. The labeled MSH(4) derivative was employed in a competitive binding assay to characterize the interactions of hMC4R with monovalent and divalent MSH(4) constructs derived from squalene. The results were compared with results from a similar assay that employed a more potent labeled ligand, Eu-DTPA-NDP-alpha-MSH. While results from the latter assay reflected only statistical effects, results from the former assay reflected a mixture of statistical, proximity, and/or cooperative binding effects. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. NSAI activity study of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives.

    PubMed

    Darias, V; Abdallah, S S; Tello, M L; Delgado, L D; Vega, S

    1994-12-01

    A series of 4-phenyl-2-thioxo-benzo[4,5]thieno[2,3-d]pyrimidine derivatives endowed with anti-inflammatory and related pharmacological properties were submitted to a more extensive study to know their exact pharmacological profile and their possible side effects. The studied compounds possess a remarkable analgesic activity, devoid of central effects. They also show an interesting anti-inflammatory profile evidenced by their effectiveness in different experimental models of inflammation. In addition, these compounds exhibit none or very little activity on CNS, scarce toxicity and low gastrointestinal aggressivity.

  17. Synthesis and biological activity of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives: in silico approach.

    PubMed

    Khobragade, Chandrahas N; Bodade, Ragini G; Dawane, Bhaskar S; Konda, Shankaraiah G; Khandare, Namdev T

    2010-10-01

    Xanthine oxidase (XO) is responsible for the pathological condition called gout. Inhibition of XO activity by various pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidine-4-one derivatives was assessed and compared with the standard inhibitor allopurinol. Out of 10 synthesized compounds, two compounds, viz. 3-amino-6-(2-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3b) and 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) were found to have promising XO inhibitory activity of the same order as allopurinol. Both compounds and allopurinol inhibited competitively with comparable Ki (3b: 3.56 microg, 3g: 2.337 microg, allopurinol: 1.816 microg) and IC(50) (3b: 4.228 microg, 3g: 3.1 microg, allopurinol: 2.9 microg) values. The enzyme-ligand interaction was studied by molecular docking using Autodock in BioMed Cache V. 6.1 software. The results revealed a significant dock score for 3b (-84.976 kcal/mol) and 3g (-90.921 kcal/mol) compared with allopurinol (-55.01 kcal/mol). The physiochemical properties and toxicity of the compounds were determined in silico using online computational tools. Overall, in vitro and in silico study revealed 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) as a potential lead compound for the design and development of XO inhibitors.

  18. 76 FR 33394 - Arkansas Disaster Number AR-00048

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12560 and 12561] Arkansas Disaster Number AR-00048 AGENCY: U.S. Small Business Administration. ACTION: Amendment 4. SUMMARY: This is an amendment of the Presidential declaration of a major disaster for the State of Arkansas (FEMA-1975-DR), dated 05/02...

  19. Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase

    PubMed Central

    Paumo, Hugues K.

    2017-01-01

    Series of the 2-unsubstituted and 2-(4-chlorophenyl)–substituted 4-anilino-6-bromoquinazolines and their 6-(4-fluorophenyl)–substituted derivatives were evaluated for in vitro cytotoxicity against MCF-7 and HeLa cells. The 2-unsubstituted 4-anilino-6-bromoquinazolines lacked activity, whereas most of their 2-(4-chlorophenyl) substituted derivatives were found to exhibit significant cytotoxicity and selectivity against HeLa cells. Replacement of bromine with 4-fluorophenyl group for the 2-unsubstituted 4-anilinoquinazolines resulted in superior activity against HeLa cells compared to Gefitinib. The presence of a 4-fluorophenyl group in the 2-(4-chlorophenyl) substituted derivatives led to increased cytotoxicity against HeLa cells, except for the 3-chloroanilino derivative. The most active compounds, namely, 3g, 3l, and 4l, were found to exhibit a moderate to significant inhibitory effect against epidermal growth factor receptor tyrosine kinase (EGFR-TK). The EGFR molecular docking model suggested that these compounds are nicely bound to the region of EGFR. PMID:29156606

  20. Quantitative structure activity relationship studies of piperazinyl phenylalanine derivatives as VLA-4/VCAM-1 inhibitors.

    PubMed

    Bhargava, Dinesh; Karthikeyan, C; Moorthy, N S H N; Trivedi, Piyush

    2009-09-01

    QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square (forward) regression method showed 85.67% variation in biological activity. The statistically significant model with high correlation coefficient (r2=0.85) was selected for further study and the resulted validation parameters of the model, crossed squared correlation coefficient (q2=0.76 and pred_r2=0.42) show the model has good predictive ability. The model showed that the parameters SaaNEindex, SsClcount slogP,and 4PathCount are highly correlated with VLA-4/VCAM-1 inhibitory activity of piperazinyl phenylalanine derivatives. The result of the study suggests that the chlorine atoms in the molecule and fourth order fragmentation patterns in the molecular skeleton favour VLA-4/VCAM-1 inhibition shown by the title compounds whereas lipophilicity and nitrogen bonded to aromatic bond are not conducive for VLA-4/VCAM-1 inhibitory activity.

  1. Understanding Am3+/Cm3+ separation with H4TPAEN and its hydrophilic derivatives: a quantum chemical study.

    PubMed

    Huang, Pin-Wen; Wang, Cong-Zhi; Wu, Qun-Yan; Lan, Jian-Hui; Song, Gang; Chai, Zhi-Fang; Shi, Wei-Qun

    2018-05-23

    Am3+/Cm3+ separation is an extremely hard but important task in nuclear waste treatment. In this study, Am and Cm complexes formed with a back-extraction agent N,N,N',N'-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylene-diamine (H4TPAEN) and its two derivatives with hydrophilic substituents (methoxy and morpholine groups) were investigated using the density functional theory (DFT). The optimized geometrical structures indicated that the Am3+ cation matched better with the cavities of the three studied ligands than Cm3+, and the Am3+ cations were located deeper in the cavities of the ligands. The bond order and quantum theory of atoms in molecules (QTAIM) analyses suggested that ionic interactions dominated An-N and An-O (An = Cm and Am) bonds. However, weak and different extents of partial covalency could also be found in the Am-N and Cm-N bonds. The O donor atoms in the carboxylate groups preferably coordinated with Cm3+ rather than Am3+, whereas the N atoms preferred Am3+. Therefore, the Am3+/Cm3+ selectivity of H4TPAEN and its two hydrophilic derivatives may be ascribed to the competition between the An-N and An-O interactions and the few dissimilarities in their geometrical structures. Based on our calculations, the methoxy and morpholine groups in the two derivatives can serve as electron-donating groups and enhance the strength of the An-NPY bonds (NPY denotes the nitrogen atom of pyridine ring). When compared with the Am-complex, the Cm-complex exhibited significant strength effect, resulting in the relatively lower Am3+/Cm3+ separation ability of the H4TPAEN's hydrophilic derivatives.

  2. 1,2,4-triazole derivative with Schiff base; thiol-thione tautomerism, DFT study and antileishmanial activity

    NASA Astrophysics Data System (ADS)

    Süleymanoğlu, Nevin; Ustabaş, Reşat; Direkel, Şahin; Alpaslan, Yelda Bingöl; Ünver, Yasemin

    2017-12-01

    Thiol-thione tautomerism of 1,2,4-triazole derivative with Schiff base was investigated by spectroscopic methods and quantum mechanical calculations. Theoretical study of thiol-thione tautomeric forms of 1,2,4-triazole derivative with Schiff base; 1,2,4-triazole-thiol form, 1-((5-mercapto-4-(thiophene-2-ylmethyleneamino)-4H-1,2,4-triazole-3-yl)methyl)-3-(thiophene-2-ylmethyl)-4-(thiophene-2-ylmethyleneamino)-1H-1,2,4-triazole-5(4H)-one (I) and 1,2,4-triazole-thione form, 3-(thiophene-2-ylmethyl)-4-(thiophene-2-ylmethyleneamino)-1-((4-(thiophene-2-ylmethyleneamino)-5-thioxo-4,5-dihydro-1H-1,2,4-triazole-3-yl)methyl)-1H-1,2,4-triazole-5(4H)-one (II) was performed by the density functional theory (DFT) method with 6-311++G(d,p) basis set. Structural parameters were obtained and spectral parameters of NMR, FTIR and UV-vis were compared with experimental ones to determine structural details. In vitro antileishmanial activity was studied against Leishmania infantum promastigots by microdilution broth assay with Alamar Blue Dye. The results indicate that 1,2,4-triazole derivative exists in both thiol and thione form and, can be evaluated as antiparasitic in term of antileishmanial activity.

  3. Territrem and Butyrolactone Derivatives from a Marine-Derived Fungus Aspergillus Terreus

    PubMed Central

    Nong, Xu-Hua; Wang, Yi-Fei; Zhang, Xiao-Yong; Zhou, Mu-Ping; Xu, Xin-Ya; Qi, Shu-Hua

    2014-01-01

    Seventeen lactones including eight territrem derivatives (1–8) and nine butyrolactone derivatives (9–17) were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162 under solid-state fermentation of rice. Compounds 1–3 and 9–10 were new, and their structures were elucidated by spectroscopic analysis. The acetylcholinesterase inhibitory activity and antiviral activity of compounds 1–17 were evaluated. Among them, compounds 1 and 2 showed strong inhibitory activity against acetylcholinesterase with IC50 values of 4.2 ± 0.6, 4.5 ± 0.6 nM, respectively. This is the first time it has been reported that 3, 6, 10, 12 had evident antiviral activity towards HSV-1 with IC50 values of 16.4 ± 0.6, 6.34 ± 0.4, 21.8 ± 0.8 and 28.9 ± 0.8 μg·mL−1, respectively. Antifouling bioassay tests showed that compounds 1, 11, 12, 15 had potent antifouling activity with EC50 values of 12.9 ± 0.5, 22.1 ± 0.8, 7.4 ± 0.6, 16.1 ± 0.6 μg·mL−1 toward barnacle Balanus amphitrite larvae, respectively. PMID:25522319

  4. 8-Methly-4-(3-diethylaminopropylamino) pyrimido [4',5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivate that causes ROS-mediated apoptosis in leukemia cell lines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shenoy, Sudheer; Vasania, Viraf S.; Gopal, M.

    2007-07-01

    The present study reports the biological activity of 8-methly-4-(3-diethylamino-propylamino) pyrimido [4';5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivative structurally related to ellipticine and suggests a possible mechanism through which the compound induces apoptosis in carcinoma cell lines. Out of the 8 cell lines used in the study as representatives of different types of cancer, MDPTQ was found to be effective only against leukemia cell lines (HL-60 and K-562) whereas it had no effect on normal human bone marrow cells (BMC) which were used as controls. Fall mitochondrial membrane potential and increased reactive oxygen species (ROS) were mainly responsible for inducingmore » apoptosis in the two cell lines. Cell death was demonstrated by increase in caspase 3 activity as well as phosphatidyl serine exposure. Pre-incubation with N-acetylcysteine (NAC) reduced the increased ROS and caspase 3 activity as well as phosphatidyl serine exposure. MDPTQ also caused cell cycle arrest in these cell lines. The above study for the first time reports the mode of action of a quinoline derivative, which could be a possible future candidate for leukemia therapy. However, there are lot of questions that need to be answered in terms of signalling pathways and its effects on animal models.« less

  5. FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells

    PubMed Central

    Zhu, Min; Zhang, Qing-Jun; Wang, Lin; Li, Hao; Liu, Zhi-Ping

    2011-01-01

    Objectives FoxO proteins are transcription factors involved in varieties of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. Although these processes are implicated in the development of atherosclerosis, very little is known about the role of FoxO proteins in the context of atherosclerosis. Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis. Methods and Results Apolipoprotein E-deficient (apoE−/−) mice were crossbred with animals lacking Foxo4 (Foxo4−/−). After 10 weeks on a high fat diet (HFD), Foxo4−/−apoE−/− mice showed elevated atherosclerosis and increased amount of macrophages and T cells in the plaque compared to apoE−/− mice. Bone marrow transplantations of chimeric C57B/6 mice reconstituted with either wild-type or Foxo4−/− bone marrows indicate that Foxo4-deficiency in bone marrow derived cells sufficiently promoted atherosclerosis. Foxo4-null macrophages produced elevated inflammatory cytokine IL-6 and levels of reactive oxygen species (ROS) in response to lipopolysaccharides in vitro. Serum levels of IL-6 were upregulated in HFD-fed Foxo4−/−apoE−/− mice compared to those of apoE−/− mice. Conclusions FoxO4 inhibits atherosclerosis through bone marrow derived cells, possibly by inhibition of ROS and inflammatory cytokines that promote monocyte recruitment and/or retention. PMID:22005198

  6. Computational Replication of the Primary Isotope Dependence of Secondary Kinetic Isotope Effects in Solution Hydride-Transfer Reactions: Supporting the Isotopically Different Tunneling Ready State Conformations.

    PubMed

    Derakhshani-Molayousefi, Mortaza; Kashefolgheta, Sadra; Eilers, James E; Lu, Yun

    2016-06-30

    We recently reported a study of the steric effect on the 1° isotope dependence of 2° KIEs for several hydride-transfer reactions in solution (J. Am. Chem. Soc. 2015, 137, 6653). The unusual 2° KIEs decrease as the 1° isotope changes from H to D, and more in the sterically hindered systems. These were explained in terms of a more crowded tunneling ready state (TRS) conformation in D-tunneling, which has a shorter donor-acceptor distance (DAD) than in H-tunneling. To examine the isotopic DAD difference explanation, in this paper, following an activated motion-assisted H-tunneling model that requires a shorter DAD in a heavier isotope transfer process, we computed the 2° KIEs at various H/D positions at different DADs (2.9 Å to 3.5 Å) for the hydride-transfer reactions from 2-propanol to the xanthylium and thioxanthylium ions (Xn(+) and TXn(+)) and their 9-phenyl substituted derivatives (Ph(T)Xn(+)). The calculated 2° KIEs match the experiments and the calculated DAD effect on the 2° KIEs fits the observed 1° isotope effect on the 2° KIEs. These support the motion-assisted H-tunneling model and the isotopically different TRS conformations. Furthermore, it was found that the TRS of the sterically hindered Ph(T)Xn(+) system does not possess a longer DAD than that of the (T)Xn(+) system. This predicts a no larger 1° KIE in the former system than in the latter. The observed 1° KIE order is, however, contrary to the prediction. This implicates the stronger DAD-compression vibrations coupled to the bulky Ph(T)Xn(+) reaction coordinate.

  7. Generation of Some First-Order Autoregressive Markovian Sequences of Positive Random Variables with Given Marginal Distributions,

    DTIC Science & Technology

    1981-03-01

    Again E( XnX 1 Xn) Xn + (l-aB)/X PlXn-1 + (l-Pl)/x 2.11) and X0 E0 gives a stationary sequence. Thus the correla- tions and regressions are the...sequence, although the sample paths will tend to have runs-up. A similar analysis given in Lawrance and Lewis [5] shows that 1 1 + i a + au (3.7) E( XnX

  8. Novel PDE4 Inhibitors Derived from Chinese Medicine Forsythia

    PubMed Central

    Coon, Tiffany A.; McKelvey, Alison C.; Weathington, Nate M.; Birru, Rahel L.; Lear, Travis; Leikauf, George D.; Chen, Bill B.

    2014-01-01

    Cyclic adenosine monophosphate (cAMP) is a crucial intracellular second messenger molecule that converts extracellular molecules to intracellular signal transduction pathways generating cell- and stimulus-specific effects. Importantly, specific phosphodiesterase (PDE) subtypes control the amplitude and duration of cAMP-induced physiological processes and are therefore a prominent pharmacological target currently used in a variety of fields. Here we tested the extracts from traditional Chinese medicine, Forsythia suspense seeds, which have been used for more than 2000 years to relieve respiratory symptoms. Using structural-functional analysis we found its major lignin, Forsynthin, acted as an immunosuppressant by inhibiting PDE4 in inflammatory and immune cell. Moreover, several novel, selective small molecule derivatives of Forsythin were tested in vitro and in murine models of viral and bacterial pneumonia, sepsis and cytokine-driven systemic inflammation. Thus, pharmacological targeting of PDE4 may be a promising strategy for immune-related disorders characterized by amplified host inflammatory response. PMID:25549252

  9. Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors.

    PubMed

    Goto, Taiji; Shiina, Akiko; Yoshino, Toshiharu; Mizukami, Kiyoshi; Hirahara, Kazuki; Suzuki, Osamu; Sogawa, Yoshitaka; Takahashi, Tomoko; Mikkaichi, Tsuyoshi; Nakao, Naoki; Takahashi, Mizuki; Hasegawa, Masashi; Sasaki, Shigeki

    2013-11-15

    5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity (IC50=200 nM). Modification of the carboxylic acid moiety of 2 gave N-neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory activity (IC50=8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)-induced pulmonary neutrophilia in mice (ID50=16 mg/kg, ip). Furthermore, based on the X-ray crystallography of 10f bound to the human PDE4B catalytic domain, we designed 7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one derivative 39 which has a fused bicyclic lactam scaffold. Compound 39 exhibited excellent inhibitory activity against LPS-induced tumor necrosis factor alpha (TNF-α) production in mouse splenocytes (IC50=0.21 nM) and in vivo anti-inflammatory activity against LPS-induced pulmonary neutrophilia in mice (41% inhibition at a dose of 1.0 mg/kg, i.t.). Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. (86)Y production via (86)Sr(p,n) for PET imaging at a cyclotron.

    PubMed

    Sadeghi, M; Aboudzadeh, M; Zali, A; Zeinali, B

    2009-01-01

    Excitation functions of (86)Y production via (86)Sr(p,xn), (86)Sr(d,xn), (85)Rb(alpha,xn), (85)Rb((3)He,xn), and (nat)Zr(d,alphaxn) reactions were studied by means of ALICE-ASH code and the results were compared with ALICE-91 code and experimental data. The greatest nuclear reaction of cyclotron (86)Y production was found out as (86)Sr(p,n)(86)Y process. (86)Y production yield was calculated too. A SrCO(3) thick film was deposited on a copper substrate by sedimentation method. The deposited (nat)SrCO(3) was irradiated with 15MeV proton at 30microA current beam. The separation of Y from Cu and Sr was carried out by means of dual ion exchange chromatography.

  11. 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors

    PubMed Central

    2016-01-01

    We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay. PMID:26741168

  12. Long Life Elastomeric Aircraft Hydraulic Seals. Part I2

    DTIC Science & Technology

    1974-10-01

    Aminox Antioxidant ZMB Dibutoxyethyl Sebacate Diethylhexyl Azelate Varox AFE-XN1925- ■25 AFE -XN1925- ■33 AFE -XN1925- -43 AFE -XN1925-44 95.0...Antioxidant ZMB Dibutoxyethyl Sebacate Diethylhexyl Azelate Varox AFE-XN1925-45 AFE -XN1925-46 100.0 AFE -XN192^47 100.0 100.0 5.0 5.0 5.0 5.0 5.0...Chemigum N917 Magna.sium Oxide Zinc Oxide N550 FEF N330 HAF Aminox Antioxidant ZMB Dibutoxethyl Sebacate Diethylhexyl Azelate Varox AFE

  13. Spinning Characteristics of the XN2Y-1 Airplane Obtained from the Spinning Balance and Compared with Results from the Spinning Tunnel and from Flight Tests

    NASA Technical Reports Server (NTRS)

    Bamber, M J; House, R O

    1937-01-01

    Report presents the results of tests of a 1/10-scale model of the XN2Y-1 airplane tested in the NACA 5-foot vertical wind tunnel in which the six components of forces and moments were measured. The model was tested in 17 attitudes in which the full-scale airplane had been observed to spin, in order to determine the effects of scale, tunnel, and interference. In addition, a series of tests was made to cover the range of angles of attack, angles of sideslip, rates of rotation, and control setting likely to be encountered by a spinning airplane. The data were used to estimate the probable attitudes in steady spins of an airplane in flight and of a model in the free-spinning tunnel. The estimated attitudes of steady spin were compared with attitudes measured in flight and in the spinning tunnel. The results indicate that corrections for certain scale and tunnel effects are necessary to estimate full-scale spinning attitudes from model results.

  14. 40 CFR 721.10559 - Morpholine, 4-C6-12 acyl derivs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... subject to reporting. (1) The chemical substance identified as morpholine, 4-C6-12 acyl derivs. (PMN P-06...), (d), (e)(concentration set at 0.1 percent), (f), (g)(1)(systemic effects), (g)(2)(i), and (g)(2)(v...) through (h) are applicable to manufacturers, importers, and processors of this substance. (2) Limitations...

  15. 40 CFR 721.10559 - Morpholine, 4-C6-12 acyl derivs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... subject to reporting. (1) The chemical substance identified as morpholine, 4-C6-12 acyl derivs. (PMN P-06...), (d), (e)(concentration set at 0.1 percent), (f), (g)(1)(systemic effects), (g)(2)(i), and (g)(2)(v...) through (h) are applicable to manufacturers, importers, and processors of this substance. (2) Limitations...

  16. 17 CFR 240.15c3-4 - Internal risk management control systems for OTC derivatives dealers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Internal risk management...-Counter Markets § 240.15c3-4 Internal risk management control systems for OTC derivatives dealers. (a) An OTC derivatives dealer shall establish, document, and maintain a system of internal risk management...

  17. Selective epitaxial growth of zinc blende-derivative on wurtzite-derivative: the case of polytypic Cu2CdSn(S1-xSex)4 nanocrystals

    NASA Astrophysics Data System (ADS)

    Wu, Liang; Fan, Feng-Jia; Gong, Ming; Ge, Jin; Yu, Shu-Hong

    2014-02-01

    Polytypic nanocrystals with zinc blende (ZB) cores and wurtzite (WZ) arms, such as tetrapod and octopod nanocrystals, have been widely reported. However, polytypic nanocrystals with WZ cores and ZB arms or ends have been rarely reported. Here, we report a facile, solution-based approach to the synthesis of polytypic Cu2CdSn(S1-xSex)4 (CCTSSe) nanocrystals with ZB-derivative selectively engineered on (000+/-2)WZ facets of WZ-derived cores. Accordingly, two typical morphologies, i.e., bullet-like nanocrystals with a WZ-derivative core and one ZB-derivative end, and rugby ball-like nanocrystals with a WZ-derivative core and two ZB-derivative ends, can be selectively prepared. The epitaxial growth mechanism is confirmed by the time-dependent experiments. The ratio of rugby ball-like and bullet-like polytypic CCTSSe nanocrystals can be tuned through changing the amount of Cd precursor to adjust the reactivity difference between (0002)WZ and (000-2)WZ facets. These unique polytypic CCTSSe nanocrystals may find applications in energetic semiconducting materials for energy conversion in the future.Polytypic nanocrystals with zinc blende (ZB) cores and wurtzite (WZ) arms, such as tetrapod and octopod nanocrystals, have been widely reported. However, polytypic nanocrystals with WZ cores and ZB arms or ends have been rarely reported. Here, we report a facile, solution-based approach to the synthesis of polytypic Cu2CdSn(S1-xSex)4 (CCTSSe) nanocrystals with ZB-derivative selectively engineered on (000+/-2)WZ facets of WZ-derived cores. Accordingly, two typical morphologies, i.e., bullet-like nanocrystals with a WZ-derivative core and one ZB-derivative end, and rugby ball-like nanocrystals with a WZ-derivative core and two ZB-derivative ends, can be selectively prepared. The epitaxial growth mechanism is confirmed by the time-dependent experiments. The ratio of rugby ball-like and bullet-like polytypic CCTSSe nanocrystals can be tuned through changing the amount of Cd precursor

  18. Preparation of four 1,4-dihydropyridine derivatives (DHPs) labeled with carbon-14.

    PubMed

    Ahmadi Faghih, Mohammad Amin; Moslemin, Mohammad Hossein; Shirvani, Gholamhossein; Javaheri, Mohsen

    2018-05-23

    The importance of DHPs compounds and the need for examining the mechanism of their effect, mandated us to synthesize a number of carbon-14 labeled 1,4-dihydropyridine derivatives for pharmacological studies. Simple preparation and suitable radiochemical yield were advantages of this preparation. This article is protected by copyright. All rights reserved.

  19. Cell death features induced in Leishmania major by 1,3,4-thiadiazole derivatives.

    PubMed

    Ardestani, Sussan K; Poorrajab, Fatemeh; Razmi, Sepideh; Foroumadi, Alireza; Ajdary, Soheila; Gharegozlou, Behnaz; Behrouzi-Fardmoghadam, Mina; Shafiee, Abbas

    2012-10-01

    Under a variety of stress conditions, Leishmania species display some morphological and biochemical features characteristic of mammalian programmed cell death or necrosis. Nitroheteroaryl-1,3,4-thiadiazoles induce cell death in Leishmania major (L. major). Putative mechanisms of action of these compounds were investigated in vitro at cellular and molecular levels. We used colorimetric assay to measure acid phosphatase activity which is an indicator of cell viability in the promastigotes. The mode of toxicity was determined by detection of phosphatidylserine translocation to the surface, evaluation of cell membrane integrity, and in situ dUTP nick end-labeling assay. We also determined poly-ADP-ribose polymerase-like protein (PARP) level in the parasites after treatment. A significant reduction of acid phosphatase level, one of the most crucial and virulent factors of the parasite was found in parasites treated with 1,3,4-thiadiazole derivatives. In addition, 1,3,4-thiadiazole derivatives induced loss of plasma membrane integrity, DNA breakage, proteolysis of PARP and necrotic-like death in the parasites. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    USDA-ARS?s Scientific Manuscript database

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  1. Effect of Different Angular Momentum Transport Mechanisms on the Radial Volatile Distribution in Protoplanetary Disks

    NASA Astrophysics Data System (ADS)

    Kalyaan, Anusha; Desch, Steven

    2018-01-01

    How circumstellar disks evolve and transport angular momentum is a mystery even until today. Magnetorotational instability (MRI; [1]) earlier thought to be a primary driver of disk evolution, has been found to be not as strong a candidate in cold insufficiently ionized protoplanetary disks where non-ideal MHD effects take over to efficiently suppress the instability [2][3]. In the past few years, recent studies have proposed different mechanisms such as magnetically-driven disk winds [4][5], convective overstability [6], and the vertical shear instability (VSI)[7] to be likely drivers of disk evolution. In this work, we consider numerically [8] and/or parametrically derived radial α profiles of three different mechanisms of angular momentum transport (hydrodynamic instabilities such as VSI, disk winds, and MRI) to understand how the underlying disk structure changes and evolves with each mechanism. We overlay our snowline model that incorporates the advection and diffusion of volatiles as well as radial drift of solids [9] to understand how different α profiles can affect the distribution of water in the disk. References: [1] Balbus, S.A., & Hawley, J.F.,1998, Rev. of Mod. Phys., 70, 1 [2] Bai, X.-N., & Stone, J.M. 2011, ApJ, 736, 144 [3] Bai, X.-N., & Stone, J.M., 2013, ApJ, 769, 76 [4] Bai, X.-N., 2016, ApJ, 821, 80 [5] Suzuki, T.K., Ogihara, M., Morbidelli, A., Crida, A., & Guillot, T., 2016, A&A, 596, A74 [6] Klahr, H., & Hubbard, A. 2014, ApJ, 788, 21 [7] Stoll, M.H.R., & Kley, W. 2014, A&A, 572, A77 [8] Kalyaan, A., Desch, S.J., & Monga, N., 2015, ApJ, 815, 112 [9] Desch, S.J., Estrada, P.R., Kalyaan, A., & Cuzzi, J.N., 2017, ApJ, 840, 86

  2. F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo.

    PubMed

    Thompson, Heather L; van Rooijen, Nico; McLelland, Bryce T; Manilay, Jennifer O

    2016-01-01

    Understanding how embryonic stem cells and their derivatives interact with the adult host immune system is critical to developing their therapeutic potential. Murine embryonic stem cell-derived hematopoietic progenitors (ESHPs) were generated via coculture with the bone marrow stromal cell line, OP9, and then transplanted into NOD.SCID.Common Gamma Chain (NSG) knockout mice, which lack B, T, and natural killer cells. Compared to control mice transplanted with adult lineage-negative bone marrow (Lin - BM) progenitors, ESHP-transplanted mice attained a low but significant level of donor hematopoietic chimerism. Based on our previous studies, we hypothesized that macrophages might contribute to the low engraftment of ESHPs in vivo . Enlarged spleens were observed in ESHP-transplanted mice and found to contain higher numbers of host F4/80 + macrophages compared to BM-transplanted controls. In vivo depletion of host macrophages using clodronate-loaded liposomes improved the ESHP-derived hematopoietic chimerism in the spleen but not in the BM. F4/80 + macrophages demonstrated a striking propensity to phagocytose ESHP targets in vitro . Taken together, these results suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP engraftment in vivo .

  3. Organocatalytic sequential α-amination/Corey-Chaykovsky reaction of aldehydes: a high yield synthesis of 4-hydroxypyrazolidine derivatives.

    PubMed

    Kumar, B Senthil; Venkataramasubramanian, V; Sudalai, Arumugam

    2012-05-18

    A tandem reaction of in situ generated α-amino aldehydes with dimethyloxosulfonium methylide under Corey-Chaykovsky reaction conditions proceeds efficiently to give 4-hydroxypyrazolidine derivatives in high yields with excellent enantio- and diastereoselectivities. This organocatalytic sequential method provides for the efficient synthesis of anti-1,2-aminoalcohols, structural subunits present in several bioactive molecules as well.

  4. Coxsackievirus B4 Can Infect Human Peripheral Blood-Derived Macrophages

    PubMed Central

    Alidjinou, Enagnon Kazali; Sané, Famara; Trauet, Jacques; Copin, Marie-Christine; Hober, Didier

    2015-01-01

    Beyond acute infections, group B coxsackieviruses (CVB) are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM) generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR) mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα) in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases. PMID:26610550

  5. Coxsackievirus B4 Can Infect Human Peripheral Blood-Derived Macrophages.

    PubMed

    Alidjinou, Enagnon Kazali; Sané, Famara; Trauet, Jacques; Copin, Marie-Christine; Hober, Didier

    2015-11-24

    Beyond acute infections, group B coxsackieviruses (CVB) are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM) generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR) mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα) in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases.

  6. Antiprotozoal Activity of 1-Phenethyl-4-Aminopiperidine Derivatives

    PubMed Central

    Dardonville, Christophe; Fernández-Fernández, Cristina; Gibbons, Sarah-Louise; Jagerovic, Nadine; Nieto, Lidia; Ryan, Gary; Kaiser, Marcel; Brun, Reto

    2009-01-01

    A series of 44 4-aminopiperidine derivatives was screened in vitro against four protozoan parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum). This screening identified 29 molecules selectively active against bloodstream-form T. b. rhodesiense trypomastigotes, with 50% inhibitory concentrations (IC50) ranging from 0.12 to 10 μM, and 33 compounds active against the chloroquine- and pyrimethamine-resistant K1 strain of P. falciparum (IC50 range, 0.17 to 5 μM). In addition, seven compounds displayed activity against intracellular T. cruzi amastigotes in the same range as the reference drug benznidazole (IC50, 1.97 μM) but were also cytotoxic to L-6 cells, showing little selectivity for T. cruzi. None of the molecules tested showed interesting antileishmanial activity against axenic amastigotes of L. donovani. To our knowledge, this is the first report of the antitrypanosomal activity of molecules bearing the 4-aminopiperidine skeleton. PMID:19564359

  7. A tandem conjugate addition/cyclization protocol for the asymmetric synthesis of 2-aryl-4-aminotetrahydroquinoline-3-carboxylic acid derivatives.

    PubMed

    Davies, Stephen G; Mujtaba, Nadeam; Roberts, Paul M; Smith, Andrew D; Thomson, James E

    2009-05-07

    Condensation of tert-butyl (E)-3-(2'-aminophenyl)propenoate with a range of aromatic and heteroaromatic aldehydes gives the corresponding imines as single diastereoisomers (>98% de). Addition of lithium (R)-N-benzyl-N-(alpha-methylbenzyl)amide initiates a tandem conjugate addition/cyclization reaction to generate 2-aryl-4-aminotetrahydroquinoline-3-carboxylic acid derivatives in >98% de, >98% ee and high isolated yield. Hydrogenolysis of an N(1)-Boc protected derivative allows selective cleavage of the N-benzyl-N-alpha-methylbenzyl protecting groups without compromise of the diastereo- or enantiopurity.

  8. Antitumor activity of 3,4-ethylenedioxythiophene derivatives and quantitative structure-activity relationship analysis

    NASA Astrophysics Data System (ADS)

    Jukić, Marijana; Rastija, Vesna; Opačak-Bernardi, Teuta; Stolić, Ivana; Krstulović, Luka; Bajić, Miroslav; Glavaš-Obrovac, Ljubica

    2017-04-01

    The aim of this study was to evaluate nine newly synthesized amidine derivatives of 3,4- ethylenedioxythiophene (3,4-EDOT) for their cytotoxic activity against a panel of human cancer cell lines and to perform a quantitative structure-activity relationship (QSAR) analysis for the antitumor activity of a total of 27 3,4-ethylenedioxythiophene derivatives. Induction of apoptosis was investigated on the selected compounds, along with delivery options for the optimization of activity. The best obtained QSAR models include the following group of descriptors: BCUT, WHIM, 2D autocorrelations, 3D-MoRSE, GETAWAY descriptors, 2D frequency fingerprint and information indices. Obtained QSAR models should be relieved in elucidation of important physicochemical and structural requirements for this biological activity. Highly potent molecules have a symmetrical arrangement of substituents along the x axis, high frequency of distance between N and O atoms at topological distance 9, as well as between C and N atoms at topological distance 10, and more C atoms located at topological distances 6 and 3. Based on the conclusion given in the QSAR analysis, a new compound with possible great activity was proposed.

  9. In vitro phototoxic potential and photochemical properties of imidazopyridine derivative: a novel 5-HT4 partial agonist.

    PubMed

    Onoue, Satomi; Igarashi, Naoko; Yamauchi, Yukinori; Kojima, Takashi; Murase, Noriaki; Zhou, Yu; Yamada, Shizuo; Tsuda, Yoshiko

    2008-10-01

    Drug-induced phototoxic skin responses have been recognized as undesirable side effects, and as we previously proposed the determination of reactive oxygen species (ROS) from photo-irradiated compounds can be effective for the prediction of phototoxic potential. In this investigation, we evaluated the photosensitizing properties of imidazopyridine derivative, a novel 5-HT(4) partial agonist, using ROS assay and several analytical/biochemical techniques. Exposure of the compound to simulated sunlight resulted in the significant production of singlet oxygen, which is indicative of its phototoxic potential. In practice, an imidazopyridine derivative under UVA/B light exposure also showed significant photodegradation and even photobiochemical events; peroxidation of fatty acid and genetic damage after DNA-binding, which are considered as causative agents for phototoxic dermatitis. Interestingly, both photodegradation and lipoperoxidation were dramatically attenuated by the addition of radical scavengers, especially singlet oxygen quenchers, suggesting the possible involvement of ROS generation in the phototoxic pathways. In the 3T3 neutral red uptake phototoxicity test, imidazopyridine derivative also showed the phototoxic effect on 3T3 mouse fibroblast cells. These results suggest the phototoxic risk of newly synthesized imidazopyridine derivative and also verify the usefulness of ROS assay for phototoxicity prediction. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  10. 40 CFR 721.1300 - [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.1300 [(Dinitrophenyl)azo]-[2,4-dia-mino-5-methoxybenzene] derivatives. (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances...

  11. A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents.

    PubMed

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-09-06

    As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone (15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.

  12. Ectopical expression of FABP4 gene can induce bovine muscle-derived stem cells adipogenesis.

    PubMed

    Zhang, Le; Zhao, Yanfang; Ning, Yue; Wang, Hongbao; Zan, Linsen

    2017-01-08

    Fatty acid binding protein 4 (FABP4) plays a key role in Fatty acid catabolism in mammals. Findings from our previous studies have indicated that FABP4 neither affect the differentiation of bovine preadipocytes nor does it change the expression of upstream genes. To investigate whether ectopically expressed FABP4 can induces Muscle-Derived Stem Cells (MDSCs) lipid synthesis and understand the regulatory mechanism behind it. In this study, adenoviruses infection is achieved to ectopically expressed FABP4 in bovine MDSCs, RNA-seq analyses at the very early stages of induction were performed to reveal gene expression level changes during MDSCs transdifferentiation. Results showed FABP4 can induce bovine Muscle-Derived Stem Cells transdifferentiation into adipocyte-like cells, 23 genes' expression levels changed after 24 h inducing although there is no significant change in cell phenotypes. Along with induction time, more differently expressed genes (256 genes changes after 48 h induction) were screened out. These genes should be at the downstream of signal pathways and be regulated by the 23 genes identified before. Our findings may provide a unique new model for studying the molecular control of cattle cross-talk between adipose and skeletal muscle. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Biocatalyst mediated production of 6β,11α-dihydroxy derivatives of 4-ene-3-one steroids.

    PubMed

    Kolet, Swati P; Niloferjahan, Siddiqui; Haldar, Saikat; Gonnade, Rajesh; Thulasiram, Hirekodathakallu V

    2013-11-01

    Biotransformation of steroids with 4-ene-3-one functionality such as progesterone (I), testosterone (II), 17α-methyltestosterone (III), 4-androstene-3,17-dione (IV) and 19-nortestosterone (V) were studied by using a fungal system belonging to the genera of Mucor (M881). The fungal system efficiently and quantitatively converted these steroids in regio- and stereo-selective manner into corresponding 6β,11α-dihydroxy compounds. Time course experiments suggested that the transformation was initiated by hydroxylation at 6β- or 11α-(10β-hydroxy in case of V) to form monohydroxy derivatives which upon prolonged incubation were converted into corresponding 6β,11α-dihydroxy derivatives. The fermentation studies carried out using 5L table-top fermentor with substrates (I and II) clearly indicates that 6β,11α-dihydroxy derivatives of steroids with 4-ene-3-one functionality can be produced in large scale by using M881. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Selective Conversion of Lignin-Derivable 4-Alkylguaiacols to 4-Alkylcyclohexanols over Noble and Non-Noble-Metal Catalysts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schutyser, Wouter; Van den Bossche, Gil; Raaffels, Anton

    2016-10-03

    Recent lignin-first catalytic lignocellulosic biorefineries produce large quantities of two potential platform chemicals, 4-n-propylguaiacol (PG) and 4-n-propylsyringol. Because conversion into 4-n-propylcyclohexanol (PCol), a precursor for novel polymer building blocks, presents a promising valorization route, reductive demethoxylation of PG was examined here in the liquid-phase over three commercial hydrogenation catalysts, viz. 5 wt % Ru/C, 5 wt % Pd/C and 65 wt % Ni/SiO2-Al2O3, at elevated temperatures ranging from 200 to 300 degrees C under hydrogen atmosphere. Kinetic profiles suggest two parallel conversion pathways: Pathway I involves PG hydrogenation to 4-n-propyl-2-methoxycyclohexanol (PMCol), followed by its demethoxylation to PCol, whereas Pathway IImore » constitutes PG hydrodemethoxylation to 4-n-propylphenol (PPh), followed by its hydrogenation into PCol. The slowest step in the catalytic formation of PCol is the reductive methoxy removal from PMCol. Moreover, under the applied reaction conditions, PCol may react further into hydrocarbons. The following criteria are therefore essential to reach a high PCol yield: (i) catalytic pathway II is preferred as this route does not involve stable intermediates; (ii) reactivity of PMCol should be higher than that of PCol, and (iii) the overall carbon balance should be high. Both the catalyst type and the reaction conditions have a substantial impact on the PCol yield. Only the commercial Ni catalyst meets the three criteria, provided the reaction is performed at 250 degrees C in hexadecane. Additional advantages of this solvent choice are a high boiling point (low operational pressure in closed reactor systems), high solubility of PG and derived products, high thermal, reductive stability, and easy derivability from fatty biomass feedstock. This Ni catalyst also showed an excellent stability in recycling runs and is capable of converting highly concentrated (up to 20 wt %) PG in hexadecane. Ru and Pd on

  15. Synthesis and antidepressant properties of novel 2-substituted 4,5-dihydro-1H-imidazole derivatives.

    PubMed

    Wentland, M P; Bailey, D M; Alexander, E J; Castaldi, M J; Ferrari, R A; Haubrich, D R; Luttinger, D A; Perrone, M H

    1987-08-01

    A unique combination of alpha 2-adrenoreceptor antagonist and serotonin-selective reuptake inhibitory activities has been identified in a series of 2-substituted 4,5-dihydro-1H-imidazole derivatives. This combination of blocking activities has provided one of these derivatives, napamezole hydrochloride (2), with potential as an antidepressant. A discussion of the syntheses of these compounds includes a convenient method for the conversion of nitriles to imidazolines with ethylenediamine and trimethylaluminum.

  16. The MIL-88A-Derived Fe3O4-Carbon Hierarchical Nanocomposites for Electrochemical Sensing

    PubMed Central

    Wang, Li; Zhang, Yayun; Li, Xia; Xie, Yingzhen; He, Juan; Yu, Jie; Song, Yonghai

    2015-01-01

    Metal or metal oxides/carbon nanocomposites with hierarchical superstructures have become one of the most promising functional materials in sensor, catalysis, energy conversion, etc. In this work, novel hierarchical Fe3O4/carbon superstructures have been fabricated based on metal-organic frameworks (MOFs)-derived method. Three kinds of Fe-MOFs (MIL-88A) with different morphologies were prepared beforehand as templates, and then pyrolyzed to fabricate the corresponding novel hierarchical Fe3O4/carbon superstructures. The systematic studies on the thermal decomposition process of the three kinds of MIL-88A and the effect of template morphology on the products were carried out in detail. Scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy and thermal analysis were employed to investigate the hierarchical Fe3O4/carbon superstructures. Based on these resulted hierarchical Fe3O4/carbon superstructures, a novel and sensitive nonenzymatic N-acetyl cysteine sensor was developed. The porous and hierarchical superstructures and large surface area of the as-formed Fe3O4/carbon superstructures eventually contributed to the good electrocatalytic activity of the prepared sensor towards the oxidation of N-acetyl cysteine. The proposed preparation method of the hierarchical Fe3O4/carbon superstructures is simple, efficient, cheap and easy to mass production. It might open up a new way for hierarchical superstructures preparation. PMID:26387535

  17. Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance.

    PubMed

    Toloza, F J K; Pérez-Matos, M C; Ricardo-Silgado, M L; Morales-Álvarez, M C; Mantilla-Rivas, J O; Pinzón-Cortés, J A; Pérez-Mayorga, M; Arévalo-García, M L; Tolosa-González, G; Mendivil, C O

    2017-09-01

    To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Synthesis and structure-activity relationship of amidine derivatives of 3,4-ethylenedioxythiophene as novel antibacterial agents.

    PubMed

    Stolić, Ivana; Čipčić Paljetak, Hana; Perić, Mihaela; Matijašić, Mario; Stepanić, Višnja; Verbanac, Donatella; Bajić, Miroslav

    2015-01-27

    Current antibacterial chemotherapeutics are facing an alarming increase in bacterial resistance pressuring the search for novel agents that would expand the available therapeutic arsenal against resistant bacterial pathogens. In line with these efforts, a series of 9 amidine derivatives of 3,4-ethylenedioxythiophene were synthesized and, together with 18 previously synthesized analogs, evaluated for their relative DNA binding affinity, in vitro antibacterial activities and preliminary in vitro safety profile. Encouraging antibacterial activity of several subclasses of tested amidine derivatives against Gram-positive (including resistant MRSA, MRSE, VRE strains) and Gram-negative bacterial strains was observed. The bis-phenyl derivatives were the most antibacterially active, while compound 19 from bis-benzimidazole class exhibited the widest spectrum of activity (with MIC of 4, 2, 0.5 and ≤0.25 μg/ml against laboratory strains of Staphyloccocus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, respectively and 4-32 μg/ml against clinical isolates of sensitive and resistant S. aureus, Staphylococcus epidermidis and Enterococcus faecium) and also demonstrated the strongest DNA binding affinity (ΔTm of 15.4 °C). Asymmetrically designed compounds and carboxamide-amidines were, in general, less active. Molecular docking indicated that the shape of the 3,4-ethylenedioxythiophene derivatives and their ability to form multiple electrostatic and hydrogen bonds with DNA, corresponds to the binding modes of other minor-groove binders. Herein reported results encourage further investigation of this class of compounds as novel antibacterial DNA binding agents. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. Regioselective 1,4- and 1,6-Conjugate Additions of Grignard Reagent-Derived Organozinc(II)ates to Polyconjugated Esters.

    PubMed

    Hatano, Manabu; Mizuno, Mai; Ishihara, Kazuaki

    2016-09-16

    Regioselective synthetic methods were developed for 1,4- and 1,6-conjugate additions of Grignard reagent-derived organozinc(II)ates to malonate-derived polyconjugated esters. By taking advantage of the tight ion-pair control of organozinc(II)ates, it was possible to switch between 1,4- and 1,6-conjugate additions by introducing a terminal ethoxy moiety in the conjugation.

  20. Aromatic derivatives of 1H-2,3-dihydropyrazolo(4,5-b)-1,5-diazepine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Orlov, V.D.; Kiroga, Kh.; Kolos, N.N.

    1987-09-01

    Aromatic derivatives of 1H-2,3-dihydropyrazole(4,5-b)-1,5-diazepine were obtained by the reaction of 1-phenyl-3-methyl-4,5-diaminopyrazole with chalcones and acetylarenes, catalyzed by acetic or sulfuric acid. The seven-membered ring in these compounds has a conformation of the boat type. The IR, UV, PMR, and mass spectra of the compounds are discussed.

  1. The Escherichia coli-Derived Thymosin β4 Concatemer Promotes Cell Proliferation and Healing Wound in Mice

    PubMed Central

    Wang, Xiaolei; Yang, Guihua; Li, Shanshuang; Gao, Meifeng; Zhao, Pangfeng; Zhao, Lingxia

    2013-01-01

    Thymosin β4 (Tβ4) is one of the most promising thymosins for future clinical applications, and it is anticipated that commercial demand for Tβ4 will increase. In order to develop a new approach to produce recombinant Tβ4, a 168 bp DNA (termed Tβ4) was designed based on the Tβ4 protein sequence and used to express a 4 × Tβ4 concatemer (four tandem copies of Tβ4, termed 4 × T β4) together with a histidine tag (6 × His) in E. coli (strain BL21). SDS-PAGE and western blot analysis were used to confirm that a recombinant 4 × Tβ4 protein of the expected size (30.87 kDa) was produced following the induction of the bacterial cultures with isopropyl β-D-thiogalactoside (IPTG). The E. coli-derived 4 × Tβ4 was purified by Ni-NTA resin, and its activities were examined with regard to both stimulating proliferation of the mice spleen cells in vitro and in vivo wound healing. The results demonstrate that these activities of the E. coli-derived recombinant 4 × Tβ4 were similar or even better than existing commercially obtained Tβ4. This production strategy therefore represents a potentially valuable approach for future commercial production of recombinant Tβ4. PMID:23762829

  2. Inhibitory properties of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) derivatives acting on glycogen metabolising enzymes.

    PubMed

    Díaz-Lobo, Mireia; Concia, Alda Lisa; Gómez, Livia; Clapés, Pere; Fita, Ignacio; Guinovart, Joan J; Ferrer, Joan C

    2016-09-26

    Glycogen synthase (GS) and glycogen phosphorylase (GP) are the key enzymes that control, respectively, the synthesis and degradation of glycogen, a multi-branched glucose polymer that serves as a form of energy storage in bacteria, fungi and animals. An abnormal glycogen metabolism is associated with several human diseases. Thus, GS and GP constitute adequate pharmacological targets to modulate cellular glycogen levels by means of their selective inhibition. The compound 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) is a known potent inhibitor of GP. We studied the inhibitory effect of DAB, its enantiomer LAB, and 29 DAB derivatives on the activity of rat muscle glycogen phosphorylase (RMGP) and E. coli glycogen synthase (EcGS). The isoform 4 of sucrose synthase (SuSy4) from Solanum tuberosum L. was also included in the study for comparative purposes. Although these three enzymes possess highly conserved catalytic site architectures, the DAB derivatives analysed showed extremely diverse inhibitory potential. Subtle changes in the positions of crucial residues in their active sites are sufficient to discriminate among the structural differences of the tested inhibitors. For the two Leloir-type enzymes, EcGS and SuSy4, which use sugar nucleotides as donors, the inhibitory potency of the compounds analysed was synergistically enhanced by more than three orders of magnitude in the presence of ADP and UDP, respectively. Our results are consistent with a model in which these compounds bind to the subsite in the active centre of the enzymes that is normally occupied by the glucosyl residue which is transferred between donor and acceptor substrates. The ability to selectively inhibit the catalytic activity of the key enzymes of the glycogen metabolism may represent a new approach for the treatment of disorders of the glycogen metabolism.

  3. Novel 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives: a patent review (2008 - 2011).

    PubMed

    Ferreira, Vitor F; da Rocha, David R; da Silva, Fernando C; Ferreira, Patrícia G; Boechat, Núbia A; Magalhães, Jorge L

    2013-03-01

    The triazoles represent a class of five-membered heterocyclic compounds of great importance for the preparation of new drugs with diverse biological activities because they may present several structural variations with the same numbers of carbon and nitrogen atoms. Due to the success of various triazoles that entered the pharmaceutical market and are still being used in medicines, many companies and research groups have shown interest in developing new methods of synthesis and biological evaluation of potential uses for these compounds. In this review, the authors explored aspects of patents for the 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole families, including prototypes being considered in clinical studies between 2008 and 2011. The triazoles have been studied for over a century as an important class of heterocyclic compounds and still attract considerable attention due to their broad range of biological activities. More recently, there has been considerable interest in the development of novel triazoles with anti-inflammatory, antiplatelet, antimicrobial, antimycobacterial, antitumoral and antiviral properties and activity against several neglected diseases. This review emphasizes recent perspective and advances in the therapeutically active 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivative patents between 2008 and 2011, covering the development of new chemical entities and new pharmaceuticals. Many studies have focused on these compounds as target structures and evaluated them in several biological targets. The preparation of 1H-1,2,3-, 2H-1,2,3-, 1H-1,2,4- and 4H-1,2,4-triazole derivatives brings to light several issues. There is a need to find new, more efficient preparations for these triazoles that take into consideration current issues in green chemistry, energy saving and sustainability. New diseases are discovered and new viruses and bacteria continue to challenge mankind, so it is imperative to find new prototypes for these

  4. Development of Intergranular Residual Stress and Its Implication to Mechanical Behaviors at Elevated Temperatures in AL6XN Austenitic Stainless Steel

    NASA Astrophysics Data System (ADS)

    Hong, Yanyan; Li, Shilei; Li, Hongjia; Li, Jian; Sun, Guangai; Wang, Yan-Dong

    2018-05-01

    Neutron diffraction was used to investigate the residual lattice strains in AL6XN austenitic stainless steel subjected to tensile loading at different temperatures, revealing the development of large intergranular stresses after plastic deformation. Elastic-plastic self-consistent modeling was employed to simulate the micromechanical behavior at room temperature. The overall variations of the modeled lattice strains as a function of the sample direction with respect to the loading axis agree in general with the experimental values, indicating that dislocation slip is the main plastic deformation mode. At 300 °C, the serrated flow in the stress-strain curve and the great amount of slip bands indicate the appearance of dynamic strain aging. Except for promoting the local strain concentration, the long-range stress field caused by the planar slip bands near the grain boundaries is also attributed to the decrease in the experimental intergranular strains. An increase in the lattice strains localized at some specific specimen orientations for reflections at 600 °C may be explained by the segregation of solute atoms (Cr and Mo) at dislocation slip bands. The evolution of full-width at half-maximum demonstrates that the dynamic recovery indeed plays an important role in alleviating the local strain concentrations during tensile loading at 600 °C.

  5. A Numerical Analysis of Smoothed Particle Hydrodynamics

    DTIC Science & Technology

    1994-09-01

    for the q terms: 1 N_ V).- Ernj(v.- iv)(X Ps4 -=0 N J) 03 R’, 1 - , P- El)( (4.54) Substitute equation (4.54) in equation (4.53) for q, then update the...p=, L ,(p,ý)2 (pn)2) Xn’+1 n + tVX (7.55) 7-17 7.4.2 Upwind. The second lower order scheme considered is motivated by upwind finite difference

  6. Synthesis, biological activity and molecular modeling of 4-fluoro-N-[ω-(1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide derivatives as cholinesterase inhibitors.

    PubMed

    Szymański, P; Markowicz, M; Bajda, M; Malawska, B; Mikiciuk-Olasik, E

    2012-12-01

    The aim of this study was to synthesize and determine the biological activity of new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition of cholinesterases. Compounds were synthesized in condensation reaction between 9-aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties towards inhibition of acetyl- and butyrylcholinesterase were estimated according to Ellman's spectrophotometric method. Among synthesized compounds the most active were compounds 4a and 4d. These compounds, in comparison with tacrine, were characterized by the similar values of IC50. Among all obtained compounds, 4d presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling studies revealed that all derivatives presented similar extended conformation in the gorge of acetylcholinesterase, however, there were 2 main conformations in the active center of butyrylcholinesterase: bent and extended conformation. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Interferon regulatory factor 4 (IRF4) controls myeloid-derived suppressor cell (MDSC) differentiation and function.

    PubMed

    Nam, Sorim; Kang, Kyeongah; Cha, Jae Seon; Kim, Jung Woo; Lee, Hee Gu; Kim, Yonghwan; Yang, Young; Lee, Myeong-Sok; Lim, Jong-Seok

    2016-12-01

    Myeloid-derived suppressor cells (MDSCs) are immature cells that do not differentiate into mature myeloid cells. Two major populations of PMN-MDSCs (Ly6G high Ly6C low Gr1 high CD11b + ) and MO-MDSCs (Ly6G - Ly6C high Gr-1 int CD11b + ) have an immune suppressive function. Interferon regulatory factor 4 (IRF4) has a role in the negative regulation of TLR signaling and is associated with lymphoid cell development. However, the roles of IRF4 in myeloid cell differentiation are unclear. In this study, we found that IRF4 expression was remarkably suppressed during the development of MDSCs in the tumor microenvironment. Both the mRNA and protein levels of IRF4 in MDSCs were gradually reduced, depending on the development of tumors in the 4T1 model. siRNA-mediated knockdown of IRF4 in bone marrow cells promoted the differentiation of PMN-MDSCs. Similarly, IRF4 inhibition in bone marrow cells using simvastatin, which has been known to inhibit IRF4 expression, increased PMN-MDSC numbers. In contrast, IRF4 overexpression in bone marrow cells inhibited the total numbers of MDSCs, especially PMN-MDSCs. Notably, treatment with IL-4, an upstream regulator of IRF4, induced IRF4 expression in the bone marrow cells, and consequently, IL-4-induced IRF4 expression resulted in a decrease in PMN-MDSC numbers. Finally, we confirmed that IRF4 expression in MDSCs can modulate their activity to inhibit T cell proliferation through IL-10 production and ROS generation, and myeloid-specific deletion of IRF4 leads to the increase of MDSC differentiation. Our present findings indicate that IRF4 reduction induced by tumor formation can increase the number of MDSCs, and increases in the IRF4 expression in MDSCs may infringe on the immune-suppressive function of MDSCs. © Society for Leukocyte Biology.

  8. Presence of CP4-EPSPS Component in Roundup Ready Soybean-Derived Food Products

    PubMed Central

    Wu, Honghong; Zhang, Yu; Zhu, Changqing; Xiao, Xiao; Zhou, Xinghu; Xu, Sheng; Shen, Wenbiao; Huang, Ming

    2012-01-01

    With the widespread use of Roundup Ready soya (event 40-3-2) (RRS), the traceability of transgenic components, especially protein residues, in different soya-related foodstuffs has become an important issue. In this report, transgenic components in commercial soya (including RRS) protein concentrates were firstly detected by using polymerase chain reaction (PCR) and western blot. The results illustrated the different degradation patterns of the cp4-epsps gene and corresponding protein in RRS-derived protein concentrates. Furthermore, western blot was applied to investigate the single factor of food processing and the matrix on the disintegration of CP4-EPSPS protein in RRS powder and soya-derived foodstuffs, and trace the degradation patterns during the food production chain. Our results suggested that the exogenous full length of CP4-EPSPS protein in RRS powder was distinctively sensitive to various heat treatments, including heat, microwave and autoclave (especially), and only one degradation fragment (23.4 kD) of CP4-EPSPS protein was apparently observed when autoclaving was applied. By tracing the protein degradation during RRS-related products, including tofu, tou-kan, and bean curd sheets, however, four degradation fragments (42.9, 38.2, 32.2 and 23.4 kD) were displayed, suggesting that both boiling and bittern adding procedures might have extensive effects on CP4-EPSPS protein degradation. Our results thus confirmed that the distinctive residues of the CP4-EPSPS component could be traced in RRS-related foodstuffs. PMID:22408431

  9. Structural and computational study of 1,2,4-triazolin-5-thione derivative and its DMSO solvate

    NASA Astrophysics Data System (ADS)

    Dybała, Izabela; Wawrzycka-Gorczyca, Irena; Struga, Marta

    2017-11-01

    The solid state structure of 3-(4-phenyl-5-oxo-1,2,4-triazolin-1-ylmethyl)-4-cyclohexyl-1,2,4-triazolin-5-thione (1) was characterized by FT-IR and X-ray diffraction experiment. Additionally, molecular and crystal structure of its DMSO solvate (1DMSO) has been determined by X-ray diffraction method. The influence of DMSO molecules incorporation to the crystal lattice on geometry of triazolin-5-thione derivative molecule and crystal packing was analyzed. Non-covalent bonds within the crystals are additionally visualized by determination of Hirshfeld surfaces. According to results of conformational analysis in gas, molecule of triazolin-5-thione derivative adopts the lowest energy conformation in 1DMSO crystal. The crystal structure of 1 and 1DMSO were compared with previously described structurally similar compounds, in which the cyclohexyl substituent was replaced by aromatic one (phenyl/methoxyphenyl). Very interesting differences in molecules association were found by comparing the crystal structures of 1 and 1DMSO with their, mentioned above, aromatic derivatives. Interesting properties of triazolin-5-thione derivatives are connected with their π-electron delocalization effects, thus aromaticity of heterocyclic fragments has been investigated by means of the HOMA index. Comparison of aromaticity calculations results with association tendency of molecules shows that triazolin-5-one fragments reach higher aromaticity when nitrogen atom from this moiety acts as a donor in strong Nsbnd H⋯N hydrogen bonds.

  10. A novel mechanism of EML4-ALK rearrangement mediated by chromothripsis in a patient-derived cell line.

    PubMed

    Kodama, Tatsushi; Motoi, Noriko; Ninomiya, Hironori; Sakamoto, Hiroshi; Kitada, Kunio; Tsukaguchi, Toshiyuki; Satoh, Yasuko; Nomura, Kimie; Nagano, Hiroko; Ishii, Nobuya; Terui, Yasuhito; Hatake, Kiyohiko; Ishikawa, Yuichi

    2014-11-01

    EML4-ALK is a driver oncogene in non-small-cell lung cancer (NSCLC) and has been developed into a promising molecular target for antitumor agents. Although EML4-ALK is reported to be formed by inversion of chromosome 2, other mechanisms of this gene fusion remain unknown. This study aimed to examine the mechanism of EML4-ALK rearrangement using a novel cell line with the EML4-ALK fusion gene. An EML4-ALK-positive cell line, termed JFCR-LC649, was established from pleomorphic carcinoma, a rare subtype of NSCLC. We investigated the chromosomal aberrations using fluorescence in situ hybridization and comparative genomic hybridization (CGH). Alectinib/CH5424802, a selective ALK inhibitor, was evaluated in the antitumor activity against JFCR-LC649 in vitro and in vivo xenograft model. We established an EML4-ALK-positive cell line, termed JFCR-LC649, derived from a patient with NSCLC and revealed that the JFCR-LC649 cells harbor variant 3 of the EML4-ALK fusion with twofold copy number gain. Interestingly, comparative genomic hybridization and metaphase-fluorescence in situ hybridization analysis showed that in addition to two normal chromosome 2, JFCR-LC649 cells contained two aberrant chromosome 2 that were fragmented and scattered. These observations provided the first evidence that EML4-ALK fusion in JFCR-LC649 cells was formed in chromosome 2 by a distinct mechanism of genomic rearrangement, termed chromothripsis. Furthermore, a selective ALK inhibitor alectinib/CH5424802 suppressed tumor growth of the JFCR-LC649 cells through inhibition of phospho-ALK in vitro and in vivo in a xenograft model. Our results suggested that chromothripsis may be a mechanism of oncogenic rearrangement of EML4-ALK. In addition, alectinib was effective against EML4-ALK-positive tumors with ALK copy number gain mediated by chromothripsis.

  11. Identification of novel thiazolo[5,4-d]pyrimidine derivatives as human A1 and A2A adenosine receptor antagonists/inverse agonists.

    PubMed

    Varano, Flavia; Catarzi, Daniela; Falsini, Matteo; Vincenzi, Fabrizio; Pasquini, Silvia; Varani, Katia; Colotta, Vittoria

    2018-07-23

    In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A 1 , A 2A , A 2B and A 3 adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA 1 and hA 2A adenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A 1 /A 2A antagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA 1 K i  = 10.2 nM; hA 2A K i  = 4.72 nM) and behaved as a potent A 1 /A 2A antagonist/inverse agonist (hA 1 IC 50  = 13.4 nM; hA 2A IC 50  = 5.34 nM). Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a mouse model of acute pain.

    PubMed

    Czopek, Anna; Sałat, Kinga; Byrtus, Hanna; Rychtyk, Joanna; Pawłowski, Maciej; Siwek, Agata; Soluch, Joanna; Mureddu, Valentina; Filipek, Barbara

    2016-06-01

    Antiepileptic drugs are commonly used in non-epileptic disorders. For example, phenytoin and levetiracetam demonstrate analgesic properties in rodent models of pain. In order to enhance their antinociceptive activity, structural features of phenytoin and levetiracetam, such as imidazolidine-2,4-dione and amide bond in alkyl chain, were combined in one molecule. Furthermore, in preliminary studies, methoxyphenylpiperazinpropyl derivatives of imidazolidine-2,4-dione acted as antinociceptive agents in several rodent models of acute pain. The final compounds and the reference drugs - levetiracetam and phenytoin were evaluated in the hot plate test to assess their antinociceptive activity in this acute pain model. Furthermore, for the analgesic active compounds the impact on animals' locomotor activity and motor performance were estimated and the affinity to serotonergic (5-HT1A, 5-HT7) and adrenergic (α1) receptors was determined. Three of the tested compounds: 7, 15 and 18 showed statistically significant antinociceptive properties at the dose of 30mg/kg. Among them, compound 18, 1-methyl-3-[1-(morpholin-4-yl)-1-oxobutan-2-yl]imidazolidine-2,4-dione, exhibited the most significant and long-lasting antinociceptive activity. Noteworthy, this activity was not associated with a negative effect on animals' motor functions. Serotonergic or adrenergic neurotransmission is not involved in this antinociceptive effect. Some amide derivatives of imidazolidine-2,4-diones possess antinociceptive properties in mice but further studies are needed to explain their mechanism of action and assess their toxicity. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Handbook for Sampling and Sample Preservation of Water and Wastewater

    DTIC Science & Technology

    1992-05-01

    integers from 1 to N. N E Xi = XI1 + X 2 + X 3 . ..... + XN i=l 1 In the above example (from Table 4.1), X1 = 35.8, X2 = 33.0, ... , XN = X52 32.4; N E...41e 0 b10) -4 r- -C) a) 5l %Dt C) ON qc -0 Cl qtr C -4 %D cvj qw a) C )L- L~~~J enC- ..4 m~a CV) .4 c P.. .4 cnm0 q5C) )n me .-4C) - (J 1 () e U m. 0-4...X(l) = X = 35.8, X(2) = X2 = 33.0,..., X(52) = X52 = 32.4. X(t) is the linear trend. X’(t) is the random component. In this case, the trend can be

  14. Role of precursor chemistry in the direct fluorination to form titanium based conversion anodes for lithium ion batteries

    DOE PAGES

    Adcock, Jamie; Dai, Sheng; Veith, Gabriel M.; ...

    2015-10-13

    In this study, a new synthetic route for the formation of titanium oxydifluoride (TiOF 2) through the process of direct fluorination via a fluidized bed reactor system and the associated electrochemical properties of the powders formed from this approach are reported. The flexibility of this synthetic route was demonstrated using precursor powders of titanium dioxide (TiO 2) nanoparticles, as well as a reduced TiO xN y. An advantage of this synthetic method is the ability to directly control the extent of fluorination as a function of reaction temperature and time. The reversible capacity of TiOF 2 anodes was found tomore » depend greatly upon the precursor employed. The TiOF 2 synthesized from TiO 2 and TiO xN y showed reversible capacities of 300 mAh g -1 and 440 mAh g -1, respectively, over 100 cycles. The higher reversible capacity of the TiOF 2 powders derived from TiO xN y likely relate to the partial reduction of the Ti in the fluorinated electrode material, highlighting a route to optimize the properties of conversion electrode materials.« less

  15. The Prenylflavonoid Xanthohumol Reduces Alzheimer-Like Changes and Modulates Multiple Pathogenic Molecular Pathways in the Neuro2a/APPswe Cell Model of AD.

    PubMed

    Huang, Xianfeng; Wang, Jing; Chen, Xiao; Liu, Pan; Wang, Shujin; Song, Fangchen; Zhang, Zaijun; Zhu, Feiqi; Huang, Xinfeng; Liu, Jianjun; Song, Guoqiang; Spencer, Peter S; Yang, Xifei

    2018-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop ( Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative

  16. Synthesis, anti-microbial and molecular docking studies of quinazolin-4(3H)-one derivatives.

    PubMed

    Mabkhot, Yahia Nasser; Al-Har, Munirah S; Barakat, Assem; Aldawsari, Fahad D; Aldalbahi, Ali; Ul-Haq, Zaheer

    2014-06-25

    In this work, synthesis, antimicrobial activities and molecular docking studies of some new series of substituted quinazolinone 2a-h and 3a-d were described. Starting form 2-aminobenzamide derivatives 1, a new series of quinazolinone derivatives has been synthesized, in high yields, assisted by microwave and classical methods. Some of these substituted quinazolinones were tested for their antimicrobial activity against Gram-negative bacteria (Pseudomonas aeruginosa and Esherichia coli) and Gram-positive bacteria (Staphylococcus aureus, and Bacillus subtilis), and anti-fungal activity against (Aspergillus fumigatus, Saccharomyces cervevisiae, and Candida albicans) using agar well diffusion method. Among the prepared products, 3-benzyl-2-(4-chlorophenyl)quinazolin-4(3H)-one (3a) was found to exhibits the most potent in vitro anti-microbial activity with MICs of 25.6±0.5, 24.3±0.4, 30.1±0.6, and 25.1±0.5 µg/mL against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Esherichia coli, respectively. Compound 3a was found to exhibits the most potent in vitro anti-fungal activity with MICs of 18.3±0.6, 23.1±0.4, and 26.1±0.5 µg/mL against Aspergillus fumigatus, Saccharomyces cervevisiae, and Candidaal bicans, respectively.

  17. Investigation on the ZBG-functionality of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase inhibitors.

    PubMed

    Musso, Loana; Cincinelli, Raffaella; Zuco, Valentina; Zunino, Franco; Nurisso, Alessandra; Cuendet, Muriel; Giannini, Giuseppe; Vesci, Loredana; Pisano, Claudio; Dallavalle, Sabrina

    2015-10-15

    A series of alternative Zn-binding groups were explored in the design of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds were less effective than the parent hydroxamic acid. However, the profile of activity shown by the analog bearing a hydroxyurea head group, makes this derivative promising for further investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor.

    PubMed

    Patel, Ami V; Krimm, Robin F

    2012-05-01

    The number of neurons in the geniculate ganglion that are available to innervate taste buds is regulated by neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF). Our goal for the current study was to examine the timing and mechanism of NT-4-mediated regulation of geniculate neuron number during development. We discovered that NT-4 mutant mice lose 33% of their geniculate neuronal cells between E10.5 and E11.5. By E11.5, geniculate axons have just reached the tongue and do not yet innervate their gustatory targets; thus, NT-4 does not function as a target-derived growth factor. At E11.5, no difference was observed in proliferating cells or the rate at which cells exit the cell cycle between NT-4 mutant and wild type ganglia. Instead, there was an increase in TUNEL-labeling, indicating an increase in cell death in Ntf4(-/-) mice compared with wild types. However, activated caspase-3, which is up-regulated in the absence of BDNF, was not increased. This finding indicates that cell death initiated by NT-4-removal occurs through a different cell death pathway than BDNF-removal. We observed no additional postnatal loss of taste buds or neurons in Ntf4(-/-) mice. Thus, during early embryonic development, NT-4 produced in the ganglion and along the projection pathway inhibits cell death through an activated caspase-3 independent mechanism. Therefore, compared to BDNF, NT-4 plays distinct roles in gustatory development; differences include timing, source of neurotrophin, and mechanism of action. Published by Elsevier Inc.

  19. Effect of Dipole Perturbation on a Good Confining Surface Near X Point

    NASA Astrophysics Data System (ADS)

    Prakash, Sushant; Witmer, Lisa; Punjabi, Alkesh; Ali, Halima

    2002-11-01

    We analyze effects of dipole perturbation on a good magnetic surface of a single null divertor tokamak using the method of maps developed by Punjabi and Boozer /1/. Unperturbed fields are represented by the Symmetric Simple Map /2/. Effects of high MN perturbation are represented by the Dipole Map (DM) /2/ given by: x_n+1 = x_n+2δ s^3x_n[(y_n-y_s+s) / [x_n+1^2+(y_n-y_s+s)^2]^2], y_n+1 = y_n+δ s^3x_n[[(y_n-y_s+s)^2-x_n+1^2] / [x_n+1^2+(y_n-y_s+s)^2]^2] The good surface is x_0=0 and y_0=0.952873. We start with the strength of perturbation, δ=0, increase it slowly, and observe how the surface changes. The results will be presented. This project is supported by the QEM network NASA Sharp Plus program and by DE-FG02-02ER54673. The work is done on the FUSION1 server under Profs. Ali and Punjabi 1. Punjabi A., Verma A. and Boozer A., Phys. Rev. Lett., 69, 3322 (1992) 2. Ali H., Punjabi A. and Boozer A., Dipole Map for Single-null Divertor Tokamak, 2002 International Congress on Plasma Physics, Manly, Australia.

  20. Exploring molecular insights into the interaction mechanism of cholesterol derivatives with the Mce4A: A combined spectroscopic and molecular dynamic simulation studies.

    PubMed

    Khan, Shagufta; Khan, Faez Iqbal; Mohammad, Taj; Khan, Parvez; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Imtaiyaz Hassan, Md

    2018-05-01

    Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Novel 4-Thiazolidinone Derivatives as Anti-Infective Agents: Synthesis, Characterization, and Antimicrobial Evaluation.

    PubMed

    Gupta, Amit; Singh, Rajendra; Sonar, Pankaj K; Saraf, Shailendra K

    2016-01-01

    A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for antimicrobial activity. All the compounds were evaluated against five Gram-positive bacteria, two Gram-negative bacteria, and two fungi, at concentrations of 50, 100, 200, 400, 800, and 1600 µg/mL, respectively. Minimum inhibitory concentrations of all the compounds were also determined and were found to be in the range of 100-400 µg/mL. All the compounds showed moderate-to-good antimicrobial activity. Compounds 4a [2-(4-fluoro-phenyl)-3-(4-methyl-5,6,7,8-tetrahydro-quinazolin-2-yl)-thiazolidin-4-one] and 4e [3-(4,6-dimethyl-pyrimidin-2-yl)-2-(2-methoxy-phenyl)-thiazolidin-4-one] were the most potent compounds of the series, exhibiting marked antimicrobial activity against Pseudomonas fluorescens, Staphylococcus aureus, and the fungal strains. Thus, on the basis of results obtained, it may be concluded that synthesized compounds exhibit a broad spectrum of antimicrobial activity.

  2. Navigation with Limited Prior Information Using Time Difference of Arrival Measurements from Signals of Opportunity

    DTIC Science & Technology

    2010-12-01

    radiolocation in CDMA cellular systems”. IEEE Communications Magazine, 36(4):38–45, April 1998. 5. Code of Federal Regulations. “AM Broadcast Stations... DS /ENG/05-02. [Online]. Available at http://handle.dtic.mil/100.2/ADA442340. 11. Foy, Wade H. “Position-Location Solutions by Taylor-Series Estimation

  3. Anti-acne activities of pulsaquinone, hydropulsaquinone, and structurally related 1, 4-quinone derivatives.

    PubMed

    Cho, Soon-Chang; Sultan, Md Zakir; Moon, Surk-Sik

    2009-04-01

    Quinone type compound, pulsaquinone 1, isolated from the aqueous ethanol extract of the roots of Pulsatilla koreana exhibited antimicrobial activities against an anaerobic non-spore-forming gram-positive bacillus, Propionibacterium acnes, which is related with the pathogenesis of the inflamed lesions in a common skin disease, acne vulgaris. Compound 1 was unstable on standing and thus converted to more stable compound 2, namely hydropulsaquinone by hydrogenation, whose activity was comparable to mother compound 1 (MIC for 1 and 2 against P. acnes: 2.0 and 4.0 microg/mL, respectively). Other structurally-related quinone derivatives (3-13) were also tested for structure-activity relationship against anaerobic and aerobic bacteria, and fungi. The antimicrobial activity was fairly good when the quinone moiety was fused with a nonpolar 6- or 7-membered ring on the right side whether or not conjugated (1,4-naphtoquinone derivatives 3-5), while simple quinone compounds 6-9 showed poor activity. It seems that the methoxy groups at the left side of the quinone function deliver no considerable antimicrobial effect.

  4. 21 CFR 184.1685 - Rennet (animal-derived) and chymosin preparation (fermentation-derived).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  5. Salivary Secretory Immunoglobulin a secretion increases after 4-weeks ingestion of chlorella-derived multicomponent supplement in humans: a randomized cross over study

    PubMed Central

    2011-01-01

    Background Chlorella, a unicellular green alga that grows in fresh water, contains high levels of proteins, vitamins, minerals, and dietary fibers. Some studies have reported favorable immune function-related effects on biological secretions such as blood and breast milk in humans who have ingested a chlorella-derived multicomponent supplement. However, the effects of chlorella-derived supplement on mucosal immune functions remain unclear. The purpose of this study was to investigate whether chlorella ingestion increases the salivary secretory immunoglobulin A (SIgA) secretion in humans using a blind, randomized, crossover study design. Methods Fifteen men took 30 placebo and 30 chlorella tablets per day for 4 weeks separated by a 12-week washout period. Before and after each trial, saliva samples were collected from a sterile cotton ball that was chewed after overnight fasting. Salivary SIgA concentrations were measured using ELISA. Results Compliance rates for placebo and chlorella ingestions were 97.0 ± 1.0% and 95.3 ± 1.6%, respectively. No difference was observed in salivary SIgA concentrations before and after placebo ingestion (P = 0.38). However, salivary SIgA concentrations were significantly elevated after chlorella ingestion compared to baseline (P < 0.01). No trial × period interaction was identified for the saliva flow rates. Although the SIgA secretion rate was not affected by placebo ingestion (P = 0.36), it significantly increased after 4-week chlorella ingestion than before intake (P < 0.01). Conclusions These results suggest 4-week ingestion of a chlorella-derived multicomponent supplement increases salivary SIgA secretion and possibly improves mucosal immune function in humans. PMID:21906314

  6. Daryamide Analogues from a Marine-Derived Streptomyces species.

    PubMed

    Fu, Peng; La, Scott; MacMillan, John B

    2017-04-28

    Three new cyclohexene amine derivatives, daryamides D-F (1-3), a new arylamine derivative, carpatamide D (4), and a new ornithine lactamization derivative, ornilactam A (5), were isolated from the marine-derived Streptomyces strain SNE-011. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and chemical methods. The carpatamide skeleton could be considered as the biosynthetic precursor of the daryamides.

  7. Synthesis, photoluminescent, antibacterial activities and theoretical studies of 4-hydroxycoumarin derivatives

    NASA Astrophysics Data System (ADS)

    Li, Jing; Hou, Zheng; Li, Fen; Zhang, Zi-dan; Zhou, Ying; Luo, Xiao-xing; Li, Ming-kai

    2014-10-01

    Two new biscoumarin and epoxydicoumarin derivatives, namely, 3,3‧-(4-di-p-tolyl-amino-benzylidene)-bis-(4-hydroxycoumarin) (DBH) and 9-(4-di-p-tolyl-amino-phenyl)-1,8-dioxo-9H-dibenzo[c,h]-2,7,10-trioxanthene (DDT), were synthesized and characterized via IR, 1H NMR, HRMS, single crystal X-ray crystallography and UV-vis absorption spectra. The fluorescence behaviors of DBH and DDT in dichloromethane solutions were observed. The in vitro antibacterial activity of DBH and DDT against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC) was evaluated by observing the minimum inhibitory concentration. The results showed that compared with compound DDT, DBH exhibited better potent antibacterial activity.

  8. Evolution from a natural flavones nucleus to obtain 2-(4-Propoxyphenyl)quinoline derivatives as potent inhibitors of the S. aureus NorA efflux pump.

    PubMed

    Sabatini, Stefano; Gosetto, Francesca; Manfroni, Giuseppe; Tabarrini, Oriana; Kaatz, Glenn W; Patel, Diixa; Cecchetti, Violetta

    2011-08-25

    Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, norA-overexpressing strains. © 2011 American Chemical Society

  9. Bis-Indole-Derived NR4A1 Ligands and Metformin Exhibit NR4A1-Dependent Glucose Metabolism and Uptake in C2C12 Cells.

    PubMed

    Mohankumar, Kumaravel; Lee, Jehoon; Wu, Chia Shan; Sun, Yuxiang; Safe, Stephen

    2018-05-01

    Treatment of C2C12 muscle cells with metformin or the NR4A1 ligand 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) induced NR4A1 and Glut4 messenger RNA and protein expression. Similar results were observed with buttressed (3- or 3,5-substituted) analogs of DIM-C-pPhOH, including 1,1-bis(3'-indolyl)-1-(3-chloro-4-hydroxy-5-methoxyphenyl)methane (DIM-C-pPhOH-3-Cl-5-OCH3), and the buttressed analogs were more potent than DIM-C-pPhOH NR4A1 agonists. Metformin and the bis-indole substituted analogs also induced expression of several glycolytic genes and Rab4, which has previously been linked to enhancing cell membrane accumulation of Glut4 and overall glucose uptake in C2C12 cells, and these responses were also observed after treatment with metformin and the NR4A1 ligands. The role of NR4A1 in mediating the responses induced by the bis-indoles and metformin was determined by knockdown of NR4A1, and this resulted in attenuating the gene and protein expression and enhanced glucose uptake responses induced by these compounds. Our results demonstrate that the bis-indole-derived NR4A1 ligands represent a class of drugs that enhance glucose uptake in C2C12 muscle cells, and we also show that the effects of metformin in this cell line are NR4A1-dependent.

  10. Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice.

    PubMed

    Lee, Hyun Gyu; Cho, Nam-Chul; Jeong, Ae Jin; Li, Yu-Chen; Rhie, Sung-Ja; Choi, Jung Sook; Lee, Kwang-Ho; Kim, Youngsoo; Kim, Yong-Nyun; Kim, Myoung-Hwan; Pae, Ae Nim; Ye, Sang-Kyu; Kim, Byung-Hak

    2016-01-01

    T-cell-mediated immune responses play an important role in body protection. However, aberrantly activated immune responses are responsible for inflammatory and autoimmune diseases. The regulation of pathologic immune responses may be a potential therapeutic strategy for the treatment of these diseases. Despite that multiple pharmacologic properties of benzoxathiole derivatives have been defined, the molecular mechanisms underlying these properties remain to be clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune responses and ameliorated experimentally induced inflammatory skin diseases both in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4(+) T-cell subsets by regulating the expression and production of T-cell lineage-specific master transcription factors and cytokines and activating the signal transducer and activator of transcription proteins. In addition, BOT-4-one inhibited TCR-mediated Akt and NF-κB signaling. Topical application of BOT-4-one ameliorated experimentally induced inflammatory skin diseases in mice models such as 2,4,6-trinitrochlorobenzene-induced contact and atopic dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing the pathogenic CD4(+) T cell differentiation and overall immune responses. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Thermodynamics and binding mode of novel structurally related 1,2,4-thiadiazole derivatives with native and modified cyclodextrins

    NASA Astrophysics Data System (ADS)

    Terekhova, Irina V.; Chislov, Mikhail V.; Brusnikina, Maria A.; Chibunova, Ekaterina S.; Volkova, Tatyana V.; Zvereva, Irina A.; Proshin, Alexey N.

    2017-03-01

    Study of complex formation of cyclodextrins with 1,2,4-thiadiazole derivatives intended for Alzheimer's disease treatment was carried out using 1H NMR, ITC and phase solubility methods. Structure of cyclodextrins and thiadiazoles affects the binding mode and thermodynamics of complexation. The larger cavity of β- and γ-cyclodextrins is more appropriate for deeper insertion of 1,2,4-thiadiazole derivatives which is accompanied by intensive dehydration and solvent reorganization. Benzene ring of the thiadiazoles is located inside macrocyclic cavity while piperidine ring is placed outside the cavity and can form H-bonds with cyclodextrin exterior. Complexation with cyclodextrins induces the enhancement of aqueous solubility of 1,2,4-thiadiazole derivatives.

  12. Synthesis, alkaline phosphatase inhibition studies and molecular docking of novel derivatives of 4-quinolones.

    PubMed

    Miliutina, Mariia; Ejaz, Syeda Abida; Khan, Shafi Ullah; Iaroshenko, Viktor O; Villinger, Alexander; Iqbal, Jamshed; Langer, Peter

    2017-01-27

    New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC 50 values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 ± 0.11 to 44.80 ± 2.34 μM, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 ± 0.32 to 192.10 ± 3.78 μM. The most active derivative exhibits a potent inhibition on IAP with a ≈14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Synthesis and biological activity of novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives.

    PubMed

    El-Sawy, Eslam R; Ebaid, Manal S; Abo-Salem, Heba M; El-Hallouty, Salwa; Kassem, Emad M; Mandour, Adel H

    2014-05-01

    A novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives 3a,b, 10a-g and 11a-g were prepared in good yields via the reaction of 4-methoxy (1a) and 4,7-dimethoxy-5-acetyl-6-hydroxybenzofurans (1b) and their α,β-unsaturated keto derivatives 6a-g and 7a-g with chlorosulfonyl isocyanate (CSI). On the other hand, N-chlorosulfonyl carbamate derivatives 4a,b, 12a,b and 13a,b were prepared and allowed to react with piperidine to give the corresponding N-piperidinosulfonyl carbamate derivatives 5a,b, 14a,b and 15a,b, respectively. Sixteen new target compounds 3a,b, 10a-g, and 11a-g were tested for their DPPH radical-scavenging, and in vitro antiproliferative activity against A-549, MCF7 and HCT-116 cancer cell lines. Compounds 10a, 11c, 11e, and 11g showed moderate DPPH radical-scavenging activity compared to ascorbic acid at 100 μg/mL. 4,9-Dimethoxy-5-substituted styrylfuro[3,2-g]-1,2,3-benzoxathiazine-7,7-dioxides 11a, 11b, and 11c were found to be highly active against A-549 and HCT-116 cancer cell lines with IC50 values ranging from 0.02 to 0.08 μmol/mL compared to doxorubicin with IC50 = 0.04 and 0.06 μmol/mL, respectively.

  14. Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

    PubMed

    Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

    2012-11-01

    A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Synthesis and biological activity of novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives

    PubMed Central

    El-Sawy, Eslam R.; Ebaid, Manal S.; Abo-Salem, Heba M.; El-Hallouty, Salwa; Kassem, Emad M.; Mandour, Adel H.

    2013-01-01

    A novel series of 4-methoxy, and 4,9-dimethoxy-5-substituted furo[2,3-g]-1,2,3-benzoxathiazine-7,7-dioxide derivatives 3a,b, 10a–g and 11a–g were prepared in good yields via the reaction of 4-methoxy (1a) and 4,7-dimethoxy-5-acetyl-6-hydroxybenzofurans (1b) and their α,β-unsaturated keto derivatives 6a–g and 7a–g with chlorosulfonyl isocyanate (CSI). On the other hand, N-chlorosulfonyl carbamate derivatives 4a,b, 12a,b and 13a,b were prepared and allowed to react with piperidine to give the corresponding N-piperidinosulfonyl carbamate derivatives 5a,b, 14a,b and 15a,b, respectively. Sixteen new target compounds 3a,b, 10a–g, and 11a–g were tested for their DPPH radical-scavenging, and in vitro antiproliferative activity against A-549, MCF7 and HCT-116 cancer cell lines. Compounds 10a, 11c, 11e, and 11g showed moderate DPPH radical-scavenging activity compared to ascorbic acid at 100 μg/mL. 4,9-Dimethoxy-5-substituted styrylfuro[3,2-g]-1,2,3-benzoxathiazine-7,7-dioxides 11a, 11b, and 11c were found to be highly active against A-549 and HCT-116 cancer cell lines with IC50 values ranging from 0.02 to 0.08 μmol/mL compared to doxorubicin with IC50 = 0.04 and 0.06 μmol/mL, respectively. PMID:25685501

  16. Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives as novel small molecule chaperone amplifiers.

    PubMed

    Zhou, Yuefen; Wei, Linyi; Brady, Thomas P; Murali Mohan Redddy, P S; Nguyen, Tram; Chen, Jinhua; Au, Qingyan; Yoon, Il Sang; Yip, Gary; Zhang, Bin; Barber, Jack R; Ng, Shi Chung

    2009-08-01

    Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC(50)=2.5microM) and significant cytoprotection in both rotenone (EC(50)=0.23microM) and oxygen-glucose deprivation cell toxicity models (80% protection at 2.5microM).

  17. A phosphine mediated sequential annulation process of 2-tosylaminochalcones with MBH carbonates to construct functionalized aza-benzobicyclo[4.3.0] derivatives.

    PubMed

    Zhang, Qinglong; Zhu, Yannan; Jin, Hongxing; Huang, You

    2017-04-04

    A novel phosphine mediated sequential annulation process to construct functionalized aza-benzobicyclo[4.3.0] derivatives has been developed involving a one-pot sequential catalytic and stoichiometric process, which generates a series of benzobicyclo[4.3.0] compounds containing one quaternary center with up to 94% yield and 20 : 1 dr value. In this reaction, MBH carbonates act as 1,2,3-C 3 synthons.

  18. Anti-mycobacterial activity of marine fungus-derived 4-deoxybostrycin and nigrosporin.

    PubMed

    Wang, Cong; Wang, Juan; Huang, Yuhong; Chen, Hong; Li, Yan; Zhong, Lili; Chen, Yi; Chen, Shengping; Wang, Jun; Kang, Juling; Peng, Yi; Yang, Bin; Lin, Yongcheng; She, Zhigang; Lai, Xiaomin

    2013-01-29

    4-Deoxybostrycin is a natural anthraquinone compound isolated from the Mangrove endophytic fungus Nigrospora sp. collected from the South China Sea. Nigrosporin is the deoxy-derivative of 4-deoxybostrycin. They were tested against mycobacteria, especially Mycobacterium tuberculosis. In the Kirby-Bauer disk diffusion susceptibility test, they both had inhibition zone sizes of over 25 mm. The results of the absolute concentration susceptibility test suggested that they had inhibitory effects against mycobacteria. Moreover, 4-deoxybostrycin exhibited good inhibition which was even better than that of first line anti-tuberculosis (TB) drugs against some clinical multidrug-resistant (MDR) M. tuberculosis strains. The gene expression profile of M. tuberculosis H37Rv after treatment with 4-deoxybostrycin was compared with untreated bacteria. One hundred and nineteen out of 3,875 genes were significantly different in M. tuberculosis exposed to 4-deoxybostrycin from control. There were 46 functionally known genes which are involved in metabolism, information storage and processing and cellular processes. The differential expressions of six genes were further confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The present study provides a useful experiment basis for exploitation of correlative new drugs against TB and for finding out new targets of anti-mycobacterial therapy.

  19. Mass spectral analysis of C3 and C4 aliphatic amino acid derivatives.

    NASA Technical Reports Server (NTRS)

    Lawless, J. G.; Chadha, M. S.

    1971-01-01

    Diagnostic criteria are obtained for the distinction of alpha, beta, gamma, and N-methyl isomers of the C3 and C4 aliphatic amino acids, using mass spectral analysis of the derivatives of these acids. The use of deuterium labeling has helped in the understanding of certain fragmentation pathways.

  20. Synthesis and properties of 2-(4-substituted)butyl derivatives of some 2,3-dihydro-1,3-dioxo-1H-pyrrolo[3,4-c]pyridines.

    PubMed

    Sladowska, H; Szkatuła, D; Filipek, B; Maciag, D; Sapa, J; Zygmunt, M

    2001-02-01

    The synthesis of 2-(4-substituted)butyl derivatives of 4-alkoxy-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (10-15) and the results of preliminary pharmacological screening are described in this paper. All the compounds tested showed a strong analgesic action, suppressed spontaneous locomotor activity and prolonged barbiturate sleep. Except 10, all significantly decreased systolic and diastolic blood pressure.

  1. Synthesis and biological evaluation of new 2-(4,5-dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine derivatives.

    PubMed

    Touzeau, Frédérique; Arrault, Axelle; Guillaumet, Gérald; Scalbert, Elizabeth; Pfeiffer, Bruno; Rettori, Marie-Claire; Renard, Pierre; Mérour, Jean-Yves

    2003-05-08

    2-(4,5-Dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine derivatives and tricyclic analogues with a fused additional ring on the nitrogen atom of the benzoxazine moiety have been prepared and evaluated for their cardiovascular effects as potential antihypertensive agents. The imidazoline ring was generated by reaction of the corresponding ethyl ester with ethylenediamine. Affinities for imidazoline binding sites (IBS) I(1) and I(2) and alpha(1) and alpha(2) adrenergic receptors were evaluated as well as the effects on mean arterial blood pressure (MAP) and heart rate (HR) of spontaneously hypertensive rats. With few exceptions the most active compounds on MAP were those with high affinities for IBS and alpha(2) receptor. Among these, compound 4h was the most interesting and is now, together with its enantiomers, under complementary pharmacological evaluation.

  2. Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate Pathogenic Skin Inflammation in Mice.

    PubMed

    Lee, Hyun Gyu; Cho, Nam-Chul; Jeong, Ae Jin; Li, Yu-Chen; Rhie, Sung-Ja; Choi, Jung Sook; Lee, Kwang-Ho; Kim, Youngsoo; Kim, Yong-Nyun; Kim, Myoung-Hwan; Pae, Ae Nim; Ye, Sang-Kyu; Kim, Byung-Hak

    2015-09-30

    T cell-mediated immune responses play an important role in body protection. However, aberrantly activated immune responses are responsible for inflammatory and autoimmune diseases. The regulation of pathological immune responses may be a potential therapeutic strategy for the treatment of these diseases. Despite multiple pharmacological properties of benzoxathiole derivatives have been defined, the molecular mechanisms underlying these properties remain to be clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune responses and ameliorated experimentally induced inflammatory skin diseases both in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4 + T-cell subsets by regulating the expression and production of T cell lineage-specific master transcription factors and cytokines and activating the signal transducer and activator of transcription (STAT) proteins. In addition, BOT-4-one inhibited T-cell receptor (TCR)-mediated Akt and nuclear factor-kappaB (NF-κB) signaling. Topical application of BOT-4-one ameliorated experimentally induced inflammatory skin diseases in mice models such as TNCB-induced contact and atopic dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing the pathogenic CD4 + T cell differentiation and the overall immune responses.Journal of Investigative Dermatology accepted article preview online, 30 September 2015. doi:10.1038/jid.2015.384.

  3. Analysis of glycerophosphocholine molecular species as derivatives of 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin.

    PubMed

    Wheelan, P; Zirrolli, J A; Clay, K L

    1992-01-01

    A method has been developed for the analysis of derivatized diradylglycerols obtained from glycerophosphocholine (GPC) of transformed murine bone marrow-derived mast cells that provided high performance liquid chromatography (HPLC) separation of GPC subclasses and molecular species separation with on-line quantitation using UV detection. In addition, the derivatized diradylglycerol species were unequivocably identified by continuous flow fast-atom bombardment mass spectrometry. GPC was initially isolated by thin-layer chromatography (TLC), the phosphocholine group was hydrolyzed, and the resultant diradylglycerol was derivatized with 7-[(chlorocarbonyl)-methoxy]-4-methylcoumarin (CMMC). After separation of the derivatized subclasses by normal phase HPLC, the individual molecular species of the alkylacyl and diacyl subclasses were quantitated and collected during a subsequent reverse phase HPLC step. With an extinction coefficient of 14,700 l mol-1 cm-1 at a wavelength detection of 320 nm, the CMMC derivatives afforded sensitive UV detection (100 pmol) and quantitation of the molecular species. Continuous flow fast-atom bombardment mass spectrometry of the alkylacyl CMMC derivatives yielded abundant [MH]+ ions and a single fragment ion formed by loss of alkylketene from the sn-2 acyl group, [MH-(R = C = O)]+. No fragmentation of the sn-1 alkyl chain was observed. Diacyl derivatives also produced abundant [MH]+ ions plus two fragment ions arising from loss of RCOOH from each of the acyl substituents and two fragment ions from the loss of alkyketene from each acyl group. Individual molecular species substituents were assigned from these ions.

  4. Simultaneous quantification of preactivated ifosfamide derivatives and of 4-hydroxyifosfamide by high performance liquid chromatography-tandem mass spectrometry in mouse plasma and its application to a pharmacokinetic study.

    PubMed

    Deroussent, Alain; Skarbek, Charles; Maury, Adeline; Chapuis, Hubert; Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Durand, Sylvère; Couvreur, Patrick; Desmaële, Didier; Paci, Angelo

    2015-06-15

    The antitumor drug, ifosfamide (IFO), requires activation by cytochrome P450 (CYP) to form the active metabolite, 4-hydroxyisfosfamide (4-OHIFO), leading to toxic by-products at high dose. In order to overcome these drawbacks, preactivated ifosfamide derivatives (RXIFO) were designed to release 4-OHIFO without CYP involvement. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the simultaneous quantification of 4-OHIFO, IFO and four derivatives RXIFO in mouse plasma using multiple reaction monitoring. Because of its instability in plasma, 4-OHIFO was immediately converted to the semi-carbazone derivative, 4-OHIFO-SCZ. For the six analytes, the calibration curves were linear from 20 to 5000ng/mL in 50μL plasma and the lower limit of quantitation was determined at 20ng/mL with accuracies within ±10% of nominal and precisions less than 12%. Their recoveries ranged from 62 to 96% by using liquid-liquid extraction. With an improved assay sensitivity compared to analogues, the derivative 4-OHIFO-SCZ was stable in plasma at 4°C for 24h and at -20°C for three months. For all compounds, the assay was validated with accuracies within ±13% and precisions less than 15%. This method was applied to a comparative pharmacokinetic study of 4-OHIFO from IFO and three derivatives RXIFO in mice. This active metabolite was produced by some of the novel conjugates with good pharmacokinetic properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands.

    PubMed

    Sadeghzadeh, Masoud; Sheibani, Shahab; Ghandi, Mehdi; Daha, Fariba Johari; Amanlou, Massoud; Arjmand, Mohammad; Hasani Bozcheloie, Abolfazl

    2013-06-01

    This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. Synthesis of 4′-aminopantetheine and derivatives to probe aminoglycoside N-6′-acetyltransferase

    PubMed Central

    Yan, Xuxu; Akinnusi, T. Olukayode; Larsen, Aaron T.; Auclair, Karine

    2011-01-01

    Summary A convenient synthesis of 4′-aminopantetheine from commercial D-pantethine is reported. The amino group was introduced by reductive amination in order to avoid substitution at a sterically congested position. Derivatives of 4′-aminopantetheine were also prepared to evaluate the effect of O-to-N substitution on inhibitors of the resistance-causing enzyme aminoglycoside N-6′-acetyltransferase. The biological results combined with docking studies indicate that in spite of its reported unusual flexibility and ability to adopt different folds, this enzyme is highly specific for AcCoA. PMID:21225062

  7. Synthesis and biological evaluation of cis-locked vinylogous combretastatin-A4 analogues: derivatives with a cyclopropyl-vinyl or a cyclopropyl-amide bridge.

    PubMed

    Ty, Nancy; Kaffy, Julia; Arrault, Alban; Thoret, Sylviane; Pontikis, Renée; Dubois, Joelle; Morin-Allory, Luc; Florent, Jean-Claude

    2009-03-01

    A series of novel combretastatin A4 analogues, in which the cis-olefinic bridge is replaced by a cyclopropyl-vinyl or a cyclopropyl-amide moiety, were synthesized and evaluated for inhibition of tubulin polymerization and antiproliferative activity. The derivative 9a with a (cis,E)-cyclopropyl-vinyl unit is the most promising compound. As expected, molecular docking of 9a has shown that only one of the cis-cyclopropyl enantiomers is a good ligand for tubulin.

  8. Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents.

    PubMed

    Luo, Wen; Wang, Ting; Hong, Chen; Yang, Ya-Chen; Chen, Ying; Cen, Juan; Xie, Song-Qiang; Wang, Chao-Jie

    2016-10-21

    A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Design, synthesis, and antiviral activity of novel rutin derivatives containing 1, 4-pentadien-3-one moiety.

    PubMed

    Han, Yu; Ding, Yan; Xie, Dandan; Hu, Deyu; Li, Pei; Li, Xiangyang; Xue, Wei; Jin, Linhong; Song, Baoan

    2015-03-06

    Rutin (compound 5) and some compounds (compounds 1-4 and 6) were isolated from Artemisia princeps Pamp (A. princeps Pamp.) and a series of novel rutin derivatives containing 1,4-pentadien-3-one moiety were designed and synthesized. The target compounds were characterized by proton nuclear magnetic resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy ((13)C NMR), and ESI-MS. Bioassay results indicated that some of the compounds showed good to excellent antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) at 500 μg/mL in vivo. The 50% effective concentrations (EC50) of the compound 7r against CMV was 394.78 μg/mL, which was better than that of Ningnanmycin (432.22 μg/mL). These results indicated that novel rutin derivatives containing 1,4-pentadien-3-one moiety can effectively control CMV. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Microwave-assisted synthesis and structure-activity relationships of neuroactive pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives.

    PubMed

    Nascimento-Júnior, Nailton M; Mendes, Thaiana C F; Leal, Daniella M; Corrêa, Claudia Maria N; Sudo, Roberto T; Zapata-Sudo, Gisele; Barreiro, Eliezer J; Fraga, Carlos A M

    2010-01-01

    We described herein the optimization of the synthetic methodology exploited to obtain the pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine sedative prototype 1a and novel analogues designed by successive molecular simplifications. By applying microwave irradiation during the hetero Diels-Alder key-step to obtain the heterotricyclic scaffold, under solvent-free conditions, we were able to obtain the desired compounds in drastically shorter times and better yields. Additionally, in vivo evaluation of the sedative effects of these heterocyclic derivatives showed that 1a and the novel structurally-related analogue 1e were the most efficient compounds to impair the locomotor activity in mice at the dose of 10micromol/kg. Copyright 2009 Elsevier Ltd. All rights reserved.

  11. Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cinnamon, increases glucose disposal by enhancing translocation of glucose transporter 4.

    PubMed

    Kim, W; Khil, L Y; Clark, R; Bok, S H; Kim, E E; Lee, S; Jun, H S; Yoon, J W

    2006-10-01

    Cinnamon extracts have anti-diabetic effects. Phenolic acids, including hydrocinnamic acids, were identified as major components of cinnamon extracts. Against this background we sought to develop a new anti-diabetic compound using derivatives of hydroxycinnamic acids purified from cinnamon. We purified hydroxycinnamic acids from cinnamon, synthesised a series of derivatives, and screened them for glucose transport activity in vitro. We then selected the compound with the highest glucose transport activity in epididymal adipocytes isolated from male Sprague-Dawley rats in vitro, tested it for glucose-lowering activity in vivo, and studied the mechanisms involved. A naphthalenemethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105) showed the highest glucose transport activity in vitro. Treatment of streptozotocin-induced diabetic C57BL/6 mice and spontaneously diabetic ob/ob mice with DHH105 decreased blood glucose levels to near normoglycaemia. Further studies revealed that DHH105 increased the maximum speed of glucose transport and the translocation of glucose transporter 4 (GLUT4, now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) in adipocytes, resulting in increased glucose uptake. In addition, DHH105 enhanced phosphorylation of the insulin receptor-beta subunit and insulin receptor substrate-1 in adipocytes, both in vitro and in vivo. This resulted in the activation of phosphatidylinositol 3-kinase and Akt/protein kinase B, contributing to the translocation of GLUT4 to the plasma membrane. We conclude that DHH105 lowers blood glucose levels through the enhancement of glucose transport, mediated by an increase in insulin-receptor signalling. DHH105 may be a valuable candidate for a new anti-diabetic drug.

  12. Gas chromatographic determination of formaldehyde in maple syrup as 2,4-dinitrophenylhydrazone derivative.

    PubMed

    Baraniak, Z; Nagpal, D S; Neidert, E

    1988-01-01

    A procedure is presented for the quantitative extraction and determination of formaldehyde in maple sap and syrup. The method is based on the reaction between formaldehyde and 2,4-dinitrophenylhydrazine and determination of the derivative by gas chromatography. The procedure was used to evaluate formaldehyde in saps and syrups of paraformaldehyde implanted trees. Average recoveries were 101.5 +/- 5.7%. The detection limit was 0.078 mg/kg.

  13. 17 CFR 240.15c3-4 - Internal risk management control systems for OTC derivatives dealers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Internal risk management control systems for OTC derivatives dealers. 240.15c3-4 Section 240.15c3-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the...

  14. Carbothermic Synthesis of ~820- m UN Kernels. Investigation of Process Variables

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lindemer, Terrence; Silva, Chinthaka M; Henry, Jr, John James

    2015-06-01

    This report details the continued investigation of process variables involved in converting sol-gel-derived, urainia-carbon microspheres to ~820-μm-dia. UN fuel kernels in flow-through, vertical refractory-metal crucibles at temperatures up to 2123 K. Experiments included calcining of air-dried UO 3-H 2O-C microspheres in Ar and H 2-containing gases, conversion of the resulting UO 2-C kernels to dense UO 2:2UC in the same gases and vacuum, and its conversion in N 2 to in UC 1-xN x. The thermodynamics of the relevant reactions were applied extensively to interpret and control the process variables. Producing the precursor UO 2:2UC kernel of ~96% theoretical densitymore » was required, but its subsequent conversion to UC 1-xN x at 2123 K was not accompanied by sintering and resulted in ~83-86% of theoretical density. Decreasing the UC 1-xN x kernel carbide component via HCN evolution was shown to be quantitatively consistent with present and past experiments and the only useful application of H2 in the entire process.« less

  15. Synthesis, antimalarial activity and molecular docking of hybrid 4-aminoquinoline-1,3,5-triazine derivatives.

    PubMed

    Bhat, Hans Raj; Singh, Udaya Pratap; Thakur, Anjali; Kumar Ghosh, Surajit; Gogoi, Kabita; Prakash, Anil; Singh, Ramendra K

    2015-10-01

    A series of novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized in a five-steps reaction and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (3D7) and chloroquine-resistant (RKL-2) strains of Plasmodium falciparum. Entire synthetic derivatives showed higher antimalarial activity on the sensitive strain while two compounds, viz., 9a and 9c displayed good activity against both the strains of P. falciparum. The observed activity was further substantiated by docking study on both wild and qradruple mutant type P. falciparum dihydrofolate reductase-thymidylate synthase (pf-DHFR-TS). Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Synthesis, molecular modelling, and preliminary anticonvulsant activity evaluation of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4] nonane-3,8-dione derivatives.

    PubMed

    Ghareb, Nagat; Abdel Daim, Mohamed M; El-Sayed, Norhan M; Elgawish, Mohamed Saleh

    2017-04-01

    The synthesis, pharmacological evaluation and molecular modelling study of novel naphthalen-2-yl acetate and 1,6-dithia-4,9-diazaspiro [4.4]nonane-3,8-dione derivatives as potential anticonvulsant agents are described. The newly synthesized compounds were characterized by both analytical and spectral data. Alkylation of 1H-imidazole or substituted piperazine with 1-(2-naphthyl)-2-bromoethanone (2) gave naphthalen-2-yl 2-(1H-imidazol-1-yl) acetate (3) and naphthalen-2-yl 2-(substituted piperazin-1-yl) acetate (4-8). Moreover, condensation of naphthalen-2-yl 2-bromoacetate or 2-bromo-1-(naphthalen-2-yl) ethanone with hydrazine hydrate and acetylacetone resulted in the formation of the cyclic pyrazole products 9 and 13. Sonication of naphthalen-2-yl acetate (1) with 2-chloropyridine, 2-chloropyrimidine and 2-(chloromethyl) oxirane gave naphthalen-2-yl 2-(pyridin-2-yl) acetate (10), naphthalen-2-yl 2-(pyrimidin-2-yl) acetate (11) and naphthalen-2-yl-3-(oxiran-2-yl) propanoate (12) respectively. Cyclocondensation reaction of 2-iminothiazolidin-4-one (14) with thioglycolic acid, thiolactic acid and thiomalic acid gave 1,6-dithia-4,9-diazaspiro [4.4]nonane-3,8-dione derivatives (15-17). The compounds were testedin vivofor the anticonvulsant activity by delaying strychnine-induced seizures. The diazaspirononane (17) and 1-(2-naphthyl)-2-bromoethanone (2) showed a high significant delay in the onset of convulsion and prolongation of survival time compared to phenobarbital. The molecular modelling study of anticonvulsant activity of synthesized compounds showed a CNS depressant activity via modulation of benzodiazepine allosteric site in GABA-A receptors. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Theoretical studies on 2-diazo-4,6-dinitrophenol derivatives aimed at finding superior propellants.

    PubMed

    Liu, Yan; Wang, Lianjun; Wang, Guixiang; Du, Hongchen; Gong, Xuedong

    2012-04-01

    In an attempt to find superior propellants, 2-diazo-4,6-dinitrophenol (DDNP) and its -NO(2), -NH(2), -CN, -NC, -ONO(2), and -NF(2) derivatives were studied at the B3LYP/6-311++G level of density functional theory (DFT). Sensitivity was evaluated using bond dissociation enthalpies (BDEs) and molecular surface electrostatic potentials. The C-NO(2) bond appears to be the trigger bond during the thermolysis process for these compounds, except for the -ONO(2) and -NF(2) derivatives. Electrostatic potential results show that electron-withdrawing substituents make the charge imbalance more anomalous, which may change the strength of the bond, especially the weakest trigger bond. Most of the DDNP derivatives have the impact sensitivities that are higher than that of DDNP, making them favorable for use as solid propellants in micro-rockets. The theoretical densities (ρ), heats of formation (HOFs), detonation energies (Q), detonation pressures (P), and detonation velocities (D) of the compounds were estimated. The effects of various substituent groups on ρ, HOF, Q, D, and P were investigated. Some derivatives exhibit perfect detonation properties. The calculated relative specific impulses (I (r,sp)) of all compounds except for -NH(2) derivatives were higher than that of DDNP, and also meet the requirements of propellants.

  18. 4-D Cloud Water Content Fields Derived from Operational Satellite Data

    NASA Technical Reports Server (NTRS)

    Smith, William L., Jr.; Minnis, Patrick

    2010-01-01

    In order to improve operational safety and efficiency, the transportation industry, including aviation, has an urgent need for accurate diagnoses and predictions of clouds and associated weather conditions. Adverse weather accounts for 70% of all air traffic delays within the U.S. National Airspace System. The Federal Aviation Administration has determined that as much as two thirds of weather-related delays are potentially avoidable with better weather information and roughly 20% of all aviation accidents are weather related. Thus, it is recognized that an important factor in meeting the goals of the Next Generation Transportation System (NexGen) vision is the improved integration of weather information. The concept of a 4-D weather cube is being developed to address that need by integrating observed and forecasted weather information into a shared 4-D database, providing an integrated and nationally consistent weather picture for a variety of users and to support operational decision support systems. Weather analyses and forecasts derived using Numerical Weather Prediction (NWP) models are a critical tool that forecasters rely on for guidance and also an important element in current and future decision support systems. For example, the Rapid Update Cycle (RUC) and the recently implemented Rapid Refresh (RR) Weather Research and Forecast (WRF) models provide high frequency forecasts and are key elements of the FAA Aviation Weather Research Program. Because clouds play a crucial role in the dynamics and thermodynamics of the atmosphere, they must be adequately accounted for in NWP models. The RUC, for example, cycles at full resolution five cloud microphysical species (cloud water, cloud ice, rain, snow, and graupel) and has the capability of updating these fields from observations. In order to improve the models initial state and subsequent forecasts, cloud top altitude (or temperature, T(sub c)) derived from operational satellite data, surface observations of

  19. Electronic structure, hydrogen bonding and spectroscopic profile of a new 1,2,4-triazole-5(4H)-thione derivative: A combined experimental and theoretical (DFT) analysis

    NASA Astrophysics Data System (ADS)

    Al-Tamimi, Abdul-Malek S.

    2016-09-01

    Density functional theory has been implemented to study the electronic structure, molecular properties and vibrational spectra of 3-(adamantan-1-yl)-4-(4-chlorophenyl)-1H-1,2,4-triazole-5(4H)-thione, a novel 1,2,4-triazole-5(4H)-thione derivative. Hydrogen bonded dimer of the title molecule has been studied using B3LYP, M06-2X and X3LYP functionals at 6-311++ G(d,p) level of theory. The intermolecular hydrogen bonding has been studied using NBO analysis of the dimer. Bader's AIM theory was also used to evaluate the strength as well as the hydrogen bonding characteristics. Experimental FT-IR and FT-Raman spectra of the title molecule were related with the spectral data obtained with DFT/B3LYP method. The 1H NMR chemical shifts of the title molecule were calculated by the GIAO method and compared with experimental results. Dipole moment, polarizability (α), first order static hyperpolarizability (β) along with molecular electrostatic potential surface have been calculated. Frequency-dependent first hyperpolarizabilities, β(-2ω;ω,ω) and β(-ω;ω,0) have also been evaluated to study the non-linear optical behavior of the title compound. UV-Vis spectrum of the title molecule was recorded and TD-DFT method has been used to calculate six lowest excited states and the corresponding excitation energies.

  20. Discovery of Pyrazolo[4,3-c]quinolines Derivatives as Potential Anti-Inflammatory Agents through Inhibiting of NO Production.

    PubMed

    Tseng, Chih-Hua; Tung, Chun-Wei; Peng, Shin-I; Chen, Yeh-Long; Tzeng, Cherng-Chyi; Cheng, Chih-Mei

    2018-04-28

    The synthesis and anti-inflammatory effects of certain pyrazolo[4,3- c ]quinoline derivatives 2a ⁻ 2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1 H -pyrazolo[4,3- c ]-quinoline ( 2i ) and 4-(3-amino-1 H -pyrazolo[4,3- c ]quinolin-4-ylamino)benzoic acid ( 2m ) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure⁻activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing.

  1. Synthesis, crystal structures, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives

    NASA Astrophysics Data System (ADS)

    Qi, De-Qiang; Yu, Chuan-Ming; You, Jin-Zong; Yang, Guang-Hui; Wang, Xue-Jie; Zhang, Yi-Ping

    2015-11-01

    A series of pyrazole-based 1,3,4-oxadiazole derivatives were rationally designed and synthesized in good yields by following a convenient route. All the newly synthesized molecules were fully characterized by IR, 1H NMR and elemental analysis. Eight compounds were structurally determined by single crystal X-ray diffraction analysis. The fluorescence properties of all the compounds were investigated in dimethyl sulfoxide media. In addition, these newly synthesized compounds were evaluated for in vitro inhibitory activity against commercial enzyme xanthine oxidase (XO) by measuring the formation of uric acid from xanthine. Among the compounds synthesized and tested, 3d and 3e were found to be moderate inhibitory activity against commercial XO with IC50 = 72.4 μM and 75.6 μM. The studies gave a new insight in further optimization of pyrazole-based 1,3,4-oxadiazole derivatives with excellent fluorescence properties and XO inhibitory activity.

  2. Synthesis, structure and stability of a chiral imine-based Schiff-based ligand derived from L-glutamic acid and its [Cu4] complex

    NASA Astrophysics Data System (ADS)

    Muche, Simon; Levacheva, Irina; Samsonova, Olga; Biernasiuk, Anna; Malm, Anna; Lonsdale, Richard; Popiołek, Łukasz; Bakowsky, Udo; Hołyńska, Małgorzata

    2017-01-01

    Studies of the stability of a ligand derived from L-glutamic acid and ortho-vanillin and its new [Cu4] complex are presented. The [Cu4] complex contains a heterocubane [CuII4O4] core and pendant carboxylic groups increasing its solubility in water, also under basic conditions. The stability of the complex in different solvents is confirmed with ESI-MS studies and such experiments as successful recrystallization. The complex is stable also under physiological conditions whereas the ligand is partly decomposed to L-glutamic acid and ortho-vanillin.

  3. Enhanced Piezoelectric Response of AlN via CrN Alloying

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Manna, Sukriti; Talley, Kevin R.; Gorai, Prashun

    2018-03-01

    Since AlN has emerged as an important piezoelectric material for a wide variety of applications, efforts have been made to increase its piezoelectric response via alloying with transition metals that can substitute for Al in the wurtzite lattice. We report on density functional theory calculations of structure and properties of the CrxAl1-xN system for Cr concentrations ranging from zero to beyond the wurtzite-rocksalt transition point. By studying the different contributions to the longitudinal piezoelectric coefficient, we propose that the physical origin of the enhanced piezoelectricity in CrxAl1-xN alloys is the increase of the internal parameter u of the wurtzite structuremore » upon substitution of Al with the larger Cr ions. Among a set of wurtzite-structured materials, we find that CrxAl1-xN has the most sensitive piezoelectric coefficient with respect to alloying concentration. Based on these results, we propose that CrxAl1-xN is a viable piezoelectric material whose properties can be tuned via Cr composition. We support this proposal by combinatorial synthesis experiments, which show that Cr can be incorporated in the AlN lattice up to 30% before a detectable transition to rocksalt occurs. At this Cr content, the piezoelectric modulus d33 is approximately 4 times larger than that of pure AlN. This finding, combined with the relative ease of synthesis under nonequilibrium conditions, may position CrxAl1-xN as a prime piezoelectric material for applications such as resonators and acoustic wave generators.« less

  4. Synthesis and Antibacterial Activity of Quaternary Ammonium 4-Deoxypyridoxine Derivatives

    PubMed Central

    Shtyrlin, Nikita V.; Sapozhnikov, Sergey V.; Galiullina, Albina S.; Kayumov, Airat R.; Bondar, Oksana V.; Mirchink, Elena P.; Isakova, Elena B.; Firsov, Alexander A.; Balakin, Konstantin V.

    2016-01-01

    A series of novel quaternary ammonium 4-deoxypyridoxine derivatives was synthesized. Two compounds demonstrated excellent activity against a panel of Gram-positive methicillin-resistant S. aureus strains with MICs in the range of 0.5–2 μg/mL, exceeding the activity of miramistin. At the same time, both compounds were inactive against the Gram-negative E. coli and P. aeruginosa strains. Cytotoxicity studies on human skin fibroblasts and embryonic kidney cells demonstrated that the active compounds possessed similar toxicity with benzalkonium chloride but were slightly more toxic than miramistin. SOS-chromotest in S. typhimurium showed the lack of DNA-damage activity of both compounds; meanwhile, one compound showed some mutagenic potential in the Ames test. The obtained results make the described chemotype a promising starting point for the development of new antibacterial therapies. PMID:27800491

  5. Synthesis and characterization of 4-(1,2,4-triazole-5-yl)furazan derivatives as high-performance insensitive energetic materials.

    PubMed

    Zhen, Xu; Cheng, Guangbin; Yang, Hongwei; Zhang, Jiaheng; Shreeve, Jean'ne M

    2018-05-15

    3-Nitro-4-(5-nitro-1,2,4-triazol-3-yl)furazan (2), N,N'-bis(trinitroethyl)-3,5'-diamino-4-(1,2,4-triazol-3-yl)furazan (3), N,N'-bis(trinitroethyl)-3,5'-dinitramino-4-(1,2,4-triazol-3-yl)furazan (4) and eighteen nitrogen-rich salts (5a, 5b,5d⁓5i, 5g-1, 6a⁓6i) were designed and synthesized. These 4-(1,2,4-triazole-5-yl)furazan derivatives were fully characterized by IR and NMR spectra, elemental analysis, and differential scanning calorimetry (DSC). The solid-state structures of 2, 5d, 5e, 5h, 5g-1, 6g, and 6i were confirmed via single crystal X-ray analysis. Detonation performance (detonation velocities and pressures) of these energetic compounds was evaluated and the impact and friction sensitivities were measured using standard BAM technology. Some of the compounds, e.g., 2 (D: 9152 m s-1, P = 37.1 GPa) and 4 (D: 9355 m s-1, P = 40.1 GPa) exhibit excellent detonation performance, which are comparable to the highly explosive benchmarks such as RDX (D: 8795 m s-1, P = 34.9 GPa) and HMX (D: 9144 m s-1, P = 39.2 GPa). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Recognition of adenosine monophosphate and H2PO4- using zinc ensemble of new hexaphenylbenzene derivative: potential bioprobe and multichannel keypad system.

    PubMed

    Bhalla, Vandana; Vij, Varun; Kumar, Manoj; Sharma, Parduman Raj; Kaur, Tandeep

    2012-02-17

    Zinc ensemble of hexaphenylbenzene derivative 3 exhibits sensitive response toward adenosine monophosphate (AMP) and H(2)PO(4)(-) ions. Further, the application of derivative 3 as a multichannel molecular keypad could be realized in the presence of inputs of Zn(2+) ions, H(2)PO(4)(-) ions, and AMP.

  7. Synthesis, spectroscopic characterization and in vitro antimicrobial, anticancer and antileishmanial activities as well interaction with Salmon sperm DNA of newly synthesized carboxylic acid derivative, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid

    NASA Astrophysics Data System (ADS)

    Sirajuddin, Muhammad; Ali, Saqib; McKee, Vickie; Ullah, Hameed

    2015-03-01

    This paper stresses on the synthesis, characterization of novel carboxylic acid derivative and its application in pharmaceutics. Carboxylic acid derivatives have a growing importance in medicine, particularly in oncology. A novel carboxylic acid, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid, was synthesized and characterized by elemental analysis, FT-IR, NMR (1H, and 13C), mass spectrometry and single crystal X-ray structural analysis. The structure of the title compound, C11H12N2O6, shows the molecules dimerised by short intramolecular Osbnd H⋯O hydrogen bonds. The compound was screened for in vitro antimicrobial, anticancer, and antileishmanial activities as well as interaction with SS-DNA. The compound was also checked for in vitro anticancer activity against BHK-21, H-157 and HCEC cell lines, and showed significant anticancer activity. The compound was almost non-toxic towards human corneal epithelial cells (HCEC) and did not show more than 7.4% antiproliferative activity when used at the 2.0 μg/mL end concentration. It was also tested for antileishmanial activity against the promastigote form of leishmania major and obtained attractive result. DNA interaction study exposes that the binding mode of the compound with SS-DNA is an intercalative as it results in hypochromism along with minor red shift. A new and efficient strategy to identify pharmacophores sites in carboxylic acid derivative for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

  8. Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives.

    PubMed

    Trotsko, Nazar; Przekora, Agata; Zalewska, Justyna; Ginalska, Grażyna; Paneth, Agata; Wujec, Monika

    2018-12-01

    In our present research, we synthesised new thiazolidine-2,4-diones (12-28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC 50 values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC 50 values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment.

  9. Identification of Furan Metabolites Derived from Cysteine-cis-2-Butene-1,4-Dial-Lysine Crosslinks

    PubMed Central

    Lu, Ding; Peterson, Lisa A.

    2010-01-01

    Furan is a rodent hepatotoxicant and carcinogen. Since this compound is an important industrial intermediate and has been detected in heat-processed foods and smoke, humans are likely exposed to this toxic compound. Characterization of urinary metabolites of furan will lead to the development of biomarkers to assess human health risks associated with furan exposure. Previous studies indicate that furan is oxidized to a reactive α, β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), in a reaction catalyzed by cytochrome P450. Five previously characterized metabolites are derived from the reaction of BDA with cellular nucleophiles such as glutathione and protein. They include the mono-glutathione reaction product, N-[4-carboxy-4-(3-mercapto-1H-pyrrol-1-yl)-1-oxobutyl]-L-cysteinylglycine cyclic sulfide and its downstream metabolite, S-[1-(1,3-dicarboxypropyl)-1H-pyrrol-3-yl]methylthiol as well as R-2-acetylamino-6-(2,5-dihydro-2-oxo-1H-pyrrol-1-yl)-1-hexanoic acid and N-acetyl-S-[1-(5-acetylamino-5-carboxypentyl)-1H-pyrrol-3-yl]-L-cysteine and its sulfoxide. The last two compounds are downstream metabolites of a BDA-derived cysteine-lysine crosslink, S-[1-(5-amino-5-carboxypentyl)-1H-pyrrol-3-yl]-L-cysteine. In this report, we present the characterization of seven additional urinary furan metabolites, all of which are derived from this crosslink. The cysteinyl residue is subject to several biotransformation reactions, including N-acetylation and S-oxidation. Alternatively, it can undergo β-elimination followed by S-methylation to a methylthiol intermediate that is further oxidized to a sulfoxide. The lysine portion of the crosslink is either N-acetylated or undergoes an oxidative transamination reaction to generate an α-ketoacid metabolite that undergoes oxidative decarboxylation. Some of these metabolites are among the most abundant furan metabolites present in urine as judged by LC-MS/MS analysis, indicating that the oxidation of furan to BDA and BDA

  10. Selective Cytotoxicity of 1,3,4-Thiadiazolium Mesoionic Derivatives on Hepatocarcinoma Cells (HepG2)

    PubMed Central

    Valdameri, Glaucio; Rocha, Maria Eliane Merlin; Martinez, Glaucia Regina; Noleto, Guilhermina Rodrigues; Acco, Alexandra; Alves de Souza, Carlos Eduardo; Echevarria, Aurea; Moretto dos Reis, Camilla; Di Pietro, Attilio; Suter Correia Cadena, Sílvia Maria

    2015-01-01

    In this work, we evaluated the cytotoxicity of mesoionic 4-phenyl-5-(2-Y, 4-X or 4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X=OH, Y=H; MI-D: X=NO2, Y=H; MI-4F: X=F, Y=H; MI-2,4diF: X=Y=F) on human hepatocellular carcinoma (HepG2), and non-tumor cells (rat hepatocytes) for comparison. MI-J, M-4F and MI-2,4diF reduced HepG2 viability by ~ 50% at 25 μM after 24-h treatment, whereas MI-D required a 50 μM concentration, as shown by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The cytotoxicity was confirmed with lactate dehydrogenase assay, of which activity was increased by 55, 24 and 16% for MI-J, MI-4F and MI-2,4diF respectively (at 25 μM after 24 h). To identify the death pathway related to cytotoxicity, the HepG2 cells treated by mesoionic compounds were labeled with both annexin V and PI, and analyzed by flow cytometry. All compounds increased the number of doubly-stained cells at 25 μM after 24 h: by 76% for MI-J, 25% for MI-4F and MI-2,4diF, and 11% for MI-D. It was also verified that increased DNA fragmentation occurred upon MI-J, MI-4F and MI-2,4diF treatments (by 12%, 9% and 8%, respectively, at 25 μM after 24 h). These compounds were only weakly, or not at all, transported by the main multidrug transporters, P-glycoprotein, ABCG2 and MRP1, and were able to slightly inhibit their drug-transport activity. It may be concluded that 1,3,4-thiadiazolium compounds, especially the hydroxy derivative MI-J, constitute promising candidates for future investigations on in-vivo treatment of hepatocellular carcinoma. PMID:26083249

  11. Preparation and characterization of [H2-DABCO][ClO4]2 as a new member of DABCO-based ionic liquids for the synthesis of pyrimido[4,5-b]-quinoline and pyrimido[4,5-d]pyrimidine derivatives

    NASA Astrophysics Data System (ADS)

    Shirini, Farhad; Langarudi, Mohaddeseh Safarpoor Nikoo; Daneshvar, Nader; Jamasbi, Negar; Irankhah-Khanghah, Mahsa

    2018-06-01

    [H2-DABCO][ClO4]2, as a novel DABCO-based ionic liquid, has been synthesized, characterized, and used as an affordable and recyclable catalyst in the synthesis of pyrimido [4,5-b]-quinoline and pyrimido [4,5-d]pyrimidine derivatives. The procedure shows several advantages over the previous methods such as simplicity, high yields, short reaction times, easy work-up, and use of a non-metal catalyst. Moreover, this paper virtually debates the impact of anions and cations on moisture-resistant property and catalytic activity in DABCO-based ionic liquids through the comparison of [DABCO](SO3H)2(Cl)2, [DABCO](SO3H)2(HSO4)2, [H2-DABCO][H2PO4]2, [H2-DABCO][HSO4]2, and [H2-DABCO][ClO4]2.

  12. Discovery of 2,4,6-trisubstitued pyrido[3,4-d]pyrimidine derivatives as new EGFR-TKIs.

    PubMed

    Zhang, Hao; Wang, Jin; Shen, Ying; Wang, Hui-Yan; Duan, Wei-Ming; Zhao, Hong-Yi; Hei, Yuan-Yuan; Xin, Minhang; Cao, Yong-Xiao; Zhang, San-Qi

    2018-03-25

    Targeting acquired drug resistance is the major challenge in the treatment of EGFR-driven non-small cell lung cancer (NSCLC). In this study, a novel class of compounds containing pyrido[3,4-d]pyrimidine scaffold was designed as new generation EGFR-TKIs to overcome this challenge. The most promising compound B30 inhibited HCC827 and H1975 cells growth with the IC 50 values of 0.044 μM and 0.40 μM, respectively. Meanwhile, B30 displayed potent inhibitory activity against the EGFR L858R (IC 50  = 1.1 nM) and EGFR L858R/T790M/C797S (IC 50  = 7.2 nM). B30 could suppress EGFR phosphorylation in a dose-dependent manner in HCC827 cell line and significantly induce the apoptosis of HCC827 cells. Molecular docking indicated that the hydroxyl in B30 could form additional hydrogen bond with mutant Ser797. These findings strongly support our assumption that 2,4,6-trisubstitued pyrido[3,4-d] pyrimidine derivatives can serve as EGFR-TKIs. The predicted hydrogen bond interaction formed by a small molecule inhibitor with mutant Ser797 is available to design the fourth-generation EGFR-TKIs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  13. Synthesis and spectral studies of some 4H-pyran derivatives: Crystal and molecular structure of isobutyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate

    NASA Astrophysics Data System (ADS)

    Udhaya Kumar, C.; Sethukumar, A.; Arul Prakasam, B.

    2013-03-01

    A series of isobutyl 6-amino-4-aryl-5-cyano-2-methyl-4H-pyran-3-carboxylates (1-9) have been synthesized by the multicomponent reaction (MCR) between isobutyl ethylacetoacetate, aryl aldehydes and malononitrile using BF3:OEt2 as catalyst. The derived compounds have been analyzed by IR and NMR (1D and 2D) spectra. Single crystal X-ray structural analysis of 1, evidences the flattened-boat conformation of pyran ring.

  14. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

    PubMed Central

    Perretti, Mauro; Chiang, Nan; La, Mylinh; Fierro, Iolanda M.; Marullo, Stefano; Getting, Stephen J; Solito, Egle; Serhan, Charles N.

    2009-01-01

    Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci. PMID:12368905

  15. A comprehensive study of the optoelectronic properties of donor-acceptor based derivatives of 1,3,4-oxadiazole

    NASA Astrophysics Data System (ADS)

    Joshi, Ankita; Ramachandran, C. N.

    2017-07-01

    A variety of 1,3,4-oxadiazole derivatives based on electron- donor pyrrole and -acceptor nitro groups are modelled. Various isomers of pyrole-oxadiazole-nitro unit and its dimer linked to substituted and unsubstituted phenyl group are studied using the dispersion corrected density functional theoretical method. The electron density distribution in frontier orbitals of the phenyl-spacer compounds bearing amino and phenylamino groups indicates the possibility of intramolecular charge transfer. The isomers of phenyl-spacer compounds absorb in visible region of electromagnetic spectrum. The compounds show high values of light harvesting efficiency, despite the weak anchoring nature of nitro groups.

  16. Synthesis, fungicidal evaluation and 3D-QSAR studies of novel 1,3,4-thiadiazole xylofuranose derivatives

    PubMed Central

    Zong, Guanghui; Yan, Xiaojing; Bi, Jiawei; Jiang, Rui; Qin, Yinan; Yuan, Huizhu; Lu, Huizhe; Dong, Yanhong; Jin, Shuhui; Zhang, Jianjun

    2017-01-01

    1,3,4-Thiadiazole and sugar-derived molecules have proven to be promising agrochemicals with growth promoting, insecticidal and fungicidal activities. In the research field of agricultural fungicide, applying union of active group we synthesized a new set of 1,3,4-thiadiazole xylofuranose derivatives and all of the compounds were characterized by 1H NMR and HRMS. In precise toxicity measurement, some of compounds exhibited more potent fungicidal activities than the most widely used commercial fungicide Chlorothalonil, promoting further research and development. Based on our experimental data, 3D-QSAR (three-dimensional quantitative structure-activity relationship) was established and investigated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques, helping to better understand the structural requirements of lead compounds with high fungicidal activity and environmental compatibility. PMID:28746366

  17. Adsorption of 2,4-dichlorophenoxyacetic acid and 4-chloro-2-metylphenoxyacetic acid onto activated carbons derived from various lignocellulosic materials.

    PubMed

    Doczekalska, Beata; Kuśmierek, Krzysztof; Świątkowski, Andrzej; Bartkowiak, Monika

    2018-05-04

    Adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-metylphenoxyacetic acid (MCPA) from aqueous solution onto activated carbons derived from various lignocellulosic materials including willow, miscanthus, flax, and hemp shives was investigated. The adsorption kinetic data were analyzed using two kinetic models: the pseudo-first order and pseudo-second order equations. The adsorption kinetics of both herbicides was better represented by the pseudo-second order model. The adsorption isotherms of 2,4-D and MCPA on the activated carbons were analyzed using the Freundlich and Langmuir isotherm models. The equilibrium data followed the Langmuir isotherm. The effect of pH on the adsorption was also studied. The results showed that the activated carbons prepared from the lignocellulosic materials are efficient adsorbents for the removal of 2,4-D and MCPA from aqueous solutions.

  18. Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer

    PubMed Central

    Tabe, Yoko; Takemura, Hiroyuki; Kimura, Konobu; Takahashi, Toshihiro; Yang, Haeun; Tsuchiya, Koji; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Ohsaka, Akimichi

    2018-01-01

    Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode “XN-BF gating algorithm” to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples. PMID:29425230

  19. Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer.

    PubMed

    Ai, Tomohiko; Tabe, Yoko; Takemura, Hiroyuki; Kimura, Konobu; Takahashi, Toshihiro; Yang, Haeun; Tsuchiya, Koji; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Ohsaka, Akimichi

    2018-01-01

    Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode "XN-BF gating algorithm" to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples.

  20. Pichia pastoris production of a prolyl 4-hydroxylase derived from Chondrosia reniformis sponge: A new biotechnological tool for the recombinant production of marine collagen.

    PubMed

    Pozzolini, Marina; Scarfì, Sonia; Mussino, Francesca; Salis, Annalisa; Damonte, Gianluca; Benatti, Umberto; Giovine, Marco

    2015-08-20

    Prolyl 4-hydroxylase (P4H) is a α2β2 tetramer catalyzing the post-translational hydroxylation of prolines in collagen. Its recombinant production is mainly pursued to realize biotechnological tools able to generate animal contaminant-free hydroxylated collagen. One promising candidate for biomedical applications is the collagen extracted from the marine sponge Chondrosia reniformis, because of its biocompatibility and because is devoid of the health risks associated with bovine and porcine collagens. Here we report on the production and selection, by enzymatic and biomolecular analyses, of a triple transformed Pichia pastoris strain expressing a stable P4H tetramer derived from C. reniformis sponge and a hydroxylated non fibrillar procollagen polypeptide from the same animal. The percentage of recombinant procollagen hydroxylated prolines inside the transformed yeast was of 36.3% analyzed by mass spectrometry indicating that the recombinant enzyme is active on its natural substrate inside the yeast cell host. Furthermore, the recombinant sponge P4H has the ability to hydroxylate its natural substrate in both X and Y positions in the Xaa-Yaa-Gly collagenous triplets. In conclusion this Pichia system seems ideal for high-level production of hydroxylated sponge- or marine-derived collagen polypeptides as well as of conotoxins or other marine proteins of high pharmacological interest needing this particular post-translational modification. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Three-dimensional quantitative structure-activity relationship study on anti-cancer activity of 3,4-dihydroquinazoline derivatives against human lung cancer A549 cells

    NASA Astrophysics Data System (ADS)

    Cho, Sehyeon; Choi, Min Ji; Kim, Minju; Lee, Sunhoe; Lee, Jinsung; Lee, Seok Joon; Cho, Haelim; Lee, Kyung-Tae; Lee, Jae Yeol

    2015-03-01

    A series of 3,4-dihydroquinazoline derivatives with anti-cancer activities against human lung cancer A549 cells were subjected to three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using the comparative molecular similarity indices analysis (CoMSIA) approaches. The most potent compound, 1 was used to align the molecules. As a result, the best prediction was obtained with CoMSIA combined the steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor fields (q2 = 0.720, r2 = 0.897). This model was validated by an external test set of 6 compounds giving satisfactory predictive r2 value of 0.923 as well as the scrambling stability test. This model would guide the design of potent 3,4-dihydroquinazoline derivatives as anti-cancer agent for the treatment of human lung cancer.

  2. CD4+CD25+ Treg derived from hepatocellular carcinoma mice inhibits tumor immunity.

    PubMed

    Chen, Xin; Du, Yong; Huang, Zhiming

    2012-01-01

    CD4+CD25+ regulatory T cells (Tregs) play an essential role in the establishment and persistence of tumor immune suppression. Tregs can prevent anti-tumor-specific T cells from clearing the tumor, making Tregs a significant barrier for effective immunotherapy. An increase in the number of Tregs has been detected in the peripheral blood and tumor infiltrating lymphocytes of patients with hepatocellular carcinoma. Dendritic cells (DCs) are antigen-presenting cells that play a pivotal role in the initiation of immune responses. The evidence for their ability to act as natural adjuvant in the stimulation of specific anti-tumor cytotoxic T lymphocytes and in the induction of protective and therapeutic anti-tumor immunity is now overwhelming. The aim of our study was to investigate the variation of Tregs in hepatocellular carcinoma mice and how Tregs derived from the tumor mice affect DCs' function. We found that Tregs derived from the tumor mice down-regulated the expression of costimulatory molecules CD80/CD86 on DCs and inhibited the production of TNF-α and IL-12 from DCs. The suppressive function of Tregs was mediated by cell-to-cell contact, CTLA-4 expression and IL-10 secretion. In conclusion, these mechanisms acting in hepatocellular carcinoma may be necessary to better understand the immunosuppression of Tregs and helpful to the tumor immunotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. 4-Aminoquinoline derivatives: Synthesis, in vitro and in vivo antiplasmodial activity against chloroquine-resistant parasites.

    PubMed

    Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum; Sharma, Manish; Nielsen, Morten A; Alifrangis, Michael; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

    2016-10-21

    Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei. The ED50 values were calculated to be 2.062, 2.231, 1.431, 1.623 and 1.18 mg/kg of body weight for each of the compounds 1m, 1o, 2c, 2j and amodiaquine, respectively. Total doses of 500 mg/kg of body weight were well received. The study suggests that these new 4-aminoquinolines should be used for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Analysis of the structure and the FT-IR and Raman spectra of 2-(4-nitrophenyl)-4H-3,1-benzoxazin-4-one. Comparisons with the chlorinated and methylated derivatives

    NASA Astrophysics Data System (ADS)

    Castillo, María V.; Rudyk, Roxana A.; Davies, Lilian; Brandán, Silvia Antonia

    2017-07-01

    In this work, the structural, topological and vibrational properties of the monomer and three dimers of the 2-(4-nitrophenyl)-4H-3,1-benzoxazin-4-one (NPB) derivative were studied combining the experimental FTIR and FT-Raman spectra in the solid phase with DFT calculations. Here, Natural Bond Orbital (NBO), Atoms in Molecules (AIM) and HOMO and LUMO calculations were performed by using the hybrid B3LYP/6-31G*and B3LYP/6-311++G** methods in order to compute those properties and to predict their reactivities. The comparisons with the properties reported for the chlorinated (Cl-PB) and methylated (CH3-PB) derivatives at the same levels of theory can be clearly justified by the activating (CH3) and deactivating (NO2 and Cl) characteristics of the different groups linked to oxaxin rings. The NBO and AIM studies evidence the following stability orders: Cl-PB > NO2-PB > CH3-PB in very good concordance with the f(νC23-X26) force constants values. The frontier orbitals analyses reveal that the Cl-PB and NO2-PB derivatives have good stabilities and high chemical hardness while CH3-PB has a higher chemical reactivity. On the other hand, the complete vibrational assignments for monomer and dimers species of NPB were presented. The presence of the IR bands at 1574 and 1037 cm-1 and, of the Raman bands at 1571 and 1038 cm-1 support clearly the presence of the different dimeric species proposed for NPB.

  5. Synthesis of 4-aminophenyl substituted indole derivatives for the instrumental analysis and molecular docking evaluation studies

    NASA Astrophysics Data System (ADS)

    Singh, Navneet; Kumar, Keshav

    2017-07-01

    The Indole has been known to maintain celebrity status since so many decades and has been a centre point at the spectrum of pharmacological research. The present work stimulates an idea of generating a pool of library of lead compounds. The data collected can be used for the mapping of biologically active compounds. The reported derivatives of 4-aminophenyl substituted Indole were prepared by the methods of Fischer Indole synthesis and Vilsemeier reaction followed by screening for instrumental analysis and molecular docking studies. The synthesized compounds 4-(1-(2-phenylhydrazono)ethyl)aniline, 1, 4-(1H-indol-2-yl)aniline, 2 and 2-(4-aminophenyl)-1H-indole-3-carbaldehyde, 3 were found to have remarkable yield and instrumental data analysis and also showed remarkable docked characteristic. The molecular docking studies revealed that ligand (amino acids) of comp. 1, 2 and 3 had been docked successfully on the binding site of the 3JUS protein selected from PDB with H bonding. The molecular docking data showed that compound 1, would possess remarkable biological activity and compd. 2 and 3 would possess mild to moderate biological activity. Thus this research work paves the way to synthesize new derivatives and thus to develop new compounds in future with accurate prediction.

  6. Synthesis and Anticancer Activity of 3-(Substituted Aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole Derivatives.

    PubMed

    Zhan, Xiao-Ping; Lan, Lan; Wang, Shuai; Zhao, Kai; Xin, Yu-Xuan; Qi, Qi; Wang, Yao-Lin; Mao, Zhen-Min

    2017-02-01

    A series of 3-(substituted aroyl)-4-(3,4,5-trimethoxyphenyl)-1H-pyrrole derivatives were synthesized and determined for their anticancer activity against eleven cancer cell lines and two normal tissue cell lines using MTT assay. Among the synthesized compounds, compound 3f was the most potent compound against A375, CT-26, HeLa, MGC80-3, NCI-H460 and SGC-7901 cells (IC 50  = 8.2 - 31.7 μm); 3g, 3n and 3a were the most potent compounds against CHO (IC 50  = 8.2 μm), HCT-15 (IC 50  = 21 μm) and MCF-7 cells (IC 50  = 18.7 μm), respectively. Importantly, all the target compounds showed no cytotoxicity towards the normal tissue cell (IC 50  > 100 μm). Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  7. Ultrasound mediated, iodine catalyzed green synthesis of novel 2-amino-3-cyano-4H-pyran derivatives.

    PubMed

    Tabassum, Sumaiya; Govindaraju, Santhosh; Khan, Riyaz-ur-Rahaman; Pasha, Mohamed Afzal

    2015-05-01

    An efficient synthesis of a novel series of twelve substituted 2-amino-3-cyano-4H-pyran derivatives was achieved by a one-pot three-component cyclocondensation reaction of heteroaryl aldehydes, malononitrile and active methylene compounds catalyzed by iodine in aqueous medium under ultrasound irradiation. In comparison with conventional methods, our protocol is convenient and offers several advantages, such as shorter reaction time, higher yields, milder conditions and environmental friendliness. We have herein successfully demonstrated the synergistic outcome of multi-component reaction (MCR) and sonication to offer a facile route for the design of these derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Successive magnetic transitions of the pseudo-ternary compounds Ho1-xRxRh2Si2 (R=Y, La)

    NASA Astrophysics Data System (ADS)

    Shigeoka, Toru; Uchima, Kiyoharu; Uwatoko, Yoshiya

    2018-05-01

    Magnetic measurements on the pseudo-ternary compounds Ho1-xRxRh2Si2 (R = Y or La = Y or La) were performed in order to get information on the origin of "the successive component-separated magnetic transitions" which appear in HoRh2Si2. The lattice parameters a and c remain almost constant during changes to Y composition x, while they increase with increasing La composition x. The c/a ratios are also constant in the Y-system, and they increase with increasing x in the La-system especially for above around x = 0.4. The transition temperatures, TN1 = 29.1 K, Tt = 27.3 K and TN2 =12.1 K at x = 0, decrease with increasing x. The rates of decrease for TN1 and TN2 in the Y-system accord with those in the La system below x = 0.4. The critical compositions for TN1 and TN2 are determined to be xN1 = 0.88 and xN2 = 0.59 in the La-system, respectively, and xN1 = 0.98 and xN2 = 0.75 in the Y-system. In both the systems, "the successive component-separated magnetic transitions" appear for the wide x regions. The magnetic ordered state persists in very dilute Ho-compounds in spite of much weak magnetic interactions. The effective magnetic moments are almost constant for the ordered compounds; μeff = 10.6 ± 0.30 μB/Ho. These behaviors are strange, indicating a strong correlation exists in these systems.

  9. Immortalized prairie vole-derived fibroblasts (VMF-K4DTs) can be transformed into pluripotent stem cells and provide a useful tool with which to determine optimal reprogramming conditions.

    PubMed

    Katayama, Masafumi; Hirayama, Takashi; Kiyono, Tohru; Onuma, Manabu; Tani, Tetsuya; Takeda, Satoru; Nishimori, Katsuhiko; Fukuda, Tomokazu

    2017-06-21

    The cellular conditions required to establish induced pluripotent stem cells (iPSCs), such as the number of reprogramming factors and/or promoter selection, differ among species. The establishment of iPSCs derived from cells of previously unstudied species therefore requires the extensive optimization of programming conditions, including promoter selection and the optimal number of reprogramming factors, through a trial-and-error approach. While the four Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc are sufficient for iPSC establishment in mice, we reported previously that six reprogramming factors were necessary for the creation of iPSCs from primary prairie vole-derived cells. Further to this study, we now show detailed data describing the optimization protocol we developed in order to obtain iPSCs from immortalized prairie vole-derived fibroblasts. Immortalized cells can be very useful tools in the optimization of cellular reprogramming conditions, as cellular senescence is known to dramatically decrease the efficiency of iPSC establishment. The immortalized prairie vole cells used in this optimization were designated K4DT cells as they contained mutant forms of CDK4, cyclin D, and telomerase reverse transcriptase (TERT). We show that iPSCs derived from these immortalized cells exhibit the transcriptional silencing of exogenous reprogramming factors while maintaining pluripotent cell morphology. There were no observed differences between the iPSCs derived from primary and immortalized prairie vole fibroblasts. Our data suggest that cells that are immortalized with mutant CDK4, cyclin D, and TERT provide a useful tool for the determination of the optimal conditions for iPSC establishment.

  10. Electrosynthesis and characterization of oligophenylene deriving from 4-(methoxyphenyl)acetonitrile

    NASA Astrophysics Data System (ADS)

    Amor, Sarra Ben; Said, Ayoub Haj; Chemek, Mourad; Ayachi, Sahbi; Massuyeau, Florian; Wéry, Jany; Alimi, Kamel; Roudesli, Sadok

    2013-01-01

    An oligophenylene deriving from the 4-(methoxyphenyl)acetonitrile (MPA), was electrosynthesized by direct anodic oxidation at a constant potential in acetonitrile on a platinium electrode. This oligomer (OMPA) showed a good solubility in common organic solvents. The results of osmometry and gel permeation chromatography analyzes indicated that the average chain length for OMPA was about 5 units. Its chemical structure was elucidated by 1H and 13C NMR, FTIR and UV spectroscopy. A thermal study carried out by thermogravimetric analysis and Differential Scanning Calorimetry showed that the oligomer was stable up to 268 °C. In addition, the photoluminescent properties of OMPA were investigated. In solution, an emission was recorded in the indigo-blue region, however, in solid state this emission was shifted to the orange-red zone. Finally a mechanism for the electro-oligomerization was evoked in the light of the electronic structures of the MPA and its radical cation obtained by DFT calculation.

  11. The influence of structural factors on the composition, spectral-luminescent properties and thermal stability of zinc(II) bis(dipyrromethenate)s crystal solvates with amines

    NASA Astrophysics Data System (ADS)

    Guseva, G. B.; Ksenofontov, A. A.; Antina, E. V.

    2017-02-01

    It was found that 3,3‧-, 2,3‧- and 2,2‧-zinc(II) bis(dipyrromethenate)s ([Zn2L2]) form stable supramolecular complexes with aromatic and aliphatic amines (X - pyridine (Py), N,N-dimethylmethanamide (DMF), diethylamine (DEA) and triethylamine (TEA)) of the composition [Zn2L2(X)n]. Composition, stability and spectral-luminescent properties of the [Zn2L2(X)n] crystal solvates were studied by means of FTIR, PXRD, thermal, mass spectral, absorption, and fluorescence analyses. Spectroscopic studies showed that the quantum yield (φ) of [Zn2L2(Х)n] in cyclohexane is much lower (to ∼ 1.4-4.0 times) than φ for the [Zn2L2]. Crystal solvates are stable up to a temperature ∼367.35-427.55 K. It is demonstrated, that the high interactions energies (Znsbnd N) in [Zn2L2(X)n] supramolecular complexes are the main cause of the fluorescence quenching of [Zn2L2] luminophores in the presence of electron-donor molecules. The obtained results are of interest for the development on the basis of [Zn2L2] of a new fluorescent sensors of the electron donor molecules.

  12. One-pot facile synthesis of 4-amino-1,8-naphthalimide derived Tröger's bases via a nucleophilic displacement approach.

    PubMed

    Shanmugaraju, Sankarasekaran; McAdams, Deirdre; Pancotti, Francesca; Hawes, Chris S; Veale, Emma B; Kitchen, Jonathan A; Gunnlaugsson, Thorfinnur

    2017-09-13

    We report here a novel one-pot synthetic strategy for the synthesis of a family of N-alkyl-1,8-naphthalimide based Tröger's bases via a nucleophilic substitution reaction of a common 'precursor' (or a 'synthon') N-aryl-1,8-naphthalimide Tröger's base heated at 80 °C in neat aliphatic primary amine, in overall yield of 65-96%. This methodology provides an efficient and one-step facile route to design 1,8-naphthalimide derived Tröger's base structures in analytically pure form without the use of column chromatography purification, that can be used in medicinal chemistry and as supramolecular scaffolds. We also report the formation of the corresponding anhydride, and the crystallographic analysis of two of the resulting products, that of the N-phenyl-4-amino-1,8-naphthalimide and the anhydride derived Tröger's bases.

  13. Molecular simplification of 1,4-diazabicyclo[4.3.0]nonan-9-ones gives piperazine derivatives that maintain high nootropic activity.

    PubMed

    Manetti, D; Ghelardini, C; Bartolini, A; Dei, S; Galeotti, N; Gualtieri, F; Romanelli, M N; Teodori, E

    2000-11-16

    Several 4-substituted 1-acylpiperazines, obtained by molecular simplification of 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones, have been synthesized and tested in vivo on the mouse passive avoidance test, to evaluate their nootropic activity. The results show that, apparently, an N-acylpiperazine group can mimic the 2-pyrrolidinone ring of 1,4-diazabicyclo[4.3.0]nonan-9-one, as the compounds of the new series maintain high nootropic activity. Moreover molecular simplification produces more clear-cut structure-activity relationships with respect to the parent series. The mechanism of action also appears to be similar in the two series. In fact, although the molecular mechanism remains to be elucidated, the most potent compound of each class (DM232 and 13, DM235) is able to increase acetylcholine release in rat brain. Piperazine derivatives represent a new class of nootropic drugs with an in vivo pharmacological profile very similar to that of piracetam, showing much higher potency with respect to the reference compound. Among the compounds studied, 13 (DM235) shows outstanding potency, being active at a dose of 0.001 mg kg(-1) sc.

  14. Inhibitors of adhesion molecules expression; the synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives.

    PubMed

    Kaneko, Toshihiko; Clark, Richard S J; Ohi, Norihito; Kawahara, Tetsuya; Akamatsu, Hiroshi; Ozaki, Fumihiro; Kamada, Atsushi; Okano, Kazuo; Yokohama, Hiromitsu; Muramoto, Kenzo; Ohkuro, Masayoshi; Takenaka, Osamu; Kobayashi, Seiichi

    2002-07-01

    During a search for novel, orally-active inhibitors of upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), we found a new series of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives to be potent ICAM-1 inhibitors. Of these compounds, N-[1-(10H-Pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)piperidin-4-yl]-N',N'-dimethylsulfamide 7p showed the potent oral inhibitory activities against neutrophil migration in a murine interleukin-1 (IL-1) induced paw inflammation model. The synthesis and structure-activity relationships of these amide derivatives are described.

  15. Identification and analytical characterization of four synthetic cathinone derivatives iso-4-BMC, β-TH-naphyrone, mexedrone, and 4-MDMC.

    PubMed

    Qian, Zhenhua; Jia, Wei; Li, Tao; Liu, Cuimei; Hua, Zhendong

    2017-02-01

    New psychoactive substances (NPS) have gained much popularity on the global market over the last number of years. The synthetic cathinone family is one of the most prominent groups and this paper reports on the analytical properties of four synthetic cathinone derivatives: (1) 1-(4-bromophenyl)-1-(methylamino)propan-2-one (iso-4-BMC or iso-brephedrone), (2) 2-(pyrrolidin-1-yl)-1-(5,6,7,8-tetrahydronaphthalen-2-yl)pentan-1-one (β-TH-naphyrone), (3) 3-methoxy-2-(methylamino)-1-(4-methylphenyl)propan-1-one (mexedrone), and (4) 2-(dimethylamino)-1-(4-methylphenyl)propan-1-one (4-MDMC). These identifications were based on liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. To our knowledge, no chemical or pharmacological data about compounds 1-3 have appeared until now, making this the first report on these compounds. The Raman and GC-MS data of 4 have been reported, but this study added the LC-MS and NMR data for additional characterization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Combretastatin A-4 derived 5-(1-methyl-4-phenyl-imidazol-5-yl)indoles with superior cytotoxic and anti-vascular effects on chemoresistant cancer cells and tumors.

    PubMed

    Mahal, Katharina; Biersack, Bernhard; Schruefer, Sebastian; Resch, Marcus; Ficner, Ralf; Schobert, Rainer; Mueller, Thomas

    2016-08-08

    5-(1-Methyl-4-phenyl-imidazol-5-yl)indoles 5 were prepared and tested as analogs of the natural vascular-disrupting agent combretastatin A-4 (CA-4). The 3-bromo-4,5-dimethoxyphenyl derivative 5c was far more active than CA-4 with low nanomolar IC50 concentrations against multidrug-resistant KB-V1/Vbl cervix and MCF-7/Topo mamma carcinoma cells, and also against CA-4-resistant HT-29 colon carcinoma cells. While not interfering markedly with the polymerization of tubulin in vitro, indole 5c completely disrupted the microtubule cytoskeleton of cancer cells at low concentrations. It also destroyed real blood vessels, both in the chorioallantoic membrane (CAM) of fertilized chicken eggs and within tumor xenografts in mice, without harming embryo or mouse, respectively. Indole 5c was less toxic than CA-4 to endothelial cells, fibroblasts, and cardiomyocytes. In highly vascularized xenograft tumors 5c induced distinct discolorations and histological features typical of vascular-disrupting agents, such as disrupted vessel structures, hemorrhages, and extensive necrosis. In a first preliminary therapy trial, indole 5c retarded the growth of resistant xenograft tumors in mice. © 2016 Elsevier Science Ltd. All rights reserved. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas.

    PubMed

    Tsujihara, K; Ozeki, M; Morikawa, T; Kawamori, M; Akaike, Y; Arai, Y

    1982-04-01

    A series of 33 N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of N-substituted glycosylamines has been prepared and tested for antitumor activities. The compounds were obtained by reaction of glycosylamines with isocyanate, followed by nitrosation with N2O4. Structure-activity relationships of these trisubstituted nitrosoureas were investigated by varying the N-substituents and disaccharide groups and by comparing them with the corresponding disubstituted analogues. A large number of the nitrosoureas bearing a maltosyl group exhibited strong antitumor activities against leukemia L1210 and Ehrlich ascites carcinoma, and 60-day survivors against leukemia L1210 were found at the optimal dose for these derivatives. In contrast, the lactosyl and the melibiosyl derivatives were almost inactive. The most interesting compound in this series, the 3-isobutyl-3-maltosyl derivative (37), was tested against leukemia L1210 by single and multiple treatment. Its therapeutic ratio (96.3) obtained by multiple treatment is 3 times larger than that (31.5) obtained by single treatment, suggesting a possible clinical utility of 37 by multiple treatment. The favorable effect of a maltosyl moiety in this class of compounds is discussed.

  18. Resveratrol derivatives as a pharmacological tool.

    PubMed

    Biasutto, Lucia; Mattarei, Andrea; Azzolini, Michele; La Spina, Martina; Sassi, Nicola; Romio, Matteo; Paradisi, Cristina; Zoratti, Mario

    2017-09-01

    Prodrugs of resveratrol are under development. Among the long-term goals, still largely elusive, are (1) modulating physical properties (e.g., water-soluble derivatives bearing polyethylene glycol chains), (2) changing distribution in the body (e.g., galactosyl derivatives restricted to the intestinal lumen), (3) increasing absorption from the gastrointestinal tract (e.g., derivatives imitating the natural substrates of endogenous transporters), and (4) hindering phase II metabolism (e.g., temporarily blocking the hydroxyls), all contributing to (5) increasing bioavailability. The chemical bonds that have been tested for functionalization include carboxyester, acetal, and carbamate groups. A second approach, which can be combined with the first, seeks to reinforce or modify the biochemical activities of resveratrol by concentrating the compound at specific subcellular sites. An example is provided by mitochondria-targeted derivatives. These proved to be pro-oxidant and cytotoxic in vitro, selectively killing fast-growing and tumor cells when supplied in the low micromolar range. This suggests the possibility of anticancer applications. © 2017 New York Academy of Sciences.

  19. Synthesis, biological evaluation and molecular modeling of 1-oxa-4-thiaspiro- and 1,4-dithiaspiro[4.5]decane derivatives as potent and selective 5-HT1A receptor agonists.

    PubMed

    Franchini, Silvia; Manasieva, Leda Ivanova; Sorbi, Claudia; Battisti, Umberto M; Fossa, Paola; Cichero, Elena; Denora, Nunzio; Iacobazzi, Rosa Maria; Cilia, Antonio; Pirona, Lorenza; Ronsisvalle, Simone; Aricò, Giuseppina; Brasili, Livio

    2017-01-05

    Recently, 1-(1,4-dioxaspiro[4,5]dec-2-ylmethyl)-4-(2-methoxyphenyl)piperazine (1) was reported as a potent 5-HT 1A R agonist with a moderate 5-HT 1A R selectivity. In an extension of this work a series of derivatives of 1, obtained by combining different heterocyclic rings with a more flexible amine chain, was synthesized and tested for binding affinity and activity at 5-HT 1A R and α 1 adrenoceptors. The results led to the identification of 14 and 15 as novel 5-HT 1A R partial agonists, the first being outstanding for selectivity (5-HT 1A /α 1d  = 80), the latter for potency (pD 2  = 9.58) and efficacy (E max  = 74%). Theoretical studies of ADME properties shows a good profile for the entire series and MDCKII-MDR1 cells permeability data predict a good BBB permeability of compound 15, which possess a promising neuroprotective activity. Furthermore, in mouse formalin test, compound 15 shows a potent antinociceptive activity suggesting a new strategy for pain control. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity.

    PubMed

    Quiliano, Miguel; Pabón, Adriana; Ramirez-Calderon, Gustavo; Barea, Carlos; Deharo, Eric; Galiano, Silvia; Aldana, Ignacio

    2017-04-15

    We report the design (in silico ADMET criteria), synthesis, cytotoxicity studies (HepG-2 cells), and biological evaluation of 15 hydrazine/hydrazide quinoxaline 1,4-di-N-oxide derivatives against the 3D7 chloroquine sensitive strain and FCR-3 multidrug resistant strain of Plasmodium falciparum and Leishmania infantum (axenic amastigotes). Fourteen of derivatives are novel quinoxaline 1,4-di-N-oxide derivatives. Compounds 18 (3D7 IC 50 =1.40μM, FCR-3 IC 50 =2.56μM) and 19 (3D7 IC 50 =0.24μM, FCR-3 IC 50 =2.8μM) were identified as the most active against P. falciparum, and they were the least cytotoxic (CC 50 -values>241μM) and most selective (SI>86). None of the compounds tested against L. infantum were considered to be active. Additionally, the functional role of the hydrazine and hydrazide structures were studied in the quinoxaline 1,4-di-N-oxide system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Synthesis and Pharmacological Evaluation of Some New Pyrimidine Derivatives Containing 1,2,4-Triazole

    PubMed Central

    Khanage, Shantaram Gajanan; Raju, S. Appala; Mohite, Popat Baban; Pandhare, Ramdas Bhanudas

    2012-01-01

    Purpose: An efficient method has been described for synthesis of 6-(substituted aryl)-4-(3,5-diphenyl-1H-1,2,4-triazol-1-yl)-1, 6-dihydropyrimidine-2-thiol, as a beneficial antimicrobial, anticonvulsant and anticancer agents. Methods: The clalcones of title compounds were synthesized in three steps and subsequently these chalcones were further reacted with thiourea in the presence of KOH in ethanol, which led to the formation of dihydropyrimidine derivatives (4a-j). Compounds 4a-j were screened for their in vitro antimicrobial activity by agar well method and their anticonvulsant activity by the MES model. Anticancer activity of two newly synthesized heterocycles were evaluated at National Cancer Institute (NCI) Maryland, USA against 60 cell lines of different human tumor at a single dose of 10-5 M. Results: Compound 4b, 4c, 4d, 4i and 4j were exhibited significant antimicrobial potential against tested strains at 50μg/ml and 100μg/ml concentrations. Out of the ten compounds studied 4a, 4b, 4c, 4h and 4j showed comparable MES activity to Phenytoin and Carbamazepine after 0.5h. Tested compounds did not showed to be more potent than standard drugs after 4h. Compound 4a and 4d were found active on Non-Small Cell Lung Cancer (HOP-92). Conclusion: Ten noveldihydropyrimidine analogues has been synthesized, characterized and found to bepromising antibacterial, anticonvulsant and antitumor agents. PMID:24312796

  2. Design, synthesis and evaluation of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives as BACE-1 inhibitors.

    PubMed

    Shangguan, Shihao; Wang, Fei; Liao, Yong; Yu, Haiping; Li, Jia; Huang, Wenhai; Hu, Haihong; Yu, Lushan; Hu, Yongzhou; Sheng, Rong

    2013-03-20

    Three series of 3-(2-aminoheterocycle)-4-benzyloxyphenylbenzamide derivatives, 2-aminooxazoles, 2-aminothiazoles, and 2-amino-6H-1,3,4-thiadizines were designed, synthesized and evaluated as β-secretase (BACE-1) inhibitors. Preliminary structure-activity relationships revealed that the existence of a 2-amino-6H-1,3,4-thiadizine moiety and α-naphthyl group were favorable for BACE-1 inhibition. Among the synthesized compounds, 5e exhibited the most potent BACE-1 inhibitory activity, with an IC50 value of 9.9 μΜ and it exhibited high brain uptake potential in Madin-Darby anine kidney cell lines (MDCK) and a Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1) model.

  3. Docking, synthesis and antimalarial activity of novel 4-anilinoquinoline derivatives.

    PubMed

    Vijayaraghavan, Shilpa; Mahajan, Supriya

    2017-04-15

    A series of 4-anilinoquinoline triazine derivatives were designed, synthesized and screened for in vivo antimalarial activity against a chloroquine-sensitive strain of Plasmodium berghei. The compounds were further subjected to in vitro antimalarial activity against chloroquine-resistant W2 strain of Plasmodium falciparum and β-haematin inhibition studies. All the compounds exhibited in vivo antimalarial activity better than that shown by the standard drug, chloroquine. Twelve out of fifteen compounds showed better inhibition than that of chloroquine against chloroquine-resistant W2 strain of Plasmodium falciparum. Ten compounds showed β-haematin inhibition, better than that of chloroquine, with IC 50 values in the range of 18-25µM. One compound, 3k, was found to be better than artemisinin against W2 strain of Plasmodium falciparum and also displayed the best β-haematin inhibitory activity, thereby becoming eligible to be explored as a potential lead for antimalarial chemotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives.

    PubMed

    Sahin, Zafer; Ertas, Merve; Berk, Barkın; Biltekin, Sevde Nur; Yurttas, Leyla; Demirayak, Seref

    2018-05-01

    Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC 50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC 50 :0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Structural diversification of the aminobicyclo[4.3.0]nonane skeleton using alkynylsilyl-derived allylic trichloroacetimidates.

    PubMed

    Mostafa, Mohamed A B; McMillan, Angus E; Sutherland, Andrew

    2017-04-05

    The amino substituted bicyclo[4.3.0]nonane is a molecular scaffold found in a wide range of natural products and medicinal agents. Despite this, synthetic methods for the general preparation of this structural motif are sparse. Here we evaluate a diastereoselective approach for the preparation of vinylsilyl derived aminobicyclo[4.3.0]nonanes using a one-pot multi-bond forming process involving a Pd(ii)-catalysed Overman rearrangement, a Ru(ii)-catalysed ring closing enyne metathesis reaction, followed by a hydrogen bonding directed Diels-Alder reaction. We show that a benzyldimethylsilyl-substituted alkene analogue is amenable to further functionalisation and the late stage generation of diverse sp 3 -rich, drug-like aminobicyclo[4.3.0]nonane scaffolds with up to six stereogenic centres.

  6. Synthesis and biological evaluation of novel quinazoline-4-piperidinesulfamide derivatives as inhibitors of NPP1.

    PubMed

    Forcellini, Elsa; Boutin, Sophie; Lefebvre, Carole-Anne; Shayhidin, Elnur Elyar; Boulanger, Marie-Chloé; Rhéaume, Gabrielle; Barbeau, Xavier; Lagüe, Patrick; Mathieu, Patrick; Paquin, Jean-François

    2018-03-10

    The ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) was recently shown to promote mineralization of the aortic valve, hence, its inhibition represents a significant target. A quinazoline-4-piperidine sulfamide compound (QPS1) has been described as a specific and non-competitive inhibitor of NPP1. We report herein the synthesis and in vitro inhibition studies of novel quinazoline-4-piperidine sulfamide analogues using QPS1 as the lead compound. Of the 26 derivatives prepared, four compounds were found to have K i  < 105 nM against human NPP1. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  7. Synthesis of C-glycosyl-bis-1,2,3-triazole derivatives from 3,4,6-tri-O-acetyl-D-glucal.

    PubMed

    Shamim, Anwar; Souza, Frederico B; Trossini, Gustavo H G; Gatti, Fernando M; Stefani, Hélio A

    2015-08-01

    We have developed an efficient, CuI-catalyzed, microwave-assisted method for the synthesis of bis-1,2,3-triazole derivatives starting from a 3,4,6-tri-O-acetyl-D-glucal-derived mesylate. This mesylate was obtained from 3,4,6-tri-O-acetyl-D-glucal through C-glycosidation, deprotection of acetate groups to alcohols, and selective mesylation of the primary alcohol. This mesylate moiety was then converted to an azide through a microwave-assisted method with good yield. The azide, once synthesized, was then treated with different terminal alkynes in the presence of CuI to synthesize various bis-triazoles in high yields and short reaction times.

  8. A study on nonlinear characteristics of speech sound with reference to some languages of North East region

    NASA Astrophysics Data System (ADS)

    Dutta, Rashmi

    INTRODUCTION : Speech science is, in fact, a sub-discipline of the Nonlinear Dynamical System [2,104 ]. There are two different types of Dynamical System. A Continuous Dynamical System may be defined for the continuous time case, by the equation: x = F (x), where x is a vector of length d, defining a point in a d- dimensional space, F is some function (linear or nonlinear) operating on x, and x is the time derivative of x. This system is deterministic, in that it is possible to completely specify its evolution or flow of trajectories in the d- dimensional space, given the initial starting conditions. A Discrete Dynamical System can be defined as a map [by the process of literations]: Xn+1 = G ( Xn ), where Xn is again a d- length vector at time step n, and G is an operator function. Given an initial state, X0, it is possible to calculate the value of xn for any n > 0. Speech has evolved as a primary form of communication between humans, i.e. speech and hearing are the man's most used means of communication [104, 114]. Analysis of human speech has been a goal of Research during the last few decades [105, 108]. With the rapid development of information technology (IT), the human-machine communication, using natural speech, has received wide attention from both academic and business communities. One highly quantitative approach of characterizing the communications potential of speech is in terms of information theory ideas as introduced by Shannon [C.E. Shannon, "A Mathematical Theory of Communication," Bell System Tech journal, Vol 27, pp623- 656, October, 1968]. According to information theory, speech can be represented in terms of its message content, or information. An alternative way of characterizing speech is in terms of the signal carrying the message information, i.e., the acoustic waveform. Although information theoretic ideas have played a major role in sophisticated communications systems, it is the speech representation based on the waveform, or some

  9. Activity of a melimine derived peptide Mel4 against Stenotrophomonas, Delftia, Elizabethkingia, Burkholderia and biocompatibility as a contact lens coating.

    PubMed

    Dutta, Debarun; Zhao, Timothy; Cheah, Kai Bing; Holmlund, Larke; Willcox, Mark D P

    2017-06-01

    To determine the antimicrobial activity of the melimine derived peptide Mel4 against Delftia, Stenotrophomonas, Elizabethkingia, Burkholderia and to investigate biocompatibility of Mel4 as an antimicrobial coating on contact lenses in animals and humans. In vitro antimicrobial activity of Mel4 was determined against the four Gram negative bacteria by investigating growth curves for 24h followed by viable counts to determine the minimum inhibitory concentration (MIC). Contact lenses were coated by covalently binding Mel4, characterized by amino acid analysis, and were investigated for changes in lens parameters. Safety of Mel-4 coated lenses were determined in a rabbit model of daily contralateral wear. A prospective, randomised, double-masked, contralateral, 1week daily wear human clinical trial was used to evaluate subjective responses and ocular physiology. Mel4 was active against all the bacteria tested (MIC 50 ranged from 31-1000μgml -1 ) and produced an antimicrobial surface on contact lenses. Mel4-coating resulted hydrophilic surface without any significant change in contact lens parameters, and showed no signs of cytotoxicity or ocular irritation during rabbit wear. During human clinical trial, there were no differences between Mel4 coated and uncoated contact lenses in lens performance indicators and ocular signs such as corneal fluorescein staining. Mel4 and control uncoated lenses had no differences in ocular symptoms during lens wear. Mel4 has achieved antimicrobial activity against variety of Gram negative bacteria that are often resistant to the action of cationic peptides and have been implicated in contact lens related adverse events. Mel4-coated contact lenses were safe to wear. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  10. Studies on quinolone antibacterials. V. Synthesis and antibacterial activity of chiral 5-amino-7-(4-substituted-3-amino-1-pyrrolidinyl)-6- fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acids and derivatives.

    PubMed

    Yoshida, T; Yamamoto, Y; Orita, H; Kakiuchi, M; Takahashi, Y; Itakura, M; Kado, N; Yasuda, S; Kato, H; Itoh, Y

    1996-07-01

    We previously demonstrated that 5-amino-7-(3-amino-1-pyrrolidinyl) -1-cyclopropyl-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (7) has strong in vitro antibacterial activity even against quinolone-resistant bacteria. We examined optimization of the 3-aminopyrrolidine moiety of 7 by introduction of C-alkyl (Me, Et, Pr, di-Me, cyclopropyl) and N-alkyl groups (Me, di-Me). C-Alkylation at the 4-position of the 3-aminopyrrolidine moiety enhanced in vitro and in vivo antibacterial activity. (S)-5-Amino-7-(7-amino-5-azaspiro[2.4]hept-5-yl)-1-cyclopropyl-pyr rolidinyl) -1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (15b) showed strong antibacterial activity (in vitro antibacterial activity including quinolone-resistant bacteria is 4 times more potent than that of ciprofloxacin (CPFX) (1); in vivo antibacterial activity is 1.5 to 20 times more potent than that of CPFX (1)) and reduced quinolone toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion when coadministered with 4-biphenylacetic acid at a dosage of 20 micrograms in rats (i.c.v.)). Their selectivity between DNA topoisomerase II (derived from eukaryotic cells) and DNA gyrase (derived from bacterial cells) was about 3000-fold.

  11. Synthesis, crystal structure, characterization and antifungal activity of 3,4-diaryl-1H-Pyrazoles derivatives

    NASA Astrophysics Data System (ADS)

    Zhang, Jin; Tan, Da-Jin; Wang, Tao; Jing, Si-Si; Kang, Yang; Zhang, Zun-Ting

    2017-12-01

    A series of 3,4-diaryl-1H-pyrazoles derivatives were designed and synthesized by the reaction of 3-heteroarylchromones and 3-phenylchromones with hydrazine hydrate in good yields. All of those compounds were characterized by 1H NMR, 13C NMR, IR, and HRMS. Moreover, 3-(2,4-dihydroxyphenyl)-4-(4-hydroxyphenyl)-1H-pyrazole and 3-(2,4-dihydroxy phenyl)-4-(4-methoxyphenyl)-1H-pyrazole were further conformed by the single crystal X-ray diffraction. In addition, the antifungal activity against five phytopathogenic fungi (Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani and Fusarium solani) of 3,4-diaryl-1H-pyrazoles were evaluated. 3-(2-Hydroxy-4-isopropoxyphenyl)-4-phenyl-1H-pyrazole was more better and broader inhibitory effect on Cytospora sp., C. gloeosporioides, A. solani and Fusarium solani with IC50 values of 26.96, 28.84, 16.77 and 22.10 μg/mL, respectively. 4-(4-Fluorophenyl)-3-(2-hydroxy-4-methoxyphenyl)-1H-pyrazole exhibited fairly effective antifungal activity against Cytospora sp., C. gloeosporioides and A. solani with IC50 values of 11.91, 14.92 and 16.98 μg/mL, respectively.

  12. Synthesis, docking, cytotoxicity, and LTA4H inhibitory activity of new gingerol derivatives as potential colorectal cancer therapy.

    PubMed

    El-Naggar, Mai H; Mira, Amira; Abdel Bar, Fatma M; Shimizu, Kuniyoshi; Amer, Mohamed M; Badria, Farid A

    2017-02-01

    Leukotriene A4 hydrolase (LTA 4 H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene which may play an important role in chronic inflammation associated carcinogenesis. [6]-gingerol, the major bioactive compound of Zingiber officinale, is a potential inhibitor of LTA 4 H, a highly expressed enzyme in colorectal carcinoma. Eighteen compounds; seven of natural origin (including [4]-, [6]-, [8]-, and [10]-gingerol), five new and six known semi-synthesized [6]-gingerol derivatives were examined using docking, in vitro cytotoxicity against human colon cancer cells (HCT-116) and LTA 4 H aminopeptidase and epoxide hydrolase inhibitory studies. Methyl shogoal (D8) showed to be the most potent compound against HCT-116 cells (IC 50 ; 1.54μM). Remarkably, D8 proved to be non-cytotoxic to normal cells; (TIG-1) and (HF-19) with high selective index (SI; 52.3). Furthermore [6]-gingerol derivatives showed potent LTA 4 H inhibitory activities in comparison to the universal positive controls (bestatin and 4BSA). Among the natural gingerols, [10]-gingerol (N3) exhibited the highest LTA 4 H aminopeptidase and epoxide hydrolase inhibitory activities with IC 50 ; 21.59 and 15.24μM, respectively. Meanwhile, methyl shogoal (D8) and 4'-O-prenyl-[6]-gingerol (D10) retained the highest inhibition with IC 50 ; 4.92 and 3.01μM, for aminopeptidase, and 11.27 and 7.25μM for epoxide hydrolase activities, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. 7-endo selenocyclization reactions on chiral 3-prenyl and 3-cinnamyl-2-hydroxymethylperhydro-1,3-benzoxazine derivatives. A way to enantiopure 1,4-oxazepanes.

    PubMed

    Nieto, Javier; Andrés, Celia; Pérez-Encabo, Alfonso

    2015-09-14

    Enantiopure 1,4-oxazepane derivatives have been prepared by selenocyclofunctionalization of chiral 3-prenyl- and 3-cinnamyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives. The 7-endo-cyclization occurs in high yields and diastereoselection. The regio- and stereochemistry of the cyclization products was dependent on the substitution pattern of the double bond, the nature of the hydroxyl group and the experimental conditions.

  14. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    PubMed

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-01-19

    Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

  15. Immature platelet fraction (IPF) as a predictive value for thrombopoietic recovery after allogeneic stem cell transplantation.

    PubMed

    Sakuragi, Mikiko; Hayashi, Satoru; Maruyama, Miho; Kiyokawa, Tomoko; Nagamine, Keisuke; Fujita, Jiro; Maeda, Tetsuo; Kato, Hisashi; Kashiwagi, Hirokazu; Kanakura, Yuzuru; Tomiyama, Yoshiaki

    2018-03-01

    We consecutively examined the utility of measurements of percentage of immature platelet fraction (IPF%) and absolute IPF number (A-IPF) in predicting thrombopoietic recovery in 15 adult patients who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT). Four patients were excluded from the evaluation due to insufficient data. Platelet count and IPF were measured by Sysmex XN-1000 (XN), a newer generation analyzer. First, we confirmed that platelet count measured by XN was more accurate than by XE-2100 (XE). IPF measurement was effective to predict the recovery in 7 of the 11 patients examined. Moreover, IPF measurement, especially IPF% measurement, suggested accelerated platelet turnover in two patients who failed to achieve platelet recovery by day 60. In addition to IPF%, A-IPF showed a complementary role on the prediction of thrombopoietic recovery. The increase in IPF% was only transient, while A-IPF values showed lasting increase during platelet recovery. In two patients (cases 6 and 7) an increase in A-IPF, but not in IPF%, was observed during platelet recovery. Our data suggest that IPF% and A-IPF measured by XN are useful for the prediction of thrombopoietic recovery and the assessment of pathogenesis of thrombocytopenia in patients after allo-SCT.

  16. Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF-kappaB and Akt as targets.

    PubMed

    Albini, Adriana; Dell'Eva, Raffaella; Vené, Roberta; Ferrari, Nicoletta; Buhler, Donald R; Noonan, Douglas M; Fassina, Gianfranco

    2006-03-01

    Xanthohumol (XN), the principal flavonoid of the hop plant (Humulus lupulus L.) and a constituent of beer, has been suggested to have potential cancer chemopreventive activities. We have observed that most cancer chemopreventive agents show antiangiogenic properties in vitro and in vivo, a concept we termed "angioprevention." Here we show for the first time that XN can inhibit growth of a vascular tumor in vivo. Histopathology and in vivo angiogenesis assays indicated that tumor angiogenesis inhibition was involved. Further, we show the mechanisms for its inhibition of angiogenesis in vivo and related endothelial cell activities in vitro. XN repressed both the NF-kappaB and Akt pathways in endothelial cells, indicating that components of these pathways are major targets in the molecular mechanism of XN. Moreover, using in vitro analyses, we show that XN interferes with several points in the angiogenic process, including inhibition of endothelial cell invasion and migration, growth, and formation of a network of tubular-like structures. Our results suggest that XN can be added to the expanding list of antiangiogenic chemopreventive drugs whose potential in cancer prevention and therapy should be evaluated.

  17. Immortalized prairie vole-derived fibroblasts (VMF-K4DTs) can be transformed into pluripotent stem cells and provide a useful tool with which to determine optimal reprogramming conditions

    PubMed Central

    KATAYAMA, Masafumi; HIRAYAMA, Takashi; KIYONO, Tohru; ONUMA, Manabu; TANI, Tetsuya; TAKEDA, Satoru; NISHIMORI, Katsuhiko; FUKUDA, Tomokazu

    2017-01-01

    The cellular conditions required to establish induced pluripotent stem cells (iPSCs), such as the number of reprogramming factors and/or promoter selection, differ among species. The establishment of iPSCs derived from cells of previously unstudied species therefore requires the extensive optimization of programming conditions, including promoter selection and the optimal number of reprogramming factors, through a trial-and-error approach. While the four Yamanaka factors Oct3/4, Sox2, Klf4, and c-Myc are sufficient for iPSC establishment in mice, we reported previously that six reprogramming factors were necessary for the creation of iPSCs from primary prairie vole-derived cells. Further to this study, we now show detailed data describing the optimization protocol we developed in order to obtain iPSCs from immortalized prairie vole-derived fibroblasts. Immortalized cells can be very useful tools in the optimization of cellular reprogramming conditions, as cellular senescence is known to dramatically decrease the efficiency of iPSC establishment. The immortalized prairie vole cells used in this optimization were designated K4DT cells as they contained mutant forms of CDK4, cyclin D, and telomerase reverse transcriptase (TERT). We show that iPSCs derived from these immortalized cells exhibit the transcriptional silencing of exogenous reprogramming factors while maintaining pluripotent cell morphology. There were no observed differences between the iPSCs derived from primary and immortalized prairie vole fibroblasts. Our data suggest that cells that are immortalized with mutant CDK4, cyclin D, and TERT provide a useful tool for the determination of the optimal conditions for iPSC establishment. PMID:28331164

  18. Teratology study of amide derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide in NMRI mice.

    PubMed

    Onishi, Yuko; Okada, Akinobu; Noyori, Hiroko; Okamura, Ai; Hen, Naama; Yagen, Boris; Bialer, Meir; Fujiwara, Michio

    2013-08-01

    Valproic acid (VPA), widely used to treat epilepsy, bipolar disorders, and migraine prophylaxis, is known to cause neural tube and skeletal defects in humans and animals. Aminobenzensulfonamide derivatives of VPA with branched aliphatic carboxylic acids, namely 2-methyl-N-(4-sulfamoyl-phenyl)-pentanamide (MSP), 2-ethyl-N-(4-sulfamoyl-phenyl)-butyramide (ESB), 2-ethyl-4-methyl-N-(4-sulfamoyl-phenyl)-pentanamide (EMSP), and 2-ethyl-N-(4-sulfamoyl-benzyl)-butyramide (ESBB), have shown more potent anticonvulsant activity than VPA in preclinical testing. Here, we investigated the teratogenic effects of these analogous compounds of VPA in NMRI mice. Pregnant NMRI mice were given a single subcutaneous injection of either VPA at 1.8 or 3.6 mmol/kg, or MSP, ESB, EMSP, or ESBB at 1.8, 3.6, or 4.8 mmol/kg on gestation day (GD) 8. Cesarean section was performed on GD 18, and the live fetuses were examined for external and skeletal malformations. Compared with VPA, which induced neural tube defects (NTDs) in fetuses at 1.8 and 3.6 mmol/kg, the analog derivatives induced no NTDs at dose levels up to 4.8 mmol/kg (except for a single case of exencephaly at 4.8 mmol/kg MSP). Skeletal examination showed several abnormalities mainly at the axial skeletal level with VPA at 1.8 mmol/kg. Fused vertebrae and/or fused ribs were also observed with MSP, ESB, EMSP, and ESBB, they were less severe and seen at a lower incidence that those induced by VPA at the same dose level. In addition to exerting more potent preclinical antiepileptic activity, teratology comparison indicates that aminobenzensulfonamide analogs are generally more weakly teratogenic than VPA. © 2013 Wiley Periodicals, Inc.

  19. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tangi, Malleswararao; Mishra, Pawan; Janjua, Bilal

    The dislocation free In{sub x}Al{sub 1-x}N nanowires (NWs) are grown on Si(111) by nitrogen plasma assisted molecular beam epitaxy in the temperature regime of 490 °C–610 °C yielding In composition ranges over 0.50 ≤ x ≤ 0.17. We study the optical properties of these NWs by spectroscopic ellipsometry (SE), photoluminescence, and Raman spectroscopies since they possesses minimal strain with reduced defects comparative to the planar films. The optical bandgap measurements of In{sub x}Al{sub 1-x}N NWs are demonstrated by SE where the absorption edges of the NW samples are evaluated irrespective of substrate transparency. A systematic Stoke shift of 0.04–0.27 eV with increasing xmore » was observed when comparing the micro-photoluminescence spectra with the Tauc plot derived from SE. The micro-Raman spectra in the NWs with x = 0.5 showed two-mode behavior for A{sub 1}(LO) phonons and single mode behavior for E{sub 2}{sup H} phonons. As for x = 0.17, i.e., high Al content, we observed a peculiar E{sub 2}{sup H} phonon mode splitting. Further, we observe composition dependent frequency shifts. The 77 to 600 K micro-Raman spectroscopy measurements show that both AlN- and InN-like modes of A{sub 1}(LO) and E{sub 2}{sup H} phonons in In{sub x}Al{sub 1-x}N NWs are redshifted with increasing temperature, similar to that of the binary III group nitride semiconductors. These studies of the optical properties of the technologically important In{sub x}Al{sub 1-x}N nanowires will path the way towards lasers and light-emitting diodes in the wavelength of the ultra-violet and visible range.« less

  20. Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta.

    PubMed

    Liu, Victoria C; Wong, Larry Y; Jang, Thomas; Shah, Ali H; Park, Irwin; Yang, Ximing; Zhang, Qiang; Lonning, Scott; Teicher, Beverly A; Lee, Chung

    2007-03-01

    CD4+CD25+ T regulatory (T(reg)) cells were initially described for their ability to suppress autoimmune diseases in animal models. An emerging interest is the potential role of T(reg) cells in cancer development and progression because they have been shown to suppress antitumor immunity. In this study, CD4+CD25- T cells cultured in conditioned medium (CM) derived from tumor cells, RENCA or TRAMP-C2, possess similar characteristics as those of naturally occurring T(reg) cells, including expression of Foxp3, a crucial transcription factor of T(reg) cells, production of low levels of IL-2, high levels of IL-10 and TGF-beta, and the ability to suppress CD4+CD25- T cell proliferation. Further investigation revealed a critical role of tumor-derived TGF-beta in converting CD4+CD25- T cells into T(reg) cells because a neutralizing Ab against TGF-beta, 1D11, completely abrogated the induction of T(reg) cells. CM from a nontumorigenic cell line, NRP-152, or irradiated tumor cells did not convert CD4+CD25- T cells to T(reg) cells because they produce low levels of TGF-beta in CM. Finally, we observed a reduced tumor burden in animals receiving 1D11. The reduction in tumor burden correlated with a decrease in tumor-derived TGF-beta. Treatment of 1D11 also reduced the conversion of CD4+ T cells into T(reg) cells and subsequent T(reg) cell-mediated suppression of antitumor immunity. In summary, we have demonstrated that tumor cells directly convert CD4+CD25- T cells to T(reg) cells through production of high levels of TGF-beta, suggesting a possible mechanism through which tumor cells evade the immune system.

  1. Trace analysis of carbonyl compounds by liquid chromatography-mass spectrometry after collection as 2,4-dinitrophenylhydrazine derivatives.

    PubMed

    Sakuragawa, A; Yoneno, T; Inoue, K; Okutani, T

    1999-06-04

    This study describes the utilization of carbonyl- 2,4-dinitrophenylhydrazine (DNPH) derivatives for the determination of a micro amount of carbonyl compounds in air by liquid chromatography-mass spectrometry (LC-MS). After the carbonyl compounds are collected using a Waters Sep-Pak C18 cartridge column with-impregnated DNPH on octadecylsilica, they are eluted by acetonitrile as carbonyl-DNPH derivatives. A 20-mm3 aliquot of eluent is injected into the LC-MS system. The four derivatives (formaldehyde-, acetaldehyde-, acrolein- and acetone-DNPH) were eluted within 7 min with acetonitrile-water (60:40, v/v) as the mobile phase. The proposed method offers sub-ppb sensitivity and good reproducibility and was applied to the determination of these carbonyl compounds in actual air samples from store rooms, laboratories and offices. The relative standard deviations for these samples (n = 6) were 1 to 3%.

  2. Serotonin transporter activity of imidazolidine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives in aspect of their acid-base properties.

    PubMed

    Zagórska, Agnieszka; Czopek, Anna; Pawłowski, Maciej; Dybała, Małgorzata; Siwek, Agata; Nowak, Gabriel

    2012-11-01

    Affinities of arylpiperazinylalkyl derivatives of imidazo[2,1-f]purine-2,4-dione and imidazolidine-2,4-dione for serotonin transporter and their acid-base properties were evaluated. The dissociation constant (pK(a)) of compounds 1-22 were determinated by potentiometric titration and calculated using pKalc 3.1 module of the Pallas system. The data from experimental methods and computational calculations were compared and suitable conclusions were reached.

  3. Synthesis and antimicrobial activity of 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl) propyl)piperidine derivatives against pathogens of Lycopersicon esculentum: a structure-activity evaluation study.

    PubMed

    Vinaya, K; Kavitha, R; Ananda Kumar, C S; Benaka Prasad, S B; Chandrappa, S; Deepak, S A; Nanjunda Swamy, S; Umesha, S; Rangappa, K S

    2009-01-01

    Several 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl)propyl)piperidine derivatives 8(a-j) were prepared by the treatment of substituted benzhydryl chlorides with 4-(3-(piperidin-4-yl)propyl)piperidine followed by N-sulfonation with sulfonyl chlorides in the presence of dry methylene dichloride and triethyl amine. The synthesized compounds were characterized by (1)H-NMR, IR, and elemental analysis. All the synthesized compounds were evaluated in vitro for their efficacy as antimicrobial agents by artificial inoculation technique against standard strains of two important bacterial viz., Xanthomonas axonopodis pv. vesicatoria and Ralstonia solanacearum as well as and two fungal pathogens namely Alternaria solani and Fusarium solani of tomato plants. We have briefly investigated the structure-activity relation studies and reveal that the nature of substitutions on benzhydryl ring and sulfonamide ring influences the antibacterial activity. Among the synthesized new compounds 8b, 8d, 8g, 8h, 8i, and 8j were showed significant potent antimicrobial activities compared to the standard drugs chloramphenicol, mancozeb.

  4. Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone.

    PubMed

    Jin, Xin; Zheng, Chang-Ji; Song, Ming-Xia; Wu, Yan; Sun, Liang-Peng; Li, Yin-Jing; Yu, Li-Jun; Piao, Hu-Ri

    2012-10-01

    Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. CXCL4 induces a unique transcriptome in monocyte-derived macrophages

    PubMed Central

    Gleissner, Christian A.; Shaked, Iftach; Little, Kristina M.; Ley, Klaus

    2012-01-01

    In atherosclerotic arteries, blood monocytes differentiate to macrophages in the presence of growth factors like macrophage colony-stimulation factor (MCSF) and chemokines like platelet factor 4 (CXCL4). To compare the gene expression signature of CXCL4-induced macrophages with MCSF-induced macrophages or macrophages polarized with IFN-γ/LPS (M1) or IL-4 (M2), we cultured primary human peripheral blood monocytes for six days. mRNA expression was measured by Affymetrix gene chips and differences were analyzed by Local Pooled Error test, Profile of Complex Functionality and Gene Set Enrichment Analysis. 375 genes were differentially expressed between MCSF- and CXCL4-induced macrophages, 206 of them overexpressed in CXCL4 macrophages coding for genes implicated in the inflammatory/immune response, antigen processing/presentation, and lipid metabolism. CXCL4-induced macrophages overexpressed some M1 and M2 genes and the corresponding cytokines at the protein level, however, their transcriptome clustered with neither M1 nor M2 transcriptomes. They almost completely lost the ability to phagocytose zymosan beads. Genes linked to atherosclerosis were not consistently up- or downregulated. Scavenger receptors showed lower and cholesterol efflux transporters higher expression in CXCL4- than MCSF-induced macrophages, resulting in lower LDL content. We conclude that CXCL4 induces a unique macrophage transcriptome distinct from known macrophage types, defining a new macrophage differentiation that we propose to call M4. PMID:20335529

  6. Cocrystal formation, crystal structure, solubility and permeability studies for novel 1,2,4-thiadiazole derivative as a potent neuroprotector.

    PubMed

    Surov, Artem O; Volkova, Tatyana V; Churakov, Andrei V; Proshin, Alexey N; Terekhova, Irina V; Perlovich, German L

    2017-11-15

    The cocrystallization approach has been applied to modify the poor solubility profile of the biologically active 1,2,4-thiadiazole derivative (TDZ). Extensive cocrystal screening with a library of coformers resulted in formation of a new solid form of TDZ with vanillic acid in a 1:1 molar ratio. The cocrystalline phase was identified and characterized by thermal and diffraction analyses including single-crystal X-ray diffraction. The energies of intermolecular interactions in the crystal were calculated by solid-state DFT and PIXEL methods. Both calculation schemes show good consistency in terms of total energy of the intermolecular interactions and suggest that the cocrystal is mainly stabilized via hydrogen bonds, which provide ca. 44% of the lattice energy. Since the cocrystal contained the hydroxybenzoic acid derivative as a coformer, the solubility profile of the cocrystal was investigated at different pHs using eutectic concentrations of the components. Furthermore, the influence of the cocrystallization on the permeability performance of the 1,2,4-thiadiazole through an artificial regenerated cellulose membrane was also evaluated. In addition, the thermodynamic functions of the cocrystal formation were estimated from the solubility of the cocrystal and the corresponding solubility of the pure compounds at various temperatures. The cocrystal formation process was found to have a relatively small value of the driving force (-5.3kJ·mol -1 ). The most significant contribution to the Gibbs energy was provided by the exothermic enthalpy of formation. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Antiplasmodial Drugs in the Gas Phase: A CID and DFT Study of Quinolon-4( 1H)-Imine Derivatives

    NASA Astrophysics Data System (ADS)

    Amorim Madeira, Paulo J.; Sitoe, Ana Raquel Fernandes; Gonçalves, Daniel; Rodrigues, Tiago; Guedes, Rita C.; Lopes, Francisca; Moreira, Rui; Bronze, M. Rosário

    2014-09-01

    The gas-phase behavior of 12 quinolon-4( 1H)-imine derivatives with antiplasmodial activity was investigated using electrospray ionization tandem mass spectrometry together with collision induced dissociation and density functional theory (DFT) calculations. The most probable protonation site was predicted by calculating the proton affinity (PA) values for each possible protonation site and it was found to be the imine nitrogen for all compounds under study. Fragmentation pathways of the protonated molecules were proposed and the assignment of product ion structures was performed taking into account theoretical calculations. The nature of the quinoline substituent was found to influence the gas-phase behavior of the compounds under study. The data acquired allowed to bracket the proton affinity of the quinolin-4-imine scaffold, which can be a useful starting point to choose appropriate references for determining PA values of this scaffold.

  8. Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis.

    PubMed

    Wetterholm, Erik; Linders, Johan; Merza, Mohammed; Regner, Sara; Thorlacius, Henrik

    2016-10-01

    Platelets are known to play an important role in acute pancreatitis (AP) via promotion of neutrophil accumulation, although mechanisms behind platelet-dependent accumulation of neutrophils in the pancreas remain elusive. Platelets contain a wide spectrum of different pro-inflammatory compounds, such as chemokines. CXCL4 (platelet factor 4) is one of the most abundant chemokine in platelets, and we hypothesized that CXCL4 might be involved in platelet-dependent accumulation of neutrophils in the inflamed pancreas. The aim of this study was to examine the role of CXCL4 in severe AP. Pancreatitis was provoked by infusion of taurocholate into the pancreatic duct or by intraperitoneal administration of L-arginine in C57BL/6 mice. Animals were treated with an antibody against platelets or CXCL4 before induction of pancreatitis. Plasma and lung levels of CXCL2, CXCL4, and interleukin (IL)-6 were determined by use of enzyme-linked immunosorbent assay. Flow cytometry was used to examine surface expression of macrophage-1 (Mac-1) on neutrophils. Plasma was obtained from healthy individuals (controls) and patients with AP. Challenge with taurocholate increased plasma levels of CXCL4, and depletion of platelets markedly reduced plasma levels of CXCL4 indicating that circulating levels of CXCL4 are mainly derived from platelets in AP. Inhibition of CXCL4 reduced taurocholate-induced neutrophil recruitment, IL-6 secretion, edema formation, amylase release, and tissue damage in the pancreas. However, immunoneutralization of CXCL4 had no effect on CXCL2-evoked neutrophil expression of Mac-1 or chemotaxis in vitro, suggesting an indirect effect of CXCL4 on neutrophil recruitment in AP. Targeting CXCL4 significantly attenuated plasma and lung levels of CXCL2, which is a potent neutrophil chemoattractant, and inhibition of the CXCL2 receptor attenuated neutrophil infiltration and tissue damage in the inflamed pancreas. A significant role of CXCL4 was confirmed in an alternate model

  9. New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation.

    PubMed

    Molinari, Aurora; Oliva, Alfonso; Arismendi-Macuer, Marlene; Guzmán, Leda; Fuentealba, Mauricio; Knox, Marcela; Vinet, Raúl; San Feliciano, Arturo

    2015-12-08

    1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, ¹H-NMR and (13)C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents.

  10. Modulation of Mycoplasma arthritidis-derived superantigen-induced cytokine gene expression by dexamethasone and interleukin-4.

    PubMed Central

    Mehindate, K; al-Daccak, R; Rink, L; Mecheri, S; Hébert, J; Mourad, W

    1994-01-01

    Activation of human monocytes or monocytic cell lines with all known stimuli coordinately induces the gene expression of various cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and the IL-1 receptor antagonist (IL-1Ra). In contrast, superantigens induce TNF-alpha and IL-1 beta but fail to affect IL-1Ra gene expression, suggesting that activation of monocytes via major histocompatibility complex class II is distinct from other signal transduction pathways. In the present study, we analyzed the regulation of the Mycoplasma arthritidis-derived superantigen (MAM)-induced IL-1 beta and TNF-alpha gene expression by studying the effects of two different anti-inflammatory agents: dexamethasone (DEX) and the T-cell-derived cytokine IL-4. Both agents contributed to the downregulation of MAM-induced IL-1 beta and TNF-alpha gene expression. They accelerated the normal decline of the gene expression of both MAM-induced cytokines by decreasing the stability of mRNAs via the induction or enhanced synthesis of one or more regulatory proteins. In addition, IL-4, but not DEX, induced a strong and rapid expression of IL-1Ra mRNA in MAM-stimulated and unstimulated THP-1 cells in a de novo protein synthesis-independent manner. The capacity of IL-4 to induce IL-1Ra gene expression reinforces its anti-inflammatory activity. This study illustrates some of the mechanisms by which MAM-induced proinflammatory monokine gene expression can be downregulated by IL-4 and DEX. Images PMID:7927746

  11. Modulation of Mycoplasma arthritidis-derived superantigen-induced cytokine gene expression by dexamethasone and interleukin-4.

    PubMed

    Mehindate, K; al-Daccak, R; Rink, L; Mecheri, S; Hébert, J; Mourad, W

    1994-11-01

    Activation of human monocytes or monocytic cell lines with all known stimuli coordinately induces the gene expression of various cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and the IL-1 receptor antagonist (IL-1Ra). In contrast, superantigens induce TNF-alpha and IL-1 beta but fail to affect IL-1Ra gene expression, suggesting that activation of monocytes via major histocompatibility complex class II is distinct from other signal transduction pathways. In the present study, we analyzed the regulation of the Mycoplasma arthritidis-derived superantigen (MAM)-induced IL-1 beta and TNF-alpha gene expression by studying the effects of two different anti-inflammatory agents: dexamethasone (DEX) and the T-cell-derived cytokine IL-4. Both agents contributed to the downregulation of MAM-induced IL-1 beta and TNF-alpha gene expression. They accelerated the normal decline of the gene expression of both MAM-induced cytokines by decreasing the stability of mRNAs via the induction or enhanced synthesis of one or more regulatory proteins. In addition, IL-4, but not DEX, induced a strong and rapid expression of IL-1Ra mRNA in MAM-stimulated and unstimulated THP-1 cells in a de novo protein synthesis-independent manner. The capacity of IL-4 to induce IL-1Ra gene expression reinforces its anti-inflammatory activity. This study illustrates some of the mechanisms by which MAM-induced proinflammatory monokine gene expression can be downregulated by IL-4 and DEX.

  12. Synthesis and structure of a stuffed derivative of α-quartz, Mg 0.5AlSiO 4

    DOE PAGES

    Xu, Hongwu; Heaney, Peter J.; Yu, Ping; ...

    2015-10-01

    A structural derivative of quartz with the composition Mg 0.5AlSiO 4 has been grown from glass and characterized using synchrotron X-ray diffraction (XRD), transmission electron microscopy (TEM), and 29Si nuclear magnetic resonance (NMR) spectroscopy. Rietveld analysis of the XRD data indicates that the framework of Mg 0.5AlSiO 4 is isostructural with α-quartz, rather than β-quartz, as is consistent with previous theoretical modeling (Sternitzke and Müller 1991). Al and Si exhibit long-range disorder over the framework tetrahedral sites, indicated by the absence of the superlattice reflections corresponding to the doubling of c relative to that of quartz. Nevertheless, 29Si NMR measurementsmore » show that Al and Si exhibit partial short-range order with an ordering degree of 56%. Electron diffraction reveals superlattice reflections indicative of doubled periodicities along the a-axes. In conclusion, Fourier electron density maps show that Mg occupies channel sites that each are bonded to six O atoms, in contrast to the tetrahedral coordination of Li in the β-quartz-type framework for β-eucryptite, LiAlSiO 4. Furthermore, the concentrations of Mg in adjacent channels are different, resulting in framework distortions that generate the superstructures along a.« less

  13. From phenothiazine to 3-phenyl-1,4-benzothiazine derivatives as inhibitors of the Staphylococcus aureus NorA multidrug efflux pump.

    PubMed

    Sabatini, Stefano; Kaatz, Glenn W; Rossolini, Gian Maria; Brandini, David; Fravolini, Arnaldo

    2008-07-24

    Overexpression of efflux pumps is an important mechanism by which bacteria evade effects of substrate antimicrobial agents and inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus multidrug efflux pump, the activity of which confers decreased susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 1,4-benzothiazine derivatives were designed and synthesized as a minimized structural template of phenothiazine MDR efflux pump inhibitors (EPIs) in an effort to identify more potent S. aureus NorA EPIs. Almost all derivatives evaluated showed good activity in combination with ciprofloxacin against S. aureus ATCC 25923; some were capable of completely restoring ciprofloxacin activity in a norA-overexpressing strain (SA-K2378). Compounds 6k and 7j displayed good activity against SA-1199B, a strain that also overexpresses norA, in an ethidium bromide (EtBr) efflux inhibition assay.

  14. Design, synthesis, antiviral activity and three-dimensional quantitative structure-activity relationship study of novel 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety.

    PubMed

    Gan, Xiuhai; Hu, Deyu; Li, Pei; Wu, Jian; Chen, Xuewen; Xue, Wei; Song, Baoan

    2016-03-01

    1,4-Pentadien-3-one and 1,3,4-oxadiazole derivatives possess good antiviral activities, and their substructure units are usually used in antiviral agent design. In order to discover novel molecules with high antiviral activities, a series of 1,4-pentadien-3-one derivatives containing the 1,3,4-oxadiazole moiety were designed and synthesised. Bioassays showed that most of the title compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV) in vivo. The compound 8f possessing the best protective activity against TMV had an EC50 value of 135.56 mg L(-1) , which was superior to that of ribavirin (435.99 mg L(-1) ). Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were used in three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of protective activities, with values of q(2) and r(2) for the CoMFA and CoMSIA models of 0.751 and 0.775 and 0.936 and 0.925 respectively. Compound 8k with higher protective activity (EC50 = 123.53 mg L(-1) ) according to bioassay was designed and synthesised on the basis of the 3D-QSAR models. Some of the title compounds displayed good antiviral activities. 3D-QSAR models revealed that the appropriate compact electron-withdrawing and hydrophobic group at the benzene ring could enhance antiviral activity. These results could provide important structural insights for the design of highly active 1,4-pentadien-3-one derivatives. © 2015 Society of Chemical Industry.

  15. 26 CFR 1.167(b)-3 - Sum of the years-digits method.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... .0346 56.7 .0347 56.6 .0347 56.5 .0348 56.4 .0348 56.3 .0349 56.2 .0350 56.1 .0350 56.0 .0351 55.9 .0351 55.8 .0352 55.7 .0353 55.6 .0353 55.5 .0354 55.4 .0355 55.3 .0355 55.2 .0356 55.1 .0356 55.0 .0357 54... 39.0 .0500 38.9 .0501 38.8 .0502 38.7 .0504 38.6 .0505 38.5 .0506 38.4 .0508 38.3 .0509 38.2 .0510 38...

  16. 26 CFR 1.167(b)-3 - Sum of the years-digits method.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... .0346 56.7 .0347 56.6 .0347 56.5 .0348 56.4 .0348 56.3 .0349 56.2 .0350 56.1 .0350 56.0 .0351 55.9 .0351 55.8 .0352 55.7 .0353 55.6 .0353 55.5 .0354 55.4 .0355 55.3 .0355 55.2 .0356 55.1 .0356 55.0 .0357 54... 39.0 .0500 38.9 .0501 38.8 .0502 38.7 .0504 38.6 .0505 38.5 .0506 38.4 .0508 38.3 .0509 38.2 .0510 38...

  17. 26 CFR 1.167(b)-3 - Sum of the years-digits method.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... .0346 56.7 .0347 56.6 .0347 56.5 .0348 56.4 .0348 56.3 .0349 56.2 .0350 56.1 .0350 56.0 .0351 55.9 .0351 55.8 .0352 55.7 .0353 55.6 .0353 55.5 .0354 55.4 .0355 55.3 .0355 55.2 .0356 55.1 .0356 55.0 .0357 54... 39.0 .0500 38.9 .0501 38.8 .0502 38.7 .0504 38.6 .0505 38.5 .0506 38.4 .0508 38.3 .0509 38.2 .0510 38...

  18. 26 CFR 1.167(b)-3 - Sum of the years-digits method.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... .0346 56.7 .0347 56.6 .0347 56.5 .0348 56.4 .0348 56.3 .0349 56.2 .0350 56.1 .0350 56.0 .0351 55.9 .0351 55.8 .0352 55.7 .0353 55.6 .0353 55.5 .0354 55.4 .0355 55.3 .0355 55.2 .0356 55.1 .0356 55.0 .0357 54... 39.0 .0500 38.9 .0501 38.8 .0502 38.7 .0504 38.6 .0505 38.5 .0506 38.4 .0508 38.3 .0509 38.2 .0510 38...

  19. 26 CFR 1.167(b)-3 - Sum of the years-digits method.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... .0346 56.7 .0347 56.6 .0347 56.5 .0348 56.4 .0348 56.3 .0349 56.2 .0350 56.1 .0350 56.0 .0351 55.9 .0351 55.8 .0352 55.7 .0353 55.6 .0353 55.5 .0354 55.4 .0355 55.3 .0355 55.2 .0356 55.1 .0356 55.0 .0357 54... 39.0 .0500 38.9 .0501 38.8 .0502 38.7 .0504 38.6 .0505 38.5 .0506 38.4 .0508 38.3 .0509 38.2 .0510 38...

  20. Synthesis of new 2-amino-4H-pyran-3,5-dicarboxylate derivatives using nanocrystalline MIIZr4(PO4)6 ceramics as reusable and robust catalysts under microwave irradiation

    NASA Astrophysics Data System (ADS)

    Safaei-Ghomi, Javad; Javidan, Abdollah; Ziarati, Abolfazl; Shahbazi-Alavi, Hossein

    2015-08-01

    In the present paper, we report the successful synthesis of nanocrystalline MIIZr4(PO4)6 ceramics (M: Mn, Ni, Fe, Co). These nano-structures were characterized by X-ray diffraction, scanning electron microscopy, and vibrating sample magnetometer (VSM). Size of nano-structures was in the range of 20-150 nm. Nano-MIIZr4(PO4)6 as an efficient and green catalyst has been used for the preparation of 2-amino-4H-pyran-3,5-dicarboxylate derivatives by the three-component condensation reaction of ethyl cyanoacetate, ethyl acetoacetate, and various aromatic aldehydes under microwave irradiation. Extraordinarily, the best results were obtained using MnZr4(PO4)6 nanocrystallines as an efficient catalyst. This method provides several advantages including easy work-up, excellent yields, short reaction times, using of microwave as green method, recoverability of the catalyst, and little catalyst loading.

  1. HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia.

    PubMed

    Saito, Yukihiro; Nakamura, Kazufumi; Yoshida, Masashi; Sugiyama, Hiroki; Takano, Makoto; Nagase, Satoshi; Morita, Hiroshi; Kusano, Kengo F; Ito, Hiroshi

    2018-05-30

    A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 10 3 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

  2. 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.

    PubMed

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

    2013-12-15

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

  3. Synthesis of carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolinium derivatives as new potential PET SKCa channel imaging agents.

    PubMed

    Gao, Mingzhang; Wang, Min; Zheng, Qi-Huang

    2008-02-01

    Small conductance Ca2+-activated K+ (SKCa) channels play an important role in many functions such as neuronal communication and behavioral plasticity, secretion, and cell proliferation. SKCa channel modulation is associated with various brain, heart, and cancer diseases. N-methyl-laudanosine and its structurally related derivatives, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums, are reversible and selective SKCa channel blockers. Carbon-11 labeled N-methyl-laudanosine and its tetrahydroisoquinolinium derivatives may serve as new probes for positron emission tomography (PET) to image SKCa channels in the brain, heart, and cancer. The key intermediates, substituted isoquinolines (3a-c), were synthesized using a modification of the Pomeranz-Fritsch procedure. The precursors, substituted 1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines (8a-c), and their corresponding reference standards, substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums (9a-c), were synthesized from compounds 3a-c with 3,4-dimethoxybenzyl chloride (2) in multiple steps with moderate to excellent chemical yields. The precursor 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline (10) was commercially available, and the methylation of compound 10 with methyl iodide provided N-methyl-laudanosine (11). The target quaternary ammonium tracers, carbon-11 labeled 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums ([11C]9a-c and [11C]11), were prepared by N-[11C]methylation of the tertiary amine precursors (8a-c and 10) with [11C]methyl triflate and isolated by a simplified solid-phase extraction (SPE) purification using a SiO2 or cation-exchange CM Sep-Pak cartridge in 40-65% radiochemical yields.

  4. Coverage Adjusted Entropy Estimation

    DTIC Science & Technology

    2007-06-05

    S )+ OP (log n/ √ n), regardless of the underlying distribution. Our theorem below together with McAllester and Schapire’s implies a rate of...Corollary 1. Suppose that ∑ k pk| log pk|q <∞. Then as n→∞, 1− C = P(Xn+1 /∈ S| S ) = OP (1/(log n)q). (27) Proof. This follows from the above theorem and...Theorem 3 of [12] which implies |Ĉ − P(Xn+1 ∈ S| S )| ≤ oP (1/(log n)q) because 0 ≤ P(Xn+1 /∈ S|S) ≤ |1− Ĉ|+ |Ĉ − P(Xn+1 ∈ S|S)| (28) and OP (1/(log

  5. Atypical 1,4-dihydropyridine derivatives, an approach to neuroprotection and memory enhancement.

    PubMed

    Klusa, Vija

    2016-11-01

    This mini review is devoted to the design and pharmacological studies of novel atypical 1,4-dihydropyridine (DHP) derivatives which differ to a great extent from the traditional DHPs either by lack of neuronal calcium channel blocking activity and/or inability to protect mitochondrial processes. About 100 new DHP derivatives were screened and the mostly active were selected for detailed studies. The compounds of the series of the amino acid ("free" plus "crypto")-containing DHPs and lipophilic di-cyclic DHPs demonstrated long-lasting neuroprotective and/or memory-enhancing action, particularly at low doses (0.005-0.05mg/kg) in different neurodeficiency rat or mice models, and exerted neurotransmitter-modulating effects. The studies have shown an ability of these atypical DHPs to normalize the expression of neuronal proteins, which participate in the regulation of neurotransmission (particularly of the GABAergic system) and synaptic plasticity that has been impaired in animal models, including Alzheimer's disease transgenic mice. The obtained results indicate that the tested DHP compounds can be considered as candidate molecules either for their further chemical modifications or for the more detailed studies to identify cell targets essential for neuroprotection and memory enhancing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. QSAR analyses of 3-(4-benzylpiperidin-1-yl)-N-phenylpropylamine derivatives as potent CCR5 antagonists.

    PubMed

    Roy, Kunal; Leonard, J Thomas

    2005-01-01

    CCR5 receptor binding affinity of a series of 3-(4-benzylpiperidin-1-yl)propylamine congeners was subjected to QSAR study using the linear free energy related (LFER) model of Hansch. Appropriate indicator variables encoding different group contributions and different physicochemical variables such as hydrophobicity (pi), electronic (Hammett sigma), and steric (molar refractivity, STERIMOL values) parameters of phenyl ring substituents of the compounds were used as predictor variables. The Hansch analysis explores the importance of the lipophilicity and electron-donating substituents for the binding affinity. However, this method could not give more insight into the structure-activity relationships because of the diverse molecular features in the data set. 3D-QSAR analyses of the same data set using Molecular Shape Analysis (MSA), Receptor Surface Analysis (RSA), and Molecular Field Analysis (MFA) techniques were also performed. The best model with acceptable statistical quality was derived from the MSA, which showed the importance of the relative negative charge (RNCG): substituents with a high RNCG value have more binding affinity than the unsubstituted piperidine and phenyl (R1 position) congeners. The relative negative charge surface area (RNCS) is detrimental (e.g. R2 = 3,4-Cl2) for the activity. An increase in the length of the molecule in the Z dimension (Lz) is conducive (e.g. R3 = sulfonylmorpholino), while an increase in the area of the molecular shadow in the XZ plane (Sxz) is detrimental (e.g. R1 = N-c-hexylmethyl-5-oxopyrrolidin-3-yl) for the binding affinity. The presence of a chiral center makes the molecule less active (e.g. R1 = N-methyl-5-oxopyrrolidin-3-yl). An increase in the van der Waals area, the molecular volume, and the difference between the volume of the individual molecule and the shape reference compound are conducive (e.g. R3 = (CH3)2NSO2-) for the binding affinity. Substituents with higher JursFPSA_2 values (fractional charged partial

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

    PubMed

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

    2013-10-01

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

  8. Enhanced resistance to stripe rust disease in transgenic wheat expressing the rice chitinase gene RC24.

    PubMed

    Huang, Xuan; Wang, Jian; Du, Zhen; Zhang, Chen; Li, Lan; Xu, Ziqin

    2013-10-01

    Stripe rust is a devastating fungal disease of wheat worldwide which is primarily caused by Puccinia striiformis f. sp tritici. Transgenic wheat (Triticum aestivum L.) expressing rice class chitinase gene RC24 were developed by particle bombardment of immature embryos and tested for resistance to Puccinia striiformis f.sp tritici. under greenhouse and field conditions. Putative transformants were selected on kanamycin-containing media. Polymease chain reaction indicated that RC24 was transferred into 17 transformants obtained from bombardment of 1,684 immature embryos. Integration of RC24 was confirmed by Southern blot with a RC24-labeled probe and expression of RC24 was verified by RT-PCR. Nine transgenic T1 lines exhibited enhanced resistance to stripe rust infection with lines XN8 and BF4 showing the highest level of resistance. Southern blot hybridization confirmed the stable inheritance of RC24 in transgenic T1 plants. Resistance to stripe rust in transgenic T2 and T3 XN8 and BF4 plants was confirmed over two consecutive years in the field. Increased yield (27-36 %) was recorded for transgenic T2 and T3 XN8 and BF4 plants compared to controls. These results suggest that rice class I chitinase RC24 can be used to engineer stripe rust resistance in wheat.

  9. Human Adipose-Derived Mesenchymal Stem Cells Cryopreservation and Thawing Decrease α4-Integrin Expression.

    PubMed

    Irioda, Ana Carolina; Cassilha, Rafael; Zocche, Larissa; Francisco, Julio Cesar; Cunha, Ricardo Correa; Ferreira, Priscila Elias; Guarita-Souza, Luiz Cesar; Ferreira, Reginaldo Justino; Mogharbel, Bassam Felipe; Garikipati, Venkata Naga Srikanth; Souza, Daiany; Beltrame, Mirian Perlingeiro; de Carvalho, Katherine Athayde Teixeira

    2016-01-01

    Aim. The effects of cryopreservation on adipose tissue-derived mesenchymal stem cells are not clearly documented, as there is a growing body of evidence about the importance of adipose-derived mesenchymal stem cells for regenerative therapies. The aim of this study was to analyze human adipose tissue-derived mesenchymal stem cells phenotypic expression (CD34, CD45, CD73, CD90, CD105, and CD49d), colony forming unit ability, viability, and differentiation potential before and after cryopreservation. Materials and Methods. 12 samples of the adipose tissue were collected from a healthy donor using the liposuction technique. The cell isolation was performed by enzymatic digestion and then the cells were cultured up to passage 2. Before and after cryopreservation the immunophenotype, cellular viability analysis by flow cytometer, colony forming units ability, differentiation potential into adipocytes and osteoblasts as demonstrated by Oil Red O and Alizarin Red staining, respectively. Results. The immunophenotypic markers expression was largely preserved, and their multipotency was maintained. However, after cryopreservation, the cells decreased α4-integrin expression (CD49d), cell viability, and number of colony forming units. Conclusions. These findings suggest that ADMSC transplanted after cryopreservation might compromise the retention of transplanted cells in the host tissue. Therefore, further studies are warranted to standardize protocols related to cryopreservation to attain full benefits of stem cell therapy.

  10. Crystal engineering: co-crystals of cinnamic acid derivatives with a pyridyl derivative co-crystallizer.

    PubMed

    Lorenzo, Daniel A; Forrest, Sebastian J K; Sparkes, Hazel A

    2016-02-01

    A number of hydrogen-bonded co-crystals, consisting of a cinnamic acid derivative and a pyridyl co-crystallizer, have been synthesized and their properties investigated by X-ray diffraction. Samples were prepared by recrystallization or solvent drop grinding of trans-cinnamic acid (1), 4-methylcinnamic acid (2), 4-methoxy cinnamic acid (3) or 3,4-methoxy cinnamic acid (4), with 4,4-dipyridyl (A), iso-nicotinamide (B) or nicotinamide (C). The X-ray single-crystal structures of seven novel co-crystals, obtained through recrystallization, are examined and the hydrogen-bonding interactions discussed. Consistent hydrogen-bonding motifs were observed for samples prepared when using 4,4-dipyridyl (A) or iso-nicotinamide (B) as the co-crystallizing agent. Powder X-ray diffraction analysis of the samples prepared by solvent drop grinding suggests the formation of ten co-crystals.

  11. Design, Synthesis and Anticonvulsant Activity of 2-(2-Phenoxy) phenyl- 1,3,4-oxadiazole Derivatives.

    PubMed

    Tabatabai, Sayyed Abbas; Barghi Lashkari, Saoka; Zarrindast, Mohammad Reza; Gholibeikian, Mohammadreza; Shafiee, Abbas

    2013-01-01

    Benzodiazepines are useful drugs for treatment of sleep disorders, anxiety, seizure cases and skeletal muscle cramps. Some derivatives of 2-(2-Phenoxy) phenyl-1, 3, 4-oxadiazole were synthesized as benzodiazepine receptor agonists. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine agonist, reveal that the main proposed benzodiazepine pharmacophores were well matched. Anticonvulsant activity of the synthesized compounds, determined by pentylenetetrazole-induced lethal convulsion test, showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 9 which has a respectable effect. The results are in agreement with SAR of benzodiazepine receptor ligands since the elimination of electronegative substituent in position 2 of phenoxy ring or position 4 of phenyl ring reduces the anticonvulsant activity.

  12. Design, Synthesis and Anticonvulsant Activity of 2-(2-Phenoxy) phenyl- 1,3,4-oxadiazole Derivatives

    PubMed Central

    Tabatabai, Sayyed Abbas; Barghi Lashkari, Saoka; Zarrindast, Mohammad Reza; Gholibeikian, Mohammadreza; Shafiee, Abbas

    2013-01-01

    Benzodiazepines are useful drugs for treatment of sleep disorders, anxiety, seizure cases and skeletal muscle cramps. Some derivatives of 2-(2-Phenoxy) phenyl-1, 3, 4-oxadiazole were synthesized as benzodiazepine receptor agonists. Conformational analysis and superimposition of energy minima conformers of the compounds on estazolam, a known benzodiazepine agonist, reveal that the main proposed benzodiazepine pharmacophores were well matched. Anticonvulsant activity of the synthesized compounds, determined by pentylenetetrazole-induced lethal convulsion test, showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 9 which has a respectable effect. The results are in agreement with SAR of benzodiazepine receptor ligands since the elimination of electronegative substituent in position 2 of phenoxy ring or position 4 of phenyl ring reduces the anticonvulsant activity. PMID:24250678

  13. A synthesis of 4-hydroxy-2-trans-nonenal and 4-(3H) 4-hydroxy-2-trans-nonenal.

    PubMed

    Chandra, A; Srivastava, S K

    1997-07-01

    4-Hydroxy-2-trans-nonenal, the most abundant and toxic unsaturated aldehyde generated during membrane lipid peroxidation, was synthesized starting from fumaraldehyde dimethyl acetal. In the first step of the synthesis, the fumaraldehyde dimethyl acetal was partially hydrolyzed using amberlyst catalyst to obtain the monoacetal. The 4-hydroxy-2-trans-nonenal was synthesized by the Grignard reaction of the fumaraldehyde monoacetal with 1-bromopentane. 4-Hydroxy-2-trans-nonenal, obtained as its dimethylacetal, was oxidized to its corresponding 4-keto derivative using pyridinium chlorochromate buffered with sodium acetate as the oxidizing agent. 4-(3H) 4-Hydroxy-2-trans-nonenal was obtained in one step by the sodium borotriteride reduction of the 4-keto derivative.

  14. Discovery of piperidin-4-yl-aminopyrimidine derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

    PubMed

    Wan, Zheng-Yong; Yao, Jin; Tao, Yuan; Mao, Tian-Qi; Wang, Xin-Long; Lu, Yi-Pei; Wang, Hai-Feng; Yin, Hong; Wu, Yan; Chen, Fen-Er; De Clercq, Erik; Daelemans, Dirk; Pannecouque, Christophe

    2015-06-05

    A novel series of piperidin-4-yl-aminopyrimidine derivatives were designed fusing the pharmacophore templates of etravirine-VRX-480773 hybrids our group previously described and piperidine-linked aminopyrimidines. Most compounds displayed significantly improved activity against wild-type HIV-1 with EC50 values in single-digit nanomolar concentrations compared to etravirine-VRX-480773 hybrids. Selected compounds were also evaluated for activity against reverse transcriptase, and had lower IC50 values than that of nevirapine. The improved potency observed in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits reverse transcriptase, and represents a remarkable step forward in the development of AIDS therapeutics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors.

    PubMed

    Chacón-Vargas, Karla Fabiola; Nogueda-Torres, Benjamin; Sánchez-Torres, Luvia E; Suarez-Contreras, Erick; Villalobos-Rocha, Juan Carlos; Torres-Martinez, Yuridia; Lara-Ramirez, Edgar E; Fiorani, Giulia; Krauth-Siegel, R Luise; Bolognesi, Maria Laura; Monge, Antonio; Rivera, Gildardo

    2017-02-01

    Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.

  16. Synthesis and antimicrobial activity of new 1-[(tetrazol-5-yl)methyl] indole derivatives, their 1,2,4-triazole thioglycosides and acyclic analogs.

    PubMed

    El-Sayed, Weal A; Abdel Megeid, Randa E; Abbas, Hebat-Allah S

    2011-07-01

    New 1-[(tetrazol-5-yl)methyl]indole derivatives, their acyclic nucleoside analogs and the corresponding glycoside derivatives were synthesized. Furthermore, the [)(1,2,4-triazol-3-yl)methyl])-2H-tetrazole derivative as well as the corresponding thioglucoside were prepared. The synthesized compounds were tested for their antimicrobial activity against Aspergillus Niger, Penicillium sp, Candida albican, Bacillus subtilis, Streptococcus lacti, Escherichia coli, Pseudomonas sp., and streptomyces sp. Compounds 3, 5 and 19b exhibited potent antibacterial activity and compounds 4, 5 and 10 exhibited high activities against the tested fungi compared with fusidic acid.

  17. Thymic DCs derived IL-27 regulates the final maturation of CD4+ SP thymocytes

    PubMed Central

    Tang, Hui; Zhang, Jie; Sun, Xiuyuan; Qian, Xiaoping; Zhang, Yu; Jin, Rong

    2016-01-01

    IL-27, as a pleiotropic cytokine, promotes the differentiation of naïve T cells to Th1, while suppressing Th2 and Th17 differentiation in the periphery. However, the role of IL-27 in the thymocyte development remains unknown. Here we showed that IL-27 was highly expressed in thymic plasmacytoid dendritic cells (pDCs) while its receptor expression was mainly detected in CD4+ single-positive (SP) thymocytes. Deletion of the p28 subunit in DCs resulted in a reduction of the most mature Qa-2+ subsets of CD4+ SP T cells. This defect was rescued by intrathymic administration of exogenous IL-27. In vitro differentiation assay further demonstrated that IL-27 alone was able to drive the maturation of the newly generated 6C10+CD69+CD4+ SP cells into Qa-2+ cells. Collectively, this study has revealed an important role of thymic DCs-derived IL-27 in the regulation of the phenotypic maturation of CD4+ SP thymocytes. PMID:27469302

  18. Technical Note: A simple calculation algorithm to separate high-resolution CH4 flux measurements into ebullition and diffusion-derived components

    NASA Astrophysics Data System (ADS)

    Hoffmann, M.; Schulz-Hanke, M.; Garcia Alba, J.; Jurisch, N.; Hagemann, U.; Sachs, T.; Sommer, M.; Augustin, J.

    2015-08-01

    Processes driving the production, transformation and transport of methane (CH4) in wetland ecosystems are highly complex. Thus, serious challenges are constitutes in terms of the mechanistic process understanding, the identification of potential environmental drivers and the calculation of reliable CH4 emission estimates. We present a simple calculation algorithm to separate open-water CH4 fluxes measured with automatic chambers into diffusion- and ebullition-derived components, which helps facilitating the identification of underlying dynamics and potential environmental drivers. Flux separation is based on ebullition related sudden concentration changes during single measurements. A variable ebullition filter is applied, using the lower and upper quartile and the interquartile range (IQR). Automation of data processing is achieved by using an established R-script, adjusted for the purpose of CH4 flux calculation. The algorithm was tested using flux measurement data (July to September 2013) from a former fen grassland site, converted into a shallow lake as a result of rewetting ebullition and diffusion contributed 46 and 55 %, respectively, to total CH4 emissions, which is comparable to those previously reported by literature. Moreover, the separation algorithm revealed a concealed shift in the diurnal trend of diffusive fluxes throughout the measurement period.

  19. The role of human cytochrome P4503A4 in biotransformation of tissue-specific derivatives of 7H-dibenzo[c,g]carbazole

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mesarosova, Monika; Valovicova, Zuzana; Srancikova, Annamaria

    2011-09-15

    The environmental pollutant 7H-dibenzo[c,g]carbazole (DBC) and its derivative, 5,9-dimethylDBC (DiMeDBC), produced significant and dose-dependent levels of micronuclei followed by a substantial increase in the frequency of apoptotic cells in the V79MZh3A4 cell line stably expressing the human cytochrome P450 (hCYP) 3A4. In contrast, neither micronuclei nor apoptosis were found in cells exposed to the sarcomagenic carcinogen, N-methylDBC (N-MeDBC). A slight but significant level of gene mutations and DNA adducts detected in V79MZh3A4 cells treated with N-MeDBC, only at the highest concentration (30 {mu}M), revealed that this sarcomagenic carcinogen was also metabolized by hCYP3A4. Surprisingly, DBC increased the frequency of 6-thioguaninemore » resistant (6-TG{sup r}) mutations only at the highest concentration (30 {mu}M), while DiMeDBC failed to increase the frequency of these mutations. The resistance to 6-thioguanine is caused by the mutations in the hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene. The molecular analysis of the coding region of Hprt gene showed a deletion of the entire exon 8 in DiMeDBC-induced 6-TG{sup r} mutants, while no changes in the nucleotide sequences were identified in 6-TG{sup r} mutants produced by DBC and N-MeDBC. Based on our results, we suggest that hCYP3A4 is involved in the metabolism of DBC and its tissue-specific derivatives. While hCYP3A4 probably plays an important role in biotransformation of the liver carcinogens, DBC and DiMeDBC, it might only have a marginal function in N-MeDBC metabolism. - Highlights: > DBC activation via CYP3A4 resulted in micronuclei, DNA adduct formation and mutations in V79MZh3A4 cells. > The CYP3A4-mediated DiMeDBC activation caused micronuclei followed by apoptosis in V79MZh3A4 cells. > The genotoxic effects produced by N-MeDBC in V79MZh3A4 cells were negligible. > The hCYP3A4 may play an important role in DBC and DiMeDBC metabolism. > The CYP3A4 might only have a marginal function in

  20. Transport and transformation of soil-derived CO2, CH4 and DOC sustain CO2 supersaturation in small boreal streams.

    PubMed

    Rasilo, Terhi; Hutchins, Ryan H S; Ruiz-González, Clara; Del Giorgio, Paul A

    2017-02-01

    Streams are typically supersaturated in carbon dioxide (CO 2 ) and methane (CH 4 ), and are recognized as important components of regional carbon (C) emissions in northern landscapes. Whereas there is consensus that in most of the systems the CO 2 emitted by streams represents C fixed in the terrestrial ecosystem, the pathways delivering this C to streams are still not well understood. We assessed the contribution of direct soil CO 2 injection versus the oxidation of soil-derived dissolved organic C (DOC) and CH 4 in supporting CO 2 supersaturation in boreal streams in Québec. We measured the concentrations of CO 2 , CH 4 and DOC in 43 streams and adjacent soil waters during summer base-flow period. A mass balance approach revealed that all three pathways are significant, and that the mineralization of soil-derived DOC and CH 4 accounted for most of the estimated stream CO 2 emissions (average 75% and 10%, respectively), and that these estimated contributions did not change significantly between the studied low order (≤3) streams. Whereas some of these transformations take place in the channel proper, our results suggest that they mainly occur in the hyporheic zones of the streams. Our results further show that stream CH 4 emissions can be fully explained by soil CH 4 inputs. This study confirms that these boreal streams, and in particular their hyporheic zones, are extremely active processors of soil derived DOC and CH 4 , not just vents for soil produced CO 2 . Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Dual little strings and their partition functions

    NASA Astrophysics Data System (ADS)

    Bastian, Brice; Hohenegger, Stefan; Iqbal, Amer; Rey, Soo-Jong

    2018-05-01

    We study the topological string partition function of a class of toric, double elliptically fibered Calabi-Yau threefolds XN ,M at a generic point in the Kähler moduli space. These manifolds engineer little string theories in five dimensions or lower and are dual to stacks of M5-branes probing a transverse orbifold singularity. Using the refined topological vertex formalism, we explicitly calculate a generic building block which allows us to compute the topological string partition function of XN ,M as a series expansion in different Kähler parameters. Using this result, we give further explicit proof for a duality found previously in the literature, which relates XN ,M˜XN',M' for N M =N'M' and gcd (N ,M )=gcd (N',M') .

  2. The use of oak chips and coconut fiber as biofilter media to remove vocs in rendering process.

    PubMed

    Tymczyna, Leszek; Chmielowiec-Korzeniowska, Anna; Paluszak, Zbigniew; Dobrowolska, Magadalena; Banach, Marcin; Pulit, Jolanta

    2013-01-01

    The study evaluated the effectiveness of air biofiltration in rendering plants. The biofilter material comprised compost soil (40%) and peat (40%) mixed up with coconut fiber (medium A) and oak bark (medium B). During biofiltration average VOCs reduction reached 88.4% for medium A and 89.7% for medium B. A positive relationship of aldehyde reduction from material humidity (r = 0.502; α<0.05) was also noted. Other biomaterial parameters did not affect the treatment efficiency.

  3. Discovery of pyrrolospirooxindole derivatives as novel cyclin dependent kinase 4 (CDK4) inhibitors by catalyst-free, green approach.

    PubMed

    Kamal, Ahmed; Mahesh, Rasala; Nayak, V Lakshma; Babu, Korrapati Suresh; Kumar, G Bharath; Shaik, Anver Basha; Kapure, Jeevak Sopanrao; Alarifi, Abdullah

    2016-01-27

    Aiming to develop a new target for the anticancer treatment, a series of 5'H-spiro[indoline-3,4'-pyrrolo [1,2-a]quinoxalin]-2-ones has been synthesized by simple, highly efficient and environmentally friendly method in excellent yields under catalyst-free conditions using ethanol as a green solvent. A simple filtration of the reaction mixture and subsequent drying affords analytically pure products. The synthesized derivatives were evaluated for their antiproliferative activity against five different human cancer cell lines, among the congeners compound 3n showed significant cytotoxicity against the human prostate cancer (DU-145). Flow cytometric analysis revealed that this compound induces cell cycle arrest in the G0/G1 phase and Western blot analysis suggested that reduction in Cdk4 expression level leads to apoptotic cell death. This was further confirmed by mitochondrial membrane potential ((ΔΨm), Annexin V-FITC assay and docking experiments. Furthermore, it was observed that there is an increase in expression levels of cyclin dependent kinase inhibitors like Cip1/p21 and Kip1/p27. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Development of a new class of aromatase inhibitors: Design, synthesis and inhibitory activity of 3-phenylchroman-4-one (isoflavanone) derivatives

    PubMed Central

    Bonfield, Kevin; Amato, Erica; Bankemper, Tony; Agard, Hannah; Steller, Jeffrey; Keeler, James M.; Roy, David; McCallum, Adam; Paula, Stefan; Ma, Lili

    2014-01-01

    Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC50 values of 2.4 μM, 0.26 μM and 5.8 μM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors. PMID:22444875

  5. High-quality III-nitride films on conductive, transparent (2̅01)-oriented β-Ga2O3 using a GaN buffer layer.

    PubMed

    Muhammed, M M; Roldan, M A; Yamashita, Y; Sahonta, S-L; Ajia, I A; Iizuka, K; Kuramata, A; Humphreys, C J; Roqan, I S

    2016-07-14

    We demonstrate the high structural and optical properties of InxGa1-xN epilayers (0 ≤ x ≤ 23) grown on conductive and transparent (01)-oriented β-Ga2O3 substrates using a low-temperature GaN buffer layer rather than AlN buffer layer, which enhances the quality and stability of the crystals compared to those grown on (100)-oriented β-Ga2O3. Raman maps show that the 2″ wafer is relaxed and uniform. Transmission electron microscopy (TEM) reveals that the dislocation density reduces considerably (~4.8 × 10(7) cm(-2)) at the grain centers. High-resolution TEM analysis demonstrates that most dislocations emerge at an angle with respect to the c-axis, whereas dislocations of the opposite phase form a loop and annihilate each other. The dislocation behavior is due to irregular (01) β-Ga2O3 surface at the interface and distorted buffer layer, followed by relaxed GaN epilayer. Photoluminescence results confirm high optical quality and time-resolved spectroscopy shows that the recombination is governed by bound excitons. We find that a low root-mean-square average (≤1.5 nm) of InxGa1-xN epilayers can be achieved with high optical quality of InxGa1-xN epilayers. We reveal that (01)-oriented β-Ga2O3 substrate has a strong potential for use in large-scale high-quality vertical light emitting device design.

  6. Modeling of drug-mediated CYP3A4 induction by using human iPS cell-derived enterocyte-like cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Negoro, Ryosuke; Takayama, Kazuo; The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research

    Many drugs have potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in small intestinal enterocytes. Therefore, a model that can accurately evaluate drug-mediated CYP3A4 induction is urgently needed. In this study, we overlaid Matrigel on the human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. By overlaying Matrigel in the maturation process of enterocyte-like cells, the gene expression levels of intestinal markers (VILLIN, sucrase-isomaltase, intestine-specific homeobox, caudal type homeobox 2, and intestinal fatty acid-binding protein) were enhanced suggesting that the enterocyte-like cellsmore » were maturated by Matrigel overlay. The percentage of VILLIN-positive cells in the hiPS-ELCs found to be approximately 55.6%. To examine the CYP3A4 induction potential, the hiPS-ELCs were treated with various drugs. Treatment with dexamethasone, phenobarbital, rifampicin, or 1α,25-dihydroxyvitamin D3 resulted in 5.8-fold, 13.4-fold, 9.8-fold, or 95.0-fold induction of CYP3A4 expression relative to that in the untreated controls, respectively. These results suggest that our hiPS-ELCs would be a useful model for CYP3A4 induction test. - Highlights: • The hiPS-ELCs were matured by Matrigel overlay. • The hiPS-ELCs expressed intestinal nuclear receptors, such as PXR, GR and VDR. • The hiPS-ELC is a useful model for the drug-mediated CYP3A4 induction test.« less

  7. Synthesis of 4'-Selenoribonucleosides, the Building Blocks of 4'-SelenoRNA, Using a Hypervalent Iodine.

    PubMed

    Saito-Tarashima, Noriko; Ota, Masashi; Minakawa, Noriaki

    2017-09-18

    Herein is described a detailed protocol for the synthesis of 4'-selenoribonucleoside derivatives that involves the use of a hypervalent iodine species. These derivatives are versatile units for the preparation of 4'-selenoRNA. Large-scale synthesis of a 4-selenosugar starting from D-ribose is achieved in eight steps, including a final chromatographic purification. The resulting 4-selenosugar is then subjected to the one-pot Pummerer-like reaction using hypervalent iodine in the presence of silylated nucleobases. The reaction with silylated uracil affords the desired 4'-selenouridine derivatives with excellent β-selectivity and in good yield. Conversely, when purine nucleobases are used in the Pummerer-like reaction, N7 4'-selenoribonucleoside isomers are obtained alongside the desired N9 isomers. However, the undesired N7 isomers can be converted to the desired N9 ones under acidic conditions. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  8. Synthesis, Structure–Activity Relationship Studies, and Antibacterial Evaluation of 4-Chromanones and Chalcones, as Well as Olympicin A and Derivatives

    PubMed Central

    2015-01-01

    On the basis of recently reported abyssinone II and olympicin A, a series of chemically modified flavonoid phytochemicals were synthesized and evaluated against Mycobacterium tuberculosis and a panel of Gram-positive and -negative bacterial pathogens. Some of the synthesized compounds exhibited good antibacterial activities against Gram-positive pathogens including methicillin resistant Staphylococcus aureus with minimum inhibitory concentration as low as 0.39 μg/mL. SAR analysis revealed that the 2-hydrophobic substituent and the 4-hydrogen bond donor/acceptor of the 4-chromanone scaffold together with the hydroxy groups at 5- and 7-positions enhanced antibacterial activities; the 2′,4′-dihydroxylated A ring and the lipophilic substituted B ring of chalcone derivatives were pharmacophoric elements for antibacterial activities. Mode of action studies performed on selected compounds revealed that they dissipated the bacterial membrane potential, resulting in the inhibition of macromolecular biosynthesis; further studies showed that selected compounds inhibited DNA topoisomerase IV, suggesting complex mechanisms of actions for compounds in this series. PMID:25238443

  9. Components in Plasma-Derived Factor VIII, But Not in Recombinant Factor VIII Downregulate Anti-Inflammatory Surface Marker CD163 in Human Macrophages through Release of CXCL4 (Platelet Factor 4)

    PubMed Central

    Bertling, Anne; Brodde, Martin F.; Visser, Mayken; Treffon, Janina; Fennen, Michelle; Fender, Anke C.; Kelsch, Reinhard; Kehrel, Beate E.

    2017-01-01

    Background Hemarthrosis, or bleeding into the joints, is a hallmark of hemophilia. Heme triggers oxidative stress, inflammation, and destruction of cartilage and bone. The haptoglobin-CD163-heme oxygenase-1 (HO-1) pathway circumvents heme toxicity through enzymatic degradation of heme and transcription of antioxidant genes. Plasma-derived factor concentrates contain many proteins that might impact on cellular pathways in joints, blood, and vessels. Methods Activation of platelets from healthy volunteers was assessed by flow cytometry analysis of fibrinogen binding and CD62P expression. Platelet CXCL4 release was measured by ELISA. Human peripheral blood mononuclear cells were exposed to CXCL4 or platelet supernatants (untreated or pre-stimulated with factor VIII (FVIII) products) during their differentiation to macrophages and analyzed for CD163 expression. Some macrophage cultures were additionally incubated with autologous hemoglobin for 18 h for analysis of HO-1 expression. Results Platelet CXCL4 release was increased by all 8 tested plasma-derived FVIII products but not the 3 recombinant products. Macrophages exposed to supernatant from platelets treated with some plasma-derived FVIII products downregulated CD163 surface expression and failed to upregulate the athero- and joint protective enzyme HO-1 in response to hemoglobin. Conclusion Plasma-derived FVIII products might promote bleeding-induced joint injury via generation of macrophages that are unable to counteract redox stress. PMID:29070980

  10. Components in Plasma-Derived Factor VIII, But Not in Recombinant Factor VIII Downregulate Anti-Inflammatory Surface Marker CD163 in Human Macrophages through Release of CXCL4 (Platelet Factor 4).

    PubMed

    Bertling, Anne; Brodde, Martin F; Visser, Mayken; Treffon, Janina; Fennen, Michelle; Fender, Anke C; Kelsch, Reinhard; Kehrel, Beate E

    2017-09-01

    Hemarthrosis, or bleeding into the joints, is a hallmark of hemophilia. Heme triggers oxidative stress, inflammation, and destruction of cartilage and bone. The haptoglobin-CD163-heme oxygenase-1 (HO-1) pathway circumvents heme toxicity through enzymatic degradation of heme and transcription of antioxidant genes. Plasma-derived factor concentrates contain many proteins that might impact on cellular pathways in joints, blood, and vessels. Activation of platelets from healthy volunteers was assessed by flow cytometry analysis of fibrinogen binding and CD62P expression. Platelet CXCL4 release was measured by ELISA. Human peripheral blood mononuclear cells were exposed to CXCL4 or platelet supernatants (untreated or pre-stimulated with factor VIII (FVIII) products) during their differentiation to macrophages and analyzed for CD163 expression. Some macrophage cultures were additionally incubated with autologous hemoglobin for 18 h for analysis of HO-1 expression. Platelet CXCL4 release was increased by all 8 tested plasma-derived FVIII products but not the 3 recombinant products. Macrophages exposed to supernatant from platelets treated with some plasma-derived FVIII products downregulated CD163 surface expression and failed to upregulate the athero- and joint protective enzyme HO-1 in response to hemoglobin. Plasma-derived FVIII products might promote bleeding-induced joint injury via generation of macrophages that are unable to counteract redox stress.

  11. Par-4 dependent modulation of cellular β-catenin by medicinal plant natural product derivative 3-azido Withaferin A.

    PubMed

    Amin, Hina; Nayak, Debasis; Ur Rasool, Reyaz; Chakraborty, Souneek; Kumar, Anmol; Yousuf, Khalid; Sharma, Parduman Raj; Ahmed, Zabeer; Sharma, Neelam; Magotra, Asmita; Mukherjee, Debaraj; Kumar, Lekha Dinesh; Goswami, Anindya

    2016-05-01

    Here, we provide evidences that natural product derivative 3-azido Withaferin A (3-AWA) abrogated EMT and invasion by modulating β-catenin localization and its transcriptional activity in the prostate as well as in breast cancer cells. This study, for the first time, reveals 3-AWA treatment consistently sequestered nuclear β-catenin and augmented its cytoplasmic pool as evidenced by reducing β-catenin transcriptional activity in these cells. Moreover, 3-AWA treatment triggered robust induction of pro-apoptotic intracellular Par-4, attenuated Akt activity and rescued Phospho-GSK3β (by Akt) to promote β-catenin destabilization. Further, our in vitro studies demonstrate that 3-AWA treatment amplified E-cadherin expression along with sharp downregulation of c-Myc and cyclin D1 proteins. Strikingly, endogenous Par-4 knock down by siRNA underscored 3-AWA mediated inhibition of nuclear β-catenin was Par-4 dependent and suppression of Par-4 activity, either by Bcl-2 or by Ras transfection, restored the nuclear β-catenin level suggesting Par-4 mediated β-catenin regulation was not promiscuous. In vivo results further demonstrated that 3-AWA was effective inhibitor of tumor growth and immunohistochemical studies indicated that increased expression of total β-catenin and decreased expression of phospho-β-catenin and Par-4 in breast cancer tissues as compared to normal breast tissue suggesting Par-4 and β-catenin proteins are mutually regulated and inversely co-related in normal as well as cancer condition. Thus, strategic regulation of intracellular Par-4 by 3-AWA in diverse cancers could be an effective tool to control cancer cell metastasis. Conclusively, this report puts forward a novel approach of controlling deregulated β-catenin signaling by 3-AWA induced Par-4 protein. © 2015 Wiley Periodicals, Inc.

  12. Crystal structures of three 3,4,5-tri-meth-oxy-benzamide-based derivatives.

    PubMed

    Gomes, Ligia R; Low, John Nicolson; Oliveira, Catarina; Cagide, Fernando; Borges, Fernanda

    2016-05-01

    The crystal structures of three benzamide derivatives, viz. N-(6-hy-droxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C16H25NO5, (1), N-(6-anilinohex-yl)-3,4,5-tri-meth-oxy-benzamide, C22H30N2O4, (2), and N-(6,6-di-eth-oxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the mol-ecules. In each mol-ecule, the m-meth-oxy substituents are virtually coplanar with the benzyl ring, while the p-meth-oxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N-H donor group and O acceptor atoms link the mol-ecules into C(4) chains. In 1, a terminal -OH group links the mol-ecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R 2 (2)(17) rings in which the ⋯O-H⋯ chain lies in the centre of the ribbon and the tri-meth-oxy-benzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N-H group to an O atom of the 4-meth-oxy group link the mol-ecules into a chain of R 2 (2)(17) rings. In 3, the mol-ecules are linked only by C(4) chains.

  13. Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration.

    PubMed

    Paris, Nicole D; Soroka, Andrew; Klose, Alanna; Liu, Wenxuan; Chakkalakal, Joe V

    2016-11-18

    Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4 , the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration.

  14. Selective neurotensin-derived internally quenched fluorogenic substrates for neurolysin (EC 3.4.24.16): comparison with thimet oligopeptidase (EC 3.4.24.15) and neprilysin (EC 3.4.24.11).

    PubMed

    Oliveira, V; Campos, M; Hemerly, J P; Ferro, E S; Camargo, A C; Juliano, M A; Juliano, L

    2001-05-15

    Internally quenched fluorescent peptides derived from neurotensin (pELYENKPRRPYIL) sequence were synthesized and assayed as substrates for neurolysin (EC 3.4.24.16), thimet oligopeptidase (EC 3.4.24.15 or TOP), and neprilysin (EC 3.4.24.11 or NEP). Abz-LYENKPRRPYILQ-EDDnp (where EDDnp is N-(2,4-dinitrophenyl)ethylenediamine and Abz is ortho-aminobenzoic acid) was derived from neurotensin by the introduction of Q-EDDnp at the C-terminal end of peptide and by the substitution of the pyroglutamic (pE) residue at N-terminus for Abz and a series of shorter peptides was obtained by deletion of amino acids residues from C-terminal, N-terminal, or both sides. Neurolysin and TOP hydrolyzed the substrates at P--Y or Y--I or R--R bonds depending on the sequence and size of the peptides, while NEP cleaved P-Y or Y-I bonds according to its S'(1) specificity. One of these substrates, Abz-NKPRRPQ-EDDnp was a specific and sensitive substrate for neurolysin (k(cat) = 7.0 s(-1), K(m) = 1.19 microM and k(cat)/K(m) = 5882 mM(-1). s(-1)), while it was completely resistant to NEP and poorly hydrolyzed by TOP and also by prolyl oligopeptidase (EC 3.4.21.26). Neurolysin concentrations as low as 1 pM were detected using this substrate under our conditions and its analogue Abz-NKPRAPQ-EDDnp was hydrolyzed by neurolysin with k(cat) = 14.03 s(-1), K(m) = 0.82 microM, and k(cat)/K(m) = 17,110 mM(-1). s(-1), being the best substrate so far described for this peptidase. Copyright 2001 Academic Press.

  15. Chemoselective amide formation using O-(4-nitrophenyl)hydroxylamines and pyruvic acid derivatives.

    PubMed

    Kumar, Sonali; Sharma, Rashi; Garcia, Megan; Kamel, Joseph; McCarthy, Caroline; Muth, Aaron; Phanstiel, Otto

    2012-12-07

    A series of O-(4-nitrophenyl)hydroxylamines were synthesized from their respective oximes using a pulsed addition of excess NaBH(3)CN at pH 3 in 65-75% yield. Steric hindrance near the oxime functional group played a key role in both the ease by which the oxime could be reduced and the subsequent reactivity of the respective hydroxylamine. Reaction of the respective hydroxylamines with pyruvic acid derivatives generated the desired amides in good yields. A comparison of phenethylamine systems bearing different leaving groups revealed significant differences in the rates of these systems and suggested that the leaving group ability of the N-OR substituent plays an important role in determining their reactivity with pyruvic acid. Competition experiments (in 68% DMSO/phosphate buffered saline) using 1 equiv of N-phenethyl-O-(4-nitrophenyl)hydroxylamine and 2 equiv of pyruvic acid in the presence of other nucleophiles such as glycine, cysteine, phenol, hexanoic acid, and lysine demonstrated that significant chemoselectivity is present in this reaction. The results suggest that this chemoselective reaction can occur in the presence of excess α-amino acids, phenols, acids, thiols, and amines.

  16. Toward the definition of stereochemical requirements for MT2-selective antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin derivatives.

    PubMed

    Bedini, Annalida; Lucarini, Simone; Spadoni, Gilberto; Tarzia, Giorgio; Scaglione, Francesco; Dugnani, Silvana; Pannacci, Marilou; Lucini, Valeria; Carmi, Caterina; Pala, Daniele; Rivara, Silvia; Mor, Marco

    2011-12-22

    New derivatives of 4-phenyl-2-propionamidotetralin (4-P-PDOT) were prepared and tested on cloned MT1 and MT2 receptors, with the purpose of merging previously reported pharmacophores for nonselective agonists and for MT2-selective antagonists. A 8-methoxy group increases binding affinity of both (±)-cis- and (±)-trans-4-P-PDOT, and it can be bioisosterically replaced by a bromine. Conformational analysis of 8-methoxy-4-P-PDOT by molecular dynamics, supported by NMR data, revealed an energetically favored conformation for the (2S,4S)-cis isomer and a less favorable conformation for the (2R,4S)-trans one, fulfilling the requirements of a pharmacophore model for nonselective melatonin receptor agonists. A new superposition model, including features characteristic of MT2-selective antagonists, suggests that MT1/MT2 agonists and MT2 antagonists can share the same arrangement for their pharmacophoric elements. The model correctly predicted the eutomers of (±)-cis- and (±)-trans-4-P-PDOT. The model was validated by preparing three dihydronaphthalene derivatives, either able or not able to reproduce the putative active conformation of 4-P-PDOT.

  17. Thiazolidine-2,4-dione derivatives: programmed chemical weapons for key protein targets of various pathological conditions.

    PubMed

    Chadha, Navriti; Bahia, Malkeet Singh; Kaur, Maninder; Silakari, Om

    2015-07-01

    Thiazolidine-2,4-dione is an extensively explored heterocyclic nucleus for designing of novel agents implicated for a wide variety of pathophysiological conditions, that is, diabetes, diabetic complications, cancer, arthritis, inflammation, microbial infection, and melanoma, etc. The current paradigm of drug development has shifted to the structure-based drug design, since high-throughput screenings have continued to generate disappointing results. The gap between hit generation and drug establishment can be narrowed down by investigation of ligand interactions with its receptor protein. Therefore, it would always be highly beneficial to gain knowledge of molecular level interactions between specific protein target and developed ligands; since this information can be maneuvered to design new molecules with improved protein fitting. Thus, considering this aspect, we have corroborated the information about molecular (target) level implementations of thiazolidine-2,4-diones (TZD) derivatives having therapeutic implementations such as, but not limited to, anti-diabetic (glitazones), anti-cancer, anti-arthritic, anti-inflammatory, anti-oxidant and anti-microbial, etc. The structure based SAR of TZD derivatives for various protein targets would serve as a benchmark for the alteration of existing ligands to design new ones with better binding interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Anatomy of a Visible Light Activated Photocatalyst for Water Splitting

    DOE PAGES

    Phivilay, Somphonh Peter; Roberts, Charles; Gamalski, Andrew; ...

    2018-06-08

    The supported mixed oxide (Rh 2-yCr yO 3)/(Ga 1-xZn x)(N 1-xO x) photocatalyst, highly active for splitting of H 2O, was extensively characterized for its bulk and surface properties with the objective of developing fundamental structure-photoactivity relationships. Raman and UV-vis spectroscopy revealed that the molecular and electronic structures, respectively, of the oxynitride (Ga 1-xZn x)(N 1-xO x) support are not perturbed by the deposition of the (Rh 2-yCr yO 3) NPs. Photoluminescence (PL) spectroscopy, however, showed that the oxynitride (Ga 1-xZn x)(N 1-xO x) support is the source of excited electrons/holes and the (Rh 2-yCr yO 3) NPs greatly reducemore » the undesirable recombination of photoexcited electron/holes by acting as efficient electron traps as well as increase the lifetimes of the excitons. High Resolution-XPS and High Sensitivity-LEIS surface analyses reveal that the surfaces of the (Rh 2-yCr yO 3) NPs consist of Rh +3 and Cr +3 mixed oxide species. In Situ AP-XPS help to reveal that the Rh+3 and surface N atoms are involved in water splitting. Dispersed RhOx species on the (Ga 1-xZn x)(N 1-xO x) support and on CrO x NPs were found to be the photocatalytic active sites for H 2 generation and N and Zn sites from the (Ga 1-xZn x)(N 1-xO x) support are the photocatalytic active site for O 2 generation. The current investigation establishes the fundamental structure-photoactivity relationships of these visible light activated photocatalysts.« less

  19. Anatomy of a Visible Light Activated Photocatalyst for Water Splitting

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Phivilay, Somphonh Peter; Roberts, Charles; Gamalski, Andrew

    The supported mixed oxide (Rh 2-yCr yO 3)/(Ga 1-xZn x)(N 1-xO x) photocatalyst, highly active for splitting of H 2O, was extensively characterized for its bulk and surface properties with the objective of developing fundamental structure-photoactivity relationships. Raman and UV-vis spectroscopy revealed that the molecular and electronic structures, respectively, of the oxynitride (Ga 1-xZn x)(N 1-xO x) support are not perturbed by the deposition of the (Rh 2-yCr yO 3) NPs. Photoluminescence (PL) spectroscopy, however, showed that the oxynitride (Ga 1-xZn x)(N 1-xO x) support is the source of excited electrons/holes and the (Rh 2-yCr yO 3) NPs greatly reducemore » the undesirable recombination of photoexcited electron/holes by acting as efficient electron traps as well as increase the lifetimes of the excitons. High Resolution-XPS and High Sensitivity-LEIS surface analyses reveal that the surfaces of the (Rh 2-yCr yO 3) NPs consist of Rh +3 and Cr +3 mixed oxide species. In Situ AP-XPS help to reveal that the Rh+3 and surface N atoms are involved in water splitting. Dispersed RhOx species on the (Ga 1-xZn x)(N 1-xO x) support and on CrO x NPs were found to be the photocatalytic active sites for H 2 generation and N and Zn sites from the (Ga 1-xZn x)(N 1-xO x) support are the photocatalytic active site for O 2 generation. The current investigation establishes the fundamental structure-photoactivity relationships of these visible light activated photocatalysts.« less

  20. Synthesis of novel quinazolin-4(3H)-one derivatives containing the 7-oxo-1,2,4-triazolo[1,5-a]pyrimidine moiety as effective agricultural bactericides against the pathogen Xanthomonas oryzae pv. oryzae.

    PubMed

    Du, Huan; Fan, Zhijiang; Yang, Lan; Bao, Xiaoping

    2018-02-01

    A series of novel quinazolin-4-one derivatives (7a-7n) bearing the 7-oxo-1,2,4-triazolo[1,5-a]pyrimidine moiety were designed, synthesized and evaluated for their inhibition activities against phytopathogenic bacteria and fungi in vitro. All of the target compounds were fully characterized through [Formula: see text] NMR, [Formula: see text] NMR, HRMS and IR spectra. Among these compounds, the structure of compound 7e was unambiguously confirmed via single-crystal X-ray diffraction analysis. The turbidimetric assays indicated that compounds 7b, 7d, 7g, 7k and 7n exhibited much more potent inhibition activities against the pathogen Xanthomonas oryzae pv. oryzae (Xoo), relative to control Bismerthiazol. Moreover, antibacterial activities of compounds 7j, 7k and 7n against the pathogen Xanthomonas axonopodis pv. citri (Xac) were comparable to that of control Bismerthiazol. As for the pathogen Ralstonia solanacearum (Rs), only compounds 7g and 7i demonstrated inhibition activities similar to control Thiadiazole-copper. Moreover, this class of compounds did not display inhibition activity against three fungi tested. The above findings indicated that quinazolin-4-one derivatives containing the 7-oxo-1,2,4-triazolo[1,5-a]pyrimidine moiety have a potential as promising candidates for the development of new and more efficient agricultural bactericides.

  1. Palladium-catalyzed cyclocarbonylation of o-iodoanilines with heterocumulenes: regioselective preparation of 4(3H)-quinazolinone derivatives

    PubMed

    Larksarp; Alper

    2000-05-09

    A catalyst system comprising palladium acetate-bidentate phosphine is effective for the cyclocarbonylation of o-iodoanilines with heterocumulenes at 70-100 degrees C for 12-24 h to give the corresponding 4(3H)-quinazolinone derivatives in good yields. Utilizing o-iodoaniline with isocyanates, carbodiimides, and ketenimines for the reaction, 2,4-(1H,3H)-quinazolinediones, 2-amino-4(3H)-quinazolinones and 2-alkyl-4(3H)-quinazolinones were obtained, respectively. The nature of the substrates including the electrophilicity of the carbon center of the carbodiimide, and the stability of the ketenimine, influence the product yields of this reaction. Urea-type intermediates are believed to be generated first in situ from the reaction of o-iodoanilines with heterocumulenes, followed by palladium-catalyzed carbonylation and cyclization to yield the products.

  2. Design, synthesis and molecular modeling studies of novel thiazolidine-2,4-dione derivatives as potential anti-cancer agents

    NASA Astrophysics Data System (ADS)

    Asati, Vivek; Bharti, Sanjay Kumar

    2018-02-01

    A series of novel thiazolidine-2,4-dione derivatives 4a-x have been designed, synthesized and evaluated for potential anti-cancer activity. The anti-cancer activity of synthesized compounds 4a-x were evaluated against selected human cancer cell line of breast (MCF-7) using sulforhodamine B (SRB) method. Among the synthesized compounds, 4x having 2-cyano phenyl group showed significant cytotoxic activity which is comparable to that of adriamycin as standard anti-cancer drug. The SAR study revealed that the substituted phenyl group on oxadiazole ring attached to thiazolidine-2,4-dione moiety showed significant growth inhibitory activity against MCF-7 cell line. The result of molecular modeling studies showed that compounds 4f, 4o and 4x having similar structural alignment as crystal ligand of protein.

  3. Selective impact of CDK4/6 suppression on patient-derived models of pancreatic cancer.

    PubMed

    Witkiewicz, Agnieszka K; Borja, Nicholas A; Franco, Jorge; Brody, Jonathan R; Yeo, Charles J; Mansour, John; Choti, Michael A; McCue, Peter; Knudsen, Erik S

    2015-06-30

    Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in 14 of the 15 explants. In the single resistant explant, we identified the rare loss of the RB tumor suppressor as the basis for resistance. Patient-derived xenografts (PDXs) were developed in parallel, and unlike the xenografts emerging from established cell lines, the PDXs maintained the histoarchitecture of the primary tumor. These PDXs were highly sensitive to CDK4/6 inhibition, yielding a complete suppression of PDA proliferation. Together, these data indicate that primary PDA is sensitive to CDK4/6 inhibition, that specific biomarkers can delineate intrinsic resistance, and that established cell line models may not represent an adequate means for evaluating therapeutic sensitivities.

  4. A Fast Estimation Algorithm for Two-Dimensional Gravity Data (GEOFAST),

    DTIC Science & Technology

    1979-11-15

    to a wide class of problems (Refs. 9 and 17). The major inhibitor to the widespread appli- ( cation of optimal gravity data processing is the severe...extends directly to two dimensions. Define the nln 2xn1 n2 diagonal window matrix W as the Kronecker product of two one-dimensional windows W = W1 0 W2 (B...Inversion of Separable Matrices Consider the linear system y = T x (B.3-1) where T is block Toeplitz of dimension nln 2xnIn 2 . Its fre- quency domain

  5. Composing chaotic music from the letter m

    NASA Astrophysics Data System (ADS)

    Sotiropoulos, Anastasios D.

    Chaotic music is composed from a proposed iterative map depicting the letter m, relating the pitch, duration and loudness of successive steps. Each of the two curves of the letter m is based on the classical logistic map. Thus, the generating map is xn+1 = r xn(1/2 - xn) for xn between 0 and 1/2 defining the first curve, and xn+1 = r (xn - 1/2)(1 - xn) for xn between 1/2 and 1 representing the second curve. The parameter r which determines the height(s) of the letter m varies from 2 to 16, the latter value ensuring fully developed chaotic solutions for the whole letter m; r = 8 yielding full chaotic solutions only for its first curve. The m-model yields fixed points, bifurcation points and chaotic regions for each separate curve, as well as values of the parameter r greater than 8 which produce inter-fixed points, inter-bifurcation points and inter-chaotic regions from the interplay of the two curves. Based on this, music is composed from mapping the m- recurrence model solutions onto actual notes. The resulting musical score strongly depends on the sequence of notes chosen by the composer to define the musical range corresponding to the range of the chaotic mathematical solutions x from 0 to 1. Here, two musical ranges are used; one is the middle chromatic scale and the other is the seven- octaves range. At the composer's will and, for aesthetics, within the same composition, notes can be the outcome of different values of r and/or shifted in any octave. Compositions with endings of non-repeating note patterns result from values of r in the m-model that do not produce bifurcations. Scores of chaotic music composed from the m-model and the classical logistic model are presented.

  6. Substituent effect study on experimental ¹³C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene)diacetate derivatives.

    PubMed

    Kara, Yesim S

    2015-12-05

    Eleven novel (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene) diacetate derivatives were synthesized in the present study. These dihydroisoxazole derivatives were characterized by IR, (1)H NMR, (13)C NMR and elemental analyses. Their (13)C NMR spectra were measured in Deuterochloroform (CDCl3). The correlation analysis for the substituent-induced chemical shift (SCS) with Hammett substituent constant (σ), inductive substituent constant (σI), different of resonance substituent constants (σR, σR(o)) and Swain-Lupton substituent parameters (F, R) were performed using SSP (single substituent parameter), and DSP (dual substituent parameter) methods, as well as single and multiple regression analysis. From the result of regression analysis, the effect of substituent on the (13)C NMR chemical shifts was explained. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Influence of the Structure of Molecules of Derivatives of 1,2,4-Triazole and 1,2,4-Triazine on Chromatographic Retention Under Conditions of Reversed Phase HPLC

    NASA Astrophysics Data System (ADS)

    Karaseva, I. N.; Karasev, M. O.; Nechaeva, O. N.; Kurbatova, S. V.

    2018-07-01

    The dependence of the chromatographic retention of 1,2,4-triazine and 1,2,4-triazole derivatives from water-acetonitrile solutions over octadecyl silica on the structure of sorbate molecules is studied. The effect the physicochemical parameters and topology of heterocycle molecules have on the retention characteristics under RP HPLC conditions is analyzed.

  8. Reduced density gradient as a novel approach for estimating QSAR descriptors, and its application to 1, 4-dihydropyridine derivatives with potential antihypertensive effects.

    PubMed

    Jardínez, Christiaan; Vela, Alberto; Cruz-Borbolla, Julián; Alvarez-Mendez, Rodrigo J; Alvarado-Rodríguez, José G

    2016-12-01

    The relationship between the chemical structure and biological activity (log IC 50 ) of 40 derivatives of 1,4-dihydropyridines (DHPs) was studied using density functional theory (DFT) and multiple linear regression analysis methods. With the aim of improving the quantitative structure-activity relationship (QSAR) model, the reduced density gradient s( r) of the optimized equilibrium geometries was used as a descriptor to include weak non-covalent interactions. The QSAR model highlights the correlation between the log IC 50 with highest molecular orbital energy (E HOMO ), molecular volume (V), partition coefficient (log P), non-covalent interactions NCI(H4-G) and the dual descriptor [Δf(r)]. The model yielded values of R 2 =79.57 and Q 2 =69.67 that were validated with the next four internal analytical validations DK=0.076, DQ=-0.006, R P =0.056, and R N =0.000, and the external validation Q 2 boot =64.26. The QSAR model found can be used to estimate biological activity with high reliability in new compounds based on a DHP series. Graphical abstract The good correlation between the log IC 50 with the NCI (H4-G) estimated by the reduced density gradient approach of the DHP derivatives.

  9. A Computational Study of Chalcogen-containing H2 X…YF and (CH3 )2 X…YF (X=O, S, Se; Y=F, Cl, H) and Pnicogen-containing H3 X'…YF and (CH3 )3 X'…YF (X'=N, P, As) Complexes.

    PubMed

    McDowell, Sean A C; Buckingham, A David

    2018-04-20

    A computational study was undertaken for the model complexes H 2 X…YF and (CH 3 ) 2 X…YF (X=O, S, Se; Y=F, Cl, H), and H 3 X'…YF and (CH 3 ) 3 X'…YF (X'=N, P, As), at the MP2/6-311++G(d,p) level of theory. For H 2 X…YF and H 3 X'…YF, noncovalent interactions dominate the binding in order of increasing YF dipole moment, except for H 3 As…F 2 , and possibly H 3 As…ClF. However, for the methyl-substituted complexes (CH 3 ) 2 X…YF and (CH 3 ) 3 X'…YF the binding is especially strong for the complexes containing F 2 , implying significant chemical bonding between the interacting molecules. The relative stability of these complexes can be rationalized by the difference in the electronegativity of the X or X' and Y atoms. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Synthesis and pharmacological properties of new derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones.

    PubMed

    Sladowska, Helena; Sabiniarz, Aleksandra; Sapa, Jacek; Filipek, Barbara

    2009-01-01

    Synthesis of 2-(2-hydroxy-3-amino)propyl derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones (24-35) is described. The chlorides used in the above synthesis exist mainly in the cyclic forms (18, 20-23). Only chloride with benzhydryl substituent at the nitrogen atom of piperazine has the chain structure (19). Among the studied imides the most active analgesics in the "writhing" syndrome test proved to be compounds 30 and 31 (with LD50 > 2000 mg/kg) containing 4-benzylpiperidino group. Furthermore, all imides suppressed significantly spontaneous locomotor activity of mice.

  11. Origin and transport of CH4 in two maar lakes fed by mantle-derived volatiles (Mt. Vulture volcano, Italy)

    NASA Astrophysics Data System (ADS)

    Caracausi, Antonio; Cosenza, Paolo; Favara, Rocco; Foresta Martin, Luigi; Galli, Nunzio; Grassa, Fausto; Nuccio, Pasquale Mario; Paternoster, Michele; Riccobono, Giuseppe

    2014-05-01

    It has been assessed that lakes contribute 6 to 16% to global CH4 emission in atmosphere. Accumulation of CH4 in the water is strongly dependent on the input of gas and the dynamic of the lake's water. Lakes located on tectonically and volcanically active areas (e.g., Kivu, Nyos) generally contain relevant amount of mantle-derived volatiles. This generated an open debate on the origin of CO2 and CH4 in volcanic lakes because the complex bio-geological cycling of these two gases. This study is a part of larger investigation carried out on two maar lakes (LPM and LGM) formed about 140.000 years ago during the last eruption of Mt. Vulture (Italy). In spite of it generally is considered to be extinct, both lakes are characterized by an active inflow of mantle-derived fluids (Caracausi et al., 2013). Although the two lakes are only 150 m apart, their respective dynamics are different being LPM a meromictic lake, while LGM a monomictic one (Caracausi et al., 2013). The stagnant waters of LPM are enriched in CO2 and CH4 but the total gas pressure is below the hydrostatic pressure, so that the transfer of gas towards the surface doesn't occur via bubbles. Vertical profiles at LPM reveal a marked decrease of the dissolved CH4 content in the shallower layers due to aerated water. The amount of CH4 dissolved in LGM water column shows seasonal variations: in autumn it is comparable to that of LPM at the same depth; in winter CH4 is fully released into atmosphere through overturn of waters. C and H isotopes of CH4 clearly indicate in both lakes an active production both by acetoclastic methanogenesis and by CO2 reduction although with different proportions. Historical reports describe intense episodic releases of gases from both lakes occurred up to about 200 years ago. Caracausi et al. (2013) highlight that these events could be caused by a release of mantle-derived CO2 accumulated in the crust or directly linked to magma degassing. In the present study the knowledge gained

  12. The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives in human gastric cancer cells.

    PubMed

    Pawłowska, Natalia; Gornowicz, Agnieszka; Bielawska, Anna; Surażyński, Arkadiusz; Szymanowska, Anna; Czarnomysy, Robert; Bielawski, Krzysztof

    2018-03-17

    Objective The aim of the current study was to examine the anticancer activity and the detailed mechanism of novel diisoquinoline derivatives in human gastric cancer cells (AGS). Methods The viability of AGS cells was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cell cycle analysis and apoptosis assay were performed by standard flow cytometric method. Confocal microscopy bioimaging was used to demonstrate the expression of pivotal proteins engaged in apoptosis (caspase-8, caspase-3, p53) and cell signaling (AKT, ERK1/2). Results All compounds decreased the number of viable cells in a dose-dependent manner after 24 and 48 h of incubation, although compound 2 was a more cytotoxic agent, with IC 50 values of 21 ± 2 and 6 ± 2 μM, compared to 80 ± 2 and 45 ± 2 μM for etoposide. The cytotoxic and antiproliferative effects of novel compounds were associated with the induction of apoptosis. The highest percentage of early and late apoptotic cells was observed after 48 h of incubation with compound 2 (89.9%). The value was higher compared to compound 1 (20.4%) and etoposide (24.1%). The novel diisoquinoline derivatives decreased the expression of AKT and ERK1/2. Their mechanism was associated with p53-mediated apoptosis, accumulation of cells in the G2/M phase of cell cycle and inhibition of topoisomerase II. Conclusion These data strongly support compound 2 as a promising molecule for treatment of gastric cancer.

  13. Structure, spectroscopic analyses (FT-IR and NMR), vibrational study, chemical reactivity and molecular docking study on 3,3'-((4-(trifluoromethyl)phenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione), a promising anticancerous bis-lawsone derivative

    NASA Astrophysics Data System (ADS)

    Yadav, Krishna Kant; Kumar, Abhishek; Kumar, Amarendra; Misra, Neeraj; Brahmachari, Goutam

    2018-02-01

    Lawsone (2-hydroxy-1,4-naphthoquinone)has been evaluated to possess a wide range of biological and pharmacological activities. The interesting structural pattern of lawsone coupled with its so-called multifaceted pharmacological potential have made this scaffolds useful in certain chemical processes, particularly in synthesizing ligands for metal complexations, and also few of its derivatives have shown a number of biological activities. The equilibrium geometry of 3,3‧-((4-(trifluoromethyl)phenyl)methylene)bis(2-hydroxynaphthalene-1,4-dione) (1; TPMHD), a promising anticancerous lawsone derivative, has been determined and analyzed at DFT method employingB3LYP/6-311++G(d,p) level of theory. The reactivity descriptors such as Fukui functions and HOMO-LUMO gap are calculated and discussed. The infrared spectra of TPMHD(1) are calculated and compared with the experimentally observed ones. Moreover, 1H and 13C NMR spectra have been calculated by using the gauge independent atomic orbital method. The docking studies reveal that the TPMHD has strong binding affinity toward target protein 2SHP. Thus the compound has a possible use as a drug in cancer therapy. The study suggests further investigation on TPMHD for their in-depth biological and pharmaceutical importance.

  14. Abinitio powder x-ray diffraction and PIXEL energy calculations on thiophene derived 1,4 dihydropyridine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karthikeyan, N., E-mail: karthin10@gmail.com; Sivakumar, K.; Pachamuthu, M. P.

    We focus on the application of powder diffraction data to get abinitio crystal structure determination of thiophene derived 1,4 DHP prepared by cyclocondensation method using solid catalyst. Crystal structure of the compound has been solved by direct-space approach on Monte Carlo search in parallel tempering mode using FOX program. Initial atomic coordinates were derived using Gaussian 09W quantum chemistry software in semi-empirical approach and Rietveld refinement was carried out using GSAS program. The crystal structure of the compound is stabilized by one N-H…O and three C-H…O hydrogen bonds. PIXEL lattice energy calculation was carried out to understand the physical naturemore » of intermolecular interactions in the crystal packing, on which the total lattice energy is contributed into Columbic, polarization, dispersion, and repulsion energies.« less

  15. Spectroscopic and biological activities studies of bivalent transition metal complexes of Schiff bases derived from condensation of 1,4-phenylenediamine and benzopyrone derivatives.

    PubMed

    Sherif, Omaima E; Abdel-Kader, Nora S

    2014-01-03

    Many tools of analysis such as elemental analyses, infrared, ultraviolet-visible, electron spin resonance (ESR) and thermal analysis, as well as conductivity and magnetic susceptibility measurements were used to elucidate the structures of the newly prepared Co(II), Ni(II) and Cu(II) complexes with Schiff bases derived from the condensation of 1,4-phenylenediamine with 6-formyl-7-hydroxy-5-methoxy-2-methylbenzo-pyran-4-one (H2L) or 5,7-dihydroxy-6-formyl-2-methylbenzopyran-4-one (H4L). The data showed that all formed complexes are 1:1 or 2:2 (M:L) and non-electrolyte chelates. The Co(II) and Cu(II) complexes of the two Schiff bases were screened for antibacterial activities by the disk diffusion method. The antibacterial activity was screened using Escherichia coli and Staphylococcus capitis but the antifungal activity was examined by using Aspergillus flavus and Candida albicans. The Results showed that the tested complexes have antibacterial, except CuH4L, but not antifungal activities. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Distinct Anaerobic Bacterial Consumers of Cellobiose-Derived Carbon in Boreal Fens with Different CO2/CH4 Production Ratios

    PubMed Central

    Eiler, Alexander; Biasi, Christina; Tuittila, Eeva-Stiina; Yrjälä, Kim; Fritze, Hannu

    2016-01-01

    ABSTRACT Northern peatlands in general have high methane (CH4) emissions, but individual peatlands show considerable variation as CH4 sources. Particularly in nutrient-poor peatlands, CH4 production can be low and exceeded by carbon dioxide (CO2) production from unresolved anaerobic processes. To clarify the role anaerobic bacterial degraders play in this variation, we compared consumers of cellobiose-derived carbon in two fens differing in nutrient status and the ratio of CO2 to CH4 produced. After [13C]cellobiose amendment, the mesotrophic fen produced equal amounts of CH4 and CO2. The oligotrophic fen had lower CH4 production but produced 3 to 59 times more CO2 than CH4. RNA stable-isotope probing revealed that in the mesotrophic fen with higher CH4 production, cellobiose-derived carbon was mainly assimilated by various recognized fermenters of Firmicutes and by Proteobacteria. The oligotrophic peat with excess CO2 production revealed a wider variety of cellobiose-C consumers, including Firmicutes and Proteobacteria, but also more unconventional degraders, such as Telmatobacter-related Acidobacteria and subphylum 3 of Verrucomicrobia. Prominent and potentially fermentative Planctomycetes and Chloroflexi did not appear to process cellobiose-C. Our results show that anaerobic degradation resulting in different levels of CH4 production can involve distinct sets of bacterial degraders. By distinguishing cellobiose degraders from the total community, this study contributes to defining anaerobic bacteria that process cellulose-derived carbon in peat. Several of the identified degraders, particularly fermenters and potential Fe(III) or humic substance reducers in the oligotrophic peat, represent promising candidates for resolving the origin of excess CO2 production in peatlands. IMPORTANCE Peatlands are major sources of the greenhouse gas methane (CH4), yet in many peatlands, CO2 production from unresolved anaerobic processes exceeds CH4 production. Anaerobic

  17. Distinct Anaerobic Bacterial Consumers of Cellobiose-Derived Carbon in Boreal Fens with Different CO2/CH4 Production Ratios.

    PubMed

    Juottonen, Heli; Eiler, Alexander; Biasi, Christina; Tuittila, Eeva-Stiina; Yrjälä, Kim; Fritze, Hannu

    2017-02-15

    Northern peatlands in general have high methane (CH 4 ) emissions, but individual peatlands show considerable variation as CH 4 sources. Particularly in nutrient-poor peatlands, CH 4 production can be low and exceeded by carbon dioxide (CO 2 ) production from unresolved anaerobic processes. To clarify the role anaerobic bacterial degraders play in this variation, we compared consumers of cellobiose-derived carbon in two fens differing in nutrient status and the ratio of CO 2 to CH 4 produced. After [ 13 C]cellobiose amendment, the mesotrophic fen produced equal amounts of CH 4 and CO 2 The oligotrophic fen had lower CH 4 production but produced 3 to 59 times more CO 2 than CH 4 RNA stable-isotope probing revealed that in the mesotrophic fen with higher CH 4 production, cellobiose-derived carbon was mainly assimilated by various recognized fermenters of Firmicutes and by Proteobacteria The oligotrophic peat with excess CO 2 production revealed a wider variety of cellobiose-C consumers, including Firmicutes and Proteobacteria, but also more unconventional degraders, such as Telmatobacter-related Acidobacteria and subphylum 3 of Verrucomicrobia Prominent and potentially fermentative Planctomycetes and Chloroflexi did not appear to process cellobiose-C. Our results show that anaerobic degradation resulting in different levels of CH 4 production can involve distinct sets of bacterial degraders. By distinguishing cellobiose degraders from the total community, this study contributes to defining anaerobic bacteria that process cellulose-derived carbon in peat. Several of the identified degraders, particularly fermenters and potential Fe(III) or humic substance reducers in the oligotrophic peat, represent promising candidates for resolving the origin of excess CO 2 production in peatlands. Peatlands are major sources of the greenhouse gas methane (CH 4 ), yet in many peatlands, CO 2 production from unresolved anaerobic processes exceeds CH 4 production. Anaerobic

  18. Synthesis and Biological Evaluation of 3-Benzylidene-4-chromanone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors.

    PubMed

    Takao, Koichi; Yamashita, Marimo; Yashiro, Aruki; Sugita, Yoshiaki

    2016-01-01

    A series of 3-benzylidene-4-chromanone derivatives (3-20) were synthesized and the structure-activity relationships for antioxidant and α-glucosidase inhibitory activities were evaluated. Among synthesized compounds, compounds 5, 13, 18, which contain catechol moiety, showed the potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (5: EC50 13 µM; 13: EC50 14 µM; 18: EC50 13 µM). The compounds 12, 14, 18 showed higher α-glucosidase inhibitory activity (12: IC50 15 µM; 14: IC50 25 µM; 18: IC50 28 µM). The compound 18 showed both of potent DPPH radical scavenging and α-glucosidase inhibitory activities. These data suggest that 3-benzylidene-4-chromanone derivatives, such as compound 18, may serve as the lead compound for the development of novel α-glucosidase inhibitors with antioxidant activity.

  19. Synthesis and evaluation of a class of 1,4,7-triazacyclononane derivatives as iron depletion antitumor agents.

    PubMed

    Wang, Sheng; Gai, Yongkang; Zhang, Shasha; Ke, Lei; Ma, Xiang; Xiang, Guangya

    2018-01-15

    Iron depletion has been confirmed as an efficient strategy for cancer treatment. In the current study, a series of 1,4,7-triazacyclononane derivatives HE-NO2A, HP-NO2A and NE2P2A, as well as the bifunctional chelators p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA were synthesized and evaluated as iron-depleting agents for the potential anti-cancer therapy against human hepatocellular carcinoma. The cytotoxicity of these chelators was measured using hepatocellular cancer cells and compared with the clinically available iron depletion agent DFO and the universal metal chelator DTPA. All these 1,4,7-triazacyclononane-based chelators exhibited much stronger antiproliferative activity than DFO and DTPA. Among them, chelators with phenylpropyl side chains, represented by p-NO 2 -PhPr-NE3TA and p-NH 2 -PhPr-NE3TA, displayed the highest antiproliferative activity against HepG2 cells. Hence, these compounds are attractive candidates for the advanced study as iron depletion agents for the potential anti-cancer therapy, and could be further in conjugation with a targeting moiety for the future development in targeted iron depletion therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Luminescence emission from Al0.3Ga0.7N/GaN multi quantum disc core/shell nanowire: Numerical approach

    NASA Astrophysics Data System (ADS)

    Namvari, E.; Shojaei, S.; Asgari, A.

    2017-09-01

    In this work, a numerical approach to investigate the room temperature luminescence emission from core/shell nanowire is presented where GaN quantum discs (QDiscs), periodically distributed in AlxGa1-xN nanowire, is considered as core and AlxGa1-xN as shell. Thin disc shaped (Ring shaped) n-doped region has been placed at the GaN/ AlxGa1-xN (AlxGa1-xN /air) interface in AlxGa1-xN region in axial (radial) directions. To obtain energy levels and related wavefunctions, self-consistent procedure has been employed to solve Schrodinger-Poisson equations with considering the spontaneous and piezoelectric polarization. Then luminescence spectrum is studied in details to recognize the parameters influent in luminescence. The results show that the amount of doping, size of QDiscs and theirs numbers have remarkable effects on the band to band luminescence emission. Our numerical calculations gives some insights into the luminescence emission of core/shell nanowire and exhibits a useful tool to analyze findings in experiments.

  1. Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine.

    PubMed

    Piergentili, Alessandro; Gentili, Francesco; Ghelfi, Francesca; Marucci, Gabriella; Pigini, Maria; Quaglia, Wilma; Giannella, Mario

    2003-09-01

    A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the variation in distance and stereochemistry of the active functions allowed us to modulate the selectivity of interaction with the M(1)-M(3) receptor subtypes. The most interesting compound was (cis,trans)-2-(2,2-diphenylethyl)-5-methyl-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole oxalate (6), which is equipotent with Pirenzepine on rabbit vas deferens (M(1)-putative) but shows a better selectivity profile.

  2. One-pot synthesis of novel 1-(1H-tetrazol-5-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine derivatives via an Ugi-azide 4CR process.

    PubMed

    Ghandi, Mehdi; Salahi, Saleh; Taheri, Abuzar; Abbasi, Alireza

    2018-05-01

    A facile one-pot method has been developed for the synthesis of novel pyrrolo[2,1-a]pyrazine scaffolds. A variety of 1-(1H-tetrazol-5-yl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine derivatives were obtained in moderate to high yields in methanol using a one-pot four-component condensation of 1-(2-bromoethyl)-1H-pyrrole-2-carbaldehyde, amine, isocyanide and sodium azide at room temperature. These reactions presumably proceed via a domino imine formation, intramolecular annulation and Ugi-azide reaction. Unambiguous assignment of the molecular structures was carried out by single-crystal X-ray diffraction.

  3. Anti-Inflammatory Activity of Tanzawaic Acid Derivatives from a Marine-Derived Fungus Penicillium steckii 108YD142

    PubMed Central

    Shin, Hee Jae; Pil, Gam Bang; Heo, Soo-Jin; Lee, Hyi-Seung; Lee, Jong Seok; Lee, Yeon-Ju; Lee, Jihoon; Won, Ho Shik

    2016-01-01

    Chemical investigation of a marine-derived fungus, Penicillium steckii 108YD142, resulted in the discovery of a new tanzawaic acid derivative, tanzawaic acid Q (1), together with four known analogues, tanzawaic acids A (2), C (3), D (4), and K (5). The structures of tanzawaic acid derivatives 1–5 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis. These compounds significantly inhibited nitric oxide (NO) production and the new tanzawaic acid Q (1) inhibited the lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA expressions in RAW 264.7 macrophages. Additionally, compound 1 reduced the mRNA levels of inflammatory cytokines. Taken together, the results of this study demonstrated that the new tanzawaic acid derivative inhibits LPS-induced inflammation. This is the first report on the anti-inflammatory activity of tanzawaic acid Q (1). PMID:26761016

  4. Integrating across Episodes: Investigating the Long-term Accessibility of Self-derived Knowledge in 4-Year-Old Children

    PubMed Central

    Varga, Nicole L.; Stewart, Rebekah A.; Bauer, Patricia J.

    2016-01-01

    Semantic memory, defined as our store of knowledge about the world, provides representational support for all of our higher order cognitive functions. As such, it is crucial that the contents of semantic memory remain accessible over time. Although memory for knowledge learned through direct observation has been previously investigated, we know very little about the retention of knowledge derived through integration of information acquired across separate learning episodes. The present research investigated cross-episode integration in 4-year-old children. Participants were presented with novel facts via distinct story episodes and tested for knowledge extension through cross-episode integration, as well as for retention of the information over a 1-week delay. In Experiment 1, children retained the self-derived knowledge over the delay, though performance was primarily evidenced in a forced-choice format. In Experiment 2, we sought to facilitate the accessibility and robustness of self-derived knowledge by providing a verbal reminder after the delay. The accessibility of self-derived knowledge increased, irrespective of whether participants successfully demonstrated knowledge of the integration facts during the first visit. The results suggest knowledge extended through integration remains accessible after delays, even in a population in which this learning process is less robust. The findings also demonstrate the facilitative effect of reminders on the accessibility and further extension of knowledge over extended time periods. PMID:26774259

  5. Smad4 restricts differentiation to promote expansion of satellite cell derived progenitors during skeletal muscle regeneration

    PubMed Central

    Paris, Nicole D; Soroka, Andrew; Klose, Alanna; Liu, Wenxuan; Chakkalakal, Joe V

    2016-01-01

    Skeletal muscle regenerative potential declines with age, in part due to deficiencies in resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of myogenic differentiation, with elevated activity in aged skeletal muscle. Surprisingly, we find reduced expression of Smad4, the downstream cofactor for canonical TGFβ superfamily signaling, and the target Id1 in aged SCs and MPs during regeneration. Specific deletion of Smad4 in adult mouse SCs led to increased propensity for terminal myogenic commitment connected to impaired proliferative potential. Furthermore, SC-specific Smad4 disruption compromised adult skeletal muscle regeneration. Finally, loss of Smad4 in aged SCs did not promote aged skeletal muscle regeneration. Therefore, SC-specific reduction of Smad4 is a feature of aged regenerating skeletal muscle and Smad4 is a critical regulator of SC and MP amplification during skeletal muscle regeneration. DOI: http://dx.doi.org/10.7554/eLife.19484.001 PMID:27855784

  6. Synthesis and Preliminary Cytotoxicity Studies of 1-[1-(4,5-Dihydrooxazol- 2-yl)-1H-indazol-3-yl]-3-phenylurea and 3-phenylthiourea Derivatives.

    PubMed

    Kornicka, Anita; Saczewski, Franciszek; Bednarski, Patrick J; Korcz, Martyna; Szumlas, Piotr; Romejko, Ewa; Sakowicz, Aneta; Sitek, Lukasz; Wojciechowska, Monika

    2017-01-01

    N-substituted 3-amino-1H-indazoles represent an interesting class of biologically active compounds. Among them, derivatives containing phenylurea moiety are of particular interest. Such compounds have been found to possess inhibitory activity against cancer cell growth. Additionally, various oxazoline-containing compounds have also been designed as potential anticancer agents. The aim of this work was to obtain a new class of N-substituted 3-amino-1H-indazole derivatives with cytotoxic activity towards cancer cells. Two series of 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylurea and 3- phenylthiourea derivatives 7-17 and 18-22, respectively, were prepared and screened for their potential in vitro cytotoxic activities against lung carcinoma LCLC-103H cell line using a crystal violet microtiter plate assay. All the urea derivatives, except the compound 8, were inactive at a concentration of 20 μM attainable in cancer cells, while the thiourea derivatives showed a pronounced cancer cell growth inhibitory effects. The most potent 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-ptolylthiourea (19) exhibited cytotoxicity on the lung cancer LCLC-103H and cervical cancer SISO cell lines at a concentration of 10 µM. Moreover, compound 19 displayed cytostatic activity against pancreas cancer DAN-G cell line. The 1-[1-(4,5-dihydrooxazol-2-yl)-1H-indazol-3-yl]-3-phenylthiourea derivatives described herein may serve as a useful scaffold for the search for novel anticancer agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Electrophilic fluorination of pyroglutamic acid derivatives: application of substrate-dependent reactivity and diastereoselectivity to the synthesis of optically active 4-fluoroglutamic acids.

    PubMed

    Konas, D W; Coward, J K

    2001-12-28

    Electrophilic fluorination of enantiomerically pure 2-pyrrolidinones (4) derived from (L)-glutamic acid has been investigated as a method for the synthesis of single stereoisomers of 4-fluorinated glutamic acids. Reaction of the lactam enolate derived from 9 with NFSi results in a completely diastereoselective monofluorination reaction to yield the monocyclic trans-substituted alpha-fluoro lactam product 21. Unfortunately, a decreased kinetic acidity in 21 and other structurally related monofluorinated products renders them resistant to a second fluorination. In contrast, the bicyclic lactam 12 is readily difluorinated under the standard conditions described to yield the alpha,alpha-difluoro lactam 24. The difference in reactivity between the two types of related lactams is attributed mainly to the presence or lack of a steric interaction between the base used for deprotonation and the protecting group present in the pyrrolidinone substrates. This conclusion was reached based on analysis of the X-ray crystal structure of 21, molecular modeling, and experimental evidence. The key intermediates 21 and 24 are converted to (2S,4R)-4-fluoroglutamic acid and (2S)-4,4-difluoroglutamic acid, respectively.

  8. Ferrocene Derived Bifunctional Phosphine-Catalyzed Asymmetric Oxa-[4+2] Cycloaddition of α-Substituted Allenones with Enones.

    PubMed

    Wang, Huamin; Lu, Weike; Zhang, Junliang

    2017-10-04

    An efficient ferrocene-derived bifunctional phosphine-catalyzed enantioselective oxa-[4+2] cycloaddition of α-substituted allenones with a broad range of enones is investigated for the preparation of stereodefined dihydropyrans in good to excellent yields (up to 99 %) and excellent enantioselectivity (up to 99 % ee). Furthermore, a series of valuable chiral polyheterocyclic frameworks can be efficiently achieved in good yields with excellent enantioselectivities. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives.

    PubMed

    Sorra, Kumaraswamy; Chang, Chi-Fen; Pusuluri, Srinivas; Mukkanti, Khagga; Laiu, Min-Chiau; Bao, Bo-Ying; Su, Chia-Hao; Chuang, Ta-Hsien

    2012-07-25

    A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.

  10. Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors.

    PubMed

    Chioua, Mourad; Samadi, Abdelouahid; Soriano, Elena; Lozach, Olivier; Meijer, Laurent; Marco-Contelles, José

    2009-08-15

    The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC(50) (microM) DYRK1A=11; CDK5=0.41; GSK-3=1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.

  11. Bonding in d9 complexes derived from EPR: Application to CuCl2-4, CuBr2-4, and CdCl2:Cu2+

    NASA Astrophysics Data System (ADS)

    Aramburu, J. A.; Moreno, M.

    1985-12-01

    In this work are reported the theoretical expressions for the [g], hyperfine, and superhyperfine (shf) tensors of a d9 square-planar complex within a molecular orbital (MO) scheme. These expressions include contributions arising from crystal field and charge transfer excitations calculated up to third and second order perturbations, respectively. This makes the present framework more general than those previously used. Through those expressions we have derived from the experimental EPR and optical data the MO coefficients corresponding to the valence b1g(x2-y2), b2g(xy), and eg(xz,yz) levels and also the core polarization contribution K to the hyperfine tensor for the systems CuCl2-4, CuBr2-4, and CdCl2:Cu2+. The 3d charge obtained for CuCl2-4 is equal to 0.61, 0.83, and 0.85 for the antibonding 3b1g, 2b2g, and 2eg levels, respectively. These figures are much closer to the Xα results by Bencini and Gatteschi [J. Am. Chem. Soc. 105, 5535 (1983)] than to those by Desjardins et al. [J. Am. Chem. Soc. 105, 4590 (1983)]. The σ and π covalency for CuBr2-4 are both higher than for CuCl2-4 in accord to the lower electronegativity for bromine. However, only for the antibonding 3b1g level of CuBr2-4 have we obtained an electronic charge lying mainly on ligands. The covalency of CdCl2:Cu2+ is smaller than that found for CuCl2-4, a fact associated to a higher metal-ligand distance for the former. Evidence of this statement are also given from the analysis of crystal-field spectra and isotropic shf constant. The values of K derived for CuCl2-4 (128.1×10-4 cm-1), CuBr2-4 (103.6×10-4 cm-1), and CdCl2:Cu2+ (123.9×10-4 cm-1) point out the dependence of K on the equatorial covalency but also on the existence of axial ligands. The [g] tensor of CuBr2-4 is dominated by the charge transfer contribution while the crystal field one is negative. Finally an analysis of the importance of each one of the involved contributions to the spin-Hamiltonian parameters is reported for the

  12. Gata4-Dependent Differentiation of c-Kit+ Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration in the Heart.

    PubMed

    Maliken, Bryan D; Kanisicak, Onur; Karch, Jason; Khalil, Hadi; Fu, Xing; Boyer, Justin G; Prasad, Vikram; Zheng, Yi; Molkentin, Jeffery D

    2018-04-17

    Background -While c-Kit + adult progenitor cells were initially reported to produce new cardiomyocytes in the heart, recent genetic evidence suggests that such events are exceedingly rare. However, to determine if these rare events represent true de novo cardiomyocyte formation we deleted the necessary cardiogenic transcription factors Gata4 and Gata6 from c-Kit-expressing cardiac progenitor cells (CPCs). Methods - Kit allele-dependent lineage tracing and fusion analysis was performed in mice following simultaneous Gata4 and Gata6 cell-type specific deletion to examine rates of putative de novo cardiomyocyte formation from c-Kit + cells. Bone marrow transplantation experiments were used to define the contribution of Kit allele-derived hematopoietic cells versus Kit lineage-dependent cells endogenous to the heart in contributing to apparent de novo lineage-traced cardiomyocytes. A Tie2 CreERT2 transgene was also used to examine the global impact of Gata4 deletion on the mature cardiac endothelial cell network, which was further evaluated with select angiogenesis assays. Results -Deletion of Gata4 in Kit lineage-derived endothelial cells or in total endothelial cells using the Tie2 CreERT2 transgene, but not from bone morrow cells, resulted in profound endothelial cell expansion, defective endothelial cell differentiation, leukocyte infiltration into the heart and a dramatic increase in Kit allele-dependent lineage-traced cardiomyocytes. However, this increase in labeled cardiomyocytes was an artefact of greater leukocyte-cardiomyocyte cellular fusion due to defective endothelial cell differentiation in the absence of Gata4 Conclusions -Past identification of presumed de novo cardiomyocyte formation in the heart from c-Kit + cells using Kit allele lineage tracing appears to be an artefact of labeled leukocyte fusion with cardiomyocytes. Deletion of Gata4 from c-Kit + endothelial progenitor cells or adult endothelial cells negatively impacted angiogenesis and

  13. Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

    PubMed

    Metcalfe, Hannah J; Biffar, Lucia; Steinbach, Sabine; Guzman, Efrain; Connelley, Tim; Morrison, Ivan; Vordermeier, H Martin; Villarreal-Ramos, Bernardo

    2018-05-11

    There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 + T cells post-boosting. Here, the capacity of Ag85A-specific CD4 + T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 + T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 + T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology. Copyright © 2018 Department for Environment Food and Rural Affairs. Published by Elsevier Ltd.. All rights reserved.

  14. Solvation Effect on Complexation of Alkali Metal Cations by a Calix[4]arene Ketone Derivative.

    PubMed

    Požar, Josip; Nikšić-Franjić, Ivana; Cvetnić, Marija; Leko, Katarina; Cindro, Nikola; Pičuljan, Katarina; Borilović, Ivana; Frkanec, Leo; Tomišić, Vladislav

    2017-09-14

    The medium effect on the complexation of alkali metal cations with a calix[4]arene ketone derivative (L) was systematically examined in methanol, ethanol, N-methylformamide, N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile. In all solvents the binding of Na + cation by L was rather efficient, whereas the complexation of other alkali metal cations was observed only in methanol and acetonitrile. Complexation reactions were enthalpically controlled, while ligand dissolution was endothermic in all cases. A notable influence of the solvent on NaL + complex stability could be mainly attributed to the differences in complexation entropies. The higher NaL + stability in comparison to complexes with other alkali metal cations in acetonitrile was predominantly due to a more favorable complexation enthalpy. The 1 H NMR investigations revealed a relatively low affinity of the calixarene sodium complex for inclusion of the solvent molecule in the calixarene hydrophobic cavity, with the exception of acetonitrile. Differences in complex stabilities in the explored solvents, apart from N,N-dimethylformamide and acetonitrile, could be mostly explained by taking into account solely the cation and complex solvation. A considerable solvent effect on the complexation equilibria was proven to be due to an interesting interplay between the transfer enthalpies and entropies of the reactants and the complexes formed.

  15. WE-AB-303-05: Breathing Motion of Liver Segments From Fiducial Tracking During Robotic Radiosurgery and Comparison with 4D-CT-Derived Fiducial Motion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sutherland, J; Pantarotto, J; Nair, V

    Purpose: To quantify respiratory-induced motion of liver segments using the positions of implanted fiducials during robotic radiosurgery. This study also compared fiducial motion derived from four-dimensional computed tomography (4D-CT) maximum intensity projections (MIP) with motion derived from imaging during treatment. Methods: Forty-two consecutive liver patients treated with liver ablative radiotherapy were accrued to an ethics approved retrospective study. The liver segment in which each fiducial resided was identified. Fiducial positions throughout each treatment fraction were determined using orthogonal kilovoltage images. Any data due to patient repositioning or motion was removed. Mean fiducial positions were calculated. Fiducial positions beyond two standardmore » deviations of the mean were discarded and remaining positions were fit to a line segment using least squares minimization (LSM). For eight patients, fiducial motion was derived from 4D-CT MIPs by calculating the CT number weighted mean position of the fiducial on each slice and fitting a line segment to these points using LSM. Treatment derived fiducial trajectories were corrected for patient rotation and compared to MIP derived trajectories. Results: The mean total magnitude of fiducial motion across all liver segments in left-right, anteroposterior, and superoinferior (SI) directions were 3.0 ± 0.2 mm, 9.3 ± 0.4 mm, and 20.5 ± 0.5 mm, respectively. Differences in per-segment mean fiducial motion were found with SI motion ranging from 12.6 ± 0.8 mm to 22.6 ± 0.9 mm for segments 3 and 8, respectively. Large, varied differences between treatment and MIP derived motion at simulation were found with the mean difference for SI motion being 2.6 mm (10.8 mm standard deviation). Conclusion: The magnitude of liver fiducial motion was found to differ by liver segment. MIP derived liver fiducial motion differed from motion observed during treatment, implying that 4D-CTs may not accurately capture

  16. Aqueous phase synthesis, crystal structure and biological study of isoxazole extensions of pyrazole-4-carbaldehyde derivatives

    NASA Astrophysics Data System (ADS)

    Wazalwar, Sachin S.; Banpurkar, Anita R.; Perdih, Franc

    2017-12-01

    A series of novel isoxazol derivatives was synthesized by green route in aqueous phase at room temperature by the reaction of 3-methyl-4H-isoxazol-5-one with 3-(substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde by one-pot Knoevenagel condensation method using sodium benzoate as a catalyst. Compounds were characterized on the basis of IR, 1H NMR, mass spectroscopy and melting point determination. Crystal structures of five compounds were determined by X-ray diffraction. The compounds formed were screened for antibacterial and antifungal activity. Some compounds showed activity close to ampicillin against E. coli, S. aureus, and S. pyogenus. Two compounds showed antifungal activity against C. albicans close to standard greseofulvin.

  17. Influence of garlic, synthetic 1,2,4-triasole derivative and herbal preparation echinovit C on selected indices of turkey-hens non-specific immunity.

    PubMed

    Truchliński, J; Krauze, M; Cendrowska-Pinkosz, M; Modzelewska-Banachiewicz, B

    2006-01-01

    Successful results of earlier studies on testing the immune-modulating and anti-microbial properties of 1,2,4-triasole derivative as well as benefitial application of natural bio-stimulators in animal's prophylaxis and treatment inspired us to undertake further investigations. The aim of the present study was to evaluate and compare the prophylaxis effects of two natural immune-modulating agents, garlic (Allium sativum) extract and Echinovit C preparation and synthetic derivative of 1,2,4-triasole on non-specific immunity indices in slaughter turkey-hens. The results obtained suggest that the strongest stimulatory effect is exerted by garlic followed by 1,2,4-triasole derivative and Echinacea juice. Immune-modulating action of the substances applied was manifested by an increase in cellular immune parameters: the percentage of phagocyting cells, NBT-positive granulocytes and lysozyme level.

  18. A facile synthesis, antibacterial activity of pulvinone and its derivatives.

    PubMed

    Xu, Hai-Wei; Xu, Chao; Fan, Zi-qi; Zhao, Ling-Jie; Liu, Hong-Min

    2013-02-01

    Pulvinone and several 3-fluoro-4-morpholino substituted pulvinone derivatives were synthesized in five steps from a common precursor, phenyl acetic acid. Most of synthetic morpholine substituted pulvinones showed inhibitory activity against Esherichia coli. For the first time, the inhibition of pulvinone and its derivatives against Gram-negative bacteria was reported. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Metal-Organic Frameworks Derived Porous Core/Shell Structured ZnO/ZnCo2O4/C Hybrids as Anodes for High-Performance Lithium-Ion Battery.

    PubMed

    Ge, Xiaoli; Li, Zhaoqiang; Wang, Chengxiang; Yin, Longwei

    2015-12-09

    Metal-organic frameworks (MOFs) derived porous core/shell ZnO/ZnCo2O4/C hybrids with ZnO as a core and ZnCo2O4 as a shell are for the first time fabricated by using core/shell ZnCo-MOF precursors as reactant templates. The unique MOFs-derived core/shell structured ZnO/ZnCo2O4/C hybrids are assembled from nanoparticles of ZnO and ZnCo2O4, with homogeneous carbon layers coated on the surface of the ZnCo2O4 shell. When acting as anode materials for lithium-ion batteries (LIBs), the MOFs-derived porous ZnO/ZnCo2O4/C anodes exhibit outstanding cycling stability, high Coulombic efficiency, and remarkable rate capability. The excellent electrochemical performance of the ZnO/ZnCo2O4/C LIB anodes can be attributed to the synergistic effect of the porous structure of the MOFs-derived core/shell ZnO/ZnCo2O4/C and homogeneous carbon layer coating on the surface of the ZnCo2O4 shells. The hierarchically porous core/shell structure offers abundant active sites, enhances the electrode/electrolyte contact area, provides abundant channels for electrolyte penetration, and also alleviates the structure decomposition induced by Li(+) insertion/extraction. The carbon layers effectively improve the conductivity of the hybrids and thus enhance the electron transfer rate, efficiently prevent ZnCo2O4 from aggregation and disintegration, and partially buffer the stress induced by the volume change during cycles. This strategy may shed light on designing new MOF-based hybrid electrodes for energy storage and conversion devices.

  20. Regularities of the sorption of 1,2,3,4-tetrahydroquinoline derivatives under conditions of reversed phase HPLC

    NASA Astrophysics Data System (ADS)

    Nekrasova, N. A.; Kurbatova, S. V.; Zemtsova, M. N.

    2016-12-01

    Regularities of the sorption of 1,2,3,4-tetrahydroquinoline derivatives on octadecylsilyl silica gel and porous graphitic carbon from aqueous acetonitrile solutions were investigated. The effect the molecular structure and physicochemical parameters of the sorbates have on their retention characteristics under conditions of reversed phase HPLC are analyzed.

  1. Isomeric yield ratios of 87m,gY from different nuclear reactions

    NASA Astrophysics Data System (ADS)

    Naik, H.; Kim, G. N.; Kim, K.; Zaman, M.; Sahid, M.; Yang, S.-C.; Lee, M. W.; Kang, Y. R.; Shin, S. G.; Cho, M.-H.; Goswami, A.; Song, T. Y.

    2014-07-01

    The independent isomeric yield ratios of 87m,gY produced from the 93Nb( γ, α2n) and natZr( γ, p xn) reactions with the end-point bremsstrahlung energy of 45-70 MeV have been determined by an off-line γ-ray spectrometric technique using 100 MeV electron linac at the Pohang accelerator laboratory, Korea. The isomeric yield ratios of 87m,gY were also determined from the natZr(p, αxn) and the 89Y(p,p2n) reactions with E P = 15-45 MeV as well as those from the 89Y( α, α2n) reaction with E α = 32-43 MeV using the MC-50 cyclotron at the Korea Institute of Radiological and Medical Science, Korea. The isomeric yield ratios of 87m,gY from the present work in the 93Nb( γ, α2n), natZr( γ, p xn), natZr(p, αxn), 89Y(p,p2n), and 89Y( α, α2n) reactions were compared with those of the literature data in the 85Rb( α, 2n), the 86,87,88Sr(d, xn), 89Y(n,3n), and the 89Y( γ, 2n) reactions to examine the role of target, projectiles, and ejectiles through compound nucleus excitation energy and input angular momentum. The isomeric yield ratios of 87m,gY in the above eleven reactions were also calculated using the computer code TALYS 1.4 and compared with the experimental data. The different behaviors between photon- and neutron-induced reactions and charged-particle-induced reactions are discussed from the viewpoint of compound and non-compound (pre-equilibrium) process.

  2. Large magnetic anisotropy predicted for rare-earth-free F e 16 - x C o x N 2 alloys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Xin; Wang, Cai -Zhuang; Yao, Yongxin

    Structures and magnetic properties of Fe 16–xCo xN 2 are studied using adaptive genetic algorithm and first-principles calculations. We show that substituting Fe with Co in Fe 16N 2 with a Co/Fe ratio ≤1 can greatly improve the magnetic anisotropy of the material. The magnetocrystalline anisotropy energy from first-principles calculations reaches 3.18 MJ/m 3 (245.6 μeV per metal atom) for Fe 12Co 4N 2, much larger than that of Fe 16N 2, and is one of the largest among the reported rare-earth-free magnets. From our systematic crystal structure searches, we show that there is a structure transition from tetragonal Femore » 16N 2 to cubic Co 16N 2 in Fe 16–xCo xN 2 as the Co concentration increases, which can be well explained by electron counting analysis. As a result, different magnetic properties between the Fe-rich (x ≤ 8) and Co-rich (x > 8) Fe 16–xCo xN 2 is closely related to the structural transition.« less

  3. Large magnetic anisotropy predicted for rare-earth-free F e 16 - x C o x N 2 alloys

    DOE PAGES

    Zhao, Xin; Wang, Cai -Zhuang; Yao, Yongxin; ...

    2016-12-23

    Structures and magnetic properties of Fe 16–xCo xN 2 are studied using adaptive genetic algorithm and first-principles calculations. We show that substituting Fe with Co in Fe 16N 2 with a Co/Fe ratio ≤1 can greatly improve the magnetic anisotropy of the material. The magnetocrystalline anisotropy energy from first-principles calculations reaches 3.18 MJ/m 3 (245.6 μeV per metal atom) for Fe 12Co 4N 2, much larger than that of Fe 16N 2, and is one of the largest among the reported rare-earth-free magnets. From our systematic crystal structure searches, we show that there is a structure transition from tetragonal Femore » 16N 2 to cubic Co 16N 2 in Fe 16–xCo xN 2 as the Co concentration increases, which can be well explained by electron counting analysis. As a result, different magnetic properties between the Fe-rich (x ≤ 8) and Co-rich (x > 8) Fe 16–xCo xN 2 is closely related to the structural transition.« less

  4. Synthesis and Antioxidant Activity of 2-Amino-5-methylthiazol Derivatives Containing 1,3,4-Oxadiazole-2-thiol Moiety.

    PubMed

    Mohana, Kikkeri N; Kumar, Chikkur B Pradeep

    2013-01-01

    A series of new 5-(2-amino-5-methylthiazol-4-yl)-1,3,4-oxadiazole-2-thiol derivatives 6(a-j) were designed and synthesized with various substituted aldehydes. The chemical structures were confirmed by elemental analyses, FT-IR, (1)H NMR, and mass spectral studies. The antioxidant activity of the synthesized compounds was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, nitric oxide, and superoxide radical scavenging assay methods. Compounds 6a, 6e, and 6c showed significant radical scavenging potential due to the presence of electron donating substituent on substituted aldehydes.

  5. Cord blood derived CD4+ CD25(high) T cells become functional regulatory T cells upon antigen encounter.

    PubMed

    Mayer, Elisabeth; Bannert, Christina; Gruber, Saskia; Klunker, Sven; Spittler, Andreas; Akdis, Cezmi A; Szépfalusi, Zsolt; Eiwegger, Thomas

    2012-01-01

    Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these "excessive" responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself. Cord blood (>37 week of gestation) and peripheral blood (healthy controls) were obtained and different Treg cell subsets were isolated. The suppressive potential of Treg populations after antigen exposure was evaluated via functional inhibition assays ([(3)H]thymidine incorporation assay and CFSE staining) with or without allergen stimulation. The frequency and markers of CD4(+)CD25(high)FoxP3(+) T cells were characterized by mRNA analysis and flow cytometry. Cord blood derived CD4(+)CD25(high) cells did not show substantial suppressor capacity upon TCR activation, in contrast to CD4(+)CD25(high) cells freshly purified from adult blood. This could not be explained by a lower frequency of FoxP3(+)CD4(+)CD25(high)cells or FOXP3 mRNA expression. However, after antigen-specific stimulation in vitro, these cells showed strong proliferation and expansion and gained potent suppressive properties. The efficiency of their suppressive capacity can be enhanced in the presence of endotoxins. If T-cells were sorted according to their CD127 expression, a tiny subset of Treg cells (CD4(+)CD25(+)CD127(low)) is highly suppressive even without prior antigen exposure. Cord blood harbors a very small subset of CD4(+)CD25(high) Treg cells that requires antigen-stimulation to show expansion and become functional suppressive Tregs.

  6. Sorption of 4-carboxyquinoline derivatives from aqueous acetonitrile solutions on the surface of porous graphitized carbon

    NASA Astrophysics Data System (ADS)

    Savchenkova, A. S.; Buryak, A. K.; Kurbatova, S. V.

    2015-09-01

    The sorption of 4-carboxyquinoline derivatives from aqueous acetonitrile solutions on porous graphitized carbon was studied. The effect of the structure of analyte molecules and the eluent composition on the characteristics of retention under the conditions of RP HPLC was analyzed. The effect of pH of the eluent on the shift of equilibrium in aqueous acetonitrile solutions was investigated.

  7. Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway.

    PubMed

    Wang, Bohan; Ning, Hongxiu; Reed-Maldonado, Amanda B; Zhou, Jun; Ruan, Yajun; Zhou, Tie; Wang, Hsun Shuan; Oh, Byung Seok; Banie, Lia; Lin, Guiting; Lue, Tom F

    2017-02-16

    Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157-an inhibitor of PERK-effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

  8. Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway

    PubMed Central

    Wang, Bohan; Ning, Hongxiu; Reed-Maldonado, Amanda B.; Zhou, Jun; Ruan, Yajun; Zhou, Tie; Wang, Hsun Shuan; Oh, Byung Seok; Banie, Lia; Lin, Guiting; Lue, Tom F.

    2017-01-01

    Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy. PMID:28212323

  9. O-Succinyl-L-homoserine-based C4-chemical production: succinic acid, homoserine lactone, γ-butyrolactone, γ-butyrolactone derivatives, and 1,4-butanediol.

    PubMed

    Hong, Kuk-Ki; Kim, Jeong Hyun; Yoon, Jong Hyun; Park, Hye-Min; Choi, Su Jin; Song, Gyu Hyeon; Lee, Jea Chun; Yang, Young-Lyeol; Shin, Hyun Kwan; Kim, Ju Nam; Cho, Kyung Ho; Lee, Jung Ho

    2014-10-01

    There has been a significant global interest to produce bulk chemicals from renewable resources using engineered microorganisms. Large research programs have been launched by academia and industry towards this goal. Particularly, C4 chemicals such as succinic acid (SA) and 1,4-butanediol have been leading the path towards the commercialization of biobased technology with the effort of replacing chemical production. Here we present O-Succinyl-L-homoserine (SH) as a new, potentially important platform biochemical and demonstrate its central role as an intermediate in the production of SA, homoserine lactone (HSL), γ-butyrolactone (GBL) and its derivatives, and 1,4-butanediol (BDO). This technology encompasses (1) the genetic manipulation of Escherichia coli to produce SH with high productivity, (2) hydrolysis into SA and homoserine (HS) or homoserine lactone hydrochloride, and (3) chemical conversion of either HS or homoserine lactone HCL (HSL·HCl) into drop-in chemicals in polymer industry. This production strategy with environmental benefits is discussed in the perspective of targeting of fermented product and a process direction compared to petroleum-based chemical conversion, which may reduce the overall manufacturing cost.

  10. The role of prenatal nutrition assistance on the prevalence of night blindness in pregnant adults.

    PubMed

    Ribeiro Neves, Paulo Augusto; Ramalho, Andrea; De Carvalho Padilha, Patricia; Saunders, Cláudia

    2014-05-01

    In developing countries, night blindness is a very common public health problem among pregnant women. Evaluate the effect of the changes occurred on prenatal care concerning prenatal nutritional care on the occurrence of night blindness (XN) in adult pregnant women in public maternity hospital in Rio de Janeiro between 1999-2001 and between 2007-2008. Two cross-sectional studies were conducted, been the first one conducted between 1999-2001 and the second one between 2007-2008. Were studied 402 puerperal women, 225 between 1999-2001 (GI) and 177 between 2007-2008 (GII). The gestational XN was investigated during the immediate puerperium (GI) and during the prenatal/puerperium (GII), diagnosed by the World Health Organization. The study collected sociodemographic, clinical, obstetric, anthropometric and prenatal care information. It verified significant reduce of prevalence of gestational XN (GI = 18.7% e GII = 0.6%, p < 0.001). The occurrence of gestational XN was associated to sanitary conditions, education level, more than six prenatal consultations, miscarriage at last pregnancy, higher average number of deliveries, average number of prenatal care consultations and prenatal nutritional (p < 0.05). There was no association between gestational XN and marital status, skin color, pre-gestational nutritional status, adequacy of gain of total gestational weight, gestational anaemia and average number of pregnancies (p > 0.05). The inclusion of nutritional care in routine prenatal care may have contributed to the reduction of gestational XN. Studies to assess the nutritional intervention in the prevention and treatment of gestational XN at regions at greatest risk are suggested. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  11. Synthesis, Biological Activity, and Docking Study of Novel Isatin Coupled Thiazolidin-4-one Derivatives as Anticonvulsants.

    PubMed

    Nikalje, Anna P; Ansari, Altamash; Bari, Sanjay; Ugale, Vinod

    2015-06-01

    A series of 2-(substituted-phenyl)-3-(2-oxoindolin-3-ylidene)amino)-thiazolidin-4-one derivatives were designed and synthesized under microwave irradiation, using an eco-friendly, efficient, microwave-assisted synthetic protocol that involves cyclocondensation of 3-substituted benzylidine-hydrazono-indolin-2-one 3a-j with thioglycolic acid in dimethyl formamide (DMF) as solvent and anhydrous zinc chloride as a catalyst, keeping in view the structural requirement of the pharmacophore. The intermediate compounds 3a-j were obtained by condensation of the hydrazone of indoline-2,3-dione with aromatic aldehydes. The synthesized derivatives were evaluated for CNS depressant activity and anticonvulsant activity in mice using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) induced seizure tests. All the derivatives showed good CNS depressant activity and showed protection in the MES test, indicative of their ability to inhibit the seizure spread. A histopathological study was performed to evaluate liver toxicity caused by the synthesized compounds. The compounds were nontoxic. A computational study was performed, in which log P values were calculated experimentally. Virtual screening was performed by molecular docking of the designed compounds into the ATP binding sites of the NMDA and AMPA receptors, to predict if these compounds have analogous binding modes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. New Metabolites and Bioactive Chlorinated Benzophenone Derivatives Produced by a Marine-Derived Fungus Pestalotiopsis heterocornis.

    PubMed

    Lei, Hui; Lin, Xiuping; Han, Li; Ma, Jian; Ma, Qingjuan; Zhong, Jialiang; Liu, Yonghong; Sun, Tiemin; Wang, Jinhui; Huang, Xueshi

    2017-03-13

    Four new compounds, including two isocoumarins, pestaloisocoumarins A and B ( 1 , 2 ), one sesquiterpenoid degradation, isopolisin B ( 4 ), and one furan derivative, pestalotiol A ( 5 ), together with one known isocoumarin, gamahorin ( 3 ), and three chlorinated benzophenone derivatives, pestalachloride B ( 6 ), pestalachloride E ( 7 ) and a mixture of pestalalactone atropisomers ( 8a/8b ), were isolated from a culture of the fungus Pestalotiopsis heterocornis associated with sponge Phakellia fusca . These new chemical structures were established using NMR and MS spectroscopic data, as well as single-crystal X-ray crystallographic analysis and CD Cotton effects. All of the isolated compounds were evaluated for their antimicrobial and cytotoxic activities. Isocoumarins 1 - 3 , showed antibacterial activities against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 25 to 100 μg/mL and weak antifungal activities. Chlorinated benzophenone derivatives 6 - 8 exhibited antibacterial activities against S. aureus and B. subtilis with MIC values ranging from 3.0 to 50 μg/mL and cytotoxicities against four human cancer cell lines with IC 50 values of 6.8-87.8 μM.

  13. Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

    PubMed Central

    Nguyen Van, Tai; Hospital, Audrey; Lionne, Corinne; Jordheim, Lars P; Dumontet, Charles; Périgaud, Christian; Chaloin, Laurent

    2016-01-01

    Summary A series of seventeen β-hydroxyphosphonate ribonucleoside analogues containing 4-substituted-1,2,3-triazoles was synthesized and fully characterized. Such compounds were designed as potential inhibitors of the cytosolic 5’-nucleotidase II (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM. PMID:27559400

  14. Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl4-Induced Liver Injury through Antioxidant Effect.

    PubMed

    Jiang, Wenqian; Tan, Youwen; Cai, Mengjie; Zhao, Ting; Mao, Fei; Zhang, Xu; Xu, Wenrong; Yan, Zhixin; Qian, Hui; Yan, Yongmin

    2018-01-01

    Mesenchymal stem cells (MSCs) have been increasingly applied into clinical therapy. Exosomes are small (30-100 nm in diameter) membrane vesicles released by different cell types and possess the similar functions with their derived cells. Human umbilical cord MSC-derived exosomes (hucMSC-Ex) play important roles in liver repair. However, the effects and mechanisms of hucMSC-Ex on liver injury development remain elusive. Mouse models of acute and chronic liver injury and liver tumor were induced by carbon tetrachloride (CCl 4 ) injection, followed by administration of hucMSC-Ex via the tail vein. Alleviation of liver injury by hucMSC-Ex was determined. We further explored the production of oxidative stress and apoptosis in the development of liver injury and compared the antioxidant effects of hucMSC-Ex with frequently used hepatic protectant, bifendate (DDB) in liver injury. hucMSC-Ex alleviated CCl 4 -induced acute liver injury and liver fibrosis and restrained the growth of liver tumors. Decreased oxidative stress and apoptosis were found in hucMSC-Ex-treated mouse models and liver cells. Compared to bifendate (DDB) treatment, hucMSC-Ex presented more distinct antioxidant and hepatoprotective effects. hucMSC-Ex may suppress CCl 4 -induced liver injury development via antioxidant potentials and could be a more effective antioxidant than DDB in CCl 4 -induced liver tumor development.

  15. RECEPTOR AFFINITY AND PHOSPHODIESTERASES 4B AND 10A ACTIVITY OF OCTAHYDRO- AND 6,7-DIMETHOXY-3,4-DIHYDRO- ISOQUINOLIN-2(1H)-YL-ALKYL DERIVATIVES OF IMIDAZO- AND PYRIMIDINO[2,1-f]PURINES.

    PubMed

    Zagórska, Agnieszka; Gryzło, Beata; Satała, Grzegorz; Bojarski, Andrzej J; Głuch-Lutwin, Monika; Mordyl, Barbara; Kazek, Grzegorz; Pawłowski, Maciej

    2016-01-01

    A series of octahydro- and 6,7-dimethoxy-3,4-dihydro- isoquinolin-2(1H)-yl-alkyl derivatives of imidazo- and pyrimidino[2,1-f]purines were synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT(1A), 5-HT(6), 5-HT(7), and dopamine D2 receptors and inhibitory potencies for phosphodiesterases - PDE4B1 and PDE10A. The structure-activity relationships allowed to determine the structural features responsible for receptor and enzyme activity. Compound 5 (8-(4-(6,7-dimethoxy-3,4-dihydroiso- quinolin-2(1H)butyl)1,3-dimethyl-H-imidazo[2,1-f]purine-2,4(3H,8H)-dione) could be regarded as promising structure for further modification and detailed mechanistic study for obtained hybrid ligands.

  16. Piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine as orally-active adhesion molecule inhibitors.

    PubMed

    Kaneko, Toshihiko; Clark, Richard S J; Ohi, Norihito; Ozaki, Fumihiro; Kawahara, Tetsuya; Kamada, Atsushi; Okano, Kazuo; Yokohama, Hiromitsu; Ohkuro, Masayoshi; Muramoto, Kenzo; Takenaka, Osamu; Kobayashi, Seiichi

    2004-06-01

    Novel piperidine carboxylic acid derivatives of 10H-pyrazino[2,3-b][1,4]benzothiazine were prepared and evaluated for their inhibitory activity on the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Replacement of the methanesulfonyl group on the piperidine ring of previously prepared derivatives with a carboxylic acid-containing moiety resulted in a number of potent adhesion molecule inhibitors. Of these, (anti) [3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-yl)methyl-3-azabicyclo[3.3.1]non-9-yl]acetic acid 2q (ER-49890), showed the most potent oral inhibitory activities against neutrophil migration in an interleukin-1 (IL-1) induced paw inflammation model using mice, and leukocyte accumulation in a carrageenan pleurisy model in the rat, and therapeutic effect on collagen-induced arthritis in rats.

  17. Direct synthesis and characterization of mixed-valent Li 0.5$-$δCoPO 4, a Li-deficient derivative of the Cmcm polymorph of LiCoPO 4

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ludwig, Jennifer; Alarcon-Suesca, Carlos; Geprags, Stephan

    While the majority of research activities on LiCoPO 4 is focussed on the thermodynamically stable olivine-type Pnma polymorph, the metastable Pna2 1 and Cmcm modifications have recently attracted considerable attention due to their interesting material properties. In this study, we present the first Li-deficient structural derivative of the Cmcm modification with the nominal composition Li 0.5–δCoPO 4. As opposed to the substoichiometric olivine ( Pnma) phases Li xCoPO 4 (x = 0; 2/3), which are exclusively accessible by electrochemical or chemical Li extraction techniques, this is also the first time that a direct soft-chemical synthesis route towards a Li xCoPOmore » 4-type material is accomplished. X-ray and neutron diffraction studies indicate that Cmcm-type Li 0.5–δCoPO 4 shows vacancies on both the Li and Co sites, whereas X-ray absorption spectra demonstrate that the structure features heterovalent Co ions (+2/+3) to compensate for the Li deficit. Magnetic measurements reveal a long-range antiferromagnetic order below 10.5 K. A thorough investigation of the thermal stability using thermogravimetric analysis, differential scanning calorimetry, and temperature-dependent in situ X-ray powder diffraction demonstrates that Li 0.5–δCoPO 4 is metastable and exhibits a complex, multi-step thermal decomposition mechanism. In the first step at 394 °C, it decomposes to α-Co 2P 2O 7 ( P2 1/c) and LiCoPO 4 ( Cmcm) upon O 2 release. The LiCoPO 4 ( Cmcm) intermediate is then irreversibly transformed to olivine-type LiCoPO 4 (Pnma) at 686 °C. Furthermore, the material properties of Li 0.5–δCoPO 4 are further compared to the fully lithiated, isostructural LiCoPO 4 ( Cmcm) phase, for which an improved structure solution as well as Co L 2,3-edge X-ray absorption spectra are reported for the first time.« less

  18. Direct synthesis and characterization of mixed-valent Li 0.5$-$δCoPO 4, a Li-deficient derivative of the Cmcm polymorph of LiCoPO 4

    DOE PAGES

    Ludwig, Jennifer; Alarcon-Suesca, Carlos; Geprags, Stephan; ...

    2017-05-26

    While the majority of research activities on LiCoPO 4 is focussed on the thermodynamically stable olivine-type Pnma polymorph, the metastable Pna2 1 and Cmcm modifications have recently attracted considerable attention due to their interesting material properties. In this study, we present the first Li-deficient structural derivative of the Cmcm modification with the nominal composition Li 0.5–δCoPO 4. As opposed to the substoichiometric olivine ( Pnma) phases Li xCoPO 4 (x = 0; 2/3), which are exclusively accessible by electrochemical or chemical Li extraction techniques, this is also the first time that a direct soft-chemical synthesis route towards a Li xCoPOmore » 4-type material is accomplished. X-ray and neutron diffraction studies indicate that Cmcm-type Li 0.5–δCoPO 4 shows vacancies on both the Li and Co sites, whereas X-ray absorption spectra demonstrate that the structure features heterovalent Co ions (+2/+3) to compensate for the Li deficit. Magnetic measurements reveal a long-range antiferromagnetic order below 10.5 K. A thorough investigation of the thermal stability using thermogravimetric analysis, differential scanning calorimetry, and temperature-dependent in situ X-ray powder diffraction demonstrates that Li 0.5–δCoPO 4 is metastable and exhibits a complex, multi-step thermal decomposition mechanism. In the first step at 394 °C, it decomposes to α-Co 2P 2O 7 ( P2 1/c) and LiCoPO 4 ( Cmcm) upon O 2 release. The LiCoPO 4 ( Cmcm) intermediate is then irreversibly transformed to olivine-type LiCoPO 4 (Pnma) at 686 °C. Furthermore, the material properties of Li 0.5–δCoPO 4 are further compared to the fully lithiated, isostructural LiCoPO 4 ( Cmcm) phase, for which an improved structure solution as well as Co L 2,3-edge X-ray absorption spectra are reported for the first time.« less

  19. Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product.

    PubMed

    Thevis, Mario; Geyer, Hans; Kamber, Matthias; Schänzer, Wilhelm

    2009-08-01

    Non-steroidal and tissue-selective anabolic agents such as selective androgen receptor modulators (SARMs) represent a promising class of therapeutics for the treatment of various diseases such as sarcopenia or cancer cachexia. Advanced compounds of SARMs are based on an arylpropionamide-derived structure and leading drug candidates have successfully completed phase-II-clinical trials. Although none of these therapeutics have been approved, their performance-enhancing qualities and the black-market availability of these products makes them a viable target for misuse in the athletic community. In 2008, SARMs were added to the Prohibited List established by the World Anti-Doping Agency (WADA). That SARMs are the subject of misuse even without clinical approval was proved for the first time by the detection of the drug candidate Andarine (also referred to as S-4, S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide), advertised, sold and supplied via the Internet. The oily liquids, declared as green tea extracts and face moisturizer, were assayed using state-of-the-art analytical procedures and S-4 was found at concentrations of approximately 150 mg/mL. The authenticity of the product was demonstrated in comparison to reference material by liquid chromatography, high resolution/high accuracy (tandem) mass spectrometry using positive and negative electrospray ionization, and comparison to reference material. Moreover, an impurity resulting from poor product purification was detected, accounting for approximately 10% of S-4. This consisted of 2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-3-(4-nitro-3-trifluoromethyl-phenylamino)-propionamide. The ease of purchasing non-approved drug candidates that could potentially increase athletic performance demonstrates the need to operate proactively in the continued fight against doping. The early inclusion of emerging drugs into routine sports drug testing procedures is a key

  20. Synthesis, cytotoxic effect and antiviral activity of 1-(beta-D-arabinofuranosyl)-5-bromo-N4-substituted cytosine and 1-(beta-D-arabinofuranosyl)-5-bromo-4-methoxypyrimidin-2(1H)-one derivatives.

    PubMed

    Saladino, R; Mezzetti, M; Mincione, E; Palamara, A T; Savini, P; Marini, S

    1999-01-01

    A convenient and mild synthesis of 5-bromo-N4-substituted-1-(beta-D-arabinofuranosyl)cytosine and 5-bromo-O4-methyl-1-(beta-D-arabinofuranosyl)pyrimidin-2(1H)-one derivatives by selective oxyfunctionalization of the corresponding 4-thionucleosides with 3,3-dimethyldioxirane is reported. The cytotoxicity and the antiviral activity against parainfluenza 1 (Sendai virus) of all new synthesized products are also reported.