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Sample records for 4-dimethylamino-n-methyl-4-stilbazolium tosylate dast

  1. Photoacoustic and dielectric spectroscopic studies of 4-dimethylamino-n-methyl-4-stilbazolium tosylate single crystal: An efficient terahertz emitter

    NASA Astrophysics Data System (ADS)

    Manivannan, M.; Martin Britto Dhas, S. A.; Jose, M.

    2016-12-01

    Bulk terahertz emitting single crystal of 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) was synthesized by condensation method and grown by slow solvent evaporation technique from methanol. The structure and cell parameters of the grown crystals were derived from single crystal and powder X-ray diffraction analyses and the optical properties of the crystal were analyzed by UV-Vis Spectrophotometer. The presence of functional groups was identified by FTIR and FT-Raman spectroscopic studies. We demonstrated that in DAST crystal, the thermal transport properties such as thermal conductivity, thermal diffusivity and thermal effusivity are better than several well recognized standard materials using photoacoustic spectrophotometer. The dielectric measurement was made as a function of frequency (1 Hz-35 MHz) at different temperatures (30-200 °C). The dielectric constant and dielectric loss were found to be strongly dependent on temperature and frequency of the applied electric field. The semicircle in the cole-cole plot showed the presence of dielectric relaxation in the crystal with its diameter representing the resistance of the crystal. The resistivity and ac conductivity were calculated from the measured dielectric data.

  2. Real-time terahertz wave imaging by nonlinear optical frequency up-conversion in a 4-dimethylamino-N'-methyl-4'-stilbazolium tosylate crystal

    NASA Astrophysics Data System (ADS)

    Fan, Shuzhen; Qi, Feng; Notake, Takashi; Nawata, Kouji; Matsukawa, Takeshi; Takida, Yuma; Minamide, Hiroaki

    2014-03-01

    Real-time terahertz (THz) wave imaging has wide applications in areas such as security, industry, biology, medicine, pharmacy, and arts. In this letter, we report on real-time room-temperature THz imaging by nonlinear optical frequency up-conversion in organic 4-dimethylamino-N'-methyl-4'-stilbazolium tosylate crystal. The active projection-imaging system consisted of (1) THz wave generation, (2) THz-near-infrared hybrid optics, (3) THz wave up-conversion, and (4) an InGaAs camera working at 60 frames per second. The pumping laser system consisted of two optical parametric oscillators pumped by a nano-second frequency-doubled Nd:YAG laser. THz-wave images of handmade samples at 19.3 THz were taken, and videos of a sample moving and a ruler stuck with a black polyethylene film moving were supplied online to show real-time ability. Thanks to the high speed and high responsivity of this technology, real-time THz imaging with a higher signal-to-noise ratio than a commercially available THz micro-bolometer camera was proven to be feasible. By changing the phase-matching condition, i.e., by changing the wavelength of the pumping laser, we suggest THz imaging with a narrow THz frequency band of interest in a wide range from approximately 2 to 30 THz is possible.

  3. Diffraction-limited real-time terahertz imaging by optical frequency up-conversion in a DAST crystal.

    PubMed

    Fan, Shuzhen; Qi, Feng; Notake, Takashi; Nawata, Kouji; Takida, Yuma; Matsukawa, Takeshi; Minamide, Hiroaki

    2015-03-23

    Real-time terahertz (THz) wave imaging has wide applications in areas such as security, industry, biology, medicine, pharmacy, and the arts. This report describes real-time room-temperature THz imaging by nonlinear optical frequency up-conversion in an organic 4-dimethylamino-N'-methyl-4'-stilbazolium tosylate (DAST) crystal, with high resolution reaching the diffraction limit. THz-wave images were converted to the near infrared region and then captured using an InGaAs camera in a tandem imaging system. The resolution of the imaging system was analyzed. Diffraction and interference of THz wave were observed in the experiments. Videos are supplied to show the interference pattern variation that occurs with sample moving and tilting.

  4. Evaluation of hydrogen-bonding distance in organic nonlinear optical crystals for high-output terahertz-wave generation

    NASA Astrophysics Data System (ADS)

    Matsukawa, Takeshi; Hoshikawa, Akinori; Ishikawa, Yoshihisa; Ishigaki, Toru

    2017-04-01

    The crystal structure of deuterated 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST-d26) was obtained by powder X-ray and neutron diffraction measurements. The scattering length density distributions of deuterium atoms were successfully obtained from neutron diffraction data using the maximum-entropy method. From the density distributions, we estimated the hydrogen-bonding distances, which contribute significantly to the vibrational modes of DAST at 1 THz. Inhibition of these hydrogen bonds could allow the development of new nonlinear optical materials with low THz absorption.

  5. Conversion of 4-N,N-dimethylamino-4’-N’-methyl-stilbazolium tosylate (DAST) from a Simple Optical Material to a Versatile Optoelectronic Material

    PubMed Central

    Xu, Xiangdong; Sun, Ziqiang; Fan, Kai; Jiang, Yadong; Huang, Rui; Wen, Yuejiang; He, Qiong; Ao, Tianhong

    2015-01-01

    4-N,N-dimethylamino-4’-N’-methyl-stilbazolium tosylate (DAST) is an important optical material, but its poor conductivity limits applications in devices. To tackle this problem, we designed, prepared, and systematically investigated novel binary composite films that are composed of two-dimensional (2D) DAST and 2D graphene. Results indicate that both electrical and optical properties of DAST can be significantly improved by graphene addition. The negative steric effects of big DAST molecules that greatly trouble ex-situ synthesis can be efficiently overcome by in-situ synthesis, thus leading to better film quality and higher physical properties. Consequently, the in-situ composite film exhibits a low sheet resistance of 7.5 × 106 ohm and high temperature coefficient of resistance of −2.79% K−1, close to the levels of the most important bolometric materials for uncooled infrared detectors. Particularly, a new low temperature reduction of graphene oxide induced by DAST, which is further enhanced by in-situ process, was discovered. This work presents valuable information about the DAST–graphene composite films, their chemical structures, mechanisms, physical properties, and comparison on in-situ and ex-situ syntheses of graphene–based composites, all of which will be helpful for not only theoretically studying the DAST and graphene materials and expanding their applications, but also for seeking new optoelectronic sensitive materials. PMID:26192068

  6. Fourth-order coherent Raman microspectroscopy for detection of material symmetry

    NASA Astrophysics Data System (ADS)

    Hashimoto, Mamoru; Kanoh, Hiroto; Niioka, Hirohiko; Araki, Tsutomu

    2014-02-01

    Coherent Raman scattering provides chemical imaging by using molecular vibrational information sensitive to molecular structure. To add another information of martial symmetry, we propose using fourth order coherent Raman scattering for imaging, because the even order nonlinear phenomenon is forbidden for centro-symmetric material. We have developed a multiplex fourth order coherent Raman scattering microscopy system using a femtosecond laser. A narrowband beam of 17 cm-1 bandwidth and a broadband beam generated by a photonic crystal fiber enables to obtain a spectrum of fourth order coherent Raman scattering at once. We demonstrate the fourth order coherent Raman, hyper-Raman and second harmonics of trans-4'-(dimethylamino)-N-methyl-4- stilbazolium tosylate crystal by using the developed microscope.

  7. Nonlinear systems for frequency conversion from IR to RF

    NASA Astrophysics Data System (ADS)

    Dolasinski, Brian D.

    The objective of this dissertation is to evaluate and develop novel sources for tunable narrowband IR generation, tunable narrowband THz generation, and ultra-wideband RF generation to be used in possible non-destructive evaluation systems. Initially a periodically poled Lithium Niobate (PPLN) based optical parametric amplifier (OPA) is designed using a double-pass configuration where a small part of the pump is used on the first pass to generate a signal, which is reflected and filtered by an off-axis etalon. The portion of the pump that is not phase matched on the first pass is retro-reflected back into the PPLN crystal and is co-aligned with the narrow bandwidth filtered signal and amplified. We demonstrate that the system is tunable in the 1.4 microm -1.6 microm signal range with a linewidth of 5.4 GHz. Next the outputs of seeded, dual periodically poled lithium niobate (PPLN) optical parametric amplifiers (OPA) are combined in the nonlinear crystal 4-dimethylamino-N-methyl-4-stilbazolium-tosylate (DAST) to produce a widely tunable narrowband THz source via difference frequency generation (DFG). We have demonstrated that this novel configuration enables the system to be seamlessly tuned, without mode-hops, from 1.2 THz to 26.3 THz with a minimum bandwidth of 3.1 GHz. The bandwidth of the source was measured by using the THz transmission spectrum of water vapor lines over a 3-meter path length. By selecting of the DFG pump wavelength to be at 1380 nm and the signal wavelength to tune over a range from 1380 nm to 1570 nm, we produced several maxima in the output THz spectrum that was dependent on the phase matching ability of the DAST crystal and the efficiency of our pyro-electric detector. Due to the effects of dispersive phase matching, filter absorption of the THz waves, and two-photon absorption multiple band gaps in the overall spectrum occur and are discussed. Employing the dual generator scheme, we have obtained THz images at several locations in the

  8. Nonlinear optical and light emission studies of special organic molecules and crystals

    NASA Astrophysics Data System (ADS)

    Bhowmik, Achintya K.

    The nonlinear optical properties and light emission characteristics of some special organic molecules and crystals have been studied in detail. The second-order nonlinear optical effects were measured in the single- crystal films of the materials. The crystallographic orientations of the films were determined using x-ray diffraction measurements. The second-order susceptibility tensor elements of 4-aminobenzophenone (ABP) and 8- (4'-acetylphenyl)-1,4-dioxa-8- azaspiro[4.5]decane (APDA) films were measured using polarization selective second-harmonic generation experiments. The d-coefficients of ABP are: d 23 = 7.3 +/- 0.4 pm/V and d22 = 0.73 +/- 0.04 pm/V, while those of APDA are: d33 = 54 +/- 6 pm/V and d15 = 18 +/- 3 pm/V at 1064 nm. Phase-matched propagation directions were identified on the films. The application of these films in measuring ultra-short laser pulse-width was demonstrated. Polarized optical absorption and photo- luminescence were measured in 4'- dimethylamino-N-methyl-4-stilbazolium tosylate (DAST). The electro-optic properties of single- crystal films of DAST and styryl pyridinium cyanine dye (SPCD) were studied over a broad range of wavelengths. The measured r-coefficients are the largest reported in any material. Thin-film electro-optic modulators were demonstrated using these films which have insignificant insertion and propagation losses compared to the traditional waveguide based devices. The response was observed to be flat over the measured frequency range (2 kHz-100 MHz), which indicates the origin of the electro-optic effect to be predominantly electronic. Thus these materials have significant potential for applications in high-speed optical signal processing. Spectral broadening of femtosecond laser pulses in poly- [2,4 hexadiyne-1,6 diol-bis-(p-toluene sulfonate)] (PTS) single-crystals due to self-phase modulation was studied. The magnitudes of the nonlinear refractive index were determined over the wavelength range of 720-1064 nm

  9. Evaluation of DAST and zinc telluride nonlinear crystals for efficient terahertz generation

    SciTech Connect

    Venkatesh, M.; Chaudhary, A. K.; Rao, K. S.

    2015-07-31

    Terahertz (THz) signal is generated from 4-N, N-dimethylamino-4’-N’-methyl-stilbazolium tosylate (i.e. DAST Crystal) and Zinc telluride (ZnTe) nonlinear crystals by employing 140 fs laser pulses at 800 nm with 80 MHz repetition rate. The semi insulating gallium arsenide photoconductive stripline antennas (gap =5 µm, length = 20 µm) is used as a Terahertz detector. The detected temporal profile of Terahertz radiation generated from DAST crystal is high as compared to ZnTe crystal in terms of amplitude. THz effective bandwidths of these crystals are extended up to 1.1 THz range. The potential of THz generation of DAST and ZnTe crystals are evaluated with respect to incident laser power.

  10. DAST Being Calibrated for Flight in Hangar

    NASA Technical Reports Server (NTRS)

    1982-01-01

    DAST-2, a modified BQM-34 Firebee II drone, undergoes calibration in a hangar at the NASA Dryden Flight Research Center. After the crash of the first DAST vehicle, project personnel fitted a second Firebee II (serial # 72-1558) with the rebuilt ARW-1 (ARW-1R) wing. The DAST-2 made a captive flight aboard the B-52 on October 29, 1982, followed by a free flight on November 3, 1982. During January and February of 1983, three launch attempts from the B-52 had to be aborted due to various problems. Following this, the project changed the launch aircraft to a DC-130A. Two captive flights occurred in May 1983. The first launch attempt from the DC-130 took place on June 1, 1983. The mothership released the DAST-2, but the recovery system immediately fired without being commanded. The parachute then disconnected from the vehicle, and the DAST-2 crashed into a farm field near Harper Dry Lake. Wags called this the 'Alfalfa Field Impact Test.' These are the image contact sheets for each image resolution of the NASA Dryden Drones for Aerodynamic and Structural Testing (DAST) Photo Gallery. From 1977 to 1983, the Dryden Flight Research Center, Edwards, California, (under two different names) conducted the DAST Program as a high-risk flight experiment using a ground-controlled, pilotless aircraft. Described by NASA engineers as a 'wind tunnel in the sky,' the DAST was a specially modified Teledyne-Ryan BQM-34E/F Firebee II supersonic target drone that was flown to validate theoretical predictions under actual flight conditions in a joint project with the Langley Research Center, Hampton, Virginia. The DAST Program merged advances in electronic remote control systems with advances in airplane design. Drones (remotely controlled, missile-like vehicles initially developed to serve as gunnery targets) had been deployed successfully during the Vietnamese conflict as reconnaissance aircraft. After the war, the energy crisis of the 1970s led NASA to seek new ways to cut fuel use and

  11. Electrical and Nonlinear Optical Studies of Specific Organic Molecular and Nonconjugated Conductive Polymeric Systems

    NASA Astrophysics Data System (ADS)

    Narayanan, Ananthakrishnan

    In this research, structural, electrical and nonlinear optical characteristics of: (a) single crystal films involving a noncentrosymmetric molecule DAST and a laser dye IR125 and (b) specific nonconjugated conducting polymers including poly(beta-pinene) and polynorbornene have been studied. 4'-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) is a well known second order nonlinear optical material. This material has exceptionally high electro-optic coefficients, high thermal stability and ultrafast response time. In this work single crystal films involving a combination of DAST and IR125 have been prepared using modified shear method and the films have been characterized using polarized optical microscopy, X-ray diffraction, polarization dependent optical absorption and photoluminescence spectroscopy. The electro-optic coefficient of these films measured at 633nm was found to be 300pm/V. Since IR-125 has a strong absorption band from 500nm to 800nm, these films are promising for various applications in nonlinear optics at longer wavelength and for light emission. Nonconjugated conducting polymers are a class of polymers that have at least one double bond in their repeat units. 1,4-cis polyisoprene, polyalloocimene, styrene butadiene rubber, poly(ethylenepyrrolediyl) derivatives, and poly(beta-pinene) are some of the well known examples of nonconjugated conducting polymers. In this work, polynorborne, a new addition to the class of nonconjugated conducting polymers is discussed. Like other polymers in this class, polynorbornene exhibits increase in electrical conductivity by many orders of magnitude upon doping with iodine. The maximum electrical conductivity of this material is 0.01 S/cm. As shown by using FTIR microscopy, the C=C bonds are transformed into cation radicals when polynorborne is doped. This is due to the charge-transfer from the double bond to the dopant (iodine). These materials like other nonconjugated conducting polymers have significant

  12. DAST in Flight Showing Diverging Wingtip Oscillations

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Two BQM-34 Firebee II drones were modified with supercritical airfoils, called the Aeroelastic Research Wing (ARW), for the Drones for Aerodynamic and Structural Testing (DAST) program, which ran from 1977 to 1983. In this view of DAST-1 (Serial # 72-1557), taken on June 12, 1980, severe wingtip flutter is visible. Moments later, the right wing failed catastrophically and the vehicle crashed near Cuddeback Dry Lake. Before the drone was lost, it had made two captive and two free flights. Its first free flight, on October 2, 1979, was cut short by an uplink receiver failure. The drone was caught in midair by an HH-3 helicopter. The second free flight, on March 12, 1980, was successful, ending in a midair recovery. The third free flight, made on June 12, was to expand the flutter envelope. All of these missions launched from the NASA B-52. From 1977 to 1983, the Dryden Flight Research Center, Edwards, California, (under two different names) conducted the DAST Program as a high-risk flight experiment using a ground-controlled, pilotless aircraft. Described by NASA engineers as a 'wind tunnel in the sky,' the DAST was a specially modified Teledyne-Ryan BQM-34E/F Firebee II supersonic target drone that was flown to validate theoretical predictions under actual flight conditions in a joint project with the Langley Research Center, Hampton, Virginia. The DAST Program merged advances in electronic remote control systems with advances in airplane design. Drones (remotely controlled, missile-like vehicles initially developed to serve as gunnery targets) had been deployed successfully during the Vietnamese conflict as reconnaissance aircraft. After the war, the energy crisis of the 1970s led NASA to seek new ways to cut fuel use and improve airplane efficiency. The DAST Program's drones provided an economical, fuel-conscious method for conducting in-flight experiments from a remote ground site. DAST explored the technology required to build wing structures with less than

  13. Experimental evidence for the exotic dibaryon d^{ast }1

    NASA Astrophysics Data System (ADS)

    Khrykin, A. S.

    2016-12-01

    We provide strong experimental evidence for the existence of a nonstrange exotic dibaryon with a mass of about 1956 MeV called d^{ast }1(1956). This dibaryon is expected to be stable against strong decay and decays predominantly into two nucleons ( NN) via the isospin-conserving radiative process d^{ast }1 to NN γ . First, we present the experimental evidence for the d^{ast }1(1956) found in the energy spectrum of the coincident photons emitted at ±900 from the reaction p p → p p γ γ at 216 MeV. Then we give an explanation why the WASA/CELSIUS Collaboration did not find signatures of this dibaryon in its proton-proton bremsstrahlung data measured at 310 and 200 MeV. We also present signatures of this dibaryon found in experimental invariant mass spectra of photon pairs from the p p → p p γ γ reaction measured by this collaboration at 1360 and 1200 MeV. These signatures provide very substantial confirmation of the existence of the d^{ast }1(1956).

  14. Palladium catalyzed alkoxy- and aminocarbonylation of vinyl tosylates.

    PubMed

    Reeves, Diana C; Rodriguez, Sonia; Lee, Heewon; Haddad, Nizar; Krishnamurthy, Dhileepkumar; Senanayake, Chris H

    2011-05-06

    The palladium catalyzed alkoxycarbonylation and aminocarbonylation of vinyl tosylates are described. A variety of ketone and aldehyde derived vinyl tosylates may be carbonylated in the presence of primary, secondary, and tertiary alcohols, or primary and secondary amines, to provide the corresponding esters and amides in good yields. The alkoxycarbonylation was applied to a short synthesis of isoguvacine.

  15. 76 FR 78669 - Determination that Bretylium Tosylate Injection, 50 Milligrams/Milliliter, Was Not Withdrawn From...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... determined that Bretylium Tosylate injection, 50 milligrams (mg)/milliliter (mL), was not withdrawn from sale... drug applications (ANDAs) for Bretylium Tosylate injection, 50 mg/mL, if all other legal and regulatory... does not refer to a listed drug. Bretylium Tosylate injection, 50 mg/mL, is the subject of NDA 19-...

  16. Validation of the Drug Abuse Screening Test (DAST-10): A study on illicit drug use among Chinese pregnant women

    PubMed Central

    Lam, Lap Po; Leung, Wing Cheong; Ip, Patrick; Chow, Chun Bong; Chan, Mei Fung; Ng, Judy Wai Ying; Sing, Chu; Lam, Ying Hoo; Mak, Wing Lai Tony; Chow, Kam Ming; Chin, Robert Kien Howe

    2015-01-01

    We assessed the Chinese version of the Drug Abuse Screening Test (DAST-10) for identifying illicit drug use during pregnancy among Chinese population. Chinese pregnant women attending their first antenatal visit or their first unbooked visit to the maternity ward were recruited during a 4-month study period in 2011. The participants completed self-administered questionnaires on demographic information, a single question on illicit drug use during pregnancy and the DAST-10. Urine samples screened positive by the urine Point-of-Care Test were confirmed by gas chromatography-mass spectrometry. DAST-10 performance was compared with three different gold standards: urinalysis, self-reported drug use, and evidence of drug use by urinalysis or self-report. 1214 Chinese pregnant women participated in the study and 1085 complete DAST-10 forms were collected. Women who had used illicit drugs had significantly different DAST-10 scores than those who had not. The sensitivity of DAST-10 for identify illicit drug use in pregnant women ranged from 79.2% to 33.3% and specificity ranged from 67.7% to 99.7% using cut-off scores from ≥1 to ≥3. The ~80% sensitivity of DAST-10 using a cut-off score of ≥1 should be sufficient for screening of illicit drug use in Chinese pregnant women, but validation tests for drug use are needed. PMID:26091290

  17. Loads calibrations of strain gage bridges on the DAST project Aeroelastic Research Wing (ARW-1)

    NASA Technical Reports Server (NTRS)

    Eckstrom, C. V.

    1980-01-01

    The details of and results from the procedure used to calibrate strain gage bridges for measurement of wing structural loads for the DAST project ARW-1 wing are presented. Results are in the form of loads equations and comparison of computed loads vs. actual loads for two simulated flight loading conditions.

  18. Generation of efficient THz radiation by optical rectification in DAST crystal using tunable femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Venkatesh, Mottamchetty; Thirupugalmani, K.; Rao, K. S.; Brahadeeswaran, S.; Chaudhary, A. K.

    2017-03-01

    We report the efficient THz generation by optical rectification from an indigenously grown organic DAST crystal using the 140 fs oscillator laser pulses tunable in between 780 and 850 nm. The generated THz pulse profile and powers have been measured using the photoconductive (PC) antennas and pyroelectric detector, respectively. The highest THz peak amplitude and power is obtained at 825 nm central wavelength. We have theoretically explained the enhancement of THz radiation based on the matching of average optical group refractive index and average THz refractive index of the DAST crystal at 825 nm. In addition, the dependence of THz peak amplitude and THz power on laser power have been carried out. The measured quantum conversion efficiency (QCE) of 0.5 and 1.5 THz bands are of the order 3.7 × 10-3, 1.4 × 10-3, respectively. Finally, an attempt has been made to study the effect of polarizations on generated THz signal.

  19. High efficiency THz generation in DSTMS, DAST and OH1 pumped by Cr:forsterite laser.

    PubMed

    Vicario, C; Jazbinsek, M; Ovchinnikov, A V; Chefonov, O V; Ashitkov, S I; Agranat, M B; Hauri, C P

    2015-02-23

    We investigated Terahertz generation in organic crystals DSTMS, DAST and OH1 directly pumped by a Cr:forsterite laser at central wavelength of 1.25 μm. This pump laser technology provides a laser-to-THz energy conversion efficiency higher than 3 percent. Phase-matching is demonstrated over a broad 0.1-8 THz frequency range. In our simple setup we achieved hundred μJ pulses in tight focus resulting in electric and magnetic field larger than 10 MV/cm and 3 Tesla.

  20. Ground vibration test results for Drones for Aerodynamic and Structural Testing (DAST)/Aeroelastic Research Wing (ARW-1R) aircraft

    NASA Technical Reports Server (NTRS)

    Cox, T. H.; Gilyard, G. B.

    1986-01-01

    The drones for aerodynamic and structural testing (DAST) project was designed to control flutter actively at high subsonic speeds. Accurate knowledge of the structural model was critical for the successful design of the control system. A ground vibration test was conducted on the DAST vehicle to determine the structural model characteristics. This report presents and discusses the vibration and test equipment, the test setup and procedures, and the antisymmetric and symmetric mode shape results. The modal characteristics were subsequently used to update the structural model employed in the control law design process.

  1. Homogeneous tosylation of agarose as an approach toward novel functional polysaccharide materials.

    PubMed

    Gericke, Martin; Heinze, Thomas

    2015-01-01

    The homogeneous tosylation of agarose was studied with respect to the effects of reaction parameters, such as reaction medium, time, and molar ratio, on the reaction course, the degree of substitution (DS) with tosyl/chloro deoxy groups, and the molecular structure. Tosyl agaroses (TOSA) with DS tosyl ≤ 1 .81 could be obtained in completely homogeneous reactions by using N,N-dimethylacetamide (DMA)/LiCl or 1,3-dimethyl-2-imidazolidinone (DMI) as solvents. The products were characterized by FT-IR and NMR spectroscopy and it was demonstrated that two types of substitution pattern can be achieved: (i) non-preferential substitution at position 6 of the 1 → 3-linked β-d-galactose unit (G-6) and position 2 of the 1 → 4-linked 3,6-anyhdro-α-L-galactose unit (LA-2) and (ii) regioselective tosylation at G-6, depending on whether the reaction is performed with or without LiCl. Finally, the nucleophilic displacement reaction of TOSA was studied using azide and ethylenediamine as representative nucleophiles. Novel deoxy-agarose derivatives were obtained that showed an interesting solubility behavior and will be used for creating functional polysaccharide materials.

  2. Palladium-catalysed mono-α-alkenylation of ketones with alkenyl tosylates.

    PubMed

    Wu, Yong; Fu, Wai Chung; Chiang, Chien-Wei; Choy, Pui Ying; Kwong, Fuk Yee; Lei, Aiwen

    2017-01-16

    The first example of palladium-catalysed selective mono-α-alkenylation of ketones with alkenyl tosylates is described. In the presence of a Pd/XPhos catalyst system (0.1-1.0 mol%), the reaction provides mono-α-alkenylated ketones in good yields and exhibits excellent substrate tolerance. Highly congested, tri- and tetra-substituted alkenyl tosylates react smoothly and even problematic heteroaryl and aliphatic ketones are applicable substrates. Notably, small β,γ-unsaturated ketones are successfully prepared using acetone as a simple three-carbon feedstock.

  3. The DAST-1 remotely piloted research vehicle development and initial flight testing

    NASA Technical Reports Server (NTRS)

    Kotsabasis, A.

    1981-01-01

    The development and initial flight testing of the DAST (drones for aerodynamic and structural testing) remotely piloted research vehicle, fitted with the first aeroelastic research wing ARW-I are presented. The ARW-I is a swept supercritical wing, designed to exhibit flutter within the vehicle's flight envelope. An active flutter suppression system (FSS) designed to increase the ARW-I flutter boundary speed by 20 percent is described. The development of the FSS was based on prediction techniques of structural and unsteady aerodynamic characteristics. A description of the supporting ground facilities and aircraft systems involved in the remotely piloted research vehicle (RPRV) flight test technique is given. The design, specification, and testing of the remotely augmented vehicle system are presented. A summary of the preflight and flight test procedures associated with the RPRV operation is given. An evaluation of the blue streak test flight and the first and second ARW-I test flights is presented.

  4. The Synthesis and Methanolysis of Benzyl Tosylates: An Advanced Organic Chemistry Laboratory Experiment.

    ERIC Educational Resources Information Center

    Garst, Michael E.; Gribble, Gordon W.

    1984-01-01

    Describes a series of experiments (requiring six hours/week for six to eight weeks) involving the synthesis and methanolysis of substituted benzyl tosylates. The experiments provide students with experiences in kinetic data manipulation and an introduction and firm basis for structure-activity relationships and solvent effects in organic…

  5. Studies on the tosylation of cellulose in mixtures of ionic liquids and a co-solvent.

    PubMed

    Gericke, Martin; Schaller, Jens; Liebert, Tim; Fardim, Pedro; Meister, Frank; Heinze, Thomas

    2012-06-20

    The tosylation of cellulose in ionic liquids (ILs) was studied. Due to the beneficial effect of different co-solvents, the reaction could be performed at 25°C without the need of heating (in order to reduce viscosity) or cooling (in order to prevent side reactions). The effects of reaction parameters, such as time, molar ratio, and type of base, on the degree of substitution (DS) with tosyl- and chloro-deoxy groups as well as on the molecular weight were evaluated. Products with a DStosyl≤1.14 and DSCl≤0.16 were obtained and characterized by means of NMR- and FT-IR spectroscopy in order to evaluate their purity and distribution of functional groups within the modified anhydroglucose unit (AGU). Tosylation of cellulose in mixtures of IL and a co-solvent was found to result in predominant substitution at the primary hydroxyl group. Size exclusion chromatography (SEC) revealed only a moderate degradation of the polymer backbone at a reaction time of 4-8h. Finally, the nucleophilic displacement (SN) of tosyl- and chloro-deoxy groups by azide as well as recycling of the ILs was studied.

  6. Effect of ring size on the direction of rearrangement in bicyclic 1-tosyl-5-ethoxy-1,2,3-triazolines

    SciTech Connect

    Semenov, V.P.; Ogloblin, K.A.

    1987-09-20

    The authors determine that the title trazoline, formed in the reaction of tosyl azide with 1-epoxycyclohexene, is converted into ethyl N-tosylcyclopentencarbimidate, which is then converted into cyclopentanecarbohydrazide. The triazoline formed in the reaction of tosyl azide with 1-epoxycyclopentene is converted into N-(2-ethoxy-1-cyclopentenyl)toluenesulfonamide, the production of which indicates the intermediate formation of 2,3-trimethylene-1-tosyl-2-ethoxyaziridine. Consequently, the triazoline does not rearrange to ethyl N-tosylcyclobutanecarbimidate, in spite of the fact that it is substituted at the C-4 atom. Data on spin-spin coupling constants and chemical shift derived from the NMR spectra are analyzed.

  7. Design verification and fabrication of active control systems for the DAST ARW-2 high aspect ratio wing, part 1

    NASA Technical Reports Server (NTRS)

    Mcgehee, C. R.

    1986-01-01

    A study was conducted under Drones for Aerodynamic and Structural Testing (DAST) program to accomplish the final design and hardware fabrication for four active control systems compatible with and ready for installation in the NASA Aeroelastic Research Wing No. 2 (ARW-2) and Firebee II drone flight test vehicle. The wing structure was designed so that Active Control Systems (ACS) are required in the normal flight envelope by integrating control system design with aerodynamics and structure technologies. The DAST ARW-2 configuration uses flutter suppression, relaxed static stability, and gust and maneuver load alleviation ACS systems, and an automatic flight control system. Performance goals and criteria were applied to individual systems and the systems collectively to assure that vehicle stability margins, flutter margins, flying qualities and load reductions are achieved.

  8. Design verification and fabrication of active control systems for the DAST ARW-2 high aspect ratio wing. Part 2: Appendices

    NASA Technical Reports Server (NTRS)

    Mcgehee, C. R.

    1986-01-01

    This is Part 2-Appendices of a study conducted under Drones for Aerodynamic and Structural Testing (DAST) Program to accomplish the final design and hardware fabrication for four active control systems compatible with and ready for installation in the NASA Aeroelastic Research Wing No. 2 (ARW-2) and Firebee II drone flight test vehicle. The wing structure was designed so that Active Control Systems (ACS) are required in the normal flight envelope by integrating control system design with aerodynamics and structure technologies. The DAST ARW-2 configuration uses flutter suppression, relaxed static stability, and gust and maneuver load alleviation ACS systems, and an automatic flight control system. Performance goals and criteria were applied to individual systems and the systems collectively to assure that vehicle stability margins, flutter margins, flying qualities, and load reductions were achieved.

  9. Iron-catalyzed cross-coupling reactions of alkyl Grignards with aryl sulfamates and tosylates.

    PubMed

    Agrawal, Toolika; Cook, Silas P

    2013-01-04

    The iron-catalyzed cross-coupling of aryl sulfamates and tosylates has been achieved with primary and secondary alkyl Grignards. This study of iron-catalyzed cross-coupling reactions also examines the isomerization and β-hydride elimination problems that are associated with the use of isopropyl nucleophiles. While a variety of iron sources were competent in the reaction, the use of FeF(3)•3H(2)O was critical to minimize nucleophile isomerization.

  10. Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer microelectrodes for transmitter detection.

    PubMed

    Larsen, Simon T; Vreeland, Richard F; Heien, Michael L; Taboryski, Rafael

    2012-04-21

    In this paper we investigate the physical and electrochemical properties of micropatterned poly(3,4-ethylenedioxythiophene):tosylate (PEDOT:tosylate) microelectrodes for neurochemical detection. PEDOT:tosylate is a promising conductive polymer electrode material for chip-based bioanalytical applications such as capillary electrophoresis, high-performance liquid chromatography, and constant potential amperometry at living cells. Band electrodes with widths down to 3 μm were fabricated on polymer substrates using UV lithographic methods. The electrodes are electrochemically stable in a range between -200 mV and 700 mV vs. Ag/AgCl and show a relatively low resistance. A wide range of transmitters is shown to oxidize readily on the electrodes. Kinetic rate constants and half wave potentials are reported. The capacitance per area was found to be high (1670 ± 130 μF cm(-2)) compared to other thin film microelectrode materials. Finally, we use constant potential amperometry to measure the release of transmitters from a group of PC 12 cells. The results show how the current response decreases for a series of stimulations with high K(+) buffer.

  11. The development of the DAST I remotely piloted research vehicle for flight testing an active flutter suppression control system. Ph.D. Thesis. Final Report

    NASA Technical Reports Server (NTRS)

    Grose, D. L.

    1979-01-01

    The development of the DAST I (drones for aerodynamic and structural testing) remotely piloted research vehicle is described. The DAST I is a highly modified BQM-34E/F Firebee II Supersonic Aerial Target incorporating a swept supercritical wing designed to flutter within the vehicle's flight envelope. The predicted flutter and rigid body characteristics are presented. A description of the analysis and design of an active flutter suppression control system (FSS) designed to increase the flutter boundary of the DAST wing (ARW-1) by a factor of 20% is given. The design and development of the digital remotely augmented primary flight control system and on-board analog backup control system is presented. An evaluation of the near real-time flight flutter testing methods is made by comparing results of five flutter testing techniques on simulated DAST I flutter data. The development of the DAST ARW-1 state variable model used to generate time histories of simulated accelerometer responses is presented. This model uses control surface commands and a Dryden model gust as inputs. The feasibility of the concept of extracting open loop flutter characteristics from closed loop FSS responses was examined. It was shown that open loop characteristics can be determined very well from closed loop subcritical responses.

  12. Tunable Terahertz-wave generation from DAST crystal pumped by a monolithic dual-wavelength fiber laser.

    PubMed

    Tang, Ming; Minamide, Hiroaki; Wang, Yuye; Notake, Takashi; Ohno, Seigo; Ito, Hiromasa

    2011-01-17

    For developing a continuous-wave (CW) tunable Terahertz-wave (THz-wave) source using difference-frequency generation (DFG) in highly nonlinear optical crystals, we proposed and demonstrated a dual-wavelength fiber ring laser system operating around 1060 nm based on wideband chirped fiber Bragg gratings (CFBGs) and semiconductor optical amplifier (SOA). Thermo-induced phase shift along the CFBG produces a very sharp transmission spike therefore two lasing wavelengths with single longitudinal mode operation are oscillating simultaneously within the fiber ring cavity. Due to the inhomogeneous gain broadening property of SOA, the wavelength spacing of our dual-wavelength fiber laser can be continuously adjusted from 0.3 to 9.5 nm. By using this single emitter dual-wavelength fiber laser to pump an organic nonlinear DAST crystal, type-0 collinear phase matching of DFG process can be fulfilled and monochromatic THz wave ranging from 0.5 to 2 THz has been successfully generated.

  13. Titania-catalyzed radiofluorination of tosylated precursors in highly aqueous medium.

    PubMed

    Sergeev, Maxim E; Morgia, Federica; Lazari, Mark; Wang, Christopher; van Dam, R Michael

    2015-05-06

    Nucleophilic radiofluorination is an efficient synthetic route to many positron-emission tomography (PET) probes, but removal of water to activate the cyclotron-produced [(18)F]fluoride has to be performed prior to reaction, which significantly increases overall radiolabeling time and causes radioactivity loss. In this report, we demonstrate the possibility of (18)F-radiofluorination in highly aqueous medium. The method utilizes titania nanoparticles, 1:1 (v/v) acetonitrile-thexyl alcohol solvent mixture, and tetra-n-butylammonium bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly performed with aqueous [(18)F]fluoride without the need for a drying/azeotroping step to significantly reduce radiosynthesis time. High radiochemical purity of the target compound is also achieved. The substrate scope of the synthetic strategy is demonstrated with a range of aromatic, aliphatic, and cycloaliphatic tosylated precursors.

  14. Titania-catalyzed radiofluorination of tosylated precursors in highly aqueous medium

    SciTech Connect

    Sergeev, Maxim E.; Morgia, Federica; Lazari, Mark; Wang, Jr., Christopher; van Dam, R. Michael

    2015-04-10

    Nucleophilic radiofluorination is an efficient synthetic route to many positron-emission tomography (PET) probes, but removal of water to activate the cyclotron-produced [18F]fluoride has to be performed prior to reaction, which significantly increases overall radiolabeling time and causes radioactivity loss. In this paper, we demonstrate the possibility of 18F-radiofluorination in highly aqueous medium. The method utilizes titania nanoparticles, 1:1 (v/v) acetonitrile–thexyl alcohol solvent mixture, and tetra-n-butylammonium bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly performed with aqueous [18F]fluoride without the need for a drying/azeotroping step to significantly reduce radiosynthesis time. High radiochemical purity of the target compound is also achieved. Finally, the substrate scope of the synthetic strategy is demonstrated with a range of aromatic, aliphatic, and cycloaliphatic tosylated precursors.

  15. Titania-catalyzed radiofluorination of tosylated precursors in highly aqueous medium

    DOE PAGES

    Sergeev, Maxim E.; Morgia, Federica; Lazari, Mark; ...

    2015-04-10

    Nucleophilic radiofluorination is an efficient synthetic route to many positron-emission tomography (PET) probes, but removal of water to activate the cyclotron-produced [18F]fluoride has to be performed prior to reaction, which significantly increases overall radiolabeling time and causes radioactivity loss. In this paper, we demonstrate the possibility of 18F-radiofluorination in highly aqueous medium. The method utilizes titania nanoparticles, 1:1 (v/v) acetonitrile–thexyl alcohol solvent mixture, and tetra-n-butylammonium bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly performed with aqueous [18F]fluoride without the need for a drying/azeotroping step to significantly reduce radiosynthesis time. High radiochemical purity of the target compound is also achieved.more » Finally, the substrate scope of the synthetic strategy is demonstrated with a range of aromatic, aliphatic, and cycloaliphatic tosylated precursors.« less

  16. Pd(Quinox)-Catalyzed Allylic Relay Suzuki Reactions of Secondary Homostyrenyl Tosylates via Alkene-Assisted Oxidative Addition.

    PubMed

    Stokes, Benjamin J; Bischoff, Amanda J; Sigman, Matthew S

    2014-06-01

    Pd-catalyzed allylic relay Suzuki cross-coupling reactions of secondary alkyl tosylates, featuring a sterically-hindered oxidative addition and precise control of β-hydride elimination, are reported. The identification of a linear free energy relationship between the relative rates of substrate consumption and the electronic nature of the substrate alkene suggests that the oxidative addition requires direct alkene involvement. A study of the effect of chain length on the reaction outcome supports a chelation-controlled oxidative addition.

  17. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    PubMed

    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

  18. Application of optimization techniques to the design of a flutter suppression control law for the DAST ARW-2

    NASA Technical Reports Server (NTRS)

    Adams, W. M., Jr.; Tiffany, S. H.

    1984-01-01

    The design of a candidate flutter suppression (FS) control law for the symmetric degrees of freedom for the DAST ARW-2 aircraft is discussed. The results illustrate the application of several currently employed control law design techniques. Subsequent designs, obtained as the mathematical model of the ARW-2 is updated, are expected to employ similar methods and to provide a control law whose performance will be flight tested. This study represents one of the steps necessary to provide an assessment of the validity of applying current control law synthesis and analysis techniques in the design of actively controlled aircraft. Mathematical models employed in the control law design and evaluation phases are described. The control problem is specified by presenting the flutter boundary predicted for the uncontrolled aircraft and by defining objectives and constraints that the controller should satisfy. A full-order controller is obtained by using Linear Quadratic Gaussian (LQG) techniques. The process of obtaining an implementable reduced-order controller is described. One example is also shown in which constrained optimization techniques are utilized to explicitly include robustness criteria within the design algorithm.

  19. 17O NMR studies of ortho-substituent effects in substituted phenyl tosylates.

    PubMed

    Nummert, Vilve; Mäemets, Vahur; Piirsalu, Mare; Koppel, Ilmar A

    2012-10-01

    (17)O NMR spectra for 35 ortho-, para-, and meta-substituted phenyl tosylates (phenyl 4-methylbenzenesulfonates), 4-CH(3)-C(6)H(4) SO(2)OC(6)H(4)-X, at natural abundance in acetonitrile at 50 °C were recorded. The (17)O NMR chemical shifts, δ((17)O), of the sulfonyl (SO(2)) and the single-bonded phenoxy (OPh) oxygens for para and meta derivatives correlated well with dual substituent parameter treatment using the Taft inductive, σ(I), and resonance, σº(R), constants. The influence of ortho substituents on the sulfonyl oxygen and the single-bonded phenoxy oxygen chemical shifts, δ((17)O), was found to be nicely described by the Charton equation: δ((17)O)(ortho) = δ((17)O)(H) + ρ(I)σ(I) + ρ(R)σ°(R) + δE(s)(B) when the data treatment was performed separately for electron-donating +R substituents and electron-attracting -R substituents. Electron-attracting meta and para substituents in the phenyl moiety caused deshielding while the electron-donating meta, para and ortho +R substituents produce shielding effects on the sulfonyl (SO(2)) and single-bonded phenoxy (OPh) oxygens. The influence of ortho inductive and resonance effects in the case of +R substituents was found to be approximately twice higher than the corresponding influence from the para position. Due to the steric effect of ortho substituents a decrease in shielding of the oxygens at the sulfonyl group (δE(s)(B) > 0, E(s)(B) < 0) was detected.

  20. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans

    PubMed Central

    Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol “Eugenol” against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1–62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2–9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs. PMID:26694966

  1. Growth and characterization of novel organic 3-Hydroxy Benzaldehyde-N-methyl 4 Stilbazolium Tosylate crystals for NLO applications.

    PubMed

    Jagannathan, K; Umarani, P; Ratchagar, V; Ramesh, V; Kalainathan, S

    2016-01-15

    The 3-Hydroxy Benzaldehyde-N-methyl 4-Stilbazolium Tosylate (3- HBST) is a new organic NLO crystal and it is a new derivative in stilbazolium tosylate family. In this work we have synthesized 3-HBST and the single crystal was grown by conventional slow cooling method. The structure and lattice parameters of the grown crystal were determined by the single crystal X-ray diffraction (XRD) technique and it is exhibiting good crystalline nature which is observed from the powder XRD. In order to check the crystalline quality the rocking curve was recorded using multi crystal X-ray diffractometer. The functional groups were identified from both FTIR and NMR spectral analyses. The π-π* and n-π* optical transition energy levels were estimated from the absorption peaks. The NLO property was confirmed by measuring relative SHG efficiency by Kurtz powder test; it shows 24 times higher SHG efficiency than that of urea. In order to test the mechanical stability the Vickers and Knoop micro hardness measurement were carried out and found that the micro hardness number decreases with increasing load. The melting point was determined from Differential Scanning Colorimetry (DSC).

  2. Growth and characterization of novel organic 3-Hydroxy Benzaldehyde-N-methyl 4 Stilbazolium Tosylate crystals for NLO applications

    NASA Astrophysics Data System (ADS)

    Jagannathan, K.; Umarani, P.; Ratchagar, V.; Ramesh, V.; Kalainathan, S.

    2016-01-01

    The 3-Hydroxy Benzaldehyde-N-methyl 4-Stilbazolium Tosylate (3- HBST) is a new organic NLO crystal and it is a new derivative in stilbazolium tosylate family. In this work we have synthesized 3-HBST and the single crystal was grown by conventional slow cooling method. The structure and lattice parameters of the grown crystal were determined by the single crystal X-ray diffraction (XRD) technique and it is exhibiting good crystalline nature which is observed from the powder XRD. In order to check the crystalline quality the rocking curve was recorded using multi crystal X-ray diffractometer. The functional groups were identified from both FTIR and NMR spectral analyses. The π-π* and n-π* optical transition energy levels were estimated from the absorption peaks. The NLO property was confirmed by measuring relative SHG efficiency by Kurtz powder test; it shows 24 times higher SHG efficiency than that of urea. In order to test the mechanical stability the Vickers and Knoop micro hardness measurement were carried out and found that the micro hardness number decreases with increasing load. The melting point was determined from Differential Scanning Colorimetry (DSC).

  3. N-heterocyclic carbene-assisted, bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates.

    PubMed

    Ke, Haihua; Chen, Xiaofeng; Zou, Gang

    2014-08-01

    Efficient bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates have been effected with an assistance of N-heterocyclic carbene (NHC) generated in situ from N,N'-dialkylimidazoliums, e.g., N-butyl-N'-methylimidazolium bromide ([Bmim]Br), in toluene using K3PO4·3H2O as base. In contrast to bis(NHC)nickel-catalyzed conventional Suzuki coupling of arylboronic acids, mono(NHC)bis(phosphine)nickel species generated in situ from Ni(PPh3)2Cl2/[Bmim]Br displayed high catalytic activities in the cross-couplings of diarylborinic acids. The structural influences from diarylborinic acids were found to be rather small, while electronic factors from aryl chlorides, tosylates, and sulfamates affected the couplings remarkably. The couplings of electronically activated aryl chlorides, tosylates, and sulfamates could be efficiently effected with 1.5 mol % NiCl2(PPh3)2/[Bmim]Br as catalyst precursor to give the biaryl products in excellent yields, while 3-5 mol % loadings had to be used for the couplings of non- and deactivated ones. A small ortho-substitutent on the aromatic ring of aryl chlorides, tosylates, and sulfamates was tolerable. Applicability of the nickel-catalyzed cross-couplings in practical synthesis of fine chemicals has been demonstrated in process development for a third-generation topical retinoid, Adapalene.

  4. Crystal growth, spectral, structural and optical studies of π-conjugated stilbazolium crystal: 4-bromobenzaldehyde-4'-N'-methylstilbazolium tosylate.

    PubMed

    Krishna Kumar, M; Sudhahar, S; Bhagavannarayana, G; Mohan Kumar, R

    2014-05-05

    Nonlinear optical (NLO) organic compound, 4-bromobenzaldehyde-4'-N'-methylstilbazolium tosylate was synthesized by reflux method. The formation of molecular complex was confirmed from (1)H NMR, FT-IR and FT-Raman spectral analyses. The single crystals were grown by slow evaporation solution growth method and the crystal structure and atomic packing of grown crystal was identified. The morphology and growth axis of grown crystal were determined. The crystal perfection was analyzed using high resolution X-ray diffraction study on (001) plane. Thermal stability, decomposition stages and melting point of the grown crystal were analyzed. The optical absorption coefficient (α) and energy band gap (E(g)) of the crystal were determined using UV-visible absorption studies. Second harmonic generation efficiency of the grown crystal was examined by Kurtz powder method with different particle size using 1064 nm laser. Laser induced damage threshold study was carried out for the grown crystal using Nd:YAG laser.

  5. overline{B}to {D}^{(ast )}τ overline{ν} excesses in ALRSM constrained from B, D decays and {D}^0-{overline{D}}^0 mixing

    NASA Astrophysics Data System (ADS)

    Hati, Chandan; Kumar, Girish; Mahajan, Namit

    2016-01-01

    Recent experimental results from the LHCb, BaBar and Belle collaborations on the semitauonic decays of B meson, overline{B}to {D}^{(ast )}τ overline{ν} , showing a significant deviation from the Standard Model (SM), hint towards a new physics scenario beyond the SM. In this work, we show that these enhanced decay rates can be explained within the framework of E 6 motivated Alternative Left-Right Symmetric Model (ALRSM), which has been successful in explaining the recent CMS excesses and has the feature of accommodating high scale leptogenesis. The R-parity conserving couplings in ALRSM can contribute universally to both overline{B}to Dτ overline{ν} and overline{B}to {D}^{ast}τ overline{ν} via the exchange of scalar leptoquarks. We study the leptonic decays {D}_s+to {τ}+overline{ν} , {B}+to {τ}+overline{ν} , {D}+to {τ}+overline{ν} and {D}^0-{overline{D}}^0 mixing to constrain the couplings involved in explaining the enhanced B decay rates and we find that ALRSM can explain the current experimental data on {R}({D}^{(ast )}) quite well while satisfying these constraints.

  6. Compact High-Repetition-Rate Monochromatic Terahertz Source Based on Difference Frequency Generation from a Dual-Wavelength Nd:YAG Laser and DAST Crystal

    NASA Astrophysics Data System (ADS)

    Zhong, Kai; Mei, Jialin; Wang, Maorong; Liu, Pengxiang; Xu, Degang; Wang, Yuye; Shi, Wei; Yao, Jianquan; Teng, Bing; Xiao, Yong

    2017-01-01

    Although high-repetition-rate dual-wavelength Nd:YAG lasers at 1319 and 1338 nm have been realized for quite a long time, we have employed it in generating monochromatic terahertz (THz) wave in this paper for the first time. The dual-wavelength laser was LD-end-pumped and acousto-optically (AO) Q-switched with the output power of watt level operating at different repetition rates from 5.5 to 30 kHz. Using a 0.6-mm-thick organic nonlinear crystal DAST for difference frequency generation (DFG), a compact terahertz source was achieved at 3.28 THz. The maximum average output power was about 0.58 μW obtained at a repetition rate of 5.5 kHz, corresponding to the conversion efficiency of about 6.4 × 10-7. The output power scaling is still feasible with higher pump power and a longer nonlinear DFG crystal. Owing to the compactness of the dual-wavelength laser and the nonlinear crystal, a palm-top terahertz source is expected for portable applications such as imaging and so on.

  7. Native FKBP12 engineering by ligand-directed tosyl chemistry: labeling properties and application to photo-cross-linking of protein complexes in vitro and in living cells.

    PubMed

    Tamura, Tomonori; Tsukiji, Shinya; Hamachi, Itaru

    2012-02-01

    The ability to modify target "native" (endogenous) proteins selectively in living cells with synthetic molecules should provide powerful tools for chemical biology. To this end, we recently developed a novel protein labeling technique termed ligand-directed tosyl (LDT) chemistry. This method uses labeling reagents in which a protein ligand and a synthetic probe are connected by a tosylate ester group. We previously demonstrated its applicability to the selective chemical labeling of several native proteins in living cells and mice. However, many fundamental features of this chemistry remain to be studied. In this work, we investigated the relationship between the LDT reagent structure and labeling properties by using native FK506-binding protein 12 (FKBP12) as a target protein. In vitro experiments revealed that the length and rigidity of the spacer structure linking the protein ligand and the tosylate group have significant effects on the overall labeling yield and labeling site. In addition to histidine, which we reported previously, tyrosine and glutamate residues were identified as amino acids that are modified by LDT-mediated labeling. Through the screening of various spacer structures, piperazine was found to be optimal for FKBP12 labeling in terms of labeling efficiency and site specificity. Using a piperazine-based LDT reagent containing a photoreactive probe, we successfully demonstrated the labeling and UV-induced covalent cross-linking of FKBP12 and its interacting proteins in vitro and in living cells. This study not only furthers our understanding of the basic reaction properties of LDT chemistry but also extends the applicability of this method to the investigation of biological processes in mammalian cells.

  8. Rapid and Efficient Radiosyntheses of Meta-substituted [18F]Fluoroarenes from [18F]Fluoride Ion and Diaryliodonium Tosylates within a Microreactor

    PubMed Central

    Chun, Joong-Hyun; Lu, Shuiyu; Pike, Victor W.

    2011-01-01

    Effective methods for the introduction of the short-lived positron-emitter fluorine-18 (t1/2 = 109.7 min) at high specific radioactivity into fluoroarenes are valuable for the development of radiotracers for molecular imaging with positron emission tomography. Here we have explored the scope of the radiofluorination of diaryliodonium salts with no-carrier-added [18F]fluoride ion for the preparation of otherwise difficult to access meta-substituted [18F]fluoroarenes. A microfluidic reaction platform was used to establish optimal radiochemical yields. Rapid, high yielding and selective radiofluorinations were achieved in unsymmetrical diaryliodonium tosylates (ArI+Ar’TsO−) in which Ar carried either a meta electron-withdrawing (CN, NO2, CF3) or a meta electron-donating (Me or MeO) group, and in which the partner aryl group (Ar’) was relatively electron-rich, such as Ph, 3-Me-C6H4, 4-MeO-C6H4, 2-thienyl or 5-Me-2-thienyl. The radiofluorination of appropriate diaryliodonium tosylates is therefore a generally useful method for the preparation of simple [18F]m-fluoroarenes ([18F]ArF). PMID:22016665

  9. Acido-basic control of the thermoelectric properties of poly(3,4-ethylenedioxythiophene)tosylate (PEDOT-Tos) thin films

    PubMed Central

    Khan, Zia Ullah; Bubnova, Olga; Jafari, Mohammad Javad; Brooke, Robert; Liu, Xianjie; Gabrielsson, Roger; Ederth, Thomas; Evans, Drew R.; Andreasen, Jens W.; Fahlman, Mats

    2015-01-01

    PEDOT-Tos is one of the conducting polymers that displays the most promising thermoelectric properties. Until now, it has been utterly difficult to control all the synthesis parameters and the morphology governing the thermoelectric properties. To improve our understanding of this material, we study the variation in the thermoelectric properties by a simple acido-basic treatment. The emphasis of this study is to elucidate the chemical changes induced by acid (HCl) or base (NaOH) treatment in PEDOT-Tos thin films using various spectroscopic and structural techniques. We could identify changes in the nanoscale morphology due to anion exchange between tosylate and Cl– or OH–. But, we identified that changing the pH leads to a tuning of the oxidation level of the polymer, which can explain the changes in thermoelectric properties. Hence, a simple acid–base treatment allows finding the optimum for the power factor in PEDOT-Tos thin films. PMID:27019715

  10. Experimental and Theoretical Studies on Rhodium-Catalyzed Coupling of Benzamides with 2,2-Difluorovinyl Tosylate: Diverse Synthesis of Fluorinated Heterocycles.

    PubMed

    Wu, Jia-Qiang; Zhang, Shang-Shi; Gao, Hui; Qi, Zisong; Zhou, Chu-Jun; Ji, Wei-Wei; Liu, Yao; Chen, Yunyun; Li, Qingjiang; Li, Xingwei; Wang, Honggen

    2017-03-08

    Fluorinated heterocycles play an important role in pharmaceutical and agrochemical industries. Herein, we report on the synthesis of four types of fluorinated heterocycles via rhodium(III)-catalyzed C-H activation of arenes/alkenes and versatile coupling with 2,2-difluorovinyl tosylate. With N-OMe benzamide being a directing group (DG), the reaction delivered a monofluorinated alkene with the retention of the tosylate functionality. Subsequent one-pot acid treatment allowed the efficient synthesis of 4-fluoroisoquinolin-1(2H)-ones and 5-fluoropyridin-2(1H)-ones. When N-OPiv benzamides were used, however, [4 + 2] cyclization occurred to provide gem-difluorinated dihydroisoquinolin-1(2H)-ones. Synthetic applications have been demonstrated and the ready availability of both the arene and the coupling partner highlighted the synthetic potentials of these protocols. Mechanistically, these two processes share a common process involving N-H deprotonation, C-H activation, and olefin insertion to form a 7-membered rhodacycle. Thereafter, different reaction pathways featuring β-F elimination and C-N bond formation are followed on the basis of density functional theory (DFT) studies. These two pathways are DG-dependent and led to the open chain and cyclization products, respectively. The mechanistic rationale was supported by detailed DFT studies. In particular, the origins of the intriguing selectivity in the competing β-F elimination versus C-N bond formation were elucidated. It was found that β-F elimination is a facile event and proceeds via a syn-coplanar transition state with a low energy barrier. The C-N bond formation proceeds via a facile migratory insertion of the Rh-C(alkyl) into the Rh(V) amido species. In both reactions, the migratory insertion of the alkene is turnover-limiting, which stays in good agreement with the experimental studies.

  11. Interaction between bioactive compound 11a-N-tosyl-5-deoxi-pterocarpan (LQB-223) and Calf thymus DNA: Spectroscopic approach, electrophoresis and theoretical studies.

    PubMed

    Silva, Marina M; Nascimento, Eduarda O O; Silva, Edeíldo F; Araújo, João Xavier de; Santana, Camilla C; Grillo, Luciano Aparecido M; de Oliveira, Rafaela S; R R Costa, Paulo; Buarque, Camilla D; Santos, Josué Carinhanha C; Figueiredo, Isis M

    2017-03-01

    The interaction of small molecules with DNA has been quite important, since this biomolecule is currently the major target for a wide range of drugs in clinical use or advanced clinical research phase. Thus, the present work aimed to assess the interaction process between the bioactive compound 11a-N-tosyl-5-carba-pterocarpan, (LQB-223), that presents antitumor activity, with DNA, employing spectroscopic techniques, electrophoresis, viscosity and theoretical studies. Through UV-vis and molecular fluorescence spectroscopy, it was possible to infer that the preferential quenching mechanism was static, characterized by non-fluorescent supramolecular complex formation between the LQB-223 and DNA. The binding constant was 1.94∙10(3)Lmol(-1) (30°C) and, according to the thermodynamic parameters, the main forces involved in the interaction process are hydrophobic. Potassium iodide assay, competition with ethidium bromide, fluorescence contact energy transfer and melting temperature profile of DNA were employed to evaluate the binding mode. Except for KI assay, all results obtained indicated minor groove as the preferential binding mode of LQB-223 to DNA. These observations were supported by ionic strength assay, viscosity and molecular dynamics and docking studies. Finally, electrophoresis analysis demonstrated that the interaction does not promote DNA fragmentation, but it leads to variation in the migration profile after increasing the ligand concentration.

  12. (25R)-6α-Hy­droxy-5α-spiro­stan-3β-yl tosyl­ate

    PubMed Central

    Fernández-Herrera, María A.; Sandoval-Ramírez, Jesús; Bernès, Sylvain; Rodríguez-Acosta, Maricela; Hernández Linares, María-Guadalupe

    2012-01-01

    The title steroid, C34H50O6S, is an inter­mediate on the synthetic route between diosgenin and brassinosteroids, which possess the A ring modified with the 2α,3α-diol functionality. The polycyclic spiro­stan system has the expected conformation, with six-membered rings adopting chair forms and the five-membered rings envelope forms (flap atoms are the methine C atom in the C/D-ring junction and the spiro C atom connecting rings E and F). The 3β-tosyl­ate group is oriented in such a way that S=O bonds are engaged in inter­molecular hydrogen bonds with O—H and C—H donors. Chains of mol­ecules are formed along [100] via O—H⋯O hydrogen bonds, and secondary weak C—H⋯O inter­actions connect two neighbouring chains in the [001] direction. PMID:23476236

  13. Insight into the Amino-Type Excited-State Intramolecular Proton Transfer Cycle Using N-Tosyl Derivatives of 2-(2'-Aminophenyl)benzothiazole.

    PubMed

    Chen, Chi-Lin; Tseng, Huan-Wei; Chen, Yi-An; Liu, Jun-Qi; Chao, Chi-Min; Liu, Kuan-Miao; Lin, Tzu-Chieh; Hung, Cheng-Hsien; Chou, Yen-Lin; Lin, Ta-Chun; Chou, Pi-Tai

    2016-02-25

    Studies have been carried out to gain insight in to an overall excited-state proton transfer cycle for a series of N-tosyl derivatives of 2-(2'-aminophenyl)benzothiazole. The results indicate that followed by ultrafast (<150 fs) excited-state intramolecular proton transfer (ESIPT), the titled compounds undergo rotational isomerization along the C1-C1' bond. For the model compound 2-(2'-tosylaminophenyl)benzothiazole (PBT-NHTs) the subsequent cis-trans isomerization process in both triplet and ground states are probed by nanosecond transient absorption (TA) and two-step laser-induced fluorescence (TSLIF) spectroscopy. Both TA and TSLIF results indicate the existence of a long-lived trans-tautomer species in the ground state with a lifetime of few microseconds. The experimental results correlate well with the theoretical approach, which suggests that PBT-NHTs proton transfer tautomer generated in the excited state undergoes intramolecular C1-C1' rotation to ∼100° between benzothiazole and phenyl moieties in which the energetics for the S1 and T1 states are nearly identical. As a result, the intersystem crossing between S1 and T1 states serves as a fast deactivation pathway for the excited-state cis-tautomer to channel into both cis- and trans-tautomer in their respective T1 states, followed by the dominant T1-S0 radiationless deactivation to populate the trans-tautomer in the ground state. The trans-tautomer species in the S0 state proceeds with intermolecular double proton transfer to regenerate the cis-normal form. An overall proton-transfer cycle describing the amino-type ESIPT and the subsequent isomerization processes is thus depicted in detail.

  14. Differential effects of Mg(ii) and N(alpha)-4-tosyl-l-arginine methyl ester hydrochloride on the recognition and catalysis in ATP hydrolysis.

    PubMed

    Ma, Yanqing; Lu, Gongxuan

    2008-02-28

    The supramolecular interactions of Mg(ii) and N(alpha)-4-tosyl-l-arginine methyl ester hydrochloride (TAME) with ATP have been investigated using (1)H and (31)P NMR spectra. Furthermore, the hydrolysis of ATP catalyzed by Mg(ii) and TAME has been studied at 60 degrees C and pH 7 using (31)P NMR spectra. In the Mg(ii)-ATP-TAME ternary system, the binding interaction of Mg(2+) with ATP involves not only N1 and N7 in the adenine ring but also beta- and gamma-phosphate of ATP. The binding forces are mainly electrostatic interaction and cation (Mg(2+))-pi interaction. The guanidinium group and the aromatic ring of TAME interacts with ATP by beta and gamma phosphate and the adenine ring of ATP. The binding forces are mainly electrostatic interactions and pi-pi stacking. A significant difference between the binary and the ternary system indicates that TAME is essential to the stablization of the intermediate. Kinetic studies show that the hydrolysis rate constant of ATP is 2.16 x 10(-2) h(-1) at pH 7 in the Mg(ii)-TAME-ATP ternary system. The Mg(ii) ion and TAME can accelerate the ATP hydrolysis process. A possible mechanism has been proposed that the hydrolysis occurs through an addition-elimination, in which the phosphoramidate intermediate was observed at 3.21 ppm in the (31)P NMR of the ternary system. These results provide further information concerning the effect of the key amino acid residue and metal ions as cofactors of ATPase on ATP synthesis/hydrolysis at the molecular level.

  15. Combined use of Saccharomyces cerevisiae, Caenorhabditis elegans and patient fibroblasts leads to the identification of clofilium tosylate as a potential therapeutic chemical against POLG-related diseases.

    PubMed

    Pitayu, Laras; Baruffini, Enrico; Rodier, Celine; Rötig, Agnès; Lodi, Tiziana; Delahodde, Agnès

    2016-02-15

    Mitochondria are organelles that have their own DNA (mitochondrial DNA, mtDNA) whose maintenance is necessary for the majority of ATP production in eukaryotic cells. Defects in mtDNA maintenance or integrity are responsible for numerous diseases. The DNA polymerase γ (POLG) ensures proper mtDNA replication and repair. Mutations in POLG are a major cause of mitochondrial disorders including hepatic insufficiency, Alpers syndrome, progressive external ophthalmoplegia, sensory neuropathy and ataxia. Mutations in POLG are also associated with parkinsonism. To date, no effective therapy is available. Based on the conservation of mitochondrial function from yeast to human, we used Saccharomyces cerevisiae and Caenorhabditis elegans as first pass filters to identify a chemical that suppresses mtDNA instability in cultured fibroblasts of a POLG-deficient patient. We showed that this unsuspected compound, clofilium tosylate (CLO), belonging to a class of anti-arrhythmic agents, prevents mtDNA loss of all yeast mitochondrial polymerase mutants tested, improves behavior and mtDNA content of polg-1-deficient worms and increases mtDNA content of quiescent POLG-deficient fibroblasts. Furthermore, the mode of action of the drug seems conserved as CLO increases POLG steady-state level in yeast and human cells. Two other anti-arrhythmic agents (FDA-approved) sharing common pharmacological properties and chemical structure also show potential benefit for POLG deficiency in C. elegans. Our findings provide evidence of the first mtDNA-stabilizing compound that may be an effective pharmacological alternative for the treatment of POLG-related diseases.

  16. A Fully-automated One-pot Synthesis of [18F]Fluoromethylcholine with Reduced Dimethylaminoethanol Contamination via [18F]Fluoromethyl Tosylate

    PubMed Central

    Rodnick, Melissa E.; Brooks, Allen F.; Hockley, Brian G.; Henderson, Bradford D.; Scott, Peter J. H.

    2013-01-01

    Introduction A novel one-pot method for preparing [18F]fluoromethylcholine ([18F]FCH) via in situ generation of [18F]fluoromethyl tosylate ([18F]FCH2OTs), and subsequent [18F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed. Methods [18F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-18 synthesis module. Initially ditosylmethane was fluorinated to generate [18F]FCH2OTs. DMAE was then added and the reaction was heated at 120°C for 10 min to generate [18F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C18-Plus and CM-Light Sep-Pak cartridges to provide [18F]FCH formulated in USP saline. The formulated product was passed through a 0.22 μm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 hours from end-of-bombardment. Results Typical non-decay-corrected yields of [18F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ~1.3 Ci [18F]fluoride), and doses passed all other quality control (QC) tests. Conclusion A one-pot liquid-phase synthesis of [18F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 μg / 10 mL dose or ~3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies. PMID:23665261

  17. Transition-metal-free synthesis of imidazo[2,1-b]thiazoles and thiazolo[3,2-a]benzimidazoles via an S-propargylation/5-exo-dig cyclization/isomerization sequence using propargyl tosylates as substrates.

    PubMed

    Omar, Mohamed A; Frey, Wolfgang; Conrad, Jürgen; Beifuss, Uwe

    2014-11-07

    A transition-metal-free route for the synthesis of several N-fused heterocycles, including thiazolo[3,2-a]benzimidazoles and imidazo[2,1-b]thiazoles, is reported. The reaction between propargyl tosylates and 2-mercaptobenzimidazoles under basic conditions results in 3-substituted thiazolo[3,2-a]benzimidazoles, in yields up to 92% in a single synthesis step. With 2-mercaptoimidazoles as the substrate, the corresponding imidazo[2,1-b]thiazoles were exclusively obtained. The transformation is considered to proceed as an intermolecular S-propargylation that is followed by 5-exo-dig ring closure and double-bond isomerization.

  18. 2-Trimethylsilylethanesulfonyl (SES) versus tosyl (Ts) protecting group in the preparation of nitrogen-containing five-membered rings. A novel route for the synthesis of substituted pyrrolines and pyrrolidines.

    PubMed

    Declerck, Valérie; Allouchi, Hassan; Martinez, Jean; Lamaty, Frédéric

    2007-02-16

    The 2-trimethylsilylethanesulfonyl (or SES) protecting group was compared to the tosyl (Ts) group in the preparation of a nitrogen-containing five-membered ring obtained by the aza-Baylis-Hillman/alkylation/RCM route. While deprotection of Ts-protected pyrrolines gave only pyrroles, deprotection of the same SES-protected compounds gave either pyrroles or free amine pyrrolines depending on the deprotection conditions. The SES-protected pyrrolines were hydrogenated to yield pyrrolidines with an excellent diastereoselectivity. Free amine pyrrolidines were obtained by HF-mediated deprotection of the SES group.

  19. Palladium-copper catalyzed synthesis of benzofused heterocycles with two heteroatoms: novel and highly regio- and stereoselective syntheses of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles and (E)-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzothiazines.

    PubMed

    Kundu, N G; Nandi, B

    2001-06-29

    A highly novel, general, and convenient palladium and copper-catalyzed procedure has been developed for the synthesis of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40. 3-(2-Aminophenylthio)prop-1-yne 1 reacts with aryl iodides 2-14 under palladium-copper catalysis to yield the disubstituted alkynes 15-27 which after tosylation undergo a novel cyclization with CuI in the presence of triethylamine in THF to (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40 rather than to the expected 3-alkylidene-4-tosyl-3,4-dihydro-2H-1,4-benzothiazines 41. The reaction is highly regio- and stereoselective. The synthesis of 2-(2-arylethyl)-3-tosylbenzothiazolines 42-47, 2-(2-arylvinyl)benzothiazoles 48-54, and a novel 5-substituted uracil derivative 55 of potential biological importance is also being reported. Similarly, the palladium-copper-catalyzed arylation of S-[2-(N-prop-2'-ynyl)aminophenyl]-N,N-dimethylthiocarbamate 58 with aryl iodides yields the disubstituted alkynes 59 which on cyclization with KOH in methanol leads to (E)-2-(2-aryl)methylidene-3,4-dihydro-2H-1,4-benzothiazines 61. The reaction of the diiodo compounds 12-14a, however, with 58 under palladium-copper-catalyzed reactions involves the participation of only one of the iodo groups in the heteroannulation process giving compounds 61i and 61j. These are amenable to further palladium-catalyzed reactions and afford polyunsaturated heteroaromatic compounds 62 and 63.

  20. Cleavage of ether, ester, and tosylate C(sp3)-O bonds by an iridium complex, initiated by oxidative addition of C-H bonds. Experimental and computational studies.

    PubMed

    Kundu, Sabuj; Choi, Jongwook; Wang, David Y; Choliy, Yuriy; Emge, Thomas J; Krogh-Jespersen, Karsten; Goldman, Alan S

    2013-04-03

    A pincer-ligated iridium complex, (PCP)Ir (PCP = κ(3)-C6H3-2,6-[CH2P(t-Bu)2]2), is found to undergo oxidative addition of C(sp(3))-O bonds of methyl esters (CH3-O2CR'), methyl tosylate (CH3-OTs), and certain electron-poor methyl aryl ethers (CH3-OAr). DFT calculations and mechanistic studies indicate that the reactions proceed via oxidative addition of C-H bonds followed by oxygenate migration, rather than by direct C-O addition. Thus, methyl aryl ethers react via addition of the methoxy C-H bond, followed by α-aryloxide migration to give cis-(PCP)Ir(H)(CH2)(OAr), followed by iridium-to-methylidene hydride migration to give (PCP)Ir(CH3)(OAr). Methyl acetate undergoes C-H bond addition at the carbomethoxy group to give (PCP)Ir(H)[κ(2)-CH2OC(O)Me] which then affords (PCP-CH2)Ir(H)(κ(2)-O2CMe) (6-Me) in which the methoxy C-O bond has been cleaved, and the methylene derived from the methoxy group has migrated into the PCP Cipso-Ir bond. Thermolysis of 6-Me ultimately gives (PCP)Ir(CH3)(κ(2)-O2CR), the net product of methoxy group C-O oxidative addition. Reaction of (PCP)Ir with species of the type ROAr, RO2CMe or ROTs, where R possesses β-C-H bonds (e.g., R = ethyl or isopropyl), results in formation of (PCP)Ir(H)(OAr), (PCP)Ir(H)(O2CMe), or (PCP)Ir(H)(OTs), respectively, along with the corresponding olefin or (PCP)Ir(olefin) complex. Like the C-O bond oxidative additions, these reactions also proceed via initial activation of a C-H bond; in this case, C-H addition at the β-position is followed by β-migration of the aryloxide, carboxylate, or tosylate group. Calculations indicate that the β-migration of the carboxylate group proceeds via an unusual six-membered cyclic transition state in which the alkoxy C-O bond is cleaved with no direct participation by the iridium center.

  1. Palladium-catalyzed heteroannulation leading to heterocyclic structures with two heteroatoms: a highly regio- and stereoselective synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines.

    PubMed

    Kundu, N G; Chaudhuri, G; Upadhyay, A

    2001-01-12

    A highly convenient method has been developed for the synthesis of (Z)-4-alkyl-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzoxazines 9 and (Z)-3-alkyl(aryl)idene-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines 34-38 through palladium-copper-catalyzed reactions. Aryl halides 7 reacted with 2-[N-alkyl(benzyl)-N-prop-2'-ynyl]aminophenyl tosylate 6 in the presence of (PPh3)2PdCl2 (3 mol %), CuI(5 mol %) in triethylamine at room temperature to yield 2-[N-alkyl(benzyl)-N-(3-aryl-prop-2'-ynyl)]-aminophenyl tosylates 8 in extremely good yields (72-96%). The latter could then be cyclized with KOH in ethanol-water to Z-9 in a highly regio- and stereoselective manner. Similarly, palladium-copper-catalyzed reaction of 2-(prop-2'-ynyloxy)aniline (21) with aryl iodides 7 led to 22-26 which after tosylation and cyclization with cuprous iodide in CH3CN in the presence of K2CO3 and Bu4-NBr led to the (Z)-3-alkyl(aryl)idene-4-tosyl 3,4-dihydro-2H-1,4-benzoxazines 34-38 in good overall yields. The Z-stereochemistry of the products was established from 1H NMR spectra, 3JCH values (between vinylic proton and methylenic carbon of the heterocyclic ring), NOE experiments, and X-ray analysis. The method was also found to be suitable for the synthesis of bis(benzoxazinylated) derivatives 17, 39, and 2-alkyl-3,4-dihydro-2H-1,4-benzoxazines 18. Our method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines is highly efficacious, using easily available starting materials under very mild conditions. Also the synthesis of some novel 5-substituted uracil derivatives 40 and 41 containing the benzoxazinyl moiety and of potential biological interest is being reported.

  2. Drones for aerodynamic and structural testing /DAST/ - A status report

    NASA Technical Reports Server (NTRS)

    Murrow, H. N.; Eckstrom, C. V.

    1978-01-01

    A program for providing research data on aerodynamic loads and active control systems on wings with supercritical airfoils in the transonic speed range is described. Analytical development, wind tunnel tests, and flight tests are included. A Firebee II target drone vehicle has been modified for use as a flight test facility. The program currently includes flight experiments on two aeroelastic research wings. The primary purpose of the first flight experiment is to demonstrate an active control system for flutter suppression on a transport-type wing. Design and fabrication of the wing are complete and after installing research instrumentation and the flutter suppression system, flight testing is expected to begin in early 1979. The experiment on the second research wing - a fuel-conservative transport type - is to demonstrate multiple active control systems including flutter suppression, maneuver load alleviation, gust load alleviation, and reduce static stability. Of special importance for this second experiment is the development and validation of integrated design methods which include the benefits of active controls in the structural design.

  3. Sorafenib Tosylate in Treating Patients With Progressive Metastatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2014-11-14

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Neuroendocrine Tumor; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma; WDHA Syndrome

  4. Using the DAST-C to Explore Colombian and Bolivian Students' Images of Scientists

    ERIC Educational Resources Information Center

    Medina-Jerez, William; Middleton, Kyndra V.; Orihuela-Rabaza, Walter

    2011-01-01

    The way in which students view science and its practitioners, particularly during their late elementary and early secondary grade levels, has been at the core of numerous studies dating back to research by Mead & Metraux (Science 126:384-390, "1957"). In this study, we used the Draw-a-Scientist Test Checklist developed by Finson,…

  5. Design of a candidate flutter suppression control law for DAST ARW-2

    NASA Technical Reports Server (NTRS)

    Adams, W. M., Jr.; Tiffany, S. H.

    1984-01-01

    A control law is developed to suppress symmetric flutter for a mathematical model of an aeroelastic research vehicle. An implementable control law is attained by including modified LQC (Linear Quadratic Gaussian) design techniques, controller order reduction, and gain scheduling. An alternate (complementary) design approach is illustrated for one flight condition wherein nongradient-based constrained optimization techniques are applied to maximize controller robustness.

  6. Sorafenib Tosylate in Treating Patients With Liver Cancer Who Have Undergone a Liver Transplant

    ClinicalTrials.gov

    2015-03-25

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

  7. Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-11-14

    Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1; Acute Myeloid Leukemia With a Variant RARA Translocation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Acute Myeloid Leukemia With Variant MLL Translocations; Untreated Adult Acute Myeloid Leukemia

  8. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  9. Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-02-14

    Advanced Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Hepatocellular Carcinoma; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Childhood Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

  10. Status and future plans of the Drones for Aerodynamic and Structural Testing (DAST) program. [Aeroelastic Research Wing (ARW)

    NASA Technical Reports Server (NTRS)

    Murrow, H. N.

    1981-01-01

    Results from flight tests of the ARW-1 research wing are presented. Preliminary loads data and experiences with the active control system for flutter suppression are included along with comparative results of test and prediction for the flutter boundary of the supercritical research wing and on performance of the flutter suppression system. The status of the ARW-2 research wing is given.

  11. Sorafenib Tosylate and Erlotinib Hydrochloride in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gallbladder Cancer or Cholangiocarcinoma

    ClinicalTrials.gov

    2015-06-03

    Extrahepatic Bile Duct Adenocarcinoma; Gallbladder Adenocarcinoma; Gallbladder Adenocarcinoma With Squamous Metaplasia; Hilar Cholangiocarcinoma; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Undifferentiated Gallbladder Carcinoma; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma

  12. Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2017-03-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  13. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-12-30

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  14. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    ClinicalTrials.gov

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  15. Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-18

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

  16. Electro-optic studies of novel organic materials and devices

    NASA Astrophysics Data System (ADS)

    Xu, Jianjun

    1997-11-01

    Specific single crystal organic materials have high potential for use in high speed optical signal processing and various other electro-optic applications. In this project some of the most important organic crystal materials were studied regarding their detailed electro- optic properties and potential device applications. In particular, the electro-optic properties of N-(4- Nitrophenyl)-L-Prolinol (NPP) and 4'-N,N- dimethylamino-4-methylstilbazolium tosylate (DAST) both of which have extremely large second order susceptibilites were studied. The orientation of the thin film crystal with respect to the substrate surface was determined using-X-ray diffraction. The principal axes of the single crystal thin film were determined by polarization transmission microscopy. The elements of the electro-optic coefficient tensor were measured by field induced birefringence measurements. Detailed measurements for NPP thin films with different orientations of the external electric field with respect to the charge transfer axis were carried out at a wavelength of 1064nm. The wavelength dependence of the electro-optic effect for DAST single crystal thin films was measured using a Ti:Sapphire laser. Several device geometries involving organic single crystal thin film materials were studied. A new method for the fabrication of channel waveguides for organic materials was initiated. Channel waveguides for NPP and ABP were obtained using this methods. Optical modulation due to the electro-optic effect based on the organic channel waveguide for NPP single crystal was demonstrated. The electro-optic modulation using NPP single crystals thin film in a Fabry-Perot cavity was measured. A device using a optical fiber half coupler and organic electro-optic thin film material was constructed, and it has potential applications in optical signal processing.

  17. Design of a candidate flutter suppression control law for DAST ARW-2. [Drones for Aerodynamic and Structural Testing Aeroelastic Research Wing

    NASA Technical Reports Server (NTRS)

    Adams, W. M., Jr.; Tiffany, S. H.

    1983-01-01

    A control law is developed to suppress symmetric flutter for a mathematical model of an aeroelastic research vehicle. An implementable control law is attained by including modified LQG (linear quadratic Gaussian) design techniques, controller order reduction, and gain scheduling. An alternate (complementary) design approach is illustrated for one flight condition wherein nongradient-based constrained optimization techniques are applied to maximize controller robustness.

  18. Implementation of the DAST ARW II control laws using an 8086 microprocessor and an 8087 floating-point coprocessor. [drones for aeroelasticity research

    NASA Technical Reports Server (NTRS)

    Kelly, G. L.; Berthold, G.; Abbott, L.

    1982-01-01

    A 5 MHZ single-board microprocessor system which incorporates an 8086 CPU and an 8087 Numeric Data Processor is used to implement the control laws for the NASA Drones for Aerodynamic and Structural Testing, Aeroelastic Research Wing II. The control laws program was executed in 7.02 msec, with initialization consuming 2.65 msec and the control law loop 4.38 msec. The software emulator execution times for these two tasks were 36.67 and 61.18, respectively, for a total of 97.68 msec. The space, weight and cost reductions achieved in the present, aircraft control application of this combination of a 16-bit microprocessor with an 80-bit floating point coprocessor may be obtainable in other real time control applications.

  19. Practical asymmetric synthesis of a potent PDE4 inhibitor via stereoselective enolate alkylation of a chiral aryl-heteroaryl secondary tosylate.

    PubMed

    O'Shea, Paul D; Chen, Cheng-yi; Chen, Weirong; Dagneau, Philippe; Frey, Lisa F; Grabowski, Edward J J; Marcantonio, Karen M; Reamer, Robert A; Tan, Lushi; Tillyer, Richard D; Roy, Amélie; Wang, Xin; Zhao, Dalian

    2005-04-15

    A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to 1 was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield.

  20. Phase equilibria study in binary systems (tetra-n-butylphosphonium tosylate ionic liquid + 1-alcohol, or benzene, or n-alkylbenzene).

    PubMed

    Domańska, Urszula; Paduszyński, Kamil

    2008-09-04

    Ambient pressure (solid + liquid) equilibria (SLE) and (liquid + liquid) equilibria (LLE) of binary systems--ionic liquid (IL) tetra- n-butylphosphonium p-toluenesulfonate + 1-alcohol (1-butanol, 1-hexanol, 1-octanol, 1-decanol, or 1-dodecanol), benzene, or n-alkylbenzene (toluene, ethylbenzene, n-propylbenzene)-have been determined by using dynamic method in a broad range of mole fractions and temperatures from 250 to 335 K. For binaries containing alcohol, simple eutectic diagrams were observed with complete miscibility in the liquid phase. Only in the case of system [IL + n-propylbenzene] was mutual immiscibility with an upper critical solution temperature (UCST) with low solubility of the IL in the alcohol and high solubility of the alcohol in the IL detected. The basic thermal properties of pure IL, i.e., melting and glass-transition temperatures as well as enthalpy of melting, have been measured with differential scanning microcalorimetry technique (DSC). Well-known UNIQUAC, Wilson, NRTL, NRTL1, and NRTL2 equations have been fitted to obtain experimental data sets. For the system containing immiscibility gap [IL + n-propylbenzene], parameters of the equations have been derived only from SLE data. As a measure of goodness of correlations, root-mean square deviations of temperature have been used. These experimental results were compared to the previously measured binary systems with tetra- n-butylphosphonium methanesulfonate. Changing anion from methanesulfonate to p-toluenesulfonate decreases solubilities in systems with alcohols and increases the solubilities in binary systems with benzene and alkylbenzenes.

  1. Synthesis of cis-C-Iodo-N-Tosyl-Aziridines using Diiodomethyllithium: Reaction Optimization, Product Scope and Stability, and a Protocol for Selection of Stationary Phase for Chromatography

    PubMed Central

    2013-01-01

    The preparation of C-iodo-N-Ts-aziridines with excellent cis-diastereoselectivity has been achieved in high yields by the addition of diiodomethyllithium to N-tosylimines and N-tosylimine–HSO2Tol adducts. This addition-cyclization protocol successfully provided a wide range of cis-iodoaziridines, including the first examples of alkyl-substituted iodoaziridines, with the reaction tolerating both aryl imines and alkyl imines. An ortho-chlorophenyl imine afforded a β-amino gem-diiodide under the optimized reaction conditions due to a postulated coordinated intermediate preventing cyclization. An effective protocol to assess the stability of the sensitive iodoaziridine functional group to chromatography was also developed. As a result of the judicious choice of stationary phase, the iodoaziridines could be purified by column chromatography; the use of deactivated basic alumina (activity IV) afforded high yield and purity. Rearrangements of electron-rich aryl-iodoaziridines have been promoted, selectively affording either novel α-iodo-N-Ts-imines or α-iodo-aldehydes in high yield. PMID:23738857

  2. Using the Draw-a-Scientist Test for Inquiry and Evaluation

    ERIC Educational Resources Information Center

    Miele, Eleanor

    2014-01-01

    The Draw-a-Scientist Test (DAST) is a tool to assess stereotypical imagery of scientists. This paper describes the use of the DAST as both a model for inquiry and as a method of assessing the affective domain. The DAST was administered in a science education methods course for undergraduate students of elementary education, a methods course for…

  3. Genetic characterization of a novel astrovirus in Pekin ducks.

    PubMed

    Liao, Qinfeng; Liu, Ning; Wang, Xiaoyan; Wang, Fumin; Zhang, Dabing

    2015-06-01

    Three divergent groups of duck astroviruses (DAstVs), namely DAstV-1, DAstV-2 (formerly duck hepatitis virus type 3) and DAstV-3 (isolate CPH), and other avastroviruses are known to infect domestic ducks. To provide more data regarding the molecular epidemiology of astroviruses in domestic ducks, we examined the prevalence of astroviruses in 136 domestic duck samples collected from four different provinces of China. Nineteen goose samples were also included. Using an astrovirus-specific reverse transcription-PCR assay, two groups of astroviruses were detected from our samples. A group of astroviruses detected from Pekin ducks, Shaoxing ducks and Landes geese were highly similar to the newly discovered DAstV-3. More interestingly, a novel group of avastroviruses, which we named DAstV-4, was detected in Pekin ducks. Following full-length sequencing and sequence analysis, the variation between DAstV-4 and other avastroviruses in terms of lengths of genome and internal component was highlighted. Sequence identity and phylogenetic analyses based on the amino acid sequences of the three open reading frames (ORFs) clearly demonstrated that DAstV-4 was highly divergent from all other avastroviruses. Further analyses showed that DAstV-4 shared low levels of genome identities (50-58%) and high levels of mean amino acid genetic distances in the ORF2 sequences (0.520-0.801) with other avastroviruses, suggesting DAstV-4 may represent an additional avastrovirus species although the taxonomic relationship of DAstV-4 to DAstV-3 remains to be resolved. The present works contribute to the understanding of epidemiology, ecology and taxonomy of astroviruses in ducks.

  4. A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance

    PubMed Central

    Akaza, Hideyuki; Oya, Mototsugu; Iijima, Masafumi; Hyodo, Ichinosuke; Gemma, Akihiko; Itoh, Hiroshi; Adachi, Masatoshi; Okayama, Yutaka; Sunaya, Toshiyuki; Inuyama, Lyo

    2015-01-01

    Objective Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. Methods All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Results Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand–foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7–8.1), and the overall survival rate at 1 year was 75.4% (73.5–77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. Conclusions Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials. PMID:26206897

  5. Children's Images of Scientists: Does Grade Level Make a Difference?

    ERIC Educational Resources Information Center

    Ozel, Murat

    2012-01-01

    The purpose of this study was to assess children's images of scientists by using the Draw-A-Scientist Test (DAST) and to determine if differences in these images exist between grade levels. The DAST was administered to 243 children who were enrolled in kindergarten (aged 6) and grade 3 and 5 (aged 9 and 11). Findings obtained from the study…

  6. Students' Views about Scientists and School Science: Engaging K-8 Teachers in a National Study.

    ERIC Educational Resources Information Center

    Barman, Charles R.

    1999-01-01

    Studies elementary and middle school students' understanding of scientists and doing science in school by using the Draw-A-Scientist Test (DAST). Recommends creating opportunities for students to see scientists in different settings and roles. (Contains 23 references.) (YDS)

  7. Aminodifluorosulfinium Tetrafluoroborate Salts as Stable and Crystalline Deoxofluorinating Reagents

    PubMed Central

    2009-01-01

    Aminodifluorosulfinium tetrafluoroborate salts were found to act as efficient deoxofluorinating reagents when promoted by an exogenous fluoride source and, in most cases, exhibited greater selectivity by providing less elimination byproduct as compared to DAST and Deoxo-Fluor. Aminodifluorosulfinium tetrafluoroborates are easy handled crystalline salts that show enhanced thermal stability over dialkylaminosulfur trifluorides, are storage-stable, and unlike DAST and Deoxo-Fluor do not react violently with water. PMID:19799406

  8. Solid State Research Quarterly Technical Report 2003:2

    DTIC Science & Technology

    2003-10-17

    cleaned ultrasonically in trichlorethylene, acetone, and methanol ; etched in HCI and diluted HF, respectively, in order to remove oxides; and rinsed in... methanol . The surfaces of the wet wafers were then placed in contact with one another to allow liquid-surface tension to pull the wafers into atomic...match the natural crystalline facet of DAST were etched 0.5-1 pm deep into the SiO 2. A DAST-water- methanol -glycerin paste was deposited, pressing it

  9. Preparation and structure of drug-carrying biodegradable microspheres designed for transarterial chemoembolization therapy.

    PubMed

    Wang, Yujing; Benzina, Abderazak; Molin, Daniel G M; Akker, Nynke van den; Gagliardi, Mick; Koole, Leo H

    2015-01-01

    Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 μm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.

  10. An Investigation of Media Influences on Elementary Students Representations of Scientists

    NASA Astrophysics Data System (ADS)

    Farland-Smith, Donna; Finson, Kevin; Boone, William J.; Yale, Melissa

    2014-04-01

    Even long before children are able to verbalize which careers may be interesting to them, they collect and store ideas about scientists. For these reasons, asking children to Draw-A-Scientist has become an accepted method to provide a glimpse into how children represent and identify with those in the science fields. Years later these representations may translate into student's career choice. Since 1995, children's illustrations of scientists have been assessed by the Draw-A-Scientist Checklist (DAST-C). The checklist was created from the common aspects or features found in illustrations from previous studies and were based initially on the scientists, broken down into "stereotypical" and "alternative" images shown in the drawings. The purpose of this paper is to describe the development, field test and reliability of the modified Draw-A-Scientist Test (DAST) and The Draw-A-Scientist Rubric designed as an improvement of the DAST-C to provide a more appropriate method of assessing students' drawings of scientists. The combination of the modified DAST and the DAST Rubric brings more refinement as it enables clarities to emerge and subsequently increased detail to what one could ascertain from students about their mental images of scientists.

  11. 1,2-Dicyclopropylethyne and (Cyclopropylethynyl)cyclobutane from an Efficient Synthesis of 1,2-(omega-Haloalkyl)ethynes and 1-Cycloalkyl-2-(omega-haloalkyl)ethynes (Pre Print)

    DTIC Science & Technology

    2012-02-09

    inconvenience carrying out reaction in liquid NH3. The difference in reactivity between triflate and bromide groups for the SN2 alkynylation of ω...chloroalkyl tosylates (3 or 4) are used for the SN2 alkynylation reaction to avoid mixture formation. Tosylation of ω-Haloalkyl Alcohols (1 & 2): The...effect of utilizing a catalytic amount (10 mol %) of sodium iodide (NaI) or tetrabutylammonium iodide (Bu4NI) for the reaction of lithium

  12. Investigation of the Solubility and Enzymatic Activity of a Thioredoxin-Gelonin Fusion Protein

    DTIC Science & Technology

    1997-05-01

    tosyl-L-lysine chloromethyl ketone TPCK N -tosyl-L-phenylalanine chloromethyl ketone Tris tris( hydroxymethyl )aminomethane trxA gene for thioredoxin UV...synthesis inhibition assay and the RIP- specific N -glycosidase assay. Thioredoxin-gelonin did not exhibit any enzymatic activity in either assay, even at...Inhibition of Purified Gelonin-XOMA ........... 61 Figure 13: UV Photograph of the Polyacrylamide Gel - N -Glycosidase Activity of Purified Gelonin-XOMA

  13. Polythiophene Derivative with a Side Chain Chromophore as Photovoltaic and Photorefractive Materials

    DTIC Science & Technology

    1993-11-17

    the desired bulk property in the polymer such as water solubility,1 8 optical activity,19 ionic conductivity 20 or liquid crystalline properties. 2 1...tosylate was dried under vacuum and was then recrystallized from petroleum ether, to produce white needle like crystals . The p- toluene sulfonate (tosyl...removed by rotary evaporator under vacuum. The residue gave yellow crystals of MDT upon recrystallization from methanol. Yield 2.2 g (88%). mp 118 ’C

  14. Conducting Electronic Polymers by Non-Redox Processes

    DTIC Science & Technology

    1988-12-31

    systematic detailed observation of competing crystalline phases in a doped polymer. The multiple structures of the erneraldine form of polyaniline , together...states and other properties has been determined. Class I of the emeraldine form of polyaniline consists of materials prepared in the conducting, doped ...tosylic acid doped polyaniline ad polyethyleneoxide. We found that a 50:50 blend of tosylic acid doped polyaniline:PEO could form a homogeneous film

  15. Bifurcated, modular syntheses of chiral annulet triazacyclononanes.

    PubMed

    Argouarch, Gilles; Stones, Graham; Gibson, Colin L; Kennedy, Alan R; Sherrington, David C

    2003-12-21

    Three chiral 2,6-disubstituted tri-N-methyl azamacrocycles have been prepared by modular methods. These macrocycles were accessed from three chiral 1,4,7-triazaheptanes intermediates that were prepared by two independent routes. The first of these routes involved the benzylamine opening of chiral tosyl aziridines followed by debenzylation but was problematic on solubility grounds. A second, more effective, route was developed which avoided debenzylation by using ammonia in the nucleophilic opening of chiral tosyl aziridines.

  16. Propargyl hydrazides: synthesis and conversion into pyrazoles through hydroamination.

    PubMed

    Yoshimatsu, Mitsuhiro; Ohta, Katsuki; Takahashi, Nami

    2012-12-03

    Pyrazoles direct: propargyl alcohols undergo hydrazination when treated with p-tosyl hydrazide in the presence of catalytic amounts of either Sc(OTf)(3) or La(OTf)(3) (see scheme; Tf=trifluoromethanesulfonyl). Propargyl hydrazides are converted into either N-tosyl or N-H pyrazoles when treated with an acid or a base, respectively. The one-step acid-catalyzed hydrazination/cyclization of propargyl alcohols directly affords pyrazoles in high yields.

  17. Estimation of Modal Parameters Using a Wavelet-Based Approach

    NASA Technical Reports Server (NTRS)

    Lind, Rick; Brenner, Marty; Haley, Sidney M.

    1997-01-01

    Modal stability parameters are extracted directly from aeroservoelastic flight test data by decomposition of accelerometer response signals into time-frequency atoms. Logarithmic sweeps and sinusoidal pulses are used to generate DAST closed loop excitation data. Novel wavelets constructed to extract modal damping and frequency explicitly from the data are introduced. The so-called Haley and Laplace wavelets are used to track time-varying modal damping and frequency in a matching pursuit algorithm. Estimation of the trend to aeroservoelastic instability is demonstrated successfully from analysis of the DAST data.

  18. In vitro and in vivo evaluation of drug-eluting microspheres designed for transarterial chemoembolization therapy.

    PubMed

    Wang, Yujing; Molin, Daniël G M; Sevrin, Chantal; Grandfils, Christian; van den Akker, Nynke M S; Gagliardi, Mick; Knetsch, Menno L; Delhaas, Tammo; Koole, Leo H

    2016-04-30

    Poly(D,L-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafenib tosylate, were prepared, characterized and studied. Degradation of the microspheres, and release of cisplatin and/or sorafenib tosylate from them, were investigated in detail. Incubation of the drug-carrying microspheres in phosphate buffered saline (pH=7.4) revealed slow degradation. Nevertheless, significant release of cisplatin and sorafenib tosylate from microspheres loaded with both drugs was apparent in vitro; this can be attributed to their porous structure. Supernatants from microspheres loaded with both drugs showed strong toxic effects on cells (i.e. endothelial cells, fibroblast cells and Renca tumor cells) and potent anti-angiogenic effect in the matrigel endothelial tube assay. In vivo anti-tumor effects of the microspheres were also observed, in a Renca tumor mouse model. The poly(D,L-lactic acid) microspheres containing both cisplatin and sorafenib tosylate revealed highest therapeutic efficacy, probably demonstrating that combined local administration of cisplatin and sorafenib tosylate synergistically inhibits tumor growth in situ. In conclusion, this study demonstrates the applicability of biodegradable poly(D,L-lactic acid) microspheres loaded with cisplatin and sorafenib tosylate for local drug delivery as well as the potential of these microspheres for future use in transarterial chemoembolization.

  19. Turkish Primary Students' Perceptions about Scientist and What Factors Affecting the Image of the Scientists

    ERIC Educational Resources Information Center

    Turkmen, Hakan

    2008-01-01

    Students' views of science and scientists have been widely studied. The purpose of this study is to analyze image of scientist from drawn picture of scientists using The Draw-a-Scientist Test (DAST) by 5th grade students and to analyze where this image comes from students minds in changing Turkish educational perspective. Two hundred eighty seven…

  20. [New methods of constructing fluorinated organic compounds and their application].

    PubMed

    Kirihara, M

    2000-04-01

    This review summarizes several effective synthetic methods of fluorinated organic compounds developed by our group. Two topics have been described in this review. The first topic describes novel fluorinations using diethylaminosulfur trifluoride (DAST). The treatment of tertiary cyclopropyl silyl ethers with DAST caused ring opening and produced allylic fluorides. The reaction of DAST with a tertiary cyclobutanol provided a fluorocyclobutane, a (fluoromethyl)cyclopropane or a homoallylic fluoride. DAST reacted with cyclic ketoximes bearing substituent(s) that can stabilize a carbocation to cause the fluorinative fragmentation which produces fluorinated carbonitrile. The second topic describes the novel syntheses of organic compounds containing the difluoromethylene moiety using fluorinated building blocks. The indium-mediated coupling of aldehydes with 3-bromo-3,3-difluoropropene gives alpha,alpha-difluorohomoallylic alcohols in high yields. alpha,alpha-Difluorohomopropargylic alcohols were also obtained from the indium-mediated coupling of aldehydes with alpha-bromo-alpha,alpha-difluoropropargyl compounds. In the presence of a palladium(0) catalyst, several nucleophiles regioselectively reacted with 3-bromo-3,3-difluoropropene at its gamma-position, and reacted with 1-substituted-3-bromo-3,3-difluoropropenes at their alpha-position. (+)-(R)-1-Amino-2,2-difluorocyclopropane-1-carboxylic acid was synthesized via the lipase-catalyzed asymmetric acetylation of a pro-chiral diol as a key step.

  1. Scientist-Image Stereotypes: The Relationships among Their Indicators

    ERIC Educational Resources Information Center

    Karaçam, Sedat

    2016-01-01

    The aim of this study is to examine primary school students' scientist-image stereotypes by considering the relationships among indicators. A total of 877 students attending Grades 6 and 7 in Düzce, Turkey participated in this study. The Draw-A-Scientist Test (DAST) was implemented during the 2013-2014 academic year to determine students' images…

  2. Turkish Elementary and Secondary Students' Views about Science and Scientist

    ERIC Educational Resources Information Center

    Akcay, Behiye

    2011-01-01

    The aim of this study was to determine elementary and secondary students' views concerning science and scientists. Data gathered from Draw-a-Scientist Test (DAST) and essays written by students were used to analyze their views. The study involved 359 students in grades 5 through 11. The results indicate that student's perceived scientists as to be…

  3. Influence of Scientific Stories on Students Ideas about Science and Scientists

    ERIC Educational Resources Information Center

    Erten, Sinan; Kiray, S. Ahmet; Sen-Gümüs, Betül

    2013-01-01

    This study was conducted to determine whether a lesson, in which context-based learning approach and scientific stories were used, changed students' (aged 11-12) stereotypical images of science and scientists. Data was collected from two separate sources: Interviews conducted with six students and Draw a Scientist Test (DAST) document that was…

  4. Influence of Scientific Stories on Students Ideas about Science and Scientists

    ERIC Educational Resources Information Center

    Erten, Sinan; Kiray, S. Ahmet; Sen-Gumus, Betul

    2013-01-01

    This study was conducted to determine whether a lesson, in which context-based learning approach and scientific stories were used, changed stereotypical images of students (aged 11-12) about science and scientists. Data was collected from two separate sources: Interviews conducted with six students and Draw a Scientist Test (DAST) document that…

  5. Putting a Human Face on Chemistry: A Project for Liberal Arts Chemistry.

    ERIC Educational Resources Information Center

    Kriz, George; Popejoy, Kate

    A collaborative project in liberal arts chemistry, involving faculty in chemistry and science education, is described. The project includes various components: an introductory test (DAST) to examine students' perceptions of scientists, a group library research exercise, oral and written presentation of the results of the library research, a…

  6. The Draw a Scientist Test: A Different Population and a Somewhat Different Story

    ERIC Educational Resources Information Center

    Thomas, Mark D.; Henley, Tracy B.; Snell, Catherine M.

    2006-01-01

    This study examined Draw-a-Scientist-Test (DAST) images solicited from 212 undergraduate students for the presence of traditional gender stereotypes. Participants were 100 males and 112 females enrolled in psychology or computer science courses with a mean age of 21.02 years. A standard multiple regression generated a model that accounts for the…

  7. Advanced aerodynamics and active controls. Selected NASA research

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Aerodynamic and active control concepts for application to commercial transport aircraft are discussed. Selected topics include in flight direct strike lightning research, triply redundant digital fly by wire control systems, tail configurations, winglets, and the drones for aerodynamic and structural testing (DAST) program.

  8. Perception of the Image of Scientist by Israeli Student Teachers from Two Distinct Communities in Israel: Arabs and Jews

    ERIC Educational Resources Information Center

    Koren, Pazit; Bar, Varda

    2009-01-01

    This is a comparative study of the image of the scientist held by Israeli Jewish and Arabic student teachers from various backgrounds. The image of female scientists among these groups was also investigated. Five groups of female students (N = 500) from four colleges were studied. Traditional tools (DAST) were combined with more informative…

  9. Investigating Gifted Middle School Students' Images about Scientists: A Cultural Similarity Perspective

    ERIC Educational Resources Information Center

    Bayri, N.; Koksal, M. S.; Ertekin, P.

    2016-01-01

    The purpose of this study is to investigate gifted middle school students' images about scientists in terms of cultural similarity. Sample of the study is 64 gifted middle school students taking courses from a formal school for gifted students. The data were collected by using Draw-a-scientist (DAST) instrument and was analysed by two researchers…

  10. Exploring High-Achieving Students' Images of Mathematicians

    ERIC Educational Resources Information Center

    Aguilar, Mario Sánchez; Rosas, Alejandro; Zavaleta, Juan Gabriel Molina; Romo-Vázquez, Avenilde

    2016-01-01

    The aim of this study is to describe the images that a group of high-achieving Mexican students hold of mathematicians. For this investigation, we used a research method based on the Draw-A-Scientist Test (DAST) with a sample of 63 Mexican high school students. The group of students' pictorial and written descriptions of mathematicians assisted us…

  11. Sixth grade students' perceptions of science and scientists following a field-based science investigation

    NASA Astrophysics Data System (ADS)

    Kielborn, Terrie Leigh

    The purpose of this study was to better understand the influences of field-based investigations on sixth graders' perceptions of science and scientists. I chose to do this study due to my desire for middle grade students to have the opportunity to learn science as scientists, to increase their interest in science, and to create a positive attitude about science at the middle school level. The implications of the findings are directed toward the future of middle school science education. Thirty-five students from two sixth grade classes drew their perceptions of a scientist using the Draw-A-Scientists Test (DAST), before and after their participation in a field-based science investigation. Three students were interviewed prior to, between each, and after the field-based investigations. Using the pre-DAST and post-DAST drawings along with the conversations of the students, I found three significant differences that indicated a change in the students' perception of scientists: (1) youth; (2) outdoors; and (3) symbols of research. Prior to the study, 74% of the sixth graders viewed scientists as middle-aged or elderly as compared to 43% after the stream investigations. The stream as "the site" for the field-based investigations, influenced 57% of the students to include the outdoors in their post-DAST drawings as compared to 26% in the pre-DAST. Students drew symbols of research 43% on the pre-DAST but increased to 69% on the post-DAST. Many of the drawings and conversations from the confirm the notion that these sixth graders preferred to learn science outside and using scientific tools. These students felt that they were doing real science, and real science is what scientists do. By using field-based science investigations regularly, I believe there is the potential for putting students on the frontier of science. This goal aligns with the National Science Education Standards that call for students to have opportunities for "inquiry into authentic questions

  12. Investigation of the atypical glass transition and recrystallization behavior of amorphous prazosin salts.

    PubMed

    Kumar, Lokesh; Popat, Dharmesh; Bansal, Arvind K

    2011-08-25

    This manuscript studied the effect of counterion on the glass transition and recrystallization behavior of amorphous salts of prazosin. Three amorphous salts of prazosin, namely, prazosin hydrochloride, prazosin mesylate and prazosin tosylate were prepared by spray drying, and characterized by optical-polarized microscopy, differential scanning calorimetry and powder X-ray diffraction. Modulated differential scanning calorimetry was used to determine the glass transition and recrystallization temperature of amorphous salts. Glass transition of amorphous salts followed the order: prazosin mesylate > prazosin tosylate ~ prazosin hydrochloride. Amorphous prazosin mesylate and prazosin tosylate showed glass transition, followed by recrystallization. In contrast, amorphous prazosin hydrochloride showed glass transition and recrystallization simultaneously. Density Functional Theory, however, suggested the expected order of glass transition as prazosin hydrochloride > prazosin mesylate > prazosin tosylate. The counterintuitive observation of amorphous prazosin hydrochloride having lower glass transition was explained in terms of its lower activation energy (206.1 kJ/mol) for molecular mobility at Tg, compared to that for amorphous prazosin mesylate (448.5 kJ/mol) and prazosin tosylate (490.7 kJ/mol), and was further correlated to a difference in hydrogen bonding strength of the amorphous and the corresponding recrystallized salts. This study has implications in selection of an optimal amorphous salt form for pharmaceutical development.

  13. Structural studies of a non-stoichiometric channel hydrate using high resolution X-ray powder diffraction, solid-state nuclear magnetic resonance, and moisture sorption methods.

    PubMed

    Kiang, Y-H; Cheung, Eugene; Stephens, Peter W; Nagapudi, Karthik

    2014-09-01

    Structural investigations of a nonstoichiometric hydrate, AMG 222 tosylate, a DPP-IV inhibitor in clinical development for type II diabetes, were performed using a multitechnique approach. The moisture sorption isotherm is in good agreement with a simple Langmuir model, suggesting that the hydrate water is located in well-defined crystallographic sites, which become vacant during dehydration. Crystal structures of AMG 222 tosylate at ambient and dry conditions were determined from high-resolution X-ray diffraction using the direct space method. On the basis of these crystal structures, hydrated water is located in channels formed by the drug framework. Upon dehydration, an isostructural dehydrate is formed with the channels remaining void and accessible to water for rehydration. Kitaigorodskii packing coefficients of the solid between relative humidity of 0% and 90% indicate that the equilibrium form of AMG 222 tosylate is the fully hydrated monohydrate.

  14. Asymmetric synthesis of anti- and syn-beta-amino alcohols by reductive cross-coupling of transition metal-coordinated planar chiral arylaldehydes with aldimines.

    PubMed

    Tanaka, Yoshie; Taniguchi, Nobukazu; Kimura, Takayuki; Uemura, Motokazu

    2002-12-27

    Samarium iodide-mediated cross-coupling of N-tosyl ferrocenylideneamine with planar chiral ferrocenecarboxaldehydes or benzaldehyde chromium complexes gave diastereoselectively the corresponding anti-beta-amino alcohol derivatives in good yields, while N-tosyl benzylideneamine produced syn-beta-amino alcohols by coupling with planar chiral arylaldehydes. Dynamic kinetic resolution of a configurationally equilibrated reactive species generated from achiral N-tosyl ferrocenilideneamine and benzylideneamine by reduction with samarium iodide was observed in the cross-coupling with planar chiral arylaldehydes giving both antipodes of beta-amino alcohols depending on the planar chirality. The obtained anti-beta-amino alcohol with the ferrocene ring was utilized as a chiral ligand for catalytic asymmetric reduction of acetophenone.

  15. Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

    PubMed Central

    Eguaogie, Olga; Conlon, Patrick F; Ravalico, Francesco; Sweet, Jamie S T; Elder, Thomas B; Conway, Louis P; Lennon, Marc E; Hodgson, David R W

    2017-01-01

    Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5′-halides or 5′-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5′-tosylate substrates with potassium selenocyanate in the presence of DMF produced the corresponding 5′-selenocyanates in variable yields over the course of between one and eleven hours thereby avoiding the preparation and use of hygroscopic tetrabutylammonium salts. PMID:28179952

  16. Preparation of Potential Radioprotective Agents Derived from Aminothiols

    DTIC Science & Technology

    1985-09-01

    cholestanylisothiouronium tosylate (described above) and 2.65 g (0.0662 mol) of sodium hydroxide in 195 mL of absolute ethanol was refluxed until the mixture became...C, 68.20 %; H, 9.39 %; N, 4.57 %; S, 10.60 % 3. Thiocholesterol A mixture of cholesterylisothiouronium tosylate (2.46 g, 0.00400 mol), sodium ...mol) of sodium borohydride in 40 mL of water at 35 0C. By the time addition was complete a white precipitate had formed. The mixture was stirred for an

  17. Chiral Bicyclic Bridgehead Phosphoramidite (Briphos) Ligands for Asymmetric Rhodium-Catalyzed 1,2- and 1,4-Addition.

    PubMed

    Lee, Ansoo; Kim, Hyunwoo

    2016-05-06

    A complementary solution for Rh-catalyzed enantioselective 1,2- and 1,4-arylation with two structurally related chiral ligands is reported. A chiral bicyclic bridgehead phosphoramidite (briphos) ligand derived from 1-aminoindane was efficient for the 1,2-arylation of N-sulfonyl imines, while that derived from 1,2,3,4-tetrahydro-1-naphthylamine was efficient for 1,4-arylation of α,β-unsaturated cyclic ketones. For α,β-unsaturated N-tosyl ketimines, the briphos derived from 1-aminoindane was found to selectively provide γ,γ-diaryl N-tosyl enamines with high yields and stereoselectivities.

  18. Exploring the Effectiveness of Curriculum Provided Through Transmedia Books for Increasing Students' Knowledge and Interest in Science

    NASA Astrophysics Data System (ADS)

    Ponners, Pamela Jones

    Transmedia books are new and emerging technologies which are beginning to be used in current classrooms. Transmedia books are a traditional printed book that uses multiple media though the use of Quick Response (QR) codes and augmented reality (AR) triggers to access web-based technology. Using the transmedia book Skills That Engage Me students in kindergarten through second grade engage in curriculum designed to introduce science skills and careers. Using the modified Draw-a-Scientist Test (mDAST), observations and interviews, researchers analyzed pre and post data to describe changes students have about science and scientists. Future study may include the development and validation of a new instrument, Draw a Science Student, and examining the mDAST checklist with the intention of updating the parameters of what is considered positive and negative in relationship with work a scientist conducts.

  19. Co-Assignment of the Molecular Vibrational Frequencies in Different Electronic States

    NASA Astrophysics Data System (ADS)

    Panchenko, Yurii; Abramenkov, Alexander

    2016-06-01

    Ultrafast electron diffraction experimental data for the structural parameters of molecules in excited electronic states are comparatively uncommon, hence these parameters are largely unknown. However, because differences between the molecular geometries of excited and ground electronic states cause differences in their experimental vibrational spectra it is important to establish a correspondence between the molecular vibrational frequencies in the ground state and those of the excited state of interest. The correct co-assignment of the experimental vibrational frequencies between two different electronic states of a molecule may be determined by the analog of the Duschinsky matrix D. This matrix D is defined as D = (LI)-1LII where LI and LII are the matrices of the vibrational modes of the two states of the molecule under investigation. They are obtained by solving the vibrational problems in the I and II electronic states, respectively. Choosing the dominant elements in columns of the D matrix and permuting these columns to arrange these elements along the diagonal of the transformed matrix Dast makes it possible to establish the correct co-assignment of the calculated frequencies in the two electronic states. The rows of Dast are for the vibrations in the I electronic state, whereas the columns are for vibrations in the II electronic state. The results obtained may be tested by analogous calculations of Dast for isotopologues. The feasibility of co-assignments of the vibrational frequencies in the ground and T_1 and S_1 excited electronic states are demonstrated for trans-C_2O_2F_2. The analogs of the Duschinsky matrix Dast were used to juxtapose the vibrational frequencies of this molecule calculated at the CASPT2/cc-pVTZ level in the S_0, T_1 and S_1 states. F. Duschinsky, Acta Physicochim. URSS, 7(4), 551-566 (1937). Yu. N. Panchenko, Vibrational spectroscopy, 68, 236-240 (2013).

  20. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

    PubMed

    Yang, Li-Cheng; Rong, Zi-Qiang; Wang, Ya-Nong; Tan, Zher Yin; Wang, Min; Zhao, Yu

    2017-03-06

    The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

  1. Facile Synthesis of Pyrazole- and Benzotriazole-Containing Selenoethers

    PubMed Central

    Potapov, Andrei S.; Chernova, Nina P.; Ogorodnikov, Vladimir D.; Petrenko, Tatiana V.; Khlebnikov, Andrei I.

    2014-01-01

    Azole-containing selenoethers, 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-selena pentane and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-selena propane were prepared by the reaction of corresponding tosylate or chloride with sodium selenide generated in situ from elemental selenium and sodium formaldehydesulfoxylate (rongalite). PMID:25506615

  2. Enantioselective addition of phenylacetylene to N-aryl arylimines catalyzed by Cu(II)-pyridine containing N-tosylatedaminoimine ligand complex.

    PubMed

    Liu, Bao; Zhong, Yao; Li, Xingshu

    2009-06-01

    Chiral tridentate N-tosylated pyridine-containing ligands were prepared and used in the Cu(II)-catalyzed enantioselective addition of phenylacetylene to N-aryl arylimines. Moderate to high enantioselectivities (up to 95% ee) were obtained in very mild reaction conditions.

  3. Fluorescence and lasing characteristics of some long-lived flashlamp-pumpable, oxazole dyes

    NASA Technical Reports Server (NTRS)

    Fletcher, A. N.; Henry, R. A.; Kubin, R. F.; Hollins, R. A.

    1984-01-01

    The effects of dye structure, cover gas, and solvent are all shown to be critical to laser output and lifetime. The N-methyl tosylate salt of 2-(4-pyridyl)-5-(4-methoxyphenyl) oxazole in ethanol under argon is found to be the longest-lived, moderate output, laser dye solution of any that have been reported.

  4. REVISITING CLASSICAL NUCLEOPHILIC SUBSTITUTIONS IN AQUEOUS MEDIUM: MICROWAVE-ASSISTED SYNTHESIS OF ALKYL AZIDES

    EPA Science Inventory

    An efficient and clean synthesis of alkyl azides using microwave (MW) radiation is described in aqueous medium by reacting alkyl halides or tosylates with alkali azides. This general and expeditious MW-enhanced approach to nucleophilic substitution reactions is applicable to the ...

  5. Effect of counterion on the solid state photodegradation behavior of prazosin salts.

    PubMed

    Kumar, Lokesh; Jog, Rajan; Singh, Saranjit; Bansal, Arvind

    2013-06-01

    The effect of counterion was evaluated on the photodegradation behavior of six prazosin salts, viz., prazosin hydrochloride anhydrous, prazosin hydrochloride polyhydrate, prazosin tosylate anhydrous, prazosin tosylate monohydrate, prazosin oxalate dihydrate, and prazosin camsylate anhydrous. The salts were subjected to UV-Visible irradiation in a photostability test chamber for 10 days. The samples were analyzed for chemical changes by a specific stability-indicating high-performance liquid chromatography method. pH of the microenvironment was determined in 10%w/v aqueous slurry of the salts. The observed order of photostability was: prazosin hydrochloride anhydrous>prazosin camsylate anhydrous~prazosin-free base>prazosin hydrochloride polyhydrate>prazosin tosylate anhydrous>prazosin oxalate dihydrate~prazosin tosylate monohydrate. Multivariate analysis of the photodegradation behavior suggested predominant contribution of the state of hydration and also intrinsic photosensitivity of the counterion. Overall, hydrated salts showed higher photodegradation compared to their anhydrous counterparts. Within the anhydrous salts, aromatic and carbonyl counterion-containing salts showed higher susceptibility to light. The pH of microenvironment furthermore contributed to photodegradation of prazosin salts, especially for drug counterions with inherent higher pH. The study reveals importance of selection of a suitable drug salt form for photosensitive drugs during preformulation stage of drug development.

  6. Conducting Thermoset Polymers.

    DTIC Science & Technology

    2007-11-02

    methods to synthesize the acetylene-terminated polyaniline oligomers were investigated. Several substituted derivatives of acetylene-terminated... polyaniline were synthesized and doped with different acids such as tosylic acid, benzenedisulfonic acid, duodecylbenzenesulfonic acid, and camphorsulfonic...whereas the acetylene-terminated polyaniline oligomers were first doped with protonic acids then cured. In the third method, an acetylene-terminated

  7. Base-mediated decomposition of amide-substituted furfuryl tosylhydrazones: synthesis and cytotoxic activities of enynyl-ketoamides.

    PubMed

    Ji, Fanghua; Peng, Hui; Zhang, Xiaoting; Lu, Wenhua; Liu, Shubin; Jiang, Huanfeng; Liu, Bo; Yin, Biaolin

    2015-02-20

    Base-mediated decomposition of amide-substituted furfuryl tosylhydrazones afforded practical access to novel multifunctionalized enynyl-ketoamides. In addition, furfuryl tosylhydrazones with stable furan rings underwent an interesting tosyl-group migration to form sulfones, which have potential synthetic applications. Some of the obtained enynyl-ketoamides demonstrated good cytotoxicities against human tumor cell lines.

  8. One-step synthesis of N-protected glycosylamines from sugar hemiacetals.

    PubMed

    Liautard, Virginie; Pillard, Christelle; Desvergnes, Valérie; Martin, Olivier R

    2008-08-11

    Protected pentofuranose, hexofuranose and hexopyranose hemiacetals were found to react efficiently with amines carrying a deactivating group (alkoxycarbonyl, tosyl or phosphoryl group) in the presence of a Lewis acid to give the corresponding, stable glycosylamines. Such glycosylamine derivatives are useful substrates for further elaboration into nitrogen-containing natural products and carbohydrate mimetics.

  9. Traceless labeling of glycoproteins and its application to the study of glycoprotein-protein interactions.

    PubMed

    Yang, Yung-Lin; Lee, Yen-Pin; Yang, Yen-Ling; Lin, Po-Chiao

    2014-02-21

    A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is displaced by an SN2 reaction with a nucleophilic residue of the boronated glycoprotein, and finally, a reporter group is tagged onto the glycoprotein via an ether linkage. In the presence of polyols, a competition reaction recovers the native glycan of the tagged glycoprotein, conserving its biological significance. The BA-tosyl probes were used successfully for the specific labeling of glycosylated fetuins in a mixed protein pool and from crude Escherichia coli (E. coli) lysate. Further, a BA-tosyl-functionalized glass slide was used to fabricate glycoprotein microarrays with highly conserved glycans. By interacting with various lectins (carbohydrate-binding proteins), such as Concanavalin A (Con A) and wheat germ agglutinin (WGA), the types of carbohydrates and specific linkages of glycoproteins (α or β) could be systematically monitored. It is believed that the newly developed method will greatly accelerate the understanding of glycoproteins.

  10. Comparison of the prevalence of substance use and psychiatric disorders between government- and self-employed commercial drivers.

    PubMed

    Lin, Shih-Ku; Lee, Chao-Hui; Pan, Chun-Hung; Hu, Wei-Hern

    2003-08-01

    Five hundred and five city government-employed bus drivers (GED) and 506 self-employed drivers (SED) who were primarily taxi drivers attending annual health check-ups were studied. A two-step survey was applied. Data on basic demographics were collected, the 12-item Chinese Health Questionnaire (CHQ), Michigan Alcoholism Screening Test (MAST), Drug Abuse Screen Test (DAST) questionnaires were administered and urine drug screening for amphetamine and benzodiazepines was performed in all subjects. Subjects with MAST scores > or =3, DAST > or =5 from both groups and CHQ > or =4 for the GED group and CHQ > or =7 for the SED group were regarded as a high-risk group; and subjects with normal MAST, DAST and CHQ results serving as the comparison group were invited for further interview by psychiatric specialists using the Mini International Neuropsychiatric Interview. The mean CHQ scores were 0.94 +/- 1.53 for the GED group and 2.08 +/- 2.42 for the SED group. The mean MAST scores for the GED and SED groups were 0.23 +/- 0.58 and 0.38 +/- 1.12; and the mean DAST scores were 1.03 +/- 0.85 and 1.41 +/- 1.89, respectively. The positive rate for benzodiazepines in urine screening by enzyme immunoassay was 8.3% for the GED group, and 8.5% for the SED group. After specification using liquid chromatography, this rate reduced to 4.6% and 3.7%, respectively. Only one subject in the SED group tested positive for urine amphetamine. The SED group had a higher rate of neurotic problems, psychiatric diagnosis and a higher frequency of substance use than the GED group. These findings suggest that different work style of commercial drivers may contribute to this phenomenon. The rate of psychiatric diagnosis was significantly higher in the high-risk subjects from both groups. Questionnaires such as CHQ, DAST and MAST are useful tools to screen out subjects at high risk of psychiatric disorders during routine health checks in labor workers.

  11. Accurate measurements of thermodynamic properties of solutes in ionic liquids using inverse gas chromatography.

    PubMed

    Mutelet, Fabrice; Jaubert, Jean-Noël

    2006-01-13

    Activity coefficients at infinite dilution of 29 organic compounds in two room temperature ionic liquids were determined using inverse gas chromatography. The measurements were carried out at different temperatures between 323.15 and 343.15K. To establish the influence of concurrent retention mechanisms on the accuracy of activity coefficients at infinite dilution for 1-butyl-3-methylimidazolium octyl sulfate and 1-ethyl-3-methylimidazolium tosylate, phase loading studies of the net retention volume per gram of packing as a function of the percent phase loading were used. It is shown that most of the solutes are retained largely by partition with a small contribution from adsorption on 1-butyl-3-methylimidazolium octyl sulfate and that the n-alkanes are retained predominantly by interfacial adsorption on 1-ethyl-3-methylimidazolium tosylate.

  12. Crystal structure of high-spin tetra­aqua­bis­(2-chloro­pyrazine-κN 4)iron(II) bis­(4-methyl­benzene­sulfonate)

    PubMed Central

    Golub, Bohdan O.; Shylin, Sergii I.; Dechert, Sebastian; Malysheva, Maria L.; Gural‘skiy, Il‘ya A.

    2015-01-01

    The title salt, [FeII(C4H3ClN2)2(H2O)4](C7H7O3S)2, contains a complex cation with point group symmetry 2/m. The high-spin FeII cation is hexa­coordinated by four symmetry-related water and two N-bound 2-chloro­pyrazine mol­ecules in a trans arrangement, forming a distorted FeN2O4 octa­hedron. The three-dimensional supra­molecular structure is supported by inter­molecular O—H⋯O hydrogen bonds between the complex cations and tosyl­ate anions, and additional π–π inter­actions between benzene and pyrazine rings. The methyl H atoms of the tosyl­ate anion are equally disordered over two positions. PMID:26279865

  13. Glycerol as Precursor of Organoselanyl and Organotellanyl Alkynes.

    PubMed

    Lenardão, Eder J; Borges, Elton L; Stach, Guilherme; Soares, Liane K; Alves, Diego; Schumacher, Ricardo F; Bagnoli, Luana; Marini, Francesca; Perin, Gelson

    2017-03-02

    Herein we describe the synthesis of organoselanyl and organotellanyl alkynes by the addition of lithium alkynylchalcogenolate (Se and Te) to tosyl solketal, easily obtained from glycerol. The alkynylchalcogenolate anions were generated in situ and added to tosyl solketal in short reaction times, furnishing in all cases the respective products of substitution in good yields. Some of the prepared compounds were deprotected using an acidic resin to afford new water-soluble 3-organotellanylpropane-1,2-diols. The synthetic versatility of the new chalcogenyl alkynes was demonstrated in the iodocyclization of 2,2-dimethyl-1,3-dioxolanylmethyl(2-methoxyphenylethynyl)selane 3f, which afforded 3-iodo-2-(2,2-dimethyl-1,3-dioxolanylmethyl) selenanylbenzo[b]furan in 85% yield, opening a new way to access water-soluble Se-functionalized benzo[b]furanes.

  14. A New Green Ionic Liquid-Based Corrosion Inhibitor for Steel in Acidic Environments.

    PubMed

    Atta, Ayman M; El-Mahdy, Gamal A; Al-Lohedan, Hamad A; Ezzat, Abdel Rahman O

    2015-06-17

    This work examines the use of new hydrophobic ionic liquid derivatives, namely octadecylammonium tosylate (ODA-TS) and oleylammonium tosylate (OA-TS) for corrosion protection of steel in 1 M hydrochloric acid solution. Their chemical structures were determined from NMR analyses. The surface activity characteristics of the prepared ODA-TS and OA-TS were evaluated from conductance, surface tension and contact angle measurements. The data indicate the presence of a double bond in the chemical structure of OA-TS modified its surface activity parameters. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) measurements, scanning electron microscope (SEM), Energy dispersive X-rays (EDX) analysis and contact angle measurements were utilized to investigate the corrosion protection performance of ODA-TS and OA-TS on steel in acidic solution. The OA-TS and ODA-TS compounds showed good protection performance in acidic chloride solution due to formation of an inhibitive film on the steel surface.

  15. A one-dimensional double-chain coordination polymer: [Mn(C12H13NO6S)(C10H8N2)]n.

    PubMed

    Liang, Fu-Pei; Chen, Man-Sheng; Hu, Rui-Xiang; Chen, Zi-Lu

    2004-06-01

    In the title compound, poly[[(2,2'-bipyridine-kappa(2)N,N')manganese(II)]-micro(3)-N-tosyl-L-glutamato-kappa(4)O,O':O":O"'], [Mn(tsgluo)(bipy)](n), where tsgluo is N-tosyl-L-glutamate (C(12)H(13)NO(6)S) and bipy is 2,2'-bipyridine (C(10)H(8)N(2)), the Mn atoms are octahedrally coordinated by two N atoms of one bipy ligand and by four O atoms of three tsgluo(2-) anions. The gamma-carboxyl group coordinates to the Mn(II) atom in a chelating mode, while the alpha-carboxyl group coordinates in a bidentate-bridging mode. The complex displays a one-dimensional double-chain structure.

  16. Aqua-bis-(4-methyl-benzene-sulfonato-κO)(η(5)-penta-methyl-cyclo-penta-dien-yl)rhodium(III) monohydrate.

    PubMed

    Roy, Christopher P; Boyer, Pauline M; Merola, Joseph S

    2013-05-01

    The title half-sandwich rhodium(III) complex, [Rh(C10H15)(C7H7O3S)2(H2O)]·H2O, consists of a π-bonded penta-methyl-cyclo-penta-dienyl group, two σ-bonded tosyl-ate groups and an aqua ligand. The structure displays both inter- and intra-molecular O-H⋯O hydrogen bonding. The inter-molecular hydrogen bonding results in an extended helical chain along a 21 screw axis parallel to c, due to hydrogen bonding from the coordinating water ligand to the lattice water mol-ecule and then to a sulfonate O atom of a different asymmetric unit.

  17. Macrocyclic lactones: A versatile source for omega radiohalogenated fatty acid analogs

    SciTech Connect

    Dougan, A.H.; Lyster, D.M.; Robertson, K.A.; Vincent, J.S.

    1984-01-01

    For each omega halogenated fatty acid there exists a potential omega hydroxy fatty acid and the corresponding macrocyclic lactone. The authors have utilized such lactones as starting materials for omega /sup 123/I fatty acid analogs intended for myocardial imaging. Macrocyclic musk lactones are industrially available; 120 analogs are described in the literature. The preparation requires saponification, tosylation, and radio-iodide substitution. Iodo-fatty acids are readily separated from tosylate fatty acids on TLC. While providing a secure source of 16-iodo-hexadecanoic acid and 17-iodo-heptadecanoic acid, the scheme allows ready access to a large number of untried fatty acid analogs. Examples presented are 16-iodo-hexadecanoic acid, 16-iodo-7-hexadecanoic acid, 16-iodo-12-oxa-hexadecanoic acid, 15-iodo-pentadecanoic acid, and 15-iodo-12-keto-pentadecanoic acid. Metabolic studies are in progress in mice and dogs to assess the utility of these analogs for myocardial imaging.

  18. K-12 Students' Perceptions of Scientists: Finding a valid measurement and exploring whether exposure to scientists makes an impact

    NASA Astrophysics Data System (ADS)

    Hillman, Susan J.; Bloodsworth, Kylie H.; Tilburg, Charles E.; Zeeman, Stephan I.; List, Henrietta E.

    2014-10-01

    This study was launched from a National Science Foundation GK-12 grant in which graduate fellows in Science, Technology, Engineering, and Mathematics (STEM) are placed in classrooms to engage K-12 students in STEM activities. The investigation explored whether the STEM Fellows' presence impacted the K-12 students' stereotypical image of a scientist. Since finding a valid instrument is critical, the study involved (1) determining the validity of the commonly administered Draw-A-Scientist Test (DAST) against a newly designed six-question survey and (2) using a combination of both instruments to determine what stereotypes are currently held by children. A pretest-posttest design was used on 485 students, grades 3-11, attending 6 different schools in suburban and rural Maine communities. A significant but low positive correlation was found between the DAST and the survey; therefore, it is imperative that the DAST not be used alone, but corroboration with interviews or survey questions should occur. Pretest results revealed that the children held common stereotypes of scientists, but these stereotypes were neither as extensive nor did they increase with the grade level as past research has indicated, suggesting that a shift has occurred with children having a broader concept of who a scientist can be. Finally, the presence of an STEM Fellow corresponded with decreased stereotypes in middle school and high school, but no change in elementary age children. More research is needed to determine whether this reflects resiliency in elementary children's perceptions or limitations in either drawing or in writing out their responses.

  19. Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-Abdominal Adhesions, and Arterial Injuries

    DTIC Science & Technology

    2009-04-01

    and resuspended in phospate buffer saline (PBS) before use. Preparation of magnetic opsonins Super - paramagnetic beads (1 mm diameter, tosyl-coated...permeability in experimental model systems. These therapies include the following: (i) a newly developed nanoparticle -based oral delivery system for...inhibitors utilized in this study: Lodamin and an Fc-conjugated endostatin fragment. • investigated the efficacy of Lodamin (a nanoparticle -based oral

  20. An Efficient Synthesis of Dicycloalkylacetylenes: 1,2-Dicyclopropylethyne and (cyclopropylethynyl)cyclobutane (Preprint)

    DTIC Science & Technology

    2008-11-05

    difference in reactivity between triflate and bromide groups in the SN2 reaction with ω- bromoalkyl triflates led Chong et al. to synthesize...Page 3 of 14 chloroalkylalkynes. Taking advantage of chemoselectivity between the tosylate and chloro group in the SN2 reaction , ω-chloroalkyl...tetrabutylammonium iodide (Bu4I) in catalytic amounts (10 mol %) had a spectacular effect on the reaction of lithium acetylides with primary halides (X = Br or Cl

  1. Growth and electrical properties on NLO crystal: 4-N,N-dimethylamino 4′-N′-methylstilbazolium iodide

    SciTech Connect

    Kumar, M. Krishna Sudhahar, S. Kumar, R. Mohan

    2014-04-24

    4-N,N-Dimethylamino-4′-N′-methylstilbazolium tosylate single crystals were grown by solution crystal growth method. The cell parameters of grown crystal have been estimated using single crystal-X-ray diffraction analysis. The variation of real (´ε) and imaginary (´ε) part of dielectric constants and dielectric loss were observed for different frequencies and temperatures. The ac and dc electrical conductivities and activation energy were determined for DMSI crystal using dielectric studies.

  2. Synthesis of pachastrissamine from phytosphingosine: a comparison of cyclic sulfate vs an epoxide intermediate in cyclization.

    PubMed

    Lee, Taeho; Lee, Sukjin; Kwak, Young Shin; Kim, Deukjoon; Kim, Sanghee

    2007-02-01

    [reaction: see text] The syntheses of the cytotoxic natural product pachastrissamine and its unnatural 4-epi-congener were accomplished starting from a natural phytosphingosine. The relatively unstrained cyclic sulfate intermediate smoothly underwent the 5-endo cyclization to yield the 2,3,4-trisubstituted tetrahydrofuran ring system of pachastrissamine. The corresponding epoxy alcohol afforded the 4-epi-congener via a tosylate-mediated double inversion process.

  3. Unexpected ring-opening reactions of aziridines with aldehydes catalyzed by nucleophilic carbenes under aerobic conditions.

    PubMed

    Liu, Yan-Kai; Li, Rui; Yue, Lei; Li, Bang-Jing; Chen, Ying-Chun; Wu, Yong; Ding, Li-Sheng

    2006-04-13

    [reaction: see text] The chemoselective ring opening of N-tosyl aziridines with aldehydes catalyzed by an N-heterocyclic carbene was investigated under aerobic conditions. Unexpected carboxylates of 1,2-amino alcohols from the corresponding aldehydes, rather than the acyl anion ring-opened beta-amino ketones, were exclusively obtained. A plausible mechanism for this unprecedented carbene-mediated reaction was also proposed.

  4. C-Glucopyranosyl-1,2,4-triazoles As New Potent Inhibitors of Glycogen Phosphorylase

    PubMed Central

    2013-01-01

    Glycogen phosphorylase inhibitors are considered as potential antidiabetic agents. 3-(β-d-Glucopyranosyl)-5-substituted-1,2,4-triazoles were prepared by acylation of O-perbenzoylated N1-tosyl-C-β-d-glucopyranosyl formamidrazone and subsequent removal of the protecting groups. The best inhibitor was 3-(β-d-glucopyranosyl)-5-(2-naphthyl)-1,2,4-triazole (Ki = 0.41 μM against rabbit muscle glycogen phosphorylase b). PMID:24900719

  5. Tandem synthesis of highly functionalized pyrazole derivatives from terminal alkynes, sulfonyl azides, diethyl azadicarboxylate, and sodium arylsulfinates.

    PubMed

    Yavari, Issa; Nematpour, Manijeh

    2012-11-01

    The reaction between ketenimine intermediates [generated from terminal alkynes and sulfonyl azides], diethyl azadicarboxylate, and sodium arylsulfinates in N, N-dimethylformamide at room temperature, affords ethyl 2,3-dihydro-3-oxo-4-phenyl-2-tosyl-5-(tosylamino)pyrazole-1-carboxylates in moderate-to-good yields. When diisopropyl azadicarboxylate was used as the ester component, diisopropyl 1-arylsulfonyl-2-{[aryl(alkyl)sulfonyl]-2-phenylethanimidoyl}-1,2-hydrazinedicarboxylates were obtained.

  6. Application of a flight test and data analysis technique to flutter of a drone aircraft

    NASA Technical Reports Server (NTRS)

    Bennett, R. M.

    1981-01-01

    Modal identification results presented were obtained from recent flight flutter tests of a drone vehicle with a research wing (DAST ARW-1 for Drones for Aerodynamic and Structural Testing, Aeroelastic Research Wing-1). This vehicle is equipped with an active flutter suppression system (FSS). Frequency and damping of several modes are determined by a time domain modal analysis of the impulse response function obtained by Fourier transformations of data from fast swept sine wave excitation by the FSS control surface on the wing. Flutter points are determined for two different altitudes with the FSS off. Data are given for near the flutter boundary with the FSS on.

  7. Real-time flutter analysis

    NASA Technical Reports Server (NTRS)

    Walker, R.; Gupta, N.

    1984-01-01

    The important algorithm issues necessary to achieve a real time flutter monitoring system; namely, the guidelines for choosing appropriate model forms, reduction of the parameter convergence transient, handling multiple modes, the effect of over parameterization, and estimate accuracy predictions, both online and for experiment design are addressed. An approach for efficiently computing continuous-time flutter parameter Cramer-Rao estimate error bounds were developed. This enables a convincing comparison of theoretical and simulation results, as well as offline studies in preparation for a flight test. Theoretical predictions, simulation and flight test results from the NASA Drones for Aerodynamic and Structural Test (DAST) Program are compared.

  8. Synthesis of active controls for flutter suppression on a flight research wing

    NASA Technical Reports Server (NTRS)

    Abel, I.; Perry, B., III; Murrow, H. N.

    1977-01-01

    This paper describes some activities associated with the preliminary design of an active control system for flutter suppression capable of demonstrating a 20% increase in flutter velocity. Results from two control system synthesis techniques are given. One technique uses classical control theory, and the other uses an 'aerodynamic energy method' where control surface rates or displacements are minimized. Analytical methods used to synthesize the control systems and evaluate their performance are described. Some aspects of a program for flight testing the active control system are also given. This program, called DAST (Drones for Aerodynamics and Structural Testing), employs modified drone-type vehicles for flight assessments and validation testing.

  9. High Velocity Jet Noise Source Location and Reduction. Task 3 - Experimental Investigation of Suppression Principles Volume III - Suppressor Concepts Optimization

    DTIC Science & Technology

    1978-12-01

    using j79 and j85 engines . .sale-.004* dast vret obtained for chese saw configuratios to hallow cosiariaon of scale-wmodl and lull- scale results...J79 and J85 engines . The suppressors evaluated were: (1) a baseline conical nozzle, (2) a 32-chute nozzle with and withouL 5 8 I Z: ,I. (0. N...without an acoustically treated ejector. J85 Engine - Conical nozzle baseline, 8-lobe nozzle, and 104-tube suppressor. rar-field acoustic data for the

  10. Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose, and their analogs.

    PubMed

    Lavrenov, Sergey N; Korolev, Alexander M; Reznikova, Marina I; Sosnov, Andrey V; Preobrazhenskaya, Maria N

    2003-01-20

    Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives.

  11. Substance abuse among high-risk sexual offenders: do measures of lifetime history of substance abuse add to the prediction of recidivism over actuarial risk assessment instruments?

    PubMed

    Looman, Jan; Abracen, Jeffrey

    2011-03-01

    There has been relatively little research on the degree to which measures of lifetime history of substance abuse add to the prediction of risk based on actuarial measures alone among sexual offenders. This issue is of relevance in that a history of substance abuse is related to relapse to substance using behavior. Furthermore, substance use has been found to be related to recidivism among sexual offenders. To investigate whether lifetime history of substance abuse adds to prediction over and above actuarial instruments alone, several measures of substance abuse were administered in conjunction with the Sex Offender Risk Appraisal Guide (SORAG). The SORAG was found to be the most accurate actuarial instrument for the prediction of serious recidivism (i.e., sexual or violent) among the sample included in the present investigation. Complete information, including follow-up data, were available for 250 offenders who attended the Regional Treatment Centre Sex Offender Treatment Program (RTCSOTP). The Michigan Alcohol Screening Test (MAST) and the Drug Abuse Screening Test (DAST) were used to assess lifetime history of substance abuse. The results of logistic regression procedures indicated that both the SORAG and the MAST independently added to the prediction of serious recidivism. The DAST did not add to prediction over the use of the SORAG alone. Implications for both the assessment and treatment of sexual offenders are discussed.

  12. The Short Inventory of Problems-Modified for Drug Use (SIP-DU): validity in a primary care sample.

    PubMed

    Allensworth-Davies, Donald; Cheng, Debbie M; Smith, Peter C; Samet, Jeffrey H; Saitz, Richard

    2012-01-01

    Primary care physicians can help drug-dependent patients mitigate adverse drug use consequences; instruments validated in primary care to measure these consequences would aid in this effort. This study evaluated the validity of the Short Inventory of Problems-Alcohol and Drugs modified for Drug Use (SIP-DU) among subjects recruited from a primary care clinic (n= 106). SIP-DU internal consistency was evaluated using Cronbach's alphas, convergent validity by correlating the total SIP-DU score with the DAST-10, and construct validity by analyzing the factor structure. The SIP-DU demonstrated high internal consistency (Cronbach's alpha for overall scale .95, subscales .72-.90) comparable with other SIP versions and correlated well with the DAST-10 (r= .70). Confirmatory factor analysis suggested an unacceptable fit of previously proposed factors; exploratory factor analyses suggested a single factor of drug use consequences. The SIP-DU offers primary care clinicians a valid and practical assessment tool for drug use consequences.

  13. Counterion and substrate effects on barrier heights of the hydrolytic kinetic resolution of terminal epoxides catalyzed by Co(III)-salen.

    PubMed

    Kennedy, Matthew R; Burns, Lori A; Sherrill, C David

    2015-01-15

    Density functional theory (DFT) has been applied to the proposed rate-limiting step of the hydrolytic kinetic resolution (HKR) of terminal epoxides as catalyzed by Co-salen-X (X = counterion) in order to resolve questions surrounding the mechanism. The present results indicate that the bimetallic mechanism proposed by Jacobsen shows nonadditive, cooperative catalysis with a larger reduction in barrier height than the sum of the barrier height reductions from the two monometallic reaction pathways. We computed barrier heights for the reaction using several counterions (chloride, acetate, tosylate, and hydroxide). For the three counterions that are experimentally active (chloride, acetate, and tosylate) the barrier heights are 35, 38, and 34 kJ mol(-1), respectively, while for hydroxide it is 48 kJ mol(-1). The similarity of the barrier heights for chloride, acetate, and tosylate is in agreement with their similar peak reaction rates. The finding that Co-salen-X with these counterions leads to rather different overall reaction profiles suggests that they have quite different rates of reaction with epoxide to form the activated Co-salen-OH required for the bimetallic mechanism. Co-salen-OH is inactive as the sole catalyst for HKR, and this inactivity is ascribed to its larger barrier height for the ring-opening step, rather than to any inability to activate epoxide. Barrier heights were also computed using propylene oxide, 1-hexene oxide, and epichlorohydrin; propylene oxide and 1-hexene oxide have similar barrier heights, 35.5 and 33.2 kJ mol(-1), respectively, and epichlorohydrin has a significantly lower barrier height of 18.8 kJ mol(-1), which is qualitatively consistent with experiments showing faster reactions for epicholorohydrin than propylene oxide when catalyzed by Co-salen-OAc.

  14. Chelating ionic liquids for reversible zinc electrochemistry.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2013-05-21

    Advanced, high energy-density, metal-air rechargeable batteries, such as zinc-air, are of intense international interest due to their important role in energy storage applications such as electric and hybrid vehicles, and to their ability to deal with the intermittency of renewable energy sources such as solar and wind. Ionic liquids offer a number of ideal thermal and physical properties as potential electrolytes in such large-scale energy storage applications. We describe here the synthesis and characterisation of a family of novel "chelating" ILs designed to chelate and solubilize the zinc ions to create electrolytes for this type of battery. These are based on quaternary alkoxy alkyl ammonium cations of varying oligo-ether side chains and anions such as p-toluene sulfonate, bis(trifluoromethylsulfonyl)amide and dicyanoamides. This work shows that increasing the ether chain length in the cation from two to four oxygens can increase the ionic conductivity and reduce the melting point from 67 °C to 15 °C for the tosylate system. Changing the anion also plays a significant role in the nature of the zinc deposition electrochemistry. We show that zinc can be reversibly deposited from [N(222(20201))][NTf2] and [N(222(202020201))][NTf2] beginning at -1.4 V and -1.7 V vs. SHE, respectively, but not in the case of tosylate based ILs. This indicates that the [NTf2] is a weaker coordinating anion with the zinc cation, compared to the tosylate anion, allowing the coordination of the ether chain to dominate the behavior of the deposition and stripping of zinc ions.

  15. Synthesis of (R)-[2-2H]isopentenyl diphosphate and determination of its enantiopurity by 2H NMR spectroscopy in a lyotropic medium.

    PubMed

    Leyes, A E; Poulter, C D

    1999-10-07

    [formula: see text] The synthesis of (R)-[2-2H]isopentenyl diphosphate from D-mannitol 1,2:5,6-bis-acetonide in 10 steps is reported. Stereospecific incorporation of the label is achieved by a BF3-catalyzed NaCNBD3 reduction of the enantiomerically pure (S)-isopropylidene oxirane intermediate. The enantiomeric excess of the penultimate precursor [2-2H]isopentenyl tosylate (> 95% ee) was determined by 2H NMR spectroscopy in a poly-gamma-benzyl-L-glutamate/CH2Cl2 liquid crystal at -50 degrees C.

  16. 1-(4-Methyl­phenyl­sulfon­yl)-5,6-di­nitro-1H-indazole

    PubMed Central

    Oulemda, Bassou; Rakib, El Mostapha; Abbassi, Najat; Saadi, Mohamed; El Ammari, Lahcen

    2014-01-01

    In the title compound, C14H10N4O6S, the indazole ring system is almost perpendicular to the tosyl ring, as indicated by the dihedral angle of 89.40 (9)° between their planes. The dihedral angles between the indazole system and the nitro groups are 57.0 (3) and 31.9 (3)°. In the crystal, mol­ecules are linked by C—H⋯O inter­actions, forming chains running along [100]. PMID:24526962

  17. Iron-Catalyzed Cross-Coupling of Alkenyl Acetates.

    PubMed

    Gärtner, Dominik; Stein, André Luiz; Grupe, Sabine; Arp, Johannes; Jacobi von Wangelin, Axel

    2015-09-01

    Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand-free catalyst (1-2 mol%).

  18. Long-lived laser dye

    SciTech Connect

    Fletcher, A.N.

    1986-07-29

    A method is described of obtaining in a flashlamp pumped laser system, a long-lived flashpumped laser dye having a low threshold of lasing and a moderate output comprising the steps of: placing a dye solution comprising a laser dye, the N-methyl tosylate salt of 2-(4-pyridyl)-5-(4-methoxphenyl)oxazole, and a solvent into a laser dye cavity; screening the dye solution from ultraviolet light with an optical filter; flushing the dye solution with an inert gas; and optically pumping the dye solution with a flashlamp to produce laser emission.

  19. Synthesis of Laser Dyes

    DTIC Science & Technology

    1988-11-09

    block number) This report describes the progress made in attempts to prepare seven laser dyes. These dyes all have a 2-(L-pyridy.)-1,3- oxazole ...structure one dye, The synthesis of one dye, 2-(Ni-met.hyl-4-pyridiniiumi)pherianthroL9,10-dJ-1,3- oxazole tosylate (I) has been com-pleted. Preliminary...1,3- oxazoles . I~ 20 [IISTRI:’UTIGTJi/AVAILABILITY OF ABSTRACT 21. ABSTRACT SECURITY CLASSIFICATION 0UNITILA-,SIFIEDI.JNLiITED 0 SAME AS RPT El DTIC

  20. A 1H, 13C and 15N NMR study in solution and in the solid state of six N-substituted pyrazoles and indazoles.

    PubMed

    Claramunt, Rosa M; Santa María, M Dolores; Sanz, Dionisia; Alkorta, Ibon; Elguero, José

    2006-05-01

    Three N-substituted pyrazoles and three N-substituted indazoles [1-(4-nitrophenyl)-3,5-dimethylpyrazole (1), 1-(2,4-dinitrophenyl)-3,5-dimethylpyrazole (2), 1-tosyl-pyrazole (3), 1-p-chlorobenzoylindazole (4), 1-tosylinda-zole (5) and 2-(2-hydroxy-2-phenylethyl)-indazole (6)] have been studied by NMR spectroscopy in solution (1H, 13C, 15N) and in the solid state (13C, 15N). The chemical shifts have been compared with GIAO/DFT calculated absolute shieldings. Some discrepancies have been analyzed.

  1. Fluorine-18 chemistry in micro-reactors

    PubMed Central

    LU, SHUIYU; CHUN, JOONG-HYUN; PIKE, VICTOR W.

    2009-01-01

    Recent applications of micro-reactor (microfluidics) technology to radiofluorination chemistry within our laboratory are presented, based on use of either a simple T-shaped glass micro-reactor or a more advanced microfluidics instrument. The topics include reaction optimization and radioligand production, in particular the study of the radiofluorination of diaryliodonium salts, [18F]fluoride ion exchange with xenon difluoride, esterification with [18F]2-fluoroethyl tosylate, and the syntheses of [18F]fallypride, [18F]FBR and [18F]SL702 from [18F]fluoride ion. PMID:20936095

  2. Kinetics of Mediated Electron Transfer Between Viologen Groups in a Self-Assembled Monolayer and Metal Complexes in Solution

    DTIC Science & Technology

    1993-05-12

    was prepared in a similar manner to 1V1OSH. Bis [N-(n-decyl)-N’-(10-mercaptodecyl)-4,4’-bypridinium] disulfide dibromide (0OV10S-) 2 was prepared as...previously reported (5). Bis [N-(cholesteryl)-N’-(5-mercaptopentyl)-4,4’bipyridium] disulfide tosylate iodide (ChoV5S-) 2 Cholesteryl p-toluene...and excess Proton Sponge which was extracted by washing with 1% HCL 3 times. Bis [N-(n-lH,1H,2H,2H-perfluorododecyl)-N’-(5-mercaptopentyl)-4, 4

  3. Synthesis of Tetrahydro-1H-indeno[1,2-b]pyridine via Cascade Cyclization and Friedel-Crafts Reaction.

    PubMed

    Borthakur, Upasana; Borah, Madhurjya; Deka, Manash J; Saikia, Anil K

    2016-10-07

    A convenient protocol has been established for the synthesis of 1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine via cascade cyclization and Friedel-Crafts reaction of 4-methyl-N-(pent-4-yn-1-yl)benzenesulfonamides and aldehydes in good yields. The methodology has been used for the total synthesis of the antidepressant agent (±)-5-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine.

  4. Design of control laws for flutter suppression based on the aerodynamic energy concept and comparisons with other design methods

    NASA Technical Reports Server (NTRS)

    Nissim, Eli

    1990-01-01

    The aerodynamic energy method is used to synthesize control laws for NASA's drone for aerodynamic and structural testing-aerodynamic research wing 1 (DAST-ARW1) mathematical model. The performance of these control laws in terms of closed-loop flutter dynamic pressure, control surface activity, and robustness is compared with other control laws that relate to the same model. A control law synthesis technique that makes use of the return difference singular values is developed. It is based on the aerodynamic energy approach and is shown to yield results that are superior to those results given in the literature and are based on optimal control theory. Nyquist plots are presented, together with a short discussion regarding the relative merits of the minimum singular value as a measure of robustness as compared with the more traditional measure involving phase and gain margins.

  5. Design of control laws for flutter suppression based on the aerodynamic energy concept and comparisons with other design methods

    NASA Technical Reports Server (NTRS)

    Nissim, E.

    1989-01-01

    The aerodynamic energy method is used in this paper to synthesize control laws for NASA's Drone for Aerodynamic and Structural Testing-Aerodynamic Research Wing 1 (DAST-ARW1) mathematical model. The performance of these control laws in terms of closed-loop flutter dynamic pressure, control surface activity, and robustness is compared against other control laws that appear in the literature and relate to the same model. A control law synthesis technique that makes use of the return difference singular values is developed in this paper. it is based on the aerodynamic energy approach and is shown to yield results superior to those given in the literature and based on optimal control theory. Nyquist plots are presented together with a short discussion regarding the relative merits of the minimum singular value as a measure of robustness, compared with the more traditional measure of robustness involving phase and gain margins.

  6. NASA DFRC Practices for Prototype Qualification

    NASA Technical Reports Server (NTRS)

    Lokos, William A.

    2009-01-01

    This slide presentation reviews the practices that Dryden uses for qualification of the prototypes of aircraft. There are many views of aircraft that Dryden has worked with. Included is a discussion of basic considerations for strength, a listing of standards and references, a discussion of typical safety of flight approaches, a discussion of the prototype design, using the X-29A as an example, and requirements for new shapes (i.e., the DAST-ARW1 , F-8 Super Critical Wing, AFTI/F-111 MAW), new control laws (i.e., AAW F-18), new operating envelope (i.e., F-18 HARV), limited sope add-on or substitute structure (i.e., SR-71 LASRE, ECLIPSE, F-16XL SLFC), and extensively modified or replaced structure (i.e., SOFIA, B747SP). There is a listing of causes for the failure of the prototype.

  7. Intense THz radiation produced in organic salt crystals for high-field applications

    NASA Astrophysics Data System (ADS)

    Vicario, C.; Ruchert, C.; Hauri, C. P.

    2013-03-01

    Organic stilbazolium salt crystals pumped by intense, ultrashort mid-infrared laser have been investigated for efficient THz generation by optical rectification. In this paper we present our latest results in view of the generation of single-cycle and high-field THz transient in the THz gap (0.1-10 THz). The organic rectifiers like DAST, OH1 and DSTMS combine extremely large optical susceptibility with excellent velocity matching between the infrared pump and the THz radiation. Our simple collinear conversion scheme provides THz beams with excellent focusing properties and single cycle electric field larger than 1.5 MV/cm and magnetic field strength beyond 0.5 Tesla. The source can potentially cover the full THz gap at field strength which is barely provided by other THz sources. The THz pulse is carrier-envelope phase stable and the polarity of the field can be easily inverted.

  8. Chiral Resolution and Serendipitous Fluorination Reaction for the Selective Dopamine D3 Receptor Antagonist BAK2-66

    PubMed Central

    2014-01-01

    The improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)1H-indole-2-carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however, it had lower D3R affinity and enantioselectivity than (R)-PG648. Further, importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutyl-product (8). PMID:24944737

  9. Ultra Broadband High Sensitivity Electro-optic Field Sensors

    NASA Astrophysics Data System (ADS)

    Wieting, Terence J.; Qadri, Syed B.; Wu, Dong Ho

    2004-03-01

    We have carried out electro-optics experiments for the development of high sensitivity EO field sensors that detect electric fields noninvasively over a very broad frequency range. Presently we have obtained a maximum field sensitivity about 2 mV/m and the sensor has been tested over the frequency range of 0.1 Hz -200 MHz. We have used various EO materials, which include LiNbO_3, (Sr,Ba)Nb_2O_6, and DAST. Currently we are testing the sensors at frequencies of 200 MHz through 50 GHz, and also improving the sensors to achieve the field sensitivity to be better than 2 μ V/m. We found that even a small variation of materials properties greatly alters the sensors characteristics. We will present detailed sensor's characteristics that are obtained with various materials' chemical and physical properties.

  10. Analysis of the B_{c}^{+} to D_{s}^{+} overline {K}^{0^{ast }} decay

    NASA Astrophysics Data System (ADS)

    Asadi, A.; Mehraban, H.

    2017-01-01

    We analysed the process of Bc+{to } Ds+overline {K}^{0^{ast } } using QCD factorization (QCDF) and final-state interaction (FSI) effects. First, the Bc+{to } Ds+overline {K}^{0^{ast } } decay is calculated using QCDF method. The value found by using the QCDF method is less than the experimental value. Then we considered FSI effect as a sizable correction where the intermediate state D^{+^{ast } }π 0 mesons via the exchange of K0(K^{0^{ast } }) are produced. To consider the amplitudes of this intermediate state, the QCDF approach was used. The experimental branching ratio of Bc+{to } Ds+overline {K}^{0^{ast } } decay is less than 0.4×10-6 and our results are (0.21±0.04)×10-7 and (0.37±0.05)×10-6 from QCDF and FSI, respectively.

  11. Steady pressure measurements on an Aeroelastic Research Wing (ARW-2)

    NASA Technical Reports Server (NTRS)

    Sandford, Maynard C.; Seidel, David A.; Eckstrom, Clinton V.

    1994-01-01

    Transonic steady and unsteady pressure tests have been conducted in the Langley transonic dynamics tunnel on a large elastic wing known as the DAST ARW-2. The wing has a supercritical airfoil, an aspect ratio of 10.3, a leading-edge sweep back angle of 28.8 degrees, and two inboard and one outboard trailing-edge control surfaces. Only the outboard control surface was deflected to generate steady and unsteady flow over the wing during this study. Only the steady surface pressure, control-surface hinge moment, wing-tip deflection, and wing-root bending moment measurements are presented. The results from this elastic wing test are in tabulated form to assist in calibrating advanced computational fluid dynamics (CFD) algorithms.

  12. Investigation and suppression of high dynamic response encountered on an elastic supercritical wing

    NASA Technical Reports Server (NTRS)

    Seidel, David A.; Adams, William M., Jr.; Eckstrom, Clinton V.; Sandford, Maynard C.

    1989-01-01

    The DAST Aeroelastic Research Wing had been previously in the NASA Langley TDT and an unusual instability boundary was predicted based upon supercritical response data. Contrary to the predictions, no instability was found during the present test. Instead a region of high dynamic wing response was observed which reached a maximum value between Mach numbers 0.92 and 0.93. The amplitude of the dynamic response increased directly with dynamic pressure. The reponse appears to be related to chordwise shock movement in conjunction with flow separation and reattachment on the upper and lower wing surfaces. The onset of flow separation coincided with the occurrence of strong shocks on a surface. A controller was designed to suppress the wing response. The control law attenuated the response as compared with the uncontrolled case and added a small but significant amount of damping for the lower density condition.

  13. Advanced solar dynamic space power systems perspectives, requirements and technology needs

    NASA Technical Reports Server (NTRS)

    Dustin, M. O.; Savino, J. M.; Lacy, D. E.; Migra, R. P.; Juhasz, A. J.; Coles, C. E.

    1986-01-01

    Projected NASA, Civil, Commercial, and Military missions will require space power systems of increased versatility and power levels. The Advanced Solar Dynamic (ASD) Power systems offer the potential for efficient, lightweight, survivable, relatively compact, long-lived space power systems applicable to a wide range of power levels (3 to 300 kWe), and a wide variety of orbits. The successful development of these systems could satisfy the power needs for a wide variety of these projected missions. Thus, the NASA Lewis Research Center has embarked upon an aggressive ASD reserach project under the direction of NASA's Office of Aeronautics and Space Technology (DAST). The project is being implemented through a combination of in-house and contracted efforts. Key elements of this project are missions analysis to determine the power systems requirements, systems analysis to identify the most attractive ASD power systems to meet these requirements, and to guide the technology development efforts, and technology development of key components.

  14. Final design and fabrication of an active control system for flutter suppression on a supercritical aeroelastic research wing

    NASA Technical Reports Server (NTRS)

    Hodges, G. E.; Mcgehee, C. R.

    1981-01-01

    The final design and hardware fabrication was completed for an active control system capable of the required flutter suppression, compatible with and ready for installation in the NASA aeroelastic research wing number 1 (ARW-1) on Firebee II drone flight test vehicle. The flutter suppression system uses vertical acceleration at win buttock line 1.930 (76), with fuselage vertical and roll accelerations subtracted out, to drive wing outboard aileron control surfaces through appropriate symmetric and antisymmetric shaping filters. The goal of providing an increase of 20 percent above the unaugmented vehicle flutter velocity but below the maximum operating condition at Mach 0.98 is exceeded by the final flutter suppression system. Results indicate that the flutter suppression system mechanical and electronic components are ready for installation on the DAST ARW-1 wing and BQM-34E/F drone fuselage.

  15. Changes in Elementary Student Perceptions of Science, Scientists and Science Careers after Participating in a Curricular Module on Health and Veterinary Science

    PubMed Central

    Shin, Soo Yeon; Parker, Loran Carleton; Adedokun, Omolola; Mennonno, Ann; Wackerly, Amy; SanMiguel, Sandra

    2015-01-01

    This study examined to what extent a curriculum module that uses animal and human health scientists and science concepts to portray science and scientists in a relevant and authentic manner could enhance elementary students’ aspiration for science careers, attitudes to science, positive perceptions of scientists, and perceived relevance of science. The curriculum was developed by a research-based university program and has been put into practice in two early elementary classrooms in an urban school in the Midwest. An attitudinal rating survey and the Draw-A-Scientist Test (DAST) were used to assess pre to post changes in student attitudes toward science, perceptions of scientists, perceived relevance of science, and aspiration for science careers. Findings indicated that the implementation of this curriculum contributed positively to student attitudes toward science, decreased students’ stereotypical images of scientists, and increased student aspirations to become a scientist. PMID:26726271

  16. Elementary and middle school students' image of science and scientists related to current science textbooks in Taiwan

    NASA Astrophysics Data System (ADS)

    She, Hsiao-Ching

    1995-12-01

    This study examined elementary and middle school students' images of science and scientists, with an analysis of how those images may be influenced by science textbooks currently in use in Taiwan. A modified Chambers' Draw-a-Scientist Test (DAST) was administered to a total 289 students from grades 1, 3, 5 and 8. Results showed that upper-grade students drew more indicators (i.e., lab coats, eyeglasses, facial features, research and knowledge symbols, and relevant captions) than did lower-grade students. An analysis of individual drawings revealed an increase in sophistication and complexity according to progressively higher grade levels. It was found that students very often drew images strikingly similar to what their science textbook presented. It implicated that our current science textbooks indeed have some degree of influence on students' image of science and scientists.

  17. Changes in Elementary Student Perceptions of Science, Scientists and Science Careers after Participating in a Curricular Module on Health and Veterinary Science.

    PubMed

    Shin, Soo Yeon; Parker, Loran Carleton; Adedokun, Omolola; Mennonno, Ann; Wackerly, Amy; SanMiguel, Sandra

    2015-10-01

    This study examined to what extent a curriculum module that uses animal and human health scientists and science concepts to portray science and scientists in a relevant and authentic manner could enhance elementary students' aspiration for science careers, attitudes to science, positive perceptions of scientists, and perceived relevance of science. The curriculum was developed by a research-based university program and has been put into practice in two early elementary classrooms in an urban school in the Midwest. An attitudinal rating survey and the Draw-A-Scientist Test (DAST) were used to assess pre to post changes in student attitudes toward science, perceptions of scientists, perceived relevance of science, and aspiration for science careers. Findings indicated that the implementation of this curriculum contributed positively to student attitudes toward science, decreased students' stereotypical images of scientists, and increased student aspirations to become a scientist.

  18. Control of neural stem cell adhesion and density by an electronic polymer surface switch.

    PubMed

    Saltó, Carmen; Saindon, Emilien; Bolin, Maria; Kanciurzewska, Anna; Fahlman, Mats; Jager, Edwin W H; Tengvall, Pentti; Arenas, Ernest; Berggren, Magnus

    2008-12-16

    Adhesion is an essential parameter for stem cells. It regulates the overall cell density along the carrying surface, which further dictates the differentiation scheme of stem cells toward a more matured and specified population as well as tissue. Electronic control of the seeding density of neural stem cells (c17.2) is here reported. Thin electrode films of poly(3,4-ethylenedioxythiophene) (PEDOT):Tosylate were manufactured along the floor of cell growth dishes. As the oxidation state of the conjugated polymer electrodes was controlled, the seeding density could be varied by a factor of 2. Along the oxidized PEDOT:Tosylate-electrodes, a relatively lower density of, and less tightly bonded, human serum albumin (HSA) was observed as compared to reduced electrodes. We found that this favors adhesion of the specific stem cells studied. Surface analysis experiments, such as photoelectron spectroscopy, and water contact angle measurements, were carried out to investigate the mechanisms responsible for the electronic control of the seeding density of the c17.2 neural stem cells. Further, our findings may provide an opening for electronic control of stem cell differentiation.

  19. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

    Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

    2014-01-01

    Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

  20. A fibrinolytic protease AfeE from Streptomyces sp. CC5, with potent thrombolytic activity in a mouse model.

    PubMed

    Sun, Zhibin; Liu, Pingping; Cheng, Guangyan; Zhang, Biying; Dong, Weiliang; Su, Xingli; Huang, Yan; Cui, Zhongli; Kong, Yi

    2016-04-01

    Fibrinolytic proteases have potential applications in cardiovascular disease therapy. A novel fibrinolytic protease, AfeE, with strong thrombolytic activity was purified from Streptomyces sp. CC5. AfeE displayed maximum activity at 40°C in the pH range of 7.0-12.0. It was strongly inhibited by serine protease inhibitor phenylmethanesulfonylfluoride, soybean trypsin inhibitor, tosyl-l-lysine chloromethyl ketone and tosyl-l-phenylalanine chloromethyl ketone. The activity of the enzyme was partially inhibited by Cu(2+), Co(2+) and Zn(2+). AfeE exhibited higher substrate specificity for fibrin than fibrinogen, which has rarely been reported in fibrinolytic enzymes. AfeE also showed high thrombolytic activity in a carrageenan-induced mouse tail thrombosis model. AfeE prolonged prothrombin time, activated partial thromboplastin time, and thrombin time in rat blood. A bleeding time assay revealed that AfeE did not prolong bleeding time in mice at a dose of 1mg/kg. No acute cytotoxicity was observed for AfeE at 320μg/well in human umbilical vein endothelial cells. The afeE gene was cloned from the genome of Streptomyces sp. CC5. Full-length AFE-CC5E contained 434 amino acids and was processed into a mature form consisting 284 amino acids by posttranslational modification, as revealed by high-resolution mass spectrometry analysis. These results indicate that AfeE is a prospective candidate for antithrombotic drug development.

  1. A study of anhydrocelluloses--is a cellulose structure with residues in a 1C4-conformation more prone to hydrolysis?

    PubMed

    Jadhav, Vrushali; Pedersen, Christian M; Bols, Mikael

    2011-11-07

    A study of the effect of introduction of 3,6-anhydroglucose residues in the cellulose structure on glycoside hydrolysis rate was performed. A cellotetrose with an 3,6-anhydroglucose as the third residue was synthesised. Acidic hydrolysis of this tetrasaccharide showed that hydrolysis of the 3,6-anhydro-β-D-glucoside linkage was 31.400 times faster than hydrolysis of cellobiose. A series of different 3,6-anhydrocelluloses with different degree of substitution were prepared by tosylation of cellulose with varying amounts of tosyl chloride in dimethylacetamide and subsequent treatment with sodium hydroxide. Anhydrocelluloses with degrees of substitution of 0.02, 0.07, 0.31 and 0.74 were obtained. The anhydrocelluloses were subjected to acidic hydrolysis in 2.0 M aqueous HCl and the rate of hydrolysis monitored by ion chromatography analysis of the amount of glucose and/or cellobiose formed. All 3,6-anhydrocelluloses hydrolyzed with a faster rate than cellulose, but the anhydrocellulose with a low degree of substitution (ds = 0.07) hydrolyzed fastest which was 90 times faster than cellulose.

  2. One-step preparation of enantiopure L- or D-amino acid benzyl esters avoiding the use of banned solvents.

    PubMed

    Bolchi, Cristiano; Bavo, Francesco; Pallavicini, Marco

    2017-03-03

    The enantiomers of amino acid benzyl esters are very important synthetic intermediates. Many of them are currently prepared by treatment with benzyl alcohol and p-toluenesulfonic acid in refluxing benzene or carbon tetrachloride, to azeotropically remove water, and then precipitated as tosylate salt by adding diethyl ether. Here, we report a very efficient preparation of eight L- or D-amino acid benzyl esters (Ala, Phe, Tyr, Phg, Val, Leu, Lys, Ser), in which these highly hazardous solvents are dismissed using cyclohexane as a water azeotroping solvent and ethyl acetate to precipitate the tosylate salt. With some work-up modifications and lower yield, the procedure can be applied also to methionine. Chiral HPLC analysis shows that all the benzyl esters, including the highly racemizable ones such as those of phenylglycine, tyrosine and methionine, are formed enantiomerically pure under these new reaction conditions thus validating the solvents replacement. Contrariwise, toluene cannot be used in place of benzene or carbon tetrachloride because leading to partially or totally racemized amino acid benzyl esters depending on the polar effect of the amino acid α-side chain as expressed by Taft's substituent constant (σ*).

  3. Hepatitis Virus Infections in Poultry.

    PubMed

    Yugo, Danielle M; Hauck, Ruediger; Shivaprasad, H L; Meng, Xiang-Jin

    2016-09-01

    Viral hepatitis in poultry is a complex disease syndrome caused by several viruses belonging to different families including avian hepatitis E virus (HEV), duck hepatitis B virus (DHBV), duck hepatitis A virus (DHAV-1, -2, -3), duck hepatitis virus Types 2 and 3, fowl adenoviruses (FAdV), and turkey hepatitis virus (THV). While these hepatitis viruses share the same target organ, the liver, they each possess unique clinical and biological features. In this article, we aim to review the common and unique features of major poultry hepatitis viruses in an effort to identify the knowledge gaps and aid the prevention and control of poultry viral hepatitis. Avian HEV is an Orthohepevirus B in the family Hepeviridae that naturally infects chickens and consists of three distinct genotypes worldwide. Avian HEV is associated with hepatitis-splenomegaly syndrome or big liver and spleen disease in chickens, although the majority of the infected birds are subclinical. Avihepadnaviruses in the family of Hepadnaviridae have been isolated from ducks, snow geese, white storks, grey herons, cranes, and parrots. DHBV evolved with the host as a noncytopathic form without clinical signs and rarely progressed to chronicity. The outcome for DHBV infection varies by the host's ability to elicit an immune response and is dose and age dependent in ducks, thus mimicking the pathogenesis of human hepatitis B virus (HBV) infections and providing an excellent animal model for human HBV. DHAV is a picornavirus that causes a highly contagious virus infection in ducks with up to 100% flock mortality in ducklings under 6 wk of age, while older birds remain unaffected. The high morbidity and mortality has an economic impact on intensive duck production farming. Duck hepatitis virus Types 2 and 3 are astroviruses in the family of Astroviridae with similarity phylogenetically to turkey astroviruses, implicating the potential for cross-species infections between strains. Duck astrovirus (DAstV) causes

  4. Enantioselective Lewis acid-catalyzed Mukaiyama-Michael reactions of acyclic enones. Catalysis by allo-threonine-derived oxazaborolidinones.

    PubMed

    Wang, Xiaowei; Adachi, Shinya; Iwai, Hiroyoshi; Takatsuki, Hiroshi; Fujita, Katsuhiro; Kubo, Mikako; Oku, Akira; Harada, Toshiro

    2003-12-26

    allo-Threonine-derived O-aroyl-B-phenyl-N-tosyl-1,3,2-oxazaborolidin-5-ones 1g,n catalyze the asymmetric Mukaiyama-Michael reaction of acyclic enones with a trimethylsilyl ketene S,O-acetal in high enantioselectivity. A range of alkenyl methyl ketones is successfully employed as Michael acceptors affording ee values of 85-90% by using 10 mol % of the catalyst. The use of 2,6-diisopropylphenol and tert-butyl methyl ether as additives is found to be essential to achieve high enantioselectivity in these reactions. The effects of the additives are discussed in terms of the retardation of an Si(+)-catalyzed racemic pathway, which seriously deteriorates the enantioselectivity of asymmetric Mukaiyama-Michael reactions. A working model for asymmetric induction is proposed based on correlation between catalyst structures and enantioselectivities.

  5. A reagent-controlled SN2-glycosylation for the direct synthesis of β-linked 2-deoxy-sugars.

    PubMed

    Issa, John Paul; Bennett, Clay S

    2014-04-16

    The efficient and stereoselective construction of glycosidic linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as β-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce β-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an α-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an SN2-pathway.

  6. Mechanistic considerations on contact-active antimicrobial surfaces with controlled functional group densities.

    PubMed

    Bieser, Arno M; Tiller, Joerg C

    2011-04-08

    A series of N-alkyl-N,N-dimethyldeoxyammonium celluloses is synthesized by converting tosyl celluloses with DBA and DDA, respectively. Surface coatings with these water-insoluble derivatives contain well-defined densities of quaternary ammonium functions and nonactive hydrophobic and hydrophilic groups. It is shown that the antimicrobial activity of such surfaces against S. aureus requires a delicate balance between DDA, BDA, and hydrophobic groups. A mechanism is proposed that involves the selective adhesion of anionic phospholipids from the bacterial cell membrane. This so-called phospholipid sponge effect is supported by the fact that all coatings could be deactivated by treatment with SDS or negatively charged phospholipids, but not with neutral phospholipids.

  7. Identification and synthesis of 2-heptanethiol, a new flavor compound found in bell peppers.

    PubMed

    Simian, Hervé; Robert, Fabien; Blank, Imre

    2004-01-28

    2-Heptanethiol was identified for the first time as a constituent of red and green bell pepper extracts. The chemical structure of this new aroma compound was proposed on the basis of mass spectra and retention indices and confirmed by chemical synthesis and nuclear magnetic resonance spectroscopy measurements. Its aroma properties were described as sulfury, onion-like, and vegetable-like, reminiscent of bell pepper at lower concentrations, with an orthonasal detection threshold of 10 microg/L of water. No differences in odor note and threshold value were observed for the enantiomeric forms, which were prepared from enantiopure 2-heptanol by tosylation, followed by thioacetylation and reduction, giving the target thiol enantiomers.

  8. Oxydifluoromethylation of Alkenes by Photoredox Catalysis: Simple Synthesis of CF2H-Containing Alcohols.

    PubMed

    Arai, Yusuke; Tomita, Ren; Ando, Gaku; Koike, Takashi; Akita, Munetaka

    2016-01-22

    We have developed a novel and simple protocol for the direct incorporation of a difluoromethyl (CF2 H) group into alkenes by visible-light-driven photoredox catalysis. The use of fac-[Ir(ppy)3] (ppy=2-pyridylphenyl) photocatalyst and shelf-stable Hu's reagent, N-tosyl-S-difluoromethyl-S-phenylsulfoximine, as a CF2 H source is the key to success. The well-designed photoredox system achieves synthesis of not only β-CF2 H-substituted alcohols but also ethers and an ester from alkenes through solvolytic processes. The present method allows a single-step and regioselective formation of C(sp(3))-CF2 H and C(sp(3))-O bonds from C=C moiety in alkenes, such as hydroxydifluoromethylation, regardless of terminal or internal alkenes. Moreover, this methodology tolerates a variety of functional groups.

  9. Nickel-Catalyzed Mizoroki–Heck Reaction of Aryl Sulfonates and Chlorides with Electronically Unbiased Terminal Olefins: High Selectivity for Branched Products**

    PubMed Central

    Tasker, Sarah Z.; Gutierrez, Alicia C.

    2014-01-01

    Achieving high selectivity in the Heck reaction of electronically unbiased alkenes has been a longstanding challenge. Using a nickel-catalyzed cationic Heck reaction, we were able to achieve excellent selectivity for branched products (≥19:1 in all cases) over a wide range of aryl electrophiles and aliphatic olefins. A bidentate ligand with a suitable bite angle and steric profile was key to obtaining high branched/linear selectivity, while the appropriate base suppressed alkene isomerization of the product. Though aryl triflates are traditionally used to access the cationic Heck pathway, we have shown that by using triethylsilyl trifluoromethanesulfonate (TESOTf), we can effect a counterion exchange of the catalytic nickel complex such that cheaper and more stable aryl chlorides, mesylates, tosylates, and sulfamates can be used to yield the same branched products with high selectivity. PMID:24402966

  10. Synthesis and supramolecular association of immobilized NCN-pincer platinum(II) complexes on hyperbranched polyglycerol supports.

    PubMed

    Stiriba, Salah-Eddine; Slagt, Martijn Q; Kautz, Holger; Klein Gebbink, Robertus J M; Thomann, Ralf; Frey, Holger; van Koten, Gerard

    2004-03-05

    Pertosylation of hyperbranched polyglycerol (M(n)=2000; M(w)/M(n)=1.3) followed by partial displacement of the tosyl groups with carboxylic acid functionalized NCN-pincer platinum(II) complexes [PtI-2,6-(NMe(2)CH(2))(2)C(6)H(2)-4-COOH], resulted in covalent attachment of the NCN-pincer complexes to the polyglycerol. These functionalized hyperbranched macromolecules have been characterized by (1)H, (13)C, and (195)Pt NMR, UV-visible, and IR spectroscopy. The presence of Pt and I atoms renders them directly visible by transmission electron microscopy (TEM) without staining procedures, which offers images of associated hyperbranched macromolecules. TEM micrographs show disk-shaped structures with a small size-distribution (15-20 nm), and characteristic core-shell ring structures. The thickness of the corona observed in TEM could be correlated with the substitution degree with pincer platinum moieties.

  11. Targeted therapy for renal cell carcinoma: a new treatment paradigm

    PubMed Central

    2007-01-01

    Metastatic clear cell renal cell cancer has traditionally been treated with cytokines (interferon or interleukin-2). Improved understanding of biology has engendered novel targeted therapeutic agents that have altered the natural history of this disease. The vascular endothelial growth factor and its related receptor and the mTOR signal transduction pathway have particularly been exploited. Sunitinib malate, sorafenib tosylate, temsirolimus, and bevacizumab have improved clinical outcomes in randomized trials. Other multitargeted tyrosine kinase inhibitors (lapatinib, axitinib, pazopanib) and antiangiogenic agents (VEGF Trap, lenalidomide) have also demonstrated activity in early studies. Combinations of these agents are being evaluated. The future of the therapy of renal cancer appears promising owing to the efficacy of these novel agents. PMID:17637878

  12. Guided desaturation of unactivated aliphatics

    NASA Astrophysics Data System (ADS)

    Voica, Ana-Florina; Mendoza, Abraham; Gutekunst, Will R.; Fraga, Jorge Otero; Baran, Phil S.

    2012-08-01

    The excision of hydrogen from an aliphatic carbon chain to produce an isolated olefin (desaturation) without overoxidation is one of the most impressive and powerful biosynthetic transformations for which there are no simple and mild laboratory substitutes. The versatility of olefins and the range of reactions they undergo are unsurpassed in functional group space. Thus, the conversion of a relatively inert aliphatic system into its unsaturated counterpart could open new possibilities in retrosynthesis. In this article, the invention of a directing group to achieve such a transformation under mild, operationally simple, metal-free conditions is outlined. This ‘portable desaturase’ (TzoCl) is a bench-stable, commercial entity (Aldrich, catalogue number L510092) that is facile to install on alcohol and amine functionalities to ultimately effect remote desaturation, while leaving behind a synthetically useful tosyl group.

  13. Regioselective reductive cleavage of bis-benzylidene acetal: stereoselective synthesis of anticancer agent OGT2378 and glycosidase inhibitor 1,4-dideoxy-1,4-imino-l-xylitol.

    PubMed

    Aravind, Appu; Sankar, Muthukumar Gomathi; Varghese, Babu; Baskaran, Sundarababu

    2009-04-03

    A highly regioselective reductive cleavage of the bis-benzylidene acetal of D-mannitol was performed using a BF(3) x Et(2)O/Et(3)SiH reagent system. A chiral intermediate 6 thus obtained was efficiently utilized in the stereoselective synthesis of the anticancer agent OGT2378 (3) and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol (22). Chemoselective reduction of azido epoxide 10 followed by regioselective intramolecular cyclization of amino epoxide 11 resulted in the exclusive formation of deoxyidonojirimycin derivative 12. By changing the order of deprotection, the chiral intermediate 6 was readily transformed to glycosidase inhibitor derivative 22.

  14. Synthesis, crystal structure and self-organization of molecules containing 2,5-bis( o-amino-phenyl)-1,3,4-oxadiazoles unit and N-tos- L-amino acid residues

    NASA Astrophysics Data System (ADS)

    Zhao, Hongwu; Wei, Yongge; Hua, Wenting

    2000-10-01

    The title compound has been synthesized by the acylation reaction of 2,5-bis( o-amino-phenyl)-1,3,4-oxadiazoles with excess chiral N-tosyl- L-leucyl chloride in dry pyridine. Its crystal structure has been determined, the crystal data are: C 40H 46N 6O 7S 2, Monoclinic, p2(1), a=11.168(2) Å, b=15.967(3) Å, c=11.641(2) Å, α=90°, β=95.28(3)°, γ=90°, V=2067.0(6) Å3, Z=2. The molecule via its intermolecular CH⋯O and NH⋯O hydrogen bonds and planar conjugate aromatic heterocycles aggregation forms a unique regular aggregation.

  15. The convenient preparation of stable aryl-coated zerovalent iron nanoparticles

    PubMed Central

    Guselnikova, Olga A; Galanov, Andrey I; Gutakovskii, Anton K

    2015-01-01

    Summary A novel approach for the in situ synthesis of zerovalent aryl-coated iron nanoparticles (NPs) based on diazonium salt chemistry is proposed. Surface-modified zerovalent iron NPs (ZVI NPs) were prepared by simple chemical reduction of iron(III) chloride aqueous solution followed by in situ modification using water soluble arenediazonium tosylate. The resulting NPs, with average iron core diameter of 21 nm, were coated with a 10 nm thick organic layer to provide long-term protection in air for the highly reactive zerovalent iron core up to 180 °C. The surface-modified iron NPs possess a high grafting density of the aryl group on the NPs surface of 1.23 mmol/g. FTIR spectroscopy, XRD, HRTEM, TGA/DTA, and elemental analysis were performed in order to characterize the resulting material. PMID:26171295

  16. Convenient synthesis of 18F-radiolabeled R-(-)-N-n-propyl-2-(3-fluoropropanoxy-11-hydroxynoraporphine.

    PubMed

    Sromek, Anna W; Zhang, Shaohui; Akurathi, Vamsidhar; Packard, Alan B; Li, Wei; Alagille, David; Morley, Thomas J; Baldwin, Ronald; Tamagnan, Gilles; Neumeyer, John L

    2014-12-01

    Aporphines are attractive candidates for imaging D2 receptor function because, as agonists rather than antagonists, they are selective for the receptor in the high affinity state. In contrast, D2 antagonists do not distinguish between the high and low affinity states, and in vitro data suggests that this distinction may be important in studying diseases characterized by D2 dysregulation, such as schizophrenia and Parkinson's disease. Accordingly, MCL-536 (R-(-)-N-n-propyl-2-(3-[(18)F]fluoropropanoxy-11-hydroxynoraporphine) was selected for labeling with (18)F based on in vitro data obtained for the non-radioactive ((19)F) compound. Fluorine-18-labeled MCL-536 was synthesized in 70% radiochemical yield, >99% radiochemical purity, and specific activity of 167 GBq/µmol (4.5 Ci/µmol) using p-toluenesulfonyl (tosyl) both as a novel protecting group for the phenol and a leaving group for the radiofluorination.

  17. All polymer chip for amperometric studies of transmitter release from large groups of neuronal cells.

    PubMed

    Larsen, Simon T; Taboryski, Rafael

    2012-11-07

    We present an all polymer electrochemical chip for simple detection of transmitter release from large groups of cultured PC 12 cells. Conductive polymer PEDOT:tosylate microelectrodes were used together with constant potential amperometry to obtain easy-to-analyze oxidation signals from potassium-induced release of transmitter molecules. The nature of the resulting current peaks is discussed, and the time for restoring transmitter reservoirs is studied. The relationship between released transmitters and potassium concentration was found to fit to a sigmoidal dose-response curve. Finally, we demonstrate how the presented device can be used for simple drug screening purposes, by measuring the increase of transmitter release due to short-term treatment with L-DOPA.

  18. Lignin Modification for Biopolymer/Conjugated Polymer Hybrids as Renewable Energy Storage Materials.

    PubMed

    Nilsson, Ting Yang; Wagner, Michal; Inganäs, Olle

    2015-12-07

    Lignin derivatives, which arise as waste products from the pulp and paper industry and are mainly used for heating, can be used as charge storage materials. The charge storage function is a result of the quinone groups formed in the lignin derivative. Herein, we modified lignins to enhance the density of such quinone groups by covalently linking monolignols and quinones through phenolation. The extra guaiacyl, syringyl, and hydroquinone groups introduced by phenolation of kraft lignin derivatives were monitored by (31) P nuclear magnetic resonance and size exclusion chromatography. Electropolymerization in ethylene glycol/tetraethylammonium tosylate electrolyte was used to synthesize the kraft lignin/polypyrrole hybrid films. These modifications changed the phenolic content of the kraft lignin with attachment of hydroquinone units yielding the highest specific capacity (around 70 mA h g(-1) ). The modification of softwood and hardwood lignin derivatives yielded 50 % and 23 % higher charge capacity than the original lignin, respectively.

  19. Selectivity in the Addition Reactions of Organometallic Reagents to Aziridine-2-carboxaldehydes: The Effects of Protecting Groups and Substitution Patterns

    PubMed Central

    Kulshrestha, Aman; Schomaker, Jennifer M.; Holmes, Daniel; Staples, Richard J.; Jackson, James E.; Borhan, Babak

    2014-01-01

    Good to excellent stereo-selectivity has been found in the addition reactions of Grignard and organo-zinc reagents to N-protected aziridine-2-carboxaldehydes. Specifically, high syn selectivity was obtained with benzyl-protected cis, tert-butyloxycar-bonyl-protected trans, and tosyl-pro-tected 2,3-disubstituted aziridine-2-car-boxaldehydes. Furthermore, rate and selectivity effects of ring substituents, temperature, solvent, and Lewis acid and base modifiers were studied. The diastereomeric preference of addition is dominated by the substrate aziri-dines’ substitution pattern and especially the electronic character and conformational preferences of the nitrogen protecting groups. To help rationalize the observed stereochemical outcomes, conformational and electronic structural analyses of a series of model systems representing the various substitution patterns have been explored by density functional calculations at the B3LYP/6–31G* level of theory with the SM8 solvation model to account for solvent effects. PMID:21928447

  20. Synthesis of 3-fluoropyrrolidines and 4-fluoropyrrolidin-2-ones from allylic fluorides.

    PubMed

    Combettes, Lorraine E; Schuler, Marie; Patel, Rakesh; Bonillo, Baltasar; Odell, Barbara; Thompson, Amber L; Claridge, Tim D W; Gouverneur, Véronique

    2012-10-08

    Various 3-fluoropyrrolidines and 4-fluoropyrrolidin-2-ones were prepared by 5-exo-trig iodocyclisation from allylic fluorides bearing a pending nitrogen nucleophile. These bench-stable precursors were made accessible upon electrophilic fluorination of the corresponding allylsilanes. The presence of the allylic fluorine substituent induces syn-stereocontrol upon iodocyclisation with diastereomeric ratios ranging from 10:1 to > 20:1 for all N-tosyl-3-fluoropent-4-en-1-amines and amides. The sense and level of stereocontrol is strikingly similar to the corresponding iodocyclisation of structurally related allylic fluorides bearing pending oxygen nucleophiles. These results suggest that the syn selectivity observed upon ring closure involves I(2)-π complexes with the fluorine positioned inside.

  1. Bis(dialkylamide)hydrogen dibromobromate precursors of hypobromite ion in reactions with nerve and blister agent simulants.

    PubMed

    Simanenko, Yuri S; Savelova, Vera A; Prokop'eva, Tatyana M; Mikhailov, Vasily A; Turovskaya, Marya K; Karpichev, Eugen A; Popov, Anatolii F; Gillitt, Nicholas D; Bunton, Clifford A

    2004-12-24

    Hypobromite ion, BrO(-), is an effective alpha-nucleophile that reacts rapidly with activated phosphorus(V) and sulfonate esters. The parent acid rapidly oxidizes organic sulfides and aryloxide ions. At pH 10-11 BrO(-) and HOBr coexist in water and are potentially useful as decontaminants of chlorosulfide blister agents and the phosphonyl nerve agents. Bis(dialkylamide)hydrogen dibromobromates are well characterized, stable, solids which rapidly form HOBr-BrO(-) in mildly alkaline water. Reactions of 4-nitrophenyl diethyl phosphate and phosphonate, which are simulants of the phosphonofluoridate nerve agents, and of 4-nitrophenyl tosylate, with BrO(-) are rapid (t(1/2) = 60-700 s) with 0.1 M BrO(-), under conditions in which oxidations of organic sulfides are too fast to be followed by conventional methods.

  2. Enantioselective Construction of Pyrrolidines by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Imines

    PubMed Central

    Trost, Barry M.; Silverman, Steven M.

    2012-01-01

    A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo-, and enantioselectivity. Use of a diphenylazetidine ligand allows the complimentary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters. PMID:22309214

  3. Aqua­bis­(4-methyl­benzene­sulfonato-κO)(η5-penta­methyl­cyclo­penta­dien­yl)rhodium(III) monohydrate

    PubMed Central

    Roy, Christopher P.; Boyer, Pauline M.; Merola, Joseph S.

    2013-01-01

    The title half-sandwich rhodium(III) complex, [Rh(C10H15)(C7H7O3S)2(H2O)]·H2O, consists of a π-bonded penta­methyl­cyclo­penta­dienyl group, two σ-bonded tosyl­ate groups and an aqua ligand. The structure displays both inter- and intra­molecular O—H⋯O hydrogen bonding. The inter­molecular hydrogen bonding results in an extended helical chain along a 21 screw axis parallel to c, due to hydrogen bonding from the coordinating water ligand to the lattice water mol­ecule and then to a sulfonate O atom of a different asymmetric unit. PMID:23723770

  4. Synthesis of a phenolic precursor and its efficient O-[18F]fluoroethylation with purified no-carrier-added [18F]2-fluoroethyl brosylate as the labeling agent.

    PubMed

    Jarkas, Nashwa; Voll, Ronald J; Goodman, Mark M

    2013-09-01

    [(18)F]2-Fluoroethyl-p-toluenesulfonate also called [(18)F]2-fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [(18)F]2-Fluoroethyl-4-bromobenzenesulfonate, also called [(18)F]2-fluoroethyl brosylate ([(18)F]F(CH2)2OBs), was used as an alternative radiolabeling agent to prepare [(18)F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O-fluoroethylating the phenolic precursor. Purified by reverse-phase HPLC, the no-carrier-added [(18)F]F(CH2)2OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [(18)F]F(CH2)2OBs with the phenolic precursor was performed by heating in DMF and successfully produced [(18)F]FEOHOMADAM, after HPLC purification, in RCY of 21%.

  5. Convenient Synthesis of 18F-Radiolabeled R-(−)-N-n-propyl-2-(3-fluoropropanoxy-11-hydroxynoraporphine

    PubMed Central

    Sromek, Anna W.; Zhang, Shaohui; Akurathi, Vamsidar; Packard, Alan B.; Li, Wei; Alagille, David; Morley, Thomas J.; Baldwin, Ronald; Tamagnan, Gilles; Neumeyer, John L.

    2014-01-01

    Aporphines are attractive candidates for imaging D2 receptor function because, as agonists rather than antagonists, they are selective for the receptor in the high affinity state. In contrast, D2 antagonists do not distinguish between the high and low affinity states, and in vitro data suggests that this distinction may be important in studying diseases characterized by D2 dysregulation, such as schizophrenia and Parkinson’s disease. Accordingly, MCL-536 (R-(−)-N-n-propyl-2-(3-[18F]fluoropropanoxy-11-hydroxynoraporphine) was selected for labeling with 18F based on in vitro data obtained for the non-radioactive (19F) compound. Fluorine-18-labeled MCL-536 was synthesized in 70% radiochemical yield, >99% radiochemical purity and specific activity of 167 GBq/μmol (4.5 Ci/μmol) using p-toluenesulfonyl (tosyl) both as a novel protecting group for the phenol and a leaving group for the radiofluorination. PMID:25400260

  6. Charge-transport model for conducting polymers

    NASA Astrophysics Data System (ADS)

    Dongmin Kang, Stephen; Jeffrey Snyder, G.

    2016-11-01

    The growing technological importance of conducting polymers makes the fundamental understanding of their charge transport extremely important for materials and process design. Various hopping and mobility edge transport mechanisms have been proposed, but their experimental verification is limited to poor conductors. Now that advanced organic and polymer semiconductors have shown high conductivity approaching that of metals, the transport mechanism should be discernible by modelling the transport like a semiconductor with a transport edge and a transport parameter s. Here we analyse the electrical conductivity and Seebeck coefficient together and determine that most polymers (except possibly PEDOT:tosylate) have s = 3 and thermally activated conductivity, whereas s = 1 and itinerant conductivity is typically found in crystalline semiconductors and metals. The different transport in polymers may result from the percolation of charge carriers from conducting ordered regions through poorly conducting disordered regions, consistent with what has been expected from structural studies.

  7. A chymotrypsin-like proteinase from the midgut of Tenebrio molitor larvae.

    PubMed

    Elpidina, E N; Tsybina, T A; Dunaevsky, Y E; Belozersky, M A; Zhuzhikov, D P; Oppert, B

    2005-08-01

    A chymotrypsin-like proteinase was isolated from the posterior midgut of larvae of the yellow mealworm, Tenebrio molitor, by ion-exchange and gel filtration chromatography. The enzyme, TmC1, was purified to homogeneity as determined by SDS-PAGE and postelectrophoretic activity detection. TmC1 had a molecular mass of 23.0 kDa, pI of 8.4, a pH optimum of 9.5, and the optimal temperature for activity was 51 degrees C. The proteinase displayed high stability at temperatures below 43 degrees C and in the pH range 6.5-11.2, which is inclusive of the pH of the posterior and middle midgut. The enzyme hydrolyzed long chymotrypsin peptide substrates SucAAPFpNA, SucAAPLpNA and GlpAALpNA and did not hydrolyze short chymotrypsin substrates. Kinetic parameters of the enzymatic reaction demonstrated that the best substrate was SucAAPFpNA, with k(cat app) 36.5 s(-1) and K(m) 1.59 mM. However, the enzyme had a lower K(m) for SucAAPLpNA, 0.5 mM. Phenylmethylsulfonyl fluoride (PMSF) was an effective inhibitor of TmC1, and the proteinase was not inhibited by either tosyl-l-phenylalanine chloromethyl ketone (TPCK) or N(alpha)-tosyl-l-lysine chloromethyl ketone (TLCK). However, the activity of TmC1 was reduced with sulfhydryl reagents. Several plant and insect proteinaceous proteinase inhibitors were active against the purified enzyme, the most effective being Kunitz soybean trypsin inhibitor (STI). The N-terminal sequence of the enzyme was IISGSAASKGQFPWQ, which was up to 67% similar to other insect chymotrypsin-like proteinases and 47% similar to mammalian chymotrypsin A. The amino acid composition of TmC1 differed significantly from previously isolated T. molitor enzymes.

  8. Radionuclide-binding compound, a radionuclide delivery system, a method of making a radium complexing compound, a method of extracting a radionuclide, and a method of delivering a radionuclide

    DOEpatents

    Fisher, Darrell R.; Wai, Chien M.; Chen, Xiaoyuan

    2000-01-01

    The invention pertains to compounds which specifically bind radionuclides, and to methods of making radionuclide complexing compounds. In one aspect, the invention includes a radionuclide delivery system comprising: a) a calix[n]arene-crown-[m]-ether compound, wherein n is an integer greater than 3, and wherein m is an integer greater than 3, the calix[n]arene-crown-[m]-ether compound comprising at least two ionizable groups; and b) an antibody attached to the calix[n]arene-crown-[m]-ether compound. In another aspect, the invention includes a method of making a radium complexing compound, comprising: a) providing a calix[n]arene compound, wherein n is an integer greater than 3, the calix[n]arene compound comprising n phenolic hydroxyl groups; b) providing a crown ether precursor, the crown ether precursor comprising a pair of tosylated ends; c) reacting the pair of tosylated ends with a pair of the phenolic hydroxyl groups to convert said pair of phenolic hydroxyl groups to ether linkages, the ether linkages connecting the crown ether precursor to the calix[n]arene to form a calix[n]arene-crown-[m]-ether compound, wherein m is an integer greater than 3; d) converting remaining phenolic hydroxyl groups to esters; e) converting the esters to acids, the acids being proximate a crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound; and f) providing a Ra.sup.2+ ion within the crown-[m]-ether portion of the calix[n]arene-crown-[m]-ether compound.

  9. A critical assessment of the effect of serine protease inhibitors on porcine fertilization and quality parameters of porcine spermatozoa in vitro.

    PubMed

    Beek, J; Maes, D; Nauwynck, H; Piepers, S; Van Soom, A

    2015-03-01

    Proteases play an important role during mammalian fertilization. Their function is frequently investigated using specific inhibitors. We analyzed four serine protease inhibitors [4-(2-aminoethyl) benzene sulfonyl fluoride hydrochloride (AEBSF), soybean trypsin inhibitor from glycine max (STI), Nα-tosyl-L-lysine-chloromethyl ketone hydrochloride (TLCK) and N(p)-tosyl-L-phenylalanine-chloromethyl ketone (TPCK)] for their in vitro effect on fertilization and sperm quality in pigs. Inhibitor concentrations were chosen based on the reduction of fertilization rate during preliminary dose-response experiments with cryopreserved epididymal spermatozoa. The inhibitor effects on in vitro fertilization (IVF) and sperm parameters (membrane and acrosomal integrity, motility and mitochondrial membrane potential - MMP) were evaluated using diluted fresh semen. AEBSF (100 μM), TLCK (100 μM) and TPCK (100 μM) decreased total fertilization and polyspermy rates by at least 50%. STI (5 μM) lowered total fertilization rates but not the level of polyspermy. AEBSF and TPCK reduced fertilization parameters to a similar degree using cryopreserved epididymal spermatozoa (dose-response experiment) or diluted fresh semen. Inhibition by STI was more pronounced using cryopreserved epididymal spermatozoa, whereas TLCK inhibited IVF only with diluted fresh semen. AEBSF and STI had no effect on sperm parameters, and TLCK significantly reduced motility. TPCK diminished MMP and motility and affected membrane and acrosomal integrity in a negative way. In summary, serine protease inhibitors differed in the way they reduce the fertilization rate. These results emphasize the necessity of inhibitor testing before they can be applied in fertilization studies. AEBSF and STI can be used in the future IVF studies without compromising sperm quality.

  10. Metal-catalysed oxidation processes in thiosemicarbazones: new complexes with the ligand N-{2-([4-N-ethylthiosemicarbazone]methyl)phenyl}-p-toluenesulfonamide.

    PubMed

    Pedrido, Rosa; Romero, María J; Bermejo, Manuel R; González-Noya, Ana M; García-Lema, Iria; Zaragoza, Guillermo

    2008-01-01

    The coordination behaviour of a new thiosemicarbazone Schiff-base building block, N-{2-([4-N-ethylthiosemicarbazone]methyl)phenyl}-p-toluenesulfonamide, H2L1 (1), incorporating a bulky tosyl group, towards Mn II, Fe II, Co II, Ni II, Cu II, Zn II, Cd II, Ag I, Sn II, and Pb II has been investigated by means of an electrochemical preparative procedure. Most metal complexes of L1 have the general formula [M(L1)]2.nX (M=Mn, Fe, Co, Ni, Cu, Cd, Pb; n=0-4, X=H2O or CH3CN), as confirmed by the structure of [Pb(L1)]2 (15), in which the lone pair on lead is stereochemically active. This lead(II) complex shows an intense fluorescence emission with a quantum yield of 0.13. In the case of silver, the complex formed was found to possess a stoichiometry of [Ag2(L1)]2.3H2O. During reactions with manganese and copper metals, interesting catalysed processes have been found to take place, with remarkable consequences regarding the ligand skeleton structure. In synthesising the manganese complex, we obtained an unexpected dithiolate thiosemicarbazone tosyl ligand, H2L2, as a side-product, which has been fully characterised, including by X-ray diffraction analysis. In the case of copper, the solid complex has the formula [CuL1]2, but the crystallised product shows the copper atoms coordinated to a new cyclised thiosemicarbazone ligand, H2L3, as in the structures of the complexes [Cu(L3)]2.CH3CN (8) and [Cu(L3)(H2O)]2.CH3CN.H2O (9). The zinc complex [Zn(L1)]4 (12) displays a particular tetranuclear zeolite-type structure capable of hosting small molecules or ions, presumably through hydrogen bonding.

  11. Asymmetric Synthesis of Spirocyclic 2-Benzopyrans for Positron Emission Tomography of σ1 Receptors in the Brain

    PubMed Central

    Holl, Katharina; Schepmann, Dirk; Fischer, Steffen; Ludwig, Friedrich-Alexander; Hiller, Achim; Donat, Cornelius K.; Deuther-Conrad, Winnie; Brust, Peter; Wünsch, Bernhard

    2014-01-01

    Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded chiral triols (R)-7 and (S)-7, which were cyclized with tosyl chloride in the presence of Bu2SnO to provide 2-benzopyrans (R)-4 and (S)-4 with high regioselectivity. The additional hydroxy moiety in the 4-position was exploited for the introduction of various substituents. Williamson ether synthesis and replacement of the Boc protective group with a benzyl moiety led to potent σ1 ligands with high σ1/σ2-selectivity. With exception of the ethoxy derivative 16, the (R)-configured enantiomers represent eutomers with eudismic ratios of up to 29 for the ester (R)-18. The methyl ether (R)-15 represents the most potent σ1 ligand of this series of compounds, with a Ki value of 1.2 nM and an eudismic ratio of 7. Tosylate (R)-21 was used as precursor for the radiosynthesis of [18F]-(R)-20, which was available by nucleophilic substitution with K[18F]F K222 carbonate complex. The radiochemical yield of [18F]-(R)-20 was 18%–20%, the radiochemical purity greater than 97% and the specific radioactivity 175–300 GBq/µmol. Although radiometabolites were detected in plasma, urine and liver samples, radiometabolites were not found in brain samples. After 30 min, the uptake of the radiotracer in the brain was 3.4% of injected dose per gram of tissue and could be reduced by coadministration of the σ1 antagonist haloperidol. [18F]-(R)-20 was able to label those regions of the brain, which were reported to have high density of σ1 receptors. PMID:24451404

  12. Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

    PubMed Central

    O’Driscoll, Luke J; Andersen, Sissel S; Solano, Marta V; Bendixen, Dan; Jensen, Morten; Duedal, Troels; Lycoops, Jess; van der Pol, Cornelia; Sørensen, Rebecca E; Larsen, Karina R; Myntman, Kenneth; Henriksen, Christian; Hansen, Stinne W

    2015-01-01

    Summary The electron-donor and unique redox properties of the tetrathiafulvalene (TTF, 1) moiety have led to diverse applications in many areas of chemistry. Monopyrrolotetrathiafulvalenes (MPTTFs, 4) and bispyrrolotetrathiafulvalenes (BPTTFs, 5) are useful structural motifs and have found widespread use in fields such as supramolecular chemistry and molecular electronics. Protocols enabling the synthesis of functionalised MPTTFs and BPTTFs are therefore of broad interest. Herein, we present the synthesis of a range of functionalised MPTTF and BPTTF species. Firstly, the large-scale preparation of the precursor species N-tosyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (6) is described, as well as the synthesis of the analogue N-tosyl-4,6-dimethyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (7). Thereafter, we show how 6 and 7 can be used to prepare BPTTFs using homocoupling reactions and functionalised MPTTFs using cross-coupling reactions with a variety of 1,3-dithiole-2-thiones (19). Subsequently, the incorporation of more complex functionality is discussed. We show how the 2-cyanoethyl protecting group can be used to afford MPTTFs functionalised with thioethers, exemplified by a series of ethylene glycol derivatives. Additionally, the merits of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an alternative to the most common deprotecting agent, CsOH·H2O are discussed. Finally, we show how a copper-mediated Ullman-type reaction can be applied to the N-arylation of MPTTFs and BPTTFs using a variety of aryl halides. PMID:26199667

  13. Sample Canister Capture Mechanism for Mars Sample Return: Functional and environmental test of the elegant breadboard model

    NASA Astrophysics Data System (ADS)

    Carta, R.; Filippetto, D.; Lavagna, M.; Mailland, F.; Falkner, P.; Larranaga, J.

    2015-12-01

    The paper provides recent updates about the ESA study: Sample Canister Capture Mechanism Design and Breadboard developed under the Mars Robotic Exploration Preparation (MREP) program. The study is part of a set of feasibility studies aimed at identifying, analysing and developing technology concepts enabling the future international Mars Sample Return (MSR) mission. The MSR is a challenging mission with the purpose of sending a Lander to Mars, acquire samples from its surface/subsurface and bring them back to Earth for further, more in depth, analyses. In particular, the technology object of the Study is relevant to the Capture Mechanism that, mounted on the Orbiter, is in charge of capturing and securing the Sample Canister, or Orbiting Sample, accommodating the Martian soil samples, previously delivered in Martian orbit by the Mars Ascent Vehicle. An elegant breadboard of such a device was implemented and qualified under an ESA contract primed by OHB-CGS S.p.A. and supported by Politecnico di Milano, Department of Aerospace Science and Technology: in particular, functional tests were conducted at PoliMi-DAST and thermal and mechanical test campaigns occurred at Serms s.r.l. facility. The effectiveness of the breadboard design was demonstrated and the obtained results, together with the design challenges, issues and adopted solutions are critically presented in the paper. The breadboard was also tested on a parabolic flight to raise its Technology Readiness Level to 6; the microgravity experiment design, adopted solutions and results are presented as well in the paper.

  14. Design and simulation of a nanoscale electro-plasmonic 1 × 2 switch based on asymmetric metal-insulator-metal stub filters.

    PubMed

    Taheri, Ahmad Naseri; Kaatuzian, Hassan

    2014-10-01

    A compact nanoscale electro-plasmonic 1 × 2 switch based on asymmetrical metal-insulator-metal stub filters is introduced. The structure is designed and analyzed based on the transmission line method, and the switching operation of the device is numerically simulated and verified by the finite element method. It is found that by adjusting the length of the stubs on each output branch of the structure the surface plasmon polaritons (SPPs) are guided to only one of the output ports. By altering the refractive index of the electro-optical material (DAST) as the core of the structure with a 35 V applied voltage, the SPPs are steered to the opposite port. The reflected SPPs from one stub filter enhance the output intensity of another filter. The operating wavelength of the switch is the communication wavelength λ=1550 nm. Nevertheless, it can be easily redesigned for another wavelength in the range of 800-2000 nm. The insertion losses and the extinction ratios guarantee an almost symmetrical switching for two outputs. The overall size of the switch is 800 nm × 450 nm × 750 nm. The bandwidth of the switch is anticipated over 100 GHz.

  15. Astronomy week: An investigation of the implementation and identity formation of participants

    NASA Astrophysics Data System (ADS)

    Dewitt, Carl

    Our society has a great need for Science, Technology, Engineering, and Mathematics (STEM) professionals and educational institutions are currently having difficulty keeping up with society's demand (Carnevale, 2011). Outreach efforts are a key strategy to encouraging young people to pursue STEM careers and evaluation methods need to be used to ensure that this outreach is efficient and effective in helping young students see themselves as a prospective STEM professionals (Moskal, 2011). The purpose of this dissertation study was to investigate the implementation of an Astronomy Week supported by the Center for Mathematics and Science Education (CMSE) and its impact on student identity formation. Three classrooms implemented the CMSE Astronomy Week curriculum and accepted a visit from the Starlab mobile planetarium. Data consisted of field notes from classroom observations, interviews with students and teachers, the Draw a Scientist Test (DAST), and surveys from both teachers and students. Results provide evidence that this outreach effort was a significant science event that helped change the stereotypical beliefs about scientists, especially in minority students. Drawings of scientists and written responses provided valuable insight into participants' identity formation and desires to pursue a career in science. Results also provide suggestions for improving the programmatic and curricular aspects of the outreach program. Teacher interviews and questionnaire responses were particularly valuable in the development of suggestions for improving the program.

  16. Health Information Technology: An Expanded Care Coordination in Rural Tennessee.

    PubMed

    Wodarski, John S; Green, Philip D

    2015-01-01

    The Expanded Care Coordination through the Use of Health Information Technology in Rural Tennessee was a 3-year initiative implemented by The University of Tennessee Children's Mental Health Services Research Center and the Helen Ross McNabb Center Regional Mental Health System. The program targeted rural adults in the East Tennessee area. This intervention utilized the Alcohol Use Disorder Identification Test (AUDIT), Drug Abuse Screening Test (DAST), and AC-COD screening tools. After the initial screening, the appropriate level of intervention was assessed. Clients completed modules on the program's website and met with a clinician for a minimum for four face-to-face meetings. Alcohol use and drug use declined significantly over the course of the program. Alcohol use and outpatient treatment for alcohol and substance abuse declined significantly over the course of the program. There were also significant decreases in days of probations, depression, physical complaints, and violent behaviors. Health information technology is becoming more common in mental health treatment facilities. However, more testing needs to be done with larger samples to assess the efficacy of the program.

  17. Validity and Reliability of the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) in University Students.

    PubMed

    Tiburcio Sainz, Marcela; Rosete-Mohedano, Ma Guadalupe; Natera Rey, Guillermina; Martínez Vélez, Nora Angélica; Carreño García, Silvia; Pérez Cisneros, Daniel

    2016-03-02

    The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), developed by the World Health Organization (WHO), has been used successfully in many countries, but there are few studies of its validity and reliability for the Mexican population. The objective of this study was to determine the psychometric properties of the self-administered ASSIST test in university students in Mexico. This was an ex post facto non-experimental study with 1,176 undergraduate students, the majority women (70.1%) aged 18-23 years (89.5%) and single (87.5%). To estimate concurrent validity, factor analysis and tests of reliability and correlation were carried out between the subscale for alcohol and AUDIT, those for tobacco and the Fagerström Test, and those for marijuana and DAST-20. Adequate reliability coefficients were obtained for ASSIST subscales for tobacco (alpha = 0.83), alcohol (alpha = 0.76), and marijuana (alpha = 0.73). Significant correlations were found only with the AUDIT (r = 0.71) and the alcohol subscale. The best balance of sensitivity and specificity of the alcohol subscale (83.8% and 80%, respectively) and the largest area under the ROC curve (81.9%) was found with a cutoff score of 8. The self-administered version of ASSIST is a valid screening instrument to identify at-risk cases due to substance use in this population.

  18. Measurements of prompt charm production cross-sections in pp collisions at sqrt{s}=13 TeV

    NASA Astrophysics Data System (ADS)

    Aaij, R.; Abellán Beteta, C.; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; d'Argent, P.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Bel, L. J.; Bellee, V.; Belloli, N.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Billoir, P.; Bird, T.; Birnkraut, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Campana, P.; Campora Perez, D.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cavallero, G.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S.-F.; Chiapolini, N.; Chrzaszcz, M.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collazuol, G.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dall'Occo, E.; Dalseno, J.; David, P. N. Y.; Davis, A.; De Aguiar Francisco, O.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Simone, P.; Dean, C.-T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Demmer, M.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Ruscio, F.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Färber, C.; Farley, N.; Farry, S.; Fay, R.; Ferguson, D.; Fernandez Albor, V.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fohl, K.; Fol, P.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Gascon, D.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianì, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Humair, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kecke, M.; Kelsey, M.; Kenyon, I. R.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Kozeiha, M.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Liu, X.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Manning, P.; Mapelli, A.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurin, B.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Meissner, M.; Melnychuk, D.; Merk, M.; Michielin, E.; Milanes, D. A.; Minard, M.-N.; Mitzel, D. S.; Molina Rodriguez, J.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morawski, P.; Mordà, A.; Morello, M. J.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, C. J. G.; Osorio Rodrigues, B.; Otalora Goicochea, J. M.; Otto, A.; Owen, P.; Oyanguren, A.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Pappenheimer, C.; Parker, W.; Parkes, C.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Pistone, A.; Piucci, A.; Playfer, S.; Plo Casasus, M.; Poikela, T.; Polci, F.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, E.; Price, J. D.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redi, F.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz Valls, P.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefkova, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Todd, J.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Volkov, V.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wyllie, K.; Xie, Y.; Xu, Z.; Yang, Z.; Yu, J.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zucchelli, S.

    2016-03-01

    Production cross-sections of prompt charm mesons are measured with the first data from pp collisions at the LHC at a centre-of-mass energy of 13 TeV. The data sample corresponds to an integrated luminosity of 4.98 ± 0.19 pb-1 collected by the LHCb experiment. The production cross-sections of D 0, D +, D s + , and D *+ mesons are measured in bins of charm meson transverse momentum, p T, and rapidity, y, and cover the range 0 < p T < 15GeV/c and 2.0 < y < 4.5. The inclusive cross-sections for the four mesons, including charge conjugation, within the range of 1 < p T < 8 GeV/c are found to be begin{array}{l}σ left(ppto {D}^0Xright)=2460± 3± 130\\upmu b \\ {}σ left(ppto {D}+Xright)=1000± 3± 110\\upmu b \\ {}σ left(ppto {D}_s+Xright)=460± 13± 100\\upmu b \\ {}σ left(ppto {D}^{ast +}Xright)=880± 5± 140\\upmu b where the uncertainties are due to statistical and systematic uncertainties, respectively. [Figure not available: see fulltext.

  19. Synthesis of 2-phenyl-4,5-substituted oxazoles by copper-catalyzed intramolecular cyclization of functionalized enamides.

    PubMed

    Vijay Kumar, S; Saraiah, B; Misra, N C; Ila, H

    2012-12-07

    An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzed cyclization of highly functionalized novel β-(methylthio)enamides as the key step has been reported. These enamides are obtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolone precursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester, N-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis-decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novel trisubstituted 4,2'-bisoxazoles through DAST/DBU-mediated cyclodehydration-dehydrohalogenation sequence. The present protocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of β-bis(methylthio)enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles.

  20. Sensitivity method for integrated structure/active control law design

    NASA Technical Reports Server (NTRS)

    Gilbert, Michael G.

    1987-01-01

    The development is described of an integrated structure/active control law design methodology for aeroelastic aircraft applications. A short motivating introduction to aeroservoelasticity is given along with the need for integrated structures/controls design algorithms. Three alternative approaches to development of an integrated design method are briefly discussed with regards to complexity, coordination and tradeoff strategies, and the nature of the resulting solutions. This leads to the formulation of the proposed approach which is based on the concepts of sensitivity of optimum solutions and multi-level decompositions. The concept of sensitivity of optimum is explained in more detail and compared with traditional sensitivity concepts of classical control theory. The analytical sensitivity expressions for the solution of the linear, quadratic cost, Gaussian (LQG) control problem are summarized in terms of the linear regulator solution and the Kalman Filter solution. Numerical results for a state space aeroelastic model of the DAST ARW-II vehicle are given, showing the changes in aircraft responses to variations of a structural parameter, in this case first wing bending natural frequency.

  1. The use of administrative data as a substitute for individual screening scores in observational studies related to problematic alcohol or drug use.

    PubMed

    Sears, Jeanne M; Krupski, Antoinette; Joesch, Jutta M; Estee, Sharon L; He, Lijian; Shah, Melissa Ford; Huber, Alice; Dunn, Chris; Ries, Richard; Roy-Byrne, Peter P

    2010-09-01

    Administrative data provide a rich resource for improving our understanding of individuals with substance use disorders. The validation of administrative proxies for moderate or high risk alcohol or drug (AOD) use could enhance the ability to carry out rigorous observational research (for example, for use in the construction of comparison groups). This study used receiver operating characteristic (ROC) curve techniques to assess how well AOD-related administrative indicators predicted self-reported AOD use obtained from AUDIT/DAST screening scores. An administrative AOD indicator, derived from a combination of medical encounter and billing data, arrest records, and publicly funded AOD-related services data, demonstrated discrimination in the acceptable range (AUC: 0.72-0.78) for identifying self-reported AOD use consistent with potential need for either (1) any AOD-related intervention, or (2) intensive AOD-related intervention or treatment. These findings held up in two distinct samples: a statewide Medicaid-only sample and a single-site mixed-payer sample that included the uninsured. Our findings suggest that indicators of AOD-related problems derived from administrative data can be useful for identifying moderate or high risk AOD use in a research context. The findings further suggest that proxies for substance use disorders, such as those evaluated here, can enhance future observational studies intended to improve health care for this population.

  2. Phylogenetic analysis of bovine astrovirus in Korean cattle.

    PubMed

    Oem, Jae-Ku; An, Dong-Jun

    2014-04-01

    Bovine astrovirus (BAstV) belongs to a genetically divergent lineage within the genus Mamastrovirus. The present study showed that BAstV was associated with the gastroenteric tracts of cattle in nine positive fecal samples from 115 cattle, whereas no positive samples were found in the brain tissues of 14 downer cattle. Interestingly, the positive diarrheal samples were obtained mainly from calves aged 14 days-3 months. Bayesian inference tree analysis of the partial ORF1ab and capsid (ORF2) gene sequences of BAstVs identified four divergent groups. Eleven BAstVs, four porcine astroviruses, and two deer astroviruses (DAstVs; CcAstV-1 and -2) belonged to group 1; group 2 contained two BAstVs (BAstK08-51 and BAstK10-96) with another two in group 3 (BAstK08-2 and BAstK08-53); and group 4 comprised the BAstV-NeuroS1 strain derived from a cattle brain tissue sample and an ovine astrovirus. The same divergent groups were obtained when the pairwise alignments were produced using both amino acid and nucleotide sequences. The Korean BAstVs isolated from infected cattle had a nationwide distribution and they belonged to groups 1, 2, and 3.

  3. The effects of perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    PubMed

    Cole, Jon C; Goudie, Andrew J; Field, Matt; Loverseed, Anne-Claire; Charlton, Sarah; Sumnall, Harry R

    2008-04-01

    Previous research has indicated that non-dependent polydrug users are willing to pay more money to buy good quality drugs as their income increased. This study sought to examine whether altering the perceived quality of controlled drugs would affect drug purchases if the monetary price remained fixed. A random sample of 80 polydrug users were recruited. All participants were administered an anonymous questionnaire consisting of the Drug Abuse Screening Test for Adolescents (DAST-A), the Severity of Dependence Scale for cannabis (SDS), the Alcohol Use Disorders Identification Test (AUDIT), the Hospital Anxiety and Depression Scale (HADS), and questions about their drug use. Participants then completed a simulation of controlled drug purchases where the price of alcohol, amphetamine, cannabis, cocaine, and ecstasy remained the same but their perceived quality changed (i.e. unit price increased as the perceived quality decreased). The demand for alcohol was quality inelastic and alcohol quality had no effects on the purchase of any other controlled drug. Demand for cannabis was quality elastic and alcohol substituted for cannabis as its unit price increased. Demand for cocaine was quality elastic and alcohol, cannabis, and ecstasy substituted for cocaine as its unit price increased. Demand for ecstasy was quality elastic and alcohol and cocaine both substituted for ecstasy as its unit price increased. These results suggest that perceived quality influences the demand for controlled drugs and that monitoring the perceived quality of controlled drugs may provide a warning of potential public health problems in the near future.

  4. ND and NB systems in quark delocalization color screening model

    NASA Astrophysics Data System (ADS)

    Zhao, Lifang; Huang, Hongxia; Ping, Jialun

    2017-02-01

    The ND and NB systems with I = 0 and 1, JP=1/2^{±}, 3/2^{±}, and 5/2^{±} are investigated within the framework of the quark delocalization color screening model. The results show that all the positive-parity states are unbound. By coupling to the ND^{ast} channel, the state ND with I = 0, JP=1/2- can form a bound state, which can be invoked to explain the observed Σ(2800) state. The mass of the ND^{ast} with I = 0, JP=3/2- is close to that of the reported Λc(2940)+, which indicates that Λc(2940)+ can be explained as a ND^{ast} molecular state in QDCSM. Besides, the Δ D^{ast} with I = 1, JP=5/2- is also a possible resonance state. The results of the bottom case of the NB system are similar to those of the ND system. Searching for these states will be a challenging subject of experiments.

  5. American and Greek Children's Visual Images of Scientists

    NASA Astrophysics Data System (ADS)

    Christidou, Vasilia; Bonoti, Fotini; Kontopoulou, Argiro

    2016-08-01

    This study explores American and Greek primary pupils' visual images of scientists by means of two nonverbal data collection tasks to identify possible convergences and divergences. Specifically, it aims to investigate whether their images of scientists vary according to the data collection instrument used and to gender. To this end, 91 third-grade American ( N = 46) and Greek ( N = 45) pupils were examined. Data collection was conducted through a drawing task based on Chambers (1983) `Draw-A-Scientist-Test' (DAST) and a picture selection task during which the children selected between 14 pairs of illustrations those that were most probable to represent scientists. Analysis focused on stereotype indicators related with scientists' appearance and work setting. Results showed that the two groups' performance varied significantly across the tasks used to explore their stereotypic perceptions, although the overall stereotypy was not differentiated according to participants' ethnic group. Moreover, boys were found to use more stereotypic indicators than girls, while the picture selection task elicited more stereotypic responses than the drawing task. In general, data collected by the two instruments revealed convergences and divergences concerning the stereotypic indicators preferred. Similarities and differences between national groups point to the influence of a globalized popular culture on the one hand and of the different sociocultural contexts underlying science curricula and their implementation on the other. Implications for science education are discussed.

  6. Alu repeats as markers for forensic DNA analyses

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Kass, D.H.

    1994-01-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 98.9% nucleotide identity with the HS subfamily consensus sequence, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 inch and 3 inch unique flanking DNA sequences from each HS Alu that allow the locus to be assayed for the presence or absence of the Alu repeat. The dimorphic HS Alu sequences probably inserted in the human genome after the radiation of modem humans (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project. HS Alu family member insertions differ from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) in that polymorphisms due to Alu insertions arise as a result of a unique event which has occurred only one time in the human population and spread through the population from that point. Therefore, individuals that share HS Alu repeats inherited these elements from a common ancestor. Most VNTR and RFLP polymorphisms may arise multiple times in parallel within a population.

  7. The images of scientists and science among Hebrew- and Arabic-speaking pre-service teachers in Israel

    NASA Astrophysics Data System (ADS)

    Rubin, Edna; Cohen, Ariel

    2003-07-01

    This study investigated the image of scientists held by Israeli pre-service teachers, the majority of whom were female. The population consisted of students belonging to two cultures, Hebrew-speaking and Arabic-speaking. The DAST ('Draw-a-Scientist-Test') tool and other tools, some of which were developed specifically for this research, tested the image of the scientist as perceived by the participants. It was found that the image of the scientist is perceived as predominantly male, a physicist or a chemist, working in a laboratory typical of the eighteenth, nineteenth or the early-twentieth century. Students did not differentiate between scientists and inventors. Different images were held in the two cultures. Most of the Arabic-speaking students put Classical Islamic scientists near the top of their lists and thought of the scientist as an Arab male, while the Hebrew-speaking students' was as a typical Western male. Recommendations, resulting from the findings, for developing a new learning unit for the purpose of altering stereotypes are suggested.

  8. Cannabis dependence as a primary drug use-related problem: the case for harm reduction-oriented treatment options.

    PubMed

    Hathaway, A D; Callaghan, R C; Macdonald, S; Erickson, P G

    2009-01-01

    Few studies have focused on cannabis dependence as compared to other drugs more commonly acknowledged as presenting a substantial need for treatment. This paper presents findings from a 2004-2005 study of drug user treatment clients in Southern Ontario, Canada. Clients with cannabis (n = 128) or cocaine (n = 300) as their primary drug problem were compared on psychosocial and demographic characteristics, drug effects, and clinical impairment. There are more similarities than differences between groups, with DAST and DSM scores showing high rates of "dependence" and reported symptoms of "abuse." However, cannabis consistently scored lower on these items, supporting the idea of a continuum of risk on which its rank compared with other potentially misused drugs holds across a wide range of symptoms of impairment. The less disruptive nature of cannabis use-related problems poses greater challenges for drug user treatment providers guided by strict abstinence agendas. The authors call for the expansion of harm reduction treatment options and educational initiatives beyond primary prevention that acknowledge benefits of moderate controlled use when addressing cannabis misuse.

  9. Digital Quantification of DNA Replication and Chromosome Segregation Enables Determination of Antimicrobial Susceptibility after only 15 Minutes of Antibiotic Exposure.

    PubMed

    Schoepp, Nathan G; Khorosheva, Eugenia M; Schlappi, Travis S; Curtis, Matthew S; Humphries, Romney M; Hindler, Janet A; Ismagilov, Rustem F

    2016-08-08

    Rapid antimicrobial susceptibility testing (AST) would decrease misuse and overuse of antibiotics. The "holy grail" of AST is a phenotype-based test that can be performed within a doctor visit. Such a test requires the ability to determine a pathogen's susceptibility after only a short antibiotic exposure. Herein, digital PCR (dPCR) was employed to test whether measuring DNA replication of the target pathogen through digital single-molecule counting would shorten the required time of antibiotic exposure. Partitioning bacterial chromosomal DNA into many small volumes during dPCR enabled AST results after short exposure times by 1) precise quantification and 2) a measurement of how antibiotics affect the states of macromolecular assembly of bacterial chromosomes. This digital AST (dAST) determined susceptibility of clinical isolates from urinary tract infections (UTIs) after 15 min of exposure for all four antibiotic classes relevant to UTIs. This work lays the foundation to develop a rapid, point-of-care AST and strengthen global antibiotic stewardship.

  10. Demonstration of 40 MHz thin-film electro-optic modulator using an organic molecular salt

    NASA Astrophysics Data System (ADS)

    Bhowmik, Achintya; Ahyi, Ayayi; Tan, Shida; Mishra, Alpana; Thakur, Mrinal

    2000-03-01

    Recently we reported the first demonstration of a single-pass thin-film electro-optic modulator based on a DAST single-crystal film.(M. Thakur, J. Xu, A. Bhowmik, and L. Zhou, Appl. Phys. Lett. 74, 635-637 (1999).) In this work, we report a larger modulation depth ( ~80%) and higher speed of operation. Excellent optical quality single-crystal films were prepared by a modified shear method.(M. Thakur and S. Meyler, Macromolecules 18, 2341 (1985); M. Thakur, Y. Shani, G. C. Chi, and K. O'Brien, Synth. Met. 28, D595 (1989).) Thin-film modulator was constructed by depositing electrodes across the polar axis. The beam from a Ti-Sapphire laser, tunable over 720-850 nm, was propagated perpendicular to the film surface. The modulated signal was detected using a fast photodetector, and displayed on a high bandwidth oscilloscope and a spectrum analyzer. The response was independent of the frequency of applied field over the measurement range (2 kHz - 40 MHz). A much higher speed (>100 GHz) of operation should be possible using these films. These modulators involve negligible losses compared to the waveguide structures, and have significant potential for a broad range of applications in high speed optical signal processing.

  11. Gold-coated magnetic particles for solid-phase immunoassays: enhancing immobilized antibody binding efficiency and analytical performance.

    PubMed

    Zhang, Hairong; Meyerhoff, Mark E

    2006-01-15

    The preparation and characterization of gold-coated magnetic particles are described for use as more efficient solid-phase materials in immunoassay development. A thin gold coating on commercial tosylated magnetic polystyrene particles (4.5 microm) is achieved via an electroless plating method involving initial reaction of the particles with Sn(II), followed by redox deposition of Ag0, that serves as a catalytic site for the subsequent reduction of Na3Au(SO3)2 in the presence of formaldehyde to yield the adhered gold layer. Scanning electron microscopy, energy-dispersive X-ray analysis, and X-ray photoelectron spectroscopy indicate the presence of the desired Au0 outer layer. To characterize the improved yield of antibody binding sites on such gold-coated phases, the modified particles are reacted with the free thiols of Fab' fragments of an anti-alkaline phosphatase (ALP) antibody to orient all the antigenic binding sites in a favorable direction. After equilibration with ALP, the amount of ALP bound to the surface of such particles is nearly 2.5-fold greater than on non-gold-coated particles possessing the same amount of immobilized anti-ALP Fab', but oriented randomly on the surface. The new gold-coated magnetic particles are further used as a solid phase for developing a sandwich-type enzyme immunoassay to detect C-reactive protein (CRP) using horseradish peroxidase as the enzyme label. The gold-coated magnetic particles with anti-CRP monoclonal Fab' reagents provide assays with enhanced assay slope (1.8-fold), lower nonspecific adsorption, and a detection limit improvement of nearly 10-fold (0.14 vs 1.9 ng/mL) compared to the same Fab' anti-CRP immobilized on the initial tosylated polystyrene magnetic particles. The improved assay performance is attributed to the more favorable binding orientation of the self-assembled monolayer of Fab' fragments on the gold-coated particles compared to the random orientation on the non-gold-coated surfaces.

  12. Studies of selected organic nonlinear optical and light-emitting materials

    NASA Astrophysics Data System (ADS)

    Tan, Shida

    In this dissertation, the nonlinear optical and light emitting properties of a selected class of organic materials have been studied in detail. Novel organic molecular salts, 4-dimethylaminostyryl-N-methylpyridinium methanesulfonate (DASMS) and 4-diethylaminostyryl-N-methylpyridinium p-toluenesulfonate (DEST), were synthesized. A few selected stilbazolium derivatives, 3-methyl-4-methoxy-4'-nitrostilbene (MMONS), 4-dimethylaminostyryl-N-methylpyridinium p-toluenesulfonate (DAST), and DASMS were grown into excellent optical quality single-crystal thin-films, on which detailed polarized UV-Vis spectroscopy and X-ray diffraction studies were carried out. The crystallographic parameters of p-nitro-benzobromide (NBB) are reported for the first time. The values of the tensor elements of second-order susceptibility of MMONS at the fundamental wavelength of 1064 nm were measured to be d33 = 195 +/- 10 pm/V and d24 = 75 +/- 5 pm/V by detailed polarization selective second-harmonic generation measurements. Both type I and type II phase-matched propagation directions were identified in the MMONS single-crystal. The electro-optic effects in MMONS and DASMS single-crystal thin-films were studied using field-induced birefringence method. Measured r-coefficients of MMONS are r33 = 55rho5 pm/V and r23 = 21rho2 pm/V at 1064 nm. The electro-optic coefficients of DASMS single-crystal thin-films were measured over a broad range of wavelengths (from 632.8 nm to 820 nm). The largest r-coefficients of DASMS were observed at 740 nm to be r11 = 552rho60 pm/V and r12 = 184rho20 pm/V. Compact free-space and fiber-coupled DAST electro-optic thin-film devices with both transmission and reflection geometries were demonstrated for the first time. DEST and 4-(4-hydroxystyryl)-N-methylpyridinium p-toluenesulfonate (HSMPT) were shown to have 20% and 30% spectrally narrowed laser-like emission conversion efficiencies without external mirrors despite their small photoluminescence efficiencies. With 55

  13. Distributed data analysis in ATLAS

    NASA Astrophysics Data System (ADS)

    Nilsson, Paul; Atlas Collaboration

    2012-12-01

    Data analysis using grid resources is one of the fundamental challenges to be addressed before the start of LHC data taking. The ATLAS detector will produce petabytes of data per year, and roughly one thousand users will need to run physics analyses on this data. Appropriate user interfaces and helper applications have been made available to ensure that the grid resources can be used without requiring expertise in grid technology. These tools enlarge the number of grid users from a few production administrators to potentially all participating physicists. ATLAS makes use of three grid infrastructures for the distributed analysis: the EGEE sites, the Open Science Grid, and Nordu Grid. These grids are managed by the gLite workload management system, the PanDA workload management system, and ARC middleware; many sites can be accessed via both the gLite WMS and PanDA. Users can choose between two front-end tools to access the distributed resources. Ganga is a tool co-developed with LHCb to provide a common interface to the multitude of execution backends (local, batch, and grid). The PanDA workload management system provides a set of utilities called PanDA Client; with these tools users can easily submit Athena analysis jobs to the PanDA-managed resources. Distributed data is managed by Don Quixote 2, a system developed by ATLAS; DQ2 is used to replicate datasets according to the data distribution policies and maintains a central catalog of file locations. The operation of the grid resources is continually monitored by the Ganga Robot functional testing system, and infrequent site stress tests are performed using the Hammer Cloud system. In addition, the DAST shift team is a group of power users who take shifts to provide distributed analysis user support; this team has effectively relieved the burden of support from the developers.

  14. Impact of residential schooling and of child abuse on substance use problem in Indigenous Peoples.

    PubMed

    Ross, Amélie; Dion, Jacinthe; Cantinotti, Michael; Collin-Vézina, Delphine; Paquette, Linda

    2015-12-01

    Residential schools were the institutions, in operation from the 19th century to the late 20th century, which Indigenous children in Canada were forced to attend. The literature shows that many young people who attended these institutions were victims of neglect and abuse. Negative psychological effects resulting from child abuse have been amply documented. However, very few studies on this subject have been carried out among Canada's Indigenous Peoples. The objective of this study is to evaluate, for an Indigenous population in Quebec (Canada), the impact of residential schooling as well as self-reported experiences of sexual and physical abuse during childhood on the development of alcohol and drug use problems in adulthood. A total of 358 Indigenous participants were interviewed (164 men [45.8%] and 194 women [54.2%]). Alcoholism was evaluated using the Michigan Alcoholism Screening Test (MAST). Drug abuse was assessed with the Drug Abuse Screening Test-20 (DAST). Child abuse and residential schooling were assessed with dichotomous questions (yes/no). Among the participants, 28.5% (n=102) had attended residential schools, 35.2% (n=121) reported having experienced sexual abuse, and 34.1% (n=117) reported having experienced physical abuse before adulthood. Results of the exact logistic regression analyses indicated that residential school attendance was linked to alcohol problems, while child abuse was related to drug use problems. The results of this study highlight the importance of considering the consequences of historical traumas related to residential schools to better understand the current situation of Indigenous Peoples in Canada.

  15. A closer look at the R D and R D* anomalies

    NASA Astrophysics Data System (ADS)

    Bardhan, Debjyoti; Byakti, Pritibhajan; Ghosh, Diptimoy

    2017-01-01

    The measurement of R D ( R D*), the ratio of the branching fraction of overline{B}to Dτ {overline{ν}}_{τ}(overline{B}to {D}^{ast}τ {overline{ν}}_{τ}) to that of overline{B}to Dl{overline{ν}}_l(overline{B}to {D}^{ast }l{overline{ν}}_l) , shows 1 .9 σ (3 .3 σ) deviation from its Standard Model (SM) prediction. The combined deviation is at the level of 4 σ according to the Heavy Flavour Averaging Group (HFAG). In this paper, we perform an effective field theory analysis (at the dimension 6 level) of these potential New Physics (NP) signals assuming SU(3)C × SU(2)L × U(1)Y gauge invariance. We first show that, in general, R D and R D* are theoretically independent observables and hence, their theoretical predictions are not correlated. We identify the operators that can explain the experimental measurements of R D and R D* individually and also together. Motivated by the recent measurement of the τ polarisation in overline{B}to {D}^{ast}τ {overline{ν}}_{τ } decay, P τ ( D *) by the Belle collaboration, we study the impact of a more precise measurement of P τ ( D *) (and a measurement of P τ ( D)) on the various possible NP explanations. Furthermore, we show that the measurement of R D* in bins of q 2, the square of the invariant mass of the lepton-neutrino system, along with the information on τ polarisation and the forward-backward asymmetry of the τ lepton, can completely distinguish the various operator structures. We also provide the full expressions of the double differential decay widths for the individual τ helicities in the presence of all the 10 dimension-6 operators that can contribute to these decays.

  16. At the Beginning of the STEM Pipeline: A Case Study Exploring Preadolescent Female Students' Attitudes Toward Science, Perceptions of Scientists, and Developing Career Aspirations

    NASA Astrophysics Data System (ADS)

    Heacock, Lucy Vogel

    The continuous underrepresentation of women in science, technology, engineering, and math (STEM), referred to as the leaky pipeline, has been examined from multiple perspectives internationally, while the attitudes and perceptions of preadolescent girls regarding STEM remain largely ignored. Employing a constructivist paradigm, this qualitative case study explored the perceptions and attitudes of 40 public elementary school female students across three grade levels regarding science, scientists, and career aspirations. Mixed-methods data collections included three survey instruments combined with semi-structured interviews. Self-efficacy, stereotype threat, and career choice theory provided the framework for the overarching research question: What are the attitudes and perceptions of female preadolescent students at the third, fourth, and fifth grade levels regarding science and scientists, and how might these dispositions affect their early development of STEM career aspirations and interests? The Three-Dimensions of Student Attitude Towards Science (TDSAS) instrument informed the exploration of self-efficacy; the modified Draw-A-Scientist Test (mDAST) and Rubric informed the exploration of stereotype threat; and the STEM-Career Interest Survey (CIS) informed the exploration of career aspirations. Semi-structured interviews were conducted with six participants. Results from this study indicated that the majority of the preadolescent girls thought science was an important topic to study and displayed an attitude of self-confident ability to learn science and be successful in science class. They highly enjoyed scientific experimentation and deeply valued problem solving. While they inferred they did not experience gender bias, the girls did engage in stereotyping scientists. Over half the girls expected to use science in their future careers, while a minority had already determined they wanted to be scientists when they grow up. The study concludes with

  17. The relationship between forgiveness, spirituality, traumatic guilt and posttraumatic stress disorder (PTSD) among people with addiction.

    PubMed

    Langman, Louise; Chung, Man Cheung

    2013-03-01

    Spirituality and forgiveness have been shown to be associated with psychological well-being, while guilt has been associated with poor health. Little is known, however, about the relationship between forgiveness, spirituality, guilt, posttraumatic stress (PTSD) and psychological co-morbidity among people in recovery from addiction. Eighty-one people (F = 36, M = 45) in recovery from drug and alcohol addiction were recruited from two residential units and two drop-in centres in a city in the United Kingdom. They completed the Posttraumatic Stress Diagnostic Scale (PDS), the General Health Questionnaire-28 (GHQ-28), the Spiritual Involvement and Beliefs Scale (SIBS), the Heartland Forgiveness Scale (HFS), the Traumatic Guilt Inventory (TGI), the Michigan Alcoholism Screening Test (MAST-22) and the Drug Abuse Screening Test (DAST-20). The control group comprised of 83 (F = 34, M = 49) individuals who confirmed that they did not have addiction and completed the PDS & GHQ-28. 54 % of the addiction group met the criteria for full PTSD and reported anxiety, somatic problems and depression. They described themselves as spiritual, had strong feelings of guilt associated with their addiction, and had difficulty in forgiving themselves. Controlling for demographics, number of events and medication management, regression analyses showed that spirituality predicted psychological co-morbidity, whilst feelings of guilt predicted PTSD symptoms and psychological co-morbidity. Unexpectedly, forgiveness did not predict outcomes. This study supports existing literature, which shows that people with drug and alcohol addiction tend to have experienced significant past trauma and PTSD symptoms. Their posttraumatic stress reactions and associated psychological difficulties can be better understood in the light of guilt and spirituality. Meanwhile, their ability to forgive themselves or others did not seem to influence health outcomes.

  18. Methoxymethyl (MOM) group nitrogen protection of pyrimidines bearing C-6 acyclic side-chains.

    PubMed

    Kraljević, Tatjana Gazivoda; Petrović, Martina; Krištafor, Svjetlana; Makuc, Damjan; Plavec, Janez; Ross, Tobias L; Ametamey, Simon M; Raić-Malić, Silvana

    2011-06-20

    Novel N-methoxymethylated (MOM) pyrimidine (4-13) and pyrimidine-2,4-diones (15-17) nucleoside mimetics in which an isobutyl side-chain is attached at the C-6 position of the pyrimidine moiety were synthesized. Synthetic methods via O-persilylated or N-anionic uracil derivatives have been evaluated for the synthesis of N-1- and/or N-3-MOM pyrimidine derivatives with C-6 acyclic side-chains. A synthetic approach using an activated N-anionic pyrimidine derivative afforded the desired N,N-1,3-diMOM and N-1-MOM pyrimidines 4 and 5 in good yield. Introduction of fluorine into the side-chain was performed with DAST as the fluorinating reagent to give a N,N-1,3-diMOM pyrimidine 13 with a 1-fluoro-3-hydroxyisobutyl moiety at C-6. Conformational study of the monotritylated N-1-MOM pyrimidine 12 by the use of the NOE experiments revealed the predominant conformation of the compound to be one where the hydroxymethyl group in the C-6 side-chain is close to the N-1-MOM moiety, while the OMTr is in proximity to the CH(3)-5 group. Contrary to this no NOE enhancements between the N-1-MOM group and hydroxymethyl or fluoromethyl protons in 13 were observed, which suggested a nonrestricted rotation along the C-6 side-chain. Fluorinated N,N-1,3-diMOM pyrimidine 13 emerged as a model compound for development of tracer molecules for non-invasive imaging of gene expression using positron emission tomography (PET).

  19. Alu repeats as markers for human population genetics

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Bazan, H.

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  20. Discovery of 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride as a deoxofluorinating agent with high thermal stability as well as unusual resistance to aqueous hydrolysis, and its diverse fluorination capabilities including deoxofluoro-arylsulfinylation with high stereoselectivity.

    PubMed

    Umemoto, Teruo; Singh, Rajendra P; Xu, Yong; Saito, Norimichi

    2010-12-29

    Versatile, safe, shelf-stable, and easy-to-handle fluorinating agents are strongly desired in both academic and industrial arenas, since fluorinated compounds have attracted considerable interest in many areas, such as drug discovery, due to the unique effects of fluorine atoms when incorporated into molecules. This article describes the synthesis, properties, and reactivity of many substituted and thermally stable phenylsulfur trifluorides, in particular, 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead, 1k), as a crystalline solid having surprisingly high stability on contact with water and superior utility as a deoxofluorinating agent compared to current reagents, such as DAST and its analogues. The roles of substituents on 1k in thermal and hydrolytic stability, fluorination reactivity, and the high-yield fluorination mechanism it undergoes have been clarified. In addition to fluorinations of alcohols, aldehydes, and enolizable ketones, 1k smoothly converts non-enolizable carbonyls to CF(2) groups, and carboxylic groups to CF(3) groups, in high yields. 1k also converts C(=S) and CH(3)SC(=S)O groups to CF(2) and CF(3)O groups, respectively, in high yields. In addition, 1k effects highly stereoselective deoxofluoro-arylsulfinylation of diols and amino alcohols to give fluoroalkyl arylsulfinates and arylsulfinamides, with complete inversion of configuration at fluorine and the simultaneous, selective formation of one conformational isomer at the sulfoxide sulfur atom. Considering the unique and diverse properties, relative safety, and ease of handling of 1k in addition to its convenient synthesis, it is expected to find considerable use as a novel fluorinating agent in both academic and industrial arenas.

  1. Λ_bto Λ_cτ {overline{ν}}_{τ } decay in scalar and vector leptoquark scenarios

    NASA Astrophysics Data System (ADS)

    Li, Xin-Qiang; Yang, Ya-Dong; Zhang, Xin

    2017-02-01

    It has been shown that the anomalies observed in overline{B}to {D}^{(ast )}τ {overline{ν}}_{τ } and overline{B}to overline{K}{ℓ}+{ℓ}- decays can be resolved by adding a single scalar or vector leptoquark to the Standard Model, while constraints from other precision measurements in the flavour sector can be satisfied without fine-tuning. To further explore these two interesting scenarios, in this paper, we study their effects in the semi-leptonic Λ_bto Λ_cτ {overline{ν}}_{τ } decay. Using the best-fit solutions for the operator coefficients allowed by the current data of mesonic decays, we find that (i) the two scenarios give similar amounts of enhancements to the branching fraction B(Λ_bto Λ_cτ {overline{ν}}_{τ}) and the ratio {R_{Λ}{_c}=B(Λ_bto Λ_cτ {overline{ν}}_{τ})/B(Λ_bto Λ_cℓ {overline{ν}}_{ℓ}) , (ii) the two best-fit solutions in each of these two scenarios are also indistinguishable from each other, (iii) both scenarios give nearly the same predictions as those of the Standard Model for the longitudinal polarizations of Λ c and τ as well as the lepton-side forward-backward asymmetry. With future measurements of these observables in Λ_bto Λ_cτ {overline{ν}}_{τ } decay at the LHCb, the two leptoquark scenarios could be further tested, and even differentiated from the other NP explanations for the {R_D}{^{(ast )}} anomalies. We also discuss the feasibility for the measurements of these observables at the LHC and the future e + e - colliders.

  2. Patterns of Substance Use among HIV-Positive Adults Over 50: Implications for Treatment and Medication Adherence

    PubMed Central

    Parsons, Jeffrey T.; Starks, Tyrel J.; Millar, Brett M.; Boonrai, Kailip; Marcotte, David

    2014-01-01

    Background The population of older adults living with HIV is increasing in the United States. Despite an increased focus on the health of HIV-positive older adults, knowledge about their substance use, a primary risk factor for HIV medication non-adherence, and the association between use, problems associated with use, and adherence behavior, is limited. Methods Data were collected from 557 HIV-positive adults aged 50 and older in the New York City area via telephone interview. Participants reported the number of days in the past month on which they missed any doses of HIV medication as well as the number of days they used alcohol, marijuana, cocaine/crack, opiates, amyl nitrite (poppers), and other drugs. The severity of substance use associated problems was assessed using the DAST-10 and AUDIT-C. Results The sample included gay/bisexual (40.4%) and heterosexual (28.1%) men as well as lesbian/bisexual (4.9%) and heterosexual (26.7%) women. Latent class analyses identified four distinct patterns of substance use: Exclusive Alcohol Use; Alcohol and Marijuana; Alcohol and Cocaine/Crack; and Multiple-Substance Use. Variability in the number of missed HIV medication days and perceptions of substance use associated problems were observed across classes, with poorest adherence reported in the Alcohol and Cocaine/Crack class, followed by the Multiple-Substance Use class. These two classes also reported the greatest perceived impairment from substance use. Conclusions Patterns of recent substance use were associated with varying levels of HIV medication adherence and perceived substance use impairment, indicating that substance type matters when considering the health of older adults living with HIV, and that multiple-substance use needs to be addressed by interventions aimed at improving medication adherence. PMID:24745475

  3. How do middle school students depict science and scientists?

    NASA Astrophysics Data System (ADS)

    Gonsoulin, Walter B., Jr.

    The purpose of this study was to investigate the perceptions that middle school students have of science and scientists. The study described focused on the gender, race, and socioeconomic status of subjects and their depictions of science and scientists. The Draw A Scientist Test Checklist (DAST-C), developed by Beaver, Crammond, and Finson (1995), was used to rate drawings according to particular characteristics present or absent in the drawings. This allowed the researcher to determine the images of science and scientists children hold. The participants for this study consisted of 353 middle grades (7 and 8) students in Starkville, Mississippi Public Schools. In the analysis of this descriptive comparative design, a Chi-square Test of Independence was used to test for statistically significant differences between gender, ethnicity, and socioeconomic groups. From the results of this study, it is concluded that middle school students still depict stereotypic images of science and scientists. First, the middle school students in this study depicted scientists as mates, white, wearing lab coats, and wearing eyeglasses. The participants depicted science as an indoor occupation. Second, male students depicted scientists as males, but females depicted scientists as both male and female. Third, examination of the ethnic groups revealed that non-minority and minority students depicted scientists as white. Fourth, the examination of the socioeconomic groups revealed that the high socioeconomic group depicted more detailed images of scientists and science than the other socioeconomic groups. It is recommended, based on the results of this study, that students be exposed to a variety of experiences of science and scientists. Field trips, hands-on activities, guest speakers representing different genders and ethnicities, and reference material including technology should be provided as methods of instructions. The goal should be to make science and scientists real to students

  4. Representation of scientific methodology in secondary science textbooks

    NASA Astrophysics Data System (ADS)

    Binns, Ian C.

    The purpose of this investigation was to assess the representation of scientific methodology in secondary science textbooks. More specifically, this study looked at how textbooks introduced scientific methodology and to what degree the examples from the rest of the textbook, the investigations, and the images were consistent with the text's description of scientific methodology, if at all. The sample included eight secondary science textbooks from two publishers, McGraw-Hill/Glencoe and Harcourt/Holt, Rinehart & Winston. Data consisted of all student text and teacher text that referred to scientific methodology. Second, all investigations in the textbooks were analyzed. Finally, any images that depicted scientists working were also collected and analyzed. The text analysis and activity analysis used the ethnographic content analysis approach developed by Altheide (1996). The rubrics used for the text analysis and activity analysis were initially guided by the Benchmarks (AAAS, 1993), the NSES (NRC, 1996), and the nature of science literature. Preliminary analyses helped to refine each of the rubrics and grounded them in the data. Image analysis used stereotypes identified in the DAST literature. Findings indicated that all eight textbooks presented mixed views of scientific methodology in their initial descriptions. Five textbooks placed more emphasis on the traditional view and three placed more emphasis on the broad view. Results also revealed that the initial descriptions, examples, investigations, and images all emphasized the broad view for Glencoe Biology and the traditional view for Chemistry: Matter and Change. The initial descriptions, examples, investigations, and images in the other six textbooks were not consistent. Overall, the textbook with the most appropriate depiction of scientific methodology was Glencoe Biology and the textbook with the least appropriate depiction of scientific methodology was Physics: Principles and Problems. These findings

  5. Intense terahertz radiation and their applications

    NASA Astrophysics Data System (ADS)

    Hafez, H. A.; Chai, X.; Ibrahim, A.; Mondal, S.; Férachou, D.; Ropagnol, X.; Ozaki, T.

    2016-09-01

    In this paper, we will review both past and recent progresses in the generation, detection and application of intense terahertz (THz) radiation. We will restrict the review to laser based intense few-cycle THz sources, and thus will not include sources such as synchrotron-based or narrowband sources. We will first review the various methods used for generating intense THz radiation, including photoconductive antennas (PCAs), optical rectification sources (especially the tilted-pulse-front lithium niobate source and the DAST source, but also those using other crystals), air plasma THz sources and relativistic laser-plasma sources. Next, we will give a brief introduction on the common methods for coherent THz detection techniques (namely the PCA technique and the electro-optic sampling), and point out the limitations of these techniques for measuring intense THz radiation. We will then review three techniques that are highly suited for detecting intense THz radiation, namely the air breakdown coherent detection technique, various single-shot THz detection techniques, and the spectral-domain interferometry technique. Finally, we will give an overview of the various applications that have been made possible with such intense THz sources, including nonlinear THz spectroscopy of condensed matter (optical-pump/THz-probe, THz-pump/THz-probe, THz-pump/optical-probe), nonlinear THz optics, resonant and non-resonant control of material (such as switching of superconductivity, magnetic and polarization switching) and controlling the nonlinear response of metamaterials. We will also provide a short perspective on the future of intense THz sources and their applications.

  6. Identification of the Binding Position of Amilorides in the Quinone Binding Pocket of Mitochondrial Complex I.

    PubMed

    Ito, Takeshi; Murai, Masatoshi; Morisaka, Hironobu; Miyoshi, Hideto

    2015-06-16

    We previously demonstrated that amilorides bind to the quinone binding pocket of bovine mitochondrial complex I, not to the hitherto suspected Na⁺/H⁺ antiporter-like subunits (ND2, ND4, and ND5) [Murai, M., et al. (2015) Biochemistry 54, 2739-2746]. To characterize the binding position of amilorides within the pocket in more detail, we conducted specific chemical labeling [alkynylation (-C≡CH)] of complex I via ligand-directed tosyl (LDT) chemistry using a newly synthesized amide-type amiloride AAT as a LDT chemistry reagent. The inhibitory potency of AAT, in terms of its IC50 value, was markedly higher (∼1000-fold) than that of prototypical guanidine-type amilorides such as commercially available EIPA and benzamil. Detailed proteomic analyses in combination with click chemistry revealed that the chemical labeling occurred at Asp160 of the 49 kDa subunit (49 kDa Asp160). This labeling was significantly suppressed in the presence of an excess amount of other amilorides or ordinary inhibitors such as quinazoline and acetogenin. Taking into consideration the fact that 49 kDa Asp160 was also specifically labeled by LDT chemistry reagents derived from acetogenin [Masuya, T., et al. (2014) Biochemistry 53, 2307-2317, 7816-7823], we found this aspartic acid to elicit very strong nucleophilicity in the local protein environment. The structural features of the quinone binding pocket in bovine complex I are discussed on the basis of this finding.

  7. Spatially selective modification of PLLA surface: From hydrophobic to hydrophilic or to repellent

    NASA Astrophysics Data System (ADS)

    Bastekova, Kristina; Guselnikova, Olga; Postnikov, Pavel; Elashnikov, Roman; Kunes, Martin; Kolska, Zdenka; Švorčík, Vaclav; Lyutakov, Oleksiy

    2017-03-01

    A universal approach to controlled surface modification of polylactic acid (PLLA) films using diazonium chemistry was proposed. The multistep procedure includes surface activation of PLLA by argon plasma treatment and chemical activation of arenediazonium tosylates by NaBH4. The surface of PLLA film was grafted with different functional organic groups (OFGs), changing the PLLA surface properties (wettability, morphology, zeta potential, chemical composition, and mechanical response). Three approaches of OFG grafting were examined: (i) plasma treatment following by PLLA immersion into diazonium salt aqueous solution; (ii) grafting of PLLA surface through the reaction with chemically created aryl radicals; (iii) mutual combination of both methods The best results were achieved in the last case, where the previous plasma treatment was combined with further reaction of PLLA surface with generated aryl radicals. Using this method PLLA surface was successfully grafted with amino, carboxyl, aliphatic and fluorinated OFGs. Further investigation of surface properties from potential biological and medical points of view was performed using zeta potential, biodegradation and biofouling tests. It was shown that proposed technique allows preparation of biorepellent or bioabsorptive surfaces, tuning of PLLA biodegradation rate and nanomechanical properties, as well as the introduction of inverse properties (such as hydrophilic and hydrophobic) on both sides of PLLA films.

  8. [Efficient synthesis of multisubstituted aromatic compounds from phenol derivatives].

    PubMed

    Ikawa, Takashi

    2014-01-01

    Phenols are abundant in nature and diverse phenols are readily available commercially at low cost. Thus, phenols can be used as the raw materials for the synthesis of valuable multisubstituted aromatic compounds by the direct activation of phenolic hydroxyl groups (C-O bond activation), followed by substitutions with other substituents. Although the derivatization of phenolic hydroxyl groups to sulfonates, such as triflates, nonaflates, tosylates and mesylates, followed by the transition-metal-catalyzed coupling reactions has been extensively investigated for this purpose, the direct C-O bond activation of phenols for subsequent functional group transformation has been a long-standing challenge in modern organic synthesis. In this review, I have summarized my recent studies on the formal direct C-O bond activation of phenols using nonafluorobutanesulfonyl fluoride (NfF) for the synthesis of multisubstituted aromatics. I have focused on the dual use of NfF, a less expensive commercially available reagent, including the tentative formation of highly reactive nonaflates from phenols and the use of the liberated fluoride ion as a nucleophile to promote the reactions of nonaflates. The following four topics are discussed: 1) palladium-catalyzed coupling reactions of phenols, 2) novel preparation of benzynes from 2-silylphenols, 3) synthesis of fluorinated aromatic compounds via the formation of benzynes, and 4) Hiyama coupling of (tert-butyldimethylsilyl)arenes activated by internal phenolic hydroxyl groups.

  9. Trypsin-like enzyme from eggs of the ascidian (protochordate), Halocynthia roretzi. Purification, properties, and physiological role.

    PubMed

    Sawada, H; Kawahigashi, M; Yokosawa, H; Ishii, S

    1985-12-15

    A trypsin-like enzyme has been purified to apparent homogeneity from eggs of the ascidian, Halocynthia roretzi, by a procedure including column chromatography on diethylaminoethyl-cellulose, phenyl-Sepharose, and soybean trypsin inhibitor-immobilized Sepharose 4B. The molecular weight of the enzyme was estimated to be 31,000 and 33,000 by gel electrophoresis in sodium dodecyl sulfate under the reducing and the nonreducing conditions, respectively. The isoelectric point of the enzyme was 4.8. The pH optimum of the activity was 8.4. The enzyme was stable between pH 6 and 9 in the presence of 0.005% Brij 35 as a stabilizer. Substrate specificity of the purified enzyme was broad toward various peptidyl-arginine (or -lysine) 4-methylcoumaryl-7-amides and was similar to that of a trypsin-like enzyme found in the fertilization product. The purified enzyme was inhibited by diisopropyl fluorophosphate and a variety of trypsin inhibitors including leupeptin, but not, or scarcely, inhibited by p-chloromercuribenzoic acid, pepstatin, chymostatin, bestatin, elastatinal, and tosyl-phenylalanyl-chloromethane. The rankings in the potencies of leupeptin and its six analogs as the inhibitors of the purified enzyme were well correlated with those found in their inhibitory effects on the expansion of perivitelline space. Thus, the trypsin-like enzyme possibly present in the fertilization product participates in the expansion of perivitelline space of the egg during fertilization of the ascidian.

  10. Synthesis, NMR conformational analysis and pharmacological evaluation of 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a']diindole analogues as melatonin receptor ligands.

    PubMed

    Attia, Mohamed I; Güclü, Deniz; Hertlein, Barbara; Julius, Justin; Witt-Enderby, Paula A; Zlotos, Darius P

    2007-07-07

    A structure for the self-condensation product of 2-(1H-indol-2-yl)ethyl tosylate 2a, previously proposed as 6,7,14,15-tetrahydro-15aH-azocino[1,2-a:6,5-b]diindole 3a, was revised based on the (13)C-2D-INADEQUATE experiment, and proved to be 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a']diindole 4a. A mechanism for the unexpected formation of this novel hexacyclic heterocycle was proposed and its NMR solution structure was elucidated. Five derivatives of the title ring skeleton 12-16 designed as melatonin receptor ligands were synthesized and their affinities for the human MT(1) and MT(2) receptors were determined. Both butyramides 13 and 15, as well as the non-methoxy acetamide 12 exhibited micromolar binding affinities for both receptors being slightly MT(2) selective. The methoxy acetamide 14 showed the best pharmacological profile exhibiting a five times higher affinity for MT(1) (K(i) = 49 nM) than for MT(2) (K(i) = 246 nM) receptor.

  11. Trypsin inactivation by intact Hymenolepis diminuta (Cestoda): some characteristics of the inactivated enzyme.

    PubMed

    Schroeder, L L; Pappas, P W; Means, G E

    1981-06-01

    In the presence of intact Hymenolepis diminuta, trypsin was inactivated; intact worms had no apparent effect on subtilisin, pepsin, or papain. Inactivation of trypsin was demonstrable using azoalbumin as a substrate, but the inactivated enzyme retained full catalytic activity against benzoyl-DL-arginine-p-nitroanilide, p-tosyl-L-arginine methyl ester (low molecular weight synthetic trypsin substrates) and p-nitro-p-guanidinobenzoate (an active site titrant). Inactivation was not reversible under conditions of heating, freezing and thawing, or prolonged dialysis of the enzyme. Analyses of inactivated 3H-trypsin by cationic and SDS-polyacrylamide gel electrophoresis, and gel chromatography failed to indicate the presence of a high molecular weight trypsin inhibitor associated with the inactivated enzyme; no low molecular weight, dissociable inhibitor was demonstrable following thermal denaturation of the inactivated enzyme. Analyses of trypsin after incubation in the presence of pulse-labeled worms also failed to demonstrate the presence of any inhibitor of worm origin associated with the inactivated enzyme. The data suggest that inactivation is the result of a small structural or conformational change in the enzyme molecule, a change which partially (rather than totally) inactivates the enzyme towards protein substrates.

  12. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    PubMed

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  13. The reflex effects of alterations in lung volume on systemic vascular resistance in the dog

    PubMed Central

    Daly, M. de Burgh; Hazzledine, Julie L.; Ungar, A.

    1967-01-01

    1. The reflex effects of alterations in lung volume on systemic vascular resistance have been studied in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow. The pressures in the isolated perfused carotid sinuses and aortic arch, and the arterial blood PO2 and PCO2 were maintained constant. 2. A maintained inflation of the lungs produced by injection of air into the trachea caused a fall in systemic arterial perfusion pressure, indicating vasodilatation. The size of the systemic vasodilator response varied directly with the pressure and volume of gas used to inflate the lungs. A similar effect was observed when the tidal volume of lungs ventilated by an intermittent positive pressure was increased. 3. Collapse of the lungs by creating a pneumothorax in closed-chest spontaneously breathing animals evoked a systemic vasoconstrictor response which was reversed when the lungs were re-expanded. 4. These vasodilator responses were abolished by dividing the pulmonary branches of the thoracic vagosympathetic nerves. Evidence is presented that the afferent fibres run in the cervical vagosympathetic nerves and through the stellate ganglia. 5. The responses were unaffected by atropine, but were abolished by hexamethonium, guanethidine and by bretylium tosylate, indicating that they are mediated via the sympathetic nervous system. 6. Evidence is presented that the lungs are a constant course of afferent impulses inhibiting the `vasomotor centre', and that the lung inflation—systemic vasodilator reflex is a potential mechanism operating in eupnoeic breathing. PMID:6032204

  14. Biotinylation of the rhizobial cyclic β-glucans and succinoglycans crucial for symbiosis with legumes.

    PubMed

    Cho, Eunae; Kwon, Chanho; Lee, Sanghoo; Tahir, Muhammad Nazir; Park, Seyeon; Jung, Seunho

    2014-05-07

    The cyclic β-glucans and succinoglycans produced by rhizobia are required for nodulation during symbiosis with legume hosts. However, only gene deletion analyses have been used to investigate their biological importance. For future studies on the physiological activity of those during symbiosis, biochemical methods need to be developed with separate carbohydrate compounds. Here, we isolated and purified rhizobial cellular carbohydrates using various chromatographic methods. Purified cyclic β-glucans, cyclosophoraoses, were monofunctionalized with biotin using the following three steps: tosylation, azidation, and amination. The mono-6-amino-cyclosophoraoses were linked with biotinamidohexanoic acid N-hydroxysuccinimide ester. Succinoglycans and monomers were tagged with biotinamidocaproyl hydrazide at the reducing sugar via reductive amination. The resulting biotinylated rhizobial carbohydrates were characterized by Fourier transform infrared and nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, and electrospray ionization mass spectrometry. The resulting neoglycoconjugates can be used as solid probes to study putative plant receptors and for non-invasive imaging for in vivo tracing.

  15. The reaction of primary aromatic amines with alkylene carbonates for the selective synthesis of bis-N-(2-hydroxy)alkylanilines: the catalytic effect of phosphonium-based ionic liquids.

    PubMed

    Selva, Maurizio; Fabris, Massimo; Lucchini, Vittorio; Perosa, Alvise; Noè, Marco

    2010-11-21

    At T≥ 140 °C, different primary aromatic amines (pX-C(6)H(4)NH(2); X = H, OCH(3), CH(3), Cl) react with both ethylene- and propylene-carbonates to yield a chemoselective N-alkylation process: bis-N-(2-hydroxyalkyl)anilines [pX-C(6)H(4)N(CH(2)CH(R)OH)(2); R = H, CH(3)] are the major products and the competitive formation of carbamates is substantially ruled out. At 140 °C, under solventless conditions, the model reaction of aniline with ethylene carbonate goes to completion by simply mixing stoichiometric amounts of the reagents. However, a class of phosphonium ionic liquids (PILs) such as tetraalkylphosphonium halides and tosylates turn out to be active organocatalysts for both aniline and other primary aromatic amines. A kinetic analysis monitored by (13)C NMR spectroscopy, shows that bromide exchanged PILs are the most efficient systems, able to impart a more than 8-fold acceleration to the reaction. The reactions of propylene carbonate take place at a higher temperature than those of ethylene carbonate, and only in the presence of PIL catalysts. A mechanism based on the Lewis acidity of tetraalkylphosphonium cations and the nucleophilicity of halide anions has been proposed to account for both the reaction chemoselectivity and the function of the catalysts.

  16. A novel plasminogen activator from Agkistrodon blomhoffii Ussurensis venom (ABUSV-PA): purification and characterization.

    PubMed

    Liu, Shuqing; Sun, Ming-Zhong; Greenaway, Frederick T

    2006-10-06

    A plasminogen activator with arginine ester hydrolysis activity (ABUSV-PA) has been identified and purified to homogeneity from Chinese Agkistrodon blomhoffii Ussurensis snake venom. ABUSV-PA, a monomeric protein with molecular mass of 27815.2 Da, was purified 180-fold with 0.02% recovery for protein and 3.6% recovery for esterase activity. ABUSV-PA reacts optimally with its substrate N(alpha)-tosyl-l-arginine-methyl ester (TAME) at approximately pH 7.5 and at 51 degrees C. Measurement from inductively coupled plasma-atomic emission spectroscopy (ICP-AES) reveals that ABUSV-PA is a Zn(2+)-containing protein with a stoichiometry of 1:1 [Zn(2+)]:[ABUSV-PA]. Analyses of esterase hydrolysis and UV absorption and CD spectra indicate that Zn(2+) plays an important role in maintaining the structural integrity rather than the esterase activity of ABUSV-PA. Divalent metal ions, including Ca(2+), Mg(2+), Cu(2+), Ni(2+), Mn(2+), and Co(2+), increase the TAME hydrolysis activity of ABUSV-PA. A red-shift of the emission wavelengths of the synchronous fluorescence of ABUSV-PA, compared to those of free Tyr and Trp, indicates a conformation where the Tyr and Trp residues are in exposed hydrophilic environments. The presence of zinc increases the hydrophobicity of the conformational environments surrounding the Trp residues of ABUSV-PA and affects the secondary structure of ABUSV-PA, as proved by UV absorption and CD spectroscopy.

  17. Synthesis and phytotoxicity of new ionic liquids incorporating chiral cations and/or chiral anions.

    PubMed

    Bałczewski, Piotr; Bachowska, Barbara; Białas, Tomasz; Biczak, Robert; Wieczorek, Wanda M; Balińska, Agnieszka

    2007-03-07

    The aim of this work was to synthesize chiral ionic liquids as chiral solvents for organic synthesis and to evaluate the phyto(eco)toxicity of the new products and starting N-alkylimidazoles and their potential environmental influence on soil and plants. Chiral ionic liquids containing anions such as Cl-, Br-, TsO-, PF6(-), NO3(-), CF3SO3(-), and (+)- and (-)-C6H5CH(OH)C(O)O- were synthesized using (-)-(1R)-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-ethyl [(-)-(1R)-nopyl] halides (X = Cl, Br) and tosylate in 62-100% yields. The chloride 7 and the nitrate 13 ionic liquids possessed a toxicity dependent on the applied concentration. The lowest concentration causing a distinct reduction in plant germination/growth was 100 mg/kg. Spring barley better tolerated the ionic liquids (200 mg/kg) than common radish (100 mg/kg). The nitrate liquid did not exhibit an inhibiting effect on the germination ability of seeds. The starting N-methylimidazole used in lower concentrations (1 and 10 mg/kg of soil dry weight) was not phytotoxic, in contrast to higher doses (>1000 mg/kg).

  18. Overexpression of Escherichia coli phytase in Pichia pastoris and its biochemical properties.

    PubMed

    Tai, Hsueh-Ming; Yin, Li-Jung; Chen, Wei-Chuan; Jiang, Shann-Tzong

    2013-06-26

    To obtain a Pichia pastoris mutant with an Escherichia coli phytase gene, which was synthesized according to P. pastoris codon preference, a mature phytase cDNA of E. coli being altered according to the codons usage preference of P. pastoris was artificially synthesized and cloned into an expression vector of pGAPZαC. The final extracellular phytase activity was 112.5 U/mL after 72 h of cultivation. The phytase, with a molecular mass of 46 kDa, was purified to electrophoretical homogeneity after Ni Sepharose 6 Fast Flow chromatography. The yield, purification fold, and specific activity were 63.97%, 26.17, and 1.57 kU/mg, respectively. It had an optimal pH and temperature of 4.0-6.0 and 50 °C, respectively, and was stable at pH 3.0-8.0 and 25-40 °C. The purified recombinant phytase was resistant to trypsin, highly inhibited by Cu(2+), Zn(2+), Hg(2+), Fe(2+), Fe(3+), phenylmethylsulfonyl fluoride, and N-tosyl-l-lysine chloromethyl ketone, but activated by Mg(2+), Ca(2+), Sr(2+), Ba(2+), glutathione, ethylenediaminetetraacetic acid, and N-ethylmaleimide. It revealed higher affinity to calcium phytate than to other phosphate conjugates.

  19. Role of Muscarinic Acetylcholine Receptor-2 in the Cerebellar Cortex in Cardiovascular Modulation in Anaesthetized Rats.

    PubMed

    Zhang, Changzheng; Sun, Tingzhe; Zhou, Peiling; Zhu, Qingfeng; Zhang, Liefeng

    2016-04-01

    Our previous investigations have demonstrated that microinjection of acetylcholine (ACh) or muscarinic ACh receptor activation in the cerebellar cortex induces a systemic blood pressure depressor response. This study aimed to determine the role of muscarinic ACh receptor-2 (M2 receptor) in the cerebellar cortex in cardiovascular function regulation in rats. A nonselective muscarinic receptor agonist (oxotremorine M, OXO; 30 mM), a selective M2 receptor agonist (arecaidine but-2-ynyl ester tosylate, ABET; 3, 10, and 30 mM), 30 mM OXO mixed with a selective M2 receptor antagonist (methoctramine hydrate, MCT; 0.3, 1, and 3 mM), and normal saline (0.9 % NaCl) were separately microinjected (0.5 µl/5 s) into the cerebellar cortex (lobule VI) of anaesthetized rats. We measured the mean arterial pressure (MAP), maximum change in MAP, and reactive time (RT; the duration required for the blood pressure to return to basal levels), heart rate (HR) and the maximum change in HR during the RT in response to drug activation. The results demonstrated that ABET dose-dependently decreased MAP and HR, increased the maximum change in MAP and the maximum change in HR, and prolonged the RT. Furthermore, MCT dose-dependently blocked the OXO-mediated cardiovascular depressor response. This study provides the first evidence that M2 receptors in the cerebellar cortex are involved in cardiovascular regulation, the activation of which evokes significant depressor and bradycardic responses.

  20. Divergent Synthetic Access to E‐ and Z‐Stereodefined All‐Carbon‐Substituted Olefin Scaffolds: Application to Parallel Synthesis of (E)‐ and (Z)‐Tamoxifens

    PubMed Central

    Ashida, Yuichiro; Honda, Atsushi; Sato, Yuka

    2017-01-01

    Abstract A highly substrate‐general synthesis of all‐carbon‐substituted E‐ and Z‐stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)‐ and (Z)‐α,β‐unsaturated esters involving two robust and distinctive reactions: 1) stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2) stereoretentive Negishi cross‐coupling using the catalysts [Pd(dppe)Cl2] (for E) and [Pd(dppb)Cl2] (for Z). The present parallel approach is categorized as both type I (convergent approach: 16 examples, 56–87 % yield) and type II (divergent approach: 18 examples, 70–95 % yield). The obtained (E)‐ and (Z)‐α,β‐unsaturated ester scaffolds are successfully transformed into various E‐ and Z‐stereodefined known and novel olefins (8×2 derivatization arrays). As a demonstration, application to the parallel synthesis of both (E)‐ and (Z)‐tamoxifens, a representative motif of all‐carbon‐substituted olefins, is accomplished in a total of eight steps with an overall yield of 58 % (average 93 %) and 57 % (average 93 %), respectively. PMID:28168153

  1. Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium.

    PubMed

    Jackson, C J; Garbett, P K; Nissen, B; Schrieber, L

    1990-06-01

    A major problem encountered when isolating human microvascular endothelium is the presence of contaminating cells such as fibroblasts that rapidly over-grow the endothelial cells. We describe here a simple, rapid technique for purifying endothelial cells derived from the microvasculature of neonatal foreskin and osteoarthritic and rheumatoid arthritic synovium. This technique is based on the selective binding of the lectin Ulex europaeus I (UEA I) to the endothelial cell surface via fucose residues. Initially UEA I was covalently bound to tosyl-activated super-paramagnetic polystyrene beads (Dynabeads) by incubation for 24 h at room temperature. Cells were isolated by extracting microvascular segments from enzyme-treated (trypsin and Pronase) cubes of tissue. The mixed population of cells obtained were purified by incubating them at 4 degrees C for 10 min with the UEA I-coated Dynabeads. Endothelium bound to the beads whilst contaminating cells were removed by five washes with HBSS using a magnetic particle concentrator. The endothelial cells thus obtained grew to confluence as a cobblestone-like monolayer and expressed von Willebrand factor antigen. The cells were released from the Dynabeads by the competitive binding of fucose (10 min at 4 degrees C). This new method is simple and reproducible and allows pure human microvascular endothelial cells to be cultured within 2 h of obtaining a specimen.

  2. Shear-induced structural and thermodynamic phase transitions in micellar systems.

    PubMed

    Martín Del Campo, Angelina; García-Sandoval, J Paulo; Soltero, J F Armando; Bautista, Fernando; Manero, Octavio; Puig, Jorge E

    2017-02-01

    In this contribution a methodology to compute and classify shear-induced structural and phase transitions in surfactant/water mixtures from rheological measurements is presented. Non-linear rheological experiments, considering variations in surfactant concentration and temperature, are analyzed. In particular, the parameters of the BMP (Bautista-Manero-Puig) model, obtained from the fitting of the shear stress versus shear rate data, which are functions of surfactant concentration and temperature, allow classifying structural and phase transition boundaries. To test this methodology, we consider the analysis of the shear-induced structural and phase transitions of two micellar systems, cetyltrimethylammonium tosylate (CTAT)/water as a function of CTAT concentrations and Pluronics P103/water as a function of temperature. We found that the CTAT/water system presents a first-order phase transition at 30 (°) C, and around 31 to 32 wt.% from isotropic to nematic phases, whereas a 20 wt.% Pluronics P103 aqueous micellar solution has two second-order (structural) phase transitions, one from spherical to cylindrical micelles at 33.1 (°) C, and another one from cylindrical micelles to a nematic phase at 35.8 (°) C and one first-order phase transition around 37.9 (°) C at high shear rates near to the cloud point previously reported. The proposed methodology is also able to identify the instability regions where the wormlike micelles are broken, producing the typical shear banding behavior.

  3. Inhibitor of nuclear factor-Kappa B activation attenuates venular constriction, leukocyte rolling-adhesion and microvessel rupture induced by ethanol in intact rat brain microcirculation: relation to ethanol-induced brain injury.

    PubMed

    Altura, Burton M; Gebrewold, Asefa

    2002-12-06

    The present study was designed to test the hypothesis that acute, local administration of a specific inhibitor of nuclear factor-Kappa B activation (which prevents rapid proteolysis of IKB-alpha) will attenuate cerebral (cortical) venular constrictions, leukocyte-endothelial wall interactions and postcapillary damage induced by medium to high concentrations of ethanol in the intact rat brain. Perivascular or i.p. administration of ethanol (100, 250 mg/dl) to the intact rat brain resulted in concentration-dependent venular vasospasm, rolling and adherence of leukocytes to venular walls and rupture of postcapillary venules with focal hemorrhages. Superfusion of the in-situ brain with N(alpha)-L-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a specific inhibitor of IKB-alpha proteolysis, attenuated greatly the spasmogenic, leukocyte rolling-endothelial cell adhesion and postcapillary hemorrhages induced by ethanol. These new data suggest that inhibition of alcohol-inducible degradation of IKB-alpha by TPKC can prevent much of the adverse microvascular actions of ethanol in the intact rat brain. Moreover, these new in-situ results suggest that activation of nuclear factor-Kappa B seems to play a major modulatory role in the adverse cerebral vascular actions of concentrations of alcohol found in the blood of alcohol-intoxicated subjects and human stroke victims.

  4. Clinical and Immunological Analysis of Cutaneous Leishmaniasis before and after Different Treatments.

    PubMed

    O'Daly, José A; Spinetti, Humberto M; Gleason, Joe; Rodríguez, María B

    2013-01-01

    Amastigotes from L. (L.)amazonensis (La), L. (L.)venezuelensis (Lv), L. (V.)brasiliensis (Lb), and L. (L.)chagasi (Lch) were cultured in a free cells liquid culture medium. Patients (n = 87) from a cutaneous leishmaniasis (CL) hyperendemic region receiving different treatments were followed up from January 1994 to August 2000. Time for remission of lesions were spontaneous remission (SR) 7 weeks; Glucantime (Glu) chemotherapy 9 weeks; immunotherapy with La, Lv, Lb, and Lch amastigotes Tosyl-Lysil Chloromethyl-ketone (TLCK) treated and Nonidet P-40(NP-40) extracted (VT) 7 weeks. Delayed type hypersensitivity (DTH) response with leishmanine intradermic reaction (IDR) was higher in CL patients than healthy controls (P < 0.05) and increased in active secondary versus primary infection (P < 0.001) with diagnostic value 1.74 for active infection and 1.81 postclinical remission. Antibodies to amastigotes characterized by Enzyme Linked Immunosorbent Assay (ELISA) decreased in sera postclinical remission versus active infections (P < 0.001), with a diagnostic value from 1.50 to 1.84. Immunoblottings antigenic bands frequency as well as Integral Optical Density (IOD) Area Densitometry decreased with sera from SR, after Glu or VT treatments in CL volunteers. Intracellular parasitism is due to normal antibodies recognizing parasite antigens after inoculation by vector. VT vaccine induced mainly cellular immunity, for remission of lesions and protection from CL infection.

  5. Effect of micellar topology on shear rheology

    NASA Astrophysics Data System (ADS)

    Rogers, Simon; Calabrese, Michelle; Wagner, Norman

    2014-03-01

    Micellar topology affects the nonlinear shear rheology of self-assembled surfactant solutions. Segmental alignment of wormlike micelles (WLMs) exhibiting varying degrees of branching was investigated under shear in the flow-gradient and flow-vorticity planes using new small angle neutron scattering (SANS) sample environments. The degree of branching in mixed cationic/anionic surfactant (CTAT/SDBS) WLMs is controlled via the addition of the hydrotropic salt sodium tosylate. Shear-induced segmental alignment of the micelles is characterized by spatially-resolved flow-small angle neutron scattering (flow-SANS). Our ability to resolve structural projections in both planes provides insight to branch behavior and kinematics under shear flows. Local segmental orientation and alignment in the flow-gradient plane is a non-monotonic function of branching level and radial position. Alignment in the flow-gradient plane is significantly higher than that observed in the flow-vorticity plane, suggesting that branches may simultaneously migrate into the vorticity direction and inhibit spatially localized flows. Shear and normal stresses calculated from micellar alignment using the stress-SANS law are favorably compared with rheological measurements under identical conditions. The results provide evidence for the effects of micellar topology on the nonlinear shear rheology of WLM solutions.

  6. Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

    PubMed Central

    Zhao, Li; Nakae, Yuki; Qin, Hongmei; Ito, Tadamasa; Kimura, Takahide; Kojima, Hideto; Chan, Lawrence

    2014-01-01

    Summary A gene vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP) has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (–OH → –OTs (tosylate) → –N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was confirmed by gel retardation assay that ND-PG-Arg8 and ND-PG-Lys8 with higher zeta potential hybridized with plasmid DNA (pDNA) through electrostatic attraction, making them promising as nonviral vectors for gene delivery. PMID:24778723

  7. Biocompatible, hyaluronic acid modified silicone elastomers.

    PubMed

    Alauzun, Johan G; Young, Stuart; D'Souza, Renita; Liu, Lina; Brook, Michael A; Sheardown, Heather D

    2010-05-01

    Although silicones possess many useful properties as biomaterials, their hydrophobicity can be problematic. To a degree, this issue can be addressed by surface modification with hydrophilic polymers such as poly(ethylene glycol), but the resulting structures are usually not conducive to cell growth. In the present work, we describe the synthesis and characterization of covalently linked hyaluronic acid (HA) (35 kDa) to poly(dimethylsiloxane) (PDMS) elastomer surfaces. HA is of interest because of its known biological properties; its presence on a surface was expected to improve the biocompatibility of silicone materials for a wide range of bioapplications. HA was introduced with a coupling agent in two steps from high-density, tosyl-modified, poly(ethylene glycol) tethered silicone surfaces. All materials synthesized were characterized by water contact angle, ATR-FTIR, XPS and (13)C solid state NMR spectroscopy. Biological interactions with these modified silicone surfaces were assessed by examining interactions with fibrinogen as a model protein as well as determining the in vitro response of fibroblast (3T3) and human corneal epithelial cells relative to unmodified poly(dimethylsiloxane) controls. The results suggest that HA modification significantly enhances cell interactions while decreasing protein adsorption and may therefore be effective for improving biocompatibility of PDMS and other materials.

  8. Competitive FRET-aptamer-based detection of methylphosphonic acid, a common nerve agent metabolite.

    PubMed

    Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Vail, Neal K; Hanson, Douglas

    2008-09-01

    Competitive fluorescence resonance energy transfer (FRET)-aptamer-based assay formats are described for one-step detection of methylphosphonic acid (MPA; a metabolite of several organophosphorus (OP) nerve agents). AminoMPA was attached to tosyl-magnetic beads and used for DNA aptamer selection from which one dominant aptamer sequence emerged. Two different FRET approaches were attempted. In one approach, the complementary DNA sequence was used as a template for labeling the aptamer with Alexa Fluor 546 (AF 546)-14-dUTP by asymmetric PCR. Following 3-dimensional (3-D), molecular modeling of the aptamer-MPA complex, a series of three fluoresceinated aptamers labeled at positions 50, 51, and 52 in the putative optimal binding pocket were synthesized. In both FRET formats, aminoMPA was linked to Black Hole Quencher (BHQ-1 or BHQ-2)-succinimides and allowed to bind the fluorescein or AF 546-labeled MPA aptamer. Following gel filtration to purify the labeled MPA aptamer-BHQ-aminoMPA FRET complexes, the complexes were competed against various concentrations of unlabeled MPA, MPA derivatives, and unrelated compounds in titration and cross-reactivity studies. Both approaches yielded low microgram per milliliter detection limits for MPA with generally low levels of cross-reactivity for unrelated compounds. However, the data suggest a pattern of traits that may effect the direction (lights on or off) and intensity of the FRET.

  9. Preparation and biodistribution of F-18 labeled FQNPe

    SciTech Connect

    Luo, H.; Beets, K.; McPherson, D.W.; Knapp, F.F. Jr.

    1996-05-01

    1-Azabicyclo[2.2.2]oct-3-yl {alpha}-(1-fluoropentan-5-yl)-{alpha}-hydroxy-{alpha}-phenylacetate (FQNPe) is an attractive candidate for the in vivo imaging of muscarinic receptors (mAChR) by PET. Initial studies with this new agent demonstrated a high binding affinity and ability to bind to regions of the brain containing mAChR. Fluorine-18 (F-18) labeling of racemic 1 was performed using X = tosyl, triflate, or mesylate group and a decay corrected radiolabeling yields of 2.6, 33, 75%, respectively, were obtained. F-18-3 in 11 % yield (decay corrected to beginning of synthesis). Initial biodistribution studies in rats (n=5) showed F-18-3 had high cerebral uptake of 0.72 ({plus_minus}0.26) and 0.83 ({plus_minus} 0.12) injected dose/gram at 15 and 30 minutes, respectively. The F-18 labeling and biodistribution study of the (-)-quinuclidinyl (-)-acetate and (-)-quinuclidinyl (+)-acetate isomers of FQNPe are currently being pursued.

  10. The Ruthenostannylene Complex [Cp*(IXy)H2 Ru-Sn-Trip]: Providing Access to Unusual Ru-Sn Bonded Stanna-imine, Stannene, and Ketenylstannyl Complexes.

    PubMed

    Liu, Hsueh-Ju; Ziegler, Micah S; Tilley, T Don

    2015-05-26

    Reactivity studies of the thermally stable ruthenostannylene complex [Cp*(IXy)(H)2 Ru-Sn-Trip] (1; IXy=1,3-bis(2,6-dimethylphenyl)imidazol-2-ylidene; Cp*=η(5) -C5 Me5 ; Trip=2,4,6-iPr3 C6 H2 ) with a variety of organic substrates are described. Complex 1 reacts with benzoin and an α,β-unsaturated ketone to undergo [1+4] cycloaddition reactions and afford [Cp*(IXy)(H)2 RuSn(κ(2) -O,O-OCPhCPhO)Trip] (2) and [Cp*(IXy)(H)2 RuSn(κ(2) -O,C-OCPhCHCHPh)Trip] (3), respectively. The reaction of 1 with ethyl diazoacetate resulted in a tin-substituted ketene complex [Cp*(IXy)(H)2 RuSn(OC2 H5 )(CHCO)Trip] (4), which is most likely a decomposition product from the putative ruthenium-substituted stannene complex. The isolation of a ruthenium-substituted stannene [Cp*(IXy)(H)2 RuSn(=Flu)Trip] (5) and stanna-imine [Cp*(IXy)(H)2 RuSn(κ(2) -N,O-NSO2 C6 H4 Me)Trip] (6) complexes was achieved by treatment of 1 with 9-diazofluorene and tosyl azide, respectively.

  11. A substituted sulfonamide and its Co (II), Cu (II), and Zn (II) complexes as potential antifungal agents.

    PubMed

    Diaz, Jorge R A; Fernández Baldo, Martín; Echeverría, Gustavo; Baldoni, Héctor; Vullo, Daniela; Soria, Delia B; Supuran, Claudiu T; Camí, Gerardo E

    2016-01-01

    A sulfonamide 1-tosyl-1-H-benzo(d)imidazol-2-amine (TBZA) and three new complexes of Co(II), Cu(II), and Zn(II) have been synthesized. The compounds have been characterized by elemental analyses, FTIR, (1)H, and (13)C-NMR spectroscopy. The structure of the TBZA, and its Co(II) and Cu(II) complexes, was determined by X-ray diffraction methods. TBZA and its Co(II) complex crystallize in the triclinic P-1 space group, while the Cu(II) complex crystallizes in the monoclinic P21/c space group. Antifungal activity was screened against eight pathogenic yeasts: Candida albicans (DMic 972576), Candida krusei (DMic 951705), Candida glabrata (DMic 982882), Candida tropicalis (DMic 982884), Candida dubliniensis (DMic 93695), Candida guilliermondii (DMic 021150), Cryptococcus neoformans (ATCC 24067), and Cryptococcus gattii (ATCC MYA-4561). Results on the inhibition of various human (h) CAs, hCA I, II, IV, VII, IX, and XII, and pathogenic beta and gamma CAs are also reported.

  12. Morphology and preliminary enzyme characterization of the salivary glands from the predatory bug Podisus nigrispinus (Heteroptera: Pentatomidae).

    PubMed

    Oliveira, J A; Oliveira, M G A; Guedes, R N C; Soares, M J

    2006-06-01

    Podisus nigrispinus (Dallas) is a common predator in agricultural and natural systems in Neotropical America. Its feeding strategy involves extra-oral digestion and to better understand this process its salivary glands were extracted and subjected to morphological and preliminary enzyme characterization. The salivary glands of P. nigrispinus are formed by a pair of main and accessory gland complexes. The main salivary glands are further divided into an anterior and a posterior lobe. The compartmentalization of the salivary gland complex is likely to be important for the production, activation and release of the digestive enzymes used in the extra-oral digestion of prey items. Proteases and lipase, important digestive enzymes involved in zoophagy, were detected in the salivary glands of P. nigrispinus. The prevailing trypsin-like protease activity was characterized by using the serine-protease substrate N-alpha-benzoyl-L-Arg-p-nitroanilidine (L-BApNA) and the trypsin inhibitors tosyl-L-lysine chloromethyl ketone (TLCK) and benzamidine. The KM value obtained for trypsin-like activity was 1.57 mm and the different peaks of optimum pH and temperature activity suggest the presence of multiple forms of this enzyme in P. nigrispinus. Detection of amylase activity in the salivary glands of this predator suggests its ability to digest starch and obtain nutrients from plants, which may have adaptative value under prey scarcity.

  13. Serine protease activities in Leishmania (Leishmania) chagasi promastigotes.

    PubMed

    da Silva-López, Raquel Elisa; dos Santos, Tatiana Resende; Morgado-Díaz, José Andrés; Tanaka, Marcelo Neves; de Simone, Salvatore Giovanni

    2010-10-01

    The present work reports the isolation, biochemical characterization, and subcellular location of serine proteases from aqueous, detergent soluble, and culture supernatant of Leishmania chagasi promastigote extracts, respectively, LCSII, LCSI, and LCSIII. The active enzyme molecular masses of LCSII were about 105, 66, and 60 kDa; of LCSI, 60 and 58 kDa; and of LCSIII, approximately 76 and 68 kDa. Optimal pH for the enzymes was 7.0 for LCSI and LCSIII and 8.5 for LCSII, and the optimal temperature for all enzymes was 37°C, using α-N-ρ-tosyl-L: -arginine methyl ester as substrate. Assay of thermal stability indicated that LCSIII is the more stable enzyme. Hemoglobin, bovine serum albumin, and ovalbumin were hydrolyzed by LCSII and LCSI but not by LCSIII. Inhibition studies suggested that enzymes belong to the serine protease class modulated by divalent cations. Rabbit antiserum against 56-kDa serine protease of Leishmania amazonensis identified proteins in all extracts of L. chagasi. Furthermore, immunocytochemistry demonstrated that serine proteases are located in flagellar pocket region and cytoplasmic vesicles of L. chagasi promastigotes. These findings indicate that L. chagasi serine proteases differ from L. amazonensis proteases and all known flagellate proteases, but display some similarities with serine proteases from other Leishmania species, suggesting a conservation of this enzymatic activity in the genus.

  14. Proteases from Canavalia ensiformis: Active and Thermostable Enzymes with Potential of Application in Biotechnology

    PubMed Central

    Gonçalves, Rayane Natshe; Gozzini Barbosa, Suellen Duarte

    2016-01-01

    Extracts of leaves, seeds, roots, and stem from a tropical legume, C. ensiformis, were prepared employing buffers and detergent in aqueous solution. Leaf extracts had the highest protein content and the most pronounced peptidase activity with optimal pH in the neutral to alkaline range. All extracts exhibited peaks of activity at various pH values, suggesting the presence of distinctive classes of proteases. N-α-Tosyl-L-arginine methyl ester hydrolysis was maximal at 30°C to 60°C and peptidase activity from all extracts presented very good thermal stability after 24 h incubation at 70°C. C. ensiformis proteases exhibited molecular masses of about 200–57, 40–37, and 20–15 kDa by SDS-PAGE analysis. These enzymes cleaved hemoglobin, bovine serum albumin, casein, and gelatin at different levels. Serine and metalloproteases are the major proteases in C. ensiformis extracts, modulated by divalent cations, stable at 1% of surfactant Triton X-100 and at different concentrations of the reducing agent β-mercaptoethanol. Thus, C. ensiformis expresses a particular set of proteases in distinctive organs with high activity and stability, making this legume an important source of proteases with biotechnological potential. PMID:27630776

  15. Effect of serine protease inhibitors on posttraumatic brain injury and neuronal apoptosis.

    PubMed

    Movsesyan, V A; Yakovlev, A G; Fan, L; Faden, A I

    2001-02-01

    N-Tosyl-l-phenylalanyl chloromethyl ketone (TPCK), an inhibitor of chymotrypsin-like serine protease (CSP), prevents DNA fragmentation and apoptotic cell death in certain blood cell lines and was reported to reduce hippocampal neuronal damage caused by cerebral ischemia. We examined the role of CSP on recovery after lateral fluid percussion-induced traumatic brain injury (TBI) in rats, as well as on cell survival in various in vitro models of neuronal cell death. TBI caused significant time-dependent upregulation of CSP activity, but not trypsin-like serine protease activity in injured cortex. Intracerebroventricular administration of TPCK to rats after TBI did not significantly affect deficits of spatial learning but exacerbated motor dysfunction after injury. Moreover, TPCK did not prevent apoptotic neuronal cell death caused by serum/K(+) deprivation or by application of staurosporine or etoposide in cultured rat cerebellar granule cells, rat cortical neurons, or in the human neuroblastoma SH-SY5Y cell line. Instead, at doses from 10 to 100 microM, TPCK was cytotoxic in all cultures tested. Similar results were obtained in cultures treated with another CSP inhibitor, 3,4-dichloroisocoumarin. Cell death caused by CSP inhibitors was neither caspase-dependent nor associated with oligonucleosomal DNA fragmentation. Taken together, these data do not support a neuroprotective role for CSP inhibitors. Rather, they suggest that CSPs may serve an endogenous neuroprotective role, possibly by modulating necrotic cell death.

  16. The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications.

    PubMed

    Baek, Sungchul; Green, Rylie A; Poole-Warren, Laura A

    2014-07-01

    Poly(3,4-ethylenedioxythiophene) (PEDOT) films have attracted substantial interest as coatings for platinum neuroprosthetic electrodes due to their excellent chemical stability and electrical properties. This study systematically examined PEDOT coatings formed with different amounts of charge and dopant ions, and investigated the combination of surface characteristics that were optimal for neural cell interactions. PEDOT samples were fabricated by varying the electrodeposition charge from 0.05 to 1 C cm(-2). Samples were doped with either poly(styrenesulfonate), tosylate (pTS) or perchlorate. Scanning electron micrographs revealed that both thickness and nodularity increased as the charge used to produce the sample was increased, and larger dopants produced smoother films across all thicknesses. X-ray photoelectron spectroscopy confirmed that the amount of charge directly corresponded to the thickness and amount of dopant in the samples. Additionally, with increased thickness and nodularity, the electrochemical properties of all PEDOT coatings improved. However, neural cell adhesion and outgrowth assays revealed that there is a direct biological tradeoff related to the thickness and nodularity. Cell attachment, growth and differentiation was poorer on the thicker, rougher samples, but thin, less nodular PEDOT films exhibited significant improvements over bare platinum. PEDOT/pTS fabricated with a charge density of <0.1Ccm(-2) provided superior electrochemical and biological properties over conventional platinum electrodes and would be the most suitable conducting polymer for neural interface applications.

  17. Selective corticotropin-releasing factor 1 receptor antagonist E2508 reduces restraint stress-induced defecation and visceral pain in rat models.

    PubMed

    Taguchi, Ryota; Shikata, Kodo; Furuya, Yoshiaki; Hirakawa, Tetsuya; Ino, Mitsuhiro; Shin, Kogyoku; Shibata, Hisashi

    2017-01-01

    N-Cyclopropylmethyl-7-(2,6-dimethoxy-4-methoxymethylphenyl)-2-ethyl-N-(tetrahydro-2H-pyran-4-ylmethyl)pyrazolo[1,5-a]pyridin-3-amine tosylate (E2508) is a newly discovered selective corticotropin-releasing factor 1 receptor antagonist. Here, we investigated the effects of E2508 on wrap restraint stress-induced defecation and visceral pain in rats. Oral pretreatment with E2508 dose-dependently decreased stool weights after 20min wrap restraint stress and significant effects were observed at doses of 30 and 100mg/kg. However, E2508 did not affect basal defecation at doses up to 100mg/kg. In contrast, alosetron, a 5-HT3 receptor antagonist, decreased both wrap restraint stress-induced and basal stool output at a dose of 0.1mg/kg. In a rat visceral pain model, subcutaneous injections of both E2508 (0.01 and 0.1mg/kg) and alosetron (0.001 and 0.01mg/kg) significantly decreased the number of abdominal muscle contractions induced by colonic distention, suggesting these drugs reduced visceral pain. Together, these results demonstrate E2508 has the potential to be an effective therapy for the treatment of irritable bowel syndrome with a lower risk of adverse events such as constipation compared with the current clinically used 5-HT3 receptor antagonist.

  18. Practical enantioselective process for a chiral phosphodiesterase-4 inhibitor.

    PubMed

    Chen, Cheng-Yi

    2005-11-01

    L-869298 is a potent and selective phosphodiesterase-4 (PDE4) inhibitor, which is potentially useful in the treatment of asthma and chronic obstructive pulmonary disorder. A catalytic asymmetric synthesis that is suitable for the preparation of kilogram quantities of L-869298, and which does not require the use of chromatography, has been developed to support the on-going drug development program of L-869298 at Merck Research Laboratories. The catalytic asymmetric hydrogenation of an aromatic heteroaromatic ketone afforded the corresponding alcohol in almost perfect enantioselectivity. Activation of the alcohol via formation of the 4-toluenesulfonate, followed by an unprecedented displacement of the tosylate via the lithium enolate of ethyl-3-pyridyl acetate N-oxide, generated the chiral tetra-substituted ethane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Deprotection of the displacement adduct followed by decarboxylation, afforded L-869298 in excellent overall yield. The methodology developed could be readily extended to the synthesis of several other chiral PDE4 inhibitors.

  19. Immunoassay for folic acid detection in vitamin-fortified milk based on electrochemical magneto sensors.

    PubMed

    Lermo, A; Fabiano, S; Hernández, S; Galve, R; Marco, M-P; Alegret, S; Pividori, M I

    2009-03-15

    An immunoassay-based strategy for folic acid in vitamin-fortified milk with electrochemical detection using magneto sensors is described for the first time. Among direct and indirect competitive formats, best performance was achieved with an indirect competitive immunoassay. The immunological reaction for folic acid (FA) detection was performed, for the first time on the magnetic bead as solid support by the covalent immobilization of a protein conjugate BSA-FA on tosyl-activated magnetic bead. Further competition for the specific antibody between FA in the food sample and FA immobilized on the magnetic bead was achieved, followed by the reaction with a secondary antibody conjugated with HRP (AntiIgG-HRP). Then, the modified magnetic beads were easily captured by a magneto sensor made of graphite-epoxy composite (m-GEC) which was also used as the transducer for the electrochemical detection. The performance of the immunoassay-based strategy with electrochemical detection using magneto sensors was successfully evaluated using spiked-milk samples and compared with a novel magneto-ELISA based on optical detection. The detection limit was found to be of the order of microgl(-1) (13.1 nmoll(-1), 5.8 microgl(-1)) for skimmed milk. Commercial vitamin-fortified milk samples were also evaluated obtaining good accuracy in the results. This novel strategy offers great promise for rapid, simple, cost-effective and on-site analysis of biological and food samples.

  20. Synthesis of globular precursors.

    PubMed

    Teixidor, Francesc; Sillanpää, Reijo; Pepiol, Ariadna; Lupu, Marius; Viñas, Clara

    2015-09-01

    o-Carborane (C2 B10 H12 ) was adapted to perform as the core of globular macromolecules, dendrons or dendrimers. To meet this objective, precisely defined substitution patterns of terminal olefin groups on the carborane framework were subjected to Heck cross-coupling reactions or hydroboration leading to hydroxyl terminated arms. These led to new terminal groups (chloro, bromo, and tosyl leaving groups, organic acid, and azide) that permitted ester production, click chemistry, and oxonium ring opening to be performed as examples of reactions that demonstrate the wide possibilities of the globular icosahedral carboranes to produce new dendritic or dendrimer-like structures. Polyanionic species were obtained in high yield through the ring-opening reaction of cyclic oxonium compound [3,3'-Co(8-C4 H8 O2 -1,2-C2 B9 H10 )(1',2'-C2 B9 H11 )] by using terminal hydroxyl groups as nucleophiles. These new polyanionic compounds that contain multiple metallacarborane clusters at their periphery may prove useful as new classes of compounds for boron neutron capture therapy with enhanced water solubility and as cores to make a new class of high-boron globular macromolecules.

  1. Synthesis of flavonoids based novel tetrahydropyran conjugates (Prins products) and their antiproliferative activity against human cancer cell lines.

    PubMed

    Ahmed, Naseem; Konduru, Naveen Kumar; Ahmad, Sarfaraz; Owais, Mohammad

    2014-03-21

    Following our previously reported Prins cyclization strategy, a series of novel and highly functionalized flavonoid based THPs (Prins products) were designed, synthesized and evaluated for their antiproliferative activity. Novel products were afforded in excellent yields (72-96%) within 20-90 min at 62 °C using flavonoid aldehydes, homoallylic alcohols, p-TSA·H2O (catalyst and reagent) and MS 4 Å in CHCl3. Deprotection of tosyl group was achieved with TFA (catalyst and solvent) at 140 °C to obtain 4-hydroxytetrahydropyrans and further reaction of 4-hydroxytetrahydropyrans with cinnamoyl chloride afforded 4-cinnamate tetrahydropyrans under neat condition. Synthesized compounds evaluated against human cancer cell lines (Hep3β, MCF-7 and Hela), have shown moderate to good antiproliferative activity in vivo. Compounds 3q and 3zb exhibited similar cytotoxicity (IC50 6.6 ± 1.4, 6.9 ± 1.0 μM, respectively) to the reference drug doxorubicin (IC50 7.6 ± 0.9 μM) against the MCF-7 cancer cell line. Compound 3zb was found equally active as the standard drug (IC50 4.48 ± 2.1 μM) against the Hep3β cell line and compounds 3c and 3q showed moderate cytotoxicity (IC50 10.40 ± 1.1, 12.9 ± 1.7 μM, respectively) against the HeLa cell line.

  2. Inhibitory effect of peroxiredoxin II (Prx II) on Ras-ERK-NFkappaB pathway in mouse embryonic fibroblast (MEF) senescence.

    PubMed

    Han, Ying-Hao; Kwon, Jeong-Hoon; Yu, Dae-Yeul; Moon, Eun-Yi

    2006-11-01

    Intracellular reactive oxygen species (ROS) were attenuated by the expression of peroxiredoxin II (Prx II). Cellular senescence as judged by senescence-associated (SA)-beta-galactosidase (Gal) positive cell formation was increased in Prx II-deficient mouse embryonic fibroblast (MEF). Ras expression was increased following passages. The level of Ras expression was higher in Prx II-/- MEF than wild type MEF. ERK activity was also augmented by the deletion of Prx II. SA-beta-Gal-positive cell formation was reduced by PD98059, ERK inhibitor. Activated nuclear transcription factor, nuclear factor-kappaB (NFkappaB) by the deletion of Prx II was inhibited by the treatment with PD98059. In contrast, no changes in SA-beta-Gal-positive cell formation were detected by NFkappaB inhibitor, N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK). Collectively, results suggest that Prx II deletion activate Ras-ERK-NFkappaB pathways and cellular senescence in Prx II-/- MEF cells was mediated by ERK activation but not by NFkappaB activation.

  3. Synthesis and Evaluation of 18F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine

    PubMed Central

    Mou, Tiantian; Zhao, Zuoquan; You, Linyi; Li, Yesen; Wang, Qian; Fang, Wei; Lu, Jie; Peng, Cheng; Zhang, Xianzhong

    2016-01-01

    This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with 18F. The total radiosynthesis time of these tracers was 70–90 min. Typical decay-corrected radiochemical yields were 47–58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34–54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [18F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [18F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [18F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent. PMID:27646847

  4. Synthesis and Biological Evaluation of an (18)Fluorine-Labeled COX Inhibitor--[(18)F]Fluorooctyl Fenbufen Amide--For Imaging of Brain Tumors.

    PubMed

    Huang, Ying-Cheng; Chang, Yu-Chia; Yeh, Chun-Nan; Yu, Chung-Shan

    2016-03-21

    Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts2O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [(18)F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [(18)F]F(-) (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown to exceed 22 GBq/μmol (EOS) based on decay-corrected calculations. Ex-vivo analysis of [(18)F]FOFA in plasma using HPLC showed that the agent had a half-life of 15 min. PET scanning showed significant accumulation of [(18)F]FOFA over tumor loci with reasonable contrast in C6-glioma bearing rats. These results suggest that this molecule is a promising agent for the visualization of brain tumors. Further investigations should focus on tumor micro-environments.

  5. Intrinsic (gas phase) thermodynamic stability of 2-adamantyl cation. Its bearing on the solvolysis rates of 2-adamantyl derivatives.

    PubMed

    Abboud, José-Luis M; Castaño, Obis; Dávalos, Juan Z; Jiménez, Pilar; Gomperts, Roberto; Müller, Paul; Roux, María Victoria

    2002-02-22

    The standard enthalpy of formation of gaseous 2-adamantyl chloride(2-Ad-Cl) was determined by calorimetric techniques. The standard Gibbs energy change for the chloride anion exchange between 1-adamantyl (1-Ad+) and 2-adamantyl (2-Ad+) cations in the gas phase was obtained by Fourier transform ion cyclotron resonance spectroscopy (FT ICR). Theoretical calculations at the G2(MP2) level were performed on these and other relevant species. This and data from the literature provided three highly consistent independent estimates of the relative stabilities of 2-Ad+ and 1-Ad+. This difference in gas-phase stability was compared to the differential structural effects on the rates of solvolysis of the corresponding chlorides and tosylates, and it was shown that the thermodynamic stability of the secondary cation is the leading factor determining the solvolytic reactivity of the precursors in the absence of solvent effects. Thus, under these conditions, the previously established linear free energy correlation between carbenium ion stability and solvolytic reactivity of bridgehead derivatives applies also to secondary derivatives.

  6. Nucleophilic substitutions of 1-alkenylcyclopropyl esters and 1-alkynylcyclopropyl chlorides catalyzed by palladium (0)

    SciTech Connect

    Stolle, A. |; Ollivier, J.; Salauen, J.

    1992-05-20

    The 1-ethenylcyclopropylsulfonates 2e,f and 2-cyclopropylideneethyl esters 10b,c, readily available from cyclopropanone hemiacetal 1, undergo regioselective Pd(0) catalyzed nucleophilic substitution via the unsymmetric 1,1-dimethylene-{pi}-allyl complex 23. With stabilized anions (enolates of malonic ester, {beta}-dicarbonyl compounds, {beta}-sulfonyl ester, and Schiff bases as well as acetate anion, sulfonamide anion, etc.) the nucleophilic substitution occurs at the terminal vinylic position exclusively, providing cyclopropylideneethyl derivatives as building blocks of high synthetic potential. Competition experiments have disclosed that 1-ethenylcyclopropyl tosylate (2e) and cyclopropylideneethyl acetate (10b) are more reactive than dimethylallyl acetates 19 and 22, respectively. Use of chiral phosphines as ligands in the palladium catalyst can provide optically active methylenecyclopropane derivatives. With phenyl-, methyl-, and even n-butylzinc chloride as nucleophiles, the reaction apparently proceeds with initial transfer of the organic residue to palladium, followed by reductive elimination entailing tertiary substitution on the cyclopropane ring exclusively; the same type of product is obtained with azide and bis(trimethylsilyl)amide. But the site of hydride attack to yield reduction products depends on the hydride source. 1-Alkynylcyclopropyl chlorides 12, 13, and 14 react only with organozinc chlorides (nonstabilized nucleophiles) to provide mixtures of ethenylidenecyclopropanes 65 and alkynylcyclopropanes 66, via the {sigma}-palladium complexes 69 and 70, while chloride 15 undergoes mainly reduction. Other transition metal catalysts (Ni, Mo) also induce substitutions, but with poorer regioselectivity. 81 refs., 9 figs., 3 tabs.

  7. Surface functionalization of a poly(butylene terephthalate) (PBT) melt-blown filtration membrane by wet chemistry and photo-grafting.

    PubMed

    Salvagnini, Claudio; Roback, Alexandre; Momtaz, Maryam; Pourcelle, Vincent; Marchand-Brynaert, Jacqueline

    2007-01-01

    The surface functionalization of PBT melt-blown membrane, making up a whole filter of blood components, was achieved via two methods. Hydroxyl chain-end activation by tosylation (method A), followed by coupling of F- and (3)H-tagged molecules (probes), led to 1% of surface derivatization (XPS) and 290 pmol/cm(2) of lysine fixation (LSC). Deposition of O-succinimidyl 4-(p-azido-phenyl)butanoate ("molecular clip") and 2 h irradiation at 254 nm led to the implanting of activated ester functions, randomly on the polymer surface (method B). Further coupling of F- and (3)H-probes by wet chemistry gave highly functionalized surface (4% by XPS and 1000 pmol/cm(2) by LSC). However, control experiments showed that about 80% of the surface derivatization resulted from the UV treatment alone. Thus, the effect of UV irradiation on PBT membrane was systematically studied and analyzed by XPS, contact angle measurements, GPC and surface reactivity assays. The optimized conditions of "molecular clip" photo-grafting (negligible polymer photo-oxidation/photo-degradation) led to the covalent fixation of 45 pmol/cm(2) of (3)H-probe. Throughout our study, the behaviour of PBT melt-blown membrane was compared to PBT film and PET track-etched membrane similarly treated. Lastly, the method B was applied to couple GRGDS peptide on the PBT membrane; this material showed improved properties of leukocyte depletion in buffy coat filtration experiments.

  8. Importance of Counterion Reactivity on the Deactivation of Co-Salen Catalysts in the Hydrolytic Kinetic Resolution of Epichlorohydrin

    SciTech Connect

    Jain,S.; Zheng, X.; Jones, C.; Weck, M.; Davis, R.

    2007-01-01

    Possible modes of deactivation of Jacobsen's Co-salen catalyst during the hydrolytic kinetic resolution (HKR) of epichlorohydrin were explored by UV-vis spectroscopy, X-ray absorption spectroscopy, and electrospray ionization mass spectrometry, combined with recycling studies. Although an active Co(III)-salen catalyst deactivated substantially after multiple cycles without regeneration, the catalyst maintained its +3 oxidation state throughout the runs. Thus, deactivation of Co-salen during HKR was not the result of Co reduction. The mass spectrum of a deactivated material showed that catalyst dimerization does not account for the loss of activity. Results from various catalyst pretreatment tests, as well as from catalysts containing various counterions (acetate, tosylate, chloride, iodide) indicated that the rate of addition of the Co-salen counterions to epoxide forming Co-OH during the reaction correlated with deactivation. The extent of counterion addition to epoxide was influenced by the exposure time and the nucleophilicity of the counterion. An oligo(cyclooctene)-supported Co-OAc salen catalyst, which was 25 times more active than the standard Co-salen catalyst, was recycled multiple times with negligible deactivation.

  9. Preparation of Nucleosides Derived from 2-Nitroimidazole and d-Arabinose, d-Ribose, and d-Galactose by the Vorbrüggen Method and Their Conversion to Potential Precursors for Tracers To Image Hypoxia

    PubMed Central

    2011-01-01

    2-Nitroimidazole was silylated using hexaethyldisilazane and then reacted with 1-O-acetyl derivatives of d-arabinose, d-ribose, and d-galactose in acetonitrile at mild temperatures (−20 °C to rt), catalyzed by triethylsilyl triflate (Vorbrüggen conditions). The α-anomer was formed in the former case and the β-anomers in the latter two cases (highly) selectively. When d-arabinose and d-ribose were silylated with tert-butyldiphenylsilyl chloride in pyridine at the hydroxyl groups at C-5 and acetylated at the other ones in a one-pot reaction, mixtures of anomeric 1-O-acetyl derivatives were obtained. These were coupled by the Vorbrüggen method and then deblocked at C-5 and tosylated to give precursors for tracers to image hypoxia in four steps without using Hg(CN)2 necessary for other methods. The Vorbrüggen conditions enable a shorter route to azomycin nucleoside analogues than the previous coupling procedures. PMID:21905640

  10. Magnetic Resonance Imaging of Atherosclerosis Using CD81-Targeted Microparticles of Iron Oxide in Mice

    PubMed Central

    Yan, Fei; Yang, Wei; Li, Xiang; Liu, Hongmei; Nan, Xiang; Xie, Lisi; Zhou, Dongliang; Xie, Guoxi; Wu, Junru; Qiu, Bensheng; Liu, Xin; Zheng, Hairong

    2015-01-01

    The goal of this study is to investigate the feasibility of using CD81- (Cluster of Differentiation 81 protein-) targeted microparticles of iron oxide (CD81-MPIO) for magnetic resonance imaging (MRI) of the murine atherosclerosis. CD81-MPIO and IgG- (Immunoglobulin G-) MPIO were prepared by covalently conjugating, respectively, with anti-CD81 monoclonal and IgG antibodies to the surface of the tosyl activated MPIO. The relevant binding capability of the MPIO was examined by incubating them with murine bEnd.3 cells stimulated with phenazine methosulfate (PMS) and its effect in shortening T2 relaxation time was also examined. MRI in apolipoprotein E-deficient mice was studied in vivo. Our results show that CD81-MPIO, but not IgG-MPIO, can bind to the PMS-stimulated bEnd.3 cells. The T2 relaxation time was significantly shortened for stimulated bEnd.3 cells when compared with IgG-MPIO. In vivo MRI in apolipoprotein E-deficient mice showed highly conspicuous areas of low signal after CD81-MPIO injection. Quantitative analysis of the area of CD81-MPIO contrast effects showed 8.96- and 6.98-fold increase in comparison with IgG-MPIO or plain MPIO, respectively (P < 0.01). Histological assay confirmed the expression of CD81 and CD81-MPIO binding onto atherosclerotic lesions. In conclusion, CD81-MPIO allows molecular assessment of murine atherosclerotic lesions by magnetic resonance imaging. PMID:26266263

  11. Investigation into the susceptibility of Burkholderia cepacia complex isolates to photodynamic antimicrobial chemotherapy (PACT)

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Watters, A. L.; Donnelly, R. F.; Tunney, M. M.

    2009-06-01

    The main cause of morbidity and mortality in cystic fibrosis (CF) sufferers is progressive pulmonary damage caused by recurrent and often unremitting respiratory tract infection. Causative organisms include Pseudomonas aeruginosa and Haemophilus influenzae, but in recent years the Burkholderia cepacia complex has come to the fore. This group of highly drug-resistant Gram-negative bacteria are associated with a rapid decline in lung function and the often fatal cepacia syndrome, with treatment limited to patient segregation and marginally effective antibacterial regimens. Thus, development of an effective treatment is of the upmost importance. PACT, a non-target specific therapy, has proven successful in killing both Gram-positive and Gram-negative bacteria. In this study, planktonic cultures of six strains of the B. cepacia complex were irradiated (635 nm, 200 J cm-2,10 minutes irradiation) following 30 seconds incubation with methylene blue (MB) or meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Rates of kill of > 99 % were achieved with MB- and TMP-PACT. A MB concentration of 50 μg ml-1 and TMP concentration of 500 μg ml-1 were associated with highest percentage kills for each photosensitizer. PACT is an attractive option for treatment of B.cepacia complex infection. Further study, involving biofilm culture susceptibility, delivery of light to the target and in vivo testing will be necessary before it PACT becomes a viable treatment option for CF patients who are colonised or infected with B. cepacia complex.

  12. Grafting of Polycaprolactone on Oxidized Nanocelluloses by Click Chemistry

    PubMed Central

    Benkaddour, Abdelhaq; Jradi, Khalil; Robert, Sylvain; Daneault, Claude

    2013-01-01

    The main objective of this work is the grafting of polycaprolactone diol (PCL) on the surface of oxidized nanocelluloses (ONC) in order to enhance the compatibility between the hydrophilic cellulose nanofibres and the hydrophobic polymer matrix. This grafting was successfully realized with a new strategy known as click chemistry. In this context, the oxidized nanocelluloses bearing alkyl groups (ONC-PR) were prepared by reacting amino groups of propargylamine (PR) with carboxyl groups of ONC. In parallel, PCL was converted into azido-polycaprolactone (PCL-N3) in two steps: (i) tosylation of polycaprolactone (PCL-OTs) and (ii) conversion of PCL-OTs into PCL-N3 by nucleophilic displacement using sodium azide. Finally, ONC-PR was reacted with PCL-N3 in heterogeneous conditions through click chemistry in order to prepare polycaprolactone grafted oxidized nanocellulose (ONC-g-PCL), which could be suitable for improving the interfacial adhesion in the composite materials. The grafted samples were characterized by transmission electron microscopy and by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and Carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR) spectroscopic techniques.

  13. Development of a New Radiofluorinated Quinoline Analog for PET Imaging of Phosphodiesterase 5 (PDE5) in Brain

    PubMed Central

    Liu, Jianrong; Wenzel, Barbara; Dukic-Stefanovic, Sladjana; Teodoro, Rodrigo; Ludwig, Friedrich-Alexander; Deuther-Conrad, Winnie; Schröder, Susann; Chezal, Jean-Michel; Moreau, Emmanuel; Brust, Peter; Maisonial-Besset, Aurélie

    2016-01-01

    Phosphodiesterases (PDEs) are enzymes that play a major role in cell signalling by hydrolysing the secondary messengers cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) throughout the body and brain. Altered cyclic nucleotide-mediated signalling has been associated with a wide array of disorders, including neurodegenerative disorders. Recently, PDE5 has been shown to be involved in neurodegenerative disorders such as Alzheimer’s disease, but its precise role has not been elucidated yet. To visualize and quantify the expression of this enzyme in brain, we developed a radiotracer for specific PET imaging of PDE5. A quinoline-based lead compound has been structurally modified resulting in the fluoroethoxymethyl derivative ICF24027 with high inhibitory activity towards PDE5 (IC50 = 1.86 nM). Radiolabelling with fluorine-18 was performed by a one-step nucleophilic substitution reaction using a tosylate precursor (RCY(EOB) = 12.9% ± 1.8%; RCP > 99%; SA(EOS) = 70–126 GBq/μmol). In vitro autoradiographic studies of [18F]ICF24027 on different mouse tissue as well as on porcine brain slices demonstrated a moderate specific binding to PDE5. In vivo studies in mice revealed that [18F]ICF24027 was metabolized under formation of brain penetrable radiometabolites making the radiotracer unsuitable for PET imaging of PDE5 in brain. PMID:27110797

  14. Synthesis of [18F]fallypride in a micro-reactor

    PubMed Central

    Lu, Shuiyu; Giamis, Anthony M.; Pike, Victor W.

    2008-01-01

    A commercial coiled-tube micro-reactor (NanoTek; Advion) was used as a convenient platform for the synthesis of [18F]fallypride in small doses (0.5–1.5 mCi) for micro-PET studies of brain dopamine subtype-2 receptors in rodents. Each radiosynthesis used low amounts (20–40 μg; 39–77 nmol) of tosylate precursor and [18F]fluoride ion (0.5–2.5 mCi). Optimization of the labeling reaction in the apparatus, with respect to the effects of precursor amount, reaction temperature, flow rate and [18F]fluoride ion to precursor ratio, was achieved rapidly and the decay-corrected radiochemical yield of [18F]fallypride (up to 88%) was reproducible. The low amounts of material used in each radiosynthesis allowed crude [18F]fallypride to be purified rapidly on an analytical-size reverse phase HPLC column, preceding formulation for intravenous injection. Scale-up of the reaction was easily achieved by continuously infusing reagent precursor solutions to obtain [18F]fallypride in much greater quantity. PMID:20047004

  15. Purification and characterization of chymotrypsin from viscera of vermiculated sailfin catfish, Pterygoplichthys disjunctivus, Weber, 1991.

    PubMed

    Villalba-Villalba, Ana Gloria; Ramírez-Suárez, Juan Carlos; Pacheco-Aguilar, Ramón; Valenzuela-Soto, Elisa Miriam; Lugo-Sánchez, María Elena; Figueroa-Soto, Ciria Guadalupe

    2013-04-01

    Pterygoplichthys disjunctivus viscera chymotrypsin was purified by fractionation with ammonium sulfate (30-70 % saturation), gel filtration, affinity, and ion exchange chromatography. Chymotrypsin molecular weight was approximately 29 kDa according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), shown a single band in zymogram. Electrofocusing study suggested being an anionic enzyme (pI ≈ 3.9), exhibiting maximal activity at pH 9 and 50 °C, using Suc-Ala-Ala-Pro-Phe-p-nitroanilide (SAAPNA) as substrate. Enzyme was effectively inhibited by phenyl methyl sulfonyl fluoride (PMSF) (99 %), and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) (94 %). Enzyme activity was affected by the following ions in decreasing order: Hg(2+), Fe(2+), Cu(2+), Li(1+), Mg(2+), K(1+), Mn(2+), while Ca(2+) had no effect. Chymotrypsin activity decreased continuously as NaCl concentration increased (from 0 to 30 %). K m and V max values were 0.72 ± 1.4 mM and 1.15 ± 0.06 μmol/min/mg of protein, respectively (SAAPNA as substrate). Results suggest the enzyme has a potential application where low processing temperatures are needed, such as in fish sauce production.

  16. The Scope of Direct Alkylation of Gold Surface with Solutions of C1–C4n-Alkylstannanes

    PubMed Central

    2015-01-01

    Treatment of cleaned gold surfaces with dilute tetrahydrofuran or chloroform solutions of tetraalkylstannanes (alkyl = methyl, ethyl, n-propyl, n-butyl) or di-n-butylmethylstannyl tosylate under ambient conditions causes a self-limited growth of disordered monolayers consisting of alkyls and tin oxide. Extensive use of deuterium labeling showed that the alkyls originate from the stannane and not from ambient impurities, and that trialkylstannyl groups are absent in the monolayers, contrary to previous proposals. Methyl groups attached to the Sn atom are not transferred to the surface. Ethyl groups are transferred slowly, and propyl and butyl rapidly. In all cases, tin oxide is codeposited in submonolayer amounts. The monolayers were characterized by ellipsometry, contact angle goniometry, polarization modulated IR reflection absorption spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy with ferrocyanide/ferricyanide, which revealed a very low charge-transfer resistance. The thermal stability of the monolayers and their resistance to solvents are comparable with those of an n-octadecanethiol monolayer. A preliminary examination of the kinetics of monolayer deposition from a THF solution of tetra-n-butylstannane revealed an approximately half-order dependence on the bulk solution concentration of the stannane, hinting that more than one alkyl can be transferred from a single stannane molecule. A detailed structure of the attachment of the alkyl groups is not known, and it is proposed that it involves direct single or multiple bonding of one or more C atoms to one or more Au atoms. PMID:26327466

  17. Kinetics and mechanism of imidazole-catalyzed acylation of cellulose in LiCl/N,N-dimethylacetamide.

    PubMed

    Nawaz, Haq; Pires, Paulo Augusto R; El Seoud, Omar A

    2013-02-15

    Cellulose acylation by anhydrides (ethanoic to hexanoic) plus tosyl chloride, TsCl, or imidazole in LiCl/N,N-dimethylacetamide solution has been studied. Contrary to a previous claim, TsCl does not catalyze acylation. For the diazole-catalyzed reaction, N-acylimidazole is the acylating agent. Third order rate constants (k(3); 40-70 °C) have been calculated from conductivity data and split, by using information from model compounds, into contributions from the primary- (k(3;Prim(OH))) and secondary- (k(3;Sec(OH))) hydroxyl groups of cellulose. Values of k(3,Prim(OH))/k(3,Sec(OH)) are >1, and increase linearly as a function of increasing the number of carbon atoms of the acyl group. Rate constants and the degree of biopolymer substitution decrease on going from ethanoic- to butanoic-, then increase for pentanoic- and hexanoic anhydride, due to enthalpy/entropy compensation. Relative to the uncatalyzed reaction, the diazole-mediated one is associated with smaller enthalpy- and larger entropy of activation, due to difference of the acylating agent.

  18. Microwave synthesis and in vitro stability of diclofenac-β-cyclodextrin conjugate for colon delivery.

    PubMed

    Vieira, Amélia C F; Serra, Arménio C; Carvalho, Rui A; Gonsalves, Alexandra; Figueiras, Ana; Veiga, Francisco J; Basit, Abdul W; Rocha Gonsalves, António M d'A

    2013-04-02

    The aim of this work was to synthesize an ester prodrug of diclofenac and β-cyclodextrin suitable for colonic delivery. The synthesis of an ester linkage between diclofenac and β-cyclodextrin was conducted by the nucleophilic substitution of mono-6-tosyl-β-cyclodextrin under microwaves irradiation. After purification, the conjugate was characterized by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry; infrared (IR) spectroscopy; proton nuclear magnetic resonance ((1)H NMR) spectroscopy; and two-dimensional rotating frame nuclear overhauser effect (ROESY) spectroscopy. The purity was qualified by high pressure liquid chromatography (HPLC). To assess its potential for colonic delivery, the conjugate was evaluated for stability in simulated gastric and small intestinal fluids, and in fecal material from humans processed within a slurry under anaerobic conditions. The conjugate was successfully synthesized with a yield of 20% following purification. The mass spectra showed the parent peak m/z 1434 corresponding to [conjugate+Na] adduct. IR and NMR results confirmed that the carboxyl group of diclofenac is covalently bound to one of the hydroxyl groups of cyclodextrin by an ester linkage. Moreover, ROESY data indicated that the formation of the conjugate is not accompanied by the inclusion of diclofenac within the cyclodextrin. The conjugate was otherwise stable in simulated gastric and small intestinal conditions, but was also readily hydrolyzed liberating diclofenac in less than 2h within the human fecal slurry. This confirmed the potential for this new prodrug as a carrier for colonic delivery.

  19. Amphiphilic behavior of two phosphonium based ionic liquids.

    PubMed

    Mukherjee, Indrajyoti; Mukherjee, Suvasree; Naskar, Bappaditya; Ghosh, Soumen; Moulik, Satya P

    2013-04-01

    Solution and surface chemical behavior of two phosphonium based ionic liquids triisobutyl (methyl) phosphonium tosylate (IL-1) and trihexyl (tetradecyl) phosphonium bis 2,4,4-(trimethylpentyl)phosphinate (IL-2) have been studied. The polar IL-1 is surface active and water soluble, whereas the weakly polar IL-2 is more surface active with very low aqueous solubility. IL-1 does not form micelles but affects the micellization properties of ionic, nonionic, and zwitterionic surfactants more strongly than conventional electrolytes. IL-2 itself forms micelles and mixed micelles with Triton X-100 (TX-100) in aqueous solution. It also forms Langmuir monolayers of liquid expanded type, at the air/water interface. IL-1 can replace water in forming microemulsions with the oil isopropylmyristate (IPM), stabilized by IL-2 (surfactant)+isopropanol (IP as a co-surfactant) like the IL-1/IPM/(IL-2+IP) system. It produces a large monophasic zone in the pseudoternary phase diagram. The thermodynamics of formation of the microemulsions of IL-1 in oil (IPM) have been examined. The dimensions and the polydispersity of the dispersed nano-droplets in the microemulsions have been determined by DLS. The thermal stability of the microemulsion forming systems has also been studied. ILs studied against Sarcoma-180 cell lines have evidenced proficient anti-cancer activity of IL-1 and moderate activity of IL-2.

  20. High-valent iron and manganese complexes of corrole and porphyrin in atom transfer and dioxygen evolving catalysis.

    PubMed

    Abu-Omar, Mahdi M

    2011-04-14

    Manganese(V) imido complexes of 5,10,15-tris(pentafluorophenyl)corrole (H(3)tpfc) can be prepared by the reaction of Mn(III)(tpfc) and organic nitrene generated from either photolytic or thermal activation of organic azides. The terminal imido complexes of manganese(V) were among the first structurally characterized examples of Mn(V) terminal imido complexes in the literature. They feature a short Mn≡N triple bond and a nearly linear M[triple bond, length as m-dash]N-C angle. The ground state of (tpfc)Mn(V)(NAr) is singlet. Contrary to expectations, arylimido complexes of manganese(V) were stable to moisture and did not undergo [NR] group transfer to olefins. Manganese(V) imido corrole with an activated tosyl imido ligand was prepared from iodoimine (ArINTs) and manganese(III) corrole. The resulting complex (tpfc)Mn(NTs) is paramagnetic (S = 1), hydrolyzes to (tpfc)Mn(O) in the presence of water, abstracts hydrogen atoms from benzylic C-H bonds, and catalyzes aziridination of alkenes. Mechanistic studies on the aziridination and hydrogen atom transfer reactions are reviewed. This perspective also describes the reaction chemistry of the heme enzyme chlorite dismutase, the mechanism by which dioxygen is formed on a single-metal site, and recent advances in functional modelling of this enzyme. We also compare the reactivity of water-soluble iron versus manganese porphyrins towards the chlorite anion.

  1. Synthesis and crystal structures of 7-bromo-5-(2‧-chloro)phenyl-3-hydroxy-1-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one and 7-bromo-5-(2‧-chloro)phenyl-1-hexyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepin-2,3-dione

    NASA Astrophysics Data System (ADS)

    Kravtsov, Victor Ch.; Fonari, Marina S.; Gdaniec, Мaria; Pavlovsky, Victor I.; Andronati, Sergei A.; Semenishyna, Ekaterina A.

    2012-06-01

    Treatment of 7-bromo-5-(2'-chloro)phenyl-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (1) with methyl or hexyl tosylate resulted in 7-bromo-5-(2'-chloro)phenyl-3-hydroxy-1-methyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (2) and 7-bromo-5-(2'-chloro)phenyl-1-hexyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepin-2,3-dione (3). As confirmed by X-ray crystallography, the two products differ not only in the identity of the alkyl substituent in position 1 of the benzodiazepine fragment but also crystallize in different molecular forms resulting from proton migration. This alteration of the molecular structure leads to a significant change in the conformation of the central molecular fragment and influences the assembly mode in the crystal. In 3, centrosymmetric dimers formed via a pair of Nsbnd H⋯O hydrogen bonds are further linked into chains via Csbnd Br⋯Odbnd C halogen bond interaction. In turn in 2 there are two symmetry independent molecules, each giving a different set of intermolecular interactions. One of the molecules forms a dimer via Osbnd H⋯O interactions whereas the second one generates chain via Csbnd Br⋯Odbnd C halogen bond that is also assisted by a weak Osbnd H⋯Br hydrogen bond.

  2. Phase equilibria and modeling of pyridinium-based ionic liquid solutions.

    PubMed

    Domańska, Urszula; Królikowski, Marek; Ramjugernath, Deresh; Letcher, Trevor M; Tumba, Kaniki

    2010-11-25

    The phase diagrams of the ionic liquid (IL) N-butyl-4-methylpyridinium bis{(trifluoromethyl)sulfonyl}imide ([BM(4)Py][NTf(2)]) with water, an alcohol (1-butanol, 1-hexanol, 1-octanol, 1-decanol), an aromatic hydrocarbon (benzene, toluene, ethylbenzene, n-propylbenzene), an alkane (n-hexane, n-heptane, n-octane), or cyclohexane have been measured at atmospheric pressure using a dynamic method. This work includes the characterization of the synthesized compound by water content and also by differential scanning calorimetry. Phase diagrams for the binary systems of [BM(4)Py][NTf(2)] with all solvents reveal eutectic systems with regards to (solid-liquid) phase equilibria and show immiscibility in the liquid phase region with an upper critical solution temperature (UCST) in most of the mixtures. The phase equilibria (solid, or liquid-liquid) for the binary systems containing aliphatic hydrocarbons reported here exhibit the lowest solubility and the highest immiscibility gap, a trend which has been observed for all ILs. The reduction of experimental data has been carried out using the nonrandom two-liquid (NRTL) correlation equation. The phase diagrams reported here have been compared with analogous phase diagrams reported previously for systems containing the IL N-butyl-4-methylpyridinium tosylate and other pyridinium-based ILs. The influence of the anion of the IL on the phase behavior has been discussed.

  3. Effect of counterions on physicochemical properties of prazosin salts.

    PubMed

    Kumar, Lokesh; Meena, Chhuttan Lal; Pawar, Yogesh B; Wahlang, Banrida; Tikoo, Kulbhushan; Jain, Rahul; Bansal, Arvind K

    2013-03-01

    This study evaluated the effect of counterions on the physicochemical properties of prazosin salts. Salt forms of prazosin, namely, mesylate, besylate, tosylate, camsylate, oxalate, and maleate, were prepared and compared with the marketed anhydrous and polyhydrate forms of prazosin hydrochloride. Physicochemical characterization was performed in the order of crystallinity, hygroscopicity, solubility, and stability to select the optimal salt(s). Permeability study in Caco-2 cell lines and in vivo bioavailability study in rat model were investigated to ascertain their biopharmaceutical advantage. All salt forms were crystalline, nonhygroscopic (except the anhydrous hydrochloride salt), and had solubility in the range of 0.2 to 1.6 mg/ml. All salts were physically and chemically stable at 40°C/75% relative humidity, but degraded in UV-visible light, except the anhydrous hydrochloride salt. Prazosin mesylate was selected as the optimal salt, as it possessed higher solubility, permeability, and bioavailability, compared to the commercial hydrochloride salts. Hydrochloride salt is reported to have poor bioavailability that is partially attributed to its low solubility and extensive common-ion effect in the gastric region. Factors like hydrophilicity of the counterion, hydration state of the salt, and melting point of the salt contribute to the physicochemical properties of the salts. This study has implications in the selection of an optimal salt form for prazosin, which is suitable for further development.

  4. Screening and characterization of protease producing actinomycetes from marine saltern.

    PubMed

    Suthindhiran, Krish; Jayasri, Mangalam Achuthananda; Dipali, Dipa; Prasar, Apurva

    2014-10-01

    In the course of systematic screening program for bioactive actinomycetes, an alkaline protease producing halophilic strain Actinopolyspora sp. VITSDK2 was isolated from marine saltern, Southern India. The strain was identified as Actinopolyspora based on its phenotypic and phylogenetic characters. The protease was partially purified using ammonium sulfate precipitation and subsequently by DEAE cellulose column chromatography. The enzyme was further purified using HPLC and the molecular weight was found to be 22 kDa as determined by SDS-PAGE analysis. The purified protease exhibited pH stability in a wide range of 4-12 with optimum at 10.0. The enzyme was found to be stable between 25 and 80 °C and displayed a maximum activity at 60 °C. The enzyme activity was increased marginally in presence of Mn(2+) , Mg(2+) , and Ca(2+) and decreased in presence of Cu(2+) . PMSF and DFP completely inhibited the activity suggesting it belongs to serine protease. Further, the proteolytic activity was abolished in presence of N-tosyl-L-lysine chloromethyl ketone suggesting this might be chymotrypsin-like serine protease. The protease was 96% active when kept for 10 days at room temperature. The results indicate that the enzyme belong to chymotrypsin-like serine protease exhibiting both pH and thermostability, which can be used for various applications in industries.

  5. Purification and characterization of a novel extracellular alkaline protease from Cellulomonas bogoriensis.

    PubMed

    Li, Fan; Yang, Liyuan; Lv, Xue; Liu, Dongbo; Xia, Hongmei; Chen, Shan

    2016-05-01

    An extracellular alkaline protease produced by the alkali-tolerant Cellulomonas bogoriensis was purified by a combination of ammonium sulfate precipitation and cation exchange chromatography. The purity of the protease was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its molecular weight was confirmed to be 18.3 kDa. The enzyme showed optimum activity at 60 °C and pH 11. The stability of the protease was maintained at a wide temperature range of 4-60 °C and pH range of 3-12. Irreversible inhibition of the enzyme activity by phenylmethylsulfonyl fluoride and tosyl-l-phenylalanine chloromethyl ketone demonstrated that the purified enzyme is a chymotrypsin of the serine protease family. The Km and Vmax of the protease activity on casein were 19.2 mg/mL and 25000 μg/min/mg, respectively. The broad substrate specificity and remarkable stability in the presence of organic solvents, salt, and commercial detergents, as well as its excellent stain removal and dehairing capability, make the purified alkaline protease a promising candidate for industrial applications.

  6. Influence of pulse-height discrimination threshold for photon counting on the accuracy of singlet oxygen luminescence measurement

    NASA Astrophysics Data System (ADS)

    Lin, Huiyun; Chen, Defu; Wang, Min; Lin, Juqiang; Li, Buhong; Xie, Shusen

    2011-12-01

    Direct measurement of near-infrared (NIR) luminescence around 1270 nm is the golden standard of singlet oxygen (1O2) identification. In this study, the influence of pulse-height discrimination threshold on measurement accuracy of the 1O2 luminescence that is generated from the photoirradiation of meso-tetra (N-methyl-4-pyridyl) morphine tetra-tosylate (TMPyP) in aqueous solution was investigated by using our custom-developed detection system. Our results indicate that the discrimination threshold has a significant influence on the absolute 1O2 luminescence counts, and the optimal threshold for our detection system is found to be about - 41.2 mV for signal discrimination. After optimization, the derived triplet-state and 1O2 lifetimes of TMPyP in aqueous solution are found to be 1.73 ± 0.03 and 3.70 ± 0.04 µs, respectively, and the accuracy of measurement was further independently demonstrated using the laser flash photolysis technique.

  7. Rationally designed dual functional block copolymers for bottlebrush-like coatings: In vitro and in vivo antimicrobial, antibiofilm, and antifouling properties.

    PubMed

    Gao, Qiang; Yu, Meng; Su, Yajuan; Xie, Meihua; Zhao, Xin; Li, Peng; Ma, Peter X

    2017-01-25

    Numerous antimicrobial coatings have been developed for biomedical devices/implants, but few can simultaneously fulfill the requirements for antimicrobial and antifouling ability and biocompatibility. In this study, to develop an antimicrobial and antibiofilm surface coating, diblock amphiphilic molecules with antimicrobial and antifouling segments in a single chain were rationally designed and synthesized. Cationic antimicrobial polypeptides (AMP) were first synthesized by N-carboxyanhydride ring-opening polymerization (NCA-ROP). Heterofunctionalized poly(ethylene glycol) with different lengths (methacrylate-PEGn-tosyl, n=10/45/90) was synthesized and site-specifically conjugated with polypeptides to form diblock amphiphiles. Along with increased PEG chain length, hemolytic activity was considerably improved, and broad-spectrum antimicrobial activity is retained. Three MA-PEGn-b-AMP copolymers were further grafted onto the surface of silicone rubber (a commonly used catheter material) via plasma/UV-induced surface polymerizations to form a bottlebrush-like coating with excellent antimicrobial activity against several pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and effectively prevent biofilm formation. This bottlebrush coating also greatly reduced protein adsorption and platelet adhesion, indicating its excellent antifouling ability. An in vitro cytotoxicity study also demonstrated that this coating is biocompatible with mammalian cells. After subcutaneous implantation of the materials in rats, we demonstrated that the g-PEG45-b-AMP bottlebrush coating exhibits significant anti-infective activity in vivo. Thus, this facilely synthesized PEGylated AMP bottlebrush coating is a feasible method to prevent biomedical devices-associated infections.

  8. One-pot pseudomorphic crystallization of mesoporous porous silica to hierarchical porous zeolites

    SciTech Connect

    Xing, Jun-Ling; Jiang, Shu-Hua; Pang, Jun-Ling; Yuan, En-Hui; Ma, Xiao-Jing; Lam, Koon-Fung; Xue, Qing-Song; Zhang, Kun

    2015-09-15

    Hierarchically porous silica with mesopore and zeolitic micropore was synthesized via pseudomorphic crystallization under high-temperature hydrothermal treatment in the presence of cetyltrimethylammonium tosylate and tetrapropylammonium ions. A combined characterization using small-angle X-ray diffraction (XRD), nitrogen adsorption, high-resolution transmission electron microscopy (TEM), thermogravimetric analysis (TG), and elemental analysis showed that dual templates, CTA{sup +} and TPA{sup +} molecules, can work in a cooperative manner to synthesize mesoporous zeolite in a one-pot system by precisely tuning the reaction conditions, such as reaction time and temperature, and type and amount of heterometal atoms. It is found that the presence of Ti precursor is critical to the successful synthesis of such nanostructure. It not only retards the nucleation and growth of crystalline MFI domains, but also acts as nano-binder or nano-glue to favor the assembly of zeolite nanoblocks. - Graphical abstract: Display Omitted - Highlights: • A facile method to synthesize mesoporous zeolites with hierarchical porosity was presented. • It gives a new insight into keeping the balance between mesoscopic and molecular ordering in hierarchical porous materials. • A new understanding on the solid–solid transformation mechanism for the synthesis of titanosilicate zeolites was proposed.

  9. Separation of carbon dioxide from nitrogen or methane by supported ionic liquid membranes (SILMs): influence of the cation charge of the ionic liquid.

    PubMed

    Hojniak, Sandra D; Khan, Asim Laeeq; Hollóczki, Oldamur; Kirchner, Barbara; Vankelecom, Ivo F J; Dehaen, Wim; Binnemans, Koen

    2013-12-05

    Supported ionic liquid membranes (SILMs) are promising tools for the separation of carbon dioxide from other gases. In this paper, new imidazolium, pyrrolidinium, piperidinium, and morpholinium ionic liquids with a triethylene glycol side chain and tosylate anions, as well as their symmetrical dicationic analogues, have been synthesized and incorporated into SILMs. The selectivities for CO2/N2 and CO2/CH4 separations have been measured. The selectivities exhibited by the dicationic ionic liquids are up to two times higher than the values of the corresponding monocationic ionic liquids. Quantum chemical calculations have been used to investigate the difference in the interaction of carbon dioxide with monocationic and dicationic ionic liquids. The reason for the increased gas separation selectivity of the dicationic ionic liquids is two-fold: (1) a decrease in permeance of nitrogen and methane through the ionic liquid layer, presumably due to their less favorable interactions with the gases, while the permeance of carbon dioxide is reduced much less; (2) an increase in the number of interaction sites for the interactions with the quadrupolar carbon dioxide molecules in the dicationic ionic liquids, compared to the monocationic analogues.

  10. Magneto immunosensor for gliadin detection in gluten-free foodstuff: towards food safety for celiac patients.

    PubMed

    Laube, T; Kergaravat, S V; Fabiano, S N; Hernández, S R; Alegret, S; Pividori, M I

    2011-09-15

    Gliadin is a constituent of the cereal protein gluten, responsible for the intolerance generated in celiac disease. Its detection is of high interest for food safety of celiac patients, since the only treatment known until now is a lifelong avoidance of this protein in the diet. Therefore, it is essential to have an easy and reliable method of analysis to control the contents in gluten-free foods. An electrochemical magneto immunosensor for the quantification of gliadin or small gliadin fragments in natural or pretreated food samples is described for the first time and compared to a novel magneto-ELISA system based on optical detection. The immunological reaction was performed on magnetic beads as solid support by the oriented covalent immobilization, of the protein gliadin on tosyl-activated beads. Direct, as well as indirect competitive immunoassays were optimized, achieving the best analytical performance with the direct competitive format. Excellent detection limits (in the order of μg L(-1)) were achieved, according to the legislation for gluten-free products. The matrix effect, as well as the performance of the assays was successfully evaluated using spiked gluten-free foodstuffs (skimmed milk and beer), obtaining excellent recovery values in the results.

  11. Extracellular trypsin-like proteases produced by Cordyceps militaris.

    PubMed

    Hattori, Maki; Isomura, Shigeki; Yokoyama, Eiji; Ujita, Minoru; Hara, Akira

    2005-12-01

    A trypsin-like protease, P-1-1, was purified from the culture supernatant of the fungus Cordyceps militaris by (NH(4))(2)SO(4) precipitation, chromatography on DEAE Bio-Gel Agarose, TSKgel CM-5PW, and gel-filtration with HiLoad 26/60 Superdex 75 pg, and its properties were examined. Purified P-1-1 showed a single band by SDS-PAGE and was estimated to have a molecular mass of 23,405 by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The optimum pH of the enzyme was between 8.5 and 12.0. It was inhibited strongly by leupeptin and diisopropyl fluorophosphate (DFP), and definitely did by N(alpha)-tosyl-L-lysine chloromethyl ketone hydrochloride (TLCK), phenylmethanesulfonyl fluoride (PMSF) and chymostatin. The carbonyl group sides of Arg and Lys were confirmed as the sites of cleavage by the enzyme toward cecropin B. These results indicate that P-1-1 is a trypsin-type serine protease. The N-terminal amino acid sequence of P-1-1 showed a high homology with those of trypsins or chymotrypsin derived from Diptera insects.

  12. Poly(ethylene oxide)-bonded stationary phase for separation of inorganic anions in capillary ion chromatography.

    PubMed

    Linda, Roza; Lim, Lee Wah; Takeuchi, Toyohide

    2013-06-14

    A tosylated-poly(ethylene oxide) (PEO) reagent was reacted with primary amino groups of an aminopropylsilica packing material (TSKgel NH2-60) in acetonitrile to form PEO-bonded stationary phase. The reaction was a single and simple step reaction. The prepared stationary phase was able to separate inorganic anions. The retention behavior of six common inorganic anions on the prepared stationary phase was examined under various eluent conditions in order to clarify its separation/retention mechanism. The elution order of the tested anions was iodate, bromate, bromide, nitrate, iodide, and thiocyanate, which was similar as observed in common ion chromatography. The retention of inorganic anions could be manipulated by ion exchange interaction which is expected that the eluent cation is coordinated among the PEO chains and it works as the anion-exchange site. Cations and anions of the eluent therefore affected the retention of sample anions. We demonstrated that the retention of the analyte anions decreased with increasing eluent concentration. The repeatability of retention time for the six anions was satisfactory on this column with relative standard deviation values from 1.1 to 4.3% when 10mM sodium chloride was used as the eluent. Compared with the unmodified TSKgel NH2-60, the prepared stationary phase retained inorganic anions more strongly and the selectivity was also improved. The present stationary phase was applied for the determination of inorganic anions contained in various water samples.

  13. Fluorous Analogue of Chloramine-T: Preparation, X-ray Structure Determination, and Use as an Oxidant for Radioiodination and s-Tetrazine Synthesis.

    PubMed

    Dzandzi, James P K; Beckford Vera, Denis R; Genady, Afaf R; Albu, Silvia A; Eltringham-Smith, Louise J; Capretta, Alfredo; Sheffield, William P; Valliant, John F

    2015-07-17

    A fluorous oxidant that can be used to introduce radioiodine into small molecules and proteins and generate iodinated tetrazines for bioorthogonal chemistry has been developed. The oxidant was prepared in 87% overall yield by combining a fluorous amine with tosyl chloride, followed by chlorination using aqueous sodium hypochlorite. A crystal structure of the oxidant, which is a fluorous analogue of chloramine-T, was obtained. The compound was shown to be stable for 7 days in EtOH and for longer than three months as a solid. The oxidant was effective at promoting the labeling of arylstannanes using [(125)I]NaI, where products were isolated in high specific activity in yields ranging from 46% to 86%. Similarly, iodinated biologically active proteins (e.g., thrombin) were successfully produced, as well as a radioiodinated tetrazine, through a concomitant oxidation-halodemetalation reaction. Because of its fluorous nature, unreacted oxidant and associated reaction byproducts can be removed quantitatively from reaction mixtures by passing solutions through fluorous solid phase extraction cartridges. This feature enables rapid and facile purification, which is critical when working with radionuclides and is similarly beneficial for general synthetic applications.

  14. Purification and characterization of an enzyme produced by Treponema denticola capable of hydrolyzing synthetic trypsin substrates.

    PubMed Central

    Ohta, K; Makinen, K K; Loesche, W J

    1986-01-01

    An enzyme from Treponema denticola that hydrolyzes a synthetic trypsin substrate, N-alpha-benzoyl-L-arginine-p-nitroanilide (BAPNA), was purified to near homogeneity, as judged by gel electrophoresis. The molecular weight of the enzyme was estimated to be ca. 69,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and ca. 50,000 by gel filtration on Sephadex G-100. The pH optimum for the hydrolysis of BAPNA was around 8.5. The enzyme was heat labile and irreversibly inactivated at low pH values. Enzyme activity was enhanced by Ca2+, Mg2+, and Ba2+ but inhibited by Mn2+, Hg2+, Co2+, and Zn2+. Metal chelators and sulfhydryl reagents had no effect on this activity. The enzyme was inhibited by certain protease inhibitors such as diisopropyl fluorophosphate, N-alpha-p-tosyl-L-lysine chloromethyl ketone, phenylmethylsulfonyl fluoride, L-1-tosylamide-2-phenylethylchloromethyl ketone, alpha-1-antitrypsin, and soybean trypsin inhibitor. The Km values for BAPNA and N-alpha-benzoyl-L-arginine ethyl ester were 0.05 and 0.12 mM, respectively, and the Vmax values were higher than those observed with trypsin. Although the purified enzyme hydrolyzed some low-molecular-weight synthetic trypsin substrates, it did not hydrolyze casein, hemoglobin, azocasein, azocoll, bovine serum albumin, or gelatin. Thus, this enzyme is probably not a protease but is capable of hydrolyzing ester, amide, and peptide bonds involving the carboxyl group of arginine and lysine. Images PMID:3013780

  15. Synthesis of 1,4-, 2,4-, and 3,4-dimethylphenanthrenes: A novel deoxygenation of arene 1,4-endoxides with trimethylsilyl iodide

    SciTech Connect

    Jung, Keeyong; Koreeda, Masato )

    1989-11-24

    A mild, efficient synthesis of the carcinogen 1,4-dimethylphenanthrene (2) and its bay-region methyl-bearing regioisomers 2,4-dimethyl- and 3,4-dimethylphenanthrenes (3 and 4) is described. The synthesis involves a generally applicable strategy that features a furan/dimethyl-1-naphthyne cycloaddition reaction followed by a convenient direct deoxygenation of the resulting enooxide with excess trimethylsilyl iodide generated in situ. The Friedel-Crafts cyclization of p-xylene with {gamma}-butyrolactone/AlCl{sub 3} or {gamma}-(2,5-dimethylphenyl)butyric acid via its trifluoromethanesulfonic anhydride derivative results in the formation of a mixture of 5,8-, 6,8-, and 5,7-dimethyl-1-tetralones (17, 20, and 21, respectively) through migration of aromatic methyl groups. The precursor to 6,8-dimethyl-1-naphthyne (10) was prepared from tetralone 20, isolable only as a 5:1 inseparable mixture with 17 from the direct Friedel-Crafts cyclization of p-xylene with {gamma}-butyrolactone, by {alpha}-dibromination with CuBr{sub 2}, dehydrobromination, and tosylation. The precursors to 5,8-dimethyl-1-naphthyne (9) and 7,8-dimethyl-1-naphthyne (11) were synthesized from the corresponding 1-naphthols 15 and 31, respectively. The synthesis of these naphthols involved cycloaddition between the corresponding dimethylated benzyne and furan followed by acid-catalyzed isomerization.

  16. β-cyclodextrin-ionic liquid polymer based dynamically coating for simultaneous determination of tetracyclines by capillary electrophoresis.

    PubMed

    Zhou, Chunyan; Deng, Jingjing; Shi, Guoyue; Zhou, Tianshu

    2016-12-16

    Tetracyclines are a group of broad spectrum antibiotics widely used in animal husbandry to prevent and treat diseases. However, the improper use of tetracyclines may result in the presence of their residues in animal tissues or waste. Recently, great attention has been drawn towards the green solvents ionic liquids. Ionic liquids have been employed as a coating material to modify the electroosmotic flow in capillary electrophoresis. In this study, a functionalized ionic liquid, mono-6-deoxy-6-(3-methylimidazolium)-β-cyclodextrin tosylate, was synthesized and used for the simultaneous separation and quantification of tetracyclines by capillary electrophoresis. Good separation efficiency could be achieved due to the multiple functions of β-cyclodextrin derived ionic liquid, including the electrostatic interaction, the hydrogen bonding, and the cavity structure in β-cyclodextrin ionic liquid which can entrap the tetracyclines to form inclusion complex. After optimization, baseline separation achieved in 25 min with the running buffer consisted of 10 mmol/L, pH 7.2 phosphate buffer and 20 mmol/L β-cyclodextrin ionic liquid. The satisfied result demonstrated that the β-cyclodextrin ionic liquid is an ideal background electrolyte modifier in the separation of tetracyclines with high stability and good reproducibility. And it is an effective strategy to design and synthesize specific ILs as additive applied in separation.

  17. Synthesis and evaluation of new bis-1,3,4,2-triazaphospholinoalkane derivatives as in vitro α-amylase and lipase inhibitors.

    PubMed

    Hamzaoui, Salwa; Ben Salah, Bochra; Hamden, Khaled; Rekik, Awatef; Kossentini, Mohamed

    2015-03-01

    A series of new 1,ω-bis-(5-alkyl-2-oxide-3-tosyl-1,3,4,2-triazaphospholino)alkanes 2 and 3 were prepared in good yields by the treatment of 1,ω-bis-(1-tosylamidrazone)alkanes 1 with two molar equivalents of phosphoryl trichloride and phenylphosphonic dichloride, respectively. All the newly synthesized compounds were characterized by IR, (1) H NMR, (13) C NMR, (31) P NMR, and elemental analysis. All the new compounds were screened for their inhibitory effect on the key enzymes related to diabetes and obesity, as α-amylase and lipase. The in vitro study revealed that these alkane derivatives exert an inhibitory action against these key enzymes, especially 2b with an IC50 of 16 μg/mL against α-amylase and lipase. Overall, the findings of the current study indicate that 2d exhibits attractive properties and can therefore be considered for future application in the development of antidiabetic and hypolipidemic drugs.

  18. Enantiomerically pure isophorone diamine [3-(aminomethyl)-3,5,5-trimethylcyclohexylamine]: a chiral 1,4-diamine building block made available on large scale.

    PubMed

    Berkessel, Albrecht; Roland, Katrin; Schröder, Michael; Neudörfl, Jörg M; Lex, Johann

    2006-12-08

    Isophorone diamine [IPDA, 3-(aminomethyl)-3,5,5-trimethylcyclohexylamine] is a chiral non-C2-symmetric 1,4-diamine which is produced industrially on large scale as the mixture of all four stereoisomers (cis/trans ca. 3:1). Starting from this industrial bulk product, the preparation of the bis-tosyl, bis-Fmoc, bis-Boc and bis-Z derivatives of cis-IPDA, the preparation of the pure cis enantiomers by HPLC on chiral stationary phase, and the assignment of absolute configurations to the isolated enantiomers are described. We furthermore report an efficient method for the optical resolution of IPDA by salt formation with dibenzoyl tartaric acid. The latter method conveniently affords enantiomerically pure cis-IPDA in 100 g quantities. A number of salen ligands have been prepared from this enantiomerically pure 1,4-diamine and fully characterized. The nickel complex of one of the salen ligands was prepared and analyzed by X-ray crystallography. The crystal structure of the Ni4L4 complex illustrates the pronounced preference of cis-IPDA for adopting the chair conformation in which both the amino- and the aminomethyl substituents occupy equatorial positions. As a consequence, the two salicylidene imine moieties of one ligand molecule do not converge on one metal ion, but act as bridging ligands between two nickel ions.

  19. A master dynamic flow diagram for the shear thickening transition in micellar solutions.

    PubMed

    Bautista, F; Tepale, N; Fernández, V V A; Landázuri, G; Hernández, E; Macías, E R; Soltero, J F A; Escalante, J I; Manero, O; Puig, J E

    2016-01-07

    The shear thickening behavior of dilute micellar solutions of hexadecyltrimethylammonium-type surfactants with different counterions (tosylate, 3- and 4-fluorobenzoate, vinylbenzoate and salicylate) and of n-alkyltetradecylammonium bromide (CnTAB), with n = 14, 16 and 18, is examined here. These solutions undergo a shear thickening transition due to the formation of shear-induced structures (SISs) in the shear range studied. Here we report a relationship between the shear thickening intensity and the differences in the hydrophobicity of counterions according to the Hofmeister-like anion series, which leads to a master flow diagram. This master flow diagram is produced by plotting a normalized shear thickening intensity (Iη - 1)/(Imax - 1) versus CD/CD,max, where Iη is the shear-thickening intensity, defined as the largest viscosity obtained in the shear-thickening transition (STT) at a given surfactant concentration CD divided by the Newtonian viscosity η0, and Imax is the largest intensity value obtained in the STT at a surfactant concentration CD,max. The master flow diagram is built using several cetyltrimethylammonium-type surfactants with different counterions, according to a Hofmeister-like series, and by n-alkyltetradecylammonium bromide surfactants with different alkyl chain lengths.

  20. Ru Catalyzed Alkene-Alkyne Coupling. Total Synthesis of Amphidinolide P

    PubMed Central

    Trost, Barry M.; Papillon, Julien P. N.; Nussbaumer, Thomas

    2008-01-01

    A coordinatively unsaturated ruthenium complex catalyzed the formation of a carbon-carbon bond between two judiciously chosen alkene and alkyne partners in good yield, and in a chemo- and regioselective fashion, in spite of the significant degree of unsaturation of the substrates. The resulting 1,4-diene forms the backbone of the cytotoxic marine natural product amphidinolide P. The alkene partner was rapidly assembled from (R)-glycidyl tosylate, which served as a linchpin in a one-flask, sequential three-components coupling process using vinyllithium and a vinyl cyanocuprate. The synthesis of the alkyne partner made use of an unusual anti-selective addition under chelation control conditions of an allyltin reagent derived from tiglic acid. In addition, a remarkably E-selective E2 process using the azodicarboxylate-triphenylphosphine system is featured. Also featured is the first example of the use of a β-lactone as a thermodynamic spring to effect macrolactonization. The oxetanone ring was thus used as a productive protecting group that increased the overall efficiency of this total synthesis. This work was also an opportunity to further probe the scope of the ruthenium-catalyzed alkene-alkyne coupling, in particular using enynes, and studies using various functionalized substrates are described. PMID:16351124

  1. Lamellar Gels and Spontaneous Vesicles in Catanionic Surfactant Mixtures

    SciTech Connect

    Coldren,B.; Warriner, H.; van Zanten, R.; Zasadzinski, J.

    2006-01-01

    Caill{acute e} analysis of the small-angle X-ray line shape of the lamellar phase of 7:3 wt/wt cetyltrimethylammonium tosylate (CTAT)/sodium dodecylbenzene sulfonate (SDBS) bilayers shows that the bending elastic constant is {kappa}= (0.62 {+-} 0.09)kBT. From this and previous results, the Gaussian curvature constant is {kappa}= (-0.9 {+-} 0.2)kBT. For 13:7 wt/wt CTAT/SDBS bilayers, the measured bending elasticity decreases with increasing water dilution, in good agreement with predictions based on renormalization theory, giving {kappa}{sub 0} = 0.28k{sub B}T. These results show that surfactant mixing is sufficient to make {kappa} {approx} k{sub B}T, which promotes strong, Helfrich-type repulsion between bilayers that can dominate the van der Waals attraction. These are necessary conditions for spontaneous vesicles to be equilibrium structures. The measurements of the bending elasticity are confirmed by the transition of the lamellar phase of CTAT/SDBS from a turbid, viscoelastic gel to a translucent fluid as the water fraction is decreased below 40 wt %. Freeze-fracture electron microscopy shows that the gel is characterized by spherulite defects made possible by spontaneous bilayer curvature and low bending elasticity. This lamellar gel phase is common to a number of catanionic surfactant mixtures, suggesting that low bending elasticity and spontaneous curvature are typical of these mixtures that form spontaneous vesicles.

  2. Automated synthesis of N-(2-[(18) F]Fluoropropionyl)-L-glutamic acid as an amino acid tracer for tumor imaging on a modified [(18) F]FDG synthesis module.

    PubMed

    Liu, Shaoyu; Sun, Aixia; Zhang, Zhanwen; Tang, Xiaolan; Nie, Dahong; Ma, Hui; Jiang, Shende; Tang, Ganghua

    2017-04-03

    N-(2-[(18) F]Fluoropropionyl)-L-glutamic acid ([(18) F]FPGLU) is a potential amino acid tracer for tumor imaging with positron emission tomography (PET). However, due to the complicated multi-step synthesis, the routine production of [(18) F]FPGLU presents many challenging laboratory requirements. In order to simplify the synthesis process of this interesting radiopharmaceutical, an efficient automated synthesis of [(18) F]FPGLU was performed on a modified commercial FDG synthesizer via a two-step on-column hydrolysis procedure, including (18) F-fluorination and on-column hydrolysis reaction. [(18) F]FPGLU was synthesized in 12 ± 2% (n = 10, uncorrected) radiochemical yield based on [(18) F]fluoride using the tosylated precursor 2. The radiochemical purity was ≥98%, and the overall synthesis time was 35 min. To further optimize the radiosynthesis conditions of [(18) F]FPGLU, a brominated precursor 3 was also used for the preparation of [(18) F]FPGLU and the improved radiochemical yield was up to 20 ± 3% (n = 10, uncorrected) in 35 min. Moreover, all these results were achieved using the similar on-column hydrolysis procedure on the modified FDG synthesis module.

  3. Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions.

    PubMed

    Malloy, Jaret L; Veldhuizen, Ruud A W; Thibodeaux, Brett A; O'Callaghan, Richard J; Wright, Jo Rae

    2005-02-01

    Pulmonary surfactant has two distinct functions within the lung: reduction of surface tension at the air-liquid interface and participation in innate host defense. Both functions are dependent on surfactant-associated proteins. Pseudomonas aeruginosa is primarily responsible for respiratory dysfunction and death in cystic fibrosis patients and is also a leading pathogen in nosocomial pneumonia. P. aeruginosa secretes a number of proteases that contribute to its virulence. We hypothesized that P. aeruginosa protease IV degrades surfactant proteins and results in a reduction in pulmonary surfactant host defense and biophysical functions. Protease IV was isolated from cultured supernatant of P. aeruginosa by gel chromatography. Incubation of cell-free bronchoalveolar lavage fluid with protease IV resulted in degradation of surfactant proteins (SP)-A, -D, and -B. SPs were degraded in a time- and dose-dependent fashion by protease IV, and degradation was inhibited by the trypsin-like serine protease inhibitor Nalpha-p-tosyl-L-lysine-chloromethyl ketone (TLCK). Degradation by protease IV inhibited SP-A- and SP-D-mediated bacterial aggregation and uptake by macrophages. Surfactant treated with protease IV was unable to reduce surface tension as effectively as untreated surfactant, and this effect was inhibited by TLCK. We speculate that protease IV may be an important contributing factor to the development and propagation of acute lung injury associated with P. aeruginosa via loss of surfactant function within the lung.

  4. Aptamer-based organic-silica hybrid affinity monolith prepared via "thiol-ene" click reaction for extraction of thrombin.

    PubMed

    Wang, Zheng; Zhao, Jin-cheng; Lian, Hong-zhen; Chen, Hong-yuan

    2015-06-01

    A novel strategy for preparing aptamer-based organic-silica hybrid monolithic column was developed via "thiol-ene" click chemistry. Due to the large specific surface area of the hybrid matrix and the simplicity, rapidness and high efficiency of "thiol-ene" click reaction, the average coverage density of aptamer on the organic-silica hybrid monolith reached 420 pmol μL(-1). Human α-thrombin can be captured on the prepared affinity monolithic column with high specificity and eluted by NaClO4 solution. N-p-tosyl-Gly-Pro-Arg p-nitroanilide acetate was used as the sensitive chromogenic substrate of thrombin. The thrombin enriched by this affinity column was detected with a detection of limit of 0.01 μM by spectrophotometry. Furthermore, the extraction recovery of thrombin at 0.15 μM in human serum was 91.8% with a relative standard deviation of 4.0%. These results indicated that "thiol-ene" click chemistry provided a promising technique to immobilize aptamer on organic-inorganic hybrid monolith and the easily-assembled affinity monolithic material could be used to realize highly selective recognition of trace proteins.

  5. A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents.

    PubMed

    Nassar, Ibrahim F; Atta-Allah, Saad R; Elgazwy, Abdel-Sattar S Hamad

    2015-06-01

    An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, d-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.

  6. Investigation into the potential of sub-lethal photodynamic antimicrobial chemotherapy (PACT) to reduce susceptibility of meticillin-resistant Staphylococcus aureus (MRSA) to antibiotics

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Donnelly, R. F.; Tunney, M. M.

    2009-06-01

    In PACT, a combination of a sensitising drug and visible light cause the selective destruction of microbial cells via singlet oxygen production. As singlet oxygen is a non-specific oxidizing agent and is only present during illumination, development of resistance to this treatment is thought to be unlikely. However, in response to oxidative stress, bacteria can up-regulate oxidative stress genes and associated antibiotic resistance genes. The up-regulation of these genes and potential transfer of genetic material may result in a resistant bacterial population. This study determined whether treatment of clinically isolated meticillin resistant Staphylococcus aureus (MRSA) strains with sub-lethal doses of methylene blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP)-PACT resulted in reduced susceptibility to antibiotics and previously lethal PACT. Exposure of strains to sub-lethal doses of photosensitizer in combination with light had no effect on susceptibility to previously lethal photosensitization. Furthermore, exposure to sub-lethal concentrations of both photosensitizers caused no significant changes in the minimum inhibitory concentration (MIC) for each strain tested. Any differences in susceptibility were not significant as they did not cross breakpoints between resistant and susceptible for any organism or antibiotic tested. Therefore, PACT remains an attractive alternative option for treatment of MRSA infections.

  7. Sustained elevation of NF-κB activity sensitizes offspring of maternal inflammation to hypertension via impairing PGC-1α recovery

    PubMed Central

    Deng, Yafei; Zhang, Qi; Luo, Hongqin; Chen, Xianhua; Han, Qi; Wang, Fangjie; Huang, Pei; Lai, Wenjing; Guan, Xiao; Pan, Xiaodong; Ji, Yan; Guo, Wei; Che, Ling; Tang, Yuan; Gu, Liangqi; Yu, Jianhua; Namaka, Michael; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Growing evidence has demonstrated that maternal detrimental factors, including inflammation, contribute to the development of hypertension in the offspring. The current study found that offspring subjected to prenatal exposure of inflammation by lipopolysaccharide (LPS) challenge during the second semester showed significantly increased systolic blood pressure. In addition, these offspring also displayed augmented vascular damage and reactive oxygen species (ROS) levels in thoracic aortas when challenged with deoxycorticosterone acetate and high-salt diet (DOCA-salt). Interestingly, the antioxidant N-acetyl-L-cysteine markedly reversed these changes. Mechanistically, prenatal LPS exposure led to pre-existing elevated peroxisome proliferators-activated receptor-γ co-activator (PGC)-1α, a critical master of ROS metabolism, which up-regulated the ROS defense capacity and maintained the balance of ROS generation and elimination under resting state. However, continued elevation of NF-κB activity significantly suppressed the rapid recovery of PGC-1α expression response to DOCA-salt challenge in offspring that underwent prenatal inflammatory stimulation. This was further confirmed by using a NF-κB inhibitor (N-p-Tosyl-L-phenylalanine chloromethyl ketone) that restored PGC-1α recovery and prevented blood pressure elevation induced by DOCA-salt. Our results suggest that maternal inflammation programmed proneness to NF-κB over-activation which impaired PGC-1α-mediated anti-oxidant capacity resulting in the increased sensitivity of offspring to hypertensive damage. PMID:27616627

  8. Sustained elevation of NF-κB activity sensitizes offspring of maternal inflammation to hypertension via impairing PGC-1α recovery.

    PubMed

    Deng, Yafei; Zhang, Qi; Luo, Hongqin; Chen, Xianhua; Han, Qi; Wang, Fangjie; Huang, Pei; Lai, Wenjing; Guan, Xiao; Pan, Xiaodong; Ji, Yan; Guo, Wei; Che, Ling; Tang, Yuan; Gu, Liangqi; Yu, Jianhua; Namaka, Michael; Deng, Youcai; Li, Xiaohui

    2016-09-12

    Growing evidence has demonstrated that maternal detrimental factors, including inflammation, contribute to the development of hypertension in the offspring. The current study found that offspring subjected to prenatal exposure of inflammation by lipopolysaccharide (LPS) challenge during the second semester showed significantly increased systolic blood pressure. In addition, these offspring also displayed augmented vascular damage and reactive oxygen species (ROS) levels in thoracic aortas when challenged with deoxycorticosterone acetate and high-salt diet (DOCA-salt). Interestingly, the antioxidant N-acetyl-L-cysteine markedly reversed these changes. Mechanistically, prenatal LPS exposure led to pre-existing elevated peroxisome proliferators-activated receptor-γ co-activator (PGC)-1α, a critical master of ROS metabolism, which up-regulated the ROS defense capacity and maintained the balance of ROS generation and elimination under resting state. However, continued elevation of NF-κB activity significantly suppressed the rapid recovery of PGC-1α expression response to DOCA-salt challenge in offspring that underwent prenatal inflammatory stimulation. This was further confirmed by using a NF-κB inhibitor (N-p-Tosyl-L-phenylalanine chloromethyl ketone) that restored PGC-1α recovery and prevented blood pressure elevation induced by DOCA-salt. Our results suggest that maternal inflammation programmed proneness to NF-κB over-activation which impaired PGC-1α-mediated anti-oxidant capacity resulting in the increased sensitivity of offspring to hypertensive damage.

  9. Optical, charge transport and structural study of PEDOT and PProDOT films.

    NASA Astrophysics Data System (ADS)

    Saprigin, A. V.; Lee, W.-P.; Epstein, A. J.; Giurgiu, I.; Reynolds, J. R.; Hwang, J.; Tanner, D. B.

    2000-03-01

    We report the reflectance, DC conductivity, microwave (6.5 GHz) and X-ray diffraction studies of electrochemically synthesized poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3,4-propylenedioxythiophene)(PProDOT) thick films doped with PF_6^- and CF_3SO_3^-. Samples demonstrate properties varying from metallic (high DC conductivity ( ~ 100 S/cm), negative microwave dielectric response down to 4 K, positive slope of W-plot at lower T and high reflectance in the infrared) to insulating (lower σ_dc, positive \\varepsilon_mw, negative slope of W-plot and lower IR reflectance). The XRD data of thick films of all studied compositions have diffraction maxima at ~ 6^o, ~ 12^o, ~ 18^o, ~ 25^o similar to the previously reported data for tosylate doped PEDOT thin films.(K.E. Aasmundveit, et. al.), Synth. Met. 101, 561 (1999). We will compare our results with data for other conducting polymers and discuss them within a model of mesoscopic quantum dots connected by 1D-wires.(V.N. Prigodin and A.J. Epstein, to be published.)

  10. The role of the anion in the toxicity of imidazolium ionic liquids.

    PubMed

    Biczak, Robert; Pawłowska, Barbara; Bałczewski, Piotr; Rychter, Piotr

    2014-06-15

    From the environmental protection point of view, the growing interest of ionic liquids in various industrial branches has raised concerns for the toxicity assessment of these compounds. The paper discusses the effect of salts containing the shared 1-ethyl-3-methylimidazolium [EMIM] cation as coupled with five different anions: bromide [Br], nitrate [NO3], p-toluenesulfonate (tosylate) [Ts], dimethylphosphate [dMP] and methanesulfonate [MS] on the growth and development of higher land plants - spring barley and common radish. The experiment was done according to the ISO Standard 11269-2:1995 and the OECD/OCDE Guide 208/2006. As the indications of phytotoxicity, the percentage of sprouts and the level of dry and fresh plant mass were used; in addition, the visual assessment of any signs of damage to the examined plant species, such as growth inhibition and chlorotic changes, was also made. Results of our study has proved the negative impact of ILs on the tested plants and the toxic effect of imidazolium salts was dependent primarily on the applied ionic liquids concentration. The common radish revealed the higher tolerance to the imidazolium as compared to spring barley. The anion type of ionic liquid was crucial for the toxicity against common radish.

  11. Phosphonium-based ionic liquids in electrokinetic capillary chromatography for the separation of neutral analytes.

    PubMed

    Wiedmer, Susanne K; King, Alistair W T; Riekkola, Marja-Liisa

    2012-08-31

    In this work we elucidated the applicability of phosphonium-based ionic liquids (ILs) as pseudostationary phase in electrokinetic capillary chromatography (EKC) with UV-detection. The phosphonium ILs studied contain bromide, chlorine, or tosylate ions, as counter ions, and alkyl side chains of variable length on the phosphorous atom. The effects of the type and concentration of the IL, pH, ionic strength, and type of background electrolyte solution on the electroosmotic flow (EOF) and on the effective electrophoretic mobilities of some neutral model analytes were investigated and large variations in the migration times were observed. Especially the IL employed remarkably affected the strength and direction of the EOF Successful separations were obtained for neutral aromatic singly substituted analytes, namely benzene, toluene, phenol, and nitrobenzene. The results demonstrated the potential of capillary electromigration methods for rapid interaction studies between ILs and analytes, which is useful for the development of novel materials for sample preparation and separation purposes or for novel catalyst and chemical processing studies.

  12. Microwave-assisted stereospecific synthesis of novel tetrahydropyran adenine isonucleosides and crystal structures determination

    NASA Astrophysics Data System (ADS)

    Silva, Fábio P. L.; Cirqueira, Marilia L.; Martins, Felipe T.; Vasconcellos, Mário L. A. A.

    2013-11-01

    We describe in this article stereospecific syntheses for new isonucleosides analogs of adenine 5-7 from tosyl derivatives 2-4 accessing by microwave irradiations (50-80%). The adenine reacts entirely at the N(9) position. Compounds 2-4 were prepared in two steps from the corresponding alcohols 1, 8 and 9 (81-92%). These tetrahydropyrans alcohols 1, 8 and 9 are achiral (Meso compounds) and were prepared in two steps with complete control of 2,4,6-cis relative configuration by Prins cyclization reaction (60-63%) preceded by the Barbier reaction between allyl bromide with benzaldehyde, 4-fluorobenzaldehyde and 2-naphthaldehyde respectively under Lewis acid conditions (96-98%). The configurations and preferential conformations of 5-7 were determined by crystal structure of 6. These novel isonucleosides 5-7 present in silico potentiality to act as GPCR ligand, kinase inhibitor and enzyme inhibitor, evaluated by Molinspiration program, consistent with the expected antiviral and anticancer bioactivities.

  13. Hybrid systems based on gold nanostructures and porphyrins as promising photosensitizers for photodynamic therapy.

    PubMed

    Ferreira, Daniele C; Monteiro, Camila S; Chaves, Claudilene R; Sáfar, Gustavo A M; Moreira, Roberto L; Pinheiro, Maurício V B; Martins, Dayse C S; Ladeira, Luiz Orlando; Krambrock, Klaus

    2017-02-01

    Gold nanostructures of two different shapes (spheres and rods) were synthesized to form a colloidal hybrid system with 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin tosylate salt (H2TM4PyP(OTs)4) (POR) for applications in photodynamic therapy (PDT) using light in the visible spectral range. Electron paramagnetic resonance (EPR) experiments in combination with spin trapping were used for the detection of reactive oxygen species (ROS) and evaluation of the efficiency of these novel hybrid systems as photosensitizers. It is shown that the hybrid system consisting of gold nanorods (AuNR) and porphyrin (POR) is by far more efficient than its isolated components. This enhanced efficiency is explained by a synergetic effect between the AuNR and the porphyrin, wherein a rapid energy transfer from the former to the latter produces a large amount of singlet oxygen followed by its conversion into hydroxyl radicals. The mechanism was investigated using different spin traps and different ROS inhibitors. On the other hand, spherical gold nanoparticles (AuNP) do not show this synergetic effect. The synergetic effect for gold nanorods/POR hybrid is attributed to a larger field enhancement close to the gold nanorod surface in addition to the electrostatic attraction between the components of the hybrid system.

  14. Reticulation des fibres lignocellulosiques

    NASA Astrophysics Data System (ADS)

    Landrevy, Christel

    Pour faire face à la crise économique la conception de papier à valeur ajoutée est développée par les industries papetières. Le but de se projet est l'amélioration des techniques actuelles de réticulation des fibres lignocellulosiques de la pâte à papier visant à produire un papier plus résistant. En effet, lors des réactions de réticulation traditionnelles, de nombreuses liaisons intra-fibres se forment ce qui affecte négativement l'amélioration anticipée des propriétés physiques du papier ou du matériau produit. Pour éviter la formation de ces liaisons intra-fibres, un greffage sur les fibres de groupements ne pouvant pas réagir entre eux est nécessaire. La réticulation des fibres par une réaction de « click chemistry » appelée cycloaddition de Huisgen entre un azide et un alcyne vrai, catalysée par du cuivre (CuAAC) a été l'une des solutions trouvée pour remédier à ce problème. De plus, une adaptation de cette réaction en milieux aqueux pourrait favoriser son utilisation en milieu industriel. L'étude que nous désirons entreprendre lors de ce projet vise à optimiser la réaction de CuAAC et les réactions intermédiaires (propargylation, tosylation et azidation) sur la pâte kraft, en milieu aqueux. Pour cela, les réactions ont été adaptées en milieu aqueux sur la cellulose microcristalline afin de vérifier sa faisabilité, puis transférée à la pâte kraft et l'influence de différents paramètres comme le temps de réaction ou la quantité de réactifs utilisée a été étudiée. Dans un second temps, une étude des différentes propriétés conférées au papier par les réactions a été réalisée à partir d'une série de tests papetiers optiques et physiques. Mots Clés Click chemistry, Huisgen, CuAAC, propargylation, tosylation, azidation, cellulose, pâte kraft, milieu aqueux, papier.

  15. Radiosynthesis of novel pitavastatin derivative ([(18) F]PTV-F1) as a tracer for hepatic OATP using a one-pot synthetic procedure.

    PubMed

    Kimura, Hiroyuki; Yagi, Yusuke; Arimitsu, Kenji; Maeda, Kazuya; Ikejiri, Kazuaki; Takano, Jun-Ichi; Kusuhara, Hiroyuki; Kagawa, Shinya; Ono, Masahiro; Sugiyama, Yuichi; Saji, Hideo

    2016-11-01

    Pitavastatin is an antihyperlipidemic agent, a potent inhibitor of 3-hydroxymethyl-glutaryl-CoA reductase, which is selectively taken up into the liver mainly via hepatic organic anion transporting polypeptide 1B1 (OATP1B1). OATP1B1 can accept a variety of organic anions, and previous reports indicated that it is responsible for the hepatic clearance of several clinically used anionic drugs. Therefore, the pharmacokinetics and the hepatic distribution of pitavastatin provide an insight into the function of OATP1B1 in humans. For the development of the in vivo evaluation of OATP1B1 function by positron emission tomography imaging, we designed a novel [(18) F]pitavastatin derivative ([(18) F]PTV-F1), in which a [(18) F]fluoroethoxy group is substituted for the [(18) F]fluoro group of [(18) F]pitavastatin, with the aim of convenient radiolabeling protocol and high radiochemical yield. In vitro studies suggested that transport activities of PTV-F1 mediated by OATP1B1 and OATP1B3 were very similar to those of pitavastatin and PTV-F1 was metabolically stable in human liver microsomes. In the radiosynthesis of [(18) F]PTV-F1 from the tosylate precursor, nucleophilic fluorination and subsequent deprotection were performed using a one-pot procedure. [(18) F]PTV-F1 was obtained with a radiochemical yield of 45% ± 3% (n = 3), and the operating time for the radiosynthesis of [(18) F]PTV-F1 is very short (30 minutes) compared with [(18) F]pitavastatin.

  16. Synthesis and biological activity of 22-iodo- and (E)-20(22)-dehydro analogues of 1alpha,25-dihydroxyvitamin D3.

    PubMed

    Sicinski, R R; DeLuca, H F

    1999-12-01

    Construction of 25-hydroxy-steroidal side chain substituted with iodine at C-22 was elaborated on a model PTAD-protected steroidal 5,7-diene and applied to a synthesis of (22R)- and (22S)-22-iodo-1alpha,25-dihydroxyvitamin D3. Configuration at C-22 in the iodinated vitamins, obtained by nucleophilic substitution of the corresponding 22S-tosylates with sodium iodide, was determined by comparison of their iodine-displacement processes and cyclizations leading to isomeric five-membered (22,25)-epoxy-1alpha-hydroxyvitamin D3 compounds. Also, 20(22)-dehydrosteroids have been obtained and their structures established by 1H NMR spectroscopy. When compared to the natural hormone, (E)-20(22)-dehydro-1alpha,25-dihydroxyvitamin D3 was found 4 times less potent in binding to the porcine intestinal vitamin D receptor (VDR) and 2 times less effective in differentiation of HL-60 cells. 22-Iodinated vitamin D analogues showed somewhat lower in vitro activity, whereas (22,25)-epoxy analogues were inactive. Interestingly, it was established that (22S)-22-iodo-1alpha,25-dihydroxyvitamin D3 was 3 times more potent than its (22R)-isomer in binding to VDR and four times more effective in HL-60 cell differentiation assay. The restricted mobility of the side chain of both 22-iodinated vitamin D compounds was analyzed by a systematic conformational search indicating different spatial regions occupied by their 25-oxygen atoms. Preliminary data on the in vivo calcemic activity of the synthesized vitamin D analogues indicate that (E)-20(22)-dehydro-1alpha,25-dihydroxyvitamin D3 and 22-iodo-1alpha,25-dihydroxyvitamin D3 isomers were ca. ten times less potent than the natural hormone 1alpha,25-(OH)2D3 both in intestinal calcium transport and bone calcium mobilization.

  17. PET radiotracer [¹⁸F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: preliminary investigation.

    PubMed

    Perrone, Maria Grazia; Malerba, Paola; Uddin, Md Jashim; Vitale, Paola; Panella, Andrea; Crews, Brenda C; Daniel, Cristina K; Ghebreselasie, Kebreab; Nickels, Mike; Tantawy, Mohammed N; Manning, H Charles; Marnett, Lawrence J; Scilimati, Antonio

    2014-06-10

    Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([(18/19)F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[(18)F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K(18)F/Kryptofix 2.2.2 complex, that afforded [(18)F]-P6 in good radiochemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [(18)F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [(18)F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1.

  18. Internucleosomal DNA cleavage triggered by plasma membrane damage during necrotic cell death. Involvement of serine but not cysteine proteases.

    PubMed Central

    Dong, Z.; Saikumar, P.; Weinberg, J. M.; Venkatachalam, M. A.

    1997-01-01

    Autolytic DNA breakdown, detected as smears in electrophoretic gels, is a late event in necrosis. On the other hand, internucleosomal DNA cleavage, visualized as ladders, is thought to be a hallmark of apoptosis. We now report that this specific form of DNA fragmentation also occurs during necrosis and is an early event but appears to be triggered by proteolytic mechanisms significantly different from those documented in apoptosis. Treatment of MDCK cells with a mitochondrial uncoupler and a Ca2+ ionophore led to ATP depletion, necrotic morphology, and progressive fragmentation of DNA in an internucleosomal or ladder pattern. DNA breakdown was immediately preceded by increased permeability of the plasma membrane to macromolecules. Provision of glycine along with the noxious agents did not modify the extent of ATP depletion, but prevented plasma membrane damage. This was accompanied by complete inhibition of DNA fragmentation. Internucleosomal DNA cleavage was observed also during necrosis after rapid permeabilization of plasma membranes by detergents or streptolysin-O in hepatocytes, thymocytes, and P19, Jurkat, and MDCK cells. DNA fragmentation associated with necrosis was Ca2+/Mg2+ dependent, was suppressed by endonuclease inhibitors, and was abolished by serine protease inhibitors but not by inhibitors of interleukin-1 beta converting enzyme (ICE)-related proteases or caspases. Moreover, unlike apoptosis, it was not accompanied by caspase-mediated proteolysis. On the other hand, the cleavage-site-directed chymotryptic inhibitor N-tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) suppressed DNA fragmentation not only in necrotic cells but also during Fas-mediated apoptosis, without inhibiting caspase-related proteolysis. The results suggest a novel pathway of endonuclease activation during necrosis not involving the participation of caspases. In addition, they indicate that techniques based on double-strand DNA breaks may not reliably differentiate between

  19. [Synthese of 1-(5-deoxy-beta-D-ribo-hexofuranosyl)cytosine and 1-(2,5-dideoxy-beta-D-erythro-hexofuranosyl)cytosine, and their phosphates. Specificity of an mammalian (rat) ribonucleotide-reductase].

    PubMed

    David, S; de Sennyey, G

    1979-12-01

    Mild, acidic hydrolysis of 3-O-benzoyl-1,2,:5,6-di-O-isopropylidene-alpha-D-allofuranose gave a diol that was selectively benzoylated at O-6 in high yield by intermediate conversion to the stannylene derivative. The 3,6-dibenzoate was converted to the 5-O-tosyl derivative and thence to a mixture of iodides, which were reduced with tributylstannane to 3,6-di-O-benzoyl-1,2-O-isopropylidene-alpha-D-ribo-hexofuranose (6). Acetolysis gave an anomeric mixture of diacetates, which, when treated with N-acetylbis(trimethylsilyl)cytosine gave the protected nucleoside, which was deprotected to free "homocytidine", 1-(5-deoxy-beta-D-ribo-hexofuranosyl)cytosine (11), by alklaine methanolysis. This was N-acetylated and then treated with acetone to give a protected nucleoside, which was labelled by oxidation to the aldehyde, reduction with sodium borotritide, and deprotection. Acidic methanolysis of 6 gave a mixture of methyl 2,6- and 3,6-di-O-benzoylfuranosides, the hydroxyl groups of which were treated by the tetrachloromethane-triphenylphosphine reagent to give the 2-chloro-2-deoxy (21) and 3-chloro-3-deoxy derivatives. Reduction of 21 gave methyl 3,6-di-O-benzoyl-2,5-dideoxy-D-erythro-furanoside, further transformed in 1-(2,5-dideoxy-beta-D-erythro-hexofuranosyl)cytosine mixed with the alpha anomer. Phosphates and diphosphates of the nucleosides were prepared by extensions of known methods. The phosphate and the diphosphate of 11 act neither as substrates nor as inhibitors of a ribonucleotide-reductase from rat asicites tumor.

  20. Sensory and sympathetic nerve contributions to the cutaneous vasodilator response from a noxious heat stimulus.

    PubMed

    Carter, Stephen J; Hodges, Gary J

    2011-11-01

    We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42 °C or rapidly to 44 °C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42 °C; (2) EMLA 42 °C; (3) control 44°C; and (4) EMLA 44 °C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42 °C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44 °C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42 °C; (2) BT 42 °C; (3) control 44 °C; and (4) BT 44 °C. Treatment with BT at the 42 °C sites resulted in a marked reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44 °C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus.

  1. Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling.

    PubMed

    Johnson, John M; Yen, Tony C; Zhao, Kun; Kosiba, Wojciech A

    2005-04-01

    Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.

  2. Role of sensory nerves in the cutaneous vasoconstrictor response to local cooling in humans.

    PubMed

    Hodges, Gary J; Traeger, J Andrew; Tang, Tri; Kosiba, Wojciech A; Zhao, Kun; Johnson, John M

    2007-07-01

    Local cooling (LC) causes a cutaneous vasoconstriction (VC). In this study, we tested whether there is a mechanism that links LC to VC nerve function via sensory nerves. Six subjects participated. Local skin and body temperatures were controlled with Peltier probe holders and water-perfused suits, respectively. Skin blood flow at four forearm sites was monitored by laser-Doppler flowmetry with the following treatments: untreated control, pretreatment with local anesthesia (LA) blocking sensory nerve function, pretreatment with bretylium tosylate (BT) blocking VC nerve function, and pretreatment with both LA and BT. Local skin temperature was slowly reduced from 34 to 29 degrees C at all four sites. Both sites treated with LA produced an increase in cutaneous vascular conductance (CVC) early in the LC process (64 +/- 55%, LA only; 42 +/- 14% LA plus BT; P < 0.05), which was absent at the control and BT-only sites (5 +/- 8 and 6 +/- 8%, respectively; P > 0.05). As cooling continued, there were significant reductions in CVC at all sites (P < 0.05). At control and LA-only sites, CVC decreased by 39 +/- 4 and 46 +/- 8% of the original baseline values, which were significantly (P < 0.05) more than the reductions in CVC at the sites treated with BT and BT plus LA (-26 +/- 8 and -22 +/- 6%). Because LA affected only the short-term response to LC, either alone or in the presence of BT, we conclude that sensory nerves are involved early in the VC response to LC, but not for either adrenergic or nonadrenergic VC with longer term LC.

  3. Analysis of organic sulfur and nitrogen in coal via tandem degradation methods. [Quarterly] technical report, 1 March--31 May 1992

    SciTech Connect

    Kruge, M.A.; Palmer, S.R.; Baudet, N.

    1992-10-01

    Sporinite, vitrinite and semi-fusinite single macerals were separated from the IBC 101 coal by the density gradient technique. In addition, a gel permeation chromatography (GPC) system was assembled and the GPC column calibrated with four polystyrene molecular weight standards. A variety of sulfur compounds were identified in the dichromate oxidation products of the IBC 101 coal, including a thiazole and isomers of C2-, C3- and C4-alkyl thiophene carboxylic acids. Precise agreement between GC-MS and FPD chromatograms were obtained for these compounds. These compounds probably originated as short alkyl chains on exterior portions of the original peat macromolecular structures and were sulfurized by H{sub 2}S shortly after burial. Thus the dichromate oxidation appears useful for the characterization of sulfur compounds. Unfortunately, this treatment yields only small amounts of products, but the reaction is relatively mild. On the other hand the peroxyacetic acid gives a very good yield in only a single step, but seems to be very degradative. It was difficult to isolate the products after lithium aluminum hydride reduction of oxidation products. It is believed that this is due to the formation of polyalcohols from polycarboxyl compounds. However polyalcohols were successfully converted to their parent hydrocarbons by the LAH reduction of tosylate intermediates. This allows for much easier separation and characterization and leads to enhanced elucidation of coal structures. To test the hypothesis that asphaltenes are similar in structure to their parent coal, IBC101 asphaltenes and the extracted coal were subjected to PAA oxidation and analytical pyrolysis. The PAA products as well as the pyrolysates show very good correlation. This indicates a very strong relationship between the organic structure of the coal and that of the asphaltenes derived from them.

  4. The effects of ventricular end-diastolic and systolic pressures on action potential and duration in anaesthetized dogs.

    PubMed Central

    Coulshed, D S; Cowan, J C; Drinkhill, M J; Hainsworth, R

    1992-01-01

    1. Although it is known that mechanical events in the heart influence the duration of the cardiac action potential, there is no quantitative information on the effects of independent changes in ventricular end-diastolic and systolic pressures. 2. Experiments were carried out on open-chest anaesthetized dogs in which the autonomic nervous influences on the heart were prevented and monophasic action potentials were recorded form the epicardial surface of the left ventricle. The duration of these action potentials was taken as the interval from the upstroke to the point of 90% repolarization. 3. Elevation of left ventricular peak systolic pressure, at constant end-diastolic pressure, significantly shortened the monophasic action potential. 4. Elevation of end-diastolic pressure at constant peak systolic pressure significantly lengthened the monophasic action potential. 5. Responses were not dependent on release of noradrenaline from sympathetic nerve terminals because they persisted after administration of bretylium tosylate. They were also not due to myocardial ischaemia because they persisted when coronary perfusion pressure was maintained at a constant high level. 6. Simultaneous recordings of changes in myocardial segment length showed the expected responses to changes in ventricular pressures: increases in shortening in response to increases in diastolic pressure and no consistent effect from changes in systolic pressure. 7. These investigations demonstrate the independent effects of changes in systolic and end-diastolic pressures on cardiac action potential duration. This effect is likely to be an effect of the mechanical events, i.e. contraction-excitation feedback. This response may be mediated through changes in myocardial fibre tension, the consequent changes in fibre shortening, or both. PMID:1297849

  5. Trypsin from the processing waste of the lane snapper (Lutjanus synagris) and its compatibility with oxidants, surfactants and commercial detergents.

    PubMed

    Espósito, Talita S; Marcuschi, Marina; Amaral, Ian P G; Carvalho, Luiz B; Bezerra, Ranilson S

    2010-05-26

    A trypsin from the viscera of the lane snapper (Lutjanus synagris) was purified by heat treatment, fractionation with ammonium sulfate and affinity chromatography. The molecular weight of the enzyme was estimated to be 28.4 kDa (SDS-PAGE). The purified enzyme was capable of hydrolyzing the specific substrate for trypsin benzoyl-arginine-p-nitroanilide (BApNA) and was inhibited by benzamidine and tosyl lysine chloromethyl ketone (TLCK), synthetic trypsin inhibitors and phenylmethylsulfonyl fluoride (PMSF), which is a serine-protease inhibitor. The enzyme exhibited maximal activity at pH 9.0 and 45 degrees C and retained 100% of the activity after incubation at the optimal temperature for 30 min. At a concentration of 10 mM, activity was slightly activated by Ca(2+) and inhibited by the following ions in decreasing order: Cd(2+) > Hg(2+) > Cu(2+) > Zn(2+) > Al(3+). The effects of Ba(2+), K(1+) and Li(1+) proved to be less intensive. Using 1% (w/v) azocasein as substrate, the enzyme revealed high resistance (60% residual activity) when incubated with 10% H(2)O(2) for 75 min. The enzyme retained more than 80% activity after 60 min in the presence of different surfactants (Tween 20, Tween 80 and sodium choleate). The alkaline protease demonstrated compatibility with commercial detergents (7 mg/mL), such as Bem-te-vi, Surf and Ala, retaining more than 50% of initial activity after 60 min at 25 degrees C and 30 min at 40 degrees C. The thermostability and compatibility of this enzyme with commercial detergents suggest a good potentiality for application in the detergent industry.

  6. Liposome dependent delivery of S-adenosyl methionine to cells by liposomes: a potential treatment for liver disease.

    PubMed

    Wagner, Eric J; Krugner-Higby, Lisa; Heath, Timothy D

    2009-02-01

    The present study demonstrates that the nutritional supplement S-adenosyl methionine (SAMe), the primary methyl donor in mammalian cells, is delivered selectively to cells by anionic liposomes, and is, therefore, a liposome dependent drug. Contrary to our expectations, free SAMe chloride was growth inhibitory in cultured cells. The growth inhibitory potency of SAMe chloride in anionic liposomes composed of distearoylphosphatidylglycerol/cholesterol 2:1 was fivefold greater than that of free SAMe. Neutral liposomes composed of distearoylphosphatidylcholine and cholesterol did not increase the potency of the drug. An improved anionic liposome SAMe formulation was produced by use of the 1,4-butanedisulfonate salt (SD4), adding a metal chelator (EDTA), and lowering the buffer pH from pH 7.0 to pH 4.0. This formulation was 15-fold more potent than free SD4, and was active after more than 28 days at 4 degrees C. SAMe and its potential degradation products were screened for toxicity. Formaldehyde was determined to have potency similar to that of free SAMe chloride in CV1-P cells, suggesting that the growth inhibitory effects of SAMe may partly arise from the formation of formaldehyde. The cytotoxic effects of formaldehyde and the less stable forms of SAMe, (SAMe chloride and SAMe tosylate) were decreased in the presence of 3 mM GSH (IC(50) approximately 0.44 mM). The cytotoxic effects of SD4 were not reduced by GSH, suggesting that this more stable form of SAMe is not toxic through the production of formaldehyde. SD4 in anionic DSPG liposomes stimulated murine IL-6 production in RAW 264 cells at concentrations 25- to 30-fold lower than free drug. This increase in potency for IL-6 production was in keeping with the increase in potency observed in our growth inhibition experiments. These results suggest that SD4 in liposomes may be a potential treatment for acute or chronic liver failure.

  7. Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression

    PubMed Central

    Daumar, Pierre; Zeglis, Brian M.; Ramos, Nicholas; Divilov, Vadim; Sevak, Kuntal Kumar; Pillarsetty, NagaVaraKishore; Lewis, Jason S.

    2015-01-01

    Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, 18F-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [18F]-18 and [18F]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. PMID:25240701

  8. Structural studies of human urinary kallikrein (urokallikrein).

    PubMed

    ole-MoiYoi, O K; Spragg, J; Austen, K F

    1979-07-01

    Human urinary kallikrein (urokallikrein) has been purified by affinity chromatography with aprotinin coupled to CH-Sepharose and by gel filtration. The isolation procedure, which was performed under mild conditions, was completed in a 36-hr period and yielded an overall recovery of more than 75% and a purification of 1727-fold. Homogeneity of the urokallikrein was demonstrated by three criteria: the coincidence of the stained protein band and functional urokallikrein in duplicate gels after alkaline disc gel electrophoresis; the appearance of a single stained band of molecular weight 48,000 on sodium dodecyl sulfate/polyacrylamide gel electrophoresis of reduced and unreduced enzyme; and the finding of a single amino-terminal residue, namely alanine after dansylation and acid hydrolysis of purified enzyme. The Km of urokallikrein on N alpha-p-tosyl-L-arginine methyl ester was 400 microM, and the Vmax was 194 mumol/min per mg of protein, which is higher than that observed with any previous preparations. The molecular weight of 48,700 determined on gel filtration and the molecular weight of 48,000 observed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis are in good agreement with the molecular weight of 48,213 calculated from the amino acid composition. The finding of a molecular weight higher than those previously reported, namely 27,000-43,500, the increased functional activity on tosylarginine methyl ester, and the detection of a single amino-terminal residue are consistent with the isolation of a more native protein by the procedure described in this paper.

  9. Purification, primary structures and evolution of coagulant proteases from Deinagkistrodon actus venom.

    PubMed

    Nikandrov, Nikolai N; Deshimaru, Masanobu; Tani, Ayako; Chijiwa, Takahito; Shibata, Hiroki; Chang, Chang-Chun; Fukumaki, Yasuyuki; Ito, Tatsumi; Ohno, Motonori

    2005-12-15

    Deinagkistrodon (formerly Agkistrodon) actus (Taiwan) snake venom was found to contain at least seven closely related coagulant proteases. One of them, named actibin, was purified to homogeneity by means of four chromatographic steps. Actibin acted on fibrinogen to form fibrin clots with extremely high specific activity of 1,630 NIH units/mg and preferentially released fibrinopeptide A. Actibin was an acidic glycoprotein (pI 3.4) with molecular weight of 41,000, which was reduced to 28,800 after deglycosylation with N-glycanase. The k(cat)/K(m) values of actibin for hydrolysis of tosyl-l-arginine methyl ester and benzoyl-l-arginine p-nitroanilide were one-third to a half those for thrombin, reflecting a high potency of actibin in fibrinogen clotting. The amidase activities of actibin and its family proteases were inhibited by 3,4-dichloroisocoumarin, a serine protease inhibitor, indicating that actibin and its family proteases are serine proteases. Four cDNAs, named DaP1 and DaP7-DaP9, encoding D. actus coagulant proteases were cloned. All cDNAs contain an open reading frame of 780 bp coding for 260 amino acid residues, including a signal peptide of 24 amino acid residues. Their amino acid sequences predicted are highly homologous to one another with one to five amino acid substitutions. When four D. actus protease cDNAs were compared with the cDNAs coding for Trimeresurus flavoviridis and T. gramineus venom serine proteases, accelerated evolution was clearly observed. Similarity of the nucleotide sequences of four D. actus protease cDNAs with no synonymous and one to five nonsynonymous substitutions seems not to be in direct conformity with accelerated evolution. This possibly suggests that they have evolved to a similar direction to enhance their clotting activity rather than to produce other physiological activities.

  10. Degradation of Human Fibrinogen by Plasma α2-Macroglobulin-Enzyme Complexes

    PubMed Central

    Harpel, Peter C.; Mosesson, Michael W.

    1973-01-01

    This study demonstrates that human plasma α2-macroglobulin preparations possess an enzymic activity that degrades fibrinogen, resulting in the formation of products whose structure resembles that of circulating fibrinogen catabolites. The sequence of degradation is similar to that observed in plasmin-catalyzed digests, in that Aα-chain fragmentation precedes that of Bβ-chain. The addition of plasminogen activators to plasma induced an increase in the N-α-tosyl-l-arginine methyl ester HCl esterase and fibrinogenolytic activity associated with α2-macroglobulin purified from this plasma, indicating that the enzymic activity of the complex was preserved and could be increased in the presence of other plasma enzyme inhibitors. Immunochemical studies demonstrated that an α2-macroglobulin-plasmin complex had formed in urokinase-treated plasma. This α2-macroglobulin preparation manifested an esterolytic profile like that of a complex prepared from plasmin and purified α2-macroglobulin. After complex formation with α2-macroglobulin in plasma, plasmin retained less than 0.1% of its fibrinogenolytic activity. That plasmin expressed its activity while bound to α2-macroglobulin was suggested by immunoprecipitation of this activity with α2-macroglobulin antibody and by the demonstration that pancreatic trypsin inhibitor did not effectively inhibit its fibrinogenolytic or esterolytic activity. These results raise the possibility that, in addition to its activity as a major plasma proteolytic enzyme inhibitor, α2-macroglobulin may modulate enzyme-substrate interactions, such as those resulting in the formation of circulating fibrinogen catabolites, by providing a mechanism for the preservation and protection of a portion of the enzymic activity in the presence of other circulating inhibitors. Images PMID:4269529

  11. Importance of dispersion forces for prediction of thermodynamic and transport properties of some common ionic liquids.

    PubMed

    Izgorodina, Ekaterina I; Golze, Dorothea; Maganti, Radha; Armel, Vanessa; Taige, Maria; Schubert, Thomas J S; MacFarlane, Douglas R

    2014-04-28

    An extensive study of interaction energies in ion pairs of pyrrolidinium and imidazolium ionic liquids is presented. The Cnmpyr and Cnmim cations with varying alkyl chains from Methyl, Ethyl, n-Propyl to n-Butyl were combined with a wide range of routinely used IL anions such as chloride, bromide, mesylate (CH3SO3 or Mes), tosylate (CH3PhSO3 or Tos), bis(trifluoromethanesulfonyl)amide (NTf2), dicyanamide (N(CN)2 or dca), tetrafluoroborate (BF4) and hexafluorophosphate (PF6). A number of energetically favourable conformations were studied for each cation-anion combination. The interaction energy and its dispersion component of the single ion pairs were calculated using a sophisticated state-of-the-art approach: a second-order of Symmetry Adapted Perturbation Theory (SAPT). A comparison of energetics depending on the cation-anion type, as well as the mode of interaction was performed. Dispersion forces were confirmed to be of importance for the overall stabilisation of ionic liquids contributing from 28 kJ mol(-1) in pyrrolidinium ion pairs to 59 kJ mol(-1) in imidazolium ion pairs. The previously proposed ratio of total interaction energy to dispersion components and melting points was assessed for this set of ionic liquids and was found to correlate with their melting points for the anionic series, producing separate trends for the Cnmim and Cmpyr series of cations. Chlorides, bromides and tetrafluoroborates formed close-to-ideal correlations when both types of cations, Cnmim and Cnmpyr, were combined in the same trend. Correlation of the dispersion component of the interaction energy with transport properties such as conductivity and viscosity was also considered. For imidazolium-based ionic liquids strong linear correlations were obtained, whereas pyrrolidinium ionic liquids appeared to be insensitive to this correlation.

  12. Down-regulation of MMP-2 through the p38 MAPK-NF-kappaB-dependent pathway by aloe-emodin leads to inhibition of nasopharyngeal carcinoma cell invasion.

    PubMed

    Lin, Meng-Liang; Lu, Yao-Cheng; Chung, Jing-Gung; Wang, Shyang-Guang; Lin, Hsin-Ting; Kang, Shang-En; Tang, Chih-Hsin; Ko, Jiunn-Liang; Chen, Shih-Shun

    2010-09-01

    Aloe-emodin (AE), extracted from the rhizome of Rheum palmatum, has an anti-proliferative effect on different human cancer cell lines. Nonetheless, the underlying mechanism by which AE inhibits nasopharyngeal carcinoma (NPC) cell invasion is still unclear. The results of this study show that treatment of NPC cells with growth suppressive concentrations of AE caused cell cycle arrest at the S-G(2)/M phase. Coimmunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE-induced cell cycle arrest in NPC cells was associated with increasing levels of cyclin B1 bound to cyclin-dependent kinase 1. The inhibition of NPC cell invasion by AE was evidenced through the suppression of matrix metalloproteinases-2 (MMP-2) expression. MMP-2 promoter activity and cell invasion were inhibited by p38 mitogen-activated protein kinase (MAPK) siRNA, inhibitor 4-(4-Fluorophenyl)-2-[4-(methylsulfinyl)phenyl]-5-(4-pyridyl)-1H-imidazole (SB203580), and AE, but not by JNK siRNA and inhibitor 1,9-pyrazoloanthrone. Treatment with AE, SB203580, NF-kappaB inhibitors N-p-tosyl-(L)-phenylalanine chloromethyl ketone (TPCK) and pyrrolidine dithiocarbamate (PDTC) or transfection with p38 MAPK siRNA significantly inhibited NF-kappaB transcriptional activity. In addition, TPCK and PDTC treatment inhibited the expression and promoter activity of MMP-2 and thereby significantly inhibited cell invasion activity. The involvement of p38 MAPK activity in NF-kappaB-mediated MMP-2 function was further confirmed through the attenuation of p38 MAPK by SB203580 and NF-kappaB ectopic expression. Collectively, our results indicate that AE inhibits invasion of NPC cells by suppressing the expression of MMP-2 via the p38 MAPK-NF-kappaB signaling pathway.

  13. Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b-polyethylenimine triblock copolymers: synthesis, characterization, and in vitro gene transfer properties.

    PubMed

    Zhong, Zhiyuan; Feijen, Jan; Lok, Martin C; Hennink, Wim E; Christensen, Lane V; Yockman, James W; Kim, Yong-Hee; Kim, Sung Wan

    2005-01-01

    Novel ABA triblock copolymers consisting of low molecular weight linear polyethylenimine (PEI) as the A block and poly(ethylene glycol) (PEG) as the B block were prepared and evaluated as polymeric transfectant. The cationic polymerization of 2-methyl-2-oxazoline (MeOZO) using PEG-bis(tosylate) as a macroinitiator followed by acid hydrolysis afforded linear PEI-PEG-PEI triblock copolymers with controlled compositions. Two copolymers, PEI-PEG-PEI 2100-3400-2100 and 4000-3400-4000, were synthesized. Both copolymers were shown to interact with and condense plasmid DNA effectively to give polymer/DNA complexes (polyplexes) of small sizes (<100 nm) and moderate zeta-potentials (approximately +10 mV) at polymer/plasmid weight ratios > or =1.5/1. These polyplexes were able to efficiently transfect COS-7 cells and primary bovine endothelial cells (BAECs) in vitro. For example, PEI-PEG-PEI 4000-3400-4000 based polyplexes showed a transfection efficiency comparable to polyplexes of branched PEI 25000. The transfection activity of polyplexes of PEI-PEG-PEI 4000-3400-4000 in BAECs using luciferase as a reporter gene was 3-fold higher than that for linear PEI 25000/DNA formulations. Importantly, the presence of serum in the transfection medium had no inhibitive effect on the transfection activity of the PEI-PEG-PEI polyplexes. These PEI-PEG-PEI triblock copolymers displayed also an improved safety profile in comparison with high molecular weight PEIs, since the cytotoxicity of the polyplex formulations was very low under conditions where high transgene expression was found. Therefore, linear PEI-PEG-PEI triblock copolymers are an attractive novel class of nonviral gene delivery systems.

  14. Insect chymotrypsins: chloromethyl ketone inactivation and substrate specificity relative to possible coevolutional adaptation of insects and plants.

    PubMed

    Lopes, Adriana R; Sato, Paloma M; Terra, Walter R

    2009-03-01

    Insect digestive chymotrypsins are present in a large variety of insect orders but their substrate specificity still remains unclear. Four insect chymotrypsins from 3 different insect orders (Dictyoptera, Coleoptera, and two Lepidoptera) were isolated using affinity chromatography. Enzymes presented molecular masses in the range of 20 to 31 kDa and pH optima in the range of 7.5 to 10.0. Kinetic characterization using different colorimetric and fluorescent substrates indicated that insect chymotrypsins differ from bovine chymotrypsin in their primary specificity toward small substrates (like N-benzoyl-L-Tyr p-nitroanilide) rather than on their preference for large substrates (exemplified by Succynil-Ala-Ala-Pro-Phe p-nitroanilide). Chloromethyl ketones (TPCK, N- alpha-tosyl-L-Phe chloromethyl ketone and Z-GGF-CK, N- carbobenzoxy-Gly-Gly-Phe-CK) inactivated all chymotrypsins tested. Inactivation rates follow apparent first-order kinetics with variable second order rates (TPCK, 42 to 130 M(-1) s(-1); Z-GGF-CK, 150 to 450 M(-1) s(-1)) that may be remarkably low for S. frugiperda chymotrypsin (TPCK, 6 M(-1) s(-1); Z-GGF-CK, 6.1 M(-1) s(-1)). Homology modelling and sequence alignment showed that in lepidopteran chymotrypsins, differences in the amino acid residues in the neighborhood of the catalytic His 57 may affect its pKa value. This is proposed as the cause of the decrease in His 57 reactivity toward chloromethyl ketones. Such amino acid replacement in the active site is proposed to be an adaptation to the presence of dietary ketones.

  15. Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promotors

    SciTech Connect

    Solanki, V.; Rana, R.S.; Slaga, T.J.

    1981-01-01

    The effects of phorbol ester tumor promoters and related compounds on superoxide dismutase (SOD) and catalase were examined. The treatment of adult mouse skin with 2 ..mu..g 12-0-tetradecanoylphorbol-13-acetate (TPA) resulted in a sustained decrease in the basal levels of both SOD and catalase activities in the epidermis. A decline in SOD activity occurred within 2 h after application and the maximum effect was seen at 16-17 h. The decrease in SOD activity was always accompanied by a similar decline in the epidermal catalase activity. The alterations in both enzymes occurred against a high background of enhanced protein synthesis which indicates that the effect of TPA is selective for SOD and catalase. Other tumor promoters such as phorbol 12,13-dibutyrate and the non-phorbol tumor promoter anthraline also lowered the activities of both the enzymes. Mezerein, a resiniferonol derivative with weak promoting activity but a potent stage-II promoter, appeared to be more potent than TPA in lowering the basal levels. These results indicate that damage which favors neoplastic progression would occur in TPA-treated mouse skin due to the accumulation of free radicals resulting from low levels of SOD and catalase activity. In addition, the TPA-caused decrease in the levels of SOD and catalase was not prevented by either retinoic acid, fluocinolone acetonide, tosyl amino-2-phenylethyl chloromethyl ketone, or butylated hydroxytoluene, suggesting that inhibition of tumor promotion by these agents is not mediated through alterations in the levels of enzymatic activities which decrease free radical concentrations.

  16. Synthesis and properties of optically active nanostructured polymers bearing amino acid moieties by direct polycondensation of 4,4'-thiobis(2-tert-butyl-5-methylphenol) with chiral diacids.

    PubMed

    Mallakpour, Shadpour; Soltanian, Samaneh

    2012-06-01

    Four derivatives of N-trimellitylimido-L-amino acid (4a-4d) were prepared by the reaction of trimellitic anhydride (1) with the L-amino acids (2a-2d) in acetic acid as diacid monomers and were used with the aim to obtain a new family of amino acid based poly(ester-imide)s (PEI)s. The polymerization was performed by direct polycondensation of chiral diacids (4a-4d) with 4,4'-thiobis(2-tert-butyl-5-methylphenol) (5) in the presence of tosyl chloride (TsCl), pyridine and N,N-dimethyl formamide (DMF). Step-growth polymerization was carried out by varying the time of heating and the molar ratio of TsCl/diacid and the optimum conditions were achieved. The synthesized polymers were characterized by means of specific rotation experiments, FT-IR, 1H-NMR, X-ray diffraction techniques and elemental analysis. The surface morphology of the obtained polymers was studied by field emission scanning electron microscopy. The result showed nanostructure morphology of the resulting polymers. The obtained PEIs were soluble in polar aprotic solvents such as DMF, N,N-dimethyl acetamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone and protic solvents such as sulfuric acid. Thermal stability and the weight-loss behavior of the PEIs were studied by thermal gravimetric analysis (TGA) techniques. TGA showed that the 10% weight loss temperature in a nitrogen atmosphere was more than 402°C, therefore they had useful levels of thermal stability associated with excellent solubility.

  17. Scales of Lewis basicities toward C-centered Lewis acids (carbocations).

    PubMed

    Mayr, Herbert; Ammer, Johannes; Baidya, Mahiuddin; Maji, Biplab; Nigst, Tobias A; Ofial, Armin R; Singer, Thomas

    2015-02-25

    Equilibria for the reactions of benzhydryl cations (Ar2CH(+)) with phosphines, tert-amines, pyridines, and related Lewis bases were determined photometrically in CH2Cl2 and CH3CN solution at 20 °C. The measured equilibrium constants can be expressed by the sum of two parameters, defined as the Lewis Acidity (LA) of the benzhydrylium ions and the Lewis basicity (LB) of the phosphines, pyridines, etc. Least-squares minimization of log K = LA + LB with the definition LA = 0 for (4-MeOC6H4)2CH(+) gave a Lewis acidity scale for 18 benzhydrylium ions covering 18 orders of magnitude in CH2Cl2 as well as Lewis basicities (with respect to C-centered Lewis acids) for 56 bases. The Lewis acidities correlated linearly with the quantum chemically calculated (B3LYP/6-311++G(3df,2pd)//B3LYP/6-31G(d,p) level) methyl anion affinities of the corresponding benzhydrylium ions, which can be used as reference compounds for characterizing a wide variety of Lewis bases. The equilibrium measurements were complemented by isothermal titration calorimetry studies. Rates of SN1 solvolyses of benzhydryl chlorides, bromides, and tosylates derived from E(13-33)(+), i.e., from highly reactive carbocations, correlate excellently with the corresponding Lewis acidities and the quantum chemically calculated methyl anion affinities. This correlation does not hold for solvolyses of derivatives of the better stabilized amino-substituted benzhydrylium ions E(1-12)(+). In contrast, the correlation between electrophilic reactivities and Lewis acidities (or methyl anion affinities) is linear for all donor-substituted benzhydrylium ions E(1-21)(+), while the acceptor-substituted benzhydrylium ions E(26-33)(+) react more slowly than expected from their thermodynamic stabilities. The boundaries of linear rate-equilibrium relationships were thus defined.

  18. Purification and characterization of an extracellular trypsin-like protease of Fusarium oxysporum var. lini.

    PubMed

    Barata, Ricardo Andrade; Andrade, Milton Hercules Guerra; Rodrigues, Roberta Dias; Castro, Ieso Miranda

    2002-01-01

    An alkaline serineprotease, capable of hydrolyzing Nalpha-benzoyl- dl arginine p-nitroanilide, was secreted by Fusarium oxysporum var. lini grown in the presence of gelatin as the sole nitrogen and carbon source. The protease was purified 65-fold to electrophoretic homogenity from the culture supernatant in a three-step procedure comprising QSepharose chromatography, affinity chromatography, and FPLC on a MonoQ column. SDS-PAGE analysis of the purified protein indicated an estimated molecular mass of 41 kDa. The protease had optimum activity at a reaction temperature of 45 degrees C and showed a rapid decrease of activity at 48 degrees C. The optimum pH was around 8.0. Characterization of the protease showed that Ca2+ and Mg2+ cations increased the activity, which was not inhibited by EDTA or 1,10-phenanthroline. The enzyme activity on Nalpha-benzoyl-DL arginine p-nitroanilide was inhibited by 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, p-aminobenzamidine dihydrochloride, aprotinin, 3-4 dichloroisocoumarin, and N-tosyl-L-lysine chloromethyl ketone. The enzyme is also inhibited by substrate concentrations higher than 2.5 x 10(-4)M. The protease had a Michaelis-Menten constant of 0.16 mM and a V(max) of 0.60 mumol released product.min(-1).mg(-1) enzyme when assayed in a non-inhibiting substrate concentration. The activity on Nalpha-benzoyl- dl arginine p-nitroanilide was competitively inhibited by p-aminobenzamidine dihydrochoride. A K(i) value of 0.04 mM was obtained.

  19. Anisotropic thermal expansion in a metal-organic framework.

    PubMed

    Madsen, Solveig Røgild; Lock, Nina; Overgaard, Jacob; Iversen, Bo Brummerstedt

    2014-06-01

    Ionothermal reaction between Mn(II)(acetate)2·4H2O and 1,3,5-benzenetricarboxylic acid (H3BTC) in either of the two ionic liquids 1-ethyl-3-methylimidazolium bromide (EMIMBr) and 1-ethyl-3-methylimidazolium tosylate (EMIMOTs) resulted in the formation of the new metal-organic framework (MOF) EMIM[Mn(II)BTC] (BTC = 1,3,5-benzenetricarboxylate). The compound crystallizes in the orthorhombic space group Pbca with unit-cell parameters of a = 14.66658 (12), b = 12.39497 (9), c = 16.63509 (14) Å at 100 K. Multi-temperature single-crystal (15-340 K) and powder X-ray diffraction studies (100-400 K) reveal strongly anisotropic thermal expansion properties. The linear thermal expansion coefficients, αL(l), attain maximum values at 400 K along the a- and b-axis, with αL(a) = 115 × 10(-6) K(-1) and αL(b) = 75 × 10(-6) K(-1). At 400 K a negative thermal expansion coefficient of -40 × 10(-6) K(-1) is observed along the c-axis. The thermal expansion is coupled to a continuous deformation of the framework, which causes the structure to expand in two directions. Due to the rigidity of the linker, the expansion in the ab plane causes the network to contract along the c-axis. Hirshfeld surface analysis has been used to describe the interaction between the framework structure and the EMIM cation that resides within the channel. This reveals a number of rather weak interactions and one governing hydrogen-bonding interactions.

  20. Fibrinolysis relating substances in marine creatures.

    PubMed

    Sumi, H; Nakajima, N; Mihara, H

    1992-05-01

    1. Extracts with physiological saline solution were obtained from about 20 species of invertebrates and seaweed. Tosyl-L-Arg-MeOH hydrolysing and fibrin plate lytic activity were detected in the invertebrates Stichopus japonicus, Crassost gigas, Tapes japonica, and Kintai-gai as well as the seaweed Codiales codium. 2. These activities were all labile against heat (at 65 degrees C for 1 hr). Except for the extract from Stichopus japonicus, lytic activities against fibrin plates with and without plasminogen were similar. 3. The extract from S. japonicus showed plasminogen activating potency as well as the existence of urokinase (UK) activity enhancing factor. 4. On the other hand, the extract of the seaweed Hizikia fusiformis showed a strong UK inhibiting activity. 5. A fraction of fibrinolytic enzyme was obtained from the extract of S. japonicus by absorption to the celite affinity chromatography. It was orally administered to rabbits at a dosage of 40 mg/kg/day. 6. Fibrinolytic activity was determined periodically on the eugloblin fraction of plasma samples collected from these animals. 7. As compared with the pretreatment value, the activity increased about 2 times (P less than 0.01) and 3 times (P less than 0.005) after 4 and 8 weeks, respectively, of the treatment. 8. After 8 weeks of treatment, the kidney of treated rabbits was extracted with 2 M KCl. The activity of tissue plasminogen activator (free-type TPA) was revealed to be enhanced significantly (P less than 0.001) in the extracts. 9. The fibrinolytic enzyme increased in the blood was recognized by zymography to be mainly the UK type plasminogen activator with mol. wt of 53,000.

  1. Acid proliferation to improve the sensitivity of EUV resists: a pulse radiolysis study

    NASA Astrophysics Data System (ADS)

    Enomoto, Kazuyuki; Arimitsu, Koji; Yoshizawa, Atsutaro; Yamamoto, Hiroki; Oshima, Akihiro; Kozawa, Takahiro; Tagawa, Seiichi

    2011-04-01

    The yields of acid have been measured in the electron-beam irradiation of triphenylsulfonium triflate (TPS-Tf) and pinanediol monosulfonates, which consist of tosylate (PiTs), 4-fluorobenzenesulfonate (Pi1F), or 4-trifluoromethylbenzenesulfonate (Pi3F), as an acid amplifier blended in 4-hydroxystyrene matrixes. The acid yields efficiency decreases when PiTs is present, while its efficiency increases in the presence of Pi3F. Reactions of the electrons with TPS-Tf and pinanediol monosulfonates have been studied using pulse radiolysis in liquid tetrahydrofuran (THF) to evaluate the kinetic contributions to acid production. The THF-solvated electrons react with PiTs, Pi1F, and Pi3F to produce the corresponding radical anions; the rate constants are estimated to be 4.1, 5.1, and 9.2 × 1010 M-1 s-1, respectively. Electron transfer from PiTs•-, Pi1F•-, and Pi3F•- radical anions to TPS-Tf occurs with the rate constants of 5.7×1010, 1.2×1011, and 6.3 × 1010 M-1 s-1, respectively. The long-lived Pi3F•- efficiently undergoes the electron transfer to TPS-Tf to form the TPS-Tf•-, which subsequently decompose to generate TfOH. On the other hand, the decay channels of PiTs•- and Pi1F•-, which possess a relatively short lifetime, are presumably dependent on its reactions with solvated protons (charge recombination) rather than the electron transfer to TPS-Tf. The novel acid production pathway via the electron transfer from pinanediol monosulfonate radical anions to TPS-Tf is presented.

  2. Specific cell components of Bacteroides gingivalis mediate binding and degradation of human fibrinogen.

    PubMed Central

    Lantz, M S; Allen, R D; Vail, T A; Switalski, L M; Hook, M

    1991-01-01

    Bacteroides (Porphyromonas) gingivalis, which has been implicated as an etiologic agent in human periodontal diseases, has been shown to bind and degrade human fibrinogen. B. gingivalis strains bind fibrinogen reversibly and with high affinity and bind to a specific region of the fibrinogen molecule that appears to be located between the D and E domains (M. S. Lantz, R. D. Allen, P. Bounelis, L. M. Switalski, and M. Hook, J. Bacteriol. 172:716-726, 1990). We now report that human fibrinogen is bound and then degraded by specific B. gingivalis components that appear to be localized at the cell surface. Fibrinogen binding to bacterial cells occurred at 4, 22, and 37 degrees C. A functional fibrinogen-binding component (Mr, 150,000) was identified when sodium dodecyl sulfate-solubilized bacteria were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and probed with 125I-fibrinogen. Fibrinogen degradation did not occur at 4 degrees C but did occur at 22 and 37 degrees C. When bacteria and iodinated fibrinogen were incubated at 37 degrees C, two major fibrinogen fragments (Mr, 97,000 and 50,000) accumulated in incubation mixture supernatant fractions. Two major fibrinogen-degrading components (Mr, 120,000 and 150,000) have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in substrate-containing gels. Fibrinogen degradation by the Mr-120,000 and -150,000 proteases was enhanced by reducing agents, completely inhibited by N-alpha-p-tosyl-L-lysyl chloromethyl ketone, and partially inhibited by n-ethyl maleimide, suggesting that these enzymes are thiol-dependent proteases with trypsinlike substrate specificity. The fibrinogen-binding component could be separated from the fibrinogen-degrading components by selective solubilization of bacteria in sodium deoxycholate. Images PMID:1987144

  3. Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanisms

    NASA Technical Reports Server (NTRS)

    Crandall, C. G.; Shibasaki, M.; Yen, T. C.

    2002-01-01

    The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through alpha-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (alpha(1)-antagonist), yohimbine (alpha(2)-antagonist), phentolamine (non-selective alpha-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 +/- 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective alpha-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering alpha-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism.

  4. Tritrichomonas foetus Induces Apoptotic Cell Death in Bovine Vaginal Epithelial Cells

    PubMed Central

    Singh, B. N.; Lucas, J. J.; Hayes, G. R.; Kumar, Ish; Beach, D. H.; Frajblat, Marcel; Gilbert, R. O.; Sommer, U.; Costello, C. E.

    2004-01-01

    Tritrichomonas foetus is a serious veterinary pathogen, causing bovine trichomoniasis, a sexually transmitted disease leading to infertility and abortion. T. foetus infects the mucosal surfaces of the reproductive tract. Infection with T. foetus leads to apoptotic cell death of bovine vaginal epithelial cells (BVECs) in culture. An affinity-purified cysteine protease (CP) fraction yielding on sodium dodecyl sulfate-polyacrylamide gel electrophoresis a single band with an apparent molecular mass of 30 kDa (CP30) also induces BVEC apoptosis. Treatment of CP30 with the protease inhibitors TLCK (Nα-p-tosyl-l-lysine chloromethyl ketone) and E-64 [l-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane] greatly reduces induction of BVEC apoptosis. Matrix-assisted laser desorption ionization-time-of-flight MALDI-TOF mass spectrometry analysis of CP30 reveals a single peak with a molecular mass of 23.7 kDa. Mass spectral peptide sequence analysis of proteolytically digested CP30 reveals homologies to a previously reported cDNA clone, CP8 (D. J. Mallinson, J. Livingstone, K. M. Appleton, S. J. Lees, G. H. Coombs, and M. J. North, Microbiology 141:3077-3085, 1995). Induction of apoptosis is highly species specific, since the related human parasite Trichomonas vaginalis and associated purified CPs did not induce BVEC death. Fluorescence microscopy along with the Cell Death Detection ELISAPLUS assay and flow cytometry analyses were used to detect apoptotic nuclear condensation, DNA fragmentation, and changes in plasma membrane asymmetry in host cells undergoing apoptosis in response to T. foetus infection or incubation with CP30. Additionally, the activation of caspase-3 and inhibition of cell death by caspase inhibitors indicates that caspases are involved in BVEC apoptosis. These results imply that apoptosis is involved in the pathogenesis of T. foetus infection in vivo, which may have important implications for therapeutic interference with host cell death that could alter

  5. Inhibition of electron transport chain assembly and function promotes photodynamic killing of Candida

    PubMed Central

    Chabrier-Roselló, Yeissa; Giesselman, Benjamin R.; De Jesús-Andino, Francisco J.; Foster, Thomas H.; Mitra, Soumya; Haidaris, Constantine G.

    2010-01-01

    Respiratory deficiency increases the sensitivity of the pathogenic fungi Candida albicans and C. glabrata to oxidative stress induced by photodynamic therapy (PDT) sensitized by the cationic porphyrin meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP-1363). Since disruption of electron transport chain (ETC) function increases intracellular levels of reactive oxygen species in yeast, we determined whether interference with ETC assembly or function increased sensitivity to TMP-1363-PDT in C. albicans, C. glabrata and the non-pathogenic yeast Saccharomyces cerevisiae. Metabolic inhibitor antimycin A and defined genetic mutants were used to identify ETC components that contribute to the sensitivity to PDT. Inhibition of cytochrome bc1 (Complex III) with antimycin A increases mitochondrial levels of reactive oxygen species. PDT performed following pretreatment with antimycin A reduced colony forming units (CFU) of C. albicans and C. glabrata by approximately two orders of magnitude relative to PDT alone. A S. cerevisiae mitochondrial glutaredoxin grx5 mutant, defective in assembly of Fe-S clusters critical for Complex III function, displayed increased sensitivity to PDT. Furthermore, C. glabrata and S. cerevisiae mutants in cytochrome c oxidase (Complex IV) synthesis and assembly were also significantly more sensitive to PDT. These included suv3, encoding an ATP-dependent RNA helicase critical for maturation of cytochrome c oxidase subunit transcripts, and pet117, encoding an essential cytochrome c oxidase assembly factor. Following PDT, the reduction in CFU of these mutants was one to two orders of magnitude greater than in their respective parental strains. The data demonstrate that selective inhibition of ETC Complexes III and IV significantly increases the sensitivity of C. albicans, C. glabrata and S. cerevisiae to PDT sensitized with TMP-1363. PMID:20381373

  6. A novel plasminogen activator from Agkistrodon blomhoffii Ussurensis venom (ABUSV-PA): Purification and characterization

    SciTech Connect

    Liu Shuqing; Sun Mingzhong . E-mail: ming-zhong.sun@case.edu; Greenaway, Frederick T.

    2006-10-06

    A plasminogen activator with arginine ester hydrolysis activity (ABUSV-PA) has been identified and purified to homogeneity from Chinese Agkistrodon blomhoffii Ussurensis snake venom. ABUSV-PA, a monomeric protein with molecular mass of 27815.2 Da, was purified 180-fold with 0.02% recovery for protein and 3.6% recovery for esterase activity. ABUSV-PA reacts optimally with its substrate N {sub {alpha}}-tosyl-L-arginine-methyl ester (TAME) at {approx}pH 7.5 and at 51 {sup o}C. Measurement from inductively coupled plasma-atomic emission spectroscopy (ICP-AES) reveals that ABUSV-PA is a Zn{sup 2+}-containing protein with a stoichiometry of 1:1 [Zn{sup 2+}]:[ABUSV-PA]. Analyses of esterase hydrolysis and UV absorption and CD spectra indicate that Zn{sup 2+} plays an important role in maintaining the structural integrity rather than the esterase activity of ABUSV-PA. Divalent metal ions, including Ca{sup 2+}, Mg{sup 2+}, Cu{sup 2+}, Ni{sup 2+}, Mn{sup 2+}, and Co{sup 2+}, increase the TAME hydrolysis activity of ABUSV-PA. A red-shift of the emission wavelengths of the synchronous fluorescence of ABUSV-PA, compared to those of free Tyr and Trp, indicates a conformation where the Tyr and Trp residues are in exposed hydrophilic environments. The presence of zinc increases the hydrophobicity of the conformational environments surrounding the Trp residues of ABUSV-PA and affects the secondary structure of ABUSV-PA, as proved by UV absorption and CD spectroscopy.

  7. Kinetic properties of three isoforms of trypsin isolated from the pyloric caeca of chum salmon (Oncorhynchus keta).

    PubMed

    Toyota, Eiko; Iyaguchi, Daisuke; Sekizaki, Haruo; Itoh, Kunihiko; Tanizawa, Kazutaka

    2007-09-01

    Three isoforms of anionic chum salmon trypsin (ST-1, ST-2, and ST-3) were purified from the pyloric caeca of chum salmon (Oncorhynchus keta). The molecular weights of the three isoforms were about 24 kDa as determined by SDS-PAGE. The isoelectric points of ST-1, ST-2, and ST-3 were 5.8, 5.4, and 5.6, respectively. The apparent K(m) values of two isoforms (ST-1 and ST-2) for BAPA (benzoyl-L-arginine-p-nitroanilide) hydrolysis at 5, 15, 25 and 35 degrees C were slightly higher than that of the main isoform ST-3, depending on temperature. The turnover numbers, k(cat), of ST-1 and ST-2 were about twice as high as that of ST-3. Consequently, the catalytic efficiencies (k(cat)/K(m)) of ST-1 and ST-2 were more efficient than ST-3. There were marked differences in both apparent K(m) and k(cat) values of three anionic chum salmon trypsins as compared to bovine cationic trypsin. K(m) values of all chum salmon trypsins were approximately 10 times lower than those of bovine trypsin, depending on the temperature. The k(cat) values of all chum salmon trypsins were about 2- to 5-fold higher than those of bovine trypsin; therefore, the catalytic efficiencies (k(cat)/K(m)) of chum salmon trypsin were 20- to 40-fold more efficient than those of bovine trypsin. On the other hand, k(cat)/K(m) values of ST-1 for TAME (tosyl-L-arginine methyl ester) hydrolysis were lower than those of bovine trypsin, whereas k(cat)/K(m) values of ST-2 and ST-3 were comparable to those of bovine trypsin, depending on the temperature.

  8. Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

    PubMed Central

    Singh, Manish K; Kumar, Mukesh; Chamala, Raghu Ram; Yedulla, Vijayender R; Wagner, Domenick; Leung, Evan; Yang, Lijia; Matin, Asha; Ahmad, Sadia

    2014-01-01

    Summary (1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From 31P{1H}, [18O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO− and AtO− produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO− is a nucleofuge, several Bt-OCH2Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO− has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis. PMID:25246951

  9. Production and Evaluation of Antibodies and Phage Display-Derived Peptide Ligands for Immunomagnetic Separation of Mycobacterium bovis

    PubMed Central

    Stewart, Linda D.; McNair, James; McCallan, Lyanne; Thompson, Suzan; Kulakov, Leonid A.

    2012-01-01

    This study describes the development and optimization of an immunomagnetic separation (IMS) method to isolate Mycobacterium bovis cells from lymph node tissues. Gamma-irradiated whole M. bovis AF2122/97 cells and ethanol-extracted surface antigens of such cells were used to produce M. bovis-specific polyclonal and monoclonal antibodies in rabbits and mice. They were also used to generate M. bovis-specific peptide ligands by phage display biopanning. The various antibodies and peptide ligands obtained were used to coat MyOne tosyl-activated Dynabeads (Life Technologies), singly or in combination, and evaluated for IMS. Initially, M. bovis capture from Middlebrook 7H9 broth suspensions (concentration range, 10 to 105 CFU/ml) was evaluated by IMS combined with an M. bovis-specific touchdown PCR. IMS-PCR results and, subsequently, IMS-culture results indicated that the beads with greatest immunocapture capability for M. bovis in broth were those coated simultaneously with a monoclonal antibody and a biotinylated 12-mer peptide. These dually coated beads exhibited minimal capture (mean of 0.36% recovery) of 12 other Mycobacterium spp. occasionally encountered in veterinary tuberculosis (TB) diagnostic laboratories. When the optimized IMS method was applied to various M. bovis-spiked lymph node matrices, it demonstrated excellent detection sensitivities (50% limits of detection of 3.16 and 57.7 CFU/ml of lymph node tissue homogenate for IMS-PCR and IMS-culture, respectively). The optimized IMS method therefore has the potential to improve isolation of M. bovis from lymph nodes and hence the diagnosis of bovine tuberculosis. PMID:22322353

  10. Biochemical characterization of a novel fibrinolytic enzyme from Cordyceps militaris.

    PubMed

    Liu, Xiaolan; Kopparapu, Narasimha-Kumar; Li, Yao; Deng, Yongping; Zheng, Xiqun

    2017-01-01

    A fibrinolytic enzyme was produced by the medicinal mushroom, Cordyceps militaris using submerged fermentation. The enzyme was purified from culture supernatant by hydrophobic interaction, ion exchange and gel filtration chromatographies. It was purified by 36 fold, with a specific activity of 1,467.4U/mg protein and the final yield was 5.8%. The molecular weight of the enzyme as determined by SDS-PAGE and gel filtration was 28kDa and 24.5kDa, respectively, and its isoelectric point (pI) was 9.0±0.2. It was found to be a glycoprotein with carbohydrate content of 1.67% (w/v). The enzyme was optimally active at 37°C and pH 7.2. The enzyme activity was strongly inhibited by soybean trypsin inhibitor (SBTI) and aprotinin which indicated it to be a serine protease, while other inhibitors like N-α-tosyl-l-phenylalanine chloromethyl ketone (TPCK), phenyl methane sulfonyl fluoride (PMSF), pepstatin and metal chelator EDTA did not inhibit its activity. Amino acid sequences of the purified enzyme were determined partially by Q-TOF2 and they were IEDFPYQVDLR; ANCGGTVISEK; YVLTAGHCAEGYTGLNIR; TNYASVTPITADMICAGFPEGK; KDSCSGDSGGPLVTGGK; VVGIVSFGTGCAR; ANKPGVYSSVASAEIR. Sequences of the seven peptides completely matched with those of a trypsin-like serine protease from Cordyceps militaris CM01 (accession no. EGX95217.1). The purified enzyme degraded α chains of fibrinogen first and then β and γ chains and also activated plasminogen into plasmin. It can act as an anticoagulant and prevent clot formation by degrading fibrinogen. Based on these studies, the purified enzyme has great potential to be developed as a natural agent for prevention and treatment of thrombolytic diseases.

  11. Different vascular responses in glabrous and nonglabrous skin with increasing core temperature during exercise.

    PubMed

    Yamazaki, Fumio; Sone, Ryoko

    2006-07-01

    To elucidate the characteristics of vasomotor control in glabrous and nonglabrous skin during dynamic exercise, we compared the vascular responses in both areas to increasing core temperature during the cycle exercise for 30 min at different intensities in the range 20-60% of peak oxygen consumption (VO(2peak)) in a total of 13 male and four female subjects in two experimental protocols. Skin blood flow was monitored using laser Doppler flowmetry. In protocol 1, the slope of the relationship between esophageal temperature (T (es)) and cutaneous vascular conductance (CVC) in the early phase of the exercise decreased (P < 0.05) with increasing exercise intensity at glabrous sites (palm) but not nonglabrous sites (dorsal hand). In protocol 2, to examine whether a difference in vascular responses in the two areas is due to the adrenergic vasoconstrictor system, the release of norepinephrine from adrenergic nerves in forearm and palmar skin was blocked locally by iontophoresis of bretylium tosylate (BT). The administration of BT diminished completely the change of CVC in the palm during the exercise but did not alter the response in the forearm compared with the untreated site. In the two areas, neither the T (es) threshold for vasodilation nor the change in CVC above the threshold in the middle and late phase of the exercise was influenced by the intensity of the exercise. These results suggest that, in the early phase of the exercise, light-to-moderate exercise reduces in an intensity-dependent manner the thermal sensitivity for vasodilation in glabrous skin but not nonglabrous skin via an adrenergic vasoconstrictor pathway.

  12. Aging and aerobic fitness affect the contribution of noradrenergic sympathetic nerves to the rapid cutaneous vasodilator response to local heating.

    PubMed

    Tew, Garry A; Saxton, John M; Klonizakis, Markos; Moss, James; Ruddock, Alan D; Hodges, Gary J

    2011-05-01

    Sedentary aging results in a diminished rapid cutaneous vasodilator response to local heating. We investigated whether this diminished response was due to altered contributions of noradrenergic sympathetic nerves by assessing 1) the age-related decline and 2) the effect of aerobic fitness. Using laser-Doppler flowmetry, we measured skin blood flow (SkBF) in young (24 ± 1 yr) and older (64 ± 1 yr) endurance-trained and sedentary men (n = 7 per group) at baseline and during 35 min of local skin heating to 42°C at 1) untreated forearm sites, 2) forearm sites treated with bretylium tosylate (BT), which prevents neurotransmitter release from noradrenergic sympathetic nerves, and 3) forearm sites treated with yohimbine + propranolol (YP), which antagonizes α- and β-adrenergic receptors. SkBF was converted to cutaneous vascular conductance (CVC = SkBF/mean arterial pressure) and normalized to maximal CVC (%CVC(max)) achieved by skin heating to 44°C. Pharmacological agents were administered using microdialysis. In the young trained group, the rapid vasodilator response was reduced at BT and YP sites (P < 0.05); by contrast, in the young sedentary and older trained groups, YP had no effect (P > 0.05), but BT did (P > 0.05). Neither BT nor YP affected the rapid vasodilator response in the older sedentary group (P > 0.05). These data suggest that the age-related reduction in the rapid vasodilator response is due to an impairment of sympathetic-dependent mechanisms, which can be partly attenuated with habitual aerobic exercise. Rapid vasodilation involves noradrenergic neurotransmitters in young trained men and nonadrenergic sympathetic cotransmitters (e.g., neuropeptide Y) in young sedentary and older trained men, possibly as a compensatory mechanism. Finally, in older sedentary men, the rapid vasodilation appears not to involve the sympathetic system.

  13. Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells.

    PubMed Central

    Wu, M; Arsura, M; Bellas, R E; FitzGerald, M J; Lee, H; Schauer, S L; Sherr, D H; Sonenshein, G E

    1996-01-01

    Treatment of WEHI 231 immature B-lymphoma cells with an antibody against their surface immunoglobulin (anti-Ig) induces apoptosis and has been studied extensively as a model of B-cell tolerance. Anti-Ig treatment of exponentially growing WEHI 231 cells results in an early transient increase in c-myc expression that is followed by a decline to below basal levels; this decrease in c-myc expression immediately precedes the induction of cell death. Here we have modulated NF-kappaB/Rel factor activity, which regulates the rate of c-myc gene transcription, to determine whether the increase or decrease in c-Myc-levels mediates apoptosis in WEHI 231 cells. Addition of the serine/threonine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), which blocks the normally rapid turnover of the specific inhibitor of NF-kappaB/Rel IkappaBalpha in these cells, caused a drop in Rel-related factor binding. TPCK treatment resulted in decreased c-myc expression, preventing the usual increase seen following anti-Ig treatment. Whereas inhibition of the induction of c-myc expression mediated by anti-Ig failed to block apoptosis, reduction of c-myc expression in exponentially growing WEHI 231 cells induced apoptosis even in the absence of anti-Ig treatment. In WEHI 231 clones ectopically expressing c-Myc, apoptosis induced by treatment with TPCK or anti-Ig was significantly diminished and cells continued to proliferate. Furthermore, apoptosis of WEHI 231 cells ensued following enhanced expression of Mad1, which has been found to reduce functional c-Myc levels. These results indicate that the decline in c-myc expression resulting from the drop in NF-kappaB/Rel binding leads to activation of apoptosis of WEHI 231 B cells. PMID:8756660

  14. Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells.

    PubMed Central

    Wu, M; Lee, H; Bellas, R E; Schauer, S L; Arsura, M; Katz, D; FitzGerald, M J; Rothstein, T L; Sherr, D H; Sonenshein, G E

    1996-01-01

    Apoptosis of the WEHI 231 immature B cell lymphoma line following membrane interaction with an antibody against the surface IgM chains (anti-IgM) is preceded by dramatic changes in Nuclear Factor-kappaB (NF-kappaB)/ Rel binding activities. An early transient increase in NF-kappaB/Rel binding is followed by a significant decrease in intensity below basal levels. Here we have explored the role of these changes in Rel-related factors in B cell apoptosis. Treatment of WEH1 231 cells with N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a protease inhibitor which prevents degradation of the inhibitor of NF-kappaB (IkappaB)-alpha, or with low doses of pyrrolidinedithiocarbamate (PDTC) selectively inhibited NF-kappaB/Rel factor binding and induced apoptosis. Bcl-XL expression protected WEHI 231 cells from apoptosis induced by these agents. Microinjection of WEHI 231 cells with either IkappaB-alpha-GST protein or a c-Rel affinity-purified antibody induced apoptosis. Ectopic c-Rel expression ablated apoptosis induced by TPCK or anti-IgM. Treatment of BALENLM 17 and A20 B lymphoma cells or normal murine splenic B lymphocytes with either TPCK or PDTC also resulted in apoptosis. These findings indicate that the drop in NF-kappaB/Rel binding following anti-IgM treatment activates apoptosis of WEHI 231 cells; furthermore, they implicate the NF-kappaB/Rel family in control of apoptosis of normal and transformed B cells. Images PMID:8887559

  15. Theoretical insight into the excited-state intramolecular proton transfer mechanisms of three amino-type hydrogen-bonding molecules

    NASA Astrophysics Data System (ADS)

    An, Beibei; Yuan, Huijuan; Zhu, Qiuling; Li, Yuanyuan; Guo, Xugeng; Zhang, Jinglai

    2017-03-01

    Excited-state intramolecular proton transfer (ESIPT) dynamics of the amino-type hydrogen-bonding compound 2-(2‧-aminophenyl)benzothiazole (PBT-NH2) as well as its two derivatives 2-(5‧-cyano-2‧-aminophenyl)benzothiazole (CN-PBT-NH2) and 2-(5‧-cyano-2‧-tosylaminophenyl)benzothiazole (CN-PBT-NHTs) were studied by the time-dependent density functional theory (TD-DFT) approach with the B3LYP density functional, and their absorption and emission spectra were also explored at the same level of theory. A good agreement is observed between the theoretical simulations and experimental spectra, indicating that the present calculations are reasonably reliable. In addition, it is also found that the energy barriers of the first excited singlet state of the three targeted molecules along the ESIPT reaction are computed to be 0.38, 0.34 and 0.12 eV, respectively, showing the trend of gradual decrease, which implies that the introduction of the electron-withdrawing cyano or tosyl group can facilitate the occurrence of the ESIPT reaction of these amino-type H-bonding systems. Following the ESIPT, both CN-PBT-NH2 and CN-PBT-NHTs dye molecules can undergo the cis-trans isomerization reactions in the ground-state and excited-state potential energy curves along the C2-C3 bond between benzothiazole and phenyl moieties, where the energy barriers of the trans-tautomer → cis-tautomer isomerizations in the ground states are calculated to be 0.83 and 0.34 eV, respectively. According to our calculations, it is plausible that there may exist the long-lived trans-tautomer species in the ground states of CN-PBT-NH2 and CN-PBT-NHTs.

  16. 18F-Glutathione Conjugate as a PET Tracer for Imaging Tumors that Overexpress L-PGDS Enzyme

    PubMed Central

    Lee, Wei-Yuan; Yeh, Chun-Nan; Lin, Kun-Ju; Yu, Chung-Shan

    2014-01-01

    Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the progression of neurological disorders. The present study aimed at evaluating the imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS has been modified from the -4-tosylate derivative via radiofluorination in 5% radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a parallel preparation has be resolved to two isomers in a ratio of 9∶1 using analytic chiral reversed phase high performance liquid chromatography (RP-HPLC). The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP-HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with positron emission tomography. The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 µM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1±4.8% and 97.6±16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3–21.7%) but not the isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST-pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been evaluated using analytic gel filtration HPLC at the presence of various concentrations of the cold competitor FBuEA-GS. The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS. PMID:25111383

  17. Bovine pancreatic trypsin inhibitor immobilized onto sepharose as a new strategy to purify a thermostable alkaline peptidase from cobia (Rachycentron canadum) processing waste.

    PubMed

    França, Renata Cristina da Penha; Assis, Caio Rodrigo Dias; Santos, Juliana Ferreira; Torquato, Ricardo José Soares; Tanaka, Aparecida Sadae; Hirata, Izaura Yoshico; Assis, Diego Magno; Juliano, Maria Aparecida; Cavalli, Ronaldo Olivera; Carvalho, Luiz Bezerra de; Bezerra, Ranilson Souza

    2016-10-15

    A thermostable alkaline peptidase was purified from the processing waste of cobia (Rachycentron canadum) using bovine pancreatic trypsin inhibitor (BPTI) immobilized onto Sepharose. The purified enzyme had an apparent molecular mass of 24kDa by both sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. Its optimal temperature and pH were 50°C and 8.5, respectively. The enzyme was thermostable until 55°C and its activity was strongly inhibited by the classic trypsin inhibitors N-ρ-tosyl-l-lysine chloromethyl ketone (TLCK) and benzamidine. BPTI column allowed at least 15 assays without loss of efficacy. The purified enzyme was identified as a trypsin and the N-terminal amino acid sequence of this trypsin was IVGGYECTPHSQAHQVSLNSGYHFC, which was highly homologous to trypsin from cold water fish species. Using Nα-benzoyl-dl-arginine ρ-nitroanilide hydrochloride (BApNA) as substrate, the apparent km value of the purified trypsin was 0.38mM, kcat value was 3.14s(-1), and kcat/km was 8.26s(-1)mM(-1). The catalytic proficiency of the purified enzyme was 2.75×10(12)M(-1) showing higher affinity for the substrate at the transition state than other fish trypsin. The activation energy (AE) of the BApNA hydrolysis catalyzed by this enzyme was estimated to be 11.93kcalmol(-1) while the resulting rate enhancement of this reaction was found to be approximately in a range from 10(9) to 10(10)-fold evidencing its efficiency in comparison to other trypsin. This new purification strategy showed to be appropriate to obtain an alkaline peptidase from cobia processing waste with high purification degree. According with N-terminal homology and kinetic parameters, R. canadum trypsin may gathers desirable properties of psychrophilic and thermostable enzymes.

  18. Evaluation of image quality and factor for international telepathology through the Internet

    NASA Astrophysics Data System (ADS)

    Yagi, Yukako; Azumi, Norio; Elsayed, Alaa M.; Mun, Seong K.

    1997-05-01

    In the telepathology, rendering devices significantly influence the perceived image quality. If the resolution and color depth are reduced beyond a certain point, however, it is not possible to obtain images which can be used in telepathology even in an ideal situation. With this in mind, we evaluated image quality, compression, size and rates of data exchange with several histological cases on several kinds of systems for our International Consortium for Internet Telepathology (ICIT) project. The ICIT network uses widely available nonpropriety hardware and software with the Internet as a means of communication.In this study, we discuss the effective image acquisition methods for telepathology. To evaluate microscopic images, various resolution size were used. The images were also evaluated at different JPEG compression ratio, including zero compression, and different format. To evaluate an entire glass slide image, a scanner in transparency mode and an NTSC camera were used. Every case showed similar results. For he microscopic image, although the high resolution images, such as 2k X 1.5k or higher, contain more diagnostic information than lower resolution images; sufficient data was retained in the latter that it does not appear to negatively effect diagnosis. The circumstance and condition for image acquisition, such as specimen thickness or dast of glass slide, are most influenced on the highest image resolution. Usually, we use 5-10 images/case for a telepathology conference. To see all images of a case at a glance before detailed observation, or to switch to the other images immediately, a lower resolution,such as 1k X 0.7k is useful. For the entire glass slide, the reviewer could select the desired area by scanner; however, selecting it by the NTSC camera, was not easy to do. On the monitor, the scanned image has almost the same information as the microscopic image captured by the NTSC camera with 2x objective lens. To ge ta high enough quality image, the

  19. The effects of "Women Are Scientists, Too" program on middle school students' perceptions of scientists and their attitudes toward women in science

    NASA Astrophysics Data System (ADS)

    Bailer, Jill

    Research has established the need for women in science and engineering fields. In response to the recommendations from noted researchers, the Women Are Scientists, Too (WAST) program was developed for implementation in middle school language arts classes. The program combines biographies of women scientists with questions that provide students practice in critical thinking skills and writing. A series of nine biographies were adapted from The Scientist Within You (1996) and were used over a nine-week period. The WAST Program integrates women scientist role models and career awareness into reading and writing activities that can be incorporated easily into a teachers' daily lessons. In addition, this program exposes both girls and boys to the idea that women are successful scientists. With its ease of use, teachers may be more likely to reuse the materials after the completion of the study. The study was quasi-experimental in design. A pretest-posttest control group design was used. Ten language arts teachers and their students (N = 500) participated in the study. Schools were chosen from a large urban school district in southeast Texas for its ethnic diversity. The effect of the WAST program on middle school students' perceptions of scientists was investigated. Students' perceptions of scientists were measured before and after the program by the Draw-A-Scientist Test. In addition students' attitudes toward women in science were investigated and measured with the Women in Science Scale. Data generated were analyzed using two stepwise multiple regression analyses. The study found that there was a statistically significant difference between students who had participated in the WAST program and those who had not participated in the program. The WAST program accounted for 2-3 percent of the variance of the scores on the DAST and the WiSS instruments (p <.001). In addition, it was found that there was a significantly linear relationship between gender and ethnicity and

  20. Addressing the clinical needs of problem drug user patients

    PubMed Central

    Krupski, Antoinette; West, Imara I.; Graves, Meredith C.; Atkins, David C.; Maynard, Charles; Bumgardner, Kristin; Donovan, Dennis; Ries, Richard; Roy-Byrne, Peter

    2016-01-01

    Introduction Illicit drug use is a serious public health problem associated with significant co-occurring medical disorders, mental disorders, and social problems. Yet most individuals with drug use disorders have never been treated, though they often seek medical treatment in primary care. The purpose of the present study was to examine baseline characteristics of persons presenting in primary care across a range of problem drug use severity to identify their clinical needs. Methods We examined socio-demographic characteristics, medical and psychiatric comorbidities, drug use severity, social and legal problems, and service utilization for 868 patients with drug problems recruited from primary care clinics in a safety-net medical setting. Based on Drug Abuse Screening Test (DAST-10) results, individuals were categorized as having low, intermediate, or substantial/severe drug use severity. Results Patients with substantial/severe drug use severity had serious drug use (opiates, stimulants, sedatives, intravenous drug use), high levels of homelessness (50%), psychiatric comorbidity (69%), arrests for serious crimes (24%), and frequent use of expensive emergency department and inpatient hospitals. Patients with low drug use severity were primarily users of marijuana with little reported use of other drugs, less psychiatric co-morbidity, and more stable lifestyles. Patients with intermediate drug use severity fell in-between the substantial/severe and low drug use severity subgroups on most variables. Conclusions Patients with highest drug use severity are likely to require specialized psychiatric and substance abuse care in addition to ongoing medical care that is equipped to address the consequences of severe/substantial drug use including intravenous drug use. Because of their milder symptoms, patients with low drug use severity may benefit from a collaborative care model that integrates psychiatric and substance abuse care in the primary care setting. Patients

  1. Irradiation up-regulates CD80 expression through induction of tumour necrosis factor-α and CD40 ligand expression on B lymphoma cells

    PubMed Central

    Ishikawa, Fumio; Nakano, Hideki; Seo, Akira; Okada, Yayoi; Torihata, Hideko; Tanaka, Yuriko; Uchida, Tetsuya; Miyake, Hidekazu; Kakiuchi, Terutaka

    2002-01-01

    Previously, we reported that 100 Gy X-ray irradiation followed by 24 hr incubation up-regulates CD80 expression in murine B lymphoma cells, A20-2J. In the present study, we analysed the underlying mechanisms of such up-regulation using A20-HL cells derived from A20-2J cells. Irradiation of A20-HL cells with 100 Gy enhanced CD80 expression. Incubation of untreated A20-HL cells with those 100 Gy irradiated induced up-regulation of CD80 expression. Irradiation of A20-HL cells also up-regulated the expression of tumour necrosis factor-α (TNF-α) and CD40 ligand (CD40L), and the amount of immunoprecipitable TNF-α and CD40L in cell lysates. The addition of anti-TNF-α or anti-CD40L monoclonal antibody (mAb) to the incubation of irradiated A20-HL cells partially inhibited up-regulation of CD80 expression, and the addition of both antibodies together almost completely inhibited the up-regulation, suggesting that irradiation up-regulated the CD80 expression through the induction of TNF-α and CD40L expression. Irradiation also increased the accumulation of CD80, TNF-α and CD40L mRNA. n-tosyl-l-phenylalanine chloromethyl ketone (TPCK), a nuclear factor (NF)-κB inhibitor, markedly decreased irradiation-induced accumulation of CD80 mRNA and CD80 expression. FK506, a calcineurin inhibitor, and nifedipine, a calcium channel inhibitor, inhibited not only the expression of TNF-α and CD40L, but also the up-regulation of CD80 on irradiated A20-HL cells. These results strongly suggested that irradiation induced TNF-α and CD40L expression, which then up-regulated CD80 mRNA and CD80 expression through activation of NF-κB transcription factor in A20-HL cells. PMID:12100723

  2. Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

    PubMed

    Friedel, H A; Campoli-Richards, D M; Goa, K L

    1989-04-01

    Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections. The chemical linkage of sulbactam and ampicillin has now produced an orally effective compound, sultamicillin, with antibacterial activity and clinical efficacy which are similar to those of the parenteral formulation. Sultamicillin has been shown to be clinically effective in non-comparative trials in patients with infections of the respiratory tract, ears, nose and throat, urinary tract, skin and soft tissues, as well as in obstetric and gynaecological infections, and in the treatment of gonorrhoea. In a small number of controlled trials, sultamicillin has shown comparable clinical efficacy to phenoxymethyl penicillin (penicillin V) and to amoxycillin (alone and in combination with clavulanic acid) in the treatment of paediatric streptococcal pharyngitis and acute otitis media, respectively; to cefaclor in the treatment of acute otitis media in adults; and to bacampicillin, cloxacillin and flucloxacillin plus ampicillin in skin and soft tissue infections in adults, children and adult diabetic patients, respectively. Sultamicillin was superior in efficacy to bacampicillin in the treatment of chronic respiratory infections, to cefaclor in the treatment of acute otitis media in adults, and to cefadroxil in the treatment of patients with complicated urinary tract infections. However, in single-dose treatment of uncomplicated gonorrhoea, sultamicillin (1500mg plus probenecid 1g) was inferior to a 2g intramuscular dose of spectinomycin. While in several studies the incidence of diarrhoea

  3. Regulation of IL-13 synthesis in human lymphocytes: implications for asthma therapy

    PubMed Central

    Pahl, Andreas; Zhang, Meixia; Kuss, Hildegard; Szelenyi, Istvan; Brune, Kay

    2002-01-01

    IL-13 is an important mediator in inflammatory diseases such as asthma. IL-13 is mainly produced by T cells. However, signalling pathways leading to induction of this cytokine are not well-characterized. We analysed the regulation of IL-13 in human peripheral blood mononuclear cells and CD4+ T cells.Cyclosporine (CsA) and FK-506 inhibited IL-13 synthesis, when cells were stimulated by TPA/ionomycin. However, stimulation by α-CD3/α-CD28 led to an enhanced IL-13 synthesis.NF-κB inhibitor N-tosyl-L-lysine chloromethylketone (TLCK) inhibited IL-13 synthesis more effectively after TPA/ionomycin stimulation. After α-CD3/α-CD28 stimulation, only 300 μM TLCK inhibited IL-13 synthesis. Dexamethasone inhibited IL-13 equally effective after α-CD3/α-CD28 and TPA/ionomycin stimulation.p38 MAPK inhibitor SB203580 inhibited IL-13 synthesis only partially. MEK inhibitor U0126 inhibited TPA/ionomycin induced IL-13 synthesis very effectively, whereas α-CD3/α-CD28 stimulated IL-13 induction was resistant to this drug.These results were confirmed in purified CD4+ T cells. In difference to PBMCs α-CD3/α-CD28 stimulated IL-13 synthesis was effectively inhibited by CsA, FK-506 and U0126.Therefore U0126 was tested in an animal model of allergic asthma. We could demonstrate for the first time that inhibition of the MEK – ERK cascade is a therapeutic option for asthma. Intraperitoneal administration of 10 mg kg−1 U0126 reduced lung eosinophilia in ovalbumin-challenged Brown Norway rats by 44%.These results demonstrate that different signalling pathways are involved in regulating IL-13 synthesis in primary human T cells. Characterizing highly potent inhibitors of IL-13 synthesis can be exploited to identify new drugs to treat immunological diseases such as asthma. PMID:11959794

  4. Dissolved Zinc Measurements Using Shipboard FIA During the 2008 GEOTRACES Cruise

    NASA Astrophysics Data System (ADS)

    Gosnell, K. J.; Landing, W. M.; Milne, A.

    2008-12-01

    Zinc concentrations in the open ocean have been measured accurately by only a few investigators due to the extreme difficulties of collecting and processing seawater samples without introducing Zn contamination. Accurate measurements of dissolved Zn are important for understanding the biogeochemical behavior of this important biochemically required element in the open ocean. Historically, reliable samples for dissolved Zn were collected using Teflon-coated GO-FLO bottles individually hung on Kevlar line. To speed up sample collection, two "Trace Metal" rosette systems were tested during Leg 1 of the GEOTRACES 2008 intercalibration cruise: a large GEOTRACES 24-bottle rosette and the smaller Measures and Landing "CLIVAR" 12-bottle rosette. Both rosettes use 12-liter, Teflon-coated GO- FLO bottles equipped with Teflon spigots and modified air-relief fittings, allowing for pressure filtration. Contamination for dissolved Zn was eliminated in the 12-liter Teflon-lined GO-FLO bottles by repeated deployments ("flushing") on both rosette systems. A Flow Injection (FIA) technique for shipboard determination of total dissolved Zn was utilized to test rosette sampling methods for Zn contamination. Samples were acidified to 0.024M HCl (pH 2) for 16 hours. Samples were buffered to pH 5.5 using ammonium acetate buffer. Dissolved Zn was pre-concentrated using a small- volume column of 8-HQ cation exchange resin. After column rinsing, Zn was eluted into the flowing stream of organic reagent p-Tosyl-8-aminoquinoline (pTAQ), which forms fluorescent complexes with Zn. A flow- through fluorometer was used to record peak heights. Calibration was performed via standard additions. Accuracy of this method was established by measuring standard SAFe D2 and S1 samples, as well as multiple samples collected and analyzed throughout Leg 1 of the GEOTRACES 2008 cruise. Dissolved Cadmium (Cd) can additionally form fluorescent complexes with pTAQ. Thus, when necessary, a small, positive, Cd

  5. Preclinical Evaluation of 18F-PF-05270430, a Novel PET Radioligand for the Phosphodiesterase 2A Enzyme

    PubMed Central

    Chen, Laigao; Nabulsi, Nabeel; Naganawa, Mika; Zasadny, Kenneth; Skaddan, Marc B.; Zhang, Lei; Najafzadeh, Soheila; Lin, Shu-fei; Helal, Christopher J.; Boyden, Tracey L.; Chang, Cheng; Ropchan, Jim; Carson, Richard E.; Villalobos, Anabella

    2016-01-01

    The enzyme phosphodiesterase 2A (PF-05270430) is a potential target for development of novel therapeutic agents for the treatment of cognitive impairments. The goal of the present study was to evaluate the PDE2A ligand 18F-PF-05270430, 4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-f][1,2,4]triazine, in nonhuman primates. Methods: 18F-PF-05270430 was radiolabeled by 2 methods via nucleophilic substitution of its tosylate precursor. Tissue metabolite analysis in rodents and PET imaging in nonhuman primates under baseline and blocking conditions were performed to determine the pharmacokinetic and binding characteristics of the new radioligand. Various kinetic modeling approaches were assessed to select the optimal method for analysis of imaging data. Results: 18F-PF-05270430 was synthesized in greater than 98% radiochemical purity and high specific activity. In the nonhuman primate brain, uptake of 18F-PF-05270430 was fast, with peak concentration (SUVs of 1.5–1.8 in rhesus monkeys) achieved within 7 min after injection. The rank order of uptake was striatum > neocortical regions > cerebellum. Regional time–activity curves were well fitted by the 2-tissue-compartment model and the multilinear analysis-1 (MA1) method to arrive at reliable estimates of regional distribution volume (VT) and binding potential (BPND) with 120 min of scan data. Regional VT values (MA1) ranged from 1.28 mL/cm3 in the cerebellum to 3.71 mL/cm3 in the putamen, with a BPND of 0.25 in the temporal cortex and 1.92 in the putamen. Regional BPND values estimated by the simplified reference tissue model (SRTM) were similar to those from MA1. Test–retest variability in high-binding regions (striatum) was 4% ± 6% for MA1 VT, 13% ± 6% for MA1 BPND, and 13% ± 7% SRTM BPND, respectively. Pretreatment of animals with the PDE2A inhibitor PF-05180999 resulted in a dose-dependent reduction of 18F-PF-05270430 specific binding, with a half

  6. Imaging of α7 nicotinic acetylcholine receptors in brain and cerebral vasculature of juvenile pigs with [18F]NS14490

    PubMed Central

    2014-01-01

    Background The α7 nicotinic acetylcholine receptor (nAChR) is an important molecular target in neuropsychiatry and oncology. Development of applicable highly specific radiotracers has been challenging due to comparably low protein expression. To identify novel ligands as candidates for positron emission tomography (PET), a library of diazabicyclononane compounds was screened regarding affinity and specificity towards α7 nAChRs. From these, [18F]NS14490 has been shown to yield reliable results in organ distribution studies; however, the radiosynthesis of [18F]NS14490 required optimization and automation to obtain the radiotracer in quantities allowing dynamic PET studies in piglets. Methods Automated radiosynthesis of [18F]NS14490 has been performed by [18F]fluorination with the tosylate precursor in the TRACERlab™ FX F-N synthesis module (Waukesha, WI, USA). After optimization, the radiochemical yield of [18F]NS14490 was consistently approximately 35%, and the total synthesis time was about 90 min. The radiotracer was prepared with >92% radiochemical purity, and the specific activity at the end of the synthesis was 226 ± 68 GBq μmol−1. PET measurements were performed in young pigs to investigate the metabolic stability and cerebral binding of [18F]NS14490 without and with administration of the α7 nAChR partial agonist NS6740 in baseline and blocking conditions. Results The total distribution volume relative to the metabolite-corrected arterial input was 3.5 to 4.0 mL g−1 throughout the telencephalon and was reduced to 2.6 mL g−1 in animals treated with NS6740. Assuming complete blockade, this displacement indicated a binding potential (BPND) of approximately 0.5 in the brain of living pigs. In addition, evidence for specific binding in major brain arteries has been obtained. Conclusion [18F]NS14490 is not only comparable to other preclinically investigated PET radiotracers for imaging of α7 nAChR in brain but also could be a potential PET

  7. Trypsin-like serine peptidase profiles in the egg, larval, and pupal stages of Aedes albopictus

    PubMed Central

    2013-01-01

    Background Aedes albopictus, a ubiquitous mosquito, is one of the main vectors of dengue and yellow fever, representing an important threat to public health worldwide. Peptidases play key roles in processes such as digestion, oogenesis, and metamorphosis of insects. However, most of the information on the proteolytic enzymes of mosquitoes is derived from insects in the adult stages and is often directed towards the understanding of blood digestion. The aim of this study was to investigate the expression of active peptidases from the preimaginal stages of Ae. albopictus. Methods Ae. albopictus eggs, larvae, and pupae were analyzed using zymography with susbtrate-SDS-PAGE. The pH, temperature and peptidase inhibitor sensitivity was evaluated. In addition, the proteolytic activities of larval instars were assayed using the fluorogenic substrate Z-Phe-Arg-AMC. Results The proteolytic profile of the larval stage was composed of 8 bands ranging from 17 to 130 kDa. These enzymes displayed activity in a broad range of pH values, from 5.5 to 10.0. The enzymatic profile of the eggs was similar to that of the larvae, although the proteolytic bands of the eggs showed lower intensities. The pupal stage showed a complex proteolytic pattern, with at least 6 bands with apparent molecular masses ranging from 30 to 150 kDa and optimal activity at pH 7.5. Peptidases from larval instars were active from 10°C to 60°C, with optimal activity at temperatures between 37°C and 50°C. The proteolytic profile of both the larval and pupal stages was inhibited by phenyl-methyl sulfonyl-fluoride (PMSF) and Nα-Tosyl L-lysine chloromethyl ketone hydrochloride (TLCK), indicating that the main peptidases expressed during these developmental stages are trypsin-like serine peptidases. Conclusion The preimaginal stages of Ae. albopictus exhibited a complex profile of trypsin-like serine peptidase activities. A comparative analysis of the active peptidase profiles revealed differential expression

  8. Dynamic self-assembly of an M3L6 molecular triangle and an M4L8 tetrahedron from naked Pd(II) ions and bis(3-pyridyl)-substituted arenes.

    PubMed

    Chand, Dillip K; Biradha, Kumar; Kawano, Masaki; Sakamoto, Shigeru; Yamaguchi, Kentaro; Fujita, Makoto

    2006-07-17

    The pyridine-appended nonchelating bidentate ligands 1,4-bis(3-pyridyl)benzene (1) and 4,4'-bis(3-pyridyl) biphenyl (2) were complexed with a naked Pd(II) ion for the construction of molecular cage compounds. Prior to these experiments, the complexation of the ligands with cis-[Pd(en)(NO3)2] was also examined, because self-assemblies from the cis-protected Pd(II) ion were expected to be simple motifs that constitute the assemblies from naked Pd(II) ion. The structures of the self-assembled compounds resulting from 1 and [Pd(en)(NO3)2] depended on the solvent employed. In aqueous solution, an M2L2 trenchlike compound was obtained. In dimethyl sulfoxide, however, a mixture of the M2L2 trench and an M3L3 macrocycle was found in equilibrium, the dynamic nature of which was confirmed by the concentration-dependent nature of the species. At higher concentration, an M4L4 macrocycle was mostly observed. The complexation of 1 with naked Pd(II) ions was expected to produce novel structures that are combinations of the M(n)L(n) type frameworks. A peculiar tetrahedral M4L8 assembly was obtained quantitatively from 1 and Pd(NO3)2, rather than the smallest possible M3L6 double-walled triangle. Interestingly, the use of Pd(CF3SO3)2 resulted in the sole formation of the latter structure. Thus, the anion is important as a template in the formation of these assemblies. Ligand 2, which contains an extra p-phenylene unit compared to 1, behaved in a similar manner when treated with [Pd(en)(NO3)2], but showed subtle differences with naked Pd(II) ions. With Pd(NO3)2, 2 gave mostly a tetrahedron along with a double-walled triangle. With Pd(CF3SO3)2, this longer ligand formed a double-walled triangle with a negligible amount of tetrahedra. A single discrete assembly of a perfect tetrahedron was obtained from 2 and Pd(II) ions by choosing p-tosylate as a counterion.

  9. Biocompatibility Implications of Polypyrrole Synthesis Techniques

    PubMed Central

    Fonner, John M.; Forciniti, Leandro; Nguyen, Hieu; Byrne, James; Kou, Yann-Fuu; Syeda-Nawaz, Jeja; Schmidt, Christine E.

    2008-01-01

    Polypyrrole (PPy) is an inherently conducting polymer that has shown great promise for biomedical applications within the nervous system. However, to effectively use PPy as a biomaterial implant, it is important to understand and reproducibly control the electrical properties, physical topography, and surface chemistry of the polymer. Although there is much research published on the use of PPy in various applications, there is no systematic study linking the methodologies used for PPy synthesis to PPy’s basic polymeric properties (e.g., hydrophilicity, surface roughness), and to the biological effects these properties have on cells. Electrochemically synthesized PPy films differ greatly in their characteristics depending on synthesis parameters such as dopant, substrate, and thickness, among other parameters. In these studies, we have used three dopants (chloride (Cl), tosylate (ToS), polystyrene sulfonate (PSS)), two substrates (gold and indium tin oxide-coated glass), and a range of thicknesses, to measure and compare the biomedically-important characteristics of surface roughness, contact angle, conductivity, dopant stability, and cell adhesion (using PC-12 cells and Schwann cells). As predicted, we discovered large differences in roughness depending on the dopant used and the thickness of the film, while substrate choice had little effect. From contact angle measurements, PSS was found to yield the most hydrophilic material, most likely because of free charges from the long PSS chains exposed on the surface of the PPy. ToS-doped PPy films were tenfold more conductive than Cl- or PSS-doped films. X-ray photoelectron spectroscopy studies were used to evaluate dopant concentrations of PPy films stored in water and phosphate buffered saline over 14 days, and conductance studies over the same timeframe measured electrical stability. PSS proved to be the most stable dopant, though all films experienced significant decay in conductivity and dopant concentration

  10. Conformationally Strained trans-Cyclooctene (sTCO) Enables the Rapid Construction of 18F-PET Probes via Tetrazine Ligation

    PubMed Central

    Wang, Mengzhe; Svatunek, Dennis; Rohlfing, Katarina; Liu, Yu; Wang, Hui; Giglio, Ben; Yuan, Hong; Wu, Zhanghong; Li, Zibo; Fox, Joseph

    2016-01-01

    The bioorthogonal reaction between tetrazines and trans-cyclooctenes is a method for the rapid construction of F-18 probes for PET imaging. Described here is a second generation 18F-labeling system based on a conformationally strained trans-cyclooctene (sTCO)—a dienophile that is approximately 2 orders of magnitude more reactive than conventional TCO dienophiles. Starting from a readily prepared tosylate precursor, an 18F labeled sTCO derivative (18F-sTCO) could be synthesized in 29.3 +/- 5.1% isolated yield and with high specific activity. Tetrazine ligation was carried out with a cyclic RGD-conjugate of a diphenyl-s-tetrazine analogue (RGD-Tz) chosen from a diene class with an excellent combination of fast reactivity and stability both for the diene as well as the Diels-Alder adduct. For both the tetrazine and the sTCO, mini-PEG spacers were included to enhance solubility and improve the in vivo distribution profile of the resulting probe. Extremely fast reactivity (up to 2.86 x 105 M-1s-1 at 25 °C in water) has been observed in kinetic studies in the reaction of sTCO with diphenyl-s-tetrazine derivatives. A kinetic study on sTCO diastereomers in 55:45 MeOH:water showed that the syn-diastereomer displayed slightly faster reactivity than the anti-diastereomer. An 18F-sTCO conjugate with RGD-Tz demonstrated prominent and persistent tumor uptake in vivo with good tumor-to-background contrast. Unlike most radiolabeled RGD peptides, the tumor uptake of this PET agent increased from 5.3 +/- 0.2% ID/g at 1 h post injection (p.i.), to 8.9 +/- 0.5% ID/g at 4 h p.i., providing evidence for prolonged blood circulation. These findings suggest that tetrazine ligations employing 18F-sTCO should serve as a powerful and general platform for the rapid construction of peptide or protein derived PET agents. PMID:27162558

  11. Enzymes produced by halotolerant spore-forming gram-positive bacterial strains isolated from a resting habitat (Restinga de Jurubatiba) in Rio de Janeiro, Brazil: focus on proteases.

    PubMed

    D Santos, Anderson Fragoso; Pacheco, Clarissa Almeida; Valle, Roberta D Santos; Seldin, Lucy; D Santos, André Luis Souza

    2014-12-01

    The screening for hydrolases-producing, halotolerant, and spore-forming gram-positive bacteria from the root, rhizosphere, and non-rhizosphere soil of Blutaparon portulacoides, a plant found in the Restinga de Jurubatiba located at the northern region of Rio de Janeiro State, Brazil, resulted in the isolation of 22 strains. These strains were identified as Halobacillus blutaparonensis (n = 2), Oceanobacillus picturae (n = 5), and Oceanobacillus iheyensis (n = 15), and all showed the ability to produce different extracellular enzymes. A total of 20 isolates (90.9 %) showed activity for protease, 5 (22.7 %) for phytase, 3 (13.6 %) for cellulase, and 2 (9.1 %) for amylase. Some bacterial strains were capable of producing three (13.6 %) or two (9.1 %) distinct hydrolytic enzymes. However, no bacterial strain with ability to produce esterase and DNase was observed. The isolate designated M9, belonging to the species H. blutaparonensis, was the best producer of protease and also yielded amylase and phytase. This strain was chosen for further studies regarding its protease activity. The M9 strain produced similar amounts of protease when grown either without or with different NaCl concentrations (from 0.5 to 10 %). A simple inspection of the cell-free culture supernatant by gelatin-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed the presence of three major alkaline proteases of 40, 50, and 70 kDa, which were fully inhibited by phenylmethylsulfonyl fluoride (PMSF) and tosyl-L-phenylalanine chloromethyl ketone (TPCK) (two classical serine protease inhibitors). The secreted proteases were detected in a wide range of temperature (from 4 to 45 °C) and their hydrolytic activities were stimulated by NaCl (up to 10 %). The serine proteases produced by the M9 strain cleaved gelatin, casein, albumin, and hemoglobin, however, in different extensions. Collectively, these results suggest the potential use of the M9 strain in biotechnological

  12. Radiofluorinated 3-(2{prime}-fluoroethyl)-2-thienylspiperone (FETS): Synthesis, pharmacologic characterization, tissue distribution and primate imaging of a selective radioligand for mapping D2 receptor sites by PET

    SciTech Connect

    Goodman, M.M.; Shi, B.; Hoffman, J.

    1995-05-01

    Abnormally high dopaminergic neurotransmission has been implicated in schizophrenia. A number of radiolabeled analogs of spiperone, a potent antipyschotic with a high (nanomolar) affinity for dopamine D2 receptors, have been synthesized for quantifying D2 receptors in humans. An undesired property accompanying high striatal uptake of radiolabeled spiperone (SPIP) analogs is high affinity for serotonin 5-IIT2 receptors. A potent spiperone analog which selectively binds to D2 receptors would be valuable in studying regional dopaminergic aberrations in schizophrenia. We have synthesized new potent radioligands [F-18] labeled 3-(2{prime}-fluoroethyl)-2-thienylspiperone (FETS) and 3-(3{prime}-fluoropropyl)-2-thienylspiperone (FPTS) for quantifying D2 receptors by PET. In vitro binding studies for D2 receptors in rat striatal homogenates using [H-3]raclopride afforded Ki`s (nM) of 1.07 for SPIP, 2.02 for FETS, 3.45 for FES and 5.45 for FPTS. In vitro binding studies for 5-HT2 receptors in rat cortical homogenates using [H-3]ketanserin afforded Ki`s (nM) of 1.86 for SPIP, 6.03 for FES, 20 for FPTS and 67 for FETS. Thus, FETS was found to be a potent and the most selective (Ki 5-HT2/Ki D2=33.5) spiperone ligand for D2 receptors. [F-18]FETS was synthesized in 41% E.O.B. by NCA K[F-18]/K222 exchange for tosylate from 3-(2{sup {prime}}-tosylethyl)-2-thienylspiperone in CH3CN at 100{degrees}C. HPLC purification afforded [F-18]FETS with a specific activity of 8 Ci/{mu}mole in a total synthesis time of 90 min. Following femoral vein injection in rats [F-18]FETS showed good uptake and retention in striatal (S) tissue (0.91% dose/g at 60 min) with clearance from the cerebellum (C) (0.24% dose/g at 60 min) giving S/C = 3.6 at 60 min. [F-18]FETS (6.0 mCi) was also administered to a rhesus monkey and showed high uptake and retention in the basal ganglia with S/C = 6.0 and 10.0 at 1 h and 2 h post injection respectively.

  13. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor

  14. Conformational study of C8 diazocine turn mimics using {sup 3}J{sub CH} coupling constants with {sup 13}C in natural abundance

    SciTech Connect

    Bean, J.W.; Briand, J.; Burgess, J.L.; Callahan, J.F.

    1994-12-01

    The conformations of two diazocine turn mimics, which were later incorporated into GPIIb/IIIa peptide antagonists, were investigated using nuclear magnetic resonance techniques. The two compounds, methyl (2,5-dioxo-3-(S)-(3-{omega}-tosylguanidino-propyl)-4-methyl-octahydro-1,4-dazocin-1-yl)acetate (1) and methyl (2,5-dioxo-3-(S)-(3-{omega}-tosyl-guanidino-propyl)-octahydro-1,5-diazocin-1-yl)acetate (2), differ only in their substituent at the diazocine position 4 nitrogen, yet this substitution results in a marked difference in the affinity of the resulting analogs for the GPIIb/IIIa receptor. It was of interest to determine if the difference observed in the antagonistic potency between these analogs was related to constitutional or, perhaps, conformational differences. The backbone conformations of these two molecules can be determined by measuring vicinal coupling constants along the trimethylene portion of the C8 ring backbone and by measuring interproton NOE intensities between the diazocine methine proton and the protons of the trimethylene group. For compound 1, {sup 3}J{sub HH} values measured from a P.E.COSY spectrum and interproton distances calculated from ROESY buildup curves indicated the presence of a single C8 ring backbone conformation where the trimethylene bridge adopted a staggered conformation and the H{alpha}1 and H{gamma}1 protons of the trimethylene group were 2.2 A from the methine proton. For compound 2, however, partial overlap of the central H{beta}1 and H{beta}2 protons made it impossible to measure {sup 3}J{sub HH} values from the P.E.COSY spectrum. We therefore used a {sup 13}C-filtered TOCSY experiment to measure the {sup 3}J{sub CH} values in both compounds 1 and 2. These heteronuclear vicinal coupling constants measured with {sup 13}C in natural abundance in conjunction with measured interproton NOE intensities indicate that these compounds share a common C8 ring backbone conformation.

  15. Synthesis of Metal Nanoparticles and Metal Fluoride Nanoparticles from Metal Amidinate Precursors in 1‐Butyl‐3‐Methylimidazolium Ionic Liquids and Propylene Carbonate

    PubMed Central

    Schütte, Kai; Barthel, Juri; Endres, Manuel; Siebels, Marvin; Smarsly, Bernd M.; Yue, Junpei

    2016-01-01

    Abstract Decomposition of transition‐metal amidinates [M{MeC(NiPr)2}n] [M(AMD)n; M=MnII, FeII, CoII, NiII, n=2; CuI, n=1) induced by microwave heating in the ionic liquids (ILs) 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIm][BF4]), 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([BMIm][PF6]), 1‐butyl‐3‐methylimidazolium trifluoromethanesulfonate (triflate) ([BMIm][TfO]), and 1‐butyl‐3‐methylimidazolium tosylate ([BMIm][Tos]) or in propylene carbonate (PC) gives transition‐metal nanoparticles (M‐NPs) in non‐fluorous media (e.g. [BMIm][Tos] and PC) or metal fluoride nanoparticles (MF2‐NPs) for M=Mn, Fe, and Co in [BMIm][BF4]. FeF2‐NPs can be prepared upon Fe(AMD)2 decomposition in [BMIm][BF4], [BMIm][PF6], and [BMIm][TfO]. The nanoparticles are stable in the absence of capping ligands (surfactants) for more than 6 weeks. The crystalline phases of the metal or metal fluoride synthesized in [BMIm][BF4] were identified by powder X‐ray diffraction (PXRD) to exclusively Ni‐ and Cu‐NPs or to solely MF2‐NPs for M=Mn, Fe, and Co. The size and size dispersion of the nanoparticles were determined by transmission electron microscopy (TEM) to an average diameter of 2(±2) to 14(±4) nm for the M‐NPs, except for the Cu‐NPs in PC, which were 51(±8) nm. The MF2‐NPs from [BMIm][BF4] were 15(±4) to 65(±18) nm. The average diameter from TEM is in fair agreement with the size evaluated from PXRD with the Scherrer equation. The characterization was complemented by energy‐dispersive X‐ray spectroscopy (EDX). Electrochemical investigations of the CoF2‐NPs as cathode materials for lithium‐ion batteries were simply evaluated by galvanostatic charge/discharge profiles, and the results indicated that the reversible capacity of the CoF2‐NPs was much lower than the theoretical value, which may have originated from the complex conversion reaction mechanism and residue on the surface of the nanoparticles. PMID:28168159

  16. X-38 Ship #2 Mated to B-52 Mothership in Flight

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This photo shows one of the X-38 lifting-body research vehicles mated to NASA's B-52 mothership in flight prior to launch. The B-52 has been a workhorse for the Dryden Flight Research Center for more than 40 years, carrying numerous research vehicles aloft and conducting a variety of other research flight experiments. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket

  17. B-52 Launch Aircraft in Flight

    NASA Technical Reports Server (NTRS)

    2001-01-01

    NASA's venerable B-52 mothership is seen here photographed from a KC-135 Tanker aircraft. The X-43 adapter is visible attached to the right wing. The B-52, used for launching experimental aircraft and for other flight research projects, has been a familiar sight in the skies over Edwards for more than 40 years and is also both the oldest B-52 still flying and the aircraft with the lowest flight time of any B-52. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported

  18. X-38 Ship #2 in Free Flight after Release from B-52 Mothership

    NASA Technical Reports Server (NTRS)

    1999-01-01

    The X-38 research vehicle drops away from NASA's B-52 mothership immediately after being released from the B-52's wing pylon. More than 30 years earlier, this same B-52 launched the original lifting-body vehicles flight tested by NASA and the Air Force at what is now called the Dryden Flight Research Center and the Air Force Flight Test Center. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the

  19. X-38 on B-52 Wing Pylon - View from Observation Window

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A unique, close-up view of the X-38 under the wing of NASA's B-52 mothership prior to launch of the lifting-body research vehicle. The photo was taken from the observation window of the B-52 bomber as it banked in flight. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster casings. It also supported eight orbiter (space shuttle) drag chute tests in 1990. In

  20. X-38 Mounted on Pylon of B-52 Mothership

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A close-up view of the X-38 research vehicle mounted under the wing of the B-52 mothership prior to a 1997 test flight. The X-38, which was designed to help develop technology for an emergency crew return vehicle (CRV) for the International Space Station, is one of many research vehicles the B-52 has carried aloft over the past 40 years. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space

  1. X-38 - First Flight

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Reminiscent of the lifting body research flights conducted more than 30 years earlier, NASA's B-52 mothership lifts off carrying a new generation of lifting body research vehicle--the X-38. The X-38 was designed to help develop an emergency crew return vehicle for the International Space Station. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster casings. It also

  2. X-38 - First Flight

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In a scene reminiscent of the lifting body research flights conducted more than 30 years earlier, this photo shows a close-up view of NASA's B-52 mothership as it lifts off carrying a new generation of lifting body research vehicle--the X-38. The X-38 was designed to help develop an emergency crew return vehicle for the International Space Station. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the

  3. B-52B Cockpit Instrument Panel

    NASA Technical Reports Server (NTRS)

    1996-01-01

    This photo shows a close-up view of the instrument panel in the cockpit of NASA's B-52 research aircraft. Over the course of more than 40 years, the B-52 launched numerous experimental aircraft, ranging from the X-15 to the HiMAT, and was also used as a flying testbed for a variety of other research projects. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster

  4. Dryden B-52 Launch Aircraft on Edwards AFB Runway

    NASA Technical Reports Server (NTRS)

    1996-01-01

    NASA's venerable workhorse, the B-52 mothership, rolls out on the Edwards AFB runway after a test flight in 1996. Over the course of more than 40 years, the B-52 launched numerous experimental aircraft, ranging from the X-15 to the X-38, and was also used as a flying testbed for a variety of other research projects. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket

  5. Dryden B-52 Launch Aircraft on Dryden Ramp

    NASA Technical Reports Server (NTRS)

    1996-01-01

    NASA's venerable B-52 mothership sits on the ramp in front of the Dryden Flight Research Center, Edwards, California. Over the course of more than 40 years, the B-52 launched numerous experimental aircraft, ranging from the X-15 to the X-38, and was also used as a flying testbed for a variety of other research projects. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket

  6. Dryden B-52 Launch Aircraft in Flight over Dryden

    NASA Technical Reports Server (NTRS)

    1996-01-01

    NASA's venerable B-52 mothership flies over the main building at the Dryden Flight Research Center, Edwards, California. The B-52, used for launching experimental aircraft and for other flight research projects, has been a familiar sight in the skies over Edwards for more than 40 years and has also been both the oldest B-52 still flying and the aircraft with the lowest flight time of any B-52. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of

  7. Close-up of Wing Fit Check of Pylon to Carry the X-38 on B-52 Launch Aircraft

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The new pylon for the X-38 following a fit-check on NASA's B-52 at the Dryden Flight Research Center, Edwards, California, in 1997. The fit-check was the first time the 1,200-pound steel pylon was mated to the B-52 following fabrication at Dryden by the Center's Experimental Fabrication Shop. The pylon was built as an 'adapter' to allow the X-38 research vehicle to be carried aloft and launched from the B-52. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the

  8. Jay L. King, Joseph D. Huxman, and Orion D. Billeter Assist Pilot Milt Thompson into the M2-F2 Attac

    NASA Technical Reports Server (NTRS)

    1966-01-01

    NASA research pilot Milt Thompson is helped into the cockpit of the M2-F2 lifting body research aircraft at NASA's Flight Research Center (now the Dryden Flight Research Center). The M2-F2 is attached to a wing pylon under the wing of NASA's B-52 mothership. The flight was a captive flight with the pilot on-board. Milt Thompson flew in the lifting body throughout the flight, but it was never dropped from the mothership. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft

  9. Mn2+ complexes with 12-membered pyridine based macrocycles bearing carboxylate or phosphonate pendant arm: crystallographic, thermodynamic, kinetic, redox, and 1H/17O relaxation studies.

    PubMed

    Drahoš, Bohuslav; Kotek, Jan; Císařová, Ivana; Hermann, Petr; Helm, Lothar; Lukeš, Ivan; Tóth, Éva

    2011-12-19

    Mn(2+) complexes represent an alternative to Gd(3+) chelates which are widely used contrast agents in magnetic resonance imaging. In this perspective, we investigated the Mn(2+) complexes of two 12-membered, pyridine-containing macrocyclic ligands bearing one pendant arm with a carboxylic acid (HL(1), 6-carboxymethyl-3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene) or a phosphonic acid function (H(2)L(2), 6-dihydroxyphosphorylmethyl-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene). Both ligands were synthesized using nosyl or tosyl amino-protecting groups (starting from diethylenetriamine or tosylaziridine). The X-ray crystal structures confirmed a coordination number of 6 for Mn(2+) in their complexes. In aqueous solution, these pentadentate ligands allow one free coordination site for a water molecule. Potentiometric titration data indicated a higher basicity for H(2)L(2) than that for HL(1), related to the electron-donating effect of the negatively charged phosphonate group. According to the protonation sequence determined by (1)H and (31)P pH-NMR titrations, the first two protons are attached to macrocyclic amino groups whereas the subsequent protonation steps occur on the pendant arm. Both ligands form thermodynamically stable complexes with Mn(2+), with full complexation at physiological pH and 1:1 metal to ligand ratio. The kinetic inertness was studied via reaction with excess of Zn(2+) under various pHs. The dissociation of MnL(2) is instantaneous (at pH 6). For MnL(1), the dissociation is very fast (k(obs) = 1-12 × 10(3) s(-1)), much faster than that for MnDOTA, MnNOTA, or the Mn(2+) complex of the 15-membered analogue. It proceeds exclusively via the dissociation of the monoprotonated complex, without any influence of Zn(2+). In aqueous solution, both complexes are air-sensitive leading to Mn(3+) species, as evidenced by UV-vis and (1)H NMRD measurements and X-ray crystallography. Cyclic voltammetry gave low oxidation peak

  10. Close-up of Wing Fit Check of Pylon to Carry the X-38 on B-52 Launch Aircraft

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Tom McMullen, Chief of Dryden's Experimental Fabrication Shop, makes adjustments to the new pylon for NASA's X-38 during a fit-check on NASA's B-52 at the Dryden Flight Research Center, Edwards, California, in 1997. The fit-check was the first time the 1,200-pound steel pylon was mated to the B-52 following fabrication at Dryden by the Center's Experimental Fabrication Shop. The pylon was built as an 'adapter' to allow the X-38 to be attached to and launched from the B-52's wing. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST

  11. Close-up of Wing Fit Check of Pylon to Carry the X-38 on B-52 Launch Aircraft

    NASA Technical Reports Server (NTRS)

    1997-01-01

    MAT (Highly Maneuverable Aircraft Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster casings. It also supported eight orbiter (space shuttle) drag chute tests in 1990. In addition, the B-52 served as the air launch platform for the first six Pegasus space boosters. During its many years of service, the B-52 has undergone several modifications. The first major modification was made by North American Aviation (now part of Boeing) in support of the X-15 program. This involved creating a launch-panel-operator station for monitoring the status of the test vehicle being carried, cutting a large notch in the right inboard wing flap to accommodate the vertical tail of the X-15 aircraft, and installing a wing pylon that enables the B-52 to carry research vehicles and test articles to be air-launched/dropped. Located on the right wing, between the inboard engine pylon and the fuselage, this wing pylon was subjected to extensive testing prior to its use. For each test vehicle the B-52 carried, minor changes were made to the launch-panel operator's station. Built originally by the Boeing Company, the NASA B-52 is powered by eight Pratt & Whitney J57-19 turbojet engines, each of which produce 12,000 pounds of thrust. The aircraft's normal launch speed has been Mach 0.8 (about 530 miles per hour) and its normal drop altitude has been 40,000 to 45,000 feet. It is 156 feet long and has a wing span of 185 feet. The heaviest load it has carried was the No. 2 X-15 aircraft at 53,100 pounds. Project manager for the aircraft is Roy Bryant.

  12. Close-up of Wing Fit Check of Pylon to Carry the X-38 on B-52 Launch Aircraft

    NASA Technical Reports Server (NTRS)

    1997-01-01

    vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster casings. It also supported eight orbiter (space shuttle) drag chute tests in 1990. In addition, the B-52 served as the air launch platform for the first six Pegasus space boosters. During its many years of service, the B-52 has undergone several modifications. The first major modification was made by North American Aviation (now part of Boeing) in support of the X-15 program. This involved creating a launch-panel-operator station for monitoring the status of the test vehicle being carried, cutting a large notch in the right inboard wing flap to accommodate the vertical tail of the X-15 aircraft, and installing a wing pylon that enables the B-52 to carry research vehicles and test articles to be air-launched/dropped. Located on the right wing, between the inboard engine pylon and the fuselage, this wing pylon was subjected to extensive testing prior to its use. For each test vehicle the B-52 carried, minor changes were made to the launch-panel operator's station. Built originally by the Boeing Company, the NASA B-52 is powered by eight Pratt & Whitney J57-19 turbojet engines, each of which produce 12,000 pounds of thrust. The aircraft's normal launch speed has been Mach 0.8 (about 530 miles per hour) and its normal drop altitude has been 40,000 to 45,000 feet. It is 156 feet long and has a wing span of 185 feet. The heaviest load it has carried was the No. 2 X-15 aircraft at 53,100 pounds. Project manager for the aircraft is Roy Bryant.

  13. Research Pilot Milt Thompson in M2-F2 Aircraft Attached to B-52 Mothership

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Technology) research vehicle, and the DAST (drones for aerodynamic and structural testing). The aircraft supported the development of parachute recovery systems used to recover the space shuttle solid rocket booster casings. It also supported eight orbiter (space shuttle) drag chute tests in 1990. In addition, the B-52 served as the air launch platform for the first six Pegasus space boosters. During its many years of service, the B-52 has undergone several modifications. The first major modification was made by North American Aviation (now part of Boeing) in support of the X-15 program. This involved creating a launch-panel-operator station for monitoring the status of the test vehicle being carried, cutting a large notch in the right inboard wing flap to accommodate the vertical tail of the X-15 aircraft, and installing a wing pylon that enables the B-52 to carry research vehicles and test articles to be air-launched/dropped. Located on the right wing, between the inboard engine pylon and the fuselage, this wing pylon was subjected to extensive testing prior to its use. For each test vehicle the B-52 carried, minor changes were made to the launch-panel operator's station. Built originally by the Boeing Company, the NASA B-52 is powered by eight Pratt & Whitney J57-19 turbojet engines, each of which produce 12,000 pounds of thrust. The aircraft's normal launch speed has been Mach 0.8 (about 530 miles per hour) and its normal drop altitude has been 40,000 to 45,000 feet. It is 156 feet long and has a wing span of 185 feet. The heaviest load it has carried was the No. 2 X-15 aircraft at 53,100 pounds. Project manager for the aircraft is Roy Bryant.

  14. Screening and brief intervention for alcohol and other abuse.

    PubMed

    Harris, Sion Kim; Louis-Jacques, Jennifer; Knight, John R

    2014-04-01

    Substance use is the most common health risk behavior among adolescents and is one of the greatest threats to their current and future health. Universal screening of adolescents in general medical settings can be instrumental in identifying substance use early, before further problems develop and when BIs are more likely to be effective. Screening in and of itself may have some therapeutic effect. Brief screening tools feasible for use by busy medical offices to quickly and reliably assess adolescent risk for a substance use disorder now are available. A recent study found that a physician-conducted CRAFFT screen interview required an average of 74 seconds to complete, whereas a computer self-administered version took an average of 49 seconds. The CRAFFT and AUDIT tools currently have the most evidence for validity among adolescents, whereas the validity of other widely used tools such as DAST-10, NIDA-modified ASSIST (Alcohol, Smoking and Substance Involvement Screening Test), and ultra-brief screens (AUDIT-C, single-item screens) has yet to be established for adolescents. Studies are needed to identify effective strategies to promote universal adolescent screening and the use of valid screening tools in general medical settings. One statewide (Massachusetts) study found that although most (86%) primary care physicians seeing adolescents reported screening adolescents for substance use annually, only 1 in 3 reported using a validated tool (the CRAFFT). The remaining physicians reporting using informal screening procedures, their own questionnaire, or the CAGE. Computerization of screening and integration into the electronic health record appear to be promising strategies to promote universal screening and standardized use of valid screening tools. Increasing adolescent screening rates necessitates supporting physicians' ability to respond effectively to the screen results. To that end, recent evidence-informed practice guides from the AAP and NIAAA provide a

  15. Lessons learned from independent central review.

    PubMed

    Ford, R; Schwartz, L; Dancey, J; Dodd, L E; Eisenhauer, E A; Gwyther, S; Rubinstein, L; Sargent, D; Shankar, L; Therasse, P; Verweij, J

    2009-01-01

    Independent central review (ICR) is advocated by regulatory authorities as a means of independent verification of clinical trial end-points dependent on medical imaging, when the data from the trials may be submitted for licensing applications [Food and Drug Administration. United States food and drug administration guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. Rockville, MD: US Department of Health and Human Services; 2007; Committee for Medicinal Products for Human Use. European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) guideline on the evaluation of anticancer medicinal products in man. London, UK: European Medicines Agency; 2006; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 21-492 (oxaliplatin). Rockville, MD: US Department of Health and Human Services; 2002; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 21-923 (sorafenib tosylate). Rockville, MD: US Department of Health and Human Services; 2005; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 22-065 (ixabepilone). Rockville, MD: US Department of Health and Human Services; 2007; United States Food and Drug Administration Center for Drug Evaluation and Research. Approval package for application number NDA 22-059 (lapatinib ditosylate). Rockville, MD: US Department of Health and Human Services; 2007; United States Food and Drug Administration Center for Biologics Evaluation and Research. Approval package for BLA numbers 97-0260 and BLA Number 97-0244 (rituximab). Rockville, MD: US Department of Health and Human Services; 1997; United States Food and Drug Administration. FDA clinical review of BLA 98-0369 (Herceptin((R)) trastuzumab (rhuMAb HER2)). FDA Center for Biologics Evaluation and Research

  16. Ligand versus Complex: C-F and C-H Bond Activation of Polyfluoroaromatics at a Cyclic (Alkyl)(Amino)Carbene.

    PubMed

    Paul, Ursula S D; Radius, Udo

    2017-03-17

    C-F and C-H bond activation reactions of polyfluoroaromatics at the cyclic (alkyl)(amino)carbene (cAAC) cAAC(methyl) (1) are reported. Studies on the C-F bond activation using the cAAC-stabilized nickel(0) complex [Ni(cAAC(methyl) )2 ] (2) have shown that 2 does not react with fluorinated arenes. However, these investigations led to the observation of C-F bond cleavage of perfluorinated arenes by the carbene ligand cAAC(methyl) (1) itself. The reaction of 1 with C6 F6 , C6 F5 -C6 F5 , C6 F5 -CF3 , and C5 F5 N afforded the insertion products of cAAC into one of the C-F bonds of the substrate, that is, the C-F bond activation products (cAAC(methyl) )F(Ar(f) ) (Ar(f) =C6 F5 4 a, C6 F4 -C6 F5 4 b, C6 F4 -CF3 4 c, C5 F4 N 4 d). These products decompose readily upon heating to 80 °C within a few hours in solution with formation of ionic iminium salts [(cAAC(methyl) )(Ar(f) )][X] 6 a-d or neutral alkenyl perfluoroaryl imine compounds 7 a-d. The compounds (cAAC(methyl) )F(Ar(f) ) 4 a-d readily transfer fluoride, which has been exemplified by the fluoride transfer of all compounds using BF3 etherate as fluoride acceptor. Fluoride transfer has also been achieved starting from (cAAC(methyl) )F(C6 F4 -CF3 ) (4 c) or (cAAC(methyl) )F(C5 F4 N) (4 d) to other selected substrates such as trimethylchlorosilane, benzoyl chloride and tosyl chloride. Instead of C-F bond activation, insertion of the cAAC into the C-H bond was observed if 1 was treated with the partially fluorinated arenes C6 F5 H, 1,2,4,5-C6 F4 H2 , 1,3,5-C6 F3 H3 , and 1,3-C6 F2 H4 . The compounds (cAAC(methyl) )H(Ar(f) ) (Ar(f) =C6 F5 12 e, 2,3,5,6-C6 F4 H 12 f, 2,4,6-C6 F3 H2 12 g and 2,6-C6 F2 H3 12 h) have been isolated in good yields and have been characterized including X-ray analysis. Fluorobenzene C6 FH5 (pKa ≈37), the least C-H acidic fluoroarene used in this study, does not react. In order to investigate the scope and limitations of this type of cAAC C-H bond activation