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Sample records for heavy-atom derivative screening

  1. A rational approach to heavy-atom derivative screening

    Joyce, M. Gordon; Radaev, Sergei; Sun, Peter D.

    2010-01-01

    In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom-derivative screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. Despite the development in recent times of a range of techniques for phasing macromolecules, the conventional heavy-atom derivatization method still plays a significant role in protein structure determination. However, this method has become less popular in modern high-throughput oriented crystallography, mostly owing to its trial-and-error nature, which often results in lengthy empirical searches requiring large numbers of well diffracting crystals. In addition, the phasing power of heavy-atom derivatives is often compromised by lack of isomorphism or even loss of diffraction. In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom derivative-screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. The method includes three basic steps: (i) the selection of likely reactive compounds for a given protein and specific crystallization conditions based on pre-defined heavy-atom compound reactivity profiles, (ii) screening of the chosen heavy-atom compounds for their ability to form protein adducts using mass spectrometry and (iii) derivatization of crystals with selected heavy-metal compounds using the quick-soak method to maximize diffraction quality and minimize non-isomorphism. Overall, this system streamlines the process of heavy-atom compound identification and minimizes the problem of non-isomorphism in phasing

  2. A rational approach to heavy-atom derivative screening

    Joyce, M. Gordon; Radaev, Sergei; Sun, Peter D., E-mail: psun@nih.gov [Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852 (United States)

    2010-04-01

    In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom-derivative screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. Despite the development in recent times of a range of techniques for phasing macromolecules, the conventional heavy-atom derivatization method still plays a significant role in protein structure determination. However, this method has become less popular in modern high-throughput oriented crystallography, mostly owing to its trial-and-error nature, which often results in lengthy empirical searches requiring large numbers of well diffracting crystals. In addition, the phasing power of heavy-atom derivatives is often compromised by lack of isomorphism or even loss of diffraction. In order to overcome the difficulties associated with the ‘classical’ heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom derivative-screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. The method includes three basic steps: (i) the selection of likely reactive compounds for a given protein and specific crystallization conditions based on pre-defined heavy-atom compound reactivity profiles, (ii) screening of the chosen heavy-atom compounds for their ability to form protein adducts using mass spectrometry and (iii) derivatization of crystals with selected heavy-metal compounds using the quick-soak method to maximize diffraction quality and minimize non-isomorphism. Overall, this system streamlines the process of heavy-atom compound identification and minimizes the problem of non-isomorphism in phasing.

  3. Towards a rational approach for heavy-atom derivative screening in protein crystallography

    Agniswamy, Johnson; Joyce, M. Gordon; Hammer, Carl H.; Sun, Peter D.

    2008-01-01

    Heavy-atom derivatization is routinely used in protein structure determination and is thus of critical importance in structural biology. In order to replace the current trial-and-error heavy-atom derivative screening with a knowledge-based rational derivative-selection method, the reactivity of more than 40 heavy-atom compounds over a wide range of buffer and pH values was systematically examined using peptides which contained a single reactive amino-acid residue. Heavy-atom derivatization is routinely used in protein structure determination and is thus of critical importance in structural biology. In order to replace the current trial-and-error heavy-atom derivative screening with a knowledge-based rational derivative-selection method, the reactivity of more than 40 heavy-atom compounds over a wide range of buffer and pH values was systematically examined using peptides which contained a single reactive amino-acid residue. Met-, Cys- and His-containing peptides were derivatized against Hg, Au and Pt compounds, while Tyr-, Glu-, Asp-, Asn- and Gln-containing peptides were assessed against Pb compounds. A total of 1668 reactive conditions were examined using mass spectrometry and were compiled into heavy-atom reactivity tables. The results showed that heavy-atom derivatization reactions are highly linked to buffer and pH, with the most accommodating buffer being MES at pH 6. A group of 21 compounds were identified as most successful irrespective of ligand or buffer/pH conditions. To assess the applicability of the peptide heavy-atom reactivity to proteins, lysozyme crystals were derivatized with a list of peptide-reactive compounds that included both known and new compounds for lysozyme derivatization. The results showed highly consistent heavy-atom reactivities between the peptides and lysozyme

  4. Membrane's Eleven: heavy-atom derivatives of membrane-protein crystals

    Morth, Jens Preben; Sørensen, Thomas Lykke-Møller; Nissen, Poul

    2006-01-01

    A database has been assembled of heavy-atom derivatives used in the structure determination of membrane proteins. The database can serve as a guide to the design of experiments in the search for heavy-atom derivatives of new membrane-protein crystals. The database pinpoints organomercurials...

  5. A rapid and rational approach to generating isomorphous heavy-atom phasing derivatives.

    Lu, Jinghua; Sun, Peter D

    2014-09-01

    In attempts to replace the conventional trial-and-error heavy-atom derivative search method with a rational approach, we previously defined heavy metal compound reactivity against peptide ligands. Here, we assembled a composite pH- and buffer-dependent peptide reactivity profile for each heavy metal compound to guide rational heavy-atom derivative search. When knowledge of the best-reacting heavy-atom compound is combined with mass spectrometry assisted derivatization, and with a quick-soak method to optimize phasing, it is likely that the traditional heavy-atom compounds could meet the demand of modern high-throughput X-ray crystallography. As an example, we applied this rational heavy-atom phasing approach to determine a previously unknown mouse serum amyloid A2 crystal structure. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  6. Derivation of a configuration space Hamiltonian for heavy atoms: three body potentials

    Mittleman, M.H.

    1981-01-01

    A brief history of the difficulties associated with the derivation of a configuration space Hamiltonian is presented. One of the problems encountered is the definition of the projection operators which must occur. A variational definition is obtained and, with simplifying assumptions, the optimum projection operators are those which project onto Hartree-Fock orbitals. This puts many previously performed numerical calculations on a firm footing. The form of the two body interactions is discussed in the context of the gauge freedom. The Coulomb gauge is the favored one but it is pointed out that it has never been proven to be the best one. Finally a form for the relativistic three election potential is given and the possibility of its observation is discussed

  7. Photoelectron spectroscopy of heavy atoms and molecules

    White, M.G.

    1979-07-01

    The importance of relativistic interactions in the photoionization of heavy atoms and molecules has been investigated by the technique of photoelectron spectroscopy. In particular, experiments are reported which illustrate the effects of the spin-orbit interaction in the neutral ground state, final ionic states and continuum states of the photoionization target

  8. Relativistic heavy-atom effects on heavy-atom nuclear shieldings

    Lantto, Perttu; Romero, Rodolfo H.; Gómez, Sergio S.; Aucar, Gustavo A.; Vaara, Juha

    2006-11-01

    The principal relativistic heavy-atom effects on the nuclear magnetic resonance (NMR) shielding tensor of the heavy atom itself (HAHA effects) are calculated using ab initio methods at the level of the Breit-Pauli Hamiltonian. This is the first systematic study of the main HAHA effects on nuclear shielding and chemical shift by perturbational relativistic approach. The dependence of the HAHA effects on the chemical environment of the heavy atom is investigated for the closed-shell X2+, X4+, XH2, and XH3- (X =Si-Pb) as well as X3+, XH3, and XF3 (X =P-Bi) systems. Fully relativistic Dirac-Hartree-Fock calculations are carried out for comparison. It is necessary in the Breit-Pauli approach to include the second-order magnetic-field-dependent spin-orbit (SO) shielding contribution as it is the larger SO term in XH3-, XH3, and XF3, and is equally large in XH2 as the conventional, third-order field-independent spin-orbit contribution. Considering the chemical shift, the third-order SO mechanism contributes two-thirds of the difference of ˜1500ppm between BiH3 and BiF3. The second-order SO mechanism and the numerically largest relativistic effect, which arises from the cross-term contribution of the Fermi contact hyperfine interaction and the relativistically modified spin-Zeeman interaction (FC/SZ-KE), are isotropic and practically independent of electron correlation effects as well as the chemical environment of the heavy atom. The third-order SO terms depend on these factors and contribute both to heavy-atom shielding anisotropy and NMR chemical shifts. While a qualitative picture of heavy-atom chemical shifts is already obtained at the nonrelativistic level of theory, reliable shifts may be expected after including the third-order SO contributions only, especially when calculations are carried out at correlated level. The FC/SZ-KE contribution to shielding is almost completely produced in the s orbitals of the heavy atom, with values diminishing with the principal

  9. Initiating heavy-atom-based phasing by multi-dimensional molecular replacement.

    Pedersen, Bjørn Panyella; Gourdon, Pontus; Liu, Xiangyu; Karlsen, Jesper Lykkegaard; Nissen, Poul

    2016-03-01

    To obtain an electron-density map from a macromolecular crystal the phase problem needs to be solved, which often involves the use of heavy-atom derivative crystals and concomitant heavy-atom substructure determination. This is typically performed by dual-space methods, direct methods or Patterson-based approaches, which however may fail when only poorly diffracting derivative crystals are available. This is often the case for, for example, membrane proteins. Here, an approach for heavy-atom site identification based on a molecular-replacement parameter matrix (MRPM) is presented. It involves an n-dimensional search to test a wide spectrum of molecular-replacement parameters, such as different data sets and search models with different conformations. Results are scored by the ability to identify heavy-atom positions from anomalous difference Fourier maps. The strategy was successfully applied in the determination of a membrane-protein structure, the copper-transporting P-type ATPase CopA, when other methods had failed to determine the heavy-atom substructure. MRPM is well suited to proteins undergoing large conformational changes where multiple search models should be considered, and it enables the identification of weak but correct molecular-replacement solutions with maximum contrast to prime experimental phasing efforts.

  10. Initiating Heavy-atom Based Phasing by Multi-Dimensional Molecular Replacement

    Pedersen, Bjørn Panyella; Gourdon, Pontus; Liu, Xiangyu

    2014-01-01

    -based approaches, which however may fail when only poorly diffracting derivative crystals are available, as often the case for e.g. membrane proteins. Here we present an approach for heavy atom site identification based on a Molecular Replacement Parameter Matrix (MRPM) search. It involves an n-dimensional search...... to test a wide spectrum of molecular replacement parameters, such as clusters of different conformations. The result is scored by the ability to identify heavy-atom positions, from anomalous difference Fourier maps, that allow meaningful phases to be determined. The strategy was successfully applied...... but correct molecular replacement solutions with maximum contrast to prime experimental phasing efforts....

  11. Electron-impact ionization of heavy atomic ions

    Pindzola, M.S.; Griffin, D.C.; Bottcher, C.

    1987-01-01

    General theoretical methods for the calculation of direct and indirect processes in the electron-impact ionization of heavy atomic ions are reviewed. Cross section results for Xe 8+ and U 89+ are presented. 12 refs., 4 figs

  12. Semiclassical perturbation theory for diffraction in heavy atom surface scattering.

    Miret-Artés, Salvador; Daon, Shauli; Pollak, Eli

    2012-05-28

    The semiclassical perturbation theory formalism of Hubbard and Miller [J. Chem. Phys. 78, 1801 (1983)] for atom surface scattering is used to explore the possibility of observation of heavy atom diffractive scattering. In the limit of vanishing ℏ the semiclassical theory is shown to reduce to the classical perturbation theory. The quantum diffraction pattern is sensitive to the characteristics of the beam of incoming particles. Necessary conditions for observation of quantum diffraction are derived for the angular width of the incoming beam. An analytic expression for the angular distribution as a function of the angular and momentum variance of the incoming beam is obtained. We show both analytically and through some numerical results that increasing the angular width of the incident beam leads to decoherence of the quantum diffraction peaks and one approaches the classical limit. However, the incoherence of the beam in the parallel direction does not destroy the diffraction pattern. We consider the specific example of Ar atoms scattered from a rigid LiF(100) surface.

  13. Halogenated salicylaldehyde azines: The heavy atom effect on aggregation-induced emission enhancement properties

    Chen, Xiao-tong; Tong, Ai-jun

    2014-01-01

    This study investigates the heavy-atom effect (HAE) on aggregation-induced emission enhancement (AIEE) properties of salicylaldehyde azines. For this purpose, a series of halogenated salicylaldehyde azine derivatives, namely, chloro-salicylaldehyde azine (1), bromo-salicylaldehyde azine (2) and iodo-salicylaldehyde azine (3) are synthesized. 1 and 2 display typical AIEE characteristics of salicylaldehyde azine compounds; whereas for the iodo-substituent in 3, is found to be effective “external” heavy atom quenchers to salicylaldehyde azine fluorescence in aggregated state. Based on its weak fluorescence in aggregated state and relative strong fluorescence in dispersed state, 3 can also be applied as a turn-on fluorescence probe for egg albumin detection attributed to hydrophobic interaction. -- Highlights: • This study investigates the heavy-atom effect (HAE) on aggregation-induced emission enhancement (AIEE) properties of salicylaldehyde azines. • Chloro- and bromo-salicylaldehyde display typical AIEE properties of salicylaldehyde azine, whereas the iodo-substitute quenches AIEE in aggregated state. • Iodo-salicylaldehyde can be applied as a turn-on fluorescence probe for egg albumin detection attributed to hydrophobic interaction

  14. HASSP and HEAVY: Tools for automated heavy atom searches and refinement

    Terwilliger, T.T.

    1994-06-01

    In this tutorial, a simple example using model data for one derivative with anomalous information will be used to demonstrate the use of HASSP and HEAVY in heavy atom determination and refinement. The data used here will actually be based on model MAD data that has been converted to MIR format using MADMRG, but the treatment is identical to that for any other SIR+anomalous data. The data nd most of the programs discussed here can be obtained by e-mail from ''terwil at sign prov2.lanl.gov'' along with VAX-specific command files to run the data through

  15. Retention of Halogenated Solutes on Stationary Phases Containing Heavy Atoms

    Toshio Miwa

    2013-05-01

    Full Text Available To examine the effects of weak intermolecular interactions on solid-phase extraction (SPE and chromatographic separation, we synthesized some novel stationary phases with a heavy atom effect layer by immobilizing halogenated aromatic rings and hydroxyl groups onto the surface of a hydrophilic base polymer. Using SPE cartridges packed with the functionalized materials, we found that the heavy atom stationary phases could selectively retain halophenols in organic solvents, such as 1-propanol which blocks the hydrogen bonding, or acetonitrile which blocks the p-p interaction. The extraction efficiency of the materials toward the halophenols depended on the dipole moments of phenoxy groups present as functional groups. On the other hand, the extraction efficiency of solutes toward the functional group depended on their molar refractions, i.e., induced dipole moments. The retention of the solutes to the stationary phase ultimately depended on not only strong intermolecular interactions, but also the effects of weak interactions such as the dispersion force.

  16. The UKB prescription and the heavy atom effects on the nuclear magnetic shielding of vicinal heavy atoms.

    Maldonado, Alejandro F; Aucar, Gustavo A

    2009-07-21

    Fully relativistic calculations of NMR magnetic shielding on XYH3 (X = C, Si, Ge and Sn; Y = Br, I), XHn (n = 1-4) molecular systems and noble gases performed with a fully relativistic polarization propagator formalism at the RPA level of approach are presented. The rate of convergence (size of basis set and time involved) for calculations with both kinetic balance prescriptions, RKB and UKB, were investigated. Calculations with UKB makes it feasible to obtain reliable results for two or more heavy-atom-containing molecules. For such XYH3 systems, the influence of heavy vicinal halogen atoms on sigma(X) is such that heavy atom effects on heavy atoms (vicinal plus their own effects or HAVHA + HAHA effects) amount to 30.50% for X = Sn and Y = I; being the HAHA effect of the order of 25%. So the vicinal effect alone is of the order of 5.5%. The vicinal heavy atom effect on light atoms (HALA effect) is of the order of 28% for X = C and Y = I. A similar behaviour, but of opposite sign, is observed for sigma(Y) for which sigmaR-NR (I; X = C) (HAHA effect) is around 27% and sigmaR-NR(I; X = Sn) (HAVHA + HAHA effects) is close to 21%. Its electronic origin is paramagnetic for halogen atoms but both dia- and paramagnetic for central atoms. The effect on two bond distant hydrogen atoms is such that the largest variation of sigma(H) within the same family of XYH3 molecules appears for X = Si and Y = I: around 20%. In this case sigma(H; X = Sn, Y = I) = 33.45 ppm and sigma(H; X = Sn, Y = H) = 27.82 ppm.

  17. Localization and orientation of heavy-atom cluster compounds in protein crystals using molecular replacement

    Dahms, Sven O.; Kuester, Miriam; Streb, Carsten; Roth, Christian; Sträter, Norbert; Than, Manuel E.

    2013-01-01

    A new approach is presented that allows the efficient localization and orientation of heavy-atom cluster compounds used in experimental phasing by a molecular replacement procedure. This permits the calculation of meaningful phases up to the highest resolution of the diffraction data. Heavy-atom clusters (HA clusters) containing a large number of specifically arranged electron-dense scatterers are especially useful for experimental phase determination of large complex structures, weakly diffracting crystals or structures with large unit cells. Often, the determination of the exact orientation of the HA cluster and hence of the individual heavy-atom positions proves to be the critical step in successful phasing and subsequent structure solution. Here, it is demonstrated that molecular replacement (MR) with either anomalous or isomorphous differences is a useful strategy for the correct placement of HA cluster compounds. The polyoxometallate cluster hexasodium α-metatungstate (HMT) was applied in phasing the structure of death receptor 6. Even though the HA cluster is bound in alternate partially occupied orientations and is located at a special position, its correct localization and orientation could be determined at resolutions as low as 4.9 Å. The broad applicability of this approach was demonstrated for five different derivative crystals that included the compounds tantalum tetradecabromide and trisodium phosphotungstate in addition to HMT. The correct placement of the HA cluster depends on the length of the intramolecular vectors chosen for MR, such that both a larger cluster size and the optimal choice of the wavelength used for anomalous data collection strongly affect the outcome

  18. Two-photon decay in heavy atoms and ions

    Mokler, P.H.; Dunford, R.W

    2003-08-01

    We review the status of and comment on current developments in the field of two-photon decay in atomic physics research. Recent work has focused on two-photon decays in highly-charged ions and two-photon decay of inner-shell vacancies in heavy neutral atoms. We emphasize the importance of measuring the shape of the continuum emission in two-photon decay as a probe of relativistic effects in the strong central fields found in heavy atomic systems. New experimental approaches and their consequences will be discussed. (orig.)

  19. Localization and orientation of heavy-atom cluster compounds in protein crystals using molecular replacement.

    Dahms, Sven O; Kuester, Miriam; Streb, Carsten; Roth, Christian; Sträter, Norbert; Than, Manuel E

    2013-02-01

    Heavy-atom clusters (HA clusters) containing a large number of specifically arranged electron-dense scatterers are especially useful for experimental phase determination of large complex structures, weakly diffracting crystals or structures with large unit cells. Often, the determination of the exact orientation of the HA cluster and hence of the individual heavy-atom positions proves to be the critical step in successful phasing and subsequent structure solution. Here, it is demonstrated that molecular replacement (MR) with either anomalous or isomorphous differences is a useful strategy for the correct placement of HA cluster compounds. The polyoxometallate cluster hexasodium α-metatungstate (HMT) was applied in phasing the structure of death receptor 6. Even though the HA cluster is bound in alternate partially occupied orientations and is located at a special position, its correct localization and orientation could be determined at resolutions as low as 4.9 Å. The broad applicability of this approach was demonstrated for five different derivative crystals that included the compounds tantalum tetradecabromide and trisodium phosphotungstate in addition to HMT. The correct placement of the HA cluster depends on the length of the intramolecular vectors chosen for MR, such that both a larger cluster size and the optimal choice of the wavelength used for anomalous data collection strongly affect the outcome.

  20. Fast Heavy-Atom Tunneling in Trifluoroacetyl Nitrene.

    Wu, Zhuang; Feng, Ruijuan; Li, Hongmin; Xu, Jian; Deng, Guohai; Abe, Manabu; Bégué, Didier; Liu, Kun; Zeng, Xiaoqing

    2017-12-04

    Chemical reactions involving quantum mechanical tunneling (QMT) increasingly attract the attention of scientists. In contrast to the hydrogen-tunneling as frequently observed in chemistry and biology, tunneling solely by heavy atoms is rare. Herein, we report heavy-atom tunneling in trifluoroacetyl nitrene, CF 3 C(O)N. The carbonyl nitrene CF 3 C(O)N in the triplet ground state was generated in cryogenic matrices by laser (193 or 266 nm) photolysis of CF 3 C(O)N 3 and characterized by IR and EPR spectroscopy. In contrast to the theoretically predicted activation barriers (>10 kcal mol -1 ), CF 3 C(O)N undergoes rapid rearrangement into CF 3 NCO with half-life times of less than 10 min and unprecedentedly large 14 N/ 15 N kinetic isotope effects (1.18-1.33) in solid Ar, Ne, and N 2 matrices even at 2.8 K. The tunneling disappearance of CF 3 C(O)N becomes much slower in the chemically active toluene and in 2-methyltetrahydrofuran at 5 K. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Synthesis and Antibacterial Screening of Novel Derivatives of Embelin

    Subramanian, L.; Leema, M.; Pradeep, N. S.; Joy, B.; Pillai, Z. S.

    2018-02-01

    Embelin, a naturally occurring compound extracted from Embelia ribes is used in Ayurvedic system of medicine owing to its wide spectrum of biological activities. In the present work, we have aimed at improving the efficacy of Embelin by appropriate structural modifications. A few novel derivatives of Embelin have been prepared. The antibacterial screening of these derivatives were carried out and compared with a well known antibiotic, Streptomycin. The derivatives exhibited better activity than Streptomycin and the lead molecule, Embelin.

  2. Effect of heavy atoms on the thermal stability of α-amylase from Aspergillus oryzae.

    Michihiro Sugahara

    Full Text Available Currently, there are no versatile and established methods for improving stability of proteins. In an entirely different approach from conventional techniques such as mutagenesis, we attempted to enhance enzyme stability of α-amylase from Aspergillus oryzae using a heavy-atom derivatization technique. We evaluated changes in stability using differential scanning calorimetry (DSC. Candidate heavy atoms were identified using the Heavy-Atom Database System HATODAS, a Web-based tool designed to assist in heavy-atom derivatization of proteins for X-ray crystallography. The denaturation temperature of α-amylase derivatized with gadolinium (Gd or samarium (Sm ions increased by 6.2 or 5.7°C, respectively, compared to that of the native protein (60.6°C. The binding of six Gd ions was confirmed by X-ray crystallography of the enzyme at 1.5 Å resolution. DSC and dynamic light-scattering data revealed a correlation between stability and the aggregation state upon addition of Gd ions. These results show that HATODAS search is an effective tool for selecting heavy atoms for stabilization of this protein.

  3. Giant resonance phenomena in the electron impact ionization of heavy atoms and ions

    Younger, S.M.

    1986-01-01

    Heavy atoms and ions offer an interesting opportunity to study atomic physics in a region where the atomic structure is dominated by the interelectronic interactions. One illustration of this is the profound term dependence of atomic orbitals for certain configurations of heavy atoms and ions. The appearance of giant scattering resonances in the cross sections for ionization of heavy atoms by electron impact is a manifestation of resonance behavior. Such resonant structures arise from the double well nature of the scattering potential and have recently been identified in the cross sections for the electron impact ionization of several xenon-like ions. The results of calculations showing effects for a variety of other ions are summarized. 7 refs., 4 figs

  4. Site specific incorporation of heavy atom-containing unnatural amino acids into proteins for structure determination

    Xie, Jianming [San Diego, CA; Wang, Lei [San Diego, CA; Wu, Ning [Boston, MA; Schultz, Peter G [La Jolla, CA

    2008-07-15

    Translation systems and other compositions including orthogonal aminoacyl tRNA-synthetases that preferentially charge an orthogonal tRNA with an iodinated or brominated amino acid are provided. Nucleic acids encoding such synthetases are also described, as are methods and kits for producing proteins including heavy atom-containing amino acids, e.g., brominated or iodinated amino acids. Methods of determining the structure of a protein, e.g., a protein into which a heavy atom has been site-specifically incorporated through use of an orthogonal tRNA/aminoacyl tRNA-synthetase pair, are also described.

  5. Limits on visibility of single heavy atoms in the scanning transmission electron microscope: an experimental study

    Wall, J.S.

    1979-01-01

    Theoretical calculations of the visibility of single heavy atoms on thin carbon substrates have predicted higher signal to noise ratios then experimentally observed. Six experimental measurements were performed to determine where the theory is inadequate, five to determine the absolute value of heavy atom scattering cross sections in practical units, and one to determine substrate noise in some practical units. The practical unit of measure was chosen to be the scattering power of one carbon atom as determined by an internal standard, Tobacco Mosaic Virus. Measurements were performed on the following targets on thin carbon substrates: single isolated uranium atoms; silicotungstate clusters; colloidal platinum particles; fd bacteriophage embedded in negative strain; and fd bacteriophage reacted with a known quantity of heavy atom reagent. These measurements suggest that the scattering power of one heavy atom is approximately 9 +- 4 carbon atom equivalents, instead of 15 to 24 predicted by theory. The same techniques were used to measure intensity fluctuations from area to area of a clean substrate. Substrate noise was found to be less than expected for squares of width less than 10A, but up to 2.5 times greater than expected for larger squares. These signal and noise measurements have been combined to give an empirical formula for calculating signal to noise ratios from specimen and microscope parameters.

  6. External heavy atom effect on intersystem crossing reactions of aromatic hydrocarbons

    Wojnarovits, L.; Foeldiak, G.

    1988-01-01

    The external heavy atom effect by xenon on the S 1 → T n and T 1 → S o transitions of naphthalene and pyrene was investigated in hydrocarbon solvents by fluorescence or absorption spectroscopy. The quencher forms a short-lived encounter complex (that may be called exciplex as well) with the excited molecules in equilibrium process. This exciplex formation in solutions with naphthalene leads to some deviation from the Stern-Volmer type concentration dependence of the quenching. (author)

  7. Effect of heavy atoms on photochemically induced dynamic nuclear polarization in liquids

    Okuno, Yusuke; Cavagnero, Silvia

    2018-01-01

    Given its short hyperpolarization time (∼10-6 s) and mostly non-perturbative nature, photo-chemically induced dynamic nuclear polarization (photo-CIDNP) is a powerful tool for sensitivity enhancement in nuclear magnetic resonance. In this study, we explore the extent of 1H-detected 13C nuclear hyperpolarization that can be gained via photo-CIDNP in the presence of small-molecule additives containing a heavy atom. The underlying rationale for this methodology is the well-known external-heavy-atom (EHA) effect, which leads to significant enhancements in the intersystem-crossing rate of selected photosensitizer dyes from photoexcited singlet to triplet. We exploited the EHA effect upon addition of moderate amounts of halogen-atom-containing cosolutes. The resulting increase in the transient triplet-state population of the photo-CIDNP sensitizer fluorescein resulted in a significant increase in the nuclear hyperpolarization achievable via photo-CIDNP in liquids. We also explored the internal-heavy-atom (IHA) effect, which is mediated by halogen atoms covalently incorporated into the photosensitizer dye. Widely different outcomes were achieved in the case of EHA and IHA, with EHA being largely preferable in terms of net hyperpolarization.

  8. Heavy Atom Substituents as Molecular Probes for Solvent Effects on the Dynamics of Short-lived Triplet Exciplexes

    Winter, Gerhard; Steiner, Ulrich

    1980-01-01

    The influence of heavy atom substituents (Br, I) in the electron donor aniline on the electron transfer reaction with thiopyronine triplet is investigated by flash spectroscopy in solvents of different viscosity and polarity. Triplet quenching constants and radical yields are determined. The results are analysed in terms of decay constants of an intermediate triplet exciplex where the heavy atom substituents significantly enhance the intersystem crossing process leading to singlet ground stat...

  9. Control of triplet state generation in heavy atom-free BODIPY-anthracene dyads by media polarity and structural factors

    Filatov, Mikhail A.; Karuthedath, Safakath; Polestshuk, Pavel M; Callaghan, Susan; Flanagan, Keith; Telitchko, Maxime; Wiesner, Thomas; Laquai, Fré dé ric; Senge, Mathias O

    2018-01-01

    A family of heavy atom-free BODIPY-anthracene dyads (BADs) exhibiting triplet excited state formation from charge-transfer states is reported. Four types of BODIPY scaffolds, different in the alkyl substitution pattern, and four anthracene derivatives have been used to access BADs. The fluorescence and intersystem crossing (ISC) in these dyads depend on donor-acceptor couplings and can be accurately controlled by the substitution or media polarity. Under conditions that do not allow charge transfer (CT), the dyads exhibit fluorescence with high quantum yields. Formation of charge-transfer states triggers ISC and the formation of long-lived triplet excited states in the dyads. The excited state properties were studied by steady-state techniques and ultrafast pump-probe spectroscopy to determine the parameters of the observed processes. Structural information for various BADs was derived from single crystal X-ray structure determinations alongside DFT molecular geometry optimization, revealing the effects of mutual orientation of subunits on the photophysical properties. The calculations showed that alkyl substituents on the BODIPY destabilize CT states in the dyads, thus controlling the charge transfer between the subunits. The effect of the dyad structure on the ISC efficiency was considered at M06-2X level of theory and a correlation between mutual orientation of the subunits and the energy gap between singlet and triplet CT states was studied using multireference CASSCF method.

  10. Control of triplet state generation in heavy atom-free BODIPY-anthracene dyads by media polarity and structural factors

    Filatov, Mikhail A.

    2018-02-12

    A family of heavy atom-free BODIPY-anthracene dyads (BADs) exhibiting triplet excited state formation from charge-transfer states is reported. Four types of BODIPY scaffolds, different in the alkyl substitution pattern, and four anthracene derivatives have been used to access BADs. The fluorescence and intersystem crossing (ISC) in these dyads depend on donor-acceptor couplings and can be accurately controlled by the substitution or media polarity. Under conditions that do not allow charge transfer (CT), the dyads exhibit fluorescence with high quantum yields. Formation of charge-transfer states triggers ISC and the formation of long-lived triplet excited states in the dyads. The excited state properties were studied by steady-state techniques and ultrafast pump-probe spectroscopy to determine the parameters of the observed processes. Structural information for various BADs was derived from single crystal X-ray structure determinations alongside DFT molecular geometry optimization, revealing the effects of mutual orientation of subunits on the photophysical properties. The calculations showed that alkyl substituents on the BODIPY destabilize CT states in the dyads, thus controlling the charge transfer between the subunits. The effect of the dyad structure on the ISC efficiency was considered at M06-2X level of theory and a correlation between mutual orientation of the subunits and the energy gap between singlet and triplet CT states was studied using multireference CASSCF method.

  11. Phosphorescence Tuning through Heavy Atom Placement in Unsymmetrical Difluoroboron β-Diketonate Materials.

    Liu, Tiandong; Zhang, Guoqing; Evans, Ruffin E; Trindle, Carl O; Altun, Zikri; DeRosa, Christopher A; Wang, Fang; Zhuang, Meng; Fraser, Cassandra L

    2018-02-06

    Difluoroboron β-diketonates (BF 2 bdks) show both fluorescence (F) and room-temperature phosphorescence (RTP) when confined to a rigid matrix, such as poly(lactic acid). These materials have been utilized as optical oxygen sensors (e.g., in tumors, wounds, and cells). Spectral features include charge transfer (CT) from the major aromatic donor to the dioxaborine acceptor. A series of naphthyl-phenyl dyes (BF 2 nbm) (1-6) were prepared to test heavy-atom placement effects. The BF 2 nbm dye (1) was substituted with Br on naphthyl (2), phenyl (3), or both rings (4) to tailor the fluorescence/phosphorescence ratio and RTP lifetime-important features for designing O 2 sensing dyes by means of the heavy atom effect. Computational studies identify the naphthyl ring as the major donor. Thus, Br substitution on the naphthyl ring produced greater effects on the optical properties, such as increased RTP intensity and decreased RTP lifetime compared to phenyl substitution. However, for electron-donating piperidyl-phenyl dyes (5), the phenyl aromatic is the major donor. As a result, Br substitution on the naphthyl ring (6) did not alter the optical properties significantly. Experimental data and computational modeling show the importance of Br position. The S 1 and T 1 states are described by two singly occupied MOs (SOMOs). When both of these SOMOs have substantial amplitude on the heavy atom, passage from S 1 to T 1 and emission from T 1 to S 0 are both favored. This shortens the excited-state lifetimes and enhances phosphorescence. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Relativistic Spin-Orbit Heavy Atom on the Light Atom NMR Chemical Shifts: General Trends Across the Periodic Table Explained.

    Vícha, Jan; Komorovsky, Stanislav; Repisky, Michal; Marek, Radek; Straka, Michal

    2018-05-10

    The importance of relativistic effects on the NMR parameters in heavy-atom (HA) compounds, particularly the SO-HALA (Spin-Orbit Heavy Atom on the Light Atom) effect on NMR chemical shifts, has been known for about 40 years. Yet, a general correlation between the electronic structure and SO-HALA effect has been missing. By analyzing 1 H NMR chemical shifts of the sixth-period hydrides (Cs-At), we discovered general electronic-structure principles and mechanisms that dictate the size and sign of the SO-HALA NMR chemical shifts. In brief, partially occupied HA valence shells induce relativistic shielding at the light atom (LA) nuclei, while empty HA valence shells induce relativistic deshielding. In particular, the LA nucleus is relativistically shielded in 5d 2 -5d 8 and 6p 4 HA hydrides and deshielded in 4f 0 , 5d 0 , 6s 0 , and 6p 0 HA hydrides. This general and intuitive concept explains periodic trends in the 1 H NMR chemical shifts along the sixth-period hydrides (Cs-At) studied in this work. We present substantial evidence that the introduced principles have a general validity across the periodic table and can be extended to nonhydride LAs. The decades-old question of why compounds with occupied frontier π molecular orbitals (MOs) cause SO-HALA shielding at the LA nuclei, while the frontier σ MOs cause deshielding is answered. We further derive connection between the SO-HALA NMR chemical shifts and Spin-Orbit-induced Electron Deformation Density (SO-EDD), a property that can be obtained easily from differential electron densities and can be represented graphically. SO-EDD provides an intuitive understanding of the SO-HALA effect in terms of the depletion/concentration of the electron density at LA nuclei caused by spin-orbit coupling due to HA in the presence of a magnetic field. Using an analogy between the SO-EDD concept and arguments from classic NMR theory, the complex question of the SO-HALA NMR chemical shifts becomes easily understandable for a wide

  13. The influence of nuclear structure on the Lamb shift in hydrogenlike heavy atoms

    Beier, T.; Plunien, G.; Soff, G.

    1997-01-01

    We evaluate and list the various contributions to the Lamb shift in hydrogenlike heavy atoms which arise from parameters describing shape, size and structure of the nucleus. We compare these contributions with those obtained from quantum electrodynamics. It is found that in heavy nuclei, nuclear contributions depending on experimental parameters and nuclear models are of the same size as QED contributions of order a 2 . Therefore, in these systems the theoretical predictions for binding energies are limited by the exact knowledge of the nuclear parameters. In addition, we tabulate all corrections contributing to the 1s 1/2 Lamb shift in hydrogenlike Pb and U. (orig.)

  14. Extended screened exchange functional derived from transcorrelated density functional theory.

    Umezawa, Naoto

    2017-09-14

    We propose a new formulation of the correlation energy functional derived from the transcorrelated method in use in density functional theory (TC-DFT). An effective Hamiltonian, H TC , is introduced by a similarity transformation of a many-body Hamiltonian, H, with respect to a complex function F: H TC =1FHF. It is proved that an expectation value of H TC for a normalized single Slater determinant, D n , corresponds to the total energy: E[n] = ⟨Ψ n |H|Ψ n ⟩/⟨Ψ n |Ψ n ⟩ = ⟨D n |H TC |D n ⟩ under the two assumptions: (1) The electron density nr associated with a trial wave function Ψ n = D n F is v-representable and (2) Ψ n and D n give rise to the same electron density nr. This formulation, therefore, provides an alternative expression of the total energy that is useful for the development of novel correlation energy functionals. By substituting a specific function for F, we successfully derived a model correlation energy functional, which resembles the functional form of the screened exchange method. The proposed functional, named the extended screened exchange (ESX) functional, is described within two-body integrals and is parametrized for a numerically exact correlation energy of the homogeneous electron gas. The ESX functional does not contain any ingredients of (semi-)local functionals and thus is totally free from self-interactions. The computational cost for solving the self-consistent-field equation is comparable to that of the Hartree-Fock method. We apply the ESX functional to electronic structure calculations for a solid silicon, H - ion, and small atoms. The results demonstrate that the TC-DFT formulation is promising for the systematic improvement of the correlation energy functional.

  15. Optically stimulated slowing of polar heavy-atom molecules with a constant beat phase

    Yin, Yanning; Xu, Supeng; Xia, Meng; Xia, Yong; Yin, Jianping

    2018-04-01

    Polar heavy-atom molecules have been well recognized as promising candidates for precision measurements and tests of fundamental physics. A much slower molecular beam to increase the interaction time should lead to a more sensitive measurement. Here we theoretically demonstrate the possibility of the stimulated longitudinal slowing of heavy-atom molecules by the coherent optical bichromatic force with a constant beat phase. Taking the YbF meolecule as an example, we show that a rapid and short-distance deceleration of heavy molecules by a phase-compensation method is feasible with moderate conditions. A molecular beam of YbF with a forward velocity of 120 m/s can be decelerated below 10 m/s within a distance of 3.5 cm and with a laser irradiance for each traveling wave of 107.2 W/cm 2 . Our proposed slowing method could be a promising approach to break through the space constraint or the limited capture efficiency of molecules loadable into a magneto-optical trap in traditional deceleration schemes, opening the possibility for a significant improvement of the precision measurement sensitivity.

  16. Functionalizing carbon nitride with heavy atom-free spin converters for enhanced 1 O 2 generation

    Wu, Wenting; Han, Congcong; Zhang, Qinhua; Zhang, Qinggang; Li, Zhongtao; Gosztola, David J.; Wiederrecht, Gary P.; Wu, Mingbo

    2018-05-01

    advanced photosensitizers for singlet oxygen (1O2) generation. However, the intersystem crossing (ISC) process is quite insufficient in carbon nitride, limiting the 1O2 generation. Here, we report a facile and general strategy to confined benzophenone as a heavy atom-free spin converter dopant in carbon nitride via the facile copolymerization. With proper energy level matching between the heavy atom-free spin converter and various ligands based on carbon nitride precursors, the proper combination can decrease the singlet-triplet energy gap (DEST) and hence generate 1O2 effectively. Due to its significant and selectivity for 1O2 generation, the as-prepared carbon nitride-based photosensitizer shows a high selective photooxidation activity for 1,5-dihydroxy-naphthalene (1,5-DHN). The product yield reached 71.8% after irradiation for 60 min, which was higher than that of cyclometalated PtII complexes (53.6%) in homogeneous photooxidation. This study can broaden the application of carbon nitride in the field of selective heterogeneous photooxidation due to simple operation, low cost, and high efficiency, making it a strong candidate for future industrialization.

  17. Density-matrix-functional calculations for matter in strong magnetic fields: Ground states of heavy atoms

    Johnsen, Kristinn; Yngvason, Jakob

    1996-01-01

    We report on a numerical study of the density matrix functional introduced by Lieb, Solovej, and Yngvason for the investigation of heavy atoms in high magnetic fields. This functional describes exactly the quantum mechanical ground state of atoms and ions in the limit when the nuclear charge Z...... and the electron number N tend to infinity with N/Z fixed, and the magnetic field B tends to infinity in such a way that B/Z4/3→∞. We have calculated electronic density profiles and ground-state energies for values of the parameters that prevail on neutron star surfaces and compared them with results obtained...... by other methods. For iron at B=1012 G the ground-state energy differs by less than 2% from the Hartree-Fock value. We have also studied the maximal negative ionization of heavy atoms in this model at various field strengths. In contrast to Thomas-Fermi type theories atoms can bind excess negative charge...

  18. Dose enhancement by synchrotron radiation and heavy atoms for the treatment of gliomas

    Bobyk, L.

    2010-11-01

    High grade gliomas are brain tumors of bad prognosis. The standard therapeutic treatment combines surgery, radiotherapy and sometimes use of temozolomide (chemotherapy agent). Healthy tissues radio-sensitivity is a major limitation for radiotherapy treatment. The stereotactic radiotherapy by synchrotron radiation is an innovative technique which combines a low energy radiation (lower 100 keV) with the presence of heavy atoms in the tumoral zone. Such an approach is used to increase the differential of dose deposited in the tumor compared to surrounding healthy tissues. In this study, several compounds containing heavy atoms such as chemotherapy agents: cisplatin/carbo-platin, a DNA base analog: 5-iodo-2'-deoxyuridine (IUdR) and gold nano-particles were considered. The dose enhancement factor induced by the presence of these compounds located for some of them in the extracellular medium or inside the cells for others, was determined using in vitro studies. Thereafter, in vivo studies on rats bearing gliomas, were performed to study the toxicity, the kinetic of distribution and the localization of these compounds together with their potential efficacy of treatment combining intracerebral injection with low energy radiation. (author)

  19. Heavy atoms as molecular probes in studying the solvent dependence of the dynamics of triplet exciplexes

    Steiner, U.; Winter, G.

    1981-01-01

    Electron transfer reactions between thiopyronine triplet (acceptor 3 A + ) and the electron donors (D), aniline, p-Br-aniline and p-I-aniline, are investigated by flash spectroscopy in solvents of different viscosity and polarity. Due to the heavy-atom effect the radical yield becomes very sensitive to the solvent influence, which can be explained by the dynamic properties of a triplet exciplex ( 3 (AD + )) formed as a primary product in the reaction between acceptor triplet and donor. Whereas on variation of solvent viscosity the solvent cage effect on the dissociation of 3 (AD + ) is observed, a change in solvent polarity is suggested to affect the radiationless deactivation of 3 (AD + ) to the ground state of the components. (author)

  20. Heavy atom induced room temperature fluorescence quenching of PAH from a glucose glass

    Marlow, Matt, E-mail: matthew.marlow@nicholls.edu

    2017-06-15

    Sugar glasses are a relatively new matrix for solid-matrix luminescence. Molecular interactions within the sugar glass are not well understood. Fluorescence quenching was used to investigate molecular interactions within the sugar glass matrix. The room temperature fluorescence quenching of pyrene and naphthalene was observed from a glucose glass. The heavy atom salt NaI was the quencher. Two solvent compositions 50/50 and 60/40 MeOH/water, used for glass preparation, were examined for their effect on glass rigidity and molecular interactions. A complex static mechanism was observed for glasses prepared with 50/50 MeOH/water. This data was fit to the sphere of action model and associations constants determined. A Stern-Volmer static mechanism of quenching was observed for glasses prepared with 60/40 MeOH/water. This data fit the Stern-Volmer equation and association constants were determined. A larger association constant was observed for pyrene compared to naphthalene for both solvent systems used. Pyrene had a larger association constant with a sugar glass prepared with 60/40 MeOH/water compared to 50/50 MeOH/water implying a greater association between pyrene and iodide. The greater association is a reflection of a more rigid internal environment for the sugar glass prepared with 60/40 MeOH/water.

  1. Sub-Angstrom Atomic-Resolution Imaging of Heavy Atoms to Light Atoms

    O' Keefe, Michael A.; Shao-Horn, Yang

    2003-05-23

    Three decades ago John Cowley and his group at ASU achieved high-resolution electron microscope images showing the crystal unit cell contents at better than 4Angstrom resolution. Over the years, this achievement has inspired improvements in resolution that have enabled researchers to pinpoint the positions of heavy atom columns within the cell. More recently, this ability has been extended to light atoms as resolution has improved. Sub-Angstrom resolution has enabled researchers to image the columns of light atoms (carbon, oxygen and nitrogen) that are present in many complex structures. By using sub-Angstrom focal-series reconstruction of the specimen exit surface wave to image columns of cobalt, oxygen, and lithium atoms in a transition metal oxide structure commonly used as positive electrodes in lithium rechargeable batteries, we show that the range of detectable light atoms extends to lithium. HRTEM at sub-Angstrom resolution will provide the essential role of experimental verification for the emergent nanotech revolution. Our results foreshadow those to be expected from next-generation TEMs with Cs-corrected lenses and monochromated electron beams.

  2. Proton exchange in acid–base complexes induced by reaction coordinates with heavy atom motions

    Alavi, Saman; Taghikhani, Mahdi

    2012-01-01

    Highlights: ► Proton exchange in acid–base complexes is studied. ► The structures, binding energies, and normal mode vibrations are calculated. ► Transition state structures of proton exchange mechanism are determined. ► In the complexes studied, the reaction coordinate involves heavy atom rocking. ► The reaction coordinate is not simply localized in the proton movements. - Abstract: We extend previous work on nitric acid–ammonia and nitric acid–alkylamine complexes to illustrate that proton exchange reaction coordinates involve the rocking motion of the base moiety in many double hydrogen-bonded gas phase strong acid–strong base complexes. The complexes studied involve the biologically and atmospherically relevant glycine, formic, acetic, propionic, and sulfuric acids with ammonia/alkylamine bases. In these complexes, the magnitude of the imaginary frequencies associated with the proton exchange transition states are −1 . This contrasts with widely studied proton exchange reactions between symmetric carboxylic acid dimers or asymmetric DNA base pair and their analogs where the reaction coordinate is localized in proton motions and the magnitude of the imaginary frequencies for the transition states are >1100 cm −1 . Calculations on complexes of these acids with water are performed for comparison. Variations of normal vibration modes along the reaction coordinate in the complexes are described.

  3. Low-energy heavy-atom impact as a tool for production and classification of doubly excited states

    Andersen, N.

    1985-01-01

    Low-energy heavy-atom impact may be an efficient way of preferentially populating doubly excited levels. Using neon as an example, this paper discusses why this is so. The similarity of the structure of the energy level diagrams for doubly excited neon and the level scheme for neutral magnesium is pointed out, suggesting that collective quantum numbers may describe the electron pair. (orig.)

  4. Discrimination of solvent from protein regions in native Fouriers as a means of evaluating heavy-atom solutions in the MIR and MAD methods

    Terwilliger, Thomas C.; Berendzen, Joel

    1999-01-01

    The presence of distinct regions of high and low density variation in electron-density maps is found to be a good indicator of the correctness of a heavy-atom solution in the MIR and MAD methods. An automated examination of the native Fourier is tested as a means of evaluation of a heavy-atom solution in MAD and MIR methods for macromolecular crystallography. It is found that the presence of distinct regions of high and low density variation in electron-density maps is a good indicator of the correctness of a heavy-atom solution in the MIR and MAD methods. The method can be used to evaluate heavy-atom solutions during MAD and MIR structure solutions and to determine the handedness of the structure if anomalous data have been measured

  5. Spin-selective depopulation of triplet sublevels in rapidly rotating triplet exciplexes detected by a heavy-atom-induced magnetic field effect

    Steiner, Ulrich

    1980-01-01

    A mechanism is presented explaining a reported heavy-atom-induced magnetic field effect as a consequence of non-equilibrium triplet sublevel population in an intermediate exciplex. The triplet exciplex spin polarization is induced by sub-level-selective intersystem crossing from the exciplex triplet to its singlet ground state and is decreased by an external magnetic field. The theory accounts almost quantitatively for the observed influence of magnetic field strength and heavy-atom substitue...

  6. REFLOS, Fuel Loading and Cost from Burnup and Heavy Atomic Mass Flow Calculation in HWR

    Boettcher, W.; Schmidt, E.

    1969-01-01

    1 - Nature of physical problem solved: REFLOS is a programme for the evaluation of fuel-loading schemes in heavy water moderated reactors. The problems involved in this study are: a) Burn-up calculation for the reactor cell. b) Determination of reactivity behaviour, power distribution, attainable burn-up for both the running-in period and the equilibrium of a 3-dimensional heterogeneous reactor model; investigation of radial fuel movement schemes. c) Evaluation of mass flows of heavy atoms through the reactor and fuel cycle costs for the running-in, the equilibrium, and the shut down of a power reactor. If the subroutine for treating the reactor cell were replaced by a suitable routine, other reactors with weakly absorbing moderators could be analyzed. 2 - Method of solution: Nuclear constants and isotopic compositions of the different fuels in the reactor are calculated by the cell-burn-up programme and tabulated as functions of the burn-up rate (MWD/T). Starting from a known state of the reactor, the 3-dimensional heterogeneous reactor programme (applying an extension of the technique of Feinberg and Galanin) calculates reactivity and neutron flux distribution using one thermal and one or two fast neutron groups. After a given irradiation time, the new state of the reactor is determined, and new nuclear constants are assigned to the various defined locations in the reactor. Reloading of fuel may occur if the prescribed life of the reactor is reached or if the effective multiplication factor or the power form factor falls below a specified level. The scheme of reloading to be carried out is specified by a load vector, giving the number of channels to be discharged, the kind of movement from one to another channel and the type of fresh fuel to be charged for each single reloading event. After having determined the core states characterizing the equilibrium period, and having decided the fuel reloading scheme for the running-in period of the reactor life, the fuel

  7. Discovery of novel selenium derivatives as Pin1 inhibitors by high-throughput screening

    Subedi, Amit; Shimizu, Takeshi; Ryo, Akihide; Sanada, Emiko; Watanabe, Nobumoto; Osada, Hiroyuki

    2016-01-01

    Peptidyl prolyl cis/trans isomerization by Pin1 regulates various oncogenic signals during cancer progression, and its inhibition through multiple approaches has established Pin1 as a therapeutic target. However, lack of simplified screening systems has limited the discovery of potent Pin1 inhibitors. We utilized phosphorylation-dependent binding of Pin1 to its specific substrate to develop a screening system for Pin1 inhibitors. Using this system, we screened a chemical library, and identified a novel selenium derivative as Pin1 inhibitor. Based on structure-activity guided chemical synthesis, we developed more potent Pin1 inhibitors that inhibited cancer cell proliferation. -- Highlights: •Novel screening for Pin1 inhibitors based on Pin1 binding is developed. •A novel selenium compound is discovered as Pin1 inhibitor. •Activity guided chemical synthesis of selenium derivatives resulted potent Pin1 inhibitors.

  8. Phase contrast scanning transmission electron microscopy imaging of light and heavy atoms at the limit of contrast and resolution.

    Yücelen, Emrah; Lazić, Ivan; Bosch, Eric G T

    2018-02-08

    Using state of the art scanning transmission electron microscopy (STEM) it is nowadays possible to directly image single atomic columns at sub-Å resolution. In standard (high angle) annular dark field STEM ((HA)ADF-STEM), however, light elements are usually invisible when imaged together with heavier elements in one image. Here we demonstrate the capability of the recently introduced Integrated Differential Phase Contrast STEM (iDPC-STEM) technique to image both light and heavy atoms in a thin sample at sub-Å resolution. We use the technique to resolve both the Gallium and Nitrogen dumbbells in a GaN crystal in [[Formula: see text

  9. Aryl nitrene rearrangements: spectroscopic observation of a benzazirine and its ring expansion to a ketenimine by heavy-atom tunneling.

    Inui, Hiroshi; Sawada, Kazuhiro; Oishi, Shigero; Ushida, Kiminori; McMahon, Robert J

    2013-07-17

    In the photodecompositions of 4-methoxyphenyl azide (1) and 4-methylthiophenyl azide (5) in argon matrixes at cryogenic temperatures, benzazirine intermediates were identified on the basis of IR spectra. As expected, the benzazirines photochemically rearranged to the corresponding ketenimines and triplet nitrenes. Interestingly, with the methylthio substituent, the rearrangement of benzazirine 8 to ketenimine 7 occurred at 1.49 × 10(-5) s(-1) even in the dark at 10 K, despite a computed activation barrier of 3.4 kcal mol(-1). Because this rate is 10(57) times higher than that calculated for passing over the barrier and because it shows no temperature dependence, the rearrangement mechanism is interpreted in terms of heavy-atom tunneling.

  10. Electron-positron pair production and bremsstrahlung at intermediate energies in the field of heavy atoms

    Lee, R.N.; Milstein, A.I.; Strakhovenko, V.M.; Schwartz, O.Ya.

    2006-01-01

    The Coulomb corrections (CC) to the processes of bremsstrahlung and pair production are investigated. The next-to-leading term in the high-energy asymptotics is found. This term becomes very essential in the region of intermediate energies. The influence of screening for CC is small for differential cross section, spectrum, and the total cross section of pair production. The same is true for the spectrum of bremsstrahlung, but not for the differential cross section, where the influence of screening can be very large. The corresponding screening corrections as well as the modification of the differential cross section of bremsstrahlung are found. A comparison of our results for the total cross section of pair production with the experimental data available is performed. This comparison has justified our analytical results and allowed to elaborate a simple ansatz for the next-to-leading correction. The influence of the electron beam shape on CC for bremsstrahlung is investigated. It turns out that the differential cross section is very sensitive to this shape

  11. Hyperthermal (10-500 eV) collisions of noble gases with Ni(100) surface. Comparison between light and heavy atom collisions

    Kim, C.

    1995-01-01

    Collisional events between 10-500 eV atomic beams (He, Ne, Ar, Kr, and Xe) and a Ni(100) surface are investigated by the classical trajectory method. The calculation employs a molecular dynamics approach combined with a Langevin method for treating energy dissipation to infinite solid. We find that low energy collisions of heavy atoms (Xe and Kr) are characterized by extensive many-body interactions with top layer surface atoms. On the other hand, light atom (Ne and He) collisions can be approximated as a sequence of binary collisions even at these energies. Such a difference in the collisional nature gives rise to the following consequences. Low energy heavy atoms transfer energy mostly to the surface atoms during 45 angle collision. They scatter from the surface with a narrow angular distribution centered in a supraspecular direction. The ratio of the scattered to incident particle energy rapidly decreases with increasing beam energy of heavy atoms. The sputtering yield for Ni atoms by heavy atom bombardment increases quite linearly with beam energy, which is attributed to a linear proportionality between the beam energy and the energy transfered to a surface. Near the threshold energy sputtering can occur more efficiently by light atom bombardment. The energy transfer ratio to solid continuously increases with beam energy for light atoms. For heavy projectiles, on the other hand, this ratio reaches a maximum at the energy of ca, 100 eV, above which it stays nearly constant but slightly decreases. ((orig.))

  12. Human iPSC-derived cardiomyocytes and tissue engineering strategies for disease modeling and drug screening.

    Smith, Alec S T; Macadangdang, Jesse; Leung, Winnie; Laflamme, Michael A; Kim, Deok-Ho

    Improved methodologies for modeling cardiac disease phenotypes and accurately screening the efficacy and toxicity of potential therapeutic compounds are actively being sought to advance drug development and improve disease modeling capabilities. To that end, much recent effort has been devoted to the development of novel engineered biomimetic cardiac tissue platforms that accurately recapitulate the structure and function of the human myocardium. Within the field of cardiac engineering, induced pluripotent stem cells (iPSCs) are an exciting tool that offer the potential to advance the current state of the art, as they are derived from somatic cells, enabling the development of personalized medical strategies and patient specific disease models. Here we review different aspects of iPSC-based cardiac engineering technologies. We highlight methods for producing iPSC-derived cardiomyocytes (iPSC-CMs) and discuss their application to compound efficacy/toxicity screening and in vitro modeling of prevalent cardiac diseases. Special attention is paid to the application of micro- and nano-engineering techniques for the development of novel iPSC-CM based platforms and their potential to advance current preclinical screening modalities. Published by Elsevier Inc.

  13. Biological screening of chitosan derivatives using Artemia spp. (brine shrimp test)

    Rozaini Mohd Zohdi; Norimah Yusof; Asnah Hassan

    2006-01-01

    The present study reported on the screening of six selected chitosan derivatives using the brine shrimp lethality bioassay. In addition, the irradiation effects towards the compounds at 25 kGy were also studied. Chitosan is a natural polysaccharide derived from chitin, extracted from the exoskeletons of crustaceans and insects as well as walls of some bacteria and fungi. Brine shrimp test is employed for the screening of toxicity of chitosan derivatives. Toxicity test was carried out by adding different concentrations of tested samples to approximately 5 to 15 Artemia salina larvae. Biological activity using the brine shrimp bioassay was recorded as LC 50 i.e. lethal concentration that kills 50% of the larvae within 24 hours of contact with the samples. Compounds are considered toxic when the LC 50 value is lower than 1 mg/ml by brine shrimp bioassay and practically non-toxic when the value is larger. Of the samples tested, none were toxic to the brine shrimp (LC 50 > 1 mg/ml). The LC 50 values of all chitosan derivatives tested, control and irradiated at 25 kGy were above 1 mg/ml thus all tested samples are considered non-toxic. This study demonstrated that irradiation at 25 kGy showed no significant effects towards the toxicity of the chitosan derivatives. After irradiation, only NO-CMC exhibited marked decrease in LC 50 value, reduced by 3-fold from 34.96 mg/ml to 11.07 mg/ml while O-CMC (5.45 mg/ml to 5 mg/ml) showed no clear differences based on rough estimation. This study suggested that brine shrimp bioassay is a simple, reliable and convenient method that could provide useful clues of the relative toxic potential of the sample tested. (Author)

  14. Direct excitation in heavy atom collisions: A propensity rule for charge cloud orientation

    Andersen, N.; Aarhus Univ.; Nielsen, S.E.; Royal Danish School of Pharmacy, Copenhagen)

    1985-01-01

    The Massey Criterion prescribes maximum electronic excitation of atoms in heavy particle collisions for collision velocities v where Δε a/ℎv ≅ π. Here Δε is the energy defect and a is the effective interaction length. Experiments with planar symmetry have revealed a preferred way of rotation of the excited charge cloud in this velocity region. We demonstrate by analysis of a simple, yet realistic model why excitation favors states with a specific orientation. A general propensity rule is derived and its validity evaluated for a specific case, the Na-He system. Implications for future experiments are pointed out. In particular, the propensity rule predicts very different collisions behaviors of oppositely oriented atoms, as prepared e.g. by circular polarized laser light. (orig.)

  15. Study of inter sub-shell and inter shell electron correlations in 4d open-shell heavy atomic ions

    Koike, Fumihiro

    2009-01-01

    The effect of correlations between 4p, 4d, and 4f has been studied extensively. The characteristic spectral structures of 4p - 4d and 4d - 4f optical transitions, due to the unique structures of N = 4 open sub-shells in heavy atomic ions, have been studied theoretically. To gain an insight of this effect, a series of careful MCDF calculations for 4d q (q = 0 to 10) atomic ions with atomic numbers Z = 48 to 56 has been carried out. The difference of orbital energy differences between 4p and 4d orbitals and 4d and 4f orbitals coincidently falls within the range of a few % for almost all the atomic ions investigated. The 4p 6 4d4f and 4p 5 4d 3 configurations may mix strongly, and the optical 4p - 4d and 4d - 4f transitions may take place coherently, providing us with quite a peculiar EUV emission spectrum. The effect of spectral narrowing and shift is expected to be quite common to the atomic specieds with the atomic numbers in the range Z = 48 to 56.

  16. Using heavy atom rare gas matrix to control the reactivity of 4-methoxybenzaldehyde: A comparison with benzaldehyde

    Kus, Nihal [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Department of Physics, Anadolu University, 26470 Eskisehir (Turkey); Sharma, Archna; Reva, Igor; Fausto, Rui [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Lapinski, Leszek [Institute of Physics, Polish Academy of Sciences, Warsaw (Poland)

    2012-04-14

    Different patterns of photochemical behavior were observed for 4-methoxybenzaldehyde (p-anisaldehyde) isolated in xenon and in argon matrices. Monomers of the compound isolated in solid Xe decarbonylate upon middle ultraviolet irradiation, yielding methoxybenzene (anisole), and CO. On the other hand, p-anisaldehyde isolated in an Ar matrix and subjected to identical irradiation, predominantly isomerizes to the closed-ring isomeric ketene (4-methoxycyclohexa-2,4-dien-1-ylidene) methanone. Experimental detection of a closed-ring ketene photoproduct, generated from an aromatic aldehyde, constitutes a rare observation. The difference between the patterns of photochemical transformations of p-anisaldehyde isolated in argon and xenon environments can be attributed to the external heavy-atom effect, where xenon enhances the rate of intersystem crossing from the singlet to the triplet manifold in which decarbonylation (via p-methoxybenzoyl radical) takes place. The parent compound, benzaldehyde, decarbonylates (to benzene + CO) when subjected to middle ultraviolet irradiation in both argon and xenon matrices. This demonstrates the role of the methoxy p-anisaldehyde substituent in activation of the reaction channel leading to the formation of the ketene photoproduct.

  17. Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

    Shikhar Gupta

    2014-01-01

    Full Text Available In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

  18. Screens

    2016-01-01

    This Sixth volume in the series The Key Debates. Mutations and Appropriations in European Film Studies investigates the question of screens in the context both of the dematerialization due to digitalization and the multiplication of media screens. Scholars offer various infomations and theories of topics such as the archeology of screen, film and media theories, contemporary art, pragmatics of new ways of screening (from home video to street screening).

  19. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-12-24

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

  20. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.

    Mazzocchi, Andrea R; Rajan, Shiny A P; Votanopoulos, Konstantinos I; Hall, Adam R; Skardal, Aleksander

    2018-02-13

    Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.

  1. Tumour auto-antibody screening: performance of protein microarrays using SEREX derived antigens

    Stempfer, René; Weinhäusel, Andreas; Syed, Parvez; Vierlinger, Klemens; Pichler, Rudolf; Meese, Eckart; Leidinger, Petra; Ludwig, Nicole; Kriegner, Albert; Nöhammer, Christa

    2010-01-01

    The simplicity and potential of minimal invasive testing using serum from patients make auto-antibody based biomarkers a very promising tool for use in diagnostics of cancer and auto-immune disease. Although several methods exist for elucidating candidate-protein markers, immobilizing these onto membranes and generating so called macroarrays is of limited use for marker validation. Especially when several hundred samples have to be analysed, microarrays could serve as a good alternative since processing macro membranes is cumbersome and reproducibility of results is moderate. Candidate markers identified by SEREX (serological identification of antigens by recombinant expression cloning) screenings of brain and lung tumour were used for macroarray and microarray production. For microarray production recombinant proteins were expressed in E. coli by autoinduction and purified His-tag (histidine-tagged) proteins were then used for the production of protein microarrays. Protein arrays were hybridized with the serum samples from brain and lung tumour patients. Methods for the generation of microarrays were successfully established when using antigens derived from membrane-based selection. Signal patterns obtained by microarrays analysis of brain and lung tumour patients' sera were highly reproducible (R = 0.92-0.96). This provides the technical foundation for diagnostic applications on the basis of auto-antibody patterns. In this limited test set, the assay provided high reproducibility and a broad dynamic range to classify all brain and lung samples correctly. Protein microarray is an efficient means for auto-antibody-based detection when using SEREX-derived clones expressing antigenic proteins. Protein microarrays are preferred to macroarrays due to the easier handling and the high reproducibility of auto-antibody testing. Especially when using only a few microliters of patient samples protein microarrays are ideally suited for validation of auto

  2. In Silico Screening and Designing Synthesis of Cinchona Alkaloids Derivatives as Potential Anticancer

    Muhammad Hanafi

    2017-06-01

    Full Text Available P-glycoprotein (P-gp resistance in cancer cells decreases intracellular accumulation of various anticancer drugs. This multidrug resistance (MDR protein can be modulated by a number of non-cytotoxic drugs. We have screened 30 chincona alkaloids derivatives as a potent P-gp inhibitor agent in silico. Hereby, we report the highest potential inhibitions of P-gp is Cinchonidine isobutanoate through molecular docking approach. with affinity energy -8.6 kcal/mol and inhibition constant, Ki is 4.89 x 10-7 M. Cinchonidine isobutanoate is also known has molecular weight below 500, Log P value 3.5, which is indicated violation free of Lipinski`s rule of five. Thus, Cinchonidine isobutanoate is the most potent compound as anticancer compare to other Cinchona alkaloids. Ultimately, we design Cinchonidine isobutanoate for further lead synthesis by using DBSA, act as a combined Brønsted acid-surfactant-catalyst (BASC to obtain high concentration of organic product by forming micellar aggregates which is very powerful catalytic application in water environment.

  3. Cnidarian-derived filamentous fungi from Brazil: isolation, characterisation and RBBR decolourisation screening.

    Da Silva, M; Passarini, M R Z; Bonugli, R C; Sette, L D

    2008-12-01

    Marine-derived fungi represent a valuable source of structurally novel and biologically active metabolites of industrial interest. They also have drawn attention for their capacity to degrade several pollutants, including textile dyes, organochlorides and polycyclic aromatic hydrocarbons (PAHs), among others. The fungal tolerance to higher concentrations of salt might be considered an advantage for bioremediation processes in the marine environment. Therefore, filamentous fungi were isolated from cnidarians (scleractinian coral and zoanthids) collected from the north coast of São Paulo State, Brazil. A total of 144 filamentous fungi were morphologically and molecularly characterised. Among them there were several species of Penicillium and Aspergillus, in addition to Cladosporium spp., Eutypella sp., Fusarium spp., Khuskia sp., Mucor sp., Peacilomyces sp., Phoma sp. and Trichoderma spp. These fungi were tested regarding their decolourisation activity for Remazol Brilliant Blue R (RBBR), a textile dye used as an initial screening for PAH-degrading fungi. The most efficient fungi for RBBR decolourisation after 12 days were Penicillium citrinum CBMAI 853 (100%), Aspergillus sulphureus CBMAI 849 (95%), Cladosporium cladosporioides CBMAI 857 (93%) and Trichoderma sp. CBMAI 852 (89%). Besides its efficiency for dye decolourisation within liquid media, C. cladosporioides CBMAI 857 also decolourised dye on solid media, forming a decolourisation halo. Further research on the biotechnological potential, including studies on PAH metabolism, of these selected fungi are in progress.

  4. Data-Driven Derivation of an "Informer Compound Set" for Improved Selection of Active Compounds in High-Throughput Screening.

    Paricharak, Shardul; IJzerman, Adriaan P; Jenkins, Jeremy L; Bender, Andreas; Nigsch, Florian

    2016-09-26

    Despite the usefulness of high-throughput screening (HTS) in drug discovery, for some systems, low assay throughput or high screening cost can prohibit the screening of large numbers of compounds. In such cases, iterative cycles of screening involving active learning (AL) are employed, creating the need for smaller "informer sets" that can be routinely screened to build predictive models for selecting compounds from the screening collection for follow-up screens. Here, we present a data-driven derivation of an informer compound set with improved predictivity of active compounds in HTS, and we validate its benefit over randomly selected training sets on 46 PubChem assays comprising at least 300,000 compounds and covering a wide range of assay biology. The informer compound set showed improvement in BEDROC(α = 100), PRAUC, and ROCAUC values averaged over all assays of 0.024, 0.014, and 0.016, respectively, compared to randomly selected training sets, all with paired t-test p-values agnostic fashion. This approach led to a consistent improvement in hit rates in follow-up screens without compromising scaffold retrieval. The informer set is adjustable in size depending on the number of compounds one intends to screen, as performance gains are realized for sets with more than 3,000 compounds, and this set is therefore applicable to a variety of situations. Finally, our results indicate that random sampling may not adequately cover descriptor space, drawing attention to the importance of the composition of the training set for predicting actives.

  5. Are Peripheral Blood Mononuclear Cells Derived from Patients with Certain Myopathies Suitable for Personalized Drug Screening?

    Andriy V. Shatillo

    2014-12-01

    Full Text Available Background: Limb girdle muscular dystrophies (LGMDs and several other disorders which share their specific phenotype are rare, predominantly hereditary conditions with no curative treatment. Differential diagnosis of these myopathies is quite challenging and expensive in many cases. Therefore, a significant proportion of patients remains undiagnosed and untreated for a long time. At the same time there is a huge amount of drugs and supplements potentially able to modify the course of some of these muscular dystrophies. That is why a simple empirical approach able to define a patient’s reaction to a specific compound seems rational. Because most common basic pathogenetic mechanisms for these quite different disorders increase the vulnerability of muscle cells (or decrease ability for reparation during mechanical stress, we propose a simple, noninvasive and inexpensive approach for individualized drug screening based on the drug’s influence on the mechanical vulnerability of peripheral blood mononuclear cells (PBMC. Methods: PBMC derived from 8 patients with Duchenne muscular dystrophy (DMD, 2 patients with LGMD2A, 1 patient with LGMD2B, 1 with MERRF syndrome, 1 with facioscapulohumeral muscular dystrophy (FSHD and 13 matched control subjects were irradiated by ultrasound in the presence of several compounds (lisinopril, vitamin D3, prednisolon, tocopherol, topiramate, glutargin, α-lipoic acid, essentiale, and physiological solution. Then viability indexes of the samples were detected by citotoxic assays based on vital dye (neutral red and resazurin metabolism. Results: In cytotoxicity tests with active transport of neutral red into PBMC derived from DMD patients, the cells showed signs of destruction at 1.06±0.52 minutes of ultrasounding compared to 1.75±0.6 minutes in control. PBMCs from patients with other myopathies have either normal or decreased resistance to ultrasound. The addition of tocopherol significantly changes the PBMC

  6. Prospective Assessment of Virtual Screening Heuristics Derived Using a Novel Fusion Score.

    Pertusi, Dante A; O'Donnell, Gregory; Homsher, Michelle F; Solly, Kelli; Patel, Amita; Stahler, Shannon L; Riley, Daniel; Finley, Michael F; Finger, Eleftheria N; Adam, Gregory C; Meng, Juncai; Bell, David J; Zuck, Paul D; Hudak, Edward M; Weber, Michael J; Nothstein, Jennifer E; Locco, Louis; Quinn, Carissa; Amoss, Adam; Squadroni, Brian; Hartnett, Michelle; Heo, Mee Ra; White, Tara; May, S Alex; Boots, Evelyn; Roberts, Kenneth; Cocchiarella, Patrick; Wolicki, Alex; Kreamer, Anthony; Kutchukian, Peter S; Wassermann, Anne Mai; Uebele, Victor N; Glick, Meir; Rusinko, Andrew; Culberson, J Christopher

    2017-09-01

    High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches. Here, we introduce a novel method of fusing these prioritizations and benchmark it prospectively on 17 screening campaigns using virtual screening methods in three descriptor spaces. We found that the fusion approach retrieves 15% to 65% more active chemical series than any single machine-learning method and that appropriately weighting contributions of similarity and machine-learning scoring techniques can increase enrichment by 1% to 19%. We also use fusion scoring to evaluate the tradeoff between screening more chemical matter initially in lieu of replicate samples to prevent false-positives and find that the former option leads to the retrieval of more active chemical series. These results represent guidelines that can increase the rate of identification of promising active compounds in future iterative screens.

  7. Heavy-Atom Tunneling Calculations in Thirteen Organic Reactions: Tunneling Contributions are Substantial, and Bell's Formula Closely Approximates Multidimensional Tunneling at ≥250 K.

    Doubleday, Charles; Armas, Randy; Walker, Dana; Cosgriff, Christopher V; Greer, Edyta M

    2017-10-09

    Multidimensional tunneling calculations are carried out for 13 reactions, to test the scope of heavy-atom tunneling in organic chemistry, and to check the accuracy of one-dimensional tunneling models. The reactions include pericyclic, cycloaromatization, radical cyclization and ring opening, and S N 2. When compared at the temperatures that give the same effective rate constant of 3×10 -5  s -1 , tunneling accounts for 25-95 % of the rate in 8 of the 13 reactions. Values of transmission coefficients predicted by Bell's formula, κ Bell  , agree well with multidimensional tunneling (canonical variational transition state theory with small curvature tunneling), κ SCT . Mean unsigned deviations of κ Bell vs. κ SCT are 0.08, 0.04, 0.02 at 250, 300 and 400 K. This suggests that κ Bell is a useful first choice for predicting transmission coefficients in heavy-atom tunnelling. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. High content screening of defined chemical libraries using normal and glioma-derived neural stem cell lines.

    Danovi, Davide; Folarin, Amos A; Baranowski, Bart; Pollard, Steven M

    2012-01-01

    Small molecules with potent biological effects on the fate of normal and cancer-derived stem cells represent both useful research tools and new drug leads for regenerative medicine and oncology. Long-term expansion of mouse and human neural stem cells is possible using adherent monolayer culture. These cultures represent a useful cellular resource to carry out image-based high content screening of small chemical libraries. Improvements in automated microscopy, desktop computational power, and freely available image processing tools, now means that such chemical screens are realistic to undertake in individual academic laboratories. Here we outline a cost effective and versatile time lapse imaging strategy suitable for chemical screening. Protocols are described for the handling and screening of human fetal Neural Stem (NS) cell lines and their malignant counterparts, Glioblastoma-derived neural stem cells (GNS). We focus on identification of cytostatic and cytotoxic "hits" and discuss future possibilities and challenges for extending this approach to assay lineage commitment and differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

    Takayama, Kazuo; Mizuguchi, Hiroyuki

    2017-02-01

    Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  10. O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

    Roman Sommer

    2016-12-01

    Full Text Available Selenoglycosides are used as reactive glycosyl donors in the syntheses of oligosaccharides. In addition, such heavy atom analogs of natural glycosides are useful tools for structure determination of their lectin receptors using X-ray crystallography. Some lectins, e.g., members of the tectonin family, only bind to carbohydrate epitopes with O-alkylated ring hydroxy groups. In this context, we report the first synthesis of an O-methylated selenoglycoside, specifically methyl 2-O-methyl-L-selenofucopyranoside, a ligand of the lectin tectonin-2 from the mushroom Laccaria bicolor. The synthetic route required a strategic revision and further optimization due to the intrinsic lability of alkyl selenoglycosides, in particular for the labile fucose. Here, we describe a successful synthetic access to methyl 2-O-methyl-L-selenofucopyranoside in 9 linear steps and 26% overall yield starting from allyl L-fucopyranoside.

  11. O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside.

    Sommer, Roman; Hauck, Dirk; Varrot, Annabelle; Imberty, Anne; Künzler, Markus; Titz, Alexander

    2016-01-01

    Selenoglycosides are used as reactive glycosyl donors in the syntheses of oligosaccharides. In addition, such heavy atom analogs of natural glycosides are useful tools for structure determination of their lectin receptors using X-ray crystallography. Some lectins, e.g., members of the tectonin family, only bind to carbohydrate epitopes with O-alkylated ring hydroxy groups. In this context, we report the first synthesis of an O -methylated selenoglycoside, specifically methyl 2- O -methyl-L-selenofucopyranoside, a ligand of the lectin tectonin-2 from the mushroom Laccaria bicolor . The synthetic route required a strategic revision and further optimization due to the intrinsic lability of alkyl selenoglycosides, in particular for the labile fucose. Here, we describe a successful synthetic access to methyl 2- O -methyl-L-selenofucopyranoside in 9 linear steps and 26% overall yield starting from allyl L-fucopyranoside.

  12. Rate-controlling two-proton transfer coupled with heavy-atom motion in the 2-pyridinone-catalyzed mutarotation of tetramethylglucose. Experimental and calculated deuterium isotope effects

    Engdahl, K.A.; Bivehed, H.; Ahlberg, P.; Saunders, W.H. Jr.

    1983-01-01

    Primary and secondary deuterium isotope effects have been measured by polarimetry, and primary isotope effects have been calculated for the classical bifunctional catalysis: 2-pyridinone-catalyzed mutarotation of 2,3,4,6-tetra-O-methyl-α-D-glucopyranose (α-TMG) in benzene. From the positively curved plot of the specific rate of epimerization vs. the mole fraction of 2 H in the ''pool'' of OH and NH hydrogens, the isotope effects k/sub HH//k/sub DD/ = 3.66 +/- 0.09, k/sub HH//k/sub DH/ = 1.5, and k/sub HH//k/sub HD/ = 2.4 have been calculated. A secondary isotope effect of 1.14 +/- 0.02 has been measured by using α-TMG and (1- 2 H)-2,3,4,6-tetra-O-methyl-α-D-glucopyranose [(l- 2 H)-α-TMG], the synthesis of which is described in detail, together with those for (N- 2 H)-2-pyridinone and (1-O- 2 H)-2,3,4,6-tetra-O-methyl-α-D-glucopyranose [(1-O- 2 H)-α-TMG]. The rate data obtained have also been analyzed by fractionation theory, yielding approximately equal fractionation factors (0.5). The interpretation of the results has been assisted by calculations of the primary deuterium isotope effects using the BEBOVIB IV program. Two models involving small and considerable coupling, respectively, of the transferring protons to heavy-atom motion have been considered. In the favored structure for the transition state of the rate-limiting step, two protons are in transit, and their motion is governed either by a potential with a barrier or by one without. Their motion is considerably coupled to the heavy-atom motion (i.e., the breakage of the ring C-O bond), and tunnel corrections to the isotope effects are found to be negligible

  13. Screening Antibacterial Agent from Crude Extract of Marine-Derived Fungi Associated with Soft Corals against MDR-Staphylococcus haemolyticus

    Sabdaningsih, A.; Cristianawati, O.; Sibero, M. T.; Nuryadi, H.; Radjasa, O. K.; Sabdono, A.; Trianto, A.

    2017-02-01

    Multidrug resistant Staphylococcus haemolyticus is a Gram-positive bacteria and member of coagulase negative staphylococci (CoNS) which has the highest level of antimicrobial resistance. This nosocomial pathogen due to skin or soft tissue infections, bacteremia, septicemia, peritonitis, otitis media, meningitis and urinary tract infections. The ability to produce enterotoxins, hemolysins, biofilm, and cytotoxins could be an important characteristic for the successful of infection. Marine-derived fungi have potency as a continuous supply of bioactive compound. The aim of this research was screening antibacterial agent from crude extracts of marine-derived fungi associated with soft corals against MDR-S. haemolyticus. Among 23 isolates of marine-derived fungi isolated from 7 soft corals, there were 4 isolates active against MDR-S. haemolyticus. The screening was conducted by using agar plug diffusion method. Isolate PPSC-27-A4 had the highest antibacterial activity with diameter 23±9,6 mm. The crude extract from this isolate had been confirmed to antibacterial susceptibility test and it had the highest antibacterial activity in 12.2 mm with concentration of 300μg/ml from mycelia extract. PPSC-27-A4 had been characterized in molecular, based on the sequence analysis of 18S rRNA, PPSC-27-A4 isolate was identified as Trichoderma longibrachiatum.

  14. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-01-01

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scienti...

  15. Earthworm-Derived Pore-Forming Toxin Lysenin and Screening of Its Inhibitors

    Neelanun Sukumwang

    2013-08-01

    Full Text Available Lysenin is a pore-forming toxin from the coelomic fluid of earthworm Eisenia foetida. This protein specifically binds to sphingomyelin and induces erythrocyte lysis. Lysenin consists of 297 amino acids with a molecular weight of 41 kDa. We screened for cellular signal transduction inhibitors of low molecular weight from microorganisms and plants. The purpose of the screening was to study the mechanism of diseases using the obtained inhibitors and to develop new chemotherapeutic agents acting in the new mechanism. Therefore, our aim was to screen for inhibitors of Lysenin-induced hemolysis from plant extracts and microbial culture filtrates. As a result, we isolated all-E-lutein from an extract of Dalbergia latifolia leaves. All-E-lutein is likely to inhibit the process of Lysenin-membrane binding and/or oligomer formation rather than pore formation. Additionally, we isolated tyrosylproline anhydride from the culture filtrate of Streptomyces as an inhibitor of Lysenin-induced hemolysis.

  16. A rapid and simple screening method for methamphetamine in urine by radioimmunoassay using a 125I-labeled metahmphetamine derivative

    Inayama, Seiichi; Tokunaga, Yukiko; Hosoya, Eikichi; Nakadate, Teruo; Niwaguchi, Tetsukichi.

    1980-01-01

    N-Carboxymethylmethamphetamine, a derivative of methamphetamine, was prepared through a new synthetic pathway from ephedrine. Specific antiserum was obtained by immunization of rabbits with the conjugate of N-carboxymethylmethamphetamine with bovine serum albumin. A radioimmunoassay procedure was established using this antibody (specific for methamphetamine) and a 125 I-methamphetamine derivative. A high degree of specificity of the antibody was confirmed by testing for cross-reaction with several methamphetamine analogs, and the sensitivity was found to be 1 ng/tube. The present micro method using radioimmunoassay is highly sensitive, rapid, simple and may be useful as a micro-scale primary screening test for methamphetamine excreted in human urine, for forensic and medical purposes. (author)

  17. Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids

    Steven D. Forsythe

    2018-04-01

    Full Text Available IntroductionEnvironmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S. have suffered from exposures to lead in drinking water or other heavy metals in food or the earth, while there is a high possibility of further places to suffer such exposures in the near future.MethodsWe employed bioengineered 3D human liver and cardiac organoids to screen a panel of environmental toxins (lead, mercury, thallium, and glyphosate, and charted the response of the organoids to these compounds. Liver and cardiac organoids were exposed to lead (10 µM–10 mM, mercury (200 nM–200 µM, thallium (10 nM–10 µM, or glyphosate (25 µM–25 mM for a duration of 48 h. The impacts of toxin exposure were then assessed by LIVE/DEAD viability and cytotoxicity staining, measuring ATP activity and determining IC50 values, and determining changes in cardiac organoid beating activity.ResultsAs expected, all of the toxins induced toxicity in the organoids. Both ATP and LIVE/DEAD assays showed toxicity in both liver and cardiac organoids. In particular, thallium was the most toxic, with IC50 values of 13.5 and 1.35 µM in liver and cardiac organoids, respectively. Conversely, glyphosate was the least toxic of the four compounds, with IC50 values of 10.53 and 10.85 mM in liver and cardiac organoids, respectively. Additionally, toxins had a negative influence on cardiac organoid beating activity as well. Thallium resulting in the most significant decreases in beating rate, followed by mercury, then glyphosate, and finally, lead. These results suggest that the 3D organoids have significant utility to be deployed in additional toxicity screening applications, and future development of treatments to mitigate exposures.Conclusion3D organoids have significant utility to be

  18. Derivation of soil screening thresholds to protect chisel-toothed kangaroo rat from uranium mine waste in northern Arizona

    Hinck, Jo E.; Linder, Greg L.; Otton, James K.; Finger, Susan E.; Little, Edward E.; Tillitt, Donald E.

    2013-01-01

    Chemical data from soil and weathered waste material samples collected from five uranium mines north of the Grand Canyon (three reclaimed, one mined but not reclaimed, and one never mined) were used in a screening-level risk analysis for the Arizona chisel-toothed kangaroo rat (Dipodomys microps leucotis); risks from radiation exposure were not evaluated. Dietary toxicity reference values were used to estimate soil-screening thresholds presenting risk to kangaroo rats. Sensitivity analyses indicated that body weight critically affected outcomes of exposed-dose calculations; juvenile kangaroo rats were more sensitive to the inorganic constituent toxicities than adult kangaroo rats. Species-specific soil-screening thresholds were derived for arsenic (137 mg/kg), cadmium (16 mg/kg), copper (1,461 mg/kg), lead (1,143 mg/kg), nickel (771 mg/kg), thallium (1.3 mg/kg), uranium (1,513 mg/kg), and zinc (731 mg/kg) using toxicity reference values that incorporate expected chronic field exposures. Inorganic contaminants in soils within and near the mine areas generally posed minimal risk to kangaroo rats. Most exceedances of soil thresholds were for arsenic and thallium and were associated with weathered mine wastes.

  19. Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

    Duintjer Tebbens, R J; Thompson, K M

    2017-01-01

    If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

  20. Screening of Natural Product Derivatives Identifies Two Structurally Related Flavonoids as Potent Quorum Sensing Inhibitors against Gram-Negative Bacteria

    Suvi Manner

    2018-05-01

    Full Text Available Owing to the failure of conventional antibiotics in biofilm control, alternative approaches are urgently needed. Inhibition of quorum sensing (QS represents an attractive target since it is involved in several processes essential for biofilm formation. In this study, a compound library of natural product derivatives (n = 3040 was screened for anti-quorum sensing activity using Chromobacterium violaceum as reporter bacteria. Screening assays, based on QS-mediated violacein production and viability, were performed in parallel to identify non-bactericidal QS inhibitors (QSIs. Nine highly active QSIs were identified, while 328 compounds were classified as moderately actives and 2062 compounds as inactives. Re-testing of the highly actives at a lower concentration against C. violaceum, complemented by a literature search, led to the identification of two flavonoid derivatives as the most potent QSIs, and their impact on biofilm maturation in Escherichia coli and Pseudomonas aeruginosa was further investigated. Finally, effects of these leads on swimming and swarming motility of P. aeruginosa were quantified. The identified flavonoids affected all the studied QS-related functions at micromolar concentrations. These compounds can serve as starting points for further optimization and development of more potent QSIs as adjunctive agents used with antibiotics in the treatment of biofilms.

  1. Synthesis, Structural Characterization and Biological Screening of Various Sulfa Drugs Derived from 2-Anisidine

    Abbasi, M.A.; Rehman, A.U.; Muhmood, T.; Khan, K.M.

    2013-01-01

    In the present study, a series of N-alkyl substituted sulfa drugs (sulfonamides) has been synthesized. The reaction of 2-anisidine (1) with 4-methylbenzenesulfonyl chloride (2) yielded N-(2-methoxyphenyl)-4-methylbenzenesulfonamide (3), which on bromination with bromine in the presence of glacial acetic acid gave N-(4,5-dibromo-2-methoxyphenyl) 4-methylbenzenesulfonamide (6). These two products 3 and 6 on further treatment with different alkyl halides in the presence of lithium hydride yielded fourteen new N-substituted sulfonamides. These compounds were characterized by their EI-MS and 1H-NMR spectra and screened against acetylcholinesterase, butyrlcholinesterase and chymotrypsin enzymes. The results revealed that N-propyl-N-(2-methoxyphenyl)-4-methylbenzenesulfonamide (5c), N-(4,5-dibromo-2-methoxy-phenyl)-4-methylbenzenesulfonamide (6) and N-methyl-N-(4,5-dibromo-2-methoxyphenyl) 4-methylbenzenesulfonamide (7e) exhibited good inhibitory potential against acetylcholinesterase, butyrlcholinesterase and chymotrypsin respectively. (author)

  2. Screening concepts, characterization and structural analysis of microbial-derived bioactive lipopeptides: a review.

    Biniarz, Piotr; Łukaszewicz, Marcin; Janek, Tomasz

    2017-05-01

    Lipopeptide biosurfactants are surface active biomolecules that are produced by a variety of microorganisms. Microbial lipopeptides have gained the interest of microbiologists, chemists and biochemists for their high biodiversity as well as efficient action, low toxicity and good biodegradability in comparison to synthetic counterparts. In this report, we review methods for the production, isolation and screening, purification and structural characterization of microbial lipopeptides. Several techniques are currently available for each step, and we describe the most commonly utilized and recently developed techniques in this review. Investigations on lipopeptide biosurfactants in natural products require efficient isolation techniques for the characterization and evaluation of chemical and biological properties. A combination of chromatographic and spectroscopic techniques offer opportunities for a better characterization of lipopeptide structures, which in turn can lead to the application of lipopeptides in food, pharmaceutical, cosmetics, agricultural and bioremediation industries.

  3. Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

    Nafiz Öncü Can

    2018-03-01

    Full Text Available Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR, 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR, 13C Nuclear Magnetic Resonance Spectroscopy (13C-NMR and Electronspray Ionisation Mass Spectroscopy (ESI-MS spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST and modified forced swimming (MFST methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

  4. Manipulation-free cultures of human iPSC-derived cardiomyocytes offer a novel screening method for cardiotoxicity.

    Rajasingh, Sheeja; Isai, Dona Greta; Samanta, Saheli; Zhou, Zhi-Gang; Dawn, Buddhadeb; Kinsey, William H; Czirok, Andras; Rajasingh, Johnson

    2018-04-05

    Induced pluripotent stem cell (iPSC)-based cardiac regenerative medicine requires the efficient generation, structural soundness and proper functioning of mature cardiomyocytes, derived from the patient's somatic cells. The most important functional property of cardiomyocytes is the ability to contract. Currently available methods routinely used to test and quantify cardiomyocyte function involve techniques that are labor-intensive, invasive, require sophisticated instruments or can adversely affect cell vitality. We recently developed optical flow imaging method analyses and quantified cardiomyocyte contractile kinetics from video microscopic recordings without compromising cell quality. Specifically, our automated particle image velocimetry (PIV) analysis of phase-contrast video images captured at a high frame rate yields statistical measures characterizing the beating frequency, amplitude, average waveform and beat-to-beat variations. Thus, it can be a powerful assessment tool to monitor cardiomyocyte quality and maturity. Here we demonstrate the ability of our analysis to characterize the chronotropic responses of human iPSC-derived cardiomyocytes to a panel of ion channel modulators and also to doxorubicin, a chemotherapy agent with known cardiotoxic side effects. We conclude that the PIV-derived beat patterns can identify the elongation or shortening of specific phases in the contractility cycle, and the obtained chronotropic responses are in accord with known clinical outcomes. Hence, this system can serve as a powerful tool to screen the new and currently available pharmacological compounds for cardiotoxic effects.

  5. Antimicrobial screening of some derivatives of methyl alpha-D-glucopyranoside

    Abdul, K.M.S.; Kawsar, S.M.S.; Rehman, S.

    2009-01-01

    In vitro antimicrobial functionality test of methyl 4,6-O-cyclohexylidene-alpha-D-glucopyranoside and its twelve acylated derivatives against ten human pathogenic bacteria and six phytopathogenic fungi comparative to Ampicillin and Nystatin revealed the tested chemicals to possess moderate to good antibacterial and antifungal activity and to be more effective against fungal phytopathogens. Many of these chemicals exhibited better antimicrobial activity than the standard antibiotics. Minimum Inhibition Concentration (MIC) of methyl 4,6-O-cyclohexylidene-2-O-myristoyl- 3-O-palmitoyl-alpha-D-glucopyranoside against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus was 25, 12.5 and 25 macro g/disc, respectively. (author)

  6. Phasing and structure of bestrophin-1: a case study in the use of heavy-atom cluster compounds with multi-subunit transmembrane proteins

    Dickson, Veronica Kane (Cambridge)

    2016-03-01

    The purification and three-dimensional crystallization of membrane proteins are commonly affected by a cumulation of pathologies that are less prevalent in their soluble counterparts. This may include severe anisotropy, poor spot shape, poor to moderate-resolution diffraction, crystal twinning, translational pseudo-symmetry and poor uptake of heavy atoms for derivatization. Such challenges must be circumvented by adaptations in the approach to crystallization and/or phasing. Here, an example of a protein that exhibited all of the above-mentioned complications is presented. Bestrophin-1 is a eukaryotic calcium-activated chloride channel, the structure of which was recently determined in complex with monoclonal antibody fragments using SAD phasing with tantalum bromide clusters (Ta6Br12·Br2). Some of the obstacles to obtaining improved diffraction and phasing for this particular channel are discussed, as well as the approach and adaptations that were key to determining the structure.

  7. Shorter Exciton Lifetimes via an External Heavy-Atom Effect: Alleviating the Effects of Bimolecular Processes in Organic Light-Emitting Diodes.

    Einzinger, Markus; Zhu, Tianyu; de Silva, Piotr; Belger, Christian; Swager, Timothy M; Van Voorhis, Troy; Baldo, Marc A

    2017-10-01

    Multiexcited-state phenomena are believed to be the root cause of two exigent challenges in organic light-emitting diodes; namely, efficiency roll-off and degradation. The development of novel strategies to reduce exciton densities under heavy load is therefore highly desirable. Here, it is shown that triplet exciton lifetimes of thermally activated delayed-fluorescence-emitter molecules can be manipulated in the solid state by exploiting intermolecular interactions. The external heavy-atom effect of brominated host molecules leads to increased spin-orbit coupling, which in turn enhances intersystem crossing rates in the guest molecule. Wave function overlap between the host and the guest is confirmed by combined molecular dynamics and density functional theory calculations. Shorter triplet exciton lifetimes are observed, while high photoluminescence quantum yields and essentially unaltered emission spectra are maintained. A change in the intersystem crossing rate ratio due to increased dielectric constants leads to almost 50% lower triplet exciton densities in the emissive layer in the steady state and results in an improved onset of the photoluminescence quantum yield roll-off at high excitation densities. Efficient organic light-emitting diodes with better roll-off behavior based on these novel hosts are fabricated, demonstrating the suitability of this concept for real-world applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Derivation and validation of the prediabetes self-assessment screening score after acute pancreatitis (PERSEUS).

    Soo, Danielle H E; Pendharkar, Sayali A; Jivanji, Chirag J; Gillies, Nicola A; Windsor, John A; Petrov, Maxim S

    2017-10-01

    Approximately 40% of patients develop abnormal glucose metabolism after a single episode of acute pancreatitis. This study aimed to develop and validate a prediabetes self-assessment screening score for patients after acute pancreatitis. Data from non-overlapping training (n=82) and validation (n=80) cohorts were analysed. Univariate logistic and linear regression identified variables associated with prediabetes after acute pancreatitis. Multivariate logistic regression developed the score, ranging from 0 to 215. The area under the receiver-operating characteristic curve (AUROC), Hosmer-Lemeshow χ 2 statistic, and calibration plots were used to assess model discrimination and calibration. The developed score was validated using data from the validation cohort. The score had an AUROC of 0.88 (95% CI, 0.80-0.97) and Hosmer-Lemeshow χ 2 statistic of 5.75 (p=0.676). Patients with a score of ≥75 had a 94.1% probability of having prediabetes, and were 29 times more likely to have prediabetes than those with a score of <75. The AUROC in the validation cohort was 0.81 (95% CI, 0.70-0.92) and the Hosmer-Lemeshow χ 2 statistic was 5.50 (p=0.599). Model calibration of the score showed good calibration in both cohorts. The developed and validated score, called PERSEUS, is the first instrument to identify individuals who are at high risk of developing abnormal glucose metabolism following an episode of acute pancreatitis. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  9. A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards.

    Mordwinkin, Nicholas M; Burridge, Paul W; Wu, Joseph C

    2013-02-01

    Drug attrition rates have increased in past years, resulting in growing costs for the pharmaceutical industry and consumers. The reasons for this include the lack of in vitro models that correlate with clinical results and poor preclinical toxicity screening assays. The in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and cardiotoxicity screening. In addition, the ability to derive human-induced pluripotent stem cells from somatic tissues, combined with current high-throughput screening and pharmacogenomics, may help realize the use of these cells to fulfill the potential of personalized medicine. In this review, we discuss the use of pluripotent stem cell-derived cardiomyocytes for drug discovery and cardiotoxicity screening, as well as current hurdles that must be overcome for wider clinical applications of this promising approach.

  10. In-vitro antimicrobial screening and molecular docking studies of synthesized 2-chloro-N-(4-phenylthiazol-2-ylacetamide derivatives

    Rahmat Ali

    2015-01-01

    Full Text Available Introduction: Glucosamine-6-phosphate (GlcN6P synthase biosynthetic pathway has been identified as potential targets for the development of new antimicrobial agents. Aim: A series of 2-chloro-N-(42-phenylthiazol-25-ylacetamide derivatives (3a-r was synthesized and evaluated their antimicrobial activity. Materials and Methods: The 2-chloro-N-(Para substituted phenylthiazol-25-yl acetamide (2a-c were synthesized by stirring intermediates (1a-c with 2-chloroacetylchloride in dichloromethane in the presence of K2CO3. The intermediate (2a-c were further reacted with different secondary amine such as pyrrolidine, N-methyl piperazine, N-ethyl piperazine, thiomorpholine, morpholine, piperidine etc in ethanol in presence of TEA Triethylamine (TEA to get desired compounds (3a-r. Compounds were characterized by a spectroscopic technique such as Fourier transform infraredFTIR, 1 H-NMR, 13 C-NMR, and mass spectrometry. The synthesized thiazole derivatives (3a-r were screened for anti-bacterial and anti-fungal activity against Escherichia coli, Staphylococcus aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, CandidaC. albicans (MTCC-183, AspergillusA. niger (MTCC 281 NCTC 10418 and AspergillusA. flavus (MTCC 277. Result and Conclusion: The results of anti-bacterial screening revealed that among all the screened compounds, eight compounds viz. 3b, 3c, 3d, 3e, 3i, 3j, 3k, and 3p showed moderate to good anti-bacterial and antifungal activity having minimum inhibitory concentration (MIC between 6.25- and 25 µg/ml. While compound 3d showed the most promising antibacterial activity against E. coli and S. aureus, while the compound 3j showed promising antifungal activity with MIC value 6.25 µg/ml against C. albicans, A. niger and A. flavus. In addition, all these eight potential molecules were also examined for possible binding on enzyme GlcN6Pglucosamine-6-phosphate synthase by molecular docking studies on (PDB ID 1JXA.

  11. Screening of soy protein-derived hypotriglyceridemic di-peptides in vitro and in vivo

    Matsui Toshiro

    2011-05-01

    Full Text Available Abstract Background Soy protein and soy peptides have attracted considerable attention because of their potentially beneficial biological properties, including antihypertensive, anticarcinogenic, and hypolipidemic effects. Although soy protein isolate contains several bioactive peptides that have distinct physiological activities in lipid metabolism, it is not clear which peptide sequences are responsible for the triglyceride (TG-lowering effects. In the present study, we investigated the effects of soy protein-derived peptides on lipid metabolism, especially TG metabolism, in HepG2 cells and obese Otsuka Long-Evans Tokushima fatty (OLETF rats. Results In the first experiment, we found that soy crude peptide (SCP-LD3, which was prepared by hydrolyze of soy protein isolate with endo-type protease, showed hypolipidemic effects in HepG2 cells and OLETF rats. In the second experiment, we found that hydrophilic fraction, separated from SCP-LD3 with hydrophobic synthetic absorbent, revealed lipid-lowering effects in HepG2 cells and OLETF rats. In the third experiment, we found that Fraction-C (Frc-C peptides, fractionated from hydrophilic peptides by gel permeation chromatography-high performance liquid chromatography, significantly reduced TG synthesis and apolipoprotein B (apoB secretion in HepG2 cells. In the fourth experiment, we found that the fraction with 0.1% trifluoroacetic acid, isolated from Frc-C peptides by octadecylsilyl column chromatography, showed hypolipidemic effects in HepG2 cells. In the final experiment, we found that 3 di-peptides, Lys-Ala, Val-Lys, and Ser-Tyr, reduced TG synthesis, and Ser-Tyr additionally reduced apoB secretion in HepG2 cells. Conclusion Novel active peptides with TG-lowering effects from soy protein have been isolated.

  12. Transition-state analysis of a Vmax mutant of AMP nucleosidase by the application of heavy-atom kinetic isotope effects

    Parkin, D.W.; Mentch, F.; Banks, G.A.; Horenstein, B.A.; Schramm, V.L.

    1991-01-01

    The transition state of the V max mutant of AMP nucleosidase from Azotobacter vinelandii has been characterized by heavy-atom kinetic isotope effects in the presence and absence of MgATP, the allosteric activator. The enzyme catalyzes hydrolysis of the N-glycosidic bond of AMP at approximately 2% of the rate of the normal enzyme with only minor changes in the K m for substrate, the activation constant for MgATP, and the K i for formycin 5'-phosphate, a tight-binding competitive inhibitor. Isotope effects were measured as a function of the allosteric activator concentration that increases the turnover number of the enzyme from 0.006 s -1 . The kinetic isotope effects were measured with the substrates [1'- 3 H]AMP, [2'- 2 H]AMP, [9- 15 N]AMP, and [1',9- 14 C, 15 N]AMP. All substrates gave significant kinetic isotope effects in a pattern that establishes that the reaction expresses intrinsic kinetic isotope effects in the presence or absence of MgATP. Transition-state analysis using bond-energy and bond-order vibrational analysis indicated that the transition state for the mutant enzyme has a similar position in the reaction coordinate compared to that for the normal enzyme. The mutant enzyme is less effective in stabilizing the carbocation-like intermediate and in the ability to protonate N7 of adenine to create a better leaving group. This altered transition-state structure was confirmed by an altered substrate specificity for the mutant protein

  13. Photochemical heavy-atom effects

    Koziar, J.C.; Cowan, D.O.

    1978-01-01

    The effects of halogenated solvents such as n-butyl chloride, n-propyl bromide, and ethyl iodide, on the photochemistry of several aromatic compounds are reviewed. Dimerization of acenaphthylene is discussed in terms of spin -orbit coupling induced by the solvents. Appropriate wave functions are given for both the solvents and the compound. Cycloaddition reactions, electrocyclic rearrangements, and photochemical cis-trans isomerization are also considered

  14. Nocturnal infrared clear sky temperatures correlated with screen temperatures and GPS-derived PWV in southern Australia

    Maghrabi, A.; Clay, R.

    2011-01-01

    Highlights: → Model to calculate nocturnal sky temperature in mid-latitude site was developed. → New data acquired from new instrument. → Sky temperature correlated with both GPS-derived PWV and screen temperature. → The model was tested theoretically against MODTRAN software. → The performance of the model was compared against 20 independent models. - Abstract: Infrared (IR) clear sky temperatures (Tsky), screen level temperature (T) and Precipitable Water Vapour (PWV) were collected for a period of 2 years from a coastal region of southern Australia. IR sky temperatures were derived from simple infrared detectors, which have been developed by the authors for inexpensive monitoring of cloud cover, while data for PWV were obtained from Global Positioning Satellite (GPS) transmissions. Meteorological data were obtained from the Australian Bureau of Meteorology. Based on these data, statistical regression analyses between nocturnal Tsky and the T and PWV (one variable fit) were conducted. Direct proportional relationships between Tsky and T and between Tsky and PWV were found. The one variable fit was further optimized by applying the multiple regression fit between Tsky and both T and PWV. The resulting multilinear model was essentially unbiased, with a correlation coefficient (R 2 ) of 0.97, mean bias error (MBE) of -2.7 x 10 -5 deg. C, and root mean square error (RMSE) of about 1.6 o C. The performance of the multilinear model was tested against a 1-year independent data set. In this case, the predictability of the model was superior, with MBE and RMSE being 0.13 deg. C and 2.23 deg. C respectively. After correcting the daytime observations for the biases caused by solar heating of the detection system, the performance of this model in calculating the daytime measurements was tested and showed MBE and RMSE values of 1.3 deg. C and 2.5 deg. C, respectively. Additionally, twenty schemes from the literature were tested and assessed for predicting the

  15. Screening obesity by direct and derived anthropometric indices with evaluation of physical efficiency among female college students of kolkata.

    Sengupta, P; Chaudhuri, P; Bhattacharya, K

    2013-10-01

    The available information regarding the obesity pattern of the undergraduate female students of Kolkata is inadequate, though there are several reports which indicate the complications and/or awful consequences of obesity on female health particularly, during the reproductive years. The present investigation has thus been carried out to report their present physiological status along with the prevalence of obesity, based on their body mass index (BMI), some direct and derived anthropometric indices, and physical fitness. This small-scale cross-sectional study conducted in randomly selected 100 female students of different colleges of Kolkata with the age of 18-22 [mean age 20.4 (2.3)] years. Measurements of body composition included total 24 variables, with thirteen direct and eleven derived anthropometric variables; while physical efficiency parameters were physical fitness index, VO2max, energy expenditure and anaerobic power. The data of the experimental group were compared with those of the control group by t-test, using SPSS v.15.0 and MS-Excel v.2013. Analysis of collected data showed majority of the students have normal range of BMI (67.95%), but, 21.95% of students found to be overweight and 3.84% are obese. They also showed higher fat mass [14.40 (4.11)], but, lower waist-to-hip ratio and conicity index. They were found to have poor to moderate physical fitness [57.60 (3.90)] and higher energy expenditure [5.61 (0.72)]. The findings of the present obesity screening reports almost one of four female students (24 out of 100 participants) are overweight/obese, indicated higher body fat distribution and increased propensity of being obese with age. Thus, the overall data along with their low physical fitness points out to health risks among female undergraduates of Kolkata.

  16. Disappointing performance of literature-derived selective screening criteria for asymptomatic Chlamydia trachomatis infection in an inner-city population

    van Valkengoed, I G; Boeke, A J; Morré, S A; van den Brule, A J; Meijer, C J; Devillé, W; Bouter, L M

    2000-01-01

    BACKGROUND: In an inner-city population with a low prevalence of Chlamydia trachomatis infection, selective screening may be indicated to increase the efficiency of screening. GOAL: To evaluate the performance of sets of selective screening criteria for asymptomatic Chlamydia trachomatis infection

  17. Synthesis, characterization and screening for antidepressant and anticonvulsant activity of 4,5-dihydropyrazole bearing indole derivatives

    Pravin O. Patil

    2016-07-01

    Full Text Available In the present study, a series of new substituted 5-(1H-Indol-3-yl-3-(phenyl-4,5-dihydropyrazoline derivatives (2a–m have been synthesized with good yield by microwave assisted synthesis. The compounds synthesized were screened for antidepressant and anticonvulsant potentialities in mice by a forced swim test and subcutaneous pentylenetetrazole (scPTZ test, respectively. Neuro-toxicities were determined by rotarod test in albino mice. The structures of all new compounds were confirmed by IR, 1H NMR, mass spectral data, and microanalyses. The results revealed that compounds 2b, 2e and 2k were found to be potent antidepressant molecules of the series, at 20 mg/kg dose level when compared with the reference drugs imipramine and fluoxetine. Whereas, compounds 2c and 2d were found to be potent anticonvulsant molecules of this series, when compared with the reference drug diazepam. None of the synthesized compounds showed neurotoxicity.

  18. Cell-based cytotoxicity assays for engineered nanomaterials safety screening: exposure of adipose derived stromal cells to titanium dioxide nanoparticles.

    Xu, Yan; Hadjiargyrou, M; Rafailovich, Miriam; Mironava, Tatsiana

    2017-07-11

    Increasing production of nanomaterials requires fast and proper assessment of its potential toxicity. Therefore, there is a need to develop new assays that can be performed in vitro, be cost effective, and allow faster screening of engineered nanomaterials (ENMs). Herein, we report that titanium dioxide (TiO 2 ) nanoparticles (NPs) can induce damage to adipose derived stromal cells (ADSCs) at concentrations which are rated as safe by standard assays such as measuring proliferation, reactive oxygen species (ROS), and lactate dehydrogenase (LDH) levels. Specifically, we demonstrated that low concentrations of TiO 2 NPs, at which cellular LDH, ROS, or proliferation profiles were not affected, induced changes in the ADSCs secretory function and differentiation capability. These two functions are essential for ADSCs in wound healing, energy expenditure, and metabolism with serious health implications in vivo. We demonstrated that cytotoxicity assays based on specialized cell functions exhibit greater sensitivity and reveal damage induced by ENMs that was not otherwise detected by traditional ROS, LDH, and proliferation assays. For proper toxicological assessment of ENMs standard ROS, LDH, and proliferation assays should be combined with assays that investigate cellular functions relevant to the specific cell type.

  19. High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

    Kaufmann, Markus; Schuffenhauer, Ansgar; Fruh, Isabelle; Klein, Jessica; Thiemeyer, Anke; Rigo, Pierre; Gomez-Mancilla, Baltazar; Heidinger-Millot, Valerie; Bouwmeester, Tewis; Schopfer, Ulrich; Mueller, Matthias; Fodor, Barna D; Cobos-Correa, Amanda

    2015-10-01

    Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention. © 2015 Society for Laboratory Automation and Screening.

  20. [Application of precursor ion scanning method in rapid screening of illegally added phosphodiesterase-5 inhibitors and their unknown derivatives in Chinese traditional patent medicines and health foods].

    Sun, Jing; Cao, Ling; Feng, Youlong; Tan, Li

    2014-11-01

    The compounds with similar structure often have similar pharmacological activities. So it is a trend for illegal addition that new derivatives of effective drugs are synthesized to avoid the statutory test. This bring challenges to crack down on illegal addition behavior, however, modified derivatives usually have similar product ions, which allow for precursor ion scanning. In this work, precursor ion scanning mode of a triple quadrupole mass spectrometer was first applied to screen illegally added drugs in complex matrix such as Chinese traditional patent medicines and healthy foods. Phosphodiesterase-5 inhibitors were used as experimental examples. Through the analysis of the structure and mass spectrum characteristics of the compounds, phosphodiesterase-5 inhibitors were classified, and their common product ions were screened by full scan of product ions of typical compounds. Then high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method with precursor ion scanning mode was established based on the optimization of MS parameters. The effect of mass parameters and the choice of fragment ions were also studied. The method was applied to determine actual samples and further refined. The results demonstrated that this method can meet the need of rapid screening of unknown derivatives of phosphodiesterase-5 inhibitors in complex matrix, and prevent unknown derivatives undetected. This method shows advantages in sensitivity, specificity and efficiency, and is worth to be further investigated.

  1. Liposomal solubilization of new 3-hydroxy-quinolinone derivatives with promising anticancer activity: a screening method to identify maximum incorporation capacity

    Di Cagno, Massimiliano; Styskala, Jakub; Hlaváč, Jan

    2011-01-01

    Four new 3-hydroxy-quinolinone derivatives with promising anticancer activity could be solubilized using liposomes as vehicle to an extent that allows their in vitro and in vivo testing without use of toxic solvent(s). A screening method to identify the maximum incorporation capacity of hydrophobic......, resulting in a 200-500-fold increase in apparent solubility. Drug-to-lipid ratios in the range of 2-5 µg/mg were obtained. Interestingly, the four quinolinone derivatives have shown different association tendencies with liposomes, probably due to the physicochemical properties of the different group bonded...

  2. Derivation and validation of REASON: a risk score identifying candidates to screen for peripheral arterial disease using ankle brachial index.

    Ramos, Rafel; Baena-Díez, Jose Miguel; Quesada, Miquel; Solanas, Pascual; Subirana, Isaac; Sala, Joan; Alzamora, Maite; Forès, Rosa; Masiá, Rafel; Elosua, Roberto; Grau, María; Cordón, Ferran; Pera, Guillem; Rigo, Fernando; Martí, Ruth; Ponjoan, Anna; Cerezo, Carlos; Brugada, Ramon; Marrugat, Jaume

    2011-02-01

    The recommendation of screening with ankle brachial index (ABI) in asymptomatic individuals is controversial. The aims of the present study were to develop and validate a pre-screening test to select candidates for ABI measurement in the Spanish population 50-79 years old, and to compare its predictive capacity to current Inter-Society Consensus (ISC) screening criteria. Two population-based cross-sectional studies were used to develop (n = 4046) and validate (n = 3285) a regression model to predict ABI guidelines, and similar sensitivity. This resulted in fewer patients screened per diagnosis of ABI < 0.9 (10.6 vs. 8.75) and a lower proportion of the population aged 50-79 years candidate to ABI screening (63.3% vs. 55.0%). This model provides accurate ABI < 0.9 risk estimates for ages 50-79, with a better predictive capacity than that of ISC criteria. Its use could reduce possible harms and unnecessary work-ups of ABI screening as a risk stratification strategy in primary prevention of peripheral vascular disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Tools for the identification of bioactives impacting the metabolic syndrome: Screening of a botanical extract library using subcutaneous and visceral human adipose-derived stem cell based assays

    Buehrer, Benjamin M.; Duffin, David J.; Lea-Currie, Y. Renee; Ribnicky, David; Raskin, Ilya; Stephens, Jacqueline M.; Cefalu, William T.; Gimble, Jeffrey M.

    2011-01-01

    Plant extracts continue to represent an untapped source of renewable therapeutic compounds for the treatment and prevention of illnesses including chronic metabolic disorders. With the increase in worldwide obesity and its related morbidities, the need for identifying safe and effective treatments is also rising. As such, use of primary human adipose-derived stem cells represents a physiologically relevant cell system to screen for bioactive agents in the prevention and treatment of obesity and its related complications. By using these cells in a primary screen, the risk and cost of identifying artifacts due to interspecies variation and immortalized cell lines is eliminated. We demonstrate that these cells can be formatted into 384-well high throughput screens to rapidly identify botanical extracts that affect lipogenesis and lipolysis. Additionally, counterscreening with human primary stem cells from distinct adipose depots can be routinely performed to identify tissue specific responses. In our study, over 500 botanical extracts were screened and 16 (2.7%) were found to affect lipogenesis and 4 (0.7%) affected lipolysis. PMID:21543201

  4. Risk- and cost-benefit analyses of breast screening programs derived from absorbed dose measurements in the Netherlands

    Zuur, C.; Broerse, J.J.

    1985-01-01

    Risk- and cost benefit analyses for breast screening programs are being performed, employing the risk-factors for induction of breast cancer from six extensive follow-up studies. For women of the age group above 35 years and for a risk period of 30 years after a 10-year latency period, a factor of extra cases of 20 x 10 -6 mGy -1 can be estimated. Measurements are being performed in Dutch hospitals to determine the mean absorbed tissue dose. These doses vary from 0.6 to 4.4 mGy per radiography. For a dose of 1 mGy per radiograph and yearly screening of women between 35 and 75 years, the risk of radiogenic breast cancer is about 1% of the natural incidence (85,000 per 10 6 women) in this group. A recommended frequency of screening has to be based on medical, social and financial considerations. The gain in woman years and in completely cured women is being estimated for screening with intervals of 12 instead of 24 months. The medical and social benefit is 1,520 years life-time and 69 more cases completely cured per 1,000 breast cancer patients. The financial profit of a completely cured instead of an ultimately fatal cancer can be roughly estimated at 55,000 guilders. In addition the costs per gained woman-year are about 5,000 guilders. In consequence, the extra costs of annual additional rounds of mammographic screening are balanced by the benefit. (Auth.)

  5. A novel interaction fingerprint derived from per atom score contributions: exhaustive evaluation of interaction fingerprint performance in docking based virtual screening.

    Jasper, Julia B; Humbeck, Lina; Brinkjost, Tobias; Koch, Oliver

    2018-03-16

    Protein ligand interaction fingerprints are a powerful approach for the analysis and assessment of docking poses to improve docking performance in virtual screening. In this study, a novel interaction fingerprint approach (PADIF, protein per atom score contributions derived interaction fingerprint) is presented which was specifically designed for utilising the GOLD scoring functions' atom contributions together with a specific scoring scheme. This allows the incorporation of known protein-ligand complex structures for a target-specific scoring. Unlike many other methods, this approach uses weighting factors reflecting the relative frequency of a specific interaction in the references and penalizes destabilizing interactions. In addition, and for the first time, an exhaustive validation study was performed that assesses the performance of PADIF and two other interaction fingerprints in virtual screening. Here, PADIF shows superior results, and some rules of thumb for a successful use of interaction fingerprints could be identified.

  6. UFLC-Q-TOF-MS/MS-Based Screening and Identification of Flavonoids and Derived Metabolites in Human Urine after Oral Administration of Exocarpium Citri Grandis Extract

    Xuan Zeng

    2018-04-01

    Full Text Available Exocarpium Citri grandis (ECG is an important Traditional Chinese Medicine (TCM for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in human have not been well investigated. ECG was extracted using boiling water and then provided to volunteers for oral administration. Following the ingestion, urine samples were collected from volunteers over 48 h. The extract and urine samples were analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS system to screen and identify flavonoids and derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were screened in urine samples collected post consumption. The overall excretion of naringenin metabolites corresponded to 5.45% of intake and occurred mainly within 4–12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were detected in urine. Obtained data revealed that flavonoids were abundant in the ECG extract, and these components underwent extensive phase II metabolism in humans. These results provided valuable information for further study of the pharmacology and mechanism of action of ECG.

  7. Synthesis, characterization, antimicrobial screening and in silico studies of Schiff bases derived from trans-para-methoxycinnamaldehyde

    Obasi, N. L.; Kaior, G. U.; Ibezim, A.; Ochonogor, Alfred E.; Rhyman, Lydia; Uahengo, Veikko; Lutter, Michael; Jurkschat, Klaus; Ramasami, Ponnadurai

    2017-12-01

    Two Schiff bases namely N,N‧-Bis-[3-(4-metoxy-phenyl)-allylidene]ethane-1,2-diamine (TPMC/EDA) and [3-(4-methoxy-phenyl)-allylidene]-phenyl-amine (TPMC/AN) were synthesized. They were characterized using elemental microanalysis, IR, NMR, UV and mass spectroscopies. Single crystals of TPMC/AN were also analyzed by X-ray diffraction and the compound was examined using B3LYP/6-311++G(d,p) method. A Monoclinic crystal system and space groups of P21/c were obtained for the crystal. Docking calculations on the compounds showed they interacted with fungal N-myristoyltransferase and bacteria DNA gyrase at 2.62-2.95 and 190.26-98.99 μM ranges. The predicted docked poses identified unique binding modes of the compounds and vital intermolecular interactions. The anti-microbial screening of the compounds were carried out against Escherichia coli, Bacillus subtillis, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger using agar well diffusion method. The standard drugs used were the anti-bacterial ciprofloxacin and the anti-fungal fluconazole. The compounds showed activity against all the microorganisms comparable to the used standard drugs. TPMC/EDA was more active than the standard fungal drug in the screening against the fungi strain, Aspergillus niger. It showed the MIC and IZD of 1.3 mg/ml and 9.0 mm respectively. These suggest that the compounds are potential bactericidal and fungicidal candidates.

  8. The MORPHEUS II protein crystallization screen

    Gorrec, Fabrice

    2015-01-01

    MORPHEUS II is a 96-condition initial crystallization screen formulated de novo. The screen incorporates reagents selected from the Protein Data Bank to yield crystals that are not observed in traditional conditions. In addition, the formulation facilitates the optimization and cryoprotection of crystals. High-quality macromolecular crystals are a prerequisite for the process of protein structure determination by X-ray diffraction. Unfortunately, the relative yield of diffraction-quality crystals from crystallization experiments is often very low. In this context, innovative crystallization screen formulations are continuously being developed. In the past, MORPHEUS, a screen in which each condition integrates a mix of additives selected from the Protein Data Bank, a cryoprotectant and a buffer system, was developed. Here, MORPHEUS II, a follow-up to the original 96-condition initial screen, is described. Reagents were selected to yield crystals when none might be observed in traditional initial screens. Besides, the screen includes heavy atoms for experimental phasing and small polyols to ensure the cryoprotection of crystals. The suitability of the resulting novel conditions is shown by the crystallization of a broad variety of protein samples and their efficiency is compared with commercially available conditions

  9. The MORPHEUS II protein crystallization screen

    Gorrec, Fabrice, E-mail: fgorrec@mrc-lmb.cam.ac.uk [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom)

    2015-06-27

    MORPHEUS II is a 96-condition initial crystallization screen formulated de novo. The screen incorporates reagents selected from the Protein Data Bank to yield crystals that are not observed in traditional conditions. In addition, the formulation facilitates the optimization and cryoprotection of crystals. High-quality macromolecular crystals are a prerequisite for the process of protein structure determination by X-ray diffraction. Unfortunately, the relative yield of diffraction-quality crystals from crystallization experiments is often very low. In this context, innovative crystallization screen formulations are continuously being developed. In the past, MORPHEUS, a screen in which each condition integrates a mix of additives selected from the Protein Data Bank, a cryoprotectant and a buffer system, was developed. Here, MORPHEUS II, a follow-up to the original 96-condition initial screen, is described. Reagents were selected to yield crystals when none might be observed in traditional initial screens. Besides, the screen includes heavy atoms for experimental phasing and small polyols to ensure the cryoprotection of crystals. The suitability of the resulting novel conditions is shown by the crystallization of a broad variety of protein samples and their efficiency is compared with commercially available conditions.

  10. Virtual screening of compounds derived from Garcinia pedunculata as an inhibitor of gamma hemolysin component A of Staphylococcus aureus

    Tarali Chowdhury

    2014-03-01

    Full Text Available With the emergence of multi-drug resistant pathogens at alarming frequency, there has been an increase interest in the development of novel drugs from natural resources. The use of higher plants and preparations made from them to treat infections is a longstanding practice in a large part of the population, especially in the developing countries, where there is dependence on traditional medicine for a variety of ailments. The virtual screening method was used in this study to analyze the docking and inhibitory activities of some natural bioactive compounds present within Garcinia pedunculata against hemolysin toxin of Staphylococcus aureus, gamma-hemolysin component A hlgA. The study resulted in identifying compounds 1,3,6,7-tetrahydroxy-xanthone and garcinone D with high binding affinity towards the target protein revealing them as potent inhibitors that could be further used to create new drug source in the treatment of staphyloccocal infections.

  11. Synthesis and Pharmacological Screening of Several Aroyl and Heteroaroyl Selenylacetic Acid Derivatives as Cytotoxic and Antiproliferative Agents

    Carmen Sanmartín

    2009-09-01

    Full Text Available The synthesis and cytotoxic activity of a series of twenty six aroyl and heteroaroyl selenylacetic acid derivatives of general formula Ar-CO-Se-CH2-COOH or Heterar-CO-Se-CH2-COOH are reported. The synthesis was carried out by reaction of acyl chlorides with sodium hydrogen selenide, prepared in situ, and this led to the formation of sodium aroylselenides that subsequently reacted with α-bromoacetic acid to produce the corresponding selenylacetic acid derivatives. All of the compounds were tested against a prostate cancer cell line (PC-3 and some of the more active compounds were assessed against a panel of four human cancer cell lines (CCRF-CEM, HTB-54, HT-29, MCF-7 and one mammary gland-derived non-malignant cell line (184B5. Some of the compounds exhibited remarkable cytotoxic and antiproliferative activities against MCF-7 and PC-3 that were higher than those of the reference compounds doxorubicin and etoposide, respectively. For example, in MCF-7 when Ar = phenyl, 3,5-dimethoxyphenyl or benzyl the TGI values were 3.69, 4.18 and 6.19 μM. On the other hand, in PC-3 these compounds showed values of 6.8, 4.0 and 2.9 μM. Furthermore, benzoylselenylacetic acid did not provoke apoptosis nor did it perturb the cell cycle in MCF-7.

  12. Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells in Phenotypic Screening: A Transforming Growth Factor-β Type 1 Receptor Kinase Inhibitor Induces Efficient Cardiac Differentiation.

    Drowley, Lauren; Koonce, Chad; Peel, Samantha; Jonebring, Anna; Plowright, Alleyn T; Kattman, Steven J; Andersson, Henrik; Anson, Blake; Swanson, Bradley J; Wang, Qing-Dong; Brolen, Gabriella

    2016-02-01

    Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies. To understand and exploit cardiac ontogeny for drug discovery efforts, we developed an in vitro human induced pluripotent stem cell-derived CPC model system using a highly enriched population of KDR(pos)/CKIT(neg)/NKX2.5(pos) CPCs. Using this model system, these CPCs were capable of generating highly enriched cultures of cardiomyocytes under directed differentiation conditions. In order to facilitate the identification of pathways and targets involved in proliferation and differentiation of resident CPCs, we developed phenotypic screening assays. Screening paradigms for therapeutic applications require a robust, scalable, and consistent methodology. In the present study, we have demonstrated the suitability of these cells for medium to high-throughput screens to assess both proliferation and multilineage differentiation. Using this CPC model system and a small directed compound set, we identified activin-like kinase 5 (transforming growth factor-β type 1 receptor kinase) inhibitors as novel and potent inducers of human CPC differentiation to cardiomyocytes. Significance: Cardiac disease is a leading cause of morbidity and mortality, with no treatment available that can result in functional repair. This study demonstrates how differentiation of induced pluripotent stem cells can be used to identify and isolate cell populations of interest that can translate to the adult human heart. Two separate examples of phenotypic

  13. A multi-screening approach for marine-derived fungal metabolites and the isolation of cyclodepsipeptides from Beauveria felina

    Aline Maria de Vita-Marques

    2008-01-01

    Full Text Available Extracts obtained from 57 marine-derived fungal strains were analyzed by HPLC-PDA, TLC and ¹H NMR. The analyses showed that the growth conditions affected the chemical profile of crude extracts. Furthermore, the majority of fungal strains which produced either bioactive of chemically distinctive crude extracts have been isolated from sediments or marine algae. The chemical investigation of the antimycobacterial and cytotoxic crude extract obtained from two strains of the fungus Beauveria felina have yielded cyclodepsipeptides related to destruxins. The present approach constitutes a valuable tool for the selection of fungal strains that produce chemically interesting or biologically active secondary metabolites.

  14. Defining the RNA Internal Loops Preferred by Benzimidazole Derivatives via Two-Dimensional Combinatorial Screening and Computational Analysis

    Velagapudi, Sai Pradeep; Seedhouse, Steven J.; French, Jonathan

    2011-01-01

    RNA is an important therapeutic target, however, RNA targets are generally underexploited due to a lack of understanding of the small molecules that bind RNA and the RNA motifs that bind small molecules. Herein, we describe the identification of the RNA internal loops derived from a 4096-member 3×3 nucleotide loop library that are the most specific and highest affinity binders to a series of four designer, drug-like benzimidazoles. These studies establish a potentially general protocol to define the highest affinity and most specific RNA motif targets for heterocyclic small molecules. Such information could be used to target functionally important RNAs in genomic sequence. PMID:21604752

  15. Peptide array-based screening of human mesenchymal stem cell-adhesive peptides derived from fibronectin type III domain

    Okochi, Mina; Nomura, Shigeyuki; Kaga, Chiaki; Honda, Hiroyuki

    2008-01-01

    Human mesenchymal stem cell-adhesive peptides were screened based on the amino acid sequence of fibronectin type III domain 8-11 (FN-III 8-11 ) using a peptide array synthesized by the Fmoc-chemistry. Using hexameric peptide library of FN-III 8-11 scan, we identified the ALNGR (Ala-Leu-Asn-Gly-Arg) peptide that induced cell adhesion as well as RGDS (Arg-Gly-Asp-Ser) peptide. After incubation for 2 h, approximately 68% of inoculated cells adhere to the ALNGR peptide disk. Adhesion inhibition assay with integrin antibodies showed that the ALNGR peptide interacts with integrin β1 but not with αvβ3, indicating that the receptors for ALNGR are different from RGDS. Additionally, the ALNGR peptide expressed cell specificities for adhesion: cell adhesion was promoted for fibroblasts but not for keratinocytes or endotherial cells. The ALNGR peptide induced cell adhesion and promoted cell proliferation without changing its property. It is therefore useful for the construction of functional biomaterials

  16. Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

    Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M.; Shell, Scott A.; Bacus, Sarah

    2015-05-15

    Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks. Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in

  17. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. (Morehouse Coll., Atlanta, GA (United States). School of Medicine); Crandall, L.A.; Moseley, R.E.; Armotrading, D. (Florida Univ., Gainesville, FL (United States). Coll. of Medicine)

    1993-01-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia's system of Children's Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  18. Screening, cloning and expression analysis of a cellulase derived from the causative agent of hypertrophy sorosis scleroteniosis, Ciboria shiraiana.

    Lü, Ruihua; Zhao, Aichun; Li, Jun; Liu, Changying; Wang, Chuanhong; Wang, Xiling; Wang, Xiaohong; Pei, Ruichao; Lu, Cheng; Yu, Maode

    2015-07-10

    A cellulase gene (KJ700939, CsCelA) from Ciboria shiraiana that is highly expressed during the infection of mulberry fruit was screened by quantitative real-time PCR (qRT-PCR). Using cDNA isolated from infected mulberry fruits as template, the full-length 1170-bp sequence of CsCelA was obtained, which encodes a 390-amino acid protein with a putative signal peptide of 24 amino acids. The 998-bp fragment encoding the mature peptide of CsCelA was cloned into the multiple cloning site of the pPIC9K vector and overexpressed as an active protein of 55.3kDa in the methylotrophic yeast Pichia pastoris. The specific activity of induced supernatants of the recombinant cellulase (CsCelA) was 17.44U/ml and 135U/g for freeze-dried powder. The Kmax and Vmax of CsCelA for sodium carboxymethylcellulose (CMC) were 4.6mg/ml and 107.2U/mg, respectively. The supernatant and freeze-dried powder of the recombinant cellulase exhibited stable activity from pH4.0 to 9.0, and at temperatures ranging from 30°C to 55°C. Finally, the activity of the recombinant cellulase was assessed by enzymatic hydrolysis of the cell walls of mulberry leaves. CsCelA showed an endo-cellulase mode of cleavage, as assessed by thin layer chromatography (TLC). Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Human Pluripotent Stem Cell-derived Cortical Neurons for High Throughput Medication Screening in Autism: A Proof of Concept Study in SHANK3 Haploinsufficiency Syndrome

    Hélène Darville

    2016-07-01

    Full Text Available Autism spectrum disorders affect millions of individuals worldwide, but their heterogeneity complicates therapeutic intervention that is essentially symptomatic. A versatile yet relevant model to rationally screen among hundreds of therapeutic options would help improving clinical practice. Here we investigated whether neurons differentiated from pluripotent stem cells can provide such a tool using SHANK3 haploinsufficiency as a proof of principle. A library of compounds was screened for potential to increase SHANK3 mRNA content in neurons differentiated from control human embryonic stem cells. Using induced pluripotent stem cell technology, active compounds were then evaluated for efficacy in correcting dysfunctional networks of neurons differentiated from individuals with deleterious point mutations of SHANK3. Among 202 compounds tested, lithium and valproic acid showed the best efficacy at corrected SHANK3 haploinsufficiency associated phenotypes in cellulo. Lithium pharmacotherapy was subsequently provided to one patient and, after one year, an encouraging decrease in autism severity was observed. This demonstrated that pluripotent stem cell-derived neurons provide a novel cellular paradigm exploitable in the search for specific disease-modifying treatments.

  20. Miniaturizing 3D assay for high-throughput drug and genetic screens for small patient-derived tumor samples (Conference Presentation)

    Rotem, Asaf; Garraway, Levi; Su, Mei-Ju; Basu, Anindita; Regev, Aviv; Struhl, Kevin

    2017-02-01

    Three-dimensional growth conditions reflect the natural environment of cancer cells and are crucial to be performed at drug screens. We developed a 3D assay for cellular transformation that involves growth in low attachment (GILA) conditions and is strongly correlated with the 50-year old benchmark assay-soft agar. Using GILA, we performed high-throughput screens for drugs and genes that selectively inhibit or increase transformation, but not proliferation. This phenotypic approach is complementary to our genetic approach that utilizes single-cell RNA-sequencing of a patient sample to identify putative oncogenes that confer sensitivity to drugs designed to specifically inhibit the identified oncoprotein. Currently, we are dealing with a big challenge in our field- the limited number of cells that might be extracted from a biopsy. Small patient-derived samples are hard to test in the traditional multiwell plate and it will be helpful to minimize the culture area and the experimental system. We managed to design a suitable microfluidic device for limited number of cells and perform the assay using image analysis. We aim to test drugs on tumor cells, outside of the patient body- and recommend on the ideal treatment that is tailored to the individual. This device will help to minimize biopsy-sampling volumes and minimize interventions in the patient's tumor.

  1. Synthesis, spectral characterization, and pharmacological screening of some 4-[{1-(arylmethylidene}-amino]-3-(4-pyridyl-5-mercapto-4H-1,2,4-triazole derivatives

    Anees A Siddiqui

    2010-01-01

    Full Text Available Background : Pain is an unpleasant and subjective sensation that results from a harmful sensorial stimulation, which alerts the body about current or potential damage to its tissues and organs. Fever is a complex physiological response triggered by infections or aseptic stimuli. Elevation in body temperature occurs when the concentration of prostaglandin E 2 (PGE 2 increases within parts of the brain. Triazole derivatives have been found to possess various pharmacological and biological activities, such as, anti-inflammatory, analgesics, antipyretic, and antifungal. Materials and Methods : Various 4-[{1-(arylmethylidene}-amino]-3-(4-pyridyl-5-mercapto-4H-1,2,4-triazole derivatives were synthesized by a sequence of reactions starting from isonicotinic acid hydrazide. The synthesized compounds were screened for in-vivo analgesic by the tail-flick method and anti-pyretic activities at a dose of 25 and 100 mg/kg body weight respectively. The antipyretic activity was evaluated using Brewer′s yeast induced pyrexia in rats. Fever was induced by subcutaneously injecting 20 ml/kg of 20% aqueous suspension of Brewer′s yeast in normal saline. Results and Discussion : The analgesic screening results revealed that the compounds 3b, 3c, and 3d exhibited excellent analgesic activity at 60 and 90 minutes compared to the standard drug (Analgin. Results revealed that the compounds 3a, 3e, and 3f significantly decreased the temperature of pyretic (P<0.001 rats at one, three and six hours after compound administration as compared to Aspirin (standard drug. Conclusion : Compounds 3b, 3c, and 3d exhibited significant analgesic activity comparable with the standard drug analgin, using the tail flick model. Compounds 3a, 3e, and 3f showed significant anti-pyretic activities comparable with the standard drug aspirin using the yeast-induced pyrexia model.

  2. Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity.

    Ryan, Kristen R; Sirenko, Oksana; Parham, Fred; Hsieh, Jui-Hua; Cromwell, Evan F; Tice, Raymond R; Behl, Mamta

    2016-03-01

    Due to the increasing prevalence of neurological disorders and the large number of untested compounds in the environment, there is a need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect neurological development. Herein, we report on a library of 80 compounds screened for their ability to inhibit neurite outgrowth, a process by which compounds may elicit developmental neurotoxicity, in a high-throughput, high-content assay using human neurons derived from induced pluripotent stem cells (iPSC). The library contains a diverse set of compounds including those that have been known to be associated with developmental neurotoxicity (DNT) and/or neurotoxicity (NT), environmental compounds with unknown neurotoxic potential (e.g., polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs)), as well as compounds with no documented neurotoxic potential. Neurons were treated for 72h across a 6-point concentration range (∼0.3-100μM) in 384-well plates. Effects on neurite outgrowth were assessed by quantifying total outgrowth, branches, and processes. We also assessed the number ofviable cells per well. Concentration-response profiles were evaluated using a Hill model to derive benchmark concentration (BMC) values. Assay performance was evaluated using positive and negative controls and test replicates. Compounds were ranked by activity and selectivity (i.e., specific effects on neurite outgrowth in the absence of concomitant cytotoxicity) and repeat studies were conducted to confirm selectivity. Among the 80 compounds tested, 38 compounds were active, of which 16 selectively inhibited neurite outgrowth. Of these 16 compounds, 12 were known to cause DNT/NT and the remaining 4 compounds included 3 PAHs and 1 FR. In independent repeat studies, 14/16 selective compounds were reproducibly active in the assay, of which only 6 were selective for inhibition of neurite outgrowth. These 6 compounds were

  3. Antibacterial and antibiofilm screening of new platinum(IV complexes with some s-alkyl derivatives of thiosalicylic acid

    Radojević Ivana

    2017-01-01

    Full Text Available The influence of 5 new Platinum(IV (Pt(IV complexes with S-alkyl derivatives of thiosalicylic acid (C1-benzyl, C2-methyl, C3-ethyl, C4-propyl and C5- butyl was studied on 16 strains of bacteria. Antibacterial activity was tested using microdilution method with resazurin while antibiofilm activity was observed by tissue culture plate method, using doxycycline as a positive control. The results were expressed as minimum inhibitory concentration (MIC, minimum bactericidal concentration (MBC and biofilm inhibitory concentration (BIC. The best result on Gram positive bacteria exhibited C1 and MIC was <7.81μg/ml against Staphylococcus aureus ATCC 25923. Bifidobacterium animalis subsp. lactis (probiotic was sensitive to C2 (MIC at 15.625 μg/ml. The highest sensitivity of Gram negative bacteria was observed in Escherichia coli ATCC 25922 treated with C1, C2, C3 and C4, in Proteus mirabilis ATCC 12453 treated with C1, and in Pseudomonas aeruginosa treated with C2, C3 and C5 (all MICs at 250 μg/ml. The C2 complex were more efficient as antibiofilm agents and the best results were obtained with C2 acting against S. aureus and S. aureus ATCC 25923 biofilms. In conclusion, we noticed that the tested compounds exhibited promising properties as antibacterial and antibiofilm agents.

  4. Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening.

    Fong, Eliza L S; Martinez, Mariane; Yang, Jun; Mikos, Antonios G; Navone, Nora M; Harrington, Daniel A; Farach-Carson, Mary C

    2014-07-07

    The lack of effective therapies for bone metastatic prostate cancer (PCa) underscores the need for accurate models of the disease to enable the discovery of new therapeutic targets and to test drug sensitivities of individual tumors. To this end, the patient-derived xenograft (PDX) PCa model using immunocompromised mice was established to model the disease with greater fidelity than is possible with currently employed cell lines grown on tissue culture plastic. However, poorly adherent PDX tumor cells exhibit low viability in standard culture, making it difficult to manipulate these cells for subsequent controlled mechanistic studies. To overcome this challenge, we encapsulated PDX tumor cells within a three-dimensional hyaluronan-based hydrogel and demonstrated that the hydrogel maintains PDX cell viability with continued native androgen receptor expression. Furthermore, a differential sensitivity to docetaxel, a chemotherapeutic drug, was observed as compared to a traditional PCa cell line. These findings underscore the potential impact of this novel 3D PDX PCa model as a diagnostic platform for rapid drug evaluation and ultimately push personalized medicine toward clinical reality.

  5. Closed-Form Solutions of the Thomas-Fermi in Heavy Atoms and the Langmuir-Blodgett in Current Flow ODEs in Mathematical Physics

    Efstathios E. Theotokoglou

    2015-01-01

    Full Text Available Two kinds of second-order nonlinear, ordinary differential equations (ODEs appearing in mathematical physics are analyzed in this paper. The first one concerns the Thomas-Fermi (TF equation, while the second concerns the Langmuir-Blodgett (LB equation in current flow. According to a mathematical methodology recently developed, the exact analytic solutions of both TF and LB ODEs are proposed. Both of these are nonlinear of the second order and by a series of admissible functional transformations are reduced to Abel’s equations of the second kind of the normal form. The closed form solutions of the TF and LB equations in the phase and physical plane are given. Finally a new interesting result has been obtained related to the derivative of the TF function at the limit.

  6. In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity

    A. G. Nerkar

    2009-01-01

    Full Text Available Dihydrofolate reductase (DHFR is the important target for anticancer drugs belonging to the class of antimetabolites as the enzyme plays important role in the de novo purine synthesis. We here report the in silico screening to obtain best fit molecules as DHFR inhibitors, synthesis of some ʻbest fitʼ quinazolinone from 2-phenyl-3-(substituted-benzilidine-amino quinazolinones (Quinazolinone Shiff's bases QSB1-5 and pyridine-4-carbohydrazide Shiff's bases (ISB1-5 derivatives and their in vitro anticancer assay. Synthesis of the molecules was performed using microwave assisted synthesis. The structures of these molecules were elucidated by IR and 1H-NMR. These compounds were then subjected for in vitro anticancer evaluation against five human cancer cell-lines for anticancer cyto-toxicity assay. Methotrexate (MTX was used as standard for this evaluation to give a comparable inhibition of the cell proliferation by DHFR inhibition. Placlitaxel, adriamycin and 5-fluoro-uracil were also used as standard to give a comparable activity of these compounds with other mechanism of anticancer activity. ISB3 (4-(N, N-dimethyl-amino-phenyl Schiff''s base derivative of pyridine carbohydrazide showed equipotent activity with the standards used in in vitro anticancer assay as per the NCI (National Cancer Institute guidelines.

  7. Screening Phosphorylation Site Mutations in Yeast Acetyl-CoA Carboxylase Using Malonyl-CoA Sensor to Improve Malonyl-CoA-Derived Product.

    Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

    2018-01-01

    Malonyl-coenzyme A (malonyl-CoA) is a critical precursor for the biosynthesis of a variety of biochemicals. It is synthesized by the catalysis of acetyl-CoA carboxylase (Acc1p), which was demonstrated to be deactivated by the phosphorylation of Snf1 protein kinase in yeast. In this study, we designed a synthetic malonyl-CoA biosensor and used it to screen phosphorylation site mutations of Acc1p in Saccharomyces cerevisiae . Thirteen phosphorylation sites were mutated, and a combination of three site mutations in Acc1p, S686A, S659A, and S1157A, was found to increase malonyl-CoA availability. ACC1 S686AS659AS1157A expression also improved the production of 3-hydroxypropionic acid, a malonyl-CoA-derived chemical, compared to both wild type and the previously reported ACC1 S659AS1157A mutation. This mutation will also be beneficial for other malonyl-CoA-derived products.

  8. F2 screen, inheritance and cross-resistance of field-derived Vip3A resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) collected from Louisiana, USA.

    Yang, Fei; Morsello, Shannon; Head, Graham P; Sansone, Chris; Huang, Fangneng; Gilreath, Ryan T; Kerns, David L

    2017-11-28

    Fall armyworm, Spodoptera frugiperda, is a target pest of the Vip3A protein used in pyramided Bt corn and cotton in the USA. In this study, we provide the first documentation of a resistance allele conferring Vip3A resistance in a field-derived population of S. frugiperda from the USA, and characterize its inheritance and cross-resistance. An F 2 screen with 104 two-parent families generated from a field collection of S. frugiperda in Louisiana, USA, resulted in one family carrying a Vip3A resistance allele. The Vip3A-resistant strain (RR) derived from the two-parent family showed a high level of resistance to Vip3A in both diet and whole-plant bioassays, with a resistance ratio of >632.0-fold relative to a susceptible population (SS) based on diet-overlay bioassays. The inheritance of Vip3A resistance was monogenic, autosomal and recessive. Furthermore, the Vip3A resistance conferred no cross-resistance to Cry1F, Cry2Ab2 or Cry2Ae purified proteins, with resistance ratios of 3.5, 5.0 and 1.1, respectively. These findings provide valuable information for characterizing Vip3A resistance, resistance monitoring, and developing effective resistance management strategies for the sustainable use of the Vip3A technology. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  9. Anti-Aβ drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer's disease.

    Naoki Yahata

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life. The AD brain is characterized by deposition of amyloid β peptide (Aβ, which is produced from amyloid precursor protein by β- and γ-secretase (presenilin complex-mediated sequential cleavage. Induced pluripotent stem (iPS cells potentially provide an opportunity to generate a human cell-based model of AD that would be crucial for drug discovery as well as for investigating mechanisms of the disease. METHODOLOGY/PRINCIPAL FINDINGS: We differentiated human iPS (hiPS cells into neuronal cells expressing the forebrain marker, Foxg1, and the neocortical markers, Cux1, Satb2, Ctip2, and Tbr1. The iPS cell-derived neuronal cells also expressed amyloid precursor protein, β-secretase, and γ-secretase components, and were capable of secreting Aβ into the conditioned media. Aβ production was inhibited by β-secretase inhibitor, γ-secretase inhibitor (GSI, and an NSAID; however, there were different susceptibilities to all three drugs between early and late differentiation stages. At the early differentiation stage, GSI treatment caused a fast increase at lower dose (Aβ surge and drastic decline of Aβ production. CONCLUSIONS/SIGNIFICANCE: These results indicate that the hiPS cell-derived neuronal cells express functional β- and γ-secretases involved in Aβ production; however, anti-Aβ drug screening using these hiPS cell-derived neuronal cells requires sufficient neuronal differentiation.

  10. Psychosis risk screening: Validation of the youth psychosis at-risk questionnaire - brief in a community-derived sample of adolescents.

    Fonseca-Pedrero, Eduardo; Ortuño-Sierra, Javier; Chocarro, Edurne; Inchausti, Felix; Debbané, Martin; Bobes, Julio

    2017-12-01

    There have been several attempts to identify individuals potentially at high risk for psychotic-spectrum disorders using brief screening measures. However, relatively few studies have tested the psychometric properties of the psychosis screening measures in representative samples of adolescents. The main purpose of the present study was to analyse the prevalence, factorial structure, measurement invariance across gender, and reliability of the Youth Psychosis At-Risk Questionnaire - Brief (YPARQ-B) in a community-derived sample of adolescents. Additionally, the relationship between YPARQ-B, depressive symptoms, psychopathology, stress manifestations, and prosocial skills was analysed. One thousand and twenty students from high schools participated in a cross-sectional survey. The YPARQ-B, the Reynolds Adolescent Depression Scale, the Strengths and Difficulties Questionnaire, and the Student Stress Inventory - Stress Manifestations were used. A total of 85.1% of the total sample self-reported at least one subclinical psychotic experience. We observed a total of 10.9% of adolescents with a cutoff score of ≥11 or 6.8% with a cutoff score of ≥13. The analysis of internal structure of the YPARQ-B yielded an essentially unidimensional structure. The YPARQ-B scores showed measurement invariance across gender. The internal consistency of the YPARQ-B total score was 0.94. Furthermore, self-reported subclinical psychotic experiences were associated with depressive symptoms, emotional and behavioural problems, poor prosocial skills, and stress manifestations. These results would appear to indicate that YPARQ-B is a brief and easy tool to assess self-reported subclinical psychotic experiences in adolescents from the general population. The assessment of these experiences in community settings, and its associations with psychopathology, may help us to enhance the possibility of an early identification of adolescents potentially at risk for psychosis and mental health

  11. Screening of bacterial strains capable of converting biodiesel-derived raw glycerol into 1,3-propanediol, 2,3-butanediol and ethanol

    Metsoviti, Maria; Paramithiotis, Spiros; Drosinos, Eleftherios H.; Galiotou-Panayotou, Maria; Nychas, George-John E.; Papanikolaou, Seraphim [Department of Food Science and Technology, Agricultural University of Athens, Athens (Greece); Zeng, An-Ping [Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology (TUHH), Hamburg (Germany)

    2012-02-15

    The ability of bacterial strains to assimilate glycerol derived from biodiesel facilities to produce metabolic compounds of importance for the food, textile and chemical industry, such as 1,3-propanediol (PD), 2,3-butanediol (BD) and ethanol (EtOH), was assessed. The screening of 84 bacterial strains was performed using glycerol as carbon source. After initial trials, 12 strains were identified capable of consuming raw glycerol under anaerobic conditions, whereas 5 strains consumed glycerol under aerobiosis. A plethora of metabolic compounds was synthesized; in anaerobic batch-bioreactor cultures PD in quantities up to 11.3 g/L was produced by Clostridium butyricum NRRL B-23495, while the respective value was 10.1 g/L for a newly isolated Citrobacter freundii. Adaptation of Cl. butyricum at higher initial glycerol concentration resulted in a PD{sub max} concentration of {proportional_to}32 g/L. BD was produced by a new Enterobacter aerogenes isolate in shake-flask experiments, under fully aerobic conditions, with a maximum concentration of {proportional_to}22 g/L which was achieved at an initial glycerol quantity of 55 g/L. A new Klebsiella oxytoca isolate converted waste glycerol into mixtures of PD, BD and EtOH at various ratios. Finally, another new C. freundii isolate converted waste glycerol into EtOH in anaerobic batch-bioreactor cultures with constant pH, achieving a final EtOH concentration of 14.5 g/L, a conversion yield of 0.45 g/g and a volumetric productivity of {proportional_to}0.7 g/L/h. As a conclusion, the current study confirmed the utilization of biodiesel-derived raw glycerol as an appropriate substrate for the production of PD, BD and EtOH by several newly isolated bacterial strains under different experimental conditions. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Insecticidal activities and phytochemical screening of crude extracts and its derived fractions from three medicinal plants Nepeta leavigata, Nepeta kurramensis and Rhynchosia reniformis

    Ahmad, N.; Shinwari, Z.K.

    2016-01-01

    The extracts and its derived fractions from three medicinal plants species Nepeta leavigata, Nepeta kurramensis and Rhynchosia reniformis were tested for insecticidal activities and preliminary phytochemical evaluation with the intention of standardization and proper manage of bioactive principles in such heterogonous botanicals and to encourage drug finding work with plants. The crude extracts and fractions from Nepeta plants showed moderate to strong insecticidal activity. Among the fractions from Nepeta kurramensis the n-butanol fraction showed strongest insecticidal activity with 89% mortality rate against Tribolium castaneum followed by methanol extract with 88% mortality ratio and in case of Nepeta leavigata the potential activity was showed by methanol extracts with 93% mortality rate against the tested insect. Surprisingly none of the extract / fractions obtained from Rhynchosia reniformis plant exhibited any insecticidal activity. The phytochemicals screening results revealed that both species of Nepeta showed similar phytochemicals profile. The group of chemicals terpenes, flavonoids and glycosides were observed in all the extracts/fractions of Nepeta plants. While phenolic compounds, acidic compounds and alkaloids were found in methanolic extracts, chloroform fraction and ethyl acetate fraction. The Rhynchosia reniformis was observed to be a good source of phenolic compounds, flavonoids, terpenes, alkaloids and fats. (author)

  13. A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

    Hsieh, Wen-Ting; Chiang, Been-Huang

    2014-07-09

    Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

  14. A high-throughput screening method of bisphenols, bisphenols digycidyl ethers and their derivatives in dairy products by ultra-high performance liquid chromatography-tandem mass spectrometry.

    Cheng, Yan; Nie, Xue-Mei; Wu, Han-Qiu; Hong, Yun-He; Yang, Bing-Cheng; Liu, Tong; Zhao, Dan; Wang, Jian-Feng; Yao, Gui-Hong; Zhang, Feng

    2017-01-15

    A simple and universal analytical method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for high throughput screening of 21 bisphenols, bisphenols digycidyl ethers and their derivatives in dairy products was developed. Response Surface Methodology (RSM) was used to optimize sample preparation conditions based on a quick, easy, cheap, effective, rugged and safe (QuEChERS) method. The analytes were extracted by using 15 mL acetonitrile with 1% acetic acid, and the extracts were further purified by using 190 mg of C18 and 390 mg of PSA. The extracts were analyzed by UHPLC-MS/MS with electrospray ionization (ESI) source. Linearity was assessed by using matrix-matched standard calibration and good correlation coefficients (r 2  > 0.99) were obtained. The limits of quantitation (LOQs) for the analytes ranged from 0.02 to 5 μg kg -1 . The extraction recoveries were in a range of 88.2%-108.2%. Good method reproducibility in terms of intra- and inter-day precision was observed, yielding relative standard deviations (RSDs) less than 8.9% and 9.9%, respectively. The validation method results revealed that the proposed method was sensitive and reliable. Finally, this method was successfully applied to dairy product analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Identification of Eusynstyelamide B as a Potent Cell Cycle Inhibitor Following the Generation and Screening of an Ascidian-Derived Extract Library Using a Real Time Cell Analyzer

    Michelle S. Liberio

    2014-10-01

    Full Text Available Ascidians are marine invertebrates that have been a source of numerous cytotoxic compounds. Of the first six marine-derived drugs that made anticancer clinical trials, three originated from ascidian specimens. In order to identify new anti-neoplastic compounds, an ascidian extract library (143 samples was generated and screened in MDA-MB-231 breast cancer cells using a real-time cell analyzer (RTCA. This resulted in 143 time-dependent cell response profiles (TCRP, which are read-outs of changes to the growth rate, morphology, and adhesive characteristics of the cell culture. Twenty-one extracts affected the TCRP of MDA-MB-231 cells and were further investigated regarding toxicity and specificity, as well as their effects on cell morphology and cell cycle. The results of these studies were used to prioritize extracts for bioassay-guided fractionation, which led to the isolation of the previously identified marine natural product, eusynstyelamide B (1. This bis-indole alkaloid was shown to display an IC50 of 5 µM in MDA-MB-231 cells. Moreover, 1 caused a strong cell cycle arrest in G2/M and induced apoptosis after 72 h treatment, making this molecule an attractive candidate for further mechanism of action studies.

  16. Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell–derived medium spiny neurons

    Marco Straccia

    Full Text Available A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ. Here, we define by a quantitative high-throughput gene expression analysis the subset of specific genes of the whole ganglionic eminence (WGE and adult human striatum. Our results demonstrate that not only the number of specific genes is crucial but also their relative expression levels between brain areas. We next used these gene profiles to characterize the differentiation of hPSCs. Our findings demonstrate a temporal progression of gene expression during striatal differentiation of hPSCs from a WGE toward an adult striatum identity. Present results establish a gene expression profile to qualitatively and quantitatively evaluate the telencephalic hPSC-derived progenitors eventually used for transplantation and mature striatal neurons for disease modeling and drug-screening.

  17. Pharmacological profile of brain-derived neurotrophic factor (BDNF) splice variant translation using a novel drug screening assay: a "quantitative code".

    Vaghi, Valentina; Polacchini, Alessio; Baj, Gabriele; Pinheiro, Vera L M; Vicario, Annalisa; Tongiorgi, Enrico

    2014-10-03

    The neurotrophin brain-derived neurotrophic factor (BDNF) is a key regulator of neuronal development and plasticity. BDNF is a major pharmaceutical target in neurodevelopmental and psychiatric disorders. However, pharmacological modulation of this neurotrophin is challenging because BDNF is generated by multiple, alternatively spliced transcripts with different 5'- and 3'UTRs. Each BDNF mRNA variant is transcribed independently, but translation regulation is unknown. To evaluate the translatability of BDNF transcripts, we developed an in vitro luciferase assay in human neuroblastoma cells. In unstimulated cells, each BDNF 5'- and 3'UTR determined a different basal translation level of the luciferase reporter gene. However, constructs with either a 5'UTR or a 3'UTR alone showed poor translation modulation by BDNF, KCl, dihydroxyphenylglycine, AMPA, NMDA, dopamine, acetylcholine, norepinephrine, or serotonin. Constructs consisting of the luciferase reporter gene flanked by the 5'UTR of one of the most abundant BDNF transcripts in the brain (exons 1, 2c, 4, and 6) and the long 3'UTR responded selectively to stimulation with the different receptor agonists, and only transcripts 2c and 6 were increased by the antidepressants desipramine and mirtazapine. We propose that BDNF mRNA variants represent "a quantitative code" for regulated expression of the protein. Thus, to discriminate the efficacy of drugs in stimulating BDNF synthesis, it is appropriate to use variant-specific in vitro screening tests. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Social Withdrawal Among Individuals Receiving Psychiatric Care: Derivation of a Scale Using Routine Clinical Assessment Data to Support Screening and Outcome Measurement.

    Rios, Sebastian; Perlman, Christopher M

    2017-04-24

    Social withdrawal is a symptom experienced by individuals with an array of mental health conditions, particularly those with schizophrenia and mood disorders. Assessments of social withdrawal are often lengthy and may not be routinely integrated within the comprehensive clinical assessment of the individual. This study utilized item response and classical test theory methods to derive a Social Withdrawal Scale (SWS) using items embedded within a routine clinical assessment, the RAI-Mental Health (RAI-MH). Using data from 60,571 inpatients in Ontario, Canada, a common factor analysis identified seven items from the RAI-MH that measure social withdrawal. A graded response model found that six items had acceptable discrimination parameters: lack of motivation, reduced interaction, decreased energy, flat affect, anhedonia, and loss of interest. Summing these items, the SWS was found to have strong internal consistency (Cronbach's alpha = 0.82) and showed a medium to large effect size (d = 0.77) from admission to discharge. Fewer individuals with high SWS scores participated in social activity or reported having a confidant compared to those with lower scores. Since the RAI-MH is available across clinical subgroups in several jurisdictions, the SWS is a useful tool for screening, clinical decision support, and evaluation.

  19. Application of micro-thin-layer chromatography as a simple fractionation tool for fast screening of raw extracts derived from complex biological, pharmaceutical and environmental samples

    Zarzycki, Pawel K., E-mail: pawel_k_z@hotmail.com [Section of Toxicology and Bioanalytics, Department of Civil and Environmental Engineering, Koszalin University of Technology, Sniadeckich 2, 75-453 Koszalin (Poland); Slaczka, Magdalena M.; Zarzycka, Magdalena B.; Wlodarczyk, Elzbieta; Baran, Michal J. [Section of Toxicology and Bioanalytics, Department of Civil and Environmental Engineering, Koszalin University of Technology, Sniadeckich 2, 75-453 Koszalin (Poland)

    2011-03-04

    The main goal of present paper is to demonstrate the separation and detection capability of micro-TLC technique involving simple one step liquid extraction protocols of complex materials without multi-steps sample pre-purification. In the present studies target components (cyanobacteria pigments, lipids and fullerenes) were isolated from heavy loading complex matrices including spirulina dried cells, birds' feathers and fatty oils as well as soot samples derived from biomass fuel and fossils-fired home heating systems. In each case isocratic separation protocol involving less that 1 mL of one component or binary mixture mobile phases can be completed within time of 5-8 min. Sensitive detection of components of interest was performed via fluorescence or staining techniques using iodine or phosphomolybdic acid. Described methodology can be applied for fast fractionation or screening of whole range of target substances as well as chemo-taxonomic studies and fingerprinting of complex mixtures, which are present in raw biological or environmental samples.

  20. Reprint of: Application of micro-thin-layer chromatography as a simple fractionation tool for fast screening of raw extracts derived from complex biological, pharmaceutical and environmental samples

    Zarzycki, Pawel K., E-mail: pawel_k_z@hotmail.com [Section of Toxicology and Bioanalytics, Department of Civil and Environmental Engineering, Koszalin University of Technology, Sniadeckich 2, 75-453 Koszalin (Poland); Slaczka, Magdalena M.; Zarzycka, Magdalena B.; Wlodarczyk, Elzbieta; Baran, Michal J. [Section of Toxicology and Bioanalytics, Department of Civil and Environmental Engineering, Koszalin University of Technology, Sniadeckich 2, 75-453 Koszalin (Poland)

    2012-02-24

    The main goal of present paper is to demonstrate the separation and detection capability of micro-TLC technique involving simple one step liquid extraction protocols of complex materials without multi-steps sample pre-purification. In the present studies target components (cyanobacteria pigments, lipids and fullerenes) were isolated from heavy loading complex matrices including spirulina dried cells, birds' feathers and fatty oils as well as soot samples derived from biomass fuel and fossils-fired home heating systems. In each case isocratic separation protocol involving less that 1 mL of one component or binary mixture mobile phases can be completed within time of 5-8 min. Sensitive detection of components of interest was performed via fluorescence or staining techniques using iodine or phosphomolybdic acid. Described methodology can be applied for fast fractionation or screening of whole range of target substances as well as chemo-taxonomic studies and fingerprinting of complex mixtures, which are present in raw biological or environmental samples.

  1. Reprint of: Application of micro-thin-layer chromatography as a simple fractionation tool for fast screening of raw extracts derived from complex biological, pharmaceutical and environmental samples

    Zarzycki, Paweł K.; Ślączka, Magdalena M.; Zarzycka, Magdalena B.; Włodarczyk, Elżbieta; Baran, Michał J.

    2012-01-01

    The main goal of present paper is to demonstrate the separation and detection capability of micro-TLC technique involving simple one step liquid extraction protocols of complex materials without multi-steps sample pre-purification. In the present studies target components (cyanobacteria pigments, lipids and fullerenes) were isolated from heavy loading complex matrices including spirulina dried cells, birds’ feathers and fatty oils as well as soot samples derived from biomass fuel and fossils-fired home heating systems. In each case isocratic separation protocol involving less that 1 mL of one component or binary mixture mobile phases can be completed within time of 5–8 min. Sensitive detection of components of interest was performed via fluorescence or staining techniques using iodine or phosphomolybdic acid. Described methodology can be applied for fast fractionation or screening of whole range of target substances as well as chemo-taxonomic studies and fingerprinting of complex mixtures, which are present in raw biological or environmental samples.

  2. Application of micro-thin-layer chromatography as a simple fractionation tool for fast screening of raw extracts derived from complex biological, pharmaceutical and environmental samples

    Zarzycki, Pawel K.; Slaczka, Magdalena M.; Zarzycka, Magdalena B.; Wlodarczyk, Elzbieta; Baran, Michal J.

    2011-01-01

    The main goal of present paper is to demonstrate the separation and detection capability of micro-TLC technique involving simple one step liquid extraction protocols of complex materials without multi-steps sample pre-purification. In the present studies target components (cyanobacteria pigments, lipids and fullerenes) were isolated from heavy loading complex matrices including spirulina dried cells, birds' feathers and fatty oils as well as soot samples derived from biomass fuel and fossils-fired home heating systems. In each case isocratic separation protocol involving less that 1 mL of one component or binary mixture mobile phases can be completed within time of 5-8 min. Sensitive detection of components of interest was performed via fluorescence or staining techniques using iodine or phosphomolybdic acid. Described methodology can be applied for fast fractionation or screening of whole range of target substances as well as chemo-taxonomic studies and fingerprinting of complex mixtures, which are present in raw biological or environmental samples.

  3. Electronic structure of super heavy atoms revisited

    Gitman, D M; Levin, A D; Tyutin, I V; Voronov, B L

    2013-01-01

    The electronic structure of an atom with Z ⩽ Z c = 137 can be described by the Dirac equation with the Coulomb field of a point charge Ze. It was believed that the Dirac equation with Z > Z c poses difficulties because the formula for the lower energy level of the Dirac Hamiltonian formally gives imaginary eigenvalues. But a strict mathematical consideration shows that difficulties with the electronic spectrum for Z > Z c do not arise if the Dirac Hamiltonian is correctly defined as a self-adjoint operator. In this paper, we briefly summarize the main physical results of that consideration in a form suitable for physicists with some additional new details and numerical calculations of the electronic spectra. (comment)

  4. Depression Screening

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Depression Screening (PHQ-9) - Instructions The following questions are ... this tool, there is also text-only version . Depression Screening - Manual Instructions The following questions are a ...

  5. Ultrafast Screening of a Novel, Moderately Hydrophilic Angiotensin-Converting-Enzyme-Inhibitory Peptide, RYL, from Silkworm Pupa Using an Fe-Doped-Silkworm-Excrement-Derived Biocarbon: Waste Conversion by Waste.

    Liu, Long; Wei, Yanan; Chang, Qing; Sun, Huaju; Chai, Kungang; Huang, Zuqiang; Zhao, Zhenxia; Zhao, Zhongxing

    2017-12-27

    A novel, moderately hydrophilic peptide (RYL) with high ACE-inhibitory activity was screened ultrafast via a concept of waste conversion using waste. This novel peptide was screened from silkworm pupa using an Fe-doped porous biocarbon (FL/Z-SE) derived from silkworm excrement. FL/Z-SE possessed magnetic properties and specific selection for peptides due to Fe's dual functions. The selected RYL, which has moderate hydrophilicity (LogP = -0.22), exhibited a comparatively high ACE-inhibitory activity (IC 50 = 3.31 ± 0.11 μM). The inhibitory kinetics and docking-simulation results show that, as a competitive ACE inhibitor, RYL formed five hydrogen bonds with the ACE residues in the S1 and S2 pockets. In this work, both the screening carbon material and the selected ACE-inhibitory peptide were derived from agricultural waste (silkworm excrement and pupa), which offers a new way of thinking about the development of advanced uses of the silkworm byproducts and wastes.

  6. A novel salt-tolerant chitobiosidase discovered by genetic screening of a metagenomic library derived from chitin-amended agricultural soil

    Cretoiu, Mariana Silvia; Berini, Francesca; Kielak, Anna Maria; Marinelli, Flavia; van Elsas, Jan Dirk

    2015-01-01

    Here, we report on the construction of a metagenomic library from a chitin-amended disease-suppressive agricultural soil and its screening for genes that encode novel chitinolytic enzymes. The library, constructed in fosmids in an Escherichia coli host, comprised 145,000 clones containing inserts of

  7. A Review of Human Pluripotent Stem Cell-Derived Cardiomyocytes for High-Throughput Drug Discovery, Cardiotoxicity Screening and Publication Standards

    Mordwinkin, Nicholas M.; Burridge, Paul W.; Wu, Joseph C.

    2012-01-01

    Drug attrition rates have increased in past years, resulting in growing costs for the pharmaceutical industry and consumers. The reasons for this include the lack of in vitro models that correlate with clinical results, and poor preclinical toxicity screening assays. The in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery, disease modeling, regenerative medicine, and ...

  8. Placental transfer of maternally-derived IgA precludes the use of guthrie card eluates as a screening tool for primary immunodeficiency diseases.

    Stephan Borte

    Full Text Available There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID. Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T, whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD, 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.

  9. Placental transfer of maternally-derived IgA precludes the use of guthrie card eluates as a screening tool for primary immunodeficiency diseases.

    Borte, Stephan; Janzi, Magdalena; Pan-Hammarström, Qiang; von Döbeln, Ulrika; Nordvall, Lennart; Winiarski, Jacek; Fasth, Anders; Hammarström, Lennart

    2012-01-01

    There is a need for neonatal screening tools to improve the long-term clinical outcome of patients with primary immunodeficiency diseases (PID). Recently, a PCR-based screening method for both TRECs and KRECs using Guthrie card samples has been developed. However, the applicability of these excision circle assays is limited to patients with severe T or B cell lymphopenia (SCID, XLA and A-T), whereas the most common forms of PID are not detected. Absence of serum IgA is seen in a major fraction of patients with immunological defects. As serum IgA in newborns is considered to be of fetal origin, eluates from routinely collected dried blood spot samples might thus be suitable for identification of children with PID. To assess the applicability of such screening assays, stored Guthrie card samples were obtained from 47 patients with various forms of primary immunodeficiency diseases (SCID, XLA, A-T, HIGM and IgAD), 20 individuals with normal serum IgA levels born to IgA-deficient mothers and 51 matched healthy newborns. Surprisingly, normal serum IgA levels were found in all SCID, XLA, A-T and HIGM patients and, additionally, in all those IgAD patients born to IgA-sufficient mothers. Conversely, no serum IgA was found in any of the 16 IgAD patients born by IgA-deficient mothers. Moreover, half of the IgA-sufficient individuals born by IgA-deficient mothers also lacked IgA at birth whereas no IgA-deficient individuals were found among the controls. IgA in neonatal dried blood samples thus appears to be of both maternal and fetal origin and precludes its use as a reliable marker for neonatal screening of primary immunodeficiency diseases.

  10. A strategy for fast screening and identification of sulfur derivatives in medicinal Pueraria species based on the fine isotopic pattern filtering method using ultra-high-resolution mass spectrometry

    Yang, Min; Zhou, Zhe; Guo, De-an

    2015-01-01

    Sulfurous compounds are commonly present in plants, fungi, and animals. Most of them were reported to possess various bioactivities. Isotopic pattern filter (IPF) is a powerful tool for screening compounds with distinct isotope pattern. Over the past decades, the IPF was used mainly to study Cl- and Br-containing compounds. To our knowledge, the algorithm was scarcely used to screen S-containing compounds, especially when combined with chromatography analyses, because the "3"4S isotopic ion is drastically affected by "1"3C_2 and "1"8O. Thus, we present a new method for a fine isotopic pattern filter (FIPF) based on the separated M + 2 ions ("1"2C_x"1H_y"1"6O_z"3"2S"1"3C_2"1"8O, "1"2C_x_+_2"1H_y"1"6O_z_+_1"3"4S, tentatively named M + 2OC and M + 2S) with an ultra-high-resolution mass (100,000 FWHM @ 400 m/z) to screen sulfur derivatives in traditional Chinese medicines (TCM).This finer algorithm operates through convenient filters, including an accurate mass shift of M + 2OC and M + 2S from M and their relative intensity compared to M. The method was validated at various mass resolutions, mass accuracies, and screening thresholds of flexible elemental compositions. Using the established FIPF method, twelve S-derivatives were found in the popular medicinal used Pueraria species, and 9 of them were tentatively identified by high-resolution multiple stage mass spectrometry (HRMS"n). The compounds were used to evaluate the sulfurous compounds' situation in commercially purchased Pueraria products. The strategy presented here provides a promising application of the IPF method in a new field. - Highlights: • We provide a new strategy for specifically screening of sulfurous compounds. • The fine isotopic pattern filter (FIPF) bases on separation of "1"3C_2+"1"8O and "3"4S. • Ultra high resolution mass (100,000 FWHM @ 400 m/z) is essential for FIPF. • IPF is applied to study the unique components of TCM for the first time. • New sulfurous components

  11. A strategy for fast screening and identification of sulfur derivatives in medicinal Pueraria species based on the fine isotopic pattern filtering method using ultra-high-resolution mass spectrometry

    Yang, Min [National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 (China); Zhou, Zhe [ThermoFisher Scientific China Co., Ltd, No 6 Building, 27 Xinjinqiao Road, Shanghai 201206 (China); Guo, De-an, E-mail: daguo@simm.ac.cn [National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 (China)

    2015-09-24

    Sulfurous compounds are commonly present in plants, fungi, and animals. Most of them were reported to possess various bioactivities. Isotopic pattern filter (IPF) is a powerful tool for screening compounds with distinct isotope pattern. Over the past decades, the IPF was used mainly to study Cl- and Br-containing compounds. To our knowledge, the algorithm was scarcely used to screen S-containing compounds, especially when combined with chromatography analyses, because the {sup 34}S isotopic ion is drastically affected by {sup 13}C{sub 2} and {sup 18}O. Thus, we present a new method for a fine isotopic pattern filter (FIPF) based on the separated M + 2 ions ({sup 12}C{sub x}{sup 1}H{sub y}{sup 16}O{sub z}{sup 32}S{sup 13}C{sub 2}{sup 18}O, {sup 12}C{sub x+2}{sup 1}H{sub y}{sup 16}O{sub z+1}{sup 34}S, tentatively named M + 2OC and M + 2S) with an ultra-high-resolution mass (100,000 FWHM @ 400 m/z) to screen sulfur derivatives in traditional Chinese medicines (TCM).This finer algorithm operates through convenient filters, including an accurate mass shift of M + 2OC and M + 2S from M and their relative intensity compared to M. The method was validated at various mass resolutions, mass accuracies, and screening thresholds of flexible elemental compositions. Using the established FIPF method, twelve S-derivatives were found in the popular medicinal used Pueraria species, and 9 of them were tentatively identified by high-resolution multiple stage mass spectrometry (HRMS{sup n}). The compounds were used to evaluate the sulfurous compounds' situation in commercially purchased Pueraria products. The strategy presented here provides a promising application of the IPF method in a new field. - Highlights: • We provide a new strategy for specifically screening of sulfurous compounds. • The fine isotopic pattern filter (FIPF) bases on separation of {sup 13}C{sub 2}+{sup 18}O and {sup 34}S. • Ultra high resolution mass (100,000 FWHM @ 400 m/z) is essential

  12. Interpretation of field potentials measured on a multi electrode array in pharmacological toxicity screening on primary and human pluripotent stem cell-derived cardiomyocytes

    Tertoolen, L.G.J.; Braam, S. R.; van Meer, B.J.; Passier, R.; Mummery, C. L.

    2018-01-01

    Multi electrode arrays (MEAs) are increasingly used to detect external field potentials in electrically active cells. Recently, in combination with cardiomyocytes derived from human (induced) pluripotent stem cells they have started to become a preferred tool to examine newly developed drugs for

  13. Synthesis of some new 4-oxo-thiazolidines, tetrazole and triazole derived from 2-SH-benzothiazole and antimicrobial screening of some synthesized

    Suaad M.H. Al-Majidi

    2014-12-01

    Triazole moieties reported condensation (MBT with ethylbromo acetate and potassium hydroxide by the fusion method and resulted in ester-2-mercaptobenzothiazole (7, which was treated with hydrazine hydrate to give a hydrazine derivative (8, then converting these compounds (8 to phenyl semicarbazide (9 and phenyl thiosemicarbazide (10 derivatives. Cyclization compounds (9,10 in alkaline media (4 N·NaOH gave triazoles compounds (11,12. Furthermore the compound (8 was converted to the dithiocarbazate salt (13 which was then cyclized with hydrazine hydrate to give substituted triazole (14. The prepared compounds were identified by spectral methods (FTIR, 1H NMR, 13C NMR and some of its physical properties were measured and furthermore the effects of the preparing compounds on some strains of bacteria were studied.

  14. High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells.

    Kumari, Daman; Swaroop, Manju; Southall, Noel; Huang, Wenwei; Zheng, Wei; Usdin, Karen

    2015-07-01

    : Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development. In this study, a specific and sensitive fluorescence resonance energy transfer-based assay for fragile X mental retardation protein detection was developed and optimized for high-throughput screening (HTS) of compound libraries using fragile X syndrome (FXS) patient-derived neural stem cells. The data suggest that this HTS format will be useful for the identification of better lead compounds for developing new therapeutics for FXS. This assay can also be adapted for FMRP detection in clinical and research settings. ©AlphaMed Press.

  15. Chemical Genomic Screening of a Saccharomyces cerevisiae Genomewide Mutant Collection Reveals Genes Required for Defense against Four Antimicrobial Peptides Derived from Proteins Found in Human Saliva

    Bhatt, Sanjay; Schoenly, Nathan E.; Lee, Anna Y.; Nislow, Corey; Bobek, Libuse A.

    2013-01-01

    To compare the effects of four antimicrobial peptides (MUC7 12-mer, histatin 12-mer, cathelicidin KR20, and a peptide containing lactoferricin amino acids 1 to 11) on the yeast Saccharomyces cerevisiae, we employed a genomewide fitness screen of combined collections of mutants with homozygous deletions of nonessential genes and heterozygous deletions of essential genes. When an arbitrary fitness score cutoffs of 1 (indicating a fitness defect, or hypersensitivity) and −1 (indicating a fitness gain, or resistance) was used, 425 of the 5,902 mutants tested exhibited altered fitness when treated with at least one peptide. Functional analysis of the 425 strains revealed enrichment among the identified deletions in gene groups associated with the Gene Ontology (GO) terms “ribosomal subunit,” “ribosome biogenesis,” “protein glycosylation,” “vacuolar transport,” “Golgi vesicle transport,” “negative regulation of transcription,” and others. Fitness profiles of all four tested peptides were highly similar, particularly among mutant strains exhibiting the greatest fitness defects. The latter group included deletions in several genes involved in induction of the RIM101 signaling pathway, including several components of the ESCRT sorting machinery. The RIM101 signaling regulates response of yeasts to alkaline and neutral pH and high salts, and our data indicate that this pathway also plays a prominent role in regulating protective measures against all four tested peptides. In summary, the results of the chemical genomic screens of S. cerevisiae mutant collection suggest that the four antimicrobial peptides, despite their differences in structure and physical properties, share many interactions with S. cerevisiae cells and consequently a high degree of similarity between their modes of action. PMID:23208710

  16. Toward a non-invasive screening tool for differentiation of pancreatic lesions based on intra-voxel incoherent motion derived parameters

    Graf, Markus; Simon, Dirk; Mang, Sarah [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Software Development for Integrated Therapy and Diagnostics; Lemke, Andreas [Heidelberg Univ., Mannheim (Germany). Dept. of Computer Assisted Clinical Medicine; Gruenberg, Katharina [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Dept. of Radiology

    2013-03-01

    Early recognition of and differential diagnosis between pancreatic cancer and chronic pancreatitis is an important step in successful therapy. Parameters of the IVIM (intra-voxel incoherent motion) theory can be used to differentiate between those lesions. The objective of this work is to evaluate the effects of rigid image registration on IVIM derived parameters for differentiation of pancreatic lesions such as pancreatic cancer and solid mass forming pancreatitis. The effects of linear image registration methods on reproducibility and accuracy of IVIM derived parameters were quantified on MR images of ten volunteers. For this purpose, they were evaluated statistically by comparison of registered and unregistered parameter data. Further, the perfusion fraction f was used to differentiate pancreatic lesions on eleven previously diagnosed patient data sets. Its diagnostic power with and without rigid registration was evaluated using receiver operating curves (ROC) analysis. The pancreas was segmented manually on MR data sets of healthy volunteers as well as the patients showing solid pancreatic lesions. Diffusion weighted imaging was performed in 10 blocks of breath-hold phases. Linear registration of the weighted image stack leads to a 3.7% decrease in variability of the IVIM derived parameter f due to an improved anatomical overlap of 5%. Consequently, after registration the area under the curve in the ROC-analysis for the differentiation approach increased by 2.7%. In conclusion, rigid registration improves the differentiation process based on f-values. (orig.)

  17. Toward a non-invasive screening tool for differentiation of pancreatic lesions based on intra-voxel incoherent motion derived parameters

    Graf, Markus; Simon, Dirk; Mang, Sarah; Lemke, Andreas; Gruenberg, Katharina

    2013-01-01

    Early recognition of and differential diagnosis between pancreatic cancer and chronic pancreatitis is an important step in successful therapy. Parameters of the IVIM (intra-voxel incoherent motion) theory can be used to differentiate between those lesions. The objective of this work is to evaluate the effects of rigid image registration on IVIM derived parameters for differentiation of pancreatic lesions such as pancreatic cancer and solid mass forming pancreatitis. The effects of linear image registration methods on reproducibility and accuracy of IVIM derived parameters were quantified on MR images of ten volunteers. For this purpose, they were evaluated statistically by comparison of registered and unregistered parameter data. Further, the perfusion fraction f was used to differentiate pancreatic lesions on eleven previously diagnosed patient data sets. Its diagnostic power with and without rigid registration was evaluated using receiver operating curves (ROC) analysis. The pancreas was segmented manually on MR data sets of healthy volunteers as well as the patients showing solid pancreatic lesions. Diffusion weighted imaging was performed in 10 blocks of breath-hold phases. Linear registration of the weighted image stack leads to a 3.7% decrease in variability of the IVIM derived parameter f due to an improved anatomical overlap of 5%. Consequently, after registration the area under the curve in the ROC-analysis for the differentiation approach increased by 2.7%. In conclusion, rigid registration improves the differentiation process based on f-values. (orig.)

  18. The additional value of bioelectrical impedance analysis-derived muscle mass as a screening tool in geriatric assessment for fall prevention.

    Van Puyenbroeck, Karolien; Roelandts, Lieven; Van Deun, Thomas; Van Royen, Paul; Verhoeven, Veronique

    2012-01-01

    The decline in skeletal muscle in old age is a factor in the development of functional limitations. The objective of this study was to assess if there is a correlation between muscle mass based on bioelectrical impedance analysis (BIA) detection and the fall incidence in nursing home residents and to examine the risk factors for falling in nursing home residents. This prospective cohort study was part of a longitudinal study on nutritional issues in 52 nursing homes in Antwerp (Belgium) from October 2007 to April 2008. Two hundred and seventy-six people aged 65 years and older were included. Each subject was assessed with BIA, the timed get-up-and-go test, the Katz score, the Mini Nutritional Assessment - Short Form and the 36-Item Short Form Health Survey. The primary outcome parameter was fall incidence during the study. The prevalence of sarcopenia varied from 24.3 to 81.5% depending on which definition was used. No association was found between BIA-derived muscle mass and fall incidence. Logistic regression analysis showed that gait speed (odds ratio 1.029; p = 0.003) and mental health (odds ratio 0.981; p = 0.015) are significantly associated with fall incidence in nursing homes. A receiver operating characteristic curve showed that none of the BIA-derived muscle parameters are good predictors of the risk of falling. This study shows that there is no association between sarcopenia based on BIA and fall incidence and that BIA-derived muscle mass has no additional value in predicting fall incidents compared to the timed get-up-and-go test. Copyright © 2012 S. Karger AG, Basel.

  19. Development of novel HER2 inhibitors against gastric cancer derived from flavonoid source of Syzygium alternifolium through molecular dynamics and pharmacophore-based screening

    Babu TMC

    2016-11-01

    Full Text Available Tirumalasetty Muni Chandra Babu,1 Aluru Rammohan,2 Vijaya Bhaskar Baki,1 Savita Devi,3 Duvvuru Gunasekar,2 Wudayagiri Rajendra1 1Bioinformatics Center, Division of Molecular Biology, Department of Zoology, 2Natural Products Division, Department of Chemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 3Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, India Abstract: Continuous usage of synthetic chemotherapeutic drugs causes adverse effects, which prompted for the development of alternative therapeutics for gastric cancer from natural source. This study was carried out with a specific aim to screen gastroprotective compounds from the fruits of Syzygium alternifolium (Myrtaceae. Three flavonoids, namely, 1 5-hydroxy-7,4'-dimethoxy-6,8-di-C-methylflavone, 2 kaempferol-3-O-β-D-glucopyranoside, and 3 kaempferol-3-O-α-L-rhamnopyranoside were isolated from the above medicinal plant by employing silica gel column chromatography and are characterized by NMR techniques. Antigastric cancer activity of these flavonoids was examined on AGS cell lines followed by cell cycle progression assay. In addition, pharmacophore-based screening and molecular dynamics of protein–ligand complex were carried out to identify potent scaffolds. The results showed that compounds 2 and 3 exhibited significant cytotoxic effect, whereas compound 1 showed moderate effect on AGS cells by inhibiting G2/M phase of cell cycle. Molecular docking analysis revealed that compound 2 has higher binding energies on human growth factor receptor-2 (HER2. The constructed pharmacophore models reveal that the compounds have more number of H-bond Acc/Don features which contribute to the inhibition of HER2 activity. By selecting these features, 34 hits were retrieved using the query compound 2. Molecular dynamic simulations (MDS of protein–ligand complexes demonstrated conspicuous

  20. Screening of Satureja subspicata Vis. Honey by HPLC-DAD, GC-FID/MS and UV/VIS: Prephenate Derivatives as Biomarkers.

    Jerković, Igor; Kranjac, Marina; Marijanović, Zvonimir; Zekić, Marina; Radonić, Ani; Tuberoso, Carlo Ignazio Giovanni

    2016-03-21

    The samples of Satureja subspicata Vis. honey were confirmed to be unifloral by melissopalynological analysis with the characteristic pollen share from 36% to 71%. Bioprospecting of the samples was performed by HPLC-DAD, GC-FID/MS, and UV/VIS. Prephenate derivatives were shown to be dominant by the HPLC-DAD analysis, particularly phenylalanine (167.8 mg/kg) and methyl syringate (MSYR, 114.1 mg/kg), followed by tyrosine and benzoic acid. Higher amounts of MSYR (3-4 times) can be pointed out for distinguishing S. subspicata Vis. honey from other Satureja spp. honey types. GC-FID/MS analysis of ultrasonic solvent extracts of the samples revealed MSYR (46.68%, solvent pentane/Et2O 1:2 (v/v); 52.98%, solvent CH2Cl2) and minor abundance of other volatile prephenate derivatives, as well as higher aliphatic compounds characteristic of the comb environment. Two combined extracts (according to the solvents) of all samples were evaluated for their antioxidant properties by FRAP and DPPH assay; the combined extracts demonstrated higher activity (at lower concentrations) in comparison with the average honey sample. UV/VIS analysis of the samples was applied for determination of CIE Lab colour coordinates, total phenolics (425.38 mg GAE/kg), and antioxidant properties (4.26 mmol Fe(2+)/kg (FRAP assay) and 0.8 mmol TEAC/kg (DDPH assay)).

  1. [Index screening and comprehensive evaluation of phenotypic traits of low nitrogen tolerance using BILs population derived from Dongxiang wild rice (Oryza rufipogon Griff)].

    Hu, Biao-lin; Li, Xia; Wan, Yong; Qiu, Zai-hui; Nie, Yuan-yuan; Xie, Jian-kun

    2015-08-01

    To identify the low nitrogen tolerance of Dongxiang wild rice (DXWR) and its progenies, ten phenotypic traits including plant height (PH), heading day (HD), panicle length (PL), number of effective tillers per plant (NETP), number of filled grains per panicle (NFGP), number of grains per panicle (NGP), grain density (GD), spikelet fertility (SF), 1000-grain mass (TGM) and grain yield per plant (GYP) were studied under normal and low nitrogen treatments, using backcross inbred lines (BILs) of Xieqingzao B//DXWR/Xieqingzao B in BC1 F12. Comprehensive evaluation on the low nitrogen tolerance of the BILs population was conducted using principal component analysis and the subordinate function. The evaluation results indicated that the low nitrogen tolerance of the line 116, 143 and 157 was the strongest, which could be served as the intermediate materials for genetic studies on the low nitrogen tolerance of DXWR and breeding for the low nitrogen tolerance in rice. The optimal regression equation of the low nitrogen tolerance in rice was established using stepwise regression analysis. The relative values of five traits including PH, NGP, SF, TGM and GYP were screened out and could be used as comprehensive evaluation indices for the low nitrogen tolerance in the whole growth stage. Therefore, more attention should be paid to the relative values of these five traits, especially for NGP and GYP, in the genetic improvement of the low nitrogen tolerance in rice.

  2. Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database

    Sommer, Thomas; Hübner, Harald; El Kerdawy, Ahmed; Gmeiner, Peter; Pischetsrieder, Monika; Clark, Timothy

    2017-03-01

    The dopamine D2 receptor (D2R) is involved in food reward and compulsive food intake. The present study developed a virtual screening (VS) method to identify food components, which may modulate D2R signalling. In contrast to their common applications in drug discovery, VS methods are rarely applied for the discovery of bioactive food compounds. Here, databases were created that exclusively contain substances occurring in food and natural sources (about 13,000 different compounds in total) as the basis for combined pharmacophore searching, hit-list clustering and molecular docking into D2R homology models. From 17 compounds finally tested in radioligand assays to determine their binding affinities, seven were classified as hits (hit rate = 41%). Functional properties of the five most active compounds were further examined in β-arrestin recruitment and cAMP inhibition experiments. D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity. Application of our databases provides new perspectives for the discovery of bioactive food constituents using VS methods. Based on its presence in beer, we suggest that hordenine significantly contributes to mood-elevating effects of beer.

  3. In vivo angiogenesis screening and mechanism of action of novel tanshinone derivatives produced by one-pot combinatorial modification of natural tanshinone mixture from Salvia miltiorrhiza.

    Zhe-Rui Zhang

    Full Text Available Natural products present in low quantity in herb medicines constitute an important source of chemical diversity. However, the isolation of sufficient amounts of these low abundant constituents for structural modification has been a challenge for several decades and subsequently halts research on the utilization of this important source of chemical entities for drug discovery and development. And, pro-angiogenic therapies are being explored as options to treat cardio-cerebral vascular diseases and wound healing recently. The present study investigates the pro-angiogenic potential of tanshinone derivatives produced by one-pot synthesis using zebrafish model.In order to address the difficulty of chemical modification of low abundant constituents in herb medicines, a novel one-pot combinatorial modification was used to diversify a partially purified tanshinone mixture from Salvia miltiorrhiza. This led to the isolation of ten new imidazole-tanshinones (Compounds 1-10 and one oxazole-tanshinone (Compound 11, the structures of which were characterized by spectroscopic methods in combination with single-crystal X-ray crystallographic analysis. The angiogenesis activities of the new tanshinone derivatives were determined in an experimental model of chemical-induced blood vessels damage in zebrafish. Of all the tested new derivatives, compound 10 exhibited the most potent vascular protective and restorative activity with an EC50 value of 0.026 µM. Moreover, the mechanism underlying the pro-angiogenesis effect of 10 probably involved the VEGF/FGF-Src-MAPK and PI3K-P38 signalling pathways by gene expression analysis and a blocking assay with pathways-specific kinase inhibitors.Taken together, our study demonstrated the more distinctive pro-angiogenic properties of 10 than other tanshinones and revealed 10 has potential for development as a pro-angiogenic agent for diseases associated with insufficient angiogenesis. Our results highlighted the great

  4. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues. Progress report

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. [Morehouse Coll., Atlanta, GA (United States). School of Medicine; Crandall, L.A.; Moseley, R.E.; Armotrading, D. [Florida Univ., Gainesville, FL (United States). Coll. of Medicine

    1993-03-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia`s system of Children`s Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  5. Toxicology screen

    ... this page: //medlineplus.gov/ency/article/003578.htm Toxicology screen To use the sharing features on this page, please enable JavaScript. A toxicology screen refers to various tests that determine the ...

  6. Antimicrobial assay and genetic screening of selected freshwater Cyanobacteria and identification of a biomolecule dihydro-2H-pyran-2-one derivative.

    Srivastava, A; Singh, V K; Patnaik, S; Tripathi, J; Singh, P; Nath, G; Asthana, R K

    2017-04-01

    Explorations of freshwater Cyanobacteria as antimicrobial (bacteria, fungi and methicillin-resistant Staphylococcus aureus (MRSA) strains) drug resource using bioassay, NRPS (non-ribosomal polypeptide synthetase) and PKS (polyketide synthase) genes, as well as in silico approach. We have bioassayed the extracts of Phormidium CCC727, Geitlerinema CCC728, Arthrospira CCC729, Leptolyngbya CCC732, Phormidium CCC730, Phormidium CCC731 against six pathogenic bacteria comprising Gram (+ve): S. aureus including seven clinical MRSA and Enterococcus faecalis, Gram (-ve): Escherichia coli, Salmonella Typhimurium, Klebsiella pneumoniae and Shigella boydii along with non-pathogenic Enterobacter aerogenes as well as fungal strains (Cryptococcus neoformans and Candida albicans, C. krusei, C. tropicalis and Aspergillus niger) exhibiting antimicrobial potential. The NRPS and PKS genes of the target strains were also amplified and sequenced. The putative protein structures were predicted using bioinformatics approach. PKS gene expression indicated β keto-acyl synthase as one of the important active domains in the biomolecules related to antitumour and antifungal group. The simultaneous identification of the biomolecule (dihydro-2H-pyran-2-one derivative) was also inferred spectroscopically. Freshwater Cyanobacteria are prolific producers of secondary metabolite(s) that may act as the antimicrobial drug resource in addition to their much explored marine counterpart. © 2016 The Society for Applied Microbiology.

  7. An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8.

    Takahashi, Toshiya; Kimura, Yutaka; Saito, Rumiko; Nakajima, Yoshihiro; Ohmiya, Yoshihiro; Yamasaki, Kenshi; Aiba, Setsuya

    2011-12-01

    Several studies have suggested that interleukin (IL)-8 can serve as a biomarker for discrimination of skin sensitizers from nonsensitizers. We established a stable THP-1-derived IL-8 reporter cell line, THP-G8, which harbors SLO and SLR luciferase genes under the control of IL-8 and glyceraldehyde 3-phosphate dehydrogenase promoters, respectively. After 6 h treatment with chemicals, normalized SLO luciferase activity (nSLO-LA) was calculated by dividing SLO-LA by SLR-LA, and the fold induction of nSLO-LA (FInSLO-LA) was calculated by dividing nSLO-LA of chemically treated cells by that of nontreated cells. The nSLO-LA of THP-G8 cells increased in response to lipopolysaccharide (LPS) and several sensitizers. The FInSLO-LA in THP-G8 cells induced by LPS or sensitizers positively correlated with their induction of IL-8 messenger RNA in THP-1 cells. The nSLO-LA value of THP-G8 cells was significantly increased (FInSLO-LA ≥ 1.4) by 13 of the 15 sensitizers as well as by 5 of the 7 nonsensitizers. Interestingly, pretreatment with N-acetylcysteine suppressed the increase in FInSLO-LA induced by all sensitizers (inhibition index (II) ≤ 0.8) but did not suppress that induced by most of the nonsensitizers. We then evaluated the performance of this assay using values of FInSLO-LA ≥ 1.4 and II ≤ 0.8 in at least two of three independent experiments as the criteria of a sensitizer, which resulted in test accuracies of 82% for the 22 chemicals used and of 88% for the chemicals proposed by European Center for the Validation of Alternative Methods. This newly developed assay is a candidate replacement for animal tests of skin sensitization because of its accuracy, convenience, and high throughput performance.

  8. Fluorescence quenching of derivatives of anthracene by organic electron donors and acceptors in acetonitrile. Electron and proton transfer mechanism

    Mac, Marek; Najbar, Jan; Wirz, Jakob

    1995-03-01

    Fluorescence quenching of anthracene derivatives by organic electron donors (amines) and acceptors was investigated using stationary fluorescence measurements. The dependence of log( kq) on Δ Get shows Rehm-Weller-type behavior. The formation of anion radicals of anthracene, bianthryl, and 9-cyanoanthracene was detected by flash photolysis in systems containing aromatic amines (aniline, 2-bromoaniline, 4-bromoaniline, N,N-dimethylaniline, 4-bromo-N,N-dimethylaniline, N,N-diethylaniline, and 1,4-diazabicyclo[2.2.2]octane). The radical yields decreased and triplet yields increased when bromo derivatives of amines were used as donor quenchers, indicating the heavy-atom effect on spin conversion within radical pairs. The importance of the heavy-atom effect decreased when the energy gap between the charge transfer and molecular triplet states was small. The formation of separated radicals decreased when primary amines were used as quenchers which indicated the existence of an additional path of deactivation of the radical pair. The behavior of amines as quenchers of bianthryl and anthracene is compared with that of inorganic anion quenchers.

  9. Colon cancer screening

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  10. Screening Information - JSNP | LSDB Archive [Life Science Database Archive metadata

    Full Text Available List Contact us JSNP Screening Information Data detail Data name Screening Information DOI 10.18908/lsdba.nb...dc00114-003 Description of data contents Information from polymorphism screening experiments. Derived from E...the sequence for polymorphism screening Screened Position position of the polymorphism in the sequence for polymorphism screeni...ng Screened Symbol gene name related to the sequence for polymorphism screening Screened ...OMIM-ID OMIM ID related to the sequence for polymorphism screening About This Dat

  11. Screen dealing

    Barlow, J.W.

    1991-01-01

    The screen dealing system provides a facility whereby buyers and sellers of spot thermal coal can make bids and offers via the medium of the Reuters screen. A sale results when a market participant notifies his acceptance of a price to a central dealing desk. Use of the system is available to all genuine participants in the coal trade. This paper reports that it provides a focus for information and for the visible making of coal prices. For years screen trading has been used successfully to trade other commodities. At last coal is being traded electronically. It makes sense. It works. Users like it

  12. Airport Screening

    Health Physics Society Specialists in Radiation Safety Airport Screening Fact Sheet Adopted: May 2011 Photo courtesy of Dan ... a safe level. An American National Standards Institute/Health Physics Society industry standard states that the maxi- mum ...

  13. Hypertension screening

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  14. Carrier Screening

    ... How accurate is carrier screening? No test is perfect. In a small number of cases, test results ... in which an egg is removed from a woman’s ovary, fertilized in a laboratory with the man’s ...

  15. Structure-based virtual screening toward the discovery of novel inhibitors for impeding the protein-protein interaction between HIV-1 integrase and human lens epithelium-derived growth factor (LEDGF/p75).

    Panwar, Umesh; Singh, Sanjeev Kumar

    2017-10-23

    HIV-1 integrase is a unique promising component of the viral replication cycle, catalyzing the integration of reverse transcribed viral cDNA into the host cell genome. Generally, IN activity requires both viral as well as a cellular co-factor in the processing replication cycle. Among them, the human lens epithelium-derived growth factor (LEDGF/p75) represented as promising cellular co-factor which supports the viral replication by tethering IN to the chromatin. Due to its major importance in the early steps of HIV replication, the interaction between IN and LEDGF/p75 has become a pleasing target for anti-HIV drug discovery. The present study involves the finding of novel inhibitor based on the information of dimeric CCD of IN in complex with known inhibitor, which were carried out by applying a structure-based virtual screening concept with molecular docking. Additionally, Free binding energy, ADME properties, PAINS analysis, Density Functional Theory, and Enrichment Calculations were performed on selected compounds for getting a best lead molecule. On the basis of these analyses, the current study proposes top 3 compounds: Enamine-Z742267384, Maybridge-HTS02400, and Specs-AE-848/37125099 with acceptable pharmacological properties and enhanced binding affinity to inhibit the interaction between IN and LEDGF/p75. Furthermore, Simulation studies were carried out on these molecules to expose their dynamics behavior and stability. We expect that the findings obtained here could be future therapeutic agents and may provide an outline for the experimental studies to stimulate the innovative strategy for research community.

  16. Physics in Screening Environments

    Certik, Ondrej

    In the current study, we investigated atoms in screening environments like plasmas. It is common practice to extract physical data, such as temperature and electron densities, from plasma experiments. We present results that address inherent computational difficulties that arise when the screening approach is extended to include the interaction between the atomic electrons. We show that there may arise an ambiguity in the interpretation of physical properties, such as temperature and charge density, from experimental data due to the opposing effects of electron-nucleus screening and electron-electron screening. The focus of the work, however, is on the resolution of inherent computational challenges that appear in the computation of two-particle matrix elements. Those enter already at the Hartree-Fock level. Furthermore, as examples of post Hartree-Fock calculations, we show second-order Green's function results and many body perturbation theory results of second order. A self-contained derivation of all necessary equations has been included. The accuracy of the implementation of the method is established by comparing standard unscreened results for various atoms and molecules against literature for Hartree-Fock as well as Green's function and many body perturbation theory. The main results of the thesis are presented in the chapter called Screened Results, where the behavior of several atomic systems depending on electron-electron and electron-nucleus Debye screening was studied. The computer code that we have developed has been made available for anybody to use. Finally, we present and discuss results obtained for screened interactions. We also examine thoroughly the computational details of the calculations and particular implementations of the method.

  17. Luminescent screens

    Lu, C.-I.

    1982-01-01

    Luminescent screens which are useful for such purposes as intensifying screens for radiographs are comprised of a support bearing a layer of finely divided particles of a phosphor dispersed in a cross-linked polymeric matrix formed by heat-curing of a coating composition comprising an unsaturated cross-linkable polymer, a polymerizable acrylic monomer, a thermoplastic polyurethane elastomer, and a heat-activatable polymerization initiator. The phosphor layer includes voids formed by evaporation of an evaporable component which is present in the coating composition from which such layer is formed. (author)

  18. Alcohol Use Screening

    ... Depression Screening Substance Abuse Screening Alcohol Use Screening Alcohol Use Screening (AUDIT-C) - Instructions The following questions ... this tool, there is also text-only version . Alcohol Use Screening (AUDIT-C) - Manual Instructions The following ...

  19. Systematic Review of Guidelines on Peripheral Artery Disease Screening

    Ferket, Bart S.; Spronk, Sandra; Colkesen, Ersen B.; Hunink, M. G. Myriam

    2012-01-01

    BACKGROUND: Peripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed.

  20. Collisional Cooling of Light Ions by Cotrapped Heavy Atoms.

    Dutta, Sourav; Sawant, Rahul; Rangwala, S A

    2017-03-17

    We experimentally demonstrate cooling of trapped ions by collisions with cotrapped, higher-mass neutral atoms. It is shown that the lighter ^{39}K^{+} ions, created by ionizing ^{39}K atoms in a magneto-optical trap (MOT), when trapped in an ion trap and subsequently allowed to cool by collisions with ultracold, heavier ^{85}Rb atoms in a MOT, exhibit a longer trap lifetime than without the localized ^{85}Rb MOT atoms. A similar cooling of trapped ^{85}Rb^{+} ions by ultracold ^{133}Cs atoms in a MOT is also demonstrated in a different experimental configuration to validate this mechanism of ion cooling by localized and centered ultracold neutral atoms. Our results suggest that the cooling of ions by localized cold atoms holds for any mass ratio, thereby enabling studies on a wider class of atom-ion systems irrespective of their masses.

  1. New experiments on few-electron very heavy atoms

    Gould, H.

    1985-07-01

    New experiments, to test quantum electrodynamics (QED) in strong Coulomb fields and to study atomic collisions at ultrarelativistic energies, are proposed. A 0.1% measurement of the 2 2 P/sub 1/2/-2 2 S/sub 1/2/ splitting in lithium like uranium (Z=92) and the 2 3 P 0 - 2 3 S 1 splitting in heliumlike uranium is proposed as a sub 1% test of the Lamb shift in a strong Coulomb field. Measurements of the hyperfine splitting of hydrogenlike thallium (Z=81) and the g/sub j/ factor of the ground state of hydrogenlike uranium are propsed as a test of the QED contribution to the magnetic moment of an electron bound in a strong Coulomb field. Measurements of capture cross sections for ultra relativistic very heavy nuclei are proposed to look for the capture of electrons from pair production. 40 refs., 7 figs., 2 tabs

  2. Ionisation of L subshells of heavy atoms by deuteron collision

    Sokhi, R.S.; Crumpton, D.; Trautmann, D.

    1989-01-01

    L i subshell ionisation cross sections for 1.2-3.0 MeV deuteron impact on thin targets of W, Au, Pb and Bi have been measured experimentally. Measurements were made with the Birmingham University's 3MV Dynamitron accelerator and the cross sections were deduced from the emitted L X-rays. These cross sections and their ratios have been compared graphically with the ECPSSR and RHSCA models. The ECPSSR model underestimates the measured L 2 subshell cross sections but shows very good agreement with the L 3 subshell values. The RHSCA theory in general exhibits good agreement with the measured cross sections for the L 1 and L 2 subshells but overestimates the L 3 cross sections by up to 60%. (orig.)

  3. Hearing Screening

    Johnson-Curiskis, Nanette

    2012-01-01

    Hearing levels are threatened by modern life--headsets for music, rock concerts, traffic noises, etc. It is crucial we know our hearing levels so that we can draw attention to potential problems. This exercise requires that students receive a hearing screening for their benefit as well as for making the connection of hearing to listening.

  4. Vision Screening

    ... an efficient and cost-effective method to identify children with visual impairment or eye conditions that are likely to lead ... main goal of vision screening is to identify children who have or are at ... visual impairment unless treated in early childhood. Other problems that ...

  5. Synthesis and photophysical properties of indium(III) phthalocyanine derivatives

    Özceşmeci, İbrahim, E-mail: ozcesmecii@itu.edu.tr [Department of Chemistry, Technical University of Istanbul, Maslak 34469, Istanbul (Turkey); Gelir, Ali [Department of Physics, Technical University of Istanbul, Maslak 34469, Istanbul (Turkey); Gül, Ahmet [Department of Chemistry, Technical University of Istanbul, Maslak 34469, Istanbul (Turkey)

    2014-03-15

    Three chloroindium(III) phthalocyanine derivatives bearing four aromatic (naphthalene or pyrene) or aliphatic (hexylthio) groups were prepared from corresponding phthalonitrile compounds. The indium(III) phthalocyanine derivatives were characterized with elemental analyses, mass, proton nuclear magnetic resonance ({sup 1}H NMR), Fourier transform infrared spectroscopy (FT-IR) and ultraviolet–visible spectroscopy (UV–vis) techniques. Quantum yields and the energy transfer from the substituents to phthalocyanine core were examined. No energy transfer was observed for 5. The energy transfer efficiency from pyrene units to indium phthalocyanine core was calculated as 0.27 for 6. Quantum yields of all samples were very small due to heavy atom effect of indium atom in the core. It was also observed that upon binding of pyrene and naphthalene units to indium phthalocyanine as substituents, the quantum yields of indium phthalocyanine parts of 5 and 6 decreased. -- Highlights: • Three chloroindium(III) phthalocyanines were prepared and characterized. • Aggregation properties of these compounds were investigated. • The energy transfer efficiency was examined. • Quantum yield of these systems were calculated.

  6. Vision Screening

    1993-01-01

    The Visi Screen OSS-C, marketed by Vision Research Corporation, incorporates image processing technology originally developed by Marshall Space Flight Center. Its advantage in eye screening is speed. Because it requires no response from a subject, it can be used to detect eye problems in very young children. An electronic flash from a 35 millimeter camera sends light into a child's eyes, which is reflected back to the camera lens. The photorefractor then analyzes the retinal reflexes generated and produces an image of the child's eyes, which enables a trained observer to identify any defects. The device is used by pediatricians, day care centers and civic organizations that concentrate on children with special needs.

  7. Cancer Screening Considerations and Cancer Screening Uptake for Lesbian, Gay, Bisexual, and Transgender Persons.

    Ceres, Marc; Quinn, Gwendolyn P; Loscalzo, Matthew; Rice, David

    2018-02-01

    To describe the current state of cancer screening and uptake for lesbian, gay, bisexual, and transgender (LGBT) persons and to propose cancer screening considerations for LGBT persons. Current and historic published literature on cancer screening and LGBT cancer screening; published national guidelines. Despite known cancer risks for members of the LGBT community, cancer screening rates are often low, and there are gaps in screening recommendations for LGBT persons. We propose evidence-based cancer screening considerations derived from the current literature and extant cancer screening recommendations. The oncology nurse plays a key role in supporting patient preventive care and screening uptake through assessment, counseling, education, advocacy, and intervention. As oncology nurses become expert in the culturally competent care of LGBT persons, they can contribute to the improvement of quality of care and overall well-being of this health care disparity population. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials.

    Juul, Nicolai; Szallasi, Zoltan; Eklund, Aron C; Li, Qiyuan; Burrell, Rebecca A; Gerlinger, Marco; Valero, Vicente; Andreopoulou, Eleni; Esteva, Francisco J; Symmans, W Fraser; Desmedt, Christine; Haibe-Kains, Benjamin; Sotiriou, Christos; Pusztai, Lajos; Swanton, Charles

    2010-04-01

    Addition of taxanes to preoperative chemotherapy in breast cancer increases the proportion of patients who have a pathological complete response (pCR). However, a substantial proportion of patients do not respond, and the prognosis is particularly poor for patients with oestrogen-receptor (ER)/progesterone-receptor (PR)/human epidermal growth factor receptor 2 (HER2; ERBB2)-negative (triple-negative) disease who do not achieve a pCR. Reliable identification of such patients is the first step in determining who might benefit from alternative treatment regimens in clinical trials. We previously identified genes involved in mitosis or ceramide metabolism that influenced sensitivity to paclitaxel, with an RNA interference (RNAi) screen in three cancer cell lines, including a triple-negative breast-cancer cell line. Here, we assess these genes as a predictor of pCR to paclitaxel combination chemotherapy in triple-negative breast cancer. We derived a paclitaxel response metagene based on mitotic and ceramide genes identified by functional genomics studies. We used area under the curve (AUC) analysis and multivariate logistic regression to retrospectively assess the metagene in six cohorts of patients with triple-negative breast cancer treated with neoadjuvant chemotherapy; two cohorts treated with paclitaxel (n=27, 30) and four treated without paclitaxel (n=88, 28, 48, 39). The metagene was associated with pCR in paclitaxel-treated cohorts (AUC 0.79 [95% CI 0.53-0.93], 0.72 [0.48-0.90]) but not in non-paclitaxel treated cohorts (0.53 [0.31-0.77], 0.59 [0.22-0.82], 0.53 [0.36-0.71], 0.64 [0.43-0.81]). In multivariate logistic regression, the metagene was associated with pCR (OR 19.92, 2.62-151.57; p=0.0039) with paclitaxel-containing chemotherapy. The paclitaxel response metagene shows promise as a paclitaxel-specific predictor of pCR in patients with triple-negative breast cancer. The metagene is suitable for development into a reverse transcription-PCR assay, for which

  9. Spasmogenic, Spasmolytic and Chemical Screening of Cigarettes

    guloona

    The aqueous and ethanolic extracts derived from cigarettes (Morven Gold) were screened for chemicals ... Pakistan, oral cancer is the second most common cancer ... E-mail: naveedjia@yahoo.com, naveedullahpharmacist@gmail.com.

  10. Water screen

    Kutepov, A.I.; Fedotov, I.N.; Prokopov, O.I.

    1981-01-01

    The invention refers to ventilation and can be used for repair-fitting operations in a blasting-dangerous gas condition, for example, during elimination of gas-oil gushers, repair of gas-oil pipelines, equipment etc. In order to improve safety of labor, the nozzle adapters of the water collector are oriented towards each other. The collector is installed on a support with the possibility of rotating and vertical movement. The proposed screen excludes the possibility of blasting-dangerous concentrations of gases and guarantees extinguishing of the impact spark during operation of the tool.

  11. RBC Antibody Screen

    ... C Cystic Fibrosis (CF) Gene Mutations Testing Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma- ... Index of Screening Recommendations Not Listed? Not Listed? Newborn Screening Screening Tests for Infants Screening Tests for ...

  12. Mental Health Screening Center

    ... Releases & Announcements Public Service Announcements Partnering with DBSA Mental Health Screening Center These online screening tools are not ... you have any concerns, see your doctor or mental health professional. Depression Screening for Adult Depression Screening for ...

  13. Breast cancer screening

    Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

  14. Global Derivatives

    Andersen, Torben Juul

    approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk......" provides comprehensive coverage of different types of derivatives, including exchange traded contracts and over-the-counter instruments as well as real options. There is an equal emphasis on the practical application of derivatives and their actual uses in business transactions and corporate risk...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  15. Obtaining the electrostatic screening from first principles

    Shaviv, N.J.; Shaviv, G.

    2003-01-01

    We derive the electrostatic screening effect from first principles and show the basic properties of the screening process. We in particular show that under the conditions prevailing in the Sun the number of particles in the Debye sphere is of the order of unity. Consequently; fluctuations play a dominant role in the screening process. The fluctuations lead to an effective time dependent potential. Particles with low kinetic energy lose on the average energy to the plasma and vice versa with high energy particles. We derive general conditions on the screening energy and show under what conditions the Salpeter approximation is obtained. The connection between the screening and relaxation processes in the plasma is exposed

  16. Screening specifications for Gulf Coast salt domes

    Brunton, G.D.; Laughon, R.B.; McClain, W.C.

    1978-01-01

    A reconnaissance survey of the salt domes of Mississippi, Louisiana, and east Texas is being planned to identify study areas for potential sites for radioactive waste disposal. Preliminary screening specifications were derived for each of the geological evaluation criteria by application of the significant factors that will have an impact on the reconnaissance survey. The procedure for the derivation of each screening specification is discussed. The screening specifications are the official OWI values to be used for the first-cut acceptance for salt dome study areas along the Gulf Coast. The derivation of the screening specifications is illustrated by (1) a statement of the geological evaluation criterion, (2) a discussion of the pertinent factors affecting the criterion, and (3) the evaluation of the value of the specification

  17. Financial Derivatives

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded...... and inherently static, capital itself is unprecedentedly mobile, fluid and fungible. As such derivatives raise the specter of ‘financial weapons of mass destruction’....

  18. Financial Derivatives

    Janečková, Alena

    2011-01-01

    1 Abstract/ Financial derivatives The purpose of this thesis is to provide an introduction to financial derivatives which has been, from the legal perspective, described in a not satisfactory manner as quite little literature that can be found about this topic. The main objectives of this thesis are to define the term "financial derivatives" and its particular types and to analyse legal nature of these financial instruments. The last objective is to try to draft future law regulation of finan...

  19. Towards Coleoptera-specific high-throughput screening systems for compounds with ecdysone activity: development of EcR reporter assays using weevil (Anthonomus grandis)-derived cell lines and in silico analysis of ligand binding to A. grandis EcR ligand-binding pocket.

    Soin, Thomas; Iga, Masatoshi; Swevers, Luc; Rougé, Pierre; Janssen, Colin R; Smagghe, Guy

    2009-08-01

    Molting in insects is regulated by ecdysteroids and juvenile hormones. Several synthetic non-steroidal ecdysone agonists are on the market as insecticides. These ecdysone agonists are dibenzoylhydrazine (DBH) analogue compounds that manifest their toxicity via interaction with the ecdysone receptor (EcR). Of the four commercial available ecdysone agonists, three (tebufenozide, methoxyfenozide and chromafenozide) are highly lepidopteran specific, one (halofenozide) is used to control coleopteran and lepidopteran insects in turf and ornamentals. However, compared to the very high binding affinity of these DBH analogues to lepidopteran EcRs, halofenozide has a low binding affinity for coleopteran EcRs. For the discovery of ecdysone agonists that target non-lepidopteran insect groups, efficient screening systems that are based on the activation of the EcR are needed. We report here the development and evaluation of two coleopteran-specific reporter-based screening systems to discover and evaluate ecdysone agonists. The screening systems are based on the cell lines BRL-AG-3A and BRL-AG-3C that are derived from the weevil Anthonomus grandis, which can be efficiently transduced with an EcR reporter cassette for evaluation of induction of reporter activity by ecdysone agonists. We also cloned the almost full length coding sequence of EcR expressed in the cell line BRL-AG-3C and used it to make an initial in silico 3D-model of its ligand-binding pocket docked with ponasterone A and tebufenozide.

  20. Skin Cancer Screening

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  1. Screening for Cancer

    Cancer screening is checking for cancer in people who don't have symptoms. Screening tests can help doctors find and treat several types of cancer early, but cancer screening can have harms as well as benefits.

  2. Colorectal Cancer Screening

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  3. Screen time and children

    ... page: //medlineplus.gov/ency/patientinstructions/000355.htm Screen time and children To use the sharing features on ... videos is considered unhealthy screen time. Current Screen Time Guidelines Children under age 2 should have no ...

  4. Stomach (Gastric) Cancer Screening

    ... Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is screening? Go ... are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a disease in ...

  5. Novel bisstyryl derivatives of bakuchiol

    Reddy, Mallepally V; Thota, Niranjan; Sangwan, Payare L

    2010-01-01

    Novel bisstyryl derivatives of bakuchiol using Heck coupling reaction as the key step were synthesized and screened against a panel of six oral cavity pathogens for their antimicrobial activity. Four compounds (9-12) showed two to fourfold and four to eightfold better activity (MIC 0.25-16 microg...

  6. Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test

    Hayato Fukusumi

    2018-01-01

    Full Text Available Since the development of human-induced pluripotent stem cells (hiPSCs, various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs derived from hiPSCs (hiPSC-NSPCs have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo. Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue—derived NSPCs (hN-NSPCs to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.

  7. Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test.

    Fukusumi, Hayato; Handa, Yukako; Shofuda, Tomoko; Kanemura, Yonehiro

    2018-01-01

    Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo . Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue-derived NSPCs (hN-NSPCs) to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.

  8. Prenatal screening and genetics

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

  9. Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.

    Sultana, Nargis; Sarfraz, Muhammad; Tanoli, Saba Tahir; Akram, Muhammad Safwan; Sadiq, Abdul; Rashid, Umer; Tariq, Muhammad Ilyas

    2017-06-01

    Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N 1 -substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC 50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Derivative chameleons

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂ μ φ∂ μ φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂ μ φ∂ μ φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type

  11. Derivative chameleons

    Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk [Theoretical Physics, Blackett Laboratory, Imperial College London, Prince Consort Road, London, SW7 2BZ (United Kingdom)

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  12. Electricity derivatives

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  13. Assessment of an RNA interference screen-derived mitotic and ceramide pathway metagene as a predictor of response to neoadjuvant paclitaxel for primary triple-negative breast cancer: a retrospective analysis of five clinical trials

    Juul, Nicolai Stefan; Szallasi, Zoltan Imre; Eklund, Aron Charles

    2010-01-01

    -negative breast cancer. METHODS: We derived a paclitaxel response metagene based on mitotic and ceramide genes identified by functional genomics studies. We used area under the curve (AUC) analysis and multivariate logistic regression to retrospectively assess the metagene in six cohorts of patients with triple......-paclitaxel treated cohorts (0.53 [0.31-0.77], 0.59 [0.22-0.82], 0.53 [0.36-0.71], 0.64 [0.43-0.81]). In multivariate logistic regression, the metagene was associated with pCR (OR 19.92, 2.62-151.57; p=0.0039) with paclitaxel-containing chemotherapy. INTERPRETATION: The paclitaxel response metagene shows promise...... as a paclitaxel-specific predictor of pCR in patients with triple-negative breast cancer. The metagene is suitable for development into a reverse transcription-PCR assay, for which clinically relevant thresholds could be established in randomised clinical trials. These results highlight the potential...

  14. Benchmarking DFT and semi-empirical methods for a reliable and cost-efficient computational screening of benzofulvene derivatives as donor materials for small-molecule organic solar cells.

    Tortorella, Sara; Talamo, Maurizio Mastropasqua; Cardone, Antonio; Pastore, Mariachiara; De Angelis, Filippo

    2016-02-24

    A systematic computational investigation on the optical properties of a group of novel benzofulvene derivatives (Martinelli 2014 Org. Lett. 16 3424-7), proposed as possible donor materials in small molecule organic photovoltaic (smOPV) devices, is presented. A benchmark evaluation against experimental results on the accuracy of different exchange and correlation functionals and semi-empirical methods in predicting both reliable ground state equilibrium geometries and electronic absorption spectra is carried out. The benchmark of the geometry optimization level indicated that the best agreement with x-ray data is achieved by using the B3LYP functional. Concerning the optical gap prediction, we found that, among the employed functionals, MPW1K provides the most accurate excitation energies over the entire set of benzofulvenes. Similarly reliable results were also obtained for range-separated hybrid functionals (CAM-B3LYP and wB97XD) and for global hybrid methods incorporating a large amount of non-local exchange (M06-2X and M06-HF). Density functional theory (DFT) hybrids with a moderate (about 20-30%) extent of Hartree-Fock exchange (HFexc) (PBE0, B3LYP and M06) were also found to deliver HOMO-LUMO energy gaps which compare well with the experimental absorption maxima, thus representing a valuable alternative for a prompt and predictive estimation of the optical gap. The possibility of using completely semi-empirical approaches (AM1/ZINDO) is also discussed.

  15. Benchmarking DFT and semi-empirical methods for a reliable and cost-efficient computational screening of benzofulvene derivatives as donor materials for small-molecule organic solar cells

    Tortorella, Sara; Talamo, Maurizio Mastropasqua; Cardone, Antonio; Pastore, Mariachiara; De Angelis, Filippo

    2016-01-01

    A systematic computational investigation on the optical properties of a group of novel benzofulvene derivatives (Martinelli 2014 Org. Lett. 16 3424–7), proposed as possible donor materials in small molecule organic photovoltaic (smOPV) devices, is presented. A benchmark evaluation against experimental results on the accuracy of different exchange and correlation functionals and semi-empirical methods in predicting both reliable ground state equilibrium geometries and electronic absorption spectra is carried out. The benchmark of the geometry optimization level indicated that the best agreement with x-ray data is achieved by using the B3LYP functional. Concerning the optical gap prediction, we found that, among the employed functionals, MPW1K provides the most accurate excitation energies over the entire set of benzofulvenes. Similarly reliable results were also obtained for range-separated hybrid functionals (CAM-B3LYP and wB97XD) and for global hybrid methods incorporating a large amount of non-local exchange (M06-2X and M06-HF). Density functional theory (DFT) hybrids with a moderate (about 20–30%) extent of Hartree–Fock exchange (HFexc) (PBE0, B3LYP and M06) were also found to deliver HOMO–LUMO energy gaps which compare well with the experimental absorption maxima, thus representing a valuable alternative for a prompt and predictive estimation of the optical gap. The possibility of using completely semi-empirical approaches (AM1/ZINDO) is also discussed. (paper)

  16. Acoustic transfer of protein crystals from agarose pedestals to micromeshes for high-throughput screening

    Cuttitta, Christina M.; Ericson, Daniel L.; Scalia, Alexander; Roessler, Christian G.; Teplitsky, Ella; Joshi, Karan; Campos, Olven; Agarwal, Rakhi; Allaire, Marc; Orville, Allen M.; Sweet, Robert M.; Soares, Alexei S.

    2015-01-01

    An acoustic high-throughput screening method is described for harvesting protein crystals and combining the protein crystals with chemicals such as a fragment library. Acoustic droplet ejection (ADE) is an emerging technology with broad applications in serial crystallography such as growing, improving and manipulating protein crystals. One application of this technology is to gently transfer crystals onto MiTeGen micromeshes with minimal solvent. Once mounted on a micromesh, each crystal can be combined with different chemicals such as crystal-improving additives or a fragment library. Acoustic crystal mounting is fast (2.33 transfers s −1 ) and all transfers occur in a sealed environment that is in vapor equilibrium with the mother liquor. Here, a system is presented to retain crystals near the ejection point and away from the inaccessible dead volume at the bottom of the well by placing the crystals on a concave agarose pedestal (CAP) with the same chemical composition as the crystal mother liquor. The bowl-shaped CAP is impenetrable to crystals. Consequently, gravity will gently move the crystals into the optimal location for acoustic ejection. It is demonstrated that an agarose pedestal of this type is compatible with most commercially available crystallization conditions and that protein crystals are readily transferred from the agarose pedestal onto micromeshes with no loss in diffraction quality. It is also shown that crystals can be grown directly on CAPs, which avoids the need to transfer the crystals from the hanging drop to a CAP. This technology has been used to combine thermolysin and lysozyme crystals with an assortment of anomalously scattering heavy atoms. The results point towards a fast nanolitre method for crystal mounting and high-throughput screening

  17. Acoustic transfer of protein crystals from agarose pedestals to micromeshes for high-throughput screening

    Cuttitta, Christina M. [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); The City University of New York, 2800 Victory Boulevard, Staten Island, NY 10314 (United States); Ericson, Daniel L. [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); University at Buffalo, SUNY, 12 Capen Hall, Buffalo, NY 14260 (United States); Scalia, Alexander [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 11973-5000 (United States); Roessler, Christian G. [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Teplitsky, Ella [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Stony Brook University, Stony Brook, NY 11794-5215 (United States); Joshi, Karan [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); PEC University of Technology, Chandigarh (India); Campos, Olven [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33414 (United States); Agarwal, Rakhi; Allaire, Marc [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Orville, Allen M. [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Sweet, Robert M.; Soares, Alexei S., E-mail: soares@bnl.gov [Brookhaven National Laboratory, Upton, NY 11973-5000 (United States)

    2015-01-01

    An acoustic high-throughput screening method is described for harvesting protein crystals and combining the protein crystals with chemicals such as a fragment library. Acoustic droplet ejection (ADE) is an emerging technology with broad applications in serial crystallography such as growing, improving and manipulating protein crystals. One application of this technology is to gently transfer crystals onto MiTeGen micromeshes with minimal solvent. Once mounted on a micromesh, each crystal can be combined with different chemicals such as crystal-improving additives or a fragment library. Acoustic crystal mounting is fast (2.33 transfers s{sup −1}) and all transfers occur in a sealed environment that is in vapor equilibrium with the mother liquor. Here, a system is presented to retain crystals near the ejection point and away from the inaccessible dead volume at the bottom of the well by placing the crystals on a concave agarose pedestal (CAP) with the same chemical composition as the crystal mother liquor. The bowl-shaped CAP is impenetrable to crystals. Consequently, gravity will gently move the crystals into the optimal location for acoustic ejection. It is demonstrated that an agarose pedestal of this type is compatible with most commercially available crystallization conditions and that protein crystals are readily transferred from the agarose pedestal onto micromeshes with no loss in diffraction quality. It is also shown that crystals can be grown directly on CAPs, which avoids the need to transfer the crystals from the hanging drop to a CAP. This technology has been used to combine thermolysin and lysozyme crystals with an assortment of anomalously scattering heavy atoms. The results point towards a fast nanolitre method for crystal mounting and high-throughput screening.

  18. Fast and simple screening for the simultaneous analysis of seven metabolites derived from five volatile organic compounds in human urine using on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry.

    Chiang, Wen-Chieh; Chen, Chao-Yu; Lee, Ting-Chen; Lee, Hui-Ling; Lin, Yu-Wen

    2015-01-01

    Recently, the International Agency for Research on cancer classified outdoor air pollution and particulate matter from outdoor air pollution as carcinogenic to humans (IARC Group 1), based on sufficient evidence of carcinogenicity in humans and experimental animals and strong mechanistic evidence. In particular, a wide variety of volatile organic compounds (VOCs) are volatized or released into the atmosphere and can become ubiquitous, as they originate from many different natural and anthropogenic sources, such as paints, pesticides, vehicle exhausts, cooking fumes, and tobacco smoke. Humans may be exposed to VOCs through inhalation, ingestion, or dermal contact, which may increase the risk of leukemia, birth defects, neurocognitive impairment, and cancer. Therefore, the focus of this study was the development of a simple, effective and rapid sample preparation method for the simultaneous determination of seven metabolites (6 mercaptic acids+t,t-muconic acid) derived from five VOCs (acrylamide, 1,3-butadiene, acrylonitrile, benzene, and xylene) in human urine by using automated on-line solid-phase extraction (SPE) coupled with liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). An aliquot of each diluted urinary sample was directly injected into an autosampler through a trap column to reduce contamination, and then the retained target compounds were eluted by back-flush mode into an analytical column for separation. Negative electrospray ionization tandem mass spectrometry was utilized for quantification. The coefficients of correlation (r(2)) for the calibration curves were greater than 0.995. Reproducibility was assessed by the precision and accuracy of intra-day and inter-day precision, which showed results for coefficient of variation (CV) that were low 0.9 to 6.6% and 3.7 to 8.5%, respectively, and results for recovery that ranged from 90.8 to 108.9% and 92.1 to 107.7%, respectively. The limits of detection (LOD) and limits of

  19. Screening for Glaucoma

    Understanding Task Force Recommendations Screening for Glaucoma The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Glaucoma . This final recommendation statement ...

  20. Liver (Hepatocellular) Cancer Screening

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  1. Hearing Loss: Screening Newborns

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table ... deafness, which account for most cases. Screening Newborns' Hearing Now Standard In 1993, children born in the ...

  2. Cervical Cancer Screening

    ... Cancer found early may be easier to treat. Cervical cancer screening is usually part of a woman's health ... may do more tests, such as a biopsy. Cervical cancer screening has risks. The results can sometimes be ...

  3. Screening for Cervical Cancer

    Understanding Task Force Recommendations Screening for Cervical Cancer The U.S. Preventive Services Task Force (Task Force) has issued final recommendations on Screening for Cervical Cancer . These recommendations are for women ...

  4. Between Stage and Screen

    Tornqvist, Egil

    1996-01-01

    Ingmar Bergman is worldwide known as a film and stage director. Yet no-one has attempted to compare his stage and screen activities. In Between stage and screen Egil Tornqvist examines formal and thematical correspondences and differences between a number of Bergman's stage, screen, and radio

  5. Screening for colorectal cancer.

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.

  6. Optimal screening and donor management in a public stool bank.

    Kazerouni, Abbas; Burgess, James; Burns, Laura J; Wein, Lawrence M

    2015-12-17

    Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.

  7. Screen Practice in Curating

    Toft, Tanya Søndergaard

    2014-01-01

    During the past one and a half decade, a curatorial orientation towards "screen practice" has expanded the moving image and digital art into the public domain, exploring alternative artistic uses of the screen. The emergence of urban LED screens in the late 1990s provided a new venue that allowed...... for digital art to expand into public space. It also offered a political point of departure, inviting for confrontation with the Spectacle and with the politics and ideology of the screen as a mass communication medium that instrumentalized spectator positions. In this article I propose that screen practice...... to the dispositif of screen practice in curating, resulting in a medium-based curatorial discourse. With reference to the nomadic exhibition project Nordic Outbreak that I co-curated with Nina Colosi in 2013 and 2014, I suggest that the topos of the defined visual display area, frequently still known as "the screen...

  8. Screening of recombinant inbred lines for salinity tolerance in bread ...

    Screening a large number of plants for salinity tolerance is not easy, therefore this investigation was performed to evaluate and screen 186 F8 recombinant inbred lines (RILs) derived from a cross between Superhead#2 (Super Seri) and Roshan wheat varieties for salinity tolerance. All the individuals were evaluated under ...

  9. Thermally activated delayed fluorescence of fluorescein derivative for time-resolved and confocal fluorescence imaging.

    Xiong, Xiaoqing; Song, Fengling; Wang, Jingyun; Zhang, Yukang; Xue, Yingying; Sun, Liangliang; Jiang, Na; Gao, Pan; Tian, Lu; Peng, Xiaojun

    2014-07-09

    Compared with fluorescence imaging utilizing fluorophores whose lifetimes are in the order of nanoseconds, time-resolved fluorescence microscopy has more advantages in monitoring target fluorescence. In this work, compound DCF-MPYM, which is based on a fluorescein derivative, showed long-lived luminescence (22.11 μs in deaerated ethanol) and was used in time-resolved fluorescence imaging in living cells. Both nanosecond time-resolved transient difference absorption spectra and time-correlated single-photon counting (TCSPC) were employed to explain the long lifetime of the compound, which is rare in pure organic fluorophores without rare earth metals and heavy atoms. A mechanism of thermally activated delayed fluorescence (TADF) that considers the long wavelength fluorescence, large Stokes shift, and long-lived triplet state of DCF-MPYM was proposed. The energy gap (ΔEST) of DCF-MPYM between the singlet and triplet state was determined to be 28.36 meV by the decay rate of DF as a function of temperature. The ΔE(ST) was small enough to allow efficient intersystem crossing (ISC) and reverse ISC, leading to efficient TADF at room temperature. The straightforward synthesis of DCF-MPYM and wide availability of its starting materials contribute to the excellent potential of the compound to replace luminescent lanthanide complexes in future time-resolved imaging technologies.

  10. Imaging characteristics of different mammographic screens.

    Kuhn, H; Knüpfer, W

    1992-01-01

    A study of mammography systems with green-emitting screens was conducted to determine how the image quality parameters (apart from dose requirement), such as modulation transfer function (MTF) and Wiener spectrum (WS), depend on the dye content of the compound and coating weight of the screen. In addition, the contribution to total noise of the individual components, i.e., film, screen, and quantum noise, was studied. The quantities derived from MTF and WS, namely detective quantum efficiency (DQE) and noise equivalent quanta (NEQ), were also investigated in regard to their dose dependency. It can be demonstrated that the MTF of the screens becomes more favorable when the dye content is increased, while noise is not significantly affected. This suggests the use of a mammography screen capable of greater detail recognition, requiring at least double the dose of today's conventional systems with approximately 80 microGy system dose. On the other hand, the manufacture of a screen with about 60% of the dose of the conventional system is possible with very little loss in image quality. For the systems in common use today (80 microGy), quantum noise represents a considerable share of the total noise at low spatial frequencies, whereas in high spatial frequencies, the graininess of the film dominates quantum noise and screen structure.

  11. Automated Groundwater Screening

    Taylor, Glenn A.; Collard, Leonard B.

    2005-01-01

    The Automated Intruder Analysis has been extended to include an Automated Ground Water Screening option. This option screens 825 radionuclides while rigorously applying the National Council on Radiation Protection (NCRP) methodology. An extension to that methodology is presented to give a more realistic screening factor for those radionuclides which have significant daughters. The extension has the promise of reducing the number of radionuclides which must be tracked by the customer. By combining the Automated Intruder Analysis with the Automated Groundwater Screening a consistent set of assumptions and databases is used. A method is proposed to eliminate trigger values by performing rigorous calculation of the screening factor thereby reducing the number of radionuclides sent to further analysis. Using the same problem definitions as in previous groundwater screenings, the automated groundwater screening found one additional nuclide, Ge-68, which failed the screening. It also found that 18 of the 57 radionuclides contained in NCRP Table 3.1 failed the screening. This report describes the automated groundwater screening computer application

  12. Screening for abdominalt aortaaneurisme

    Lindholt, J S; Juul, Svend; Henneberg, E W

    1997-01-01

    rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...... on uncertain assumptions concerning prevalence, incidence and risk of rupture. Therefore a randomized trial screening of 65-73 year old males is taking place in the County of Viborg in Denmark. Udgivelsesdato: 1997-Mar-24...

  13. Cathode ray tube screens

    Cockayne, B.; Robbins, D.J.; Glasper, J.L.

    1982-01-01

    An improved cathode ray tube screen is described which consists of a single- or a poly-crystalline slice of a material such as yttrium aluminium garnet in which dopants such as Tb 3 + , Eu 3 + , Ce 3 + or Tm 3 + are ion implanted to different depths or in different areas of the screen. Annealing the screen removes lattice damage caused by the ion implanting and assists the diffusion of the dopant into the crystal. (U.K.)

  14. Colorectal Cancer Screening

    Quintero, Enrique; Saito, Yutaka; Hassan, Cessare; Senore, Carlo

    2012-01-01

    Colorectal cancer, which is the leading cancer in Singapore, can be prevented by increased use of screening and polypectomy. A range of screening strategies such as stool-based tests, flexible sigmoidoscopy, colonoscopy and computed tomography colonography are available, each with different strengths and limitations. Primary care physicians should discuss appropriate screening modalities with their patients, tailored to their individual needs. Physicians, patients and the government should wo...

  15. Colorectal cancer screening

    Plumb, A. A.; Halligan, S.

    2015-01-01

    Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. In addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can...

  16. In-bead screening

    2013-01-01

    The present invention relates to screening of one-bead-one-compound (OBOC) combinatorial libraries which is useful for the discovery of compounds displaying molecular interactions with a biological or a physicochemical system, such as substrates and inhibitors of enzymes and the like. The invention...... provides a method for screening a library of compounds for their interaction with a physico- chemical or biological system and a corresponding kit for performing the method of screening a one-bead-one-compound library of compounds....

  17. Screening for colorectal cancer

    Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  18. [Overdiagnosis in cancer screening].

    Cervera Deval, J; Sentís Crivillé, M; Zulueta, J J

    2015-01-01

    In screening programs, overdiagnosis is defined as the detection of a disease that would have gone undetected without screening when that disease would not have resulted in morbimortality and was treated unnecessarily. Overdiagnosis is a bias inherent in screening and an undesired effect of secondary prevention and improved sensitivity of diagnostic techniques. It is difficult to discriminate a priori between clinically relevant diagnoses and those in which treatment is unnecessary. To minimize the effects of overdiagnosis, screening should be done in patients at risk. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  19. Cancer screening guidelines.

    Zoorob, R; Anderson, R; Cefalu, C; Sidani, M

    2001-03-15

    Numerous medical organizations have developed cancer screening guidelines. Faced with the broad, and sometimes conflicting, range of recommendations for cancer screening, family physicians must determine the most reasonable and up-to-date method of screening. Major medical organizations have generally achieved consensus on screening guidelines for breast, cervical and colorectal cancer. For breast cancer screening in women ages 50 to 70, clinical breast examination and mammography are generally recommended every one or two years, depending on the medical organization. For cervical cancer screening, most organizations recommend a Papanicolaou test and pelvic examination at least every three years in patients between 20 and 65 years of age. Annual fecal occult blood testing along with flexible sigmoidoscopy at five-year to 10-year intervals is the standard recommendation for colorectal cancer screening in patients older than 50 years. Screening for prostate cancer remains a matter of debate. Some organizations recommend digital rectal examination and a serum prostate-specific antigen test for men older than 50 years, while others do not. In the absence of compelling evidence to indicate a high risk of endometrial cancer, lung cancer, oral cancer and ovarian cancer, almost no medical organizations have developed cancer screening guidelines for these types of cancer.

  20. Obesity Prevention and Screening.

    Mackey, Eleanor R; Olson, Alexandra; DiFazio, Marc; Cassidy, Omni

    2016-03-01

    Obesity is widespread, associated with several physical and psychosocial comorbidities, and is difficult to treat. Prevention of obesity across the lifespan is critical to improving the health of individuals and society. Screening and prevention efforts in primary care are an important step in addressing the obesity epidemic. Each period of human development is associated with unique risks, challenges, and opportunities for prevention and intervention. Screening tools for overweight/obesity, although imperfect, are quick and easy to administer. Screening should be conducted at every primary care visit and tracked longitudinally. Screening tools and cutoffs for overweight and obesity vary by age group. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. ScreenOS Cookbook

    Brunner, Stefan; Delcourt, David

    2008-01-01

    In the only book that completely covers ScreenOS, six key members of Juniper Network's ScreenOS development team help you troubleshoot secure networks using ScreenOS firewall appliances. Over 200 recipes address a wide range of security issues, provide step-by-step solutions, and include discussions of why the recipes work, so you can easily set up and keep ScreenOS systems on track. The easy-to-follow format enables you to find the topic and specific recipe you need right away.

  2. Mammography screening in Denmark

    Vejborg, Ilse; Mikkelsen, Ellen Margrethe; Garne, Jens Peter

    2011-01-01

    Mammography screening is offered healthy women, and a high standard on professional and organizational level is mandatory not only in the screening programme but even in the diagnostic work-up and treatment. The main goal is to achieve a substantial reduction in disease specific mortality......, but it is not possible to evaluate the effect on mortality until several years later, and continuously monitoring of the quality of all aspects of a screening programme is necessary. Based on other European guidelines, 11 quality indicators have been defined, and guidelines concerning organizational requirements...... for a Danish screening programme as well as recommendations for the radiographic and radiological work have been drawn up....

  3. Analyzing Screening Policies for Childhood Obesity

    Yang, Yan; Goldhaber-Fiebert, Jeremy D.; Wein, Lawrence M.

    2013-01-01

    Due to the health and economic costs of childhood obesity, coupled with studies suggesting the benefits of comprehensive (dietary, physical activity and behavioral counseling) intervention, the United States Preventive Services Task Force recently recommended childhood screening and intervention for obesity beginning at age six. Using a longitudinal data set consisting of the body mass index of 3164 children up to age 18 and another longitudinal data set containing the body mass index at ages 18 and 40 and the presence or absence of disease (hypertension and diabetes) at age 40 for 747 people, we formulate and numerically solve – separately for boys and girls – a dynamic programming problem for the optimal biennial (i.e., at ages 2, 4, …, 16) obesity screening thresholds. Unlike most screening problem formulations, we take a societal viewpoint, where the state of the system at each age is the population-wide probability density function of the body mass index. Compared to the biennial version of the task force’s recommendation, the screening thresholds derived from the dynamic program achieve a relative reduction in disease prevalence of 3% at the same screening (and treatment) cost, or – due to the flatness of the disease vs. screening tradeoff curve – achieves the same disease prevalence at a 28% relative reduction in cost. Compared to the task force’s policy, which uses the 95th percentile of body mass index (from cross-sectional growth charts tabulated by the Centers for Disease Control and Prevention) as the screening threshold for each age, the dynamic programming policy treats mostly 16 year olds (including many who are not obese) and very few males under 14 years old. While our results suggest that adult hypertension and diabetes are minimized by focusing childhood obesity screening and treatment on older adolescents, the shortcomings in the available data and the narrowness of the medical outcomes considered prevent us from making a

  4. Screening Obesity by Direct and Derived Anthropometric Indices ...

    Background: The available information regarding the obesity pattern of the undergraduate female students of Kolkata is inadequate, though there are several reports which indicate the complications and/or awful consequences of obesity on female health particularly, during the reproductive years. Aim: The present ...

  5. Screening of in vitro derived mutants of banana against nematodes ...

    The rest of the mutants namely Ro Im V4 6-1-2 and Si Im V4 6-2-5 were found to be susceptible to nematodes. The resistant and moderately resistant mutants of banana could be further used in breeding programmes as well as being recognized as potential cultivars of commerce. Key words: Banana, nematode, resistance, ...

  6. Screening Obesity by Direct and Derived Anthropometric Indices ...

    while physical efficiency parameters were physical fitness index, VO2max, energy expenditure and anaerobic power ... Keywords: Anthropometry, Blood pressure, Body mass index, Conicity index, Obesity, Physical fitness, ..... and Psychology.

  7. International Cancer Screening Network

    The International Cancer Screening Network promotes evidence-based cancer screening implementation and evaluation with cooperation from multilateral organizations around the globe. Learn more about how ICSN aims to reduce the global burden of cancer by supporting research and international collaboration.

  8. Touch screens go optical

    Hanson, Steen Grüner; Jakobsen, Michael Linde; Pedersen, Henrik Chresten

    2012-01-01

    A simple optical implementation of a touch screen is made possible by disrupting the total internal reflection in a 2D waveguide.......A simple optical implementation of a touch screen is made possible by disrupting the total internal reflection in a 2D waveguide....

  9. EIA screening in Denmark

    Nielsen, Eskild Holm; Christensen, Per; Kørnøv, Lone

    2005-01-01

    The article points out that EIA screening is effectively a regulatory instrument and it can be a cost-effective instrument with environmental benefits.......The article points out that EIA screening is effectively a regulatory instrument and it can be a cost-effective instrument with environmental benefits....

  10. Substance Abuse Screening

    ... information is collected, stored or sent over the Internet. To ensure complete privacy, exit your web browser after completing this screening. ... information is collected, stored or sent over the Internet. To ensure complete privacy, exit your web browser after completing this screening. ...

  11. Screen-film mammography

    Logan, W.W.; Janus, J.A.

    1987-01-01

    The development of screen-film mammography has resulted in the re-emergence of confidence, rather than fear, in mammography. When screen-film mammography is performed with state-of-the-art dedicated equipment utilizing vigorous breast compression and a ''soft'' x-ray beam for improved contrast, screen-film images are equivalent or superior to those of reduced-dose xeromammography and superior to those of nonscreen film mammography. Technological aids for conversion from xeromammographic or nonscreen film mammographic techniques to screen-film techniques have been described. Screen-film mammography should not be attempted until dedicated equipment has been obtained and the importance of vigorous compression has been understood

  12. Molecular HIV screening.

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  13. Screening for abdominalt aortaaneurisme

    Lindholt, Jes Sanddal; Juul, Søren; Henneberg, E W

    1997-01-01

    In spite of increasing number of elective resections of abdominal aortic aneurysms (AAA) the mortality or ruptured AAA is increasing. The advantages of elective operations are obvious; the lethality is 2-6% while the lethality of ruptured AAA is 75-95%. However, AAA seldom causes symptoms before...... rupture. Ultrasonographic screening for AAA takes 10 minutes per scan, and the sensitivity and specificity are high. Ultrasonographic screening for AAA is a reliable, safe and inexpensive method for screening, and screening for AAA is discussed worldwide. One point four percent of deaths among men from 65...... to 80 year of age are caused by ruptured AAA. Screening men over 65 for AAA can theoretically prevent a substantial number of deaths. Our calculations predict one prevented AAA-death per 200-300 scans for a cost of about 4000 DKK per saved year of life. However, cost-benefit analyses are based...

  14. Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures

    McLean, Larry R.; Zhang, Ying; Degnen, William; Peppard, Jane; Cabel, Dasha; Zou, Chao; Tsay, Joseph T.; Subramaniam, Arun; Vaz, Roy J.; Li, Yi (Sanofi)

    2010-10-28

    Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by virtual screening, biochemical, and X-ray crystallographic studies. X-ray structures showed that 1 and 2 bind to DHODH as predicted by virtual screening, but 3 and 4 were found to be structurally different from the corresponding compounds initially identified by virtual screening.

  15. Screening for skin cancer.

    Helfand, M; Mahon, S M; Eden, K B; Frame, P S; Orleans, C T

    2001-04-01

    Malignant melanoma is often lethal, and its incidence in the United States has increased rapidly over the past 2 decades. Nonmelanoma skin cancer is seldom lethal, but, if advanced, can cause severe disfigurement and morbidity. Early detection and treatment of melanoma might reduce mortality, while early detection and treatment of nonmelanoma skin cancer might prevent major disfigurement and to a lesser extent prevent mortality. Current recommendations from professional societies regarding screening for skin cancer vary. To examine published data on the effectiveness of routine screening for skin cancer by a primary care provider, as part of an assessment for the U.S. Preventive Services Task Force. We searched the MEDLINE database for papers published between 1994 and June 1999, using search terms for screening, physical examination, morbidity, and skin neoplasms. For information on accuracy of screening tests, we used the search terms sensitivity and specificity. We identified the most important studies from before 1994 from the Guide to Clinical Preventive Services, second edition, and from high-quality reviews. We used reference lists and expert recommendations to locate additional articles. Two reviewers independently reviewed a subset of 500 abstracts. Once consistency was established, the remainder were reviewed by one reviewer. We included studies if they contained data on yield of screening, screening tests, risk factors, risk assessment, effectiveness of early detection, or cost effectiveness. We abstracted the following descriptive information from full-text published studies of screening and recorded it in an electronic database: type of screening study, study design, setting, population, patient recruitment, screening test description, examiner, advertising targeted at high-risk groups or not targeted, reported risk factors of participants, and procedure for referrals. We also abstracted the yield of screening data including probabilities and numbers

  16. Synthesis and Antimicrobial Activity of Some New Formazan Derivatives

    S. I. Marjadi

    2009-01-01

    Full Text Available A series of new substituted formazan derivatives has been synthesized from corresponding aryl diazonium chloride and Schiff base in pyridine. The synthesized compounds were identified by spectral studies and screened for their antimicrobial activities.

  17. Generation and purification of human stem cell-derived cardiomyocytes

    Schwach, Verena; Passier, Robert

    2016-01-01

    © 2016 International Society of Differentiation Efficient and reproducible generation and purification of human stem cell-derived cardiomyocytes (CMs) is crucial for regenerative medicine, disease modeling, drug screening and study of developmental events during cardiac specification. Established

  18. The West Midlands breast cancer screening status algorithm - methodology and use as an audit tool.

    Lawrence, Gill; Kearins, Olive; O'Sullivan, Emma; Tappenden, Nancy; Wallis, Matthew; Walton, Jackie

    2005-01-01

    To illustrate the ability of the West Midlands breast screening status algorithm to assign a screening status to women with malignant breast cancer, and its uses as a quality assurance and audit tool. Breast cancers diagnosed between the introduction of the National Health Service [NHS] Breast Screening Programme and 31 March 2001 were obtained from the West Midlands Cancer Intelligence Unit (WMCIU). Screen-detected tumours were identified via breast screening units, and the remaining cancers were assigned to one of eight screening status categories. Multiple primaries and recurrences were excluded. A screening status was assigned to 14,680 women (96% of the cohort examined), 110 cancers were not registered at the WMCIU and the cohort included 120 screen-detected recurrences. The West Midlands breast screening status algorithm is a robust simple tool which can be used to derive data to evaluate the efficacy and impact of the NHS Breast Screening Programme.

  19. Test equality between two binary screening tests with a confirmatory procedure restricted on screen positives.

    Lui, Kung-Jong; Chang, Kuang-Chao

    2015-01-01

    In studies of screening accuracy, we may commonly encounter the data in which a confirmatory procedure is administered to only those subjects with screen positives for ethical concerns. We focus our discussion on simultaneously testing equality of sensitivity and specificity between two binary screening tests when only subjects with screen positives receive the confirmatory procedure. We develop four asymptotic test procedures and one exact test procedure. We derive sample size calculation formula for a desired power of detecting a difference at a given nominal [Formula: see text]-level. We employ Monte Carlo simulation to evaluate the performance of these test procedures and the accuracy of the sample size calculation formula developed here in a variety of situations. Finally, we use the data obtained from a study of the prostate-specific-antigen test and digital rectal examination test on 949 Black men to illustrate the practical use of these test procedures and the sample size calculation formula.

  20. [Breast cancer screening in Austria: Key figures, age limits, screening intervals and evidence].

    Jeitler, Klaus; Semlitsch, Thomas; Posch, Nicole; Siebenhofer, Andrea; Horvath, Karl

    2015-01-01

    In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged ≥ 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected. Copyright © 2015

  1. Preimplantation genetic screening.

    Harper, Joyce C

    2018-03-01

    Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.

  2. Screening sensitivity theory

    Oblow, E.M.; Perey, F.G.

    1984-01-01

    A comprehensive rigorous theory is developed for screening sensitivity coefficients in largescale modeling applications. The theory uses Bayesian inference and group theory to establish a probabilistic framework for solving an underdetermined system of linear equations. The underdetermined problem is directly related to statistical screening sensitivity theory as developed in recent years. Several examples of the new approach to screening are worked out in detail and comparisons are made with statistical approaches to the problem. The drawbacks of these latter methods are discussed at some length

  3. Risks of Colorectal Cancer Screening

    ... Genetics of Colorectal Cancer Colorectal Cancer Screening Research Colorectal Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Colorectal Cancer Key Points Colorectal cancer is a disease in ...

  4. Cervical cancer - screening and prevention

    Cancer cervix - screening; HPV - cervical cancer screening; Dysplasia - cervical cancer screening; Cervical cancer - HPV vaccine ... Almost all cervical cancers are caused by HPV (human papilloma virus). HPV is a common virus that spreads through sexual contact. Certain ...

  5. Prostate Cancer Screening

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  6. SCREENING FOR CERVICAL CANCER

    Enrique

    Cervical cancer remains a major health concern worldwide, especially in devel- ... Important aspects of cervical cancer screening include the age at which .... High-risk types HPV (16,18) are impli- cated in the pathogenesis of cervical cancer.

  7. Breast Cancer Screening

    Altaf, Fadwa J.

    2004-01-01

    Breast cancer is a very common health problem in Saudi females that can be reduced by early detection through introducing breast cancer screening. Literature review reveals significant reduction in breast cancer incidence and outcome after the beginning of breast cancer screening. The objectives of this article are to highlight the significance of breast cancer screening in different international societies and to write the major guidelines of breast cancer screening in relation to other departments involved with more emphasis on the Pathology Department guidelines in tissue handling, diagnostic criteria and significance of the diagnosis. This article summaries and acknowledges major work carried out before, and recommends similar modified work in order to meet the requirement for the Saudi society. (author)

  8. Urine drug screen

    Drug screen - urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence may indicate that you recently used these drugs. Some drugs may remain in your system for ...

  9. Breast cancer screening

    Vandenbroucke, A.

    1987-01-01

    Many studies have shown that breast cancer screening is able to reduce breast cancer mortality, including the HIP study, the Swedish Trial and the Netherlands studies. Mammography is considered as the most effective method for breast cancer screening but it might be unfeasible for some reasons: - the population acceptability of the method might be low. Indeed, most populations of the South of Europe are less compliant to mass screening than populations of the North of Europe; - the medical equipment and personnel - radiologists and pathologists - might be insufficient; - it might be too costly for the National Health Service, specially where the incidence rate of breast cancer is relatively low (i.e. Greece, Portugal). The validity of screening tests is judged by their sensitivity and their specificity

  10. Neonatal cystic fibrosis screening test

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  11. Lung cancer screening: Update

    Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

    2015-09-15

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

  12. Lung cancer screening: Update

    Kim, Hyea Young

    2015-01-01

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

  13. Pharmacological screening technologies for venom peptide discovery.

    Prashanth, Jutty Rajan; Hasaballah, Nojod; Vetter, Irina

    2017-12-01

    Venomous animals occupy one of the most successful evolutionary niches and occur on nearly every continent. They deliver venoms via biting and stinging apparatuses with the aim to rapidly incapacitate prey and deter predators. This has led to the evolution of venom components that act at a number of biological targets - including ion channels, G-protein coupled receptors, transporters and enzymes - with exquisite selectivity and potency, making venom-derived components attractive pharmacological tool compounds and drug leads. In recent years, plate-based pharmacological screening approaches have been introduced to accelerate venom-derived drug discovery. A range of assays are amenable to this purpose, including high-throughput electrophysiology, fluorescence-based functional and binding assays. However, despite these technological advances, the traditional activity-guided fractionation approach is time-consuming and resource-intensive. The combination of screening techniques suitable for miniaturization with sequence-based discovery approaches - supported by advanced proteomics, mass spectrometry, chromatography as well as synthesis and expression techniques - promises to further improve venom peptide discovery. Here, we discuss practical aspects of establishing a pipeline for venom peptide drug discovery with a particular emphasis on pharmacology and pharmacological screening approaches. This article is part of the Special Issue entitled 'Venom-derived Peptides as Pharmacological Tools.' Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Behavioral Screening for Toxicology | Science Inventory | US ...

    Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols used in pharmacology, toxicology, and psychology. Although there is a range of protocols in use today, all focus on detailed observations and specific tests of reflexes and responses. Several neurological functions are typically assessed, including autonomic, neuromuscular, and sensory, as well as levels of activity and excitability. The tests have been shown to be valid in detecting expected effects of known neurotoxicants, and reliable and reproducible whn compared across laboratories. Regardless of the specific protocol used, proper conduct and statistical analyses of the data are critical. Interpretation is based on the information from individual end points as well as the profile, or pattern, of effects observed. As long as continual refinements are made, behavioral screening methods will continue to be important tools with which to protect human health in the future.autonomic function; behavior; behavioral phenotypes; behavioral toxicity; excitability; functional observational battery ; motor activity; mouse; neuromuscular function; positive controls; rat; screening battery ; sensory function Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; how

  15. [Organized breast cancer screening].

    Rouëssé, Jacques; Sancho-Garnier, Hélèn

    2014-02-01

    Breast screening programs are increasingly controversial, especially regarding two points: the number of breast cancer deaths they avoid, and the problem of over-diagnosis and over-treatment. The French national breast cancer screening program was extended to cover the whole country in 2004. Ten years later it is time to examine the risk/benefit ratio of this program and to discuss the need for change. Like all forms of cancer management, screening must be regularly updated, taking into account the state of the art, new evidence, and uncertainties. All screening providers should keep themselves informed of the latest findings. In the French program, women aged 50-74 with no major individual or familial risk factors for breast cancer are offered screening mammography and clinical breast examination every two years. Images considered non suspicious of malignancy by a first reader are re-examined by a second reader. The devices and procedures are subjected to quality controls. Participating radiologists (both public and private) are required to read at least 500 mammographies per year. The program's national participation rate was 52.7 % in 2012. When individual screening outside of the national program is taken into account (nearly 15 % of women), coverage appears close to the European recommendation of 65 %. Breast cancer mortality has been falling in France by 0.6 % per year for over 30 years, starting before mass screening was implemented, and by 1.5 % since 2005. This decline can be attributed in part to earlier diagnosis and better treatment, so that the specific impact of screening cannot easily be measured. Over-treatment, defined as the detection and treatment of low-malignancy tumors that would otherwise not have been detected in a person's lifetime, is a major negative effect of screening, but its frequency is not precisely known (reported to range from 1 % to 30 %). In view of these uncertainties, it would be advisable to modify the program in order to

  16. More comprehensive discussion of CRC screening associated with higher screening.

    Mosen, David M; Feldstein, Adrianne C; Perrin, Nancy A; Rosales, A Gabriella; Smith, David H; Liles, Elizabeth G; Schneider, Jennifer L; Meyers, Ronald E; Elston-Lafata, Jennifer

    2013-04-01

    Examine association of comprehensiveness of colorectal cancer (CRC) screening discussion by primary care physicians (PCPs) with completion of CRC screening. Observational study in Kaiser Permanente Northwest, a group-model health maintenance organization. A total of 883 participants overdue for CRC screening received an automated telephone call (ATC) between April and June 2009 encouraging CRC screening. Between January and March 2010, participants completed a survey on PCPs' discussion of CRC screening and patient beliefs regarding screening. receipt of CRC screening (assessed by electronic medical record [EMR], 9 months after ATC). Primary independent variable: comprehensiveness of CRC screening discussion by PCPs (7-item scale). Secondary independent variables: perceived benefits of screening (4-item scale assessing respondents' agreement with benefits of timely screening) and primary care utilization (EMR; 9 months after ATC). The independent association of variables with CRC screening was assessed with logistic regression. Average scores for comprehensiveness of CRC discussion and perceived benefits were 0.4 (range 0-1) and 4.0 (range 1-5), respectively. A total of 28.2% (n = 249) completed screening, 84% of whom had survey assessments after their screening date. Of screeners, 95.2% completed the fecal immunochemical test. More comprehensive discussion of CRC screening was associated with increased screening (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.03-2.21). Higher perceived benefits (OR = 1.46, 95% CI = 1.13-1.90) and 1 or more PCP visits (OR = 5.82, 95% CI = 3.87-8.74) were also associated with increased screening. More comprehensive discussion of CRC screening was independently associated with increased CRC screening. Primary care utilization was even more strongly associated with CRC screening, irrespective of discussion of CRC screening.

  17. Bodipy–C60 triple hydrogen bonding assemblies as heavy atom-free triplet photosensitizers: preparation and study of the singlet/triplet energy transfer† †Electronic supplementary information (ESI) available: Syntheses, structure characterization data, and UV/vis absorption and emission spectra. See DOI: 10.1039/c4sc03865g

    Guo, Song; Xu, Liang; Xu, Kejing; Küçüköz, Betül; Karatay, Ahmet; Yaglioglu, Halime Gul; Hayvali, Mustafa; Elmali, Ayhan

    2015-01-01

    Supramolecular triplet photosensitizers based on hydrogen bonding-mediated molecular assemblies were prepared. Three thymine-containing visible light-harvesting Bodipy derivatives (B-1, B-2 and B-3, which show absorption at 505 nm, 630 nm and 593 nm, respectively) were used as H-bonding modules, and 1,6-diaminopyridine-appended C60 was used as the complementary hydrogen bonding module (C-1), in which the C60 part acts as a spin converter for triplet formation. Visible light-harvesting antennae with methylated thymine were prepared as references (B-1-Me, B-2-Me and B-3-Me), which are unable to form strong H-bonds with C-1. Triple H-bonds are formed between each Bodipy antenna (B-1, B-2 and B-3) and the C60 module (C-1). The photophysical properties of the H-bonding assemblies and the reference non-hydrogen bond-forming mixtures were studied using steady state UV/vis absorption spectroscopy, fluorescence emission spectroscopy, electrochemical characterization, and nanosecond transient absorption spectroscopy. Singlet energy transfer from the Bodipy antenna to the C60 module was confirmed by fluorescence quenching studies. The intersystem crossing of the latter produced the triplet excited state. The nanosecond transient absorption spectroscopy showed that the triplet state is either localized on the C60 module (for assembly B-1·C-1), or on the styryl-Bodipy antenna (for assemblies B-2·C-1 and B-3·C-1). Intra-assembly forward–backward (ping-pong) singlet/triplet energy transfer was proposed. In contrast to the H-bonding assemblies, slow triplet energy transfer was observed for the non-hydrogen bonding mixtures. As a proof of concept, these supramolecular assemblies were used as triplet photosensitizers for triplet–triplet annihilation upconversion. PMID:29218142

  18. Newborn hearing screening.

    Stewart, D L; Pearlman, A

    1994-11-01

    Congenital deafness is a relatively common problem with an incidence of 1/300 to 1/1000. Most states have no mass screening program for hearing loss, but the state of Kentucky compiles a High Risk Registry which is a historical survey of parents relating to risk factors for hearing loss. Unfortunately this survey can miss 50% of those who have a hearing deficit. If not detected prior to discharge, there is often a delay in diagnosis of deafness which prevents early intervention. We report 2 years' experience at Kosair Children's Hospital where 1,987 infants admitted to well baby, intermediate, or intensive care nurseries were screened using the ALGO-1 screener (Natus Medical Inc, Foster City, CA) which is a modified auditory brain stem evoked response (ABR). Our screening of this population led to an 11% incidence of referral for complete audiological evaluation. There were no significant complications. Forty-eight infants were found to have nonspecified, sensorineural, or conductive hearing loss. The positive predictive value of the test was 96%. Therefore, we feel that the use of the modified ABR in the newborn is a timely, cost efficient method of screening for hearing loss and should be used for mass screening of all newborns.

  19. Surface Resistance Measurements of LHC Dipole Beam Screen Samples

    Caspers, Friedhelm; Ruggiero, F; Tan, J; Tsutsui, H

    2000-01-01

    An estimate of the resistive losses in the LHC dipole beam screen is given from cold surface resistance measurements using the shielded pair technique. Several beam screen samples have been evaluated, with different copper coating methods, including a sample with ribbed surface envisaged to reduce electron cloud losses thanks to its low reflectivity. Experimental data, derived by a proper analysis of the measured Q-factors and including error estimates are compared with theoretical predictions of the anomalous skin effect.

  20. Screening for oral cancer.

    Jitender, Solanki; Sarika, Gupta; Varada, Hiremath R; Omprakash, Yadav; Mohsin, Khan

    2016-11-01

    Oral cancer is considered as a serious health problem resulting in high morbidity and mortality. Early detection and prevention play a key role in controlling the burden of oral cancer worldwide. The five-year survival rate of oral cancer still remains low and delayed diagnosis is considered as one of the major reasons. This increases the demand for oral screening. Currently, screening of oral cancer is largely based on visual examination. Various evidence strongly suggest the validity of visual inspection in reducing mortality in patients at risk for oral cancer. Simple visual examination is accompanied with adjunctive techniques for subjective interpretation of dysplastic changes. These include toluidine blue staining, brush biopsy, chemiluminescence and tissue autofluorescence. This review highlights the efficacy of various diagnostic methods in screening of oral cancer. © 2016 Old City Publishing, Inc.

  1. Radiographic intensifying screens

    Van Landeghem, W.K.; Suys, A.R.

    1979-01-01

    A fluorescent x-ray image intensifying screen is described which comprises discrete particles of fluorescent material dispersed in a binder layer. Intensifying screens are employed to increase the exposure of a photosensitive plate or film without increasing the x-ray exposure dose when struck by x-rays. The screen has an outermost layer containing solid particulate material protruding from a coherent film-forming organic binder medium and having a static friction coefficient at room temperature not higher than 0.50 on steel. The outermost layer may be characterized by micro-unevennesses of at least 3 μm and at least 9 protruding particles per 0.35 sq. cm. These particles have a static friction coefficient less than 0.3 and are made of a solid polystyrene, polyaklylene and/or a solid organic fluorinated polymer. (JTA)

  2. Screening Risk Evaluation methodology

    Hopper, K.M.

    1994-01-01

    The Screening Risk Evaluation (SRE) Guidance document is a set of guidelines provided for the uniform implementation of SREs performed on D ampersand D facilities. These guidelines are designed specifically for the completion of the second (semi-quantitative screening) phase of the D ampersand D Risk-Based Process. The SRE Guidance produces screening risk scores reflecting levels of risk through the use of risk ranking indices. Five types of possible risk are calculated from the SRE: current releases, worker exposures, future releases, physical hazards, and criticality. The Current Release Index (CRI) calculates the risk to human health and the environment from ongoing or probable releases within a one year time period. The Worker Exposure Index (WEI) calculates the risk to workers, occupants, and visitors in D ampersand D facilities of contaminant exposure. The Future Release Index (FRI) calculates the risk of future releases of contaminants, after one year, to human health and the environment. The Physical Hazards Index (PHI) calculates the risk-to human health due to factors other than that of contaminants. The index of Criticality is approached as a modifying factor to the entire SRE, due to the fact that criticality issues are strictly regulated under DOE. Screening risk results will be tabulated in matrix form and Total Risk will be calculated (weighted equation) to produce a score on which to base early action recommendations. Other recommendations from the screening risk scores will be made based either on individual index scores or from reweighted Total Risk calculations. All recommendations based on the SRE will be made based on a combination of screening risk scores, decision drivers, and other considerations, determined on a project by project basis. The SRE is the first and most important step in the overall D ampersand D project level decision making process

  3. Newborn screening for galactosaemia.

    Lak, Rohollah; Yazdizadeh, Bahareh; Davari, Majid; Nouhi, Mojtaba; Kelishadi, Roya

    2017-12-23

    Classical galactosaemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase. This is a rare and potentially lethal condition that classically presents in the first week of life once milk feeds have commenced. Affected babies may present with any or all of the following: cataracts; fulminant liver failure; prolonged jaundice; or Escherichia coli sepsis. Once the diagnosis is suspected, feeds containing galactose must be stopped immediately and replaced with a soya-based formula. The majority of babies will recover, however a number will not survive. There are long-term complications of galactosaemia, despite treatment, including learning disabilities and female infertility. It has been postulated that galactosaemia could be detected on newborn screening and this would prevent the immediate severe liver dysfunction and sepsis. To assess whether there is evidence that newborn screening for galactosaemia prevents or reduces mortality and morbidity and improves clinical outcomes in affected neonates and the quality of life in older children. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from electronic database searches, handsearches of relevant journals and conference abstract books. We also searched online trials registries and the reference lists of relevant articles and reviews.Date of the most recent search of Cochrane Cystic Fibrosis Group's Trials Register: 18 December 2017.Date of the most recent search of additional resources: 11 October 2017. Randomised controlled studies and controlled clinical studies, published or unpublished comparing the use of any newborn screening test to diagnose infants with galactosaemia and presenting a comparison between a screened population versus a non-screened population. No studies of newborn screening for galactosaemia were found. No studies were identified for inclusion in the

  4. Colorectal cancer screening

    McLoughlin, Monica Ramona

    2008-01-01

    Colorectal cancer is a major public health burden and is the most common cause of mortality from cancer in Europe. Over the last two decades robust evidence from randomised clinical trials and case-control series have confirmed that the mortality from colorectal cancer can be reduced by screening. The challenge over the next decade is how to implement this in clinical practice. This is what we set out to answer with this thesis. Not all individuals are equal when it comes to screening and tho...

  5. Charge degeneracy removal in the screened hydrogen atom

    Penna, Andre L A; Diniz, Joao B; Oliveira, Fernando A

    2009-01-01

    We derive an analytical model for the states of the screened hydrogen atom by using a new charge degeneracy removal approach. Starting from the nonzero Thomas-Fermi parameter q, we show that screening effect is due to breaks of the charge degeneracy in each quantum level of the hydrogen atom. The charge degeneracy removal reparametrizes the atomic system through the effective nuclear charge α n,l and the appearance of a dual charge γ n,l for each quantum level. In this approach, we show that the screening of a quantum state depends hierarchically on the screening from all previous quantum states with the same angular quantum numbers. The excited state energies E n,l (q) are analytically found taking into account the contribution of this new charge degeneracy for each quantum level. Finally, we also have estimated accurate critical screening parameters q* n,l for the bound-unbound transition.

  6. Lunar Dust Mitigation Screens

    Knutson, Shawn; Holloway, Nancy

    With plans for the United States to return to the moon, and establish a sustainable human presence on the lunar surface many issues must be successfully overcome. Lunar dust is one of a number of issues with the potential to create a myriad of problems if not adequately addressed. Samples of dust brought back from Apollo missions show it to be soft, yet sharp and abrasive. The dust consists of a variety of morphologies including spherical, angular blocks, shards, and a number of irregular shapes. One of the main issues with lunar dust is its attraction to stick to anything it comes in contact with (i.e. astronauts, equipment, habitats, etc.). Ionized radiation from the sun strikes the moon's surface and creates an electrostatic charge on the dust. Further, the dust harbors van der Waals forces making it especially difficult to separate once it sticks to a surface. During the Apollo missions, it was discovered that trying to brush the lunar dust from spacesuits was not effective, and rubbing it caused degradation of the suit material. Further, when entering the lunar module after moonwalks, the astronauts noted that the dust was so prolific inside the cabin that they inhaled and ingested it, causing at least one of them, Harrison "Jack" Schmidt, to report irritation of the throat and lungs. It is speculated that the dust could also harm an astronaut's nervous and cardiovascular systems, especially during an extended stay. In addition to health issues, the dust can also cause problems by scouring reflective coatings off of thermal blankets, and roughening surfaces of windows and optics. Further, panels on solar cells and photovoltaics can also be compromised due to dust sticking on the surfaces. Lunar dust has the capacity to penetrate seals, interfere with connectors, as well as mechanisms on digging machines, all of which can lead to problems and failure. To address lunar dust issues, development of electrostatic screens to mitigate dust on sur-faces is currently

  7. Approaches to virtual screening and screening library selection.

    Wildman, Scott A

    2013-01-01

    The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. This review aims to identify many of the common difficulties associated with virtual screening and allow researchers to better assess the reliability of their virtual screening effort.

  8. Exploiting PubChem for Virtual Screening.

    Xie, Xiang-Qun

    2010-12-01

    IMPORTANCE OF THE FIELD: PubChem is a public molecular information repository, a scientific showcase of the NIH Roadmap Initiative. The PubChem database holds over 27 million records of unique chemical structures of compounds (CID) derived from nearly 70 million substance depositions (SID), and contains more than 449,000 bioassay records with over thousands of in vitro biochemical and cell-based screening bioassays established, with targeting more than 7000 proteins and genes linking to over 1.8 million of substances. AREAS COVERED IN THIS REVIEW: This review builds on recent PubChem-related computational chemistry research reported by other authors while providing readers with an overview of the PubChem database, focusing on its increasing role in cheminformatics, virtual screening and toxicity prediction modeling. WHAT THE READER WILL GAIN: These publicly available datasets in PubChem provide great opportunities for scientists to perform cheminformatics and virtual screening research for computer-aided drug design. However, the high volume and complexity of the datasets, in particular the bioassay-associated false positives/negatives and highly imbalanced datasets in PubChem, also creates major challenges. Several approaches regarding the modeling of PubChem datasets and development of virtual screening models for bioactivity and toxicity predictions are also reviewed. TAKE HOME MESSAGE: Novel data-mining cheminformatics tools and virtual screening algorithms are being developed and used to retrieve, annotate and analyze the large-scale and highly complex PubChem biological screening data for drug design.

  9. Screening for Atrial Fibrillation

    Freedman, Ben; Camm, John; Calkins, Hugh

    2017-01-01

    Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed...

  10. Early Dementia Screening

    Peter K. Panegyres

    2016-01-01

    Full Text Available As the population of the world increases, there will be larger numbers of people with dementia and an emerging need for prompt diagnosis and treatment. Early dementia screening is the process by which a patient who might be in the prodromal phases of a dementing illness is determined as having, or not having, the hallmarks of a neurodegenerative condition. The concepts of mild cognitive impairment, or mild neurocognitive disorder, are useful in analyzing the patient in the prodromal phase of a dementing disease; however, the transformation to dementia may be as low as 10% per annum. The search for early dementia requires a comprehensive clinical evaluation, cognitive assessment, determination of functional status, corroborative history and imaging (including MRI, FDG-PET and maybe amyloid PET, cerebrospinal fluid (CSF examination assaying Aβ1–42, T-τ and P-τ might also be helpful. Primary care physicians are fundamental in the screening process and are vital in initiating specialist investigation and treatment. Early dementia screening is especially important in an age where there is a search for disease modifying therapies, where there is mounting evidence that treatment, if given early, might influence the natural history—hence the need for cost-effective screening measures for early dementia.

  11. Hazard screening application guide

    1992-06-01

    The basic purpose of hazard screening is to group precesses, facilities, and proposed modifications according to the magnitude of their hazards so as to determine the need for and extent of follow on safety analysis. A hazard is defined as a material, energy source, or operation that has the potential to cause injury or illness in human beings. The purpose of this document is to give guidance and provide standard methods for performing hazard screening. Hazard screening is applied to new and existing facilities and processes as well as to proposed modifications to existing facilities and processes. The hazard screening process evaluates an identified hazards in terms of the effects on people, both on-site and off-site. The process uses bounding analyses with no credit given for mitigation of an accident with the exception of certain containers meeting DOT specifications. The process is restricted to human safety issues only. Environmental effects are addressed by the environmental program. Interfaces with environmental organizations will be established in order to share information

  12. Radiological protective screen

    Flaugnatti, R.B.

    1976-01-01

    A radiological screen for placing on a patient's skin is discussed, comprising a flat jacket containing a fine particulate filler and a settable resin binder, the fine particulate filler being of a material which absorbs medical radiation, and the jacket including a window to transmit such radiation through the flat jacket. 16 claims, 4 drawing figures

  13. Screening Devices at School

    Ratner, Helene Gad

    2011-01-01

    ethnographic data from a Danish school, the article explores,first, the script and agencement of the SMTTE and, second, how the screening properties of the SMTTE are achieved, including how these properties challenge management-­‐teacher relations when the SMTTE travels to other networks at the school...

  14. Colorec tal cancer screening

    2009-05-12

    May 12, 2009 ... The operator must be skilled in the management of adverse events. • The operator must arrange appropriate follow-up of histopathological results. • The operator must provide appropriate recommendations for follow-up surveil- lance and screening. The average- risk person has a lifetime risk of developing.

  15. [ASCUS in screening].

    Caprara, L; Monari, F; De Bianchi, P S; Amadori, A; Bondi, A

    2001-12-01

    The significance and use of the cytological diagnosis "atypical squamous cells of undetermined significance" (ASCUS) remain a major problem in cervical cancer screening. The prevalence of ASCUS by patient age has seldom been investigated. The present paper reports the prevalence of ASCUS in a large series of screening Pap smears from the Italian region of Emilia-Romagna. The study was based on the data collected by the Department of Health of the Emilia-Romagna Region for the first 3-year round (1997-1999) of a population-based screening programme (target age, 25-64 years). The age-specific frequency of ASCUS has been calculated as a prevalence rate per 1000 screened patients. A total of 597,386 women participated in the programme. Women diagnosed with ASCUS (n = 8205 or 13.7 per 1000) accounted for 49% of the recalls for colposcopy (n = 16,871, or 28.2 per 1000). The prevalence of diagnoses of low-grade squamous intraepithelial lesions (LG-SIL) decreased progressively with age while that of high-grade SIL was slightly higher between 30 and 39 years. The prevalence of ASCUS peaked at age 45-49 years (17.3 per 1000 subjects). The observed peak reflects the prevalence of (1) cytological changes closely associated with perimenopausal age and at least compatible with the ASCUS diagnosis, and (2) cytological abnormalities induced by hormone replacement therapy.

  16. Screening for lung cancer

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

  17. Screening for asbestbetingede sygdomme?

    Brauer, Charlotte; Baandrup, Ulrik; Jacobsen, Peter

    2009-01-01

    in asbestos-exposed populations. Data do not currently support implementation of screening programs for asbestos-exposed persons in Denmark. Since mesothelioma is most often an occupational disease, these patients should be admitted to an occupational clinic for aetiological evaluation. Udgivelsesdato: 2009...

  18. Engineering aspects of Passavant screening

    Siddle, K.R.; Sharma, R.K.

    1978-01-01

    The Passavant screen was developed in Europe almost 30 years ago. The Passavant screen is a vertical traveling screen; however, the basic difference between the conventional vertical traveling screen and the Passavant screen is that in the conventional screen water passes through the front screen belt and then the back screen belt, whereas in the Passavant screen the water enters in between the two belts and passes laterally through either of the belts. Thus, theoretically, the screening surface of the Passavant screen is doubled as compared to the same size conventional vertical traveling screen. Various design and operational modifications of the Passavant screen are possible to yield optimum design and performance characteristics which make it amenable to installation at power plants for safe removal of not only fish but also smaller organisms such as fish eggs and larvae. In this paper, details of the screen design and operational characteristics are discussed with notes on how these features can be modified to suit site- and organism-specific requirements

  19. Interest rate derivatives

    Svenstrup, Mikkel

    This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered.......This Ph.D. thesis consists of four self-contained essays on valuation of interest rate derivatives. In particular derivatives related to management of interest rate risk care are considered....

  20. Psychometric Evaluation of a Brief Parent- and Teacher-Rated Screen for Children at Risk of Conduct Disorder

    Duncombe, Melissa E.; Havighurst, Sophie S.; Holland, Kerry A.; Frankling, Emma J.

    2012-01-01

    This study examined the psychometric properties of the Conduct Problems Risk Screen (CPRS), a seven-item screen derived from DSM-IV-TR criteria that can be completed by parents or teachers. The sample consisted of 4,752 Australian five- to nine-year-old primary school children. The results showed the parent and teacher screens had very good…

  1. Screening for chlamydial infection.

    Nelson, H D; Helfand, M

    2001-04-01

    To examine data on the effectiveness of screening for chlamydial infection by a physician or other health care professional. Specifically, we examine the evidence that early treatment of chlamydial infection improves health outcomes, as well as evidence of the effectiveness of screening strategies in nonpregnant women, pregnant women, and men, and the accuracy of tests used for screening. This review updates the literature since the last recommendation of the U.S. Preventive Services Task Force published in 1996. We searched the topic of chlamydia in the MEDLINE, HealthSTAR, and Cochrane Library databases from January 1994 to July 2000, supplemented by reference lists of relevant articles and from experts in the field. Articles published prior to 1994 and research abstracts were cited if particularly important to the key questions or to the interpretation of included articles. A single reader reviewed all English abstracts. Articles were selected for full review if they were about Chlamydia trachomatis genitourinary infections in nonpregnant women, pregnant women, or men and were relevant to key questions in the analytic framework. Investigators read the full-text version of the retrieved articles and applied additional eligibility criteria. For all topics, we excluded articles if they did not provide sufficient information to determine the methods for selecting subjects and for analyzing data. We systematically reviewed three types of studies about screening in nonpregnant women that relate to three key questions: (1) studies about the effectiveness of screening programs in reducing prevalence rates of infection, (2) studies about risk factors for chlamydial infection in women, and (3) studies about chlamydial screening tests in women. Our search found too few studies on pregnant women to systematically review, although pertinent studies are described. We systematically reviewed two types of studies about screening in men: (1) studies about prevalence rates and

  2. A comparison of the screening performance of braided coaxial and triaxial cables

    Fowler, E.P.

    1975-03-01

    The screening performance of a coaxial screened circuit is derived from measurements of the surface transfer impedance, capacitive coupling and conductor eccentricity on short lengths of cable. This is then extended to a triaxial screen considering all the ways the two screens can be connected. Comparison of calculated performance and measured results on a 10m length show that the mechanisms of coupling interact to make triaxial cable screening worse than expected and, in fact, frequently no better than a coaxial cable. The use of superscreened cables is found to overcome all the problems known in triaxial cables. (author)

  3. Screening for Chronic Kidney Disease

    Understanding Task Force Recommendations Screening for Chronic Kidney Disease The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Chronic Kidney Disease (CKD) . This recommendation ...

  4. Glucose screening tests during pregnancy

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... screening test between 24 and 28 weeks of pregnancy. The test may be done earlier if you ...

  5. Risks of Endometrial Cancer Screening

    ... Health history and certain medicines can affect the risk of developing endometrial cancer. Anything that increases your ... have abnormal vaginal bleeding, check with your doctor. Risks of Endometrial Cancer Screening Key Points Screening tests ...

  6. Risks of Esophageal Cancer Screening

    ... alcohol use, and Barrett esophagus can affect the risk of developing esophageal cancer. Anything that increases the ... tissue gives off less light than normal tissue. Risks of Esophageal Cancer Screening Key Points Screening tests ...

  7. Risks of Cervical Cancer Screening

    ... women. Human papillomavirus (HPV) infection is the major risk factor for cervical cancer. Although most women with ... clinical trials is available from the NCI website . Risks of Cervical Cancer Screening Key Points Screening tests ...

  8. Mammographic screening programmes in Europe

    Giordano, Livia; von Karsa, Lawrence; Tomatis, Mariano

    2012-01-01

    To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe.......To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe....

  9. Exploring Urban Screens

    Zlatan Krajina

    2009-12-01

    Full Text Available There is a tautological tendency in the widespread claims that urban space is 'me-diated'. Never before has the citizen, it is argued, been confronted with such an unprecedented array of signage. I depart from the rhetoric of 'biggest-ever-saturation' as not necessarily untrue, but as insufficient in exploring the diverse spatial operations of urban screens. I examine some contemporary cases of ani-mated architectural surfaces, informational panels, and advertising billboards, with reference to much longer standing cultural practices of spatial management in modern cities, such as illumination, to suggest that the contemporary display media do not mediate the city anew but re-invent urban space as a field of ubiqui-tous mediation. From that standpoint I suggest exploring urban screens as a both singular visual agents and indivisible items in plural structural assemblages, b complementary forces of public illumination, and c complex perceptual platforms in visual play of scale and distance.

  10. An experience of qualified preventive screening: shiraz smart screening software.

    Islami Parkoohi, Parisa; Zare, Hashem; Abdollahifard, Gholamreza

    2015-01-01

    Computerized preventive screening software is a cost effective intervention tool to address non-communicable chronic diseases. Shiraz Smart Screening Software (SSSS) was developed as an innovative tool for qualified screening. It allows simultaneous smart screening of several high-burden chronic diseases and supports reminder notification functionality. The extent in which SSSS affects screening quality is also described. Following software development, preventive screening and annual health examinations of 261 school staff (Medical School of Shiraz, Iran) was carried out in a software-assisted manner. To evaluate the quality of the software-assisted screening, we used quasi-experimental study design and determined coverage, irregular attendance and inappropriateness proportions in relation with the manual and software-assisted screening as well as the corresponding number of requested tests. In manual screening method, 27% of employees were covered (with 94% irregular attendance) while by software-assisted screening, the coverage proportion was 79% (attendance status will clear after the specified time). The frequency of inappropriate screening test requests, before the software implementation, was 41.37% for fasting plasma glucose, 41.37% for lipid profile, 0.84% for occult blood, 0.19% for flexible sigmoidoscopy/colonoscopy, 35.29% for Pap smear, 19.20% for mammography and 11.2% for prostate specific antigen. All of the above were corrected by the software application. In total, 366 manual screening and 334 software-assisted screening tests were requested. SSSS is an innovative tool to improve the quality of preventive screening plans in terms of increased screening coverage, reduction in inappropriateness and the total number of requested tests.

  11. Ellipticity Weakens Chameleon Screening

    Burrage, Clare; Copeland, Edmund J.; Stevenson, James

    2014-01-01

    The chameleon mechanism enables a long range fifth force to be screened in dense environments when non-trivial self interactions of the field cause its mass to increase with the local density. To date, chameleon fifth forces have mainly been studied for spherically symmetric sources, however the non-linear self interactions mean that the chameleon responds to changes in the shape of the source differently to gravity. In this work we focus on ellipsoidal departures from spherical symmetry and ...

  12. New generation expandable sand screens

    Syltøy, Christer

    2014-01-01

    Master's thesis in Petroleum engineering This thesis aims to give a general insight into sand control and various sorts of sand control measures and applications of sand control tools. Special focus will be given to expandable sand screens – a technology which came about in the late 1990’s through the use of flexible, expandable tubulars as base pipe in sand screens. More specifically Darcy’s Hydraulic Endurance Screens, a compliant sand screen system using hydraulic activation, and the fu...

  13. SCREENING FOR PERSONALITY DISORDERS

    Morse, Jennifer Q.; Pilkonis, Paul A.

    2010-01-01

    A brief but valid self-report measure to screen for personality disorders (PDs) would be a valuable tool in making decisions about further assessment and in planning optimal treatments. In psychiatric and nonpsychiatric samples, we compared the validity of three screening measures: the PD scales from the Inventory of Interpersonal Problems, a self-report version of the Iowa Personality Disorder Screen, and the self-directedness scale of the Temperament and Character Inventory. Despite their different theoretical origins, the screeners were highly correlated in a range from .71 to .77. As a result, the use of multiple screeners was not a significant improvement over any individual screener, and no single screener stood out as clearly superior to the others. Each performed modestly in predicting the presence of any PD diagnosis in both the psychiatric and nonpsychiatric groups. Performance was best when predicting a more severe PD diagnosis in the psychiatric sample. The results also highlight the potential value of multiple assessments when relying on self-reports. PMID:17492920

  14. Automated screening for retinopathy

    A. S. Rodin

    2014-07-01

    Full Text Available Retinal pathology is a common cause of an irreversible decrease of central vision commonly found amongst senior population. Detection of the earliest signs of retinal diseases can be facilitated by viewing retinal images available from the telemedicine networks. To facilitate the process of retinal images, screening software applications based on image recognition technology are currently on the various stages of development.Purpose: To develop and implement computerized image recognition software that can be used as a decision support technologyfor retinal image screening for various types of retinopathies.Methods: The software application for the retina image recognition has been developed using C++ language. It was tested on dataset of 70 images with various types of pathological features (age related macular degeneration, chorioretinitis, central serous chorioretinopathy and diabetic retinopathy.Results: It was shown that the system can achieve a sensitivity of 73 % and specificity of 72 %.Conclusion: Automated detection of macular lesions using proposed software can significantly reduce manual grading workflow. In addition, automated detection of retinal lesions can be implemented as a clinical decision support system for telemedicine screening. It is anticipated that further development of this technology can become a part of diagnostic image analysis system for the electronic health records.

  15. Screening Resonances In Plasmas

    Winkler, P.

    1998-01-01

    When it was suggested that a new recombination mechanism (Resonant Radiative Recombination (RRR)) which, based on very general physical arguments, should happen in dense plasmas and promises to provide useful information for the local temperature and density diagnostics of plasmas, they assumed the existence of screening resonances. For model potentials the existence of screening resonances has been demonstrated beyond reasonable doubt in a number of calculations. The key question, how well those potentials describe the dominant effects of a real plasma remains open. The relation of theoretical predictions to experimentally measurable effects is an important issue at the present stage of their research. In particular, RRR is expected to account for enhanced recombination rates of low energetic electrons with their ions, since the first stage is the resonant capture of a slow electron by an atom or ion. The mechanism that traps an electron is a combination of complicated many-body interactions of the ions and electrons. For clarity they start here, however, with a discussion in terms of local potential traps the shapes of which are determined predominantly and in an average way by two factors: the degree of screening present at the ionic site and the degree of short-range order in the immediate neighborhood of this ion

  16. Nutrition screening: science behind simplicity

    Nutrition screening triggers entry into the nutrition care process.1 Screening has informally been described as simple, quick or low-intensity proxy for more complex procedures. More formal definitions for the nutrition setting have been proposed, describing nutrition screening as a process of identifying patients, clients, or ...

  17. Push for the Second Screen

    Sørensen, Jannick Kirk; Sørensen, Lene Tolstrup

    Users’ perception of the relation between the TV screen and a secondary screen (e.g. smartphone or tablet) is examined empirically in a pilot project through a low-fi prototype and interviews. Early observations indicate that the user value/acceptance of push-messages delivered to the second screen...

  18. Abnormal Cervical Cancer Screening Test Results

    ... AQ FREQUENTLY ASKED QUESTIONS FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test ...

  19. Surface modelling on heavy atom crystalline compounds: HfO2 and UO2 fluorite structures

    Evarestov, Robert; Bandura, Andrei; Blokhin, Eugeny

    2009-01-01

    The study of the bulk and surface properties of cubic (fluorite structure) HfO 2 and UO 2 was performed using the hybrid Hartree-Fock density functional theory linear combination of atomic orbitals simulations via the CRYSTAL06 computer code. The Stuttgart small-core pseudopotentials and corresponding basis sets were used for the core-valence interactions. The influence of relativistic effects on the structure and properties of the systems was studied. It was found that surface properties of Mott-Hubbard dielectric UO 2 differ from those found for other metal oxides with the closed-shell configuration of d-electrons

  20. Atomic displacement distributions for light energetic atoms incident on heavy atom targets

    Brice, D.K.

    1975-01-01

    The depth distributions of atomic displacements produced by 4 to 100 keV H, D, and He ions incident on Cr, Mo, and W targets have been calculated using a sharp displacement threshold, E/sub d/ = 35 eV, and a previously described calculational procedure. These displacement depth distributions have been compared with the depth distributions of energy deposited into atomic processes to determine if a proportionality (modified Kinchin--Pease relationship) can be established. Such a relationship does exist for He ions and D ions incident on these metals at energies above 4 keV and 20 keV, respectively. For H ions the two distributions have significantly different shapes at all incident energies considered

  1. BODIPY-pyrene and perylene dyads as heavy atom-free singlet oxygen sensitizers

    Filatov, Mikhail A.

    2018-02-23

    Dyads combining BODIPY as an electron acceptor and pyrene or perylene as electron donor subunits were prepared and studied their photophysical properties studied by steady-state and transient spectroscopy. Depending on the structure of the subunits and polarity of the media, the dyads show either bright fluorescence or photo-induced electron transfer (PeT) in solution. Charge-transfer (CT) states formed as a result of PeT and were found to yield triplet excited states of the BODIPY. In the presence of molecular oxygen, the dyads sensitize singlet oxygen (1O2) with quantum yields of up to 0.75.

  2. Electron structure of molecules with very heavy atoms using effective core potentials

    Pitzer, K.S.

    1982-01-01

    Topics covered include effective potential, Hamiltonian for valence-electron motion, molecular calculations, spin-spin coupling, L-S coupling, numerical results of molecular calculations, and results of configuration-interaction Slater-orbital calculations in L-S coupling

  3. Heavy-atom isotope effects on binding of reactants to lactate dehydrogenase and pyruvate kinase

    Gawlita, E.

    1993-04-01

    18 O and 13 C kinetic isotope effects have been measured on the reaction of pyruvate kinase with phospho-enol-pyruvate and ADP using a remote label technique. The magnitude of both investigated isotope effects showed a dependence on the concentration of ADP. However, while the carbon effect was simply 'washed out' to unity at high ATP concentration, the oxygen effect becomes inverse and reached 0.9928 at the highest used concentration of ADP. Such a result testifies that the assumption of the negligible effect of isotopic substitution on enzyme-substrate associations remains correct only for carbon effects. An equilibrium 18 O isotope effect on association of oxalate with lactate dehydrogenase in the presence of NADHP has been evaluated by both experimental and theoretical means. Experimental methods, which involved equilibrium dialysis and gas chromatographic/mass spectrometric measurement of isotopic ration, yielded an inverse value of 0.9840. Semiempirical methods involved vibrational analysis of oxalate in two different environments. The comparison of calculated values with the experimentally determined isotope effect indicated that the AM 1 Hamiltonian proved superior to its PM 3 counterpart in this modelling. 160 refs, 8 figs, 18 tabs

  4. Two-photon decay of K-shell vacancy states in heavy atoms

    Ilakovac, K.; Uroic, M.; Majer, M.; Pasic, S.; Vukovic, B.

    2006-01-01

    Two-photon decay has been extensively studied in atomic, nuclear and particle physics since the 1930s when the problem of stability of the 2s state of the hydrogen atom emerged. Since then, many theoretical and experimental investigations have been made on hydrogen and one-electron (H-like) ions and on helium and two-electron (He-like) ions. The work on two-photon decay in many-electron systems involving inner shells started about 30 years ago and, in the meantime, two-photon decay of the K-shell vacancy state has been the subject of many theoretical and experimental studies. Experimental results have been obtained for 2s->1s and higher-state electron ->1s two-photon transitions in molybdenum, and for 2s -> 1s, 3s -> 1s, 3d -> 1s and 4sd -> 1s two-photon transitions in silver, xenon, hafnium and mercury. Nonrelativistic and relativistic calculations of the processes have been made. The relativistic calculations for transitions in molybdenum, silver and xenon atoms are in a reasonable agreement with the experimental results, but some problems remain to be solved. A review of investigations of two-photon transitions in atomic systems is presented

  5. Nuclear polarization contribution to the Lamb-shift in heavy atoms

    Plunien, G.; Mueller, B.; Greiner, W.

    1988-08-01

    The energy shift of the 1s 1/2 -state in 238 92 U due to virtual excitation of nuclear rotational modes is shown to be considerable correction for atomic high precision experiments. In contrast to this nuclear polarization effects are of minor importance for Lamb-shift studies in 208 82 Pb. (orig.)

  6. K-Vacancy Production in the Collision of Highly Charged Relativistic Ions With Heavy Atoms

    KHABIBULLAEV, P. K.

    2014-01-01

    A general expression for the cross section of the inelastic collision of relativistic highly charged ion with heavy (relativistic) atoms is obtained using the generalized eikonal approximation. In the ultrarelativistic limit, the obtained formula coincides with a known exact one. As an application of the obtained result, probability and cross section of the K-vacany production in the U92+ - U91+ collision are calculated.

  7. Relativistic total energy and chemical potential of heavy atoms and positive ions

    Hill, S.H.; Grout, P.J.; March, N.H.

    1984-01-01

    The relativistic Thomas-Fermi theory, with a finite nucleus, is used to study the variation of the chemical potential μ with atomic number Z and number of electrons N (N <= Z). The difference between the total energy of positive ions and that of the corresponding neutral atom has been obtained. The scaling predictions are confirmed by numerical calculations. The first principles calculation of the relativistic Thomas-Fermi total energy of neutral atoms is also studied. (author)

  8. Heavy-atom neutral beams for tandem-mirror end plugs

    Post, D.E.; Grisham, L.R.; Santarius, J.F.; Emmert, G.A.

    1981-05-01

    The advantages of neutral beams with Z greater than or equal to 3 formed from negative ions, accelerated to 0.5 to 1.0 MeV/amu, and neutralized with high efficiency, are investigated for use in tandem mirror reactor end plugs. These beams can produce Q's of 20 to 30, and thus can replace the currently proposed 200 to 500 keV neutral proton beams presently planned for tandem mirror reactors. Thus, these Z greater than or equal to 3 neutral beams increase the potential attractiveness of tandem mirror reactors by offering a substitute for difficult high energy neutral hydrogen end plug beams

  9. Unresolved spectral structures emitted from heavy atom plasmas produced by short pulse laser

    Fraenkel, M.; Zigler, A.

    1999-01-01

    Spectra of rare earth elements emitted from ultra short pulse laser produced plasma were recorded using simultaneously high and low resolution, spectrometers. A study of the broad band emission of the Δn = 1 transitions in highly ionized Ba and Sm plasma showed that this band is completely unresolved. The spectra were analyzed using the LTE based on super-transition array (STA) model. The theory reconstructs the entire Ba spectrum using a single temperature and density, whereas for Sm the discrepancies between the theory and experiment are not reconcilable. The agreement in the Ba case is attributed to the fact that BaF 2 target is transparent to the laser's prepulse effects, producing a homogeneous dense plasma, whereas for Sm the dilute plasma created by the prepulse is far from LTE. The obtained results posses a significant implication to the applicability of the STA model, in particular for calculations of opacities and conversion of laser light to X-rays. (orig.)

  10. Heavy atom enhanced room-temperature phosphorimetry for ultratrace determination of harmane

    Flávia F. de Carvalho Marques; Flávia da Silva Figueiredo; Ricardo Queiroz Aucelio

    2008-01-01

    Harmane has been proposed for the treatment of epilepsy, AIDS and leshmaniosis. Its room-temperature phosphorescence was induced using either AgNO3 or TlNO3, enabling absolute limits of detection of 0.12 and 2.4 ng respectively, with linear dynamic ranges extending up to 456 ng (AgNO3) and 911 ng (TlNO3). Relative standard deviations around 3% were observed for substrates containing 46 ng of harmane. Such sensitivity and precision are needed because harmane intake must be strictly controlled ...

  11. Heavy atom enhanced room-temperature phosphorimetry for ultratrace determination of harmane

    Flávia F. de Carvalho Marques

    2008-01-01

    Full Text Available Harmane has been proposed for the treatment of epilepsy, AIDS and leshmaniosis. Its room-temperature phosphorescence was induced using either AgNO3 or TlNO3, enabling absolute limits of detection of 0.12 and 2.4 ng respectively, with linear dynamic ranges extending up to 456 ng (AgNO3 and 911 ng (TlNO3. Relative standard deviations around 3% were observed for substrates containing 46 ng of harmane. Such sensitivity and precision are needed because harmane intake must be strictly controlled to achieve proper therapeutic response. Interference studies were performed using thalidomide, reserpine and yohimbine. Recovery of 104±6% was achieved using solid surface room-temperature phosphorimetry. The result was comparable to the one obtained by micellar electrokinetic chromatography.

  12. BODIPY-pyrene and perylene dyads as heavy atom-free singlet oxygen sensitizers

    Filatov, Mikhail A.; Karuthedath, Safakath; Polestshuk, Pavel M.; Callaghan, Susan; Flanagan, Keith J.; Wiesner, Thomas; Laquai, Fré dé ric; Senge, Mathias O.

    2018-01-01

    Dyads combining BODIPY as an electron acceptor and pyrene or perylene as electron donor subunits were prepared and studied their photophysical properties studied by steady-state and transient spectroscopy. Depending on the structure of the subunits and polarity of the media, the dyads show either bright fluorescence or photo-induced electron transfer (PeT) in solution. Charge-transfer (CT) states formed as a result of PeT and were found to yield triplet excited states of the BODIPY. In the presence of molecular oxygen, the dyads sensitize singlet oxygen (1O2) with quantum yields of up to 0.75.

  13. Multiple ionization and coupling effects in L-subshell ionization of heavy atoms by oxygen ions

    Pajek, M.; Banas, D.; Semaniak, J.; Braziewicz, J.; Majewska, U.; Chojnacki, S.; Czyzewski, T.; Fijal, I.; Jaskola, M.; Glombik, A.; Kretschmer, W.; Trautmann, D.; Lapicki, G.; Mukoyama, T.

    2003-01-01

    The multiple-ionization and coupling effects in L-shell ionization of atoms by heavy-ion impact have been studied by measuring the L x-ray production cross sections in solid targets of Au, Bi, Th, and U bombarded by oxygen ions in the energy range 6.4-70 MeV. The measured L x-ray spectra were analyzed using the recently proposed method accounting for the multiple-ionization effects, such as x-ray line shifting and broadening, which enables one to obtain the ionization probabilities for outer shells. The L-subshell ionization cross sections have been obtained from measured x-ray production cross sections for resolved Lα 1,2 , Lγ 1 , and Lγ 2,3 transitions using the L-shell fluorescence and Coster-Kronig yields being substantially modified by the multiple ionization in the M and N shells. In particular, the effect of closing of strong L 1 -L 3 M 4,5 Coster-Kronig transitions in multiple-ionized atoms was evidenced and discussed. The experimental ionization cross sections for the L 1 , L 2 , and L 3 subshells have been compared with the predictions of the semiclassical approximation (SCA) and the ECPSSR theory that includes the corrections for the binding-polarization effect within the perturbed stationary states approximation, the projecticle energy loss, and Coulomb deflection effects as well as the relativistic description of inner-shell electrons. These approaches were further modified to include the L-subshell couplings within the ''coupled-subshell model'' (CSM). Both approaches, when modified for the coupling effects, are in better agreement with the data. Particularly, the predictions of the SCA-CSM calculations reproduce the experimental L-subshell ionization cross section reasonably well. Remaining discrepancies are discussed qualitatively, in terms of further modifications of the L-shell decay rates caused by a change of electronic wave functions in multiple-ionized atoms

  14. Heavy atom vibrational modes and low-energy vibrational autodetachment in nitromethane anions

    Thompson, Michael C.; Weber, J. Mathias; Baraban, Joshua H.; Matthews, Devin A.; Stanton, John F.

    2015-01-01

    We report infrared spectra of nitromethane anion, CH 3 NO 2 − , in the region 700–2150 cm −1 , obtained by Ar predissociation spectroscopy and electron detachment spectroscopy. The data are interpreted in the framework of second-order vibrational perturbation theory based on coupled-cluster electronic structure calculations. The modes in the spectroscopic region studied here are mainly based on vibrations involving the heavier atoms; this work complements earlier studies on nitromethane anion that focused on the CH stretching region of the spectrum. Electron detachment begins at photon energies far below the adiabatic electron affinity due to thermal population of excited vibrational states

  15. Unresolved spectral structures emitted from heavy atom plasmas produced by short pulse laser

    Fraenkel, M.; Zigler, A. [Hebrew Univ., Jerusalem (Israel). Racah Inst. of Physics; Bar-Shalom, A.; Oreg, J. [Israel Atomic Energy Commission, Beersheba (Israel). Nuclear Research Center-Negev; Faenov, A.Ya.; Pikuz, T.A. [Multicharged Ions Spectra Data Center of VNIIFTRI, Russian Committee of Standards Moscow region (Russian Federation)

    1999-09-01

    Spectra of rare earth elements emitted from ultra short pulse laser produced plasma were recorded using simultaneously high and low resolution, spectrometers. A study of the broad band emission of the {delta}n = 1 transitions in highly ionized Ba and Sm plasma showed that this band is completely unresolved. The spectra were analyzed using the LTE based on super-transition array (STA) model. The theory reconstructs the entire Ba spectrum using a single temperature and density, whereas for Sm the discrepancies between the theory and experiment are not reconcilable. The agreement in the Ba case is attributed to the fact that BaF{sub 2} target is transparent to the laser's prepulse effects, producing a homogeneous dense plasma, whereas for Sm the dilute plasma created by the prepulse is far from LTE. The obtained results posses a significant implication to the applicability of the STA model, in particular for calculations of opacities and conversion of laser light to X-rays. (orig.)

  16. Screening diagnostic program breast cancer

    Portnoj, L.M.; Zhakova, I.I.; Budnikova, N.V.; Rukhlyadko, E.D.

    1995-01-01

    The authors propose their screening program for detection of breast cancer. It includes the entire complex of present-day screening diagnostic methods, starting from an original system for the formation of groups at risk of breast cancer and completed by the direct diagnostic model of detection of the condition, oriented at a differentiated approach to the use of mammographic techniques. The proposed organizational and methodologic screening measures are both economic and diagnostically effective, thus meeting the principal requirements to screening programs. Screening of 8541 risk-groups patients helped detect 867 nodular formations, 244 of which were cancer and 623 benign formations. 8 refs., 3 figs.,

  17. Triazolyl tryptoline derivatives as β-secretase inhibitors

    Jiaranaikulwanitch, Jutamas; Boonyarat, Chantana; Fokin, Valery V.; Vajragupta, Opa

    2010-01-01

    Tryptoline, a core structure of ochrolifuanine E, which is a hit compound from virtual screening of the Thai herbal database against BACE1 was used as a scaffold for the design of BACE1 inhibitors. The tryptoline was linked with different side chains by 1,2,3-triazole ring readily synthesized by catalytic azide-alkyne cycloaddition reactions. Twenty two triazolyl tryptoline derivatives were synthesized and screened for the inhibitory action against BACE1. JJCA-140 was the most potent inhibito...

  18. Atmospheric Pathway Screening Analysis for Saltstone Disposal Facility Vault 4

    COOK, JAMES

    2004-01-01

    A sequential screening process using a methodology developed by the National Council on Radiation Protection and Measurements, professional judgment and process knowledge has been used to produce a list of radionuclides requiring detailed analysis to derive disposal limits for the Saltstone Disposal Facility based on the atmospheric pathway

  19. What is new in recommendations on ophthalmological screening in ...

    ... complication-toxic retinopathy. The present recommendations warn against making premature decision on medicine withdrawal, especially in the light of the most recent studies on their beneficial systemic influence. This paper systematizes the information on ophthalmological screening in chloroquine derivatives users.

  20. Bottom-up derivation of conservative and dissipative interactions for coarse-grained molecular liquids with the conditional reversible work method

    Deichmann, Gregor; Marcon, Valentina; Vegt, Nico F. A. van der

    2014-01-01

    Molecular simulations of soft matter systems have been performed in recent years using a variety of systematically coarse-grained models. With these models, structural or thermodynamic properties can be quite accurately represented while the prediction of dynamic properties remains difficult, especially for multi-component systems. In this work, we use constraint molecular dynamics simulations for calculating dissipative pair forces which are used together with conditional reversible work (CRW) conservative forces in dissipative particle dynamics (DPD) simulations. The combined CRW-DPD approach aims to extend the representability of CRW models to dynamic properties and uses a bottom-up approach. Dissipative pair forces are derived from fluctuations of the direct atomistic forces between mapped groups. The conservative CRW potential is obtained from a similar series of constraint dynamics simulations and represents the reversible work performed to couple the direct atomistic interactions between the mapped atom groups. Neopentane, tetrachloromethane, cyclohexane, and n-hexane have been considered as model systems. These molecular liquids are simulated with atomistic molecular dynamics, coarse-grained molecular dynamics, and DPD. We find that the CRW-DPD models reproduce the liquid structure and diffusive dynamics of the liquid systems in reasonable agreement with the atomistic models when using single-site mapping schemes with beads containing five or six heavy atoms. For a two-site representation of n-hexane (3 carbons per bead), time scale separation can no longer be assumed and the DPD approach consequently fails to reproduce the atomistic dynamics

  1. Bottom-up derivation of conservative and dissipative interactions for coarse-grained molecular liquids with the conditional reversible work method

    Deichmann, Gregor; Marcon, Valentina; Vegt, Nico F. A. van der, E-mail: vandervegt@csi.tu-darmstadt.de [Center of Smart Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Straße 10, 64287 Darmstadt (Germany)

    2014-12-14

    Molecular simulations of soft matter systems have been performed in recent years using a variety of systematically coarse-grained models. With these models, structural or thermodynamic properties can be quite accurately represented while the prediction of dynamic properties remains difficult, especially for multi-component systems. In this work, we use constraint molecular dynamics simulations for calculating dissipative pair forces which are used together with conditional reversible work (CRW) conservative forces in dissipative particle dynamics (DPD) simulations. The combined CRW-DPD approach aims to extend the representability of CRW models to dynamic properties and uses a bottom-up approach. Dissipative pair forces are derived from fluctuations of the direct atomistic forces between mapped groups. The conservative CRW potential is obtained from a similar series of constraint dynamics simulations and represents the reversible work performed to couple the direct atomistic interactions between the mapped atom groups. Neopentane, tetrachloromethane, cyclohexane, and n-hexane have been considered as model systems. These molecular liquids are simulated with atomistic molecular dynamics, coarse-grained molecular dynamics, and DPD. We find that the CRW-DPD models reproduce the liquid structure and diffusive dynamics of the liquid systems in reasonable agreement with the atomistic models when using single-site mapping schemes with beads containing five or six heavy atoms. For a two-site representation of n-hexane (3 carbons per bead), time scale separation can no longer be assumed and the DPD approach consequently fails to reproduce the atomistic dynamics.

  2. Derivatives in emerging markets

    Dubravko Mihaljek; Frank Packer

    2010-01-01

    Turnover of derivatives has grown more rapidly in emerging markets than in developed countries. Foreign exchange derivatives are the most commonly traded of all risk categories, with increasingly frequent turnover in emerging market currencies and a growing share of cross-border transactions. As the global reach of the financial centres in emerging Asia has expanded, the offshore trading of many emerging market currency derivatives has risen as well. Growth in derivatives turnover is positive...

  3. Photon attenuation by intensifying screens

    Holje, G.

    1983-01-01

    The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

  4. Enhancing citizen engagement in cancer screening through deliberative democracy.

    Rychetnik, Lucie; Carter, Stacy M; Abelson, Julia; Thornton, Hazel; Barratt, Alexandra; Entwistle, Vikki A; Mackenzie, Geraldine; Salkeld, Glenn; Glasziou, Paul

    2013-03-20

    Cancer screening is widely practiced and participation is promoted by various social, technical, and commercial drivers, but there are growing concerns about the emerging harms, risks, and costs of cancer screening. Deliberative democracy methods engage citizens in dialogue on substantial and complex problems: especially when evidence and values are important and people need time to understand and consider the relevant issues. Information derived from such deliberations can provide important guidance to cancer screening policies: citizens' values are made explicit, revealing what really matters to people and why. Policy makers can see what informed, rather than uninformed, citizens would decide on the provision of services and information on cancer screening. Caveats can be elicited to guide changes to existing policies and practices. Policies that take account of citizens' opinions through a deliberative democracy process can be considered more legitimate, justifiable, and feasible than those that don't.

  5. Systematic review of guidelines on peripheral artery disease screening.

    Ferket, Bart S; Spronk, Sandra; Colkesen, Ersen B; Hunink, M G Myriam

    2012-02-01

    Peripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed. We performed a systematic review of guidelines to evaluate the value of PAD screening in asymptomatic adults. Guidelines in English published between January 1, 2003 and January 20, 2011 were retrieved using MEDLINE, CINAHL, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the G-I-N International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on PAD screening, were included. Two reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was validated by a second reviewer. Of 2779 titles identified, 8 guidelines were included. AGREE scores varied from 33% to 81%. Five guidelines advocated PAD screening, others found insufficient evidence for PAD screening or were against it. Measurement of the ankle-brachial index (ABI) was generally recommended for middle-aged populations with elevated cardiovascular risk levels. Those identified as having PAD are reclassified as high risk, warranting intensive preventive interventions to reduce their risk of a cardiovascular event. The underlying evidence mainly consisted of studies performed in patients with established PAD. A meta-analysis that evaluated ABI testing in the context of traditional cardiovascular risk assessment was interpreted differently. Recommendations on PAD screening vary across current guidelines, making the value of PAD screening uncertain. The variation seems to reflect lack of studies that show added value of

  6. Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval

    Yousaf-Khan, U.; Aalst, C. van der; Jong, P.A. de; Heuvelmans, M.; Scholten, E.T.; Lammers, J.-W.J.; Ooijen, P. van; Nackaerts, K.; Weenink, C.; Groen, H.; Vliegenthart, R.; Haaf, K. Ten; Oudkerk, M.; Koning, H. de

    2016-01-01

    In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  7. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    BACKGROUND: In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  8. Final screening round of the NELSON lung cancer screening trial : the effect of a 2.5-year screening interval

    Yousaf-Khan, Uraujh; van der Aalst, Carlijn; de Jong, Pim A.; Heuvelmans, Marjolein; Scholten, Ernst; Lammers, Jan-Willem; van Ooijen, Peter; Nackaerts, Kristiaan; Weenink, Carla; Groen, Harry; Vliegenthart, Rozemarijn; Ten Haaf, Kevin; Oudkerk, Matthijs; de Koning, Harry

    Background In the USA annual lung cancer screening is recommended. However, the optimal screening strategy (eg, screening interval, screening rounds) is unknown. This study provides results of the fourth screening round after a 2.5-year interval in the Dutch-Belgian Lung Cancer Screening trial

  9. The Novel Language-Systematic Aphasia Screening SAPS: Screening-Based Therapy in Combination with Computerised Home Training

    Krzok, Franziska; Rieger, Verena; Niemann, Katharina; Nobis-Bosch, Ruth; Radermacher, Irmgard; Huber, Walter; Willmes, Klaus; Abel, Stefanie

    2018-01-01

    Background: SAPS--'Sprachsystematisches Aphasiescreening'--is a novel language-systematic aphasia screening developed for the German language, which already had been positively evaluated. It offers a fast assessment of modality-specific psycholinguistic components at different levels of complexity and the derivation of impairment-based treatment…

  10. Korean Screen Cultures

    Screen Cultures sets out to redress this imbalance with a broad selection of essays spanning both North and South as well as different methodological approaches, from ethnographic and audience studies to cultural materialist readings. The first section of the book, «The South», highlights popular media...... new approaches to Korean popular culture beyond national borders and includes work on K-pop and Korean television drama. This book is a vital addition to existing scholarship on Korean popular culture, offering a unique view by providing an imaginary unification of the two Koreas negotiated through...

  11. Air-water screen

    Prokopov, O.I.; Kutepov, A.I.

    1980-12-08

    The air-water screen based on inventor's certificate No. 577364 contains horizontal water and air lines with water and air nozzles. The air line is situated inside the water line eccentrically and contracts it in the area of the nozzle, whose orifices are situated along the line of contact, while the orifices of the water nozzle are situated symmetrically relative to the air orifices and are located at an acute angle to them. To raise the protective properties, on the end of the water line is a lateral nozzle water distributor is an additional nozzle, connected to this container.

  12. Study of the nonlinear three-dimensional Debye screening in plasmas

    Lin Chang; Zhao Jinbao; Zhang Xiulian

    2000-01-01

    The nonlinear three-dimensional Debye screening in plasmas is investigated. New analytical solutions for the three-dimensional Poisson equation have been obtained for the nonlinear Debye potential for the first time. We derive exact analytical expression for the special case of the nonlinear three-dimensional Debye screening in plasmas. (orig.)

  13. Molecular screening in galactosemia

    Elsas, L.J.; Singh, R.; Fernhoff, P.M. [Emory Univ., Atlanta, GA (United States)] [and others

    1994-09-01

    Classical galactosemia (G/G) is caused by the absence of galactose-1-phosphate uridyl transferase (GALT) activity while the Duarte allele produces partial impairment and a specific biochemical phenotype. Cloning and sequencing of the human GALT gene has enabled the identification of prevalent mutations for both Classical and Duarte alleles. The G allele is caused by a Q188R codon mutation in exon 6 in 70% of a Caucasian population while the D allele is caused by an N134D codon mutation in exon 10. Since the Q188R sequence creates a new Hpa II site and the N314D sequence creates a new Sin I site, it is relatively easy to screen for both mutations by multiplex PCR and restriction digest. Here we describe a method for detection of new mutations producing impaired GALT. Patient DNAs are subjected to SSCP (single strand conformational polymorphism) analysis of their 11 GALT exons. Direct sequencing of the exons targeted by SSCP has revealed many codon changes: IVSC 956 (a splice acceptor site loss), S135L, V151A, E203K, A320T, and Y323D. Two of these codon changes, V151A and S135L, have been confirmed as mutations by finding impaired GALT activity in a yeast expression system. We conclude that molecular screening of GALT DNA will clarify the structural biology of GALT and the pathophysiology of galactosemia.

  14. SUPER-screening

    Brax, Philippe, E-mail: Philippe.Brax@cea.fr [Institut de Physique Theorique, CEA, IPhT, CNRS, URA 2306, F-91191Gif/Yvette Cedex (France); Davis, Anne-Christine, E-mail: A.C.Davis@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Sakstein, Jeremy, E-mail: J.A.Sakstein@damtp.cam.ac.uk [DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

    2013-02-26

    We present a framework for embedding scalar–tensor models of screened modified gravity such as chameleons, symmetrons and environmental dilatons into global supersymmetry. This achieved by secluding the dark sector from both the observable and supersymmetry breaking sectors. We examine the resulting supersymmetric features in a model-independent manner and find that, when the theory follows from an underlying supergravity, the mediation of supersymmetry breaking to the dark sector induces a soft mass for the scalar of order the gravitino mass. This is enough to forbid the construction of supersymmetric symmetrons and ensures that when other screening mechanisms operate, no object in the Universe is unscreened thereby precluding any observable signatures. In view of a possible origin of modified gravity within fundamental physics, we find that only no-scale models can circumvent these features. We also present a novel mechanism where the coupling of the scalar to two other scalars charged under U(1) can dynamically generate a small cosmological constant at late times in the form of a Fayet–Iliopoulos term.

  15. [Primary cervical cancer screening].

    Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

    2015-01-01

    Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

  16. Assessing Screening Policies for Childhood Obesity

    Wein, Lawrence M.; Yang, Yan; Goldhaber-Fiebert, Jeremy D.

    2014-01-01

    To address growing concerns over childhood obesity, the United States Preventive Services Task Force (USPSTF) recently recommended that children undergo obesity screening beginning at age 6 [1]. An Expert Committee recommends starting at age 2 [2]. Analysis is needed to assess these recommendations and investigate whether there are better alternatives. We model the age- and sex-specific population-wide distribution of body mass index (BMI) through age 18 using National Longitudinal Survey of Youth data [3]. The impact of treatment on BMI is estimated using the targeted systematic review performed to aid the USPSTF [4]. The prevalence of hypertension and diabetes at age 40 are estimated from the Panel Study of Income Dynamics [5]. We fix the screening interval at 2 years, and derive the age- and sex-dependent BMI thresholds that minimize adult disease prevalence, subject to referring a specified percentage of children for treatment yearly. We compare this optimal biennial policy to biennial versions of the USPSTF and Expert Committee recommendations. Compared to the USPSTF recommendation, the optimal policy reduces adult disease prevalence by 3% in relative terms (the absolute reductions are disease prevalence at a 28% reduction in treatment referral rate. If compared to the Expert Committee recommendation, the reductions change to 6% and 40%, respectively. The optimal policy treats mostly 16 year olds and few children under age 14. Our results suggest that adult disease is minimized by focusing childhood obesity screening and treatment on older adolescents. PMID:22240724

  17. Identifying Communication Barriers to Colorectal Cancer Screening Adherence among Appalachian Kentuckians.

    Bachman, Audrey Smith; Cohen, Elisia L; Collins, Tom; Hatcher, Jennifer; Crosby, Richard; Vanderpool, Robin C

    2017-08-18

    Utilizing data from 40 in-depth interviews, this article identifies both barriers and facilitators to colorectal screening guideline adherence among Appalachian Kentucky adults recruited through a community-based research network. Key findings identify (a) varying levels of knowledge about screening guidelines, (b) reticence to engage in screening processes, and (c) nuanced communication with healthcare providers and family members regarding screening adherence. What participants knew about the screening process was often derived from personal stories or recalled stories from family members about their screening experiences. Reticence to engage in screening processes reflected reports of cumbersome preparation, privacy issues, embarrassment, medical mistrust, fear of receiving a cancer diagnosis, and lack of symptoms. Participants cited many ways to enhance patient-centered communication, and the findings from this study have implications for health communication message design and communication strategies for healthcare practices in Appalachian Kentucky clinics.

  18. Structure-activity relationships of bumetanide derivatives

    Pedersen, Kasper Lykke; Töllner, Kathrin; Römermann, Kerstin

    2015-01-01

    of diuretics such as bumetanide. Bumetanide was discovered by screening ∼5000 3-amino-5-sulfamoylbenzoic acid derivatives, long before NKCC2 was identified in the kidney. Therefore, structure-activity studies on effects of bumetanide derivatives on NKCC2 are not available. EXPERIMENTAL APPROACH: In this study......, the effect of a series of diuretically active bumetanide derivatives was investigated on human NKCC2 variant A (hNKCC2A) expressed in Xenopus laevis oocytes. KEY RESULTS: Bumetanide blocked hNKCC2A transport with an IC50 of 4 μM. There was good correlation between the diuretic potency of bumetanide and its...... of the structural requirements that determine relative potency of loop diuretics on human NKCC2 splice variants, and may lead to the discovery of novel high-ceiling diuretics....

  19. Mass screening in breast cancer

    Strax, P.

    1977-01-01

    Some questions about mass screening in breast cancer are answered it being concluded that: 1. mass screening for the detection of early breast cancer is the only means with proven potential for lowering the death rate of the disease; 2. mammography is an importante - if not the most important modality in mass screening; 3. new film - screen combinations generally available are capable of producing mammograms of excelent quality with radiation doses down to .1 rad into the body of breast. The risk of malignant changes from such dosage - even when given periodically is negligeable. New equipment, to be available, shortly, will use the new film - screen combinations in an automated manner with must reduce cost in time, filme, personnel and processing - of more than 50%. This would make mass screening more practical. (M.A.) [pt

  20. Current Cervical Carcinoma Screening Guidelines

    Megan J. Schlichte

    2015-05-01

    Full Text Available A formidable threat to the health of women, cervical carcinoma can be prevented in many cases with adequate screening. The current guidelines for cervical carcinoma screening were created as joint recommendations of the American Cancer Society (ACS, the American Society for Colposcopy and Cervical Pathology (ASCCP and the American Society for Clinical Pathology (ASCP in 2012, and later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG. The 2012 recommendations underscore the utility of molecular testing as an adjunct to cytology screening for certain women and provide guidance to clinicians based on different risk-benefit considerations for different ages. This manuscript will review screening techniques and current recommendations for cervical cancer screening and human papilloma virus (HPV testing, as well as possible future screening strategies.

  1. Luminescence studies on phosphor screens

    Panayiotakis, G.; Nomikos, C.; Bakas, A.; Proimos, B.

    1994-01-01

    We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors)

  2. Luminescence studies on phosphor screens

    Panayiotakis, G; Nomikos, C; Bakas, A; Proimos, B [Medical Physics Department, University of Patras, 265 00 Patras, Greece (Greece)

    1994-12-31

    We report our results on x-ray phosphor screens prepared of some new materials focusing attention on their efficiency under fluoroscopy conditions, on optimization conditions and on comparisons among the various materials. All data are presented in absolute values. A theoretical model is presented, that takes into account the granular structure of the screens, permitting the explanation and prediction of the luminescence properties of the screens. (authors). 12 refs, 3 figs.

  3. Newborn Screening for Phenylketonuria

    Gustavo J. C. Borrajo PhD

    2016-12-01

    Full Text Available Newborn screening (NBS for phenylketonuria in Latin America gave its first step in an organized way 3 decades ago when the first national NBS program was implemented in Cuba. From then onward, it experienced a slow but continuous growing, being currently possible to find from countries where no NBS activity is known to several countries with consolidated NBS programs. This complex scenario gave rise to a great diversity in the criteria used for sample collection, selection of analytical methods, and definition of cutoff values. Considering this context, a consensus meeting was held in order to unify such criteria, focusing the discussion in the following aspects—recommended blood specimens and sample collection time; influence of early discharge, fasting, parenteral nutrition, blood transfusions, extracorporeal life support, and antibiotics; main causes of transient hyperphenylalaninemias; required characteristics for methods used in phenylalanine measurement; and finally, criteria to define the more appropriate cutoff values.

  4. Taking place, screening place

    Hansen, Kim Toft; Waade, Anne Marit

    2019-01-01

    We introduce location studies as a new empirical approach to screen studies. Location studies represent an interdisciplinary perspective, including media, aesthetics and geography, and reflect a growing interest in places in a global media and consumption culture. The chapter analyses two recent......) with one being traditional and the other being commercial; both dramas include discussions of localities and social heritage, and both use local sports as a common metaphor for social cohesion; and both series have been partly funded by a local film Danish commissioner. However, The Legacy is shot...... to a large extent in studios, while Norskov is shot entirely on location. The study is based on interviews with producers, broadcasters, location scouts, production designers and writers, as well as quantitative and qualitative textual analyses of television drama series, the geographical places, and related...

  5. Congenital cataract screening

    Zhale Rajavi

    2016-01-01

    Full Text Available Congenital cataract is a leading cause of visual deprivation which can damage the developing visual system of a child; therefore early diagnosis, management and long-term follow-up are essential. It is recommended that all neonates be screened by red reflex examination at birth and suspected cases be referred to ophthalmic centers. Early surgery (1 year is highly recommended. After surgery, amblyopia treatment and periodic follow-up examinations should be started as soon as possible to achieve a satisfactory visual outcome. Practitioners should consider the possibility of posterior capsular opacity, elevated intraocular pressure and amblyopia during follow-up, especially in eyes with microphthalmia and/or associated congenital anomalies. All strabismic children should undergo slit lamp examination prior to strabismus surgery to rule out congenital lens opacities. From a social point of view, equal and fair medical care should be provided to all children regardless of gender.

  6. Diabetes screening in the workplace.

    Gulley, Tauna; Boggs, Dusta; Mullins, Rebecca; Brock, Emily

    2014-11-01

    The prevalence of diabetes has increased worldwide and the pathophysiological problems associated with diabetes increase the potential for employees' physical disabilities. These complications, including neuropathy, nephropathy, and visual impairment, negatively impact the job performance of employees and compromise workplace safety. Occupational health nurses can provide diabetes screening programs to employees and identify chronic disease risk factors early. This article describes an occupational diabetes screening program at a major corporation in Belize, Central America, defines diabetes, outlines the diabetes teaching plan, and presents the demographics of the participants and results of the screening. Cultural considerations and recommendations for future occupational diabetes screenings are proposed. Copyright 2014, SLACK Incorporated.

  7. Industrial screening programs for workers

    Lavine, M.P.

    1982-01-01

    Industrial screening efforts to identify classes of workers who are more susceptible to workplace hazards, by virtue of their fertility, genetic, or lifestyle characteristics, represent a relatively new approach to reducing workplace risks. Screening has already raised some important economic, legal, social, medical, and moral questions. Employers, employees, administrative agencies, and the courts are offering different, often conflicting answers. Ultimately the acceptability of various screening schemes rests upon judgments about how a society justifies the distribution of risk. The questions that industrial screening programs raise are only partially answered by empirical evidence; the rest is a matter of values

  8. Advances in cervical screening technology.

    Stoler, M H

    2000-03-01

    The Pap smear unquestionably is a successful screening test for cervical cancer. However, recent advances in technology have raised questions regarding whether the conventional Pap smear is still the standard of care. This article relates issues of screening and cost-effectiveness to the state of the art in thin layer preparations, cytology automation, human papillomavirus screening, human papillomavirus vaccines, and other cervical screening adjuncts. Perhaps nowhere in medicine is clinical decision making being more strongly influenced by market and other external forces than in cervical cytopathology.

  9. A comprehensive platform for highly multiplexed mammalian functional genetic screens

    Cheung-Ong Kahlin

    2011-05-01

    Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.

  10. Global Derivatives Market

    Stankovska Aleksandra

    2017-06-01

    Full Text Available Globalization of financial markets led to the enormous growth of volume and diversification of financial transactions. Financial derivatives were the basic elements of this growth. Derivatives play a useful and important role in hedging and risk management, but they also pose several dangers to the stability of financial markets and thereby the overall economy. Derivatives are used to hedge and speculate the risk associated with commerce and finance.

  11. Self-Screening for Malnutrition Risk in Outpatient Inflammatory Bowel Disease Patients Using the Malnutrition Universal Screening Tool (MUST).

    Sandhu, Amindeep; Mosli, Mahmoud; Yan, Brian; Wu, Thomas; Gregor, Jamie; Chande, Nilesh; Ponich, Terry; Beaton, Melanie; Rahman, Adam

    2016-05-01

    Malnutrition is common in patients with inflammatory bowel disease (IBD) and is associated with poor outcomes. Our aim is to determine if patient self-administered malnutrition screening using the malnutrition universal screening tool (MUST) is reliable by comparing patient scores with those derived from the healthcare practitioner (HCP), the gold standard. We conducted a prospective validation study at a tertiary Canadian academic center that included 154 adult outpatients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score followed by an independent MUST assessment performed by HCPs. The main outcome measure was chance-corrected agreement (κ) of malnutrition risk categorization. For patient-administered MUST, the chance-corrected agreement κ (95% confidence interval [CI]) was 0.83 (0.74-0.92) when comparing low-risk and combined medium- and high-risk patients with HCP screening. Weighted κ analysis comparing all 3 risks groups yielded a κ (95% CI) of 0.85 (0.77-0.93) between patient and HCP screening. All patients were able to screen themselves. Overall, 96% of patients reported the MUST questionnaire as either very easy or easy to understand and to complete. Self-administered nutrition screening in outpatients with IBD is valid using the MUST screening tool and is easy to use. If adopted, this tool will increase utilization of malnutrition screening in hectic outpatient clinic settings and will help HCPs determine which patients require additional nutrition support. © 2015 American Society for Parenteral and Enteral Nutrition.

  12. Combined first- and second-trimester screening for Down syndrome

    Rode, Line; Wøjdemann, Karen R; Shalmi, Anne-Cathrine

    2003-01-01

    and their correlations, derived from our normal material and Down syndrome cases from the literature. RESULTS: Using a fixed screen-positive rate (SPR) of 5%, the first-trimester combined test [nuchal translucency (NT), PAPP-A and free beta-hCG] yielded a detection rate (DR) of 76%, and the integrated test (NT, PAPP......%. CONCLUSION: These results suggest that proMBP may be an important new marker in Down syndrome screening and, in particular, a good substitute for inhibin A....

  13. Risk and Derivative Price

    Yusuke Osaki

    2007-01-01

    We consider an asset market traded three types of assets: the risk–free asset, the market portfolio and derivatives written on the market portfolio return. We determine a sufficient condition to guarantee that noise risk monotonically changes their derivatives. The condition is that Arrow–Pratt absolute risk aversion is decreasing and convex.

  14. Financial Derivatives in China

    2006-01-01

    Francis Repka sees bright prospects for the future development of the financial derivatives market in China. Repka,Vice President of the Asian Bond Finance Department of Societe Generale, says the situation in France just after the birth of derivatives was very similar to the situation in China today.

  15. Vitamin D derivatives

    Deluca, H.F.; Schnoes, H.K.; Napoli, J.L.; Fivizzani, M.A.

    1982-01-01

    The chemical preparation of 26,27-isotopically labelled vitamin D 3 derivatives of high specific activity is described. These labelled vitamin D derivatives are useful in the determination of vitamin D metabolite levels in the blood and tissues of man and animals. (U.K.)

  16. Developments in Colorectal Cancer Screening

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Past Issues / Summer 2016 Table of ... at the National Cancer Institute, shared developments in colorectal cancer screening methods with NIH MedlinePlus magazine. What ...

  17. Costs of Colorectal Cancer Screening

    2017-04-04

    A health economist talks about studies on figuring out the costs of running a colorectal cancer screening program, and how this can lead to better screening.  Created: 4/4/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/4/2017.

  18. Screening College Students for Hypercholesterolemia.

    Faigel, Harris C.

    1992-01-01

    Describes one college's mandatory mass cholesterol screening for new students. Each year, over 30 beginning students with unknown hypercholesterolemia were detected. The program suggests that mass screening efficiently and economically identifies students who would benefit from cholesterol reduction, a modifiable risk in coronary artery disease.…

  19. Overdiagnosis in breast cancer screening

    Lynge, Elsebeth; Beau, Anna-Belle; Christiansen, Peer

    2017-01-01

    Overdiagnosis in breast cancer screening is an important issue. A recent study from Denmark concluded that one in three breast cancers diagnosed in screening areas in women aged 50-69 years were overdiagnosed. The purpose of this short communication was to disentangle the study's methodology...

  20. Taxation of Derivatives

    Dyppel, Katja Joo

    2013-01-01

    The main objective for this thesis is to analyse and systematise the Danish legislation on taxation of derivatives. According to financial terminology, a derivative is a financial instrument. Its value is derived from changes in the value of one or more underlying assets.The most common derivatives...... in the Danish tax legislation. However, contracts known as forwards (terminskontrakter) and options (aftaler om køberetter og salgsretter) are generally included in the term financials contracts covered by the Danish Act on Taxation of Gains and Losses on Claims and Debt. The main part of the analysis deals...... with the scope of sections 29-33 of the Danish Act on Taxation of Gains and Losses on Claims and Debt and the tax consequences for the covered financial contracts. In the analysis of taxation of derivatives, the fundamental issues of qualification and tax treatment of the instruments are dealt with....

  1. Prenatal Screening Using Maternal Markers

    Howard Cuckle

    2014-05-01

    Full Text Available Maternal markers are widely used to screen for fetal neural tube defects (NTDs, chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.

  2. Cervical cancer screening at crossroads

    Lynge, Elsebeth; Rygaard, Carsten; Baillet, Miguel Vazquez-Prada

    2014-01-01

    Cervical screening has been one of the most successful public health prevention programmes. For 50 years, cytology formed the basis for screening, and detected cervical intraepithelial lesions (CIN) were treated surgically to prevent progression to cancer. In a high-risk country as Denmark......, screening decreased the incidence of cervical cancer from 34 to 11 per 100,000, age-standardized rate (World Standard Population). Screening is, however, also expensive; Denmark (population: 5.6 million) undertakes close to half a million tests per year, and has 6-8 CIN-treated women for each prevented...... cancer case. The discovery of human papillomavirus (HPV) as the cause of cervical cancer dramatically changed perspectives for disease control. Screening with HPV testing was launched around 1990, and preventive HPV vaccination was licensed in 2006. Long-term randomized controlled trials (RCT...

  3. Plant regeneration from leaf-derived callus in Plectranthus barbatus ...

    RAMA

    2013-05-01

    May 1, 2013 ... produces an ancient root-derived drug traditionally used in the treatment of ... has opened up vistas for bio medical research. The fasciculated ... stored mainly in the cytoplasmic vesicles of cork cells in ... After screening of suitable ..... vitro of embryos and plantlets in stem tissue cultures of Tylophora indica.

  4. Dysphonia risk screening protocol

    Katia Nemr

    2016-03-01

    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  5. Data Quality Screening Service

    Strub, Richard; Lynnes, Christopher; Hearty, Thomas; Won, Young-In; Fox, Peter; Zednik, Stephan

    2013-01-01

    A report describes the Data Quality Screening Service (DQSS), which is designed to help automate the filtering of remote sensing data on behalf of science users. Whereas this process often involves much research through quality documents followed by laborious coding, the DQSS is a Web Service that provides data users with data pre-filtered to their particular criteria, while at the same time guiding the user with filtering recommendations of the cognizant data experts. The DQSS design is based on a formal semantic Web ontology that describes data fields and the quality fields for applying quality control within a data product. The accompanying code base handles several remote sensing datasets and quality control schemes for data products stored in Hierarchical Data Format (HDF), a common format for NASA remote sensing data. Together, the ontology and code support a variety of quality control schemes through the implementation of the Boolean expression with simple, reusable conditional expressions as operands. Additional datasets are added to the DQSS simply by registering instances in the ontology if they follow a quality scheme that is already modeled in the ontology. New quality schemes are added by extending the ontology and adding code for each new scheme.

  6. Dysphonia risk screening protocol

    Nemr, Katia; Simões-Zenari, Marcia; da Trindade Duarte, João Marcos; Lobrigate, Karen Elena; Bagatini, Flavia Alves

    2016-01-01

    OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors) divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children), 29.25 (adult women), 22.75 (adult men), and 27.10 (seniors). CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics. PMID:27074171

  7. Magnetic field screens

    Mansfield, P.; Turner, R.; Chapman, B.L.W.; Bowley, R.M.

    1990-01-01

    A screen for a magnetic coil, for producing, for example, a homogeneous, gradient or RF field in nuclear magnetic resonance imaging, is described. It is provided by surround the coil with a set of electrical conductors. The currents within the conductors are controlled in such a manner that the field is neutralised in a specific region of space. The current distribution within the conductors is determined by calculating the current within a hypothetical superconductive shield which would have the effect of neutralising the field, the current through the conductors thereby being a substitute for the superconductive shield. The conductors may be evenly spaced and connected in parallel, their resistances being determined by thickness or composition to provide the desired current, or they may carry equal currents but be differently spaced. A further set or sets of controlled conductors outside the first set may ensure that the first set does not upset the field from the NMR coil. The shield may selectively reflect certain fields while transmitting others and may prevent acoustic vibration e.g. when switching gradient fields. An RF coil arrangement may consist of two orthogonal coils, one coil within the other for use as a transmit/receive set or as a double resonance transmitter; a shield between the coils is in series with, and formed from the same winding as, the inner coil. (author)

  8. Touch/Screen

    Daniel Ross

    2015-12-01

    Full Text Available In 2004 Bernard Stiegler posed “the tragic question of cinema” as that of the germ of regres-­‐‑ sion to television and pornography it has always contained, just as in 1944 Adorno and Hork-­‐‑ heimer argued that Enlightenment reason has always contained a germ of regression making possible a prostitution of theory leading only to the threat of fascism. If comparable threats attend Stiegler’s cinematic question, then this implies the need for an account of this potential for regression, that is, an account of the relationship between desire, technology and knowledge. Tracing the aporias of the origin of desire and trauma in psychoanalysis is one crucial way to pursue this account. Exiting these aporias depends on recognizing that the origin of desire has for human beings always been technical, and hence that the instruments of desire form its conditions and condition its forms. By thus analysing the staging of desire and the setting of fantasy it becomes possible to reflect, for example, on what it means that for Genet fascism was theatre, that for Syberberg Hitler was cinema, and that for Stiegler the new prostitution of the tele-­‐‑visual graphic is digital and algorithmic. Hence arises the potentially tragic question of the possibility or otherwise, in the age of the ubiquitous screen, of a new cinematic invention and a new cinematic practice.

  9. [Toxicologic blood emergency screening].

    Cohen, Sabine; Manat, Aurélie; Dumont, Benoit; Bévalot, Fabien; Manchon, Monique; Berny, Claudette

    2010-01-01

    In order to overcome the stop marketing by Biorad company of automated high performance liquid chromatograph with UV detection (Remedi), we developed a gas chromatography-mass spectrometry (GC-MS) to detect and to give an approximation of the overdose of molecules frequently encountered in drug intoxications. Therefore two hundred eighty seventeen blood samples were collected over a period of one year and allowed us to evaluate and compare the performance of these two techniques. As identification, GC-MS does not identify all molecules detected by Remedi in 24.2% of cases; there is a lack of sensitivity for opiates and the systematic absence of certain molecules such as betablockers. However, in 75.8% of cases the GC-MS detects all molecules found by Remedi and other molecules such as meprobamate, paracetamol, benzodiazepines and phenobarbital. The concentrations obtained are interpreted in terms of overdose showed 15.7% of discrepancy and 84.3% of concordance between the two techniques. The GC-MS technique described here is robust, fast and relatively simple to implement; the identification is facilitated by macro commands and the semi quantification remains manual. Despite a sequence of cleaning the column after each sample, carryover of a sample to the next remains possible. This technique can be used for toxicologic screening in acute intoxications. Nevertheless it must be supplemented by a HPLC with UV detection if molecules such as betablockers are suspected.

  10. Methicillin-resistant Staphylococcus aureus screening as a patient safety initiative: using patients' experiences to improve the quality of screening practices.

    Currie, Kay; Knussen, Christina; Price, Lesley; Reilly, Jacqui

    2014-01-01

    To explore the patient experience and acceptability of methicillin-resistant Staphylococcus aureus screening of inpatient admissions to acute hospital settings. Prevention of healthcare-associated infections such as methicillin-resistant Staphylococcus aureus is a major patient safety concern internationally. Screening of patients for methicillin-resistant Staphylococcus aureus colonisation is becoming a routine aspect of hospital admission; however, evidence of the patient experience and acceptability of methicillin-resistant Staphylococcus aureus screening is limited. A mixed-methods study set in six acute care hospitals in three Scottish regions. Data collection involved postdischarge self-report survey of patients who had been screened (n = 54) and qualitative patient interviews (n = 10). Theoretical constructs derived from the Health Belief Model and Theory of Planned Behaviour used in analysis. Findings indicated that methicillin-resistant Staphylococcus aureus screening was broadly acceptable to patients. The experience of screening did not appear to be problematic; responses demonstrate that screening provided reassurance and generated confidence that health organisations were tackling healthcare-associated infections. Patients were less positive regarding the provision of information, the possibility of refusing a screen and the consequences of a positive test result. Furthermore, there were indications that patients wanted to be told the results of the screen and strong support for screening of hospital staff. Analysis of constructs from our theoretical frameworks provides evidence that attitudes were largely positive; responses indicate a belief in the beneficial impact of methicillin-resistant Staphylococcus aureus screening for patients and the wider community. However, it is important that health professionals continually assess the patient experience of 'routine' aspects of health care such as MRSA screening. The findings from this study suggest that

  11. Automatic detection of anomalies in screening mammograms

    2013-01-01

    Background Diagnostic performance in breast screening programs may be influenced by the prior probability of disease. Since breast cancer incidence is roughly half a percent in the general population there is a large probability that the screening exam will be normal. That factor may contribute to false negatives. Screening programs typically exhibit about 83% sensitivity and 91% specificity. This investigation was undertaken to determine if a system could be developed to pre-sort screening-images into normal and suspicious bins based on their likelihood to contain disease. Wavelets were investigated as a method to parse the image data, potentially removing confounding information. The development of a classification system based on features extracted from wavelet transformed mammograms is reported. Methods In the multi-step procedure images were processed using 2D discrete wavelet transforms to create a set of maps at different size scales. Next, statistical features were computed from each map, and a subset of these features was the input for a concerted-effort set of naïve Bayesian classifiers. The classifier network was constructed to calculate the probability that the parent mammography image contained an abnormality. The abnormalities were not identified, nor were they regionalized. The algorithm was tested on two publicly available databases: the Digital Database for Screening Mammography (DDSM) and the Mammographic Images Analysis Society’s database (MIAS). These databases contain radiologist-verified images and feature common abnormalities including: spiculations, masses, geometric deformations and fibroid tissues. Results The classifier-network designs tested achieved sensitivities and specificities sufficient to be potentially useful in a clinical setting. This first series of tests identified networks with 100% sensitivity and up to 79% specificity for abnormalities. This performance significantly exceeds the mean sensitivity reported in literature

  12. Domestic violence screening in pregnancy.

    Bunn, Mikiko Yazawa; Higa, Nicole A; Parker, Willie J; Kaneshiro, Bliss

    2009-11-01

    Domestic violence is an important health concern that has been shown to have adverse effects on maternal and neonatal outcomes. The objectives of this study were to compare the prevalence of prenatal screening for domestic violence in a hospital-based resident clinic setting with screening practices in private obstetric offices in Honolulu, Hawai'i and to explore physician attitudes towards domestic violence screening during pregnancy. A retrospective chart review was conducted at Queen's Medical Center in Honolulu, Hawai'i in women who delivered between 2003 and 2004. A 6 item written survey was also given to all attending and resident physicians with obstetric privileges. Descriptive statistics including frequency measures were generated and chi square tests were used to compare categorical variables. A total of 270 charts were reviewed. There was a statistically significant difference (p obstetric practices (39.3 percent) that were screened for domestic violence. While the majority of respondents (77.6%) to the domestic violence survey were aware that the American College of Obstetricians and Gynecologists recommends domestic violence screening in pregnancy most respondents (69.0 percent) indicated that they "never or rarely" screened their patients for domestic violence. Despite professional recommendations and an awareness of these recommendations, between 2003 and 2004, routine prenatal screening for domestic violence was markedly lacking for patients in this study population.

  13. Promoting breast screening in Glasgow.

    Cohen, L; Dobson, H; McGuire, F

    2000-03-01

    To establish whether there is a role for advertising in the promotion of the Breast Screening Programme and what the role of advertising might be. Four hundred and sixty questionnaires were completed by women attending their breast screening appointment. Quantitative and qualitative data were collected from the static unit at Calder Street and the mobile unit in Govan. The advertising (budget 30,000 Pounds) campaign ran over an eight week period in the Govan, Paisley Road West and Cardonald areas of Glasgow. Media used included press advertising, The Glasgow Underground, adshells, bus advertising (interiors) and poster distribution via local outlets. Forty-two per cent of the sample were aware of the campaign. Ninety-seven per cent liked the campaign images. Eighty eight per cent felt that breast screening should be advertised more. Screening uptake increased in the areas covered by the advertising campaign. Govan -58%-71% and Ibrox (Paisley Road West and Cardonald) -59%-61%. Women were very supportive of the role of advertising for the Breast Screening Programme. In particular they found the campaign images and messages reassuring, supportive and credible. Their views suggest that the role of advertising should be: To raise awareness of the service To make women more conscious of the benefits of screening To change public perceptions of the screening process However, it is recognised that a fully integrated approach is required for the promotion of the service to account for the improvement in uptake, as advertising cannot be expected to work in isolation.

  14. Parameterised post-Newtonian expansion in screened regions

    McManus, Ryan; Lombriser, Lucas; Peñarrubia, Jorge

    2017-12-01

    The parameterised post-Newtonian (PPN) formalism has enabled stringent tests of static weak-field gravity in a theory-independent manner. Here we incorporate screening mechanisms of modified gravity theories into the framework by introducing an effective gravitational coupling and defining the PPN parameters as functions of position. To determine these functions we develop a general method for efficiently performing the post-Newtonian expansion in screened regimes. For illustration, we derive all the PPN functions for a cubic galileon and a chameleon model. We also analyse the Shapiro time delay effect for these two models and find no deviations from General Relativity insofar as the signal path and the perturbing mass reside in a screened region of space.

  15. Screening in dense ionic fluids

    Tosi, M.P.

    1991-01-01

    There has been great progress in recent years in determining and understanding the structure of molten salts. I focus on molten alkali halides and discuss two main points concerning their liquid structure and its relationship with static electrical response in these dense ionic conductors. These are (i) the nature of screening and the related definitions and properties of the screening length and of the dielectric function, and (ii) developments in integral equations techniques for the evaluation of molten salt structure and static screening from given pair potentials. (author). 26 refs, 3 figs, 2 tabs

  16. Virtual screening of compound libraries.

    Cerqueira, Nuno M F S A; Sousa, Sérgio F; Fernandes, Pedro A; Ramos, Maria João

    2009-01-01

    During the last decade, Virtual Screening (VS) has definitively established itself as an important part of the drug discovery and development process. VS involves the selection of likely drug candidates from large libraries of chemical structures by using computational methodologies, but the generic definition of VS encompasses many different methodologies. This chapter provides an introduction to the field by reviewing a variety of important aspects, including the different types of virtual screening methods, and the several steps required for a successful virtual screening campaign within a state-of-the-art approach, from target selection to postfilter application. This analysis is further complemented with a small collection important VS success stories.

  17. Intensifying screens in transaxial tomography

    Debelder, M.H.; Bollen, R.H.

    1981-01-01

    This patent claim by Agfa-Gevaert relates to a method for the production of transaxial tomographs, a combination of materials therefor and X-ray intensifying screens incorporating at least one reflecting element for use in transaxial tomography, wherein the exposure of a photographic silver halide emulsion material proceeds at an angle within the range of 2 0 to 10 0 in conjunction with an X-ray fluorescent intensifying screen including an ultra-violet and/or visible radiation reflective coating or sheet to increase the radiation output of the screen and to reduce the exposure time and radiation dose e.g. in medical X-ray applications. (author)

  18. Superstability of Generalized Derivations

    Ansari-Piri Esmaeil

    2010-01-01

    Full Text Available We investigate the superstability of the functional equation , where and are the mappings on Banach algebra . We have also proved the superstability of generalized derivations associated to the linear functional equation , where .

  19. Amphetamine derivative related deaths.

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  20. Investigation - Derived Waste Program

    Beardsley, C.; Anderson, R.

    1998-06-01

    The Investigation-Derived Waste Program is a software application that was developed to identify the groundwater monitoring wells at the Savannah River Site that require containerization and treatment for purge water generated during sampling

  1. Development of Derivatives Reporting

    Pejčochová, Kristina

    2012-01-01

    This thesis aims to summarise the theoretical principles, concepts and considerations pertaining to accounting for and reporting of derivatives and to describe and analyse the development of major accounting standards dealing with related issues. Sections 1 and 2 provide a basic overview of derivative instruments'categorisation, mechanics, valuation and uses. Section 3 studies the principles that ensure the provision of useful financial information, with specific focus on financial instrument...

  2. On higher derivative gravity

    Accioly, A.J.

    1987-01-01

    A possible classical route conducting towards a general relativity theory with higher-derivatives starting, in a sense, from first principles, is analysed. A completely causal vacuum solution with the symmetries of the Goedel universe is obtained in the framework of this higher-derivative gravity. This very peculiar and rare result is the first known vcuum solution of the fourth-order gravity theory that is not a solution of the corresponding Einstein's equations.(Author) [pt

  3. Brain derived neurotrophic factor

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  4. Gorenstein derived functions

    Holm, Henrik Granau

    2004-01-01

    Over any associative ring R it is standard to derive HomR(􀀀;􀀀) using projective resolutions in the rst variable, or injective resolutions in the second variable, and doing this, one obtains Extn R(􀀀;􀀀) in both cases. We examine the situation where projective...... and injective modules are replaced by Gorenstein projective and Gorenstein injective ones, respectively. Furthermore, we derive the tensor product 􀀀 R 􀀀 using Gorenstein at modules....

  5. Newborn Screening: MedlinePlus Health Topic

    ... more articles Reference Desk Glossary (National Center for Biotechnology Information) Find an Expert Eunice Kennedy Shriver National ... other than English on Newborn Screening NIH MedlinePlus Magazine Hearing Loss: Screening Newborns Screening Newborns' Hearing Now ...

  6. BREAST CANCER SCREENING IN A RESOURCE POOR ...

    al rates of breast cancer, hence screening of asympto- matic, apparently healthy ... screening tools in women who attended free breast cancer screening exercise in a ..... signs of malignancy. www.appliedradiology.mobi/uploadedfiles/Issues/2.

  7. Risk Profiling May Improve Lung Cancer Screening

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  8. Phloroglucinol derivatives and flavones from Helichrysum paronychioides

    J. Mutanyatta-Comar

    2006-06-01

    Full Text Available Investigation of Helichrysum paronychioides afforded a total of nine compounds: 4 phloroglucinol derivatives, 2 of which are novel natural products, and 5 flavone derivatives. Structures were established by various spectroscopic techniques (NMR, MS, UV, IR, CD and by comparison with literature data for the known compounds. The four phloroglucinols, trans-(2R,3R-5,7-dihydroxy-2,3-dimethyl-4-chromanone (1, 2-butanoyl-4-prenyl-1-methoxy phloroglucinol (2, 2-(2-methylpropanoyl-4-prenylphloroglucinol (3 and 2-(2-methyl- butanoyl-4-prenylphloroglucinol (4 were screened for antioxidant activity against Cu-induced LDL oxidation. Compound 4 was found to be the most active inhibiting LDL oxidation at all concentrations (0.5-10 μM while the other three showed moderate to no activity.

  9. Nurses' roles in screening for intimate partner violence: a phenomenological study.

    Al-Natour, A; Qandil, A; Gillespie, G L

    2016-09-01

    To describe Jordanian nurses' roles and practices in screening for intimate partner violence. Intimate partner violence is a recognized global health problem with a prevalence of 37% for the Eastern Mediterranean region. Jordanian nurses screening for intimate partner violence is as low as 10.8%. Nurses have encountered institutional and personal barriers hindering their screening practice. A descriptive phenomenological design was used for this study. A purposive sample of 12 male and female Jordanian nurses working at a university hospital in Jordan participated. Participants were interviewed in 2014 using a semi-structured, face-to-face interview. Steps of Colaizzi's phenomenological method were used to analyse the qualitative data. Four themes were derived from the data: (1) screening practices and roles for suspected IPV cases, (2) advantages for screening and disadvantages for not screening for intimate partner violence, (3) factors hindering screening practice and (4) feelings towards screening and not screening for intimate partner violence. Increasing Jordanian nurses' awareness of the need for intimate partner violence screening in this sample was needed. Professional education and training may facilitate the adoption of intimate partner violence screening practices. A key barrier to intimate partner violence screening is Jordanian nurses' personal beliefs. Overcoming these personal beliefs will necessitate a multi-faceted approach starting with schools of nursing and bridging into healthcare settings. Healthcare professionals including nursing and policy makers at health institutions should enforce screening policies and protocols for all receipt of care at first contact. In addition, an emphasis on modelling culturally congruent approaches to develop the trusting nurse-patient relationships and process for screening patients for intimate partner violence. © 2016 International Council of Nurses.

  10. Inventions on GUI for Touch Sensitive Screens

    Mishra, Umakant

    2014-01-01

    A touch sensitive screen displays the information on the screen and also receives the input by sensing a user's touch on the same screen. This mechanism facilitates system interaction directly through the screen without needing a mouse or keyboard. This method has the advantage to make the system compact by removing keyboard, mouse and similar interactive device. However there are certain difficulties to implement a touch screen interface. The display screens of portable devices are becoming ...

  11. Effectiveness of testis cancer screening

    Feucht, H.

    1983-04-01

    In the Federal Republic of Germany there are about thousand to two-thousand incidences of testis cancer yearly. The screening (and examination) program currently used for the early detection of cancer includes the screening of malignant tumours of the testis. Since only males 45 years and older are invited to make use of the preventive measures, the most seriously affected age-group between twenty and forty is hereby not considered. The objective of this study is to find out which of the generally conceivable preventive measures could lead to an improvement of the present situation. The analysis shows that, for a diagnostic accuracy of 1 and a participation of 100%, the quantifyable cost of a yearly performed special screening is higher than the quantifyable cost savings achieved. A final judgement of other ways of execution is only possible when the diagnostic accuracy of suitable screening methods and the percentage of the participants of the groups of people concerned are known. (orig.)

  12. RAS - Screens & Assays - Drug Discovery

    The RAS Drug Discovery group aims to develop assays that will reveal aspects of RAS biology upon which cancer cells depend. Successful assay formats are made available for high-throughput screening programs to yield potentially effective drug compounds.

  13. Screening for Abdominal Aortic Aneurysm

    ... benefits. When there is not enough evidence to judge benefits and harms, the Task Force does not ... nurse practitioners, physician assistants, and nurses. selectively offer Decide whether screening is right for a patient on ...

  14. Screening Tests for Birth Defects

    ... that best fit your needs. What are the advantages and disadvantages of diagnostic tests compared with screening ... Us Contact Us Copyright Information Privacy Statement RSS Advertising Opportunities Careers at ACOG Sitemap Website Feedback American ...

  15. PHYTOCHEMICAL SCREENING AND THROMBOLYTIC ACTIVITY ...

    2014-12-31

    Dec 31, 2014 ... followed by chemical screening, random selection followed by one or more biological ... These were identified by characteristic color changes .... [1] Samuelsson, G. Drugs of Natural Origin: A Textbook of Pharmacognosy.

  16. X-ray screening materials

    Wardley, R.B.

    1981-01-01

    This invention relates to x-ray screening materials and especially to materials in sheet form for use in the production of, for example, protective clothing such as aprons and lower back shields, curtains, mobile screens and suspended shields. The invention is based on the observation that x-ray screening materials in sheet form having greater flexiblity than the hitherto known x-ray screening materials of the same x-ray absorber content can be produced if, instead of using a single sheet of filled sheet material of increased thickness, one uses a plurality of sheets of lesser thickness together forming a laminar material of the desired thickness and one bonds the individual sheets together at their edges and, optionally, at other spaced apart points away from the edges thereby allowing one sheet to move relative to another. (U.K.)

  17. Risks of Lung Cancer Screening

    ... in women. Different factors increase or decrease the risk of lung cancer. Anything that increases your chance ... been studied to see if they decrease the risk of dying from lung cancer. The following screening ...

  18. Breast Cancer Screening in Denmark

    Jørgensen, Karsten Juhl; Gøtzsche, Peter C; Kalager, Mette

    2017-01-01

    Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Design......) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing...... rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted...

  19. Pennsylvania's experience in mass screening

    Gerusky, T.M.

    1975-01-01

    A policy statement issued in 1972 by the Assistant Secretary for Health and Scientific Affairs of the Department of Health, Education, and Welfare recommended that community chest x-ray surveys should not be used as a screening procedure for the detection of cardiopulmonary disorders and that when chest x-ray screening programs are justified for selected population groups, the full size photograph, rather than the miniature film, is preferred. A survey conducted in 1974--75 revealed that chest x rays were required for prisoners, prison employees, school employees, food handlers, and students who wished to participate in sports. Meetings were held with medical associations in the hope of stopping the local mass-screening operations. Of 27 groups in Pennsylvania involved in tuberculosis screening, 12 groups refused or were unwilling to phase out their photofluorographic procedures. The problem will be resolved by regulation

  20. Transforming Security Screening With Biometrics

    Hearnsberger, Brian J

    2003-01-01

    ... and identity theft to dramatically improve physical security. Today, biometric technology could be implemented to transform physical security by enhancing screening procedures currently in use at U.S...

  1. Combinatorial drug screening identifies Ewing sarcoma-specific sensitivities

    Radic-Sarikas, Branka; Tsafou, Kalliopi P.; Emdal, Kristina B.; Papamarkou, Theodore; Huber, Kilian V.M.; Mutz, Cornelia; Toretsky, Jeffrey A.; Bennett, Keiryn L.; Olsen, Jesper V.; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

    2017-01-01

    Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three p...

  2. [Mokken scaling of the Cognitive Screening Test].

    Diesfeldt, H F A

    2009-10-01

    The Cognitive Screening Test (CST) is a twenty-item orientation questionnaire in Dutch, that is commonly used to evaluate cognitive impairment. This study applied Mokken Scale Analysis, a non-parametric set of techniques derived from item response theory (IRT), to CST-data of 466 consecutive participants in psychogeriatric day care. The full item set and the standard short version of fourteen items both met the assumptions of the monotone homogeneity model, with scalability coefficient H = 0.39, which is considered weak. In order to select items that would fulfil the assumption of invariant item ordering or the double monotonicity model, the subjects were randomly partitioned into a training set (50% of the sample) and a test set (the remaining half). By means of an automated item selection eleven items were found to measure one latent trait, with H = 0.67 and item H coefficients larger than 0.51. Cross-validation of the item analysis in the remaining half of the subjects gave comparable values (H = 0.66; item H coefficients larger than 0.56). The selected items involve year, place of residence, birth date, the monarch's and prime minister's names, and their predecessors. Applying optimal discriminant analysis (ODA) it was found that the full set of twenty CST items performed best in distinguishing two predefined groups of patients of lower or higher cognitive ability, as established by an independent criterion derived from the Amsterdam Dementia Screening Test. The chance corrected predictive value or prognostic utility was 47.5% for the full item set, 45.2% for the fourteen items of the standard short version of the CST, and 46.1% for the homogeneous, unidimensional set of selected eleven items. The results of the item analysis support the application of the CST in cognitive assessment, and revealed a more reliable 'short' version of the CST than the standard short version (CST14).

  3. THE DEVELOPMENT OF SCREEN TRANSLATION

    Sang Ayu Isnu Maharani

    2014-01-01

    Screen translations involve oral translation known as dubbing and revoicing. Re-voicing consists of lip-sync dubbing, free commentary, narration and voice over. The written version is called subtitle. Dubbing and subtitling are two preferred mode used in the screen translation even though various numbers of current options are available nowadays. Dubbing commenced to be used in larger countries in Europe meanwhile smaller countries apply subtitling because it is more...

  4. Industrial radiography with phosphor screens

    Broadhead, P.

    1981-01-01

    An experimental system that comprises a film of low silver content and a pair of high resolution phosphor intensifying screens and a commercial industrial X-ray film of similar speed are compared for image quality. It is concluded that the use of phosphor screens offers an increase in image quality when the information is limited by the graininess or quantum mottle of a radiograph which is frequently the case in practical radiography. (author)

  5. Fish screens at hydroelectric diversions

    Ott, R.F.

    1994-01-01

    Preventing downstream migrating fish from entering the turbines at hydroelectric projects is a standard mitigation goal of state and federal fishery management agencies. The object is to minimize the adverse impacts to the fish associated with the exclusion and passage through the bypass water conveyance facilities. In the western United States, most of the fishery management agencies have fish screen design criteria that focus on the approach and transportational velocities, maximum opening dimensions of the screen material, and the cleaning standards. Recently, more attention has been given to fish behavioral traits such as attraction and sustained and darting swimming speed, which has resulted in more attention to the position of the screens to the flow and the length of time the downstream migrants are exposed to the screens. Criteria for length of time of exposure, size and position of bypass, flow and velocities in the bypass entrances, discharge requirements back into the receiving water, and exposure to predation have created unique challenges to the fish screen designer. This paper discusses some of the more recent types of fixed fish screens that are being installed at hydroelectric plants that meet these challenges

  6. Retinopathy of prematurity screening criteria in Iran: new screening guidelines.

    Roohipoor, Ramak; Karkhaneh, Reza; Farahani, Afsar; Ebrahimiadib, Nazanin; Modjtahedi, Bobeck; Fotouhi, Akbar; Yaseri, Mehdi; Khodabande, Alireza; Zarei, Mohammad; Imani Fuladi, Marjan; Taheri, Arash; Riazi Esfahani, Mohammad; Loewenstein, John

    2016-07-01

    To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. Both eyes of 1932 infants born ≤37 weeks of gestation and/or weighting ≤3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. Patients with ROP requiring treatment. The mean GA±SD and birth weight (BW)±SD of the screened patients were 32±2.7 weeks and 1713±516 g, respectively. Using criteria of GA≤32 weeks or BW ≤2000 yielded sensitivity and specificity of 100% and 26.7%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4% of ROP and 8.4%ROP requiring treatment in our cohort. Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. Variations in screening outcome among pairs of screening radiologists at non-blinded double reading of screening mammograms: a population-based study

    Klompenhouwer, E. G.; Duijm, L. E. M.; Voogd, A. C.; den Heeten, G. J.; Nederend, J.; Jansen, F. H.; Broeders, M. J. M.

    2014-01-01

    Substantial inter-observer variability in screening mammography interpretation has been reported at single reading. However, screening results of pairs of screening radiologists have not yet been published. We determined variations in screening performances among pairs of screening radiologists at

  8. Effects of ion and electron screening on thermonuclear reaction rates

    Brady, L.R. Jr.

    1977-01-01

    The effects of screening by ions and electrons on thermonuclear reaction rates in stellar plasmas are considered. The enhancement of the reaction rate ranges from negligible to extremely large (on the order of 10 26 or greater). In order to calculate these effects, the potential about a given reacting nucleus is determined. First, Boltzmann-Vlasov and Poisson-Boltzmann equations are solved to yield a Yukawa potential. A suitable approximation to this potential is integrated in the action integral to give the barrier penetration. The screened reaction rate is then found by the saddle-point method. In developing a general formalism to calculate the screened reaction rate and the screening factor, effects due to the finite size of the nucleus are considered and found to be negligible. An expression for the screening factor for resonant reaction rates is also derived. A different and relatively simple approach, based on work of Stewart and Pyatt (1966), is used to find the barrier penetration from the action integral in two approximations: a modified Coulomb potential and a constant-shift potential. Screening factors are calculated for carbon burning at T 6 = 100 and T 6 = 400 for a wide range of densities and also for several examples in late stellar evolution. These screening factors are, for the most part, greater than those given by most others by a few percent at low density to 4 or more orders of magnitude at T 6 = 100 and rho = 10 10 g/cm 3 . Near the edge of the crystalline lattice region, however, they are significantly lower than those of some others. The increase in reaction rates for carbon burning indicates that carbon ignition may occur at lower densities than previously thought and may affect the density at which a supernova shock may occur

  9. Screening_mgmt: a Python module for managing screening data.

    Helfenstein, Andreas; Tammela, Päivi

    2015-02-01

    High-throughput screening is an established technique in drug discovery and, as such, has also found its way into academia. High-throughput screening generates a considerable amount of data, which is why specific software is used for its analysis and management. The commercially available software packages are often beyond the financial limits of small-scale academic laboratories and, furthermore, lack the flexibility to fulfill certain user-specific requirements. We have developed a Python module, screening_mgmt, which is a lightweight tool for flexible data retrieval, analysis, and storage for different screening assays in one central database. The module reads custom-made analysis scripts and plotting instructions, and it offers a graphical user interface to import, modify, and display the data in a uniform manner. During the test phase, we used this module for the management of 10,000 data points of various origins. It has provided a practical, user-friendly tool for sharing and exchanging information between researchers. © 2014 Society for Laboratory Automation and Screening.

  10. Asia Pacific energy derivatives

    Fusaro, P.C.

    1997-09-01

    Asia Pacific Energy Derivatives, from FT Energy, is the first report of its kind to examine the growth of energy derivatives within Asia Pacific and their increasing importance within this region. It provides a comprehensive overview of the subject, including analysis of: deregulation as a market driver; the impact of privatisation; the future for energy risk management tools; the unique characteristics of the Asia Pacific energy market; the role of futures exchanges in Asia; existing indexes and their performance; the differences between the Asia Pacific markets and their more mature counterparts in London and New York; non-oil derivatives, project finance and cross commodity arbitrage; the thriving Pacific Rim Over the Counter (OTC) markets. (author)

  11. 4-Aminoquinoline derivatives

    Singh, Shailja; Agarwal, Drishti; Sharma, Kumkum

    2016-01-01

    and found them to be effective against Plasmodium falciparum under in vitro conditions. Further, we selected four most active derivatives 1m, 1o, 2c and 2j and evaluated their antimalarial potential against Plasmodium berghei in vivo. These 4-aminoquinolines cured BALB/c mice infected with P. berghei......Synthetic quinoline derivatives continue to be considered as candidates for new drug discovery if they act against CQ-resistant strains of malaria even after the widespread emergence of resistance to CQ. In this study, we explored the activities of two series of new 4-aminoquinoline derivatives...... for structure activity relationship to find lead molecules for treating multidrug-resistant Plasmodium falciparum and Plasmodium vivax....

  12. Essays on Derivatives Pricing

    Kokholm, Thomas

    . With the existence of a liquid market for derivatives with variance as underlying, such as VIX options, VIX futures and a well-developed over-the-counter market for options on variance swaps, it is important to consider models that are able to fit these markets while consistently pricing vanilla options...... financial models, and most importantly, to be aware of their limitations. Following that belief, this thesis consists of three independent and self-contained papers, all dealing with topics in derivatives pricing. The first paper considers the pricing of traffic light options, which are appropriate...... the market for multivariate credit instruments, we take a step back and focus on single-name default modeling and introduce two new model classes for modeling of the default time of a company. Finally, in the third paper we propose a consistent pricing model for index and volatility derivatives...

  13. The combinatorial derivation

    Igor V. Protasov

    2013-09-01

    $\\Delta(A=\\{g\\in G:|gA\\cap A|=\\infty\\}$. The mapping $\\Delta:\\mathcal{P}_G\\rightarrow\\mathcal{P}_G$, $A\\mapsto\\Delta(A$, is called a combinatorial derivation and can be considered as an analogue of the topological derivation $d:\\mathcal{P}_X\\rightarrow\\mathcal{P}_X$, $A\\mapsto A^d$, where $X$ is a topological space and $A^d$ is the set of all limit points of $A$. Content: elementary properties, thin and almost thin subsets, partitions, inverse construction and $\\Delta$-trajectories,  $\\Delta$ and $d$.

  14. CLAD DEGRADATION - FEPS SCREENING ARGUMENTS

    R. Schreiner

    2004-01-01

    The purpose of this report is to evaluate and document the screening of the clad degradation features, events, and processes (FEPs) with respect to modeling used to support the Total System Performance Assessment-License Application (TSPA-LA). This report also addresses the effect of certain FEPs on both the cladding and the commercial spent nuclear fuel (CSNF), DOE-owned spent nuclear fuel (DSNF), and defense high-level waste (DHLW) waste forms, as appropriate to address the effects on multiple materials and both components (FEPs 2.1.09.09.0A, 2.1.09.11.0A, 2.1.11.05.0A, 2.1.12.02.0A, and 2.1.12.03.0A). These FEPs are expected to affect the repository performance during the postclosure regulatory period of 10,000 years after permanent closure. Table 1-1 provides the list of cladding FEPs, including their screening decisions (include or exclude). The primary purpose of this report is to identify and document the analysis, screening decision, and TSPA-LA disposition (for included FEPs) or screening argument (for excluded FEPs) for these FEPs related to clad degradation. In some cases, where a FEP covers multiple technical areas and is shared with other FEP reports, this report may provide only a partial technical basis for the screening of the FEP. The full technical basis for shared FEPs is addressed collectively by the sharing FEP reports. The screening decisions and associated TSPA-LA dispositions or screening arguments from all of the FEP reports are cataloged in a project-specific FEPs database

  15. The Evaluation of Novel Camphor-derived Ligands as Catalysts in ...

    The evaluation of a series of camphor-derived ligands as catalysts in the asymmetric Henry reaction is reported. The synthesis of two novel derivatives is detailed and these molecules are also screened as catalysts in this reaction. The single crystal X-ray structure of one of the novel compounds is reported. The reaction is ...

  16. Pi sampling: a methodical and flexible approach to initial macromolecular crystallization screening

    Gorrec, Fabrice; Palmer, Colin M.; Lebon, Guillaume; Warne, Tony

    2011-01-01

    Pi sampling, derived from the incomplete factorial approach, is an effort to maximize the diversity of macromolecular crystallization conditions and to facilitate the preparation of 96-condition initial screens. The Pi sampling method is derived from the incomplete factorial approach to macromolecular crystallization screen design. The resulting ‘Pi screens’ have a modular distribution of a given set of up to 36 stock solutions. Maximally diverse conditions can be produced by taking into account the properties of the chemicals used in the formulation and the concentrations of the corresponding solutions. The Pi sampling method has been implemented in a web-based application that generates screen formulations and recipes. It is particularly adapted to screens consisting of 96 different conditions. The flexibility and efficiency of Pi sampling is demonstrated by the crystallization of soluble proteins and of an integral membrane-protein sample

  17. Screening on urogenital Chlamydia trachomatis

    Busse, Reinhard

    2005-12-01

    Full Text Available Introduction: Around 92 million urogenital infections are caused yearly by Chlamydia trachomatis worldwide [1]. The overall incidence of sexually transmitted diseases is increasing, as shown by the increases in the number of reported cases of syphilis and gonorrhea [2]. Chlamydia trachomatis infections are associated with various serious diseases in women, men and newborns, which could be, at least partially, avoided by means of early diagnosis and therapy. The Federal Joint Committee - responsible for decision-making concerning the benefit package of the German Social Health Insurance - has publicly announced the starting of deliberations on the issue of screening for Chlamydia trachomatis. Research Questions: The leading question to be answered is whether screening for Chlamydia trachomatis should be included in the German benefit basket. The aim of this report is to provide a summary of the available evidence concerning the issue of screening for Chlamydia trachomatis. Methods: The summary of published scientific evidence, including HTA reports, systematic reviews, guidelines and primary research is represented. The synthesis follows the structure given by the criteria of Wilson and Jungner [3] for the introduction of screening in a population: relevance of the condition, availability of an adequate test, effectiveness of screening, acceptance of the programme, and economical issues. A literature search was conducted for each aspect of the synthesis and the evidence has been summarised in evidence tables. Results: We identified five HTA reports from three European agencies [4], [5], [6], [7] and one from the USA [8]. In addition, we identified four guidelines from Northamerica [9], [10], [11], [12] and one from Europe [13]. A total of 56 primary research publications were included: relevance of the disease (n=26, availability of test (n=1, effectiveness of screening (n=11, acceptance of the programme (n=11, economical issues (n=7. Discussion

  18. 20 CFR 654.408 - Screening.

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Screening. 654.408 Section 654.408 Employees... EMPLOYMENT SERVICE SYSTEM Housing for Agricultural Workers Housing Standards § 654.408 Screening. (a) All outside openings shall be protected with screening of not less than 16 mesh. (b) All screen doors shall be...

  19. Quinazolin-4-one derivatives

    Mosley, Cara A; Acker, Timothy M; Hansen, Kasper Bø

    2010-01-01

    We describe a new class of subunit-selective antagonists of N-methyl D-aspartate (NMDA)-selective ionotropic glutamate receptors that contain the (E)-3-phenyl-2-styrylquinazolin-4(3H)-one backbone. The inhibition of recombinant NMDA receptor function induced by these quinazolin-4-one derivatives...

  20. Metal borohydrides and derivatives

    Paskevicius, Mark; Haarh Jepsen, Lars; Schouwink, Pascal

    2017-01-01

    major classes of metal borohydride derivatives have also been discovered: anion-substituted compounds where the complex borohydride anion, BH4 -, is replaced by another anion, i.e. a halide or amide ion; and metal borohydrides modified with neutral molecules, such as NH3, NH3BH3, N2H4, etc. Here, we...

  1. 78 FR 32191 - Derivatives

    2013-05-29

    ... rate risk. This proposed rule applies to federal credit unions and any federally insured, state... risk to the National Credit Union Share Insurance Fund (NCUSIF). \\1\\ A derivative is an instrument... degrees of risk to a credit union. Accordingly, this risk calls for a more robust asset/ liability...

  2. Superstability of Generalized Derivations

    Esmaeil Ansari-Piri

    2010-01-01

    Full Text Available We investigate the superstability of the functional equation f(xy=xf(y+g(xy, where f and g are the mappings on Banach algebra A. We have also proved the superstability of generalized derivations associated to the linear functional equation f(γx+βy=γf(x+βf(y, where γ,β∈ℂ.

  3. The Diabetic Retinopathy Screening Workflow

    Bolster, Nigel M.; Giardini, Mario E.; Bastawrous, Andrew

    2015-01-01

    Complications of diabetes mellitus, namely diabetic retinopathy and diabetic maculopathy, are the leading cause of blindness in working aged people. Sufferers can avoid blindness if identified early via retinal imaging. Systematic screening of the diabetic population has been shown to greatly reduce the prevalence and incidence of blindness within the population. Many national screening programs have digital fundus photography as their basis. In the past 5 years several techniques and adapters have been developed that allow digital fundus photography to be performed using smartphones. We review recent progress in smartphone-based fundus imaging and discuss its potential for integration into national systematic diabetic retinopathy screening programs. Some systems have produced promising initial results with respect to their agreement with reference standards. However further multisite trialling of such systems’ use within implementable screening workflows is required if an evidence base strong enough to affect policy change is to be established. If this were to occur national diabetic retinopathy screening would, for the first time, become possible in low- and middle-income settings where cost and availability of trained eye care personnel are currently key barriers to implementation. As diabetes prevalence and incidence is increasing sharply in these settings, the impact on global blindness could be profound. PMID:26596630

  4. Mass spectrometry for fragment screening.

    Chan, Daniel Shiu-Hin; Whitehouse, Andrew J; Coyne, Anthony G; Abell, Chris

    2017-11-08

    Fragment-based approaches in chemical biology and drug discovery have been widely adopted worldwide in both academia and industry. Fragment hits tend to interact weakly with their targets, necessitating the use of sensitive biophysical techniques to detect their binding. Common fragment screening techniques include differential scanning fluorimetry (DSF) and ligand-observed NMR. Validation and characterization of hits is usually performed using a combination of protein-observed NMR, isothermal titration calorimetry (ITC) and X-ray crystallography. In this context, MS is a relatively underutilized technique in fragment screening for drug discovery. MS-based techniques have the advantage of high sensitivity, low sample consumption and being label-free. This review highlights recent examples of the emerging use of MS-based techniques in fragment screening. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Colour screening and quark confinement

    Mack, G.

    1978-03-01

    It is proposed that in Quantum Chromodynamics the colour charge of gluons and of anything with zero triality is screened by a dynamical Higgs mechanism with Higgs scalars made out of gluons. The center Z 3 of the gauge group SU(3) is left unbroken in this way, and single quarks, which have nonzero triality, cannot be screened. Long range forces between them persist therefore. Given that the Higgs mechanism produces a mass gap, the most favorable configuration of field lines between e.g. quark and antiquark will be in strings analogous to magnetic field lines in a superconductor. The strings confine the quarks. The screening mechanism, on the other hand, produces not only the mass gap (which leads to string formation) but is also responsible for saturation of forces, i.e. absence of bound states of six quarks etc. (orig.) [de

  6. Colour screening and quark confinement

    Mack, G.

    1978-01-01

    It is proposed that in quantum chromodynamics the colour charge of gluons and of anything with zero triality is screened by a dynamic Higgs mechanism with Higgs scalars made out of gluons, but the center Z 3 of the gauge group SU(3) is left unbroken, and single quarks, which have nonzero triality, are not screened. Long range forces between them persist therefore. Given that the Higgs mechanism produces a mass gap, the most favourable configuration of field lines between e.g., quark and antiquark will be in strings analogous to magnetic field lines in a superconductor. The string confine the quarks. The screening mechanism, on the other hand, produces not only the mass gap (which leads to string formation) but is also responsible for saturation of forces, i.e. absence of bound states of six quarks, etc. (Auth.)

  7. A history of breast cancer screening and future problems in Japan

    Morimoto, Tadaoki

    2009-01-01

    In Europe and the United States, mortality due to breast cancer is decreasing. There are various reasons for this trend, including an increase in the detection of early-stage breast cancers due to the increased use of mammographic screening, and the establishment of standardized systemic treatments derived from evidence-based medicine (EBM). On the other hand, in Japanese women, both morbidity and mortality due to breast cancer are increasing. This paper describes the process of breast cancer screening in the past, its current status, and the quality control system for mammographic screening in Japan, as well as the status of breast cancer screening in Europe and the United States. Furthermore, problems of breast cancer screening in Japan discussed, together with the need for practical measures such as implementation of quality control systems aimed at improving the cancer screening rate (with a target of 50%), financial support, and population-based screening (organized screening), based on the Cancer Control Act. Current measures for screening of dense breast tissue in women in their 40s in Japan are also described. (author)

  8. More misinformation on breast cancer screening

    Kopans, Daniel B.

    2017-01-01

    Unfortunately, a great deal of misinformation has accumulated in the breast cancer screening literature that is based on flawed analyses in an effort to reduce access to screening. Quite remarkably, much of this has come from publications in previously highly respected medical journals. In several papers the intervention (mammography screening) is faulted yet the analyses provided no data on who participated in mammography screening, and which cancers were detected by mammography screening. I...

  9. Approximate *-derivations and approximate quadratic *-derivations on C*-algebras

    Park Choonkil

    2011-01-01

    Full Text Available Abstract In this paper, we prove the stability of *-derivations and of quadratic *-derivations on Banach *-algebras. We moreover prove the superstability of *-derivations and of quadratic *-derivations on C*-algebras. 2000 Mathematics Subject Classification: 39B52; 47B47; 46L05; 39B72.

  10. Arvelig hemokromatose - nytten av screening

    Arne Åsberg

    2009-10-01

    Full Text Available Arvelig hemokromatose fører til jernopphopning i kroppen, men gir sjelden alvorlig helseskade. Nesten alle hemokromatosepasienter i vårt land er homozygote for C282Y-mutasjonen i HFE-genet. Omtrent 7 per 1000 innbyggere har denne genotypen. Alvorlig syke blir bare omkring 5-15% av homozygote menn og nesten ingen kvinner. Likevel er det holdepunkter for at screening for hemokromatose blant friske, yngre menn kan være kostnadseffektivt. Det er relativt lett å påvise om en person er disponert for sykdommen, i god tid før den bryter ut, og forebyggende behandling er billig og effektiv. Imidlertid kan vi ikke forutsi hvilke screeningpositive personer som ubehandlet får alvorlig sykdom. Et kontrollert forsøk med screening bør gjennomføresHereditary hemochromatosis – benefits of screening. Hereditary hemochromatosis leads to iron accumulation in the body; however, serious illness due to hemochromatosis is rare. In Norway, almost all patients with hemochromatosis are homozygous for the C282Ymutation in the HFE-gene, a genotype carried by about 7 per 1000 inhabitants. Serious complications are seen in only about 5-15% of homozygous men and in very few women. Nevertheless, screening young men for hemochromatosis may be cost-effective. Detecting predisposed men is relatively straightforward, and prophylactic treatment is cheap and effective. However, we can not predict, among screen-positive men, the few who untreated will become seriously ill. A controlled screening trial should be conducted.

  11. Screening for deformed teeth; Screening for saere taender

    Vermeulen, A.; Dall, P.C.; Hansen, F.G.

    1996-04-01

    Water pollution by pesticides and heavy metals causes sublethal effects in larvae of the Chironomidae midges. These effects are particularly noticeable in the deformities of the oral parts and antennae. Possibilities of using these deformities for the purpose of water/sediment biomonitoring are very promising. Here the first results of screening in a Danish stream are presented. (EG) 9 refs.

  12. Nutritional Screening of Children: A Manual for Screening & Followup.

    Bureau of Community Health Services (DHHS/PHS), Rockville, MD.

    This manual shows health providers how to perform precisely and expertly each step of several procedures used in screening children for nutritional problems. It is intended for all health providers who are involved in weighing and measuring children, recording and plotting measurements on growth charts, taking blood samples to test for iron…

  13. Faraday screen sputtering on TPX

    Ehst, D.A.

    1994-12-01

    The TPX design stipulates that the ion-cyclotron resonance frequency (ICRF) antenna must have a Faraday screen (FS). The author considers here possible low Z coatings for the screen, as well as sputtering behavior of the Ni and Ti substrates. The theory of rf-induced sputtering has been developed, and he follows those theoretical approaches. The author's emphasis will be on both impurity generation as a possible source of increased Z eff , and also on actual erosion-lifetime of the materials under worst case conditions

  14. THE DEVELOPMENT OF SCREEN TRANSLATION

    Sang Ayu Isnu Maharani

    2014-05-01

    Full Text Available Screen translations involve oral translation known as dubbing and revoicing. Re-voicing consists of lip-sync dubbing, free commentary, narration and voice over. The written version is called subtitle. Dubbing and subtitling are two preferred mode used in the screen translation even though various numbers of current options are available nowadays. Dubbing commenced to be used in larger countries in Europe meanwhile smaller countries apply subtitling because it is more economical than dubbing. In Indonesia, the use of dubbing as well as subtitle are found.

  15. RNAi Screening in Spodoptera frugiperda.

    Ghosh, Subhanita; Singh, Gatikrushna; Sachdev, Bindiya; Kumar, Ajit; Malhotra, Pawan; Mukherjee, Sunil K; Bhatnagar, Raj K

    2016-01-01

    RNA interference is a potent and precise reverse genetic approach to carryout large-scale functional genomic studies in a given organism. During the past decade, RNAi has also emerged as an important investigative tool to understand the process of viral pathogenesis. Our laboratory has successfully generated transgenic reporter and RNAi sensor line of Spodoptera frugiperda (Sf21) cells and developed a reversal of silencing assay via siRNA or shRNA guided screening to investigate RNAi factors or viral pathogenic factors with extraordinary fidelity. Here we describe empirical approaches and conceptual understanding to execute successful RNAi screening in Spodoptera frugiperda 21-cell line.

  16. Icons and Emoticons: Screen Wars

    Duerfahrd, Lance

    2015-01-01

    The cinema is being upstaged by a device paradoxically meant (in part) to transmit it: the iPhone. How do films change, how is their impact altered, when viewed on these devices? What aspects of the movie screen (and subsequently our movie experience) are lost or threatened when they are displaced by this new technological format? This is not an abstract war: it is going on (in the dark) every time we attend a screening. My paper will explore what is at stake in our decision to illuminate our...

  17. Hierarchical screening for multiple mental disorders.

    Batterham, Philip J; Calear, Alison L; Sunderland, Matthew; Carragher, Natacha; Christensen, Helen; Mackinnon, Andrew J

    2013-10-01

    There is a need for brief, accurate screening when assessing multiple mental disorders. Two-stage hierarchical screening, consisting of brief pre-screening followed by a battery of disorder-specific scales for those who meet diagnostic criteria, may increase the efficiency of screening without sacrificing precision. This study tested whether more efficient screening could be gained using two-stage hierarchical screening than by administering multiple separate tests. Two Australian adult samples (N=1990) with high rates of psychopathology were recruited using Facebook advertising to examine four methods of hierarchical screening for four mental disorders: major depressive disorder, generalised anxiety disorder, panic disorder and social phobia. Using K6 scores to determine whether full screening was required did not increase screening efficiency. However, pre-screening based on two decision tree approaches or item gating led to considerable reductions in the mean number of items presented per disorder screened, with estimated item reductions of up to 54%. The sensitivity of these hierarchical methods approached 100% relative to the full screening battery. Further testing of the hierarchical screening approach based on clinical criteria and in other samples is warranted. The results demonstrate that a two-phase hierarchical approach to screening multiple mental disorders leads to considerable increases efficiency gains without reducing accuracy. Screening programs should take advantage of prescreeners based on gating items or decision trees to reduce the burden on respondents. © 2013 Elsevier B.V. All rights reserved.

  18. Derived enriched uranium market

    Rutkowski, E.

    1996-01-01

    The potential impact on the uranium market of highly enriched uranium from nuclear weapons dismantling in the Russian Federation and the USA is analyzed. Uranium supply, conversion, and enrichment factors are outlined for each country; inventories are also listed. The enrichment component and conversion components are expected to cause little disruption to uranium markets. The uranium component of Russian derived enriched uranium hexafluoride is unresolved; US legislation places constraints on its introduction into the US market

  19. Computation of Mie derivatives.

    Li, Yang; Bowler, Nicola

    2013-07-10

    Analytical expressions are obtained for the derivatives of Mie scattering coefficients with respect to the electrical radius of the spherical scattering particle, and to the relative permittivity and permeability of both the particle and the surrounding medium. Their corresponding approximate expressions are developed to avoid numerical overflow based on the logarithmic derivative of Riccati-Bessel functions. The analytical expressions have been verified by comparing their results with those calculated by analytical expressions developed by Mathematica. Compared with the numerical derivative, the analytical expressions and approximate expressions show a higher accuracy and are 2.0 and 2.8 times, respectively, faster in the case of a single magnetodielectric sphere. Generally, for spheres with an electrical radius in a large range, the approximate expressions can yield acceptable accuracy and computation time up to a high order. This work can be used in the design of nonmetallic metamaterials, and in the retrieval of aerosol properties from remote sensing data. An example calculation is given for the design of an optical, all-dielectric, mu-negative metamaterial consisting of a simple cubic array of tellurium nanoparticles.

  20. Carnitine derivatives: clinical usefulness.

    Malaguarnera, Mariano

    2012-03-01

    Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.

  1. Multifunctional Cinnamic Acid Derivatives

    Aikaterini Peperidou

    2017-07-01

    Full Text Available Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX inhibition (IC50 = 6 μΜ and antiproteolytic activity (IC50 = 0.425 μΜ. The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ and good LOX inhibitory activity (IC50 = 66 μΜ. Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

  2. High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

    Stoltz, Brian

    2010-06-14

    The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto-ester derived- and an α-phenyl cyclohexanone-derived enol carbonate.

  3. High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

    Stoltz, Brian; McDougal, Nolan; Virgil, Scott

    2010-01-01

    The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a non-polar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto-ester derived- and an α-phenyl cyclohexanone-derived enol carbonate.

  4. Newborn screening for MCAD deficiency

    Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G

    2008-01-01

    . Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second...

  5. Transitivity and partial screening off

    Peijnenburg, Jeanne; Atkinson, David

    2013-01-01

    The notion of probabilistic support is beset by well-known problems. In this paper we add a new one to the list: the problem of transitivity. Tomoji Shogenji has shown that positive probabilistic support, or confirmation, is transitive under the condition of screening off. However, under that same

  6. Developments in SPR Fragment Screening.

    Chavanieu, Alain; Pugnière, Martine

    2016-01-01

    Fragment-based approaches have played an increasing role alongside high-throughput screening in drug discovery for 15 years. The label-free biosensor technology based on surface plasmon resonance (SPR) is now sensitive and informative enough to serve during primary screens and validation steps. In this review, the authors discuss the role of SPR in fragment screening. After a brief description of the underlying principles of the technique and main device developments, they evaluate the advantages and adaptations of SPR for fragment-based drug discovery. SPR can also be applied to challenging targets such as membrane receptors and enzymes. The high-level of immobilization of the protein target and its stability are key points for a relevant screening that can be optimized using oriented immobilized proteins and regenerable sensors. Furthermore, to decrease the rate of false negatives, a selectivity test may be performed in parallel on the main target bearing the binding site mutated or blocked with a low-off-rate ligand. Fragment-based drug design, integrated in a rational workflow led by SPR, will thus have a predominant role for the next wave of drug discovery which could be greatly enhanced by new improvements in SPR devices.

  7. Screening Tools for Kindergarten Children

    Georgia Kokkalia

    2017-12-01

    Full Text Available The current paper review gives a brief and representative description of some of the most used screening tools for kindergarten education. The significant role that early education plays in every child’s academic life is underlined by the importance of tools that give his learning profiles.  Therefore many researchers note that screening tools paly a notable role for the kindergarten teachers, the family and of course for the child in order to offer the appropriate intervention program, the proper support and draw the most suitable teaching method for the child and the class. Thus, the research team of this paper gives the description of some screening tools that are used by kindergarten teachers and specialist’s worldwide-with focus in Greek kindergarten- scoping to underlie strengths and weaknesses of preschoolers. Finally, it is thought worthwhile to say that the screening tools that are presented are used with the traditional way while some of them with the support of new technology.

  8. Disciplining and Screening Top Executives

    S. Dominguez Martinez (Silvia); O.H. Swank (Otto); B. Visser (Bauke)

    2006-01-01

    textabstractBoards of directors face the twin task of disciplining and screening executives. To perform these tasks directors do not have detailed information about executives' behaviour, and only infrequently have information about the success or failure of initiated strategies, reorganizations,

  9. Comparative Phytochemical screening and Physicochemical ...

    Physicochemical characterization was carried out to determine the saponification value, refractive index, specific gravity, peroxide value and acid value of the oil. The results of the phytochemical screening showed that alkaloid, carbohydrate, saponins, glycosides were present in the sample obtained from Romi New ...

  10. Keuringspanele ("Screening Panels") as Gepaste ...

    In this particular article attention is paid to screening panels as pre-trial mechanism with the exclusive purpose to select malpractice disputes, discourage unfounded disputes and to encourage an early settlement in case of a prima facie case. Several objections have been raised by critics in this regard, for instance, ...

  11. Shadows Cast on the Screen?

    Jensen, Sisse Siggaard

    cast on the screen. This understanding is questioned with reference to a semiotic understanding of avatars if seen as triadic relationships of sign processes—that is, as something that stands for something for someone. This understanding is exemplified by the case of Thomas and his businessman avatar...

  12. Colorectal Cancer Awareness and Screening

    2017-04-06

    An oncologist (cancer doctor) shares her medical and personal advice for people between the ages of 50 and 75 about getting screened for colorectal cancer.  Created: 4/6/2017 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 4/6/2017.

  13. FAST MRI breast screening revisited

    Jain, Manish; Jain, Arushi; Hyzy, Marek D.; Werth, Graziella

    2017-01-01

    Screening for breast cancer in high-risk women takes about 40 minutes to acquire an MRI scan and is time-intensive to report. There is recent interest in the performance of an abbreviated MRI protocol (FAST) in the screening setting. FAST scans have a reported negative predictive value of 99.8%. This study evaluates the false positive rates (FPR) and recall rates for FAST scans as compared to full diagnostic studies (FD). A database of all screening breast MRI scans performed at our institution between 30 June 2013 and 1 July 2014 (n = 591) was created by one of the researchers, who did not subsequently analyse the MRI scans. The T1W and first post-contrast and subtracted images from each of these scans (FAST protocol) were assessed by experienced breast MRI radiologists, blinded to the final diagnosis. The findings were then compared with the FD result. The recall rates were 6.6% for FAST scans and 5.8% for FD scans. FPR rates were 4.7% and 3.9% respectively. There is no statistically significant difference in the recall rates or FPR of FAST scans in comparison with full diagnostic studies. Given the absence of statistically significant difference in the FPR and recall rates in comparison with FD, FAST scans can replace FD for screening of breast cancer.

  14. Screen violence and youth behavior

    Anderson, Craig A.; Bushman, Brad J.; Bartholow, Bruce D.; Cantor, Joanne; Christakis, Dimitri; Coyne, Sarah M.; Donnerstein, Edward; Brockmyer, Jeanne Funk; Gentile, Douglas A.; Green, C. Shawn; Huesmann, Rowell; Hummer, Tom; Krahé, Barbara; Strasburger, Victor C.; Warburton, Wayne; Wilson, Barbara J.; Ybarra, Michele

    2017-01-01

    Violence in screen entertainment media (ie, television, film, video games, and the Internet), defined as depictions of characters (or players) trying to physically harm other characters (or players), is ubiquitous. The Workgroup on Media Violence and Violent Video Games reviewed numerous

  15. Screening for autologous blood transfusions

    Mørkeberg, J; Belhage, B; Ashenden, M

    2009-01-01

    parameter in the screening for autologous blood doping. Three bags of blood (approximately 201+/-11 g of Hb) were withdrawn from 16 males and stored at either -80 degrees C (-80 T, n=8) or +4 degrees C (+4 T, n=8) and reinfused 10 weeks or 4 weeks later, respectively. Seven subjects served as controls...

  16. Walkthrough screening evaluation field guide

    Eder, S.J.; Eli, M.W.; Salmon, M.W.

    1993-11-01

    The US Department of Energy (DOE) has a large inventory of existing facilities. Many of these facilities were not designed and constructed to current natural phenomena hazard (NPH) criteria. The NPH events include earthquakes, extreme winds and tornadoes, and floods. DOE Order 5480.28 establishes policy and requirements for NPH mitigation for DOE facilities. DOE is conducting a multiyear project to develop evaluation guidelines for assessing the condition and determining the need for upgrades at DOE facilities. One element of the NPH evaluation guidelines' development involves the existing systems and components at DOE facilities. This effort is described in detail in a cited reference. In the interim period prior to availability of the final guidelines, DOE facilities are encouraged to implement an NPH walk through screening evaluation process by which systems and components that need attention can be rapidly identified. Guidelines for conducting the walk through screening evaluations are contained herein. The result of the NPH walk through screening evaluation should be a prioritized list of systems and components that need further action. Simple and inexpensive fixes for items identified in the walk through as marginal or inadequate should be implemented without further study. By implementing an NPH walk through screening evaluation, DOE facilities may realize significant reduction in risk from NPH in the short term

  17. Review of Autism Screening Tests

    Farin Soleimani

    2014-10-01

    Full Text Available Background: Autism is a neurodevelopmental disorder that onset in the first 3 years of life and led to lifelong disability.Despite the early onset of symptoms, diagnosis of thissyndromedoes not happenuntil severalyears later, somany childrenlosethe opportunityfor earlyintervention.There arevarious toolsforscreening anddiagnosis, buttheirdesign, strengths and weaknesses aredifferent. The aim of this study was assess these tools from various aspects to provide a comprehensive view. Materials and methods: This study is a narrative literature review on screeningtoolsof autism. Comprehensive searches of the scientific literature were conducted in textbooks and 8 electronic databases(proquest,wiley,google scholar,SID,Scopus, Web of Science ،Science Direct ، and Medline and Pediatric book. language restriction (Persian and English was applied. The search strategy consisted of keywords and medical subject headings for autism and various screening tests. Result: In this study, 28 screening tests were identified from 1992 to 2014. CHAT is oldest test and the most recent test is CAST The minimum age that can perform the screening is six months that related to ITC. Minimum time of testing was 5 minutes  for CHAT and the maximum time was 90-120 minutes for ASIEP-3.RAADS-R test was the highest specificity and specificity (100% and the lowest specificity was 14% in ESAT test Conclusion: The results of this study indicate that any of the autism screening tools consider specific skill and various aspects of the disease, careful evaluation is need to choose proper test.

  18. Designing a Pediatric Severe Sepsis Screening Tool

    Robert eSepanski

    2014-06-01

    Full Text Available We sought to create a screening tool with improved predictive value for pediatric severe sepsis and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric Emergency Department (ED. Gold standard severe sepsis cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over two months. The tool’s identification of severe sepsis was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating curve (ROC characteristics. Age-specific normal and abnormal values for heart rate (HR and respiratory rate (RR were empirically derived from 143,603 children seen in a second pediatric ED over three years. Univariate analyses were performed for each measure in the tool to assess its association with severe sepsis and to characterize it as an early or late indicator of severe sepsis. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly three-fold improvement over the original ICCPS tool. False positive Systemic Inflammatory Response Syndrome (SIRS identifications were nearly six-fold lower.

  19. Credit derivatives and risk management

    Michael S. Gibson

    2007-01-01

    The striking growth of credit derivatives suggests that market participants find them to be useful tools for risk management. I illustrate the value of credit derivatives with three examples. A commercial bank can use credit derivatives to manage the risk of its loan portfolio. An investment bank can use credit derivatives to manage the risks it incurs when underwriting securities. An investor, such as an insurance company, asset manager, or hedge fund, can use credit derivatives to align its...

  20. Credit derivatives in emerging markets

    Romain Rancière

    2002-01-01

    Credit Derivatives are securities that offer protection against credit or default risk of bonds or loans. The credit derivatives emerging market has grown rapidly and credit derivatives are widely used. This paper describes the emerging credit derivatives market structure. The current market activity is analyzed through elementary pricing dynamics and the study of the term structure of default risk. Focusing on the performance of credit derivatives in stress situation, including legal and mar...

  1. Primary care colorectal cancer screening correlates with breast cancer screening: implications for colorectal cancer screening improvement interventions.

    Weiss, Jennifer M; Pandhi, Nancy; Kraft, Sally; Potvien, Aaron; Carayon, Pascale; Smith, Maureen A

    2018-04-25

    National colorectal cancer (CRC) screening rates have plateaued. To optimize interventions targeting those unscreened, a better understanding is needed of how this preventive service fits in with multiple preventive and chronic care needs managed by primary care providers (PCPs). This study examines whether PCP practices of other preventive and chronic care needs correlate with CRC screening. We performed a retrospective cohort study of 90 PCPs and 33,137 CRC screening-eligible patients. Five PCP quality metrics (breast cancer screening, cervical cancer screening, HgbA1c and LDL testing, and blood pressure control) were measured. A baseline correlation test was performed between these metrics and PCP CRC screening rates. Multivariable logistic regression with clustering at the clinic-level estimated odds ratios and 95% confidence intervals for these PCP quality metrics, patient and PCP characteristics, and their relationship to CRC screening. PCP CRC screening rates have a strong correlation with breast cancer screening rates (r = 0.7414, p < 0.001) and a weak correlation with the other quality metrics. In the final adjusted model, the only PCP quality metric that significantly predicted CRC screening was breast cancer screening (OR 1.25; 95% CI 1.11-1.42; p < 0.001). PCP CRC screening rates are highly concordant with breast cancer screening. CRC screening is weakly concordant with cervical cancer screening and chronic disease management metrics. Efforts targeting PCPs to increase CRC screening rates could be bundled with breast cancer screening improvement interventions to increase their impact and success.

  2. Chemical compatibility screening test results

    Nigrey, P.J.; Dickens, T.G.

    1997-12-01

    A program for evaluating packaging components that may be used in transporting mixed-waste forms has been developed and the first phase has been completed. This effort involved the screening of ten plastic materials in four simulant mixed-waste types. These plastics were butadiene-acrylonitrile copolymer rubber, cross-linked polyethylene (XLPE), epichlorohydrin rubber, ethylene-propylene rubber (EPDM), fluorocarbon (Viton or Kel-F), polytetrafluoroethylene, high-density polyethylene (HDPE), isobutylene-isoprene copolymer rubber (butyl), polypropylene, and styrene-butadiene rubber (SBR). The selected simulant mixed wastes were (1) an aqueous alkaline mixture of sodium nitrate and sodium nitrite; (2) a chlorinated hydrocarbon mixture; (3) a simulant liquid scintillation fluid; and (4) a mixture of ketones. The testing protocol involved exposing the respective materials to 286,000 rads of gamma radiation followed by 14-day exposures to the waste types at 60 degrees C. The seal materials were tested using vapor transport rate (VTR) measurements while the liner materials were tested using specific gravity as a metric. For these tests, a screening criterion of 0.9 g/hr/m 2 for VTR and a specific gravity change of 10% was used. Based on this work, it was concluded that while all seal materials passed exposure to the aqueous simulant mixed waste, EPDM and SBR had the lowest VTRs. In the chlorinated hydrocarbon simulant mixed waste, only Viton passed the screening tests. In both the simulant scintillation fluid mixed waste and the ketone mixture simulant mixed waste, none of the seal materials met the screening criteria. For specific gravity testing of liner materials, the data showed that while all materials with the exception of polypropylene passed the screening criteria, Kel-F, HDPE, and XLPE offered the greatest resistance to the combination of radiation and chemicals

  3. Synthesis and biological evaluation of 2-substituted benzimidazole derivatives

    Gurusamy Mariappan

    2015-09-01

    Full Text Available A novel series of 2-substituted benzimidazole derivatives (3a–3j were synthesized by the reaction of 2-chloro methyl benzimidazole with substituted primary aromatic amines. All the compounds were characterized by UV, IR, 1H NMR, mass spectral data and CHN elemental analysis. The synthesized derivatives were screened for analgesic and anti-inflammatory activities. All the compounds showed significant effect at 100 mg/kg p.o. and the experimental data are statistically significant at p < 0.01 level.

  4. Smoking cessation and lung cancer screening

    Pedersen, Jesper Johannes Holst; Tønnesen, Philip; Ashraf, Haseem

    2016-01-01

    Smoking behavior may have a substantial influence on the overall effect of lung cancer screening. Non-randomized studies of smoking behavior during screening have indicated that computer tomography (CT) screening induces smoking cessation. Randomized studies have further elaborated that this effect...... and decrease smoking relapse rate. Also low smoking dependency and high motivation to quit smoking at baseline predicted smoking abstinence in screening trials. Lung cancer screening therefore seems to be a teachable moment for smoking cessation. Targeted smoking cessation counselling should be an integrated...... part of future lung cancer screening trials....

  5. Increasing Cervical Cancer Screening in Underserved Populations.

    Dorsainvil, Merlyn A

    The incidence of cervical cancer has declined dramatically due to Papanicolaou smear testing. However, some minority populations continue to suffer with high incidences and/or death rates of cervical cancer, due to lack of screening. This article updates on cervical cancer screening and prevention and discusses cultural impacts on screening. Knowledge deficits disproportionately affect ethnic minority groups and contribute to cancer incidence, whereas lack of healthcare coverage and low socioeconomic status contribute to screening disparities. Although minority women have cultural beliefs and practices that influence screening, recommendation and/or education from a provider often lead to screening.

  6. Determination of a Screening Metric for High Diversity DNA Libraries.

    Guido, Nicholas J; Handerson, Steven; Joseph, Elaine M; Leake, Devin; Kung, Li A

    2016-01-01

    The fields of antibody engineering, enzyme optimization and pathway construction rely increasingly on screening complex variant DNA libraries. These highly diverse libraries allow researchers to sample a maximized sequence space; and therefore, more rapidly identify proteins with significantly improved activity. The current state of the art in synthetic biology allows for libraries with billions of variants, pushing the limits of researchers' ability to qualify libraries for screening by measuring the traditional quality metrics of fidelity and diversity of variants. Instead, when screening variant libraries, researchers typically use a generic, and often insufficient, oversampling rate based on a common rule-of-thumb. We have developed methods to calculate a library-specific oversampling metric, based on fidelity, diversity, and representation of variants, which informs researchers, prior to screening the library, of the amount of oversampling required to ensure that the desired fraction of variant molecules will be sampled. To derive this oversampling metric, we developed a novel alignment tool to efficiently measure frequency counts of individual nucleotide variant positions using next-generation sequencing data. Next, we apply a method based on the "coupon collector" probability theory to construct a curve of upper bound estimates of the sampling size required for any desired variant coverage. The calculated oversampling metric will guide researchers to maximize their efficiency in using highly variant libraries.

  7. Determination of a Screening Metric for High Diversity DNA Libraries.

    Nicholas J Guido

    Full Text Available The fields of antibody engineering, enzyme optimization and pathway construction rely increasingly on screening complex variant DNA libraries. These highly diverse libraries allow researchers to sample a maximized sequence space; and therefore, more rapidly identify proteins with significantly improved activity. The current state of the art in synthetic biology allows for libraries with billions of variants, pushing the limits of researchers' ability to qualify libraries for screening by measuring the traditional quality metrics of fidelity and diversity of variants. Instead, when screening variant libraries, researchers typically use a generic, and often insufficient, oversampling rate based on a common rule-of-thumb. We have developed methods to calculate a library-specific oversampling metric, based on fidelity, diversity, and representation of variants, which informs researchers, prior to screening the library, of the amount of oversampling required to ensure that the desired fraction of variant molecules will be sampled. To derive this oversampling metric, we developed a novel alignment tool to efficiently measure frequency counts of individual nucleotide variant positions using next-generation sequencing data. Next, we apply a method based on the "coupon collector" probability theory to construct a curve of upper bound estimates of the sampling size required for any desired variant coverage. The calculated oversampling metric will guide researchers to maximize their efficiency in using highly variant libraries.

  8. Synthesis and antibacterial studies of some novel isoxazoline derivatives

    TEJASKUMAR SHAH

    2007-05-01

    Full Text Available A series of 3-[3-(2,4-dichloro-5-fluorophenyl-5-(2-furyl-4,5-dihydro-1H-pyrazol-1-yl]-5-(substituted phenyl/2-thienylisoxazolines (4a-j were prepared. The structures of the isoxazoline derivatives were confirmed on the bases of elemental analysis and spectral data. The compounds were screened for their in vitro antibacterial activity using gram-positive bacteria and gram-negative bacteria.

  9. Screening history in women with cervical cancer in a Danish population-based screening program

    Kirschner, Benny; Poll, Susanne; Rygaard, Carsten

    2011-01-01

    The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer.......The aim of this study was to explore the screening histories of all cervical cancers in a Danish screening population. The intention was to decide suboptimal sides of the screening program and to evaluate the significance of routine screening in the development of cervical cancer....

  10. Nonabelian Debye screening and the {open_quotes}tsunami{close_quotes} problem

    Pisarski, R.D. [Brookhaven National Lab., Upton, NY (United States)

    1997-09-22

    The phenomenon of Debye screening is familiar from electrolytes and many other systems. Recently, it has been recognized that in nonabelian gauge theories at high temperature, even perturbatively Debye screening is much more complicated than in nonrelativistic systems. This was originally derived as {open_quotes}hard thermal loops{close_quotes}. Hard thermal loops have been derived perturbatively, by a semiclassical truncation of the Schwinger-Dyson equations, and by classical kinetic theory. In this talk I give a pedagogical derivation, following that of Kelly, Liu, Lucchesi, and Manuel. The derivation is valid not just for a thermal distribution, but (modulo certain obvious restrictions) for an arbitrary initial distribution of particles. Consider, for example, the {open_quotes}tsunami{close_quotes} problem: suppose that one starts, at time t = 0, with a spatially homogenous, infinite wall of particles, all moving with the same velocity at the speed of light.

  11. In defense of derivations

    Mungan, Carl E.

    2016-05-01

    At the 2015 AAPT Summer Meeting, I presented four derivations of the formula for motional emf. Such physics derivations involve the construction of explanatory frameworks involving diagrams and mathematical models. Although textbooks devote considerable space to such explanations, many teachers and students spend their time on worksheets, end-of-chapter problems, and the like. The book is reduced to a bank of solved (i.e., example) and unsolved (i.e., homework) questions, along with equations in colored boxes that presumably are to be used to answer those questions. Such an approach encourages fragmentation of knowledge, the view that there is only one right answer to a problem with the goal of physics being to find that answer (neatly boxed of course), and the inability to reason about even a slightly different (much less a novel) situation. If we are to develop scientific literacy, significant course time must be devoted to explaining the structure of and support for the models and equations we use.

  12. Cloud screening Coastal Zone Color Scanner images using channel 5

    Eckstein, B. A.; Simpson, J. J.

    1991-01-01

    Clouds are removed from Coastal Zone Color Scanner (CZCS) data using channel 5. Instrumentation problems require pre-processing of channel 5 before an intelligent cloud-screening algorithm can be used. For example, at intervals of about 16 lines, the sensor records anomalously low radiances. Moreover, the calibration equation yields negative radiances when the sensor records zero counts, and pixels corrupted by electronic overshoot must also be excluded. The remaining pixels may then be used in conjunction with the procedure of Simpson and Humphrey to determine the CZCS cloud mask. These results plus in situ observations of phytoplankton pigment concentration show that pre-processing and proper cloud-screening of CZCS data are necessary for accurate satellite-derived pigment concentrations. This is especially true in the coastal margins, where pigment content is high and image distortion associated with electronic overshoot is also present. The pre-processing algorithm is critical to obtaining accurate global estimates of pigment from spacecraft data.

  13. Screening Sex: revelando e dissimulando o sexo Screening Sex

    Linda Williams

    2012-06-01

    Full Text Available Neste texto, procura-se contar a história da exibição do sexo em filmes majoritariamente produzidos nos Estados Unidos no período de quase um século. Ao se perguntar quando, porque e como os Estados Unidos se transformaram de uma cultura que não exibia o sexo em uma que o exibe, a autora insiste no duplo significado do verbo screen (tanto como uma revelação quanto uma dissimulação. Exibir é revelar em uma tela. Mas um segundo e igualmente importante significado, como diz o dicionário é "proteger ou esconder atrás de uma tela". Os filmes tanto revelam como escondem. O artigo analisa a forma como mudanças sociais ocorridas nos Estados Unidos, como, por exemplo, a Revolução sexual dos anos 60 e novas visões a respeito da sexualidade, possibilitaram novas maneiras de representação do sexo no cinema, reorganizando a relação entre o público e o privado. O artigo se pergunta também sobre como nossos corpos e sentidos reagem ao encontro com o sexo na tela, introduzindo a ideia de "saber carnal" (carnal knowledge.In this paper, we try to tell the history of the exhibition of sex in movies mainly produced in the United States in almost a century. Asking when, why and how the United States became - from a culture that did not exhibit sex - into a culture that exhibits it, the author insists in the double sense of the verb to screen (as both a revelation and a dissimulation. To exhibit is to reveal in a screen. But another, and important, sense, as says the dictionary, is "to protect or hide behind a screen". Movies show as well as they reveal. The paper analyzes the way social change in the United States, for example the sexual revolution of the sixties and new views on sexuality allowed new ways of representing sex in the movies, creating a new relation between public and private. The paper also asks how our bodies and senses react to sex in the screen, introducing the idea of "carnal knowledge".

  14. Screening and classification of ceramic powders

    Miwa, S.

    1983-01-01

    A summary is given of the classification technology of ceramic powders. Advantages and disadvantages of the wet and dry screening and classification methods are discussed. Improvements of wind force screening devices are described.

  15. Prostate Cancer Screening Results from PLCO

    Learn the results of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a large-scale clinical trial to determine whether certain cancer screening tests can help reduce deaths from prostate, lung, colorectal, and ovarian cancer.

  16. Screening for Hepatitis C Infections in Adults

    Understanding Task Force Recommendations Screening for Hepatitis C Virus Infection in Adults The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation statement on Screening for Hepatitis C Virus ...

  17. Breast cancer screening: ''reassuring'' the worried well?

    Brodersen, John; Siersma, Volkert; Ryle, Mette

    2011-01-01

    of women offered screening compared to a population of women not offered screening for breast cancer. METHODS: One thousand women, aged 50-69 years, were randomly drawn from the Danish Civil Registration System to receive part I of the questionnaire Consequences of Screening in Breast Cancer (COS-BC1......): the sample consisted of 500 women living in a geographical area where screening mammography had been offered for more than 10 years and 500 women living in an area where the public health authorities had never invited women to breast cancer screening. RESULTS: A total of 759 women returned the questionnaire....... Those living in areas where screening was not offered reported more negative psychosocial aspects compared to women living in areas where screening was offered. CONCLUSIONS: The results indicate that women tend to perceive breast cancer screening as a reassuring preventive initiative. Alternatively...

  18. Health Screening: MedlinePlus Health Topic

    ... I Have an Eye Exam? (Prevent Blindness America) Lipid Panel (American Association for Clinical Chemistry) Lung Cancer Screening (Mayo Foundation for Medical Education and Research) Also in Spanish Skin Cancer Screening (National Cancer ...

  19. Retinopathy of prematurity screening criteria and workload ...

    Larger infants require screening to include a few outliers, but they ... Making local screening criteria narrower on the basis of a limited evidence base may be dangerous. Risk factors for CSROP in larger infants need to be researched.

  20. Retinopathy of prematurity screening criteria and workload ...

    Larger infants require screening to include a few outliers, but they require ... Making local screening criteria narrower on the basis of a limited evidence base may be dangerous. Risk factors for CSROP in larger infants need to be researched.