Role of association in chiral catalysis: from asymmetric synthesis to spin selectivity

"This is the peer reviewed version of the following article: Ageeva, Aleksandra A., Ekaterina A. Khramtsova, Ilya M. Magin, Peter A. Purtov, Miguel A. Miranda, and Tatyana V. Leshina. 2018. Role of Association in Chiral Catalysis: From Asymmetric Synthesis to Spin Selectivity. Chemistry A European Journal 24 (70). Wiley: 18587 600. doi:10.1002/chem.201801625, which has been published in final form at https://doi.org/10.1002/chem.201801625. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] The origin of biomolecules in the pre-biological period is still a matter of debate, as is the unclarified nature of the differences in enantiomer properties, especially for the medically important activity of chiral drugs. With regards to the first issue, significant progress was made in the last decade of the 20th century through experimental confirmation of Frank's popular theory on chiral catalysis in spontaneous asymmetric synthesis. Soai examined the chiral catalysis of the alkylation of achiral aldehydes by achiral reagents. Attempts to model this process demonstrated the key role of chiral compounds associates as templates for chiral synthesis. However, the elementary mechanism of alkylation and the role of free radicals in this process are still incompletely understood. Meanwhile, the influence of external magnetic fields on chiral enrichment in the radical path of alkylation has been predicted. In addition, the role of chiral dyad association in another radical process, electron transfer (ET), has been recently demonstrated by the following methods: chemically induced dynamic nuclear polarisation (CIDNP), NMR spectroscopy, XRD and photochemistry. The CIDNP analysis of ET in two dyads has revealed a phenomenon first observed for chiral systems, spin selectivity, which results in the difference between the CIDNP enhancement coefficients of dyad diastereomers. These dyads are linked systems consisting of the widespread drug (S)-naproxen (NPX) or its R analogue and electron donors, namely, (S)-tryptophan and (S)-N-methylpyrrolidine. Because NPX is one of the most striking examples of the difference in the therapeutic properties of enantiomers, the appearance of spin selectivity in dyads with (S)- and (R)-NPX and S donors can shed light on the chemical nature of these differences. This review is devoted to discussing the chemical nature of spin selectivity and the role of chiral associates in the chiral catalysis of an elementary radical reaction: ET in chiral dyads.The work was supported by the Russian Science Foundation (18-13-00047).Ageeva, A.; Khramtsova, E.; Magin, I.; Purtov, P.; Miranda Alonso, MÁ.; Leshina, T. (2018). Role of association in chiral catalysis: from asymmetric synthesis to spin selectivity. Chemistry - A European Journal. 24(70):18587-18600. https://doi.org/10.1002/chem.201801625S18587186002470Avalos, M., Babiano, R., Cintas, P., Jiménez, J. L., Palacios, J. C., & Barron, L. D. (1998). Absolute Asymmetric Synthesis under Physical Fields:  Facts and Fictions. Chemical Reviews, 98(7), 2391-2404. doi:10.1021/cr970096oLin, G.-Q., Zhang, J.-G., & Cheng, J.-F. (2011). Overview of Chirality and Chiral Drugs. Chiral Drugs, 3-28. doi:10.1002/9781118075647.ch1Liu, Y., & Gu, X.-H. (2011). Pharmacology of Chiral Drugs. Chiral Drugs, 323-345. doi:10.1002/9781118075647.ch8Frank, F. C. (1953). On spontaneous asymmetric synthesis. Biochimica et Biophysica Acta, 11, 459-463. doi:10.1016/0006-3002(53)90082-1Soai, K., Kawasaki, T., & Matsumoto, A. (2014). Asymmetric Autocatalysis of Pyrimidyl Alkanol and Its Application to the Study on the Origin of Homochirality. Accounts of Chemical Research, 47(12), 3643-3654. doi:10.1021/ar5003208Soai, K., Kawasaki, T., & Matsumoto, A. (2014). The Origins of Homochirality Examined by Using Asymmetric Autocatalysis. The Chemical Record, 14(1), 70-83. doi:10.1002/tcr.201300028Soai, K., Matsumoto, A., & Kawasaki, T. (2017). Asymmetric Autocatalysis and the Origins of Homochirality of Organic Compounds. An Overview. Advances in Asymmetric Autocatalysis and Related Topics, 1-30. doi:10.1016/b978-0-12-812824-4.00001-0Matsumoto, A., Kawasaki, T., & Soai, K. (2017). Structural Study of Asymmetric Autocatalysis by X-Ray Crystallography. Advances in Asymmetric Autocatalysis and Related Topics, 183-202. doi:10.1016/b978-0-12-812824-4.00010-1Schiaffino, L., & Ercolani, G. (2010). Mechanism of the Asymmetric Autocatalytic Soai Reaction Studied by Density Functional Theory. Chemistry - A European Journal, 16(10), 3147-3156. doi:10.1002/chem.200902543Buono, F. G., & Blackmond, D. G. (2003). Kinetic Evidence for a Tetrameric Transition State in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes†. Journal of the American Chemical Society, 125(30), 8978-8979. doi:10.1021/ja034705nGridnev, I. D., & Vorobiev, A. K. (2012). Quantification of Sophisticated Equilibria in the Reaction Pool and Amplifying Catalytic Cycle of the Soai Reaction. ACS Catalysis, 2(10), 2137-2149. doi:10.1021/cs300497hGridnev, I. D., Serafimov, J. M., & Brown, J. M. (2004). Solution Structure and Reagent Binding of the Zinc Alkoxide Catalyst in the Soai Asymmetric Autocatalytic Reaction. Angewandte Chemie International Edition, 43(37), 4884-4887. doi:10.1002/anie.200353572Gridnev, I. D., Serafimov, J. M., & Brown, J. M. (2004). Solution Structure and Reagent Binding of the Zinc Alkoxide Catalyst in the Soai Asymmetric Autocatalytic Reaction. Angewandte Chemie, 116(37), 4992-4995. doi:10.1002/ange.200353572Noble-Terán, M. E., Cruz, J.-M., Micheau, J.-C., & Buhse, T. (2018). A Quantification of the Soai Reaction. ChemCatChem, 10(3), 642-648. doi:10.1002/cctc.201701554Girard, C., & Kagan, H. B. (1998). Nonlinear Effects in Asymmetric Synthesis and Stereoselective Reactions: Ten Years of Investigation. Angewandte Chemie International Edition, 37(21), 2922-2959. doi:10.1002/(sici)1521-3773(19981116)37:213.0.co;2-1Girard, C., & Kagan, H. B. (1998). Nichtlineare Effekte bei asymmetrischen Synthesen und stereoselektiven Reaktionen. Angewandte Chemie, 110(21), 3088-3127. doi:10.1002/(sici)1521-3757(19981102)110:213.0.co;2-aNoble-Terán, M. E., Buhse, T., Cruz, J.-M., Coudret, C., & Micheau, J.-C. (2016). Nonlinear Effects in Asymmetric Synthesis: A Practical Tool for the Discrimination between Monomer and Dimer Catalysis. ChemCatChem, 8(10), 1836-1845. doi:10.1002/cctc.201600216Blackmond, D. G. (2000). Kinetic Aspects of Nonlinear Effects in Asymmetric Catalysis. Accounts of Chemical Research, 33(6), 402-411. doi:10.1021/ar990083sMatsumoto, A., Abe, T., Hara, A., Tobita, T., Sasagawa, T., Kawasaki, T., & Soai, K. (2015). Crystal Structure of the Isopropylzinc Alkoxide of Pyrimidyl Alkanol: Mechanistic Insights for Asymmetric Autocatalysis with Amplification of Enantiomeric Excess. Angewandte Chemie International Edition, 54(50), 15218-15221. doi:10.1002/anie.201508036Matsumoto, A., Abe, T., Hara, A., Tobita, T., Sasagawa, T., Kawasaki, T., & Soai, K. (2015). Crystal Structure of the Isopropylzinc Alkoxide of Pyrimidyl Alkanol: Mechanistic Insights for Asymmetric Autocatalysis with Amplification of Enantiomeric Excess. Angewandte Chemie, 127(50), 15433-15436. doi:10.1002/ange.201508036Ashby, E. C., Lopp, I. G., & Buhler, J. D. (1975). Mechanisms of Grignard reactions with ketones. Polar vs. single electron transfer pathways. Journal of the American Chemical Society, 97(7), 1964-1966. doi:10.1021/ja00840a066Ashby, E. C. (1988). Single-electron transfer, a major reaction pathway in organic chemistry. An answer to recent criticisms. Accounts of Chemical Research, 21(11), 414-421. doi:10.1021/ar00155a005Hegstrom, R. A., & Kondepudi, D. K. (1996). Influence of static magnetic fields on chirally autocatalytic radical-pair reactions. Chemical Physics Letters, 253(3-4), 322-326. doi:10.1016/0009-2614(96)00248-5K. M. Salikhov Yu. N. Molin R. Z. Sagdeev A. L. Buchachenko Spin Polarization and Magnetic Effects in Radical Reactions 1984 Akademiai Kiado Budapest Hungary 65 72Welch, C. J., Zawatzky, K., Makarov, A. A., Fujiwara, S., Matsumoto, A., & Soai, K. (2017). Can the analyte-triggered asymmetric autocatalytic Soai reaction serve as a universal analytical tool for measuring enantiopurity and assigning absolute configuration? Organic & Biomolecular Chemistry, 15(1), 96-101. doi:10.1039/c6ob01939kAgeeva, A. A., Khramtsova, E. A., Magin, I. M., Rychkov, D. A., Purtov, P. A., Miranda, M. A., & Leshina, T. V. (2018). Spin Selectivity in Chiral Linked Systems. Chemistry - A European Journal, 24(15), 3882-3892. doi:10.1002/chem.201705863Khramtsova, E. A., Sosnovsky, D. V., Ageeva, A. A., Nuin, E., Marin, M. L., Purtov, P. A., … Leshina, T. V. (2016). Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers. Physical Chemistry Chemical Physics, 18(18), 12733-12741. doi:10.1039/c5cp07305gKhramtsova, E. A., Ageeva, A. A., Stepanov, A. A., Plyusnin, V. F., & Leshina, T. V. (2017). Photoinduced Electron Transfer in Dyads with (R)-/(S)-Naproxen and (S)-Tryptophan. Zeitschrift für Physikalische Chemie, 231(3). doi:10.1515/zpch-2016-0842Magin, I. M., Polyakov, N. E., Kruppa, A. I., Purtov, P. A., Leshina, T. V., Kiryutin, A. S., … Marin, M. L. (2016). Low field photo-CIDNP in the intramolecular electron transfer of naproxen–pyrrolidine dyads. Physical Chemistry Chemical Physics, 18(2), 901-907. doi:10.1039/c5cp04233jDuggan, K. C., Hermanson, D. J., Musee, J., Prusakiewicz, J. J., Scheib, J. L., Carter, B. D., … Marnett, L. J. (2011). (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. Nature Chemical Biology, 7(11), 803-809. doi:10.1038/nchembio.663Duggan, K. C., Walters, M. J., Musee, J., Harp, J. M., Kiefer, J. R., Oates, J. A., & Marnett, L. J. (2010). Molecular Basis for Cyclooxygenase Inhibition by the Non-steroidal Anti-inflammatory Drug Naproxen. Journal of Biological Chemistry, 285(45), 34950-34959. doi:10.1074/jbc.m110.162982Miners, J. O., Coulter, S., Tukey, R. H., Veronese, M. E., & Birkett, D. J. (1996). Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. Biochemical Pharmacology, 51(8), 1003-1008. doi:10.1016/0006-2952(96)85085-4Levkin, P. A., Kokorin, A. I., Schurig, V., & Kostyanovsky, R. G. (2006). Solid-state ESR differentiation between racemate versus enantiomer. Chirality, 18(4), 232-238. doi:10.1002/chir.20242Khlestkin, V. K., Glasachev, Y. I., Kokorin, A. I., & Kostyanovsky, R. G. (2004). ESR study of stereochemistry in chiral nitroxide radical crystals. Mendeleev Communications, 14(6), 318-320. doi:10.1070/mc2004v014n06abeh002055Mäurer, M., & Stegmann, H. B. (1990). Chiral recognition of diastereomeric esters and acetals by EPR and NMR investigations. Chemische Berichte, 123(8), 1679-1685. doi:10.1002/cber.19901230817Kreilick, R. W., Becher, J., & Ullman, E. F. (1969). Stable free radicals. V. Electron spin resonance studies of nitronylnitroxide radicals with asymmetric centers. Journal of the American Chemical Society, 91(18), 5121-5124. doi:10.1021/ja01046a032Schuler, P., Schaber, F.-M., Stegmann, H. B., & Janzen, E. (1999). Recognition of chirality in nitroxides using EPR and ENDOR spectroscopy. Magnetic Resonance in Chemistry, 37(11), 805-813. doi:10.1002/(sici)1097-458x(199911)37:113.0.co;2-kNaaman, R., & Waldeck, D. H. (2012). Chiral-Induced Spin Selectivity Effect. The Journal of Physical Chemistry Letters, 3(16), 2178-2187. doi:10.1021/jz300793yYin, P., Zhang, Z.-M., Lv, H., Li, T., Haso, F., Hu, L., … Liu, T. (2015). Chiral recognition and selection during the self-assembly process of protein-mimic macroanions. Nature Communications, 6(1). doi:10.1038/ncomms7475Ishida, Y., & Aida, T. (2002). Homochiral Supramolecular Polymerization of an «S»-Shaped Chiral Monomer:  Translation of Optical Purity into Molecular Weight Distribution. Journal of the American Chemical Society, 124(47), 14017-14019. doi:10.1021/ja028403hSato, K., Itoh, Y., & Aida, T. (2014). Homochiral supramolecular polymerization of bowl-shaped chiral macrocycles in solution. Chem. Sci., 5(1), 136-140. doi:10.1039/c3sc52449cDubinets, N. O., Safonov, A. A., & Bagaturyants, A. A. (2016). Structures and Binding Energies of the Naphthalene Dimer in Its Ground and Excited States. The Journal of Physical Chemistry A, 120(17), 2779-2782. doi:10.1021/acs.jpca.6b03761‘Excimer’ fluorescence VII. Spectral studies of naphthalene and its derivatives. (1965). Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences, 284(1399), 551-565. doi:10.1098/rspa.1965.0080Jiménez, M. C., Pischel, U., & Miranda, M. A. (2007). Photoinduced processes in naproxen-based chiral dyads. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 8(3), 128-142. doi:10.1016/j.jphotochemrev.2007.10.001Kerr, H. E., Softley, L. K., Suresh, K., Hodgkinson, P., & Evans, I. R. (2017). Structure and physicochemical characterization of a naproxen–picolinamide cocrystal. Acta Crystallographica Section C Structural Chemistry, 73(3), 168-175. doi:10.1107/s2053229616011980Hatton, J. V., & Richards, R. E. (1962). Solvent effects in N.M.R. spectra of amide solutions. Molecular Physics, 5(2), 139-152. doi:10.1080/00268976200100141Muñoz, M. ., Ferrero, R., Carmona, C., & Balón, M. (2004). Hydrogen bonding interactions between indole and benzenoid-π-bases. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 60(1-2), 193-200. doi:10.1016/s1386-1425(03)00206-3Mäurer, M., Stegmann, H. B., Hiller, W., & Müller, B. (1992). Stereoelectronic and Steric Effects in the Synthesis and Recognition of Diastereomeric Ethers by NMR and EPR Spectroscopy. Chemische Berichte, 125(4), 857-865. doi:10.1002/cber.1992125041

Endobronchial ultrasound application for diagnosis of tracheobronchial tree invasion by esophageal cancer

INTRODUCTION: Esophageal cancer staging has been performed through bronchoscopy, computerized tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS). Whereas CT and PET scan provide assessments of distant metastasis, bronchoscopy importantly diagnoses tracheobronchial involvement, complementing chest CT findings. EUS is the most accurate examination for T and N staging but is technically limited when tumoral stenoses cannot be traversed. Endobronchial ultrasound (EBUS) appears to present greater accuracy than EUS, CT, and bronchoscopy for assessing tracheobronchial wall involvement. EBUS has been recently associated with EUS for esophageal cancer staging in our unit. OBJECTIVE: To compare EBUS findings in esophageal cancer patients without evident signs of tracheobronchial invasion on conventional bronchoscopy with EUS and CT. METHODS: Fourteen patients with esophageal cancer underwent CT, conventional bronchoscopy, EUS, and EBUS for preoperative staging. All patients underwent EBUS and EUS with an Olympus® MH-908 echoendoscope at 7.5 MHz. Seven patients were eligible for the study according to the inclusion criteria. RESULTS: The echoendoscope could not traverse tumoral esophageal stenosis to perform EUS in two patients, and invasion was effectively diagnosed by EBUS. In 4 (57%) of 7 patients EBUS revealed additional information to staging. In the remaining 3 cases the invasion findings were the same under both EUS and EBUS. CONCLUSION: EBUS showed signs of tracheobronchial invasion not observed by conventional bronchoscopy, adding information to staging in most of the cases when compared with CT and EUS

A New Cosmological Scenario in String Theory

We consider new cosmological solutions with a collapsing, an intermediate and an expanding phase. The boundary between the expanding (collapsing) phase and the intermediate phase is seen by comoving observers as a cosmological past (future) horizon. The solutions are naturally embedded in string and M-theory. In the particular case of a two-dimensional cosmology, space-time is flat with an identification under boost and translation transformations. We consider the corresponding string theory orbifold and calculate the modular invariant one-loop partition function. In this case there is a strong parallel with the BTZ black hole. The higher dimensional cosmologies have a time-like curvature singularity in the intermediate region. In some cases the string coupling can be made small throughout all of space-time but string corrections become important at the singularity. This happens where string winding modes become light which could resolve the singularity. The new proposed space-time casual structure could have implications for cosmology, independently of string theory.Comment: 28 pages, 3 figures; v2: Added new subsection relating two-dimensional model to BTZ black hole, typos corrected and references added; v3: minor corrections, PRD versio

Verbreitung und Abundanz von Beta patula Aiton und anderen mit Kulturrüben verwandten Wildarten auf Madeira

In the Archipelago of Madeira four crop wild relatives of beets are native: Beta patula, Beta vulgaris subsp. maritima, Patellifolia procumbens, and Patellifolia patellaris. All species are valuable genetic resources for the sugar beet breeding. Only in the very eastern part of the Madeira Island on the islet Ilhéu do Desembarcadouro and Ilhéu Chão the endemic species Beta patula can be found. On both islets the plant number of this very rare species, and of the two widely distributed species B. vulgaris subsp. maritima and P. procumbens was established and the habitat described. The results of the species census are presented. The establishment of a genetic reserve for Beta patula is suggested in this paper with the objective to protect this species more effectively.Auf Madeira und benachbarten Inseln sind vier mit Kulturrüben verwandte Wildarten heimisch: Beta patula, Beta vulgaris subsp. maritima, Patellifolia procumbens, and Patellifolia patellaris. Alle Arten sind wertvolle genetische Ressourcen für die Zuckerrübenzüchtung. Die endemische Art Beta patula kommt nur im östlichen Teil von Madeira auf den Schären Ilhéu do Desembarcadouro und Ilhéu Chão vor. Auf beiden Schären wurde die Anzahl der Individuen dieser sehr seltenen Art sowie von zwei weiter verbreiteten Arten, B. vulgaris subsp. maritima und P. procumbens, ermittelt und ihr Lebensraum beschrieben. Die Einrichtung eines genetischen Schutzgebietes für Beta patula wird in diesem Beitrag vorgeschlagen, um diese Art effektiver schützen zu können.PNM (Parque Natural da Madeira), Dra. Rosa Pires, the Nature Wardens of PNM (Claudio Alves, Gil Pereira, João Paulo Mendes, Nelson Santos, Isamberto Silva and Filipe Viveiros), Paulo Costa, as well as the Portuguese Navy for the safety navigation to “Ilhéu Chão” and back to the Madeira Island. We would also like to thank DRIGOT for providing us with all the necessary maps. This work is part of Workpage 6, case study Beta, of the EU project “An integrated European in situ management work plan: implementing genetic reserves and on farm concepts”, AGRI GENRES 057, coordinated by the Julius Kühn-Institute and co-funded by the EU Commission, DG AGRI within the framework of council regulation 870/2004.info:eu-repo/semantics/publishedVersio

Distribution and abundance of Beta patula Aiton and other crop wild relatives of cultivated beets on Madeira

Auf Madeira und benachbarten Inseln sind vier mit Kulturrüben verwandte Wildarten heimisch: Beta patula, Beta vulgaris subsp. maritima, Patellifolia procumbens, and Patellifolia patellaris. Alle Arten sind wertvolle genetische Ressourcen für die Zuckerrübenzüchtung. Die endemische Art Beta patula kommt nur im östlichen Teil von Madeira auf den Schären Ilhéu do Desembarcadouro und Ilhéu Chão vor. Auf beiden Schären wurde die Anzahl der Individuen dieser sehr seltenen Art sowie von zwei weiter verbreiteten Arten, B. vulgaris subsp. mari­tima und P. procumbens, ermittelt und ihr Lebensraum beschrieben. Die Einrichtung eines genetischen Schutzgebietes für Beta patula wird in diesem Beitrag vorgeschlagen, um diese Art effektiver schützen zu können.In the Archipelago of Madeira four crop wild relatives of beets are native: Beta patula, Beta vulgaris subsp. mari­tima, Patellifolia procumbens, and Patellifolia patellaris. All species are valuable genetic resources for the sugar beet breeding. Only in the very eastern part of the Madeira Island on the islet Ilhéu do Desembarcadouro and Ilhéu Chão the endemic species Beta patula can be found. On both islets the plant number of this very rare species, and of the two widely distributed species B. vulgaris subsp. maritima and P. procumbens was established and the habitat described. The results of the species census are presented. The establishment of a genetic reserve for Beta patula is suggested in this paper with the objective to protect this species more effectively

Androgenic Effect and Phytochimie of the Bark of Trunk of Buchholzia coriacea Engl. (Capparidaceae)

The testosterone is the main androgen produced by the testes among the males.  Her absence is responsible for erectile dysfunction and the loss of the sexual performance. The aim of the present study is to evaluate the androgenic effect and to determine the profile phytochemestry of the barks of trunk of B. coriacea. Fifteen days after the castration, the animals left in group and, received the aqueous extract of B. coriacea (100, 250 and 500 mg/kg, p.o). The sexual parameters (mounts sexual, number of erections, number of ejaculations and the time of latency) have been valued, and compared, to the witnesses groups: water distilled (0,5 ml/100 mg, p.o) and Enanthate of testosterone (1 mg/mL, i.m). The dosage of the testosterone has been achieved by the technic of ELYSA analysis. The determination of the chemical families has been achieved by the technique of coloration in tubes. The aqueous extract of B. coriacea (100,250 and 500 mg/kg, p.o) has an effect androgenic because managed daily during 15 days, it provokes an increase of the rate plasmatic of the testosterone and the bodily weight of the rats, maintains the sexual parameters among the castrated rat, extract the number of ejaculations. The barks of trunk of B. coriacea would contain the stérols, the flavonoides, the saponosids that could be responsible for the sexual effects and androgénic observed. The aqueous extract of the plant would possess the properties androgenic would be to advise the patients presenting problems of masculine barrenness.  Keywords:  Androgen - Phytochimie - Buchholzia - coriacea&nbsp

Landau Damping and Coherent Structures in Narrow-Banded 1+1 Deep Water Gravity Waves

We study the nonlinear energy transfer around the peak of the spectrum of surface gravity waves by taking into account nonhomogeneous effects. In the narrow-banded approximation the kinetic equation resulting from a nonhomogeneous wave field is a Vlasov-Poisson type equation which includes at the same time the random version of the Benjamin-Feir instability and the Landau damping phenomenon. We analytically derive the values of the Phillips' constant $\alpha$ and the enhancement factor $\gamma$ for which the narrow-banded approximation of the JONSWAP spectrum is unstable. By performing numerical simulations of the nonlinear Schr\"{o}dinger equation we check the validity of the prediction of the related kinetic equation. We find that the effect of Landau damping is to suppress the formation of coherent structures. The problem of predicting freak waves is briefly discussed.Comment: 4 pages, 3 figure

Multi-Platform Detection of Small Ruminant Lentivirus Antibodies and Provirus as Biomarkers of Production Losses

Small ruminant lentiviruses (SRLVs) are endemic in most areas of Europe, causing a chronic infection and a multisystemic disease affecting the udder, carpal joints, lungs, and central nervous system. Due to the lack of treatments and protective vaccination strategies, infection control is focused on the identification of infected animals through serological or molecular techniques. However, antigenic and genetic heterogeneity of SRLVs represent a clear drawback for diagnosis. Infected animals may present lower animal production parameters such as birth weight or milk production and quality, depending on productive systems considered and, likely, to the diagnostic method applied. In this study, four sheep flocks dedicated to dairy or meat production were evaluated using three different ELISA and two PCR strategies to classify animal population according to SRLV infection status. Productive parameters were recorded along one whole lactation or reproductive period and compared between positive and negative animals. SRLV was present in 19% of the total population, being unequally distributed in the different flocks. Less than half of the infected animals were detected by a single diagnostic method, highlighting the importance of combining different diagnostic techniques. Statistical analysis employing animal classification using all the diagnostic methods associated lambing size, lamb weight at birth, and daily weight gain with SRLV infection status in meat flocks. Milk production, somatic cell count, fat, and protein content in the milk were associated with SRLV infection in dairy flocks, to a greater extent in the flock showing higher seroprevalence. A multi-platform SRLV diagnostic strategy was useful for ensuring correct animal classification, thus validating downstream studies investigating production traits

Convex domains of Finsler and Riemannian manifolds

A detailed study of the notions of convexity for a hypersurface in a Finsler manifold is carried out. In particular, the infinitesimal and local notions of convexity are shown to be equivalent. Our approach differs from Bishop's one in his classical result (Bishop, Indiana Univ Math J 24:169-172, 1974) for the Riemannian case. Ours not only can be extended to the Finsler setting but it also reduces the typical requirements of differentiability for the metric and it yields consequences on the multiplicity of connecting geodesics in the convex domain defined by the hypersurface.Comment: 22 pages, AMSLaTex. Typos corrected, references update

Eating Disorder Awareness Campaigns:Thematic and Quantitative Analysis Using Twitter

Background: Health awareness initiatives are frequent but their efficacy is a matter of controversy. We have investigated the effect of the Eating Disorder Awareness Week and Wake Up Weight Watchers campaigns on Twitter. Objective: We aimed to examine whether the Eating Disorder Awareness Week and Wake Up Weight Watchers initiatives increased the volume and dissemination of Twitter conversations related to eating disorders and investigate what content generates the most interest on Twitter. Methods: Over a period of 12 consecutive days in 2018, we collected tweets containing the hashtag #wakeupweightwatchers and hashtags related to Eating Disorder Awareness Week (#eatingdisorderawarenessweek, #eatingdisorderawareness, or #EDAW), with the hashtag #eatingdisorder as a control. The content of each tweet was rated as medical, testimony, help offer, awareness, pro-ana, or anti-ana. We analyzed the number of retweets and favorites generated, as well as the potential reach and impact of the hashtags and the characteristics of contributors. Results: The number of #wakeupweightwatchers tweets was higher than that of Eating Disorder Awareness Week and #eatingdisorder tweets (3900, 2056, and 1057, respectively). The content of tweets was significantly different between the hashtags analyzed (P<.001). Medical content was lower in the awareness campaigns. Awareness and help offer content were lower in #wakeupweightwatchers tweets. Retweet and favorite ratios were highest in #wakeupweightwatchers tweets. Eating Disorder Awareness Week achieved the highest impact, and very influential contributors participated. Conclusions: Both awareness campaigns effectively promoted tweeting about eating disorders. The majority of tweets did not promote any specific preventive or help-seeking behaviors