17 research outputs found

    Impulsive motions of the floating zone

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    A set of problems concerning the behaviour of a suddenly disturbed ideal floating zone is considered. Mathematical techniques of asymptotic expansions arc used to solve these problems. It is seen that many already available solutions, most of them concerning liquids enclosed in cavities, will be regarded as starting approximations which are valid except in the proximity of the free surface which laterally bounds the floating zone. In particular, the problem of the linear spin-up of an initially cylindrical floating zone is considered in some detail. The presence of a recircuiating fluid pattern near the free surface is detected. This configuration is attributed to the interplay between Coriolis forces and the azimuthal component of the viscous forces

    Comportamiento aerodinámico de barreras cortavientos 1

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    El trabajo presenta resultados de la exploración del campo de velocidades en estelas de distintos modelos de barreras porosas, con vistas a suposible utilización para proteger plantaciones o zonas habitadas de los efectos perniciosos del viento. Los ensayos se han hecho en túnel aerodinámico y, para las medidas, se ha utilizado un anemómetro de hilo caliente. Se ha medido: la velocidad media temporal, el nivel de turbulencia y, en algunos casos, el transporte turbulento y la inclinación del vector velocidad, en cuatro secciones distintas corriente abajo de cada barrera. El trabajo está dividido en ocho capítulos. En el primero se discute la posible utilidad de las barreras en agricultura. En el segundo se revisan ciertas características de las estelas turbulentas de diferentes obstáculos,con el fin de contrastar los resultados obtenidos con otros análogos. En el capítulo tercero se describen los métodos de medida. El cuarto presenta el grueso de los resultados, y los cuatro siguientes: la influencia del número de Reynolds, rugosidad del suelo, perfil del viento incidente y presencia de las paredes y techo del túnel, respectivamente. Los ensayos muestran que los perfiles de velocidades correspondientes a secciones situadas a cierta distancia de la barrera (mayor de seis a ocho veces la altura de ésta) se asemejan a los de un semichorro de baja velocidad que descarga paralelamente a una corriente más rápida. Los perfiles próximos y las condiciones iniciales del semichorro dependen de la configuración de la barrera. El modelo del semichorro equivalente permite calcular las características de la estela a distancias mayores que las que es posible reproducir en los experimentos. Por otra parte, sugiere ciertas modificaciones de la forma de la barrera para aumentar la longitud de la zona protegida del viento. La rugosidad del suelo y la existencia de perfiles de viento distintos del uniforme y más ajustados a la realidad, contribuyen a disminuir la longitud de la zona protegida. Esta observación está de acuerdo con los resultados de otros autores. Se observa que el nivel de turbulencia es muy sensible a las características geométricas de la barrera, lo que sugiere la posibilidad de controlar la capa límite sobre el terreno y, por tanto, el transporte de calor y masa en provecho de la productividad de cultivo. El trabajo que se presenta es parte de un programa más amplio, que tiene por objeto transmitir tecnología avanzada a ciertos dominios de interés para la agricultura y la industria

    Implementing a privacy-enhanced attribute-based credential system for online social networks with co-ownership management

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    Online social network (OSN) users are exhibiting an increased privacy-protective behaviour especially since multimedia sharing has emerged as a popular activity over most OSN sites. Popular OSN applications could reveal much of the users' personal information or let it easily derived, hence favouring different types of misbehaviour. In this article the authors deal with these privacy concerns by applying fine-grained access control and co-ownership management over the shared data. This proposal defines access policy as any linear boolean formula that is collectively determined by all users being exposed in that data collection namely the co-owners. All co-owners are empowered to take part in the process of data sharing by expressing (secretly) their privacy preferences and, as a result, jointly agreeing on the access policy. Access policies are built upon the concept of secret sharing systems. A number of predicates such as gender, affiliation or postal code can define a particular privacy setting. User attributes are then used as predicate values. In addition, by the deployment of privacy-enhanced attribute-based credential technologies, users satisfying the access policy will gain access without disclosing their real identities. The authors have implemented this system as a Facebook application demonstrating its viability, and procuring reasonable performance costs

    Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis

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    From a high-throughput screen of 42 444 knownhuman kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold wasidentified to begin optimization for the treatment of human Africantrypanosomiasis. Previously reported data for analogous com-pounds against human kinases GSK-3β, CDK-2, and CDK-4 wereleveraged to try to improve the selectivity of the series, resulting in23awhich showed selectivity forT. b. bruceiover these threehuman enzymes. In parallel, properties known to influence theabsorption, distribution, metabolism, and excretion (ADME)profile of the series were optimized resulting in20gbeingprogressed into an efficacy study in mice. Though20gshowedtoxicity in mice, it also demonstrated CNS penetration in a PKstudy and significant reduction of parasitemia in four out of the sixmice.This work was supported by National Institutes of HealthGrants (R01AI114685 (M.P.P. and M.N.), R01AI082577(M.P.P.), R56AI099476 (M.P.P.), R01AI124046 (M.P.P.),R21AI127594 (M.P.P.), the Spanish Ministerio de Economía,Industria y Competitividad (M.N., Grant SAF2015-71444-P;D.G.P., Grant SAF2016-79957-R., and Subdirección Generalde Redes y Centros de Investigación Cooperativa (RICET)(M.N., Grant RD16/0027/0019; D.G.P., Grant RD16/0027/0014), Grant RTI2018-097210-B-100 (MINCIU-FEDER) toF.G. C.R.C. acknowledges grant support from the NIH-NIAID(Grant R21AI126296) and the Bill and Melinda GatesFoundation (Grant OPP1171488), as well as the technicalassistance of Brian M. Suzuki for screening adultS. mansoni.We are grateful to AstraZeneca for performing thein vitroADME experiments presented throughout and to CharlesRiver Labs for thein vitroADME data presented inTables S3−S5 in the Supporting Information. We thank GSK Tres Cantosopen lab foundation for running the PK studies discussed inthis publication. An academic license for ChemAxon (https://www.chemaxon.com) is gratefully acknowledged. We thankDr. Melissa Buskes for help in the preparation of thismanuscri

    Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents

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    New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. We herein report the results of further investigation of one of these clusters consisting of substituted isatin derivatives, focusing on establishing structure-activity and -property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best activity-property profile, pharmacokinetic parameters were measured in mice.The authors wish to acknowledge funding from the National Institute of Allergy and Infectious Diseases (MPP & MN: R01AI114685; MPP R21AI126296, R21AI127594; CRC: R21AI126296, R21AI133393. https://www.niaid.nih.gov/), the Spanish Ministerio de Economía, Industria y Competitividad, (MN: SAF2015-71444-P; DG-P: SAF2016-79957-R. http://www.mineco.gob.es), Junta de Andalucía (FG: CTS-7282. https://www.juntadeandalucia.es) and Subdirección General de Redes y Centros de Investigación Cooperativa (RICET) (MN: RD16/0027/0019; DG-P: RD16/0027/0014. https://bit.ly/2OegOnX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

    Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.

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    New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. We herein report the results of further investigation of one of these clusters consisting of substituted isatin derivatives, focusing on establishing structure-activity and -property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best activity-property profile, pharmacokinetic parameters were measured in mice
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