Modélisation toxicocinétique du benzo(a)pyrène et 3-hydroxybenzo(a)pyrène pour l’interprétation des données de surveillance biologique de l’exposition chez les travailleurs

De nombreux travailleurs sont exposés aux hydrocarbures aromatiques polycycliques (HAP). Le benzo(a)pyrène (BaP) fait partie de ce groupe de polluants. Cette substance a été classée cancérogène reconnu chez l’humain. Pour évaluer l'exposition aux HAP cancérogènes, plusieurs chercheurs ont proposé d’utiliser la mesure du 3-hydroxybenzo(a)pyrène (3-OHBaP) dans l’urine des travailleurs exposés. Dans le cadre du présent projet, deux approches de modélisation ont été développées et appliquées pour permettre une meilleure compréhension de la toxicocinétique du BaP et son biomarqueur d’intérêt actuel, le 3-OHBaP, et pour aider à interpréter les résultats de surveillance biologique. Un modèle toxicocinétique à plusieurs compartiments a été développé sur la base des données préalablement obtenues sur le rat par notre groupe. Selon le modèle, le BaP injecté par voie intraveineuse est rapidement distribué du sang vers les tissus (t½ ≈ 4 h), avec une affinité particulière pour les poumons et les composantes lipidiques des tissus. Le BaP est ensuite distribué vers la peau et le foie. Au foie, le BaP est promptement métabolisé et le 3-OHBaP est formé avec une demi-vie de ≈ 3 h. Le métabolisme pulmonaire du BaP a également été pris en compte, mais sa contribution à la cinétique globale du BaP a été jugée négligeable. Une fois formé, le 3-OHBaP est distribué vers les différents organes presque aussi rapidement que la molécule mère (t½ ≈ 2 h). Le profil temporel du 3-OHBaP dans le rein montre une accumulation transitoire en raison de la différence observée entre le taux d’entrée (t½ = 28 min) et le taux de sortie (t½ = 4,5 h). La clairance totale de 3-OHBaP du corps est principalement gouvernée par le taux de transfert de la bile vers le tractus gastro-intestinal (t½ ≈ 4 h). Le modèle toxicocinétique à plusieurs compartiments a réussi à simuler un ensemble indépendant de profils urinaires publiés sur le 3-OHBaP. Ce modèle toxicocinétique à compartiments s'est avéré utile pour la determination des facteurs biologiques déterminants de la cinétique du BaP et du 3-OHBaP. Par la suite, un modèle pharmacocinétique à base physiologique (PCBP) reproduisant le devenir du BaP et du 3-OHBaP chez le rat a été construit. Les organes (ou tissus) représentés comme des compartiments ont été choisis en fonction de données expérimentales obtenues in vivo chez le rat. Les coefficients de partition, les coefficients de perméabilité, les taux de métabolisation, les paramètres d'excrétion, les fractions absorbées et les taux d'absorption pour différentes voies d’exposition ont été obtenus directement à partir des profils sanguins, tissulaires, urinaires et fécaux du BaP et du 3-OHBaP. Les valeurs de ces derniers paramètres ont été calculées par des procédures Monte-Carlo. Des analyses de sensibilité ont ensuite été réalisées pour s’assurer de la stabilité du modèle et pour établir les paramètres les plus sensibles de la cinétique globale. Cette modélisation a permis d’identifier les facteurs déterminants de la cinétique: 1) la sensibilité élevée des paramètres de la métabolisation hépatique du BaP et du 3-OHBaP ainsi que du taux d'élimination; 2) la forte distribution du BaP dans les poumons par rapport à d'autres tissus; 3) la distribution considérable du BaP dans les tissus adipeux et le foie; 4) la forte distribution du 3-OHBaP dans les reins; 5) le transfert limité du BaP par la diffusion tissulaire dans les poumons; 6) le transfert limité du 3-OHBaP par la diffusion tissulaire dans les poumons, les tissus adipeux et les reins; 7) la recirculation entéro-hépatique significative du 3-OHBaP. Suite à des analyses de qualité des ajustements des équations du modèle aux données observées, les probabilités que les simulations reproduisent les données expérimentales par pur hasard se sont avérées toujours inférieures à 10% pour les quatre voies d’exposition : intraveineuse, orale, cutanée et respiratoire. Nous avons extrapolé les modèles cinétiques du rat à l’humain afin de se doter d’un outil permettant de reconstituer les doses absorbées chez des travailleurs exposés dans diverses industries à partir de mesures de l'évolution temporelle du 3-OHBaP dans leur urine. Les résultats de ces modélisations ont ensuite été comparés à ceux de simulations obtenues avec un modèle toxicocinétique à compartiment unique pour vérifier l’utilité comparative d’un modèle simple et complexe. Les deux types de modèle ont ainsi été construits à partir de profils sanguins, tissulaires, urinaires et fécaux du BaP et du 3-OHBaP sur des rats exposés. Ces données ont été obtenues in vivo par voie intraveineuse, cutanée, respiratoire et orale. Ensuite, les modèles ont été extrapolés à l’humain en tenant compte des déterminants biologiques essentiels des différences cinétiques entre le rat et l’humain. Les résultats ont montré que l'inhalation n'était pas la principale voie d'exposition pour plusieurs travailleurs étudiés. Les valeurs de concentrations de BaP dans l’air utilisées afin de simuler les profils d’excrétion urinaire chez les travailleurs étaient différentes des valeurs de concentrations de BaP mesurées dans l’air. Une exposition au BaP par voie cutanée semblait mieux prédire les profils temporels observés. Finalement, les deux types de modélisation se sont avérés utiles pour reproduire et pour interpréter les données disponibles chez des travailleurs.Many workers are exposed to polycyclic aromatic hydrocarbons (PAHs). Benzo(a) pyrene (BaP) is part of this group of pollutants. This substance has been classified as a known carcinogen in humans. To assess exposure to carcinogenic PAHs, several researchers have proposed using the measurement of 3-hydroxybenzo(a)pyrene (3-OHBaP) in the urine of exposed workers. In this project, two modeling approaches were developed and applied to enable a better understanding of the toxicokinetics of BaP and its biomarker of current interest, 3-OHBaP, to help interpret the results of biological monitoring. A multi-compartment toxicokinetic model was developed based on the data previously obtained in rats by our group of research. According to the model, BaP injected intravenously is rapidly distributed from blood to tissues (t½ ≈ 4 h), with a particular affinity for lungs and lipid components of tissues. Subsequently, BaP is distributed to the liver and the skin. Once in the liver, BaP is promptly metabolized and 3-OHBaP is formed with a half-life of about 3 h. Pulmonary biotransformation of BaP was also taken into account, but its contribution to the overall kinetics of BaP was considered negligible. Once formed, 3-OHBaP is distributed to various organs almost as fast as the parent compound (t½ ≈ 2 h). An accumulation of 3-OHBaP profile is present in the kidneys because of the difference between the uptake rate (t½ = 28 min) and the ouput rate (t½ = 4.5 h). Total clearance of 3-OHBaP from the blood stream is primarily governed by the rate of transfer of the bile to the gastrointestinal tract (t ½ ≈ 4 h). The multi-compartment toxicokinetic model was able to simulate an independent set of published 3-OHBaP urinary profiles. This toxicokinetic compartmental model has proved useful for the determination of the main biological features of the kinetics of BaP and 3-OHBaP. Thereafter, a physiological pharmacokinetic model (PBPK) reproducing the fate of BaP and 3-OHBaP rats was built. Organs (or tissues) represented as compartments were selected based on experimental data obtained in vivo in rats. Partition coefficients, coefficients of permeability, biotransformation rates, excretion parameters, and absorption fraction for different exposure routes were obtained directly from the profiles of BaP and 3-OHBaP in blood, various tissues and excreta. The values of these parameters were calculated by Monte Carlo procedures. Sensitivity analyses were then performed to ensure the stability of the model and to determine the most sensitive parameters. This modeling has identified the following features: 1) a high sensitivity of hepatic metabolism and elimination rates of BaP and 3-OHBaP; 2) a large distribution of BaP in the lungs compared to other tissues; 3) a considerable distribution of BaP in adipose tissues and liver; 4) a significant distribution of 3-OHBaP in the kidneys; 5) a diffusion-limited transfer of BaP in the lungs, 6) a diffusion-limited transfer of 3-OHBaP in lungs, adipose tissues and kidneys; and 7) a significant entero-hepatic recycling of 3-OHBaP. Following a series of analysis of goodness of fit, the probabilites that the model simulations reproduced the experimental data due to pure chance were always below 10%, for the four routes of exposure: intravenous, oral, dermal and respiratory. Subsequently, we have extrapolated the kinetic models from rats to humans in order reproduce the temporal evolution of 3-OHBaP biomarker of exposure in the urine of workers occupationally expose. Results of these models were then compared to simulations obtained with a single compartment toxicokinetic model to verify the comparative usefulness of simple and complex model. Both types of models have been constructed from blood, tissue, urinary and faecal profiles of BaP and 3-OHBaP in rats. These data were obtained in vivo by intravenous, subcutaneous, oral and respiratory exposure. The models were extrapolated to humans taking into account the essential biological determinants of kinetic differences between rats and humans. Results showed that inhalation was not the primary route of exposure for many workers studied. The values of air concentrations of BaP used to simulate the urinary excretion profiles were different from those measured in the air. Dermal exposure to BaP seemed to better predict the temporal patterns observed. Finally, the two types of modeling have been proved useful to reproduce and to interpret experimental data obtained in workers

Economic model predictive control of wastewater treatment plants based on BSM1 using linear prediction models

Comunicación presentada en IEEE 15th International Conference on Control and Automation (ICCA), 16-19 July 2019, Edinburgh, United Kingdom,.In this paper, we have developed an Economical Model Predictive Control (EMPC) for a Wastewater Treatment Plant (WWTP) with the use of a standard semidefinite programming solver. In this case, the objective has been to keep the ammonium concentration in the effluent under limits manipulating the air insufflation pumps at the biological reactor and an internal recycle valve. The minimized cost function consists of the product of the energy consumed by the air insufflator and the cost of the electricity, taking into account the variations of the tariffs over the day. We have simulated the behaviour of the WWTP using the Benchmark Model Simulation n° 1 (BSMI), and we have developed a linear prediction model in order to apply the EMPC method

Gerencial games in business administration

This work aims at identifying the perception of modern languages students with emphasis on administration and students of other areas about the management simulators which are Zoo Tycoon and Papa’s Freezeria. This is done In order to contribute to a macro project at ECCI University which is the creation of a management simulator. To develop our research, a qualitative analysis was applied to five participants. The information was collected through matrixes and also via bibliographic research nationally and internationally to guide and contrast concepts. At the end of the investigation, the results were positive and negative because perceptions vary according to the simulators and the four management areas of the company.INTRODUCTION THEORETICAL FRAMEWORK State of Art RESEARCH DESIGN DATA ANALYSIS Analysis of the Management Area Analysis of the Finance Area Analysis of the Human Resources Area Analysis of the Marketing Area CONCLUSIONS AND RECOMMENDATIONS Recommendations REFERENCES APPENDIXPregradoProfesional en Lenguas ModernasLenguas Moderna

Albergue Flor de mayo

Albergue en el Cabanyal. Por una parte, se proyectan grandes espacios públicos en los que se realizan funciones comunes, y, por otra parte, se crean módulos de habitación compartida con los elementos indispensables para estancias cortas. El edificio cuenta con un sótano, una planta baja, en la que se encuentra el spa, la recepción, la cafetería, los vestuarios y los baños; hace la función de área de llegada y es un espacio libre de obstáculos. La primera planta tiene carácter de planta-plaza, en ella se produce todo el movimiento del edificio; aquí encontramos el restaurante, la zona de trabajo y de reunión, los espacios deportivos y de ocio. La segunda planta es a doble altura y alberga la zona de administración del edificio. La planta tercera acoge los dormitorios; son habitaciones lineales compartidas, aunque se pueden compartimentar gracias al uso de paneles. Por último, encontramos la terraza que realiza una función de mirador. En la fachada se utiliza cerámica vidriada como homenaje al Cabanyal.Heredia Del Rey, R. (2011). Albergue Flor de mayo. http://hdl.handle.net/10251/34425.Archivo delegad

A Detailed Urinary Excretion Time Course Study of Captan and Folpet Biomarkers in Workers for the Estimation of Dose, Main Route-of-Entry and Most Appropriate Sampling and Analysis Strategies

Captan and folpet are two fungicides largely used in agriculture, but biomonitoring data are mostly limited to measurements of captan metabolite concentrations in spot urine samples of workers, which complicate interpretation of results in terms of internal dose estimation, daily variations according to tasks performed, and most plausible routes of exposure. This study aimed at performing repeated biological measurements of exposure to captan and folpet in field workers (i) to better assess internal dose along with main routes-of-entry according to tasks and (ii) to establish most appropriate sampling and analysis strategies. The detailed urinary excretion time courses of specific and non-specific biomarkers of exposure to captan and folpet were established in tree farmers (n = 2) and grape growers (n = 3) over a typical workweek (seven consecutive days), including spraying and harvest activities. The impact of the expression of urinary measurements [excretion rate values adjusted or not for creatinine or cumulative amounts over given time periods (8, 12, and 24 h)] was evaluated. Absorbed doses and main routes-of-entry were then estimated from the 24-h cumulative urinary amounts through the use of a kinetic model. The time courses showed that exposure levels were higher during spraying than harvest activities. Model simulations also suggest a limited absorption in the studied workers and an exposure mostly through the dermal route. It further pointed out the advantage of expressing biomarker values in terms of body weight-adjusted amounts in repeated 24-h urine collections as compared to concentrations or excretion rates in spot samples, without the necessity for creatinine correction

Interactions between wood-rotting fungi (Agaricomycetes) and native and exotic trees from an urban ecosystem (Córdoba, Argentina)

El reemplazo de áreas naturales por zonas urbanizadas afecta la composición de las comunidades arbóreas, generalmente favoreciendo la ocurrencia de especies vegetales exóticas. Esto tendría implicancias directas en la estructuración de las comunidades de hongos patógenos que hospedan estas especies arbóreas. En este trabajo se propuso examinar: a) la estructura de la red de interacciones entre especies del arbolado urbano y los hongos patógenos degradadores de la madera, b) la composición de hongos patógenos en especies nativas y exóticas. Se observó que la red de interacciones mostró un patrón de anidamiento en donde varias especies de hongos patógenos establecen múltiples interacciones con diversas especies arbóreas, tanto nativas como exóticas, mientras que otras establecieron interacciones más específicas. Se observó mayor riqueza de hongos en árboles exóticos en comparación a sus pares nativos. Trece de las especies fúngicas se registraron exclusivamente en árboles exóticos, una exclusivamente en sustrato nativo y las nueve restantes compartieron tanto árboles exóticos como nativos.The replacement of natural areas by urban areas promotes changes in the composition of tree communities, frequently favoring the occurrence of exotic species. This may have direct implications in the structure of pathogenic fungal communities which grow in these hosts. Here we examine: a) the structure of the interaction networks between urban tree species and their pathogenic wood-decay fungi, b) the composition of pathogenic fungi in native and exotic hosts. The interactions network shows a nested pattern where several species of pathogenic fungi establish multiple interactions with various tree species, both native and exotic; while others establish more specific interactions. Richness of pathogenic fungi was higher in exotic trees than in natives. Thirteen fungal species occurred exclusively in exotic hosts, one in natives and the remaining nine species shared both exotic and native hosts.Fil: Cagnolo, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); ArgentinaFil: Heredia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); ArgentinaFil: Morera, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); ArgentinaFil: Robledo, Gerardo Lucio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); ArgentinaFil: Urcelay, Roberto Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinario de Biología Vegetal (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentin

Las plantas medicinales de la organización de parteras y médicos indígenas tradicionales de Ixhuatlancillo, Veracruz, México y su significancia cultural

Se registró la significancia cultural de las especies medicinales utilizadas por la Organización de Parteras y Médicos Indígenas Tradicionales "Nahuatlxihuilt" para la atención primaria de la salud, mediante el enfoque cuantitativo de la etnobotánica. Se utilizaron herramientas participativas, y se determinaron dos índices etnobotánicos: el de fidelidad de Friedman et al. (1986), que incluye el valor de uso, el rango de prioridad (ROP) y el rango de popularidad (RPL) y el índice de valor de uso de Gómez- Beloz (2002) para las partes de las plantas utilizadas. Las familias mejor representadas fueron: Compositae, Rosaceae, Lamiaceae y Solanaceae y que los géneros más importantes fueron Amaranthus, Plantago, Piper, Smilax y Urtica con dos especies cada uno. La mayor signifi cancia cultural fue: Cestrum nocturnum L., Chenopodium ambroisoides L., Chenopodium graveolens L., Urtica mexicana Liebm, U. urens Liebm y Lepidium virginicum L. (r = 0.95) (ROP = 100 y 90.9) y el índice de valor de uso para las partes de las plantas fue para las hojas (35.32) siendo las especies: Citrus sinensis (L.) Osbeck, Oncimun selloi Benth., Salvia polystachya J.G. Ortega, Psidium guajava L., Plantago lanceolata L., Plantago major L., Plantago australis L., Polygonum acuminatum Kunth, Ruta graveolens L., Sambucus nigra var. canadensis (L.) Bolli, Taraxacum offi cinale G.H. Weber ex Wigg., Tithonia tubiformis (Jacq.) Cass., Urtica chamaedryoides Pursh y los géneros Ageratina y Ageratum, las mejor representadas. De esta forma, se concluye con el análisis de la información sobre las especies propias del grupo participante y su importancia cultural lo cual fortalecen el proceso actual y dinámico de la medicina tradicional en la zona centro del estado de Veracruz

Role of floral strips and semi-natural habitats as enhancers of wild bee functional diversity in intensive agricultural landscapes

Los autores de la UAM pertenecen al Terrestrial Ecology Group, Department of EcologyInstalling patches of flowering plants is a commonly used strategy to enhance refuge and food resources for pollinators in intensive agricultural landscapes. Here, we evaluated how floral strips and semi-natural habitats impact the taxonomic and functional diversity of wild bees in intensively farmed sunflower fields. Pan traps were used to assess bee richness and functional diversity at 22 sampling sites (11 sites were positioned in sunflower fields with floral strips, and 11 control sites were adjacent to semi-natural habitats). Five sampling levels were established in each field, positioned at different distances from the flower strip or semi-natural habitat. Wild bee species richness and functional richness were significantly higher inside floral strips and semi-natural habitats compared to sunflower fields. Functional redundancy was significantly higher inside agricultural fields compared to inside floral strips and semi-natural habitats. Sunflower fields with floral strips had lower Rao values compared to sunflower fields adjacent to semi-natural habitats. The community-weighted mean (CWM) of intertegular distance (distance between where wings attach to body) of wild bees was significantly higher in sunflower fields adjacent to semi-natural habitats. In comparison, the CWM of wing length varied across sampling levels in sunflower fields with semi-natural habitats. Our results show it is essential to have semi-natural habitats within intensive agricultural landscapes to ensure the conservation of wild bee diversity, while the installation of floral strips offers a partial substitute to enhance wild bee diversity when semi-natural habitats are scarce or absentFinancial support was provided by the European Union FEDER INTERREG SUDOE Program (SOE1/P5/E0129). CPC was supported by the Estonian Ministry of Education and Research (PSG293) and the European Regional Development Fund (Centre of Excellence EcolChange

Simulation of Single Crystalline CdZnTe Solidification Process

Single crystals of Cd1-xZnxTe (0 ≤ x ≤ 0.1) (CZT/CdZnTe) are used in manufacture of gamma and X-ray detectors and as substrates for epitaxial growth of HgCdTe. Computer simulation for the solidification of CZT was performed using finite elements. The simulation results indicate that a lower translation speed of the quartz ampoule within the Bridgman furnace determines a lower concavity of the liquid interface which assures a good crystalline quality. When the rate is 3.32 mm/h the concavity is 58% greater than for a speed of 0.50 mm/h. It was experimentally found that when growing at low speed, 1.66 mm/h, the process is more stable and improves the crystalline quality due that only two grains were generated in CZT ingots. Meanwhile a faster growth speed- 3.32 mm/h- generates a large amount of grains in the CZT ingot.Fil: Martinez, Ana Maria. Provincia de Misiones. Comite de Desarrollo E Innovacion Tecnologica; ArgentinaFil: Rosenberger, Mario Roberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico Nordeste. Instituto de Materiales de Misiones; ArgentinaFil: Trigubo, Alicia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégicos Para la Defensa; Argentina. Universidad Tecnologica Nacional; ArgentinaFil: D'elia, Raul Luis. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; ArgentinaFil: Heredia, Eduardo Armando. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas Para la Defensa; Argentin

Influence of drying method on steviol glycosides and antioxidants in Stevia Rebaudiana leaves

The application of different drying conditions (hot air drying at 100 degrees C and 180 degrees C, freeze drying and shade drying) on steviol glycosides (stevioside, dulcoside A, rebaudioside A and rebaudioside C) and antioxidants in Stevia leaves was evaluated. Stevioside, the major glycoside found in fresh leaves (81.2 mg/g), suffered an important reduction in all cases, although shade drying was the least aggressive treatment. Considering the antioxidant parameters (total phenols, flavonoids and total antioxidants), the most suitable drying method was hot air at 180 degrees C, since it substantially increased all of them (76.8 mg gallic acid, 45.1 mg catechin and 126 mg Trolox, all equivalent/g Stevia, respectively), with respect to those present in fresh leaves (44.4, 2.5 and 52.9 mg equivalent/g). Therefore, the ideal method for drying Stevia leaves depends on their final use (sweetener or antioxidant), although, hot air at 180 degrees C is the most recommendable if only one treatment has to be chosen.The authors thank the Universitat Politecnica de Valencia (Spain) (for funding the project PAID 2011-ref: 2012 and the PhD scholarship), and the Generalitat Valenciana (Spain) (for the project GV/2013/029).Periche Santamaría, A.; Castelló Gómez, ML.; Heredia Gutiérrez, AB.; Escriche Roberto, MI. (2015). Influence of drying method on steviol glycosides and antioxidants in Stevia Rebaudiana leaves. Food Chemistry. 172:1-6. https://doi.org/10.1016/j.foodchem.2014.09.029S1617