Search results for: Alberto Martí Ezpeleta
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 127

Search results for: Alberto Martí Ezpeleta

37 Cr (VI) Adsorption on Ce0.25Zr0.75O2.nH2O-Kinetics and Thermodynamics

Authors: Carlos Alberto Rivera-corredor, Angie Dayana Vargas-Ceballos, Edison Gilpavas, Izabela Dobrosz-Gómez, Miguel Ángel Gómez-García

Abstract:

Hexavalent chromium, Cr (VI) is present in the effluents from different industries such as electroplating, mining, leather tanning, etc. This compound is of great academic and industrial concern because of its toxic and carcinogenic behavior. Its dumping to both environmental and public health for animals and humans causes serious problems in water sources. The amount of Cr (VI) in industrial wastewaters ranges from 0.5 to 270,000 mgL-1. According to the Colombian standard for water quality (NTC-813-2010), the maximum allowed concentration for the Cr (VI) in drinking water is 0.05 mg L-1. To comply with this limit, it is essential that industries treat their effluent to reduce the Cr (VI) to acceptable levels. Numerous methods have been reported for the treatment removing metal ions from aqueous solutions such as: reduction, ion exchange, electrodialysis, etc. Adsorption has become a promising method for the purification of metal ions in water, since its application corresponds with an economic and efficient technology. The absorbent selection and the kinetic and thermodynamic study of the adsorption conditions are key to the development of a suitable adsorption technology. The Ce0.25Zr0.75O2.nH2O presents higher adsorption capacity between a series of hydrated mixed oxides Ce1-xZrxO2 (x = 0, 0.25, 0.5, 0.75, 1). This work presents the kinetic and thermodynamic study of Cr (VI) adsorption on Ce0.25Zr0.75O2.nH2O. Experiments were performed under the following experimental conditions: initial Cr (VI) concentration = 25, 50 and 100 mgL-1, pH = 2, adsorbent charge = 4 gL-1, stirring time = 60 min, temperature=20, 28 and 40 °C. The Cr (VI) concentration was spectrophotometrically estimated by the method of difenilcarbazide with monitoring the absorbance at 540 nm. The Cr (VI) adsorption over hydrated Ce0.25Zr0.75O2.nH2O models was analyzed using pseudo-first and pseudo-second order kinetics. The Langmuir and Freundlich models were used to model the experimental data. The convergence between the experimental values and those predicted by the model, is expressed as a linear regression correlation coefficient (R2) and was employed as the model selection criterion. The adsorption process followed the pseudo-second order kinetic model and obeyed the Langmuir isotherm model. The thermodynamic parameters were calculated as: ΔH°=9.04 kJmol-1,ΔS°=0.03 kJmol-1 K-1, ΔG°=-0.35 kJmol-1 and indicated the endothermic and spontaneous nature of the adsorption process, governed by physisorption interactions.

Keywords: adsorption, hexavalent chromium, kinetics, thermodynamics

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36 Design and Assessment of Base Isolated Structures under Spectrum-Compatible Bidirectional Earthquakes

Authors: Marco Furinghetti, Alberto Pavese, Michele Rinaldi

Abstract:

Concave Surface Slider devices have been more and more used in real applications for seismic protection of both bridge and building structures. Several research activities have been carried out, in order to investigate the lateral response of such a typology of devices, and a reasonably high level of knowledge has been reached. If radial analysis is performed, the frictional force is always aligned with respect to the restoring force, whereas under bidirectional seismic events, a bi-axial interaction of the directions of motion occurs, due to the step-wise projection of the main frictional force, which is assumed to be aligned to the trajectory of the isolator. Nonetheless, if non-linear time history analyses have to be performed, standard codes provide precise rules for the definition of an averagely spectrum-compatible set of accelerograms in radial conditions, whereas for bidirectional motions different combinations of the single components spectra can be found. Moreover, nowadays software for the adjustment of natural accelerograms are available, which lead to a higher quality of spectrum-compatibility and to a smaller dispersion of results for radial motions. In this endeavor a simplified design procedure is defined, for building structures, base-isolated by means of Concave Surface Slider devices. Different case study structures have been analyzed. In a first stage, the capacity curve has been computed, by means of non-linear static analyses on the fixed-base structures: inelastic fiber elements have been adopted and different direction angles of lateral forces have been studied. Thanks to these results, a linear elastic Finite Element Model has been defined, characterized by the same global stiffness of the linear elastic branch of the non-linear capacity curve. Then, non-linear time history analyses have been performed on the base-isolated structures, by applying seven bidirectional seismic events. The spectrum-compatibility of bidirectional earthquakes has been studied, by considering different combinations of single components and adjusting single records: thanks to the proposed procedure, results have shown a small dispersion and a good agreement in comparison to the assumed design values.

Keywords: concave surface slider, spectrum-compatibility, bidirectional earthquake, base isolation

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35 Nanostructured Multi-Responsive Coatings for Tuning Surface Properties

Authors: Suzanne Giasson, Alberto Guerron

Abstract:

Stimuli-responsive polymer coatings can be used as functional elements in nanotechnologies, such as valves in microfluidic devices, as membranes in biomedical engineering, as substrates for the culture of biological tissues or in developing nanomaterials for targeted therapies in different diseases. However, such coatings usually suffer from major shortcomings, such as a lack of selectivity and poor environmental stability. The study will present multi-responsive hierarchical and hybrid polymer-based coatings aiming to overcome some of these limitations. Hierarchical polymer coatings, consisting of two-dimensional arrays of thermo-responsive cationic PNIPAM-based microgels and surface-functionalized with non-responsive or pH-responsive polymers, were covalently grafted to substrates to tune the surface chemistry and the elasticity of the surface independently using different stimuli. The characteristic dimensions (i.e., layer thickness) and surface properties (i.e., adhesion, friction) of the microgel coatings were assessed using the Surface Forces Apparatus. The ability to independently control the swelling and surface properties using temperature and pH as triggers were investigated for microgels in aqueous suspension and microgels immobilized on substrates. Polymer chain grafting did not impede the ability of cationic PNIPAM microgels to undergo a volume phase transition above the VPTT, either in suspension or immobilized on a substrate. Due to the presence of amino groups throughout the entirety of the microgel polymer network, the swelling behavior was also pH dependent. However, the thermo-responsive swelling was more significant than the pH-triggered one. The microgels functionalized with PEG exhibited the most promising behavior. Indeed, the thermo-triggered swelling of microgel-co-PEG did not give rise to changes in the microgel surface properties (i.e., surface potential and adhesion) within a wide range of pH values. It was possible for the immobilized microgel-co-PEG to undergo a volume transition (swelling/shrinking) with no change in adhesion, suggesting that the surface of the thermal-responsive microgels remains rather hydrophilic above the VPTT. This work confirms the possibility of tuning the swelling behavior of microgels without changing the adhesive properties. Responsive surfaces whose swelling properties can be reversibly and externally altered over space and time regardless of the surface chemistry are very innovative and will enable revolutionary advances in technologies, particularly in biomedical surface engineering and microfluidics, where advanced assembly of functional components is increasingly required.

Keywords: responsive materials, polymers, surfaces, cell culture

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34 Localization of Radioactive Sources with a Mobile Radiation Detection System using Profit Functions

Authors: Luís Miguel Cabeça Marques, Alberto Manuel Martinho Vale, José Pedro Miragaia Trancoso Vaz, Ana Sofia Baptista Fernandes, Rui Alexandre de Barros Coito, Tiago Miguel Prates da Costa

Abstract:

The detection and localization of hidden radioactive sources are of significant importance in countering the illicit traffic of Special Nuclear Materials and other radioactive sources and materials. Radiation portal monitors are commonly used at airports, seaports, and international land borders for inspecting cargo and vehicles. However, these equipment can be expensive and are not available at all checkpoints. Consequently, the localization of SNM and other radioactive sources often relies on handheld equipment, which can be time-consuming. The current study presents the advantages of real-time analysis of gamma-ray count rate data from a mobile radiation detection system based on simulated data and field tests. The incorporation of profit functions and decision criteria to optimize the detection system's path significantly enhances the radiation field information and reduces survey time during cargo inspection. For source position estimation, a maximum likelihood estimation algorithm is employed, and confidence intervals are derived using the Fisher information. The study also explores the impact of uncertainties, baselines, and thresholds on the performance of the profit function. The proposed detection system, utilizing a plastic scintillator with silicon photomultiplier sensors, boasts several benefits, including cost-effectiveness, high geometric efficiency, compactness, and lightweight design. This versatility allows for seamless integration into any mobile platform, be it air, land, maritime, or hybrid, and it can also serve as a handheld device. Furthermore, integration of the detection system into drones, particularly multirotors, and its affordability enable the automation of source search and substantial reduction in survey time, particularly when deploying a fleet of drones. While the primary focus is on inspecting maritime container cargo, the methodologies explored in this research can be applied to the inspection of other infrastructures, such as nuclear facilities or vehicles.

Keywords: plastic scintillators, profit functions, path planning, gamma-ray detection, source localization, mobile radiation detection system, security scenario

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33 Manufacturing and Calibration of Material Standards for Optical Microscopy in Industrial Environments

Authors: Alberto Mínguez-Martínez, Jesús De Vicente Y Oliva

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It seems that we live in a world in which the trend in industrial environments is the miniaturization of systems and materials and the fabrication of parts at the micro-and nano-scale. The problem arises when manufacturers want to study the quality of their production. This characteristic is becoming crucial due to the evolution of the industry and the development of Industry 4.0. As Industry 4.0 is based on digital models of production and processes, having accurate measurements becomes capital. At this point, the metrology field plays an important role as it is a powerful tool to ensure more stable production to reduce scrap and the cost of non-conformities. The most extended measuring instruments that allow us to carry out accurate measurements at these scales are optical microscopes, whether they are traditional, confocal, focus variation microscopes, profile projectors, or any other similar measurement system. However, the accuracy of measurements is connected to the traceability of them to the SI unit of length (the meter). The fact of providing adequate traceability to 2D and 3D dimensional measurements at micro-and nano-scale in industrial environments is a problem that is being studied, and it does not have a unique answer. In addition, if commercial material standards for micro-and nano-scale are considered, we can find that there are two main problems. On the one hand, those material standards that could be considered complete and very interesting do not give traceability of dimensional measurements and, on the other hand, their calibration is very expensive. This situation implies that these kinds of standards will not succeed in industrial environments and, as a result, they will work in the absence of traceability. To solve this problem in industrial environments, it becomes necessary to have material standards that are easy to use, agile, adaptive to different forms, cheap to manufacture and, of course, traceable to the definition of meter with simple methods. By using these ‘customized standards’, it would be possible to adapt and design measuring procedures for each application and manufacturers will work with some traceability. It is important to note that, despite the fact that this traceability is clearly incomplete, this situation is preferable to working in the absence of it. Recently, it has been demonstrated the versatility and the utility of using laser technology and other AM technologies to manufacture customized material standards. In this paper, the authors propose to manufacture a customized material standard using an ultraviolet laser system and a method to calibrate it. To conclude, the results of the calibration carried out in an accredited dimensional metrology laboratory are presented.

Keywords: industrial environment, material standards, optical measuring instrument, traceability

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32 Analysis of a Faience Enema Found in the Assasif Tomb No. -28- of the Vizier Amenhotep Huy: Contributions to the Study of the Mummification Ritual Practiced in the Theban Necropolis

Authors: Alberto Abello Moreno-Cid

Abstract:

Mummification was the process through which immortality was granted to the deceased, so it was of extreme importance to the Egyptians. The techniques of embalming had evolved over the centuries, and specialists created increasingly sophisticated tools. However, due to its eminently religious nature, knowledge about everything related to this practice was jealously preserved, and the testimonies that have survived to our time are scarce. For this reason, embalming instruments found in archaeological excavations are uncommon. The tomb of the Vizier Amenhotep Huy (AT No. -28-), located in the el-Assasif necropolis that is being excavated since 2009 by the team of the Institute of Ancient Egyptian Studies, has been the scene of some discoveries of this type that evidences the existence of mummification practices in this place after the New Kingdom. The clysters or enemas are the fundamental tools in the second type of mummification described by the historian Herodotus to introduce caustic solutions inside the body of the deceased. Nevertheless, such objects only have been found in three locations: the tomb of Ankh-Hor in Luxor, where a copper enema belonged to the prophet of Ammon Uah-ib-Ra came to light; the excavation of the tomb of Menekh-ib-Nekau in Abusir, where was also found one made of copper; and the excavations in the Bucheum, where two more artifacts were discovered, also made of copper but in different shapes and sizes. Both of them were used for the mummification of sacred animals and this is the reason they vary significantly. Therefore, the object found in the tomb No. -28-, is the first known made of faience of all these peculiar tools and the oldest known until now, dated in the Third Intermediate Period (circa 1070-650 B.C.). This paper bases its investigation on the study of those parallelisms, the material, the current archaeological context and the full analysis and reconstruction of the object in question. The key point is the use of faience in the production of this item: creating a device intended to be in constant use seems to be a first illogical compared to other samples made of copper. Faience around the area of Deir el-Bahari had a strong religious component, associated with solar myths and principles of the resurrection, connected to the Osirian that characterises the mummification procedure. The study allows to refute some of the premises which are held unalterable in Egyptology, verifying the utilization of these sort of pieces, understanding its way of use and showing that this type of mummification was also applied to the highest social stratum, in which case the tools were thought out of an exceptional quality and religious symbolism.

Keywords: clyster, el-Assasif, embalming, faience enema mummification, Theban necropolis

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31 Dynamic Two-Way FSI Simulation for a Blade of a Small Wind Turbine

Authors: Alberto Jiménez-Vargas, Manuel de Jesús Palacios-Gallegos, Miguel Ángel Hernández-López, Rafael Campos-Amezcua, Julio Cesar Solís-Sanchez

Abstract:

An optimal wind turbine blade design must be able of capturing as much energy as possible from the wind source available at the area of interest. Many times, an optimal design means the use of large quantities of material and complicated processes that make the wind turbine more expensive, and therefore, less cost-effective. For the construction and installation of a wind turbine, the blades may cost up to 20% of the outline pricing, and become more important due to they are part of the rotor system that is in charge of transmitting the energy from the wind to the power train, and where the static and dynamic design loads for the whole wind turbine are produced. The aim of this work is the develop of a blade fluid-structure interaction (FSI) simulation that allows the identification of the major damage zones during the normal production situation, and thus better decisions for design and optimization can be taken. The simulation is a dynamic case, since we have a time-history wind velocity as inlet condition instead of a constant wind velocity. The process begins with the free-use software NuMAD (NREL), to model the blade and assign material properties to the blade, then the 3D model is exported to ANSYS Workbench platform where before setting the FSI system, a modal analysis is made for identification of natural frequencies and modal shapes. FSI analysis is carried out with the two-way technic which begins with a CFD simulation to obtain the pressure distribution on the blade surface, then these results are used as boundary condition for the FEA simulation to obtain the deformation levels for the first time-step. For the second time-step, CFD simulation is reconfigured automatically with the next time-step inlet wind velocity and the deformation results from the previous time-step. The analysis continues the iterative cycle solving time-step by time-step until the entire load case is completed. This work is part of a set of projects that are managed by a national consortium called “CEMIE-Eólico” (Mexican Center in Wind Energy Research), created for strengthen technological and scientific capacities, the promotion of creation of specialized human resources, and to link the academic with private sector in national territory. The analysis belongs to the design of a rotor system for a 5 kW wind turbine design thought to be installed at the Isthmus of Tehuantepec, Oaxaca, Mexico.

Keywords: blade, dynamic, fsi, wind turbine

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30 Bed Evolution under One-Episode Flushing in a Truck Sewer in Paris, France

Authors: Gashin Shahsavari, Gilles Arnaud-Fassetta, Alberto Campisano, Roberto Bertilotti, Fabien Riou

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Sewer deposits have been identified as a major cause of dysfunctions in combined sewer systems regarding sewer management, which induces different negative consequents resulting in poor hydraulic conveyance, environmental damages as well as worker’s health. In order to overcome the problematics of sedimentation, flushing has been considered as the most operative and cost-effective way to minimize the sediments impacts and prevent such challenges. Flushing, by prompting turbulent wave effects, can modify the bed form depending on the hydraulic properties and geometrical characteristics of the conduit. So far, the dynamics of the bed-load during high-flow events in combined sewer systems as a complex environment is not well understood, mostly due to lack of measuring devices capable to work in the “hostile” in combined sewer system correctly. In this regards, a one-episode flushing issue from an opening gate valve with weir function was carried out in a trunk sewer in Paris to understanding its cleansing efficiency on the sediments (thickness: 0-30 cm). During more than 1h of flushing within 5 m distance in downstream of this flushing device, a maximum flowrate and a maximum level of water have been recorded at 5 m in downstream of the gate as 4.1 m3/s and 2.1 m respectively. This paper is aimed to evaluate the efficiency of this type of gate for around 1.1 km (from the point -50 m to +1050 m in downstream from the gate) by (i) determining bed grain-size distribution and sediments evolution through the sewer channel, as well as their organic matter content, and (ii) identifying sections that exhibit more changes in their texture after the flush. For the first one, two series of sampling were taken from the sewer length and then analyzed in laboratory, one before flushing and second after, at same points among the sewer channel. Hence, a non-intrusive sampling instrument has undertaken to extract the sediments smaller than the fine gravels. The comparison between sediments texture after the flush operation and the initial state, revealed the most modified zones by the flush effect, regarding the sewer invert slope and hydraulic parameters in the zone up to 400 m from the gate. At this distance, despite the increase of sediment grain-size rages, D50 (median grain-size) varies between 0.6 mm and 1.1 mm compared to 0.8 mm and 10 mm before and after flushing, respectively. Overall, regarding the sewer channel invert slope, results indicate that grains smaller than sands (< 2 mm) are more transported to downstream along about 400 m from the gate: in average 69% before against 38% after the flush with more dispersion of grain-sizes distributions. Furthermore, high effect of the channel bed irregularities on the bed material evolution has been observed after the flush.

Keywords: bed-load evolution, combined sewer systems, flushing efficiency, sediments transport

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29 Development and Structural Characterization of a Snack Food with Added Type 4 Extruded Resistant Starch

Authors: Alberto A. Escobar Puentes, G. Adriana García, Luis F. Cuevas G., Alejandro P. Zepeda, Fernando B. Martínez, Susana A. Rincón

Abstract:

Snack foods are usually classified as ‘junk food’ because have little nutritional value. However, due to the increase on the demand and third generation (3G) snacks market, low price and easy to prepare, can be considered as carriers of compounds with certain nutritional value. Resistant starch (RS) is classified as a prebiotic fiber it helps to control metabolic problems and has anti-cancer colon properties. The active compound can be developed by chemical cross-linking of starch with phosphate salts to obtain a type 4 resistant starch (RS4). The chemical reaction can be achieved by extrusion, a process widely used to produce snack foods, since it's versatile and a low-cost procedure. Starch is the major ingredient for snacks 3G manufacture, and the seeds of sorghum contain high levels of starch (70%), the most drought-tolerant gluten-free cereal. Due to this, the aim of this research was to develop a snack (3G), with RS4 in optimal conditions extrusion (previously determined) from sorghum starch, and carry on a sensory, chemically and structural characterization. A sample (200 g) of sorghum starch was conditioned with 4% sodium trimetaphosphate/ sodium tripolyphosphate (99:1) and set to 28.5% of moisture content. Then, the sample was processed in a single screw extruder equipped with rectangular die. The inlet, transport and output temperatures were 60°C, 134°C and 70°C, respectively. The resulting pellets were expanded in a microwave oven. The expansion index (EI), penetration force (PF) and sensory analysis were evaluated in the expanded pellets. The pellets were milled to obtain flour and RS content, degree of substitution (DS), and percentage of phosphorus (% P) were measured. Spectroscopy [Fourier Transform Infrared (FTIR)], X-ray diffraction, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) analysis were performed in order to determine structural changes after the process. The results in 3G were as follows: RS, 17.14 ± 0.29%; EI, 5.66 ± 0.35 and PF, 5.73 ± 0.15 (N). Groups of phosphate were identified in the starch molecule by FTIR: DS, 0.024 ± 0.003 and %P, 0.35±0.15 [values permitted as food additives (<4 %P)]. In this work an increase of the gelatinization temperature after the crosslinking of starch was detected; the loss of granular and vapor bubbles after expansion were observed by SEM; By using X-ray diffraction, loss of crystallinity was observed after extrusion process. Finally, a snack (3G) was obtained with RS4 developed by extrusion technology. The sorghum starch was efficient for snack 3G production.

Keywords: extrusion, resistant starch, snack (3G), Sorghum

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28 Calibration of 2D and 3D Optical Measuring Instruments in Industrial Environments at Submillimeter Range

Authors: Alberto Mínguez-Martínez, Jesús de Vicente y Oliva

Abstract:

Modern manufacturing processes have led to the miniaturization of systems and, as a result, parts at the micro-and nanoscale are produced. This trend seems to become increasingly important in the near future. Besides, as a requirement of Industry 4.0, the digitalization of the models of production and processes makes it very important to ensure that the dimensions of newly manufactured parts meet the specifications of the models. Therefore, it is possible to reduce the scrap and the cost of non-conformities, ensuring the stability of the production at the same time. To ensure the quality of manufactured parts, it becomes necessary to carry out traceable measurements at scales lower than one millimeter. Providing adequate traceability to the SI unit of length (the meter) to 2D and 3D measurements at this scale is a problem that does not have a unique solution in industrial environments. Researchers in the field of dimensional metrology all around the world are working on this issue. A solution for industrial environments, even if it is not complete, will enable working with some traceability. At this point, we believe that the study of the surfaces could provide us with a first approximation to a solution. Among the different options proposed in the literature, the areal topography methods may be the most relevant because they could be compared to those measurements performed using Coordinate Measuring Machines (CMM’s). These measuring methods give (x, y, z) coordinates for each point, expressing it in two different ways, either expressing the z coordinate as a function of x, denoting it as z(x), for each Y-axis coordinate, or as a function of the x and y coordinates, denoting it as z (x, y). Between others, optical measuring instruments, mainly microscopes, are extensively used to carry out measurements at scales lower than one millimeter because it is a non-destructive measuring method. In this paper, the authors propose a calibration procedure for the scales of optical measuring instruments, particularizing for a confocal microscope, using material standards easy to find and calibrate in metrology and quality laboratories in industrial environments. Confocal microscopes are measuring instruments capable of filtering the out-of-focus reflected light so that when it reaches the detector, it is possible to take pictures of the part of the surface that is focused. Varying and taking pictures at different Z levels of the focus, a specialized software interpolates between the different planes, and it could reconstruct the surface geometry into a 3D model. As it is easy to deduce, it is necessary to give traceability to each axis. As a complementary result, the roughness Ra parameter will be traced to the reference. Although the solution is designed for a confocal microscope, it may be used for the calibration of other optical measuring instruments by applying minor changes.

Keywords: industrial environment, confocal microscope, optical measuring instrument, traceability

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27 Sorghum Polyphenols Encapsulated by Spray Drying, Using Modified Starches as Wall Materials

Authors: Adriana Garcia G., Alberto A. Escobar P., Amira D. Calvo L., Gabriel Lizama U., Alejandro Zepeda P., Fernando Martínez B., Susana Rincón A.

Abstract:

Different studies have recently been focused on the use of antioxidants such as polyphenols because of to its anticarcinogenic capacity. However, these compounds are highly sensible to environmental factors such as light and heat, so lose its long-term stability, besides possess an astringent and bitter taste. Nevertheless, the polyphenols can be protected by microcapsule formulation. In this sense, a rich source of polyphenols is sorghum, besides presenting a high starch content. Due to the above, the aim of this work was to obtain modified starches from sorghum by extrusion to encapsulate polyphenols the sorghum by spray drying. Polyphenols were extracted by ethanol solution from sorghum (Pajarero/red) and determined by the method of Folin-Ciocalteu, obtaining GAE at 30 mg/g. Moreover, was extracted starch of sorghum (Sinaloense/white) through wet milling (yield 32 %). The hydrolyzed starch was modified with three treatments: acetic anhydride (2.5g/100g), sodium tripolyphosphate (4g/100g), and sodium tripolyphosphate/ acetic anhydride (2g/1.25g by each 100 g) by extrusion. Processing conditions of extrusion were as follows: barrel temperatures were of 60, 130 and 170 °C at the feeding, transition, and high-pressure extrusion zones, respectively. Analysis of Fourier Transform Infrared spectroscopy (FTIR), showed bands exhibited of acetyl groups (1735 cm-1) and phosphates (1170 cm-1, 910 cm-1 and 525 cm-1), indicating the respective modification of starch. Besides, all modified starches not developed viscosity, which is a characteristic required for use in the encapsulation of polyphenols using the spray drying technique. As result of the modification starch, was obtained a water solubility index (WSI) from 33.8 to 44.8 %, and crystallinity from 8 to 11 %, indicating the destruction of the starch granule. Afterwards, microencapsulation of polyphenols was developed by spray drying, with a blend of 10 g of modified starch, 60 ml polyphenol extract and 30 ml of distilled water. Drying conditions were as follows: inlet air temperature 150 °C ± 1, outlet air temperature 80°C ± 5. As result of the microencapsulation: were obtained yields of 56.8 to 77.4 % and an efficiency of encapsulation from 84.6 to 91.4 %. The FTIR analysis showed evidence of microcapsules loaded with polyphenols in bands 1042 cm-1, 1038 cm-1 and 1148 cm-1. Analysis Differential scanning calorimetry (DSC) showed transition temperatures from 144.1 to 173.9 °C. For the order hand, analysis of Scanning Electron Microscopy (SEM), were observed rounded surfaces with concavities, typical feature of microcapsules produced by spray drying, how result of rapid evaporation of water. Finally, the modified starches were obtained by extrusion with good characteristics for use as cover materials by spray drying, where the phosphorylated starch was the best treatment in this work, according to the encapsulation yield, efficiency, and transition temperature.

Keywords: encapsulation, extrusion, modified starch, polyphenols, spray drying

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26 A Theragnostic Approach for Alzheimer’s Disease Focused on Phosphorylated Tau

Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro

Abstract:

Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.

Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies

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25 Approach on Conceptual Design and Dimensional Synthesis of the Linear Delta Robot for Additive Manufacturing

Authors: Efrain Rodriguez, Cristhian Riano, Alberto Alvares

Abstract:

In recent years, robots manipulators with parallel architectures are used in additive manufacturing processes – 3D printing. These robots have advantages such as speed and lightness that make them suitable to help with the efficiency and productivity of these processes. Consequently, the interest for the development of parallel robots for additive manufacturing applications has increased. This article deals with the conceptual design and dimensional synthesis of the linear delta robot for additive manufacturing. Firstly, a methodology based on structured processes for the development of products through the phases of informational design, conceptual design and detailed design is adopted: a) In the informational design phase the Mudge diagram and the QFD matrix are used to aid a set of technical requirements, to define the form, functions and features of the robot. b) In the conceptual design phase, the functional modeling of the system through of an IDEF0 diagram is performed, and the solution principles for the requirements are formulated using a morphological matrix. This phase includes the description of the mechanical, electro-electronic and computational subsystems that constitute the general architecture of the robot. c) In the detailed design phase, a digital model of the robot is drawn on CAD software. A list of commercial and manufactured parts is detailed. Tolerances and adjustments are defined for some parts of the robot structure. The necessary manufacturing processes and tools are also listed, including: milling, turning and 3D printing. Secondly, a dimensional synthesis method applied on design of the linear delta robot is presented. One of the most important key factors in the design of a parallel robot is the useful workspace, which strongly depends on the joint space, the dimensions of the mechanism bodies and the possible interferences between these bodies. The objective function is based on the verification of the kinematic model for a prescribed cylindrical workspace, considering geometric constraints that possibly lead to singularities of the mechanism. The aim is to determine the minimum dimensional parameters of the mechanism bodies for the proposed workspace. A method based on genetic algorithms was used to solve this problem. The method uses a cloud of points with the cylindrical shape of the workspace and checks the kinematic model for each of the points within the cloud. The evolution of the population (point cloud) provides the optimal parameters for the design of the delta robot. The development process of the linear delta robot with optimal dimensions for additive manufacture is presented. The dimensional synthesis enabled to design the mechanism of the delta robot in function of the prescribed workspace. Finally, the implementation of the robotic platform developed based on a linear delta robot in an additive manufacturing application using the Fused Deposition Modeling (FDM) technique is presented.

Keywords: additive manufacturing, delta parallel robot, dimensional synthesis, genetic algorithms

Procedia PDF Downloads 164
24 Solutions to Reduce CO2 Emissions in Autonomous Robotics

Authors: Antoni Grau, Yolanda Bolea, Alberto Sanfeliu

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Mobile robots can be used in many different applications, including mapping, search, rescue, reconnaissance, hazard detection, and carpet cleaning, exploration, etc. However, they are limited due to their reliance on traditional energy sources such as electricity and oil which cannot always provide a convenient energy source in all situations. In an ever more eco-conscious world, solar energy offers the most environmentally clean option of all energy sources. Electricity presents threats of pollution resulting from its production process, and oil poses a huge threat to the environment. Not only does it pose harm by the toxic emissions (for instance CO2 emissions), it produces the combustion process necessary to produce energy, but there is the ever present risk of oil spillages and damages to ecosystems. Solar energy can help to mitigate carbon emissions by replacing more carbon intensive sources of heat and power. The challenge of this work is to propose the design and the implementation of electric battery recharge stations. Those recharge docks are based on the use of renewable energy such as solar energy (with photovoltaic panels) with the object to reduce the CO2 emissions. In this paper, a comparative study of the CO2 emission productions (from the use of different energy sources: natural gas, gas oil, fuel and solar panels) in the charging process of the Segway PT batteries is carried out. To make the study with solar energy, a photovoltaic panel, and a Buck-Boost DC/DC block has been used. Specifically, the STP005S-12/Db solar panel has been used to carry out our experiments. This module is a 5Wp-photovoltaic (PV) module, configured with 36 monocrystalline cells serially connected. With those elements, a battery recharge station is made to recharge the robot batteries. For the energy storage DC/DC block, a series of ultracapacitors have been used. Due to the variation of the PV panel with the temperature and irradiation, and the non-integer behavior of the ultracapacitors as well as the non-linearities of the whole system, authors have been used a fractional control method to achieve that solar panels supply the maximum allowed power to recharge the robots in the lesser time. Greenhouse gas emissions for production of electricity vary due to regional differences in source fuel. The impact of an energy technology on the climate can be characterised by its carbon emission intensity, a measure of the amount of CO2, or CO2 equivalent emitted by unit of energy generated. In our work, the coal is the fossil energy more hazardous, providing a 53% more of gas emissions than natural gas and a 30% more than fuel. Moreover, it is remarkable that existing fossil fuel technologies produce high carbon emission intensity through the combustion of carbon-rich fuels, whilst renewable technologies such as solar produce little or no emissions during operation, but may incur emissions during manufacture. The solar energy thus can help to mitigate carbon emissions.

Keywords: autonomous robots, CO2 emissions, DC/DC buck-boost, solar energy

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23 Gender Specific Differences in Clinical Outcomes of Knee Osteoarthritis Treated with Micro-Fragmented Adipose Tissue

Authors: Tiffanie-Marie Borg, Yasmin Zeinolabediny, Nima Heidari, Ali Noorani, Mark Slevin, Angel Cullen, Stefano Olgiati, Alberto Zerbi, Alessandro Danovi, Adrian Wilson

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Knee Osteoarthritis (OA) is a critical cause of disability globally. In recent years, there has been growing interest in non-invasive treatments, such as intra-articular injection of micro-fragmented fat (MFAT), showing great potential in treating OA. Mesenchymal stem cells (MSCs), originating from pericytes of micro-vessels in MFAT, can differentiate into mesenchymal lineage cells such as cartilage, osteocytes, adipocytes, and osteoblasts. Secretion of growth factor and cytokines from MSCs have the capability to inhibit T cell growth, reduced pain and inflammation, and create a micro-environment that through paracrine signaling, can promote joint repair and cartilage regeneration. Here we have shown, for the first time, data supporting the hypothesis that women respond better in terms of improvements in pain and function to MFAT injection compared to men. Historically, women have been underrepresented in studies, and studies with both sexes regularly fail to analyse the results by sex. To mitigate this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. This observational, intention-to-treat study included the complete sample of 456 patients who agreed to be scored for pain (visual analogue scale (VAS)) and function (Oxford knee score (OKS)) at baseline regardless of subsequent changes to adherence or status during follow-up. We report that a significantly larger number of women responded to treatment than men: [90% vs. 60% change in VAS scores with 87% vs. 65% change in OKS scores, respectively]. Women overall had a stronger positive response to treatment with reduced pain and improved mobility and function. Pre-injection, our cohort of women were in more pain with worse joint function which is quite common to see in orthopaedics. However, during the 2-year follow-up, they consistently maintained a lower incidence of discomfort with superior joint function. This data clearly identifies a clear need for further studies to identify the cell and molecular biological and other basis for these differences and be able to utilize this information for stratification in order to improve outcome for both women and men.

Keywords: gender differences, micro-fragmented adipose tissue, knee osteoarthritis, stem cells

Procedia PDF Downloads 164
22 Influence of Glass Plates Different Boundary Conditions on Human Impact Resistance

Authors: Alberto Sanchidrián, José A. Parra, Jesús Alonso, Julián Pecharromán, Antonia Pacios, Consuelo Huerta

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Glass is a commonly used material in building; there is not a unique design solution as plates with a different number of layers and interlayers may be used. In most façades, a security glazing have to be used according to its performance in the impact pendulum. The European Standard EN 12600 establishes an impact test procedure for classification under the point of view of the human security, of flat plates with different thickness, using a pendulum of two tires and 50 kg mass that impacts against the plate from different heights. However, this test does not replicate the actual dimensions and border conditions used in building configurations and so the real stress distribution is not determined with this test. The influence of different boundary conditions, as the ones employed in construction sites, is not well taking into account when testing the behaviour of safety glazing and there is not a detailed procedure and criteria to determinate the glass resistance against human impact. To reproduce the actual boundary conditions on site, when needed, the pendulum test is arranged to be used "in situ", with no account for load control, stiffness, and without a standard procedure. Fracture stress of small and large glass plates fit a Weibull distribution with quite a big dispersion so conservative values are adopted for admissible fracture stress under static loads. In fact, test performed for human impact gives a fracture strength two or three times higher, and many times without a total fracture of the glass plate. Newest standards, as for example DIN 18008-4, states for an admissible fracture stress 2.5 times higher than the ones used for static and wing loads. Now two working areas are open: a) to define a standard for the ‘in situ’ test; b) to prepare a laboratory procedure that allows testing with more real stress distribution. To work on both research lines a laboratory that allows to test medium size specimens with different border conditions, has been developed. A special steel frame allows reproducing the stiffness of the glass support substructure, including a rigid condition used as reference. The dynamic behaviour of the glass plate and its support substructure have been characterized with finite elements models updated with modal tests results. In addition, a new portable impact machine is being used to get enough force and direction control during the impact test. Impact based on 100 J is used. To avoid problems with broken glass plates, the test have been done using an aluminium plate of 1000 mm x 700 mm size and 10 mm thickness supported on four sides; three different substructure stiffness conditions are used. A detailed control of the dynamic stiffness and the behaviour of the plate is done with modal tests. Repeatability of the test and reproducibility of results prove that procedure to control both, stiffness of the plate and the impact level, is necessary.

Keywords: glass plates, human impact test, modal test, plate boundary conditions

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21 Financial Analysis of the Foreign Direct in Mexico

Authors: Juan Peña Aguilar, Lilia Villasana, Rodrigo Valencia, Alberto Pastrana, Martin Vivanco, Juan Peña C

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Each year a growing number of companies entering Mexico in search of the domestic market share. These activities, including stores, telephone long distance and local raw materials and energy, and particularly the financial sector, have managed to significantly increase its weight in the flows of FDI in Mexico , however, you should consider whether these trends FDI are positive for the Mexican economy and these activities increase Mexican exports in the medium term , and its share in GDP , gross fixed capital formation and employment. In general stresses that these activities, by far, have been unable to significantly generate linkages with the rest of the economy, a process that has not favored with competitiveness policies and activities aimed at these neutral or horizontal. Since the nineties foreign direct investment (FDI) has shown a remarkable dynamism, both internationally and in Latin America and in Mexico. Only in Mexico the first recipient of FDI in importance in Latin America during 1990-1995 and was displaced by Brazil since FDI increased from levels below 1 % of GDP during the eighties to around 3 % of GDP during the nineties. Its impact has been significant not only from a macroeconomic perspective , it has also allowed the generation of a new industrial production structure and organization, parallel to a significant modernization of a segment of the economy. The case of Mexico also is particularly interesting and relevant because the destination of FDI until 1993 had focused on the purchase of state assets during privatization process. This paper aims to present FDI flows in Mexico and analyze the different business strategies that have been touched and encouraged by the FDI. On the one hand, looking briefly discuss regulatory issues and source and recipient of FDI sectors. Furthermore, the paper presents in more detail the impacts and changes that generated the FDI contribution of FDI in the Mexican economy , besides the macroeconomic context and later legislative changes that resulted in the current regulations is examined around FDI in Mexico, including aspects of the Free Trade Agreement (NAFTA). It is worth noting that foreign investment can not only be considered from the perspective of the receiving economic units. Instead, these flows also reflect the strategic interests of transnational corporations (TNCs) and other companies seeking access to markets and increased competitiveness of their production networks and global distribution, among other reasons. Similarly it is important to note that foreign investment in its various forms is critically dependent on historical and temporal aspects. Thus, the same functionality can vary significantly depending on the specific characteristics of both receptor units as sources of FDI, including macroeconomic, institutional, industrial organization, and social aspects, among others.

Keywords: foreign direct investment (FDI), competitiveness, neoliberal regime, globalization, gross domestic product (GDP), NAFTA, macroeconomic

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20 Gas Metal Arc Welding of Clad Plates API 5L X-60/316L Applying External Magnetic Fields during Welding

Authors: Blanca A. Pichardo, Victor H. Lopez, Melchor Salazar, Rafael Garcia, Alberto Ruiz

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Clad pipes in comparison to plain carbon steel pipes offer the oil and gas industry high corrosion resistance, reduction in economic losses due to pipeline failures and maintenance, lower labor risk, prevent pollution and environmental damage due to hydrocarbons spills caused by deteriorated pipelines. In this context, it is paramount to establish reliable welding procedures to join bimetallic plates or pipes. Thus, the aim of this work is to study the microstructure and mechanical behavior of clad plates welded by the gas metal arc welding (GMAW) process. A clad of 316L stainless steel was deposited onto API 5L X-60 plates by overlay welding with the GMAW process. Welding parameters were, 22.5 V, 271 A, heat input 1,25 kJ/mm, shielding gas 98% Ar + 2% O₂, reverse polarity, torch displacement speed 3.6 mm/s, feed rate 120 mm/s, electrode diameter 1.2 mm and application of an electromagnetic field of 3.5 mT. The overlay welds were subjected to macro-structural and microstructural characterization. After manufacturing the clad plates, a single V groove joint was machined with a 60° bevel and 1 mm root face. GMA welding of the bimetallic plates was performed in four passes with ER316L-Si filler for the root pass and an ER70s-6 electrode for the subsequent welding passes. For joining the clad plates, an electromagnetic field was applied with 2 purposes; to improve the microstructural characteristics and to assist the stability of the electric arc during welding in order to avoid magnetic arc blow. The welds were macro and microstructurally characterized and the mechanical properties were also evaluated. Vickers microhardness (100 g load for 10 s) measurements were made across the welded joints at three levels. The first profile, at the 316L stainless steel cladding, was quite even with a value of approximately 230 HV. The second microhardness profile showed high values in the weld metal, ~400 HV, this was due to the formation of a martensitic microstructure by dilution of the first welding pass with the second. The third profile crossed the third and fourth welding passes and an average value of 240 HV was measured. In the tensile tests, yield strength was between 400 to 450 MPa with a tensile strength of ~512 MPa. In the Charpy impact tests, the results were 86 and 96 J for specimens with the notch in the face and in the root of the weld bead, respectively. The results of the mechanical properties were in the range of the API 5L X-60 base material. The overlap welding process used for cladding is not suitable for large components, however, it guarantees a metallurgical bond, unlike the most commonly used processes such as thermal expansion. For welding bimetallic plates, control of the temperature gradients is key to avoid distortions. Besides, the dissimilar nature of the bimetallic plates gives rise to the formation of a martensitic microstructure during welding.

Keywords: clad pipe, dissimilar welding, gas metal arc welding, magnetic fields

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19 Impact of Material Chemistry and Morphology on Attrition Behavior of Excipients during Blending

Authors: Sri Sharath Kulkarni, Pauline Janssen, Alberto Berardi, Bastiaan Dickhoff, Sander van Gessel

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Blending is a common process in the production of pharmaceutical dosage forms where the high shear is used to obtain a homogenous dosage. The shear required can lead to uncontrolled attrition of excipients and affect API’s. This has an impact on the performance of the formulation as this can alter the structure of the mixture. Therefore, it is important to understand the driving mechanisms for attrition. The aim of this study was to increase the fundamental understanding of the attrition behavior of excipients. Attrition behavior of the excipients was evaluated using a high shear blender (Procept Form-8, Zele, Belgium). Twelve pure excipients are tested, with morphologies varying from crystalline (sieved), granulated to spray dried (round to fibrous). Furthermore, materials include lactose, microcrystalline cellulose (MCC), di-calcium phosphate (DCP), and mannitol. The rotational speed of the blender was set at 1370 rpm to have the highest shear with a Froude (Fr) number 9. Varying blending times of 2-10 min were used. Subsequently, after blending, the excipients were analyzed for changes in particle size distribution (PSD). This was determined (n = 3) by dry laser diffraction (Helos/KR, Sympatec, Germany). Attrition was found to be a surface phenomenon which occurs in the first minutes of the high shear blending process. An increase of blending time above 2 mins showed no change in particle size distribution. Material chemistry was identified as a key driver for differences in the attrition behavior between different excipients. This is mainly related to the proneness to fragmentation, which is known to be higher for materials such as DCP and mannitol compared to lactose and MCC. Secondly, morphology also was identified as a driver of the degree of attrition. Granular products consisting of irregular surfaces showed the highest reduction in particle size. This is due to the weak solid bonds created between the primary particles during the granulation process. Granular DCP and mannitol show a reduction of 80-90% in x10(µm) compared to a 20-30% drop for granular lactose (monohydrate and anhydrous). Apart from the granular lactose, all the remaining morphologies of lactose (spray dried-round, sieved-tomahawk, milled) show little change in particle size. Similar observations have been made for spray-dried fibrous MCC. All these morphologies have little irregular or sharp surfaces and thereby are less prone to fragmentation. Therefore, products containing brittle materials such as mannitol and DCP are more prone to fragmentation when exposed to shear. Granular products with irregular surfaces lead to an increase in attrition. While spherical, crystalline, or fibrous morphologies show reduced impact during high shear blending. These changes in size will affect the functionality attributes of the formulation, such as flow, API homogeneity, tableting, formation of dust, etc. Hence it is important for formulators to fully understand the excipients to make the right choices.

Keywords: attrition, blending, continuous manufacturing, excipients, lactose, microcrystalline cellulose, shear

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18 Safety Profile of Human Papillomavirus Vaccines: A Post-Licensure Analysis of the Vaccine Adverse Events Reporting System, 2007-2017

Authors: Giulia Bonaldo, Alberto Vaccheri, Ottavio D'Annibali, Domenico Motola

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The Human Papilloma Virus (HPV) was shown to be the cause of different types of carcinomas, first of all of the cervical intraepithelial neoplasia. Since the early 80s to today, thanks first to the preventive screening campaigns (pap-test) and following to the introduction of HPV vaccines on the market; the number of new cases of cervical cancer has decreased significantly. The HPV vaccines currently approved are three: Cervarix® (HPV2 - virus type: 16 and 18), Gardasil® (HPV4 - 6, 11, 16, 18) and Gardasil 9® (HPV9 - 6, 11, 16, 18, 31, 33, 45, 52, 58), which all protect against the two high-risk HPVs (6, 11) that are mainly involved in cervical cancers. Despite the remarkable effectiveness of these vaccines has been demonstrated, in the recent years, there have been many complaints about their risk-benefit profile due to Adverse Events Following Immunization (AEFI). The purpose of this study is to provide a support about the ongoing discussion on the safety profile of HPV vaccines based on real life data deriving from spontaneous reports of suspected AEFIs collected in the Vaccine Adverse Events Reporting System (VAERS). VAERS is a freely-available national vaccine safety surveillance database of AEFI, co-administered by the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). We collected all the reports between January 2007 to December 2017 related to the HPV vaccines with a brand name (HPV2, HPV4, HPV9) or without (HPVX). A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% confidence interval and p value ≤ 0.05 was performed. Over the 10-year period, 54889 reports of AEFI related to HPV vaccines reported in VAERS, corresponding to 224863 vaccine-event pairs, were retrieved. The highest number of reports was related to Gardasil (n = 42244), followed by Gardasil 9 (7212) and Cervarix (3904). The brand name of the HPV vaccine was not reported in 1529 cases. The two events more frequently reported and statistically significant for each vaccine were: dizziness (n = 5053) ROR = 1.28 (CI95% 1.24 – 1.31) and syncope (4808) ROR = 1.21 (1.17 – 1.25) for Gardasil. For Gardasil 9, injection site pain (305) ROR = 1.40 (1.25 – 1.57) and injection site erythema (297) ROR = 1.88 (1.67 – 2.10) and for Cervarix, headache (672) ROR = 1.14 (1.06 – 1.23) and loss of consciousness (528) ROR = 1.71 (1.57 – 1.87). In total, we collected 406 reports of death and 2461 cases of permanent disability in the ten-year period. The events consisting of incorrect vaccine storage or incorrect administration were not considered. The AEFI analysis showed that the most frequently reported events are non-serious and listed in the corresponding SmPCs. In addition to these, potential safety signals arose regarding less frequent and severe AEFIs that would deserve further investigation. This already happened with the referral of the European Medicines Agency (EMA) for the adverse events POTS (Postural Orthostatic Tachycardia Syndrome) and CRPS (Complex Regional Pain Syndrome) associated with anti-papillomavirus vaccines.

Keywords: adverse drug reactions, pharmacovigilance, safety, vaccines

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17 Monitoring Air Pollution Effects on Children for Supporting Public Health Policy: Preliminary Results of MAPEC_LIFE Project

Authors: Elisabetta Ceretti, Silvia Bonizzoni, Alberto Bonetti, Milena Villarini, Marco Verani, Maria Antonella De Donno, Sara Bonetta, Umberto Gelatti

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Introduction: Air pollution is a global problem. In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and particulate matter as carcinogenic to human. The study of the health effects of air pollution in children is very important because they are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. Methods: The study was carried out on 6-8-year-old children living in five Italian towns in two different seasons. Two biomarkers of early biological effects, primary DNA damage detected with the comet assay and frequency of micronuclei, were investigated in buccal cells of children. Details of children diseases, socio-economic status, exposures to other pollutants and life-style were collected using a questionnaire administered to children’s parents. Child exposure to urban air pollution was assessed by analysing PM0.5 samples collected in the school areas for PAHs and nitro-PAHs concentration, lung toxicity and in vitro genotoxicity on bacterial and human cells. Data on the chemical features of the urban air during the study period were obtained from the Regional Agency for Environmental Protection. The project created also the opportunity to approach the issue of air pollution with the children, trying to raise their awareness on air quality, its health effects and some healthy behaviors by means of an educational intervention in the schools. Results: 1315 children were recruited for the study and participate in the first sampling campaign in the five towns. The second campaign, on the same children, is still ongoing. The preliminary results of the tests on buccal mucosa cells of children will be presented during the conference as well as the preliminary data about the chemical composition and the toxicity and genotoxicity features of PM0.5 samples. The educational package was tested on 250 children of the primary school and showed to be very useful, improving children knowledge about air pollution and its effects and stimulating their interest. Conclusions: The associations between levels of air pollutants, air mutagenicity and biomarkers of early effects will be investigated. A tentative model to calculate the global absolute risk of having early biological effects for air pollution and other variables together will be proposed and may be useful to support policy-making and community interventions to protect children from possible health effects of air pollutants.

Keywords: air pollution exposure, biomarkers of early effects, children, public health policy

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16 Learning Trajectories of Mexican Language Teachers: A Cross-Cultural Comparative Study

Authors: Alberto Mora-Vazquez, Nelly Paulina Trejo Guzmán

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This study examines the learning trajectories of twelve language teachers who were former students of a BA in applied linguistics at a Mexican state university. In particular, the study compares the social, academic and professional trajectories of two groups of teachers, six locally raised and educated ones and six repatriated ones from the U.S. Our interest in undertaking this research lies in the wide variety of students’ backgrounds we as professors in the BA program have witnessed throughout the years it has been around. Ever since the academic program started back in 2006, the student population has been made up of students whose backgrounds are highly diverse in terms of English language proficiency level, professional orientations and degree of cross-cultural awareness. Such diversity is further evidenced by the ongoing incorporation of some transnational students who have lived and studied in the United States for a significant period of time before their enrolment in the BA program. This, however, is not an isolated event as other researchers have reported this phenomenon in other TESOL-related programs of Mexican universities in the literature. Therefore, this suggests that their social and educational experiences are quite different from those of their Mexican born and educated counterparts. In addition, an informal comparison of the participation in formal teaching activities of the two groups at the beginning of their careers also suggested that significant differences in teacher training and development needs could also be identified. This issue raised questions about the need to examine the life and learning trajectories of these two groups of student teachers so as to develop an intervention plan aimed at supporting and encouraging their academic and professional advancement based on their particular needs. To achieve this goal, the study makes use of a combination of retrospective life-history research and the analysis of academic documents. The first approach uses interviews for data-collection. Through the use of a narrative life-history interview protocol, teachers were asked about their childhood home context, their language learning and teaching experiences, their stories of studying applied linguistics, and self-description. For the analysis of participants’ educational outcomes, a wide range of academic records, including reports of language proficiency exams results and language teacher training certificates, were used. The analysis revealed marked differences between the two groups of teachers in terms of academic and professional orientations. The locally educated teachers tended to graduate first, to look for further educational opportunities after graduation, to enter the language teaching profession earlier, and to expand their professional development options more than their peers. It is argued that these differences can be explained by their identities, which are made up of the interplay of influences such as their home context, their previous educational experiences and their cultural background. Implications for language teacher trainers and applied linguistics academic program administrators are provided.

Keywords: beginning language teachers, life-history research, Mexican context, transnational students

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15 Advanced Bio-Fuels for Biorefineries: Incorporation of Waste Tires and Calcium-Based Catalysts to the Pyrolysis of Biomass

Authors: Alberto Veses, Olga Sanhauja, María Soledad Callén, Tomás García

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The appropriate use of renewable sources emerges as a decisive point to minimize the environmental impact caused by fossil fuels use. Particularly, the use of lignocellulosic biomass becomes one of the best promising alternatives since it is the only carbon-containing renewable source that can produce bioproducts similar to fossil fuels and it does not compete with food market. Among all the processes that can valorize lignocellulosic biomass, pyrolysis is an attractive alternative because it is the only thermochemical process that can produce a liquid biofuel (bio-oil) in a simple way and solid and gas fractions that can be used as energy sources to support the process. However, in order to incorporate bio-oils in current infrastructures and further process in future biorefineries, their quality needs to be improved. Introducing different low-cost catalysts and/or incorporating different polymer residues to the process are some of the new, simple and low-cost strategies that allow the user to directly obtain advanced bio-oils to be used in future biorefineries in an economic way. In this manner, from previous thermogravimetric analyses, local agricultural wastes such as grape seeds (GS) were selected as lignocellulosic biomass while, waste tires (WT) were selected as polymer residue. On the other hand, CaO was selected as low-cost catalyst based on previous experiences by the group. To reach this aim, a specially-designed fixed bed reactor using N₂ as a carrier gas was used. This reactor has the peculiarity to incorporate a vertical mobile liner that allows the user to introduce the feedstock in the oven once the selected temperature (550 ºC) is reached, ensuring higher heating rates needed for the process. Obtaining a well-defined phase distribution in the resulting bio-oil is crucial to ensure the viability to the process. Thus, once experiments were carried out, not only a well-defined two layers was observed introducing several mixtures (reaching values up to 40 wt.% of WT) but also, an upgraded organic phase, which is the one considered to be processed in further biorefineries. Radical interactions between GS and WT released during the pyrolysis process and dehydration reactions enhanced by CaO can promote the formation of better-quality bio-oils. The latter was reflected in a reduction of water and oxygen content of bio-oil and hence, a substantial increase of its heating value and its stability. Moreover, not only sulphur content was reduced from solely WT pyrolysis but also potential and negative issues related to a strong acidic environment of conventional bio-oils were minimized due to its basic pH and lower total acid numbers. Therefore, acidic compounds obtained in the pyrolysis such as CO₂-like substances can react with the CaO and minimize acidic problems related to lignocellulosic bio-oils. Moreover, this CO₂ capture promotes H₂ production from water gas shift reaction favoring hydrogen-transfer reactions, improving the final quality of the bio-oil. These results show the great potential of grapes seeds to carry out the catalytic co-pyrolysis process with different plastic residues in order to produce a liquid bio-oil that can be considered as a high-quality renewable vector.

Keywords: advanced bio-oils, biorefinery, catalytic co-pyrolysis of biomass and waste tires, lignocellulosic biomass

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14 A Flipped Learning Experience in an Introductory Course of Information and Communication Technology in Two Bachelor's Degrees: Combining the Best of Online and Face-to-Face Teaching

Authors: Begona del Pino, Beatriz Prieto, Alberto Prieto

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Two opposite approaches to teaching can be considered: in-class learning (teacher-oriented) versus virtual learning (student-oriented). The most known example of the latter is Massive Online Open Courses (MOOCs). Both methodologies have pros and cons. Nowadays there is an increasing trend towards combining both of them. Blending learning is considered a valuable tool for improving learning since it combines student-centred interactive e-learning and face to face instruction. The aim of this contribution is to exchange and share the experience and research results of a blended-learning project that took place in the University of Granada (Spain). The research objective was to prove how combining didactic resources of a MOOC with in-class teaching, interacting directly with students, can substantially improve academic results, as well as student acceptance. The proposed methodology is based on the use of flipped learning technics applied to the subject ‘Fundamentals of Computer Science’ of the first course of two degrees: Telecommunications Engineering, and Industrial Electronics. In this proposal, students acquire the theoretical knowledges at home through a MOOC platform, where they watch video-lectures, do self-evaluation tests, and use other academic multimedia online resources. Afterwards, they have to attend to in-class teaching where they do other activities in order to interact with teachers and the rest of students (discussing of the videos, solving of doubts and practical exercises, etc.), trying to overcome the disadvantages of self-regulated learning. The results are obtained through the grades of the students and their assessment of the blended experience, based on an opinion survey conducted at the end of the course. The major findings of the study are the following: The percentage of students passing the subject has grown from 53% (average from 2011 to 2014 using traditional learning methodology) to 76% (average from 2015 to 2018 using blended methodology). The average grade has improved from 5.20±1.99 to 6.38±1.66. The results of the opinion survey indicate that most students preferred blended methodology to traditional approaches, and positively valued both courses. In fact, 69% of students felt ‘quite’ or ‘very’ satisfied with the classroom activities; 65% of students preferred the flipped classroom methodology to traditional in-class lectures, and finally, 79% said they were ‘quite’ or ‘very’ satisfied with the course in general. The main conclusions of the experience are the improvement in academic results, as well as the highly satisfactory assessments obtained in the opinion surveys. The results confirm the huge potential of combining MOOCs in formal undergraduate studies with on-campus learning activities. Nevertheless, the results in terms of students’ participation and follow-up have a wide margin for improvement. The method is highly demanding for both students and teachers. As a recommendation, students must perform the assigned tasks with perseverance, every week, in order to take advantage of the face-to-face classes. This perseverance is precisely what needs to be promoted among students because it clearly brings about an improvement in learning.

Keywords: blended learning, educational paradigm, flipped classroom, flipped learning technologies, lessons learned, massive online open course, MOOC, teacher roles through technology

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13 The U.S. Missile Defense Shield and Global Security Destabilization: An Inconclusive Link

Authors: Michael A. Unbehauen, Gregory D. Sloan, Alberto J. Squatrito

Abstract:

Missile proliferation and global stability are intrinsically linked. Missile threats continually appear at the forefront of global security issues. North Korea’s recently demonstrated nuclear and intercontinental ballistic missile (ICBM) capabilities, for the first time since the Cold War, renewed public interest in strategic missile defense capabilities. To protect from limited ICBM attacks from so-called rogue actors, the United States developed the Ground-based Midcourse Defense (GMD) system. This study examines if the GMD missile defense shield has contributed to a safer world or triggered a new arms race. Based upon increased missile-related developments and the lack of adherence to international missile treaties, it is generally perceived that the GMD system is a destabilizing factor for global security. By examining the current state of arms control treaties as well as existing missile arsenals and ongoing efforts in technologies to overcome U.S. missile defenses, this study seeks to analyze the contribution of GMD to global stability. A thorough investigation cannot ignore that, through the establishment of this limited capability, the U.S. violated longstanding, successful weapons treaties and caused concern among states that possess ICBMs. GMD capability contributes to the perception that ICBM arsenals could become ineffective, creating an imbalance in favor of the United States, leading to increased global instability and tension. While blame for the deterioration of global stability and non-adherence to arms control treaties is often placed on U.S. missile defense, the facts do not necessarily support this view. The notion of a renewed arms race due to GMD is supported neither by current missile arsenals nor by the inevitable development of new and enhanced missile technology, to include multiple independently targeted reentry vehicles (MIRVs), maneuverable reentry vehicles (MaRVs), and hypersonic glide vehicles (HGVs). The methodology in this study encapsulates a period of time, pre- and post-GMD introduction, while analyzing international treaty adherence, missile counts and types, and research in new missile technologies. The decline in international treaty adherence, coupled with a measurable increase in the number and types of missiles or research in new missile technologies during the period after the introduction of GMD, could be perceived as a clear indicator of GMD contributing to global instability. However, research into improved technology (MIRV, MaRV and HGV) prior to GMD, as well as a decline of various global missile inventories and testing of systems during this same period, would seem to invalidate this theory. U.S. adversaries have exploited the perception of the U.S. missile defense shield as a destabilizing factor as a pretext to strengthen and modernize their militaries and justify their policies. As a result, it can be concluded that global stability has not significantly decreased due to GMD; but rather, the natural progression of technological and missile development would inherently include innovative and dynamic approaches to target engagement, deterrence, and national defense.

Keywords: arms control, arms race, global security, GMD, ICBM, missile defense, proliferation

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12 The Role of a Biphasic Implant Based on a Bioactive Silk Fibroin for Osteochondral Tissue Regeneration

Authors: Lizeth Fuentes-Mera, Vanessa Perez-Silos, Nidia K. Moncada-Saucedo, Alejandro Garcia-Ruiz, Alberto Camacho, Jorge Lara-Arias, Ivan Marino-Martinez, Victor Romero-Diaz, Adolfo Soto-Dominguez, Humberto Rodriguez-Rocha, Hang Lin, Victor Pena-Martinez

Abstract:

Biphasic scaffolds in cartilage tissue engineering have been designed to influence not only the recapitulation of the osteochondral architecture but also to take advantage of the healing ability of bone to promote the implant integration with the surrounding tissue and then bone restoration and cartilage regeneration. This study reports the development and characterization of a biphasic scaffold based on the assembly of a cartilage phase constituted by fibroin biofunctionalized with bovine cartilage matrix; cellularized with differentiated pre-chondrocytes from adipose tissue stem cells (autologous) and well attached to a bone phase (bone bovine decellularized) to mimic the structure of the nature of native tissue and to promote the cartilage regeneration in a model of joint damage in pigs. Biphasic scaffolds were assembled by fibroin crystallization with methanol. The histological and ultrastructural architectures were evaluated by optical and scanning electron microscopy respectively. Mechanical tests were conducted to evaluate Young's modulus of the implant. For the biological evaluation, pre-chondrocytes were loaded onto the scaffolds and cellular adhesion, proliferation, and gene expression analysis of cartilage extracellular matrix components was performed. The scaffolds that were cellularized and matured for 10 days were implanted into critical 3 mm in diameter and 9-mm in depth osteochondral defects in a porcine model (n=4). Three treatments were applied per knee: Group 1: monophasic cellular scaffold (MS) (single chondral phase), group 2: biphasic scaffold, cellularized only in the chondral phase (BS1), group 3: BS cellularized in both bone and chondral phases (BS2). Simultaneously, a control without treatment was evaluated. After 4 weeks of surgery, integration and regeneration tissues were analyzed by x-rays, histology and immunohistochemistry evaluation. The mechanical assessment showed that the acellular biphasic composites exhibited Young's modulus of 805.01 kPa similar to native cartilage (400-800 kPa). In vitro biological studies revealed the chondroinductive ability of the biphasic implant, evidenced by an increase in sulfated glycosaminoglycan (GAGs) and type II collagen, both secreted by the chondrocytes cultured on the scaffold during 28 days. No evidence of adverse or inflammatory reactions was observed in the in vivo trial; however, In group 1, the defects were not reconstructed. In group 2 and 3 a good integration of the implant with the surrounding tissue was observed. Defects in group 2 were fulfilled by hyaline cartilage and normal bone. Group 3 defects showed fibrous repair tissue. In conclusion; our findings demonstrated the efficacy of biphasic and bioactive scaffold based on silk fibroin, which entwined chondroinductive features and biomechanical capability with appropriate integration with the surrounding tissue, representing a promising alternative for osteochondral tissue-engineering applications.

Keywords: biphasic scaffold, extracellular cartilage matrix, silk fibroin, osteochondral tissue engineering

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11 Invasion of Scaevola sericea (Goodeniaceae) in Cuba: Invasive Dynamic and Density-Dependent Relationship with the Native Species Tournefortia gnaphalodes (Boraginaceae)

Authors: Jorge Ferro-Diaz, Lazaro Marquez-Llauger, Jose Alberto Camejo-Lamas, Lazaro Marquez-Govea

Abstract:

The invasion of Scaevola sericea Vahl (Goodeniaceae) in Cuba is a recent process, this exotic invasive species was reported for the first time, in the national territory, by 2008. S. sericea is native to the coasts around the Indian Ocean and western Pacific, common on sandy beaches; it has expanded rapidly around the planet by either natural or anthropic causes, mainly due to its use in hotel gardening. Cuba is highly vulnerable to the colonization of these species, mainly due to tropical hurricanes which have increased in the last decades; it also affects other native species such as Tournefortia gnaphalodes (L.) R. Br. (Boraginaceae) that show invasive manifestations because of the unbalanced state of demographic processes of littoral vegetation, which has been studied by authors during the last 10 years. The fast development of Cuban tourism has encouraged the use of exotic species in gardening that invade large sectors of sandy coasts. Taking into account the importance of assessing the impacts dimensions and adopting effective control measures, a monitoring program for the invasion of S. sericea in Cuba was undertaken. The program has been implemented since 2013 and the main objective was to identify invasive patterns and interactions with other native species of coastal vegetation. This experience also aimed to validate the design and propose a standardized monitoring protocol to be applied throughout the country. In the Cuban territory, 12 sites were chosen, where there were established 24 permanent plots of 100 m2; measurements were taken twice a year taking into consideration variables such as abundance, plant height, soil cover, flora and companion vegetation, density and frequency; other physical variables of the beaches were also measured. Similarly, for associated individuals of T. gnaphalodes, the same variables were measured. The results of these first four years allowed us to document patterns of S. sericea invasion, highlighting the use of adventitious roots to enhance their colonization, and to characterize demographic indicators, ecosystem affections, and interactions with native plants. A density-dependent relationship with T. gnaphalodes was documented, finding a controlling effect on S. sericea, so that a manipulation experiment was applied to evaluate possible management actions to be incorporated in the Plans of the protected areas involved. With these results, it was concluded, for the evaluated sites, that S. sericea has had an invasion dynamics ruled by effects of coastal dynamics, more intense in beaches with affectations to the native vegetation, and more controlled in beaches with more preserved vegetation. It was found that when S. sericea is established, the mechanism that most reinforces its invasion is the use of adventitious roots, used to expand the patches and colonize beach sectors. It was also found that when the density of T. gnaphalodes increases, it detains the expansion of S. sericea and reduces its colonization possibilities, behaving as a natural controller of its biological invasion. The results include a proposal of a new Monitoring Protocol for Scaevola sericea in Cuba, with the possibility of extending its implementation to other countries in the region.

Keywords: biological invasion, exotic invasive species, plant interactions, Scaevola sericea

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10 Water Monitoring Sentinel Cloud Platform: Water Monitoring Platform Based on Satellite Imagery and Modeling Data

Authors: Alberto Azevedo, Ricardo Martins, André B. Fortunato, Anabela Oliveira

Abstract:

Water is under severe threat today because of the rising population, increased agricultural and industrial needs, and the intensifying effects of climate change. Due to sea-level rise, erosion, and demographic pressure, the coastal regions are of significant concern to the scientific community. The Water Monitoring Sentinel Cloud platform (WORSICA) service is focused on providing new tools for monitoring water in coastal and inland areas, taking advantage of remote sensing, in situ and tidal modeling data. WORSICA is a service that can be used to determine the coastline, coastal inundation areas, and the limits of inland water bodies using remote sensing (satellite and Unmanned Aerial Vehicles - UAVs) and in situ data (from field surveys). It applies to various purposes, from determining flooded areas (from rainfall, storms, hurricanes, or tsunamis) to detecting large water leaks in major water distribution networks. This service was built on components developed in national and European projects, integrated to provide a one-stop-shop service for remote sensing information, integrating data from the Copernicus satellite and drone/unmanned aerial vehicles, validated by existing online in-situ data. Since WORSICA is operational using the European Open Science Cloud (EOSC) computational infrastructures, the service can be accessed via a web browser and is freely available to all European public research groups without additional costs. In addition, the private sector will be able to use the service, but some usage costs may be applied, depending on the type of computational resources needed by each application/user. Although the service has three main sub-services i) coastline detection; ii) inland water detection; iii) water leak detection in irrigation networks, in the present study, an application of the service to Óbidos lagoon in Portugal is shown, where the user can monitor the evolution of the lagoon inlet and estimate the topography of the intertidal areas without any additional costs. The service has several distinct methodologies implemented based on the computations of the water indexes (e.g., NDWI, MNDWI, AWEI, and AWEIsh) retrieved from the satellite image processing. In conjunction with the tidal data obtained from the FES model, the system can estimate a coastline with the corresponding level or even topography of the inter-tidal areas based on the Flood2Topo methodology. The outcomes of the WORSICA service can be helpful for several intervention areas such as i) emergency by providing fast access to inundated areas to support emergency rescue operations; ii) support of management decisions on hydraulic infrastructures operation to minimize damage downstream; iii) climate change mitigation by minimizing water losses and reduce water mains operation costs; iv) early detection of water leakages in difficult-to-access water irrigation networks, promoting their fast repair.

Keywords: remote sensing, coastline detection, water detection, satellite data, sentinel, Copernicus, EOSC

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9 Nanocomposite Effect Based on Silver Nanoparticles and Anemposis Californica Extract as Skin Restorer

Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

Abstract:

Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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8 The Regulation of the Cancer Epigenetic Landscape Lies in the Realm of the Long Non-coding RNAs

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

Abstract:

Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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