Search results for: Juan Andrés López Barreras
Commenced in January 2007
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Edition: International
Paper Count: 618

Search results for: Juan Andrés López Barreras

78 Metabolic Profiling in Breast Cancer Applying Micro-Sampling of Biological Fluids and Analysis by Gas Chromatography – Mass Spectrometry

Authors: Mónica P. Cala, Juan S. Carreño, Roland J.W. Meesters

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Recently, collection of biological fluids on special filter papers has become a popular micro-sampling technique. Especially, the dried blood spot (DBS) micro-sampling technique has gained much attention and is momently applied in various life sciences reserach areas. As a result of this popularity, DBS are not only intensively competing with the venous blood sampling method but are at this moment widely applied in numerous bioanalytical assays. In particular, in the screening of inherited metabolic diseases, pharmacokinetic modeling and in therapeutic drug monitoring. Recently, microsampling techniques were also introduced in “omics” areas, whereunder metabolomics. For a metabolic profiling study we applied micro-sampling of biological fluids (blood and plasma) from healthy controls and from women with breast cancer. From blood samples, dried blood and plasma samples were prepared by spotting 8uL sample onto pre-cutted 5-mm paper disks followed by drying of the disks for 100 minutes. Dried disks were then extracted by 100 uL of methanol. From liquid blood and plasma samples 40 uL were deproteinized with methanol followed by centrifugation and collection of supernatants. Supernatants and extracts were evaporated until dryness by nitrogen gas and residues derivated by O-methyxyamine and MSTFA. As internal standard C17:0-methylester in heptane (10 ppm) was used. Deconvolution and alignment of and full scan (m/z 50-500) MS data were done by AMDIS and SpectConnect (http://spectconnect.mit.edu) software, respectively. Statistical Data analysis was done by Principal Component Analysis (PCA) using R software. The results obtained from our preliminary study indicate that the use of dried blood/plasma on paper disks could be a powerful new tool in metabolic profiling. Many of the metabolites observed in plasma (liquid/dried) were also positively identified in whole blood samples (liquid/dried). Whole blood could be a potential substitute matrix for plasma in Metabolomic profiling studies as well also micro-sampling techniques for the collection of samples in clinical studies. It was concluded that the separation of the different sample methodologies (liquid vs. dried) as observed by PCA was due to different sample treatment protocols applied. More experiments need to be done to confirm obtained observations as well also a more rigorous validation .of these micro-sampling techniques is needed. The novelty of our approach can be found in the application of different biological fluid micro-sampling techniques for metabolic profiling.

Keywords: biofluids, breast cancer, metabolic profiling, micro-sampling

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77 Variation of Carbon Isotope Ratio (δ13C) and Leaf-Productivity Traits in Aquilaria Species (Thymelaeceae)

Authors: Arlene López-Sampson, Tony Page, Betsy Jackes

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Aquilaria genus produces a highly valuable fragrant oleoresin known as agarwood. Agarwood forms in a few trees in the wild as a response to injure or pathogen attack. The resin is used in perfume and incense industry and medicine. Cultivation of Aquilaria species as a sustainable source of the resin is now a common strategy. Physiological traits are frequently used as a proxy of crop and tree productivity. Aquilaria species growing in Queensland, Australia were studied to investigate relationship between leaf-productivity traits with tree growth. Specifically, 28 trees, representing 12 plus trees and 16 trees from yield plots, were selected to conduct carbon isotope analysis (δ13C) and monitor six leaf attributes. Trees were grouped on four diametric classes (diameter at 150 mm above ground level) ensuring the variability in growth of the whole population was sampled. Model averaging technique based on the Akaike’s information criterion (AIC) was computed to identify whether leaf traits could assist in diameter prediction. Carbon isotope values were correlated with height classes and leaf traits to determine any relationship. In average four leaves per shoot were recorded. Approximately one new leaf per week is produced by a shoot. Rate of leaf expansion was estimated in 1.45 mm day-1. There were no statistical differences between diametric classes and leaf expansion rate and number of new leaves per week (p > 0.05). Range of δ13C values in leaves of Aquilaria species was from -25.5 ‰ to -31 ‰ with an average of -28.4 ‰ (± 1.5 ‰). Only 39% of the variability in height can be explained by δ13C in leaf. Leaf δ13C and nitrogen content values were positively correlated. This relationship implies that leaves with higher photosynthetic capacities also had lower intercellular carbon dioxide concentrations (ci/ca) and less depleted values of 13C. Most of the predictor variables have a weak correlation with diameter (D). However, analysis of the 95% confidence of best-ranked regression models indicated that the predictors that could likely explain growth in Aquilaria species are petiole length (PeLen), values of δ13C (true13C) and δ15N (true15N), leaf area (LA), specific leaf area (SLA) and number of new leaf produced per week (NL.week). The model constructed with PeLen, true13C, true15N, LA, SLA and NL.week could explain 45% (R2 0.4573) of the variability in D. The leaf traits studied gave a better understanding of the leaf attributes that could assist in the selection of high-productivity trees in Aquilaria.

Keywords: 13C, petiole length, specific leaf area, tree growth

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76 Studying the Effect of Reducing Thermal Processing over the Bioactive Composition of Non-Centrifugal Cane Sugar: Towards Natural Products with High Therapeutic Value

Authors: Laura Rueda-Gensini, Jader Rodríguez, Juan C. Cruz, Carolina Munoz-Camargo

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There is an emerging interest in botanicals and plant extracts for medicinal practices due to their widely reported health benefits. A large variety of phytochemicals found in plants have been correlated with antioxidant, immunomodulatory, and analgesic properties, which makes plant-derived products promising candidates for modulating the progression and treatment of numerous diseases. Non-centrifugal cane sugar (NCS), in particular, has been known for its high antioxidant and nutritional value, but composition-wise variability due to changing environmental and processing conditions have considerably limited its use in the nutraceutical and biomedical fields. This work is therefore aimed at assessing the effect of thermal exposure during NCS production over its bioactive composition and, in turn, its therapeutic value. Accordingly, two modified dehydration methods are proposed that employ: (i) vacuum-aided evaporation, which reduces the necessary temperatures to dehydrate the sample, and (ii) window refractance evaporation, which reduces thermal exposure time. The biochemical composition of NCS produced under these two methods was compared to traditionally-produced NCS by estimating their total polyphenolic and protein content with Folin-Ciocalteu and Bradford assays, as well as identifying the major phenolic compounds in each sample via HPLC-coupled mass spectrometry. Their antioxidant activities were also compared as measured by their scavenging potential of ABTS and DPPH radicals. Results show that the two modified production methods enhance polyphenolic and protein yield in resulting NCS samples when compared to traditional production methods. In particular, reducing employed temperatures with vacuum-aided evaporation demonstrated to be superior at preserving polyphenolic compounds, as evidenced both in the total and individual polyphenol concentrations. However, antioxidant activities were not significantly different between these. Although additional studies should be performed to determine if the observed compositional differences affect other therapeutic activities (e.g., anti-inflammatory, analgesic, and immunoprotective), these results suggest that reducing thermal exposure holds great promise for the production of natural products with enhanced nutritional value.

Keywords: non-centrifugal cane sugar, polyphenolic compounds, thermal processing, antioxidant activity

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75 Effects of Bone Marrow Derived Mesenchymal Stem Cells (MSC) in Acute Respiratory Distress Syndrome (ARDS) Lung Remodeling

Authors: Diana Islam, Juan Fang, Vito Fanelli, Bing Han, Julie Khang, Jianfeng Wu, Arthur S. Slutsky, Haibo Zhang

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Introduction: MSC delivery in preclinical models of ARDS has demonstrated significant improvements in lung function and recovery from acute injury. However, the role of MSC delivery in ARDS associated pulmonary fibrosis is not well understood. Some animal studies using bleomycin, asbestos, and silica-induced pulmonary fibrosis show that MSC delivery can suppress fibrosis. While other animal studies using radiation induced pulmonary fibrosis, liver, and kidney fibrosis models show that MSC delivery can contribute to fibrosis. Hypothesis: The beneficial and deleterious effects of MSC in ARDS are modulated by the lung microenvironment at the time of MSC delivery. Methods: To induce ARDS a two-hit mouse model of Hydrochloric acid (HCl) aspiration (day 0) and mechanical ventilation (MV) (day 2) was used. HCl and injurious MV generated fibrosis within 14-28 days. 0.5x106 mouse MSCs were delivered (via both intratracheal and intravenous routes) either in the active inflammatory phase (day 2) or during the remodeling phase (day 14) of ARDS (mouse fibroblasts or PBS used as a control). Lung injury accessed using inflammation score and elastance measurement. Pulmonary fibrosis was accessed using histological score, tissue collagen level, and collagen expression. In addition alveolar epithelial (E) and mesenchymal (M) marker expression profile was also measured. All measurements were taken at day 2, 14, and 28. Results: MSC delivery 2 days after HCl exacerbated lung injury and fibrosis compared to HCl alone, while the day 14 delivery showed protective effects. However in the absence of HCl, MSC significantly reduced the injurious MV-induced fibrosis. HCl injury suppressed E markers and up-regulated M markers. MSC delivery 2 days after HCl further amplified M marker expression, indicating their role in myofibroblast proliferation/activation. While with 14-day delivery E marker up-regulation was observed indicating their role in epithelial restoration. Conclusions: Early MSC delivery can be protective of injurious MV. Late MSC delivery during repair phase may also aid in recovery. However, early MSC delivery during the exudative inflammatory phase of HCl-induced ARDS can result in pro-fibrotic profiles. It is critical to understand the interaction between MSC and the lung microenvironment before MSC-based therapies are utilized for ARDS.

Keywords: acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC), hydrochloric acid (HCl), mechanical ventilation (MV)

Procedia PDF Downloads 652
74 Analysis of Eco-Efficiency and the Determinants of Family Agriculture in Southeast Spain

Authors: Emilio Galdeano-Gómez, Ángeles Godoy-Durán, Juan C. Pérez-Mesa, Laura Piedra-Muñoz

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Eco-efficiency is receiving ever-increasing interest as an indicator of sustainability, as it links environmental and economic performances in productive activities. In agriculture, these indicators and their determinants prove relevant due to the close relationships in this activity between the use of natural resources, which is generally limited, and the provision of basic goods to society. In this context, various analyses have focused on eco-efficiency by considering individual family farms as the basic production unit. However, not only must the measure of efficiency be taken into account, but also the existence of a series of factors which constitute socio-economic, political-institutional, and environmental determinants. Said factors have been studied to a lesser extent in the literature. The present work analyzes eco-efficiency at a micro level, focusing on small-scale family farms as the main decision-making units in horticulture in southeast Spain, a sector which represents about 30% of the fresh vegetables produced in the country and about 20% of those consumed in Europe. The objectives of this study are a) to obtain a series of eco-efficiency indicators by estimating several pressure ratios and economic value added in farming, b) to analyze the influence of specific social, economic and environmental variables on the aforementioned eco-efficiency indicators. The present work applies the method of Data Envelopment Analysis (DEA), which calculates different combinations of environmental pressures (water usage, phytosanitary contamination, waste management, etc.) and aggregate economic value. In a second stage, an analysis is conducted on the influence of the socio-economic and environmental characteristics of family farms on the eco-efficiency indicators, as endogeneous variables, through the use of truncated regression and bootstrapping techniques, following Simar-Wilson methodology. The results reveal considerable inefficiency in aspects such as waste management, while there is relatively little inefficiency in water usage and nitrogen balance. On the other hand, characteristics, such as product specialization, the adoption of quality certifications and belonging to a cooperative do have a positive impact on eco-efficiency. These results are deemed to be of interest to agri-food systems structured on small-scale producers, and they may prove useful to policy-makers as regards managing public environmental programs in agriculture.

Keywords: data envelopment analysis, eco-efficiency, family farms, horticulture, socioeconomic features

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73 Fuzzy Time Series- Markov Chain Method for Corn and Soybean Price Forecasting in North Carolina Markets

Authors: Selin Guney, Andres Riquelme

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Among the main purposes of optimal and efficient forecasts of agricultural commodity prices is to guide the firms to advance the economic decision making process such as planning business operations and marketing decisions. Governments are also the beneficiaries and suppliers of agricultural price forecasts. They use this information to establish a proper agricultural policy, and hence, the forecasts affect social welfare and systematic errors in forecasts could lead to a misallocation of scarce resources. Various empirical approaches have been applied to forecast commodity prices that have used different methodologies. Most commonly-used approaches to forecast commodity sectors depend on classical time series models that assume values of the response variables are precise which is quite often not true in reality. Recently, this literature has mostly evolved to a consideration of fuzzy time series models that provide more flexibility in terms of the classical time series models assumptions such as stationarity, and large sample size requirement. Besides, fuzzy modeling approach allows decision making with estimated values under incomplete information or uncertainty. A number of fuzzy time series models have been developed and implemented over the last decades; however, most of them are not appropriate for forecasting repeated and nonconsecutive transitions in the data. The modeling scheme used in this paper eliminates this problem by introducing Markov modeling approach that takes into account both the repeated and nonconsecutive transitions. Also, the determination of length of interval is crucial in terms of the accuracy of forecasts. The problem of determining the length of interval arbitrarily is overcome and a methodology to determine the proper length of interval based on the distribution or mean of the first differences of series to improve forecast accuracy is proposed. The specific purpose of this paper is to propose and investigate the potential of a new forecasting model that integrates methodologies for determining the proper length of interval based on the distribution or mean of the first differences of series and Fuzzy Time Series- Markov Chain model. Moreover, the accuracy of the forecasting performance of proposed integrated model is compared to different univariate time series models and the superiority of proposed method over competing methods in respect of modelling and forecasting on the basis of forecast evaluation criteria is demonstrated. The application is to daily corn and soybean prices observed at three commercially important North Carolina markets; Candor, Cofield and Roaring River for corn and Fayetteville, Cofield and Greenville City for soybeans respectively. One main conclusion from this paper is that using fuzzy logic improves the forecast performance and accuracy; the effectiveness and potential benefits of the proposed model is confirmed with small selection criteria value such MAPE. The paper concludes with a discussion of the implications of integrating fuzzy logic and nonarbitrary determination of length of interval for the reliability and accuracy of price forecasts. The empirical results represent a significant contribution to our understanding of the applicability of fuzzy modeling in commodity price forecasts.

Keywords: commodity, forecast, fuzzy, Markov

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72 Challenge in Teaching Physics during the Pandemic: Another Way of Teaching and Learning

Authors: Edson Pierre, Gustavo de Jesus Lopez Nunez

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The objective of this work is to analyze how physics can be taught remotely through the use of platforms and software to attract the attention of 2nd-year high school students at Colégio Cívico Militar Professor Carmelita Souza Dias and point out how remote teaching can be a teaching-learning strategy during the period of social distancing. Teaching physics has been a challenge for teachers and students, permeating common sense with the great difficulty of teaching and learning the subject. The challenge increased in 2020 and 2021 with the impact caused by the new coronavirus pandemic (Sars-Cov-2) and its variants that have affected the entire world. With these changes, a new teaching modality emerged: remote teaching. It brought new challenges and one of them was promoting distance research experiences, especially in physics teaching, since there are learning difficulties and it is often impossible for the student to relate the theory observed in class with the reality that surrounds them. Teaching physics in schools faces some difficulties, which makes it increasingly less attractive for young people to choose this profession. Bearing in mind that the study of physics is very important, as it puts students in front of concrete and real situations, situations that physical principles can respond to, helping to understand nature, nourishing and nurturing a taste for science. The use of new platforms and software, such as PhET Interactive Simulations from the University of Colorado at Boulder, is a virtual laboratory that has numerous simulations of scientific experiments, which serve to improve the understanding of the content taught practically, facilitating student learning and absorption of content, being a simple, practical and free simulation tool, attracts more attention from students, causing them to acquire greater knowledge about the subject studied, or even a quiz, bringing certain healthy competitiveness to students, generating knowledge and interest in the themes used. The present study takes the Theory of Social Representations as a theoretical reference, examining the content and process of constructing the representations of teachers, subjects of our investigation, on the evaluation of teaching and learning processes, through a methodology of qualitative. The result of this work has shown that remote teaching was really a very important strategy for the process of teaching and learning physics in the 2nd year of high school. It provided greater interaction between the teacher and the student. Therefore, the teacher also plays a fundamental role since technology is increasingly present in the educational environment, and he is the main protagonist of this process.

Keywords: physics teaching, technologies, remote learning, pandemic

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71 Life Cycle Assessment to Study the Acidification and Eutrophication Impacts of Sweet Cherry Production

Authors: G. Bravo, D. Lopez, A. Iriarte

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Several organizations and governments have created a demand for information about the environmental impacts of agricultural products. Today, the export oriented fruit sector in Chile is being challenged to quantify and reduce their environmental impacts. Chile is the largest southern hemisphere producer and exporter of sweet cherry fruit. Chilean sweet cherry production reached a volume of 80,000 tons in 2012. The main destination market for the Chilean cherry in 2012 was Asia (including Hong Kong and China), taking in 69% of exported volume. Another important market was the United States with 16% participation, followed by Latin America (7%) and Europe (6%). Concerning geographical distribution, the Chilean conventional cherry production is focused in the center-south area, between the regions of Maule and O’Higgins; both regions represent 81% of the planted surface. The Life Cycle Assessment (LCA) is widely accepted as one of the major methodologies for assessing environmental impacts of products or services. The LCA identifies the material, energy, material, and waste flows of a product or service, and their impact on the environment. There are scant studies that examine the impacts of sweet cherry cultivation, such as acidification and eutrophication. Within this context, the main objective of this study is to evaluate, using the LCA, the acidification and eutrophication impacts of sweet cherry production in Chile. The additional objective is to identify the agricultural inputs that contributed significantly to the impacts of this fruit. The system under study included all the life cycle stages from the cradle to the farm gate (harvested sweet cherry). The data of sweet cherry production correspond to nationwide representative practices and are based on technical-economic studies and field information obtained in several face-to-face interviews. The study takes into account the following agricultural inputs: fertilizers, pesticides, diesel consumption for agricultural operations, machinery and electricity for irrigation. The results indicated that the mineral fertilizers are the most important contributors to the acidification and eutrophication impacts of the sheet cherry cultivation. Improvement options are suggested for the hotspot in order to reduce the environmental impacts. The results allow planning and promoting low impacts procedures across fruit companies, as well as policymakers, and other stakeholders on the subject. In this context, this study is one of the first assessments of the environmental impacts of sweet cherry production. New field data or evaluation of other life cycle stages could further improve the knowledge on the impacts of this fruit. This study may contribute to environmental information in other countries where there is similar agricultural production for sweet cherry.

Keywords: acidification, eutrophication, life cycle assessment, sweet cherry production

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70 Antibiotic Prophylaxis Habits in Oral Implant Surgery in the Netherlands: A Cross-Sectional Survey

Authors: Fabio Rodriguez Sanchez, Josef Bruers, Iciar Arteagoitia, Carlos Rodriguez Andres

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Background: Oral implants are a routine treatment to replace lost teeth. Although they have a high rate of success, implant failures do occur. Perioperative antibiotics have been suggested to prevent postoperative infections and dental implant failures, but they remain a controversial treatment among healthy patients. The objective of this study was to determine whether antibiotic prophylaxis is a common treatment in the Netherlands among general dentists, maxillofacial-surgeons, periodontists and implantologists in conjunction with oral implant surgery among healthy patients and to assess the nature of antibiotics prescriptions in order to evaluate whether any consensus has been reached and the current recommendations are being followed. Methodology: Observational cross-sectional study based on a web-survey reported according to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines. A validated questionnaire, developed by Deeb et al. (2015), was translated and slightly adjusted to circumstances in the Netherlands. It was used with the explicit permission of the authors. This questionnaire contained both close-ended and some open-ended questions in relation to the following topics: demographics, qualification, antibiotic type, prescription-duration and dosage. An email was sent February 2018 to a sample of 600 general dentists and all 302 oral implantologists, periodontists and maxillofacial surgeons who were recognized by the Dutch Association of Oral Implantology (NVOI) as oral health care providers placing oral implants. The email included a brief introduction about the study objectives and a link to the web questionnaire, which could be filled in anonymously. Overall, 902 questionnaires were sent. However, 29 questionnaires were not correctly received due to an incorrect email address. So a total number of 873 professionals were reached. Collected data were analyzed using SPSS (IBM Corp., released 2012, Armonk, NY). Results: The questionnaire was sent back by a total number of 218 participants (response rate=24.2%), 45 female (20.8%) and 171 male (79.2%). Two respondents were excluded from the study group because they were not currently working as oral health providers. Overall 151 (69.9%) placed oral implants on regular basis. Approximately 79 (52.7%) of these participants prescribed antibiotics only in determined situations, 66 (44.0%) prescribed antibiotics always and 5 dentists (3.3%) did not prescribe antibiotics at all when placing oral implants. Overall, 83 participants who prescribed antibiotics, did so both pre- and postoperatively (58.5%), 12 exclusively postoperative (8.5%), and 47 followed an exclusive preoperative regime (33.1%). A single dose of 2,000 mg amoxicillin orally 1-hour prior treatment was the most prescribed preoperative regimen. The most frequent prescribed postoperative regimen was 500 mg amoxicillin three times daily for 7 days after surgery. On average, oral health professionals prescribed 6,923 mg antibiotics in conjunction with oral implant surgery, varying from 500 to 14,600 mg. Conclusions: Antibiotic prophylaxis in conjunction with oral implant surgery is prescribed in the Netherlands on a rather large scale. Dutch professionals might prescribe antibiotics more cautiously than in other countries and there seems to be a lower range on the different antibiotic types and regimens being prescribed. Anyway, recommendations based on last-published evidence are frequently not being followed.

Keywords: clinical decision making, infection control, antibiotic prophylaxis, dental implants

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69 Effect of Fermented Orange Juice Intake on Urinary 6‑Sulfatoxymelatonin in Healthy Volunteers

Authors: I. Cerrillo, A. Carrillo-Vico, M. A. Ortega, B. Escudero-López, N. Álvarez-Sánchez, F. Martín, M. S. Fernández-Pachón

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Melatonin is a bioactive compound involved in multiple biological activities such as glucose tolerance, circadian rhythm regulation, antioxidant defense or immune system action. In elderly subjects the intake of foods and drinks rich in melatonin is very important due to its endogenous level decreases with age. Alcoholic fermentation is a process carried out in fruits, vegetables and legumes to obtain new products with improved bioactive compounds profile in relation to original substrates. Alcoholic fermentation process carried out by Saccharomycetaceae var. Pichia kluyveri induces an important synthesis of melatonin in orange juice. A novel beverage derived of fermented orange juice could be a promising source of this bioactive compound. The aim of the present study was to determine whether the acute intake of fermented orange juice increase the levels of urinary 6-sulfatoxymelatonin in healthy humans. Nine healthy volunteers (7 women and 2 men), aged between 20 and 25 years old and BMI of 21.1  2.4 kg/m2, were recruited. On the study day, participants ingested 500 mL of fermented orange juice. The first urine collection was made before fermented orange juice consumption (basal). The rest of urine collections were made in the following time intervals after fermented orange juice consumption: 0-2, 2-5, 5-10, 10- 15 and 15-24 hours. During the experimental period only the consumption of water was allowed. At lunch time a meal was provided (60 g of white bread, two slices of ham, a slice of cheese, 125 g of sweetened natural yoghurt and water). The subjects repeated the protocol with orange juice following a 2-wk washout period between both types of beverages. The levels of 6-sulfatoxymelatonin (6-SMT) were measured in urine recollected at different time points using the Melatonin-Sulfate Urine ELISA (IBL International GMBH, Hamburg, Germany). Levels of 6-SMT were corrected to those of creatinine for each sample. A significant (p < 0.05) increase in urinary 6-SMT levels was observed between 2-5 hours after fermented orange juice ingestion with respect to basal values (increase of 67,8 %). The consumption of orange juice did not induce any significant change in urinary 6-SMT levels. In addition, urinary 6-SMT levels obtained between 2-5 hours after fermented orange juice ingestion (115,6 ng/mg) were significantly different (p < 0.05) from those of orange juice (42,4 ng/mg). The enhancement of urinary 6-SMT after the ingestion of 500 mL of fermented orange juice in healthy humans compared to orange juice could be an important advantage of this novel product as an excellent source of melatonin. Fermented orange juice could be a new functional food, and its consumption could exert a potentially positive effect on health in both the maintenance of health status and the prevention of chronic diseases.

Keywords: fermented orange juice, functional beverage, healthy human, melatonin

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68 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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67 Electron Bernstein Wave Heating in the Toroidally Magnetized System

Authors: Johan Buermans, Kristel Crombé, Niek Desmet, Laura Dittrich, Andrei Goriaev, Yurii Kovtun, Daniel López-Rodriguez, Sören Möller, Per Petersson, Maja Verstraeten

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The International Thermonuclear Experimental Reactor (ITER) will rely on three sources of external heating to produce and sustain a plasma; Neutral Beam Injection (NBI), Ion Cyclotron Resonance Heating (ICRH), and Electron Cyclotron Resonance Heating (ECRH). ECRH is a way to heat the electrons in a plasma by resonant absorption of electromagnetic waves. The energy of the electrons is transferred indirectly to the ions by collisions. The electron cyclotron heating system can be directed to deposit heat in particular regions in the plasma (https://www.iter.org/mach/Heating). Electron Cyclotron Resonance Heating (ECRH) at the fundamental resonance in X-mode is limited by a low cut-off density. Electromagnetic waves cannot propagate in the region between this cut-off and the Upper Hybrid Resonance (UHR) and cannot reach the Electron Cyclotron Resonance (ECR) position. Higher harmonic heating is hence preferred in heating scenarios nowadays to overcome this problem. Additional power deposition mechanisms can occur above this threshold to increase the plasma density. This includes collisional losses in the evanescent region, resonant power coupling at the UHR, tunneling of the X-wave with resonant coupling at the ECR, and conversion to the Electron Bernstein Wave (EBW) with resonant coupling at the ECR. A more profound knowledge of these deposition mechanisms can help determine the optimal plasma production scenarios. Several ECRH experiments are performed on the TOroidally MAgnetized System (TOMAS) to identify the conditions for Electron Bernstein Wave (EBW) heating. Density and temperature profiles are measured with movable Triple Langmuir Probes in the horizontal and vertical directions. Measurements of the forwarded and reflected power allow evaluation of the coupling efficiency. Optical emission spectroscopy and camera images also contribute to plasma characterization. The influence of the injected power, magnetic field, gas pressure, and wave polarization on the different deposition mechanisms is studied, and the contribution of the Electron Bernstein Wave is evaluated. The TOMATOR 1D hydrogen-helium plasma simulator numerically describes the evolution of current less magnetized Radio Frequency plasmas in a tokamak based on Braginskii’s legal continuity and heat balance equations. This code was initially benchmarked with experimental data from TCV to determine the transport coefficients. The code is used to model the plasma parameters and the power deposition profiles. The modeling is compared with the data from the experiments.

Keywords: electron Bernstein wave, Langmuir probe, plasma characterization, TOMAS

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66 Analyzing the Relationship between Physical Fitness and Academic Achievement in Chinese High School Students

Authors: Juan Li, Hui Tian, Min Wang

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In China, under the considerable pressure of 'Gaokao' –the highly competitive college entrance examination, high school teachers and parents often worry that doing physical activity would take away the students’ precious study time and may have a negative impact on the academic grades. There was a tendency to achieve high academic scores at the cost of physical exercise. Therefore, the purpose of this study was to examine the relationship between the physical fitness and academic achievement of Chinese high school students. The participants were 968 grade one (N=457) and grade two students (N=511) with an average age of 16 years from three high schools of different levels in Beijing, China. 479 were boys, and 489 were girls. One of the schools is a top high school in China, another is a key high school in Beijing, and the other is an ordinary high school. All analyses were weighted using SAS 9.4 to ensure the representatives of the sample. The weights were based on 12 strata of schools, sex, and grades. Physical fitness data were collected using the scores of the National Physical Fitness Test, which is an annual official test administered by the Ministry of Education in China. It includes 50m run, sits and reach test, standing long jump, 1000m run (for boys), 800m run (for girls), pull-ups for 1 minute (for boys), and bent-knee sit-ups for 1 minute (for girls). The test is an overall evaluation of the students’ physical health on the major indexes of strength, endurance, flexibility, and cardiorespiratory function. Academic scores were obtained from the three schools with the students’ consent. The statistical analysis was conducted with SPSS 24. Independent-Samples T-test was used to examine the gender group differences. Spearman’s Rho bivariate correlation was adopted to test for associations between physical test results and academic performance. Statistical significance was set at p<.05. The study found that girls obtained higher fitness scores than boys (p=.000). The girls’ physical fitness test scores were positively associated with the total academic grades (rs=.103, p=.029), English (rs=.096, p=.042), physics (rs=.202, p=.000) and chemistry scores (rs=.131, p=.009). No significant relationship was observed in boys. Cardiorespiratory fitness had a positive association with physics (rs=.196, p=.000) and biology scores (rs=.168, p=.023) in girls, and with English score in boys (rs=.104, p=.029). A possible explanation for the greater association between physical fitness and academic achievement in girls rather than boys was that girls showed stronger motivation in achieving high scores in whether academic tests or fitness tests. More driven by the test results, girls probably tended to invest more time and energy in training for the fitness test. Higher fitness levels were associated with an academic benefit among girls generally in Chinese high schools. Therefore, physical fitness needs to be given greater emphasis among Chinese adolescents and gender differences need to be taken into consideration.

Keywords: physical fitness; adolescents; academic achievement; high school

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65 Genetic Diversity of Cord Blood of the National Center of Blood Transfusion, Mexico (NCBT)

Authors: J. Manuel Bello-López, Julieta Rojo-Medina

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Introduction: The transplant of Umbilical Cord Blood Units (UCBU) are a therapeutic possibility for patients with oncohaematological disorders, especially in children. In Mexico, 48.5% of oncological diseases in children 1-4 years old are leukemias; whereas in patients 5-14 and 15-24 years old, lymphomas and leukemias represent the second and third cause of death in these groups respectively. Therefore it is necessary to have more registries of UCBU in order to ensure genetic diversity in the country; the above because the search for appropriate a UCBU is increasingly difficult for patients of mixed ethnicity. Objective: To estimate the genetic diversity (polymorphisms) of Human Leucocyte Antigen (HLA) Class I (A, B) and Class II (DRB1) in UCBU cryopreserved for transplant at Cord Blood Bank of the NCBT. Material and Methods: HLA typing of 533 UCBU for transplant was performed from 2003-2012 at the Histocompatibility Laboratory from the Research Department (evaluated by Los Angeles Ca. Immunogenetics Center) of the NCBT. Class I HLA-A, HLA-B and Class II HLA-DRB1 typing was performed using medium resolution Sequence-Specific Primer (SSP). In cases of an ambiguity detected by SSP; Sequence-Specific Oligonucleotide (SSO) method was carried out. A strict analysis of populations genetic parameters were done in 5 representative UCBU populations. Results: 46.5% of UCBU were collected from Mexico City, State of Mexico (30.95%), Puebla (8.06%), Morelos (6.37%) and Veracruz (3.37%). The remaining UCBU (4.75%) are represented by other states. The identified genotypes correspond to Amerindian origins (HLA-A*02, 31; HLA-B*39, 15, 48), Caucasian (HLA-A*02, 68, 01, 30, 31; HLA-B*35, 15, 40, 44, 07 y HLA-DRB1*04, 08, 07, 15, 03, 14), Oriental (HLA-A*02, 30, 01, 31; HLA-B* 35, 39, 15, 40, 44, 07,48 y HLA-DRB1*04, 07,15, 03) and African (HLA-A*30 y HLA-DRB1*03). The genetic distances obtained by Cavalli-Sforza analysis of the five states showed significant genetic differences by comparing genetic frequencies. The shortest genetic distance exists between Mexico City and the state of Puebla (0.0039) and the largest between Veracruz and Morelos (0.0084). In order to identify significant differences between this states, the ANOVA test was performed. This demonstrates that UCBU is significantly different according to their origin (P <0.05). This is shown by the divergence between arms at the Dendogram of Neighbor-Joining. Conclusions: The NCBT provides UCBU in patients with oncohaematological disorders in all the country. There is a group of patients for which not compatible UCBU can be find due to the mixed ethnic origin. For example, the population of northern Mexico is mostly Caucasian. Most of the NCBT donors are of various ethnic origins, predominantly Amerindians and Caucasians; although some ethnic minorities like Oriental, African and pure Indian ethnics are not represented. The NCBT is, therefore, establishing agreements with different states of Mexico to promote the altruistic donation of Umbilical Cord Blood in order to enrich the genetic diversity in its files.

Keywords: cord blood, genetic diversity, human leucocyte antigen, transplant

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64 Educational Infrastructure a Barrier for Teaching and Learning Architecture

Authors: Alejandra Torres-Landa López

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Introduction: Can architecture students be creative in spaces conformed by an educational infrastructure build with paradigms of the past?, this question and others related are answered in this paper as it presents the PhD research: An anthropic conflict in Mexican Higher Education Institutes, problems and challenges of the educational infrastructure in teaching and learning History of Architecture. This research was finished in 2013 and is one of the first studies conducted nationwide in Mexico that analysis the educational infrastructure impact in learning architecture; its objective was to identify which elements of the educational infrastructure of Mexican Higher Education Institutes where architects are formed, hinder or contribute to the teaching and learning of History of Architecture; how and why it happens. The methodology: A mixed methodology was used combining quantitative and qualitative analysis. Different resources and strategies for data collection were used, such as questionnaires for students and teachers, interviews to architecture research experts, direct observations in Architecture classes, among others; the data collected was analyses using SPSS and MAXQDA. The veracity of the quantitative data was supported by the Cronbach’s Alpha Coefficient, obtaining a 0.86, figure that gives the data enough support. All the above enabled to certify the anthropic conflict in which Mexican Universities are. Major findings of the study: Although some of findings were probably not unknown, they haven’t been systematized and analyzed with the depth to which it’s done in this research. So, it can be said, that the educational infrastructure of most of the Higher Education Institutes studied, is a barrier to the educational process, some of the reasons are: the little morphological variation of space, the inadequate control of lighting, noise, temperature, equipment and furniture, the poor or none accessibility for disable people; as well as the absence, obsolescence and / or insufficiency of information technologies are some of the issues that generate an anthropic conflict understanding it as the trouble that teachers and students have to relate between them, in order to achieve significant learning). It is clear that most of the educational infrastructure of Mexican Higher Education Institutes is anchored to paradigms of the past; it seems that they respond to the previous era of industrialization. The results confirm that the educational infrastructure of Mexican Higher Education Institutes where architects are formed, is perceived as a "closed container" of people and data; infrastructure that becomes a barrier to teaching and learning process. Conclusion: The research results show it's time to change the paradigm in which we conceive the educational infrastructure, it’s time to stop seen it just only as classrooms, workshops, laboratories and libraries, as it must be seen from a constructive, urban, architectural and human point of view, taking into account their different dimensions: physical, technological, documental, social, among others; so the educational infrastructure can become a set of elements that organize and create spaces where ideas and thoughts can be shared; to be a social catalyst where people can interact between each other and with the space itself.

Keywords: educational infrastructure, impact of space in learning architecture outcomes, learning environments, teaching architecture, learning architecture

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63 Stability of a Biofilm Reactor Able to Degrade a Mixture of the Organochlorine Herbicides Atrazine, Simazine, Diuron and 2,4-Dichlorophenoxyacetic Acid to Changes in the Composition of the Supply Medium

Authors: I. Nava-Arenas, N. Ruiz-Ordaz, C. J. Galindez-Mayer, M. L. Luna-Guido, S. L. Ruiz-López, A. Cabrera-Orozco, D. Nava-Arenas

Abstract:

Among the most important herbicides, the organochlorine compounds are of considerable interest due to their recalcitrance to the chemical, biological, and photolytic degradation, their persistence in the environment, their mobility, and their bioacummulation. The most widely used herbicides in North America are primarily 2,4-dichlorophenoxyacetic acid (2,4-D), the triazines (atrazine and simazine), and to a lesser extent diuron. The contamination of soils and water bodies frequently occurs by mixtures of these xenobiotics. For this reason, in this work, the operational stability to changes in the composition of the medium supplied to an aerobic biofilm reactor was studied. The reactor was packed with fragments of volcanic rock that retained a complex microbial film, able to degrade a mixture of organochlorine herbicides atrazine, simazine, diuron and 2,4-D, and whose members have microbial genes encoding the main catabolic enzymes atzABCD, tfdACD and puhB. To acclimate the attached microbial community, the biofilm reactor was fed continuously with a mineral minimal medium containing the herbicides (in mg•L-1): diuron, 20.4; atrazine, 14.2, simazine, 11.4, and 2,4-D, 59.7, as carbon and nitrogen sources. Throughout the bioprocess, removal efficiencies of 92-100% for herbicides, 78-90% for COD, 92-96% for TOC and 61-83% for dehalogenation were reached. In the microbial community, the genes encoding catabolic enzymes of different herbicides tfdACD, puhB and, occasionally, the genes atzA and atzC were detected. After the acclimatization, the triazine herbicides were eliminated from the mixture formulation. Volumetric loading rates of the mixture 2,4-D and diuron were continuously supplied to the reactor (1.9-21.5 mg herbicides •L-1 •h-1). Along the bioprocess, the removal efficiencies obtained were 86-100% for the mixture of herbicides, 63-94% for for COD, 90-100% for COT, and dehalogenation values of 63-100%. It was also observed that the genes encoding the enzymes in the catabolism of both herbicides, tfdACD and puhB, were consistently detected; and, occasionally, the atzA and atzC. Subsequently, the triazine herbicide atrazine and simazine were restored to the medium supply. Different volumetric charges of this mixture were continuously fed to the reactor (2.9 to 12.6 mg herbicides •L-1 •h-1). During this new treatment process, removal efficiencies of 65-95% for the mixture of herbicides, 63-92% for COD, 66-89% for TOC and 73-94% of dehalogenation were observed. In this last case, the genes tfdACD, puhB and atzABC encoding for the enzymes involved in the catabolism of the distinct herbicides were consistently detected. The atzD gene, encoding the cyanuric hydrolase enzyme, could not be detected, though it was determined that there was partial degradation of cyanuric acid. In general, the community in the biofilm reactor showed some catabolic stability, adapting to changes in loading rates and composition of the mixture of herbicides, and preserving their ability to degrade the four herbicides tested; although, there was a significant delay in the response time to recover to degradation of the herbicides.

Keywords: biodegradation, biofilm reactor, microbial community, organochlorine herbicides

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62 Effect of Self-Lubricating Carbon Materials on the Tribological Performance of Ultra-High Molecular Weight Polyethylene

Authors: Nayeli Camacho, Fernanda Lara-Perez, Carolina Ortega-Portilla, Diego G. Espinosa-Arbelaez, Juan M. Alvarado-Orozco, Guillermo C. Mondragon-Rodriguez

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Ultra-high molecular weight polyethylene (UHMWPE) has been the gold standard material for total knee replacements for almost five decades. Wear damage to UHMWPE articulating surface is inevitable due to the natural sliding and rolling movements of the knee. This generates a considerable amount of wear debris, which results in mechanical instability of the joint, reduces joint mobility, increases pain with detrimental biologic responses, and causes component loosening. The presence of wear particles has been closely related to adverse reactions in the knee joint surrounding tissue, especially for particles in the range of 0.3 to 2 μm. Carbon-based materials possess excellent mechanical properties and have shown great promise in tribological applications. In this study, diamond-like carbon coatings (DLC) and carbon nanotubes (CNTs) were used to decrease the wear rate of ultra-high molecular weight polyethylene. A titanium doped DLC (Ti-DLC) was deposited by magnetron sputtering on stainless steel precision spheres while CNTs were used as a second phase reinforcement in UHMWPE at a concentration of 1.25 wt.%. A comparative tribological analysis of the wear of UHMWPE and UHMWPE-CNTs with a stainless steel counterpart with and without Ti-DLC coating is presented. The experimental wear testing was performed on a pin-on-disc tribometer under dry conditions, using a reciprocating movement with a load of 1 N at a frequency of 2 Hz for 100,000 and 200,000 cycles. The wear tracks were analyzed with high-resolution scanning electron microscopy to determine wear modes and observe the size and shape of the wear debris. Furthermore, profilometry was used to study the depth of the wear tracks and to map the wear of the articulating surface. The wear tracks at 100,000 and 200,000 cycles on all samples were relatively shallow, and they were in the range of average roughness. It was observed that the Ti-DLC coating decreases the mass loss in the UHMWPE and the depth of the wear track. The combination of both carbon-based materials decreased the material loss compared to the system of stainless steel and UHMWPE. Burnishing of the surface was the predominant wear mode observed with all the systems, more subtle for the systems with Ti-DLC coatings. Meanwhile, in the system composed of stainless steel-UHMWPE, the intrinsic surface roughness of the material was completely replaced by the wear tracks.

Keywords: CNT reinforcement, self-lubricating materials, Ti-DLC, UHMWPE tribological performance

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61 Acrylamide Concentration in Cakes with Different Caloric Sweeteners

Authors: L. García, N. Cobas, M. López

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Acrylamide, a probable carcinogen, is formed in high-temperature processed food (>120ºC) when the free amino acid asparagine reacts with reducing sugars, mainly glucose and fructose. Cane juices' repeated heating would potentially form acrylamide during brown sugar production. This study aims to determine if using panela in yogurt cake preparation increases acrylamide formation. A secondary aim is to analyze the acrylamide concentration in four cake confections with different caloric sweetener ingredients: beet sugar (BS), cane sugar (CS), panela (P), and a panela and chocolate mix (PC). The doughs were obtained by combining ingredients in a planetary mixer. A model system made up of flour (25%), caloric sweeteners (25 %), eggs (23%), yogurt (15.7%), sunflower oil (9.4%), and brewer's yeast (2 %) was applied to BS, CS and P cakes. The ingredients of PC cakes varied: flour (21.5 %), panela chocolate (21.5 %), eggs (25.9 %), yogurt (18 %), sunflower oil (10.8 %), and brewer’s yeast (2.3 %). The preparations were baked for 45' at 180 ºC. Moisture was estimated by AOAC. Protein was determined by the Kjeldahl method. Ash percentage was calculated by weight loss after pyrolysis (≈ 600 °C). Fat content was measured using liquid-solid extraction in hydrolyzed raw ingredients and final confections. Carbohydrates were determined by difference and total sugars by the Luff-Schoorl method, based on the iodometric determination of copper ions. Finally, acrylamide content was determined by LC-MS by the isocratic system (phase A: 97.5 % water with 0.1% formic acid; phase B: 2.5 % methanol), using a standard internal procedure. Statistical analysis was performed using SPSS v.23. One-way variance analysis determined differences between acrylamide content and compositional analysis, with caloric sweeteners as fixed effect. Significance levels were determined by applying Duncan's t-test (p<0.05). P cakes showed a lower energy value than the other baked products; sugar content was similar to BS and CS, with 6.1 % mean crude protein. Acrylamide content in caloric sweeteners was similar to previously reported values. However, P and PC showed significantly higher concentrations, probably explained by the applied procedure. Acrylamide formation depends on both reducing sugars and asparagine concentration and availability. Beet sugar samples did not present acrylamide concentrations within the detection and quantification limit. However, the highest acrylamide content was measured in the BS. This may be due to the higher concentration of reducing sugars and asparagine in other raw ingredients. The cakes made with panela, cane sugar, or panela with chocolate did not differ in acrylamide content. The lack of asparagine measures constitutes a limitation. Cakes made with panela showed lower acrylamide formation than products elaborated with beet or cane sugar.

Keywords: beet sugar, cane sugar, panela, yogurt cake

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60 The Use of Non-Parametric Bootstrap in Computing of Microbial Risk Assessment from Lettuce Consumption Irrigated with Contaminated Water by Sanitary Sewage in Infulene Valley

Authors: Mario Tauzene Afonso Matangue, Ivan Andres Sanchez Ortiz

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The Metropolitan area of Maputo (Mozambique Capital City) is located in semi-arid zone (800 mm annual rainfall) with 1101170 million inhabitants. On the west side, there are the flatlands of Infulene where the Mulauze River flows towards to the Indian Ocean, receiving at this site, the storm water contaminated with sanitary sewage from Maputo, transported through a concrete open channel. In Infulene, local communities grow salads crops such as tomato, onion, garlic, lettuce, and cabbage, which are then commercialized and consumed in several markets in Maputo City. Lettuce is the most daily consumed salad crop in different meals, generally in fast-foods, breakfasts, lunches, and dinners. However, the risk of infection by several pathogens due to the consumption of lettuce, using the Quantitative Microbial Risk Assessment (QMRA) tools, is still unknown since there are few studies or publications concerning to this matter in Mozambique. This work is aimed at determining the annual risk arising from the consumption of lettuce grown in Infulene valley, in Maputo, using QMRA tools. The exposure model was constructed upon the volume of contaminated water remaining in the lettuce leaves, the empirical relations between the number of pathogens and the indicator of microorganisms (E. coli), the consumption of lettuce (g) and reduction of pathogens (days). The reference pathogens were Vibrio cholerae, Cryptosporidium, norovirus, and Ascaris. The water quality samples (E. coli) were collected in the storm water channel from January 2016 to December 2018, comprising 65 samples, and the urban lettuce consumption data were collected through inquiry in Maputo Metropolis covering 350 persons. A non-parametric bootstrap was performed involving 10,000 iterations over the collected dataset, namely, water quality (E. coli) and lettuce consumption. The dose-response models were: Exponential for Cryptosporidium, Kummer Confluent hypergeomtric function (1F1) for Vibrio and Ascaris Gaussian hypergeometric function (2F1-(a,b;c;z) for norovirus. The annual infection risk estimates were performed using R 3.6.0 (CoreTeam) software by Monte Carlo (Latin hypercubes), a sampling technique involving 10,000 iterations. The annual infection risks values expressed by Median and the 95th percentile, per person per year (pppy) arising from the consumption of lettuce are as follows: Vibrio cholerae (1.00, 1.00), Cryptosporidium (3.91x10⁻³, 9.72x 10⁻³), nororvirus (5.22x10⁻¹, 9.99x10⁻¹) and Ascaris (2.59x10⁻¹, 9.65x10⁻¹). Thus, the consumption of the lettuce would result in greater risks than the tolerable levels ( < 10⁻³ pppy or 10⁻⁶ DALY) for all pathogens, and the Vibrio cholerae is the most virulent pathogens, according to the hit-single models followed by the Ascaris lumbricoides and norovirus. The sensitivity analysis carried out in this work pointed out that in the whole QMRA, the most important input variable was the reduction of pathogens (Spearman rank value was 0.69) between harvest and consumption followed by water quality (Spearman rank value was 0.69). The decision-makers (Mozambique Government) must strengthen the prevention measures related to pathogens reduction in lettuce (i.e., washing) and engage in wastewater treatment engineering.

Keywords: annual infections risk, lettuce, non-parametric bootstrapping, quantitative microbial risk assessment tools

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59 The Role of Goal Orientation on the Structural-Psychological Empowerment Link in the Public Sector

Authors: Beatriz Garcia-Juan, Ana B. Escrig-Tena, Vicente Roca-Puig

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The aim of this article is to conduct a theoretical and empirical study in order to examine how the goal orientation (GO) of public employees affects the relationship between the structural and psychological empowerment that they experience at their workplaces. In doing so, we follow structural empowerment (SE) and psychological empowerment (PE) conceptualizations, and relate them to the public administration framework. Moreover, we review arguments from GO theories, and previous related contributions. Empowerment has emerged as an important issue in the public sector organization setting in the wake of mainstream New Public Management (NPM), the new orientation in the public sector that aims to provide a better service for citizens. It is closely linked to the drive to improve organizational effectiveness through the wise use of human resources. Nevertheless, it is necessary to combine structural (managerial) and psychological (individual) approaches in an integrative study of empowerment. SE refers to a set of initiatives that aim the transference of power from managerial positions to the rest of employees. PE is defined as psychological state of competence, self-determination, impact, and meaning that an employee feels at work. Linking these two perspectives will lead to arrive at a broader understanding of the empowerment process. Specifically in the public sector, empirical contributions on this relationship are therefore important, particularly as empowerment is a very useful tool with which to face the challenges of the new public context. There is also a need to examine the moderating variables involved in this relationship, as well as to extend research on work motivation in public management. It is proposed the study of the effect of individual orientations, such as GO. GO concept refers to the individual disposition toward developing or confirming one’s capacity in achievement situations. Employees’ GO may be a key factor at work and in workforce selection processes, since it explains the differences in personal work interests, and in receptiveness to and interpretations of professional development activities. SE practices could affect PE feelings in different ways, depending on employees’ GO, since they perceive and respond differently to such practices, which is likely to yield distinct PE results. The model is tested on a sample of 521 Spanish local authority employees. Hierarchical regression analysis was conducted to test the research hypotheses using SPSS 22 computer software. The results do not confirm the direct link between SE and PE, but show that learning goal orientation has considerable moderating power in this relationship, and its interaction with SE affects employees’ PE levels. Therefore, the combination of SE practices and employees’ high levels of LGO are important factors for creating psychologically empowered staff in public organizations.

Keywords: goal orientation, moderating effect, psychological empowerment, structural empowerment

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58 Evaluation of Differential Interaction between Flavanols and Saliva Proteins by Diffusion and Precipitation Assays on Cellulose Membranes

Authors: E. Obreque-Slier, V. Contreras-Cortez, R. López-Solís

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Astringency is a drying, roughing, and sometimes puckering sensation that is experienced on the various oral surfaces during or immediately after tasting foods. This sensation has been closely related to the interaction and precipitation between salivary proteins and polyphenols, specifically flavanols or proanthocyanidins. In addition, the type and concentration of proanthocyanidin influences significantly the intensity of the astringency and consequently the protein/proanthocyanidin interaction. However, most of the studies are based on the interaction between saliva and highly complex polyphenols, without considering the effect of monomeric proanthoancyanidins present in different foods. The aim of this study was to evaluate the effect of different monomeric proanthocyanidins on the diffusion and precipitation of salivary proteins. Thus, solutions of catechin, epicatechin, epigallocatechin and gallocatechin (0, 2.0, 4.0, 6.0, 8.0 and 10 mg/mL) were mixed with human saliva (1: 1 v/v). After incubation for 5 min at room temperature, 15 µL aliquots of each mix were dotted on a cellulose membrane and allowed to dry spontaneously at room temperature. The membrane was fixed, rinsed and stained for proteins with Coomassie blue. After exhaustive washing in 7% acetic acid, the membrane was rinsed once in distilled water and dried under a heat lamp. Both diffusion area and stain intensity of the protein spots were semiqualitative estimates for protein-tannin interaction (diffusion test). The rest of the whole saliva-phenol solution mixtures of the diffusion assay were centrifuged, and 15-μL aliquots from each of the supernatants were dotted on a cellulose membrane. The membrane was processed for protein staining as indicated above. The blue-stained area of protein distribution corresponding to each of the extract dilution-saliva mixtures was quantified by Image J 1.45 software. Each of the assays was performed at least three times. Initially, salivary proteins display a biphasic distribution on cellulose membranes, that is, when aliquots of saliva are placed on absorbing cellulose membranes, and free diffusion of saliva is allowed to occur, a non-diffusible protein fraction becomes surrounded by highly diffusible salivary proteins. In effect, once diffusion has ended, a protein-binding dye shows an intense blue-stained roughly circular area close to the spotting site (non-diffusible fraction) (NDF) which becomes surrounded by a weaker blue-stained outer band (diffusible fraction) (DF). Likewise, the diffusion test showed that epicatechin caused the complete disappearance of DF from saliva with 2 mg/mL. Also, epigallocatechin and gallocatechin caused a similar effect with 4 mg/mL, while catechin generated the same effect at 8 mg/mL. In the precipitation test, the use of epicatechin and gallocatechin generated evident precipitates at the bottom of the Eppendorf tubes. In summary, the flavanol type differentially affects the diffusion and precipitation of saliva, which would affect the sensation of astringency perceived by consumers.

Keywords: astringency, polyphenols, tannins, tannin-protein interaction

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57 Building Environmental Citizenship in Spain: Urban Movements and Ecologist Protest in Las Palmas De Gran Canaria, 1970-1983

Authors: Juan Manuel Brito-Diaz

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The emergence of urban environmentalism in Spain is related to the processes of economic transformation and growing urbanization that occurred during the end of the Franco regime and the democratic transition. This paper analyzes the urban environmental mobilizations and their impacts as relevant democratizing agents in the processes of political change in cities. It’s an under-researched topic and studies on environmental movements in Spain have paid little attention to it. This research takes as its starting point the close link between democratization and environmentalism, since it considers that environmental conflicts are largely a consequence of democratic problems, and that the impacts of environmental movements are directly linked to the democratization. The study argues that the environmental movements that emerged in Spain at the end of the dictatorship and the democratic transition are an important part of the broad and complex associative fabric that promoted the democratization process. The research focuses on investigating the environmental protest in Las Palmas de Gran Canaria—the most important city in the Canary Islands—between 1970 and 1983, concurrently with the last local governments of the dictatorship and the first democratic city councils. As it is a case study, it opens up the possibility to ask multiple specific questions and assess each of the responses obtained. Although several research methodologies have been applied, such as the analysis of historical archives documentation or oral history interviews, mainly a very widespread methodology in the sociology of social movements, although very little used by social historians, has been used: the Protest Event Analysis (PEA). This methodology, which consists of generating a catalog of protest events by coding data around previously established variables, has allowed me to map, analyze and interpret the occurrence of protests over time and space, and associated factors, through content analysis. For data collection, news from local newspapers have provided a large enough sample to analyze the properties of social protest -frequency, size, demands, forms, organizers, etc.—and relate them to another type of information related to political structures and mobilization repertoires, encouraging the establishment of connections between the protest and the political impacts of urban movements. Finally, the study argues that the environmental movements of this period were essential to the construction of the new democratic city in Spain, not only because they established the issues of sustainability and urban environmental justice on the public agenda, but also because they proposed that conflicts derived from such matters should ultimately be resolved through public deliberation and citizen participation.

Keywords: democratization, environmental movements, political impacts, social movements

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56 Corpus Linguistics as a Tool for Translation Studies Analysis: A Bilingual Parallel Corpus of Students’ Translations

Authors: Juan-Pedro Rica-Peromingo

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Nowadays, corpus linguistics has become a key research methodology for Translation Studies, which broadens the scope of cross-linguistic studies. In the case of the study presented here, the approach used focuses on learners with little or no experience to study, at an early stage, general mistakes and errors, the correct or incorrect use of translation strategies, and to improve the translational competence of the students. Led by Sylviane Granger and Marie-Aude Lefer of the Centre for English Corpus Linguistics of the University of Louvain, the MUST corpus (MUltilingual Student Translation Corpus) is an international project which brings together partners from Europe and worldwide universities and connects Learner Corpus Research (LCR) and Translation Studies (TS). It aims to build a corpus of translations carried out by students including both direct (L2 > L1) an indirect (L1 > L2) translations, from a great variety of text types, genres, and registers in a wide variety of languages: audiovisual translations (including dubbing, subtitling for hearing population and for deaf population), scientific, humanistic, literary, economic and legal translation texts. This paper focuses on the work carried out by the Spanish team from the Complutense University (UCMA), which is part of the MUST project, and it describes the specific features of the corpus built by its members. All the texts used by UCMA are either direct or indirect translations between English and Spanish. Students’ profiles comprise translation trainees, foreign language students with a major in English, engineers studying EFL and MA students, all of them with different English levels (from B1 to C1); for some of the students, this would be their first experience with translation. The MUST corpus is searchable via Hypal4MUST, a web-based interface developed by Adam Obrusnik from Masaryk University (Czech Republic), which includes a translation-oriented annotation system (TAS). A distinctive feature of the interface is that it allows source texts and target texts to be aligned, so we can be able to observe and compare in detail both language structures and study translation strategies used by students. The initial data obtained point out the kind of difficulties encountered by the students and reveal the most frequent strategies implemented by the learners according to their level of English, their translation experience and the text genres. We have also found common errors in the graduate and postgraduate university students’ translations: transfer errors, lexical errors, grammatical errors, text-specific translation errors, and cultural-related errors have been identified. Analyzing all these parameters will provide more material to bring better solutions to improve the quality of teaching and the translations produced by the students.

Keywords: corpus studies, students’ corpus, the MUST corpus, translation studies

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55 Neural Network Based Control Algorithm for Inhabitable Spaces Applying Emotional Domotics

Authors: Sergio A. Navarro Tuch, Martin Rogelio Bustamante Bello, Leopoldo Julian Lechuga Lopez

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In recent years, Mexico’s population has seen a rise of different physiological and mental negative states. Two main consequences of this problematic are deficient work performance and high levels of stress generating and important impact on a person’s physical, mental and emotional health. Several approaches, such as the use of audiovisual stimulus to induce emotions and modify a person’s emotional state, can be applied in an effort to decreases these negative effects. With the use of different non-invasive physiological sensors such as EEG, luminosity and face recognition we gather information of the subject’s current emotional state. In a controlled environment, a subject is shown a series of selected images from the International Affective Picture System (IAPS) in order to induce a specific set of emotions and obtain information from the sensors. The raw data obtained is statistically analyzed in order to filter only the specific groups of information that relate to a subject’s emotions and current values of the physical variables in the controlled environment such as, luminosity, RGB light color, temperature, oxygen level and noise. Finally, a neural network based control algorithm is given the data obtained in order to feedback the system and automate the modification of the environment variables and audiovisual content shown in an effort that these changes can positively alter the subject’s emotional state. During the research, it was found that the light color was directly related to the type of impact generated by the audiovisual content on the subject’s emotional state. Red illumination increased the impact of violent images and green illumination along with relaxing images decreased the subject’s levels of anxiety. Specific differences between men and women were found as to which type of images generated a greater impact in either gender. The population sample was mainly constituted by college students whose data analysis showed a decreased sensibility to violence towards humans. Despite the early stage of the control algorithm, the results obtained from the population sample give us a better insight into the possibilities of emotional domotics and the applications that can be created towards the improvement of performance in people’s lives. The objective of this research is to create a positive impact with the application of technology to everyday activities; nonetheless, an ethical problem arises since this can also be applied to control a person’s emotions and shift their decision making.

Keywords: data analysis, emotional domotics, performance improvement, neural network

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54 Harsh Discipline and Later Disruptive Behavior Disorder in Two Contexts

Authors: Olga Santesteban, Glorisa Canino, Hector R. Bird, Cristiane S. Duarte

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Objective: To address whether harsh discipline is associated with disruptive behavior disorders (DBD) in Puerto Rican children over time. Background: Both cross-sectional and longitudinal studies report that rates of DBD vary by gender, age and other demographics, being more frequent among boys, later in life and among those who live in urban areas. Also, the literature supports the direct, positive association between harsh discipline and externalizing behaviors. Nevertheless, scholars have underscored the important role of race and ethnicity in understanding discipline effects on children. The impact of harsh discipline in a Puerto Rican population remains to be studied. Methods: Sample: This is a secondary analysis of the Boricua Youth Study which assessed yearly (3 times) Puerto Rican children aged 5-15 in two different sites: San Juan (Puerto Rico) and the South Bronx (NY), N=2951. Participants that did not have scores of harsh discipline in the 3 waves were excluded for this analysis (N=2091). Main Measures: a) Harsh Discipline (Parent report) was measured using 6 items from the “Parental Discipline Scale” that measures various forms of punishment, including physical and verbal abuse, and withholding affection; b) Disruptive Behavior Disorder (Parent report): Parent version of the Diagnostic Interview Schedule for Children-IV (DISC-IV) was used to asses children’s conduct disorders; c) Demographic factors: Child gender, child age, family income, marital status; d) Parental factors: parental psychopathology, parental monitoring, familism, parent support; e) Children characteristics: Controlling for any diagnostic at wave 1 (internalizing or externalizing). Data Analysis: Logistic regression was carried out relating the likelihood of DBD to harsh discipline along waves controlling for potential confounders as demographics, child and parent characteristics. Results: There were no significant differences in harsh discipline by site in wave 1 and wave 2 but there was a significant difference in wave 3. Also, there were no significant differences in DBD by site in wave 1 and wave 2 but there was a significant difference in wave 3. There was a significant difference of discipline by gender and age in all the waves. We calculated unadjusted (OR) and adjusted (AOD) and 95% confidence intervals (95%CI) showing the relation between harsh discipline at wave 1 and the presence of child disruptive behavior disorder at wave 3 for both South Bronx and Puerto Rico. There was an association between harsh discipline and the likelihood of having DBD in The Bronx (AOR=1.76; 95%CI=1.13-2.74, p.013) and in Puerto Rico (AOR=2.17; 95%CI=1.28-3.67, p.004) having controlled for demographic, parental and individual factors. Conclusions: Context may be an important differential factor shaping the potential risk of harsh discipline toward DBD for Puerto Rican children.

Keywords: disruptive behavior disorders, harsh discipline, puerto rican, psychological education

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53 Hyperelastic Constitutive Modelling of the Male Pelvic System to Understand the Prostate Motion, Deformation and Neoplasms Location with the Influence of MRI-TRUS Fusion Biopsy

Authors: Muhammad Qasim, Dolors Puigjaner, Josep Maria López, Joan Herrero, Carme Olivé, Gerard Fortuny

Abstract:

Computational modeling of the human pelvis using the finite element (FE) method has become extremely important to understand the mechanics of prostate motion and deformation when transrectal ultrasound (TRUS) guided biopsy is performed. The number of reliable and validated hyperelastic constitutive FE models of the male pelvis region is limited, and given models did not precisely describe the anatomical behavior of pelvis organs, mainly of the prostate and its neoplasms location. The motion and deformation of the prostate during TRUS-guided biopsy makes it difficult to know the location of potential lesions in advance. When using this procedure, practitioners can only provide roughly estimations for the lesions locations. Consequently, multiple biopsy samples are required to target one single lesion. In this study, the whole pelvis model (comprised of the rectum, bladder, pelvic muscles, prostate transitional zone (TZ), and peripheral zone (PZ)) is used for the simulation results. An isotropic hyperelastic approach (Signorini model) was used for all the soft tissues except the vesical muscles. The vesical muscles are assumed to have a linear elastic behavior due to the lack of experimental data to determine the constants involved in hyperelastic models. The tissues and organ geometry is taken from the existing literature for 3D meshes. Then the biomechanical parameters were obtained under different testing techniques described in the literature. The acquired parametric values for uniaxial stress/strain data are used in the Signorini model to see the anatomical behavior of the pelvis model. The five mesh nodes in terms of small prostate lesions are selected prior to biopsy and each lesion’s final position is targeted when TRUS probe force of 30 N is applied at the inside rectum wall. Code_Aster open-source software is used for numerical simulations. Moreover, the overall effects of pelvis organ deformation were demonstrated when TRUS–guided biopsy is induced. The deformation of the prostate and neoplasms displacement showed that the appropriate material properties to organs altered the resulting lesion's migration parametrically. As a result, the distance traveled by these lesions ranged between 3.77 and 9.42 mm. The lesion displacement and organ deformation are compared and analyzed with our previous study in which we used linear elastic properties for all pelvic organs. Furthermore, the visual comparison of axial and sagittal slices are also compared, which is taken for Magnetic Resource Imaging (MRI) and TRUS images with our preliminary study.

Keywords: code-aster, magnetic resonance imaging, neoplasms, transrectal ultrasound, TRUS-guided biopsy

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52 Effect of Phenolic Acids on Human Saliva: Evaluation by Diffusion and Precipitation Assays on Cellulose Membranes

Authors: E. Obreque-Slier, F. Orellana-Rodríguez, R. López-Solís

Abstract:

Phenolic compounds are secondary metabolites present in some foods, such as wine. Polyphenols comprise two main groups: flavonoids (anthocyanins, flavanols, and flavonols) and non-flavonoids (stilbenes and phenolic acids). Phenolic acids are low molecular weight non flavonoid compounds that are usually grouped into benzoic (gallic, vanillinic and protocatechuic acids) and cinnamic acids (ferulic, p-coumaric and caffeic acids). Likewise, tannic acid is an important polyphenol constituted mainly by gallic acid. Phenolic compounds are responsible for important properties in foods and drinks, such as color, aroma, bitterness, and astringency. Astringency is a drying, roughing, and sometimes puckering sensation that is experienced on the various oral surfaces during or immediately after tasting foods. Astringency perception has been associated with interactions between flavanols present in some foods and salivary proteins. Despite the quantitative relevance of phenolic acids in food and beverages, there is no information about its effect on salivary proteins and consequently on the sensation of astringency. The objective of this study was assessed the interaction of several phenolic acids (gallic, vanillinic, protocatechuic, ferulic, p-coumaric and caffeic acids) with saliva. Tannic acid was used as control. Thus, solutions of each phenolic acids (5 mg/mL) were mixed with human saliva (1:1 v/v). After incubation for 5 min at room temperature, 15-μL aliquots of the mixtures were dotted on a cellulose membrane and allowed to diffuse. The dry membrane was fixed in 50 g/L trichloroacetic acid, rinsed in 800 mL/L ethanol and stained for protein with Coomassie blue for 20 min, destained with several rinses of 73 g/L acetic acid and dried under a heat lamp. Both diffusion area and stain intensity of the protein spots were semiqualitative estimates for protein-tannin interaction (diffusion test). The rest of the whole saliva-phenol solution mixtures of the diffusion assay were centrifuged and fifteen-μL aliquots of each supernatant were dotted on a cellulose membrane, allowed to diffuse and processed for protein staining, as indicated above. In this latter assay, reduced protein staining was taken as indicative of protein precipitation (precipitation test). The diffusion of the salivary protein was restricted by the presence of each phenolic acids (anti-diffusive effect), while tannic acid did not alter diffusion of the salivary protein. By contrast, phenolic acids did not provoke precipitation of the salivary protein, while tannic acid produced precipitation of salivary proteins. In addition, binary mixtures (mixtures of two components) of various phenolic acids with gallic acid provoked a restriction of saliva. Similar effect was observed by the corresponding individual phenolic acids. Contrary, binary mixtures of phenolic acid with tannic acid, as well tannic acid alone, did not affect the diffusion of the saliva but they provoked an evident precipitation. In summary, phenolic acids showed a relevant interaction with the salivary proteins, thus suggesting that these wine compounds can also contribute to the sensation of astringency.

Keywords: astringency, polyphenols, tannins, tannin-protein interaction

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51 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

Abstract:

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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50 The Attitudes of Senior High School Students Toward Work Immersion Programs of Nazareth School of National University

Authors: Kim Katherine Castillo, Nelson John Datubatang, Terrence Phillip Dy, Norelie Hampac, Reichen Crismark Martinez, Nina Faith Pantinople, Jose Dante Santos II, Marchel Ann Santos, Sophia Abigail Santiago, Zyrill Xsar San Juan, Aira Mae Tagao, Crystal Kylla Viagedor

Abstract:

The Work Immersion Program was implemented to help students gain abundant work-related experiences while on-site; additionally, the program aims to help students improve their competencies and interpersonal skills as they are given the option to join the workforce if they ever choose to do so after senior high school. The work immersion experience posed diverse challenges for students, spanning personal, financial, engagement, environmental, and equipment-related domains. These included the need for assistance in time management, transportation expenses, and procurement of materials. Furthermore, students faced difficulties in independent task completion and encountered suboptimal work environments. Addressing these multifaceted obstacles is crucial to optimize the educational outcomes of work immersion programs. In addition to the challenges, several other issues have been identified, including the absence of standardized work immersion programs across schools and industries, the challenges in securing appropriate work immersion placements, the necessity for enhanced monitoring and evaluation of program effectiveness, and the limited availability of field programs aligned with students' chosen courses. Furthermore, there is a lack of comprehensive information regarding the attitudes of Senior High School students toward work immersion programs within their respective schools. This study aims to investigate the attitudes of senior high school students at Nazareth School of National University towards work immersion programs, with a focus on identifying factors that influence their perception and participation, including collegiality and expectations. By exploring the students' attitudes, the research endeavors to enhance the school's work immersion programs and contribute to the overall educational experience of the students. This study addresses challenges related to work immersion programs, focusing on six subtopics: Work Immersion, Work Immersion in the Philippines, Students' Attitudes, Factors Affecting Students' Attitudes, Effectiveness of Work Immersion for Senior High School Students, and Students' Perception and Willingness to Participate. Using a descriptive research design, the study examines the attitudes of senior high school students at Nazareth School of National University in Manila. Data was collected from 100 students, representing different academic strands, through a 35-item researcher-made survey. Descriptive statistics, including measures of central tendency and variability, will be used to analyze the data using JASP, providing valuable insights into the students' attitudes toward work immersion.

Keywords: attitudes, challenges, educational outcomes, work immersion programs

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49 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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