Search results for: direct immunofluorescence assay (DFA)

Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le

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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.

Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis

Procedia PDF Downloads 379

Authors: Fariza Yunus, Jasmee Jaafar, Zamalia Mahmud, Nurul Nisa’ Khairul Azmi, Nursalleh K. Chang, Nursalleh K. Chang

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Variation of air temperature from one place to another is cause by air temperature controls. In general, the most important control of air temperature is elevation. Another significant independent variable in estimating air temperature is the location of meteorological stations. Distances to coastline and land use type are also contributed to significant variations in the air temperature. On the other hand, in homogeneous terrain direct interpolation of discrete points of air temperature work well to estimate air temperature values in un-sampled area. In this process the estimation is solely based on discrete points of air temperature. However, this study presents that air temperature controls also play significant roles in estimating air temperature over homogenous terrain of Peninsular Malaysia. An Inverse Distance Weighting (IDW) interpolation technique was adopted to generate continuous data of air temperature. This study compared two different datasets, observed mean monthly data of T, and estimation error of T–T’, where T’ estimated value from a multiple regression model. The multiple regression model considered eight independent variables of elevation, latitude, longitude, coastline, and four land use types of water bodies, forest, agriculture and build up areas, to represent the role of air temperature controls. Cross validation analysis was conducted to review accuracy of the estimation values. Final results show, estimation values of T–T’ produced lower errors for mean monthly mean air temperature over homogeneous terrain in Peninsular Malaysia.

Keywords: air temperature control, interpolation analysis, peninsular Malaysia, regression model, air temperature

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Authors: Sthephanie A. Colmenares, Fabio A. Rojas, Pablo A. Arbeláez, Johann F. Osma, Diana Narvaez

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The loss of functional tissue is a ubiquitous and expensive health care problem, with very limited treatment options for these patients. The golden standard for large bone damage is a cadaveric bone as an allograft with stainless steel support; however, this solution only applies to bones with simple morphologies (long bones), has a limited material supply and presents long term problems regarding mechanical strength, integration, differentiation and induction of native bone tissue. Therefore, the fabrication of a scaffold with biological, physical and chemical properties similar to the human bone with a fabrication method for morphology manipulation is the focus of this investigation. Towards this goal, an alginate and coral matrix was created using two production techniques; the coral was chosen because of its chemical composition and the alginate due to its compatibility and mechanical properties. In order to construct the coral alginate scaffold the following methodology was employed; cleaning of the coral, its pulverization, scaffold fabrication and finally the mechanical and biological characterization. The experimental design had: mill method and proportion of alginate and coral, as the two factors, with two and three levels each, using 5 replicates. The coral was cleaned with sodium hypochlorite and hydrogen peroxide in an ultrasonic bath. Then, it was milled with both a horizontal and a ball mill in order to evaluate the morphology of the particles obtained. After this, using a combination of alginate and coral powder and water as a binder, scaffolds of 1cm3 were printed with a SpectrumTM Z510 3D printer. This resulted in solid cubes that were resistant to small compression stress. Then, using a ESQUIM DP-143 silicon mold, constructs used for the mechanical and biological assays were made. An INSTRON 2267® was implemented for the compression tests; the density and porosity were calculated with an analytical balance and the biological tests were performed using cell cultures with VERO fibroblast, and Scanning Electron Microscope (SEM) as visualization tool. The Young’s moduli were dependent of the pulverization method, the proportion of coral and alginate and the interaction between these factors. The maximum value was 5,4MPa for the 50/50 proportion of alginate and horizontally milled coral. The biological assay showed more extracellular matrix in the scaffolds consisting of more alginate and less coral. The density and porosity were proportional to the amount of coral in the powder mix. These results showed that this composite has potential as a biomaterial, but its behavior is elastic with a small Young’s Modulus, which leads to the conclusion that the application may not be for long bones but for tissues similar to cartilage.

Keywords: alginate, biomaterial, bone engineering, coral, Porites asteroids, SEM

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Authors: Alessandra Pardu, Elena Curti, Marco Caredda, Alessio Dedola, Margherita Addis, Massimo Pes, Antonio Pirisi, Tonina Roggio, Sergio Uzzau, Roberto Anedda

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Some of the artisanal cheeses products of European Countries certificated as PDO (Protected Designation of Origin) are made from raw milk. To recognise potential frauds (e.g. pasteurisation or thermisation of milk aimed at raw milk cheese production), the alkaline phosphatase (ALP) assay is currently applied only for pasteurisation, although it is known to have notable limitations for the validation of ALP enzymatic state in nonbovine milk. It is known that frauds considerably impact on customers and certificating institutions, sometimes resulting in a damage of the product image and potential economic losses for cheesemaking producers. Robust, validated, and univocal analytical methods are therefore needed to allow Food Control and Security Organisms, to recognise a potential fraud. In an attempt to develop a new reliable method to overcome this issue, Time-Domain Nuclear Magnetic Resonance (TD-NMR) spectroscopy has been applied in the described work. Daily fresh milk was analysed raw (680.00 µL in each 10-mm NMR glass tube) at least in triplicate. Thermally treated samples were also produced, by putting each NMR tube of fresh raw milk in water pre-heated at temperatures from 68°C up to 72°C and for up to 3 min, with continuous agitation, and quench-cooled to 25°C in a water and ice solution. Raw and thermally treated samples were analysed in terms of 1H T2 transverse relaxation times with a CPMG sequence (Recycle Delay: 6 s, interpulse spacing: 0.05 ms, 8000 data points) and quasi-continuous distributions of T2 relaxation times were obtained by CONTIN analysis. In line with previous data collected by high field NMR techniques, a decrease in the spin-spin relaxation constant T2 of the predominant 1H population was detected in heat-treated milk as compared to raw milk. The decrease of T2 parameter is consistent with changes in chemical exchange and diffusive phenomena, likely associated to changes in milk protein (i.e. whey proteins and casein) arrangement promoted by heat treatment. Furthermore, experimental data suggest that molecular alterations are strictly dependent on the specific heat treatment conditions (temperature/time). Such molecular variations in milk, which are likely transferred to cheese during cheesemaking, highlight the possibility to extend the TD-NMR technique directly on cheese to develop a method for assessing a fraud related to the use of a milk thermal treatment in PDO raw milk cheese. Results suggest that TDNMR assays might pave a new way to the detailed characterisation of heat treatments of milk.

Keywords: cheese fraud, milk, pasteurisation, TD-NMR

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Authors: Mustafa M. Donma, Orkide Donma

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Spexin, expressed in central nervous system, has attracted much interest in feeding behavior, obesity, diabetes, energy metabolism and cardiovascular functions. Fetuin A is known as negative acute phase reactant synthesized in the liver. So far, it has become a major concern of many studies in numerous clinical states. The relationship between the concentrations of spexin as well as fetuin A and the risk for cardiovascular diseases (CVDs) were also investigated. Eosinophils, suggested to be associated with the development of CVDs, are introduced as early indicators of cardiometabolic complications. Patients with elevated platelet count, associated with hypercoagulable state in the body, are also more liable to CVDs. In this study, the aim is to examine the profiles of spexin and fetuin A concomitant with the course of variations detected in eosinophil as well as platelet counts in morbid obese children. Thirty-four children with normal-body mass index (N-BMI) and fifty-one morbid obese (MO) children participated in the study. Written-informed consent forms were obtained prior to the study. Institutional ethics committee approved the study protocol. Age- and sex-adjusted BMI percentile tables prepared by World Health Organization were used to classify healthy and obese children. Mean age ± SEM of the children were 9.3 ± 0.6 years and 10.7 ± 0.5 years in N-BMI and MO groups, respectively. Anthropometric measurements of the children were taken. Body mass index values were calculated from weight and height values. Blood samples were obtained after an overnight fasting. Routine hematologic and biochemical tests were performed. Within this context, fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein-cholesterol (HDL-C) concentrations were measured. Homeostatic model assessment for insulin resistance (HOMA-IR) values were calculated. Spexin and fetuin A levels were determined by enzyme-linked immunosorbent assay. Data were evaluated from the statistical point of view. Statistically significant differences were found between groups in terms of BMI, fat mass index, INS, HOMA-IR and HDL-C. In MO group, all parameters increased as HDL-C decreased. Elevated concentrations in MO group were detected in eosinophils (p<0.05) and platelets (p>0.05). Fetuin A levels decreased in MO group (p>0.05). However, decrease was statistically significant in spexin levels for this group (p<0.05). In conclusion, these results have suggested that increases in eosinophils and platelets exhibit behavior as cardiovascular risk factors. Decreased fetuin A behaved as a risk factor suitable to increased risk for cardiovascular problems associated with the severity of obesity. Along with increased eosinophils, increased platelets and decreased fetuin A, decreased spexin was the parameter, which reflects best its possible participation in the early development of CVD risk in MO children.

Keywords: cardiovascular diseases , eosinophils , fetuin A , pediatric morbid obesity , platelets , spexin

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

Procedia PDF Downloads 266

Authors: Ömer Faruk Ada, Türker Baş, M. Yaman Öztek

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In this study, we aim to investigate the skills to be owned by procurement professionals in order to fulfill their developing and changing role completely. Market conditions, competitive pressure, and high financial costs make it more important than ever for organizations to be able to use resources more efficiently. Research shows that procurement expenses consist more than 50 % of the operating expenses. With increasing profit impact of procurement, reviewing the position of the procurement function within the organization has become inevitable. This study is significant as it indicates the necessary skills that procurement professionals must have to keep in step with the transformation of procurement units from transaction oriented to value chain oriented. In this study, the transformation of procurement is investigated from the perspective of procurement professionals and we aim to answer following research questions: • How do procurement professionals perceive their role within the organization? • How has their role changed and what challenges have they had to face? • What portfolio of skills do they believe will enable them to fulfill their role effectively? Literature review consists of the first part of the study by investigating the changing role of procurement from different perspectives. In the second part, we present the results of the in-depth interviews with 15 procurement professionals and we used descriptive analysis as a methodology. In the light of these results, we classified procurement skills under operational, tactical and strategic levels and Procurement Skills Framework has been developed. This study shows the differences in the perception of purchasing by professionals and the organizations. The differences in the perception are considered as an important barrier beyond the procurement transformation. Although having the necessary skills has a significant effect for procurement professionals to fulfill their role completely and keep in step with the transformation of the procurement function, It is not the only factor and the degree of high-level management and organizational support has also a direct impact during this transformation.

Keywords: procuement skills, procurement transformation, strategic procurement, value chain

Procedia PDF Downloads 412

Authors: Ana Fouto

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Background: Continuing Personal Development (CPD) enables professionals to keep up to date with the professional requirements, broadening their knowledge and expertise. However, much of the research explores the registered professionals’ experiences and the factors that influence their choice of engaging, despite the unregistered staff providing the majority of the direct patient care. Aim: To explore the Nursing/Midwifery Assistants’ (NAs) perception of the concept of CPD, as well as explore the factors that influence the NAs to engage (or not) with CPD experiences. Methodology: This pilot study used a qualitative approach through a case study, where a semi-structured interview was applied to three NAs to explore the factors that influence the decision-making of process of CPD engagement. Thematic analysis was used to analyse their answers and interpret patterns and associations. Findings: All the participants agreed that CPD is important and relevant to their practice and personal lives. Five main categories were identified: NAs’ scope of practice, the impact of CPD; decision-making process; challenges; changes required. Although similar findings to the registered nurses were identified, the lack of CPD regulation for NAs and the rapid evolution of their role make the CPD engagement more problematic. Conclusion: Engagement with CPD is influenced by a wide range of professional (organisational and national) and personal factors. NAs perceive lack of management support at different stages of the CPD activities as a main influence. Organisations should be more flexible in the recruitment, offer of CPD choices, content, delivery, and contractual arrangements of NAs, which may increase engagement.

Keywords: nursing assistants, engagement, factors, pilot, continuing professional development (CPD)

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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Authors: Huong Nguyen Thi Thanh, Van Mai Thi Khanh

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For around the world, payments for environmental services have been implemented since the late 1970s in Europe and North America; then, it was spread to Latin America, Asia, Africa, and finally Oceania in 2008. In Vietnam, payments for environmental services are an interesting issue recently with the forest as the main focus and therefore known as the program on payment for forest environmental services (PFES). PFES was piloted in Lam Dong and Son La in 2008 and has been widely applied in many provinces after 2010. PFES is in the orientation for the socialization of national forest protection in Vietnam and has made great strides in the last decade. By using the primary data and secondary data simultaneously, the paper clarifies two cases of implementing PFES in the Vietnam North Central area with the different mechanisms of payment. In the first case at Phu Loc district (Thua Thien Hue province), PFES is an indirect method by a water supply company via the Forest Protection and Development Fund. In the second one at Phong Nha – Ke Bang National Park (Quang Binh Province), tourism companies are the direct payers to forest owners. The paper describes the PFES implementation process at each site, clarifies the payment mechanism, and models the relationship between stakeholders in PFES implementation. Based on the current status of PFES sites, the paper compares and analyzes the advantages and disadvantages of the two payment methods. Finally, the paper proposes recommendations to improve the existing shortcomings in each payment mechanism.

Keywords: advantages and disadvantages, forest environmental services, forest protection, payment mechanism

Procedia PDF Downloads 119

Authors: A. B. Benshak, M. G. Yilkangnha, V. Y. Nanle

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Social crises and violent conflict can inflict direct (short-term) impact on the environment like poisoning water bodies, climate change, deforestation, destroying the chemical component of the soil due to the chemical and biological weapons used. It can also impact the environment indirectly (long-term), e.g., the destruction of political and economic infrastructure to manage the environmental resources and breaking down traditional conservation practices, population displacement and refugee flows which puts pressure on the already inadequate resources, infrastructure, facilities, amenities, services etc. This study therefore examines the impact of social crises on the environment in Jos Plateau State with emphasis on the long-term impact, analyze the relationship between crises and the environment and assess the perception of people on social crises because much work have concentrated on other repercussions such as the economy, health etc that are more politically expedient. The data for this research were collected mostly through interviews, questionnaire, dailies and reports on the subject matter. The data and findings were presented in tables and results showed that the environment is directly and indirectly impacted by crises and that these impacts can in turn result to a continuous cycle of violent activities if not addressed because of the inadequacies in the supply of infrastructural facilities, resources and so on caused by the inflow of displaced population. Recommendations were made on providing security to minimize conflict occurrences in Jos and its environs, minimizing the impact of social crises on the environment, provision of adequate infrastructural facilities to carter for population rise, renewal and regeneration schemes, etc. which will go a long way in mitigating the impact of crises on the environment.

Keywords: environment, impact, long-term, social crises

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Authors: Marina Kartseva, Polina Kuznetsova

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In our work, we estimate the contribution of inequality of opportunity to inequality in the health of the Russian population aged 25 to 74 years. The empirical basis of the study is the nationally representative data of the RLMS for 2018. Individual health is measured using a self-reported status on five-point scale. The startconditions are characterized by parental education and place of birth (country, type of settlement). Personal efforts to maintain health include the level of education, smoking status, and physical activity. To understand how start opportunities affect an individual's health, we use the methodology proposed in (Trannoy et al., 2010), which takes into account both direct and indirect (through the influence on efforts) effects. Regression analysis shows that all other things being equal, the starting capabilities of individuals have a significant impact on their health. In particular, parental education has a positive effect on self-reported health. Birth in another country, in another settlement, and in an urban area, on the contrary, reduceself-reported health. This allows to conclude that there exists an unfair inequality in health, namely inequality caused by factors that are independent of a person's own efforts. We estimate the contribution of inequality of opportunity to inequality in health using a nonparametric approach (Checchi, Peragine, 2010; Lazar, 2013). According to the obtained results, the contribution of unfair inequality as 72-74% for the population as a whole, being slightly higher for women (62-74% and 60-69% for men and women, respectively) and for older age (59- 62% and 67-75% for groups 25-44 years old and 45-74 years old, respectively). The obtained estimates are comparable with the results for other countries and indicate the importance of the problem of inequality of opportunities in health in Russia.

Keywords: inequality of opportunity, inequality in health, self-reported health, efforts, health-related lifestyle, Russia, RLMS

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Authors: Chiagoziem A. Otuechere, Ebenezer O. Farombi

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The protective effect of dichloromethane: methanol extract of Pterocarpus mildbraedii (PME), a widely consumed Nigerian leafy vegetable, on the toxicity of propanil was investigated in male rats. Animals were distributed into eight groups of five each. Group 1 served as control and received normal saline while rats in groups 2, 3, and 4 received 100 mg/kg, 200 mg/kg, and 400 mg/kg extract doses respectively. Group 5 rats were orally administered 200 mg/kg propanil while groups 6, 7, and 8 rats were given propanil plus extract. Oral administration of propanil elicited a 14.8%, 5%, 122%, and 78% increase in the activity of serum enzymes; alanine aminotransferase (AST), alanine aminotransferase(ALT), Alkaline phoshatase (ALP) and Gamma glutamyl transferase (ﻻGT). There were also increase in Lactate dehydrogenase (LDH) activity, direct bilirubin and lipid peroxidation levels. Furthermore, PME significantly attenuated the marked hepatic oxidative damage that accompanied propanil treatment. The extract significantly decreased LDH activity and bilirubin levels following propanil treatment. Furthermore, propanil-induced alterations in the activities of antioxidant enzymes: Superoxide dismutase (SOD), catalase (CAT) and glutathione s-transferase (GST) in these rats were modulated by the extract. The percentage DPPH Radical Scavenging Activity of the extract was determined as 55% and compared to those of Gallic acid (49%). Hepatic histology examination further confirmed the damage to the liver as it revealed severe periportal cellular infiltration of the hepatocytes. These biochemical and morphological alterations were attenuated in rats pre-treated with 100 mg/kg and 200 mg/kg doses of the extract. These results suggest that PME possesses protective effect against propanil-induced hepatotoxicity.

Keywords: antioxidant, hepatoprotection, Pterocarpus mildbraedii, propanil

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Authors: Marcus Maia

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The present study reports and discusses the use of eye tracking qualitative data in reading workshops in Brazilian middle and high schools and in Generative Syntax and Sentence Processing courses at the undergraduate and graduate levels at the Federal University of Rio de Janeiro, respectively. Both endeavors take the sentential level as the proper object to be metacognitively explored in language education (cf. Chomsky, Gallego & Ott, 2019) to develop innate science forming capacity and knowledge of language. In both projects, non-discrepant qualitative eye tracking data collected and quantitatively analyzed in experimental syntax and psycholinguistic studies carried out in Lapex (Experimental Psycholinguistics Laboratory of the Federal University of Rio de Janeiro) were displayed to students as a point of departure, triggering discussions. Classes would generally start with the display of videos showing eye tracking data, such as gaze plots and heatmaps from several studies in Psycholinguistics and Experimental Syntax that we had already developed in our laboratory. The videos usually triggered discussions with students about linguistic and psycholinguistic issues, such as the reading of sentences for gist, garden-path sentences, syntactic and semantic anomalies, the filled-gap effect, island effects, direct and indirect cause, and recursive constructions, among other topics. Active, problem-solving based methodologies were employed with the objective of stimulating student participation. The communication also discusses the importance of developing full literacy, epistemic vigilance and intellectual self-defense in an infodemic world in the lines of Maia (2022).

Keywords: reading, educational psycholinguistics, eye-tracking, active methodology

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Changde Zhang, Qiang Zhang, Shilong Zheng, Jiawang Liu, Shanchun Guo, Qiu Zhong, Guangdi Wang

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Fulvestrant was approved by FDA to treat breast cancer as a selective estrogen receptor downregulator (SERD) with intramuscular injection administration. ZB716, a fulvestarnt-3 boronic acid, is an SERD with comparable anticancer effect to fulvestrant, but could produce good pharmacokinetic properties under oral administration with mice or rat models. To understand why ZB716 produced much better oral bioavailability, it was proposed that the boronic acid blocked the phase II direct biotransformation with the hydroxyl group on the 3 position of the aromatic ring on fulvestrant. In this study, ZB716 or fulvestrant was incubated with human liver microsome and oxidation cofactor NADPH in vitro. Their metabolites after oxidation were profiled with the Q-Exactive, a high-resolution mass spectrometer. The result showed that ZB716 blocked the forming of hydroxyl groups on its benzene ring except for the oxidation of C-B bond forming fulvestrant in its metabolites, and the concentration of fulvestrant with one more hydroxyl group found in the metabolites from incubation with fulvestrant was about 34 fold high as that formed from incubation with ZB716. Compared to fulvestrant, ZB716 is expected to be much difficult to be further bio-transformed into more hydrophilic compounds, to be difficult excreted out of blood system, and to have longer residence time in blood, which can lead to higher oral bioavailability. This study provided evidence to explain the high bioavailability of ZB716 after oral administration from the perspective of its difficulty of oxidation, a phase I biotransformation, on positions on its aromatic ring.

Keywords: biotransformation, fulvestrant, metabolite profiling, ZB716

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Authors: Rani Danavath, V. B. Narsimha

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Cloud computing is emerging as a new paradigm of large scale distributed computing. Cloud computing is a model for enabling ubiquitous, convenient, on-demand network access to a shared pool of configurable computing resources (e.g., three service models, and four deployment networks, servers, storage, applications, and services) that can be rapidly provisioned and released with minimal management effort or service provider interaction. This cloud model is composed of five essential characteristics models. Load balancing is one of the main challenges in cloud computing, which is required to distribute the dynamic workload across multiple nodes, to ensure that no single node is overloaded. It helps in optimal utilization of resources, enhancing the performance of the system. The goal of the load balancing is to minimize the resource consumption and carbon emission rate, that is the direct need of cloud computing. This determined the need of new metrics energy consumption and carbon emission for energy-efficiency load balancing techniques in cloud computing. Existing load balancing techniques mainly focuses on reducing overhead, services, response time and improving performance etc. In this paper we introduced a Technique for energy-efficiency, but none of the techniques have considered the energy consumption and carbon emission. Therefore, our proposed work will go towards energy – efficiency. So this energy-efficiency load balancing technique can be used to improve the performance of cloud computing by balancing the workload across all the nodes in the cloud with the minimum resource utilization, in turn, reducing energy consumption, and carbon emission to an extent, which will help to achieve green computing.

Keywords: cloud computing, distributed computing, energy efficiency, green computing, load balancing, energy consumption, carbon emission

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Authors: Trunal Bhujangrao, Catherine Froustey, Fernando Veiga, Philippe Darnis, Franck Girot Mata

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The understanding of the material behavior under shear loading has great importance for a researcher in manufacturing processes like cutting, machining, milling, turning, friction stir welding, etc. where the material experiences large deformation at high temperature. For such material behavior analysis, hot shear tests provide a useful means to investigate the evolution of the microstructure at a wide range of temperature and to improve the material behavior model. Shear tests can be performed by direct shear loading (e.g. torsion of thin-walled tubular samples), or appropriate specimen design to convert a tensile or compressive load into shear (e.g. simple shear tests). The simple shear tests are straightforward and designed to obtained very large deformation. However, many of these shear tests are concerned only with the elastic response of the material. It is becoming increasingly important to capture a plastic response of the material. Plastic deformation is significantly more complex and is known to depend more heavily on the strain rate, temperature, deformation, etc. Besides, there is not enough work is done on high-temperature shear loading, because of geometrical instability occurred during the plastic deformation. The aim of this study is to design a new shear tensile specimen geometry to convert the tensile load into dominant shear loading under plastic deformation. Design of the specimen geometry is based on FEM. The material used in this paper is AA7075 alloy, tested quasi statically under elevated temperature. Finally, the microstructural changes taking place during

Keywords: AA7075 alloy, dynamic recrystallization, edge effect, large strain, shear tensile test

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Authors: Pedro A. Medina-Rios, Marly Yolie Quintana-Daza

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Having the opportunity to communicate in a social, academic and work context is very relevant for any individual and more for a deaf person when oral language is not their natural language, and written language is their second language. Currently, in Colombia, there is not a specialized dictionary for our best knowledge in sign language archiving. Archival is one of the areas that the deaf community has a greater chance of performing. Nourishing new signs in dictionaries for deaf people extends the possibility that they have the appropriate signs to communicate and improve their performance. The aim of this work was to illustrate the importance of designing pedagogical and technological strategies of knowledge management, for the academic inclusion of deaf people through proposals of lexicon in Colombian sign language (LSC) in the area of archival. As a method, the analytical study was used to identify relevant words in the technical area of the archival and its counterpart with the LSC, 30 deaf people, apprentices - students of the Servicio Nacional de Aprendizaje (SENA) in Documentary or Archival Management programs, were evaluated through direct interviews in LSC. For the analysis tools were maintained to evaluate correlation patterns and linguistic methods of visual, gestural analysis and corpus; besides, methods of linear regression were used. Among the results, significant data were found among the variables socioeconomic stratum, academic level, labor location. The need to generate new signals on the subject of the file to improve communication between the deaf person, listener and the sign language interpreter. It is concluded that the generation of new signs to nourish the LSC dictionary in archival subjects is necessary to improve the labor inclusion of deaf people in Colombia.

Keywords: archival, inclusion, deaf, thesaurus

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Authors: Betül Garda

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Technological developments have diversified marketing activities of the tourism sector and it has increased tourism opportunities to compete on a global scale for tourism businesses. Tourism businesses have been forced to use its core skills and knowledge effectively with the increase in effectiveness of the technology in the global competitive environment. Tourism businesses have been reached beyond the traditional boundaries because of their commercial activities, so, the boundaries of the national market either eliminated or blurred. Therefore, the internet is the alternative promotion tool and distribution channel to providing unlimited facilities for tourism suppliers. For example, the internet provides an opportunity to reach customers on a global scale with direct email marketing, advertising, customer service, promotion, sales, and marketing. Tourism businesses have improved themselves with the continuous information flows and also they have provided the permanence of the changes. Especially in terms of tourism businesses, social media is emerging as an extremely important tool in the use of knowledge effectively. This research paper investigates the impact of social media on the tourism businesses. A social networking site is a type of social media that provides a platform for business and people to connect with each other. Social media is so flexible that it can be used for both leisure and business purposes. In the tourism industry, social networking sites are one of the essential tools that play an important and beneficial role. The topic that will be discussed in this research paper are consumer behavior, connection with consumers, effectiveness in terms of time and cost, creating brand awareness and building the image of the company, promoting company, targeting consumers in a conceptual frame.

Keywords: branding, promoting, social media in tourism, tourism marketing tools

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Authors: Berger Aida

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Social entrepreneurship has emerged as an active area of practice and research within the last three decades and has called for a focus on Social Entrepreneurship innovation. Areas such as academics, practitioners , institutions or governments have placed Social Entrepreneurship on the priority list of reflexion and action. It has been accepted that Social entrepreneurship (SE) shares large similarities with its parent, Traditional Entrepreneurship (TE). SE has grown over the past ten years exploring entrepreneurial cognition and the analysis of the ways of thinking of entrepreneurs. The research community believes that value exists in grounding entrepreneurship in neuroscience and notes that SE, like Traditional Entrepreneurship, needs to undergo efforts in clarification, definition and differentiation. Moreover, gaps in SE research call for integrative multistage and multilevel framework for further research. The cognitive processes underpinning entrepreneurial action are similar for SE and TE even if Social Entrepreneurship orientation shows an increased empathy value. Theoretically, there is a need to develop sound models of how to process functions and how to work more effectively as entrepreneurs and research on efficiency improvement calls for the analysis of the most common practices in entrepreneurship. Multitasking has been recognized as a daily and unavoidable habit of entrepreneurs. Hence, we believe in the need of analyzing the multiple task phenomena as a methodology for skill acquisition. We will conduct our paper including Social Entrepreneurship within the wider spectrum of Traditional Entrepreneurship, for the purpose of simplifying the neuroscientific lecture of the entrepreneurial cognition. A question to be inquired is to know if there is a way of developing multitasking habits in order to improve entrepreneurial skills such as speed of information processing , creativity and adaptability . Nevertheless, the direct link between the neuroscientific approach to multitasking and entrepreneurship effectiveness is yet to be uncovered. That is why an extensive Literature Review on Multitasking is a propos.

Keywords: cognitive, entrepreneurial, empathy, multitasking

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Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa

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This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.

Keywords: C. sinensis, function indices, harvest time, leaf essential oil.

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Authors: M. Al Zallouha, Y. Landkocz, J. Brunet, R. Cousin, J. M. Halket, E. Genty, P. J. Martin, A. Verdin, D. Courcot, S. Siffert, P. Shirali, S. Billet

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Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry. Amongst VOCs, Benzene, Toluene, Ethylbenzene and Xylenes (BTEX) emitted into the atmosphere have a major and direct impact on human health. It is, therefore, necessary to minimize emissions directly at source. Catalytic oxidation is an industrial technique which provides remediation efficiency in the treatment of these organic compounds. However, during operation, the catalysts can release some compounds, called byproducts, more toxic than the original VOCs. The catalytic oxidation of a gas stream containing 1000ppm of toluene on Pd/α-Al2O3 can release a few ppm of benzene, according to the operating temperature of the catalyst. The development of new catalysts must, therefore, include chemical and toxicological validation phases. In this project, A549 human lung cells were exposed in air/liquid interface (Vitrocell®) to gas mixtures derived from the oxidation of toluene with a catalyst of Pd/α-Al2O3. Both exposure concentrations (i.e. 10 and 100% of catalytic emission) resulted in increased gene expression of Xenobiotics Metabolising Enzymes (XME) (CYP2E1 CYP2S1, CYP1A1, CYP1B1, EPHX1, and NQO1). Some of these XMEs are known to be induced by polycyclic organic compounds conventionally not searched during the development of catalysts for VOCs degradation. The increase in gene expression suggests the presence of undetected compounds whose toxicity must be assessed before the adoption of new catalyst. This enhances the relevance of toxicological validation of such systems before scaling-up and marketing.

Keywords: BTEX toxicity, air/liquid interface cell exposure, Vitrocell®, catalytic oxidation

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Authors: Inkyong Yi

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Acute kidney injury (AKI) in trauma patients is known to be associated with multiple factors, especially shock and consequent inadequate renal perfusion, yet its clinical presentation is little known in severe trauma patients. Our aim was to investigate the clinical presentation of acute kidney injury and its outcome in severe trauma patients at a level I trauma center. A total of 93 consecutive adult trauma patients with an injury severity score (ISS) of more than 15 were analyzed retrospectively from our Level I trauma center data base. Patients with direct renal injury were excluded. Patients were dichotomized into two groups, according to the presence of AKI. Various clinical parameters were compared between two groups, with Student’s T test and Mann-Whitney’s U test. The AKI group was further dichotomized into patients who recovered within seven days, and those who required more than 7days for recovery or those who did not recover at all. Various clinical parameters associated with outcome were further analyzed. Patients with AKI (n=33, 35%) presented with significantly higher age (61.4±17.3 vs. 45.4±17.3, p < 0.0001), incidence of comorbidities (hypertension; 51.5% vs. 13.3%, OR 6.906 95%CI 2.515-18.967, diabetes; 27.3% vs. 6.7%, OR 5.250, 95%CI 1.472-18.722), odds of head and neck trauma (69.7% vs. 41.7%, OR 3.220, 95%CI 1.306-7.942) and presence of shock during emergency room care (66.7% vs 21.7% OR 7.231, 95%CI, 2.798-18.687). Among AKI patients, patients who recovered within 1 week showed lower peak lactate (4.7mmol/L, 95%CI 2.9-6.5 vs 7.3mmol/L, 95%CI 5.0-9.6, p < 0.0287), lesser units of transfusion during first 24 hours (pRBC; 20.4unit, 95%CI 12.5-28.3 vs. 58.9unit, 95%CI 39.4-78.5, p=0.0003, FFP; 16.6unit, 95%CI 6.8-26.4 vs. 56.1unit, 95%CI 26.9-85.2, p=0.0027). In severe trauma patients, patients with AKI showed different clinical presentations and worse outcomes. Initial presence of shock and higher DIC profiles may be important risk factors for AKI in severe trauma patients. In patients with AKI, peak lactate level and amounts of transfusion are related to recovery.

Keywords: acute kidney injury, lactate, transfusion, trauma

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Authors: Mehrnaz Mostafavi

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The current research aims to explore a method for creating nano-ring structures through chemical reduction. By employing a direct reduction process at a controlled, slow pace, and concurrently introducing specific reduction agents, the goal is to fabricate these unique nano-ring formations. The deliberate slow reduction of nanoparticles within this process helps prevent spatial hindrances caused by the reduction agents. The timing of the reduction of metal atoms, facilitated by these agents, emerges as a crucial factor influencing the creation of nano-ring structures. In investigation involves a chemical approach utilizing bovine serum albumin and human serum albumin as organic reducing agents to produce gold nano-rings. The controlled reduction of metal atoms at a slow pace and under specific pH conditions plays a pivotal role in the successful fabrication of these nanostructures. Optical spectroscopic analyses revealed distinctive plasmonic behavior in both visible and infrared spectra, owing to the collective movement of electrons along the inner and outer walls of the gold nano-rings. Importantly, these ring-shaped nanoparticles exhibit customizable plasmon resonances in the near-infrared spectrum, a characteristic absent in solid particles of similar sizes. This unique attribute makes the generated samples valuable for applications in Nanomedicine and Nanobiotechnology, leveraging the distinct optical properties of these nanostructures.

Keywords: nano-ring structure, nano-particles, reductant agents, plasmon resonace

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Authors: A. Yanik, U. Aldemir

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This study investigates the benefits of implementing the semi-active devices in relation to passive viscous damping in the context of seismically isolated bridge structures. Since the intrinsically nonlinear nature of semi-active devices prevents the direct evaluation of Laplace transforms, frequency response functions are compiled from the computed time history response to sinusoidal and pulse-like seismic excitation. A simple semi-active control policy is used in regard to passive linear viscous damping and an optimal non-causal semi-active control strategy. The control strategy requires optimization. Euler-Lagrange equations are solved numerically during this procedure. The optimal closed-loop performance is evaluated for an idealized controllable dash-pot. A simplified single-degree-of-freedom model of an isolated bridge is used as numerical example. Two bridge cases are investigated. These cases are; bridge deck without the isolation bearing and bridge deck with the isolation bearing. To compare the performances of the passive and semi-active control cases, frequency dependent acceleration, velocity and displacement response transmissibility ratios T_a(w), T_v(w), and T_d(w) are defined. To fully investigate the behavior of the structure subjected to the sinusoidal and pulse type excitations, different damping levels are considered. Numerical results showed that, under the effect of external excitation, bridge deck with semi-active control showed better structural performance than the passive bridge deck case.

Keywords: bridge structures, passive control, seismic, semi-active control, viscous damping

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Authors: Muhammad Ali Asadullah, Zafarullah Amir

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In recent years, Vocational Education and Training (VET) has been under discussion by the academic researchers and remained in focus in the political grounds. Due to potential contribution of VET, the World Bank and United Nations Educational, Scientific and Cultural Organization (UNESCO) support vocational education to reduce poverty, enhance economic growth and increase competitiveness. This paper examines the impact of Vocational Education and Training on the Economic Growth and Social Inclusion with direct and mediation effect of Social Inclusion. The basic purpose of this study is to assess economic pay-offs as a result of long term investments in VET. Based on the review of Anderson Nilsson, initially we explored the increasing or decreasing trend in investment on VET. Further, the study explores that the countries which invest more on VET, tend to get more economic growth and are socially more ‘inclusive’. It is a longitudinal / panel data study with 12 years of registered data which involves 24 OECD countries. The results of the study indicate the VET has positive association with Social Inclusion and Economic Growth. Further, there is also a positive association of VET and Economic Growth through mediation of Social Inclusion. The current study considers not only issue and challenges in developing VET systems but also contributes to develop the theoretical framework for considering how VET can directly and indirectly improve economic growth and social inclusion. A wider appreciation of how VET’s benefits operate may influence a country’s decisions to invest in it. If policy makers increase investment on VET, the result would be positive in Economic Growth and Social Inclusion. It is also recommended that the same OECD model may be implemented in developing countries like Pakistan.

Keywords: Vocational Education and Training (VET), Social Inclusion, Economic Growth, OECD countries

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: Hannah K. M. Tang, Muhammad Ateeq, Mark J. Lake, Badr Abdullah, Frederic A. Bezombes

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Based on a theoretical assessment of current literature, virtual reality (VR) could help to treat sporting injuries in a number of ways. However, it is important to obtain rehabilitation specialists’ perspectives in order to design, develop and validate suitable content for a VR application focused on treatment. Subsequently, a one-day observation and interview study focused on the use of VR for the treatment of lower limb musculoskeletal conditions in athletes was conducted at St George’s Park England National Football Centre with rehabilitation specialists. The current paper established the methods suitable for obtaining practitioner’s viewpoints through observation and interview in this context. Particular detail was provided regarding the method of qualitatively processing interview results using the qualitative data analysis software tool NVivo, in order to produce a narrative of overarching themes. The observations and overarching themes identified could be used as a framework and success criteria of a VR application developed in future research. In conclusion, this work explained the methods deemed suitable for obtaining practitioner’s viewpoints through observation and interview. This was required in order to highlight characteristics and features of a VR application designed to treat lower limb musculoskeletal injury of athletes and could be built upon to direct future work.

Keywords: athletes, lower-limb musculoskeletal injury, rehabilitation, return-to-sport, virtual reality

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