Search results for: core protein

Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

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Authors: Jong H. Kim, Kathleen L. Chan, Luisa W. Cheng

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Control of fungal pathogens, such as foodborne mycotoxin producers, is problematic as effective antimycotic agents are often very limited. Mycotoxin contamination significantly interferes with the safe production of foods or crops worldwide. Moreover, expansion of fungal resistance to commercial drugs or fungicides is a global human health concern. Therefore, there is a persistent need to enhance the efficacy of commercial antimycotic agents or to develop new intervention strategies. Disruption of the cellular antioxidant system should be an effective method for pathogen control. Such disruption can be achieved with safe, redox-active compounds. Natural phenolic derivatives are potent redox cyclers that inhibit fungal growth through destabilization of the cellular antioxidant system. The goal of this study is to identify novel, redox-active compounds that disrupt the fungal antioxidant system. The identified compounds could also function as sensitizing agents to conventional antimycotics (i.e., chemosensitization) to improve antifungal efficacy. Various benzo derivatives were tested against fungal pathogens. Gene deletion mutants of the yeast Saccharomyces cerevisiae were used as model systems for identifying molecular targets of benzo analogs. The efficacy of identified compounds as potent antifungal agents or as chemosensitizing agents to commercial drugs or fungicides was examined with methods outlined by the Clinical Laboratory Standards Institute or the European Committee on Antimicrobial Susceptibility Testing. Selected benzo derivatives possessed potent antifungal or antimycotoxigenic activity. Molecular analyses by using S. cerevisiae mutants indicated antifungal activity of benzo derivatives was through disruption of cellular antioxidant or cell wall integrity system. Certain benzo analogs screened overcame tolerance of Aspergillus signaling mutants, namely mitogen-activated protein kinase mutants, to fludioxonil fungicide. Synergistic antifungal chemosensitization greatly lowered minimum inhibitory or fungicidal concentrations of test compounds, including inhibitors of mitochondrial respiration. Of note, salicylaldehyde is a potent antimycotic volatile that has some practical application as a fumigant. Altogether, benzo derivatives targeting cellular antioxidant system of fungi (along with cell wall integrity system) effectively suppress fungal growth. Candidate compounds possess the antifungal, antimycotoxigenic or chemosensitizing capacity to augment the efficacy of commercial antifungals. Therefore, chemogenetic approaches can lead to the development of novel antifungal intervention strategies, which enhance the efficacy of established microbe intervention practices and overcome drug/fungicide resistance. Chemosensitization further reduces costs and alleviates negative side effects associated with current antifungal treatments.

Keywords: antifungals, antioxidant system, benzo derivatives, chemosensitization

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Authors: Yohann R. J. Thomas, Sébastien Solan

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Conventional battery technology includes the assembly of electrode/separator/electrode by standard techniques such as stacking or winding, depending on the format size. In that type of batteries, coating or pasting techniques are only used for the electrode process. The processes are suited for large scale production of batteries and perfectly adapted to plenty of application requirements. Nevertheless, as the demand for both easier and cost-efficient production modes, flexible, custom-shaped and efficient small sized batteries is rising. Thin-film, printable batteries are one of the key areas for printed electronics. In the frame of European BASMATI project, we are investigating the feasibility of a new design of lithium-ion battery: interdigitated planar core design. Polymer substrate is used to produce bendable and flexible rechargeable accumulators. Direct fully printed batteries lead to interconnect the accumulator with other electronic functions for example organic solar cells (harvesting function), printed sensors (autonomous sensors) or RFID (communication function) on a common substrate to produce fully integrated, thin and flexible new devices. To fulfill those specifications, a high resolution printing process have been selected: Aerosol jet printing. In order to fit with this process parameters, we worked on nanomaterials formulation for current collectors and electrodes. In addition, an advanced printed polymer-electrolyte is developed to be implemented directly in the printing process in order to avoid the liquid electrolyte filling step and to improve safety and flexibility. Results: Three different current collectors has been studied and printed successfully. An ink of commercial copper nanoparticles has been formulated and printed, then a flash sintering was applied to the interdigitated design. A gold ink was also printed, the resulting material was partially self-sintered and did not require any high temperature post treatment. Finally, carbon nanotubes were also printed with a high resolution and well defined patterns. Different electrode materials were formulated and printed according to the interdigitated design. For cathodes, NMC and LFP were efficaciously printed. For anodes, LTO and graphite have shown to be good candidates for the fully printed battery. The electrochemical performances of those materials have been evaluated in a standard coin cell with lithium-metal counter electrode and the results are similar with those of a traditional ink formulation and process. A jellified plastic crystal solid state electrolyte has been developed and showed comparable performances to classical liquid carbonate electrolytes with two different materials. In our future developments, focus will be put on several tasks. In a first place, we will synthesize and formulate new specific nano-materials based on metal-oxyde. Then a fully printed device will be produced and its electrochemical performance will be evaluated.

Keywords: high resolution digital printing, lithium-ion battery, nanomaterials, solid-state electrolytes

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Authors: Farhat Jabeen, Muhammad Asad

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The study assessed the curative potential of Moringa olifera seeds against copper oxide nanoparticles induced toxicity in Oreochromis mossambicus. In order to investigate the curative potential of M. olifera seeds, firstly we examine its chemical composition, secondary metabolites, and bioactive compounds including hydroxyl-cinnamic acids, flavanols and hydroxybenzoic acids through standard methods and high performance liquid chromatography. In current study, the potential sub-lethal toxic dose of CuO-NPs (0.12 mg/l) was investigated through pilot experiment and three non-lethal doses (low=32, medium=48 and high=96 mg/l) of M. olifera were selected on the basis of its LC50 value for O. mossambicus. The experimental fish, O. mossambicus (n=100 of approximately 20 g each) were procured from Manawan Fisheries Complex, Lahore, and acclimatized for two weeks in glass aquaria. Experiment was conducted in accordance with the guidelines of Institutional Animal Ethics Committee, Government College University Faisalabad, Pakistan. During acclimatization and experimental period, fish received the commercial fish feed at 2.5% body weight daily. In order to assess the curative effect of M. olifera against CuO NPs induced toxicity, O. mossambicus were randomly divided into five groups and were designated as control (C) without any treatment, positive control (G*) exposed to potential toxic dose of CuO-NPs at 0.12 mg/l, and three treated groups namely G1, G2, and G3 co-treated with 0.12 mg/l of CuO-NPs plus different doses of M. olifera seed extract at 32, 48, and 96 mg/l, respectively for 56 days. Fish were exposed to waterborne CuO NPs and M. olifera seed extract. CuO-NPs treatment was ceased after 28 days but the doses of M. olifera were continued for 56 days. Blood was taken after 28 and 56 days through caudal venipuncture. Liver and intestine were taken for oxidative stress and histological studies after 56 days. In M. olifera seeds, moisture contents, crude protein, lipids, carbohydrates and ash were recorded as 3.8, 37.83, 32.52, 46.12, and 7.75%, respectively on dry weight basis. Total energy was recorded as 627.36 kcal/100g. Qualitative analysis of M. olifera seeds showed the presence of terpenoids, saponins, flavonoids, alkaloids and phenolics, while its quantitative analysis showed the considerable amount of total phenolics, flavonoids, saponins, and alkaloids as 134.75, 170.15, 1.57, and 0.4 µg/mg, respectively. Analysis of bioactive compounds in M. olifera seeds showed the presence of hydroxy-cinnamic acids (6.07 µg/ml), flavanols (71.72 µg/ml), and hydroxyl benzoic acids (97.82 µg/ml). The results showed that M. oliefera seed extract at 48 and 56 mg/l was able to cure against the toxic effects of CuO-NPs. The significant changes were observed in G* and G1 for sero-hepatic enzymes, anti-oxidants and histological profile. The investigations of this study showed that M. olifera is a good curative agent against potential induced toxicity of CuO-NPs in O. mossambicus. The curative effect of M. olifera is attributed to the presence of higher amount of secondary metabolites and bioactive compounds. This study suggested the use of M. olifera to curate different ailments in fish and other organisms.

Keywords: CuO nanoparticles, curative, Moringa olifera, Oreochromis mossambicus

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Authors: Mahnaz Khalafehnilsaz, Rozina Rahnama

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Introduction: The aging process has been linked to a wide range of non-communicable diseases that cause a loss of health-related quality of life. This process can be worsened if an active and healthy lifestyle is not followed by adults, especially in the workplace. This setting not only may create a sedentary lifestyle but will lead to obesity and overweight in the long term and create unhealthy and inactive aging. In addition, eating habits are always known to be associated with active aging. Therefore, it is very valuable to know the eating patterns of people at work in order to detect and prevent diseases in the coming years. This study aimed to design and test a model to improve eating habits among employees at an industrial complex as a practical strategy. Material and method: The present research was a mixed-method study with a subsequent exploratory design which was carried out in two phases, qualitative and quantitative, in 2018 year. In the first step, participants were selected by purposive sampling (n=34) to ensure representation of different job roles; hours worked, gender, grade, and age groups, and semi-structured interviews were used. All interviews were conducted in the workplace and were audio recorded, transcribed verbatim, and analyzed using the Strauss and Corbin approach. The interview question was, “what were their experiences of eating at work, and how could these nutritional habits affect their health in old age.” Finally, a total of 1500 basic codes were oriented at the open coding step, and they were merged together to create the 17 classes, and six concepts and a conceptual model were designed. The second phase of the study was conducted in the form of a cross-sectional study. After verification of the research tool, the developed questionnaire was examined in a group of employees. In order to test the conceptual model of the study, a total of 500 subjects were included in psychometry. Findings: Six main concepts have been known, including 1. undesirable control of stress, 2. lack of eating knowledge, 3. effect of the social network, 4. lack of motivation for healthy habits, 5. environmental-organizational intensifier, 6. unhealthy eating behaviors. The core concept was “Motivation Loss to do preventive behavior.” The main constructs of the motivational-based model for the promotion of eating habits are “modification and promote of eating habits,” increase of knowledge and competency, convey of healthy nutrition behavior culture and effecting of behavioral model especially in older age, desirable of control stress. Conclusion: A key factor for unhealthy eating behavior at the workplace is a lack of motivation, which can be an obstacle to conduct preventive behaviors at work that can affect the healthy aging process in the long term. The motivational-based model could be considered an effective conceptual framework and instrument for designing interventions for the promotion to create healthy and active aging.

Keywords: aging, eating habits, older age, workplace

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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Authors: Amina Sa'id Muhammad, Asmau Ishaq Alhassan, Beba Raymond, Fatima Bello

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Severe acute malnutrition (SAM) remains a major killer of children under five years of age. Nigeria has the second highest burden of stunted children in the world, with a national prevalence rate of 32 percent of children under five. An estimated 2 million children in Nigeria suffer from severe acute malnutrition (SAM), and 3.9% of children in northwest Nigeria suffer from SAM, which is significantly higher than the national average of 2.1%. Community-Based Management of Acute Malnutrition (CMAM) has proven to be an effective intervention in the treatment of SAM in children using Ready-to-Use Therapeutic Food (RUTF). Ready-to-use therapeutic food (RUTF) is a key component for the treatment of Severe Acute Malnutrition. It contains all the energy and nutrients required for rapid catch-up growth and used particularly in the treatment of children over 6 months of age with SAM without medical complications. However, almost all RUTFs are currently imported to Nigeria from other countries. Shortages of RUTF due to logistics (shipping costs, delays, donor fatigue etc) and funding issues present a threat to the achievement of the 2030 World Health Assembly (WHA) targets for reducing malnutrition in addition to 2030 SDGs 2 (Zero Hunger), 3 (Good Health and Wellbeing), 12 (Responsible Consumption and Production), and 17 (Partnerships for the Goals), thus undermining its effectiveness in combating malnutrition On the other hand, the availability of human and material resources that will aid local production of RUTF presents an opportunity to fill in the gap in regular RUTF supply. About one thousand Nigerian children die of malnutrition-related causes every day, reaching a total of 361,000 each year. Owing to the high burden of malnutrition in Nigeria, the local production of RUTF is a logical step, that will ensure increased availability, acceptability, access, and efficiency in supply, and at lower costs. Objective(s): The objectives of this study were therefore, to formulate RUTF from locally available resources and to determine its energy and nutrients composition, incommensurate with the standard/commercial RUTF. Methods: Three samples of RUTF were formulated using locally available resources (soya beans, wheat, rice, baobab, brown-sugar, date palm and soya oil); which were subjected to various analysis to determine their energy/proximate composition, vitamin and mineral contents and organoleptic properties were also determined using sensory evaluation. Results: The energy values of the three samples of locally produced RUTF were found to be in conformity with WHO recommendation of ≥ 500 kcal per 100g. The energy values of the three RUTF samples produced in the current study were found to be 563.08, 503.67 and 528.98 kcal respectively. Sample A, B and C had protein content of 13.56% 16.71% and 14.62% respectively, which were higher than that of commercial RUTF (10.9%). Conclusions/recommendations: The locally formulated RUTF samples had energy value of more than 500 kcal per 100g; with an appreciable amount of macro and micro nutrients. The appearance, taste, flavor and general acceptability of the formulated RUTF samples were also commendable.

Keywords: energy, malnutrition, nutrients, RUTF

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Authors: Andrey Cherdantsev, Mikhail Cherdantsev, Sergey Isaenkov, Dmitriy Markovich

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In annular gas-liquid flow, liquid flows as a film along pipe walls sheared by high-velocity gas stream. Film surface is covered by large-scale disturbance waves which affect pressure drop and heat transfer in the system and are necessary for entrainment of liquid droplets from film surface into the core of gas stream. Disturbance waves are a highly complex and their properties are affected by numerous parameters. One of such aspects is flow development, i.e., change of flow properties with the distance from the inlet. In the present work, this question is studied using brightness-based laser-induced fluorescence (BBLIF) technique. This method enables one to perform simultaneous measurements of local film thickness in large number of points with high sampling frequency. In the present experiments first 50 cm of upward and downward annular flow in a vertical pipe of 11.7 mm i.d. is studied with temporal resolution of 10 kHz and spatial resolution of 0.5 mm. Thus, spatiotemporal evolution of film surface can be investigated, including scenarios of formation, acceleration and coalescence of disturbance waves. The behaviour of disturbance waves' velocity depending on phases flow rates and downstream distance was investigated. Besides measuring the waves properties, the goal of the work was to investigate the interrelation between disturbance waves properties and integral characteristics of the flow such as interfacial shear stress and flow rate of dispersed phase. In particular, it was shown that the initial acceleration of disturbance waves, defined by the value of shear stress, linearly decays with downstream distance. This lack of acceleration which may even lead to deceleration is related to liquid entrainment. Flow rate of disperse phase linearly grows with downstream distance. During entrainment events, liquid is extracted directly from disturbance waves, reducing their mass, area of interaction to the gas shear and, hence, velocity. Passing frequency of disturbance waves at each downstream position was measured automatically with a new algorithm of identification of characteristic lines of individual disturbance waves. Scenarios of coalescence of individual disturbance waves were identified. Transition from initial high-frequency Kelvin-Helmholtz waves appearing at the inlet to highly nonlinear disturbance waves with lower frequency was studied near the inlet using 3D realisation of BBLIF method in the same cylindrical channel and in a rectangular duct with cross-section of 5 mm by 50 mm. It was shown that the initial waves are generally two-dimensional but are promptly broken into localised three-dimensional wavelets. Coalescence of these wavelets leads to formation of quasi two-dimensional disturbance waves. Using cross-correlation analysis, loss and restoration of two-dimensionality of film surface with downstream distance were studied quantitatively. It was shown that all the processes occur closer to the inlet at higher gas velocities.

Keywords: annular flow, disturbance waves, entrainment, flow development

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Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan

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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).

Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay

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Authors: Kaushalendra Kumar, Abhishek Kumar, Chandra Moni, Sanjay Kumar, P. K. Singh, Ajeet Kumar

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Present study investigated the dietary inclusion of Moringa oleifera leaf meal (MOLM) on production efficiency, hemato-biochemical profile and economy of Vanaraja birds under tropical condition. Experiment was conducted for a period of 56 days on 300 Vanaraja birds randomly divided in to five different experimental groups including control of 60 birds each group replicated with 20 chicks in each replicate. T1, T2, T3, T4, and T5 were offered with 0, 5, 10, 15, and 20% Moringa oleifera leaf meal along with basal ration. All the standard managemental practices were followed during experimental period including vaccination schedule. Locally available Moringa oleifera leaves were harvested at mature stage and allowed to dry under shady and aerated conditions. Thereafter, dried leaves were milled to make a leaf meal and stored in the airtight nylon bags to avoid any possible contamination from foreign material and use for experiment. Production parameters were calculated based on the amount of feed consumed and weight gain every weeks. The body weight gain of T2 group was significantly (P < 0.05) higher side whereas T3 group was comparable with control. The feed conversion ratio for T2 group was found to be significantly (P < 0.05) lower than all other treatment groups, while none of the group was comparable with each other. At the end of the experiment blood samples were collected from birds for haematology study while serum biochemistry performed using spectrophotometer following statndard protocols. The haematological attributes were significantly (P > 0.05) not differed among the groups. However, serum biochemistry showed significant reduction (P < 0.05) of blood urea nitrogen, uric acid and creatinine level with higher level of MOLM diet, indicates better utilization of protein supplemented through MOLM. The total cholesterol and triglyceride level was declined significantly (P < 0.05) as compare to control group with increased level of MOLM in basal diet, decreasing trend of serum cholesterol noted. However, value of HDL for T3 group was highest and for T1 group was lowest but no significant difference (P < 0.05) found among the groups. It might be due to presence of β-sitosterol a bioactive compound present in MOLM which causes lowering of plasma concentration of LDL. During experiment total, LDL and VLDL level was found to be decreased significantly (P < 0.05) as compare to control group. It was observed that the production efficiency of birds significantly improved with 5% followed by 10% Moringa oleifera leaf meal among the treatment groups. However, the maximum profit per kg live weight was noted in 10 % level and least profit observed in 20% MOLM fed group. It was concluded that the dietary inclusion of MOLM improved overall performances without affecting metabolic status and effective in reducing cholesterol level reflects healthy chicken production for human consumption.

Keywords: hemato biochemistry, Moringa oleifera leaf meal, performance, Vanaraja birds

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Authors: Nien-Te Kuo, Yi-Sung Cheng, Kuo-Chien Chang

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Cultural festival tourism is now seen by many as an opportunity to facilitate community development because it has significant influences on the economic, social, cultural, and political aspects of local communities. The potential for tourist attraction has been recognized as a useful tool to strengthen local economies from governments. However, most community festivals in Taiwan are short-lived, often only lasting for a few years or occasionally not making it past a one-off event. Researchers suggested that most governments and other stakeholders do not recognize the importance of building a partnership with residents when developing community tourism. Thus, the sustainable community tourism development still remains a key issue in the existing literature. The success of community tourism is related to the attitudes and lifestyles of local residents. In order to maintain sustainable tourism, residents need to be seen as development partners. Residents’ support intention for tourism development not only helps to increase awareness of local culture, history, the natural environment, and infrastructure, but also improves the interactive relationship between the host community and tourists. Furthermore, researchers have identified the social capital theory as the core of sustainable community tourism development. The social capital of residents has been seen as a good way to solve issues of tourism governance, forecast the participation behavior and improve support intention of residents. In addition, previous studies have pointed out the role of community participation and place identity in increasing resident support intention for tourism development. A lack of place identity is one of the main reasons that community tourism has become a mere formality and is not sustainable. It refers to how much residents participate during tourism development and is mainly influenced by individual interest. Scholars believed that the place identity of residents is the soul of community festivals. It shows the community spirit to visitors and has significant impacts on tourism benefits and support intention of residents in community tourism development. Although the importance of community participation and place identity have been confirmed by both governmental and non-governmental organizations, real-life execution still needs to be improved. This study aimed to use social capital theory to investigate the social structure between community residents, participation levels in festival tourism, degrees of place identity, and resident support intention for future community tourism development, and the causal relationship that these factors have with cultural festival tourism. A quantitative research approach was employed to examine the proposed model. Structural equation model was used to test and verify the proposed hypotheses. This was a case study of the Kaohsiung Zuoying Wannian Folklore Festival. The festival was located in the Zuoying District of Kaohsiung City, Taiwan. The target population of this study was residents who attended the festival. The results reveal significant correlations among social capital, community participation, place identity and support intention. The results also confirm that impacts of social capital on support intention were significantly mediated by community participation and place identity. Practical suggestions were provided for tourism operators and policy makers. This work was supported by the Ministry of Science and Technology of Taiwan, Republic of China, under the grant MOST-105-2410-H-328-013.

Keywords: community participation, place identity, social capital, support intention

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Authors: Vangelis Papadimitropoulos

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This paper is part of the research program “Techno-Social Innovation in the Collaborative Economy”, funded by the Hellenic Foundation for Research and Innovation (H.F.R.I.) for the years 2022-2024. The paper showcases the Open Food Network (OFN) as an open-sourced digital platform supporting short food supply chains in local agricultural production and consumption. The paper outlines the research hypothesis, the theoretical framework, and the methodology of research as well as the findings and conclusions. Research hypothesis: The model of open cooperativism as a vehicle for systemic change in the agricultural sector. Theoretical framework: The research reviews the OFN as an illustrative case study of the three-zoned model of open cooperativism. The OFN is considered a paradigmatic case of the model of open cooperativism inasmuch as it produces commons, it consists of multiple stakeholders including ethical market entities, and it is variously supported by local authorities across the globe, the latter prefiguring the mini role of a partner state. Methodology: Research employs Ernesto Laclau and Chantal Mouffe’s discourse analysis -elements, floating signifiers, nodal points, discourses, logics of equivalence and difference- to analyse the breadth of empirical data gathered through literature review, digital ethnography, a survey, and in-depth interviews with core OFN members. Discourse analysis classifies OFN floating signifiers, nodal points, and discourses into four themes: value proposition, governance, economic policy, and legal policy. Findings: OFN floating signifiers align around the following nodal points and discourses: “digital commons”, “short food supply chains”, “sustainability”, “local”, “the elimination of intermediaries” and “systemic change”. The current research identifies a lack of common ground of what the discourse of “systemic change” signifies on the premises of the OFN’s value proposition. The lack of a common mission may be detrimental to the formation of a common strategy that would be perhaps deemed necessary to bring about systemic change in agriculture. Conclusions: Drawing on Laclau and Mouffe’s discourse theory of hegemony, research introduces a chain of equivalence by aligning discourses such as “agro-ecology”, “commons-based peer production”, “partner state” and “ethical market entities” under the model of open cooperativism, juxtaposed against the current hegemony of neoliberalism, which articulates discourses such as “market fundamentalism”, “privatization”, “green growth” and “the capitalist state” to promote corporatism and entrepreneurship. Research makes the case that for OFN to further agroecology and challenge the current hegemony of industrial agriculture, it is vital that it opens up its supply chains into equivalent sectors of the economy, civil society, and politics to form a chain of equivalence linking together ethical market entities, the commons and a partner state around the model of open cooperativism.

Keywords: sustainability, the digital commons, open cooperativism, innovation

Procedia PDF Downloads 53

Authors: Huseyin Apdik, Aysegul Dogan, Selami Demirci, Ezgi Avsar Apdik, Fikrettin Sahin

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Mesenchymal stem cells (MSCs) are crucial cell types for bone maintenance and growth along with resident bone progenitor cells providing bone tissue integrity during osteogenesis and skeletal growth. Any deficiency in this regulation would result in vital bone diseases. Of those, osteoporosis, characterized by a reduction in bone mass and mineral density, is a critical skeletal disease for especially elderly people. The commonly used drugs for the osteoporosis treatment are bisphosphonates (BPs). The most prominent role of BPs is to prevent bone resorption arisen from high osteoclast activity. However, administrations of bisphosphonates may also cause bisphosphonate-induced osteonecrosis of the jaw (BIONJ). Up to the present, the researchers have proposed several circumstances for BIONJ. However, effects of long-term and/or high dose usage of BPs on stem cell’s proliferation, survival, differentiation or maintenance capacity have not been evaluated yet. The present study will be held to; figure out BPs’ effects on MSCs in vitro in the aspect of cell proliferation and toxicity, migration, angiogenic activity, lineage specific gene and protein expression levels, mesenchymal stem cell properties and potential signaling pathways affected by BP treatment. Firstly, mesenchymal stem cell characteristics of Dental Pulp Stem Cells (DPSCs) and Periodontal Ligament Stem Cells (PDLSCs) were proved using flow cytometry analysis. Cell viability analysis was completed to determine the cytotoxic effects of BPs (Zoledronate (Zol), Alendronate (Ale) and Risedronate (Ris)) on DPSCs and PDLSCs by the 3-(4,5-di-methyl-thiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium (MTS) assay. Non-toxic concentrations of BPs were determined at 24 h under growth condition, and at 21 days under osteogenic differentiation condition for both cells. The scratch assay was performed to evaluate their migration capacity under the usage of determined of BPs concentrations at 24 h. The results revealed that while the scratch closure is 70% in the control group for DPSCs, it was 57%, 66% and 66% in Zol, Ale and Ris groups, respectively. For PDLSs, while wound closure is 71% in control group, it was 65%, 66% and 66% in Zol, Ale and Ris groups, respectively. As future experiments, tube formation assay and aortic ring assay will be done to determinate angiogenesis abilities of DPSCs and PDLSCs treated with BPs. Expression levels of osteogenic differentiation marker genes involved in bone development will be determined using real time-polymerase change reaction (RT-PCR) assay and expression profiles of important proteins involved in osteogenesis will be evaluated using western blotting assay for osteogenically differentiated MSCs treated with or without BPs. In addition to these, von Kossa staining will be performed to measure calcium mineralization status of MSCs.

Keywords: bisphosphonates, bisphosphonate-induced osteonecrosis of the jaw, mesenchymal stem cells, osteogenesis

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Authors: Bhupendra G. Prajapati, Alpesh R. Patel

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The aim of this research work is to develop sustained release multi-particulates dosage form of Dexketoprofen trometamol, which is the pharmacologically active isomer of ketoprofen. The objective is to utilization of active enantiomer with minimal dose and administration frequency, extended release multi-particulates dosage form development for better patience compliance was explored. Drug loaded and sustained release coated pellets were prepared by fluidized bed coating principle by wurster coater. Microcrystalline cellulose as core pellets, povidone as binder and talc as anti-tacking agents were selected during drug loading while Kollicoat SR 30D as sustained release polymer, triethyl citrate as plasticizer and micronized talc as an anti-adherent were used in sustained release coating. Binder optimization trial in drug loading showed that there was increase in process efficiency with increase in the binder concentration. 5 and 7.5%w/w concentration of Povidone K30 with respect to drug amount gave more than 90% process efficiency while higher amount of rejects (agglomerates) were observed for drug layering trial batch taken with 7.5% binder. So for drug loading, optimum Povidone concentration was selected as 5% of drug substance quantity since this trial had good process feasibility and good adhesion of the drug onto the MCC pellets. 2% w/w concentration of talc with respect to total drug layering solid mass shows better anti-tacking property to remove unnecessary static charge as well as agglomeration generation during spraying process. Optimized drug loaded pellets were coated for sustained release coating from 16 to 28% w/w coating to get desired drug release profile and results suggested that 22% w/w coating weight gain is necessary to get the required drug release profile. Three critical process parameters of Wurster coating for sustained release were further statistically optimized for desired quality target product profile attributes like agglomerates formation, process efficiency, and drug release profile using central composite design (CCD) by Minitab software. Results show that derived design space consisting 1.0 to 1.2 bar atomization air pressure, 7.8 to 10.0 gm/min spray rate and 29-34°C product bed temperature gave pre-defined drug product quality attributes. Scanning Image microscopy study results were also dictate that optimized batch pellets had very narrow particle size distribution and smooth surface which were ideal properties for reproducible drug release profile. The study also focused on optimized dexketoprofen trometamol pellets formulation retain its quality attributes while administering with common vehicle, a liquid (water) or semisolid food (apple sauce). Conclusion: Sustained release multi-particulates were successfully developed for dexketoprofen trometamol which may be useful to improve acceptability and palatability of a dosage form for better patient compliance.

Keywords: dexketoprofen trometamol, pellets, fluid bed technology, central composite design

Procedia PDF Downloads 122

Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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Authors: Jo Anne Rey

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Caring for Country (Ngurrain Dharug language) is core to Aboriginal identity, Law/Lore, practice, and resilience within the continent called ‘Australia’. It is the basis of thousands of years of sustainability. However, when Ngurra is a city known as Sydney, due to 235 years of colonial impact, caring for the Country is limited, being controlled by the State and private ownership of the land title. Recent research indicates that localised Indigenous activism is most successful when community members are geographically proximate to the presences and places of connection, caring, and belonging. This article frames these findings through the cadence that proximity provides. This presentation is centred on the proximate agency that is being exercised by Dharug community through three significant sites within the Sydney basin. Those sites include, firstly, Shaw’s Creek Aboriginal Place, at the foot of the Blue Mountains in far western Sydney. Second inclusion is the site of Blacktown Native Institution, that was the part of the authoritarian colonial governance of British Governor Lachlan Macquarie (after who Macquarie University is named), which saw the beginnings of the removal of children from their families and culture to ‘civilize’ them. The third site is that of the so-called Brown’s Waterhole in the State government administered Lane Cove National Park. Each of these sites is being activated through Dharug and, more broadly, Aboriginalways of knowing, doing, and being. These ways involvethe land, water, wind, and star-based ecologies interwoven with traditional transgenerational storying of the presences (Ancestral and spiritual) creating them. Activations include, but are not limited to, the return of cultural fire for reviving plants, soils, animals, and birds. These fire practices have traditionally been at the basis of sustainable, regenerative biodiversity. These practices involve the literacy of reading Ngurra and the seasonal interactions across the ecologies. Together, they both care for the Country and support humanity, and have done so across thousands of years. However, when the cost of real-estate and rental accommodation prevents community members from being able to live on Dharug Ngurra when bureaucratic governance restricts and/or excludes traditional custodial relationships, and when private treaty land title destroys the presences and places while disconnecting people from their Ancestral practices, it becomes clear that caring for Country is only possible when the community can afford to live nearby. Recognising the cadence of proximityas the agency that underpinscaring for Country-in-the-city, sustainable change opportunities don’t have to only focus on regional and remote areas. Urban-based Aboriginal relationality offers an alternative to the unsustainable practices that underpin human-centric disconnection. Weaving Indigenous cadence offers opportunities for sustainable futures even when facing the extremes of climate changing catastrophes.

Keywords: australian aboriginal, biocultural knowledges, climate change, dharug ngurra, sustainability, resilience

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Authors: Cristobal García

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The visual inspection of bolted joints in wind turbines is dangerous, expensive, and impractical due to the non-possibility to access the platform by workboat in certain sea state conditions, as well as the high costs derived from the transportation of maintenance technicians to offshore platforms located far away from the coast, especially if helicopters are involved. Consequently, the wind turbine operators have the need for simpler and less demanding techniques for the analysis of the bolts tightening. Vibration-based structural health monitoring is one of the oldest and most widely-used means for monitoring the health of onshore and offshore wind turbines. The core of this work is to find out if the modal parameters can be efficiently used as a key performance indicator (KPIs) for the assessment of joint bolts in a 1:50 scale tower of a floating offshore wind turbine (12 MW). A non-destructive vibration test is used to extract the vibration signals of the towers with different damage statuses. The procedure can be summarized in three consecutive steps. First, an artificial excitation is introduced by means of a commercial shaker mounted on the top of the tower. Second, the vibration signals of the towers are recorded for 8 s at a sampling rate of 20 kHz using an array of commercial accelerometers (Endevco, 44A16-1032). Third, the natural frequencies, damping, and overall vibration mode shapes are calculated using the software Siemens LMS 16A. Experiments show that the natural frequencies, damping, and mode shapes of the tower are directly dependent on the fixing conditions of the towers, and therefore, the variations of both parameters are a good indicator for the estimation of the static axial force acting in the bolt. Thus, this vibration-based structural method proposed can be potentially used as a diagnostic tool to evaluate the tightening torques of the bolted joints with the advantages of being an economical, straightforward, and multidisciplinary approach that can be applied for different typologies of connections by operation and maintenance technicians. In conclusion, TSI, in collaboration with the consortium of the FIBREGY project, is conducting innovative research where vibrations are utilized for the estimation of the tightening torque of a 1:50 scale steel-based tower prototype. The findings of this research carried out in the context of FIBREGY possess multiple implications for the assessment of the bolted joint integrity in multiple types of connections such as tower-to-nacelle, modular, tower-to-column, tube-to-tube, etc. This research is contextualized in the framework of the FIBREGY project. The EU-funded FIBREGY project (H2020, grant number 952966) will evaluate the feasibility of the design and construction of a new generation of marine renewable energy platforms using lightweight FRP materials in certain structural elements (e.g., tower, floating platform). The FIBREGY consortium is composed of 11 partners specialized in the offshore renewable energy sector and funded partially by the H2020 program of the European Commission with an overall budget of 8 million Euros.

Keywords: SHM, vibrations, connections, floating offshore platform

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Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

Procedia PDF Downloads 94

Authors: Swati Vohra

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A genuine economic and social transformation requires equal contribution and participation from both men and women; however, achieving this gender parity is a global concern. In the patriarchal societies around the world, women have been silenced, oppressed, and subjugated. Girls and women comprise half of the world’s population. This, however, must not be the lone reason for recognizing and providing equal opportunities to them. Every individual has a right to develop through opportunities without the biases of gender, caste, race, or ethnicity. The world today is confronted by pressing issues of climate change, economic crisis, violence against women and children, escalating conflicts, to name a few. Achieving gender parity is thus an essential component in meeting this wide array of challenges in order to create just, robust and inclusive societies. In 2015, The United Nation enunciated achieving 17 Sustainable Development Goals by 2030, one of which is SGD#5- Gender Equality, that is not merely a stand-alone goal. It is central to the achievement of all 17 SDG’s. Without progress on gender equality, the global community will not only fail to achieve the SDG5, but it will also lose the impetus towards achieving the broad 2030 agenda. This research is based on a hypothesis that aims to connect the targets laid by the UN under SDG#5 - 5.4 (Recognize and value unpaid care and domestic work) and 5.5 (Ensure women participation for leadership at all levels of decision-making). The study evaluates the impact of unpaid household responsibilities on women’s leadership in India. In Indian society, women have experienced a low social status for centuries, which is reflected throughout the Indian history with preference of a male child and common occurrences of female infanticides that are still prevalent in many parts of the country. Insistence on the traditional gender roles builds patriarchal inequalities into the structure of Indian society. It is argued that a burden of unpaid labor on women is placed, which narrows the opportunities and life chances women are given and the choices they are able to make, thereby shutting them from shared participation in public and economic leadership. The study investigates theoretical framework of social construction of gender, unpaid labor, challenges to women leaders and peace theorist perspective as the core components. The methodology used is qualitative research of comprehensive literature, accompanied by the data collected through interviews of representatives of women leaders from various fields within Delhi-National Capital Region (NCR). The women leaders interviewed had the privilege of receiving good education and a conducive family support; however, post marriage and children it was not the case and the social obligations weighed heavy on them. The research concludes by recommending the importance of gender-neutral parenting and education along with government ratified paternal leaves for at least six months and childcare facilities available for both the parents at workplace.

Keywords: gender equality, gender roles, peace studies, sustainable development goals, social construction, unpaid labor, women’s leadership

Procedia PDF Downloads 103

Authors: Eliane Abdo, Olivier Colot

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SMEs are always considered as a national priority due to their contribution to job creation, innovation and growth. Once the start-up phase is crossed with encouraging results, the company enters the phase of growth. In order to improve its competitiveness, maintain and increase its market share, the company is in the necessity even the obligation to develop its tangible and intangible investments. SMEs are generally closed companies with special and critical financial situation, limited resources and difficulty to access the capital markets; their shareholders are always living in a conflict between their independence and their need to increase capital that leads to the entry of new shareholder. The capital structure was always considered the core of research in corporate finance; moreover, the financial crisis and its repercussions on the credit’s availability, especially for SMEs make SME financing a hot topic. On the other hand, financial theories do not provide answers to capital structure’s questions; they offer tools and mode of financing that are more accessible to larger companies. Yet, SME’s capital structure can’t be independent of their governance structure. The classic financial theory supposes independence between the investment decision and the financing decision. Thus, investment determines the volume of funding, but not the split between internal or external funds. In this context, we find interesting to study the hypothesis that SMEs respond positively to the financial theories applied to large firms and to check if they are constrained by conventional solutions used by large companies. In this context, this research focuses on the analysis of the resource’s structure of SME in parallel with their investments’ structure, in order to highlight a link between their assets and liabilities structure. We founded our conceptual model based on two main theoretical frameworks: the Pecking order theory, and the Trade Off theory taking into consideration the SME’s characteristics. Our data were generated from DIANE database. Five hypotheses were tested via a panel regression to understand the type of dependence between the financing methods of 3,244 French SMEs and the development of their investment over a period of 10 years (2007-2016). The results show dependence between equity and internal financing in case of intangible investments development. Moreover, this type of business is constraint to financial debts since the guarantees provided are not sufficient to meet the banks' requirements. However, for tangible investments development, SMEs count sequentially on internal financing, bank borrowing, and new shares issuance or hybrid financing. This is compliant to the Pecking Order Theory. We, therefore, conclude that unlisted SMEs incur more financial debts to finance their tangible investments more than their intangible. However, they always prefer internal financing as a first choice. This seems to be confirmed by the assumption that the profitability of the company is negatively related to the increase of the financial debt. Thus, the Pecking Order Theory predictions seem to be the most plausible. Consequently, SMEs primarily rely on self-financing and then go, into debt as a priority to finance their financial deficit.

Keywords: capital structure, investments, life cycle, pecking order theory, trade off theory

Procedia PDF Downloads 95

Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Aungkana Kmonpetch

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Protection of trafficked victims and partnership among stakeholders are established as core principles in 5P’ strategies in international and national anti-human trafficking policies. In this article, it is of interest to discuss how the role of public-private partnerships in promoting the occupation development for employment in wage will enhance the better protection for victims of trafficking who affirmatively decide they want a criminal justice intervention, using Thailand as a case. Most of the victims who have accepted to be witness in the criminal justice system have lost income during their absence from work. The analysis of Thailand case is based on two methodological approaches: 1) interview with victims of trafficking, protection authorities, service providers, trainers and teachers, social workers, NGOs, police, prosecutors, business owners and enterprises, ILO, UNDP etc.; 2) create collaborative effort through workshops/consultation meetings in participation of all stakeholders – governmental agencies, private organizations, UN and international agencies. The linking of protection and partnership is anchored in international conventions and human trafficking directives. While this is actually framed as a responsive advantage for 5P strategies of anti-human trafficking – prevention, protection, persecution, punishment, and partnership, in reality, there might have more practical requirements of care and support. The article addresses how the partnership between governmental agencies and private organizations provide opportunities for trafficked victims to engage in high-skilled occupational development such as Silk-Sewing and Tailoring. The discussion is also focused how this approach of capacity building of the trainer for trainee, be enable the trafficked victims to cultivate the practices of high-skilled training to engage them into the business of social enterprise with employment in wage. The partnership coordination draws specifically to two aspects: firstly, to formulate appropriate assistance for promotion and protection of human rights of the trafficked victims in response to the 5P’ strategies of anti-human trafficking policy; secondly, to empower them to settle some economic stability for livelihood opportunity in the country of origin on their return and reintegration. Therefore, they can define how they want to move forward to prevent them at risk of vulnerable situations where they might being trafficked again or going on to work in exploitative conditions. It strengthens proper access to protection and assistance, depending on how the incentive of protection for cooperation is perceived to be and how useful the capacity building in occupation development for employment in wage will be implemented practically both in the host country and in the country of origin. This also brings into question how the victim of trafficking are able to access to the trade of market and are supported the employment opportunity according to the concept of decent work as they are constituted as witnesses. We discuss these issues in the area of a broader literature on social protection, economic security, gender, law, and victimhood.

Keywords: employment opportunity, occupation development, protection for victim of trafficking, public-private partnership

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Authors: Guoheng Liu, Zhilong Huang

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For more than the past ten years, oil and gas production from marine shale such as the Barnett shale. In addition, in recent years, major breakthroughs have also been made in lacustrine shale gas exploration, such as the Yanchang Formation of the Ordos Basin in China. Lucaogou Formation shale, which is also lacustrine shale, has also yielded a high production in recent years, for wells such as M1, M6, and ML2, yielding a daily oil production of 5.6 tons, 37.4 tons and 13.56 tons, respectively. Lithologic identification and classification of reservoirs are the base and keys to oil and gas exploration. Lithology and lithofacies obviously control the distribution of oil and gas in lithological reservoirs, so it is of great significance to describe characteristics of lithology and lithofacies of reservoirs finely. Lithofacies is an intrinsic property of rock formed under certain conditions of sedimentation. Fine-grained sedimentary rocks such as shale formed under different sedimentary conditions display great particularity and distinctiveness. Hence, to our best knowledge, no constant and unified criteria and methods exist for fine-grained sedimentary rocks regarding lithofacies definition and classification. Consequently, multi-parameters and multi-disciplines are necessary. A series of qualitative descriptions and quantitative analysis were used to figure out the lithofacies characteristics and its effect on oil accumulation of Lucaogou formation fine-grained sedimentary rocks in Santanghu basin. The qualitative description includes core description, petrographic thin section observation, fluorescent thin-section observation, cathode luminescence observation and scanning electron microscope observation. The quantitative analyses include X-ray diffraction, total organic content analysis, ROCK-EVAL.II Methodology, soxhlet extraction, porosity and permeability analysis and oil saturation analysis. Three types of lithofacies were mainly well-developed in this study area, which is organic-rich massive shale lithofacies, organic-rich laminated and cloddy hybrid sedimentary lithofacies and organic-lean massive carbonate lithofacies. Organic-rich massive shale lithofacies mainly include massive shale and tuffaceous shale, of which quartz and clay minerals are the major components. Organic-rich laminated and cloddy hybrid sedimentary lithofacies contain lamina and cloddy structure. Rocks from this lithofacies chiefly consist of dolomite and quartz. Organic-lean massive carbonate lithofacies mainly contains massive bedding fine-grained carbonate rocks, of which fine-grained dolomite accounts for the main part. Organic-rich massive shale lithofacies contain the highest content of free hydrocarbon and solid organic matter. Moreover, more pores were developed in organic-rich massive shale lithofacies. Organic-lean massive carbonate lithofacies contain the lowest content solid organic matter and develop the least amount of pores. Organic-rich laminated and cloddy hybrid sedimentary lithofacies develop the largest number of cracks and fractures. To sum up, organic-rich massive shale lithofacies is the most favorable type of lithofacies. Organic-lean massive carbonate lithofacies is impossible for large scale oil accumulation.

Keywords: lithofacies classification, tuffaceous shale, oil enrichment, Lucaogou formation

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Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

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Authors: Shagufta Jabeen, Faez Jesse Firdaus Abdullah, Zunita Zakaria, Nurulfiza Mat Isa, Yung Chie Tan, Wai Yan Yee, Abdul Rahman Omar

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Pasteurella multocida is associated with acute, as well as, chronic infections in avian and bovine such as pasteurellosis and hemorrhagic septicemia (HS) in cattle and buffaloes. Iron is one of the most important nutrients for pathogenic bacteria including Pasteurella and acts as a cofactor or prosthetic group in several essential enzymes and is needed for amino acid, pyrimidine, and DNA biosynthesis. In our recent study, we showed that 2% of Pasteurella multocida serotype A strain PMTB2.1 encode for iron regulating genes (Accession number CP007205.1). Genome sequencing of other Pasteurella multocida serotypes namely PM70 and HB01 also indicated up to 2.5% of the respective genome encode for iron regulating genes, suggesting that Pasteurella multocida genome comprises of multiple systems for iron uptake. Since P. multocida PMTB2.1 has more than 40 CDs out of 2097 CDs (approximately 2%), encode for iron-regulated. The gene expression profiling of four iron-regulating genes namely fbpb, yfea, fece and fur were characterized under iron-restricted environment. The P. multocida strain PMTB2.1 was grown in broth with and without iron chelating agent and samples were collected at different time points. Relative mRNA expression profile of these genes was determined using Taqman probe based real-time PCR assay. The data analysis, normalization with two house-keeping genes and the quantification of fold changes were carried out using Bio-Rad CFX manager software version 3.1. Results of this study reflect that iron reduced environment has significant effect on expression profile of iron regulating genes (p < 0.05) when compared to control (normal broth) and all evaluated genes act differently with response to iron reduction in media. The highest relative fold change of fece gene was observed at early stage of treatment indicating that PMTB2.1 may utilize its periplasmic protein at early stage to acquire iron. Furthermore, down-regulation expression of fece with the elevated expression of other genes at later time points suggests that PMTB2.1 control their iron requirements in response to iron availability by down-regulating the expression of iron proteins. Moreover, significantly high relative fold change (p ≤ 0.05) of fbpb gene is probably associated with the ability of P. multocida to directly use host iron complex such as hem, hemoglobin. In addition, the significant increase (p ≤ 0.05) in fbpb and yfea expressions also reflects the utilization of multiple iron systems in P. multocida strain PMTB2.1. The findings of this study are very much important as relative scarcity of free iron within hosts creates a major barrier to microbial growth inside host and utilization of outer-membrane proteins system in iron acquisition probably occurred at early stage of infection with P. multocida. In conclusion, the presence and utilization of multiple iron system in P. multocida strain PMTB2.1 revealed the importance of iron in the survival of P. multocida.

Keywords: iron-related genes, real-time PCR, gene expression profiling, fold changes

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Authors: Liou Shyhnan, Chia Han Yang

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The study aims to investigate the promotion of innovation in the development of cultural and creative industries (CCI) and apply research on culture and creativity to this promotion. Using the research perspectives of culture and creativity as the starting points, this study has examined the challenges, trends, and opportunities that have emerged from the development of the CCI until the present. It is found that a definite context of cause and effect exist between them, and that a homologous theoretical basis can be used to understand and interpret them. Based on the characteristics of the aforementioned challenges and trends, this study has compiled two main theoretical systems for conducting research on culture and creativity: (i) reciprocal process between creativity and culture, and (ii) a mechanism for innovation involving multicultural convergence. Both theoretical systems were then used as the foundation to arrive at possible research propositions relating to the two developmental systems. This was respectively done through identification of the theoretical context through a literature review, and interviews and observations of actual case studies within Taiwan’s CCI. In so doing, the critical factors that can address the aforementioned challenges and trends were discovered. Our results indicated that, for reciprocal process between creativity and culture, we recognize that culture serves as creative resources in cultural and creative industries. According to shared consensus, culture provides symbolic meanings and emotional attachment for products and experiences offered by CCI. Besides, different cultures vary in their effects on creativity processes and standards, thus engendering distinctive preferences for and evaluations of the creative expressions and experiences of CCIs. In addition, we identify that creativity serves as the engine for driving the continuation and rebirth of cultures. Accounting for the core of culture, the employment of technology, design, and business facilitates the transformation and innovation mechanism for promoting culture continuity. In addition, with cultural centered, the digital technology, design thinking, and business model are critical constitutes of the innovation mechanism to promote the cultural continuity. Regarding cultural preservation and regeneration of local spaces and folk customs, we argue that the preservation and regeneration of local spaces and cultural cultures must embody the interactive experiences of present-day life. And cultural space and folk custom would regenerate with interact and experience in modern life. Regarding innovation mechanism for multicultural convergence, we propose that innovative stakeholders from different disciplines (e.g., creators, designers, engineers, and marketers) in CCIs rely on the establishment of a cocreation mechanism to promote interdisciplinary interaction. Furthermore, CCI development needs to develop a cocreation mechanism for enhancing the interdisciplinary collaboration among CCI innovation stakeholders. We further argue multicultural mixing would enhance innovation in developing CCI, and assuming an open and mutually enlightening attitude to enrich one another’s cultures in the multicultural exchanges under globalization will create diversity in homogenous CCIs. Finally, for promoting innovation in developing cultural and creative industries, we further propose a model for joint knowledge creation that can be established for enhancing the mutual reinforcement of theoretical and practical research on culture and creativity.

Keywords: culture and creativity, innovation, cultural and creative industries, cultural mixing

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Authors: Mathula Thangarajh

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Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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Authors: Bosiacki Mateusz, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Exposure to cold temperatures can be considered a stressor that can lead to adaptive responses. The present study hypothesized the possibility of a positive effect of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The purpose of this study was to evaluate the effects of cold water exercise on energy status, purine compounds, and mitochondrial biogenesis in the muscles of aging rats as indicators of the effects of cold water exercise and their usefulness in monitoring adaptive changes. The study was conducted on 64 aging rats of both sexes, 15 months old at the time of the experiment. The rats (male and female separately) were randomly assigned to the following study groups: control, sedentary animals; 5°C groups animals - training swimming in cold water at 5°C; 36°C groups - animals training swimming in water at thermal comfort temperature. The study was conducted with the approval of the Local Ethical Committee for Animal Experiments. The animals in the experiment were subjected to swimming training for 9 weeks. During the first week of the study, the duration of the first swimming training was 2 minutes (on the first day), increasing daily by 0.5 minutes up to 4 minutes on the fifth day of the first week. From the second to the eighth week, the swimming training was 4 minutes per day, five days a week. At the end of the study, forty-eight hours after the last swim training, the animals were dissected. In the skeletal muscle tissue of the thighs of the rats, we determined the concentrations of ATP, ADP, AMP, Ado (HPLC), PGC-1a protein expression (Western blot), PGC1A, Mfn1, Mfn2, Opa1, and Drp1 gene expression (qRT PCR). The study showed that swimming in water at a thermally comfortable temperature improved the energy metabolism of the aging rat muscles by increasing the metabolic rate (increase in ATP, ADP, TAN, AEC) and enhancing mitochondrial fusion (increase in mRNA expression of regulatory proteins Mfn1 and Mfn2). Cold water swimming improved muscle energy metabolism in aging rats by increasing the rate of muscle energy metabolism (increase in ATP, ADP, TAN, AEC concentrations) and enhancing mitochondrial biogenesis and dynamics (increase in the mRNA expression of proteins of fusion-regulating factors – Mfn1, Mfn2, and Opa1, and the factor regulating mitochondrial fission – Drp1). The concentration of high-energy compounds and the expression of proteins regulating mitochondrial dynamics in the muscle may be a useful indicator in monitoring adaptive changes occurring in aging muscles under the influence of exercise in cold water. It represents a short-term adaptation to changing environmental conditions and has a beneficial effect on maintaining the bioenergetic capacity of muscles in the long term. Conclusion: exercise in cold water can exert positive effects on energy metabolism, biogenesis and dynamics of mitochondria in aging rat muscles. Enhancement of mitochondrial dynamics under cold water exercise conditions can improve mitochondrial function and optimize the bioenergetic capacity of mitochondria in aging rat muscles.

Keywords: cold water immersion, adaptive responses, muscle energy metabolism, aging

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Authors: Pedro Llanos, Diego García

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This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model for assessing predicted versus observed physiological responses. A group of individuals with diverse Science Technology Engineering Mathematics (STEM) backgrounds conducted a hypobaric training session to an altitude up to 22,000 ft (FL220) or 6,705 meters, where heart rate (HR), breathing rate (BR) and core temperature (Tc) were monitored with the use of a chest strap sensor pre and post HH exposure. A pulse oximeter registered levels of saturation of oxygen (SpO₂), number and duration of desaturations during the HH chamber flight. Hypoxia symptoms as described by the SACs during the HH training session were also registered. This data allowed to generate a preliminary predictive model of the oxygen desaturation and O₂ pressure curve for each subject, which consists of a sixth-order polynomial fit during exposure, and a fifth or fourth-order polynomial fit during recovery. Data analysis showed that HR and BR showed no significant differences between pre and post HH exposure in most of the SACs, while Tc measures showed slight but consistent decrement changes. All subjects registered SpO₂ greater than 94% for the majority of their individual HH exposures, but all of them presented at least one clinically significant desaturation (SpO₂ < 85% for more than 5 seconds) and half of the individuals showed SpO₂ below 87% for at least 30% of their HH exposure time. Finally, real time collection of HH symptoms presented temperature somatosensory perceptions (SP) for 65% of individuals, and task-focus issues for 52.5% of individuals as the most common HH indications. 95% of the subjects experienced HH onset symptoms below FL180; all participants achieved full recovery of HH symptoms within 1 minute of donning their O₂ mask. The current HH study performed on this group of individuals suggests a rapid and fully reversible physiologic response after HH exposure as expected and obtained in previous studies. Our data showed consistent results between predicted versus observed SpO₂ curves during HH suggesting a mathematical function that may be used to model HH performance deficiencies. During the HH study, real-time HH symptoms were registered providing evidenced SP and task focusing as the earliest and most common indicators. Finally, an assessment of HH signs of symptoms in a group of heterogeneous, non-pilot individuals showed similar results to previous studies in homogeneous populations of pilots.

Keywords: slow onset hypoxia, hypobaric chamber training, altitude sickness, symptoms and altitude, pressure cabin

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