Search results for: induction furnaces
131 Establishing a Drug Discovery Platform to Progress Compounds into the Clinic
Authors: Sheraz Gul
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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics
Procedia PDF Downloads 167130 Toxicological and Histopathological Studies on the Effect of Tartrazine in Male Albino Rats
Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer
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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD50) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.Keywords: albino rats, tartrazine, toxicity, pathology
Procedia PDF Downloads 350129 Inhibitory Effect of Coumaroyl Lupendioic Acid on Inflammation Mediator Generation in Complete Freund’s Adjuvant-Induced Arthritis
Authors: Rayhana Begum, Manju Sharma
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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2
Procedia PDF Downloads 137128 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells
Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh
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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt
Procedia PDF Downloads 278127 IL-23, an Inflammatory Cytokine, Decreased by Shark Cartilage and Vitamin A Oral Treatment in Patient with Gastric Cancer
Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade
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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer
Procedia PDF Downloads 387126 Beneficial Effect of Micropropagation Coupled with Mycorrhization on Enhancement of Growth Performance of Medicinal Plants
Authors: D. H. Tejavathi
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Medicinal plants are globally valuable sources of herbal products. Wild populations of many medicinal plants are facing threat of extinction because of their narrow distribution, endemicity, and degradation of specific habitats. Micropropagation is an established in vitro technique by which large number of clones can be obtained from a small bit of explants in a short span of time within a limited space. Mycorrhization can minimize the transient transplantation shock, experienced by the micropropagated plants when they are transferred from lab to land. AM fungal association improves the physiological status of the host plants through better uptake of water and nutrients, particularly phosphorus. Consequently, the growth performance and biosynthesis of active principles are significantly enhanced in AM fungal treated plants. Bacopa monnieri, Andrographis paniculata, Agave vera-curz, Drymaria cordata and Majorana hortensis, important medicinal plants used in various indigenous systems of medicines, are selected for the present study. They form the main constituents of many herbal formulations. Standard in vitro techniques were followed to obtain the micropropagated plants. Shoot tips and nodal segments were used as explants. Explants were cultured on Murashige and Skoog, and Phillips and Collins media supplemented with various combinations of growth regulators. Multiple shoots were obtained on a media containing both auxins and cytokinins at various concentrations and combinations. Multiple shoots were then transferred to rooting media containing auxins for root induction. Thus, obtained in vitro regenerated plants were subjected to brief acclimatization before transferring them to land. One-month-old in vitro plants were treated with AM fungi, and the symbiotic effect on the overall growth parameters was analyzed. It was found that micropropagation coupled with mycorrhization has significant effect on the enhancement of biomass and biosynthesis of active principles in these selected medicinal plants. In vitro techniques coupled with mycorrhization have opened a possibility of obtaining better clones in respect of enhancement of biomass and biosynthesis of active principles. Beneficial effects of AM fungal association with medicinal plants are discussed.Keywords: cultivation, medicinal plants, micropropagation, mycorrhization
Procedia PDF Downloads 166125 A Prospective Audit to Look into Antimicrobial Prescribing in the Clinical Setting: In a Teaching Hospital in the UK
Authors: Richa Sinha, Mohammad Irfan Javed, Sanjay Singh
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Introduction: Good antimicrobial prescribing reduces length of stay in hospital, risk of adverse events, antimicrobial resistance, and unnecessary hospital expenditure. The aim of this prospective audit was to identify any problems with antimicrobial prescribing including documentation of the relevant aspects as well as appropriateness of antibiotics use. The audit was conducted on the surgical wards in a teaching hospital in the UK. Methods: Standards included the indication, duration, choice, and prescription of antibiotic should be in line with current Regional Guidelines and should be clearly documented on the prescription chart. There should be an entry in each patients’ medical record of the diagnosis and indication for each acute antibiotic prescription issued. All prescriptions should clearly document the route, frequency and dose of antibiotic. Data collection was done for 2 weeks in the month of March 2014. A proforma including all the questions above was completed for all the patients. The results were analysed using Excel. Results: 35 patients in total were selected for the audit. 85.7% of patients had indication of antibiotic documented on the prescription chart and 68.5% of patients had indication documented in the notes. The antibiotic used was in line with hospital guidelines in 45.7% of patients, however, in a further 28.5% of patients the reason for the antibiotic prescription was microbiology approved. Therefore, in total 74.2% of patients had been prescribed appropriate antibiotics. The duration of antibiotic was documented in 68.6% of patients and the antibiotic was reviewed in 37.1% of patients. The dose, frequency and route was documented clearly in 100% of patients. Conclusion: Overall, prescribing can be improved on the surgical wards in this hospital. Only 37.1% of patients had clear documentation of a review of antibiotics. It may be that antibiotics have been reviewed but this should be clearly highlighted on the prescription chart or the notes. Failure to review antibiotics can lead to poor patient care and antimicrobial resistance and therefore it is important to address this. It is also important to address the appropriateness of antibiotics as inappropriate antibiotic prescription can lead to failure of treatment as well as antimicrobial resistance. The good points from the audit was that all patients had clear documentation of dose, route and frequency which is extremely important in the administration of antibiotics. Recommendations from this audit included to emphasize good antimicrobial prescribing at induction (twice yearly), an antimicrobial handbook for junior doctors, and re-audit in 6 months time.Keywords: prescribing, antimicrobial, indication, duration
Procedia PDF Downloads 295124 Impact of Two Xenobiotics in Mosquitofish: Gambusia affinis: Several Approaches
Authors: Chouahda Salima, Soltani Noureddine
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The present study is a part of biological control against mosquitoes. It aims to assess the impact of two xenobiotics (a selective insect growth regulator: halofenozide and heavy metals: cadmium, more toxic and widespread in the region) in mosquitofish: Gambusia affinis. Several approaches were examined: Acute toxicity of cadmium and halofenozide: The acute toxicity of cadmium and halofenozide was examined in juvenile and adult males and females of G. affinis at different concentrations, cadmium causes mortality of the species studied with a relation dose-response. In laboratory conditions, the impact of cadmium was determined on two biomarkers of environmental stress: glutathione and acetylcholinesterase. The results show that the juvenile followed by adult males are more susceptible than adult females, while the halofenozide does not have any effect on the mortality of juvenile and adult males and females of G.affinis. Chronic toxicity of cadmium and halofenozide: both xenobiotics were added to the water fish raising at different doses tested in juveniles and adults males and females during two months of experience. Growth and metric indices; results show that halofenozide added to the water juveniles of G. affinis has no effect on their growth (length and weight). On the other side, the cadmium at the dose 5 µg/L shows a higher toxicity against juvenile, where he appears to reduce significantly their linear growth and weight. In females, the both xenobiotics have significant effects on metric indices, but these effects are more important on the hepatosomatic index that the gonadosomatic index and the coefficient of condition. Biomarkers; acetylcholinesterase (AChE), glutathione S-transferase (GST) and glutathione (GSH) used in assessing of environmental stress were measured in juveniles and adults males and females. The response of these biomarkers reveals an inhibition of AChE specific activity, an induction of GST activity, and decrease of GSH rates in juveniles in the end of experiment and during chronic treatment adult males and females. The effect of these biomarkers is more pronounced in females compared to males and juveniles. These different biomarkers have a similar profile for the duration of exposure.Keywords: gambusia affinis, insecticide, heavy metal, morphology, biomarkers, chronic toxicity, acute toxicity, pollution
Procedia PDF Downloads 306123 Distance Learning and Modern Challenges of Education Management in Georgia
Authors: Giorgi Gaganidze, Eter Kharaishvili
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The atypical crisis has created new challenges in the education system. Globally, including in Georgia, traditional methods of managing the education system have appeared particularly vulnerable. In addition, new opportunities for the introduction of innovative management of learning processes have emerged. The aim of the research is to identify the main challenges in the field of education management in the distance learning process in Georgia and to develop recommendations on the opportunities for the introduction of innovative management. The paper substantiates the relevance of the research, in particular, it notes that in Georgia, as in many countries, distance learning in higher education institutions became particularly crucial during the Covid-19 pandemic. What is more, theoretical and practical aspects of distance learning are less proven, and a number of problems have been identified in the field of education management in Georgia. The article justifies the need to study the challenges of distance learning for the formation of a sustainable education management system. Within the bibliographic research, there are grouped the opinions of researchers on the modern problems of distance learning and education management in the article. Based on scientific papers, the expectations formed about distance learning are studied, and the main focus is on the existing problems of education management during the atypical crisis. The article discusses the forms and opportunities of distance learning in different countries, evaluates different approaches and challenges to distance learning, and justifies the role of education management in effective distance learning. The paper uses various theoretical-methodological tools of research, including desk research on the research topic; Data selection-grouping, problem identification is carried out by analysis, synthesis, sampling, induction, and other methods;SWOT analysis is used to assess the strengths, weaknesses, opportunities, and threats of distance education and management; The level of student satisfaction with distance learning is determined through the Population-based / Census-based approach; The results of the research are processed by SPSS program. Quantitative research and semi-structured interviews with relevant focus groups were conducted to identify working directions for innovative management of distance learning and education. Research has shown that the demand for distance education is growing in Georgia, but the need to introduce innovative education management remains a particular challenge. Conclusions have been made on the introduction of innovative education management, and the relevant recommendations have been developed.Keywords: distance learning, management challenges, education management, innovative management
Procedia PDF Downloads 122122 A Proposal for Professional Development of Mathematics Teachers in the Kingdom of Saudi Arabia According to the Orientation of Science, Technology, Engineering and Mathematics (STEM)
Authors: Ali Taher Othman Ali
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The aim of this research is to provide a draft proposal for the professional development of mathematics teachers in accordance with the orientation of science, technology, engineering and mathematics which is known by the abbreviation STEM, as a modern and contemporary orientation in the teaching and learning of mathematics and in order to achieve the objective of the research, the researcher used the theoretical descriptive method through the induction of the literature of education and the previous studies and experiments related to the topic. The researcher concluded by providing the proposal according to five basic axes, the first axe: professional development as a system, and its requirements include: development of educational systems, and allocate sufficient budgets to support the requirements of teaching STEM, identifying mechanisms for incentives and rewards for teachers attending professional development programs based on STEM; the second: development of in-depth knowledge content and its requirements include: basic sciences content development for STEM, linking the scientific understanding of teachers with real-world issues and problems, to provide the necessary resources to expand teachers' knowledge in this area; the third: the necessary pedagogical skills of teachers in the field of STEM, and its requirements include: identification of the required training and development needs and the mechanism of determining these needs, the types of professional development programs and the mechanism of designing it, the mechanisms and places of execution, evaluation and follow-up; the fourth: professional development strategies and mechanisms in the field of STEM, and its requirements include: using a variety of strategies to enable teachers to design and transfer effective educational experiences which reflect their scientific mastery in the fields of STEM, provide learning opportunities, and developing the skills of procedural research to generate new knowledge about the STEM; the fifth: to support professional development in the area of STEM, and its requirements include: support leadership within the school, provide a clear and appropriate opportunities for professional development for teachers within the school through professional learning communities, building partnerships between the Ministry of education and the local and international community institutions. The proposal includes other factors that should be considered when implementing professional development programs for mathematics teachers in the field of STEM.Keywords: professional development, mathematics teachers, the orientation of science, technology, engineering and mathematics (STEM)
Procedia PDF Downloads 395121 Effects of Magnetic Field on 4H-SiC P-N Junctions
Authors: Khimmatali Nomozovich Juraev
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Silicon carbide is one of the promising materials with potential applications in electronic devices using high power, high frequency and high electric field. Currently, silicon carbide is used to manufacture high power and frequency diodes, transistors, radiation detectors, light emitting diodes (LEDs) and other functional devices. In this work, the effects of magnetic field on p-n junctions based on 4H-SiC were experimentally studied. As a research material, monocrystalline silicon carbide wafers (Cree Research, Inc., USA) with relatively few growth defects grown by physical vapor transport (PVT) method were used: Nd dislocations 104 cm², Nm micropipes ~ 10–10² cm-², thickness ~ 300-600 μm, surface ~ 0.25 cm², resistivity ~ 3.6–20 Ωcm, the concentration of background impurities Nd − Na ~ (0.5–1.0)×1017cm-³. The initial parameters of the samples were determined on a Hall Effect Measurement System HMS-7000 (Ecopia) measuring device. Diffusing Ni nickel atoms were covered to the silicon surface of silicon carbide in a Universal Vacuum Post device at a vacuum of 10-⁵ -10-⁶ Torr by thermal sputtering and kept at a temperature of 600-650°C for 30 minutes. Then Ni atoms were diffused into the silicon carbide 4H-SiC sample at a temperature of 1150-1300°C by low temperature diffusion method in an air atmosphere, and the effects of the magnetic field on the I-V characteristics of the samples were studied. I-V characteristics of silicon carbide 4H-SiCKeywords: 4H-SiC, diffusion Ni, effects of magnetic field, I-V characteristics
Procedia PDF Downloads 90120 Numerical Analysis of CO₂ Storage as Clathrates in Depleted Natural Gas Hydrate Formation
Authors: Sheraz Ahmad, Li Yiming, Li XiangFang, Xia Wei, Zeen Chen
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Holding CO₂ at massive scale in the enclathrated solid matter called hydrate can be perceived as one of the most reliable methods for CO₂ sequestration to take greenhouse gases emission control measures and global warming preventive actions. In this study, a dynamically coupled mass and heat transfer mathematical model is developed which elaborates the unsteady behavior of CO₂ flowing into a porous medium and converting itself into hydrates. The combined numerical model solution by implicit finite difference method is explained and through coupling the mass, momentum and heat conservation relations, an integrated model can be established to analyze the CO₂ hydrate growth within P-T equilibrium conditions. CO₂ phase transition, effect of hydrate nucleation by exothermic heat release and variations of thermo-physical properties has been studied during hydrate nucleation. The results illustrate that formation pressure distribution becomes stable at the early stage of hydrate nucleation process and always remains stable afterward, but formation temperature is unable to keep stable and varies during CO₂ injection and hydrate nucleation process. Initially, the temperature drops due to cold high-pressure CO₂ injection since when the massive hydrate growth triggers and temperature increases under the influence of exothermic heat evolution. Intermittently, it surpasses the initial formation temperature before CO₂ injection initiates. The hydrate growth rate increases by increasing injection pressure in the long formation and it also expands overall hydrate covered length in the same induction period. The results also show that the injection pressure conditions and hydrate growth rate affect other parameters like CO₂ velocity, CO₂ permeability, CO₂ density, CO₂ and H₂O saturation inside the porous medium. In order to enhance the hydrate growth rate and expand hydrate covered length, the injection temperature is reduced, but it did not give satisfactory outcomes. Hence, CO₂ injection in vacated natural gas hydrate porous sediment may form hydrate under low temperature and high-pressure conditions, but it seems very challenging on a huge scale in lengthy formations.Keywords: CO₂ hydrates, CO₂ injection, CO₂ Phase transition, CO₂ sequestration
Procedia PDF Downloads 127119 Export and Import Indicators of Georgian Agri-food Products during the Pandemic: Challenges and Opportunities
Authors: Eteri Kharaishvili
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Introduction. The paper analyzes the main indicators of export and import of Georgian agri-food products; identifies positive and negative trends under the pandemic; based on the revealed problemssubstantiates the need formodernization ofin agri-food sector. It is argued that low production and productivity rates of food products negatively impact achieving the optimal export-to-import ratio; therefore, it leads toincreaseddependence on other countries andreduces the level of food security. Research objectives. The objective of the research is to identify the key challenges based on the analysis of export-import indicators of Georgian food products during the pandemic period and develop recommendations on the possibilities of post-pandemic perspectives. Research methods. Various theoretical and methodological research tools are used in the paper; in particular, a desk research is carried out on the research topic; endogenous and exogenous variables affecting export and import are determined through factor analysis; SWOT and PESTEL analysis are used to identify development opportunities; selection and groupingof data, identification of similarities and differences is carried outby using analysis, synthesis, sampling, induction and other methods; a qualitative study is conducted based on a survey of agri-food experts and exporters for clarifying the factors that impede export-import flows. Contributions. The factors that impede the export of Georgian agri-food products in the short run under COVID-19 pandemic are identified. These are: reduced income of farmers, delays in the supply of raw materials and supplies to the agri-food sectorfrom the neighboring industries, as well as in harvesting, processing, marketing, transportation, and other sectors; increased indirect costs, etc. The factors that impede the export in the long run areas follows loss of public confidence in the industry, risk of losing positions in traditional markets, etc. Conclusions are made on the problems in the field of export and import of Georgian agri-food products in terms of the pandemic; development opportunities are evaluated based on the analysis of the agri-food sector potential. Recommendations on the development opportunities for export and import of Georgian agri-food products in the post-pandemic period are proposed.Keywords: agri-food products, export, and import, pandemic period, hindering factor, development potential
Procedia PDF Downloads 134118 Polyphenol Stability and Antioxidant Properties of Freeze-Dried Sour Cherry Encapsulates
Authors: Gordana Ćetković, Vesna Tumbas Šaponjac, Jasna Čanadanović-Brunet, Sonja Đilas, Slađana Stajčić, Jelena Vulić, Mirjana Jakišić
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Despite the recommended amount of daily intake of fruits, the consumption in modern age remains very low. Therefore there is a need for delivering valuable phytochemicals into the human body through different foods by developing functional food products fortified with natural bioactive compounds from plant sources. Recently, a growing interest rises in exploiting the fruit and vegetable by-products as sources of phytochemicals such as polyphenols, carotenoids, vitamins etc. Cherry contain high amounts of polyphenols, which are known to display a wide range of biological activities like antioxidant, anti-inflammatory, antimicrobial or anti-carcinogenic activities, improvement of vision, induction of apoptosis and neuroprotective effects. Also, cherry pomace, a by-product in juice processing, can also be promising source of phenolic compounds. However, the application of polyphenols as food additives is limited because after extraction these compounds are susceptible to degradation. Microencapsulation is one of the alternative approaches to protect bioactive compounds from degradation during processing and storage. Freeze-drying is one of the most used microencapsulation methods for the protection of thermosensitive and unstable molecules. In this study sour cherry pomace was extracted with food-grade solvent (50% ethanol) to be suitable for application in products for human use. Extracted polyphenols have been concentrated and stabilized on whey (WP) and soy (SP) proteins. Encapsulation efficiency in SP was higher (94.90%), however not significantly (p<0.05) from the one in WP (90.10%). Storage properties of WP and SP encapsulate in terms of total polyphenols, anthocyanins and antioxidant activity was tested for 6 weeks. It was found that the retention of polyphenols after 6 weeks in WP and SP (67.33 and 69.30%, respectively) was similar. The content of anthocyanins has increased in WP (for 47.97%), while their content in SP has very slightly decreased (for 1.45%) after 6-week storage period. In accordance with anthocyanins the decrease in antioxidant activity in WP (87.78%) was higher than in SP (43.02%). According to the results obtained in this study, the technique reported herewith can be used for obtaining quality encapsulates for their further use as functional food additives, and, on the other hand, for fruit waste valorization.Keywords: cherry pomace, microencapsulation, polyphenols, storage
Procedia PDF Downloads 362117 Economic Policy to Stimulate Industrial Development in Georgia
Authors: Gulnaz Erkomaishvili
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The article analyzes the modern level of industrial production in Georgia, shows the export-import of industrial products and evaluates the results of the activities of institutions implementing industrial policy. The research showed us that the level of development of industry in the country and its export potential are quite low. The article concludes that in the modern phase of industrial development, the country should choose a model focused on technological development and maximum growth of export potential. Objectives. The aim of the research is to develop an economic policy that promotes the development of industry and to look for ways to implement it effectively. Methodologies This paper uses general and specific methods, in particular, analysis, synthesis, induction, deduction, scientific abstraction, comparative and statistical methods, as well as experts’ evaluation. In-depth interviews with experts were conducted to determine quantitative and qualitative indicators; Publications of the National Statistics Office of Georgia are used to determine the regularity between analytical and statistical estimations. Also, theoretical and applied research of international organizations and scientist-economists are used. Contributions Based on the identified challenges in the area of industry, recommendations for the implementation of an active industrial policy in short and long term periods were developed. In particular: the government's priority orientation of industrial development; paying special attention to the processing industry sectors that Georgia has the potential to produce; supporting the development of scientific fields; Determination of certain benefits for those investors who invest money in industrial production; State partnership with the private sector, manifested in the fight against bureaucracy, corruption and crime, creating favorable business conditions for entrepreneurs; Coordination between education - science - production should be implemented in the country. Much attention should be paid to basic scientific research, which does not require purely commercial returns in the short term, science should become a real productive force; Special importance should be given to the creation of an environment that will support the expansion of export-oriented production; Overcoming barriers to entry into export markets.Keywords: industry, sectoral structure of industry, exsport-import of industrial products, industrial policy
Procedia PDF Downloads 98116 Ways to Effectively Use Tourism Potential Through International Marketing and PR Communication Strategy in the Post-pandemic Period (On the Example of Georgia)
Authors: Marine Kobalava
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The article analyzes the level of Georgia's tourism potential usage during the pandemic. The conclusion is drawnthat Georgia, as a tourism brand, is in a significant crisis at this stage, revenues from this sector have been substantially reduced, communication with potential customers is interrupted, no international marketing and PR communication strategies have been developed for the post-pandemic period. In order to rehabilitate the tourism industry of Georgia, it is considered vital to take measures using international marketing and PR communication strategies adjusted to the needs of the sectorthat will improve the use of tourism potential and stimulate the development of the sector. The goal of the research is to identify the factors hindering the use of tourism potential in the direction of international marketing and PR communication strategies in the post-pandemic period and to develop recommendations on ways to solve them. Research methods. The paper uses various theoretical and methodological tools of research, including Bibliographic research has been conducted on the main research issues; Analysis, synthesis, induction, and other methods are used to select and group data, identify similarities and differences, and identify trends; Endogenous and exogenous factors affecting the field of tourism have been studied by means of SWOT and PESTEL analyzes. A comparison model is used to analyze the strategy documents. Primary accounting materials are obtained from the National Statistics Office and the relevant ministries. Based on the results of the research, the directions of correct positioning of tourism products and marketing communication in the post-pandemic period have been developed. It is substantiated that a short-term international marketing strategy should include: probable goals of communication, maintaining a position on a potential traveler's “radar,” focusing communication on key motivating factors (gastronomy, winemaking, folklore, protected areas, mountainous regions). From a marketing point of view, it is important: holding international marketing events, compiling a list of target countries, formation of stimulus mechanisms, development of incentive programs for international tour operators, etc. The paper draws conclusions about the problems of using the tourism potential, recommendations on ways to solve this problems through international marketing and PR communication strategies are offeredKeywords: PR communication, international marketing strategy, tourism potential, post-pandemic period
Procedia PDF Downloads 170115 Estimation of Biomedical Waste Generated in a Tertiary Care Hospital in New Delhi
Authors: Priyanka Sharma, Manoj Jais, Poonam Gupta, Suraiya K. Ansari, Ravinder Kaur
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Introduction: As much as the Health Care is necessary for the population, so is the management of the Biomedical waste produced. Biomedical waste is a wide terminology used for the waste material produced during the diagnosis, treatment or immunization of human beings and animals, in research or in the production or testing of biological products. Biomedical waste management is a chain of processes from the point of generation of Biomedical waste to its final disposal in the correct and proper way, assigned for that particular type of waste. Any deviation from the said processes leads to improper disposal of Biomedical waste which itself is a major health hazard. Proper segregation of Biomedical waste is the key for Biomedical Waste management. Improper disposal of BMW can cause sharp injuries which may lead to HIV, Hepatitis-B virus, Hepatitis-C virus infections. Therefore, proper disposal of BMW is of upmost importance. Health care establishments segregate the Biomedical waste and dispose it as per the Biomedical waste management rules in India. Objectives: This study was done to observe the current trends of Biomedical waste generated in a tertiary care Hospital in Delhi. Methodology: Biomedical waste management rounds were conducted in the hospital wards. Relevant details were collected and analysed and sites with maximum Biomedical waste generation were identified. All the data was cross checked with the commons collection site. Results: The total amount of waste generated in the hospital during January 2014 till December 2014 was 6,39,547 kg, of which 70.5% was General (non-hazardous) waste and the rest 29.5% was BMW which consisted highly infectious waste (12.2%), disposable plastic waste (16.3%) and sharps (1%). The maximum quantity of Biomedical waste producing sites were Obstetrics and Gynaecology wards with a total Biomedical waste production of 45.8%, followed by Paediatrics, Surgery and Medicine wards with 21.2 %, 4.6% and 4.3% respectively. The maximum average Biomedical waste generated was by Obstetrics and Gynaecology ward with 0.7 kg/bed/day, followed by Paediatrics, Surgery and Medicine wards with 0.29, 0.28 and 0.18 kg/bed/day respectively. Conclusions: Hospitals should pay attention to the sites which produce a large amount of BMW to avoid improper segregation of Biomedical waste. Also, induction and refresher training Program of Biomedical waste management should be conducted to avoid improper management of Biomedical waste. Healthcare workers should be made aware of risks of poor Biomedical waste management.Keywords: biomedical waste, biomedical waste management, hospital-tertiary care, New Delhi
Procedia PDF Downloads 241114 Shaped Crystal Growth of Fe-Ga and Fe-Al Alloy Plates by the Micro Pulling down Method
Authors: Kei Kamada, Rikito Murakami, Masahiko Ito, Mototaka Arakawa, Yasuhiro Shoji, Toshiyuki Ueno, Masao Yoshino, Akihiro Yamaji, Shunsuke Kurosawa, Yuui Yokota, Yuji Ohashi, Akira Yoshikawa
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Techniques of energy harvesting y have been widely developed in recent years, due to high demand on the power supply for ‘Internet of things’ devices such as wireless sensor nodes. In these applications, conversion technique of mechanical vibration energy into electrical energy using magnetostrictive materials n have been brought to attention. Among the magnetostrictive materials, Fe-Ga and Fe-Al alloys are attractive materials due to the figure of merits such price, mechanical strength, high magnetostrictive constant. Up to now, bulk crystals of these alloys are produced by the Bridgman–Stockbarger method or the Czochralski method. Using these method big bulk crystal up to 2~3 inch diameter can be grown. However, non-uniformity of chemical composition along to the crystal growth direction cannot be avoid, which results in non-uniformity of magnetostriction constant and reduction of the production yield. The micro-pulling down (μ-PD) method has been developed as a shaped crystal growth technique. Our group have reported shaped crystal growth of oxide, fluoride single crystals with different shape such rod, plate tube, thin fiber, etc. Advantages of this method is low segregation due to high growth rate and small diffusion of melt at the solid-liquid interface, and small kerf loss due to near net shape crystal. In this presentation, we report the shaped long plate crystal growth of Fe-Ga and Fe-Al alloys using the μ-PD method. Alloy crystals were grown by the μ-PD method using calcium oxide crucible and induction heating system under the nitrogen atmosphere. The bottom hole of crucibles was 5 x 1mm² size. A <100> oriented iron-based alloy was used as a seed crystal. 5 x 1 x 320 mm³ alloy crystal plates were successfully grown. The results of crystal growth, chemical composition analysis, magnetostrictive properties and a prototype vibration energy harvester are reported. Furthermore, continuous crystal growth using powder supply system will be reported to minimize the chemical composition non-uniformity along the growth direction.Keywords: crystal growth, micro-pulling-down method, Fe-Ga, Fe-Al
Procedia PDF Downloads 327113 A Review Investigating the Potential Of Zooxanthellae to Be Genetically Engineered to Combat Coral Bleaching
Authors: Anuschka Curran, Sandra Barnard
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Coral reefs are of the most diverse and productive ecosystems on the planet, but due to the impact of climate change, these infrastructures are dying off primarily through coral bleaching. Coral bleaching can be described as the process by which zooxanthellae (algal endosymbionts) are expelled from the gastrodermal cavity of the respective coral host, causing increased coral whitening. The general consensus is that mass coral bleaching is due to the dysfunction of photosynthetic processes in the zooxanthellae as a result of the combined action of elevated temperature and light-stress. The question then is, do zooxanthellae have the potential to play a key role in the future of coral reef restoration through genetic engineering? The aim of this study is firstly to review the different zooxanthellae taxa and their traits with respect to environmental stress, and secondly, to review the information available on the protective mechanisms present in zooxanthellae cells when experiencing temperature fluctuations, specifically concentrating on heat shock proteins and the antioxidant stress response of zooxanthellae. The eight clades (A-H) previously recognized were redefined into seven genera. Different zooxanthellae taxa exhibit different traits, such as their photosynthetic stress responses to light and temperature. Zooxanthellae have the ability to determine the amount and type of heat shock proteins (hsps) present during a heat response. The zooxanthellae can regulate both the host’s respective hsps as well as their own. Hsps, generally found in genotype C3 zooxanthellae, such as Hsp70 and Hsp90, contribute to the thermal stress response of the respective coral host. Antioxidant activity found both within exposed coral tissue, and the zooxanthellae cells can prevent coral hosts from expelling their endosymbionts. The up-regulation of gene expression, which may mitigate thermal stress induction of any of the physiological aspects discussed, can ensure stable coral-zooxanthellae symbiosis in the future. It presents a viable alternative strategy to preserve reefs amidst climate change. In conclusion, despite their unusual molecular design, genetic engineering poses as a useful tool in understanding and manipulating variables and systems within zooxanthellae and therefore presents a solution that can ensure stable coral-zooxanthellae symbiosis in the future.Keywords: antioxidant enzymes, genetic engineering, heat-shock proteins, Symbiodinium
Procedia PDF Downloads 182112 Recursion, Merge and Event Sequence: A Bio-Mathematical Perspective
Authors: Noury Bakrim
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Formalization is indeed a foundational Mathematical Linguistics as demonstrated by the pioneering works. While dialoguing with this frame, we nonetheless propone, in our approach of language as a real object, a mathematical linguistics/biosemiotics defined as a dialectical synthesis between induction and computational deduction. Therefore, relying on the parametric interaction of cycles, rules, and features giving way to a sub-hypothetic biological point of view, we first hypothesize a factorial equation as an explanatory principle within Category Mathematics of the Ergobrain: our computation proposal of Universal Grammar rules per cycle or a scalar determination (multiplying right/left columns of the determinant matrix and right/left columns of the logarithmic matrix) of the transformable matrix for rule addition/deletion and cycles within representational mapping/cycle heredity basing on the factorial example, being the logarithmic exponent or power of rule deletion/addition. It enables us to propone an extension of minimalist merge/label notions to a Language Merge (as a computing principle) within cycle recursion relying on combinatorial mapping of rules hierarchies on external Entax of the Event Sequence. Therefore, to define combinatorial maps as language merge of features and combinatorial hierarchical restrictions (governing, commanding, and other rules), we secondly hypothesize from our results feature/hierarchy exponentiation on graph representation deriving from Gromov's Symbolic Dynamics where combinatorial vertices from Fe are set to combinatorial vertices of Hie and edges from Fe to Hie such as for all combinatorial group, there are restriction maps representing different derivational levels that are subgraphs: the intersection on I defines pullbacks and deletion rules (under restriction maps) then under disjunction edges H such that for the combinatorial map P belonging to Hie exponentiation by intersection there are pullbacks and projections that are equal to restriction maps RM₁ and RM₂. The model will draw on experimental biomathematics as well as structural frames with focus on Amazigh and English (cases from phonology/micro-semantics, Syntax) shift from Structure to event (especially Amazigh formant principle resolving its morphological heterogeneity).Keywords: rule/cycle addition/deletion, bio-mathematical methodology, general merge calculation, feature exponentiation, combinatorial maps, event sequence
Procedia PDF Downloads 121111 Effect of Auraptene on the Enzymatic Glutathione Redox-System in Nrf2 Knockout Mice
Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis
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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.Keywords: auraptene, glutathione, GST, Nrf2
Procedia PDF Downloads 141110 Sulforaphane Alleviates Muscular Dystrophy in Mdx Mice by Activation of Nrf2
Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li
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Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress
Procedia PDF Downloads 319109 The Mechanism Underlying Empathy-Related Helping Behavior: An Investigation of Empathy-Attitude- Action Model
Authors: Wan-Ting Liao, Angela K. Tzeng
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Empathy has been an important issue in psychology, education, as well as cognitive neuroscience. Empathy has two major components: cognitive and emotional. Cognitive component refers to the ability to understand others’ perspectives, thoughts, and actions, whereas emotional component refers to understand how others feel. Empathy can be induced, attitude can then be changed, and with enough attitude change, helping behavior can occur. This finding leads us to two questions: is attitude change really necessary for prosocial behavior? And, what roles cognitive and affective empathy play? For the second question, participants with different psychopathic personality (PP) traits are critical because high PP people were found to suffer only affective empathy deficit. Their cognitive empathy shows no significant difference from the control group. 132 college students voluntarily participated in the current three-stage study. Stage 1 was to collect basic information including Interpersonal Reactivity Index (IRI), Psychopathic Personality Inventory-Revised (PPI-R), Attitude Scale, Visual Analogue Scale (VAS), and demographic data. Stage two was for empathy induction with three controversial scenarios, namely domestic violence, depression with a suicide attempt, and an ex-offender. Participants read all three stories and then rewrite the stories by one of two perspectives (empathetic vs. objective). They would then complete the VAS and Attitude Scale one more time for their post-attitude and emotional status. Three IVs were introduced for data analysis: PP (High vs. Low), Responsibility (whether or not the character is responsible for what happened), and Perspective-taking (Empathic vs. Objective). Stage 3 was for the action. Participants were instructed to freely use the 17 tokens they received as donations. They were debriefed and interviewed at the end of the experiment. The major findings were people with higher empathy tend to take more action in helping. Attitude change is not necessary for prosocial behavior. The controversy of the scenarios and how familiar participants are towards target groups play very important roles. Finally, people with high PP tend to show more public prosocial behavior due to their affective empathy deficit. Pre-existing value and belief as well as recent dramatic social events seem to have a big impact and possibly reduce the effect of the independent variables (IV) in our paradigm.Keywords: empathy, cognitive, emotional, psychopathy
Procedia PDF Downloads 125108 Metformin and Its Combination with Sodium Hydrosulfide Influences Plasma Galectin-3 and CSE/H₂S System in Diabetic Rat's Heart
Authors: I. V. Palamarchuk, N. V. Zaichko
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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide
Procedia PDF Downloads 218107 Pregnancy - The Unique Immunological Paradigm
Authors: Husham Bayazed
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Purpose of presentation: Pregnancy represents the most important period for the conservation of the species. The immune system is one of the most important systems protecting the mother against the environment and preventing damage to the fetus. This presentation aims to review and discuss the role of the immune system during pregnancy, the evolutionary inflammatory process through pregnancy, infectious and environmental exposure influences on the mother and the fetus, and the impacts of sexual dimorphism of the placenta on offspring susceptibility to different disorders. Recent Findings: In 1960, Peter Medawar (Nobel Prize Winner) proposed that the fetus, a semi-allograft, is similar to a tissue graft that escapes rejection through a mechanism involving systemic immune suppression (Graft –Host response). However, recent researchers and studies have documented that implantation means inflammation, and the inflammatory process is considered a breach of tolerance in pregnancy with immune induction, which is necessary for the protection of the mother and the fetus against infections and environmental triggers. This inflammatory process should be maintained during different pregnancy phases till parturition, and any block at any phase will be associated with pregnancy complications, including pregnancy failure or loss, miscarriage, and preterm birth subsequently. Maternal immune activation following any trigger can have a positive effect on the fetus. The old concept of the placenta being asexual is inaccurate, and being with sexual dimorphism with clear differences in susceptibility to different factors that stimulate maternal immunity. Summary: The presence of different immune cells ((i.e., T cells, B cells, NK cells, etc.) at the implantation site is considered proof of a strong maternal immune response to the fetus. Therefore, human pregnancy is considered a unique immunological paradigm requiring maternal immune modulation rather than suppression. So Medawar's postulation of maternal systemic immunosuppression is wrong. Maternal immune system activation triggered by infections, stress, diet, and pollution can have a positive effect on the fetus, with the development of fetal-trained immunity necessary for survival. The sexual dimorphism of the placenta seems to have an impact on the differences in sex susceptible to the environment maternal risk stimuli. This link to why the incidence of autism is increasing more among boys than girls.Keywords: pregnancy, maternal immunity, implantation and inflammation, placenta sexual dimorphism
Procedia PDF Downloads 86106 The Effects of Orally Administered Bacillus Coagulans and Inulin on Prevention and Progression of Rheumatoid Arthritis in Rats
Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh
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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model
Procedia PDF Downloads 348105 A Mixed Thought Pattern and the Question of Justification: A Feminist Project
Authors: Angana Chatterjee
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The feminist scholars point out the various problematic issues in the traditional mainstream western thought and theories. The thought practices behind the discriminatory and oppressive social practices are based on concepts that play a pivotal role in theorisation. Therefore, many feminist philosophers take up reformation or reconceptualisation projects. Such projects have bearings on various aspects of philosophical thought, namely, ontology, epistemology, logic, ethics, social, political thought, and so on. In tune with this spirit, the present paper suggests a well-established thought pattern which is not western but has got the potential to deal with the problems of mainstream western thought culture that are identified by the feminist critics. The Indian thought pattern is theorised in the domain of Indian logic, which is a study of inference patterns. As, in the Indian context, the inference is considered as a source of knowledge, certain epistemological questions are linked with the discussion of inference. One of the key epistemological issues is one regarding justification. The study about the nature of derivation of knowledge from available evidence, and the nature of the evidence itself, are integral parts of the discipline called Indian logic. But if we contrast the western tradition of thought with the Indian one, we can find that the Indian logic has got some peculiar features which may be shown to deal with the problems identified by the feminist scholars in western thought culture more plausibly. The tradition of western logic, starting from Aristotle, has been maintaining sharp differences between two forms of reasoning, namely, deductive and inductive. These two different forms of reasoning have been theorised and dealt with separately within the domain of the study called ‘logic.’ There are various philosophical problems that are raised around concepts and issues regarding both deductive and inductive reasoning. Indian logic does not distinguish between deduction and induction as thought patterns, but their distinction is very usual to make in the western tradition. Though there can be found various interpretations about this peculiarity of Indian thought pattern, these mixed patterns were actually very close to the cross-cultural pattern in which human beings would tend to argue or infer from the available data or evidence. The feminist theories can successfully operate in the domain of lived experience if they make use of such a mixed pattern of reasoning or inference. By offering sound inferential knowledge on contextual evidences, the Indian thought pattern is potent to serve the feminist purposes in a meaningful way.Keywords: feminist thought, Indian logic, inference, justification, mixed thought pattern
Procedia PDF Downloads 96104 Investigating the Effects of Cylinder Disablement on Diesel Engine Fuel Economy and Exhaust Temperature Management
Authors: Hasan Ustun Basaran
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Diesel engines are widely used in transportation sector due to their high thermal efficiency. However, they also release high rates of NOₓ and PM (particulate matter) emissions into the environment which have hazardous effects on human health. Therefore, environmental protection agencies have issued strict emission regulations on automotive diesel engines. Recently, these regulations are even increasingly strengthened. Engine producers search novel on-engine methods such as advanced combustion techniques, utilization of renewable fuels, exhaust gas recirculation, advanced fuel injection methods or use exhaust after-treatment (EAT) systems in order to reduce emission rates on diesel engines. Although those aforementioned on-engine methods are effective to curb emission rates, they result in inefficiency or cannot decrease emission rates satisfactorily at all operating conditions. Therefore, engine manufacturers apply both on-engine techniques and EAT systems to meet the stringent emission norms. EAT systems are highly effective to diminish emission rates, however, they perform inefficiently at low loads due to low exhaust gas temperatures (below 250°C). Therefore, the objective of this study is to demonstrate that engine-out temperatures can be elevated above 250°C at low-loaded cases via cylinder disablement. The engine studied and modeled via Lotus Engine Simulation (LES) software is a six-cylinder turbocharged and intercooled diesel engine. Exhaust temperatures and mass flow rates are predicted at 1200 rpm engine speed and several low loaded conditions using LES program. It is seen that cylinder deactivation results in a considerable exhaust temperature rise (up to 100°C) at low loads which ensures effective EAT management. The method also improves fuel efficiency through reduced total pumping loss. Decreased total air induction due to inactive cylinders is thought to be responsible for improved engine pumping loss. The technique reduces exhaust gas flow rate as air flow is cut off on disabled cylinders. Still, heat transfer rates to the after-treatment catalyst bed do not decrease that much since exhaust temperatures are increased sufficiently. Simulation results are promising; however, further experimental studies are needed to identify the true potential of the method on fuel consumption and EAT improvement.Keywords: cylinder disablement, diesel engines, exhaust after-treatment, exhaust temperature, fuel efficiency
Procedia PDF Downloads 171103 Triploid Rainbow Trout (Oncorhynchus mykiss) for Better Aquaculture and Ecological Risk Management
Authors: N. N. Pandey, Raghvendra Singh, Biju S. Kamlam, Bipin K. Vishwakarma, Preetam Kala
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The rainbow trout (Oncorhynchus mykiss) is an exotic salmonid fish, well known for its fast growth, tremendous ability to thrive in diverse conditions, delicious flesh and hard fighting nature in Europe and other countries. Rainbow trout farming has a great potential for its contribution to the mainstream economy of Himalayan states in India and other temperate countries. These characteristics establish them as one of the most widely introduced and cultured fish across the globe, and its farming is also prominent in the cold water regions of India. Nevertheless, genetic fatigue, slow growth, early maturity, and low productivity are limiting the expansion of trout production. Moreover, farms adjacent to natural streams or other water sources are subject to escape of domesticated rainbow trout into the wild, which is a serious environmental concern as the escaped fish is subject to contaminate and disrupt the receiving ecosystem. A decline in production traits due to early maturity prolongs the culture duration and affects the profit margin of rainbow trout farms in India. A viable strategy that could overcome these farming constraints in large scale operation is the production of triploid fish that are sterile and more heterozygous. For better triploidy induction rate (TR), heat shock at 28°C for 10 minutes and pressure shock 9500 psi pressure for 5 minutes is applied to green eggs with 90-100% of triploidy success and 72-80% survival upto swim-up fry stage. There is 20% better growth in aquaculture with triploids rainbow trout over diploids. As compared to wild diploid fish, larger sized and fitter triploid rainbow trout in natural waters attract to trout anglers, and support the development of recreational fisheries by state fisheries departments without the risk of contaminating existing gene pools and disrupting local fish diversity. Overall, enhancement of productivity in rainbow trout farms and trout production in coldwater regions, development of lucrative trout angling and better ecological management is feasible with triploid rainbow trout.Keywords: rainbow trout, triploids fish, heat shock, pressure shock, trout angling
Procedia PDF Downloads 120102 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells
Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi
Abstract:
Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1
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