Search results for: complement receptor 1
501 Molecular Dynamics Simulation of Beta-Glucosidase of Streptomyces
Authors: Adam Abate, Elham Rasti, Philip Romero
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Beta-glucosidase is the key enzyme component present in cellulase and completes the final step during cellulose hydrolysis by converting the cellobiose to glucose. The regulatory properties of beta-glucosidases are most commonly found for the retaining and inverting enzymes. Hydrolysis of a glycoside typically occurs with general acid and general base assistance from two amino acid side chains, normally glutamic or aspartic acids. In order to obtain more detailed information on the dynamic events origination from the interaction with enzyme active site, we carried out molecular dynamics simulations of beta-glycosidase in protonated state (Glu-H178) and deprotonated state (Glu178). The theoretical models generated from our molecular dynamics simulations complement and advance the structural information currently available, leading to a more detailed understanding of Beta-glycosidase structure and function. This article presents the important role of Asn307 in enzyme activity of beta-glucosidaseKeywords: Beta-glucosidase, GROMACS, molecular dynamics simulation, structural parameters
Procedia PDF Downloads 399500 Docking and Dynamic Molecular Study of Isoniazid Derivatives as Anti-Tuberculosis Drug Candidate
Authors: Richa Mardianingrum, Srie R. N. Endah
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In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide
Procedia PDF Downloads 181499 Liturgical Elements and Symbolism of Light in Christian Sacred Space
Authors: Zorana Sokol Gojnik, Igor Gojnik, Marina Simunic Bursic
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The light is one of the major themes of theology of sacred space. Christian theology, but also architecture in its complexity, is permeated by the symbolism of light from its beginning. The aim of this paper is to deeply analyse the symbolism of light in every single element of contemporary Christian sacred space such as altar, ambo, baptistery, tabernacle, confessionals, stations of the cross, etc. The research will be carried out using the methodology of research of literature and comparatively observation of contemporary examples of sacred architecture. The research will use the insights of analyzed literature and examples of sacred architecture in order to describe the background of the problem as well as to complement the received results with the reliable scientific findings. The paper will highlight the importance of symbolic and theological points of view in contemporary church design using the light as a building part of every single part of sacred architecture as there is an insight that, in contemporary sacred architecture, there is a lack of understanding of symbolic and theological aspect of light while designing new sacred spaces.Keywords: architecture, liturgy, sacred architecture, theology of space
Procedia PDF Downloads 191498 Distribution of Putative Dopaminergic Neurons and Identification of D2 Receptors in the Brain of Fish
Authors: Shweta Dhindhwal
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Dopamine is an essential neurotransmitter in the central nervous system of all vertebrates and plays an important role in many processes such as motor function, learning and behavior, and sensory activity. One of the important functions of dopamine is release of pituitary hormones. It is synthesized from the amino acid tyrosine. Two types of dopamine receptors, D1-like and D2-like, have been reported in fish. The dopamine containing neurons are located in the olfactory bulbs, the ventral regions of the pre-optic area and tuberal hypothalamus. Distribution of the dopaminergic system has not been studied in the murrel, Channa punctatus. The present study deals with identification of D2 receptors in the brain of murrel. A phylogenetic tree has been constructed using partial sequence of D2 receptor. Distribution of putative dopaminergic neurons in the brain has been investigated. Also, formalin induced hypertrophy of neurosecretory cells in murrel has been studied.Keywords: dopamine, fish, pre-optic area, murrel
Procedia PDF Downloads 421497 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma
Authors: Aoxue Yang, Weili Tian, Haikun Liu
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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides
Procedia PDF Downloads 132496 Activation of TNF-α from Human Endothelial Cells by Exposure of the Mitochondrial Stress Protein (Hsp60) Secreted from THP-1 Monocytes to High Glucose
Authors: Ryan D. Martinus
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Inflammation of the endothelium is an important process leading to diabetic atherosclerosis. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Using In-vitro cultured Human cells and Hsp60 specific ELISA assays, we show that Hsp60 is not only induced in Human monocyte cells under hyperglycaemic conditions but that the Hsp60 is also secreted from these cells. Furthermore, we also demonstrate that the Hsp60 secreted from these monocyte cells is also able to activate Toll-like receptor-4 (TLR4) from Human endothelial cells. This suggests that a potential link may exist between the hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could, therefore, be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.Keywords: mitochondria, Hsp60, inflammation, diabetes mellitus
Procedia PDF Downloads 182495 Feel Good - Think Positive: A Positive Psychology Intervention for Enhancing Optimism and Hope in Elementary School Students - A Pilot Study
Authors: Stephanos Vassilopoulos
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Positive psychology interventions (PPIs) targeting optimism and hope in young children are scarce. This pilot study explored the feasibility and promise of the “Feel Good - Think Positive” intervention, a brief, manualized, multicomponent group PPI for young children. The intervention aimed to enhance participants’ optimism, hope, and self-esteem while reducing their anxiety levels. Forty-one students (Mage = 9.68, SD = 1.64) participated in the intervention and provided data on optimism, hope, self-esteem, and anxiety at baseline and after the intervention was concluded. Analyses showed a significant increase in optimism and self-esteem and a significant decrease in anxiety. However, no change was observed in hope levels. The results complement previous studies of school-based PPIs and hint at the promise of designing feasible interventions that can be easily incorporated into school curriculum and produce both a promoting and a remedial effect in young children.Keywords: positive psychology intervention, positive education, hope, children
Procedia PDF Downloads 106494 Puereria mirifica Replacement Improves Skeletal Muscle Performance Associated with Increasing Parvalbumin Levels in Ovariectomized Rat
Authors: Uraporn Vongvatcharanon, Kochakorn Sukjan, Wandee Udomuksorn, Ekkasit Kumarnsit, Surapong Vongvatcharanon
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Sarcopenia is a loss of muscle mass, and strength frequently found in menopause. Estrogen replacement has been shown to improve such a loss of muscle functions. However, there is an increased risk of cancer that has to be considered because of the estrogen replacement therapy. Thus, phytoestrogen supplementation has been suggested as an alternative therapy. Pueraria mirifica (PM) is a plant in the family Leguminosae, that is known to be phytoestrogen-rich and has been traditionally used for the treatment of menopausal symptoms. It contains isoflavones and other compounds such as miroestrol and its derivatives. Parvalbumin (PV) is a calcium binding protein and functions as a relaxing factor in fast twitch muscle fibers. A decrease of the PV level results in a reduction of the speed of the twitch relaxation. Therefore, this study aimed to investigate the effect of an ethanolic extract from Pueraria mirifica on the estrogen levels, skeletal muscle functions and PV levels in the extensor digitorum longus (EDL) and gastrocnemius of ovariectomized rats. Twelve-week old female Wistar rats (200-250 g) were divided into 6 groups: SHAM (un-ovariectomized rats, that received double distilled water), PM-0 (ovariectomized rats, OVX, receiving double distilled water), E (OVX, receiving an estradiol benzoate dose of 0.04 mg/kg), PM-50 (OVX receiving PM 50 mg/kg), PM-500 (OVX receiving PM 500 mg/kg), PM-1000 (OVX receiving PM 1000 mg/kg) all for 90 days. The PM-0 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation and parvalbumin levels of both EDL and gastrocnemius that were significantly reduced compared to those of the SHAM group (p<0.05). Also the α and β estrogen receptor immunoreactivities and the parvalbumin immunoreactivities of both EDL and gastrocnemius were decreased in the PM-0 group. In contrast the E, PM-50, PM-500 and PM-1000 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation of both EDL and gastrocnemius that were significantly increased compared with PM-0 group (p<0.05). In addition, the α and β estrogen receptor immunoreactivities and parvalbumin immunoreactivity of both the EDL and gastrocnemius were increased in the E, PM-50, PM-500 and PM-1000 group. In addition the extract of Pueraria mirifica replacement group at 50 and 500 mg/kg had significantly increased parvalbumin levels in the EDL muscle but in the gastrocnemius, only the dose of 500 mg/kg increased the parvalbumin levels (p<0.05). These results have demonstrated that the use of the Pueraria mirifica extract as a replacement therapy for estrogen produced estrogenic activity that was similar to that produced by the estradiol benzoate replacement. It seems that the phytoestrogens could bind with the estrogen receptors and stimulate the transcriptional activity to synthesise muscle protein that caused an increase in muscle mass and parvalbumin levels. Thus, muscle synthesis may restore parvalbumin levels resulting in an enhanced relaxation efficiency that would lead to a shortened latent period before the next contraction.Keywords: Puereria mirifica, Parvalbumin, estrogen, ovariectomized rats
Procedia PDF Downloads 382493 Quantifying Firm-Level Environmental Innovation Performance: Determining the Sustainability Value of Patent Portfolios
Authors: Maximilian Elsen, Frank Tietze
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The development and diffusion of green technologies are crucial for achieving our ambitious climate targets. The Paris Agreement commits its members to develop strategies for achieving net zero greenhouse gas emissions by the second half of the century. Governments, executives, and academics are working on net-zero strategies and the business of rating organisations on their environmental, social and governance (ESG) performance has grown tremendously in its public interest. ESG data is now commonly integrated into traditional investment analysis and an important factor in investment decisions. Creating these metrics, however, is inherently challenging as environmental and social impacts are hard to measure and uniform requirements on ESG reporting are lacking. ESG metrics are often incomplete and inconsistent as they lack fully accepted reporting standards and are often of qualitative nature. This study explores the use of patent data for assessing the environmental performance of companies by focusing on their patented inventions in the space of climate change mitigation and adaptation technologies (CCMAT). The present study builds on the successful identification of CCMAT patents. In this context, the study adopts the Y02 patent classification, a fully cross-sectional tagging scheme that is fully incorporated in the Cooperative Patent Classification (CPC), to identify Climate Change Adaptation Technologies. The Y02 classification was jointly developed by the European Patent Office (EPO) and the United States Patent and Trademark Office (USPTO) and provides means to examine technologies in the field of mitigation and adaptation to climate change across relevant technologies. This paper develops sustainability-related metrics for firm-level patent portfolios. We do so by adopting a three-step approach. First, we identify relevant CCMAT patents based on their classification as Y02 CPC patents. Second, we examine the technological strength of the identified CCMAT patents by including more traditional metrics from the field of patent analytics while considering their relevance in the space of CCMAT. Such metrics include, among others, the number of forward citations a patent receives, as well as the backward citations and the size of the focal patent family. Third, we conduct our analysis on a firm level by sector for a sample of companies from different industries and compare the derived sustainability performance metrics with the firms’ environmental and financial performance based on carbon emissions and revenue data. The main outcome of this research is the development of sustainability-related metrics for firm-level environmental performance based on patent data. This research has the potential to complement existing ESG metrics from an innovation perspective by focusing on the environmental performance of companies and putting them into perspective to conventional financial performance metrics. We further provide insights into the environmental performance of companies on a sector level. This study has implications of both academic and practical nature. Academically, it contributes to the research on eco-innovation and the literature on innovation and intellectual property (IP). Practically, the study has implications for policymakers by deriving meaningful insights into the environmental performance from an innovation and IP perspective. Such metrics are further relevant for investors and potentially complement existing ESG data.Keywords: climate change mitigation, innovation, patent portfolios, sustainability
Procedia PDF Downloads 85492 Inhibition of Influenza Replication through the Restrictive Factors Modulation by CCR5 and CXCR4 Receptor Ligands
Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda
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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.Keywords: chemokine receptors, gp120, influenza, virus restriction factors
Procedia PDF Downloads 142491 Human Absorbed Dose Assessment of 68Ga-Dotatoc Based on Biodistribution Data in Syrian Rats
Authors: S. Zolghadri, M. Naderi, H. Yousefnia, A. Ramazani, A. R. Jalilian
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The aim of this work was to evaluate the values of absorbed dose of 68Ga-DOTATOC in numerous human organs. 68Ga-DOTATOC was prepared with the radiochemical purity of higher than 98% and by specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37° C at least 2 h after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreas and adrenal. The absorbed dose received by human organs was evaluated based on biodistribution studies in Syrian rats by the radiation absorbed dose assessment resource (RADAR) method. Maximum absorbed dose was obtained in the pancreas, kidneys, and adrenal with 0.105, 0.074, and 0.010 mGy/MBq, respectively. The effective absorbed dose was 0.026 mSv/MBq for 68Ga-DOTATOC. The results showed that 68Ga-DOTATOC can be considered as a safe and effective agent for clinically PET imaging applications.Keywords: effective absorbed dose, Ga-68, octreotide, MIRD
Procedia PDF Downloads 527490 Comparative Effects of Resveratrol and Energy Restriction on Liver Fat Accumulation and Hepatic Fatty Acid Oxidation
Authors: Iñaki Milton-Laskibar, Leixuri Aguirre, Maria P. Portillo
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Introduction: Energy restriction is an effective approach in preventing liver steatosis. However, due to social and economic reasons among others, compliance with this treatment protocol is often very poor, especially in the long term. Resveratrol, a natural polyphenolic compound that belongs to stilbene group, has been widely reported to imitate the effects of energy restriction. Objective: To analyze the effects of resveratrol under normoenergetic feeding conditions and under a mild energy restriction on liver fat accumulation and hepatic fatty acid oxidation. Methods: 36 male six-week-old rats were fed a high-fat high-sucrose diet for 6 weeks in order to induce steatosis. Then, rats were divided into four groups and fed a standard diet for 6 additional weeks: control group (C), resveratrol group (RSV, resveratrol 30 mg/kg/d), restricted group (R, 15 % energy restriction) and combined group (RR, 15 % energy restriction and resveratrol 30 mg/kg/d). Liver triacylglycerols (TG) and total cholesterol contents were measured by using commercial kits. Carnitine palmitoyl transferase 1a (CPT 1a) and citrate synthase (CS) activities were measured spectrophotometrically. TFAM (mitochondrial transcription factor A) and peroxisome proliferator-activator receptor alpha (PPARα) protein contents, as well as the ratio acetylated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/Total PGC1α were analyzed by Western blot. Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: No differences were observed among the four groups regarding liver weight and cholesterol content, but the three treated groups showed reduced TG when compared to the control group, being the restricted groups the ones showing the lowest values (with no differences between them). Higher CPT 1a and CS activities were observed in the groups supplemented with resveratrol (RSV and RR), with no difference between them. The acetylated PGC1α /total PGC1α ratio was lower in the treated groups (RSV, R and RR) than in the control group, with no differences among them. As far as TFAM protein expression is concerned, only the RR group reached a higher value. Finally, no changes were observed in PPARα protein expression. Conclusions: Resveratrol administration is an effective intervention for liver triacylglycerol content reduction, but a mild energy restriction is even more effective. The mechanisms of action of these two strategies are different. Thus resveratrol, but not energy restriction, seems to act by increasing fatty acid oxidation, although mitochondriogenesis seems not to be induced. When both treatments (resveratrol administration and a mild energy restriction) were combined, no additive or synergic effects were appreciated. Acknowledgements: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.Keywords: energy restriction, fat, liver, oxidation, resveratrol
Procedia PDF Downloads 212489 Bioinformatic Prediction of Hub Genes by Analysis of Signaling Pathways, Transcriptional Regulatory Networks and DNA Methylation Pattern in Colon Cancer
Authors: Ankan Roy, Niharika, Samir Kumar Patra
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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions
Procedia PDF Downloads 132488 Preparation and Characterization of Poly (ε-caprolactone) Loaded with Layered Double Hydroxide Nanohybrid Intercalated with Alendronate for Osteoporosis Treatment
Authors: Seyedeh Faranak Baniahmad, Soroor Yousefi
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Osteoporosis is a bone disease which increases the bone fracture risk, reduces the bone mineral density (BMD) and alters the amount and variety of proteins in bones. Antiresorptive therapy is one the most popular Osteoporosis treatment methods. In this method the bisphosphonates, hormones, calcitonin or the selective estrogen receptor modulators is replaced. In order to reduce undesirable effects and to increase the bioavailability of drug agents, the controlled drug delivery systems have been utilized. In current study, the controlled release of Alendronate from LDH-PCL with (0, 5, 10, 15 % wt. of LDH) was investigated. The results showed that the release of alendronate from the lamellar LDH incorporated into the PCL matrix is much slower than the release of alendronate from the PCL. Therefore such systems are very promising, in which the antiresorptive drug has to remain in the matrix for longer time and can be released in controlled manner.Keywords: osteoporosis, alendronate, poly (ε–caprolactone), layered double hydroxide
Procedia PDF Downloads 394487 Interactive Systems in B2B Marketing: Perceptions of Sales Configurator Use
Authors: Tommi Mahlamaki, Mika Ojala
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Digitalization is changing our lives in many ways. As consumers, we are accustomed using different online interactive sales systems. However, while many online selling sites offer systems that have evolved from simple selling functions, the change has not been as rapid in business-to-business (B2B) markets. This is because many B2B companies rely on personal sales and personal communication. The main objective of this research is to clarify perceptions towards digital interactive sales systems and, more specifically, sales configurators. It also aims to identify trends towards the use of sales configurators. To reach these objectives, an online questionnaire was created that targets Finnish B2B distributors who are, by definition, part of B2B markets. The questionnaire was sent to 340 distributors, and it was returned by 150 respondents. The results showed that 82% of respondents had heard about sales configurators, and 64% had used them. The results also showed that 48% of respondents felt that the use of sales configurators would increase in the future, while only 2% felt they would be used less. The future use of sales configurators was not seen as affecting the level of personal sales. In light of the results, we recommend that B2B companies create marketing strategies that integrate and complement traditional sales processes with digital interactive systems.Keywords: digitalization, interactive systems, marketing, sales process
Procedia PDF Downloads 247486 Double Liposomes Based Dual Drug Delivery System for Effective Eradication of Helicobacter pylori
Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo
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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems
Procedia PDF Downloads 208485 Detection of Nutrients Using Honeybee-Mimic Bioelectronic Tongue Systems
Authors: Soo Ho Lim, Minju Lee, Dong In Kim, Gi Youn Han, Seunghun Hong, Hyung Wook Kwon
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We report a floating electrode-based bioelectronic tongue mimicking honeybee taste systems for the detection and discrimination of various nutrients. Here, carbon nanotube field effect transistors with floating electrodes (CNT-FET) were hybridized with nanovesicles containing honeybee nutrient receptors, gustatory receptors of Apis mellifera. This strategy enables us to detect nutrient substance with a high sensitivity and selectivity. It could also be utilized for the detection of nutrients in liquid food. This floating electrode-based bioelectronic tongue mimicking insect taste systems can be a simple, but highly effective strategy in many different basic research areas about sensory systems. Moreover, our research provides opportunities to develop various applications such as food screening, and it also can provide valuable insights on insect taste systems.Keywords: taste system, CNT-FET, insect gustatory receptor, biolelectronic tongue
Procedia PDF Downloads 219484 Relating Symptoms with Protein Production Abnormality in Patients with Down Syndrome
Authors: Ruolan Zhou
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Trisomy of human chromosome 21 is the primary cause of Down Syndrome (DS), and this genetic disease has significantly burdened families and countries, causing great controversy. To address this problem, the research takes an approach in exploring the relationship between genetic abnormality and this disease's symptoms, adopting several techniques, including data analysis and enrichment analysis. It also explores open-source websites, such as NCBI, DAVID, SOURCE, STRING, as well as UCSC, to complement its result. This research has analyzed the variety of genes on human chromosome 21 with simple coding, and by using analysis, it has specified the protein-coding genes, their function, and their location. By using enrichment analysis, this paper has found the abundance of keratin production-related coding-proteins on human chromosome 21. By adopting past researches, this research has attempted to disclose the relationship between trisomy of human chromosome 21 and keratin production abnormality, which might be the reason for common diseases in patients with Down Syndrome. At last, by addressing the advantage and insufficiency of this research, the discussion has provided specific directions for future research.Keywords: Down Syndrome, protein production, genome, enrichment analysis
Procedia PDF Downloads 127483 Investigating the Expression of NR1/NR2 Receptors in Boys Between 6 to 16 with ADHD Compared to a Healthy Controlled Group
Authors: Sajad Haghshenas
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Emerging evidence from clinical, genetic, and animal model studies suggests that the N-methyl-D-aspartate (NMDA) glutamate receptors (NMDAR) may contribute to the pathophysiology and aetiology of neurological and psychiatric disorders and the patients with impaired NMDR receptors experience psychological symptoms. Therefore, we hypothesised that NMDAR receptors play a key role in the development of attention deficit hyperactivity disorder (ADHD). In this comparative analytical study, we utilized western blotting method to assay the expression levels of NMDA subunits NR1 and NR2 in the blood plasma of 50 male individuals diagnosed with ADHD in comparison to 20 healthy controls. The findings from the western blotting analysis provide support for the hypothesis that individuals with ADHD exhibit significantly lower levels of NR1/2 receptors compared to those without the disorder. Further research is needed to explore the potential causal relationship between reduced NR1/NR2 receptor levels and the development of ADHD.Keywords: expression, glutamate receptors, NR1, NR2, ADHD
Procedia PDF Downloads 74482 Targeted Photoactivatable Multiagent Nanoconjugates for Imaging and Photodynamic Therapy
Authors: Shazia Bano
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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates
Procedia PDF Downloads 143481 Designing an Introductory Python Course for Finance Students
Authors: Joelle Thng, Li Fang
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Objective: As programming becomes a highly valued and sought-after skill in the economy, many universities have started offering Python courses to help students keep up with the demands of employers. This study focuses on designing a university module that effectively educates undergraduate students on financial analysis using Python programming. Methodology: To better satisfy the specific demands for each sector, this study adopted a qualitative research modus operandi to craft a module that would complement students’ existing financial skills. The lessons were structured using research-backed educational learning tools, and important Python concepts were prudently screened before being included in the syllabus. The course contents were streamlined based on criteria such as ease of learning and versatility. In particular, the skills taught were modelled in a way to ensure they were beneficial for financial data processing and analysis. Results: Through this study, a 6-week course containing the chosen topics and programming applications was carefully constructed for finance students. Conclusion: The findings in this paper will provide valuable insights as to how teaching programming could be customised for students hailing from various academic backgrounds.Keywords: curriculum development, designing effective instruction, higher education strategy, python for finance students
Procedia PDF Downloads 79480 O-(2-18F-Fluoroethyl)-L-Tyrosine Positron Emission Tomography/Computed Tomography in Patients with Suspicious Recurrent Low and High-Grade Glioma
Authors: Mahkameh Asadi, Habibollah Dadgar
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The precise definition margin of high and low-grade glioma is crucial for choosing best treatment approach after surgery and radio-chemotherapy. The aim of the current study was to assess the O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) positron emission tomography (PET)/computed tomography (CT) in patients with low (LGG) and high grade glioma (HGG). We retrospectively analyzed 18F-FET PET/CT of 10 patients (age: 33 ± 12 years) with suspicious for recurrent LGG and HGG. The final decision of recurrence was made by magnetic resonance imaging (MRI) and registered clinical data. While response to radio-chemotherapy by MRI is often complex and sophisticated due to the edema, necrosis, and inflammation, emerging amino acid PET leading to better interpretations with more specifically differentiate true tumor boundaries from equivocal lesions. Therefore, integrating amino acid PET in the management of glioma to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.Keywords: positron emission tomography, amino acid positron emission tomography, magnetic resonance imaging, low and high grade glioma
Procedia PDF Downloads 177479 An Improved Modular Multilevel Converter Voltage Balancing Approach for Grid Connected PV System
Authors: Safia Bashir, Zulfiqar Memon
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During the last decade, renewable energy sources in particular solar photovoltaic (PV) has gained increased attention. Therefore, various PV converters topologies have emerged. Among this topology, the modular multilevel converter (MMC) is considered as one of the most promising topologies for the grid-connected PV system due to its modularity and transformerless features. When it comes to the safe operation of MMC, the balancing of the Submodules Voltages (SMs) plays a critical role. This paper proposes a balancing approach based on space vector PWM (SVPWM). Unlike the existing techniques, this method generates the switching vectors for the MMC by using only one SVPWM for the upper arm. The lower arm switching vectors are obtained by finding the complement of the upper arm switching vectors. The use of one SVPWM not only simplifies the calculation but also helped in reducing the circulating current in the MMC. The proposed method is varied through simulation using Matlab/Simulink and compared with other available modulation methods. The results validate the ability of the suggested method in balancing the SMs capacitors voltages and reducing the circulating current which will help in reducing the power loss of the PV system.Keywords: capacitor voltage balancing, circulating current, modular multilevel converter, PV system
Procedia PDF Downloads 160478 The Impact of Ship Traffic and Harbor Activities on the Atmospheric Pollution in Two Northern Adriatic Ports: Venice and Rijeka
Authors: Elena Barbaro, Elena Gregoris, Rossano Piazza, Boris Mifka, Tatjana Ivošević, Ivo Orlić, Ana Alebić-Juretić, Andrea Gambaro, Daniele Contini
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The aim of the POSEIDON project is to quantify the relative contribution of maritime traffic and harbor activities to atmospheric pollutants concentration in four port-cities of the Adriatic Sea. This study focuses on the harbors of Venice and Rijeka. In order to investigate the main pollution sources, emission inventories were used as input for receptor models: PMF (positive matrix factorization) and PCA (principal components analysis); moreover source identification was also conducted using PAHs diagnostic ratios. The ship traffic impact was quantified: i) on gaseous and particulate PAHs, collected using a new method which consisted in a double simultaneous sampling, in different wind sectors; ii) applying PMF to data of metals, PAHs and ions in PM10; iii) using the vanadium concentration according to the Agrawal methodology.Keywords: ship traffic, PMF, harbor, POSEIDON
Procedia PDF Downloads 602477 COVID-19: Potential Effects of Nutritional Factors on Inflammation Relief
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
Procedia PDF Downloads 174476 Proposed Location of Grid Connected Wind-Pv Hybrid System Based on Load Flow and Voltage Stability Indices Study
Authors: Bazilah Ismail, Muhammad Mat Naain, Ibrahim Alhamrouni, Lilik Jamilatul Awalin, Fadi Albatsh, Mohd Fairuz Abdul Hamid
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Rapid depletion and prices of the conventional energy sources have stimulated the development of the renewable energy source (RES). Due to the unpredicted and intermittent nature of RES, the hybrid renewable energy system (HRES) is the best solution to complement the nature of the respective sources, and the combination of the wind and solar energy is rapidly gaining popularity. The significant challenges on the operation and planning of the grid system with a high HRES penetration has become an important subject since the location of HRES plant give impact towards the existing system. This paper aims to propose the location of the grid connected Wind-PV hybrid plant (WPHP) based on load flow and voltage stability indices study. Several case studies are carried out using IEEE 14 bus system, and the system is modeled and tested in DigSILENT PowerFactory.Keywords: hybrid renewable energy system, wind farm, photovoltaic system, voltage stability and load flow
Procedia PDF Downloads 316475 Experiential Learning for Upholding Entrepreneurship Education: A Case Study from Egypt
Authors: Randa El Bedawy
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Exchanging best practices in the scope of entrepreneurship education and the use of experiential learning approaches are growing lately at a very fast pace. Educators should be challenged to promote such a learning approach to bridge the gap between entrepreneurship students and the actual business work environment. The study aims to share best practices, experiences, and knowledge to support entrepreneurship education. The study is exploratory qualitative research based on a case study approach to demonstrate how experiential learning can be used for supporting learning effectiveness in entrepreneurship education through demonstrating a set of fourteen tasks that were used to engage practically the students who were studying a course of entrepreneurship at the American University in Cairo. The study sheds the light on the rational process of using experiential learning to endorse entrepreneurship education through the illustration of each task along with its learning outcomes. The study explores the benefits and obstacles that educators may face when implementing such an experiential approach. The results of the study confirm that developing an experiential learning approach based on constructing a set of well designed practical tasks that complement the overall intended learning outcomes has proven very effective for promoting the students’ learning of entrepreneurship education. However, good preparation for both educators and students is needed primarily to ensure the effective implementation of such an experiential learning approach.Keywords: business education, entrepreneurship, entrepreneurship education, experiential learning
Procedia PDF Downloads 163474 Hereditary Angioedema: Case Presentation and Review of Anaesthetic Implications
Authors: Joshua Chew, Vesa Cheng, David Thomson
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Background: Hereditary angioedema (HAE) or C1 esterase deficiency is a relatively rare entity that has a potential for significant anesthetic complications. Methods: A literature review was performed of published cases of surgery in patients with HAE. Results were limited to English language only and cases were examined for management strategies and successful prevention of acute attacks. Results: The literature revealed the successful use of C1 esterase inhibitors as the most common agent in surgical prophylaxis therapy. Other therapeutic targets described included kallikrein inhibitors and bradykinin B2 receptor antagonists. Conclusions: Therapeutic targets that exist for the management of acute attacks in HAE have been successfully employed in the setting of surgery. The data is currently limited and could not be used as a firm evidence base, but the limited outcomes seen are positive and reassuring for the prospective anesthetic management of this potentially fatal condition.Keywords: anesthesia, C1 esterase deficiency, hereditary angioedema, surgical prophylaxis
Procedia PDF Downloads 406473 Is Brain Death Reversal Possible in Near Future: Intrathecal Sodium Nitroprusside (SNP) Superfusion in Brain Death Patients=The 10,000 Fold Effect
Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta
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Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect
Procedia PDF Downloads 405472 Temporary Autonomous Areas in Time and Space: Psytrance Rave Parties as an Expression Area of Altered States of Consciousness in Turkey
Authors: Ugur Cihat Sakarya
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This research focuses on psychedelic trance music events in Turkey in the context of altered states of consciousness (ASC). The fieldwork that was conducted from 2018 to 2019 is the main source of the research. Participant observation method was followed in 15 selected events. To direct the musical experiences of participants, performances were also presented as a Dj. Ten of these events are open-air festivals. Five of them are indoor parties. The observations made during fieldwork and suitable answers for inference from the interviews with participants, artists, DJs, and volunteers were selected, compiled, and presented. In the result, findings showed that these activities are perceived as temporary autonomous areas by the participants both in time and space and that these activities are suitable areas for expressing themselves as a group (psyfamily) against mainstream culture. It has been observed that the elements that complement the altered states of consciousness in these events are music, visual arts, drug use, and desire to experience spiritual experiences. It is thought that this first academic study -about this topic in Turkey- will open a door for future researches.Keywords: consciousness, psychedelic, psytrance, rave, Turkey
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