Search results for: transcription regulation
1238 Natural Monopolies and Their Regulation in Georgia
Authors: Marina Chavleishvili
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Introduction: Today, the study of monopolies, including natural monopolies, is topical. In real life, pure monopolies are natural monopolies. Natural monopolies are used widely and are regulated by the state. In particular, the prices and rates are regulated. The paper considers the problems associated with the operation of natural monopolies in Georgia, in particular, their microeconomic analysis, pricing mechanisms, and legal mechanisms of their operation. The analysis was carried out on the example of the power industry. The rates of natural monopolies in Georgia are controlled by the Georgian National Energy and Water Supply Regulation Commission. The paper analyzes the positive role and importance of the regulatory body and the issues of improving the legislative base that will support the efficient operation of the branch. Methodology: In order to highlight natural monopolies market tendencies, the domestic and international markets are studied. An analysis of monopolies is carried out based on the endogenous and exogenous factors that determine the condition of companies, as well as the strategies chosen by firms to increase the market share. According to the productivity-based competitiveness assessment scheme, the segmentation opportunities, business environment, resources, and geographical location of monopolist companies are revealed. Main Findings: As a result of the analysis, certain assessments and conclusions were made. Natural monopolies are quite a complex and versatile economic element, and it is important to specify and duly control their frame conditions. It is important to determine the pricing policy of natural monopolies. The rates should be transparent, should show the level of life in the country, and should correspond to the incomes. The analysis confirmed the significance of the role of the Antimonopoly Service in the efficient management of natural monopolies. The law should adapt to reality and should be applied only to regulate the market. The present-day differential electricity tariffs varying depending on the consumed electrical power need revision. The effects of the electricity price discrimination are important, segmentation in different seasons in particular. Consumers use more electricity in winter than in summer, which is associated with extra capacities and maintenance costs. If the price of electricity in winter is higher than in summer, the electricity consumption will decrease in winter. The consumers will start to consume the electricity more economically, what will allow reducing extra capacities. Conclusion: Thus, the practical realization of the views given in the paper will contribute to the efficient operation of natural monopolies. Consequently, their activity will be oriented not on the reduction but on the increase of increments of the consumers or producers. Overall, the optimal management of the given fields will allow for improving the well-being throughout the country. In the article, conclusions are made, and the recommendations are developed to deliver effective policies and regulations toward the natural monopolies in Georgia.Keywords: monopolies, natural monopolies, regulation, antimonopoly service
Procedia PDF Downloads 861237 Evaluation of Green Infrastructure with Different Woody Plants Practice and Benefit Using the Stormwater Management-HYDRUS Model
Authors: Bei Zhang, Zhaoxin Zhang, Lidong Zhao
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Green infrastructures (GIs) for rainwater management can directly meet the multiple purposes of urban greening and non-point source pollution control. To reveal the overall layout law of GIs dominated by typical woody plants and their impact on urban environmental effects, we constructed a HYDRUS-1D and Stormwater management (SWMM) coupling model to simulate the response of typical root woody plant planting methods on urban hydrological. The results showed that the coupling model had high adaptability to the simulation of urban surface runoff control effect under different woody plant planting methods (NSE ≥0.64 and R² ≥ 0.71). The regulation effect on surface runoff showed that the average runoff reduction rate of GIs increased from 60 % to 71 % with the increase of planting area (5% to 25%) under the design rainfall event of the 2-year recurrence interval. Sophora japonica with tap roots was slightly higher than that of without plants (control) and Malus baccata (M. baccata) with fibrous roots. The comprehensive benefit evaluation system of rainwater utilization technology was constructed by using an analytic hierarchy process. The coupling model was used to evaluate the comprehensive benefits of woody plants with different planting areas in the study area in terms of environment, economy, and society. The comprehensive benefit value of planting 15% M. baccata was the highest, which was the first choice for the planting of woody plants in the study area. This study can provide a scientific basis for the decision-making of green facility layouts of woody plants.Keywords: green infrastructure, comprehensive benefits, runoff regulation, woody plant layout, coupling model
Procedia PDF Downloads 691236 Characterization of (GRAS37) Gibberellin Acid Insensitive (GAI), Repressor (RGA), and Scarecrow (SCR) Gene by Using Bioinformatics Tools
Authors: Yusra Tariq
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The Grass 37 gene is presently known in tomatoes, which are the source of healthy substances such as ascorbic acid, polyphenols, carotenoids and nutrients. It has a significant impact on the growth and development of humans. The GRASS 37 gene is a plant Transcription factor group assuming significant parts in various reactions of different Abiotic stresses such as (drought, salinity, thermal stresses, temperature, and bright waves) which could highly affect the growth. Tomatoes are very sensitive to temperature, and their growth or production occurs optimally in a temperature range from 21 C to 29.5 C during the daytime and from 18.5 C to 21 C during the night. This protein acts as a positive regulator of salt stress response and abscisic acid signaling. This study summarizes the structure characterized by molecular formula and protein-binding domains by different bioinformatics tools such as Expasy translate tool, Expasy Portparam, Swiss Prot and Inter Pro Scan, Clustal W tool regulatory procedure of GRASS gene components, also their reactions to both biotic and Abiotic stresses.Keywords: GRAS37, gene, bioinformatics, tool
Procedia PDF Downloads 531235 Structural Design and Environmental Analysis of Oyster Mushroom Cultivation House in Korea
Authors: Lee Sunghyoun, Yu Byeongkee, Kim Hyuckjoo, Yun Namkyu, Jung Jongcheon
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Most of the recent on-sale oyster mushrooms are raised in a oyster mushroom house, in which the necessary adjustment of growing condition is feasible. The rationale for such artificial growing is the impossibility of successive cultivation in the case of a natural cultivation due to external weather conditions. A oyster mushroom house adopts an equipment called growing bed, laying one growing bed upon another in a multi-column fashion, growing and developing the mushrooms on the respective equipments. The indispensable environment management factors of mushroom cultivation are temperature, humidity, and CO2; on which an appropriate regulation of the three requisites is a necessitated condition for the sake of the total output’s increase. However, due to the multiple layers of growing bed’s disturbance on air circulation, a oyster mushroom house’s internal environmental uniformity meets with considerable instability. This research presents a technology which assures the facilitation of environment regulation over all the internal space of a oyster mushroom house, irrespective of its location. The research staff reinforced the oyster mushroom house’s insulation in order to minimize the external environment’s influence on the oyster mushroom house’s internal environment and installed circulation fan to improve the oyster mushroom house’s interior environmental uniformity. Also, the humidifier nozzle’s position was set to prevent dew condensation when humidifying. As a result, a highly sophisticated management over all the oyster mushroom house‘s internal space was realized with the temperature of 0.2~1.3℃, and the relative humidity of 2~7% at the cultivating stage of mushroom’s growth. Therefore, to maximize oyster mushroom house‘s internal environmental uniformity, it can be concluded that consideration of various factors such as insulation reinforcement, decision on the humidifier nozzle’s location, disposition of circulation fan’s installation and the direction of wind discharge is needed.Keywords: mushroom growing facility, environmental uniformity, temperature, relative humidity, CO2 concentration
Procedia PDF Downloads 5311234 Lack of Regulation Leads to Complexity: A Case Study of the Free Range Chicken Meat Sector in the Western Cape, South Africa
Authors: A. Coetzee, C. F. Kelly, E. Even-Zahav
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Dominant approaches to livestock production are harmful to the environment, human health and animal welfare, yet global meat consumption is rising. Sustainable alternative production approaches are therefore urgently required, and ‘free range’ is the main alternative for chicken meat offered in South Africa (and globally). Although the South African Poultry Association provides non-binding guidelines, there is a lack of formal definition and regulation of free range chicken production, meaning it is unclear what this alternative entails and if it is consistently practised (a trend observed globally). The objective of this exploratory qualitative case study is therefore to investigate who and what determines free range chicken. The case study, conducted from a social constructivist worldview, uses semi-structured interviews, photographs and document analysis to collect data. Interviews are conducted with those involved with bringing free range chicken to the market - farmers, chefs, retailers, and regulators. Data is analysed using thematic analysis to establish dominant patterns in the data. The five major themes identified (based on prevalence in data and on achieving the research objective) are: 1) free range means a bird reared with good animal welfare in mind, 2) free range means quality meat, 3) free range means a profitable business, 4) free range is determined by decision makers or by access to markets, and 5) free range is coupled with concerns about the lack of regulation. Unpacking the findings in the context of the literature reveals who and what determines free range. The research uncovers wide-ranging interpretations of ‘free range’, driven by the absence of formal regulation for free range chicken practices and the lack of independent private certification. This means that the term ‘free range’ is socially constructed, thus varied and complex. The case study also shows that whether chicken meat is free range is generally determined by those who have access to markets. Large retailers claim adherence to the internationally recognised Five Freedoms, also include in the South African Poultry Association Code of Good Practice, which others in the sector say are too broad to be meaningful. Producers describe animal welfare concerns as the main driver for how they practice/view free range production, yet these interpretations vary. An additional driver is a focus on human health, which participants achieve mainly through the use of antibiotic-free feed, resulting in what participants regard as higher quality meat. The participants are also strongly driven by business imperatives, with most stating that free range chicken should carry a higher price than conventionally-reared chicken due to increased production costs. Recommendations from this study focus on, inter alia, a need to understand consumers’ perspectives on free range chicken, given that those in the sector claim they are responding to consumer demand, and conducting environmental research such as life cycle assessment studies to establish the true (environmental) sustainability of free range production. At present, it seems the sector mostly responds to social sustainability: human health and animal welfare.Keywords: chicken meat production, free range, socially constructed, sustainability
Procedia PDF Downloads 1571233 Ecological Concerns in Food Systems: An Ethnographical Approach on Vegan Impact in Governmentality
Authors: Jessica Gonzalez
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Veganism, along with different types of vegetarianism, consists in the abstinence of animal products. Far from being only an alimentary regulation, it stands as a political posture against the food industry generating itself a set of beliefs, prohibitions, and attitudes that compel the individual to a reevaluation of his obligations towards the environment. Veganism defends animal rights and at the same time reinforces a different conception of natural resources embodying it in alimentary restrictions. These practices emerge in the context of alimentary modernity, which is characterized by bringing new concerns to the consumer. An increased skepticism towards the government ability to protect food supply; a notable distrust toward the market guaranties on providing safe food with sustainable techniques and the desire to react to the neoliberal forms of exploitation are some of its consequences of this phenomenon. This study aims to approach the concept of governmentality as a coproduced system of legitimized practices and knowledge, formed by the interaction of the different actors that are involved. In a scenario where the State seems to retreat from centralized regulation of food production giving up importance to citizens, dietary consultants, farmers, and stockbreeders, veganism plays its role on the conformation of distinctive forms of environmentalism, nature rights and responses to ecological crisis. The ethnographic method allows observing the mechanisms of interaction of consumers and discourses with the mainstream food system, providing evidence about the means of generation of new conceptions about nature and the environment. The paper focuses on how the dietary restrictions, consumption patterns and public discourses of vegans in Barcelona impact local consumption, demonstrating its relevance as a mechanism that associates particular concerns about food with political economy.Keywords: animal rights, environmentalism, food system, governmentality, veganism
Procedia PDF Downloads 1271232 Transcriptomine: The Nuclear Receptor Signaling Transcriptome Database
Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna
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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.Keywords: target gene database, informatics, gene expression, transcriptomics
Procedia PDF Downloads 2731231 An Integrated Theoretical Framework on Mobile-Assisted Language Learning: User’s Acceptance Behavior
Authors: Gyoomi Kim, Jiyoung Bae
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In the field of language education research, there are not many tries to empirically examine learners’ acceptance behavior and related factors of mobile-assisted language learning (MALL). This study is one of the few attempts to propose an integrated theoretical framework that explains MALL users’ acceptance behavior and potential factors. Constructs from technology acceptance model (TAM) and MALL research are tested in the integrated framework. Based on previous studies, a hypothetical model was developed. Four external variables related to the MALL user’s acceptance behavior were selected: subjective norm, content reliability, interactivity, self-regulation. The model was also composed of four other constructs: two latent variables, perceived ease of use and perceived usefulness, were considered as cognitive constructs; attitude toward MALL as an affective construct; behavioral intention to use MALL as a behavioral construct. The participants were 438 undergraduate students who enrolled in an intensive English program at one university in Korea. This particular program was held in January 2018 using the vacation period. The students were given eight hours of English classes each day from Monday to Friday for four weeks and asked to complete MALL courses for practice outside the classroom. Therefore, all participants experienced blended MALL environment. The instrument was a self-response questionnaire, and each construct was measured by five questions. Once the questionnaire was developed, it was distributed to the participants at the final ceremony of the intensive program in order to collect the data from a large number of the participants at a time. The data showed significant evidence to support the hypothetical model. The results confirmed through structural equation modeling analysis are as follows: First, four external variables such as subjective norm, content reliability, interactivity, and self-regulation significantly affected perceived ease of use. Second, subjective norm, content reliability, self-regulation, perceived ease of use significantly affected perceived usefulness. Third, perceived usefulness and perceived ease of use significantly affected attitude toward MALL. Fourth, attitude toward MALL and perceived usefulness significantly affected behavioral intention to use MALL. These results implied that the integrated framework from TAM and MALL could be useful when adopting MALL environment to university students or adult English learners. Key constructs except interactivity showed significant relationships with one another and had direct and indirect impacts on MALL user’s acceptance behavior. Therefore, the constructs and validated metrics is valuable for language researchers and educators who are interested in MALL.Keywords: blended MALL, learner factors/variables, mobile-assisted language learning, MALL, technology acceptance model, TAM, theoretical framework
Procedia PDF Downloads 2381230 The Results of Reading Test on Movement Staff Notation System
Authors: Sonay Ödemiş
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Movement Staff Notation System (MSNS) is a movement transcription, analyzing method, and it's been constantly improved since it was first developed in 2005. This method is based on human anatomy, is being used and applied in the lessons at The Department of Turkish Folk Dances in Istanbul Technical University, nowadays. In this research, it is aimed to discover, how MSNS can help to participants about learning the basic movements of lower extremity. This experiment has six volunteers who were randomly selected. Each volunteer has been graded for their dance backgrounds and all the volunteers have been studied for six weeks. Each week has included different topic and examples such as contacts on foot, jumps, timing, directions and basic symbols of MSNS. Examples have changed from easy to hard. On conclusion, 6 volunteer subjects were tested in final test. The tests were recorded with the camera. In this presentation, it will be explained and detailed the results of the reading test on MSNS. Some of important video records will be watched and interpreted after the test. As a conclusion, all the scores will be interpreted and assessed from different perspectives.Keywords: dance notation, Turkish dances, reading test, Education
Procedia PDF Downloads 2331229 Studying the Antiapoptotic Activity of Β Cells from Cord Blood Based Mesenchymal Stem Cells as an Approach to Treat Diabetes Mellitus
Authors: Parcha Sreenivasa Rao, P. Lakshmi
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Diabetes Mellitus is metabolic disorder, characterized by high glucose levels in the blood due to one of the reason i.e., the death of β cells. The lack of β cells leads to the reduced insulin levels. The β cell death generally occurs due to apoptosis induced by the several cytokines. IL-1β, IFN- ϒ and TNF –α cytokines that are generally cause apoptosis to the β cell. The nutrient based apoptosis is generally seen with high glucose and free fatty acids. It is also noted that the β cell death triggered by Fas ligand and its receptor Fas at the surface of the activated CD8+ T- lymphocytes. Reports also reveal that the β cell apoptosis is under control of the transcription factors NF-kB and STAT- 1. The arresting or opposing of the β cell apoptosis can be overcome by the different growth factors like GLP-1, growth hormone, prolactin, VEGF, Dipeptidyl peptidase-4, Vildagliptin, suberoylanilidehydroxamic acid, trichistatin-A, XIAP, Bcl-2, FGF-21. Present investigation explains antiapoptotic property of the β cells derived from the mesenchymal stem cells of umbilical cord.Keywords: stem cells, umblical cord, diabetes, apoptosis
Procedia PDF Downloads 3801228 Cancer Stem Cell-Associated Serum Proteins Obtained by Maldi TOF/TOF Mass Spectrometry in Women with Triple-Negative Breast Cancer
Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso
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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells
Procedia PDF Downloads 2151227 The Immunology Evolutionary Relationship between Signal Transducer and Activator of Transcription Genes from Three Different Shrimp Species in Response to White Spot Syndrome Virus Infection
Authors: T. C. C. Soo, S. Bhassu
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Unlike the common presence of both innate and adaptive immunity in vertebrates, crustaceans, in particular, shrimps, have been discovered to possess only innate immunity. This further emphasizes the importance of innate immunity within shrimps in pathogenic resistance. Under the study of pathogenic immune challenge, different shrimp species actually exhibit varying degrees of immune resistance towards the same pathogen. Furthermore, even within the same shrimp species, different batches of challenged shrimps can have different strengths of immune defence. Several important pathways are activated within shrimps during pathogenic infection. One of them is JAK-STAT pathway that is activated during bacterial, viral and fungal infections by which STAT(Signal Transducer and Activator of Transcription) gene is the core element of the pathway. Based on theory of Central Dogma, the genomic information is transmitted in the order of DNA, RNA and protein. This study is focused in uncovering the important evolutionary patterns present within the DNA (non-coding region) and RNA (coding region). The three shrimp species involved are Macrobrachium rosenbergii, Penaeus monodon and Litopenaeus vannamei which all possess commercial significance. The shrimp species were challenged with a famous penaeid shrimp virus called white spot syndrome virus (WSSV) which can cause serious lethality. Tissue samples were collected during time intervals of 0h, 3h, 6h, 12h, 24h, 36h and 48h. The DNA and RNA samples were then extracted using conventional kits from the hepatopancreas tissue samples. PCR technique together with designed STAT gene conserved primers were utilized for identification of the STAT coding sequences using RNA-converted cDNA samples and subsequent characterization using various bioinformatics approaches including Ramachandran plot, ProtParam and SWISS-MODEL. The varying levels of immune STAT gene activation for the three shrimp species during WSSV infection were confirmed using qRT-PCR technique. For one sample, three biological replicates with three technical replicates each were used for qRT-PCR. On the other hand, DNA samples were important for uncovering the structural variations within the genomic region of STAT gene which would greatly assist in understanding the STAT protein functional variations. The partially-overlapping primers technique was used for the genomic region sequencing. The evolutionary inferences and event predictions were then conducted through the Bayesian Inference method using all the acquired coding and non-coding sequences. This was supplemented by the construction of conventional phylogenetic trees using Maximum likelihood method. The results showed that adaptive evolution caused STAT gene sequence mutations between different shrimp species which led to evolutionary divergence event. Subsequently, the divergent sites were correlated to the differing expressions of STAT gene. Ultimately, this study assists in knowing the shrimp species innate immune variability and selection of disease resistant shrimps for breeding purpose. The deeper understanding of STAT gene evolution from the perspective of both purifying and adaptive approaches not only can provide better immunological insight among shrimp species, but also can be used as a good reference for immunological studies in humans or other model organisms.Keywords: gene evolution, JAK-STAT pathway, immunology, STAT gene
Procedia PDF Downloads 1501226 New Isolate of Cucumber Mosaic Virus Infecting Banana
Authors: Abdelsabour G. A. Khaled, Ahmed W. A. Abdalla And Sabry Y. M. Mahmoud
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Banana plants showing typical mosaic and yellow stripes on leaves as symptoms were collected from Assiut Governorate in Egypt. The causal agent was identified as Cucumber mosaic virus (CMV) on the basis of symptoms, transmission, serology, transmission electron microscopy and reverse transcription polymerase chain reaction (RT-PCR). Coat protein (CP) gene was amplified using gene specific primers for coat protein (CP), followed by cloning into desired cloning vector for sequencing. In this study the CMV was transmitted into propagation host either by aphid or mechanically. The transmission was confirmed through Direct Antigen Coating Enzyme Linked Immuno Sorbent Assay (DAC-ELISA). Analysis of the 120 deduced amino acid sequence of the coat protein gene revealed that the EG-A strain of CMV shared from 97.50 to 98.33% with those strains belonging to subgroup IA. The cluster analysis grouped the Egyptian isolate with strains Fny and Ri8 belonging sub-group IA. It appears that there occurs a high incidence of CMV infecting banana belonging to IA subgroup in most parts of Egypt.Keywords: banana, CMV, transmission, CP gene, RT-PCR
Procedia PDF Downloads 3411225 Circadian-Clock Controlled Drug Transport Across Blood-Cerebrospinal Fluid Barrier
Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela
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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy
Procedia PDF Downloads 131224 mRNA Expression of NFKB1 with Parkinson's Disease
Authors: Ali Bayram, Burak Uz, Remzi Yiğiter
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The aim of the present study was to investigate the expression levels of homo sapiens nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, transcript variant 1 (NFKB1*1) mRNA in the peripheral blood of patients with Parkinson to elucidate the role in the pathogenesis of Parkinson disease (PD). The study group comprised 50 patients with the diagnosis of PD who have applied to Gaziantep University Faculty of Medicine, and Department of Neurology. 50 healthy individuals without any neuro degenerative disease are included as controls. Ribonucleic acid (RNA) was obtained from blood samples of patient and control groups. Complementary deoxyribonucleic acid (cDNA) was obtained from RNA samples using reverse transcription polymerase chain reaction (RT-PCR) technique. The gene expression of NFKB1*1 in patient/control groups were observed to decrease significantly, and the differences between groups with the Mann-Whitney method within 95% confidence interval (p<0.05) were analyzed. This salient finding provide a clue for our hypothesis that reduced activity of NFKB1*1 gene might play a role, at least partly, in the pathophysiology of PD.Keywords: Parkinson’s Disease, NFKB1, mRNA expression, RT-PCR
Procedia PDF Downloads 5021223 Pharmacological Mechanisms of an Indolic Compound in Chemoprevention of Colonic Acf Formation in Azoxymethane-Induced Colon Cancer Rat Model and Cell Lines
Authors: Nima Samie, Sekaran Muniandy, Zahurin Mohamed, M. S. Kanthimathi
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Although number of indole containing compounds have been reported to have anticancer properties in vitro but only a few of them show potential as anticancer compounds in vivo. The current study was to evaluate the mechanism of cytotoxicity of selected indolic compound in vivo and in vitro. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, human monocyte/macrophage CRL-9855, and B lymphocyte CCL-156 cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content, measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results displayed a potent suppressive effect on HT-29 and WiDr after 24 h of treatment with IC50 value of 2.52±0.34 µg/ml and 2.13±0.65 µg/ml respectively. This cytotoxic effect on normal, monocyte/macrophage and B-cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the compound. Activation of this pathway was further evidenced by significant activation of caspase-9 and 3/7. The compound was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. These findings were further investigated for inhibitory efficiency of the compound on colonic aberrant crypt foci in male rats. Rats were divided in to 5 groups: vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of compounds for 10 weeks. Administration of compound suppressed total colonic ACF formation up to 73.4%. The results also showed that treatment with the compound significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. The outcome of this study suggest sthat the indolic compound is a potent anti-cancer agent against colon cancer and can be further evaluated by animal trial.Keywords: indolic compound, chemoprevention, crypt, azoxymethane, colon cancer
Procedia PDF Downloads 3481222 Coumestrol Induced Apoptosis in Breast Cancer MCF-7 Cells via Redox Cycling of Copper and ROS Generation: Implications of Copper Chelation Strategy in Cancer Treatment
Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem
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Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling
Procedia PDF Downloads 2451221 The Role of Cholesterol Oxidase of Mycobacterium tuberculosis in the Down-Regulation of TLR2-Signaling Pathway in Human Macrophages during Infection Process
Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink
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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, PolandKeywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway
Procedia PDF Downloads 4191220 The Mechanical and Comfort Properties of Cotton/Micro-Tencel Lawn Fabrics
Authors: Abdul Basit, Shahid Latif, Shah Mehmood
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Lawn fabric was usually prepared from originally of linen but at present chiefly cotton. Lawn fabric is worn in summer. Cotton Lawn is a lightweight pure cloth which is heavier than voile. It is so fine that it is somewhat transparent. It is soft and superb to wear thus it is perfect for summer clothes or for regular wear in hotter climates. Tencel (Lyocell) fiber is considered as the fiber of the future as Tencel fibers are absorbent, soft, and extremely strong when wet or dry, and resistant to wrinkles. Fibers are more absorbent than cotton, softer than silk and cooler than linen. High water absorption and water vapor absorption give more heat capacity and heat balancing effect for thermo-regulation. This thermo-regulation is analogous with the action of phase-change-materials. The thermal wear properties result in cool and dry touch that gives cooling effect in sportswear, and the warmth properties (when used as an insulation layer). These cooling and warming effects are adaptive to the environment giving comfort in a broad range of climatic conditions. In this work, single yarns of Ne 80s were made. Yarns were made from conventional ring spinning. Different yarns of 100% cotton, 100% micro-Tencel and Cotton:micro-Tencel blends (67:33, 50:50:33:67) were made. The mechanical and comfort properties of the woven fabrics were compared. The mechanical properties include the tensile and tear strength, bending length, pilling and abrasion resistance whereas comfort properties include the air permeability, moisture management and thermal resistance. It is found that as the content of the micro-Tencel is increased, the mechanical and comfort properties of the woven fabric are also increased.Keywords: combed cotton, comfort properties , mechanical properties, micro-Tencel
Procedia PDF Downloads 3161219 Effects of a School-Based Mindfulness Intervention on Stress and Emotions on Students Enrolled in an Independent School
Authors: Tracie Catlett
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Students enrolled in high-achieving schools are under tremendous pressure to perform at high levels inside and outside the classroom. Achievement pressure is a prevalent source of stress for students enrolled in high-achieving schools, and female students in particular experience a higher frequency and higher levels of stress compared to their male peers. The practice of mindfulness in a school setting is one tool that has been linked to improved self-regulation of emotions, increased positive emotions, and stress reduction. A mixed methods randomized pretest-posttest no-treatment control trial, evaluated the effects of a six-session mindfulness intervention taught during a regularly scheduled life skills period in an independent day school, one type of high-achieving school. Twenty-nine students in Grades 10 and 11 were randomized by class where Grade 11 students were in the intervention group (n = 14) and Grade 10 students were in the control group (n = 15). Findings from the study produced mixed results. There was no evidence that the mindfulness program reduced participants’ stress levels and negative emotions. In fact, contrary to what was expected, students enrolled in the intervention group experienced higher levels of stress and increased negative emotions at posttreatment when compared to pretreatment. Neither the within-group nor the between-groups changes in stress level were statistically significant, p > .05, and the between-groups effect size was small, d = .2. The study found evidence that the mindfulness program may have had a positive impact on students’ ability to regulate their emotions. The within-group comparison and the between-groups comparison at posttreatment found that students in the mindfulness course experienced statistically significant improvement in the in their ability to regulate their emotions at posttreatment, p = .009 < .05 and p =. 034 < .05, respectively. The between-groups effect size was medium, d =.7, suggesting that the positive differences in emotion regulation difficulties were substantial and have practical implications. The analysis of gender differences as they relate to stress and emotions revealed that female students perceive higher levels of stress and report experiencing stress more often than males. There were no gender differences when analyzing sources of stress experienced by the student participants. Both females and males experience regular achievement pressures related to their school performance and worry about their future, college acceptance, grades, and parental expectations. Females reported an increased awareness of their stress and actively engaged in practicing mindfulness to manage their stress. Students in the treatment group expressed that the practice of mindfulness resulted in feelings of relaxation and calmness.Keywords: achievement pressure, adolescents, emotion regulation, emotions, high-achieving schools, independent schools, mindfulness, negative affect, positive affect, stress
Procedia PDF Downloads 711218 Workers’ Prevention from Occupational Chemical Exposures during Container Handling
Authors: Balázs Ádám, Randi Nørgaard Fløe Pedersen, Jørgen Riis Jepsen
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Volatile chemicals that accumulate and release from freight containers constitute significant health risks. Fumigation to prevent spread of pests and off-gassing of freight are sources of hazardous chemicals. The aim of our study was to investigate the regulation and practice of container handling with focus on preventive measures applied against chemical exposures in Denmark. A comprehensive systematic search of scientific literature and organizational domains of international and Danish regulatory bodies was performed to explore regulations related to safe work with transport containers. The practice of container work was investigated in a series of semi-structured interviews with managers and health and safety representatives of organizations that handle transport containers. Although there are several international and national regulations and local safety instructions that relate to container handling, the provided information is not specific or up-to-date enough to conduct safe practice in many aspects. The interviewees estimate high frequency of containers with chemical exposure and deem that they can potentially damage health, although recognizable health effects are rare. Knowledge is limited about the chemicals and most of them cannot be measured by available devices. Typical preventive measures are passive ventilation and personal protective equipment but their use is not consistent and may not provide adequate protection. Hazardous chemicals are frequently present in transport containers; however, managers, workers and even occupational health professionals have limited knowledge about the problem. Detailed risk assessment and specific instructions on risk management are needed to provide safe conditions for work with containers.Keywords: chemical exposure, fumigation, occupational health and safety regulation, transport container
Procedia PDF Downloads 3811217 High-Throughput, Purification-Free, Multiplexed Profiling of Circulating miRNA for Discovery, Validation, and Diagnostics
Authors: J. Hidalgo de Quintana, I. Stoner, M. Tackett, G. Doran, C. Rafferty, A. Windemuth, J. Tytell, D. Pregibon
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We have developed the Multiplexed Circulating microRNA assay that allows the detection of up to 68 microRNA targets per sample. The assay combines particlebased multiplexing, using patented Firefly hydrogel particles, with single step RT-PCR signal. Thus, the Circulating microRNA assay leverages PCR sensitivity while eliminating the need for separate reverse transcription reactions and mitigating amplification biases introduced by target-specific qPCR. Furthermore, the ability to multiplex targets in each well eliminates the need to split valuable samples into multiple reactions. Results from the Circulating microRNA assay are interpreted using Firefly Analysis Workbench, which allows visualization, normalization, and export of experimental data. To aid discovery and validation of biomarkers, we have generated fixed panels for Oncology, Cardiology, Neurology, Immunology, and Liver Toxicology. Here we present the data from several studies investigating circulating and tumor microRNA, showcasing the ability of the technology to sensitively and specifically detect microRNA biomarker signatures from fluid specimens.Keywords: biomarkers, biofluids, miRNA, photolithography, flowcytometry
Procedia PDF Downloads 3691216 Role of Long Noncoding RNA HULC on Colorectal Carcinoma Progression through Epigenetically Repressing NKD2 Expression
Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li
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Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis
Procedia PDF Downloads 2251215 Services-Oriented Model for the Regulation of Learning
Authors: Mohamed Bendahmane, Brahim Elfalaki, Mohammed Benattou
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One of the major sources of learners' professional difficulties is their heterogeneity. Whether on cognitive, social, cultural or emotional level, learners being part of the same group have many differences. These differences do not allow to apply the same learning process at all learners. Thus, an optimal learning path for one, is not necessarily the same for the other. We present in this paper a model-oriented service to offer to each learner a personalized learning path to acquire the targeted skills.Keywords: learning path, web service, trace analysis, personalization
Procedia PDF Downloads 3561214 Morphology and Permeability of Biomimetic Cellulose Triacetate-Impregnated Membranes: in situ Synchrotron Imaging and Experimental Studies
Authors: Amira Abdelrasoul
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This study aimed to ascertain the controlled permeability of biomimetic cellulose triacetate (CTA) membranes by investigating the electrical oscillatory behavior across impregnated membranes (IM). The biomimetic CTA membranes were infused with a fatty acid to induce electrical oscillatory behavior and, hence, to ensure controlled permeability. In situ synchrotron radiation micro-computed tomography (SR-μCT) at the BioMedical Imaging and Therapy (BMIT) Beamline at the Canadian Light Source (CLS) was used to evaluate the main morphology of IMs compared to neat CTA membranes to ensure fatty acid impregnation inside the pores of the membrane matrices. A monochromatic beam at 20 keV was used for the visualization of the morphology of the membrane. The X-ray radiographs were recorded by means of a beam monitor AA-40 (500 μm LuAG scintillator, Hamamatsu, Japan) coupled with a high-resolution camera, providing a pixel size of 5.5 μm and a field of view (FOV) of 4.4 mm × 2.2 mm. Changes were evident in the phase transition temperatures of the impregnated CTA membrane at the melting temperature of the fatty acid. The pulsations of measured voltages were related to changes in the salt concentration of KCl in the vicinity of the electrode. Amplitudes and frequencies of voltage pulsations were dependent on the temperature and concentration of the KCl solution, which controlled the permeability of the biomimetic membranes. The presented smart biomimetic membrane successfully combined porous polymer support and impregnating liquid not only imitate the main barrier properties of the biological membranes but could be easily modified to achieve some new properties, such as facilitated and active transport, regulation by chemical, physical and pharmaceutical factors. These results open new frontiers for the facilitation and regulation of active transport and permeability through biomimetic smart membranes for a variety of biomedical and drug delivery applications.Keywords: biomimetic, membrane, synchrotron, permeability, morphology
Procedia PDF Downloads 1011213 Taking What Each Needs - The Basic Logic of Everyday Practice in State-backed Cultural Infrastructure in China
Authors: Yiling Shao, Megan Dai
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This paper attempts to explore whether the cultural infrastructure supported by the Chinese government is still subject to a logic of “strict regulation”.Previous studies have pointed out that the "paternalism" tendency of China's cultural policy always leads to excessive government intervention in cultural development, while Chinese cultural practitioners can only seek cultural autonomy in the cracks of supervision. This can also explain why Chinese cultural policies sometimes have different effects than the official expectations.But this only reflects one aspect of China's cultural policy. In fact, the welfare cultural infrastructure funded by the government seems to highlight the principles of "safeguarding citizens' cultural rights" and "citizens' voluntary" rather than "indoctrination" and "enlightenment", What new features of China's cultural policy are reflected behind this policy orientation that is completely different from the logic of "regulation", which has also become an important issue in this paper. Based on the field survey of a cultural infrastructure (Gao ming District Cultural Center) in Gao ming District, Fo shan City, Guangdong Province, China, for nearly one year, the authors have obtained many text and picture materials.The paper discusses the dual role of cultural centers in China's cultural policy -both as a formal commitment by the state to protect citizens' basic cultural rights and as a social space for citizens to use preferential policies to obtain cultural capital. All in all, the author have conclued three operational logics of the cultural infrastructure currently supported by the Chinese government (at least in developed areas): first, the cultural center has become a versatile cultural space; second, grass-roots cultural cadres can be described as "policy entrepreneurs"; third, ordinary citizens will use the officially supported cultural infrastructure to increase cultural capital. This paper argues that, in comparison to the common “regulatory hand” in the field of cultural industries, in cultural infrastructure supported by state, the authorities and citizens are not in conflict. On the contrary, authorities must adopt a de-regulatory "pleasing" strategy to gain the support of citizens.Keywords: cultural infrastructure, cultural capital, deregulation, policy entrepreneur
Procedia PDF Downloads 971212 Efficient Sampling of Probabilistic Program for Biological Systems
Authors: Keerthi S. Shetty, Annappa Basava
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In recent years, modelling of biological systems represented by biochemical reactions has become increasingly important in Systems Biology. Biological systems represented by biochemical reactions are highly stochastic in nature. Probabilistic model is often used to describe such systems. One of the main challenges in Systems biology is to combine absolute experimental data into probabilistic model. This challenge arises because (1) some molecules may be present in relatively small quantities, (2) there is a switching between individual elements present in the system, and (3) the process is inherently stochastic on the level at which observations are made. In this paper, we describe a novel idea of combining absolute experimental data into probabilistic model using tool R2. Through a case study of the Transcription Process in Prokaryotes we explain how biological systems can be written as probabilistic program to combine experimental data into the model. The model developed is then analysed in terms of intrinsic noise and exact sampling of switching times between individual elements in the system. We have mainly concentrated on inferring number of genes in ON and OFF states from experimental data.Keywords: systems biology, probabilistic model, inference, biology, model
Procedia PDF Downloads 3491211 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease
Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian
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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK
Procedia PDF Downloads 3041210 Calycosin Ameliorates Osteoarthritis by Regulating the Imbalance Between Chondrocyte Synthesis and Catabolism
Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao
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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2
Procedia PDF Downloads 1021209 African Personhood and the Regulation of Brain-Computer Interface (BCI) Technologies: A South African view
Authors: Meshandren Naidoo, Amy Gooden
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Implantable brain-computer interface (BCI) technologies have developed to the point where brain-computer communication is possible. This has great potential in the medical field, as it allows persons who have lost capacities. However, ethicists and regulators call for a strict approach to these technologies due to the impact on personhood. This research demonstrates that the personhood debate is more nuanced and that where an African approach to personhood is used, it may produce results more favorable to the development and use of this technology.Keywords: artificial intelligence, law, neuroscience, ethics
Procedia PDF Downloads 131