Search results for: decentred regulation
523 Carbon Based Classification of Aquaporin Proteins: A New Proposal
Authors: Parul Johri, Mala Trivedi
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Major Intrinsic proteins (MIPs), actively involved in the passive transport of small polar molecules across the membranes of almost all living organisms. MIPs that specifically transport water molecules are named aquaporins (AQPs). The permeability of membranes is actively controlled by the regulation of the amount of different MIPs present but also in some cases by phosphorylation and dephosphorylation of the channel. Based on sequence similarity, MIPs have been classified into many categories. All of the proteins are made up of the 20 amino acids, the only difference is there in their orientations. Again all the 20 amino acids are made up of the basic five elements namely: carbon, hydrogen, oxygen, sulphur and nitrogen. These elements are responsible for giving the amino acids the properties of hydrophilicity/hydrophobicity which play an important role in protein interactions. The hydrophobic amino acids characteristically have greater number of carbon atoms as carbon is the main element which contributes to hydrophobic interactions in proteins. It is observed that the carbon level of proteins in different species is different. In the present work, we have taken a sample set of 150 aquaporins proteins from Uniprot database and a dynamic programming code was written to calculate the carbon percentage for each sequence. This carbon percentage was further used to barcode the aqauporins of animals and plants. The protein taken from Oryza sativa, Zea mays and Arabidopsis thaliana preferred to have carbon percentage of 31.8 to 35, whereas on the other hand sequences taken from Mus musculus, Saccharomyces cerevisiae, Homo sapiens, Bos Taurus, and Rattus norvegicus preferred to have carbon percentage of 31 to 33.7. This clearly demarks the carbon range in the aquaporin proteins from plant and animal origin. Hence the atom level analysis of protein sequences can provide us with better results as compared to the residue level comparison.Keywords: aquaporins, carbon, dynamic prgramming, MIPs
Procedia PDF Downloads 361522 The Severity of Electric Bicycle Injuries Compared to Classic Bicycle Injuries in Children: A Retrospective Review
Authors: Tali Capua, Karin Hermon, Miguel Glatstein, Oren Tavor, Ayelet Rimon
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Background: Electric bicycles (E-bikes) are one of a wide range of light electric vehicles that provide convenient local transportation and attractive recreational opportunities. Along with their growing use worldwide, the E-bike related injury rate increases. To the best of our knowledge, this study is the first to specifically compare E-bike with classic bicycle related injuries in children. Methods: Data of all pediatric ( < 16 years of age) bicycle related injuries presenting to an urban level I trauma center between 2014 and 2015 were collected and analyzed. The recorded data included age, gender, details of the accident, as well severity of injury, medical diagnosis, and the outcome. Abbreviated Injury Score (AIS) and Injury Severity Score (ISS) were calculated for each patient. Data of E-bike related injuries and classic bicycle were then compared. Results: A total of 124 bicycle related injuries and 97 E-bike related injuries presented to the emergency department. Once pedestrians and bicycle passengers were removed, the groups of riders consisted of 111 bikers and 85 E-bikers. The mean age of bikers was 9.9 years (range 3-16 years) and of E-bikers was 13.7 years (range 7.5-16 years). Injuries to the head and the extremities were common in both groups. Compared to bikers, E-bikers had significantly more injuries to intra-abdominal organs (p = 0.04). Twenty patients (16%) with bicycle related injuries were admitted, and 13 (15%) patients with E-bike related injuries, of the latter group four underwent surgical intervention. ISS scores were low overall, but the injuries of higher severity (ISS > 9) were among the E-bikers. Conclusions: This study provides unique information which suggests that injuries in E-bikers tend to be more severe than in classic bikers. There is a need for regulation regarding the use of E-bikes to enhance the safety of both bikers and other road and pavement users.Keywords: bicycle, electric bicycle, injury, pediatric, trauma
Procedia PDF Downloads 177521 Study on the Effect of Different Media on Green Roof Water Retention
Authors: Chen Zhi-Wei, Hsieh Wei-Fang
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Taiwan annual rainfall is global average of 2.5 times, plus city excessive development, green constantly to reduced, instead of is big area of artificial base disc, makes Taiwan rainy season during occurred of storm cannot timely of emissions, led to flood constantly, and rain also cannot was retained again using, led to city hydrological balance suffered damage, and to Regulation city of by brings of negative effect, increased green covered rate became most effective of method, and city land limited, so roof green gradually became a alternative program. Green roofs have become one of the Central and local government policy initiatives for urban development, in foreign countries, such as the United States, and Japan, and Singapore etc. Development of roof greening as an important policy, has become a trend of the times. In recent years, many experts and scholars are also on the roof greening all aspects of research, mostly for green roof for the environmental impact of benefits, such as: carbon reduction, cooling, thermostat, but research on the benefits of green roofs under water cut but it is rare. Therefore, this research literature from green roof in to view and analyze what kind of medium suitable for roof greening and use of green base plate combination simulated green roof structure, via different proportions of the medium with water retention plate and drainage board, experiment with different planting base plate combination of water conservation performance. Research will want to test the effect of roof planting base mix, promotion of relevant departments and agencies in future implementation of green roofs, prompted the development of green roofs, which in the end Taiwan achieve sustainable development of the urban environment help.Keywords: thin-layer roof greening and planting medium, water efficiency
Procedia PDF Downloads 342520 Assessing Significance of Correlation with Binomial Distribution
Authors: Vijay Kumar Singh, Pooja Kushwaha, Prabhat Ranjan, Krishna Kumar Ojha, Jitendra Kumar
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Present day high-throughput genomic technologies, NGS/microarrays, are producing large volume of data that require improved analysis methods to make sense of the data. The correlation between genes and samples has been regularly used to gain insight into many biological phenomena including, but not limited to, co-expression/co-regulation, gene regulatory networks, clustering and pattern identification. However, presence of outliers and violation of assumptions underlying Pearson correlation is frequent and may distort the actual correlation between the genes and lead to spurious conclusions. Here, we report a method to measure the strength of association between genes. The method assumes that the expression values of a gene are Bernoulli random variables whose outcome depends on the sample being probed. The method considers the two genes as uncorrelated if the number of sample with same outcome for both the genes (Ns) is equal to certainly expected number (Es). The extent of correlation depends on how far Ns can deviate from the Es. The method does not assume normality for the parent population, fairly unaffected by the presence of outliers, can be applied to qualitative data and it uses the binomial distribution to assess the significance of association. At this stage, we would not claim about the superiority of the method over other existing correlation methods, but our method could be another way of calculating correlation in addition to existing methods. The method uses binomial distribution, which has not been used until yet, to assess the significance of association between two variables. We are evaluating the performance of our method on NGS/microarray data, which is noisy and pierce by the outliers, to see if our method can differentiate between spurious and actual correlation. While working with the method, it has not escaped our notice that the method could also be generalized to measure the association of more than two variables which has been proven difficult with the existing methods.Keywords: binomial distribution, correlation, microarray, outliers, transcriptome
Procedia PDF Downloads 405519 Anti-Phosphorylcholine T Cell Dependent Antibody
Authors: M. M. Rahman, A. Liu, A. Frostegard, J. Frostegard
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The human immune system plays an essential role in cardiovascular disease (CVD) and atherosclerosis. Our earlier studies showed that major immunocompetent cells including T cells are activated by phosphorylcholine epitope. Further, we have determined for the first time in a clinical cohort that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with the development of atherosclerosis and thus a low risk of cardiovascular diseases. It is still unknown whether activated T cells play a role in anti-PC production. Here we aim to clarify the role of T cells in anti-PC production. B cell alone, or with CD3 T, CD4 T or with CD8 T cells were cultured in polystyrene plates to examine anti-PC IgM production. In addition to mixed B cell with CD3 T cell culture, B cells with CD3 T cells were also cultured in transwell co-culture plates. Further, B cells alone and mixed B cell with CD3 T cell cultures with or without anti-HLA 2 antibody were cultured for 6 days. Anti-PC IgM was detected by ELISA in independent experiments. More than 8 fold higher levels of anti-PC IgM were detected by ELISA in mixed B cell with CD3 T cell cultures in comparison to B cells alone. After the co-culture of B and CD3 T cells in transwell plates, there were no increased antibody levels indicating that B and T cells need to interact to augment anti-PC IgM production. Furthermore, anti-PC IgM was abolished by anti-HLA 2 blocking antibody in mixed B and CD3 T cells culture. In addition, the lack of increased anti-PC IgM in mixed B with CD8 T cells culture and the increased levels of anti-PC in mixed B with CD4 T cells culture support the role of helper T cell for the anti-PC IgM production. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC IgM is a protection marker for atherosclerosis development. Understanding the mechanism involved in the anti-PC IgM regulation could play an important role in strategies to raise anti-PC IgM. Studies suggest that anti-PC is T-cell independent antibody, but our study shows the major role of T cell in anti-PC IgM production. Activation of helper T cells by immunization could be a possible mechanism for raising anti-PC levels.Keywords: anti-PC, atherosclerosis, aardiovascular diseases, phosphorylcholine
Procedia PDF Downloads 335518 The Sustainable Governance of Aquifer Injection Using Treated Coal Seam Gas Water in Queensland, Australia: Lessons for Integrated Water Resource Management
Authors: Jacqui Robertson
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The sustainable governance of groundwater is of the utmost importance in an arid country like Australia. Groundwater has been relied on by our agricultural and pastoral communities since the State was settled by European colonialists. Nevertheless, the rapid establishment of a coal seam gas (CSG) industry in Queensland, Australia, has had extensive impacts on the pre-existing groundwater users. Managed aquifer recharge of important aquifers in Queensland, Australia, using treated coal seam gas produced water has been used to reduce the impacts of CSG development in Queensland Australia. However, the process has not been widely adopted. Negative environmental outcomes are now acknowledged as not only engineering, scientific or technical problems to be solved but also the result of governance failures. An analysis of the regulatory context for aquifer injection using treated CSG water in Queensland, Australia, using Ostrom’s Common Pool Resource (CPR) theory and a ‘heat map’ designed by the author, highlights the importance of governance arrangements. The analysis reveals the costs and benefits for relevant stakeholders of artificial recharge of groundwater resources in this context. The research also reveals missed opportunities to further active management of the aquifer and resolve existing conflicts between users. The research illustrates the importance of strategically and holistically evaluating innovations in technology that impact water resources to reveal incentives that impact resource user behaviors. The paper presents a proactive step that can be adapted to support integrated water resource management and sustainable groundwater development.Keywords: managed aquifer recharge, groundwater regulation, common-pool resources, integrated water resource management, Australia
Procedia PDF Downloads 224517 Oxidosqualene Cyclase: A Novel Inhibitor
Authors: Devadrita Dey Sarkar
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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.Keywords: anticholesteraemic, crystallization, statins, homeostasis
Procedia PDF Downloads 344516 Ghrelin, Obestatin and Ghrelin/Obestatin Ratio: A Postprandial Study in Healthy Subjects of Normal Weight
Authors: Panagiotis T. Kanellos, Vaios T. Karathanos, Andriana C. Kaliora
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Introduction: The role of ghrelin and obestatin in appetite regulation has been investigated. However, data on ghrelin and obestatin changes after food ingestion are negligible. Objective: We aimed at assessing the appetite-regulating hormones, ghrelin, and obestatin, and furthermore calculate ghrelin/obestatin ratio in healthy normal-weight subjects after consumption of raisins. This survey is a comparative study of a glucose control with raisins containing fructose and glucose in similar concentrations as well as fibers. Methodology: Ten apparently healthy subjects who reported no history of glucose intolerance, diabetes, gastrointestinal disorders, or recent use of any antibiotics were enrolled in the study. The raisins used (Vitis vinifera) originate in Greece and are distributed worldwide as Corinthian raisins. In a randomized crossover design, all subjects after an overnight fast consumed, either 50g of glucose diluted in 240 mL of water (control) or 74 g of raisins (sugar content 50 g) with a 5-day interval between individual trials. Vein blood samples were collected at baseline and at 60, 120 and 180 min postprandially. In blood samples ghrelin and obestatin were measured applying specific enzyme linked immuno absorbent assays. Results: The subjects were of mean age 26.3 years, with BMI of 21.6 kg/m2, waist circumference of 77.7 cm, normal serum lipidemic parameters and normal HbA1c levels. Ghrelin levels were significantly lower after raisin consumption compared to glucose at 120 and at 180 min post-ingestion (p= 0.011 and p= 0.035, respectively). However, obestatin did not reach statistical significance between the two interventions. The ghrelin/obestatin ratio was found significantly lower (p=0.020) at 120 min after raisin ingestion compared to control. Conclusion: Two isocaloric foods containing equal amounts of sugars, however with a different composition, have different effects on appetite hormones ghrelin and obestatin in normal-weight healthy subjects.Keywords: appetite, ghrelin, obestatin, raisins
Procedia PDF Downloads 391515 Infused Mesenchymal Stem Cells Ameliorate Organs Morphology in Cerebral Malaria Infection
Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das
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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death
Procedia PDF Downloads 100514 A Framework for Auditing Multilevel Models Using Explainability Methods
Authors: Debarati Bhaumik, Diptish Dey
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Multilevel models, increasingly deployed in industries such as insurance, food production, and entertainment within functions such as marketing and supply chain management, need to be transparent and ethical. Applications usually result in binary classification within groups or hierarchies based on a set of input features. Using open-source datasets, we demonstrate that popular explainability methods, such as SHAP and LIME, consistently underperform inaccuracy when interpreting these models. They fail to predict the order of feature importance, the magnitudes, and occasionally even the nature of the feature contribution (negative versus positive contribution to the outcome). Besides accuracy, the computational intractability of SHAP for binomial classification is a cause of concern. For transparent and ethical applications of these hierarchical statistical models, sound audit frameworks need to be developed. In this paper, we propose an audit framework for technical assessment of multilevel regression models focusing on three aspects: (i) model assumptions & statistical properties, (ii) model transparency using different explainability methods, and (iii) discrimination assessment. To this end, we undertake a quantitative approach and compare intrinsic model methods with SHAP and LIME. The framework comprises a shortlist of KPIs, such as PoCE (Percentage of Correct Explanations) and MDG (Mean Discriminatory Gap) per feature, for each of these three aspects. A traffic light risk assessment method is furthermore coupled to these KPIs. The audit framework will assist regulatory bodies in performing conformity assessments of AI systems using multilevel binomial classification models at businesses. It will also benefit businesses deploying multilevel models to be future-proof and aligned with the European Commission’s proposed Regulation on Artificial Intelligence.Keywords: audit, multilevel model, model transparency, model explainability, discrimination, ethics
Procedia PDF Downloads 87513 Antifungal Susceptibility of Saprolegnia parasitica Isolated from Rainbow Trout and Its Host Pathogen Interaction in Zebrafish Disease Model
Authors: Sangyeop Shin, D. C. M. Kulatunga, S. H. S. Dananjaya, Chamilani Nikapitiya, Jehee Lee, Mahanama De Zoysa
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Saprolegniasis is one of the most devastating fungal diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated fungi belong to the member of S. parasitica, supported by its typical fungal features including cotton-like whitish mycelium, zoospores (primary and secondary) and phylogenetic analysis with internal transcribed spacer (ITS) region. Pathogenicity of isolated S. parasitica was developed in embryo, larvae, juvenile and adult zebrafish as a disease model. Up regulation of host genes encoding ZfTnf-α, Zfc-Rel, ZfIl-12, ZfLyz-c, Zfβ-def, and ZfHsp-70 was identified in zebrafish larvae after experimental challenge of S. parasitica showing the host immune responses against the S. parasitica. Survival of the juveniles upon fungal infection might be due to the increased immune protection in the host. Investigation of antifungal susceptibility of S. parasitica with natural lawsone (2-hydroxy-1,4-naphthoquinone) revealed the minimum inhibitory concentration (MIC) and percentage inhibition of radial growth (PIRG %) as 200 µg/mL and 31.8%, respectively. Lawsone was able to change the membrane permeability, and cause irreversible damage and disintegration to the cellular membranes of S. parasitica which might have effect on fungi growth inhibition. Moreover, the mycelium exposed to lawsone (MIC level) changed the transcriptional responses of S. parasitica genes. Overall results indicate that lawsone could be a potential and novel anti-S. parasitica agent for controlling S. parasitica infection.Keywords: host-pathogen interactions, lawsone, rainbow trout, Saprolegnia parasitica, Saprolegniasis, zebrafish
Procedia PDF Downloads 242512 Regulation Aspects for a Radioisotope Production Installation in Brazil
Authors: Rian O. Miranda, Lidia V. de Sa, Julio C. Suita
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The Brazilian Nuclear Energy Commission (CNEN) is the main manufacturer of radiopharmaceuticals in Brazil. The Nuclear Engineering Institute (IEN), located at Rio de Janeiro, is one of its main centers of research and production, attending public and private hospitals in the state. This radiopharmaceutical production is used in diagnostic and therapy procedures and allows one and a half million nuclear medicine procedures annually. Despite this, the country is not self-sufficient to meet national demand, creating the need for importation and consequent dependence on other countries. However, IEN facilities were designed in the 60's, and today its structure is inadequate in relation to the good manufacturing practices established by sanitary regulator (ANVISA) and radiological protection leading to the need for a new project. In order to adapt and increase production in the country, a new plant will be built and integrated to the existing facilities with a new 30 MeV Cyclotron that is actually in project detailing process. Thus, it is proposed to survey current CNEN and ANVISA standards for radiopharmaceutical production facilities, as well as the radiological protection analysis of each area of the plant, following good manufacturing practices recommendations adopted nationally besides licensing exigencies for radioactive facilities. In this way, the main requirements for proper operation, equipment location, building materials, area classification, and maintenance program have been implemented. The access controls, interlocks, segregation zones and pass-through boxes integrated into the project were also analyzed. As a result, IEN will in future have the flexibility to produce all necessary radioisotopes for nuclear medicine application, more efficiently by simultaneously bombarding two targets, allowing the simultaneous production of two different radioisotopes, minimizing radiation exposure and saving operating costs.Keywords: cyclotron, legislation, norms, production, radiopharmaceuticals
Procedia PDF Downloads 129511 The Development of Nursing Model for Pregnant Women to Prevention of Early Postpartum Hemorrhage
Authors: Wadsana Sarakarn, Pimonpan Charoensri, Baliya Chaiyara
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Objectives: To study the outcomes of the developed nursing model to prevent early postpartum hemorrhage (PPH). Materials and Methods: The analytical study was conducted in Sunpasitthiprasong Hospital during October 1st, 2015, until May 31st, 2017. After review the prevalence, risk factors, and outcomes of postpartum hemorrhage of the parturient who gave birth in Sunpasitthiprasong Hospital, the nursing model was developed under research regulation of Kemmis&McTaggart using 4 steps of operating procedures: 1) analyzing problem situation and gathering 2) creating the plan 3) noticing and performing 4) reflecting the result of the operation. The nursing model consisted of the screening tools for risk factors associated with PPH, the clinical nursing practice guideline (CNPG), and the collecting bag for measuring postpartum blood loss. Primary outcome was early postpartum hemorrhage. Secondary outcomes were postpartum hysterectomy, maternal mortality, personnel’s practice, knowledge, and satisfaction of the nursing model. The data were analyzed by using content analysis for qualitative data and descriptive statistics for quantitative data. Results: Before using the nursing model, the prevalence of early postpartum hemorrhage was under estimated (2.97%). There were 5 cases of postpartum hysterectomy and 2 cases of maternal death due to postpartum hemorrhage. During the study period, there was 22.7% prevalence of postpartum hemorrhage among 220 pregnant women who were vaginally delivered at Sunpasitthiprasong Hospital. No maternal death or postpartum hysterectomy was reported after using the nursing model. Among 16 registered nurses at the delivery room who evaluated using of the nursing model, they reported the high level of practice, knowledge, and satisfaction Conclusion: The nursing model for the prevention of early PPH is effective to decrease early PPH and other serious complications.Keywords: the development of a nursing model, prevention of postpartum hemorrhage, pregnant women, postpartum hemorrhage
Procedia PDF Downloads 94510 Impact of Totiviridae L-A dsRNA Virus on Saccharomyces Cerevisiae Host: Transcriptomic and Proteomic Approach
Authors: Juliana Lukša, Bazilė Ravoitytė, Elena Servienė, Saulius Serva
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Totiviridae L-A virus is a persistent Saccharomyces cerevisiae dsRNA virus. It encodes the major structural capsid protein Gag and Gag-Pol fusion protein, responsible for virus replication and encapsulation. These features also enable the copying of satellite dsRNAs (called M dsRNAs) encoding a secreted toxin and immunity to it (known as killer toxin). Viral capsid pore presumably functions in nucleotide uptake and viral mRNA release. During cell division, sporogenesis, and cell fusion, the virions remain intracellular and are transferred to daughter cells. By employing high throughput RNA sequencing data analysis, we describe the influence of solely L-A virus on the expression of genes in three different S. cerevisiae hosts. We provide a new perception into Totiviridae L-A virus-related transcriptional regulation, encompassing multiple bioinformatics analyses. Transcriptional responses to L-A infection were similar to those induced upon stress or availability of nutrients. It also delves into the connection between the cell metabolism and L-A virus-conferred demands to the host transcriptome by uncovering host proteins that may be associated with intact virions. To better understand the virus-host interaction, we applied differential proteomic analysis of virus particle-enriched fractions of yeast strains that harboreither complete killer system (L-A-lus and M-2 virus), M-2 depleted orvirus-free. Our analysis resulted in the identification of host proteins, associated with structural proteins of the virus (Gag and Gag-Pol). This research was funded by the European Social Fund under the No.09.3.3-LMT-K-712-19-0157“Development of Competences of Scientists, other Researchers, and Students through Practical Research Activities” measure.Keywords: totiviridae, killer virus, proteomics, transcriptomics
Procedia PDF Downloads 135509 Induced Affectivity and Impact on Creativity: Personal Growth and Perceived Adjustment when Narrating an Intense Emotional Experience
Authors: S. Da Costa, D. Páez, F. Sánchez
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We examine the causal role of positive affect on creativity, the association of creativity or innovation in the ideation phase with functional emotional regulation, successful adjustment to stress and dispositional emotional creativity, as well as the predictive role of creativity for positive emotions and social adjustment. The study examines the effects of modification of positive affect on creativity. Participants write three poems, narrate an infatuation episode, answer a scale of personal growth after this episode and perform a creativity task, answer a flow scale after creativity task and fill a dispositional emotional creativity scale. High and low positive effect was induced by asking subjects to write three poems about high and low positive connotation stimuli. In a neutral condition, tasks were performed without previous affect induction. Subjects on the condition of high positive affect report more positive and less negative emotions, more personal growth (effect size r = .24) and their last poem was rated as more original by judges (effect size r = .33). Mediational analysis showed that positive emotions explain the influence of the manipulation on personal growth - positive affect correlates r = .33 to personal growth. The emotional creativity scale correlated to creativity scores of the creative task (r = .14), to the creativity of the narration of the infatuation episode (r = .21). Emotional creativity was also associated, during performing the creativity task, with flow (r = .27) and with affect balance (r = .26). The mediational analysis showed that emotional creativity predicts flow through positive affect. Results suggest that innovation in the phase of ideation is associated with a positive affect balance and satisfactory performance, as well as dispositional emotional creativity is adaptive.Keywords: affectivity, creativity, induction, innovation, psychological factors
Procedia PDF Downloads 104508 Effect of a GABA/5-HTP Mixture on Behavioral Changes and Biomodulation in an Invertebrate Model
Authors: Kyungae Jo, Eun Young Kim, Byungsoo Shin, Kwang Soon Shin, Hyung Joo Suh
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Gamma-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) are amino acids of digested nutrients or food ingredients and these can possibly be utilized as non-pharmacologic treatment for sleep disorder. We previously investigated the GABA/5-HTP mixture is the principal concept of sleep-promoting and activity-repressing management in nervous system of D. melanogaster. Two experiments in this study were designed to evaluate sleep-promoting effect of GABA/5-HTP mixture, to clarify the possible ratio of sleep-promoting action in the Drosophila invertebrate model system. Behavioral assays were applied to investigate distance traveled, velocity, movement, mobility, turn angle, angular velocity and meander of two amino acids and GABA/5-HTP mixture with caffeine treated flies. In addition, differentially expressed gene (DEG) analyses from next generation sequencing (NGS) were applied to investigate the signaling pathway and functional interaction network of GABA/5-HTP mixture administration. GABA/5-HTP mixture resulted in significant differences between groups related to behavior (p < 0.01) and significantly induced locomotor activity in the awake model (p < 0.05). As a result of the sequencing, the molecular function of various genes has relationship with motor activity and biological regulation. These results showed that GABA/5-HTP mixture administration significantly involved the inhibition of motor behavior. In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates locomotor activity to a greater extent than single administration of each amino acid, and that this modulation occurs via the neuronal system, neurotransmitter release cycle and transmission across chemical synapses.Keywords: sleep, γ-aminobutyric acid, 5-hydroxytryptophan, Drosophila melanogaster
Procedia PDF Downloads 302507 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells
Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra
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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.Keywords: breast cancer, microRNA, metastasis, EMT
Procedia PDF Downloads 547506 Stem Cell Differentiation Toward Secretory Progenitors after Intestinal Ischemia-Reperfusion in a Rat is Accompanied by Inhibited Notch Signaling Cascade
Authors: Igor Sukhotnik
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Objectives: Notch signaling is thought to act to drive cell versification in the lining of the small intestine. When Notch signaling is blocked, proliferation ceases, and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiation in a rat model of intestinal ischemia-reperfusion (IR). Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry. Wax histology and immunohistochemistry was used to determine cell differentiation toward absorptive (enterocytes) or secretory progenitors (goblet cells, enteroendocrine cells or Paneth cells). Results: IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum and ileum as well as Hes-1 positive cells in jejunum and ileum compared to Sham-48 rats. A significant down-regulation of Notch signaling related genes and proteins in IR animals was accompanied by a significant increase in the number of goblet and Paneth cells and decreased number of absorptive cells compared to control rats. Conclusions: Forty-eight hours following intestinal IR in rats, inhibited Notch signaling pathway was accompanied by intestinal stem cells differentiation toward secretory progenitors.Keywords: Intestine, notch, ischemia-reperfusion, cell differentiation, secretory
Procedia PDF Downloads 55505 Vertical Distribution of the Monthly Average Values of the Air Temperature above the Territory of Kakheti in 2012-2017
Authors: Khatia Tavidashvili, Nino Jamrishvili, Valerian Omsarashvili
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Studies of the vertical distribution of the air temperature in the atmosphere have great value for the solution of different problems of meteorology and climatology (meteorological forecast of showers, thunderstorms, and hail, weather modification, estimation of climate change, etc.). From the end of May 2015 in Kakheti after 25-year interruption, the work of anti-hail service was restored. Therefore, in connection with climate change, the need for the detailed study of the contemporary regime of the vertical distribution of the air temperature above this territory arose. In particular, the indicated information is necessary for the optimum selection of rocket means with the works on the weather modification (fight with the hail, the regulation of atmospheric precipitations, etc.). Construction of the detailed maps of the potential damage distribution of agricultural crops from the hail, etc. taking into account the dimensions of hailstones in the clouds according to the data of radar measurements and height of locality are the most important factors. For now, in Georgia, there is no aerological probing of atmosphere. To solve given problem we processed information about air temperature profiles above Telavi, at 27 km above earth's surface. Information was gathered during four observation time (4, 10, 16, 22 hours with local time. After research, we found vertical distribution of the average monthly values of the air temperature above Kakheti in 2012-2017 from January to December. Research was conducted from 0.543 to 27 km above sea level during four periods of research. In particular, it is obtained: -during January the monthly average air temperature linearly diminishes with 2.6 °C on the earth's surface to -57.1 °C at the height of 10 km, then little it changes up to the height of 26 km; the gradient of the air temperature in the layer of the atmosphere from 0.543 to 8 km - 6.3 °C/km; height of zero isotherm - is 1.33 km. -during July the air temperature linearly diminishes with 23.5 °C to -64.7 °C at the height of 17 km, then it grows to -47.5 °C at the height of 27 km; the gradient of the air temperature of - 6.1 °C/km; height of zero isotherm - is 4.39 km, which on 0.16 km is higher than in the sixties of past century.Keywords: hail, Kakheti, meteorology, vertical distribution of the air temperature
Procedia PDF Downloads 165504 Analysing “The Direction of Artificial Intelligence Legislation from a Global Perspective” from the Perspective of “AIGC Copyright Protection” Content
Authors: Xiaochen Mu
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Due to the diversity of stakeholders and the ambiguity of ownership boundaries, the current protection models for Artificial Intelligence Generated Content (AIGC) have many disadvantages. In response to this situation, there are three different protection models worldwide. The United States Copyright Office stipulates that works autonomously generated by artificial intelligence ‘lack’ the element of human creation, and non-human AI cannot create works. To protect and promote investment in the field of artificial intelligence, UK legislation, through Section 9(3) of the CDPA, designates the author of AI-generated works as ‘the person by whom the arrangements necessary for the creation of the work are undertaken.’ China neither simply excludes the work attributes of AI-generated content based on the lack of a natural person subject as the sole reason, nor does it generalize that AIGC should or should not be protected. Instead, it combines specific case circumstances and comprehensively evaluates the degree of originality of AIGC and the contributions of natural persons to AIGC. In China's first AI drawing case, the court determined that the image in question was the result of the plaintiff's design and selection through inputting prompt words and setting parameters, reflecting the plaintiff's intellectual investment and personalized expression, and should be recognized as a work in the sense of copyright law. Despite opposition, the ruling also established the feasibility of the AIGC copyright protection path. The recognition of the work attributes of AIGC will not lead to overprotection that hinders the overall development of the AI industry. Just as with the legislation and regulation of AI by various countries, there is a need for a balance between protection and development. For example, the provisional agreement reached on the EU AI Act, based on a risk classification approach, seeks a dynamic balance between copyright protection and the development of the AI industry.Keywords: generative artificial intelligence, originality, works, copyright
Procedia PDF Downloads 29503 Role of Human Wharton’s Jelly Mesenchymal Stem Cells Conditioned Media in Alleviating Kidney Injury via Inhibition of Renin-Angiotensin System in Diabetic Nephropathy
Authors: Pardis Abolghasemi, Benyamin Hatamsaz
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Background: Diabetic nephropathy is a serious health problem described by specific kidney structure and functional disturbance. Renoprotective effects of the stem cells secretase have been shown in many kidney diseases. The aim is to evaluate the capability of human Wharton’s jelly mesenchymal stem cells conditioned media (hWJMSCs-CM) to alleviate DN in streptozotocin (STZ)-induced diabetes. Methods: Diabetic nephropathy was induced by injection of STZ (60 mg/kg, IP) in twenty rats. Conditioned media was extracted from hWJMSCs at third passages. At week 8, diabetic rats were divided into two groups: treated (hWJMSCs-CM, 500 μl/rat for three weeks, IP) and not treated (DN). In the 11th week, three groups (control, DN and DN+hWJMSCs-CM) were kept in metabolic cages and urine was collected for 24h. Blood pressure (BP) and heart rate (HR) were continuously recorded. The serum samples were maintained for measuring BUN, Cr and angiotensin-converting enzyme (ACE) activity. The left kidney was kept at -80°C for ACE activity assessment. The right kidney and pancreas were used for histopathologic evaluation. Result: Diabetic nephropathy was detected by microalbuminuria and increased albumin/creatinine ratio, as well as the pancreas and renal structural disturbance. Glomerular filtration rate, BP and HR increased in the DN group. The ACE activity was elevated in the serum and kidneys of the DN group. Administration of hWJMSCs-CM modulated the renal functional and structural disturbance and decreased the ACE activity. Conclusion: Conditioned media was extracted from hWJMSCs may have a Renoprotective effect in diabetic nephropathy. This may happen through regulation of ACE activity and renin-angiotensin system inhibition.Keywords: diabetic nephropathy, mesenchymal stem cells, immunomodulation, anti-inflammation
Procedia PDF Downloads 196502 Hsa-miR-192-5p, and Hsa-miR-129-5p Prominent Biomarkers in Regulation Glioblastoma Cancer Stem Cells Genes Microenvironment
Authors: Rasha Ahmadi
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Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment
Procedia PDF Downloads 132501 Potentials and Challenges of Implementing Participatory Irrigation Management, Tanzania
Authors: Pilly Joseph Kagosi
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The study aims at assessing challenges observed during implementation of participatory irrigation management (PIM) approach for food security in semi-arid areas of Tanzania. Data were collected through questionnaire, PRA tools, key informants discussion, Focus Group Discussion (FGD), participant observation and literature review. Data collected from questionnaire was analyzed using SPSS while PRA data was analyzed with the help of local communities during PRA exercise. Data from other methods were analyzed using content analysis. The study revealed that PIM approach has contribution in improved food security at household level due to involvement of communities in water management activities and decision making which enhanced availability of water for irrigation and increased crop production. However there were challenges observed during implementation of the approach including; minimum participation of beneficiaries in decision making during planning and designing stages, meaning inadequate devolution of power among scheme owners; Inadequate and lack of transparency on income expenditure in Water Utilization Associations’ (WUAs), water conflict among WUAs members, conflict between farmers and livestock keepers and conflict between WUAs leaders and village government regarding training opportunities and status; WUAs rules and regulation are not legally recognized by the National court and few farmers involved in planting trees around water sources. However it was realized that some of the mentioned challenges were rectified by farmers themselves facilitated by government officials. The study recommends that, the identified challenges need to be rectified for farmers to realize impotence of PIM approach as it was realized by other Asian countries.Keywords: potentials of implementing participatory approach, challenges of participatory approach, irrigation management, Tanzania
Procedia PDF Downloads 299500 MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligoa
Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera
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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.Keywords: metabolism, microRNA, mitochondria, vitiligo
Procedia PDF Downloads 358499 Need for Privacy in the Technological Era: An Analysis in the Indian Perspective
Authors: Amrashaa Singh
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In the digital age and the large cyberspace, Data Protection and Privacy have become major issues in this technological era. There was a time when social media and online shopping websites were treated as a blessing for the people. But now the tables have turned, and the people have started to look at them with suspicion. They are getting aware of the privacy implications, and they do not feel as safe as they used to initially. When Edward Snowden informed the world about the snooping United States Security Agencies had been doing, that is when the picture became clear for the people. After the Cambridge Analytica case where the data of Facebook users were stored without their consent, the doubts arose in the minds of people about how safe they actually are. In India, the case of spyware Pegasus also raised a lot of concerns. It was used to snoop on a lot of human right activists and lawyers and the company which invented the spyware claims that it only sells it to the government. The paper will be dealing with the privacy concerns in the Indian perspective with an analytical methodology. The Supreme Court here had recently declared a right to privacy a Fundamental Right under Article 21 of the Constitution of India. Further, the Government is also working on the Data Protection Bill. The point to note is that India is still a developing country, and with the bill, the government aims at data localization. But there are doubts in the minds of many people that the Government would actually be snooping on the data of the individuals. It looks more like an attempt to curb dissenters ‘lawfully’. The focus of the paper would be on these issues in India in light of the European Union (EU) General Data Protection Regulation (GDPR). The Indian Data Protection Bill is also said to be loosely based on EU GDPR. But how helpful would these laws actually be is another concern since the economic and social conditions in both countries are very different? The paper aims at discussing these concerns, how good or bad is the intention of the government behind the bill, and how the nations can act together and draft common regulations so that there is some uniformity in the laws and their application.Keywords: Article 21, data protection, dissent, fundamental right, India, privacy
Procedia PDF Downloads 110498 Association of Brain-Derived Neurotrophic Factor (BDNF) Gene with Obesity and Metabolic Traits in Malaysian Adults
Authors: Yamunah Devi Apalasamy, Sanjay Rampal, Tin Tin Su, Foong Ming Moy, Hazreen Abdul Majid, Awang Bulgiba, Zahurin Mohamed
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Obesity is a growing global health issue. Obesity results from a combination of environmental and genetics factors. Brain-derived neurotrophic factor (BDNF), a gene encodes the BDNF protein and the BDNF gene have been linked to regulation of body weight and appetite. Genome-wide association studies have identified the BDNF variants to be related to obesity among Caucasians, East Asians, and Filipinos. However, the role of BDNF in other ethnic groups remains inconclusive. This case control study aims to investigate the associations of BDNF gene polymorphisms with obesity and metabolic parameters in Malaysian Malays. BDNF rs4074134, BDNF rs10501087 and BDNF rs6265 were genotyped using Sequenom MassARRAY. Anthropometric, body fat, fasting lipids and glucose levels were measured. A total of 663 subjects (194 obese and 469 non-obese) were included in this study. There were no significant associations association between BDNF SNPs and obesity. The allelic and genotype frequencies of the BDNF SNPs were similar in the obese and non-obese groups. After adjustment for age and sex, the BDNF variants were not associated with obesity, body fat, fasting lipids and glucose levels. Haplotypes at the BDNF gene region, were not significantly associated with obesity. The BDNF rs4074134 was in strong LD with BDNF rs10501087 (D'=0.98) and BDNF rs6265 (D'=0.87). The BDNF rs10501087 was also in strong LD with BDNF rs6265 (D'=0.91). Our findings suggest that the BDNF variants and the haplotypes of BDNF gene were not associated with obesity and metabolic traits in this study population. Further research is needed to explore other BDNF variants with a larger sample size with gene-environment interactions in multi ethnic Malaysian population.Keywords: genomics of obesity, SNP, BMI, haplotypes
Procedia PDF Downloads 428497 Rating Agreement: Machine Learning for Environmental, Social, and Governance Disclosure
Authors: Nico Rosamilia
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The study evaluates the importance of non-financial disclosure practices for regulators, investors, businesses, and markets. It aims to create a sector-specific set of indicators for environmental, social, and governance (ESG) performances alternative to the ratings of the agencies. The existing literature extensively studies the implementation of ESG rating systems. Conversely, this study has a twofold outcome. Firstly, it should generalize incentive systems and governance policies for ESG and sustainable principles. Therefore, it should contribute to the EU Sustainable Finance Disclosure Regulation. Secondly, it concerns the market and the investors by highlighting successful sustainable investing. Indeed, the study contemplates the effect of ESG adoption practices on corporate value. The research explores the asset pricing angle in order to shed light on the fragmented argument on the finance of ESG. Investors may be misguided about the positive or negative effects of ESG on performances. The paper proposes a different method to evaluate ESG performances. By comparing the results of a traditional econometric approach (Lasso) with a machine learning algorithm (Random Forest), the study establishes a set of indicators for ESG performance. Therefore, the research also empirically contributes to the theoretical strands of literature regarding model selection and variable importance in a finance framework. The algorithms will spit out sector-specific indicators. This set of indicators defines an alternative to the compounded scores of ESG rating agencies and avoids the possible offsetting effect of scores. With this approach, the paper defines a sector-specific set of indicators to standardize ESG disclosure. Additionally, it tries to shed light on the absence of a clear understanding of the direction of the ESG effect on corporate value (the problem of endogeneity).Keywords: ESG ratings, non-financial information, value of firms, sustainable finance
Procedia PDF Downloads 77496 Association of MMP-2,-9 Overexpression and Imbalance PGR-A/PGR-B Ratio in Endometriosis
Authors: P. Afsharian, S. Mousazadeh, M. Shahhoseini, R. Aflatoonian
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Introduction: Matrix MetalloProteinases (MMPs) degrade extracellular matrix components to provide normal remodeling and contribute to pathological tissue destruction and cell migration in endometriosis. It is accepted that MMPs are resistant to suppression by progesterone in endometriotic tissues. The physiological effects of progesterone are mediated by its two progesterone receptor (PGR) isoforms, namely PGR-A and PGR-B. The capacity of progesterone affect to gene expression is dependent on the PGR-A/PGR-B ratio. The imbalance ratio in endometriotic tissue may be an important mechanism to be resulted in Progesterone resistance and modify progesterone action via differential regulation of specific progesterone response genes and improve endometriosis disease. Material and methods: RNA was extracted from twenty ectopic (endometriotic) and eutopic (endometrial) tissue samples of women undergoing laparoscopy for endometriosis and 20 healthy fertile women at Royan Institute, Tehran, Iran. Analysis of PGR-A, PGR-B, MMP-2 and MMP-9 mRNA expression was performed using Real-time PCR in ectopic and eutopic tissues. Then, Statistical analysis was calculated according to the 2-ΔΔCT equation for all samples. Results: Quantitative RT–PCR analyses of PGR-A and PGR-B mRNA revealed that there were differences in both isoformes of PGRs mRNA expressions between ectopic and control eutopic tissues. We were able to demonstrate low expression levels of PGR-B isoforms in ectopic tissues. Although, PGR-A expression was significantly higher in the same ectopic samples compare to controls.This method permitted us to demonstrate significant overexpression of MMP-2 and MMP-9 in ectopic samples compared to control endometrial tissues, as well. Conclusions: Our data suggest that low expression levels of PGR-B and overexpression of PGR-A can alter PGR-A/PGR-B ratio in endometriotic ectopic tissues. Imbalance ratio of PGRs in endometriotic tissue may be able to consequence MMP-2 and MMP-9 overexpression which can be important in pathogenesis and treatment of disease.Keywords: endometriosis, matrix metalloproteinases, progesterone receptor -A and -B, PGR-A/PGR-B ratio
Procedia PDF Downloads 314495 The Predictive Value of Micro Rna 451 on the Outcome of Imatinib Treatment in Chronic Myeloid Leukemia Patients
Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa
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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction
Procedia PDF Downloads 287494 The Impact of Corporate Finance on Financial Stability in the Western Balkan Countries
Authors: Luan Vardari, Dena Arapi-Vardari
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Financial stability is a critical component of economic growth and development, and it has been recognized as a key policy objective in many countries around the world. In the Western Balkans, financial stability has been a key issue in recent years, with a number of challenges facing the region, including high levels of public debt, weak banking systems, and economic volatility. Corporate finance, which refers to the financial management practices of firms, is an important factor that can impact financial stability. This paper aims to investigate corporate finance's impact on financial stability in Western Balkan countries. This study will use a mixed-methods approach to investigate the impact of corporate finance on financial stability in the Western Balkans. The study will begin with a comprehensive review of the existing literature on corporate finance and financial stability, focusing on the Western Balkan region. This will be followed by an empirical analysis of regional corporate finance practices using data from various industries and firms. The analysis will explore the relationship between corporate finance practices and financial stability, taking into account factors such as regulatory frameworks, economic conditions, and firm size. The results of the study are expected to provide insights into the impact of corporate finance on financial stability in the Western Balkans. Specifically, the study will identify the key corporate finance practices that contribute to financial stability in the region, as well as the challenges and obstacles that firms face in implementing effective corporate finance strategies. The study will also provide recommendations for policymakers and firms looking to enhance financial stability and resilience in the region.Keywords: financial regulation, debt management, investment decisions, dividend policies, economic volatility, banking systems, public debt, prudent financial management, firm size, policy recommendations
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