Search results for: entry inhibitors
265 Building and Development of the Stock Market Institutional Infrastructure in Russia
Authors: Irina Bondarenko, Olga Vandina
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The theory of evolutionary economics is the basis for preparation and application of methods forming the stock market infrastructure development concept. The authors believe that the basis for the process of formation and development of the stock market model infrastructure in Russia is the theory of large systems. This theory considers the financial market infrastructure as a whole on the basis of macroeconomic approach with the further definition of its aims and objectives. Evaluation of the prospects for interaction of securities market institutions will enable identifying the problems associated with the development of this system. The interaction of elements of the stock market infrastructure allows to reduce the costs and time of transactions, thereby freeing up resources of market participants for more efficient operation. Thus, methodology of the transaction analysis allows to determine the financial infrastructure as a set of specialized institutions that form a modern quasi-stable system. The financial infrastructure, based on international standards, should include trading systems, regulatory and supervisory bodies, rating agencies, settlement, clearing and depository organizations. Distribution of financial assets, reducing the magnitude of transaction costs, increased transparency of the market are promising tasks in the solution for questions of services level and quality increase provided by institutions of the securities market financial infrastructure. In order to improve the efficiency of the regulatory system, it is necessary to provide "standards" for all market participants. The development of a clear regulation for the barrier to the stock market entry and exit, provision of conditions for the development and implementation of new laws regulating the activities of participants in the securities market, as well as formulation of proposals aimed at minimizing risks and costs, will enable the achievement of positive results. The latter will be manifested in increasing the level of market participant security and, accordingly, the attractiveness of this market for investors and issuers.Keywords: institutional infrastructure, financial assets, regulatory system, stock market, transparency of the market
Procedia PDF Downloads 134264 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers
Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality
Procedia PDF Downloads 129263 A Review of Pharmacological Prevention of Peri-and Post-Procedural Myocardial Injury After Percutaneous Coronary Intervention
Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam
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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology
Procedia PDF Downloads 451262 Production and Purification of Monosaccharides by Hydrolysis of Sugar Cane Bagasse in an Ionic Liquid Medium
Authors: T. R. Bandara, H. Jaelani, G. J. Griffin
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The conversion of lignocellulosic waste materials, such as sugar cane bagasse, to biofuels such as ethanol has attracted significant interest as a potential element for transforming transport fuel supplies to totally renewable sources. However, the refractory nature of the cellulosic structure of lignocellulosic materials has impeded progress on developing an economic process, whereby the cellulose component may be effectively broken down to glucose monosaccharides and then purified to allow downstream fermentation. Ionic liquid (IL) treatment of lignocellulosic biomass has been shown to disrupt the crystalline structure of cellulose thus potentially enabling the cellulose to be more readily hydrolysed to monosaccharides. Furthermore, conventional hydrolysis of lignocellulosic materials yields byproducts that are inhibitors for efficient fermentation of the monosaccharides. However, selective extraction of monosaccharides from an aqueous/IL phase into an organic phase utilizing a combination of boronic acids and quaternary amines has shown promise as a purification process. Hydrolysis of sugar cane bagasse immersed in an aqueous solution with IL (1-ethyl-3-methylimidazolium acetate) was conducted at different pH and temperature below 100 ºC. It was found that the use of a high concentration of hydrochloric acid to acidify the solution inhibited the hydrolysis of bagasse. At high pH (i.e. basic conditions), using sodium hydroxide, catalyst yields were reduced for total reducing sugars (TRS) due to the rapid degradation of the sugars formed. For purification trials, a supported liquid membrane (SLM) apparatus was constructed, whereby a synthetic solution containing xylose and glucose in an aqueous IL phase was transported across a membrane impregnated with phenyl boronic acid/Aliquat 336 to an aqueous phase. The transport rate of xylose was generally higher than that of glucose indicating that a SLM scheme may not only be useful for purifying sugars from undesirable toxic compounds, but also for fractionating sugars to improve fermentation efficiency.Keywords: biomass, bagasse, hydrolysis, monosaccharide, supported liquid membrane, purification
Procedia PDF Downloads 254261 Use Cloud-Based Watson Deep Learning Platform to Train Models Faster and More Accurate
Authors: Susan Diamond
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Machine Learning workloads have traditionally been run in high-performance computing (HPC) environments, where users log in to dedicated machines and utilize the attached GPUs to run training jobs on huge datasets. Training of large neural network models is very resource intensive, and even after exploiting parallelism and accelerators such as GPUs, a single training job can still take days. Consequently, the cost of hardware is a barrier to entry. Even when upfront cost is not a concern, the lead time to set up such an HPC environment takes months from acquiring hardware to set up the hardware with the right set of firmware, software installed and configured. Furthermore, scalability is hard to achieve in a rigid traditional lab environment. Therefore, it is slow to react to the dynamic change in the artificial intelligent industry. Watson Deep Learning as a service, a cloud-based deep learning platform that mitigates the long lead time and high upfront investment in hardware. It enables robust and scalable sharing of resources among the teams in an organization. It is designed for on-demand cloud environments. Providing a similar user experience in a multi-tenant cloud environment comes with its own unique challenges regarding fault tolerance, performance, and security. Watson Deep Learning as a service tackles these challenges and present a deep learning stack for the cloud environments in a secure, scalable and fault-tolerant manner. It supports a wide range of deep-learning frameworks such as Tensorflow, PyTorch, Caffe, Torch, Theano, and MXNet etc. These frameworks reduce the effort and skillset required to design, train, and use deep learning models. Deep Learning as a service is used at IBM by AI researchers in areas including machine translation, computer vision, and healthcare.Keywords: deep learning, machine learning, cognitive computing, model training
Procedia PDF Downloads 209260 Low Enrollment in Civil Engineering Departments: Challenges and Opportunities
Authors: Alaa Yehia, Ayatollah Yehia, Sherif Yehia
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There is a recurring issue of low enrollments across many civil engineering departments in postsecondary institutions. While there have been moments where enrollments begin to increase, civil engineering departments find themselves facing low enrollments at around 60% over the last five years across the Middle East. There are many reasons that could be attributed to this decline, such as low entry-level salaries, over-saturation of civil engineering graduates in the job market, and a lack of construction projects due to the impending or current recession. However, this recurring problem alludes to an intrinsic issue of the curriculum. The societal shift to the usage of high technology such as machine learning (ML) and artificial intelligence (AI) demands individuals who are proficient at utilizing it. Therefore, existing curriculums must adapt to this change in order to provide an education that is suitable for potential and current students. In this paper, In order to provide potential solutions for this issue, the analysis considers two possible implementations of high technology into the civil engineering curriculum. The first approach is to implement a course that introduces applications of high technology in Civil Engineering contexts. While the other approach is to intertwine applications of high technology throughout the degree. Both approaches, however, should meet requirements of accreditation agencies. In addition to the proposed improvement in civil engineering curriculum, a different pedagogical practice must be adapted as well. The passive learning approach might not be appropriate for Gen Z students; current students, now more than ever, need to be introduced to engineering topics and practice following different learning methods to ensure they will have the necessary skills for the job market. Different learning methods that incorporate high technology applications, like AI, must be integrated throughout the curriculum to make the civil engineering degree more attractive to prospective students. Moreover, the paper provides insight on the importance and approach of adapting the Civil Engineering curriculum to address the current low enrollment crisis that civil engineering departments globally, but specifically in the Middle East, are facing.Keywords: artificial intelligence (AI), civil engineering curriculum, high technology, low enrollment, pedagogy
Procedia PDF Downloads 166259 A Profile of an Exercise Addict: The Relationship between Exercise Addiction and Personality
Authors: Klary Geisler, Dalit Lev-Arey, Yael Hacohen
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It is a well-known fact that exercise has favorable effects on people's physical health, as well as mental well-being. However, as for as excessive exercise, it may likely elevate negative consequences (e.g., physical injuries, negligence of everyday responsibilities such as work, family life). Lately, there is a growing interest in exercise addiction, sometimes referred to as exercise dependence, which is defined as a craving for physical activity that results in extreme work-out sessions and generates negative physiological and psychological symptoms (e.g., withdrawal symptoms, tolerance, social conflict). Exercise addiction is considered a behavioral addiction, yet it was not included in the latest editions of the diagnostic and statistical manual of mental disorders (DSM-IV), due to lack of significant research. Specifically, there is scarce research on the relationship between exercise addiction and personality dimensions. The purpose of the current research was to examine the relationship between primary exercise addiction symptoms and the big five dimensions, perfectionism (high performance expectations and self-critical performance evaluations) and subjective affect. participants were 152 trainees on a variety of aerobic sports activities (running, cycling, swimming) that were recruited through sports groups and trainers. 88% of participants trained for at least 5 hours per week, 24% of the participants trained above 10 hours per week. To test the predictive ability of the IVs a hierarchical linear regression with forced block entry was performed. It was found that Neuroticism significantly predicted exercise addiction symptoms (20% of the variance, p<0.001), while consciousness was negatively correlated with exercise addiction symptoms (14% of variance p<0.05); both had a unique contribution. Other dimensions of the big five (agreeableness, openness and extraversion) did not have any contribution to the dependent. Moreover, maladaptive perfectionism (self-critical performance evaluations) significantly predicted exercise addiction symptoms as well (10% of the variance P < 0.05). The overall regression model explained 54% of variance.Keywords: big five, consciousness, excessive exercise, exercise addiction, neuroticism, perfectionism, personality
Procedia PDF Downloads 229258 Inhibition of Echis ocellatus Venom Metalloprotease by Flavonoid-Rich Ethyl Acetate Sub-fraction of Moringa oleifera Leaves (Lam.): in vitro and in silico Approaches
Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji
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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking
Procedia PDF Downloads 149257 In vitro α-Amylase and α-Glucosidase Inhibitory Activities of Bitter Melon (Momordica charantia) with Different Stage of Maturity
Authors: P. S. Percin, O. Inanli, S. Karakaya
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Bitter melon (Momordica charantia) is a medicinal vegetable, which is used traditionally to remedy diabetes. Bitter melon contains several classes of primary and secondary metabolites. In traditional Turkish medicine bitter melon is used for wound healing and treatment of peptic ulcers. Nowadays, bitter melon is used for the treatment of diabetes and ulcerative colitis in many countries. The main constituents of bitter melon, which are responsible for the anti-diabetic effects, are triterpene, protein, steroid, alkaloid and phenolic compounds. In this study total phenolics, total carotenoids and β-carotene contents of mature and immature bitter melons were determined. In addition, in vitro α-amylase and α-glucosidase activities of mature and immature bitter melons were studied. Total phenolic contents of immature and mature bitter melon were 74 and 123 mg CE/g bitter melon respectively. Although total phenolics of mature bitter melon was higher than that of immature bitter melon, this difference was not found statistically significant (p > 0.05). Carotenoids, a diverse group of more than 600 naturally occurring red, orange and yellow pigments, play important roles in many physiological processes both in plants and humans. The total carotenoid content of mature bitter melon was 4.36 fold higher than the total carotenoid content of immature bitter melon. The compounds that have hypoglycaemic effect of bitter melon are steroidal saponins known as charantin, insulin-like peptides and alkaloids. α-Amylase is one of the main enzymes in human that is responsible for the breakdown of starch to more simple sugars. Therefore, the inhibitors of this enzyme can delay the carbohydrate digestion and reduce the rate of glucose absorption. The immature bitter melon extract showed α-amylase and α-glucosidase inhibitory activities in vitro. α-Amylase inhibitory activity was higher than that of α-glucosidase inhibitory activity when IC50 values were compared. In conclusion, the present results provide evidence that aqueous extract of bitter melon may have an inhibitory effect on carbohydrate breakdown enzymes.Keywords: bitter melon, in vitro antidiabetic activity, total carotenoids, total phenols
Procedia PDF Downloads 241256 The Analysis of Underground Economy Transaction Existence of Junk Night Market (JNM) in Malang City
Authors: Sebastiana Viphindratin, Silvi Asna
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The under ground economy phenomenon is exist in Indonesia. There are some factors which affect the existence this underground economy activity. One of them is a hierarchy power structure that handles the underground economy existence. The example of the existence of underground economy is the occurring informal market in Indonesia. Malang city is one of the city which has this kind of market. Junk night market (JNM) as an underground economy activity is arising in that city. The JNM is located in Gatot Subroto Sidewalk Street. The JNM is a illegal market which sell thrift, antique, imitation and black market goods. The JNM is interesting topic to be discussed, because this market is running in long time without any policy from local government. The JNM activity has their own “power” that run the market rules. Thus, it is important to analyze how the existence and power structure of JNM actors community are in Malang city. This research using qualitative method with phenomenological approach where we try to understand the phenomenon and related actors deeply. The aim of this research is to know the existence and power structure of JNM actors community in Malang. In JNM, there is no any entry barriers and tax charge from Malang government itself. Price competition also occurs because the buyer can do a bargain with the seller. In maintaining buyer loyalty, the JNM actors also do pre-order system. Even though, this market is an illegal market but the JNM actors also give the goods guarantee (without legal contract) as a formal market. In JNM actor’s community, there is no hierarchy and formal power structure. The role in JNM is managed by informal leaders who come up from the trading activity problems that are sidewalk and parking area dividing. Therefore, can be concluded that even the JNM is illegal market but it can survive with natural market pattern. In JNM development, JNM has positive and negative impact for Malang city. The positive impact of JNM is this market can open a new employment but the negative impact is there is no tax income from that market. Therefore, suggested that the government of Malang city should manage and give appropriate policies in this case.Keywords: junk night market (JNM), Malang city, underground economy, illegal
Procedia PDF Downloads 407255 Comparative Assessment of Microplastic Pollution in Surface Water and Sediment of the Gomati and Saryu Rivers, India
Authors: Amit K. Mishra, Jaswant Singh
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The menace of plastic, which significantly pollutes the aquatic environment, has emerged as a global problem. There is an emerging concern about microplastics (MPs) accumulation in aquatic ecosystems. It is familiar to everyone that the ultimate end for most of the plastic debris is the ocean. Rivers are the efficient carriers for transferring MPs from terrestrial to aquatic, further from upstream to downstream areas, and ultimately to oceans. The root cause study can provide an effective solution to a problem; hence, tracing of MPs in the riverine system can illustrate the long-term microplastic pollution. This study aimed to investigate the occurrence and distribution of microplastic contamination in surface water and sediment of the two major river systems of Uttar Pradesh, India. One is the Gomti River, Lucknow, a tributary of the Ganga, and the second is the Saryu River, the lower part of the Ghagra River, which flows through the city of Ayodhya. In this study, the distribution and abundance of MPs in surface water and sediments of two rivers were compared. Samples of water and sediment were collected from different (four from each river) sampling stations in the river catchment of two rivers. Plastic particles were classified according to type, shape, and color. In this study, 1523 (average abundance 254) and 143 (average abundance 26) microplastics were identified in all studied sites in the Gomati River and Saryu River, respectively. Observations on samples of water showed that the average MPs concentration was 392 (±69.6) and 63 ((±18.9) particles per 50l of water, whereas the sediment sample showed that the average MPs concentration was 116 (±42.9) and 46 (±12.5) particles per 250gm of dry sediment in the Gomati River and Saryu River, respectively. The high concentration of microplastics in the Lucknow area can be attributed to human activities, population density, and the entry of various effluents into the river. Microplastics with fibrous shapes were dominated, followed by fragment shapes in all the samples. The present study is a pioneering effort to count MPs in the Gomati and Saryu River systems.Keywords: freshwater, Gomati, microplastics, Saryu, sediment
Procedia PDF Downloads 82254 The Evaluation of the Effect of a Weed-Killer Sulfonylurea on Durum Wheat (Triticum durum Desf)
Authors: Meksem Amara Leila, Ferfar Meriem, Meksem Nabila, Djebar Mohammed Reda
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The wheat is the cereal the most consumed in the world. In Algeria, the production of this cereal covers only 20 in 25 % of the needs for the country, the rest being imported. To improve the efficiency and the productivity of the durum wheat, the farmers turn to the use of pesticides: weed-killers, fungicides and insecticides. However this use often entrains losses of products more at least important contaminating the environment and all the food chain. Weed-killers are substances developed to control or destroy plants considered unwanted. That they are natural or produced by the human being (molecule of synthesis), the absorption and the metabolization of weed-killers by plants cause the death of these plants.In this work, we set as goal the evaluation of the effect of a weed-killer sulfonylurea, the CossackOD with various concentrations (0, 2, 4 and 9 µg) on variety of Triticum durum: Cirta. We evaluated the plant growth by measuring the leaves and root length, compared with the witness as well as the content of proline and analyze the level of one of the antioxydative enzymes: catalse, after 14 days of treatment. Sulfonylurea is foliar and root weed-killers inhibiting the acetolactate synthase: a vegetable enzyme essential to the development of the plant. This inhibition causes the ruling of the growth then the death. The obtained results show a diminution of the average length of leaves and roots this can be explained by the fact that the ALS inhibitors are more active in the young and increasing regions of the plant, what inhibits the cellular division and talks a limitation of the foliar and root’s growth. We also recorded a highly significant increase in the proline levels and a stimulation of the catalase activity. As a response to increasing the herbicide concentrations a particular increases in antioxidative mechanisms in wheat cultivar Cirta suggest that the high sensitivity of Cirta to this sulfonylurea herbicide is related to the enhanced production and oxidative damage of reactive oxygen species.Keywords: sulfonylurea, Triticum durum, oxydative stress, Toxicity
Procedia PDF Downloads 424253 3D Microscopy, Image Processing, and Analysis of Lymphangiogenesis in Biological Models
Authors: Thomas Louis, Irina Primac, Florent Morfoisse, Tania Durre, Silvia Blacher, Agnes Noel
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In vitro and in vivo lymphangiogenesis assays are essential for the identification of potential lymphangiogenic agents and the screening of pharmacological inhibitors. In the present study, we analyse three biological models: in vitro lymphatic endothelial cell spheroids, in vivo ear sponge assay, and in vivo lymph node colonisation by tumour cells. These assays provide suitable 3D models to test pro- and anti-lymphangiogenic factors or drugs. 3D images were acquired by confocal laser scanning and light sheet fluorescence microscopy. Virtual scan microscopy followed by 3D reconstruction by image aligning methods was also used to obtain 3D images of whole large sponge and ganglion samples. 3D reconstruction, image segmentation, skeletonisation, and other image processing algorithms are described. Fixed and time-lapse imaging techniques are used to analyse lymphatic endothelial cell spheroids behaviour. The study of cell spatial distribution in spheroid models enables to detect interactions between cells and to identify invasion hierarchy and guidance patterns. Global measurements such as volume, length, and density of lymphatic vessels are measured in both in vivo models. Branching density and tortuosity evaluation are also proposed to determine structure complexity. Those properties combined with vessel spatial distribution are evaluated in order to determine lymphangiogenesis extent. Lymphatic endothelial cell invasion and lymphangiogenesis were evaluated under various experimental conditions. The comparison of these conditions enables to identify lymphangiogenic agents and to better comprehend their roles in the lymphangiogenesis process. The proposed methodology is validated by its application on the three presented models.Keywords: 3D image segmentation, 3D image skeletonisation, cell invasion, confocal microscopy, ear sponges, light sheet microscopy, lymph nodes, lymphangiogenesis, spheroids
Procedia PDF Downloads 377252 Abridging Pharmaceutical Analysis and Drug Discovery via LC-MS-TOF, NMR, in-silico Toxicity-Bioactivity Profiling for Therapeutic Purposing Zileuton Impurities: Need of Hour
Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar
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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity
Procedia PDF Downloads 195251 Teacher Education: Teacher Development and Support
Authors: Khadem Hichem
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With the new technology challenges, dynamics and challenges of the contemporary world, most teachers are struggling to maintain effective and successful teaching /learning environment for learners. Teachers as a key to the success of reforms in the educational setting, they must improve their competencies to teach effectively. Many researchers emphasis on the ongoing professional development of the teacher by enhancing their experiences and encouraging their responsibility for learning, and thus promoting self-reliance, collaboration, and reflection. In short, teachers are considered as learners and they need to learn together. The educational system must support, both conceptually and financially, the teachers’ development as lifelong learners Teachers need opportunities to grow in language proficiency and in knowledge. Changing nature of language and culture in the world, all teachers must have opportunities to update their knowledge and practices. Many researchers in the field of foreign or additional languages indicate that teachers keep side by side of effective instructional practices and they need special support with the challenging task of developing and administering proficiency tests to their students. For significant change to occur, each individual teacher’s needs must be addressed. The teacher must be involved experientially in the process of development, since, by itself, knowledge of how to change does not mean change will be initiated. For improvement to occur, new skills have to be guided, practiced, and reflected upon in collaboration with colleagues. Clearly, teachers are at different places developmentally; therefore, allowances for various entry levels and individual differences need to be built into the professional development structure. Objectives must be meaningful to the participant and teacher improvement must be stated terms of student knowledge, student performance, and motivation. The most successful professional development process acknowledges the student-centered nature of good teaching. This paper highlights the importance of teacher professional development process and institutional supports as way to enhance good teaching and learning environment.Keywords: teacher professional development, teacher competencies, institutional support, teacher education
Procedia PDF Downloads 354250 Effect of Facilitation in a Problem-Based Environment on the Metacognition, Motivation and Self-Directed Learning in Nursing: A Quasi-Experimental Study among Nurse Students in Tanzania
Authors: Walter M. Millanzi, Stephen M. Kibusi
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Background: Currently, there has been a progressive shortage not only to the number but also the quality of medical practitioners for the most of nursing. Despite that, those who are present exhibit unethical and illegal practices, under standard care and malpractices. The concern is raised in the ways they are prepared, or there might be something missing in nursing curricula or how it is delivered. There is a need for transforming or testing new teaching modalities to enhance competent health workforces. Objective: to investigate the Effect of Facilitation in a Problem-based Environment (FPBE) on metacognition, self-directed learning and learning motivation to undergraduate nurse student in Tanzanian higher learning institutions. Methods: quasi-experimental study (quantitative research approach). A purposive sampling technique was employed to select institutions and achieving a sample size of 401 participants (interventional = 134 and control = 267). Self-administered semi-structured questionnaire; was the main data collection methods and the Statistical Package for Service Solution (v. 20) software program was used for data entry, data analysis, and presentations. Results: The pre-post test results between groups indicated noticeably significant change on metacognition in an intervention (M = 1.52, SD = 0.501) against the control (M = 1.40, SD = 0.490), t (399) = 2.398, p < 0.05). SDL in an intervention (M = 1.52, SD = 0.501) against the control (M = 1.40, SD = 0.490), t (399) = 2.398, p < 0.05. Motivation to learn in an intervention (M = 62.67, SD = 14.14) and the control (n = 267, M = 57.75), t (399) = 2.907, p < 0.01). A FPBE teaching pedagogy, was observed to be effective on the metacognition (AOR = 1.603, p < 0.05), SDL (OR = 1.729, p < 0.05) and Intrinsic motivation in learning (AOR = 1.720, p < 0.05) against conventional teaching pedagogy. Needless, was less likely to enhance Extrinsic motivation (AOR = 0.676, p > 0.05) and Amotivation (AOR = 0.538, p > 0.05). Conclusion and recommendation: FPBE teaching pedagogy, can improve student’s metacognition, self-directed learning and intrinsic motivation to learn among nurse students. Nursing curricula developers should incorporate it to produce 21st century competent and qualified nurses.Keywords: facilitation, metacognition, motivation, self-directed
Procedia PDF Downloads 188249 Challenges Associated with Recruitment of Professional Doctorate Degree Holders into Ghanaian Universities
Authors: Joseph E. Cobbinah, Abigail A. Aryeh-Adjei
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Over the years, entry into the academia in any Ghanaian university requires an advanced research degree, more preferably traditional doctorate (PhD or DPhil). It is however argued that PhD is more research intensive, so since university teaching involves a lot of research, those having traditional doctorate have good research background to teach in a university and are thus recruited as lecturers. However, in the last ten years, a reasonable number of academics enter Ghanaian universities with professional doctorate degrees, which hitherto was considered to be only suitable for industry, because it gives individuals with just basic research skills needed for professional practice, unlike the traditional PhD which is research intensive degree. Currently, there are a reasonable number of professional doctorate degree holders with qualifications like DBA, EdD, PsychD, DPharm, EngD, among others in various departments in many Ghanaian universities. Maybe, because such degree holders also use the title Dr, some university authorities put them at par with their counterparts with traditional doctorate, although some lecturers with PhD seem to look down upon those with traditional doctorate degrees and this has created some tension amongst those academics. This makes their promotions and holding of university academic positions very problematic in some ways. This paper therefore seeks to investigate the types of professional doctorate degree holders working as lecturers in some selected universities in Ghana and the challenges associated with their recruitment, acceptability and proper integration into universities’ teaching and learning. The paper adopted qualitative research methodology. In all, respondents from three state-owned and privately owned universities were involved in the study. Administrators, lecturers, heads of departments and deans of faculty were interviewed to assess the challenges associated with the recruitment of professional doctorate degree holders and any problems they face in the departments they work. It became evident that, although some lecturers enter the academia with professional doctorate degrees, their counterparts seem not to give them the recognition and respect they deserve. Although there is little or no evidence that professional doctorate degree holders are under performing, recruiting professional doctorate degree holders does not only become a challenge, but also their progression into the university’s promotion ladder become very slow compared to their counterparts with traditional PhD degrees.Keywords: professional doctorate, academia, lecturers, Ghanaian universities, orate
Procedia PDF Downloads 308248 Evaluation of the Effect of Lactose Derived Monosaccharide on Galactooligosaccharides Production by β-Galactosidase
Authors: Yenny Paola Morales Cortés, Fabián Rico Rodríguez, Juan Carlos Serrato Bermúdez, Carlos Arturo Martínez Riascos
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Numerous benefits of galactooligosaccharides (GOS) as prebiotics have motivated the study of enzymatic processes for their production. These processes have special complexities due to several factors that make difficult high productivity, such as enzyme type, reaction medium pH, substrate concentrations and presence of inhibitors, among others. In the present work the production of galactooligosaccharides (with different degrees of polymerization: two, three and four) from lactose was studied. The study considers the formulation of a mathematical model that predicts the production of GOS from lactose using the enzyme β-galactosidase. The effect of pH in the reaction was studied. For that, phosphate buffer was used and with this was evaluated three pH values (6.0.6.5 and 7.0). Thus it was observed that at pH 6.0 the enzymatic activity insignificant. On the other hand, at pH 7.0 the enzymatic activity was approximately 27 times greater than at 6.5. The last result differs from previously reported results. Therefore, pH 7.0 was chosen as working pH. Additionally, the enzyme concentration was analyzed, which allowed observing that the effect of the concentration depends on the pH and the concentration was set for the following studies in 0.272 mM. Afterwards, experiments were performed varying the lactose concentration to evaluate its effects on the process and to generate the data for the adjustment of the mathematical model parameters. The mathematical model considers the reactions of lactose hydrolysis and transgalactosylation for the production of disaccharides and trisaccharides, with their inverse reactions. The production of tetrasaccharides was negligible and, because of that, it was not included in the model. The reaction was monitored by HPLC and for the quantitative analysis of the experimental data the Matlab programming language was used, including solvers for differential equations systems integration (ode15s) and nonlinear problems optimization (fminunc). The results confirm that the transgalactosylation and hydrolysis reactions are reversible, additionally inhibition by glucose and galactose is observed on the production of GOS. In relation to the production process of galactooligosaccharides, the results show that it is necessary to have high initial concentrations of lactose considering that favors the transgalactosylation reaction, while low concentrations favor hydrolysis reactions.Keywords: β-galactosidase, galactooligosaccharides, inhibition, lactose, Matlab, modeling
Procedia PDF Downloads 358247 Investigation of The Effects of Hydroxytyrosol on Cytotoxicity, Apoptosis, PI3K/Akt, and ERK 1/2 Pathways in Ovarian Cancer Cell Cultures
Authors: Latife Merve Oktay, Berrin Tugrul
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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer
Procedia PDF Downloads 354246 Hormone Replacement Therapy (HRT) and Its Impact on the All-Cause Mortality of UK Women: A Matched Cohort Study 1984-2017
Authors: Nurunnahar Akter, Elena Kulinskaya, Nicholas Steel, Ilyas Bakbergenuly
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Although Hormone Replacement Therapy (HRT) is an effective treatment in ameliorating menopausal symptoms, it has mixed effects on different health outcomes, increasing, for instance, the risk of breast cancer. Because of this, many symptomatic women are left untreated. Untreated menopausal symptoms may result in other health issues, which eventually put an extra burden and costs to the health care system. All-cause mortality analysis may explain the net benefits and risks of the HRT therapy. However, it received far less attention in HRT studies. This study investigated the impact of HRT on all-cause mortality using electronically recorded primary care data from The Health Improvement Network (THIN) that broadly represents the female population in the United Kingdom (UK). The study entry date for this study was the record of the first HRT prescription from 1984, and patients were followed up until death or transfer to another GP practice or study end date, which was January 2017. 112,354 HRT users (cases) were matched with 245,320 non-users by age at HRT initiation and general practice (GP). The hazards of all-cause mortality associated with HRT were estimated by a parametric Weibull-Cox model adjusting for a wide range of important medical, lifestyle, and socio-demographic factors. The multilevel multiple imputation techniques were used to deal with missing data. This study found that during 32 years of follow-up, combined HRT reduced the hazard ratio (HR) of all-cause mortality by 9% (HR: 0.91; 95% Confidence Interval, 0.88-0.94) in women of age between 46 to 65 at first treatment compared to the non-users of the same age. Age-specific mortality analyses found that combined HRT decreased mortality by 13% (HR: 0.87; 95% CI, 0.82-0.92), 12% (HR: 0.88; 95% CI, 0.82-0.93), and 8% (HR: 0.92; 95% CI, 0.85-0.98), in 51 to 55, 56 to 60, and 61 to 65 age group at first treatment, respectively. There was no association between estrogen-only HRT and women’s all-cause mortality. The findings from this study may help to inform the choices of women at menopause and to further educate the clinicians and resource planners.Keywords: hormone replacement therapy, multiple imputations, primary care data, the health improvement network (THIN)
Procedia PDF Downloads 170245 Host Cell Membrane Lipid Rafts Are Required for Influenza A Virus Adsorption to Host Cell Surface
Authors: Dileep K. Verma, Sunil K. Lal
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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Previous studies suggest that influenza hemagglutinin is essential for viral attachment to host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Studies also reported selective nature of Influenza virus to utilize rafts micro-domain for efficient virus assembly and budding. However, the detailed mechanism of Influenza A Virus (IAV) binding to host cell membrane and entry inside the host remains elusive. In the present study, we investigated if host membrane lipid rafts play any significant role in early life cycle events of influenza A virus. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol and Methyl-β-Cyclodextrin was used to remove membrane cholesterol. We observed co-localization of Influenza A Virus to lipid rafts by visualization of known lipid raft marker GM1 on host cell membrane. Co-localization suggest direct involvement of these micro-domain in initiation of IAV life cycle. We found significant reduction in influenza A virus adsorption in raft disrupted target host cells indicating poor binding and attachment in absence of coherent membrane rafts. Taken together, the results of present study provide evidence for critical involvement of host lipid rafts and its constituents in adsorption process of Influenza A Virus and suggests crucial involvement in other early events of IAV life cycle. The present study opens a new domain to study influenza virus-host interaction and to combat flu at the very early steps of viral life cycle.Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1
Procedia PDF Downloads 297244 The Role of Financial and Non-Financial Institutions in Promoting Entrepreneurship in Micro small and Medium Enterprises
Authors: Lemuel David
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The importance of the Micro, Small, and Medium Enterprises sector is well recognized for its legitimate contribution to the Macroeconomic objectives of the Republic of Liberia, like generation of employment, input t, exports, and enhancing entrepreneurship. Right now, Medium and Small enterprises accounts for about 99 percent of the industrial units in the country, contributing 60 percent of the manufacturing sector output and approximately one-third of the nation’s exports. The role of various financial institutions like ECO bank and Non-financial Institutions like Bearch Limited support promoting the growth of Micro, Small, and Medium Enterprises is unique. A small enterprise or entrepreneur gets many types of assistance from different institutions for varied purposes in the course of his entrepreneurial journey. This paper focuses on the factors related to financial institutional support and non-financial institutional support entrepreneurs to the growth of Medium and Small enterprises in the Republic of Liberia. The significance of this paper is to support Policy and Institutional Support for Medium and Small enterprises to know the views of entrepreneurs about financial and non-financial support systems in the Republic of Liberia. This study was carried out through a survey method, with the use of questionnaires. The population for this study consisted of all registered Medium and Small enterprises which have been registered during the years 2004-2014 in the republic of Liberia. The sampling method employed for this study was a simple random technique and determined a sample size of 400. Data for the study was collected using a standard questionnaire. The questionnaire consisted of two parts: the first part consisted of questions on the profile of the respondents. The second part covers (1) financial, promotional factors and (2) non-financial promotional factors. The results of the study are based on financial and non-financial supporting activities provided by institutions to Medium and Small enterprises. After investigation, it has been found that there is no difference in the support given by Financial Institutions and non-financial Institutions. Entrepreneurs perceived “collateral-free schemes and physical infrastructure support factors are highest contributing to entry and growth of Medium and Small enterprises.Keywords: micro, small, and medium enterprises financial institutions, entrepreneurship
Procedia PDF Downloads 98243 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection
Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder
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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance
Procedia PDF Downloads 191242 The Effect of Acute Toxicity and Thyroid Hormone Treatments on Hormonal Changes during Embryogenesis of Acipenser persicus
Authors: Samaneh Nazeri, Bagher Mojazi Amiri, Hamid Farahmand
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Production of high quality fish eggs with reasonable hatching rate makes a success in aquaculture industries. It is influenced by the environmental stimulators and inhibitors. Diazinon is a widely-used pesticide in Golestan province (Southern Caspian Sea, North of Iran) which is washed to the aquatic environment (3 mg/L in the river). It is little known about the effect of this pesticide on the embryogenesis of sturgeon fish, the valuable species of the Caspian Sea. Hormonal content of the egg is an important factor to guaranty the successful passes of embryonic stages. In this study, the fate of Persian sturgeon embryo to 24, 48, 72, and 96-hours exposure of diazinon (LC50 dose) was tested. Also, the effect of thyroid hormones (T3 and T4) on these embryos was tested concurrently or separately with diazinon LC 50 dose. Fertilized eggs are exposed to T3 (low dose: 1 ng/ml, high dose: 10 ng/ml), T4 (low dose: 1 ng/ml, high dose: 10 ng/ml). Six eggs were randomly selected from each treatment (with three replicates) in five developmental stages (two cell- division, neural, heart present, heart beaten, and hatched larvae). The possibility of changing T3, T4, and cortisol contents of the embryos were determined in all treated groups and in every mentioned embryonic stage. The hatching rate in treated groups was assayed at the end of the embryogenesis to clarify the effect of thyroid hormones and diazinon. The results indicated significant differences in thyroid hormone contents, but no significant differences were recognized in cortisol levels at various early life stages of embryos. There was also significant difference in thyroid hormones in (T3, T4) + diazinon treated embryos (P˂0.05), while no significant difference between control and treatments in cortisol levels was observed. The highest hatching rate was recorded in HT3 treatment, while the lowest hatching rate was recorded for diazinon LC50 treatment. The result confirmed that Persian sturgeon embryo is less sensitive to diazinon compared to teleost embryos, and thyroid hormones may increase hatching rate even in the presence of diazinon.Keywords: Persian sturgeon, diazinon, thyroid hormones, cortisol, embryo
Procedia PDF Downloads 303241 Malignant Ovarian Cancer Ascites Confers Platinum Chemoresistance to Ovarian Cancer Cells: A Combination Treatment with Crizotinib and 2 Hydroxyestradiol Restore Platinum Sensitivity
Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna
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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib
Procedia PDF Downloads 68240 Regulation of Differentiating Intramuscular Stromal Vascular Cells Isolated from Hanwoo Beef Cattle by Retinoic Acid and Calcium
Authors: Seong Gu Hwang, Young Kyoon Oh, Joseph F. dela Cruz
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Marbling, or intramuscular fat, has been consistently identified as one of the top beef quality problems. Intramuscular adipocytes distribute throughout the perimysial connective tissue of skeletal muscle and are the major site for the deposition of intramuscular fat, which is essential for the eating quality of meat. The stromal vascular fraction of the skeletal muscle contains progenitor cells that can be enhanced to differentiate to adipocytes and increase intramuscular fat. Primary cultures of bovine intramuscular stromal vascular cells were used in this study to elucidate the effects of extracellular calcium and retinoic acid concentration on adipocyte differentiation. Cell viability assay revealed that even at different concentrations of calcium and retinoic acid, there was no significant difference on cell viability. Monitoring of the adipocyte differentiation showed that bovine intramuscular stromal vascular cells cultured in a low concentration of extracellular calcium and retinoic acid had a better degree of fat accumulation. The mRNA and protein expressions of PPARγ, C/EBPα, SREBP-1c and aP2 were analyzed and showed a significant upregulation upon the reduction in the level of extracellular calcium and retinoic acid. The upregulation of these adipogenic related genes means that the decreasing concentration of calcium and retinoic acid is able to stimulate the adipogenic differentiation of bovine intramuscular stromal vascular cells. To further elucidate the effect of calcium, the expression level of calreticulin was measured. Calreticulin which is known to be an inhibitor of PPARγ was down regulated by the decreased level of calcium and retinoic acid in the culture media. The same tendency was observed on retinoic acid receptors RARα and CRABP-II. These receptors are recognized as adipogenic inhibitors, and the downregulation of their expression allowed a better level of differentiation in bovine intramuscular stromal vascular cells. In conclusion, data show that decreasing the level of extracellular calcium and retinoic acid can significantly promote adipogenesis in intramuscular stromal vascular cells of Hanwoo beef cattle. These findings may provide new insights in enhancing intramuscular adipogenesis and marbling in beef cattle.Keywords: calcium, calreticulin, hanwoo beef, retinoic acid
Procedia PDF Downloads 305239 Social Comparison at the Workplace: Evidence from a Field Experiment in Kolkata, India
Authors: Pooja Balasubramanian, Ghida Karbala
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Unfair treatment at the workplace encourages workers to adjust their behavior in order to restore fairness and align monetary returns to costs. This adjustment of behavior, however, may differ depending on the reference group considered to evaluate equity. In this aspect two main questions are to be considered: How do workers respond to unfair treatment at the workplace? And how does this response change depending on the identity of the reference group? To answer the above research questions, this paper utilizes data from a randomized field experiment conducted in Kolkata, India where student assistants were hired to help in a data entry task. Recruited workers were working in a team of two and were offered a fixed wage per hour. Workers were randomly assigned to one of the following treatment groups: A control group not subjected (1) to wage cuts (2) A general wage cut (3) A unilateral wage cut in reference to colleagues with similar social identity (4) A unilateral wage cut in reference to colleagues with a different social identity, where social identity is defined in terms of gender. Results show a significant decrease in the quantity and quality of work following a general wage cut. A more severe drop in productivity was presented by men in the case of unilateral wage cut, while women experiencing unilateral wage cuts didn’t exhibit a similar behavior regardless of the gender of the team member. To the contrary, women matched with a male colleague and experiencing unilateral wage cut show a slight increase in productivity, a result that contributes to the discussion regarding the paradox of the 'content female worker'. These findings highlight the necessity of a better understanding of the social comparison processes prevailing at the workplace, given the major role they play in determining the level of productivity supplied.Keywords: effort supply, fairness, reference groups, social comparison
Procedia PDF Downloads 149238 Purification and Characterization of a Novel Extracellular Chitinase from Bacillus licheniformis LHH100
Authors: Laribi-Habchi Hasiba, Bouanane-Darenfed Amel, Drouiche Nadjib, Pausse André, Mameri Nabil
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Chitin, a linear 1, 4-linked N-acetyl-d-glucosamine (GlcNAc) polysaccharide is the major structural component of fungal cell walls, insect exoskeletons and shells of crustaceans. It is one of the most abundant naturally occurring polysaccharides and has attracted tremendous attention in the fields of agriculture, pharmacology and biotechnology. Each year, a vast amount of chitin waste is released from the aquatic food industry, where crustaceans (prawn, crab, Shrimp and lobster) constitute one of the main agricultural products. This creates a serious environmental problem. This linear polymer can be hydrolyzed by bases, acids or enzymes such as chitinase. In this context an extracellular chitinase (ChiA-65) was produced and purified from a newly isolated LHH100. Pure protein was obtained after heat treatment and ammonium sulphate precipitation followed by Sephacryl S-200 chromatography. Based on matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, the purified enzyme is a monomer with a molecular mass of 65,195.13 Da. The sequence of the 27 N-terminal residues of the mature ChiA-65 showed high homology with family-18 chitinases. Optimal activity was achieved at pH 4 and 75◦C. Among the inhibitors and metals tested p-chloromercuribenzoic acid, N-ethylmaleimide, Hg2+ and Hg + completelyinhibited enzyme activity. Chitinase activity was high on colloidal chitin, glycol chitin, glycol chitosane, chitotriose and chitooligosaccharide. Chitinase activity towards synthetic substrates in the order of p-NP-(GlcNAc) n (n = 2–4) was p-NP-(GlcNAc)2> p-NP-(GlcNAc)4> p-NP-(GlcNAc)3. Our results suggest that ChiA-65 preferentially hydrolyzed the second glycosidic link from the non-reducing end of (GlcNAc) n. ChiA-65 obeyed Michaelis Menten kinetics the Km and kcat values being 0.385 mg, colloidal chitin/ml and5000 s−1, respectively. ChiA-65 exhibited remarkable biochemical properties suggesting that this enzyme is suitable for bioconversion of chitin waste.Keywords: Bacillus licheniformis LHH100, characterization, extracellular chitinase, purification
Procedia PDF Downloads 437237 Adsorption of Chlorinated Pesticides in Drinking Water by Carbon Nanotubes
Authors: Hacer Sule Gonul, Vedat Uyak
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Intensive use of pesticides in agricultural activity causes mixing of these compounds into water sources with surface flow. Especially after the 1970s, a number of limitations imposed on the use of chlorinated pesticides that have a carcinogenic risk potential and regulatory limit have been established. These chlorinated pesticides discharge to water resources, transport in the water and land environment and accumulation in the human body through the food chain raises serious health concerns. Carbon nanotubes (CNTs) have attracted considerable attention from on all because of their excellent mechanical, electrical, and environmental characteristics. Due to CNT particles' high degree of hydrophobic surfaces, these nanoparticles play critical role in the removal of water contaminants of natural organic matters, pesticides and phenolic compounds in water sources. Health concerns associated with chlorinated pesticides requires the removal of such contaminants from aquatic environment. Although the use of aldrin and atrazine was restricted in our country, repatriation of illegal entry and widespread use of such chemicals in agricultural areas cause increases for the concentration of these chemicals in the water supply. In this study, the compounds of chlorinated pesticides such as aldrin and atrazine compounds would be tried to eliminate from drinking water with carbon nanotube adsorption method. Within this study, 2 different types of CNT would be used including single-wall (SWCNT) and multi-wall (MWCNT) carbon nanotubes. Adsorption isotherms within the scope of work, the parameters affecting the adsorption of chlorinated pesticides in water are considered as pH, contact time, CNT type, CNT dose and initial concentration of pesticides. As a result, under conditions of neutral pH conditions with MWCNT respectively for atrazine and aldrin obtained adsorption capacity of determined as 2.24 µg/mg ve 3.84 µg/mg. On the other hand, the determined adsorption capacity rates for SWCNT for aldrin and atrazine has identified as 3.91 µg/mg ve 3.92 µg/mg. After all, each type of pesticide that provides superior performance in relieving SWCNT particles has emerged.Keywords: pesticide, drinking water, carbon nanotube, adsorption
Procedia PDF Downloads 170236 Phase Composition Analysis of Ternary Alloy Materials for Gas Turbine Applications
Authors: Mayandi Ramanathan
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Gas turbine blades see the most aggressive thermal stress conditions within the engine, due to high Turbine Entry Temperatures in the range of 1500 to 1600°C. The blades rotate at very high rotation rates and remove a significant amount of thermal power from the gas stream. At high temperatures, the major component failure mechanism is a creep. During its service over time under high thermal loads, the blade will deform, lengthen and rupture. High strength and stiffness in the longitudinal direction up to elevated service temperatures are certainly the most needed properties of turbine blades and gas turbine components. The proposed advanced Ti alloy material needs a process that provides a strategic orientation of metallic ordering, uniformity in composition and high metallic strength. The chemical composition of the proposed Ti alloy material (25% Ta/(Al+Ta) ratio), unlike Ti-47Al-2Cr-2Nb, has less excess Al that could limit the service life of turbine blades. Properties and performance of Ti-47Al-2Cr-2Nb and Ti-6Al-4V materials will be compared with that of the proposed Ti alloy material to generalize the performance metrics of various gas turbine components. This paper will involve the summary of the effects of additive manufacturing and heat treatment process conditions on the changes in the phase composition, grain structure, lattice structure of the material, tensile strength, creep strain rate, thermal expansion coefficient and fracture toughness at different temperatures. Based on these results, additive manufacturing and heat treatment process conditions will be optimized to fabricate turbine blade with Ti-43Al matrix alloyed with an optimized amount of refractory Ta metal. Improvement in service temperature of the turbine blades and corrosion resistance dependence on the coercivity of the alloy material will be reported. A correlation of phase composition and creep strain rate will also be discussed.Keywords: high temperature materials, aerospace, specific strength, creep strain, phase composition
Procedia PDF Downloads 115